ICU Manual - Nodrm by Prem Kumar

ICU
MANUAL
ICU
MANUAL
Editor-in-Chief
Prem Kumar
MD DA DNB
Assistant Professor
Department of Anesthesiology
Critical Care and Pain Medicine
Saveetha Medical College and Hospital
Chennai, Tamil Nadu, India
Editors
TA Naufal Rizwan Sushma Vijay Pingale
MD CCEBDM (Diabetology) MD DA
Assistant Professor Assistant Professor
Department of Internal Medicine Department of Anesthesiology
Saveetha Medical College and Hospital Critical Care and Pain Medicine
Chennai, Tamil Nadu, India Saveetha Medical College
and Hospital
G Ninoo George Marun Raj

MD DM MS MCh
Consultant Assistant Professor
Department of Nephrology Department of Vascular Surgery
Billroth Hospitals Saveetha Medical College and Hospital
Chennai, Tamil Nadu, India Chennai, Tamil Nadu, India
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ICU Manual
First Edition: Digital Version 2018
ISBN: 978-93-5270-030-1
Dedicated to
My Lord Jesus Christ, whom I love more for His grace and
mercy towards me and He is the reason for all the exaltation
in my life.
My dear wife Vero, and my loving son Sammy, who are my
greatest joy.
My dear parents, sister and in-laws, especially Dr Joseph,
who encouraged me to write this book.
All my teachers, especially to my mentor Professor Naheed
Azhar, who inspired me to become anesthesiologist and
intensivist.
CONTRIBUTORS
A Meenakshi Sundaram MS DNB Sumathy MD

Assistant Professor Assistant Professor
Department of Otorhinolaryngology Institute of Anesthesiology and Critical
Saveetha Medical College and Hospital Care
Chennai, Tamil Nadu, India Madras Medical College and Hospital
Deepalakshmi MBBS Chennai, Tamil Nadu, India
Postgraduate
Department of Biochemistry Surendran GD MD
KAPV Medical College Assistant Professor
Trichy, Tamil Nadu, India Department of Cardiology
Dianitta Devapriya Veronica MBBS Kilpauk Medical College and Hospital
Postgraduate Chennai, Tamil Nadu, India
Department of Otorhinolaryngology
Kilpauk Medical College and Hospital Sushma Vijay Pingale MD DA
Chennai, Tamil Nadu, India Assistant Professor
Department of Anesthesiology
G Ninoo George MD DM
Critical Care and Pain Medicine
Consultant
Saveetha Medical College and Hospital
Department of Nephrology
Billroth Hospitals Chennai, Tamil Nadu, India
S Yuvaraj MBBS DA
Jenu Santhosh MD Consultant Intensivist
Assistant Professor Raghavendra Multispeciality Hospital
Department of Internal Medicine
Madurai, Tamil Nadu, India
Thoothukudi Medical College and Hospital
Thoothukudi, Tamil Nadu, India
TA Naufal Rizwan MD CCEBDM (Diabetology)
K Gunalan MS Assistant Professor
Assistant Professor Department of Internal Medicine
Department of Orthopedics Saveetha Medical College and Hospital
Saveetha Medical College and Hospital Chennai, Tamil Nadu, India
Marun Raj MS MCh Vinoj MBBS DA PGDHS (Diabetology)
Assistant Professor Postgraduate
Department of Vascular Surgery Department of Internal Medicine
Saveetha Medical College and Hospital Tirunelveli Medical College and Hospital
Chennai, Tamil Nadu, India Tirunelveli, Tamil Nadu, India
Prem Kumar MD DA DNB
Assistant Professor V Thanga Thirupathi Rajan MS MCh
Department of Anesthesiology Associate Professor
Critical Care and Pain Medicine Department of Neurosurgery
Saveetha Medical College and Hospital Saveetha Medical College and Hospital
Chennai, Tamil Nadu, India Chennai, Tamil Nadu, India
PREFACE
Critical care medicine is relatively new but increasingly important medical

specialty, which has become fully established in the current decade. ICU Manual
focuses on the basic principles of intensive care which every practicing intensivist
and postgraduate should be aware of. The concept of conditions commonly
prevalent in intensive care has been dealt with in detail making it useful for the
reader to gain a thorough knowledge of the intensive care. The scientific content
is streamlined so that it would be of immense use for practicing intensivists in
developing countries.
Flow charts, tables, algorithms and pictures have also been added to facilitate
easy understanding of the subject. Many authors from various specialties have
contributed for this book. It covers extensively on all the essentials—from the
basics and system-specific topics to the recent advances—thereby making it
comprehensive for intensive care. The recent articles and the current guidelines
of sepsis and deep vein thrombosis (DVT) have also been included. The special
feature of this book is the inclusion of the chapter ‘Role of Ultrasound in Critical
Care’, since the use of ultrasound in critical care has tremendously increased in
the past five years and has totally changed the practice of intensive care in certain
areas.
We hope that this book will be a good resource to all the readers and help in
intensive care practice and would be of immense use in treating the critically ill
patients.
Prem Kumar
ACKNOWLEDGMENTS
I offer my gratitude to all the contributors and editors of this book, without whom,
this book would have not been possible. I thank our respected Chancellor of
Saveetha University, Dr NM Veeraiyan; and, our Director, Dr Saveetha Rajesh,
for their constant motivation in writing this book. To my professors, colleagues,
postgraduates, illustrators and all the supporting staff, who helped me in bringing
this book to its present shape. Finally, I thank Mr Jayanandan, Mrs Samina Khan,
Ms Saima Rashid, and all the supporting staff of M/s Jaypee Brothers Medical
Publishers (P) Ltd., New Delhi, India, for their support in bringing up this ICU
Manual, which would be of immense help to the readers.
CONTENTS
SECTION 1: ICU
1. Setting Up an ICU 3
Prem Kumar
Initial Planning 3; Infrastructure 3; Indian Society of Critical Care
Medicine (ISCCM) Provide Guidelines for Each Level ICU Planning in
India 4; Other Issues 6
SECTION 2: Physiology of Critically Ill Patient

2. Critically Ill Patient and Oxygenation 9
Prem Kumar
Oxygen Cascade 9; Tissue Oxygenation 12
SECTION 3: Vascular Access and Hemodynamic Monitoring

3. Peripheral Arterial Catheterization 17
Prem Kumar
Indications 17; Equipment 17; Monitoring Sites 17;
Technique 18
4. Peripheral Venous Catheterization 24
Prem Kumar
Insertion Techniques 24; Precautions 24; Equipment 24;
Principle 24; Midline Catheters 26
5. Central Venous Catheterization 27
Prem Kumar
Applied Anatomy 28; Techniques 30; Ultrasound-Guided
Techniques 38
6. Pulmonary Artery Catheterization 43
Prem Kumar
History 43; Perioperative Indications 44; Physiological Variables
with PA Catheterization 46
7. Hemodynamic Monitoring 51
Prem Kumar
Thoracic Bioimpedance Plethysmography 51; Esophageal
and Transcutaneous Doppler Monitoring 51; Mucosal
Tonometry 53; Systolic Pressure Variation 58; Limitations of
Dynamic Parameters 59
xiv ICU Manual
SECTION 4: Shock
8. An Overview of Shock 65
Prem Kumar
Definition 65; Classification 65; Clinical Features 66
9. Hypovolemic Shock 71
Prem Kumar
Etiology 71; Pathophysiology 71; Key Elements of Managing
Hemorrhagic Shock 74
10. Obstructive Shock 77
Prem Kumar
Causes 77; Pathophysiology 77; Clinical Features 77; Air
Embolism 78
11. Cardiogenic Shock 81
TA Naufal Rizwan
Definition 81; Characteristics 81; Pathogenesis 82; Clinical
Features 82; High-risk Patients for Cardiogenic Shock 82; Left
Heart Catheterization and Angiography 83; Invasive Procedures in
Cardiogenic Shock 84; Vasopressors 85
12. Multiple Organ Dysfunction Syndrome 87
Prem Kumar
Definition 87; Etiology 87; Pathophysiology 87; Clinical
Syndromes 89; Scoring Systems 89
SECTION 5: Infection and Immune Disorders in ICU

13. Approach to Nosocomial Infections 97
Prem Kumar
Risk Factors 97; Mechanisms of Drug Resistance 98; Nosocomial
Pneumonia 98
14. Urinary Tract Infections 108
Prem Kumar
Definitions 108; Risks 108; Common Organisms Causing Urinary
Tract Infection 109; Prevention of CAUTI—Recommendations by
HICPAC (Healthcare Infection Control Practices Advisory Committee)
2009 Guidelines 113
15. Sepsis and Septic Shock 115
Prem Kumar
Definitions 115; Pathogenesis 115; Sepsis 117; Severe
Sepsis 117; Antimicrobial Therapy 121; Hemodynamic
Support 122
16. Principles of Antibiotic Use in ICU 127
Prem Kumar
Principles of Antibiotic Prescription 127; Common Causes of
Infection in ICU 128; Pharmacokinetic Principles 128;
Steps Taken to Prevent Antibiotic Resistance 131
Contents xv
17. Tropical Infections 134

Jenu Santhosh
Severe Malaria 134; Dengue 137
18. Anaphylaxis 140
Prem Kumar
Definitions 140; Etiology and Predisposing Factors 140; Clinical
Manifestations 141; Role of Epinephrine in Anaphylaxis 144
SECTION 6: Poisoning and Envenomation

19. General Principles of Poisoning 149
Jenu Santhosh
Manifestations 149; Neurological Examination 149;
Cardiovascular 150; Metabolic 150; Management 150
20. Poisoning 153
Jenu Santhosh, TA Naufal Rizwan
Organophosphorus and Carbamate Poisoning 153; Organochlorine
and Pyrethroid Poisoning 155
21. Drug Overdose 159
Sedatives and Hypnotics 159; Antidepressants 159; Acetaminophen
Poisoning 160; Opioids 160; Beta-blockers 161
22. Envenomation 162
Jenu Santhosh
Scorpions (Scorpionidae) 162; Caterpillars and Moths
(Lepidoptera) 162; Reptile Bites 163
SECTION 7: Burns
23. Classification and Evaluation of Burns 173
Prem Kumar
Classification 173; Physiological Disturbances 173; Burns
Assessment 174; Secondary Survey 179
24. Management of Burns 180
Prem Kumar
Early Resuscitative Phase 180; Wound Management Phase 182;
Rehabilitative Phase 183; Management of Carbon Monoxide
Poisoning 183; Complications 184
SECTION 8: Respiratory Diseases in ICU

25. Approach to Acute Respiratory Failure 187
Prem Kumar
Pathophysiology 188; Clinical Presentation 188; Treatment 189
26. Acute Lung Injury and Acute Respiratory Distress Syndrome 193
Prem Kumar
Definition 193; Pathophysiology 194; Management 195; Weaning
Protocol for ARDS 196; Fluid Management 197; Nutritional
Support 197
xvi ICU Manual
27. Acute Exacerbation of Chronic Obstructive Pulmonary Disease 199

Prem Kumar
Risk Factors 199; Pathophysiology 199; Diagnosis 200; Clinical
Assessment 202
28. Acute Severe Asthma 206
Prem Kumar
Clinical Features 206; Diagnosis 206; Management 209
29. Deep Venous Thrombosis and Pulmonary Embolism 214
Prem Kumar, Marun Raj
Pathophysiology 214; Clinical Features and Diagnosis 214;
Prevention 218; Treatment 222
30. Obstructive Sleep Apnea and Obesity Hypoventilation
Syndrome 225
Prem Kumar
History 225; Obstructive Sleep Apnea 226; Obesity Hypoventilation
Syndrome 227
SECTION 9: Approach to Mechanical Ventilation

31. Basics of Mechanical Ventilation 233
Prem Kumar, S Yuvaraj
Negative Pressure Ventilation 233; Positive Pressure Ventilation 233;
Ventilator Design 233; Nomenclatures and their Significance 234;
Breath Type 234
32. Initiation of Ventilation 239
Prem Kumar
Initial Ventilator Settings 240
33. Modes of Ventilation 245
Prem Kumar
Basic Modes of Ventilation 245; Pressure Support Ventilation 249
34. Weaning from Mechanical Ventilation 258
Prem Kumar
Definition of Weaning 258; Weaning Criteria 258
35. Patient Ventilator Asynchrony 264
Prem Kumar
Variables Contributing to Asynchrony 265
36. Noninvasive Ventilation 269
Equipment (Interface) 269; Protocol for Managing Patients Planned
for NIPPV 269; Asthma 272; Pneumonia 272
SECTION 10: Cardiovascular Diseases in ICU

37. Cardiac Arrhythmias 277
Surendran GD
Supraventricular Arrhythmias 277; Ventricular Arrhythmias 286
Contents xvii
38. Acute Heart Failure 296

Surendran GD
Definition 296; Classification 296; Pathophysiology 296; Clinical
Features 296; Biomarkers 297; Specific Therapies for Acute Heart
Failure 299; Vasodilators 299; Other Drugs Used in the Treatment
of Acute Heart Failure 302
39. Approach to Acute Myocardial Infarction 306
Surendran GD
Definition 306; Universal Definition of Myocardial
Infarction 306; Universal Myocardial Infarction Classification of
Type 306; Clinical Features 307; ECG Manifestations of Ischemia
in the Setting of LBBB 310; Antiplatelet Therapy 312; Pain
Control 313; Limitations of Infarct Size 315; Percutaneous
Coronary Intervention 316
40. Hypertensive Crisis 322
Surendran GD
Definition 322; Hypertensive Emergency (Previously Malignant
Hypertension) 322; Hypertensive Urgency 323; Investigations 324
41. Cardiac Tamponade 328
Surendran GD
Definition 328; Pathophysiology 328; Precipitating
Factors 328; Clinical Features 328; Becks Triad (Useful
Clue for Diagnosis of Tamponade) 329; Differential
Diagnosis 329; Investigations 329; Management 330
SECTION 11: Renal and Electrolyte Disturbances in ICU

42. Acute Kidney Injury 335
Jenu Santhosh, Prem Kumar
Characteristics 335; Categories 335; Diagnosis 337; Markers for
Renal Dysfunction in AKI 338
43. Renal Replacement Therapy 342
G Ninoo George
Access 343; Hemodialysis Versus Peritoneal Dialysis 344;
Intermittent Hemodialysis Versus Slow Low Efficiency Dialysis 344;
Slow Low Efficiency Dialysis Versus Continuous Renal Replacement
Therapy 344; Adverse Effects of Renal Replacement Therapy 344
44. Hyponatremia 346
TA Naufal Rizwan
Causes 346; Pseudohyponatremia 347; True Hyponatremia (< 275
mOsm/Kg) 347; Asymptomatic Hyponatremia 348; Symptomatic
Hyponatremia 348; Osmotic Demyelination Syndrome 349;
Hypernatremia 349; Management of Diabetes Insipidus 351
45. Potassium 353
Prem Kumar, Sushma Vijay Pingale
Potassium Balance in Health and Disease 353; Hypokalemia 353;
Hyperkalemia 355
xviii ICU Manual
46. Calcium 359

TA Naufal Rizwan
Calcium Metabolism 359; Hypocalcemia 359; Chvostek’s Sign 360;
Trousseau Sign 360; Hypercalcemia 361; Diagnostic Workup 362
47. Phosphorus 366
TA Naufal Rizwan
Metabolism 366; Hypophosphatemia 366; Hyperphosphatemia 369
48. Magnesium 372
TA Naufal Rizwan
Hypomagnesemia 372; Hypermagnesemia 374
SECTION 12: Gastrointestinal Diseases in ICU

49. Upper Gastrointestinal Bleeding 379
TA Naufal Rizwan
Peptic Ulcer 379; Variceal Bleed 379; Mallory-Weiss
Tear 380; Boerhaave’s Syndrome 380; Vascular
Anomalies 380; Management 380; Pharmacologic
Therapy 382; Endoscopy 382; Specific Conditions 382
50. Lower Gastrointestinal Bleeding 385
TA Naufal Rizwan
Etiology 385; Investigations 386; Treatment 386;
Specific Measures 387
51. Acute Pancreatitis 389
TA Naufal Rizwan
General Considerations 389; Etiology 389; Pathogenesis 389;
Clinical Features 390; Investigations 390; Radiology 391;
Differential Diagnosis 392; Management 392
52. Acute Liver Failure 394
TA Naufal Rizwan
Classification 394; Causes of Acute Liver Failure 394;
Pathophysiology 395; Clinical Features 395; Associations of Acute
Hepatic Failure 395; Prognosis 398; Treatment 398; Liver
Transplantation 400
53. Abdominal Infections in ICU 402
TA Naufal Rizwan
Classification 402; Pathophysiology 403; Clinical Features 403;
Investigations 404; Management 404; Duration of Treatment 406
SECTION 13: Hematological Disorders in ICU

54. Hemolytic Anemia and Sickle Cell Crisis 411
Vinoj
Hemolytic Anemia 411; Sickle Cell Crisis 413
55. Disseminated Intravascular Coagulation and Heparin-induced
Thrombocytopenia 416
Vinoj
Disseminated Intravascular Coagulation 416; Heparin-induced
Thrombocytopenia 418
Contents xix
56. Immune Thrombocytopenic Purpura 420

Vinoj
Pathogenesis 420; Classification of Immune Thrombocytopenic
Purpura 420; Clinical Features 421; Laboratory Finding 421;
Treatment 422; Emergency Treatment of Acute Bleeding 423
SECTION 14: Endocrine Disorders in ICU

57. Diabetic Ketoacidosis 427
Vinoj, G Ninoo George
Precipitating Factors 428; Basic Pathophysiology of Diabetic
Ketoacidosis 428; Clinical Features 428; Management Goals 429;
Assessment and Monitoring 430; Fluid Replacement 430; Insulin
Therapy 430; Electrolyte Correction 430
58. Hyperosmolar Hyperglycemic State 432
Pathophysiology 432; Clinical Features 433
59. Diabetes Insipidus 435
Vasopressin: Neural Hormone 435; Etiology 436;
Complications 439
60. Syndrome of Inappropriate Secretion of Antidiuretic Hormone 441
Pathophysiology 441
61. Thyroid Emergencies 449
Thyroid Storm 449; Myxedema Coma 451; Pathogenesis 452
62. Adrenal Emergencies 455
Adrenal Crisis 455; Primary (↑ ACTH) 455
SECTION 15: Obstetric Emergencies

63. Obstetric Hemorrhage 463
Prem Kumar
Causes of Obstetric Hemorrhage 463; Classification 463;
Antepartum Hemorrhage 464; Postpartum Hemorrhage 465
64. Hypertensive Disorders of Pregnancy 469
Prem Kumar
Classification of Hypertensive Disorders in
Pregnancy 469; Definitions 469; Pre-eclampsia 469; HELLP
Syndrome 473; Eclampsia 474
65. Acute Fatty Liver of Pregnancy 476
Prem Kumar
Pathophysiology 476; Clinical Presentation 476; Lab
Investigations 476; Differential Diagnosis 476;
Complications 477; Management 477
xx ICU Manual
66. Amniotic Fluid Embolism 479

Prem Kumar
Pathophysiology 479; Clinical Features 479; Lab Investigations 480;
Management 480
SECTION 16: Neurological Disorders in ICU

67. Cerebrovascular Diseases 483
TA Naufal Rizwan
Transient Ischemic Attack 483; Stroke 484; Ischemic Stroke
(80%) 484; Clinical Features 485; Hemorrhagic Stroke 486;
Clinical Features of Hemorrhagic Stroke 486; Management of
Cerebral Edema 487
68. Status Epilepticus 490
TA Naufal Rizwan
Definition 490; Etiology 490; Types 490; Convulsive 490;
Simple Partial Status Epilepticus 491; Complications 491;
Investigations 491; Treatment 491
69. Meningitis and Encephalitis 494
TA Naufal Rizwan
Definition 494; Classification 494; Acute Bacterial Meningitis 494;
Pathogenesis 495; Clinical Features 495; Investigations 496;
Imaging 496; Differential Diagnosis 497; Treatment 497;
Antibiotics Based on Organisms 497; Viral Meningitis 499;
Investigations 500; Tubercular Meningitis 501; Fungal
Meningitis 502; Viral Encephalitis 503; Treatment 504
70. Alcohol Withdrawal Syndrome 506
TA Naufal Rizwan
Symptoms 506; Delirium Tremens 507; Management of Delirium
Tremens 508
71. Delirium in Intensive Care Unit 510
TA Naufal Rizwan
Definition 510; Clinical Features 510; Terminal Delirium 510
SECTION 17: Neuromuscular Disorders

72. Guillain-Barré Syndrome 517
TA Naufal Rizwan
General Considerations 517; Etiology 517; Pathogenesis 517;
Clinical Features 518
73. Myasthenia Gravis 521
TA Naufal Rizwan
Etiology 521; Pathogenesis 521; Clinical Features 522;
Investigations 523; Treatment 524; Evaluating the Effectiveness of
Treatment 526; Myasthenic Crisis 526
74. Periodic Paralysis 528
TA Naufal Rizwan
Hypokalemic Periodic Paralysis 528; Hyperkalemic Periodic
Paralysis 529; Anderson’s Syndrome 530
Contents xxi
75. Critical Illness Polyneuropathy 531

TA Naufal Rizwan
Predisposing Factors 531; Pathology 531; Pathogenesis 531;
Clinical Features 531; Treatment 533
SECTION 18: Approach to a Trauma Patient

76. Advanced Trauma Life Support 537
Prem Kumar
Airway 537; Breathing 539; Circulation 539;
Massive Transfusion 541; Complications 542
77. Open Fractures 545
K Gunalan
Classification 545; Antibiotic Cover 546; Surgical Debridement and
Irrigation 546; Wound Closure 547; Skeletal Fixation 547
78. Pelvic Fractures 551
K Gunalan
Advanced Trauma Life Support 552; Hemodynamic Status 552;
Fracture Stability 552; Pneumatic Antishock Garment 553; Pelvic
Binders 553; Anterior External Fixator 553; Acute Fracture
Fixation 554; Angiography 554; Pelvic Packing 555; Open Pelvic
Fractures 555
79. Fat Embolism Syndrome 557
Sushma Vijay Pingale
Etiology 557; Pathogenesis 557; Clinical Features 557;
Diagnosis 558; Management 559
80. Abdominal Trauma 560
Marun Raj
Mechanism of Injury 560; Diagnostic Principles in
General 560; Lab Investigations 562; Diagnostic
Peritoneal Lavage 562; Angiography 563; Preoperative
Management 563; Damage Control Surgery 564; Abdominal
Compartment Syndrome 564
81. Vascular Trauma of Extremities 567
Marun Raj
Historical Perspective 567; Epidemiology 567; Clinical
Presentation 568; Noninvasive Imaging 568; Management of
Extremity Trauma 570; Compartment Syndrome 574
82. Traumatic Head Injury 576
Sushma Vijay Pingale, V Thanga Thirupathi Rajan
Primary Injury 576; Secondary Injury 579
83. Thoracic Trauma 588
Sushma Vijay Pingale, Marun Raj
Injury to Chest Wall 588; Injury to Pleura 589; Injury to Lung 591;
Injury to Heart 591; Injury to Aorta 592; Injury to Esophagus 594
xxii ICU Manual
SECTION 19: Ultrasonography

84. Role of Ultrasound in Critical Care 597
Prem Kumar
Physics of Ultrasound 598; Ultrasound Image Characteristics 600;
Needle Orientation 602; Pulmonary Embolism 603; Procedural
Uses of Ultrasound 608
SECTION 20: Acid-Base Disorders

85. Basics of Acid-Base Balance 617
Basic Concepts and Terminologies 617
86. Metabolic and Respiratory Acid-Base Disorders 623
Metabolic Acidosis 623
87. Interpretation of Acid-Base Disorder 631
Stepwise Approach for Interpretation of ABG 631; Arterial Blood Gas
Exercises 632
SECTION 21: Nutritional Support

88. Nutrition and Metabolism in Critically Ill Patients 639
Pathophysiology of Nutrition in Illness 639; Nutritional
Assessment 640
89. Enteral and Parenteral Nutrition 647
Timing of Nutritional Support 647; Routes for Giving Nutritional
Support 647; Refeeding Syndrome 653
SECTION 22: Sedation and Analgesia in ICU

90. Sedation and Analgesia for Critical Care Patients 657
Prem Kumar
Issues to be Addressed for Management of Pain and Sedation in
ICU 657; Pain and Sedation Considerations 657; Assessment of
Pain 658; Pain Scales 659
91. Patient-Controlled Analgesia 670
Prem Kumar
Pre-requisites 670; Mechanics about the Device 670; How to Write
an Order for PCA? 670
SECTION 23: Airway Management in ICU

92. Rapid Sequence Induction 677
Prem Kumar
Essential Components of Rapid Sequence Induction 677; Indications
of Rapid Sequence Induction 678; Cricoid Pressure 678
Contents xxiii
93. Endotracheal Intubation in Critical Care 680

Prem Kumar, Dianitta Devapriya Veronica
Basic Anatomy 680; Fast-track Evaluation and Airway Assessment
before Intubation 680; Adjuncts for Airway Management 682;
Intubation Techniques 687; Management of Difficult Airway 688;
Care of Endotracheal Tube in ICU 690
94. Tracheostomy 693
A Meenakshi Sundaram
Emergency Tracheostomy 693; Elective Tracheostomy 694; Types
of Tracheostomy 695; Cricothyroidotomy/Minitracheostomy 696
SECTION 24: Transfusion Practice in ICU

95. Blood Transfusion: Components and Indications 703
Prem Kumar
Component Separation 703
96. Complications of Blood Transfusion 709
Prem Kumar
Adverse Reactions to Transfusion 709; Massive Blood
Transfusion 713
SECTION 25: Fluid Management

97. Perioperative Fluid Balance 717
Prem Kumar
Basic Physiology of Fluid Balance 717
98. Fluid Resuscitation 722
Prem Kumar
Fluid Management in Perioperative Patients 722
SECTION 26: Cardiopulmonary Resuscitation

99. Basic Life Support 731
Prem Kumar
Physiology of Cardiopulmonary Resuscitation 732; Adult Basic
Life Support Sequence 733; Sequence of Adult Basic Life Support
Skills 734; Airway Management 735
100. Advanced Cardiac Life Support 739
Prem Kumar
Adjuncts for Airway Management 740; Management of Adult Cardiac
Arrest 741
101. Cardiac Arrest in Special Situations 750
Prem Kumar
Anaphylaxis 750; Pregnancy 751; Trauma 752;
Hypothermia 753; Asthma 754; Drowning 755; Percutaneous
Coronary Intervention 756; Cardiac Tamponade 756; Cardiac
Surgery 756
xxiv ICU Manual
SECTION 27: Brain Death

102. Care of a Brain Dead Patient 761
Sumathy, Prem Kumar, Deepalakshmi
Definition 761; Physiology of Brain Death 761; Steps
for Determining Brain Death 763; Diagnostic Criteria for
the Clinical Diagnosis of Brain Death 764; Management of
Heartbeating Brain Death Organ Donor 766; Management of 2nd
Phase 768; Management of Respiratory System 769; Management
of Endocrine System 770; Quadruple Hormonal Replacement
Therapy 770
SECTION 28: Medical Ethics

103. Ethics in Critical Care 775
Prem Kumar
End-of-life Care 775
SECTION 29: Appendices

1. Normal Biochemical Values 781
Reference Values for Laboratory Tests 781
2. Clinical Scores, Indices and Equations 789
APACHE II Scoring System 789; MODS Scoring System 790; SOFA
Scoring System 790; Gold Criteria for Grading Severity of
COPD 791; Levels of Risk Associated with Increasing Body Mass
Index 791; Waist Circumference and Risk 791; SF-MPQ (Short
Form–Mcgill Pain Questionnaire) 792; Ramsay Sedation Scale
(RSS) 793; Richmond Agitation Sedation Scale (RASS) 793
3. Drugs, Dosages and Side Effects 797
Cardiovascular System 797; Respiratory System 801; Electrolyte
Imbalance 803; Endocrine Disorders 804; Gastrointestinal
Disorders 806; Hepatic Dysfunction 806; Hematopoietic
Disorders 807; Central Nervous System 807; Infectious
Diseases 809
4. ICU Rounds 815
Essential Data and Assessment for Management of Critically Ill
Patients 815
Index 817
SECTION
1 INTENSIVE CARE UNIT
Chapter 1 Setting Up an ICU

Prem Kumar
CHAPTER
1 Prem Kumar
SETTING UP AN ICU
Intensive care unit (ICU) is a specified area in a hospital designed to manage

critically ill patients. It is an emerging specialty and all specialties merge to
give a comprehensive care to the patient. Currently, it is managed by either the
anesthesiologists or critical care physicians. Team consists of physicians, nursing
staff and other paramedical staff trained in critical care.
INITIAL PLANNING
Initial planning includes formation of a team consisting of team leader along
with nursing and paramedical personnel. Allocation of budget is based on the
resources and infrastructure.
INFRASTRUCTURE
Planning of infrastructure is based on the level of ICU which would fit the
resources. Number of ICUs and beds, design of each bed along with layout, space
and ventilation. The next important planning for any ICU is the requirement of
equipment. Equipment required for ICU are basic and advanced monitors (7 lead
ECG, SpO2 (oxygen saturation), noninvasive and invasive blood pressure, EtCO2
(end tidal carbon dioxide analysis), stroke volume variation, pulse pressure
variation, central venous pressure, pulmonary artery pressure monitoring,
transthoracic echocardiography), ventilators–containing basic and advanced
modes of ventilation, wall mount with oxygen and suction outlet. Environmental
planning includes plan for (ceiling—height, color, lighting), flooring, ICU
infection control program, air conditioning and ventilation, biomedical waste
management, visitors timing and entry dress protocol. Data management—
entry and storage of data by computers for medical records and intra- and inter-
hospital communication. Internet should be available for hospital staff. Library for
doctors with all the latest edition books for ICU management should be arranged.
Adequate space should be allocated for central nursing station with data storage
and central monitoring. Rooms for doctors, nursing and paramedical staff should
be included in the plan. Waiting room for relatives should be planned outside the
ICU.
4 Section 1 Intensive Care Unit
INDIAN SOCIETY OF CRITICAL CARE MEDICINE (ISCCM) PROVIDE

GUIDELINES FOR EACH LEVEL ICU PLANNING IN INDIA
Level I (Table 1.1)

Level I ICU is recommended for small hospitals. ICU bed strength should be 6–8
and the set-up should be equipped to put a patient on mechanical ventilation
for at least 1–2 days. Noninvasive monitors (ECG, SpO2, NIBP) along with blood
gas analysis should be available. ICU personnel (nursing and paramedical staff )
should be trained in providing basic life support to patients admitted in ICU. The
intensivist should be able to provide basic and advanced cardiac life support and
should be a trained person in critical care. The hospital should have a clinical
laboratory doing complete blood count, blood sugar, electrolyte, liver and renal
function test, X-ray and ultrasonography (USG) along with microbiology support.
Blood bank should be available round the clock and at least one critical care book
should be available for reference.
Level II (Table 1.2)

The recommendations for level II ICU include all the recommendations of level I
ICU plus the following recommendations:
Table 1.1 ICU staffing
Personnel Comments
Intensivist He is the team leader and should be a qualified,
experienced and full time intensivist who should
lead the whole team
Senior registrars and resident doctors They can be postgraduates from anesthesia,
general medicine or respiratory medicine or allied
surgical specialties. Recommendation is one
doctor for ≤5 patients who are critically ill (on
ventilator and/or undergoing invasive monitoring
with Multiorgan failure). One postgraduate
resident with one graduate resident for an ICU of
10 to 14 beds
Nursing staff 1/1—patient/nurse ratio for ventilated patients or
in multiorgan failure (MOF). Ratio should not be
<2 nurses for 3 patients. The most important
factor for success in any ICU is the quality of care
given by nursing staff trained in critical care
Respiratory therapist Physiotherapy and ventilator management of
mechanically ventilated patients
Nutritionist They play a vital role in feeding and calorie
calculation in ICU patients
Class IV workers and security They play a role in the prevention of nosocomial
infections by keeping the ICU clean. They also
protect the ICU from overcrowding
Clinical lab staff, microbiology,
imaging staff and biomedical engineer
Chapter 1 Setting Up an ICU 5
Table 1.2 ICU bed and space recommendations
ICU bed 1 to 4 per 100 hospital beds

recommendation Total bed strength in ICU should be between 8 to 12 and
should not be <6 or not >24
ICU space Space per bed should be 125–150 sq ft area per bed.
recommendation 1–2 rooms are kept designated for isolation.
There should be 100–150% extra space to accommodate
nursing station, storage, patient movement area, equipment
area, doctors and nurses rooms and toilet
Level II ICU is recommended for larger hospitals where the ICU bed strength
can be 6–12. ICU should have a qualified intensivist along with junior doctors
and nursing staff trained in critical care. The ICU staff should attend Continuing
Medical Education (CME’s) and workshops in critical care every year to update
themselves. Advanced monitoring such as invasive blood pressure, EtCO2, stroke
volume variation, pulse pressure variation, central venous pressure, pulmonary
artery pressure monitoring, transthoracic echocardiography (TTE) should be
available. ICU should be equipped to deliver long-term mechanical ventilation
with advanced modes of ventilation along with organ support system. Access
to clinical laboratory, microbiology support for diagnosis including fungus
identification, blood bank, imaging (CT, MRI) should be available for 24 hours.
Other specialty support such as neurology, cardiology, etc. should be available
in case of requirement (e.g. Transvenous pacing). There should be an integrated
HDU (high dependency unit) for stepping down patients from ICU. Institution
protocols should be formulated for ICU along with ethical clinical research.
Level III
The recommendations for level III ICU includes all the recommendations of level
I and II ICU plus the following recommendations:
Level III ICU is recommended for tertiary care hospitals where the ICU bed
strength can be 10 to 16 with one or multiple ICUs as per requirement and the
ICU is preferably a closed one with multidisciplinary unit headed by a qualified
intensivist along with senior registrar, junior residents and nursing staff trained
in critical are. ICU should be able to deliver care at the highest standard along
with a very good transport facility available both for inter-hospital and intra-
hospital transport. All the multisystem care should be available round the clock
with referrals being taken from all the other hospitals. Apart from the advanced
monitoring, bedside X-ray, USG, 2D-Echo, Fibreoptic bronchoscopy, bedside
dialysis and renal replacement therapy (RRT) should be available. Optimum
patient/nurse ratio is maintained with 1/1 patient/nurse ratio in ventilated
patients and the patient area should not be <100 sq ft per patient. Hospital should
train doctors for fellowship courses and conduct research in critical care and
actively participate in national and international research programs. Institution
should have infection control and ethical committee.
6 Section 1 Intensive Care Unit
OTHER ISSUES
• Keep bed 2 feet away from the bed wall to access the head end in case of
emergency.
• Two beds should be especially designated for RRT.
• An alarm bell which has both sound and light indicators must be provided to
each patient.
• The International Noise Council recommends that the noise level in an ICU
be under 45 dB in the daytime, 40 dB in the evening and 20 dB at night.
• Natural light is recommended in the ICU.
• Vitrified nonslippery tiles for the floors, wall height of 4–5 feet, ceiling design
enhanced by soft colors and decorating with patterns make it patient friendly.
• It is mandatory to have four covered pans (Yellow, blue, red, black) provided
for each patient.
• Each bed must have alcohol-based handwash solution which is used before
caregiver handles the patient. There should be at least two barriers to the
entry of ICU.
• There should be only one entry and exit to ICU to allow free access to
machines and 2 barriers before entering ICU.
• Proper fire-fighting/extinguishing machines should be there.
Heating, Ventilation and Air-conditioning (HVAC) System of ICU

The ICU should be fully air-conditioned which allows control of temperature,
humidity and air change. It is recommended to have a minimum of six total air
changes per room per hour, with two air changes per hour composed of outside
air. The dirty utility and laboratory need five changes per hour. It is recommended
that all air should be filtered to 99% efficiency down to 5 microns. Smoking should
not be allowed in the ICU complex. For critical care units, temperatures from
16oC to 25oC is desirable. A few cubicles may have a choice of positive or negative
operating pressures. Power back up in ICU should be available.
BIBLIOGRAPHY
1. American College of Critical Care Medicine’s Task Force on Guidelines: Guidelines for
Intensive Care Unit Design. SCCM and AACN; 1993.
2. Flynn J, Segil A, Steffy G. Architectural Interior Systents Lighting/Acoustics/Air
Conditioning. 2nd edn. New York. Van Norstrand Reinhold; 1988.
3. Integration of the Professional Nurse and the Technical Nurse in Critical Care; 1987.
4. Intensive Care Unit Planning and Designing in India Guidelines 2010. Guidelines
Committee ISCCM; 2010.
SECTION
2
PHYSIOLOGY OF CRITICALLY
ILL PATIENT
Chapter 2 Critically Ill Patient and Oxygenation

Prem Kumar
CHAPTER
2 Prem Kumar
CRITICALLY ILL PATIENT AND

OXYGENATION
The fight of the body is to ensure tissue oxygenation in critically ill patients.
Oxygen transport, delivery and utilization are complex process and its
understanding is especially useful in critically ill patient since both oxygen
transport and delivery are disturbed due to various factors. In this chapter, we
deal with the basics of O2 transport and delivery and the various factors which
affect them.
OXYGEN CASCADE
Definition
Oxygen cascade is transfer of O2 from atmosphere to mitochondria of cells.
The steps of oxygen cascade are:
• Inspired oxygen
• Alveolar oxygen
• Arterial blood
• Microcirculation
• Interstitium
• Mitochondria.
Inspired Oxygen
Partial pressure gradient for O2 is the key to gas movement. O2 flows downhill from
the air through the alveoli and blood into the tissues. At sea level, the atmospheric
pressure is 760 mm Hg and O2 makes up to 21% of inspired air.
PiO2 = FiO2 × (Pb – PH2O)
PiO2 = 0.21 × (760 – 47)
PiO2 = 149 mm Hg
where Pb-Barometric pressure, PH2O-Water vapor pressure
10 Section 2 Physiology of Critically Ill Patient
Alveolar Oxygen
As the O2 reaches the alveoli CO2 is present in large amounts, the alveolar CO2
level (PACO2) is usually the same as PaCO2.
Now the partial pressure of alveolar O2,
PAO2 = PiO2 – PACO2/R.
R is respiratory quotient, which is the amount of CO2 excreted for the amount
of O2 utilized.
R is 0.8, then PAO2 will be 149 – 40/0.8 = 99 mm Hg.
Arterial Oxygen
The next step is movement of O2 from alveolus to artery, there is significant
gradient usually 5–10 mm Hg explained by V/Q mismatch, diffusion gradient and
physiologic shunt.
Four factors influence transmission of O2 from alveoli to capillaries. They are:
1. V/Q mismatch
2. R – L shunt
3. Cardiac output
4. Diffusion defect.
Microcirculation and Interstitium

As the blood saturated with O2 from the alveolus reaches the pulmonary artery,
the systemic circulation transports this oxygenated blood to the tissues. The steps
of this transport and the further drop in partial pressure of O2 are explained here:
Oxygen content (CaO2) = (Hb × SaO2 × 1.39) + (0.003 × PaO2)
Approximately, CaO2 is 20.8 mL per 100 mL of blood
(Where SaO2 is arterial O2 saturation,
1.39-Amount of O2 per gram of normal hemoglobin,
PaO2-Partial pressure of arterial oxygen,
0.003-Dissolved oxygen)
Oxygen dissociation curve guides in understanding the oxygen content of
blood. Each molecule of hemoglobin binds 4 molecules of O2 and binding of 1
oxygen molecule to hemoglobin binding site favors binding of another oxygen
molecule to other binding sites on hemoglobin which is the reason for the S-shape
of ODC curve. This property is called cooperativity. The affinity of hemoglobin to
PO2 is not consistent at all levels of PO2 which can be seen in the Figure 2.1.
Oxygen flux or delivery (DO2) is defined as the quantity of oxygen made
available to the tissues in one minute.
Delivery of oxygen (DO2) = CaO2 × Q, where Q is cardiac output.
DO2 = 20.8/100 × 5000
= 1000 mL (Approx)
Amount of O2 consumption per minute is VO2
VO2 = Q × (CaO2 – CvO2)
Chapter 2 Critically Ill Patient and Oxygenation 11
Fig. 2.1 Oxygen dissociation curve
where CaO2=Content of O2 in arterial blood = 20 mL, CvO2=Content of O2 in

venous blood = 15 mL).
Difference is 5 mL per 100 mL
Now VO2 is 5000 × 5/100 = 250 mL/minute
Therefore, the oxygen extraction ratio (VO2/DO2) is approximately 25%.
Mitochondrial Level
At tissue level, PO2 is 3–4 mm Hg. This PO2 keeps the mitochondria of the cell to
do aerobic metabolism. When this PO2 falls below 1 mm Hg the mitochondria
switches to anaerobic metabolism, this point of switching is called Pasteur point
(Fig. 2.2).
Indices of Pulmonary O2 Transfer

• A-a gradient
• PaO2/FiO2 ratio
• Qs/Qt (venous admixture)
• Estimated shunt fraction.
Indices of Oxygen Dynamics

• Oxygen delivery index
• Oxygen consumption index—methods to measure this index is by reverse
Fick method and indirect colorimetry
• Mixed venous oxygen tension (SVO2)
• Mixed central venous oxygen saturation (ScvO2).
Fig. 2.2 Oxygen cascade
Regional Oxygen Indices

• CO2 gap–normal = 8–10 mm Hg
• Gastric intramucosal pH
• Tissue PO2.
TISSUE OXYGENATION
Adequacy of tissue oxygenation is based on the balance between oxygen supply
(DO2) to O2 demand or the amount of O2 required to maintain aerobic metabolism.
When there is disruption or imbalance, tissue hypoxia ensues, which without
treatment would lead to dysoxia (shock). Under physiological conditions, O2
demand equals VO2 (2.5 mL/kg/minute) for a DO2 of 12 mL/kg/minute with an
Oxygen extraction ratio (OER) of 20%. During severe hypoxemia or shock, DO2
decreases consequent to a decrease in cardiac output which is compensated by
increase in OER.
Critical DO2 = 4 mL/kg/minute
Critical OER = 60%
Increase in OER due to increased sympathetic drive causes vasoconstriction
and redistribution of blood flow.
Chapter 2 Critically Ill Patient and Oxygenation 13
VO2
VO2 is used as a measure of tissue O2 consumption. It can be calculated by
Fick’s equation but it is not reliable since it can vary with many factors (e.g.
Lung disease). VO2 can be calculated indirectly by measures of PA catheter but
metabolic cart is required to directly measure VO2. Hence, VO2 of <100 mL/min/
m2 can be used as a measure of reduced tissue oxygenation. As VO2 falls, lactate
level starts increasing.
VO2 is not a good parameter to reflect tissue oxygenation in sepsis since O2
is consumed for the inflammatory process in sepsis, thereby showing a falsely
elevated VO2. But in sepsis, the problem is not tissue oxygenation but O2 utiliza
tion at tissues which on increased severity leads to multiorgan failure. Thus, VO2
is not a good indicator of tissue oxygenation in sepsis. This VO2 deficit is called
O2 debt which is treated by increasing cardiac output in case of poor ventricular
function, increasing FiO2 in case of decrease in SaO2, correcting anemia, if it is
present. Although correction of all these parameters is done based on early goal
directed therapy in sepsis, still the outcome is very poor.
Mixed Venous O2 Tension (SvO2)

SvO2 can be used as a surrogate indicator for assessing the adequacy of global
tissue oxygenation (VO2 – DO2 balance).
SaO2 – SvO2
OER =
SaO2
Normal SvO2 = 65 – 70%. Increased SvO2 indicates significant fall in DO2 with
or without an increase in O2 demand. 40% SvO2 is the critical value for the patient
resulting in dysoxia/shock (Table 2.1).
Measures of O2 Exchange
• P(A – a)O2
• PaO2/FiO2 (P/F) ratio
• PaO2/PAO2 (a/A) ratio.
Measures to indicate the severity of disease based on interventions (e.g.
PEEP) is assessed by a parameter called oxygen index (OI).
(FiO2 × mean Paw)
OI = PaO2
Table 2.1 Causes of increased and decreased SvO2
Causes of ↑ SvO2 Causes of ↓ SvO2

High cardiac output Hypoxia
Impaired tissue oxygenation Anemia
Sepsis Reduced cardiac output
Hypothermia Thyroid storm
Left-to-right shunting Malignant hyperthermia
ScvO2 (Mixed Venous O2 Saturation)

ScvO2 >70% is used as an end point in early goal directed therapy. It is also used
as a surrogate marker for SvO2 but differs from SvO2 by ± 5%.
Lactate
By large, it is the most commonly used parameter to evaluate O2 supply and
demand imbalance. And 2 mEq/L is abnormal which occurs due to switch over
form aerobic to anaerobic metabolism. Just checking a single value is not reliable
but evaluating the trend of serum lactate is a good method to indicate tissue
oxygenation. Survival rate decreases as lactate level increases.
BIBLIOGRAPHY
1. Bakker J, Coffernils M, Leon M, et al. Blood lactate levels are superior to oxygen-
derived variables in predicting outcome in septic shock. Chest. 1991;99:956-62.
2. Dellinger, et al. Surviving Sepsis Campaign: International guidelines for management
of severe sepsis and septic shock (2012). Crit Care Med. 2013;41:580-637.
3. Dunham CM, Seigel JH, Weireter L, et al. Oxygen debt and metabolic acidemia
as quantitative predictors of mortality and the severity of the ischemic insult in
hemorrhagic shock. Crit Care Med. 1991;19:231-43.
4. Fink MP. Impaired cellular use of oxygen in critically ill patients. J Crit Illness. 2001;
16(suppl):S28-32.
5. Guyton and Hall. Textbook of medical physiology, 11th edn. Elsevier publications.
2006.
6. Hameed SM, Aird WC, Cohn SM. Oxygen delivery. Crit Care Med. 2003;31(suppl).
S658-67.
7. Leach RM, Treacher DF. The relationship between oxygen delivery and consumption.
Dis Mon. 1994;30:301-68.
8. Nunn JF. Nonrespiratory functions of the lung. In: Nunn JF (Ed). Applied Respiratory
Physiology. London: Butterworths. 1993:306-17.
9. Shoemaker WC. Oxygen transport and oxygen metabolism in shock and critical
illness. Crit Care Clin. 1996;12:939-69.
10. William F Ganong. Review of medical physiology, 21st edn. McGraw-Hill publications,
2003.
SECTION
3
VASCULAR ACCESS AND
HEMODYNAMIC MONITORING
Chapter 3 Peripheral Arterial Catheterization

Prem Kumar
Chapter 4 Peripheral Venous Catheterization

Prem Kumar
Chapter 5 Central Venous Catheterization

Prem Kumar
Chapter 6 Pulmonary Artery Catheterization

Prem Kumar
Chapter 7 Hemodynamic Monitoring

Prem Kumar
CHAPTER
3 Prem Kumar
PERIPHERAL ARTERIAL CATHETERIZATION
Peripheral arterial catheterization is one of the common invasive procedures

done in ICU after central venous catheterization. It is performed in patients
where beat-to-beat arterial blood pressure monitoring is required and where
severe blood loss and major cardiovascular changes are expected. Also indicated
when frequent arterial blood sampling is required and when cardiac output is
indirectly measured using pulse contour analysis.
INDICATIONS
• Continuous beat-to-beat blood pressure monitoring—hemodynamic
monitoring
• Frequent blood sampling
• Arterial drug administration—thrombolytics
• Intra-aortic balloon pump (IABP)
• Assessing volume responsiveness from pulse pressure variation (PPV) or
systolic pressure variation (SPV)
• Determination of cardiac output by pulse contour analysis.
EQUIPMENT
• Arterial cannula
• Pressure transducer
• Monitor
• Heparinized saline-filled noncompliant tubing
• Stopcocks.
MONITORING SITES
• Radial artery—most common
• Femoral artery
• Axillary artery
• Dorsalis pedis artery
• Brachial artery
• Ulnar artery
• Posterior tibial artery.
18 Section 3 Vascular Access and Hemodynamic Monitoring
Safer Arteries for Cannulation in Chronological Order

Radial > femoral > dorsalis pedis > axillary > brachial artery
TECHNIQUE
Pre-requisites
• Modified Allen test—done to assess the adequacy of collateral flow to the
hand. The intensivist compresses the radial and ulnar arteries and the palm
is exsanguinated by making a tight fist. Then the patient should open the fist
and the occlusion of the ulnar artery is released, then there is flushing of the
palm within a few seconds with normal collaterals, severely reduced collateral
flow is present when the palm remains pale for more than 10 seconds. The
other artery is also checked with the same procedure. Disadvantage is that
the sensitivity of modified Allen test is 80%.
• Doppler
Arterial cannulation can be done by various techniques:
• Seldinger’s technique
• Transfixion technique
• Ultrasound-guided Seldinger’s technique.
Seldinger’s Technique
Radial artery: Position of the hand is 40–60° dorsiflexion and wrist is prepared
and given local anesthesia with 0.5 mL of 1% lignocaine on both sides of the
radial artery (to reduce vasospasm and produce local anesthesia). A 20-gauge
catheter-over-needle apparatus is used for puncture and the needle is entered at
30–60° angle to the skin 3 cm proximal to the distal wrist crease. The cannula is
advanced until there is return of blood and the guidewire is passed into the artery
after viewing the pulsatile blood flow and thereafter the cannula is guided over
the guidewire.
In the transfixion technique, the anterior and the posterior walls of the artery
are punctured intentionally and after the needle is removed from the catheter, the
catheter is pushed into the vessel lumen.
Ultrasound-guided percutaneous technique can be done but the learning
curve is little steep.
Brachial artery: Although brachial artery does not have collateral circulation.
Many studies have proven the safety of its use.
Femoral artery: Its waveform closely resembles aorta. Risk of distal ischemia is
less due to its large size.
Axillary artery: It is used for long-term monitoring catheterization and the left
side is preferred over the right because the tip of catheter will lie distal to the
aortic arch and great vessels.
Chapter 3 Peripheral Arterial Catheterization 19
Complications
• Distal ischemia
• Hematoma
• Hemorrhage
• Arterio–venous fistula
• Pseudoaneurysm
• Thrombosis
• Embolization
• Local infection
• Nerve damage
• Peripheral neuropathy
• Cerebral embolization— in case of cannulation of central arteries.
Continuous flush devices used with arterial cannulas are designed to release
3 mL/hour of heparinized saline from an infusion bag pressurized to 300 mm Hg.
Air embolism can be prevented by clearing all the air bubbles in the tubing and
not putting flush valve for more than 2–3 seconds.
Arterial Waveform (Figs 3.1 and 3.2)

• Systole—ejection of blood from the left ventricle into the aorta
• Diastole—peripheral arterial run off of this stroke volume
• Mean arterial pressure—diastolic pressure plus one third times pulse
pressure. It can be calculated by adding the area under the waveform divided
by the duration of cardiac cycle.
The duration of time taken for the electrical events of depolarization through
the ventricle and ejection of left ventricle and transmission to aorta with resultant
change in the pressure transducer ending up in a arterial waveform is 120–180
msec after the R wave of an ECG. As the arterial pressure wave travels from the
aorta to the periphery, changes noticed in the waveform are a steeper arterial
upstroke, higher systolic peak and the dicrotic notch appears later, prominent
Fig. 3.1 Arterial pressure waveforms

Fig. 3.2 Phases of arterial waveform

1 – systolic upstroke; 2 – systolic peak
3 – systolic decline; 4 – dicrotic notch (corresponds with closure of aortic valve)
5 – diastolic runoff; 6 – end-diastolic pressure
Fig. 3.3 Waveform of central and peripheral arteries
diastolic wave and lower end-diastolic pressure. So in comparison with the

aorta, peripheral arterial waveforms have higher systolic pressure, lower diastolic
pressure, and wider pulse pressure. Though the systolic pressure rises towards
the periphery, mean arterial pressure changes very little because of the narrowing
of the systolic wave. Hence, mean arterial pressure is a better measure of central
arterial pressure (Fig. 3.3).
Recent Advances in Arterial Pressure Monitoring

The following parameters are used as dynamic parameters in assessing volume
responsiveness:
• Systolic pressure variation (SPV).
• Pulse pressure variation (PPV).
• Stroke volume variation (SVV).
Artifacts of the Monitoring System

The operating characteristics of the system depends on natural frequency,
frequency response and damping coefficient. The fluid-filled tubing measures
the blood pressure through the transducers. This system can produce artifacts by
oscillating spontaneously and distorting the arterial waveform. To get an accurate
frequency response, the resonant frequency of the system should be at least
5 times more than the highest frequency in the input signal. Resonant frequency
of the system should be more than 20 Hz.
To ensure a flat frequency response (accurate recording across a spectrum of
frequencies), the resonant frequency of a monitoring system should be at least 5
times higher than the highest frequency in the input signal. Physiologic peripheral
arterial waveforms have a fundamental frequency of 3–5 Hz, and therefore the
resonant frequency of a system used to monitor arterial pressure should ideally be
greater than 20 Hz to avoid ringing and systolic overshoot. The damping coefficient
is a measure of the system’s ability to cause attenuation of the incoming signal.
The catheter-transducer systems are designed to be underdamped but with an
acceptable resonant frequency (> 12 Hz). If the system’s resonant frequency is
lower than 7.5 Hz, the pressure waveform becomes distorted.
• Hence, higher the resonant frequency, damping will have very less effect on
the waveform
• Lower the resonant frequency (e.g. 10–15 Hz), damping coefficient should be
very low (0.4–0.6) to achieve an accurate waveform
• Very low resonant frequency (< 7.5 Hz) will distort the waveform irrespective
of the damping factor.
Despite whether the system becomes underdamped or overdamped, mean
arterial pressure remains unchanged (Fig. 3.4 and Table 3.1).
Fast-flush Test (Square Wave Test)

Fast-flush test is a method of determining the dynamic response of the monitoring
system to assess the amount of distortion existing in the system. The fast-flush
valve is opened for a short time and the resulting flush artifact is examined (Fig.
3.5).
An optimal fast-flush test results in one undershoot followed by small
overshoot, then followed by the waveform. An adequate fast-flush test usually
corresponds to a resonant frequency of 10–20 Hz with a damping coefficient of
0.5–0.7 for peripheral arterial pressure monitoring.
Fig. 3.4 Dampening of arterial waveforms
Fig. 3.5 Effects of fast flush test on dampening
Table 3.1 Causes of dampening
Overdampening Underdampening
Air bubbles Excessive tubing length
Clot Patient on inotropes
Kink
Deflated pressure bag
Over compliant tubing
Poor connections of stopcock
When is Fast Flush Test Done?

• Every 8 hours
• If significant change appears in patient hemodynamic status
• After zeroing and sampling
• Change in tubing
• Damped waveform seen in monitor.
BIBLIOGRAPHY
1. Bazaral MG, Welch M, Golding LAR, Badhwar K. Comparison of brachial and radial
arterial pressure monitoring in patients undergoing coronary artery bypass surgery.
Anesthesiology. 1990;73:38-45.
2. Darovic GO, Vanriper S, Vanriper J. Fluid-filled monitoring systems. In: Darovic GO,
ed. Hemodynamic monitoring, 2nd ed. Philadelphia: WB Saunders; 1995.pp.149-75.
3. Gardner R: Direct arterial pressure monitoring. Curr Anaesth Crit Care. 1990;1:239–
46.
4. Gardner RM. Direct blood pressure measurement—dynamic response requirements.
Anesthesiology. 1981;54:227-36.
5. Kleinman B, Powell S, Kumar P, Gardner RM. The fast flush test measures the dynamic
response of the entire blood pressure monitoring system. Anesthesiology. 1992;77:
1215-22.
6. Levin PD, Sheinin O, Gozal Y. Use of ultrasound guidance in the insertion of radial
artery catheters. Crit Care Med. 2003;31:481-4.
7. Mark JB. Technical requirements for direct blood pressure measurement. In: Mark JB,
ed. Atlas of Cardiovascular Monitoring, New York: Churchill Livingstone. 1998:99-126.
8. O’Rourke MF, Yaginuma T. Wave reflections and the arterial pulse. Arch Intern Med.
1984;144(2):366-71.
9. Pauca AL, Wallenhaupt SL, Kon ND, et al. Does radial artery pressure accurately
reflect aortic pressure? Chest. 1992;102(4):1193-8.
CHAPTER
4 Prem Kumar
PERIPHERAL VENOUS CATHETERIZATION
One of the most common procedures done in ICU and the catheter which almost
all the patients have in the ICU is a peripheral venous catheter.
INSERTION TECHNIQUES (FIGS 4.1A TO F)

• Catheter over needle technique
• Ultrasound-guided technique.
PRECAUTIONS
• Handwashing with disinfectant before doing the procedure
• Non-sterile gloves is used for peripheral venous cannulation
• Skin around the insertion site should be disinfected before inserting the
catheter. CDC recommends chlorhexidine. Other agents which can be
used are povidone-iodine. The disinfectant should not be wiped rather it is
allowed to dry to obtain its full anti-infective effect.
EQUIPMENT
The catheter is made of polymers and short-term catheters are made of
polyurethane and long-term catheters are made of silicone polymers. The size
of catheters are expressed in gauge. The gauge size was actually introduced for
solid wires and gauge size tells the information about the number of wires that
can be placed side-by-side in a given space. The gauge size varies inversely with
the diameter of the catheter.
PRINCIPLE
Hagen-Poiseuille formula is the principle by which venous catheter’s flow rate
is determined. Hence according to this equation, radius of the catheter is the
primary determinant of flow. So according to this principle, rapid infusion of
fluids are better obtained with short catheters with large diameters.
Q = ∆P(pr4/8µL)
Where, Q – flow; P – pressure gradient; r – radius; µ – viscosity; L– length of
catheter.
Chapter 4 Peripheral Venous Catheterization 25
A B
C D
E F
Figs 4.1A to F Steps of peripheral venous cannulation. (A) Tourniquet application
over the forearm to make veins prominent and cleaning the site of cannulation with
antiseptic solution; (B) Insertion of the IV cannula over the vein; (C) Backflow of blood
seen on the back of stylet indicating the presence of cannula inside the vein; (D) Slight
withdrawal of the stylet; (E) The cannula is pushed into the vein gently; (F) The IV cannula
is secured with tapes
Hence, because of the low resistance in a short catheter, a well placed

2-wide bore peripheral cannula is far more superior for rapid infusion than
central venous catheter. This is well seen in clinical scenarios such as trauma,
gastrointestinal bleeding, obstetric hemorrhage, etc. Large catheters (7 fr) can be
inserted in an antecubital vein and used for this purpose. This is well located by
ultrasound in case of obese patients or when there is difficulty in identifying the
peripheral veins.
Advantages
• Ease of insertion
• Ability to infuse fastly in emergency
• Low risk of infection
• Cost-effective.
Disadvantages
• Difficult to cannulate in critically ill patients since most of their veins are
either thrombosed or they are edematous
• Hypertonic agents (e.g. Hypertonic saline) and vasoactive agents cannot be
administered into a peripheral vein
• Need to replace every 3–4 days due to the risk of thrombophlebitis.
MIDLINE CATHETERS
It is devoid of the limitations of peripheral vein catheter such as the risk of
phlebitis is low, need not be replaced early. They are usually 4–8 inches long and
thereby inserted into a large peripheral vein either by vision or ultrasound.
BIBLIOGRAPHY
1. Centers for Disease Control and Prevention. Guidelines for the prevention of
intravascular catheter-related infections. MMWR. 2002;51(No.RR-10):1-30.
2. Paul N Lanken, et al. The intensive care unit manual. 2nd edn, PA. Elsevier
Publications; 2014.
CHAPTER
5 Prem Kumar
CENTRAL VENOUS CATHETERIZATION
Central venous pressure (CVP) is a clinical measure of right ventricular filling

pressure and it identifies the ventricular filling volume which is the preload by
Frank-Starling law. CVP placement remains one of the most commonly done
procedures in intensive care unit (ICU) for many clinical uses, but the procedure
is not without complications. Hence, the applied anatomy of major veins namely
internal jugular vein, subclavian vein and femoral vein will be highlighted. Also
the indications (Tables 5.1 and 5.2), techniques, and complications of central
venous catheterization along with catheter management will be discussed in this
chapter.
Table 5.1 Indications of central venous catheterization
• Central venous pressure monitoring

• Pulmonary artery catheterization
• Total parenteral nutrition
• Acute hemodialysis
• Transvenous cardiac pacing
• Plasmapheresis
• Inability to achieve peripheral venous catheterization
• Perioperative—aspiration of air emboli, vasopressor/inotrope administration, cardiac
surgeries, major surgeries with major fluid shifts
• Drug administration—chemotherapy, vasoactive agents, prolonged antibiotic therapy,
drugs irritable to peripheral veins
• Cardiopulmonary arrest
Table 5.2 Site selection and its indications
Internal jugular vein Subclavian vein Femoral vein

• Acute hemodialysis • Shock • Acute hemodialysis/
• Emergency transvenous • Long-term total plasmapheresis
pacemakers parenteral nutrition • Trauma
• Pulmonary artery catheters • Neurosurgery • Severe lung disease
• Patients with coagulopathy (e.g. Posterior fossa • Angioplasty
• Low-risk of pneumothorax tumors) • Cardiopulmonary
compared with subclavian vein • Trauma arrest
Fig. 5.1 Anatomy of right internal jugular vein
APPLIED ANATOMY
Internal Jugular Vein (Fig. 5.1)

The internal jugular vein (IJV) originates at the jugular foramen from the sigmoid
sinus in the skull and the internal jugular vein lies in the groove between the
sternal and clavicular heads of the sternocleidomastoid muscle, lateral and
slightly anterior to the carotid artery and terminates behind the sternal end
of clavicle, where it joins the subclavian vein to form the brachiocephalic vein
although the relationship between the IJV and the carotid artery can vary in a
group of population. The vagus lies between and rather behind the artery and
vein. The junction of the right IJV (averages 2–3 cm in diameter) with the right
subclavian vein forming the innominate vein follows a straight path to the
superior vena cava (SVC). In contrast, a catheter passed through the left IJV must
enter a sharp turn at the left IJV—subclavian junction, which results in a greater
percentage of catheter malpositions.
The external jugular vein crosses the sternocleidomastoid in the superficial
fascia traversing the roof of the posterior triangle of the neck and then enters the
deep fascia 2.5 cm above the clavicle to drain into the subclavian vein.
Subclavian Vein (Fig. 5.2)

The subclavian vein (SV) is the continuation of the axillary vein and extends from
the outer border of the 1st rib to the medial border of scalenus anterior extending
3–4 cm along the undersurface of the clavicle and becomes the brachiocephalic
vein where it joins the ipsilateral IJV at Pirogoff’s confluence behind the
sternoclavicular articulation. The vein is 1–2 cm in diameter, posteriorly, the SV is
separated from the subclavian artery and brachial plexus by the scalenus anterior.
Inferiorly, the vein rests on the first rib, Sibson’s fascia, dome of the pleura. On the
left side, it receives the termination of the thoracic duct.
Chapter 5 Central Venous Catheterization 29
Fig. 5.2 Anatomy of right subclavian vein
Fig. 5.3 Anatomy of right femoral vein
Femoral Vein (Fig. 5.3)

The femoral vein is continuation of the popliteal vein and becomes the external
iliac vein at the inguinal ligament. At the inguinal ligament, femoral vein lies
within the femoral sheath and lies medial to the femoral artery, which in turn lies
medial to the femoral branch of the genitofemoral nerve (famously called by the
mnemonic—Vein, artery and nerve (VAN).
TECHNIQUES
Internal Jugular Vein

There are three approaches:
1. Central—most commonly used approach.
2. Anterior
3. Posterior.
Central Approach (Fig. 5.4)

Positioning of right IJV cannulation: This was demonstrated by Daily and
colleagues and right IJV cannulation is most commonly catheterized. The patient
is placed in the supine position with 15° Trendelenburg position to distend the
vein and minimize the risk of air embolism with the head slightly turned to the
left to expose the right side of the neck. Pillows that cause the neck to be flexed
should be removed and excessive neck extension or left-sided rotation of the head
should be avoided because this may cause the internal jugular vein to collapse
over the carotid artery, hence increasing the risk for carotid arterial puncture.
Landmarks: Sternal notch, clavicle, and sternocleidomastoid muscle (lateral and
medial head).
Monitoring and sedation: The patient should be sedated, receiving supplemental
oxygen, and monitored with an electrocardiogram (ECG), blood pressure
monitor, and pulse oximeter.
Fig. 5.4 Technique of catheterizing right internal jugular vein—central approach

Aseptic technique: The skin is cleaned from earlobe to clavicle to sternal notch,
preferably with 2% chlorhexidine and draped.
Equipment: Standard triple-lumen catheter kits include the equivalent of a
7-French triple-lumen catheter with 15 (recommended), 20, or 30 cm of catheter
length, a 0.032-inch diameter guidewire with J tip, an 18-gauge needle, an
18-gauge catheter-over-needle, a 7-Fr vessel dilator, and appropriate syringes and
suture material. All lumens of the catheter should be flushed with heparinized
saline and the cap to the distal lumen removed. Heparinized saline is prepared
by adding 1000 IU to 100 mL of saline.
Technique: The pulsation of the carotid artery can be felt medial to the medial
border of the sternomastoid muscle. The vein lies lateral to the artery, often
beneath the belly of the muscle itself. Lower in the neck, it passes deep to the
groove between the sternal and clavicular heads of the muscle. For the central
approach, skin puncture is done at the apex of the triangle formed by the two
muscle heads of the sternomastoid and the clavicle after the skin is anesthetized
by subcutaneous infiltration of 1% lignocaine with a 25-gauge needle. Before
puncture, a finder needle is introduced. At an angle of 30° to skin, the needle is
advanced steadily with constant negative pressure in the syringe, and usually the
vein is punctured within 1–5 cm. If the first attempt is unsuccessful, the operator
should reassess patient position, landmarks, and techniques. Subsequent
attempts may be directed slightly laterally or medially to the initial site of
puncture, as long as the plane of the internal carotid artery (ICA) is not violated.
Once the vein is punctured, the syringe is removed after ensuring that the blood
flow is not pulsatile and the hub is then occluded with a finger to prevent air
embolism or excessive bleeding. The guidewire, with the J-tip oriented correctly,
is then inserted and should pass freely up to 20 cm. Guidewire insertion beyond
20 cm should be avoided since it may cause ventricular arrhythmias or cardiac
perforation. The guidewire should pass easily, if resistance is still encountered,
rotation of the guidewire during insertion often allows passage, but forceful
insertion only leads to complications. With the guidewire in place, a scalpel is
used for making incision at the skin entry site to facilitate passage of the 7-Fr
vessel dilator. The dilator is inserted down the wire to a depth while maintaining
control and sterility of the guidewire. The triple-lumen catheter is then inserted
over the guidewire, ensuring that the operator has control of the guidewire,
proximal to the catheter to avoid intravascular loss of the wire. The catheter
is then advanced 15–17 cm (17–19 cm for left IJV) into the vein, the guidewire
withdrawn, and the distal lumen capped. The catheter is sutured securely to limit
tip migration and bandaged properly. A chest radiograph should be obtained to
detect complications and the location of the catheter tip.
Anterior Approach (Fig. 5.5)

Anatomical landmark for anterior approach is the midpoint on the sterna head
of sternomastoid. Carotid artery can be palpated 1 cm medial to the lateral
border of the sternal head. Fingers are kept to palpate the artery and the needle is
introduced just lateral to the pulsation at an angle of 45° and directed downwards
towards the ipsilateral nipple. Usually, the IJV is punctured within 3 cm. If IJV is
not punctured, the needle is directed 5° laterally.
Fig. 5.5 Technique of catheterizing right internal jugular vein—anterior approach
Fig. 5.6 Technique of catheterizing right internal jugular vein—posterior approach
Posterior Approach (Fig. 5.6)

In the posterior approach, external jugular vein is used as a landmark. The
needle is introduced 1 cm anterior to the point where the external jujular vein
(EJV) crosses the posterior border of the sternomastoid or 5 cm upward from
the clavicle along the lateral head of the sternomastoid. The needle is directed
caudally and posteriorly toward the suprasternal notch at an angle of 45° with
the sagittal plane, with a 15° upward angulation. IJV is usually punctured within
6 cm. If the attempt is not successful, the needle should be directed slightly more
cephalad on the next attempt.
Complications: Operator’s inexperience appears to increase the number of
complications. Overall incidence of complications in IJV catheterization is 0.1–
4%. Coagulopathy is a relative contraindication to IJV catheterization.
• Internal carotid artery (ICA) puncture—most common complication
• Pneumothorax
• Thrombosis
• Infection
• Vascular erosions
• Air embolism
• Cardiac perforation
• Cardiac arrhythmias.
Subclavian vein cannulation
There are two approaches:
1. Infraclavicular approach—most common.
2. Supraclavicular approach.
Position: The patient is put in 30° Trendelenburg position with a folded roll
between the shoulder blades. The head is turned towards the opposite side of
cannulation and both the arms are adducted.
Infraclavicular Approach (Figs 5.7A and B)

Landmarks—clavicle, 2 heads of sternomastoid, suprasternal notch.
Technique
The intensivist stands on the side of the patient’s shoulder where the vein is to
be cannulated. Right subclavian vein is preferred. The skin is punctured 2–3 cm
caudal to the midpoint of the clavicle or in the junction of medial 1/3rd or lateral
2/3 just inferior to the clavicle and needle is inserted just beneath the posterior
surface of the clavicle. The needle tip is directed toward the suprasternal notch
which is identified by the intensivist’s other hand. If the subclavian vein is not
punctured in the first attempt, the needle is withdrawn and a second attempt
is done in a slightly more cephalad direction. In order to avoid pneumothorax,
the needle should stay parallel to the base and not angle down toward the chest.
Subclavian vein catheterization should not be the first choice for patients with
high-risk pulmonary disease or coagulopathy.
Advantages
• Lower risk of infection compared with internal jugular vein or femoral vein
catheterization
• Ease of cannulation in trauma patients or patients with cervical collar
• Better for long term maintenance especially for chemotherapy and total
parenteral nutrition (TPN)
• Patient comfort.
B
Figs 5.7A and B Technique of catheterizing right subclavian—vein infraclavicular
approach
Complications
• Pneumothorax incidence is high compared with IJV cannulation
• Subclavian artery puncture
• Catheter tip malposition.
Supraclavicular Approach (Figs 5.8A and B)

Position of the intensivist—Intensivist stands on the head end of the patient on
the side of cannulation.
Landmarks—clavicular head of sternomastoid, sternoclavicular joint.
Figs 5.8A and B Technique of catheterizing right subclavian vein—supraclavicular

approach
Technique
The site of puncture is just lateral to the clavicular head of sternomastoid above
the clavicle. The needle is advanced toward or just caudal to the contralateral
nipple just under the clavicle. The needle is angled at 45° at sagittal plane and
directed towards a dividing line between the sternoclavicular joint and clavicular
head of the sternomastoid. The depth of insertion is just beneath the clavicular
head of sternomastoid at an angle of 15° below the coronal plane. The needle
should enter the subclavian jugular junction after 1–4 cm, and after the vein is
punctured, catheterization is done.
Femoral Vein Cannulation

Position—supine position with the leg extended and slightly abducted at the hip.
Technique (Figs 5.9A and B)

Femoral vein puncture is done 3 cm below the inguinal ligament just medial to
the palpated femoral artery at an angle of 45° and with tip angulated in cephalad
and medial direction. Either a long (40–70 cm) catheter or short (15–20 cm ) is
used. Long catheter is positioned under ECG or fluoroscopic guidance. Short
catheter can be kept in the common iliac vein. Femoral vein cannulation is the
easiest among all the 3 veins.
Advantages
• Burns or trauma
• Surgical procedures involving the head, neck, and upper part of the thorax
• Cardiopulmonary resuscitation
• Can be used in patients with severe lung disease since reduced incidence of
pulmonary complications.
Complications
• Arterial puncture
• Thromboembolism
• Infection
• Scrotal hemorrhage
• Intestinal perforation.
Peripherally Inserted Central Venous Catheters

Peripherally inserted central venous catheters (PICC) has become a popular
alternative to centrally inserted catheters in patients requiring long-term
intravenous therapy. Venous access for a PICC is obtained either through an
antecubital vein, preferably the basilic vein, which can be catheterized easily
than the cephalic vein because of its more linear course. Most PICC catheters are
flexible and nonthrombogenic silicone catheters.
Advantages
• Used for long-term intravenous therapy—chemotherapy or total parenteral
nutrition (TPN)
• Can be done in bedside by even less trained personnel
• Low risk catheter related complications—pneumothorax, infection
• Cost-effective.
B
Figs 5.9A and B Technique of catheterizing right femoral vein
Disadvantages
• Central venous pressure (CVP) recorded via PICCs is slightly higher than the
pressure measured with centrally inserted catheters
• Increased risk of cardiac perforation and arrhythmias.
ULTRASOUND-GUIDED TECHNIQUES
The use of ultrasound for central venous cannulation has revolutionized
anesthesia and critical care because of the reduction in the complications hence
enhancing the safety profile of the invasive technique.
There are two techniques for using 2D ultrasound:
1. Static approach.
2. Real time approach.
Static approach: A mark is placed on the skin indicating the placement of insertion
of needle with the help of ultrasound and cannulation is done thereafter without
ultrasound.
Real time approach: Needle insertion is visualized while performing the
procedure.
All the three veins—internal jugular, subclavian or femoral vein can be
cannulated with ultrasound technique (Figs 5.10 to 5.13).
A B
Figs 5.10A and B Ultrasound image of left internal jugular vein—short-axis view
Fig. 5.11 Ultrasound image of right internal jugular vein—long-axis view

Fig. 5.12 Ultrasound image of right femoral vein—short-axis view
Fig. 5.13 Ultrasound image of right subclavian vein—infraclavicular region
Advantages of Ultrasound Over Landmark Technique

• Increased success rate in first attempt
• Reduction in complications—reduced carotid artery puncture, pneumo
thorax, hemothorax, hematoma, catheter tip malpositions
• Reduced number of attempts
• Reduced duration of cannulation
• Reduction in central venous catheter-associated blood stream infection
• Improved identification of preexisting thrombus formation and anatomical

variations in the IJV location thus facilitating safer and more successful
cannulation of the vessel
• Visualization of both transverse and longitudinal axis in ultrasound prevents
the double wall puncture during the needle insertion.
Confirming Catheter Tip Position

• Radiological identification is done and the tip of the catheter should lie
within the superior vena cava and positioned below the inferior border of
the clavicles and above the level of the third rib, the T4 to T5 interspace, the
tracheal carina, or at the branching of the right mainstem bronchus. The
right tracheobronchial angle is the most reliable landmark on plain chest
radiograph for the upper margin of the SVC and is mostly at least 3 cm above
the caval—atrial junction. The tip of the catheter should lie about 1 cm below
this landmark.
• The ideal location for the catheter tip is the proximal superior vena cava 3
to 5 cm proximal to the caval-atrial junction. Positioning of the catheter tip
within the right atrium or right ventricle should be avoided.
• The use of ECG electrode in the central venous catheter can be used as a
method of confirming the catheter tip. It is based on the P-wave. This
technique is based on the CVP catheter being used as an exploring electrode.
The P wave would be increasing in negativity as it moves away from the right
atrium and increasing positivity as it moves into right atrium (Fig. 5.14).
Management of Catheter
Catheter-related Infection
Catheter-related blood stream infection is defined as at least two blood cultures
positive with the same organism, obtained from at least two separate sites at
different times. An exit site infection presents with erythema, tenderness. A tunnel
infection is characterized by pain and induration along the track of the catheter.
Catheters can become infected from four potential sources: the skin insertion
site, the catheter hub, hematogenous seeding, and infusate contamination.
Protocol for Catheter Management

Chlorhexidine is a better disinfectant and should be used instead of iodine-based
solutions for site preparation before catheter insertion. Replacement of fluid
administration sets every 72–96 hours is safe. Transparent polyurethane dressings
are better than gauzes and tapes. It is recommended that gauze be changed
every 2 days and transparent dressing changed every 7 days. Chlorhexidine
impregnated gauze has been shown to reduce infection. Subcutaneous tunneling
of catheters reduces the incidence of infection. Avoid guidewire exchanges since
it has been shown to increase the infection rate.
Fig. 5.14 ECG electrode method of confirming the position of catheter tip
BIBLIOGRAPHY
1. Daily PO, Griepp RB, Shumway NE. Percutaneous internal jugular vein cannulation.
Arch Surg. 1970; 101:534-6.
2. Eerola R, Kaukinen L, Kaukinen S. Analysis of 13,800 subclavian vein catheterizations.
Acta Anaesthesiol Scand. 1985;29:193.
3. Hayashi H, Amano M. Does ultrasound imaging before puncture facilitate internal
jugular vein cannulation? Prospective randomized comparison with landmark-
guided puncture in ventilated patients. J Cardiothorac Vasc Anesth. 2002;16:572-5.
4. Karakitsos D, Labropoulos N, De Groot E, et al. Real-time ultrasound-guided
catheterization of the internal jugular vein: a prospective comparison with the
landmark technique in critical care patients. Crit Care. 2006;10(6):R162.
5. Maki DG, Botticelli JT, LeRoy ML, et al. Prospective study of replacing administration
sets for intravenous therapy at 48- vs. 72-hour intervals. 72 hours is safe and cost-
effective. JAMA. 1987;258:1777.
6. Maki DG, Ringer M, Alvarado CJ. Prospective randomised trial of povidone-iodine,
alcohol, and chlorhexidine for prevention of infection associated with central venous
and arterial catheters. Lancet. 1991;338(8763):339-43.
7. Malloy DL, McGee WT, Shawker TH, Brenner M, Bailey KR, Evans RG, Parker MM,
Farmer JC, Parillo JE. Ultrasound guidance improves the success rate of internal
jugular vein cannulation: a prospective, randomized trial. Chest. 1990;98:157-60.
8. McDonnell JE, Perez H, Pitts SR, et al. Supraclavicular subclavian vein catheterization:
modified landmarks for needle insertion. Ann Emerg Med. 1992;21:421.
9. Merrer J, De Jonghe B, Golliot R, et al. Complications of femoral and subcalvian
venous catheterization in critically ill patients. A randomized controlled trial. JAMA.
2001;286:700-7.
10. Milling TJ, Jr Rose J, Briggs WM, et al. Randomized, controlled clinical trial of point-
of-care limited ultrasonography assistance of central venous cannulation: the Third
Sonography Outcomes Assessment Program (SOAP-3) Trial. Crit Care Med. 2005;
33(8):1764-9.
11. Mimoz O, Pieroni L, Lawrence C, et al. Prospective, randomized trial of two antiseptic
solutions for prevention of central venous or arterial catheter colonization and
infection in intensive care unit patients. Crit Care Med. 1996;24(11):1818-23.
12. Moosman DA. The anatomy of infraclavicular subclavian vein catheterization and its
complications. Surg Gynecol Obstet. 1973;136:71.
13. Netter FH. Atlas of human anatomy. Summit, NJ, Cibn-Geigy, 1989.
14. O’Grady NP, Alexander M, Dellionger EP, et al. Guidelines for prevention of
intravascular catheter–related infections. Centers for Disease Control and Prevention.
MMWR Recomm Rep. 2002;51(RR-10):1-29.
15. Parras F, Ena J, Bouza E, et al. Impact of an educational program for the prevention of
colonization of intravascular catheters. Infect Control Hosp Epidemiol. 1994;15:239.
16. Pinsky MR. Hemodynamic monitoring in the intensive care unit. Clin Chest Med.
2003;24:549-60.
17. Randolph AG, Cook DJ, Gonzales CA, Pribble CG. Ultrasound guidance for placement
of central venous catheters: a meta-analysis of the literature. Crit Care Med. 1996;24:
2053-8.
18. Williams PL, Warwick R. Gray’s Anatomy, 8th ed. Philadelphia, WB Saunders, 1980.
CHAPTER
6 Prem Kumar
PULMONARY ARTERY CATHETERIZATION
HISTORY
In 1970, Swan and Ganz introduced pulmonary artery catheterization (PAC) into
clinical practice for hemodynamic assessment of patients with acute myocardial
infarction and from then, its use in clinical practice has increased because of the
measurement of various physiologic variables in critical care.
Pulmonary Artery Catheter

Pulmonary artery catheter (PAC) has a 7.0- to 9.0-Fr circumference (1 Fr =
0.0335 mm) and the length is 110 cm marked at 10-cm intervals, and contains
four internal lumens (Fig. 6.1). The catheter is made of polyvinylchloride coated
with heparin to prevent thrombosis. PAC is passed through a sterile sheath that
attaches to the hub of the introducer and allows sterile manipulation of PAC
position during use. The balloon is tested by filling it completely with 1.5 mL of
air from a volume-limited syringe to ensure symmetry of expansion and patency.
The function of the air-filled balloon at the catheter tip is to float the catheter
forward with blood flow through the right heart chambers and into the pulmonary
Fig. 6.1 Patient with pulmonary artery catheter with different lumens
artery. Pacing PA catheters has two groups of electrodes on the catheter surface,
enabling intracardiac electrocardiographic (ECG) recording or can be used also
for temporary cardiac pacing.
The distal port at the catheter tip is used for monitoring of pulmonary artery
pressure, whereas the proximal lumen second is 30 cm proximal and is used
for monitoring of CVP. The third lumen leads to a balloon near the tip, and the
fourth lumen is for a temperature thermistor. The end of the thermistor lies just
proximal to the balloon.
PA Catheter Lumens
• Distal lumen: Connected to pressure monitoring system to monitor
pressures in the pulmonary artery. It is used for withdrawing blood mixed
venous saturation samples and it is not used for continuous fluid/drug
administration.
• Proximal injectate lumen: It is used to monitor CVP and inject solution to
intermittently assess cardiac output through thermodilution.
• Proximal infusion lumen: For administration of fluids/drugs.
• Inflation valve lumen and syringe: It connects to balloon to inflate air
(typically 1.5 mL) into the balloon for wedging.
• Thermistor connector lumen: PA blood temperature and allows thermo
dilution CO measurements.
Indications
According to the ACCF/AHA guidelines, pulmonary artery catheterization is
appropriate in the following settings.
• Cardiogenic shock during supportive therapy
• Severe chronic heart failure requiring inotropic, vasopressor, and vasodilator
therapy
• Suspected “pseudosepsis” (high cardiac output, low systemic vascular
resistance, elevated right atrial and pulmonary capillary wedge pressures)
• Potentially reversible systolic heart failure such as fulminant myocarditis
and peripartum cardiomyopathy
• Discordant right and left ventricular failure
• Transplantation work-up
• Not indicated as routine in high-risk cardiac and noncardiac patients
• To detect hemodynamic differential diagnosis of pulmonary hypertension
• To assess response to therapy in patients with precapillary and mixed types
of pulmonary hypertension
• Aspiration of air emboli.
PERIOPERATIVE INDICATIONS
CLASS I
Placement of a pulmonary artery catheter is indicated, preferably before the
induction of anesthesia or surgical incision, in patients in cardiogenic shock
undergoing CABG (Level of Evidence: C).
Chapter 6 Pulmonary Artery Catheterization 45
CLASS IIa
Placement of a pulmonary artery catheter can be useful in the intraoperative or
early postoperative period in patients with acute hemodynamic instability (Level
of Evidence: B).
CLASS IIb
Placement of a pulmonary artery catheter may be reasonable in clinically stable
patients undergoing CABG after consideration of baseline patient risk, the planned
surgical procedure, and the practice setting (Level of Evidence: B).
Technique
• After checking for the balloon integrity, deflate it and check the pressure
tubing, transducers and stopcocks.
• Right internal jugular veins is cannulated and with the guidewire in place,
enlarge the puncture site using a scalpel and a vessel dilator sheath apparatus
is introduced through the guidewire using a twisting motion. The guidewire
and vessel dilator are removed, leaving the introducer sheath in the vessel
and the sheath is sutured.
• Stopcocks are attached to the right atrium and PA ports of the PA catheter
and the proximal and distal catheter lumens are filled with flush solution.
Close the stopcocks to keep flush solution within the lumens and to avoid
introduction of air into the circulation.
• After the PA catheter is introduced into a right internal jugular vein, the right
atrium is reached when the PAC is inserted 20–25 cm, the right ventricle
at 30–35 cm, the pulmonary artery at 40–45 cm, and the wedge position at
45 to 55 cm. RA length indication—35–40 cm from the left antecubital fossa,
10 to 15 cm from the internal jugular vein, 10 cm from the subclavian vein,
and 35–40 cm from the femoral vein.
• The distances are rough guided and waveform morphology is used as a
guide for catheter placement and catheter position confirmed with a chest
radiograph. The tip of the PAC should be within 2 cm of the cardiac silhouette
on a chest radiograph.
• Once the catheter is in right atrium, measure the pressure, waveform and
inflate the balloon with the recommended amount of air anticipating the
catheter is in the right atrium. Inflation of the balloon should be associated
with a slight feeling of resistance.
• With the balloon inflated, advance the catheter until a RV pressure tracing
is seen on the monitor. Record the right ventricle pressure. This is the time
when cardiac arrhythmias are encountered. If there is difficulty in reaching
the right ventricle, elevation of head to 5° and a right-tilt position will facilitate
the entry of the catheter into the right ventricle.
• The catheter is advanced further until there is rise in diastolic pressure
tracing which indicates PA placement. If a RV trace appears even after the
catheter is advanced 15 cm, suspect coiling in the right ventricle, then deflate
the balloon and withdraw it to the right atrium, then reinflate it and repeat
the same steps again.
Fig. 6.2 Zones of lung and the placement of PA catheter
• As the catheter is advanced, there is fall on the pressure tracing from the
levels of systolic pressure noted in the RV and PA which indicates that PA
catheter is in the pulmonary artery occlusion pressure position. A typical
pulmonary artery occlusion pressure tracing should be noted with a and
v waves. Deflate the balloon, a phasic PA pressure should appear on the
pressure tracing. A PAC positioned in both zone 1 and 2 will be susceptible
to alveolar pressure, and the measurements will reflect alveolar or airway
pressure rather than left ventricular filling pressure. Hence, the tip of the PAC
must lie in zone 3 for PAWP to be accurate (Fig. 6.2).
• Secure the catheter in the correct PA position by suturing it to the skin.
• Take a chest radiograph to confirm catheter tip position.
Special Situations of Difficulty in PA Catheterization

After successful internal jugular vein (IJV) cannulation, if attempts to advance
the PAC to the right ventricle prove difficult, the physician should consider the
possibility of abnormal venous anatomy. Among the abnormalities, the most
common abnormality of the systemic veins is persistence of the left superior vena
cava and a rare form of atrial septal defect called as unroofed coronary sinus, can
also be seen in some patients where there is a potential for the PAC to enter the
left atrium and systemic circulation. These abnormalities can be detected by
waveform characteristics which show a downstream right atrial pressure and a
transmitted dampened left ventricular pressure waveform.
PHYSIOLOGICAL VARIABLES WITH PA CATHETERIZATION

(TABLES 6.1 TO 6.3)
Pulmonary artery (PA) catheter can measure hemodynamic parameters such as
cardiac output, pulmonary artery diastolic and wedge pressure and indirectly
Table 6.1 Oxygen saturation at various chambers and vessels
Sampling chamber or vessel Oxygen saturation (in %)

SVC 70
IVC 80
RA 75
RV 75
Pulmonary artery 75
Table 6.2 Parameters measured by PA catheter
Variable Normal range (units)

Central venous pressure (CVP) 0–8 mm Hg
Right ventricular systolic pressure (RVSP) 15–30 mm Hg
Right ventricular end-diastolic pressure (RVEDP) 0–8 mm Hg
Pulmonary artery systolic pressure (PAP) 15–30 mm Hg
Pulmonary artery diastolic pressure (PADP) 4–12 mm Hg
Pulmonary artery occlusion pressure (PAOP) 2–12 mm Hg
Mean pulmonary artery pressure 10–18 mm Hg
measure ventricular filling pressures. It can also measure mixed venous oxygen
saturation. With the PA catheter in position and the balloon deflated, the distal
lumen transmits PA pressure and the PA waveform is characterized by a systolic
peak and diastolic trough with a dicrotic notch due to closure of the pulmonary
valve (Fig. 6.3). The peak PA systolic pressure corresponds to the T wave of an
ECG.
Pulmonary artery occlusion pressure (PAOP) reflects left atrial pressure,
and is an indirect indicator of left ventricular filling pressure. To confirm the
PA catheter position is in zone 3, the catheter tip should be below the level of
the left atrium in a chest X-ray in supine position and also by withdrawing a
blood specimen from the distal lumen and measuring oxygen saturation which
should be >95%. With the patient having a normal mitral valve and normal left
ventricular function, the mean PAOP correlates well with left ventricular end-
diastolic pressure (LVEDP).
Measuring Cardiac Output

• It can be measured by thermodilution principle
• It can be approximately measured merely by mixed venous oxygen saturation.
Normal mixed venous oxygen saturation (SvO2) is 70–75%. Reduced SvO2
occurs in patients with shock, heart failure. Fiberoptic reflectance oximetry
can continuously measure SvO2 and indicate cardiac output indirectly. This
is used as a derived measure of oxygen consumption and oxygen delivery
to guide the treatment of critically ill patients. Currently used as a guide for
septic shock in goal-directed therapy.
Table 6.3 Derived parameters obtained with data from PA catheter
Variable Formula Normal range

Arterial oxygen content (CaO2) SaO2 × Hb × 1.39 + PaO2 180 mL liter–1
(mm Hg) × 0.003
Mixed venous oxygen content SvO2 × Hb × 1.39 + PvO2 130 mL liter–1
(CvO2) (mm Hg) × 0.003
Oxygen delivery (DO2) Ǭ × CaO2 800–1000 mL min–1
Oxygen consumption (VO2) Ǭ/(CaO2 / CvO2) 180–300 mL min–1
Oxygen delivery index (DO2I) Do2/BSA 500–650 mL min–1 m–2
Oxygen consumption (VO2I) Vo2/BSA 100–180 mL min–1 m–2
Cardiac index (CI) Ǭ/BSA 2.5–4.0 liter min–1 m–2
Stroke volume (SV) Ǭ/HR 60–80 mL
Stroke index (SI) SV/BSA 30–65 mL m–2
Left ventricular stroke work CI × (MAP–PAOP) × 40–60 g m–1 m–2
index (LVSWI) 0.0136
Systemic vascular resistance (MAP–CVP) × 80/Ǭ 900–1200 dyns cm–5 m–2
(SVR)
Systemic vascular resistance (MAP–CVP)×80/CI 1500–2500 dyns
index (SVRI) cm–5 m–2
Mean pulmonary artery [PASP + (2×PADP)]/3 10–20 mm Hg
pressure (mPAP)
Right ventricular stroke work Cl × (MPAP–CVP) × 0.0136 6–12 g m–1 m–2
index (RVSWI)
Pulmonary vascular resistance (MPAP–PAOP) × 80/Ǭ 50–150 dyns cm–5 m–2
(PVR)
Pulmonary vascular resistance (MPAP–PAOP) × 80/CI 250–350 dyns cm–1 m–2
index (PVRI)
Body surface area (BSA) = Weight (Kg)0.425 × height (cm)0.725 × 0.007184; Ǭ, cardiac output
Fig. 6.3 Waveforms showing the position of PA catheter

Table 6.4 Effects of various conditions on the pulmonary parameters
Condition Abnormality
Positive end-expiratory pressure Mean PAWP > mean LAP
Mitral stenosis Mean LAP > LVEDP
Mitral regurgitation Mean LAP > LVEDP
Aortic regurgitation LAP < LVEDP
Pulmonary arterial hypertension PADP > mean PAWP
Pulmonary veno-occlusive disease Mean PAWP > mean LAP
Postpneumonectomy PAWP < LAP or LVEDP
Pulmonary Artery Occlusion Pressure (Table 6.4)

• It is mostly interchanged with pulmonary artery wedge pressure
• Pathophysiologic conditions involving the left-sided cardiac chambers or
valves produce characteristic changes in the pulmonary artery and wedge
pressure waveforms. One among the following is the tall v wave of mitral
regurgitation.
• In mitral regurgitation, distortion of the systolic portion of the wedge pressure
waveform is present whereas in mitral stenosis, distortion in diastolic portion
is present.
• Constrictive pericarditis—rapid early diastolic ventricular filling resulting in
square root sign.
• During positive-pressure ventilation, inspiration increases pulmonary artery
and wedge pressure. These effects are minimized, if the PAP and PAWP are
measured at the end of expiration.
• PAWP and PADP can be used as surrogate measures of left ventricular filling.
• Alteration in PAWP alters pulmonary capillary pressure though both are not
the same, which in turn reflects the hydrostatic pressure (important factor
for development of pulmonary edema).
• The end-diastolic wedge pressure after atrial contraction best predicts left
ventricular end-diastolic filling pressure or preload.
Factors Causing Variability of PAOP in Measuring Preload

Catheter outside zone 3 Atrial or mitral Ventricular compliance
Increased PVR valve disease
PAOP LAP LVEDP LVEDV
Complications
• All the complications associated with central vein catheterization
• Pulmonary thrombosis
• Pulmonary infarction
• Pulmonary artery perforation
• Cardiac arrhythmias
• Balloon rupture
• Catheter coiling and knotting
• Infection
• Intracardiac damage to walls, valve, endocardial disruption.
BIBLIOGRAPHY
1. 2011 ACCF/AHA guideline for coronary artery bypass graft surgery: executive
summary: a report of the American College of Cardiology Foundation/American
Heart Association Task Force on Practice Guidelines. J Am Coll Cardiol. 2011;58:2584-
614.
2. Azocar RJ, Narang P, Talmor D, et al. Persistent left superior vena cava identified after
cannulation of the right subclavian vein. Anesth Analg. 2002;95:305-7.
3. Barash PG, Nardi D, Hammond G, et al. Catheter-induced pulmonary artery
perforation: mechanisms, management and modifications. J Thorac Cardiovasc Surg.
1981;82:5.
4. Chatterjee K, Swan JHC, Ganz W, et al. Use of a balloon-tipped flotation electrode
catheter for cardiac monitoring. Am J Cardiol. 1975;36:56.
5. Foote GA, Schabel SI, Hodges M. Pulmonary complications of the flow-directed
balloon-tipped catheter. N Engl J Med. 1974;290:927.
6. JM Gore, JS Alpert, JR Benotti, et al. Handbook of Hemodynamic Monitoring. Boston:
Little Brown; 1984.
7. Lange HW, Galliani CA, Edwards JE. Local complications associated with indwelling
Swan-Ganz catheters. Am J Cardiol. 1983;52:1108.
8. Lange RA, Moore DM, Cigarroa RG, et al. Use of pulmonary capillary occlusion
pressure to assess severity of mitral stenosis: is true left atrial pressure needed in this
condition? J Am Coll Cardiol. 1989;13:825.
9. Meister SG, Furr CM, Engel TR, et al. Knotting of a flow-directed catheter about a
cardiac structure. Cathet Cardiovasc Diagn. 1977;3:171.
10. Pace NL, Horton W. Indwelling pulmonary artery catheters: their relationship to
aseptic thrombotic endocardial vegetations. JAMA. 1975;233:893.
11. Pearson KS, Gomez MN, Moyers JR, et al. A cost/benefit analysis of randomized
invasive monitoring for patients undergoing cardiac surgery. Anesth Analg. 1989;69:
336-41.
12. Practice Guidelines For Pulmonary Artery Catheterization: an Updated Report
by the American Society of Anesthesiologists Task Force on Pulmonary Artery
Catheterization. Anesthesiology. 2003;99:988-1014.
13. Resano FG, Kapetanakis EI, Hill PC, et al. Clinical outcomes of low-risk patients
undergoing beating-heart surgery with or without pulmonary artery catheterization. J
Cardiothorac Vasc Anesth. 2006;20:300-6.
14. Roizen MF, Berger DL, Gabel RA, et al. Practice guidelines for pulmonary artery
catheterization. An updated report by the American Society of Anesthesiologists Task
Force on Pulmonary Artery Catheterization. Anesthesiology. 2003;99:988-1014.
15. Schwann TA, Zacharias A, Riordan CJ, et al. Safe, highly selective use of pulmonary
artery catheters in coronary artery bypass grafting: an objective patient selection
method. Ann Thorac Surg. 2002;73:1394-401.
16. Stewart RD, Psyhojos T, Lahey SJ, et al. Central venous catheter use in low-risk
coronary artery bypass grafting. Ann Thorac Surg. 1998;66:1306-11.
17. Swan HJC, Ganz W, Forrester J, et al. Catheterization of the heart in man with use of a
flow-directed balloon-tipped catheter. N Engl J Med. 1970;283:447.
18. Sweitzer BJ, Hoffman WJ, Allyn JW, Daggett WJ. Diagnosis of a left-sided superior vena
cava during placement of a pulmonary artery catheter. J Clin Anesth. 1993;5:500-4.
CHAPTER
7 Prem Kumar
HEMODYNAMIC MONITORING
Critically ill patients require hemodynamic monitoring not only for diagnostic
purpose but also for intervention aimed for supporting organs and it can be
used as a guide to therapy. Although vital signs are still used widely in ICU, they
are poor predictors of the hemodynamic state. Recently, fluid responsiveness
by noninvasive methods have become better predictors of preload rather than
static measures like central venous pressure. Now there are methods of assessing
cardiac output by noninvasive methods rather than thermodilution method.
With the recent evidence about hemodynamic monitoring, we will discuss the
various methods and parameters of hemodynamic monitoring and its clinical
significance (Table 7.1).
Hemodynamic variables can be either measured or calculated. Using direct
arterial blood pressure monitoring and PA catheter monitoring, hemodynamic
variables of both systemic and pulmonary circulation can be measured or
calculated.
THORACIC BIOIMPEDANCE PLETHYSMOGRAPHY

Electrodes are placed in the neck and thorax region and the fluctuations in
electrical impedance are measured. The change in aortic flow is measured by the
change in the thoracic bioimpedance through the cardiac cycle.
ESOPHAGEAL AND TRANSCUTANEOUS DOPPLER MONITORING

It measures blood flow velocity in the descending aorta by a Doppler probe kept in
the esophagus 40 cm from the mouth. It is a useful monitor for measuring cardiac
output. It has been used for high-risk surgical patients but its use in critical care
is yet to be validated. Transcutaneous Doppler monitoring by an external probe
can measure transpulmonary and transaortic cardiac output.
Capnography
Uses of Capnography in ICU

• Detection of return of spontaneous circulation after cardiac arrest
• Detection of esophageal intubation and accidental extubation
Table 7.1 Parameters of hemodynamic monitoring
Noninvasive methods
• Transthoracic echocardiography
• Thoracic Bioimpedance Plethysmography
• Esophageal Doppler
• Transcutaneous Doppler Ultrasonography
• End tidal CO2 monitoring
• Pulse oximetry
• Mucosal tonometry
Static measures
• Invasive arterial blood pressure
• Central venous pressure
• IVC diameter by ultrasound
• Hemodynamic measures with PA catheter
• Cardiac output by thermodilution method
• Left ventricular end-diastolic area index (LVEDAI)
Dynamic parameters
• Pulse pressure variation
• Stroke volume variation
• Systolic pressure variation
• Pleth variability index (PVI)
• Distensibility index of IVC
• Collapsibility index of the superior vena cava
• End-expiratory occlusion test
• Preload responsiveness by passive leg raising test
• Pulse contour cardiac output analysis—PiCCO, NICOM system
Abbreviations: PiCCO, pulse index contour continuous cardiac output; NICOM, noninvasive cardiac
output Monfoss
• Diagnosing air and pulmonary embolism

• Indirect indicator of cardiac output.
Pulse Oximetry
It is considered as an essential monitor for all ICU patients receiving supplemental
oxygen. It is useful in trauma patients to detect pulmonary embolism. A sudden
drop in saturation in the presence of a normal chest X-ray in trauma patients is
highly predictive of pulmonary embolism.
Chapter 7 Hemodynamic Monitoring 53
MUCOSAL TONOMETRY
A tube with balloon tip is inserted into the stomach and gastric tonometry
monitors gastric circulation and is an early indicator of splanchnic hypoperfusion.
Intermittently, the saline or air is aspirated and the CO2 level is measured. The CO2
from the mucosa diffuses to the gastric lumen and is detected by the tonometry.
Gastric mucosal CO2 and pH are good predictors of trauma or perioperative
complications.
CVP/RAP Can indirectly measure RVEDP RV preload
PAWP can indirectly measure LVEDP LV preload
Mean Arterial Pressure

Mean arterial pressure (MAP) is a better indicator of tissue perfusion pressure
than systolic and diastolic pressure because it is least dependent on the technique
and the site of measurement. The normal MAP is 60–70 mm Hg. Though it is a
useful parameter for tissue perfusion, still its reliability is low because MAP does
not adequately reflect perfusion at tissue level in critically ill patients. There
can be normal MAP yet the patient may have impaired tissue perfusion. Tissue
autoregulation is also disturbed in severely ill patients.
Invasive Arterial Blood Pressure Monitoring

The character of the arterial waveform depends upon two factors:
1. Stroke volume.
2. Compliance of arteries and arterioles.
Clinical Applications of IBP Monitoring

• In case of hypotension, if the arterial waveform shows spike pattern with
prominent dicrotic notch, it indicates hypovolemia.
• Continuous beat-to-beat blood pressure monitoring which would be useful
in critically ill patients.
• Pulse contour analysis—estimation of stroke volume and cardiac output can
be done by analysis of invasive blood pressure (IBP) waveform. It calculates
stroke volume from the area under the systolic portion of the waveform.
Cardiac output (CO) is derived by stroke volume and heart rate and both
these parameters can be monitored continuously on a beat-to-beat basis.
This analysis is reliable even in patients with hemodynamic instability but its
reliability and validity with arrhythmias is yet to be ascertained. This analysis
has been shown to have good comparability with thermodilution method.
• Systolic time interval can provide information about the ventricular
contractile function.
Central Venous Pressure Monitoring (Fig. 7.1)

Normal central venous pressure (CVP) is 0–5 mm Hg and with positive pressure
ventilation it can be up to 10 mm Hg.
Fig. 7.1 Waveforms of central venous monitoring
Fig. 7.2 Effect of systolic dysfunction on the pressure-volume loop of the left ventricle.
The isovolumic pressure-volume curve is shifted to the right, decreasing the stroke
volume
Dynamic change in CVP in response to volume challenge or respiratory cycle

can help in evaluation of volume status. Monitoring of cardiac filling pressures
are done to estimate cardiac-filling volumes, which in turn determine the stroke
volumes of both the left and right ventricles. According to the Frank-Starling
law, the force of contraction is proportional to end-diastolic muscle fiber length
at any given level of intrinsic contractility or inotropy. This muscle fiber length
(preload) is proportional to end-diastolic volume. The relationship between
ventricular stroke volume and end-diastolic volume is called the Frank-Starling
curve. Increase in CVP in response to fluid challenge suggests that the heart is in
the plateau portion of the frank starling curve (Figs 7.2 and 7.3).
ScvO2
The sample is obtained from the superior vena cava. This parameter can be used
as an outcome measure in patients with sepsis and high-risk surgical patients
treated in ICU. The difference between ScvO2 and SvO2 is that ScvO2 is 3–5%
Fig. 7.3 Diastolic dysfunction increases end-diastolic volume and shifts the diastolic
pressure-volume relationship upward and to the left. This reduces the stroke volume
Table 7.2 Measured parameters from PA catheter
Variable Normal range (units)

lower than SvO2. It can be used as an alternative to SvO2 in managing septic shock
patients.
Monitoring with PA Catheter

PA catheter measures various hemodynamic variables both measured and
calculated which is shown in Table 7.2.
Apart from these variables, mixed venous oxygen saturation and cardiac
output are also measured. This information derived from the PA catheter directly
Table 7.3 Derived parameters obtained with data from PA catheter

Cardiac index (CI) Ǭ/BSA 2.5–4.0 litre min–1 m–2
Left ventricular stroke work CI × (MAP – PAOP) × 40–60 g m–1 m–2
index (LVSWI) 0.0136
Systemic vascular resistance (MAP–CVP) × 80/Ǭ 900–1200 dyn s cm–5 m–2
(SVR)
Systemic vascular resistance (MAP – CVP) × 80/CI 1500–2500 dyn s cm–5 m–2
index(SVRI)
Mean Pulmonary Artery Pressure [PASP + (2 × PADP)]/3 10–20 mm Hg
(MPAP)
Right ventricular stroke work Cl × (MPAP – CVP)× 6–12 g m–1 m–2
index (RVSWI) 0.0136
Pulmonary Vascular resistance (MPAP–PAOP) × 80/Ǭ 50–150 dyn s cm–5 m–2
(PVR)
Pulmonary vascular resistance (MPAP – PAOP) × 80/ 250–350 dyn s cm–1 m–2
index (PVRI) CI
Arterial oxygen content (CaO2) SaO2 × Hb × 1.39 + 180 mL litre–1
PaO2 (mm Hg) × 0.003
Mixed venous oxygen content SvO2 × Hb × 1.39 + 130 mL litre–1
(CVO2) PvO2 (mm Hg) × 0.003
Oxygen delivery (DO2) Ǭ × CaO2 800–1000 mL min–1
Oxygen consumption (VO2) Ǭ/(CaO2/CvO2) 180–300 mL min–1
Oxygen delivery index (DO2I) DO2/BSA 500–650 mL min–1 m–2
Oxygen consumption (VO2 I) VO2/BSA 100–180 mL min–1 m–2
Body surface area (BSA) = Weight (Kg)0.425 × height(cm)0.725 × 0.007184; Ǭ, cardiac output
or indirectly will estimate left ventricular filling pressure and will guide the
administration of fluids and inotrope/vasopressor agents. These parameters
are measured at end-expiration to minimize the effect of inspiratory increase in
intrathoracic pressure which can produce confounding results. The tip of the PA
catheter should be in west zone 3 (Table 7.3). The following criteria suggest that
the tip of PA catheter is in zone 3:
• Application of PEEP causes < 50% alteration in PAOP
• Atrial waveforms
• In chest radiography—tip should be below the left atrium.
Measures of Left Ventricular Preload

• PADP
• PAWP
• Intrathoracic blood volume index (ITBI)
• CVP.
Mixed Venous Oxygen Saturation (SvO2)

Sampling is done by aspirating blood from the distal port of PA catheter. Thus, the
blood collected here is from SVC, IVC and coronary sinus. It can be monitored
even continuously with fiberoptic reflectance oximetry. It utilizes the concept
of Fick’s method. It indicates the balance between oxygen delivery and oxygen
consumption at the tissues. Normal ScvO2 is ≥70%. This parameter is useful in
guiding therapy of septic shock (River’s protocol—early goal directed therapy).
Hence, it is an indirect indicator of cardiac output and tissue hypoxia. An arbitrary
calculation is that, a SvO2 of 0.5 corresponds to venous PO2 of 25 mm Hg.
Measurement of cardiac output in critically ill patients provides a global
assessment of the circulation, and with other hemodynamic measurements
(heart rate, arterial blood pressure, CVP, PAP, and PAWP), it can derive circulatory
variables such as systemic vascular resistance (SVR), pulmonary vascular
resistance (PVR) and ventricular stroke work. Reduced CO increases mortality
and thermodilution method is used. Commonly used injectate is cold normal
saline (alternative is lithium) and is injected in superior vena cava and by
detecting the blood temperature by a thermistor near the distal tip, the device
estimates the flow.
Transpulmonary dilution technique is an alternative to PAC where a tracer
is injected through a CVP line and detected in an arterial line (e.g. radial artery).
Echocardiography
Transesophageal echo can visualize cardiac chambers by which the volumetric
changes between systole and diastole are measured. With this information, stroke
volume and cardiac output can be estimated. Left ventricular end-diastolic area
index (LVEDAI) is a static measure of LV preload.
Ultrasonography
A B
Figs 7.4A and B Ultrasound-guided IVC imaging showing collapsibility in the
second image
Interpretations
• Spontaneous breathing patients—fluid responsive, if
– IVC measuring < 2 cm in diameter coupled with IVC collapse >50% with
each breath or
– IVC collapsibility >12%
• Mechanically ventilated patiens—fluid responsive, if IVC distensibility >18%.
• IVC collapsibility = (Max diameter – min diameter)/(mean diameter) × 100
IVC distensibility = (Max diameter – min diameter)/(min diameter) × 100
• Caval index (the fractional change in the IVC diameter during respiration).
• A greater than 50% decrease in IVC diameter is associated with a CVP
<8 mm Hg in management of sepsis.
Doppler ultrasound can be used to measure blood velocity in descending
aorta and can be used for estimating cardiac output (Figs 7.4A and B).
Dynamic Parameters of Fluid Responsiveness

Dynamic parameters can predict increased cardiac output from volume challenge
even when volume expansion is not done, and hence they are better predictors
of fluid responsiveness than static measures. The first idea of conception of fluid
responsiveness was the variation in arterial blood pressure observed during
positive-pressure mechanical ventilation. These are measured using invasive
arterial pressure monitoring, and these parameters result from the changes in
intrathoracic pressure and lung volume that occur during the respiratory cycle
(Flow chart 7.1).
SYSTOLIC PRESSURE VARIATION

Systolic pressure variation (SPV) is divided into inspiratory and expiratory
components by measuring the increase (ΔP) and decrease (ΔD) in systolic
pressure in relation to the end-expiratory and apneic baseline pressure.
Interpretation of SPV
• During positive pressure ventilation, normal SPV = 7–10 mm Hg
• Hypovolemia—increase in SPV especially the ΔD component.
Flow chart 7.1 Cyclical variation of systemic arterial pressure
Studies have proven that SPV is a better indicator of LV preload than PAOP,
CVP.
Pulse Pressure Variation

The maximum difference in arterial pulse pressure measured during a respiratory
cycle in a patient on mechanical ventilation divided by the mean of maximal and
minimal pulse pressure. Normal pulse pressure variation (PPV) is <13%. It is a
better indicator for fluid responsiveness than most static measures of preload.
Stroke Volume Variation

Recent methods of cardiac output measurement based on pulse contour analysis
like stroke volume variation (SVV) is a good indicator of volume responsiveness.
Normal SVV is 10% and patients with increased variability will be fluid responsive.
LIMITATIONS OF DYNAMIC PARAMETERS

• They can vary with tidal volume, peak inspiratory pressure and lung dynamics
• Can vary with cardiac arrhythmias
• Only validated in mechanically ventilated patients
• Their validation in spontaneously breathing patients is yet to be proved.
Preload Responsiveness by Passive Leg Raising Test

Passive leg raising (PLR) is a simple maneuver that can resemble a rapid volume
expansion of approximately 300–500 mL. Passive leg raising induces a gravitational
transfer of blood from the lower limb to the right side of the heart. A 45° elevation
is given to legs for 3 minutes and it has been found to have a good test of preload
responsiveness in critically ill patients. Advantage of this technique is that it can
be used for spontaneously breathing patients and patients with arrhythmias

unlike PPV, SVV which can be used only in mechanically ventilated patients.
PiCCO/NiCOM System
It uses the transpulmonary dilution method to measure cardiac output and an
increase in pulse contour cardiac output by more than 10% in response to PLR
has been shown to predict volume responsiveness in mechanically ventilated
patients with spontaneous breathing activity.
BIBLIOGRAPHY
1. Berkenstadt H, Margalit N, Hanani M, et al. Stroke volume variation as a predictor
of fluid responsiveness in patients undergoing brain surgery. Anesth Analg. 2001;
92:984-9.
2. Biais M, Vidil L, Sarrabay P, Cottenceau V, Revel P, Sztark F. Changes in stroke volume
induced by passive leg raising in spontaneously breathing patients: comparison
between echocardiography and Vigileo/FloTrac device. Crit Care. 2009;13:R195.
3. Bloos F, Reinhart K. Venous oximetry. Intensive Care Med. 2005;31:911-3.
4. Cavallaro F, Sandroni C, Marano C, La TG, Mannocci A, De WC, Bello G, Maviglia
R, Antonelli M. Diagnostic accuracy of passive leg raising for prediction of fluid
responsiveness in adults: systematic review and meta-analysis of clinical studies.
Intensive Care Med. 2010;36:1475-83.
5. C Otto. Textbook of Clinical Echocardiography, 3rd ed. Philadelphia, Pa, USA: Elsevier
Saunders, 2004.
6. Donati A, Loggi S, Preiser JC, et al. Goal-directed intraoperative therapy reduces
morbidity and length of hospital stay in high-risk surgical patients. Chest. 2007;132:
1817-24.
7. Feissel M, Michard F, Mangin I, et al. Respiratory changes in aortic blood velocity as an
indicator of fluid responsiveness in ventilated patients with septic shock. Chest. 2001;
119:867-73.
8. Gunn SR, Pinsky MR. Implications of arterial pressure variation in patients in the
intensive care unit. Curr Opin Crit Care. 2001;7:212-7.
9. Ma OJ, Mateer J. Emergency Ultrasound. McGraw-Hill, New York, NY, USA, 2003.
10. Marx G, Cope T, McCrossan L, et al. Assessing fluid responsiveness by stroke volume
variation in mechanically ventilated patients with severe sepsis. Eur J Anaesthesiol.
2004;21:132-8.
11. Michard F, Teboul JL. Predicting fluid responsiveness in ICU patients: a critical
analysis of the evidence, Chest. 2002;121(6):2000-8.
12. Monnet X, Rienzo M, Osman D, Anguel N, Richard C, Pinsky MR, Teboul JL. Passive
leg raising predicts fluid responsiveness in the critically ill. Crit Care Med. 2006,34:
1402-7.
13. Nagdev AD, Merchant RC, Tirado-Gonzalez A, Sisson CA, Murphy MC. Emergency
department bedside ultrasonographic measurement of the caval index for noninvasive
determination of low central venous pressure.” Annals of Emergency Medicine.
2010;55(3):290-5.
14. Preisman S, Kogan S, Berkenstadt H, Perel H. Predicting fluid responsiveness in
patients undergoing cardiac surgery: Functional hemodynamic parameters including
the respiratory systolic variation test and static preload indicators. Br J Anaesth.
2005;95:746-55.
15. Pölönen P, Ruokonen E, Hippeläinen M, et al. A prospective, randomized study of
goal-oriented hemodynamic therapy in cardiac surgical patients. Anesth Analg. 2000;
90:1052-9.
16. Reuter DA, Kirchner A, Felbinger TW, et al. Usefulness of left ventricular stroke volume
variation to assess fluid responsiveness in patients with reduced cardiac function. Crit
Care Med. 2003;31:1399-404.
17. Rex S, et al. Prediction of fluid responsiveness in patients during cardiac surgery.
British Journal of Anaesthesia. 2004;93(6):782-8.
18. Rivers E, Nguyen B, Havstad S, et al. Early goal-directed therapy in the treatment of
severe sepsis and septic shock. N Engl J Med. 2001;345:1368-77.
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1313-21.
SECTION
4 SHOCK
Chapter 8
An Overview of Shock
Prem Kumar
Chapter 9
Hypovolemic Shock
Prem Kumar
Chapter 10 Obstructive Shock

Prem Kumar
Chapter 11 Cardiogenic Shock

TA Naufal Rizwan
Chapter 12 Multiple Organ Dysfunction

Syndrome
Prem Kumar
CHAPTER
8 Prem Kumar
AN OVERVIEW OF SHOCK
Shock is one of the common problem prevalent in intensive care unit (ICU) and
the mortality and morbidity due to shock is high. It can be due to various causes
like hypovolemia, cardiac causes, sepsis and medical disorders like pulmonary
vascular disease. In this chapter, we will discuss the pathophysiology, clinical
features, diagnosis, hemodynamic monitoring and management.
DEFINITION
It is an acute clinical syndrome resulting in cellular dysoxia ultimately resulting in
organ dysfunction and failure. Cellular hypoxia due to reduced tissue perfusion is
the primary pathophysiology of shock.
CLASSIFICATION (TABLE 8.1)

It can be classified into four types:
1. Hypovolemic shock.
2. Cardiogenic shock.
3. Distributive shock—septic, anaphylactic, neurogenic, adrenal, drug-
induced.
4. Obstructive shock.
Table 8.1 Hemodynamic variations in various types of shock
Mixed venous
Type of Cardiac oxygen saturation
shock CVP output (CO) PCWP SVR (SvO2)
Hypovolemic ↓↓ ↓ ↓ ↑ ↓
Cardiogenic ↑ ↓↓ ↑ ↑ ↓
Distributive Normal or ↑ ↑ Normal or ↓ ↓ or ↑ Normal or ↑
Obstructive ↑ ↓↓ Normal or ↓ ↑ ↓
Abbreviations: CVP, central venous pressure; PCWP, pulmonary capillary wedge pressure; SVR, systemic
vascular resistance
66 Section 4 Shock
CLINICAL FEATURES
Hypotension as such is not an exclusive feature of shock. Clinical manifestations
of organ dysfunction is good indicator of shock. Tachycardia, hypotension,
tachypnea and irritability, if the cause of shock is not corrected are all early
manifestations of shock. Reduced organ perfusion as indicated by reduced
urine output, lactic acidosis, hepatic dysfunction are all late features if shock is
uncorrected or is refractory to treatment. In case of cardiogenic shock, patient
may have elevated jugular venous pressure, arrhythmias, pulmonary edema.
Diagnosis (Table 8.2 and Flow Chart 8.1)

It is based on the history, physical examination, lab investigations and
hemodynamic monitoring. Arterial blood gas analysis to see lactate level,
acidosis. Hemoglobin, urea, creatinine, cortisol level can be used for diagnosis.
central venous pressure (CVP), PAWP, CO, EtCO2, and echocardiogram will help
in diagnosis and management.
Management
Primary goals of management in shock are:
• Early recognition
• Diagnosis of etiology
• Improving tissue perfusion to prevent cellular injury
• Primary treatment of etiology
• Prevention of end-organ failure.
Table 8.2 Clinical manifestations of shock
Organ Clinical features Etiology

Heart Tachycardia, arrhythmias Myocardial depression
CCF
MI, coronary ischemia,
sympathetic stimulation
Peripheral circulation Hypotension, ↑ JVP Hyponatremia
↓ SVR
CCF
CNS Irritable, confused, somnolent ↓ cerebral perfusion
RS Tachypnea, crepitation Pulmonary edema sepsis
Kidney Oliguria ↓ renal perfusion
AKI
Liver Jaundice (late) ↓ hepatic perfusion
↑ liver enzymes
Skin Cold, clammy, cyanosis Vasoconstriction hypoxemia
Metabolic Lactic acidosis, fever ↓ tissue perfusion infection
Flow chart 8.1 Diagnosis of shock based on history
Chapter 8 An Overview of Shock
67
68 Section 4 Shock
End Points of Resuscitation

• Normal tissue perfusion—primary tissue perfusion
• Normal vital signs
• Normal end-organ perfusion—adequate urine output, improved mental
status
• Normal serum lactate and base deficit
• Hemodynamic variable-based end points:
– SvO2 >70%
– Oxygen delivery
– CVP = 8–10 mm Hg
– PAWP >12 mm Hg
– Cardiac output
– EtCO2 = 35–45 mm Hg
– Dynamic parameters of fluid responsiveness—PPV (<13%), SVV (<10%),
etc.
Apart from the specific therapies for each type of shock which would be
discussed in the respective chapters, the overall management of resuscitation in
shock are:
• Fluid resuscitation and blood component transfusion
• Administration of vasopressors/inotropes
• Use of mechanical support if necessary like IABP
• Adjunctive therapies.
Fluid Management
The initial management of all the types of shock is fluid administration. The goal
is to restore the lost volume and improve the tissue perfusion in terms of oxygen
transport to optimize the perfusion of end-organ and cellular oxygenation.
Initial fluid of administration should be a balanced salt solution with a volume
of 20 mL/kg given intravenously. In hemodynamically unstable patients, invasive
monitoring would help in guiding therapy. Goals of resuscitation are given above.
Crystalloid vs Colloid (Table 8.3)

There has been long-term debate about which fluid is superior. Till date the
current evidence shows that colloids are not superior to crystalloids in terms of
survival, hence isotonic crystalloids are the preferred fluid for initial resuscitation
although colloids can be used for specific indications. Normal saline and ringer
Table 8.3 Points of mention about crystalloids
Normal saline Ringer lactate

• Osmolality – 308 • Osmolality – 273
• Hypernatremia and hyperchloremic • Considered to be more physiologic
metabolic acidosis are complications than normal saline
that can occur on large volume • Lactate in RL buffers metabolic acidosis
administration • Higher lactate produces CO2 causing
respiratory acidosis
Chapter 8 An Overview of Shock 69
lactate are the crystalloids used although recently certain isotonic fluids like
plasmalyte is more isotonic than normal saline and ringer lactate.
Recently, the management of hypovolemic shock has shifted towards
hypotensive resuscitation. This is an emerging idea in hypovolemic shock and is
applicable in mechanical causes of bleeding where the cause of bleeding is not
achieved.
Vasopressors/Inotropes (Table 8.4)

The balance obtained between fluid volume and vasopressor/inotrope
administration according to the cause of shock is the main component of
Table 8.4 Commonly used vasopressors/inotropes for shock
Drug Dose Comments Adverse effects

Dopamine 1–20 µg/kg/minute Renal 1–5 µg/ Tachycardia, tissue
kg/min necrosis
Beta action
5–10 µg/kg/min
Alpha action
>10 µg/kg/min
Initial drug of
choice for any
type of shock
Dobutamine 2–20 µg/kg/minute Beta agonistic Beta-2 action may cause
used in hypotension hence
cardiogenic cautious use in patients
shock with hypotension
Epinephrine 0.01–0.1 µg/kg/ Used in Tachycardia, arrhythmias,
minute cardiac arrest splanchnic and renal
and in severe vasoconstriction,
hypotension with myocardial ischemia
bradycardia
Norepinephrine 0.01–1 µg/kg/minute Vasopressor of Myocardial ischemia,
choice for septic tissue hypoxia
shock
Vasopressin 0.01–0.04 U/minute Alternative drug Splanchnic hypoperfusion,
for cardiac hyponatremia
arrest, used in
the treatment of
catecholamine
resistant shock,
has a role in
septic shock
Milrinone 50 µg/kg bolus Congestive Thrombocytopenia
infusion—0.375– cardiac failure
0.75 µg/kg/minute with cardiogenic
shock
Phenylephrine 0.5–10 µg/kg/minute Pure alpha 1 Reduced cardiac output
agonist
70 Section 4 Shock
resuscitation in shock. Vasopressors are started in patients where fluid bolus had
failed in attaining the end point of resuscitation. Vasopressors reduce the need of
large volume resuscitation, but it causes adverse effects due to end organ damage
(due to peripheral vasoconstriction).
BIBLIOGRAPHY
1. Blair SD, Janvrin SB, McCollum CN, et al. Effect of early blood transfusion on
gastrointestinal hemorrhage. Brit J Surg. 1986;73:783.
2. Choi PTL, Yip G, Quinonez LG, et al. Crystalloids vs. colloids in fluid resuscitation: a
systematic review. Crit Care Med. 1999;27:200.
3. Civetta JM, Taylor RW, Kirby RR. Critical Care, 4th edn. Philadelphia: Lippincott-
Raven; 2009.
4. Cochrane Injuries Group Albumin Reviewers: Human albumin administration in
critically ill patients: systematic review of randomized controlled trials. BMJ. 1998;
317:235.
5. Dellinger, et al. Surviving Sepsis Campaign: International Guidelines for Management
of Severe Sepsis and Septic Shock: 2012. Crit Care Med. 2013;41:580-637.
6. Dutton RP, MacKenzie CF, Scalea TM. Hypotensive resuscitation during active
hemorrhage: impact on in-hospital mortality. J Trauma. 2002;52:1141.
7. Roberts K, Revell M, Youssef H, Bradbury AW, Adam DJ. Hypotensive resuscitation
in patients with ruptured abdominal aortic aneurysm. Eur J Vasc Endovasc Surg.
2006;31:339-44.
8. Schierhout G, Roberts I. Fluid resuscitation with colloid or crystalloid solutions in
critically ill patients: a systematic review of randomized trials. BMJ. 1998;316:961.
9. Vermeulen LC Jr, Ratko TA, Erstad BL, et al. A paradigm for consensus. The University
Hospital Consortium guidelines for the use of albumin, nonprotein colloid, and
crystalloid solutions. Arch Intern Med. 1995;155:373.
10. Viega C, Mello PM, Sharma VK, et al. Shock overview. Semin Respir Crit Care Med.
2004;25:619.
CHAPTER
9 Prem Kumar
HYPOVOLEMIC SHOCK
Hypovolemic shock can be due to hemorrhage or nonhemorrhagic causes but it

is commonly caused by hemorrhage. Hemorrhagic shock results in hypovolemia
and causes tissue hypoperfusion due to blood loss. It is a fact that other types of
shock also have a component of hypovolemia during its course.
ETIOLOGY
• Hemorrhage
• GI loss—diarrhea, vomiting, fistula
• Pancreatitis
• Burns
• Renal loss—trauma-induced diabetes insipidus, postobstructive diuresis
• Major abdominal surgery
• Retroperitoneal—ruptured abdominal aortic aneurysm.
PATHOPHYSIOLOGY (FLOW CHART 9.1)

The lethal triad of traumatic hemorrhagic shock are:
• Metabolic acidosis
• Hypothermia
• Coagulopathy.
Diagnosis
• Physical findings of hypovolemia are cold and clammy skin, tachypnea,
tachycardia, hypotension and irritability
• The absence of tachycardia and hypotension does not exclude shock hence
there can be presentation of occult shock and the compensatory mechanisms
can be blunted in patients on drugs such as beta-blockers
• Once a patient presents with hemorrhagic shock, the patient has assessed
for recognizing the degree of shock. For this, American College of Surgeon’s
classification of blood loss and its manifestations is useful for assessment
and management. Classification is given in the Table 9.1.
• Identification of the source of hemorrhage–external regions, thorax,
abdomen, retroperitoneum, pelvis and long bone fractures (Table 9.2).
Flow chart 9.1 Pathophysiology of hemorrhagic shock 72 Section 4 Shock
Abbreviations: ACTH, adrenocorticotropic hormone; ADH, antidiuretic hormone; Adr/NA, adrenaline/nor adrenaline; PVR, pulmonary vascular resistance; RAAS, renin
angiotensin aldosterone system; TNF, tumor necrosis factor; SIRS, systemic inflammatory response syndrome; ROS, reactive oxygen species
Chapter 9 Hypovolemic Shock 73
Table 9.1 Classification of the degrees of shock
Factors Class I Class II Class III Class IV

Blood loss 15 15-30 30–40 ≥ 40
(% blood volume)
Pulse (beats/min) 100 100 120 ≥ 140
Blood pressure Normal Normal Decreased Decreased
Pulse pressure (mm Hg) Normal or Decreased Decreased Decreased
increased
Capillary refill test Normal Positive Positive Positive
Respirations/min 14–20 Tachypnoec Tachypnoec Tachypnoec
Urine output (mL/hr) 30 20–30 5–10 Negligible
Central nervous system: Slightly Mildly Anxious, Confused,
mental status anxious anxious confused lethargic
Fluid replacement Crystalloid Crystalloid Crystalloid Crystalloid
(3–1 rule) + blood + blood
Table 9.2 Etiology and source of hemorrhage
Source of
hemorrhage Cause Diagnosis
External region Deep tissue wounds Physical examination
Scalp laceration
Vascular injury
Thorax Hemothorax Chest X-ray or CT-scan
Abdomen Liver or spleen or Ultrasound, diagnostic peritoneal
gastrointestinal injury lavage (DPL), CT-scan
Retroperitoneum Renal or vascular injury like CT-scan, angiography
aortic injury
Pelvis Pelvic fractures Pelvic radiography
Long bone fracture Femur or tibia fracture Radiography
• Recently the use of ultrasound has a major role in diagnosing the cause of
the shock and it is extremely useful in the management of patients with
hemorrhagic shock. Many protocols are there but the commonly followed
protocol is e-FAST and rapid ultrasound in shock (RUSH) protocol.
Management
The initial management of any patient with post-shock cardiac arrest is based
on advanced cardiac life support (ACLS) where circulation, airway, breathing
(CAB) is followed. Circulation, airway and breathing is initiated until the patient
has return of spontaneous circulation and postcardiac arrest care is given. If
the patient comes to the emergency department (ED) with hypovolemic shock,
advanced trauma life support (ATLS) guidelines are followed (Table 9.3).
74 Section 4 Shock
Table 9.3 Primary survey
Airway Breathing Circulation Disability Exposure

Diagnosis Auscultation Pulse Vital signs, Glassgow Full physical
oximetry, e-FAST, coma scale examination,
arterial typing and cross (GCS) score, Detailed
blood gas matching, neurological history,
analysis coagulation examination, Other lab
(ABG), chest parameters, cervical spine studies to
X-ray complete blood films, support
count, pelvic CT-brain diagnosis
X-ray
Management Triple Mechanical IV access, Cervical Removal of
maneuver, ventilation, fluid infusion, collar, clothes and
oxygen, intercostal pressure on emergency thorough
intubation drainage wounds, surgery, examination
O –ve blood, intracranial surgery,
thoracotomy, pressure (ICP) detailed
surgery, pelvic monitoring review
binder
Primary survey is done to identify and treat life and limb threatening injuries
and the focus should be on the injuries which needs immediate management
and is based on the golden hour. Once the patient is stabilized, secondary survey
is done with further diagnostic studies to diagnose the missed injuries. ATLS
emphasizes the ABCDE mnemonic: airway, breathing, circulation, disability, and
exposure.
KEY ELEMENTS OF MANAGING HEMORRHAGIC SHOCK

• Recognition of hemorrhagic shock and the need of rapid initiation of damage
control operative treatment.
• Maintaining hypotensive resuscitation during active bleeding by infusing
limited volume of crystalloid and blood components.
• Airway management plan with rapid-sequence induction of anesthesia
accompanied by cricoid pressure (Sellick’s maneuver) and in-line cervical
stabilization, followed by direct laryngoscopy.
• Wide bore peripheral cannula is better for rapid infusion than a central
venous catheter in hemorrhagic shock.
• Isotonic crystalloids (ringer lactate, normal saline) are administered and any
visible hemorrhage is controlled with direct pressure.
• Hemodynamics should be monitored with heart rate, ECG and noninvasive
or invasive blood pressure monitoring. Although the parameters of cardiac
preload like central venous pressure, pulmonary artery wedge pressure
(PAWP) are useful in guiding fluid therapy in hemorrhagic shock, still its
reliability is less and better methods of volume responsiveness are pulse
pressure variation where the measurements are more reliable than static
preload parameters.
Chapter 9 Hypovolemic Shock 75
• Urinary catheter is placed soon to assess the renal perfusion

• Initial administration of 20 mL/kg of crystalloid is done and if the source of
hemorrhage is not identified and the vitals are not stabilized with the initial
infusion of crystalloids, crystalloid infusion is minimized and packed RBC is
given.
• There is no specific transfusion trigger in trauma patients with hemorrhagic
shock but Hb of 7 g/dL is a generally accepted value.
• Current evidence recommends the application of hypotensive resuscitation
[or Damage Control Resuscitation (DCR)] in patients with hemorrhagic
shock with active bleeding where the source of bleeding is unknown and
the definitive control of bleeding is not done although this approach has not
been shown to improve mortality. DCR is a strategy combining hemostatic
resuscitation, permissive hypotension and damage control surgery. The
goals of this strategy are initial stabilization of the patient, reducing metabolic
acidosis, hypothermia, hypocalcemia and coagulopathy.
• This hypotensive resuscitation strategy reduces transfusion requirement
and severe postoperative coagulopathy in trauma patients with hemorrhagic
shock. Mean arterial pressure of 65 mm Hg is the goal for this resuscitation.
• Thromoboelastometry (TEG) is used as a guide for transfusion of
procoagulant blood components in patients with traumatic hemorrhagic
shock.
• Current evidence recommends the administration of PRBC: Fresh Frozen
Plasma: Platelets in a ratio of 1:1:1 in patients with massive blood loss. This
approach has been shown to improve survival due its impact on the early
intervention in preventing trauma induced coagulopathy.
• The use of tranexamic acid and rFVIIa should be considered in patients
with uncontrolled hemorrhage following trauma even after optimization of
acidosis, platelet count and procoagulant factors.
BIBLIOGRAPHY
1. Committee on Trauma. Advanced Trauma Life Support Manual. Chicago: American
College of Surgeons; 1997.pp.103-12.
2. Duchesne JC, McSwain NE, Jr, Cotton BA, Hunt JP, Dellavolpe J, Lafaro K, et al. Damage
control resuscitation: The new face of damage control. J Trauma. 2010;69:976-90.
3. Holcomb JB, Jenkins D, Rhee P, Johannigman J, Mahoney P, Mehta S, et al. Damage
control resuscitation: Directly addressing the early coagulopathy of trauma. J Trauma.
2007;62:307-10.
4. Morrison CA, Carrick MM, Norman MA, Scott BG, Welsh FJ, Tsai P, Liscum KR, Wall
MJ Jr, Mattox KL. Hypotensive resuscitation strategy reduces transfusion requirements
and severe postoperative coagulopathy in trauma patients with hemorrhagic shock:
preliminary results of a randomized controlled trial. J Trauma. 2011;70(3):652-63.
5. Rugeri L, Levrat A, David JS, Delecroix E, Floccard B, Gros A, et al. Diagnosis of
early coagulation abnormalities in trauma patients by rotation thrombelastography.
J Thromb Haemost. 2007;5:289-95.
6. Schöchl H, Nienaber U, Hofer G, Voelckel W, Jambor C, Scharbert G, et al. Goal-directed
coagulation management of major trauma patients using thromboelastometry
(ROTEM)-guided administration of fibrinogen concentrate and prothrombin
complex concentrate. Crit Care. 2010;14:R55.
76 Section 4 Shock
7. Shakur H, Roberts I, Bautista R, Caballero J, Coats T, Dewan Y, et al. Effects of

tranexamic acid on death, vascular occlusive events, and blood transfusion in trauma
patients with significant haemorrhage (CRASH-2): A randomised, placebo-controlled
trial. Lancet. 2010;376:23-32.
8. Spinella PC, Perkins JG, McLaughlin DF, Niles SE, Grathwohl KW, Beekley AC, et
al. The effect of recombinant activated factor VII on mortality in combat-related
casualties with severe trauma and massive transfusion. J Trauma. 2008;64:286.
CHAPTER
10 Prem Kumar
OBSTRUCTIVE SHOCK
Obstructive shock is also called as mechanical shock and they are a group of
conditions which cause acute increase in pulmonary vascular resistance either
through direct obstruction of pulmonary vessels or through release of mediators
which cause pulmonary vasoconstriction (Table 10.1).
CAUSES
• Pulmonary embolism—most common cause
• Cardiac tamponade
• Air or fat or amniotic fluid embolism.
PATHOPHYSIOLOGY
Flow chart 10.1 shows pathophysiology of obstructive shock.
CLINICAL FEATURES
Without any preexisting cardiopulmonary disease, acute increase in mean
pulmonary artery pressure results in acute increase in right ventricle (RV) afterload
results in RV failure resulting in reduced cardiac output and shock. Tachycardia,
tachypnea, hypotension are signs of tissue hypoperfusion. Hypoxemia results due
to ventilation perfusion mismatching. If RV failure is present, patient presents
with hepatojugular reflux, Kussmaul sign, and jugular venous distension with
tricuspid regurgitation. If the embolism is very massive, patient may end up with
cardiac arrest.
Table 10.1 Etiology and mechanism of obstructive shock
Type Mechanism Etiology

Obstructive Mechanical interference with Cardiac tamponade, inferior vena cava
ventricular filling compression, atrial tumor or clot
Interference with ventricular Pulmonary or air or fat or amniotic fluid
emptying embolism
78 Section 4 Shock
Flow chart 10.1 Pathophysiology of obstructive shock
Abbreviations: PVR, pulmonary vascular resistance; RV, right ventricle; RVEDV, right ventricle end diastolic
volume; RVEDP, right ventricle end diastolic pressure; RAP, right atrial pressure; LV, left ventricle; CO,
cardiac output
Diagnosis
Electrocardiography shows sinus tachycardia and ST-T wave changes in
anterolateral chest leads. Signs of myocardial ischemia may be present in case
of reduced coronary perfusion. Transthoracic echo shows hypokinesia of RV,
tricuspid regurgitation, flattening of interventricular septum (Table 10.2).
Pulmonary embolism, fat embolism, amniotic fluid embolism and peri
cardial tamponade are discussed in the respective chapters in detail. Hence a
brief outline of clinical features and management of all these conditions would
be discussed in this chapter. Air embolism would be discussed in detail in this
chapter.
AIR EMBOLISM
Air embolism occurs when air entrains the venous or arterial circulation
through peripheral or central venous veins and if air embolism is large, it can
cause hemodynamic instability, cardiac failure and even cardiac arrest. In the
intraoperative period, the rate of occurrence of venous air embolism varies
Chapter 10 Obstructive Shock 79
Table 10.2 Risk factors associated with the conditions
Condition Risk factors

Cardiac Post MI, trauma, infectious, carcinoma, postcatheter complications,
Tamponade postcardiothoracic surgery, postradiation, idiopathic
Pulmonary Immobilization, previous history of thromboembolism, major surgery
embolism within 3 months, obesity, trauma, hypercoagulable states
Fat embolism Long bone and pelvic fractures within 48–72 hours, orthopedic
procedures, burns, diabetes mellitus, postliposuction, acute pancreatitis
Amniotic fluid Peripartum period, use of labor induction agents like oxytocin, difficult
embolism labor, amniocentesis, trauma
Air embolism Craniotomy especially for posterior fossa procedures in sitting position,
laparoscopy, barotraumas, airway procedures, large air entrainment
into central or peripheral venous catheters, trauma
according to the procedure, the intraoperative position, and the detection

method used. The incidence is more in posterior fossa procedures done in
sitting position. Other causes are during CO2 insufflation during laparoscopic
procedures and it can occur during administration of pulmonary vasodilators.
The severity of hemodynamic changes are based upon the rate at which air enters
the pulmonary circulation, preexisting cardiopulmonary disease, volume and the
inflammatory response triggered by the embolism.
Arterial embolism is more dangerous than venous embolism because of the
fact that it can result in cardiogenic shock by entering the coronary circulation.
Significant volume of venous air embolism that can cause clinical effect was
found to be around 100 mL but clinical effects with even 50 mL has been recorded.
Cardiac arrest secondary to massive pulmonary embolism was found to be 300–
500 mL. The clinical features resemble that of massive pulmonary embolism
and there is chance of paradoxical embolism in case of anatomic septal defects.
In sitting craniotomy, the common sources of venous air embolism are the
transverse, the sigmoid, and the sagittal sinus.
Diagnosis
• Transesophageal echocardiography (TEE)—most sensitive
• Precordial Doppler
• Expired nitrogen analysis
• End tidal CO2 analysis.
The combination of precordial Doppler and EtCO2 is the standard of care
for detecting venous air embolism in patients undergoing sitting craniotomy.
Doppler probe is placed in a left or right parasternal location between the second
and third or third and fourth ribs has a high sensitivity level of detection rate for
air embolism.
Management
The mainstay of therapy for air embolism is supportive. Therapy consists of:
• Terminating the route of air entry
80 Section 4 Shock
Table 10.3 Specific conditions causing obstructive shock and its management
Condition Management
Cardiac tamponade Nontraumatic—immediate pericardiocentesis
Traumatic—surgical decompression
Pulmonary embolism Anticoagulation
Thrombolysis
Surgical thrombolectomy
Hemodynamic support in case of cardiac failure and hypotension
Fat embolism Supportive corticosteroids
Amniotic fluid embolism Supportive blood component therapy
CPR
• Treating the intravascular air embolism

• Maintaining hemodynamic stability.
Steps of managing air embolism during sitting craniotomy in the intra
operative period:
• Flood the surgical site with saline
• Jugular compression
• Lowering the head
• Place the patient in left lateral decubitus position
• Aspirate the central venous catheter
• Keep FiO2 of 100%
• Discontinue nitrous oxide
• Start vasopressors/inotropes in case of hemodynamic instability (Table
10.3).
BIBLIOGRAPHY
1. Black S, Muzzi DA, Nishimura RA, et al. Preoperative and intraoperative echocardio
graphy to detect right-to-left shunt in patients undergoing neurosurgical procedures
in the sitting position. Anesthesiology. 1990;72:436-8.
2. Cucchiara RF, Seward JB, Nishimura RA, et al. Identification of patent foramen
ovale during sitting position craniotomy by transesophageal echocardiography with
positive airway pressure. Anesthesiology. 1985;63:107-9.
3. Mammoto T, Hayashi Y, Ohnishi Y, et al. Incidence of venous and paradoxical air
embolism in neurosurgical patients in the sitting position: Detection by trans
esophageal echocardiography. Acta Anaesthesiol Scand. 1998;42:643-7.
4. Mellor A, Soni N. Review article: Fat embolism. Anaesthesia. 2001;56:145-60.
5. Michenfelder JD, Miller RH, Gronert GA. Evaluation of an ultrasonic device (Doppler)
for the diagnosis of venous air embolism. Anesthesiology. 1972;36:164-7.
6. Mirski MA, Lele AV, Fitzsimmons L, et al. Diagnosis and treatment of vascular air
embolism. Anesthesiology. 2007;106:164-77.
7. Papadopoulos G, Kuhly P, Brock M, et al. Venous and paradoxical air embolism in
the sitting position: A prospective study with transesophageal echocardiography. Acta
Neurochir. 1994;126:140-3.
8. Schubert A, Deogaonkar A, Drummond JC. Precordial Doppler probe placement for
optimal detection of venous air embolism during craniotomy. Anesth Analg. 2006;
102:1543-7.
CHAPTER
11 TA Naufal Rizwan
CARDIOGENIC SHOCK
DEFINITION
Cardiogenic shock is a condition characterized by reduction in the cardiac output
resulting in tissue hypoxia which leads on to various functional and structural
disturbances in vital organs. Etiology is given in Table 11.1.
CHARACTERISTICS
Cardiogenic shock is characterized by:
• Cardiac index <2.2 L/min/m2
• Systolic BP <90 mm Hg
• Pulmonary capillary wedge pressure (PCWP) >18 mm Hg.
Table 11.1 Etiology
Common causes
• Coronary artery disease—Acute myocardial infarction (MI) is the most common cause
(90%)
Causes of cardiogenic shock in MI
– LV failure (85%)
– Acquired VSD
– Mitral regurgitation
• Arrhythmias—refractory sustained tachy and bradyarrhythmias
• Valvular heart disease, e.g. severe MS, AR
• Cardiomyopathies/myocarditis
• Postcardiopulmonary bypass/prosthetic valve dysfunction
Uncommon causes
• Pulmonary embolism, acute cor pulmonale
• Pericardial tamponade
• Severe metabolic acidosis
Abbreviations: VSD, ventricular septal defect; LV failure, left ventricular failure; MS, mitral stenosis; AR,
aortic regurgitation
82 Section 4 Shock
PATHOGENESIS (FLOW CHART 11.1)

Pathogenesis of cardiogenic shock is given in Flow chart 11.1.
Flow chart 11.1 Pathogenesis of cardiogenic shock
CLINICAL FEATURES
Cardiogenic shock may or may not be associated with acute pulmonary edema.
The usual presenting complaints are chest pain and breathlessness. The affected
patients are confused, drowsy, diaphoretic and apprehensive.
On examination, the pulse is weak and rapid (although in severe heart block,
bradycardia is noted). Hypotension with reduced systolic and narrow pulse
pressure is seen. Jugular venous distension is usually present. Cardiovascular
auscultation may demonstrate S3 gallop and pansystolic murmur of ventricular
septal defect (VSD) and mitral regurgitation (MR). Rales are seen in left ventricular
(LV) failure producing cardiogenic shock. Metabolic acidosis and oliguria (urine
output < 30 mL/hr) are also present in a few patients.
HIGH-RISK PATIENTS FOR CARDIOGENIC SHOCK

• Acute MI (more common with anterior wall MI)
• Reinfarction
• Old age and female sex
• Diabetes mellitus.
Chapter 11 Cardiogenic Shock 83
Investigations
• Renal function tests—elevated urea, creatinine due to renal hypoperfusion
• Liver function tests—elevated liver enzymes due to liver hypoperfusion
• ABG—metabolic acidosis/hypoxemia.
Electrocardiogram
Electrocardiogram (ECG) changes seen in cardiogenic shock are usually
consistent with a massive acute infarct or severe and diffuse ischemia or prior
myocardial damage. A relative lack of ECG abnormalities in contrast to the
severity of the hemodynamic status should alert one to consider another cause
of cardiogenic shock such as aortic dissection or rupture of the myocardium (i.e.
free wall, ventricular septum, papillary muscle, or chordae).
Chest X-ray
Pulmonary venous congestion and pulmonary edema may be noted.
Echocardiography with Color Flow Doppler

Echocardiography is helpful in determining the following:
• LV and RV function
• Cardiac output estimation
• Detection of MR and ventricular septal rupture
• Proximal aortic dissection with aortic insufficiency.
Pulmonary Artery Catheterization

The advantages of doing pulmonary artery catheterization are:
• Estimation of filling pressures and cardiac output
• Optimizing the use of IV fluids, inotropic agents and vasopressors.
LEFT HEART CATHETERIZATION AND ANGIOGRAPHY

It is indicated when immediate coronary intervention is required or when a
definite diagnosis has not been made.
Treatment
84 Section 4 Shock
General Measures
Patients in cardiogenic shock are usually hypotensive and this should be managed
with IV fluids and if necessary, blood transfusions. Positive pressure ventilation
plays a great role in the correction of hypoxemia and metabolic acidosis. Pacing,
preferably dual chamber is recommended for AV block and bradycardia.
Tachyarrhythmias (VT/AF) are corrected by cardioversion or drugs.
Pharmacotherapy
The management of cardiogenic shock is outlined based on the three different
scenarios:
1. Cardiogenic shock with hypovolemia
2. Cardiogenic shock with low cardiac output
3. Cardiogenic shock with pulmonary edema
Cardiogenic shock with hypovolemia: Managed with IV fluids, blood transfusions
and vasopressors
Cardiogenic shock with low cardiac output
• If SBP > 100 mm Hg, Inj. nitroglycerin IV infusion 10–20 µg/min
• If SBP is 70–100 mm Hg and no signs of shock—Inj. dobutamine IV infusion
2–20 µg/kg/minute
• If SBP is <100 mm Hg and signs of shock present—Inj. norepinephrine IV
infusion 0.5–30 µg/min or Inj. dopamine 5–15 µg/kg/min
Cardiogenic shock with pulmonary edema: General measures like oxygen therapy,
positive pressure ventilation.
Specific measures for cardiogenic shock with pulmonary edema
• Morphine IV 2–4 mg
• Furosemide IV 0.5–1 mg/kg
It is not necessary to continue the diuretics in pulmonary congestion
even after the patient has improved because it may lead to volume depletion,
thereby worsening the ischemia and pulmonary edema
• Nitroglycerin-sublingual or Inj. nitroglycerin IV infusion 10–20 µg/minute if
SBP >100 mm Hg)
• If SBP is <100 mm Hg and signs of shock present—Inj. Norepinephrine IV
infusion
0.5–30 µg/minute or Inj. dopamine 5–15 µg/kg/minute
• If SBP is 70–100 mm Hg and no signs of shock—Inj. dobutamine IV infusion
2–20 µg/kg/minute
INVASIVE PROCEDURES IN CARDIOGENIC SHOCK
Aortic Counter Pulsation

It is a procedure which improves hemodynamic status temporarily in
cardiogenic shock patients, till the patient is taken up for coronary intervention
or urgent surgery. Intra-aortic balloon pump (IABP) is contraindicated in aortic
regurgitation and aortic dissection.
Chapter 11 Cardiogenic Shock 85
Procedure
A sausage-shaped balloon is placed into the aorta via the femoral artery. This
balloon inflates automatically during diastole and collapses during systole. Thus,
the afterload during systole is reduced and coronary blood flow during diastole is
increased, thereby myocardial oxygen demand and ischemia are reduced.
Ventricular Assist Devices

It can be used as a stop-gap procedure in patients with refractory shock until the
patients are planned for cardiac transplantation.
Reperfusion-revascularization
Percutaneous coronary intervention (PCI) or coronary artery bypass grafting
(CABG) should be considered for coronary artery disease.
VASOPRESSORS
Vasopressors play an important role in the management of cardiogenic shock as
they cause an increase in the blood pressure and thus the cardiac output.
Following are the vasopressors used in the management of cardiogenic shock:
• Norepinephrine
Action: Potent vasoconstrictor and positive inotropic
Dose: Start with 2–4 µg/minute—can be increased up to 30 µg/minute
• Dopamine
Action: Renal vasodilatation, positive inotropic, positive chronotropic, vaso
constriction
Dose: <2 µg/kg/minute—dilates renal vascular bed (dopamine receptors)
2–10 µg/kg/minute—+ve inotropic and +ve chronotropic (beta adrenergic
stimulation)
>10 µg/kg/min—vasoconstrictor effects (alpha receptor stimulation)
• Dobutamine
Action: Positive inotropic and chronotropic effect
Dose: 2–20 µg/kg/minute
BIBLIOGRAPHY
1. Bates ER, Moscucci M. Post-myocardial infarction cardiogenic shock. In: Brown DL
(Ed). Cardiac Intensive Care. Philadelphia: Pa: Saunders; 1998.pp.215-27.
2. Dan L Longo, Dennis L Kasper, J Larry Jameson, Anthony S Fauci, Stephen L Hauser,
Joseph Loscalzo. Harrison’s principles of internal medicine. 18th ed. 2012. McGraw
Hill publications. pp.3896-4006.
3. David Hasai, Peter B Berger, Alexander Battler, David R Holmes Jr. Cardiogenic Shock:
Diagnosis and Treatment. Br J Anaesth. 2002;89(4):665-6.
4. Fincke R, Hochman JS, Lowe AM, et al. SHOCK investigators. Cardiac power is the
strongest hemodynamic correlate of mortality in cardiogenic shock: a report from the
SHOCK trial registry. J Am Coll Cardiol. 2004;44:340-8.
5. Hochman J. Annual Scientific Sessions. Dallas, TX: In: Cardiogenic shock. American
Heart Association; 1998.
86 Section 4 Shock
6. Hochman JS, Buller CE, Sleeper LA, et al. Cardiogenic shock complicating acute
myocardial infarction: etiologies, management and outcome: a report from the
SHOCK trial registry. J Am Coll Cardiol. 2000;36:1063-70.
7. Khalid L, Dhakam SH. A review of cardiogenic shock in acute myocardial infarction;
Curr Cardiol Rev. 2008;4(1):34-40.
8. Leslie M. Cardiogenic shock in acute myocardial infarction: The era of mechanical
support. J Am Coll Cardiol. 2016;67(16):1881-4.
9. Lindholm MG, Boesgaard S, Torp-Pedersen C, Kober L. TRACE registry study group.
Diabetes mellitus and cardiogenic shock in acute myocardial infarction. Eur J Heart
Fail. 2005;7:834-9.
10. Lindholm MG, Kober L, Boesgaard S, Torp-Pedersen C, Aldershvile J. Cardiogenic
shock complicating acute myocardial infarction; prognostic impact of early and late
shock development. Eur Heart J. 2003;24:258-5.
11. Mann DL, Zipes DP, Libby P, Bonow RO. Braunwald’s Heart Disease: A Textbook of
Cardiovascular Medicine, 2-Volume Set, 10th ed.
12. Maxine AP, Stephen JM, Michael WR. Acute heart failure and pulmonary edema. 54th
edn. Current Medical Diagnosis and Treatment. 2015.pp.398-412.
13. Souhami RL, Moxham J. Cardiogenic shock. Textbook of medicine. 4th edn, pp.493-4.
14. St Tone GW, Ohman EM, Miller MF, Joseph DL, Christenson JT, Cohen M, Urban
PM, Reddy RC, Freedman RJ, Staman KL, Ferguson JJ. Contemporary utilization and
outcomes of intra-aortic balloon counterpulsation in acute myocardial infarction: the
benchmark registry. J Am Coll Cardiol. 2003;41:1940-5.
15. Valentin Fuster, Richard Walsh Robert Harrington. Hurst’s the Heart, 13th Edn. 2011.
McGraw-Hill publications.
16. Williams SG, Wright DJ, Tan LB. Management of cardiogenic shock complicating
acute myocardial infarction: towards evidence based medical practice; Heart. 2000;83:
621-6.
CHAPTER
12 Prem Kumar
MULTIPLE ORGAN DYSFUNCTION

SYNDROME
Multiple organ dysfunction syndrome (MODS) is one of the common

consequences seen in a critically ill patient. It is the end point of sepsis and
pronounces increased incidence of mortality. The mortality increases as the
number of organs dysfunctioned increases.
DEFINITION
It is the presence of simultaneous or sequential dysfunction or failure of two
or more organs (or) altered organ function in an acutely ill patient such that
homeostasis could not be maintained without intervention.
ETIOLOGY
• Sepsis—most common
• Congestive cardiac failure
• Postcardiac arrest
• Gastrointestinal bleeding
• End-stage liver disease.
PATHOPHYSIOLOGY
The organ failure occurs in a particular sequence in patients who are more prone
for MODS (Flow charts 12.1 and 12.2). They are as follows:
Although the pathophysiology is less understood, there are theories regarding
its mechanisms.
More important among them are:
• Gut hypothesis
• Two hit hypothesis
• Tissue hypoxia hypothesis
• Endotoxin hypothesis
• Theory of apoptosis
Zeng et al. found that the receptor for advanced glycation end products
(RAGE) [transmembrane receptor of the immunoglobulin family] plays a role in
88 Section 4 Shock
innate immune response and its activation along with polymorphism has been
found to release proinflammatory cytokines which in turn causes cellular injury
thus can predispose to MODS.
Flow chart 12.1 Sequence of organ failure in MODS
Abbreviation GI, gastrointestinal
Flow chart 12.2 Pathophysiology of MODS
Abbreviations ROS, reactive oxygen species; TNF, tumor necrosis factor; IL, interleukin; TXA2,
thromboxane A2; NO, nitric oxide
Chapter 12 Multiple Organ Dysfunction Syndrome 89
CLINICAL SYNDROMES
The clinical syndromes associated with MODS are:
• Cardiovascular system—congestive cardiac failure, shock
• Respiratory system—ARDS
• Central nervous system—encephalopathy
• Kidney—acute tubular necrosis
• GIT—paralytic ileus, intestinal ischemia, upper GI bleeding
• Hematology—DIC, thrombocytopenia, leukopenia
• Neuromuscular—polyneuropathy
• Hepatic dysfunction resulting in hepatic failure
• Endocrine—hyperglycemia from insulin resistance, hypertriglyceridemia,
hypoalbuminemia, weight loss, and hypercatabolism
• Immune—pyrexia, nosocomial pneumonia.
SCORING SYSTEMS
There are different scoring systems which can assess the severity of MODS
and predict the mortality rate of patients with MODS (Table 12.1). The most
commonly used scoring systems in ICU’s are SOFA (sequential organ failure
assessment) score (Table 12.2) and MODS (multiple organ dysfunction score).
These scores have the advantage of being measured daily and usually done at
the time of ICU admission and predict the clinical course of the patient in ICU
unlike the APACHE (Acute Physiology and Chronic Health Evaluation) II score
(Table 12.3). Another advantage is the ability to know the impact of a therapeutic
intervention. Cardiovascular dysfunction is better related to outcome with the
SOFA score than with the MODS score.
Table 12.1 MODS scoring system
MODS scoring system

Variable 0 1 2 3 4
PaO2/FiO2 >300 226–300 151–225 76–150 ≤5
Platelet count >120 80–120 50–80 21–50 ≤20
(103/mm3)
Bilirubin (mg/dL) ≤1.2 1.2–3.5 3.5–7.0 7.0–14 ≥14
HR × CVP/MAP ≤10 10.1–15 15.1–20 20.1–30 >30
Glasgow Coma 15 13–14 10–12 7–9 ≤6
Scale score
Creatinine ≤1.1 1.1–2.3 2.3–4 4.0–5.7 5.7
(mg/dL)
Abbreviation: HR, heart rate; CVP, central venous pressure; MAP, mean arterial pressure; PaO2, arterial
oxygenation; FiO2, inspired concentration of oxygen
90 Section 4 Shock
Table 12.2 SOFA scoring system
Variable 1 2 3 4
Pao2 (mm Hg) <400 ± MV <300 ± MV <200 + MV <100 + MV
Platelet count <150 <100 <50 <20

(103/mm3)
Cardiovascular MAP <70 Dopa/ Dopa > 5 μg/ Dopa > 15 μg/
system mm Hg dobutamine kg/min, kg min, adr/NA
≤ 5 μg/kg min adr/NA ≤ 0.1 > 0.1 μg/min
μg/min
Glasgow Coma 13–15 10–12 6–9 <6
Scale
Bilirubin 1.2–1.9 2–5.9 6–11.9 >12
(mg/dL)
Cr (mg/dL) or 1.2–1.9 2–3.4 3.5–4.9 or >5 or
Urine output <500 mL/day <200 mL/day
Abbreviations: MV, mechanical ventilation; MAP, mean arterial pressure; NA, noradrenaline
Prevention
Till date the current strategy followed for management of MODS is prevention.
The steps taken care in critically ill patients for preventing MODS are:
• Maintaining adequate tissue oxygen delivery in terms of packed RBC
transfusion in anemic patients to increase oxygen carrying capacity,
advocating inotropic/vasopressor support to increase cardiac output and
maintain arterial blood pressure to increase tissue perfusion pressure.
• Early intubation and ventilatory support to support ventilation and
oxygenation.
• Maintaining hemodynamic stability by administering adequate fluids and
vasopressors/inotropes and the fluid responsiveness is guided by pulse
pressure variation, stroke volume variation.
• Early administration of nutritional support especially the enteral route
(glutamine supplemented) is preferred since it has been found to maintain
the intestinal mucosal barrier integrity and reduce bacterial translocation
and endotoxin release which plays a role in the development of MODS.
Reduction in gastric mucosal Ph and increased serum lactate has been found
to be associated with development of MODS.
• Antiendotoxin therapy with monoclonal antibodies.
• There is some role in using continuous venovenous hemofiltration (CVVH)
to remove circulating inflammatory mediators.
• Selective decontamination of GIT to reduce the risk of autoinfection with
gut organisms to prevent bacterial translocation has been suggested by few
studies in preventing MODS.
• Certain studies have demonstrated the role of ketoconazole in preventing
ARDS.
• Antithrombin III infusion has been found to improve oxygenation.
Table 12.3 APACHE II scoring system
APACHE II score = Acute physiology score + Age points + Chronic health points
+4 +3 +2 +1 0 +1 +2 +3 +4
Rectal ≥41 39– 38– 36– 34– 32– 30– <29.9
temperature 40.9 38.9 38.4 35.9 33.9 31.9
(°C)
MAP >160 130– 110– 70– 50– 69 <49
(mm Hg) 159 129 109
HR >180 140– 110– 70– 55– 69 40– <39
(beats/min) 179 139 109 54
RR >50 35–49 25– 12–24 10– 11 6–9 <5
(beats/min) 34
O2 delivery >500 350– 200– <200
(mL/min) 499 349
PaO2 >70 61– 70 55–60 <55
(mm Hg)
pH >7.7 7.6– 7.5– 7.3– 7.25– 7.15 <7.15
7.69 7.59 7.49 7.3 –7.2
Na >180 160– 155– 150– 130– 120– 111– <110
179 159 154 149 129 119
K >7 6–6.9 5.5– 3.5– 3–3.4 2.5– <2.5
1.9 5.4 2.9
Cr >3.5 2–3.4 1.5– 0.6– <0.6
1.9 1.4
Hct >60 50– 46– 30– 20– <20
59.9 49.9 45.9 29.9
WBC count >40 20– 15– 3–14.9 1–2.9 <1
39.9 19.9
Age Points
<44 0
45–54 2
55–64 3
65–74 5
>75 6
History of severe organ insufficiency Points

Nonoperative patients 5
Emergency postoperative patients 5
Elective postoperative patients 2
92 Section 4 Shock
• Selenium replacement therapy has been shown by one study to improve the
function of the immunocompetent cells but its therapy is not recommended
by SSC 2012 guidelines.
Management
• The treatment is primarily supportive and treatment of the underlying cause.
• Sepsis is a common condition predisposing to MODS and hence appropriate
treatment to mitigate the infection by antimicrobial therapy is done.
• Maintenance of adequate tissue oxygen delivery with fluid, blood component
transfusion and inotropes/vasopressors.
• Supporting ventilation and oxygenation.
• Nutritional support.
• To add H2 blockers for preventing stress related GI bleeding.
• Deep vein thrombosis (DVT) prophylaxis with low molecular weight heparin.
• Avoiding neuromuscular blocking agents which can precipitate poly
neuropathy.
• Correction of electrolyte disturbances.
Prognosis
MODS has a very high mortality rate varying from 30% to 100% depending on
the number of organ systems involved and the duration of dysfunction. The
mortality rate increases as the number of organ system involved increases.
The pathogenesis is complex and combination of factors is responsible for the
development of MODS. The mortality rate is increased if brain, liver, lung, and
kidney are involved. MODS score is used as a prognostic indicator.
BIBLIOGRAPHY
1. Baue AE. Multiple organ failure, multiple organ dysfunction syndrome, and systemic
inflammatory response syndrome: why no magic bullets? Arch Surg. 1997; 132(7):703-
7.
2. Bone RC, Balk RA, Cerra FB, et al. Definitions for sepsis and organ failure and
guidelines for the use of innovative therapies in sepsis. The ACCP/SCCM Consensus
Conference Committee. Chest. 1992;101:1644-55.
3. Carrico CJ, Meakins JL, Marshall JC. Multiple organ failure syndrome. Arch Surg. 1986;
121:196-202.
4. Cerra FB. Metabolic manifestations of multiple systems organ failure. Crit Care Clin.
1989;5:119-31.
5. Fink MP. Adequacy of gut oxygenation in endotoxemia and sepsis. Crit Care Med.
1993;21:S4-S8.
6. Kale IT, Kuzu MA, Berkem H, et al. The presence of hemorrhagic shock increases the
rate of bacterial translocation in blunt abdominal trauma. J Trauma. 1998;44:171-4.
7. Marshall JC, Cook DJ, Christou NV, et al. Multiple organ dysfunction score: a reliable
descriptor of a complex clinical outcome. Crit Care Med. 1995;23:1638-52.
8. Mavrommatis AC, Theodoridis T, Orfanidou A, et al. Coagulation system and platelets
are fully activated in uncomplicated sepsis. Crit Care Med. 2000;28:451-7.
9. Moore FA, Moore EE. Evolving concepts in the pathogenesis of postinjury multiple
organ failure. Surg Clin North Am. 1995;75:257-77.
10. Morrison DC, Ryan JL. Endotoxins and disease mechanisms. Annu Rev Med. 1987;
38:417-32.
11. Pastores SM, Katz DP, Kvetan V. Splanchnic ischemia and gut mucosal injury in sepsis
and the multiple organ dysfunction syndrome. Am J Gastroenterol. 1996;91:1697-10.
12. Peres Bota D, Melot C, Lopes Ferreira F, Nguyen Ba V, Vincent JL. The Multiple Organ
Dysfunction Score (MODS) versus the Sequential Organ Failure Assessment (SOFA)
score in outcome prediction. Intensive Care Med. 2002;28(11):1619-24.
13. Terregino CA, Lopez BL, Karras DJ, et al. Endogenous mediators in emergency
department patients with presumed sepsis: are levels associated with progression to
severe sepsis and death? Ann Emerg Med. 2000;35:26-34.
14. Unno N, Wang H, Menconi MJ, et al. Inhibition of inducible nitric oxide synthase
ameliorates endotoxin-induced gut mucosal barrier dysfunction in rats.
Gastroenterology. 1997;113:1246-57.
15. Vincent JL, Angus DC, Artigas A, et al. Effects of drotrecogin alfa (activated) on organ
dysfunction in the PROWESS trial. Crit Care Med. 2003;31:834-40.
16. Vincent JL, Moreno R, Takala J, et al. The SOFA (Sepsis-related Organ Failure
Assessment) score to describe organ dysfunction/failure. On behalf of the Working
Group on Sepsis-Related Problems of the European Society of Intensive Care
Medicine. Intensive Care Med. 1996;22:707-10.
17. Zeng L, Du J, Gu W, Zhang AQ, Wang HY, Wen DL, Qiu L, Yang XT, Sun JH, Zhang
M, Hao J, Jiang JX. Rs 1800625 in the receptor for advanced glycation end products
gene predisposes to sepsis and multiple organ dysfunction syndrome in patients with
major trauma. Crit Care. 2015;19(1):6.
SECTION
5
INFECTION AND IMMUNE
DISORDERS IN ICU
Chapter 13 Approach to Nosocomial Infections

Prem Kumar
Chapter 14 Urinary Tract Infections

Prem Kumar
Chapter 15 Sepsis and Septic Shock

Prem Kumar
Chapter 16 Principles of Antibiotic Use in ICU

Prem Kumar
Chapter 17 Tropical Infections

Jenu Santhosh
Chapter 18 Anaphylaxis
Prem Kumar
CHAPTER
13 Prem Kumar
APPROACH TO NOSOCOMIAL INFECTIONS
Nosocomial infections or hospital acquired infections are one of the major

problems in the hospital because it carries economic burden on the patient.
Intensive care (ICU) is responsible for one-fourth of all the hospital-based
infections. The prevalence according to centers for disease control and prevention
(CDC) is 5–10% and the mortality due to nosocomial infections is 10–25%. The
most common ICU infections are urinary tract infection (UTI), pneumonia, and
blood stream infections (BSI) and most infections are usually device related. The
combined factor of the ease of transmission and organism resistance to antibiotics
makes intensive care unit a vulnerable place for nosocomial infections.
RISK FACTORS
The three important factors which increase the risk of infection are device, patient
factors and cross infection.
• Invasive devices
• Severity of the underlying condition
• Prolonged ICU stay
• Mechanical ventilation
• Poor nutrition
• Poor hand hygiene of the health care providers
• Pathogenicity of the organism
• Resistance of the organism to antibiotics
• Immunosuppression.
Host becomes vulnerable to nosocomial infections if they have associated
chronic diseases like diabetes, chronic steroid intake, breach of natural defence
in certain group of patients (e.g. burns, invasive devices like endotracheal tube,
central venous catheter) and misuse of broad spectrum antibiotics (e.g. invasive
candidiasis).
Common Causes of Nosocomial Infection in ICU

• Catheter-associated urinary tract infection (CAUTI)
• Catheter-related bloodstream infection—arterial and central venous
catheters
• Ventilator-associated pneumonia (VAP)
98 Section 5 Infection and Immune Disorders in ICU
• Surgical wound infections—necrotizing fasciitis

• Abdominal infections—intra-abdominal sepsis, postsplenectomy sepsis
• Central nervous system infection—meningitis
• Device infection—replacement prosthesis infections.
Timeline of Evolution of Organisms

Causing Nosocomial Infections in ICU
(Stenotrophomonas, Acinetobacter)
MECHANISMS OF DRUG RESISTANCE

• Beta-lactamase and extended spectrum beta-lactamase (ESBL) produces
cross resistance to multiple antibiotics like beta-lactams, fluoroquinolones
and aminoglycosides.
• Methicillin-resistant staphylococcus aureus (MRSA) methicillin-resistant
staphylococcus aureus it occurs due to altered penicillin binding protein
which is linked to Mec A gene.
• Pneumococcal resistance—penicillin resistance is acquired due to low-
affinity penicillin-binding proteins. Resistance to macrolides, lincosamides,
and streptogramin B type antibiotics is acquired due to target-site
modification caused by ribosomal methylation in 23S rRNA encoded by the
ermB gene and efflux mechanism encoded by the mef gene. Resistance to
fluoroquinolones is due to mutations in the gyrA and parC genes. The most
important risk factor for antibiotic-resistant pneumococcal infection is use
of a specific antibiotic within the previous three months.
• Among the gram –ve bacilli, E. coli is developing resistance to fluoroquinolones
and Enterobacter has become resistant to cephalosporins.
NOSOCOMIAL PNEUMONIA
Hospital-acquired pneumonia (HAP), ventilator-associated pneumonia (VAP),
and healthcare-associated pneumonia (HCAP) are all part of the spectrum of
nosocomial pneumonia. They are all important causes of morbidity and mortality
in ICU patients. The prevalence rate of VAP in mechanically ventilated patients in
ICU is around 20%.
Definitions
HAP: Pneumonia that occurs 48 hours or more after admission, which was not
incubating at the time of admission.
VAP: Pneumonia that occurs more than 48–72 hours after endotracheal
intubation.
Chapter 13 Approach to Nosocomial Infections 99
HCAP: Condition where the patient was hospitalized in hospital for ≥ 2 days
within 90 days of the infection; admitted in a nursing home resided or long-term
care facility; received recent intravenous antibiotic therapy, or wound care within
the past 30 days of the current infection; or attended a hospital or hemodialysis
clinic.
Microbiology of HAP/VAP (Tables 13.1 and 13.2)

Among the nonmultidrug resistant strains—S. pneumoniae, S. aureus,
H. influenza, Legionella, Gram–ve bacilli, serratia. Among the MDR strains - P.
aeruginosa, methicillin-resistant staphylococcus aureus (MRSA), Antibiotic-
resistant enterobacteriaceae, Acinetobacter, Klebsiella, Legionella, extended-
spectrum beta-lactamase (ESBL) positive strains. Polymicrobial infection is
common in patients with acute respiratory distress syndrome (ARDS). Influenza
(most common), parainfluenza, adenovirus, and respiratory syncytial virus
account for 70% of the nosocomial viral infections.
Table 13.1 Common organisms causing nosocomial infections
Site of infection Common bacteria

Nosocomial pneumonia Streptococcus pneumoniae
Staphylococcus aureus
Haemophilus Influenzae
Legionella
Gram –ve bacilli
Multidrug resistance (MDR):
Pseuolomonas Aeruginosa
Meticillin-reristant Staphylococcus aureus (MRSA)
Antibiotic-resistant Enterobacteriaceae
Acinetobacter
Klebsiella
Legionella
Extended spectrum beta-lactamase (ESBL) positive
Intra-abdominal sepsis E. coli
P. aeruginosa
Enterococcus species
Bacteroides species
Catheter-related blood Staphylococcus species
stream infection Enterobacteriaceae
P. aeruginosa
Surgical-wound infections Streptococcus species
Staphylococcus species
Gram-negative bacilli
Urinary tract infections Gram negative enteric bacilli (E. coli–most common),
Klebsiella, Enterobacter, Citrobacter, Proteus, Morganella,
Staphylococcus aureus, Enterococcus
Nosocomial diarrhea Clostridium difficile-associated diarrhea
Table 13.2 Common organisms causing nosocomial infections
Organism Comment
Pseudomonas Opportunistic pathogen causing pneumonia in critically ill
aeruginosa patient and has resistance to many broad spectrum antibiotics.
Combination therapy is currently used for its treatment
Klebsiella Resistance to antibiotics due to extended-spectrum beta-lactamase
(ESBL)
Staphylococcus Methicillin-resistant staphylococcus aureus (MRSA) is widely seen
aureus in ICU but is treated with glycopeptides like vancomycin. Recently
glycopeptides resistant strains have been identified
Enterobacter It produces ESBL and thus developing resistance to antibiotics.
Implicated in cross colonization
Enterococcus These organisms emerged with the increased use of cephalosporins.
It has developed resistance to penicillin, aminoglycosides and
recently vancomycin resistant enterococcus (VRE)
Tuberculosis Multidrug-resistant tuberculosis (MDR-TB)
Clostridium difficile This emerged after the use of broad spectrum antibiotics
especially clindamycin. Organism releases toxin which causes
pseudomembranous colitis.
Candida C. glabrata and C. krusei strains are seen in ICU. They develop
due to antibiotic effect
Acinetobacter Its incidence is increasing in ICU and has high incidence of cross
infection. They are multidrug resistant. Previously they were sensitive
to carbapenems but resistance to carbapenems has developed
recently making the infection with this organism extremely difficult
to treat
Stenotrophomonas This organism is multidrug resistant and is resistant to beta-lactams,
maltophilia aminoglycosides, fluoroquinolones and because it produces
carbapenemase, it has developed resistance to carbapenems.
That’s why this agent is called super-resistant organism
Risk Factors for MDR Pathogens

• Antimicrobial therapy in the preceding 3 months
• Current hospitalization of ≥5 days
• High frequency of antibiotic resistance in the community or in the specific
hospital unit
• Immunosuppressive disease and/or therapy
• Presence of risk factors for HCAP:
– Hospitalization for ≥2 days in the preceding 3 months
– Resided in a nursing home
– Received recent intravenous antibiotic therapy
– Chronic dialysis within 30 days
– Wound care.
Pathogenesis
The critical factors associated with VAP are:
• Oropharyngeal colonization with pathogenic microorganisms
• Aspiration of oropharyngeal organisms during intubation or leakage of
secretions containing bacteria after intubation through microaspiration
around the tube into the lower respiratory tract
• Abnormal host defense mechanisms.
Other factors for pathogenesis:
• Source of infection are healthcare devices and health care personnel
• Host and treatment related colonization factors—severity of the patient’s
underlying disease, prior surgery, exposure to antibiotics and exposure to
invasive respiratory devices.
• Bacterial translocation from the gastrointestinal tract.
• The stomach and sinuses can be potential reservoirs of nosocomial
pathogens and may cause nosocomial infections.
HAP requires the entry of microbial pathogens into the lower respiratory
tract, followed by colonization, which has to overcome the host’s defence
mechanisms to establish infection.
Clinical Features
All the features of pneumonia like fever, leukocytosis, tachypnea, tachycardia,
hypoxemia, pulmonary consolidation on physical examination, increase in
respiratory secretions. Chest radiography shows new or evolving lung infiltrates.
Diagnosis
The presence of clinical features of pneumonia (fever, leukocytosis, or purulent
tracheal secretions) and radiographic infiltrate point towards the diagnosis of
HAP/VAP. In the presence of clinical suspicion of VAP, samples of lower respiratory
tract secretions (endotracheal aspirate, bronchoalveolar lavage sample, or
protected specimen brush sample) should be obtained from all patients with
suspected HAP, and is collected before administration of antibiotics. The purpose
of the quantitative-culture approach is to differentiate between colonization and
true infection. A sterile culture in the absence of antibiotics in the past 72 hours
though rules out bacterial pneumonia, still a possibility of viral or legionella
infection is present. Arterial oxygenation saturation should be measured in
all patients to determine the need for supplemental oxygen and it can point
towards the diagnosis of multiple organ dysfunction syndrome (MODS) or acute
respiratory dysfunctions syndrome (ARDS) if it is associated. Unnecessary use
of antibiotics and duration of antibiotic use was reduced in patients who were
done quantitative culture methods and it also reduced the mortality in patients
with HAP/VAP. Clinical features carry high sensitivity but has low specificity.
Quantitative culture methods has high specificity. Hence in patients suspected
with VAP, both clinical criteria and diagnostic culture methods will point towards
the diagnosis of HAP/VAP.
Pugin et al. developed a surrogate clinical criteria for increasing the

specificity of clinical diagnosis of VAP. The criteria is named clinical pulmonary
infection score (CPIS). CPIS combines clinical, radiographic, physiological, and
microbiologic data into a score (Table 13.3). The maximal score is 12. CPIS score
>6 correlates well with VAP. Singh et al. demonstrated that patients with a low
suspicion of VAP (CPIS of 6 or less) can have antibiotics safely discontinued after
3 days.
Table 13.3 Clinical pulmonary infection score
Criteria Score
Temperature (°C)
38.5–38.9 1
≥39.0 and ≤36.0 2
Leukocytosis
< 4000 or >11,000/µL 1
Bands >50% 2
Oxygenation (mm Hg)
PaO2/FIO2 <250 and no ARDS 2
Tracheal aspirate
Pathogenic bacteria cultured ≤1 or no growth 0
Pathogenic bacteria cultured >1+ 1
Plus same pathogenic bacteria on Gram stain >1+ 2
Chest radiography
No infiltrate 0
Diffuse or patchy infiltrate 1
Localized infiltrate 2
Tracheal secretions
≥14+ 1
Plus purulence 2
Management (Flow chart 13.1 and Table 13.4)

Table 13.4 Initial empiric therapy for HAP/VAP
Risk factor Pathogens Antimicrobial therapy

Patients with no • Streptococcus Ceftriaxone
known risk factors pneumoniae Or
for • Haemophilus influenzae Levofloxacin, moxifloxacin, or
MDR pathogens, • Methicillin-sensitive ciprofloxacin
early onset and no • Staphylococcus aureus Or
disease severity • Enteric Gram-negative Ampicillin/sulbactam
bacilli Or
Antibiotic sensitive Ertapenem
• Escherichia coli
• Klebsiella pneumoniae
• Enterobacter species
• Proteus species
• Serratia spp.
Contd…
Contd…
Risk factor Pathogens Antimicrobial therapy

Patients with known Pseudomonas aeruginosa Antipseudomonal cephalosporin
risk factors for MDR Klebsiella pneumoniae, (cefepime, ceftazidime)
pathogens, late Extended-spectrum beta- Or
onset and disease lactamase (ESBL) Beta-lactam/Beta lactamase
severity Acinetobacter species inhibitor (piperacillin–tazobactam)
Methicillin-resistant Or
Staphylococcus aureus Antipseudomonal carbepenem
(MRSA) (imipenem or meropenem) plus
Legionella pneumophila Antipseudomonal fluoroquinolone
(ciprofloxacin or levofloxacin)
Or
Aminoglycoside (amikacin,
gentamicin, or tobramycin) plus
Linezolid or vancomycin
For Legionella – macrolide +
fluoroquinolone is used
Key recommendations for MDR pathogens

• If ESBL positive Enterobacteriaceae are isolated—carbapenem is preferred
• P. aeruginosa—combination therapy
• Acinetobacter—carbapenems, sulbactam, colistin, and polymyxin are
preferred
• MRSA VAP—linezolid is an alternative to vancomycin in case of renal
insufficiency and if patients is receiving nephrotoxic agents.
• Restricting the duration of antibiotic therapy and antibiotic cycling is done to
limit antibiotic resistance
A negative tracheal-aspirate culture or if the growth is below the threshold for
quantitative cultures, and if the sample was taken before any antibiotic change,
strongly suggests that antibiotics should be discontinued. If CPIS reduces over
2–3 days, then the antibiotic course should stopped after 8 days. 7–8 days course
is associated with less incidence of antibiotic resistance. There is high failure
rate of therapy with MRSA and other MDR pathogens and hence regular CPIS
assessment and quantitative culture is done to see the response to therapy.
Prevention
Surveillance for nosocomial infections is the mainstay for prevention and control
of nosocomial infections. It is very clear from the prospective studies that the
use of evidence-based guidelines through bundled interventions in ICU reduce
the rate of nosocomial infections (Table 13.5). The success of any guideline is
increased by following the specific, measurable, achievable, relevant, and time
bound (SMART) approach.
SMART Approach
• Choose specific objectives that precisely define and quantify desired
outcomes
Flow chart 13.1 Management of suspected HAP/VAP
• Avoid unrealistic objectives which are not measurable—measure, monitor,

provide feedback
• Make achievable objectives by engaging people involved in implementation
like intensivists, nurses and others.
• The objectives should be relevant to the institution so that the management
could provide resources.
Table 13.5 Guidelines for preventing VAP
Effective interventions Ineffective interventions

• Infection control program • Routine changes of ventilator circuit
• Avoidance of unnecessary reintubation • Routine use of antibiotic prophylaxis,
• Continuous subglottic suctioning SDD, or oral chlorhexidine
• Hand hygiene between contact with • Daily changes of heat and moisture
patients exchangers
• Head end elevation by 30° to 45° • Chest physiotherapy
• Enteral nutrition • Passive humidifier or heat-moisture
For selected indications (not routine): exchanger
• Antibiotic prophylaxis for patients with • Sulcrafate, histamine type-2 antagonist)
head injuries to prevent stress ulcers
• Selective digestive decontamination for • Postural changes
MDR outbreaks
• Oral chlorhexidine
• Make time bound objectives for data collection and evaluation of the
intervention.
Guidelines for Prevention of Catheter-associated of Urinary Tract Infection

(CAUTI)
Effective interventions
• Catheterization done only when there are proper indications
• Maintain good hand hygiene
• Use of aseptic technique and sterile equipment for catheter insertion
• Proper securing of catheter
• Maintenance of closed sterile drainage
• Aseptic methods for obtaining urine samples
• Maintenance of unobstructed urine flow
• Educating healthcare providers to perform correct techniques of catheter
insertion and maintenance.
Interventions to be avoided
• Regular bacteriologic monitoring
• Routine use of prophylactic antibiotics.
Guidelines for Prevention of Catheter-related Bloodstream Infections

• Educating healthcare providers to perform correct techniques of catheter
insertion and maintenance and only trained designated personnel to
perform the procedure with strict adherence to guidelines
• Maintaining proper hand hygiene before performing procedure
• Performing with aseptic technique during catheter insertion and care—
clean gloves for peripheral catheters and sterile gloves for invasive lines,
sterile barrier precautions for central line insertion.
• Care of catheter site—skin disinfection with 2% chlorhexidine or 70% alcohol,

use of sterile transparent, semipermeable dressing, replacement of soiled
dressing
• Prompt removal of catheter that is not necessary
• Selection of catheter, insertion technique, and site with lowest complication
risk
• Cleansing of injection port with 70% alcohol or iodophor before access
• Replacement of administration sets not more frequently than every 72 hours
• Appropriate preparation and quality control of intravenous admixtures
• Surveillance to determine infection rates, trends, and lapses in infection
control.
• Routine antibiotic prophylaxis—topical, intranasal, and systemic
formulations
• Routine use of antibiotic lock solution
• Routine use of arterial or venous cut-down for catheter insertion
• Routine use of in-line filters for infection control.
Guidelines for Preventing Surgical Site Infections

• Preoperative preparation of patient
• Hand and forearm antisepsis of surgical personnel
• Administration of antimicrobial prophylaxis only when indicated, with
dosing to maintain bactericidal levels throughout surgery
• Intraoperative ventilation, cleaning and disinfection of environmental
surfaces, sterilization of surgical instruments, and use of surgical attire and
drapes
• Intraoperative asepsis
• Aseptic surgical technique
• Protecting incision site postoperatively with sterile dressing for 24–48 hours
• Doing handwash before and after any contact with surgical site
• Surveillance to identify infection.
• Routine antibiotic prophylaxis with vancomycin
• Routine environmental sampling of operating room.
BIBLIOGRAPHY
1. Arya SC, Agarwal N, Agarwal S, George S, Singh K. Nosocomial infection: hospital
infection surveillance and control. J Hosp Infect 2004;58:242-3.
2. Bersten AD, Soni N, TE Oh. Oh’s Intensive Care Manual, 5th edn. 2009. Butterworth-
Heinemann publications, Philadelphia.
3. Chastre J, Fagon JY. Ventilator-associated pneumonia. Am J Respir Crit Care Med.
2002;165:867-903.
4. Craven DE, Kunches LM, Kilinsky V, Lichtenberg DA, Make BJ, McCabe WR. Risk
factors for pneumonia and fatality in patients receiving continuous mechanical
ventilation. Am Rev Respir Dis. 1986;133:792-6.
5. Drucker P. The practice of management. New York. NY: Harper and Row, 1954.
6. Fartoukh M, Maitre B, Honore S, Cerf C, Zahar JR, Brun-Buisson C. Diagnosing
pneumonia during mechanical ventilation: the clinical pulmonary infection score
revisited. Am J Respir Crit Care Med. 2003;168:173-9.
7. Fink MP, Snydman DR, Niederman MS, Leeper KVJ, Johnson RH, Heard SO, Wunderink
RG, Caldwell JW, Schentag JJ, Siami GA, et al. Severe Pneumonia Study Group.
Treatment of severe pneumonia in hospitalized patients: results of a multicenter,
randomized, doubleblind trial comparing intravenous ciprofloxacin with imipenem–
cilastatin. Antimicrob Agents Chemother. 1994;38:547-57.
8. Gruson D, Hilbert G, Vargas F, Valentino R, Bui N, Pereyre S, Bebear C, Bebear CM,
Gbikpi-Benissan G. Strategy of antibiotic rotation: long-term effect on incidence
and susceptibilities of gram-negative bacilli responsible for ventilator-associated
pneumonia. Crit Care Med. 2003;31:1908-14.
9. Hutt E, Kramer AM. Evidence-based guidelines for management of nursing home-
acquired pneumonia. J Fam Pract. 2002;51:709-16.
10. Kollef MH, Ward S, Sherman G, Prentice D, Schaiff R, Huey W, Fraser VJ. Inadequate
treatment of nosocomial infections is associated with certain empiric antibiotic
choices. Crit Care Med. 2000;28:3456-64.
11. Longo DL, Kasper DL, Jameson JL, Fauci AS, Hauser SL, Loscalzo J. Harrison’s
principles of internal medicine, 18th edn. 2012. McGraw Hill Publications.
12. Loveday HP, et al. National evidence-based guidelines for preventing healthcare-
associated Infections in NHS Hospitals in England. Journal of Hospital Infection.
2014;86S1:S1-S70.
13. Niederman MS, et al. Guidelines for the management of adults with hospital-acquired,
ventilator-associated, and healthcare-associated pneumonia. Am J Respir Crit Care
Med. 2005;171:388-416.
14. Niederman MS. Guidelines for the management of respiratory infection: why do we
need them, how should they be developed, and can they be useful? Curr Opin Pulm
Med. 1996;2:161-5.
15. Pugin J, Auckenthaler R, Mili N, et al. Diagnosis of ventilator-associated pneumonia
by bacteriologic analysis of bronchoscopic and nonbronchoscopic “blind” broncho
alveolar lavage fluid. Am Rev Respir Dis. 1991;143:1121-9.
16. Sarink MS, et al. Antimicrobial therapy in the intensive care unit. Indian Journal of
Clinical Practice, 2013;23(10).
17. Singh N, Rogers P, Atwood CW, Wagener MM, Yu VL. Short-course empiric antibiotic
therapy for patients with pulmonary infiltrates in the intensive care unit: a proposed
solution for indiscriminate antibiotic prescription. Am J Respir Crit Care Med. 2000;
162:505-11.
18. Tablan OC, Anderson LJ, Besser R, Bridges C, Hajjeh R. Healthcare Infection Control
Practices Advisory Committee, Centers for Disease Control and Prevention. Guidelines
for preventing healthcare–associated pneumonia, 2003: recommendations of the
CDC and the Healthcare Infection Control Practices Advisory Committee. MMWR
Recomm Rep. 2004;53(RR-3):1-36.
19 Yehia Aly AN, et al. Nosocomial infections in a medical-surgical intensive care unit.
Med Princ Pract. 2008;17:373-7.
CHAPTER
14 Prem Kumar
URINARY TRACT INFECTIONS
Urinary tract infection (UTI) is the most common nosocomial infection prevalent
in intensive care unit (ICU). It is the most common source of gram –ve sepsis
present in ICU causing morbidity and mortality. Predominant number of
patients who had UTI had an indwelling urinary catheter. Urinary tract infections
associated with indwelling catheter is called catheter-associated UTI (CAUTI).
We will discuss the diagnosis, management and methods of prevention in this
chapter.
DEFINITIONS
• UTI—symptomatic infection of bladder and kidneys. Cystitis and pyelo
nephritis.
• Uncomplicated UTI—acute cystitis or pyelonephritis in nonpregnant women
without anatomic abnormalities or instrumentation of the urinary tract.
• Complicated UTI—symptomatic cystitis or pyelonephritis with structural or
functional abnormalities of the urinary tract or with a foreign body or with
delayed response to therapy.
Urinary tract infections (UTIs) are defined using symptomatic urinary tract
infection (SUTI) criteria, asymptomatic bacteremic UTI (ABUTI), or urinary
system infection (USI) criteria.
Catheter-associated UTI (CAUTI): UTI where an indwelling urinary catheter was
in place for >2 days on the date of event or the day before. If an indwelling urinary
catheter was in place for >2 calendar days and then removed, the date of event
for the UTI must be the day of discontinuation or the next day for the UTI to be
catheter-associated.
RISKS (TABLE 14.1)

Most of the organisms are colonized from perineum, rectum, vagina and distal
urethra. The catheter and the growth in the urine bag can also cause infection.
Incomplete emptying of the bladder while the catheter is in place can also cause
UTI.
Chapter 14 Urinary Tract Infections 109
Table 14.1 Risk factors associated with urinary tract infection (UTI)
• Use of urinary catheter

• Duration of catheterization
• Urinary drainage bag colonization
• Diabetes mellitus
• Female patient
• Old age
• Elevated renal parameters
• Unsterile techniques of catheter insertion and catheter care
• Patients with structural or functional abnormalities of urinary system
• Neurological disease—neurogenic bladder, CVA, etc.
• Patients with urological diseases like benign prostatic hyperplasia, bladder or ureteric
stone, epididymo-orchitis, etc.
Abbreviation: CVA, cerebrovascular accident
COMMON ORGANISMS CAUSING URINARY TRACT INFECTION

UTI is commonly caused by Gram-negative enteric bacilli. E. coli is the most
common organism among the Gram-negative bacteria. Specific type of E. coli
which has P-pili has the ability to adhere the uroepithelial membranes and cause
UTI. Patients receiving antibiotics or anatomical defects in urinary system are
colonized with Klebsiella, Enterobacter, Citrobacter, Proteus, Morganella. Less
common organisms causing UTI are gram +ve organisms like Staphylococcus
aureus, Enterococcus. Enterococcus are resistant to antibiotics. Candida-
associated UTI occurs with hematological dissemination and is the common
organism among fungal organisms.
Diagnosis (Flow chart 14.1 and Tables 14.2 and 14.3)

Patients may complain of increased frequency and urgency, nocturia, dysuria,
hematuria. Loin pain and fever should preclude the diagnosis to pyelonephritis.
Perineal pain may indicate prostatitis. Hence, urinary frequency, urgency, loin
tenderness and fever should point the diagnosis towards upper urinary tract
infection. The absence of pyuria and significant bacteriuria does not exclude the
diagnosis of UTI.
Urine Analysis
• Increased leukocytes
• Dipstick test for leukocyte esterase and nitrate
• Increased number of bacteria with absence of contamination by epithelial
cells
Flow chart 14.1 Diagnostic algorithm of UTI
Abbreviations: UTI, urinary tract infection; CFU, colony-forming unit; CAUTI, catheter-associated urinary
tract infection; ABUTI, asymptomatic bacteremic
• Urinary gram stain

• >1 organism/high-powered field is indicative of greater than 105 colony-
forming units (CFUs) per mL.
Patients with clinical diagnosis of UTI should be done quantitative urinary
culture before initiation of antibiotics. In patients with severe sepsis suspected
due to UTI should have blood culture done in case of a negative urinary culture.
Some complicated UTIs may require radiological methods for diagnosis.
Management (Table 14.4)

Antimicrobial therapy is instituted for symptomatic UTI. The choice of the
antibiotic and the dose and duration of therapy depends on the infection site and
the complicating conditions. Asymptomatic bacteriuria in the absence of pyuria
Table 14.2 Diagnostic criteria
CAUTI Non-CAUTI
Must meet at least one of the following Patient must meet all the criteria given
criteria (A or B): below:
Criteria A • One of the following is true.
• Patient has an indwelling urinary – Patient has/had an indwelling
catheter in place for the entire day on urinary catheter but it has/had not
the date of event and such catheter had been in place >2 calendar days,
been in place for >2 calendar days, (OR)
on that date (day of device placement – Patient did not have a urinary
= Day 1) catheter in place on the date of
• Patient has at least one of the following event nor the day before the date
signs or symptoms. of event
– Fever (>38.0°C) • P
atient has at least one of the following
– Suprapubic tenderness signs or symptoms.
– Costovertebral angle pain or – Fever (>38°C)
tenderness – Suprapubic tenderness
• Patient has a urine culture with no more – Costovertebral angle pain or
than two species of organisms, at least tenderness
one of which is a bacteria of ≥105 – Urinary frequency
CFU/mL. – Urinary urgency
OR – Dysuria
• Patient has a urine culture with no
Criteria B more than two species of organisms,
• Patient had an indwelling urinary at least one of which is a bacteria of
catheter in place for >2 calendar days ≥105 CFU/mL.
which was removed on the day of, or
day before the date of event
• Patient has at least one of the following
signs or symptoms.
– Fever (>38.0°C)
– Suprapubic tenderness
– Costovertebral angle pain or
tenderness
– Urinary urgency
– Urinary frequency
– Dysuria
• Patient has a urine culture with no more
than two species of organisms, at least
one of which is a bacteria of
≥105 CFU/mL.
Table 14.3 Diagnostic criteria of ABUTI
Asymptomatic bacteremic urinary tract infection

Patient must meet all the criteria given below:
• Patient with or without an indwelling urinary catheter has no signs or symptoms of
symptomatic urinary tract infection.
• Patient has a urine culture with no more than two species of organisms, at least one of
which is a bacteria of ≥105 CFU/mL.
• Patient has a positive blood culture with at least one matching bacteria to the urine
culture and matching common commensals in the urine.
Table 14.4 Management of uncomplicated UTI
Men Women Pregnant women

• Trimethoprim 1st line • Ampicillin,
sulfamethoxazole for • Trimethoprim cephalosporins and
14 days sulfamethoxazole– nitrofurantoin are safe
• Fluoroquinolones 1 DS tab 12th hourly for in pregnancy
(ofloxacin–200 mg 3 days • Ampicillin and
12th hourly, Double strength cephalosporins are
ciprofloxacin 500 (DS: 160 mg/800 mg = the drugs of choice
mg 12th hourly, and TMP/SMX) for the treatment of
levofloxacin) for 14 days • Nitrofurantoin 100 mg asymptomatic or
• With urine culture twice daily for 5–7 days symptomatic UTI
results, antibiotic 2nd line • Sulphonamides and
continued for 2–4 weeks • Fluoroquinolones fluoroquinolones are
Comment–a prolonged (ofloxacin, ciprofloxacin, contraindicated due to
course of antibiotics is given and levofloxacin) for 3 its teratogenic effects
in male to prevent chronic days
prostatitis • Beta lactams for 7 days
does not require treatment with antibiotics except in pregnancy, neutropenic

patients, renal transplant recipients and patients undergoing urology procedures.
Complicated UTI
• Antibiotics are guided by urine culture or empirically started with prior
urinary culture results until new culture results.
• Nephrectomy is done in case of Xanthogranulomatous pyelonephritis.
• Emphysematous pyelonephritis—percutaneous drainage can be used as the
initial therapy followed by elective nephrectomy.
Pyelonephritis
• Fluoroquinolones (500 mg 12th hourly) are the first-line therapy for acute
uncomplicated pyelonephritis. Its given for 7 days orally or parenterally.
• Initially, 2 g of IV ceftriaxone is given if trimethoprim/sulfamethoxazole is
started and the culture results are awaited.
• Generally pyelonephritis is best treated by urine culture results.
Treatment of CAUTI
The formation of biofilm on the urinary catheter is the prime cause for the
pathogenesis of CAUTI and it affects both therapeutic and preventive manage
ment. Change of catheter can be done during the treatment of CAUTI. Ampicillin
with beta-lactamase inhibitor, cephalosporins, aminoglycosides are started
initially. In case of poor response to therapy in 2–3 days or in severe cases, anti-
pseudomonal antibiotics (fluoroquinolone, carbapenem with aminoglycoside,
cephalosporin with antipseudomonal activity) are started. In case of Candida,
fluconazole and amphotericin B are used.
Treatment of Urosepsis
Fluoroquinolones and cephalosporins are used and if secondary to urological
procedures, antipseudomonal antibiotics are started like ampicillin with beta
lactamase inhibitor, carbapenem, aminoglycosides.
PREVENTION OF CAUTI—RECOMMENDATIONS BY HICPAC

(HEALTHCARE INFECTION CONTROL PRACTICES ADVISORY
COMMITTEE) 2009 GUIDELINES
The best way of preventing CAUTI in ICU is its use for appropriate indications:
• Acute urinary retention or bladder outlet obstruction
• For accurate measurements of urinary output in critically ill patients
• For selected surgical procedures:
– Patients undergoing urologic surgery or other surgery on contiguous
structures of the genitourinary tract
– Anticipated prolonged duration of surgery. Catheters inserted for this
reason should be removed in PACU.
– Patients anticipated to receive large-volume infusions or diuretics
during surgery
– Need for intraoperative monitoring of urinary output.
• Patient requiring prolonged immobilization
• To assist in healing of open sacral or perineal wounds in incontinent patients
• For terminally ill patients.
Key Recommendations for Prevention of CAUTI

• Insert catheters only for appropriate indications and leave in place only as
long as needed.
• Avoid use of urinary catheters in patients and nursing home residents for
management of incontinence.
• Use urinary catheters in operative patients only as necessary, rather than
routinely.
• For operative patients who have an indication for an indwelling catheter,
remove the catheter as soon as possible postoperatively, preferably within 24
hours, unless there are appropriate indications for continued use.
• Consider using alternatives to indwelling urethral catheterization in selected
patients when appropriate.
• Perform hand hygiene immediately before and after insertion or any
manipulation of the catheter device or site.
• Ensure that only properly trained persons perform the technique.
• In the acute care hospital setting, insert urinary catheters using aseptic
technique and sterile equipment. Use sterile gloves, drape, sponges, an
appropriate antiseptic or sterile solution for periurethral cleaning, and a
single-use packet of lubricant jelly for insertion.
• In the nonacute care setting, clean (i.e. nonsterile) technique for intermittent
catheterization is an acceptable and more practical alternative to sterile
technique for patients requiring chronic intermittent catheterization.
• Properly secure indwelling catheters after insertion to prevent movement

and urethral traction.
• If intermittent catheterization is used, perform it at regular intervals to
prevent bladder overdistension.
Recommendations for urinary catheter maintenance:
• Following aseptic insertion of the urinary catheter, maintain a closed
drainage system.
• Maintain unobstructed urine flow after inserting a urinary catheter.
• Use standard precautions, including the use of gloves and gown as
appropriate, during any manipulation of the catheter or collecting system.
• Unless clinical indications exist, do not use systemic antimicrobials
routinely to prevent CAUTI in patients requiring either short or long-term
catheterization.
• Do not clean the periurethral area with antiseptics to prevent CAUTI while
the catheter is in place. Routine hygiene is appropriate.
• Routine irrigation of the bladder with antimicrobials is not recommended.
• Clamping indwelling catheters prior to removal is not necessary.
BIBLIOGRAPHY
1. Carolyn v. Gould, et al. Guideline for prevention of catheter-associated urinary tract
infections. Healthcare infection control practices advisory committee. 2009.
2. Dolin SJ, Cashman JN. Tolerability of acute postoperative pain management: nausea,
vomiting, sedation, pruritus, and urinary retention. Evidence from published data. Br
J Anaesth. 2005;95(5):584-91.
3. Dudeck MA, Horan TC, Peterson KD. National Healthcare Safety Network (NHSN)
Report, Data Summary for 2009, “Device-associated Module”. Am J Infect Control.
2011;39:349-67.
4. Garner JS, Jarvis WR, Emori TG, et al. CDC definitions for nosocomial infections, 1988.
Am J Infect Control. 1988;16:128-40.
5. Lo E, Nicolle L, Classen D, et al. Strategies to prevent catheter-associated urinary tract
infections in acute care hospitals. Infect Control Hosp Epidemiol. 2008;29:S41-S50.
6. Stephan F, Sax H, Wachsmuth M, Hoffmeyer P, Clergue F, Pittet D. Reduction of urinary
tract infection and antibiotic use after surgery: a controlled, prospective, before-after
intervention study. Clin Infect Dis. 2006;42(11):1544-51.
7. Wong ES. Guideline for prevention of catheter-associated urinary tract infections. Am
J Infect Control. 1983;11(1):28-36.
CHAPTER
15 Prem Kumar
SEPSIS AND SEPTIC SHOCK
Sepsis is a major health problem in intensive care unit (ICU) and it accounts for
a predominant cause of morbidity and mortality in ICU and it varies from 10%
to 30% and it increases if the patient ends up with multiple organ dysfunction
syndrome (MODS). Although the understanding of the pathophysiology and
management of sepsis and septic shock has improved in the past decade, the
mortality has still not improved despite antimicrobial therapy and hemodynamic
support. This chapter discusses the clinical spectrum of sepsis and septic shock
from the latest update of surviving sepsis campaign guidelines, 2012.
DEFINITIONS
SIRS: Presence of signs of systemic inflammation is called SIRS (systemic
inflammatory response syndrome).
Sepsis: Presence of infection along with systemic manifestations.
Severe sepsis: Sepsis accompanied with sepsis-induced organ dysfunction or
tissue hypoperfusion.
Septic shock: Severe sepsis-induced hypotension which is persistent inspite of
adequate fluid resuscitation.
Sepsis-induced hypotension: Systolic blood pressure (SBP) <90 mm Hg or mean
arterial pressure (MAP) <70 mm Hg or a SBP decrease >40 mm Hg or <2 SD below
normal for age in the absence of other causes of hypotension.
MODS: It is the presence of simultaneous or sequential dysfunction or failure of
two or more organs (or) altered organ function in an acutely ill patient such that
homeostasis could not be maintained without intervention.
PATHOGENESIS
Pathogenesis of septic shock is shown in Flow chart 15.1. Venn diagram depicting
spectrum of sepsis is shown in Figure 15.1.
Clinical syndromes associated with sepsis:
• Cardiovascular system—congestive cardiac failure, shock due to reduced
intravascular volume. Peripheral vasodilatation resulting in reduced systemic
Flow chart 15.1 Pathogenesis of septic shock
Abbreviations: IL, interleukin; TNF, tumor necrosis factor; ROS, reactive oxygen species; IFN, interferon;
CARS, compensatory anti-inflammatory response syndrome; MOF, multiple organ failure
Fig. 15.1 Venn diagram depicting spectrum of sepsis

Abbreviation: SIRS, systemic inflammatory response syndrome
vascular resistance and vasopressor resistance due to release of nitric oxide

(NO). Myocardial depression with systolic and diastolic dysfunction.
• Respiratory system—ARDS
• Central nervous system—septic encephalopathy
• Kidney—acute tubular necrosis
Chapter 15 Sepsis and Septic Shock 117
• GIT—paralytic ileus, intestinal ischemia, upper GI bleeding, gastric stress

ulcers, intestinal mucosal injury
• Hematology—DIC, thrombocytopenia, leukopenia
• Neuromuscular—critical illness polyneuropathy, myopathy
• Hepatic—intrahepatic cholestasis, hepatic failure
• Endocrine—hyperglycemia from insulin resistance, hypertriglyceridemia,
hypoalbuminemia, weight loss, and hypercatabolism
• Immune—pyrexia, nosocomial pneumonia, neutrophil dysfunction.
Diagnosis
Sepsis can present initially with tachycardia, hypotension, tachypnea, fever.
Altered mental status, hypothermia, organ dysfunction, leukopenia indicates
poor prognosis. Hypoxemia, thrombocytopenia, consumptive coagulopathy,
acute tubular necrosis, elevated transaminases, hyperglycemia, pneumonia and
intra-abdominal infection are the other manifestations. Previously Gram –ve
infections were common in patients with sepsis but trend of infection is hanging
towards Gram +ve and fungal infections. Abdomen and lung are major sources
of infection.
Diagnostic Criteria
SIRS: SIRS is the systemic inflammatory response to any insult—infection or non-
infection. The current sepsis guidelines have removed this terminology but still
the term is being used by many authors.
It is characterized by two or more of the following:
1. Temperature <36°C or > 38°C
2. Heart rate >90/min
3. Respiratory rate >20 breaths/minute or PaCO2 <32 mm Hg
4. White blood cell count <4000/µL or >12,000/µL or 10% immature band forms.
SEPSIS
Documented or suspected infection and some of the following variables are given
in Table 15.1.
SEVERE SEPSIS
• Sepsis-induced hypotension
• Lactate above upper limit of laboratory normal
• Urine output <0.5 mL/kg/hr for more than 2 hours despite adequate fluid
resuscitation
• Acute lung injury with PaO2/FiO2 <250 in the absence of pneumonia as
infection source
• Acute lung injury with PaO2/FiO2 <200 in the presence of pneumonia as
infection source
• Creatinine >2.0 mg/dL (176.8 μmol/L)
Table 15.1 Criteria for sepsis
General variables
• Fever (>38.3°C)
• Hypothermia (core temperature <36°C)
• Heart rate >90/min or >2 SD above the normal value for age
• Tachypnea
• Altered mental status
• Significant edema or positive fluid balance (>20 mL/kg over 24 hour)
• Hyperglycemia (plasma glucose >140 mg/dL or 7.7 mmol/L) in the absence of
diabetes
Inflammatory variables
• Leukocytosis (WBC count >12,000/μL)
• Leukopenia (WBC count <4000/μL)
• Normal WBC count with greater than 10% immature forms
• Plasma C-reactive protein >2 SD above the normal value
• Plasma procalcitonin >2 SD above the normal value
Hemodynamic variables
• Arterial hypotension (SBP <90 mm Hg, MAP <70 mm Hg, or an SBP decrease
> 40 mm Hg in adults or <2 SD below normal for age)
Organ dysfunction variables
• Arterial hypoxemia (PaO2/FiO2 <300)
• Acute oliguria (urine output <0.5 mL/kg/hour for at least 2 hours despite adequate
fluid resuscitation)
• Creatinine increase >0.5 mg/dL or 44.2 μmol/L
• Coagulation abnormalities (INR >1.5 or aPTT >60 s)
• Ileus (absent bowel sounds)
• Thrombocytopenia (platelet count <100,000/μL)
• Hyperbilirubinemia (plasma total bilirubin >4 mg/dL or 70 μmol/L)
Tissue perfusion variables
• Hyperlactatemia (>1 mmol/L)
• Decreased capillary refill or mottling
Abbreviations: WBC, white blood cell; SBP, systolic blood pressure; MAP, mean arterial pressure; INR,
international normalized ratio; aPTT, activated partial thromboplastin time
• Bilirubin >2 mg/dL (34.2 μmol/L)

• Platelet count < 100,000 μL
• Coagulopathy (international normalized ratio >1.5).
Management of Severe Sepsis and Septic Shock

The three areas to be optimized in severe sepsis and septic shock are:
1. Trigger
2. Amplification cascade
3. Organ dysfunction.
Trigger is usually infection and it is treated by antimicrobial therapy.
Amplification is managed by administering activated protein C which exerts anti-
inflammatory and antithrombotic effects and reduces the progression of sepsis.
Organ dysfunction is treated by supportive measures like fluid resuscitation,

vasopressors/inotropes.
The management of severe sepsis and septic shock is done by the following
protocol.
• Initial resuscitation and infection issues
– Initial resuscitation
– Screening and diagnosis of sepsis
– Antimicrobial therapy
– Source control
– Infection prevention
• Hemodynamic support
– Fluid resuscitation
– Vasopressors/inotropes
• Adjunctive therapy
– Corticosteroids
• Supportive therapy
– Blood component administration
– Immunoglobulins
– Selenium
– Recombinant activated protein C (APC)
– Ventilatory management of ARDS
– Sedation, analgesia and neuromuscular blockade
– Glycemic control
– Renal replacement therapy
– Bicarbonate therapy
– DVT prophylaxis
– Stress ulcer prophylaxis
– Nutrition.
Initial Resuscitation
Sepsis-induced tissue hypoperfusion should be resuscitated with the following
guidelines. This resuscitation protocol was demonstrated by Rivers et al., and it
is called early goal directed therapy (Table 15.2 and Flow chart 15.2). Target of
resuscitation is normalizing lactate level.
But recently 3 trials (Protocolized Care for Early Septic Shock [ProCESS]
trial), (Australasian Resuscitation in Sepsis Evaluation [ARISE] trial), and
Table 15.2 Goals of initial resuscitation in septic shock
During the first 6 hours of resuscitation, the goals of initial resuscitation are:
• CVP 8–12 mm Hg. In mechanically ventilated patients or decreased ventricular
compliance, CVP of 12–15 mm Hg is maintained
• MAP ≥65 mm Hg
• Urine output ≥0.5 mL/kg/hour
• Superior vena cava oxygenation saturation (ScvO2) or mixed venous oxygen
saturation (SvO2) 70% or 65%, respectively.
Flow chart 15.2 Early goal-directed therapy
Abbreviations: CVP, central venous pressure; MAP, mean arterial pressure; ScvO2, mixed venous oxygen
saturation in central vein
(Protocolized Management in Sepsis [ProMISe] trial) has challenged early goal

directed therapy demonstrating that early goal-directed therapy (EGDT) did not
lead to an improvement in outcome. These studies demonstrated that there was
no significant difference in mortality at 90 days among those receiving 6 hours of
EGDT and those receiving usual resuscitation.
Screening and Diagnosis of Sepsis

The critical component in reducing mortality from sepsis-related multiple organ
dysfunction is the time taken to diagnose severe sepsis. Hence, early diagnosis of
sepsis and early intervention is recommended. A sample of blood should be sent
for blood culture early before administering empirical antibiotics. Cultures of
other sites such as urine, CSF, wounds, respiratory secretions, or other body fluids
that may be the source of infection, should also be obtained before antimicrobial
therapy. Early lab studies and imaging studies should be done to support or
confirm the diagnosis.
Surviving sepsis campaign (SSC) bundles (Table 15.3) have reduced
the mortality rate in ICU and are recommended for resuscitation and early
management of sepsis patients as they are admitted in the hospital.
Table 15.3 Surviving sepsis campaign bundles
To be completed within 3 hours:

• Measure lactate level
• Obtain blood cultures prior to administration of antibiotics
• Administer broad spectrum antibiotics
• Administer 30 mL/kg crystalloid for hypotension or lactate 4 mmol/L
To be completed within 6 hours:
• Apply vasopressors (for hypotension that does not respond to initial fluid resuscitation)
to maintain a mean arterial pressure (MAP) ≥65 mm Hg
• In the event of persistent arterial hypotension despite volume resuscitation (septic
shock) or initial lactate ≥4 mmol/L:
– Measure central venous pressure (CVP)
– Measure central venous oxygen saturation (ScvO2)
*Targets for quantitative resuscitation included in the guidelines are CVP of ≥8 mm Hg,
ScvO2 of ≥70%, and normalization of lactate.
• Remeasure lactate if initial lactate was elevated.
ANTIMICROBIAL THERAPY
Recommendation is to administer intravenous antibiotics within the 1st hour
of recognition of severe sepsis and septic shock. Initial empirical antimicrobial
therapy should include 1 or more drugs which have activity against bacterial, viral
and fungal organisms presumed to be the source of infection. The most common
pathogens causing septic shock in hospitalized patients are Gram-positive
bacteria, followed by Gram-negative and mixed bacterial microorganisms.
Candidiasis and toxic shock syndromes though uncommon should be suspected
in certain patients (immunosuppressed or neutropenic state, prior intense
antibiotic therapy, or colonization in multiple sites). Low procalcitonin level
can be used as a guide to discontinue empiric antibiotics but the evidence
is very less for its routine use in patients with severe sepsis. Empiric antibiotic
therapy should not be administered for more than 3–5 days and de-escalation
should be done as soon as possible. Typical duration of therapy is 7–10 days but
may be needed longer in patients with neutropenia, viral or fungal infections.
Antimicrobial therapy should not be used for patients with severe inflammatory
states of noninfectious cause.
• Severe sepsis with neutropenia and multidrug resistant organisms like
Acinetobacter and Pseudomonas—combination empirical therapy
• Severe infection with respiratory failure and septic shock—combination
therapy with an extended spectrum beta-lactam and aminoglycoside/
fluoroquinolone for P. aeruginosa bacteremia
• Streptococcus pneumoniae with septic shock—combination of beta-lactam
and macrolide
• IV drug abusers—vancomycin
• In case of neutropenic patients, empirical antifungal agents can be started
empirically if neutropenia persists for more than 5 days
• Empirical antifungal drugs—amphotericin B is used for all life-threatening
fungal infections. Fluconazole or echinocandins is recommended by
recent Infectious Diseases Society of America (IDSA) guidelines for severe
candidiasis. Echinocandins is used for severe illness or when the patient is

recently treated with antifungal agents.
• Severe sepsis with neutropenia with suspected pseudomonas infection—
ceftazidime or piperacillin – tazobactam or meropenem + aminoglycoside.
Source Control
A specific diagnosis of local infection is sought or diagnosed or excluded early and
intervention is started within first 12 hours after diagnosis to control the source.
Vascular access sites thought to be a source of infection should be removed and
the intervention as far as possible should be less invasive. Surgical control or
percutaneous drainage of the infection is essential in patients with severe intra-
abdominal infections.
Prevention of Infection
Selective oral decontamination (SOD) and selective digestive decontamination
(SDD) can be given to reduce the incidence of ventilator-associated pneumonia
(VAP). Oral chlorhexidine is used for oropharyngeal decontamination in ICU
patients with severe sepsis.
HEMODYNAMIC SUPPORT
Fluid Therapy
Crystalloids are the initial fluid of choice to be used in the resuscitation of severe
sepsis and septic shock. Colloids are not advised. Albumin has a role when
patients require substantial amounts of crystalloids. Initial fluid challenge of
30 mL/kg of crystalloids is administered in patients with septic shock when there
is suspicion of hypovolemia and the fluid challenge is continued until the patient
has improvement in hemodynamics as indicated by dynamic parameters like
PPV, SVV or static parameters like arterial blood pressure, CVP, heart rate.
Vasopressors/Inotropes
All patients requiring vasopressors or inotropes should have an invasive arterial
blood pressure monitoring. Norepinephrine is the first choice vasopressor in
septic shock and the target mean arterial pressure is 65 mm Hg. Dopamine is
an alternative to norepinephrine. Epinephrine can be added if an additional
vasopressor is required and low dose dopamine for renal vasodilatation is not
recommended. Vasopressin and phenylephrine are not recommended as the
first choice but can be used for refractory cases of septic shock. Vasopressin dose
is 0.03 U/minute. Phenylephrine is used when norepinephrine is associated with
serious arrhythmias, persistently low blood pressure with high cardiac output,
or as salvage therapy when combined inotrope/vasopressor drugs and low dose
vasopressin have failed to achieve the target MAP. In the presence of myocardial
dysfunction and low cardiac output or ongoing signs of hypoperfusion despite
achieving adequate intravascular volume and adequate MAP, dobutamine

infusion of 20 µg/kg/minute is started.
Adjunctive Therapy
Intravenous hydrocortisone is not routinely used to treat patients with septic
shock if hemodynamic stability is achieved with fluids and vasopressors. If this
is not possible, intravenous hydrocortisone is used as a continuous infusion
of 200 mg/day. Corticosteroids should not be administered for the treatment
of sepsis in the absence of shock and adrenocorticotropic hormone (ACTH)
stimulation test is done to identify patients who require steroids. Hydrocortisone
infusion is tapered when vasopressors are not required.
Supportive Therapy
Blood Component Administration

After resolution of tissue hypoperfusion packed RBC transfusion is recommended
when Hb is <7 g/dL in the absence of cardiac disease, acute hemorrhage and the
target Hb concentration is 7–9 g/dL. The use of erythropoietin and antithrombin
is not recommended in severe sepsis and septic shock. Fresh frozen plasma is
not used in clotting disorders in the absence of bleeding. In patients with severe
sepsis, prophylactic platelet are administered when counts are <10,000/mm3
(10 × 109/L) in the absence of apparent bleeding. Prophylactic platelet transfusion
when counts are <20,000/mm3 (20 × 109/L) if the patient has a significant risk of
bleeding. Higher platelet counts (≥50,000/mm3 [50 × 109/L]) are taken as cut off
for active bleeding, surgery, or invasive procedures.
Immunoglobulins and Selenium

They are not recommended in severe sepsis and septic shock.
Recombinant Activated Protein C (rhAPC)

The first ever trial showing the role of rhAPC in severe sepsis was PROWESS
(Recombinant Human-activated Protein C Worldwide Evaluation in Severe
Sepsis) trial in 2001 which demonstrated reduction in mortality but the PROWESS
SHOCK trial done in 2011, showed no benefit of rhAPC in patients with septic
shock and hence not recommended in severe sepsis and septic shock.
Mechanical Ventilation of Sepsis-induced

Acute Respiratory Distress Syndrome
A tidal volume of 6 mL/kg predicted body weight is initiated in acute respiratory
distress syndrome (ARDS) and the plateau pressure is limited to ≤30 cm H2O.
positive end-expiratory pressure (PEEP) is applied to prevent alveolar collapse at
end expiration and higher PEEP is required in case of hypoxemia not responding
to low PEEP. Head end elevation of head of 30–45° is given to prevent aspiration
and the development of ventilator-associated pneumonia (VAP). Recruitment

maneuver and prone positioning is used in severe refractory hypoxemia and
when PaO2/FiO2 ratio is ≤100 mm Hg. A weaning protocol is recommended
with frequent spontaneous breath trials in patients who meet weaning criteria
and extubated if fit for extubation. Noninvasive ventilation can be considered in
specific group of ARDS patients. SSC guidelines does not recommend the routine
use of pulmonary artery catheter (PAC) and beta-2 agonists in ARDS patients
unless there are specific indications. A conservative fluid strategy is used for
patients who do not have tissue hypoperfusion.
Sedation, Analgesia, and Neuromuscular Blockade

Sedation is minimized in patients put on mechanical ventilation and neuro
muscular blocking agents are avoided in patients without ARDS and if used,
it should be used with train-of-four monitoring. In patients with ARDS,
neuromuscular blocking agents are not used >48 hours.
Glycemic Control
Blood glucose should be managed by a protocol in patients with severe sepsis
and insulin is started when two consecutive blood glucose levels are >180 mg/
dL. The target for upper limit should be ≤180 mg/dL and blood glucose should
be monitored every 1–2 hours until glucose values and insulin infusion rates
are stable and then every 4 hours thereafter. Point of care monitors should be
interpreted with caution because of its unreliability. Treatment should avoid
hyperglycemia (>180 mg/dL), hypoglycemia, and wide swings in glucose levels.
Many studies have shown that the variability in glucose levels over time is an
important determinant of mortality.
Renal Replacement Therapy

There is no mortality benefit between continuous renal replacement therapy
(CRRT) and intermittent hemodialysis in patients with severe sepsis and acute
renal failure. CRRT is used in hemodynamically unstable sepsis patients for fluid
balance.
Bicarbonate Therapy
Sodium bicarbonate therapy is not recommended for improving hemodynamics
or reducing vasopressor requirements in patients with tissue hypoperfusion-
induced lactic acidosis with pH ≥7.15.
DVT Prophylaxis
ICU patients are at risk for deep vein thrombosis and hence patients with
severe sepsis are recommended daily pharmacoprophylaxis against venous
thromboembolism (VTE). Daily subcutaneous low-molecular weight heparin
(LMWH) which is preferred or twice daily unfractionated heparin (UFH) or
thrice daily UFH. If creatinine clearance is <30 mL/min, dalteparin or UFH is

used. Combination of heparin and intermittent pneumatic compression device
is better than heparin alone. In patients where heparin is contraindicated,
graduated compression stockings or intermittent compression devices is used.
Stress Ulcer Prophylaxis

H2 blocker or proton pump inhibitor is given to patients with severe sepsis/septic
shock who have risk factors for bleeding. Patients without risk factors for bleeding
are not given prophylaxis routinely.
Nutrition
Once the patient is diagnosed with severe sepsis or septic shock, oral or enteral
feeding are started within 48 hours in low dose feeding rather than full caloric
feeding in the first week and the patient should not be left with fasting or only
given intravenous glucose. Underfeeding (60−70% of target) or trophic feeding
(upper limit of 500 kcal) is probably a better nutritional strategy in the first
week of severe sepsis/septic shock. The recommendation is to use intravenous
glucose and enteral nutrition rather than total parenteral nutrition (TPN) alone
or parenteral nutrition in conjunction with enteral feeding in the first week.
The use of immunomodulators like arginine, glutamine or omega-3 fatty acids
supplementation with enteral nutrition is not advised by the SSC 2012 guidelines.
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1. Antonelli M, Conti G, Rocco M, et al. A comparison of noninvasive positive-pressure
ventilation and conventional mechanical ventilation in patients with acute respiratory
failure. N Engl J Med. 1998;339:429-35.
2. Basso N, Bagarani M, Materia A, et al. Cimetidine and antacid prophylaxis of acute
upper gastrointestinal bleeding in high risk patients. Controlled, randomized trial.
Am J Surg. 1981;141:339-41.
3. Beale RJ, Bryg DJ, Bihari DJ. Immunonutrition in the critically ill: a systematic review
of clinical outcome. Crit Care Med. 1999;27:2799-805.
4. Chuntrasakul C, Siltharm S, Chinswangwatanakul V, et al. Early nutritional support in
severe traumatic patients. J Med Assoc Thai. 1996;79:21-6.
5. Cooper DJ, Walley KR, Wiggs BR, et al. Bicarbonate does not improve hemodynamics
in critically ill patients who have lactic acidosis: A prospective, controlled clinical
study. Ann Intern Med. 1990;112:492-8.
6. Dellinger, et al. Surviving sepsis campaign: International guidelines for management
of severe sepsis and septic shock: 2012. Crit Care Med. 2013;41:580-637.
7. Drakulovic MB, Torres A, Bauer TT, et al. Supine body position as a risk factor for
nosocomial pneumonia in mechanically ventilated patients: A randomized trial.
Lancet. 1999;354:1851-8.
8. Egi M, Bellomo R, Stachowski E, et al. Variability of blood glucose concentration and
short-term mortality in critically ill patients. Anesthesiology. 2006;105:244-52.
9. Gao Smith F, Perkins GD, Gates S, et al. BALTI-2 study investigators: Effect of
intravenous ß-2 agonist treatment on clinical outcomes in acute respiratory distress
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379:229-35.
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critical care. J Crit Care. 2002;17:95-104.
11. Krinsley JS. Glycemic variability: a strong independent predictor of mortality in
critically ill patients. Crit Care Med. 2008;36:3008-13.
12. Mackenzie IM, Whitehouse T, Nightingale PG. The metrics of glycaemic control in
critical care. Intensive Care Med. 2011;37:435-43.
13. Marx WH, DeMaintenon NL, Mooney KF, et al. Cost reduction and outcome
improvement in the intensive care unit. J Trauma. 1999;46:625-9.
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(ARDS) Clinical Trials Network; Wiedemann HP, Wheeler AP, Bernard GR, et al.
Comparison of two fluid-management strategies in acute lung injury. N Engl J Med.
2006;354:2564-75.
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The Berlin definition. JAMA. 2012;307:25226-33.
16. Rhodes A, Bennett ED. Early goal-directed therapy: an evidence-based review. Crit
Care Med. 2004;32:S448-S450.
17. Rice TW, Mogan S, Hays MA, et al. Randomized trial of initial trophic versus full-
energy enteral nutrition in mechanically ventilated patients with acute respiratory
failure. Crit Care Med. 2011;39:967-74.
19. Rudis MI, Sikora CA, Angus E, et al. A prospective, randomized, controlled evaluation
of peripheral nerve stimulation versus standard clinical dosing of neuromuscular
blocking agents in critically ill patients. Crit Care Med. 1997;25:575-83.
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A randomized, controlled trial of the use of pulmonary artery catheters in high-risk
surgical patients. N Engl J Med. 2003;348:5-14.
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ventilation improve survival in patients with severe ARDS. Chest. 1997;111:1008-17.
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resuscitation for patients with early septic shock. N Engl J Med. 2014;371:1496-506.
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in critically ill patients. N Engl J Med. 2009;360:1283-97.
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of protocol-based care for early septic shock. N Engl J Med. 2014;370:1683-93.
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mized trial. Lancet. 2006;368:379-85.
CHAPTER
16 Prem Kumar
PRINCIPLES OF ANTIBIOTIC USE IN ICU
Due to the increasing incidence of new infections in the last two decades and
the development of drug-resistant bacteria, use of antibiotics has drastically
changed in ICU. The major cause of drug-resistant microorganism are due to
wrong initiation and combination of antibiotics. Prevention of infection is the
best step in preventing antibiotic use in ICU patients. This chapter deals with the
principles of antibiotic use in ICU with the recent guidelines.
PRINCIPLES OF ANTIBIOTIC PRESCRIPTION

• Appropriate investigations required for diagnosis and culture should be sent.
• Risk stratification of patient and the condition is done.
• Culture should be sent before initiating antibiotics.
• An institutional antibiotic policy for prescribing antibiotics for various
infections should be formulated.
• Before prescribing antibiotics, review of various clinical factors interacting
with the antibiotics should be done such as renal, hepatic function, allergy
and drug interaction.
• Antibiotic stewardship is a strategy followed to limit antibiotic resistance. It
involves the selection of an appropriate drug with optimal dose and duration
while minimizing toxicity.
• Initiation of empirical antibiotics should be done based on clinical severity
and should be de-escalated according to culture results (e.g. Severe sepsis).
• To check whether the appropriate dose is advocated for that illness.
• The need for antibiotics should be reviewed daily.
• Parenteral administration is usually reserved for patients who cannot take
oral medications and in seriously ill patients.
• With the opinion of ID physicians, investigations such as antibiotic
assay, minimum inhibitory concentration (MIC) of the antibiotic, serum
bactericidal activity is done which would be useful in severe nosocomial
infections.
• In case of failure of response to antibiotics, opinion is obtained from a
microbiologist/clinical pharmacologist/infectious disease physician regard
ing change of antibiotics.
• The usual prescription of 2-week course of antibiotics is unnecessary and the
duration of antibiotic course should be shorter.
• Switching of one combination of antibiotics to another—antibiotic surfing.

It should not be done in case of poor response to therapy without properly
investigating the cause of the persistent infection (Table 16.1).
COMMON CAUSES OF INFECTION IN ICU

Nosocomial infections are common in ICU. The most common causes of
infections are:
• Catheter-associated urinary tract infection (CAUTI)
• Catheter-related bloodstream infection
• Ventilator-associated pneumonia (VAP)
• Surgical wound infections—necrotizing fasciitis
• Abdominal infections—intra-abdominal sepsis, postsplenectomy sepsis
• Central nervous system infection—meningitis
• Device infection—replacement prosthesis infection.
PHARMACOKINETIC PRINCIPLES (TABLE 16.2)

The success of the therapy depends on the drug concentration achieved to
inhibit or kill bacteria at the site of infection. The location of the infection points
towards the choice of drug and the route of administration. The minimal drug
concentration achieved at the infected site should be approximately equal to the
MIC for the infecting organism, and in fact multiples of MIC is required in certain
severe infections. Most of the antibiotics are excreted through the kidneys, hence
the dosage is altered according to the creatinine clearance in patients with renal
dysfunction. The pharmacokinetics is changed in ICU patients due to body fluid
alteration, hypoalbuminemia, alteration in volume of distribution, clearance and
elimination.
Table 16.1 Antibiotics and their site of action
Bactericidal Bacteriostatic
Cell wall—beta-lactams (e.g. penicillins, Inhibition of protein synthesis—
cephalosporins, and carbapenems) sulfonamides, tetracyclines,
Cell membrane—polymyxin, daptomycin macrolides, chloramphenicol,
streptogramins, and linezolid
Bacterial DNA—fluoroquinolones
Alteration of protein synthesis—aminoglycosides
Table 16.2 Pharmacodynamic characteristics of certain antibiotics in ICU
Characteristic Antibiotic
Time dependent Beta-lactams, carbapenems, glycopeptides
Concentration dependent Aminoglycosides
Both concentration and time dependent Fluorquinolones
Chapter 16 Principles of Antibiotic Use in ICU 129
Empirical Therapy for Sepsis without an

Obvious Focus of Primary Infection
The choice of empirical antimicrobial therapy depends on the following factors:
• History
• Physical examination
• Recent antibiotic treatment in the past 3 months
• Drug allergy
• Clinical condition
• Drug susceptibility pattern for various pathogens in the ICU.
In patients with severe sepsis or septic shock, antibiotic therapy should be
initiated within an hour of therapy according to surviving sepsis 2012 guidelines.
Sufficient evidence exists that delay or failure to initiate antimicrobial therapy is
associated with increased morbidity and mortality in patients with severe sepsis
or septic shock. Every hour of delay in initiating antibiotics in severe sepsis will
decrease the survival by 7% approximately. Recommendation is to administer
broadspectrum intravenous antibiotics within the 1st hour of recognition of
severe sepsis and septic shock. Initial empirical antimicrobial therapy should
include one or more drugs which have activity against bacterial, viral and fungal
organisms presumed to be the source of infection.
The most common pathogens causing septic shock in hospitalized patients
are Gram-positive bacteria, followed by Gram-negative and mixed bacterial
microorganisms. Candidiasis and toxic shock syndromes though uncommon
should be suspected in certain patients (immunosuppressed or neutropenic
state, prior intense antibiotic therapy, or colonization in multiple sites). Low
procalcitonin level can be used as a guide to discontinue empiric antibiotics but
the evidence is very less for its routine use in patients with severe sepsis. Empiric
antibiotic therapy should not be administered for more than 3–5 days and de-
escalation should be done as soon as possible. Typical duration of therapy is
7–10 days but may needed longer in patients with neutropenia, viral or fungal
infections. Antimicrobial therapy should not be used for patients with severe
inflammatory states of noninfectious cause.
• Severe sepsis with neutropenia and multidrug resistant organisms such
as Acinetobacter and Pseudomonas—combination empirical therapy with
Piperacillin—Tazobactam/Meropenem/Cefepime + Aminoglycoside ±
Vancomycin
• Severe infection with respiratory failure and septic shock—combination
therapy with an extended spectrum beta-lactam and aminoglycoside/
fluoroquinolone for P. aeruginosa bacteremia
• Streptococcus pneumoniae with septic shock—combination of beta-lactam
and macrolide
• IV drug abusers—vancomycin
• In case of neutropenic patients, empirical antifungal agents can be started
empirically, if neutropenia persists for more than 5 days.
• Empirical antifungal drugs—amphotericin B is used for all life-threatening
fungal infections. Fluconazole or Echinocandins is recommended by
recent Infectious Diseases Society of America (IDSA) guidelines for severe
candidiasis. Echinocandins is used for severe illness or when the patient is

recently treated with antifungal agents.
• Severe sepsis with neutropenia with suspected Pseudomonas infection-
ceftazidime or piperacillin—tazobactam or meropenem + aminoglycoside.
Empirical Antibiotic Therapy Based on Infection Site (Table 16.3)

Catheter-associated urinary tract infections (CAUTI) are discussed in detail
under the chapter urinary tract infections.
Table 16.3 Empirical antibiotic therapy based on infection site
Site of infection Common bacteria Appropriate antibiotic

Nosocomial S. pneumonia Ceftriaxone (2 g IV OD)
pneumonia S. aureus Or
H. Influenzae Ciprofloxacin (400 Mg IV 8th hourly), Or
Legionella Levofloxacin (750 mg IV OD)
Gram-negative Bacilli Or
Ampicillin/Sulbactam (3 g IV 6th hourly)
Or
Ertapenem (1 g IV OD)
MDR
MDR Ceftazidime (2 g IV 8th hourly)
P. aeruginosa Or
MRSA Cefepime (2 g IV 12th hourly)
Antibiotic-resistant Or
Enterobacteriaceae Piperacillin/Tazobactam (4.5 g IV 6th
Acinetobacter hourly), Imipenem (1 g IV 8th hourly), Or
Klebsiella Meropenem (1 g IV 8th hourly)
Legionella
Plus
ESBL-positive
Gentamicin (7 mg/kg IV OD) Or
Amikacin (20 mg/kg IV OD)
Or
Ciprofloxacin (400 mg IV 8th hourly), Or
Levofloxacin (750 mg IV OD)
Plus
Linezolid (600 mg IV 12th hourly) Or
Vancomycin (15 mg/kg, up To 1 g IV, 12th
hourly
Intra-abdominal E. coli Ertapenem
sepsis P. aeruginosa Or
Enterococcus species Piperacillin-Tazobactam
Bacteroides species (4.5 gm IV every 6 hours)
Or
Third- or Fourth-generation Cephalosporin
(Active Against P. aeruginosa)
Contd…
Contd…
Site of infection Common bacteria Appropriate antibiotic

Or
Cefepime 2 g IV Every 8 hours
PLUS Metronidazole
500 mg IV every 6 hours
Or
In case of penicillin allergy, Aztreonam 2
gm IV every 8 hours
Plus
Metronidazole 500 mg IV every 6 hours
Plus
Vancomycin
In case of Vancomycin-resistant
Enterococci, Add Linezolid/ Daptomycin/
Tigecycline.
Antifungal therapy with micafungin may
be considered in critically ill patients.
Antifungal therapy should be used in
patients where fungi are isolated in culture.
Catheter-related Staphylococcus species B-lactam with activity against
blood stream Enterobacteriaceae P. aeruginosa
infection P. aeruginosa Plus
Vancomycin
Surgical—wound Streptococcus species B-lactam + B-lactamase inhibitor
Infections Staphylococcus species (Clavulanic Acid)
Gram-negative bacilli Piperacillin-Tazobactam
Meropenem
STEPS TAKEN TO PREVENT ANTIBIOTIC RESISTANCE

Multidrug resistant pathogen (MDR): Isolates resistant to drugs from three or
more antimicrobial classes with different mechanisms of action are considered
MDR.
The incidence of multidrug resistant pathogens (Table 16.4) in ICU is
increasing and the reason for this is due to the improper use of antibiotics with
relation to condition, dose, duration, interval of dosage.
• Broadspectrum antibiotics are used only in life-threatening infections and
de-escalation is done once the culture results are obtained.
• Antibiotic cycling or rotation—class of antibiotics or a specific antibiotic is
withdrawn for a defined time period from usage and reintroduced at later
time in an attempt to limit bacterial resistance.
• The most important risk factor for antibiotic-resistant pneumococcal
infection is use of a specific antibiotic within the previous three months.
Hence, patient’s history of prior treatment with antibiotics is a critical factor
in avoiding the use of an inappropriate antibiotic. Use of the antibiotic which
Table 16.4 MDR Gram-positive and negative bacteria
Bacteria Treatment
MRSA Vancomycin, Daptomycin, Linezolid,
Tigecycline, Quinupristin/Dalfopristin
Streptococci Vancomycin, Tigecycline
ESBL-producing Enterobacteriaceae Carbapenem
Piperacillin-Tazobactam, Fluoroquinolones
Carbapenem-resistant Enterobacteriaceae Tigecycline, Fosfomycin
MDR—Pseudomonas aeruginosa Meropenem
Abbreviations: MRSA, methicillin-resistant Staphylococcus aureus; ESBL, extended-spectrum beta-
lactamase; MDR, multidrug resistant
was given 3 months prior to infection will be likely to be less effective for the
present infection and hence an alternative antibiotic should be prescribed.
This mechanism of resistance is commonly seen in streptococcus pneumonia.
• Use of combination therapy will prevent emergence of resistant mutant
bacteria, and thus would have a better option of at least one drug effectivity
against the bacteria.
• Host factors such as age, hepatic and renal function, genetic variation, allergy
should be considered.
• Persistent bacteremia despite administration of antibiotics can be associated
with the emergence of antimicrobial resistance.
Common scenarios where antibiotics are misused:
• Excessive use of certain antibiotics (e.g. fluoroquinolones)
• Prolonged empiric antibiotic treatment without clear evidence of infection
• Treatment of positive culture in absence of active clinical infection
• Prolonged prophylaxis
• Failure to narrow antibiotic therapy after the causative organism is identified.
Presurgery Antibiotic Prophylaxis

A single dose of antibiotic administered within 1 hour before the incision is
appropriate for most surgical procedures. Duration of prophylaxis for surgical
site infection should not exceed 24 hours in most cases. This prophylaxis ensures
to target the skin bacterial flora while avoiding broadspectrum activity.
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invasive pneumococcal disease in children: a population-based case-control study in
North America. Pediatrics. 1999;103(3):E28.
Principles of Internal Medicine, 18th edn. McGraw Hill Publications; 2012.
11. MS Krishna Sarin, et al. Antimicrobial Therapy in the Intensive Care Unit. Indian
Journal of Clinical Practice. 2013;23(10).
12. Schuetz P, Albrich W, Mueller B. Procalcitonin for diagnosis of infection and guide to
antibiotic decisions: past, present and future. BMC Med. 2011;9:107.
CHAPTER
17 Jenu Santhosh
TROPICAL INFECTIONS
SEVERE MALARIA
Management of severe malaria comprises four main areas: assessment of the
patient, specific antimalarial treatment, adjunctive therapy, and supportive care.
Vital organ dysfunction or increase in the infected total proportion of erythrocytes
infected >2% (a level corresponding to >1012 parasites in an adult) is an indicator
of increased mortality.
Diagnosis
Severe malaria is a medical emergency. The airway should be secured in
unconscious patients and breathing and circulation assessed. The patient should
be weighed or weight estimated—to give correct dosage of drugs and immediate
measurements of blood glucose (stick test), hematocrit, parasitemia (parasite
count, stage of malaria parasite development, and proportion of neutrophils-
containing malaria pigment), and in adults, renal function (blood urea or
creatinine) should be taken. The degree of acidosis is an important determinant
of outcome; indicators of poor prognosis is given in Table 17.1 The plasma
bicarbonate or venous lactate should be measured, if possible. If facilities are
available, arterial or capillary blood pH and gases should be measured in patients
who are unconscious, hyperventilating, or in shock. Blood should be taken for
cross-match, and (if possible) full blood count, platelet count, clotting studies,
bacterial culture, and full biochemistry (Table 17.2).
The assessment of fluid balance is critical in severe malaria. Acidotic
breathing or respiratory distress, particularly in severely anemic children, often
indicates hypovolemia and requires prompt but careful rehydration. Careful and
frequent evaluations of the jugular venous pressure, peripheral perfusion, venous
filling, skin turgor, and urine output should be made. Reduced hydration causes
acidosis and over hydration causes pulmonary edema.
In uncertainty, central venous catheter should be inserted and the pressure
(CVP) measured directly. Unconscious patients must have a diagnostic lumbar
puncture to exclude bacterial meningitis. The opening pressure should be
recorded and the rise and fall with respiration noted.
Management
Currently, four commonly used parenteral drug treatments are recommended
for severe malaria—artesunate, artemether, quinine, and quinidine (Table 17.3).
Chapter 17 Tropical Infections 135
Table 17.1 Indicators of poor prognosis
Clinical Lab parameters

• Hemodynamic instability/shock • Metabolic acidosis (arterial pH <7.3, serum
• Temperature <36°C HCO3 <15 mmol/L)
• Respiratory distress • ↑ serum bilirubin (>3 mg/dL), creatinine
• Renal failure (>3 mg/dL), liver enzymes, urate, CPK, lactate
• Marked agitation, coma (>5 mmol/L).
• Seizures • Hypoglycemia (<40 mg/dL)
• Bleeding • Leukocytosis
• Severe anemia (PCV <15%)
• Decreased fibrinogen (<200 mg/dL)
• Platelet count (<50,000/µL)
• Prolonged PT, aPTT
• Hyperparasitemia (>20% of parasites
identified as pigment-containing trophozoites
and schizonts, >5% of neutrophils with visible
pigment, parasitemia level >1,00,000/µL )
Abbreviations: CPK, creative phosphokinase; PCN, packed cell volume; PT, prothrombin time; PTT, partial
thromboplastin time
Table 17.2 Manifestations of severe malaria
• Hypotension
• Respiratory distress
• Noncardiogenic pulmonary edema/ARDS
• Renal failure
• Hypoglycemia
• Seizures
• DIC
• Anemia
• Coma
• Hemoglobinuria
• Muscle weakness
• Jaundice
• Parasitemia level of >5% in nonimmune patients (>20% in any patient)
Abbreviations: ARDS, acute respiratory distress syndrome; DIC, disseminated intravascular coagulation
Among these drugs, parenteral artesunate is the drug of choice for severe malaria
for all patients. Most of the severe malaria are commonly caused by falciparum.
Even in a patient considered to need parenteral treatment for P. vivax, P. ovale, or
P. malariae infection, it is best to treat for falciparum malaria because there may
be a mixed infection. Severe malaria requires ICU admission and care.
The pharmacokinetic properties of artesunate are superior to those of
artemether and arteether because it is water soluble and can be given either by
intravenous or intramuscular injection. Quinidine is more toxic than quinine
and should be used only when none of the other effective parenteral drugs are
available.
Table 17.3 Dosages of antimalarial drugs
Drugs and dosages

Artesunate IV: 2.4 mg/kg stat, at 12 and 24 hours, then daily
or
Artemether IM: Initial dose of 3.2 mg/kg followed by 1.6 mg/kg every 24 hours until oral
medication is tolerated
or
Quinine IV: Loading dose 20 mg/kg given over 4 hours, then 10 mg/kg given 8 hours after
the loading dose was started, followed by 10 mg/kg every 8 hours
or
Quinine IM: Loading dose of 20 mg/kg is given as two simultaneous injections in the
anterior thigh (10 mg/kg in each) after dilution of quinine in sterile water to a concentration
of 60–100 mg/mL, maintenance dose of 10 mg/kg is given as one IM injection every
8 hours using the same dilution
or
Quinidine IV: 10 mg/kg infused over 1–2 hours followed by 1.2 mg/kg per hour by
constant infusion.
Total plasma concentrations of 8–15 mg/L
For Quinine and 3.5–8.0 mg/L for quinidine are effective and don’t cause toxicity.
Electrocardiographic monitoring is necessary especially for patients on

quinidine. Total treatment duration for all regimens is 7 days. Once the patient
has recovered sufficiently to tolerate oral medication reliably, the parenteral
treatment can be discontinued and a second drug should be added, such as
doxycyline 3 mg/kg for 7 days, clindamycin 10 mg/kg bid for 7 days, or atovaquone
20 mg/kg/day proguanil 8 mg/kg/day for 3 days.
Supportive Care
These should include recording of vital signs, with an accurate assessment of
respiratory rate and pattern, assessment of the coma score, and urine output.
The blood glucose should be checked, with rapid stick tests every 4 hours, if
possible. Convulsions should be treated promptly with anticonvulsants such
as intravenous or rectal diazepam. Physician treads a narrow path between
underhydration, and thus worsening renal impairment, and overhydration, with
the risk of precipitating pulmonary edema. So monitoring the hydration status is
essential.
If the patient becomes oliguric (< 0.4 mL/kg/hr) despite adequate rehydration
and the blood urea or creatinine are rising or already high, fluids should be
restricted to replace insensible losses only. In acute renal failure or severe
metabolic acidosis, hemofiltration or hemodialysis should be initiated as early
as possible. Hypoglycemia should be suspected in any patient who deteriorates
suddenly and treated with 10% dextrose.
Patients with acute pulmonary edema should be nursed upright and given
oxygen, and the right-sided filling pressures should be reduced with whichever
treatments are available (loop diuretics, opiates, venodilators, hemofiltration,
dialysis). Positive pressure ventilation should be started if indicated. In case of
DIC, fresh-frozen plasma or platelets can be given according to clinical features.
Severe Malaria in Pregnancy

Pregnant women in the second and third trimesters are more likely to develop
severe malaria than other adults often complicated by pulmonary edema and
hypoglycemia. Hypoglycemia should be expected and is often recurrent, if
the patient is receiving quinine. The antimalarial drugs should be given in full
doses. Postpartum bacterial infection is a common complication in these cases.
Artemisinin derivatives should not be used in the first trimester of pregnancy.
In the second and third trimesters of pregnancy, artesunate (2 mg/kg/day for 7
days) may be given with one of the other drugs. When the patient with severe
malaria has recovered sufficiently, oral medication should be substituted.
DENGUE
Dengue is a viral hemorrhagic fever transmitted by Aedes aegypti mosquito and
there are 4 distinct viruses which can cause this infection. Dengue patients gets
admitted to ICU for dengue hemorrhagic fever (DHF) or dengue shock syndrome
(DSS). It is also known by the name breakbone fever. This disease is common
in children although it can occur in any age group. Macrophage or monocyte
infection is the main pathogenesis of DHF/DSS.
Clinical Features
The clinical features of DHF-DSS are hemorrhagic phenomena and hypovolemic
shock which are caused by increased vascular permeability and plasma
leakage. The early features in patients who ultimately develop DHF-DSS are
indistinguishable from those of ordinary dengue fever, namely, fever, malaise,
headache, musculoskeletal pain, facial flushing, anorexia, nausea, and vomiting.
Fever has a biphasic curve with initial phase of 3–7 days, remission of few hours
to 2 days and second phase with 1–2 days. Macular rash appears on the first day
along with adenopathy, palatal vesicles, and scleral injection. It has a biphasic
rash with evanescent maculopapular, scarlatiniform, morbilliform, or petechial
changes which proceeds from extremities to the torso. However, with the
defervescence of fever 2–7 days later, reduced perfusion and early signs of shock
are manifested by central cyanosis, restlessness, diaphoresis, and cool, clammy
skin and extremities.
Abdominal pain is a common complaint. A rapid and weak pulse, narrowing
of the pulse pressure to less than 20 mm Hg, and, in the most extreme cases, an
unrecordable blood pressure establish the shock syndrome. The platelet count
declines and petechiae appear with spontaneous ecchymoses. Bleeding occurs at
mucosal surfaces from the gastrointestinal tract and at venipuncture sites. The liver
is palpably enlarged in up to 75% of patients, with variable splenomegaly. Increased
amylase levels and sonographic evidence of pancreatic enlargement may be seen
in 40% of patients. Pleural effusions can be detected in more than 80% of cases,
if a decubitus film is taken. The presence of pleural and peritoneal effusions is
associated with severe disease. Capillary-alveolar leakage may cause ARDS.
In untreated patients, hypoperfusion due to myocardial dysfunction and
reduced ejection fraction results in metabolic acidosis and organ failure. With
adequate support, spontaneous resolution of vasculopathy and circulatory failure
usually can be expected within 2–3 days, with complete recovery afterward. The
duration of illness ranges from 7 to 10 days in most cases. Fatality rates have
reached 50% in underserved populations, but in experienced centers, fewer
than 1% of cases are fatal. Encephalopathy (often reflecting CNS hemorrhage),
prolonged shock, and hepatic or renal failure are rare but if present, they are
associated with a poor prognosis. Concurrent infection with bacteria, parasites,
and other viral pathogens occurs frequently in areas with high transmission.
Dual infections, principally Gram-negative sepsis, have been reported in patients
hospitalized with dengue, resulting in prolonged fever and hospitalization. In two
thirds of patients with DHF, reactivation of herpesvirus-6 infection may be seen.
Differential Diagnosis
It is difficult to clinically diagnose dengue from other febrile illness. But the
diagnosis is aided, if laboratory examination indicates leukopenia, neutropenia,
thrombocytopenia, or mildly elevated AST levels. Specificity of tourniquet
test, a requirement in the DHF case definition is also low. In comparison with
chikungunya, another epidemic A. aegypti–borne infection, dengue patients are
less likely to have conjunctivitis, rash, and musculoskeletal pain. The difficulty
of differentiating dengue from rubella, measles, and even influenza has been
underscored by the early misrecognition of entire epidemics. The clinical
differentiation of DHF from YF and other viral hemorrhagic fevers is also difficult,
and diagnosis requires laboratory confirmation.
Investigations
Clinical or laboratory differentiation, at the time of first presentation, of patients
who can develop DHF would facilitate intervention before the sudden onset of
shock. AST elevations greater than 60 U/mL, leukocyte counts less than 5000/
mm3 (characteristic), and absolute neutrophil counts less than 3000/mm3,
thrombocytopenia (<1,00,000/µL) are features which can be present in DHF/
DSS. Tourniquet test can be done for differentiating dengue from other febrile
illnesses. Increased IL-8 levels may have prognostic value. Studies to discover the
pathogenic roles of other cytokines are in progress. Other findings are elevated
hematocrit, hypoalbuminemia, hemoconcentration. Ultrasonography has been
more sensitive in detecting pleural effusions, ascites, and gallbladder edema in
more than 95% of severe cases, and pararenal and perirenal effusions in 77%, as
well as hepatic and splenic subcapsular and pericardial effusions. IgM and IgG
enzyme-linked immunosorbent assays (ELISAs) after the febrile phase is done
for diagnosis, PCR or detection of the specific viral protein NS1 by ELISA can be
diagnostic during the first few days of infection.
Management of Dengue and Dengue Hemorrhagic Fever

Antipyretics may help to relieve the symptoms of dengue fever. Aspirin should not
be used as it may cause Reye’s syndrome. Oral rehydration is indicated to replace
losses from vomiting and high fever. Attentive clinical monitoring of patients with
suspected DHF-DSS is necessary. Careful monitoring of circulation and vascular
leakage by serial clinical assessments of pulse, blood pressure, skin perfusion,
urine output, and hematocrit, to trigger intravenous fluid therapy is essential.

An increase in hematocrit of greater than 20% indicates a significant loss of
intravascular volume and the urgent need for fluid resuscitation. Normal saline
is administered to maintain circulation and, under continued monitoring, for
recurrent shock. Shock necessitates rapid intervention with isotonic crystalloid
or colloid solutions, or, if needed, plasma or whole-blood transfusions.
Vascular integrity is usually restored spontaneously in 48 hours. Hence
overhydration resulting in pulmonary edema is a risk, and positive-pressure
ventilation with positive end-expiratory pressure may be needed. Whole blood,
platelet, and fresh-frozen plasma transfusions may be needed, if there is significant
hemorrhage, but caution is indicated in the administration of heparin except in
patients with clear signs of disseminated intravascular coagulopathy. Platelet
transfusions can be considered for patients with severe thrombocytopenia
(<10,000/µL) or when there is evidence of bleeding.
Preventive transfusions may be harmful and should be avoided, and invasive
procedures should be minimized to avoid hemorrhagic complications. Treatment
to end virus replication could be beneficial, although viremia levels are already
decreasing dramatically at the time of presentation to healthcare providers. In
some locations, intravenous gamma-globulin has been used empirically, but
no benefit has been established in a controlled evaluation. Neither high-dose
methylprednisolone (30 mg/kg) nor AC-17 (carbazochrome sodium sulfonate),
which is believed to reduce vascular permeability, was beneficial in controlled
trials. Treatment with anti-TNF antibody has increased survivability in a lethal
mouse model of dengue. Secondary and concurrent infections should be
investigated and treated.
BIBLIOGRAPHY
1. Centers for Disease Control and Prevention: Treatment of Malaria (guidelines for
clinicians). Atlanta, Department of Health and Human Services, 2010.
2. Centers for Disease Control and Prevention: Update: Management of patients with
suspected viral hemorrhagic fever—United States. MMWR Morb Mortal Wkly Rep.
1995;44:475.
3. Dondorp A, et al. Artesunate versus quinine in the treatment of severe falciparum
malaria in African children (AQUAMAT): An open-label randomized trial. Lancet.
2010;376(9753):1647-57.
4. Lee IK, et al. Clinical characteristics, risk factors, and outcomes in adults experiencing
dengue hemorrhagic fever complicated with acute renal failure. Am J Trop Med Hyg.
2009;80(4):651-5.
Principles of Internal Medicine. 18th edn. McGraw Hill Publications, 2012.
6. Pasvol G. Management of severe malaria: interventions and controversies. Infect Dis
Clinic North Am. 2005;19(1):211-40.
7. Potts JA, et al. Clinical and laboratory features that distinguish dengue from other
febrile illnesses in endemic populations. Trop Med Int Health. 2008;13(11):1328-40.
8. Rosenthal PJ. Artesunate for the treatment of severe falciparum malaria. N Engl J Med.
2008;358(17):1829-36.
9. World Health Organization: Guidelines for the Treatment of Malaria, 2nd ed. Geneva,
World Health Organization, 2010.
10. Yadav SP, et al. Control of massive bleeding in dengue hemorrhagic fever with severe
thrombocytopenia by use of intravenous anti-D globulin. Pediatr Blood Cancer. 2008;
51(6):812-3.
CHAPTER
18 Prem Kumar
ANAPHYLAXIS
INTRODUCTION
Anaphylaxis is a severe, life-threatening, generalized or systemic hypersensitivity
reaction. It is characterized by rapidly developing, life-threatening problems
involving the airway, breathing and circulation. Classically, anaphylaxis comes
under systemic immediate type 1 hypersensitivity. Incidence is 8:1,00,000
persons/year for general population. It is between 1:3500 and 1:13,000 during
anesthesia.
DEFINITIONS
Anaphylaxis—rapid, severe life-threatening generalized immunologically
mediated events involving an antigen-specific IgE-mediated mechanism that
occur after exposure to foreign substances in previously sensitized persons.
Anaphylactoid reaction is clinically indistinguishable from anaphylaxis and is
coined when the mechanism of the reaction is not immunologically mediated
and prior exposure of the antigen is not required. They are due to mast cell
degranulation which can occur due to drug like nonsteroidal anti-inflammatory
drugs (NSAIDs).
Recent consensus is to avoid the term anaphylactoid reaction. Anaphylaxis is
divided into immune, nonimmune or idiopathic.
ETIOLOGY AND PREDISPOSING FACTORS

• Insect venoms, foods (e.g. peanuts), drugs, latex are common factors causing
immune-mediated anaphylactic reaction. Certain drugs can also cause non-
immune mediated reactions. A small number of patients have clinical effects
of allergic reactions, but not identifiable cause which are classified under the
idiopathic type.
• Causes of nonimmune-mediated reactions are complement activation due
to blood transfusion, NSAIDs, colloids (dextran, starch), local anesthetics,
protamine, opioids, chemotherapeutic agents.
• Other causes of anaphylactic reactions are antibiotics (penicillin group of
drugs), anesthetic drugs [neuromuscular blocking drugs—vecuronium,
atracurium, succinyl choline, pancuronium, rocuronium, mivacurium and
Chapter 18 Anaphylaxis 141
gallamine in that order, hypnotics, colloids, opioids, local anesthetics],

contrast media, blood products, cosmetic products, hormones, enzymes,
pollen extracts.
• Common causes of mortality are due to antibiotics, radiocontrast dye, foods,
insect stings in that order. Food is a common triggering agent in children.
• Patients with asthma are more prone to have severe bronchospasm.
• Patients on beta blockers tend to have severe reactions.
• Previously it was thought that patients with history of atopy had high risk of
developing anaphylaxis, but according to recent studies, it is clear that atopy
does not increase the risk of anaphylaxis.
Pathophysiology
• Specific IgE cross-linked by allergen (drug)
• Complement activation by specific IgG or IgM binding to antigen (drug)
• Direct complement activation by way of the alternate pathway
• Direct activation of mast cells or basophils.
The angioedema and urticarial manifestations of anaphylactic reactions are
due to the release of histamine. Chemical mediators in anaphylaxis are cysteinyl
leukotrienes (LTC4, LTD4, and LTE4), PAF, and bradykinin. Leukotrienes cause
bronchiolar constriction. Hemodynamic collapse is due to release of prostaglandin
D2 and histamine. Other factors which play a role in anaphylactic reaction are
platelet activating factor, eosinophil and neutrophil chemotactic factor. The
microscopic findings in the bronchi shows luminal secretions, submucosal
edema, and eosinophilic infiltration, and intractable bronchospasm. Laryngeal
angioedema cause airway obstruction. Nonimmune-mediated reaction is caused
by NSAIDs, radiocontrast media which are mediated by mast cell degranulation.
CLINICAL MANIFESTATIONS
The hallmark of anaphylactic reaction is its onset within seconds to few minutes.
• Respiratory system—hoarseness of voice, stridor due to laryngeal edema,
bronchospasm.
• Cardiovascular system—tachycardia, bradycardia, hypotension, and cardiac
arrest.
• Gastrointestinal system—nausea, vomiting, diarrhea, abdominal pain.
• Skin manifestations—erythema, urticaria, angioneurotic edema, pale,
cyanosis, conjunctival congestion. Characteristic feature is the eruption of
well-circumscribed, erythematous wheals with raised serpiginous borders
and blanched centers.
• Central nervous system—confused, anxious, choking sensation, seizures,
loss of consciousness.
Anaphylactic reactions are most likely if these three criterias are fulfilled:
1. Sudden onset and rapid progression of symptoms
2. Life-threatening ABC problems
3. Skin and/or mucosal changes.
Table 18.1 ABCDE approach for diagnosing anaphylactic reaction
Airway
• Airway swelling
• Difficulty in breathing and swallowing
• Sensation that throat is ‘closing up’
• Hoarse voice
• Stridor
Breathing
• Shortness of breath, increased respiratory rate
• Wheeze, cyanosis, confusion due to hypoxia
• Respiratory arrest
Circulation
• Signs of shock
• Tachycardia, hypotension
• Myocardial ischemia/angina
• Cardiac arrest
Disability
• Sense of impending doom
• Anxiety
• Decreased conscious level
Exposure
• Skin and mucosal changes
• Erythema
• Urticaria, angioedema
Diagnosis
Initial blood sampling is not useful but sample collected during the episode and
assayed later for histamine and tryptase is helpful for diagnosing anaphylaxis.
The basal tryptase concentration is 0.8–1.5 ng/mL and the normal value usually
<1 ng/mL. The half-life of tryptase is approximately 2.5 hours and maximum
concentrations occur rapidly within 1 hour, serum tryptase concentrations of >20
ng/mL may be seen after anaphylactic reactions.
Measurement of specific IgE antibodies by a radioallergosorbent test (RAST)
can be helpful for diagnosis. Intracutaneous skin testing can be helpful to find the
instigating agent causing the reaction but should not be done within 6 weeks of
the reaction. Serum tryptase level is elevated within 4 hours of a reaction and it is
helpful in reactions occurring under general anesthesia. Diagnosis can be done
by the ABCDE approach (Table 18.1).
Treatment (Flow chart 18.1)

Early recognition and treatment is vital in the management of anaphylaxis. Once
there is anaphylactic reaction, cardiopulmonary resuscitation is critical. Adequate
intravenous access with two 18-gauge or larger peripheral catheters should be
Flow chart 18.1 Algorithm for management of anaphylaxis

secured soon. Fluid administration, aggressive use of vasopressors, epinephrine

are mainstay of treatment. Monitoring heart rhythm, blood pressure, oxygenation
is important. Mild symptoms of anaphylaxis like skin rashes and pruritus can be
managed by administering 0.3–0.5 mL of 1:1000 (1 mg/mL) epinephrine SC or IM
and repeated at 5–10 minute intervals. In case of hypotension, crystalloids and
vasopressors (dopamine).
ROLE OF EPINEPHRINE IN ANAPHYLAXIS

• Receptor action—alpha and beta adrenergic effects
• Causes vasoconstriction (α1) and bronchial smooth-muscle relaxation (β2)
• Delays antigen absorption when infiltrated locally into an injection or sting
site
• Attenuation of increased venous permeability.
In case of desaturation, oxygen is administered through face mask. If patient
goes for respiratory arrest, bag and mask ventilation and endotracheal intubation
may be necessary. In case of large tongue edema, laryngeal or vocal cord edema
where oropharyngeal intubation is difficult, cricothyroidotomy or tracheotomy
may be needed. Cricothyroidotomy is preferred to tracheotomy in an emergency,
as the cricothyroidotomy is easier to perform and is usually safer. In case of
bronchospasm, inhaled β2 agonists such as albuterol would be useful.
Other drugs which would be useful for anaphylaxis are:
• Antihistamine—diphenhydramine, 50–100 mg or 1–2 mg per kg IM or
IV. Antihistamines are more effective in prevention than in treatment of
anaphylaxis. Hence, it should never be used as the primary therapy for
anaphylactic shock.
• Intravenous glucocorticoids—initial dose of hydrocortisone is 5 mg/kg to a
maximum of 200 mg given intravenously, followed by 2.5 mg/kg to 200 mg
given intravenously every 4–6 hours for 24–48 hours. Steroids are not useful
for acute episodes but prevents recurrence of bronchospasm, hypotension,
or urticaria.
• Aminophylline, 0.25–0.5 g IV.
Prevention
• Eliciting history carefully about the precipitants causing anaphylactic
reactions.
• Awareness of cross reacting agents (e.g. penicillin and cephalosporins)
• If there is a history of a previous anaphylactic reaction to an agent/drug, it is
advisable to select a structurally unrelated agent.
• Penicillin cause the highest incidence of anaphylactic reactions and hence
positive skin tests to benzylpenicillin products is indicate that anaphylactic
reactions can occur with treatment.
• Desensitization can be done with the drug if an alternative is not available for
that drug and that the drug is necessary for treatment.
• Agents or drugs with preservatives like metabisulfite and methylparaben are
associated with reactions (e.g. local anesthetics).
• Patients with history of anaphylaxis should wear a Medic-Alert bracelet or

necklace which details precipitating agents and potential cross-reacting
agents.
• Patient should be well educated about the agents causing reactions and
advised to avoid it.
• Consultation with the allergist is done and proper evaluation and planning
of the management of the patients prone for anaphylactic agents are done.
BIBLIOGRAPHY
1. Boyd AD, Romita MC, Conlan AA, et al. A clinical evaluation of cricothyroidotomy.
Surg Gynecol Obstet. 1979;149:365-8.
2. Fisher MM, Baldo BA. Anaphylaxis during anaesthesia; current aspects of diagnosis
and prevention. Eur J Anaesthesiol. 1994;11:263-84.
3. Lieberman P. Anaphylactic reactions during surgical and medical procedures. J
Allergy Clin Immunol. 2002;110:S64-S9.
4. McGrath K, Patterson R, Grammer LC, Greenberger PA (Eds). Allergic Diseases. In:
Anaphylaxis Diagnosis and Management. Philadelphia: Lippincott-Raven; 1997.
pp.439-58.
5. Schwartz LB, Metcalfe DD, Miller JS, et al. Tryptase levels as an indicator of mast-cell
activation in systemic anaphylaxis and mastocytosis. N Engl J Med. 1987;316:1622-6.
6. Sheffer AL. Anaphylaxis. J Allergy Clin Immunol. 1985;75:227-33.
7. Soar J, Pumphrey R, Cant A, et al. Working group of the resuscitation Council (UK).
Emergency treatment of anaphylactic reactions–guidelines for healthcare providers.
Resuscitation. 2008;77(2):157-69.
8. The diagnosis and management of anaphylaxis: an updated practice parameter. J
Allergy Clin Immunol. 2005;115:S483-S523.
9. Valentine MD. Anaphylaxis and stinging insect hypersensitivity. JAMA. 1992;268:
2830-3.
10. Whittington T, Fisher MM. Anaphylactic and Anaphylactoid Reactions in Bailliére’s
Clinical Anesthesiology. 1998.pp.301-21.
SECTION
6
POISONING AND
ENVENOMATION
Chapter 19 General Principles of Poisoning

Jenu Santhosh
Chapter 20 Poisoning
Chapter 21 Drug Overdose

Chapter 22 Envenomation
Jenu Santhosh
CHAPTER
19 Jenu Santhosh
GENERAL PRINCIPLES OF POISONING
Poison is defined as the substance producing harmful effects in living things.

In humans, clinical features of poisoning may be seen within a period of three
hours for most poisons except for a few where the manifestations are delayed
(e.g. aspirin, paracetamol, iron, TCAs).
MANIFESTATIONS
Clinical manifestations vary with each poison. Always consider poisoning in
any patient who presents with bizarre clinical manifestations. Since the history
is usually unreliable, it is always better to ask the relatives regarding certain
evidences of poisoning such as presence of containers, missing pills, etc.
Following are to be examined:
• Vitals: Heart rate, respiration, blood pressure, temperature
• Odor: Alcohol, solvents, insecticides
• Skin:
– Color change: blue- methemoglobinemia, flushed—serotonin syndrome
– Sweating—organophosphorous poisoning, sympathomimetics
– Bruising—anticoagulants
– ��
Blisters—pressure related, barbiturates (if associated with unconscious-
ness for >6 hours)
• Neurological
• Cardiovascular system
• Systemic examination.
NEUROLOGICAL EXAMINATION
Coma: If coma is associated with localizing signs, it is unlikely due to poisoning.
But transient localizing signs may be associated with barbiturates and dilantin
(phenytoin). Coma is seen with alcohol, sedatives and antipsychotics.
Pupils: It may be constricted or dilated but sometimes may be unequal. It is the
size of the pupil that is more important than the reflexes.
• Miosis: Organophosphate, cholinergics, opiates, barbiturates.
• Mydriasis: Atropine, dhatura, ephedrine, amphetamine, cyanide, cocaine.
150 Section 6 Poisoning and Envenomation
Seizures: Seizures may be caused by tricyclic antidepressants, theophylline,

serotonin syndrome, alcohol withdrawal or sedatives, insecticides, antihista
minics.
Temperature
• Decreased: Opiates, barbiturates, carbon monoxide
• Increased: Anticholinergics, antihistaminics, phenothiazines, amphetamine,
neuroleptic malignant syndrome.
CARDIOVASCULAR
• Tachycardia: Atropine, dhatura, alcohol, sympathomimetics
• Bradycardia: Organophosphates, carbamates, digoxin, beta-blockers. If
bradycardia is associated with hypertension, think of intracranial bleed
(Cushing’s reflex), clonidine, cocaine.
• Hypertension: Sympathomimetics
• Hypotension: Antihypertensives, sedatives.
METABOLIC
• Metabolic acidosis: Aspirin, methanol, ferrous sulphate
• Hypoglycemia: Insulin, oral hypoglycemic agents, quinine, hepatotoxic
agents
• Hypokalemia: Diuretics, Cleistanthus collinus (odduvanthalai-local name in
South India)
• Hepatotoxic: Paracetamol, copper, antituberculous agents (ATT).
MANAGEMENT
Criteria for ICU admission:
• Respiratory failure, inability to protect airway
• GCS < 8, seizures
• Metabolic abnormalities such as hypoglycemia, electrolyte abnormalities,
metabolic acidosis, coagulopathy, hepatic failure
• Sinus tachycardia (HR >110), arrhythmias, SBP <90 mm Hg, heart block, QRS
>0.12 second.
Assessment
• Ensure clear airway and suction the secretions, look for cough and gag reflex,
consider endotracheal intubation.
• Check SpO2 and give oxygen, if necessary, observe the breathing and its
pattern, ventilate if necessary.
• Monitor heart rate and rhythm; check blood pressure.
• Check GCS; control seizures and agitation; observe for muscle spasm and
rigidity; look for pupil size and reaction.
Chapter 19 General Principles of Poisoning 151
• Look for odor, skin color, temperature. Search for rashes, skin lesions,
cyanosis, jaundice.
• Look for abdominal guarding and rigidity, UGI or LGI bleed.
• Monitor for adequacy of urine output. Look for urine color.
Specific Treatment
• Reduce absorption
• Increase elimination
• Specific antidotes.
Reduce Absorption
• Surface decontamination—washing the skin and eye
• Gastrointestinal-induced vomiting, stomach wash, activated charcoal,
catharsis, whole bowel irrigation.
Induced vomiting
It is contraindicated in comatose patients and in those who are convulsing and in
those who have consumed corrosives.
Gastric lavage
It is safer than induced vomiting. It is more effective, if it is given within 60
minutes of poison ingestion. It can be also given late in poisons with delayed
gastric emptying, viz. salicylates and anticholinergics. It can be done in comatose
patients after securing the airway.
Activated charcoal
It is effective for most poisons except alcohol, ethylene glycol, mineral acids,
alkali, lithium, fluoride, iron. Multidose-activated charcoal (MDAC) is useful
than single dose charcoal. Dose is 12.5 g hourly to 50 g 4th hourly. If the quantity
of the substance ingested is not known, 10 times the ingested dose by weight
should be given.
Cathartics
There is a controversy regarding the use of cathartics to hasten the elimination
of charcoal/poison complex. Commonly used cathartics are sorbitol and
magnesium citrate.
Increase Elimination
It is possible only if the drug is distributed predominantly in the extracellular
space and low protein bound. It is better to maintain urinary output of all patients
with poisoning to 150–200 mL per hour. Urinary alkalinization is recommended
for salicylate poisoning.
Other modes are hemodialysis (barbiturates), charcoal/resin hemoperfusion
(theophylline), hemofiltration, peritoneal dialysis. Albumin dialysis (MARS) is
used for protein-bound drugs.
Specific Antidotes
Specific antidotes are shown in Table 19.1.
Table 19.1 Specific antidotes
Drug Antidote Dose

Acetaminophen N-acetyl Oral: 140 mg/kg loading dose followed by 70
cysteine mg/kg every 4 hourly for 17 doses
Intravenous:150 mg/kg in 200 mL 5% dextrose
over 15 minutes; then 50 mg/kg diluted in 500
mL over 4 hours; then 100 mg/kg diluted in
1000 mL over 16 hours
Benzodiazepines Flumazenil 0.2–0.3 mg bolus;
Infusion: 0.2–1 mg/hourly
Carbon monoxide 100% Oxygen
Digoxin Digoxin specific
antibodies
Ethylene glycol, Ethanol 750 mg/kg as loading dose followed by
methanol 100–250 mg/kg per hour infusion
Fomipezole 15 mg/kg up to 1 g over 30 minutes as a
loading dose
10–15 mg/kg every 12 hours as maintenance
Copper Penicillamine 20–30 mg/kg/day; max 2 g/day
Iron Desferrioxamine 15 mg/kg per hour up to max of 6 g
Methemoglobinia Methylene blue 1–2 mg/kg slow intravenous over 5 minutes;
repeat in 60 minutes
Opiates Naloxone 0.4–2 mg every 2–3 minutes as bolus
Infusion: 0.4–0.8 mg/hour
Organophosphorous Atropine Bolus: 0.6–3 g every 5 minutes till atropinization
occurs. Oximes should also be given
Glycopyrrolate Bolus: 0.4–1 mg
BIBLIOGRAPHY
1. Eddleston M, Juszczak E, Buckley NA, Senarathna L, Mohamed F, Dissanayake W, et al.
Multiple-dose activated charcoal in acute self-poisoning: A randomised controlled
trial. Lancet. 2008;371:579-87.
2. In: Critical Care Toxicology, Diagnosis and Management of the Critically Poisoned
Patient, 1st edn. Brent, Wallace, Burkhart, Phillips, Donovan (Eds), 2005.
Principles of Internal Medicine. 18th edn. McGraw Hill-publications, 2012
4. Olson KR. Poisoning and Drug Overdose, 5th edn. McGraw Hill Publications, 2006.
5. Parikh CK. Parikh Textbook of Medical Jurisprudence and Toxicology, 4th edn.
Mumbai: Medical Publication; 1989.pp.912-4.
CHAPTER
20 Jenu Santhosh, TA Naufal Rizwan
POISONING
Pesticides include:
• Organophosphorus
• Carbamate
• Organochlorine
• Pyrethroids.
ORGANOPHOSPHORUS AND CARBAMATE POISONING (TABLE 20.1)

Organophosphorus pesticides inhibit acetylcholinesterase in synapses
and on red-cell membranes, and butyrylcholinesterase in plasma. Acute
acetylcholinesterase inhibition results in accumulation of acetylcholine and
stimulation of acetylcholine receptors in synapses of the neuromuscular
junctions, autonomic nervous system.
Clinical Features
Although both organophosphorus compound (OPC) and carbamate poisoning
produce cholinergic and nicotinic symptoms, the symptoms in carbamates are
less severe.
Table 20.1 Organophosphorus compounds and carbamates
Organophosphorus compounds
• Parathion
• Monocrotophos
• Chlorpyrifos
• Diazinon
• Fenthion
Carbamates
• Aldicarb
• Bendiocarb
• Carbofuran
Cholinergic Symptoms
These include increased secretions like salivation, lacrimation, urination,
defecation, bronchial secretions, etc. Patients can also have confusion, seizures,
miosis and bradycardia.
Nicotinic Symptoms
These include muscle twitching, fasciculations, muscle weakness and respiratory
paralysis.
Intermediate Syndrome
This develops 12 hours–4 days after the consumption of poison and is
characterized by weakness of ocular muscles, neck, bulbar, proximal limb and
respiratory muscles. This is due to prolonged action of acetylcholine on the
nicotinic receptors.
Delayed Polyneuropathy
This occurs many months after the consumption of poison and is characterized
by weakness of the distal muscles of the legs (foot drop) and small muscles of the
hands.
Investigations
• Serum cholinesterase and RBC cholinesterase
• Gastric aspirate and blood samples for toxicological analysis
• Complete blood count, electrolytes
• Renal and liver function test
• ECG may show ST-T wave changes and arrhythmias
• Nerve conduction studies.
Management
General Measures
• Maintain airway, breathing and circulation
• Body should be washed thoroughly as OPC can get absorbed through skin
also
• Gastric lavage using normal saline
• Activated charcoal can be given ( 1g/kg every 6th hourly for 1–2 days).
Specific Measures
• Atropine: It is the antidote of choice. It should be given at a dose of 1–2 mg
every 3–5 minutes till the signs of atropinization occurs which include dry
Chapter 20 Poisoning 155
axilla, clear lungs, heart rate >80/minute, absent pinpoint pupils and systolic
blood pressure >90 mm Hg. But high dose can cause delirium.
• Pralidoxime: It is a cholinesterase reactivator and is given at a dose of
30 mg/kg bolus infusion (in 100 mL normal saline over a period of 1 hour)
followed by 8 mg/kg/hour for next 2 days and 1–2 g IV tds for next 5 days.
Certain studies showed lack of benefit when given in low dose but still
World Helath Organization (WHO) recommends use of oximes in patients
with organophosphorus poisoning who is on atropine. It is not indicated in
carbamate poisoning.
• Benzodiazepines: It is indicated if seizures are present or if the patient
develops atropine delirium.
ORGANOCHLORINE AND PYRETHROID POISONING (TABLE 20.2)
Table 20.2 Organochlorine compounds and pyrethroids
Organochlorine compounds
• Endosulfan
• Aldrin
• Dieldrin
• Chlordane
• Endrin, etc.
Pyrethroids
• Cypermethrin
• Cyclothrin
• Deltamethrin, etc.
Clinical Features
Organochlorine toxicity produces nausea, vomiting, diarrhea, paraesthesias,
confusion, seizures and coma. The other complications include respiratory
failure and liver cell failure. Pyrethroids usually causes only sensory disturbances
like burning, tingling sensation and numbness.
Management
This includes the general measures that have been outlined under
organophosphorus poisoning. There is no specific antidote for these poisons.
Commonly seen plant poisoning include:
• Oleander
• Cleistanthus collinus (oduvanthalai).
Oleander Poisoning
The common plants are Nerium oleander and Thevetia peruviana. All parts of the
plants are poisonous.
Clinical features
Patients usually present with nausea, vomiting, abdominal pain and numbness
in the mouth. Oleander poisoning can affect the heart and in fact, the cardiac
involvement is the most common cause of death in this poisoning. The various
cardiac effects are bradyarrhythmias, conduction block, myocarditis and cardiac
arrest. Hyperkalemia and metabolic acidosis are also seen with this poison.
Management
General measures as outlined above should be followed. If the patient has
bradycardia, Inj. atropine 0.6–1.2 mg IV should be given. Oral orciprenaline 10
mg tds can also be given. Temporary pacing should be done in case of significant
conduction block.
Oduvanthalai Poisoning
It belongs to Cleistanthus collinus and the toxic constituents are dyphyllin,
cleistanthin and collinusin. This poison acts by inhibiting Na-K ATPase,
cholinesterase and DNA synthesis.
Clinical features
Patient usually presents with nausea, vomiting, diarrhea and abdominal pain. The
complications include cardiotoxicity (VT, VF, asystole), renal tubular acidosis,
renal failure, coagulopathy, neuromuscular blockade, respiratory failure and
hypokalemia (due to renal loss of potassium).
Investigations
These include serum electrolytes, ABG, renal and liver function test, coagulation
profile. The ECG changes of this poisoning are QT prolongation, ST depression,
VPCs, etc.
Treatment
Apart from the general measures in the management, hypokalemia should be
corrected by potassium chloride (KCL) infusion at a rate of around 20 mEq/hr.
Serum potassium should be monitored every 4th hourly till it is corrected and
then twice a day for the next 5 days. Bradycardia should be managed with Inj.
atropine/tab. Orciprenaline/ temporary pacing. Ventilatory support and dialysis
are indicated in appropriate cases.
Rodenticide Poisoning
Rodenticides are used to kill mice, rats and other small rodents. It contain various
constituents such as aluminum phosphide, zinc phosphide, warfarin, strychnine,
etc.
Clinical features
The clinical features and complications depend on the constituent present in
it. Phosphides present as chest pain, pulmonary edema, renal failure and liver
failure. Arsenic content cause diarrhea, shock and delirium whereas warfarin
causes bleeding diathesis. Stiffness of the limbs is noted in strychnine.
Chapter 20 Poisoning 157
Treatment
General measures as outlined previously. Specific measures include Inj. vitamin
K (1 amp IV for 3 days) and fresh frozen plasma are given for bleeding diathesis
and benzodiazepines (diazepam/midazolam) are given if fits occur. Hemodialysis
is indicated if renal failure is present.
Corrosive Poisoning
Corrosives include acids or alkali or both. Alkalis are more dangerous than the
acids as it has the tendency to cause liquefactive necrosis. Common corrosives
which are used as poisons are household bleaches and toilet cleaners.
Clinical features
Corrosives cause damage to the skin and produce redness, edema and charring.
Consumption of corrosives also cause serious damage to the oral cavity,
respiratory tract and gastrointestinal (GIT) resulting in complications like GIT
perforation, bronchospasm, pulmonary edema, mediastinitis and shock.
Treatment
Maintain airway, breathing and circulation. Nasogastric tube, neutralization with
milk and activated charcoal are contraindicated. Adequate hydration through IV
fluids is a must and signs of peritonitis or mediastinitis has to be looked for. Upper
GI scopy should be done within 48 hours to assess the severity of the injury.
Kerosene Poisoning
Kerosene is a hydrocarbon and accidental ingestion is common in children.
It predominantly affects the respiratory system as this volatile chemical may
displace alveolar oxygen and also cause damage to the alveolar membranes.
Clinical features
Patient usually presents with cough, fever, nausea, vomiting, abdominal pain,
lethargy, etc. On examination, patient may have cyanosis, tachypnea, wheeze
and crackles. The complications include seizures, coma, ARDS, myocarditis and
arrhythmias.
Investigations
Chest X-ray
Chest X-ray should be taken for all symptomatic patients. Positive findings are
usually seen only after few hours of ingestion and these include perihilar opacities,
bibasal infiltrates, atelectasis and rarely pneumothorax or pneumomediastinum.
Treatment
The priority is given to airway stabilization and if necessary, intubation and
mechanical ventilation with PEEP should be provided. Routine prophylactic use
of corticosteroids or antibiotics is not warranted.
BIBLIOGRAPHY
1. Aaron CK. Organophosphates and carbamates. In: Ford MD, Delaney KA, Ling LJ,
Erickson T, (Eds) Clinical toxicology. WB Saunders Company; Philadelphia; 2001. pp.
819-28.
2. Aggarwal R, Diddee S. Organophosphate or organochlorines or something else….?
Indian J Crit Care Med. 2009;13(1):31-3.
3. Cannon RD, Ruha AM. Insecticides, herbicides, and rodenticides. In: Adams JG (Ed).
Emergency Medicine Clinical Essentials, 2nd edn. Philadelphia, PA: Elsevier Saunder;
2013.
4. Cherian AM, Peter JV, Samuel J. Effectiveness of P2AM (PAM-pralidoxime) in the
treatment of organophosphorus poisoning. A randomized, double blind placebo
controlled trial. J Assoc Physicians India. 1997;45:22-4.
5. Eade NR, Taussig LM, Marks MI. Hydrocarbon pneumonitis. Pediatrics. 1974;54:351-
7.
6. Eddleston M, Buckley NA, Eyer P, Dawson AH. Management of acute organophosphorus
pesticide poisoning. Lancet. 2008;371(9612):597-607.
7. Eddleston M, Singh S, Buckley N. Organophosphorus poisoning (acute). Clin Evid.
2005;13:1744-55.
8. Fengsheng He. Synthetic pyrethroids. Toxicology. 1994;91:43-9.
9. He F, Wang S, Liu L, Chen S, Zhang Z, Sun J. Clinical manifestations and diagnosis of
acute pyrethroid poisoning. Arch Toxicol. 1989;63:54-8.
10. Jeyaratnam J. Acute pesticide poisoning: a major global health problem. World Health
Stat Q. 1990;43:139-44.
11. Johnson MK, Jacobsen D, Meredith TJ. Evaluation of antidotes for poisoning by
organophosphorus pesticides. Emerg Med. 2000;12:22-37.
12. Johnson S, Peter JV, Thomas K, Jeyaseelan L, Cherian AM. Evaluation of two treatment
regimens of pralidoxime (1 gm single bolus dose vs 12 gm infusion) in the management
of organophosphorus poisoning. J Assoc Physicians India. 1996;44:529-31.
13. Langford SD, Boor PJ. Oleander toxicity: an examination of the human and animal
toxic exposures. Toxicology. 1996;109:1-13.
14. Lotti M. Clinical toxicology of anticholinesterase agents in humans. In: Krieger R (Ed).
Handbook of Pesticide Toxicology. 2nd edn. Academic Press; San Diego. 2001;2:1043-
85.
15. McConnell R, Hruska AJ. An epidemic of pesticide poisoning in Nicaragua: implications
for prevention in developing countries. Am J Public Health.1993;83:1559-62.
16. Namba T, Hiraki K. PAM (pyridine-2-aldoxime methiodide) therapy of alkylphosphate
poisoning. JAMA. 1958;166:1834-9.
17. Parikh CK. Parikh Textbook of Medical Jurisprudence and Toxicology, 4th edn.
Bombay, Medical Publication; 1989.pp.912-4.
18. Raghu R, Naik R, Vadivelan M. Corrosive poisoning. Indian J Clini Practice. 2012;23(3).
19. Thomas K, Dayal AK, Gijsbers A, Seshadri MS. Oduvanthalai leaf poisoning. J Assoc
Physicians India. 1987;35:769-71.
CHAPTER
21 Jenu Santhosh, TA Naufal Rizwan
DRUG OVERDOSE
SEDATIVES AND HYPNOTICS

These drugs are used in the treatment of insomnia and anxiety disorders.
Barbiturates and benzodiazepines are the most important drugs of this group.
Clinical Features
The symptoms common to overdose of both these drugs include decreased
mentation, hypotension, dysarthria, slurred speech, bradycardia and loss of
reflexes. Respiratory depression is seen with overdose of both the drugs, although
more severe with the barbiturates. Extensor plantar response, coma and blisters
over pressure spots and dorsum of the fingers are seen with barbiturates overdose.
Treatment
• General measures, as previously explained under the chapter of general
principles, have to be followed.
• Forced alkaline diuresis and hemoperfusion are indicated in severe
barbiturate poisoning (they are not useful in benzodiazepine poisoning)
• Flumazenil is the antidote for benzodiazepine poisoning. The dose is 0.2 mg
over 30 seconds followed by 0.3 mg at 1 minute intervals to a total dose of 3 mg.
ANTIDEPRESSANTS
The commonly used antidepressants are tricyclic antidepressants and SSRIs.
Newer drugs such as mirtazepine and venlafaxine are usually less toxic than the
tricyclics.
Clinical Features
Patients usually present with anticholinergic features such as dilated pupils,
urinary retention, dryness of mouth and fever. The two important complications
of this poisoning are cardiotoxicity and neurotoxicity. Cardiac involvement is
manifested by supraventricular tachycardia, ventricular tachycardia (predicted
by QRS duration of limb leads >160 msec), conduction blocks and pulmonary
edema whereas CNS involvement is manifested as agitation, confusion, seizures
and coma.
Treatment
In addition to the general measures, the cardiotoxic effects of antidepressants
are treated by forced alkaline diuresis, hyperventilating the intubated patient
(to keep PCO2 no lower than 25 mm Hg) and temporary pacing for conduction
blocks. Seizures are treated with benzodiazepines and the CNS depression can be
reversed with Inj. Physostigmine (2 mg IV over 1 min).
ACETAMINOPHEN POISONING
Acetaminophen poisoning is very common since the drug is freely available over
the counter. It mainly affects the liver and the toxicity dose is 140 mg/kg or at
least 7.5 g. The mechanism involved in hepatic toxicity is due to the depletion of
hepatic glutathione and the subsequent accumulation of a metabolite, N-acetyl-
p-benzoquinoneimine.
Clinical Features
The usual initial complaints are nausea, vomiting and loss of appetite. Patient will
have elevated liver enzymes that can even reach 1000 U/L. Other manifestations are
encephalopathy, renal failure, hypoglycemia, metabolic acidosis. Death may be due
to fulminant hepatic failure, ARDS, multiorgan failure, sepsis and cerebral edema.
Treatment
General measures as discussed under the chapter of general principles have to
be followed. Charcoal is not effective when it is given 30 min after drug ingestion.
N-acetyl cysteine is the specific antidote and it can be given either IV or oral.
The oral dose is 140 mg/kg followed by 70 mg/kg for a total of 17 doses. The IV
dose is 150 mg/kg in 200 mL of 5% dextrose over 1 hour followed by 50 mg/kg
over 4 hours and 100 mg/kg over 16 hours. N-acetyl cysteine (NAC) prevents
the severity of hepatic necrosis in patients who have high acetaminophen levels
(>200 µg/mL measured at 4 hour or >50 µg/mL at 12 hour after ingestion). NAC
is most effective if it is given within 8 hours of drug ingestion but can be given
even till 36 hours of ingestion. Liver transplantation is the treatment in case of
fulfillment of the below criteria (Table 21.1).
Table 21.1 Criteria for orthotopic liver transplantation in acetaminophen toxicity
• Acute hepatic failure (e.g. mental confusion, jaundice, coagulation disturbances)

• Metabolic acidosis despite fluid resuscitation (pH <7.3, lactate levels >3.5 mmol/L)
• PT >100 sec, INR >6.5
• Serum creatinine >3.3 mg/dL or 300 µmol/L
• Encephalopathy grade ≥III within 24 hour period.
OPIOIDS
Opioids cause sedation and respiratory depression at high doses and the peak
effect of most opioids occurs within 3 hours but the elimination half-life differs
Chapter 21 Drug Overdose 161
with most opioids. Clinical features include pinpoint pupils, bradycardia,

hypotension, lethargy, respiratory depression, seizures. Proper history along with
lab investigations—serum electrolytes, glucose, arterial blood gases or oximetry,
chest X-ray, routine toxic screening is done. Treatment includes usual general
measures. Specific treatment includes administration of opioid antagonist—
naloxone, nalmefene. Naloxone 0.4–2 mg IV and doses are repeated every 2–3
minutes and upto a total dose of 10–20 mg can be given. Duration of naloxone
is 1–2 hours and patient is not discharged until 3–4 hours since the last dose
of naloxone. It is better to observe for 6–12 hours. Intubation and mechanical
ventilation may be required in case of respiratory failure.
BETA-BLOCKERS
Beta-blockers are widely used for the treatment of hypertension, angina pectoris,
cardiac arrhythmias, heart failure, glaucoma, etc. Beta-blockers overdose can
occur and complications are more with those with cardiac disease. Clinical
features include hypotension, bradycardia, prolonged PR interval, heart block,
pulmonary edema, cardiac arrest, hyperkalemia. Bronchospasm, seizures,
hypoglycemia and coma are not uncommon. Atropine is not effective in these
patients although it is commonly used by most physicians. Glucagon is given
at a dose of 5–10 mg and followed by infusion of 1–5 mg/hour. Alternatively,
adrenaline infusion can be given at a dose of 1–4 µg/minute. Cardiac pacing is done
in case of severe bradycardia not responding to medical management. Torsades
de pointes can result from Sotalol which can be treated with isoproterenol and
magnesium. Correction of hypokalemia may be necessary.
BIBLIOGRAPHY
1. Barnett R, Grace M, Boothe P, et al. Flumazenil in drug overdose: randomized,
placebo-controlled study to assess cost effectiveness. Crit Care Med. 1999;27(1):78-81.
2. Blackford MG, Felter T, Gothard MD, Reed MD. Assessment of the clinical use of
intravenous and oral N-acetylcysteine in the treatment of acute acetaminophen
poisoning in children: a retrospective review. Clin Ther. 2011;33(9):1322-30.
3. Jay SJ, Johanson WG Jr, Pierce AK. Respiratory complications of overdose with sedative
drugs. Am Rev Respir Dis. 1975;112(5):591-8.
Principles of Internal Medicine, 18th edn. McGraw Hill publications; 2012.
5. Mindikoglu AL, et al. Outcome of liver transplantation for drug-induced acute
liver failure in the United States: Analysis of the United Network for Organ Sharing
database. Liver Transpl. 2009;15:719.
6. Navarro VJ, Senior JR. Drug-related hepatotoxicity. N Engl J Med. 2006;354:731.
7. Olson KR. Poisoning and Drug Overdose, 5th edn. McGraw Hill-Publications; 2006.
8. Smilkstein MJ, Knapp GL, Kulig KW, Rumack BH. Efficacy of oral N-acetylcysteine in
the treatment of acetaminophen overdose. Analysis of the national multicenter study
(1976 to 1985). N Engl J Med. 1988;319(24):1557-62.
9. Spiller HA, Krenzelok EP, Grande GA, Safir EF, Diamond JJ. A prospective evaluation
of the effect of activated charcoal before oral N-acetylcysteine in acetaminophen
overdose. Ann Emerg Med. 1994;23(3):519-23.
10. Worthley LI. Clinical toxicology: part I. Diagnosis and management of common drug
overdosage. Crit Care Resusc. 2002;4(3):192-215.
CHAPTER
22 Jenu Santhosh
ENVENOMATION
SCORPIONS (SCORPIONIDAE)
Scorpions are found in many parts of the world. Toxic species of scorpions are
found in India also. They are generally nocturnal and capable of stinging humans.
They have paired venom glands in a bulbous segment called the telson.
Clinical Features
C. exilicauda venom causes prolonged depolarization due to opening of
neuronal sodium channels. Somatic and autonomic nerves can be affected.
Cranial nerve palsy can occur in severe cases causing abnormal eye movements,
blurred vision and respiratory failure. Motor dysfunction can present with jerking
of limbs mimicking like seizures. Symptoms like nausea, vomiting, agitation
and tachycardia can be severe due to the sting especially in children. Pain,
paresthesias in the area of sting are the initial symptoms which later may become
generalized. Symptoms can last for 24–48 hours without antivenom treatment.
The complications of scorpion sting include pulmonary edema, cardiac
dysfunction, pancreatitis, bleeding diathesis, skin necrosis and occasionally
death. Diagnosis of scorpion sting is primarily clinical since it can be confused
with other conditions causing local pain.
Treatment
Initial treatment is mainly supportive with analgesics. Scorpion antivenom can
be used if available. Local toxic agency help should be sought for dosage and
use of antivenom. Both immediate and delayed allergic reactions including
serum sickness can occur with the use of antivenom and hence antivenom
administration should be reserved for cases of severe systemic toxicity. Some
studies have demonstrated lack of benefit in the routine administration of
antivenom for scorpion stings although antivenom produces rapid resolution of
symptoms in severe toxicity. Usually 1–2 vials are sufficient for severe cases.
CATERPILLARS AND MOTHS (LEPIDOPTERA)

The adverse effects resulting from contact with caterpillars, butterflies and moths
are called lepidopterism.
Chapter 22 Envenomation 163
Clinical Features
Caterpillars are the larval stage of moths and have either spines or hairs for
protection. The spines and hairs may cause mechanical irritation, whereas the
venom can produce additional symptoms. Most of the caterpillars are harmless
to humans. Pruritus from localized caterpillar dermatitis and diffuse urticaria
are the predominant symptoms with exposure to the hairs and venom. With
certain species, intense local burning pain rather than pruritus is typical. A grid
like pattern of hemorrhagic papules may be seen within 2–3 hours of exposure
and may last for several days. Regional lymphadenopathy is common, and the
affected limb can swell considerably. Other symptoms include headaches, fever,
hypotension, and convulsions. Mortality due to caterpillar contact is rare.
Treatment
No antivenom is available till date and the treatment is mainly symptomatic
and supportive. Spines of caterpillars can be removed by adhesive tape.
Antihistamines and steroids may be administered for pruritus. Intravenous fluids
and subcutaneous epinephrine may be needed if hypotension arises.
REPTILE BITES
Introduction
Snake bite is very common in India since most of the population resides in the
rural areas which is a home for many species of snakes. Mortality due to snake
bite is quite high in India due to superstitions and delay in the administration
of antivenom. The major venomous snakes can be divided into the following
groups.
• Viperidae (vipers)
• Elapidae
• Hydrophinae (sea snakes).
Crotalinae (Pit Viper) Bites

Crotaline snakes are also called as pit vipers and they are distinguished from
other snakes by the presence of two fangs that fold against the roof of the mouth,
in contrast to the coral snakes, which have shorter, fixed, and erect fangs and
bilateral pits present midway below and between the eye and the nostril.
Pathophysiology
The venom of these species contains a complex enzyme which can cause
systemic and local tissue injury. Hemolysis, fibrinolysis, increased vascular
permeability, hypovolemia and dysfunction of the neuromuscular junction
are the manifestations. Coagulopathy is due to activation and consumption of
fibrinogen and platelets. Ptosis due to cranial nerve palsy, respiratory failure and
mental confusion are other features.
Clinical Features
Clinical manifestations of snake bite depend on the following:
• Age of the victim
• Species of snake
• Characteristics of the bite (location, depth, and number, the amount of
venom injected)
• Time elapsed since the bite.
About 1/4th of the snake bites are dry and do not result in any manifestations.
Usually fang marks are seen, localized pain, edema on the site of bite which can be
progressive, oral numbness, tingling sensation, tachycardia, muscle fasciculation,
altered consciousness can be seen. Usually local edema occurs within 30 minutes
but in severe cases, edema can be very severe and that too can progress very fast
to the entire limb. Airway edema can occur which in turn causes upper airway
obstruction. Ecchymosis and coagulopathy are other clinical manifestations.
Diagnosis
It is based on eliciting history and the presence of fang marks. Snake bite can
manifest with the features given in Flow chart 22.1.
The absence of any of these manifestations for a period of 8–12 hours
following the bite indicates a dry bite.
Treatment
First aid
First aid measures should never substitute or delay the definitive treatment
for snake bite (administration of antivenom). All patients bitten by a pit viper
should be taken to a hospital (Table 22.1). Suction of the bite site, ice application,
application of electric shock, tourniquet application and incision of the site of bite
Flow chart 22.1 Manifestations of snake bite
Table 22.1 Recommended first aid measures for snake bite
• Evacuate the patient from the danger zone to prevent another bite
• Immobilization of the bitten limb in a neutral position to prevent absorption of venom
• Minimize physical activity
• Transfer the patient to hospital where antivenom is available.
are dangerous and should not be performed. Application of tourniquet obstructs

arterial flow and can cause ischemia, hence is contraindicated.
Emergency Management
As an emergency measure, an intravenous access, administration of oxygen
and limb immobilization can be done before transfer to a health facility where
antivenom is available. Tourniquets and constriction bands if present should not
be removed until intravenous access is established and in case of hypotension,
rapid intravenous isotonic fluid infusion is given.
Antivenom is the mainstay of therapy for poisonous snakebite. Composition
of antivenom is antibodies derived from the serum of animals injected and
immunized with snake venom. Patients who show progressive signs and
symptoms (local signs, coagulopathy and hypotension) after snake bites with
pit vipers should be given antivenom immediately. Recent trials have shown
that FabAV is more effective and safe than polyvalent antivenom. FabAV does
not require local skin testing and administered as a single large initial dose
followed by three maintenance doses. Initial dose is 4–6 vials which can be
repeated if necessary based on initial control (cessation of progression of local
signs, systemic effects, and coagulopathy). After initial control has been achieved,
2 vials are given as maintenance doses. Antivenom should be administered only
in ICU with all the resuscitative drugs for anaphylactic reaction kept ready.
Dilution of antivenom is done with 250 mL of crystalloid and intravenously
infused slowly over 10 minutes initially to watch for anaphylaxis followed by total
infusion within 1 hour. Intramuscular route is not recommended. In case of any
anaphylactic/anaphylactoid reaction, infusion is terminated immediately and
antihistaminics, corticosteroids are given. Adrenaline is administered in case of
severe allergic reactions. In case of hypotension, isotonic fluids like normal saline
or ringer lactate is used, if hypotension sustains after fluid administration, then
vasopressors are given. Antivenom administration itself corrects coagulopathy
but in case of active bleeding despite antivenom may require plasma. Monitoring
limb circumference every 30 minutes is one of the guides for antivenom
effectiveness. Lab parameters are done every 4 hours.
Compartment syndrome is one of the complications which occurs due
to increased compartment pressure due to venom spread into the muscle
compartment which manifests as severe pain. The use of fasciotomy in
compartment syndrome due to snake bite is controversial (Table 22.2).
Table 22.2 Management of compartment syndrome
• Determine intracompartmental pressure

• If not elevated, continue the usual management
• If signs of compartment syndrome are present and compartment pressure is >30 mm Hg:
– Elevate limb
– Mannitol is given at a dose of 1–2 g/kg IV over 30 minutes
– Simultaneously administer additional antivenom, 4–6 vials IV over 60 minutes
– Consider fasciotomy in case of elevation in compartment pressure which is
persistent for another 1 hour.
Tetanus immunization is done and antibiotic therapy should be started

only if there is presence of infection. The use of steroids is controversial. Delayed
serum sickness can present with fever, rash, and arthralgias and should be treated
with oral prednisone 60 mg/day and tapered over 1–2 weeks.
Discharge Criteria
Patients can be discharged once the swelling begins to subside, coagulopathy is
reversed, and patient is ambulatory. Patients with dry bites should be observed
for at least 8 hours. Follow-up is required.
Coral Snake (Elapid) Bite

Elapids are found throughout the world in tropical and warm climates. Cobras
(Naja), kraits and mambas belong to this group. Elapid bites produce primarily
neurologic effects like diplopia, dysarthria, ptosis along with bulbar paralysis,
dysphagia, dyspnea, contracted pupils, tremors, salivation, respiratory failure
and rarely seizures. The usual immediate cause of death is paralysis of respiratory
muscles although the clinical manifestations can be delayed up to 12 hours.
Respiratory failure results from the effects of neurotoxin, hence measuring
maximal inspiratory pressure and vital capacity can be useful in these patients.
Patient needs to be observed for signs of respiratory muscle weakness and
reduced ventilation. Local swelling is monitored every hour after snake bite by
measuring limb circumference, the presence and extent of local ecchymosis, and
assessment of circulation.
Treatment
First aid measure
Aim of initial first aid measure is to delay absorption of venom till the patient is
shifted to hospital where antivenom is available. Patients with elapid snake bites
should have their limb wrapped in an elastic bandage applied initially over the
bite site and then covering the entire limb. The limb is then splinted to prevent
movement. The principles behind these measures are to prevent systemic
absorption of the venom. Application of tourniquet obstructs arterial flow and
can cause ischemia, hence is contraindicated.
Emergency Management
History of snakebite or suspected cases should prompt the initiation of
investigation and observation. The pressure bandage should be kept in place
until the patient receives antivenom. If there is immediate deterioration of the
patient after bandage removal, the bandage can be reapplied while antivenom
is given.
Antivenom should be administered only in patients who have clinical or
laboratory evidence of envenomation. Investigations include complete blood
count, serum electrolytes, renal and liver function test, coagulation profile,
creatine kinase, and urine testing for hematuria or myoglobinuria. Abnormal renal
Table 22.3 Indications of antivenom
• Neurological effects such as diplopia, dysarthria, ptosis along with bulbar paralysis,
dysphagia, dyspnea, contracted pupils, tremors
• Vomiting and severe headache
• Progressive muscle weakness with diaphragmatic involvement
• Coagulopathy
or coagulation parameters should warn the physician of imminent neurological

effects since systemic envenomation has occurred. In case of increased PT, aPTT,
serum fibrinogen and FDP degradation products are done (Table 22.3).
It is recommended that 3–5 vials of antivenom be administered to patients
who have been bitten if there is evidence of the above indications. If there is
no clinical or laboratory evidence of venom effect, the elastic bandage should
be removed and the patient observed for 12 hours. Coagulation profile should
be repeated every 2 hours after bandage removal. When indicated, antivenom
should be given immediately and there is no difference in dosage between an
adult and children. Pregnancy is not a contraindication to antivenom therapy.
Skin testing before antivenom administration is not recommended as it
may sensitize the patient to future antivenom use and delays definitive therapy.
Anaphylaxis is a rare complication of antivenom therapy, hence administration
of a small subcutaneous dose of 0.3 mL of 1:1000 epinephrine (adrenaline) in an
adult or 0.1 mL in a child along with a parenteral antihistamine is the author’s
suggestion. A 5-day course of oral prednisolone can be prescribed to reduce
the incidence of serum sickness in those patients who receive large doses of
antivenom.
Cobra Bite
Cobras are mostly found in southern Asia and very commonly seen in India and
also in Africa. Nearly ½ of the bites are dry. Certain species of cobras have the
ability to spit jets of venom toward the victim’s eyes.
Cobra venom contains a mixture of toxins.
• Neurotoxin is the predominant effect of cobra snakes. They bind to
postsynaptic acetylcholine receptors and produce depolarizing neuro
muscular blockade.
• Cell membrane toxins produce cardiac arrhythmias and impaired contractility.
• Enzymes can breakdown protein and connective tissue.
Clinical Features
Pain at the bite site, local swelling, cranial nerve dysfunction (ptosis, diplopia,
dysphagia), generalized muscle weakness followed by paralysis, respiratory
failure, altered sensorium, hemodynamic instability and parasympathetic
stimulation (salivation and bronchorrhea) are all clinical manifestations. Victims
injured in the eye of venom present with pain, burning sensation, and blurred
vision. Skin reaction around the bite site may develop over 48 hours with local
hemorrhage and necrosis. Coagulopathy is rare following a cobra bite with

exception of spitting cobra.
Treatment
First aid
The pressure-immobilization technique used for common snakes has not been
found to be useful with cobra bites. The constricting elastic bandage can be used
although still not recommended. In case of venom exposure to the eyes, irrigation
of eyes is useful.
Emergency treatment
The mainstay of treatment found to be effective for cobra bite is administration
of polyvalent antivenom. Antivenom is obtained by antibodies derived from
the serum of animals injected and immunized with snake venom obtained
from several cobra species in that region but there is high incidence of allergic
reactions with this antivenom. Antivenom is started before releasing the
bandage in patients with evidence of systemic toxicity but antivenom is effective
only for reducing systemic toxicity and not for reducing local tissue injury. For
patients with significant muscle weakness or paralysis, anticholinesterases
like neostigmine can produce short-term benefit till antivenom are available.
Hypotension is treated with fluids and vasopressors. In case of respiratory failure,
intubation and mechanical ventilation is started.
Disposition
Patients without signs of envenomation should be observed in ICU for 24
hours since signs of systemic toxicity usually occur in 2–6 hours and mortality
is common during this period. Patient may take 1 week to recovery in case of
antivenom administration and supportive treatment.
BIBLIOGRAPHY
1. Burgess JL, Dart RC, Egen NB, Mayersohn M. The effects of constriction bands on
rattlesnake venom absorption: A pharmacokinetic study. Ann Emerg Med. 1992;
21:1086.
2. Bush SP, Hegewald K, Green SM, et al. Effects of a negative pressure venom extraction
device (Extractor) on local tissue injury after artificial rattlesnake envenomation in a
porcine model. Wilderness Environ Med. 2000;11:180.
3. Dart RC, McNally J. Efficacy, safety, and use of snake antivenoms in the United States.
Ann Emerg Med. 2001;37:181.
4. Dart RC, Stark Y, Fulton B, et al. Insufficient stocking of poisoning antidotes in hospital
emergency departments. JAMA. 1996;276:1508.
5. Davidson TM, Schafer S, Killfoil J. Cobras. Wilderness Environ Med. 1995;6:203.
6. Gold BS, Dart RC, Barish RA. Bites of venomous snakes. New Engl J Med. 2002;347:347.
7. Gold BS. Neostigmine for the treatment of neurotoxicity following envenomation by
the Asiatic cobra. Ann Emerg Med. 1996;28:87.
8. Hawdon GM, Winkel KD. Could this be snakebite? Aust Fam Physician. 1997;26:1386-
94.
9. Howath DM, Southee AE, Whyte IM. Lymphatic flow rates and first-aid in simulated
peripheral snake or spider envenomation. Med J Aust. 1994;161:695.
10. Kent R Olson. Poisoning and Drug Overdose, 5th edn. 2006. McGraw Hill Publications.
11. Kitchens CS, Van Mierop LHS. Envenomation by the eastern coral snake (Micrurus
fulvius fulvius): A study of 39 victims. JAMA. 1987;258:1615.
12. Langley RL, Morrow WE. Deaths resulting from animal attacks in the United States.
Wilderness Environ Med. 1997;8:8.
13. Lee C, Ryan M, Arnold T. Local manifestations of Agkistrodon contortrix (copperhead)
envenomation treated successfully with Crotalidae polyvalent immune Fab (ovine)
Crofab [abstract 214]. J Toxicol Clin Toxicol. 2001;39:559.
14. Offerman SR, Bush SP, Moynihan JA, Clark RF. Crotaline Fab antivenom for the
treatment of children with rattle snake envenomation. Pediatrics. 2002;110:968.
15. Pochanugool C, Limthongkul S, Wilde H. Management of Thai cobra bites with a
single bolus of antivenin. Wilderness Environ Med. 1997;8:20.
16. Ruha AM, Curry SC, Beuhler M. Initial postmarketing experience with Crotalidae
Polyvalent Immune Fab for treatment of rattlesnake envenomation. Ann Emerg Med.
2002;39:609.
17. Sutherland SK. Antivenom use in Australia. Premedication, adverse reactions and the
use of venom detection kits. Med J Aust. 1992;157:734.
18. Sutherland SK. Deaths from snake bite in Australia, 1981–1991. Med J Aust. 1992;157:
740.
19. Tagwireyi DD, Ball DE, Nhachi CF. Routine prophylactic antibiotic use in the
management of snakebite. BMC Clin Pharmacol. 2001;1:4.
20. Tibballs J. Premedication for snake antivenom. Med J Aust. 1994;160:4.
21. White J. Bites and stings from venomous animals: A global overview. Ther Drug Monit.
2000;22:65.
22. White J. CSL Antivenom Handbook. Melbourne, Australia, CSL Ltd, 2001.
23. White J. Envenoming and antivenom use in Australia. Toxicon. 1998;36:1483.
SECTION
7 BURNS
Chapter 23 Classification and Evaluation

of Burns
Prem Kumar
Chapter 24 Management of Burns

Prem Kumar
CHAPTER
23 Prem Kumar
CLASSIFICATION AND EVALUATION

OF BURNS
The incidence of burns in India is 6–7 million per year. About 10% of these are
life-threatening and require hospitalization, and they require multiple surgeries
and prolonged rehabilitation.
CLASSIFICATION
There are 3 zones, 5 depths and 5 causative types of burns injury.
Three Zones
1. Zone of coagulation
2. Zone of stasis
3. Zone of hyperemia.
Five Depths (Fig. 23.1)

1. First degree—superficial two epidermal
2. Second degree—it has two types: Superficial and deep partial thickness
3. Third degree—full thickness
4. Fourth degree—involvement of deep structures such as muscle and bone.
Five Causative Types

1. Hot liquids
2. Fire—flame
3. Contact with hot objects
4. Chemical
5. Electrical conduction.
PHYSIOLOGICAL DISTURBANCES (TABLE 23.1 AND FLOW CHART 23.1)

Burns can affect all systems but it depends on the type of burns, depth of
involvement and the timing of postinjury.
174 Section 7 Burns
Fig. 23.1 Layers of skin and depth of burns
Table 23.1 Physiological disturbances due to burns on various systems
• Respiratory system:
– Early phase—Inhalational injury causing airway obstruction, CO poisoning.
– Delayed phase–After few days, patient may develop ARDS, pulmonary embolism,
pneumonia, respiratory failure.
– Presence of inhalational injury is an indication for endotracheal intubation.
• Cardiovascular system: Hypovolemia causing reduced tissue perfusion and lactic
acidosis. Myocardial depression and venous thromboembolism.
• Central nervous system: Seizures due to hyponatremia, peripheral nerve injury.
• Gastrointestinal system: Curling’s ulcer, acute necrotizing enterocolitis, acalculous
cholecystitis, pancreatitis, hepatic dysfunction due to reduced hepatic blood flow.
• Renal system: Acute renal failure occur due to reduced renal blood flow.
• Endocrine system: Acute adrenal insufficiency can occur due to necrosis.
• Hematology: Anemia, platelet dysfunction, thrombocytopenia, DIC.
• Eye: Corneal ulcer, ectopia.
BURNS ASSESSMENT
History: Ample history is asked and the cause and duration of burns is elicited.
Clinical assessment of burns is based on:
• Burns surface area estimation—rule of Nines, Lund and Browder chart, hand
method (Figs 23.2 and 23.3).
• Depth of burns (Table 23.2)
• Presence or absence of circumferential burns.
Chapter 23 Classification and Evaluation of Burns 175
Flowchart 23.1 Pathophysiology of burns
Abbreviations: ROS, reactive O2 species; SIRS, systemic inflammatory response syndrome
Fig. 23.2 Rule of Nine chart

176 Section 7 Burns
Fig. 23.3 Lund and Browder chart
Table 23.2 Depth of burns and its features
Depth of burns Skin color Sensory Blisters Wound healing

1st degree (Figs Red and blanch Painful Absent • Within 1 week
23.4A and B) to touch • No scarring
2nd degree— Pink, may Painful Present • Within 2 weeks
superficial partial blanch to touch • May need skin grafting
(Figs 23.5A to C) • Heals with scarring
2nd degree—deep Red/white Painful Variable • Within 2–3 weeks
partial (Figs 23.6A • Needs skin grafting
to C) • Heals with scarring
3rd degree—full Black or cherry Painless Absent • Needs skin grafting
thickness (Figs 23.7A red • Heals with scarring
to C)
A B
Figs 23.4A and B I Degree: Burns
A B
C
Figs 23.5A to C II Degree: Superficial burns
A B
C
Figs 23.6A to C II Degree: Deep burns
In the hand method of burns assessment, 1% of total body surface area

equals palm and fingers of the patient’s hand.
Patient with burns requires complete initial evaluation similar to evaluation
of a trauma patient but with some differences. Once the initial evaluation is
over, burn specific secondary survey should be done to recognize the insults on
various systems.
178 Section 7 Burns
A C
Figs 23.7A to C III Degree, burns (Courtesy: Dr Surya C Rao MS, MCH, Plastic
Surgeon)
Initial Evaluation
Airway compromise can occur due to pharyngeal edema/laryngeal edema which
can cause airway obstruction. Hence, the decision to intubate the patient should
be done at the earliest with clinical judgment. Securing the airway in burns
patient is quite challenging due to airway edema. Endotracheal tube is secured
with a tie over the back of neck.
Indications of Endotracheal Intubation

• Airway obstruction due to pharyngeal or laryngeal edema
• Depressed level of consciousness
• Hypoxemia not responding to treatment with oxygen
• Circumferential full thickness nasolabial burns.
Modes of Securing the Airway

• Nasal/oral intubation—blind or fiberoptic bronchoscopy guided
• Laryngeal mask airway
• Needle/surgical cricothyroidotomy
• Surgical tracheostomy
Intravenous access is initially done with peripheral vein for initial
resuscitation followed by central venous access for fluid management.
SECONDARY SURVEY
• History of injury
• Head and face evaluation: Look for eye globe injury (clouded appearance
over cornea), signs of inhalational injury (singed hairs, carbonaceous
debris), any pressure point over injured areas, whether endotracheal tube is
secured with tie.
• Central nervous system evaluation: Look for neurologic injury, order for CT-
brain and spine, if needed, pain and sedation management should be started
as early as possible (narcotics, benzodiazepines), determine CO-Hb level to
avoid CO toxicity.
• Look for chest wall movement and examine neck: If there is deep circumferen
tial burns, patient may require escharotomy to increase ventilation and
increase venous drainage.
• Evaluation of volume status: Most of the patients are hypovolemic. Start
resuscitation according to calculated fluid volumes with various formulas.
• Evaluation of extremities: In case of fracture, external splinting is done.
Doppler is done to determine blood flow so that escharotomy or fasciotomy
can be done, if there is vascular compromise.
• Look for lab investigations: Do arterial blood gas analysis, CO-Hb level, serum
urea, creatinine to rule out renal involvement, chest radiography is done to
rule out rib injury, pneumothorax, placement of central venous catheter.
BIBLIOGRAPHY
1. C Brunicardi F. Schwartz’s Principles of Surgery, 8th edn. McGraw-Hill Publications;
2004.
Raven; 2009.
3. Gupta JL, et al. National Programme for Prevention of Burn Injuries. Indian J Plast
Surg. 2010;43(Suppl):S6-10.
4. Hettiaratchy S, Papini R. Initial management of a major burn: Overview. BMJ. 2004;
328(7455):1555-7.
5. Irwin, Richard S Rippe, James M Irwin, Rippe’s Intensive Care Medicine, 6th edn.
Lippincott Williams and Wilkins Publications; 2008.
6. Stabilization, transfer and transport, in Advanced Burn Life Support Course Instructor
Manual. Chicago, American Burn Association. 2005.pp.73-8.
CHAPTER
24 Prem Kumar
MANAGEMENT OF BURNS
Burns are managed in three phases:

1. Early resuscitative phase
2. Wound management phase
3. Rehabilitative and reconstructive phase.
Gupta et al. proposed a strategy for management of patient with burns—
maintain circulation and blood pressure (shock management), maintain airway,
increase body resistance, avoid bacterial toxemia, avoid autotoxemia, watch for
renal complications and multiple organ dysfunctions, maintain nutrition, abide
by principles of biomechanical physiotherapy and rehabilitation and analyze
factors for reducing mortality. Burns referral criteria is given in Table 24.1 and
priorities in managing burns patient is given in Table 24.2.
EARLY RESUSCITATIVE PHASE

Massive capillary leak leading to increased capillary permeability ending up in
hypovolemia is the major alteration in this phase. Other reasons for fluid loss
are decreased reflection coefficient to proteins, increased evaporation of fluid
from wound surface, increased metabolic rate. Hence, fluid resuscitation plays a
major role in the management of this phase. Burns >15% requires calculation of
fluid infusion. There are many formulas for calculating volume requirements but
Table 24.1 Burn center referral criteria
The American Burn Association (ABA) criteria for referral

• Partial-thickness burns involving more than 10% of the total body surface area
• Full-thickness burns involving 1% or more of the total body surface area
• Less-extensive burns involving face, hands, feet, genitalia, perineum, or major joints
• Significant electric burns (including lightning injury), significant chemical burns,
significant inhalation injury
• Lesser burns in patients with preexisting medical conditions that can complicate
management, prolong recovery, or affect mortality
• Lesser burns in association with concomitant trauma sufficient to influence outcome
• Any size burn in a child in a hospital without qualified personnel or the equipment
needed for the care of children
• Any size burn in a patient who will require special social or psychiatric intervention or
long-term rehabilitation
Chapter 24 Management of Burns 181
Table 24.2 Priorities in managing burns patient
A Airway management
B Breathing
C Circulation
D Drugs-analgesics/vasopressors/inotropes/antibiotics/sedatives
E Escharotomy
F Fluid management
G General supportive care—physiotherapy/nutrition
Table 24.3 Formulas for fluid calculation in burns
Formula Initial 24 hours Next 24 hours

Parkland Ringer’s lactated (RL) solution 4 mL/ Colloids given as 20–60% of
kg/% burn, of which 50 % should be calculated plasma volume. Glucose
administered over 1st 8 hours in water (5%) is added in amounts
required to maintain a urinary output
of 0.5–1 mL/hour
Modified RL 4 mL/kg/% burn Begin colloid infusion of 5% albumin
Parkland 0.3–1 mL/kg/% burn/per hour
Brooke RL solution 1.5 mL/kg/% burn plus RL 0.5 mL/kg/% burn, colloids 0.25
colloids 0.5 mL/kg/% burn plus mL/kg/% burn and the same amount
2000 mL glucose in water (5%) of glucose in water (5%) as in the first
24 hours
Modified RL solution 2 mL/kg/% burn Colloids at 0.3–0.5 mL/kg/% burn.
Brooke Glucose in water (5%) is added in the
amounts required to maintain good
urinary output (0.5–1 mL/hour).
Evan’s Crystalloids 1 mL/kg/% burn plus Crystalloids at 0.5 mL/kg/% burn,
colloids at 1 mL/kg/% burn plus colloids at 0.5 mL/kg/% burn and
2000 mL glucose in water (5%). the same amount of glucose in water
(5%) as in the first 24 hours
Monafo Recommends using a solution Solution is titrated with 1/3 normal
containing 250 mEq Na, 150 mEq saline according to urinary output
lactate and 100 mEq Cl. The amount
is adjusted according to the urine
output.
repeated re-evaluation is necessary. Currently, crystalloids are the recommended

fluid for burns patient. Although the role of colloid has been conflicting, still it is
used in some certain European countries.
Formulas used for fluid volume calculation (Table 24.3) are:
• Parkland formula
• Modified Parkland formula
• Brooke formula
• Modified Brooke formula
182 Section 7 Burns
• Muir and Barclay formula

• Evan’s formula
• Monafo formula.
These formulas take body surface area and body weight into account for fluid
volume calculation in adults.
End Points of Fluid Resuscitation

• Clinical—peripheral pulses felt and consciousness not obtunded
• Urine output >0.5 mL/kg/hour
• Base deficit <2
• Systolic blood pressure >90 mm Hg.
WOUND MANAGEMENT PHASE

After 18–24 hours of burns injury, patient goes into a hypermetabolic phase (Table
24.4). In case of full thickness burns, excision and grafting is required unless they
are less than 1 cm in diameter. Grafting is done within three weeks to minimize
scarring. Determination of immunization status is done for tetanus.
Perioperative Care of Burns Patient

Burns patient often come to OT for wound excision, closure, fasciotomy/
escharotomy. Hence proper perioperative management should be done with the
Table 24.4 Issues to be addressed in the hypermetabolic phase
Fluid Nutritional Temperature

management support control Infection control Analgesia
Adequate • Enteral • Avoid • Topical agents Can be based on
fluid nutrition hypothermia (0.5% silver whether patients
management through since nitrate, mafenide are intubated or
should nasogastric hypothermia acetate, silver nonintubated:
be done tube increases sulfadiazine) • Intravenous
according to • If there is ileus, fluid loss • Excision of deep opioids are
the formulas hemodynamic • Maintain burn tissue is the the mainstay
given above. instability— high ambient best method to of analgesia
start parenteral temperature prevent sepsis in burns
nutrition and humidity • If there is patient. (e.g.
Calorie = 1.5 × suspected morphine,
BMR (REE) infection, start fentanyl)
Protein = 2.5 g/ empirical • Ketamine
kg/day antibiotics until can be used
culture report is in low doses
awaited (0.5–1 mg/
• As such kg) in case of
prophylactic opioid tolerant
antibiotics patients or
are not burns dressing
recommended
Chapter 24 Management of Burns 183
pathophysiological understanding. Airway assessment and management is the

key in managing burns patient. Difficult airway guidelines should be followed in
case of anticipated difficult airway with all the alternative airway equipment such
as fiberoptic bronchoscope, laryngeal mask airway, cricothyroidotomy in place.
Use of depolarizing muscle relaxants (succinylcholine) is usually avoided after
the 24 hours of burns until 1 year due to the risk of hyperkalemia (extrajunctional
receptors).
REHABILITATIVE PHASE
Occupational therapy is done by using range of motion exercises and splinting to
avoid contracture at various sites. Multidisciplinary team should help the patient
return to the community but it is time consuming.
Carbon Monoxide Poisoning

Those who have history of structural fires have increased risk of carbon monoxide
(CO) poisoning. CO-Hb because of its higher affinity to O2 causes inhibition of
cytochrome enzymes and causes ODC curve to be shifted to the left which in
turn leads to tissue hypoxia. CO-Hb > 50% can obtund consciousness and cause
cardiovascular depression.
MANAGEMENT OF CARBON MONOXIDE POISONING

100% normobaric O2/HBO (Hyperbaric O2) can be given. Though there are
conflicting evidence in the usage of HBO for CO poisoning, still it is imperative
to use HBO in patients who are comatose and with high CO-Hb levels.
Recommendation is to use 2–3 atm for 90 minutes with three 10 minutes airbreak.
Chemical Burns
Most agents can be irrigated with tap water for half an hour. Litmus paper can
be used as a guide for irrigation until we get neutral pH. Hydrofluoric acid cause
chemical injury to skin and it binds calcium and cause severe hypocalcemia,
hence 10% calcium gluconate is used. Deep burns require immediate wound
debridement.
Electric Injury
It can cause both local and systemic effects. Voltage up to 1000 volts have
local wounds which may need debridement and closure with skin grafts and
flaps. High voltage electric injury (>1000 volts) cause systemic effects such as
myocardial injury, fractures, compartment syndrome, rhabdomyolysis. Hence,
monitoring should be done for at least 2–3 days. Compartment syndrome will
require decompression if diagnosed over serial examination. Fluid resuscitation
may be tricky in these patients since the percentage of burns does not correlate
well with tissue injury.
184 Section 7 Burns
COMPLICATIONS
• Fluid loss, hypovolemia and shock
• Respiratory distress due to inhalational injury
• Infection
• Increased plasma viscosity and thrombosis
• Distal ischemia due to circumferential burns
• Severe muscle damage leading to rhabdomyolysis which in-turn may cause
renal failure
• Hemoglobinuria and renal damage
• Cyanide poisoning
• Hypertrophic scarring.
BIBLIOGRAPHY
1. Barret JP. In: Principles and practice of burn surgery. Barret-Nerin JP, Herndon DN,
Eds. New York: Marsel Dekker; 2005. pp. 1-32.
2. Baxter C. Fluid volume and electrolyte changes in the early post-burn period. Clin
Plastic Surg. 1974;1:693-703.
3. Baxter CR. Fluid resuscitation, burn percentage, and physiologic age. J Trauma.
1979;19:864-6.
4. Fodor L, Fodor A, Ramon Y, Shoshani O, Rissin Y, Ullman Y. Controversies in fluid
resuscitation for burn management: Literature review and our experience. Injury Int J
Care injured. 2006;37:374-9.
5. Gupta JL. Ten commandments of burn management. Indian J Burns. 2012;20:7-10.
6. Haberal M, Sakallioglu Abali AE, Karakayali H. Fluid management in major burn
injuries. Indian J Plast Surg. 2010;43(Suppl):S29-36.
7. Kucan JO. Thermal burns: resuscitation and management. In: Cohen M, Goldwyn
RM, eds. Mastery of plastic and reconstructive surgery. New York: Little Brown; 1994.
pp. 400-6.
8. Monafo WW. Treatment of burn shock by intravenous and oral administration of
hypertonic lactated saline solution. J Trauma. 1970;10:575-86.
9. Scheulen JJ, Munster AM. The Parkland formula in patients with burns and inhalation
injury. J Trauma.1982;22:869-71.
10. Warden GD. Burn shock resuscitation. World J Surg. 1992;16:16-23.
SECTION
8
RESPIRATORY DISEASES
IN INTENSIVE CARE UNIT
Chapter 25 Approach to Acute Respiratory

Failure
Prem Kumar
Chapter 26 Acute Lung Injury and Acute

Respiratory Distress Syndrome
Prem Kumar
Chapter 27 Acute Exacerbation of Chonic

Obstructive Pulmonary Disease
Prem Kumar
Chapter 28 Acute Severe Asthma

Prem Kumar
Chapter 29 Deep Venous Thrombosis and

Pulmonary Embolism
Prem Kumar, Marun Raj
Chapter 30 Obstructive Sleep Apnea and

Obesity Hypoventilation Syndrome
Prem Kumar
CHAPTER
25 Prem Kumar
APPROACH TO ACUTE
RESPIRATORY FAILURE
Respiratory failure is a common problem in intensive care unit (ICU) and its
management is vital to any intensivist. Respiratory failure is broadly divided into
four broad categories (Tables 25.1 and 25.2).
1. Hypoxemic (Type 1)
2. Hypercapnic (Type 2)
3. Perioperative (Type 3)
4. Shock (Type 4).
• Hypoxemic respiratory failure is defined as a partial pressure of oxygen in
arterial blood (PaO2) of less than 60 mm Hg when the fraction of inspired
oxygen (FiO2) is 0.60 or more.
• Hypercapnic respiratory failure is defined as a partial pressure of carbon
dioxide in arterial blood (PaCO2) of more than 45 mm Hg.
• Type 3 respiratory failure is perioperative respiratory failure usually due to
atelectasis and shunting.
• Type 4 respiratory failure is due to shock and hypoperfusion of respiratory
muscles.
Table 25.1 Causes of acute respiratory failure
• C
entral causes: Trauma, cerebrovascular accident, central nervous system infections,
raised intracranial tension, drugs like opioids, intravenous anesthetics (e.g. thiopentone),
sedative agents (e.g. midazolam)
• N euromuscular disorders and drugs: Myasthenia gravis, Guillain Barré syndrome,
drugs like organophosphates, neuromuscular blockers, botulism
• Electrolyte disturbances: Hypokalemia, hypophosphatemia
• A irway disorders: Bronchial asthma, acute exacerbation of chronic bronchitis or
emphysema, obstruction of airway by foreign body, edema or mass
• L ung parenchymal diseases: Pneumonia, aspiration, lung contusion, pulmonary edema
• Circulation: Pulmonary embolism, heart failure
• Chest wall: Rib fracture, flail chest
• Pleural disorders: Pneumothorax, pleural effusion
188 Section 8 Respiratory Diseases in Intensive Care Unit
Table 25.2 Etiology of various types of respiratory failure
Type 1 Type 2 Type 3 Type 4

Pulmonary edema COPD Atelectasis in the Hypoperfusion
Lung infection Bronchial asthma perioperative of respiratory
Aspiration Myasthenia gravis period after muscles in shock
Near drowning GBS general anesthesia
Alveolar hemorrhage Phrenic nerve injury
ARDS Myopathy
Pulmonary embolism Electrolyte disturbances
Fat embolism Drug overdose
Cervical cord injury
Obstructive sleep apnea
syndrome, Alveolar
hypoventilation
ARDS
Laryngeal edema
Obstruction of airway
by edema, foreign body,
mass
Abbreviations: ARDS, acute respiratory distress syndrome; COPD, chronic obstructive pulmonary disease;
GBS, Guillain-Barrré syndrome
PATHOPHYSIOLOGY
Type 1: The above mentioned conditions affect the parenchyma, interstitium
and alveoli of the lung and cause V/Q mismatch and in turn cause hypoxemia.
Ventilation increases as compensatory mechanism to combat hypoxia and causes
normal or low PaCO2.
Type 2: Most common causes causing type 2 failure are those conditions causing
obstructive lung disease which ends up with alveolar hypoventilation causing
rise in PaCO2. Central causes like trauma or opioids reduces the respiratory drive
hence causing hypercarbia whereas impaired ventilation due to neuromuscular
disorders like myasthenia gravis is due to reduced strength of respiratory muscles
to wash out CO2.
Type 3: This type of respiratory failure caused by atelectasis occurs primarily in the
perioperative period after general anesthesia. This atelectasis causes reduction in
the functional residual capacity in the dependent regions of lung which in turn
causes V/Q mismatch and hypoxemia.
CLINICAL PRESENTATION
Signs and symptoms are based upon the cause of respiratory failure. The primary
symptom of hypoxemia is dyspnea. Other signs and symptoms of hypoxemia
includes restlessness, clouding of consciousness, tachypnea, cyanosis, bradycar
dia, tachycardia, hypertension and later followed by hypotension, cardiac
arrhythmias. Hypercarbia can produce somnolence, tremors, seizures and coma.
But in patients with chronic obstructive pulmonary disease (COPD) symptoms
manifest later because the level of PaCO2 causing symptoms and signs are higher
in COPD patients.
Chapter 25 Approach to Acute Respiratory Failure 189
Signs of hypoxemia include cyanosis, restlessness, confusion, anxiety,

delirium, tachypnea, bradycardia or tachycardia, hypertension, cardiac
dysrhythmias, and tremor. Dyspnea and headache are the cardinal symptoms
of hypercapnia. Signs of hypercapnia include peripheral and conjunctival
hyperemia, hypertension, tachycardia, tachypnea, impaired consciousness,
papilledema, and asterixis. The symptoms and signs of acute respiratory failure
are both insensitive and nonspecific; therefore, the physician must maintain a
high index of suspicion and obtain arterial blood gas analysis if respiratory failure
is suspected.
Analysis of arterial blood gas will show widened alveolar arterial gradient,
hypoxia, hypercarbia and PaO2/FiO2 ratio. Chest radiography will be useful in
diagnosing conditions like pneumothorax, rib fracture and pulmonary pathology.
Bilateral infiltrates will point towards pulmonary edema. CT scan may be taken if
needed for specific conditions.
TREATMENT (FLOW CHART 25.1)

Management aims towards two things:
1. Therapy directed towards the cause.
2. Respiratory care to ensure adequate gas exchange.
Respiratory Care
It can be done in the following ways:
• Nonventilator therapies
• Noninvasive positive-pressure ventilation (NIPPV) therapy
• Invasive mechanical ventilation with tracheal intubation.
Nonventilator Therapy
Mainstay of nonventilator management is administration through nasal prongs
or venturi mask to increase oxygenation. In conditions where lung parenchymal
pathology is present (e.g. pneumonia) and ARDS, oxygen inhalation improves
oxygenation. Oxygen therapy should be given even to COPD patients in respiratory
failure in a lower flow (1–3 L/min) in order to maintain the hypoxic drive in these
patients. In patients with type 1 failure, the goal of oxygen therapy is to improve
oxygenation and the PaO2 >65 mm Hg and SpO2 >90%. Oxygen therapy with mask
is of little benefit if the alveolar arterial gradient is very wide. Venturi mask can
provide FiO2 of up to 0.4 and if more concentration of FiO2 is needed, mask with
reservoir bag is used.
Noninvasive Ventilation
The NIPPV is the current first-line of therapy for COPD patients with type 2
respiratory failure since it reduces the need for tracheal intubation and invasive
ventilation and reduces the length of ICU stay. BiPAP (bilevel positive airway
pressure ventilation) is preferred for such patients. In patients with COPD,
inhaled bronchodilators are administered. Prerequisites for using NIPPV is given
in Table 25.3. If not responding to bronchodilators, corticosteroids (intravenous
Flow chart 25.1 Algorithm for approaching a patient with respiratory failure
Abbreviations: NIPPV, noninvasive positive-pressure ventilation
Table 25.3 Prerequisites for using NIPPV
• Patients able to maintain a patent airway

• Patients with ability to clear secretions
• Hemodynamically stable
• Intact consciousness
• Tolerant to face mask
methylprednisolone 40–100 mg 6th hourly) should be given. A course of

antibiotics is given if infection is suspected or if associated with sputum.
Chapter 25 Approach to Acute Respiratory Failure 191
Factors associated with NIPPV failure:

• GCS < 11
• Respiratory rate ≥30/minute
• pH <7.25 at admission or 2 hours after therapy
• APACHE II ≥9.
Patients with acute respiratory distress syndrome (ARDS) or severe
hypoxemia benefit less with noninvasive ventilation. Hence, in patients with
ARDS, invasive mechanical ventilation is preferred.
Intubation and Mechanical Ventilation (Table 25.4)

The ARDS needs low tidal volume ventilation (6 mL/kg predicted body weight)
and the goals and ventilation strategy is discussed in the chapter ALI/ARDS. Any
mode of ventilation which controls the ventilation and produces less ventilator
patient dyssynchrony can be used. Traditional modes of ventilation such as
assist control (A/C) mode and synchronized intermittent mandatory ventilation
(SIMV) can be used. On weaning the patient, pressure support ventilation (PSV)
or CPAP, BiPAP can be used.
The goals of mechanical ventilation in these patients are to improve PaO2,
optimize PaCO2 according to the underlying cause and giving rest to respiratory
muscles which enables the patient to revert back to spontaneous breathing once
the underlying cause is corrected and the lung dynamics and gas exchange returns
back to normal. Nutrition support is required to bring back the respiratory muscle
function and hence, nutritional support is recommended for all ICU patients on
invasive ventilation.
These goals of mechanical ventilation to improve oxygenation are primarily
achieved by increasing mean airway pressure (using PEEP) and the FiO2. But
positive end-expiratory pressure (PEEP) should be cautiously used in patients
with hypotension and patients prone for barotrauma like lung parenchymal
disease. PEEP reduces intrapulmonary shunting and thus, improves oxygenation.
This increase in PaO2 can be achieved with lower inspired concentration of
oxygen. There is a possibility of auto–PEEP or intrinsic PEEP developing in
patients with obstructive lung disease. This intrinsic PEEP develops due to air
trapping. Tidal volume and ventilator rate are adjusted to normalize pH, PaO2,
PaCO2 and base deficit. Weaning and extubation can be challenging but daily
reassessment and periodic spontaneous breath trial will help the intensivist to
wean off these patients.
Table 25.4 Indications of intubation and mechanical ventilation
• Apnea
• Severe hypoxemia despite supplemental oxygen with high FiO2
• Acute hypercarbia resulting in respiratory acidosis not responding to drugs
• Altered mental status
• Inability to clear secretions
• Inability to protect airway
• Increased work of breathing (RR >35/min)
BIBLIOGRAPHY
1. Bardsley PA, Howard P, DeBacker W, et al. Two years treatment with almitrine
bismesylate in patients with hypoxic chronic obstructive airways disease. Eur Respir J.
1991;4:308.
2. Bone RC, Pierce AK, Johnson RL Jr. Controlled oxygen administration in acute
respiratory failure in chronic obstructive pulmonary disease: a reappraisal. Am J Med.
1978;65:896.
3. Cohen CA, Zagelbaum G, Gross D, et al. Clinical manifestations of inspiratory muscle
fatigue. Am J Med. 1982;73:308.
4. Conti G, Antonelli M, Navalesi P, et al. Noninvasive vs. conventional mechanical
ventilation in patients with chronic obstructive pulmonary disease after failure of
medical treatment in the ward: a randomized trial. Intensive Care Med. 2002;28:1701.
5. Driver AG, LeBrun M. Iatrogenic malnutrition in patients receiving ventilatory
support. JAMA. 1980;244:2195.
6. Falke KJ, Pontoppidon H, Kumar A, et al. Ventilation with end-expiratory pressure in
acute lung disease. J Clin Invest. 1972;51:2315-23.
7. Marini JJ, Copps JS, Culver BH. The inspiratory work of breathing during assisted
mechanical ventilation. Chest. 1985;87:612.
8. Schumaker GL, Epstein SK. Managing acute respiratory failure during exacerbation of
chronic obstructive pulmonary disease. Respir Care. 2004;49:766-82.
9. The ARDS network ventilation with lower tidal volumes as compared with traditional
tidal volumes for acute lung injury and the acute respiratory distress syndrome. N
Engl J Med. 2000;342:1301-8.
CHAPTER
26 Prem Kumar
ACUTE LUNG INJURY AND ACUTE

RESPIRATORY DISTRESS SYNDROME
Acute lung injury and acute respiratory distress syndrome are common
occurrences in the intensive care unit (ICU). Sepsis is the most common cause
and the morbidity and mortality caused by this problem is quite high (30–60%).
Indirect causes contribute to almost 50% cases of ARDS. In recent years because
of the new developments in the ventilation strategy, the mortality has improved.
Incidence of ARDS annually is 79/100,000 person-years. Predisposing risk factors
is given in Table 26.1.
DEFINITION
ALI/ARDS is defined by the following criteria:
• Acute onset
• PaO2/FiO2 (P/F) ratio <300 in ALI and <200 in ARDS
• Non-cardiogenic pulmonary edema by clinical evidence of normal left atrial
pressure or pulmonary artery occlusion pressure <18 mm Hg
• Bilateral diffuse infiltrates on chest radiograph.
Table 26.1 Predisposing risk factors
Indirect lung injury

• Sepsis
• Polytrauma
• Acute pancreatitis
• Transfusion reaction (TRALI)
• Drug overdose
• Cardiopulmonary bypass
Direct lung injury
• Pneumonia
• Pulmonary contusion
• Aspiration pneumonitis
• Burns causing inhalational injury
• Near drowning
• Fat embolism syndrome
Low serum albumin has been found to be a risk factor for development of ARDS
PATHOPHYSIOLOGY
The pathophysiology of acute lung injury is incompletely understood. The
hallmark of ALI is diffuse alveolar damage. The disease process goes into three
phases:
1. Exudative phase
2. Proliferative phase
3. Fibrotic phase.
Pathophysiology of ALI/ARDS
It is given in Flow chart 26.1.
Diagnosis
American European consensus clinical definition of ALI/ARDS is as follows:
The diagnostic criteria should be that ARDS should be of acute onset, PaO2/
FiO2 (P/F) ratio <300 in ALI and <200 in ARDS, non-cardiogenic pulmonary
edema by evidence of normal left atrial pressure or pulmonary artery occlusion
pressure <18 mm Hg and bilateral diffuse infiltrates on chest radiograph.
Apart from the diagnostic criteria, other methods to support the diagnosis,
although not specific are pulmonary edema fluid to plasma protein ratio, brain
Flow chart 26.1 Pathophysiology of ALI/ARDS

Chapter 26 Acute Lung Injury and Acute Respiratory Distress Syndrome 195
natriuretic peptide level <100 pg/mL, bronchoalveolar lavage (BAL) fluid showing
neutrophils.
Radiographic Findings
Chest X-ray shows bilateral diffuse infiltrates, vascular pedicle width <70 mm and
absence of Kerley B lines and CT scan will show heterogeneous opacities and
ground-glass opacities concentrated more over the lower regions of lung.
MANAGEMENT
• Treatment of the cause is the primary aim for ARDS. Sepsis is the common
cause for indirect lung injury, hence appropriate management should be
done with antibiotics.
• Ventilator management.
In the older methods of treatment, higher tidal volume (12 mL/kg) was
used which is not recommended nowadays. The current recommendation for
ARDS includes lung protective strategy with low tidal volume ventilation. ARDS
network has recommended a protocol for managing ALI/ARDS patients. This low
tidal volume ventilation has drastically reduced the mortality by 20%.
Initial Ventilator Settings

• Calculate predicted body weight (PBW)
Males = 50 + 2.3 [height (inches) – 60]
Females = 45.5 + 2.3 [height (inches) – 60]
Goals
• pH goal: 7.30–7.45
• Oxygenation goal: PaO2 55–80 mm Hg or SpO2 88–95%
• Plateau pressure goal: ≤30 cm H2O
• I:E ratio goal: 1:1–1:3.
WEANING PROTOCOL FOR ARDS

Criteria for conducting spontaneous breathing trial (SBT) daily
• FiO2 ≤ 0.40 and PEEP ≤ 8
• PEEP and FiO2 ≤ values of previous day
• Patient has good spontaneous breathing efforts
• Systolic blood pressure ≥90 mm Hg without vasopressor support
• Patient not on muscle relaxants.
↓
With all the above criteria being met and if the patient tolerates weaning
with CPAP/PS < 5 cm H2O for > 2 hours, FiO2 ≤ 0.5, PEEP ≤ 5, start unassisted
breathing trial
↓
Place the patient on T-piece or CPAP ≤5 cm H2O. Assess for tolerance up to two
hours by the following criteria
↓
• SpO2 ≥90 and /or PaO2 ≥60 mm Hg
• Spontaneous tidal volume (VT) ≥4 mL/kg PBW
• RR ≤35/minute
• pH ≥7.3
• HR <120/minute
• No respiratory distress
↓
If tolerated for at least 30 minutes, consider extubation, If not tolerated, resume
to SBT settings
↓
• Oxygenation goal: PaO2 55–80 mm Hg or SpO2 88–95%
Use a minimum PEEP of 5 cm H2O. Use the combination to achieve the goal.
PEEP/FiO2 combination
FiO2 0.3 0.4 0.4 0.5 0.5 0.6 0.7 0.7
PEEP 5 5 8 8 10 10 10 12
FiO2 0.7 0.8 0.9 0.9 0.9 1.0

PEEP 14 14 14 16 18 18–24
• Plateau pressure goal (Pplat): ≤30 cm H2O

Check plat of 0.5 second inspiratory pause for at least 4th hourly and after
each change in PEEP or VT.
If Pplat > 30 cm H2O: decrease VT by 1 mL/kg steps (minimum = 4 mL/kg)
If Pplat <25 cm H2O and VT <6 mL/kg, increase VT by 1 mL/kg until plat
>25 cm H2O or
VT = 6 mL/kg.
• pH goal: 7.30–7.45
Acidosis management (pH<7.30), if pH 7.15-7.30:
Increase RR until pH >7.30 or PaCO2 <25 (Maximum set RR = 35)
If pH <7.15: Increase RR to 35.
If pH remains <7.15, VT may be increased in 1 mL/kg steps until
Chapter 26 Acute Lung Injury and Acute Respiratory Distress Syndrome 197
pH > 7.15 (Pplat target of 30 may be exceeded).

Consider giving NaHCO3
Alkalosis management: (pH>7.45) Decrease ventilator rate if possible.
• I:E ratio goal: 1:1–1:3.
Adjunctive therapies
Criteria for adjunctive therapy:
Adjunctive therapies are indicated when PaO2 <55 mm Hg or SpO2 <88% with
FiO2 ≥0.7 and plateau pressure >30 cm H2O.
• Inhaled nitric oxide: It improves ventilator perfusion mismatching. It is not
recommended routinely for patients with ARDS rather it can be used as a
rescue therapy to improve oxygenation in patients with ARDS with severe
hypoxemia and increased pulmonary artery pressure. Dose is 2.5–5 µg
inhaled 6–9 times.
• Glucocorticoids: The use of glucocorticoids is not routinely recommended.
They can be used in the late fibroproliferative phase of ARDS to improve
oxygenation but their use has not shown to improve mortality.
• Prone positioning: Prone positioning improves ventilator perfusion mismatch
and improves lung compliance, increases functional residual capacity and
oxygenation. The Proning Severe ARDS Patients (PROSEVA) study group
evaluated the effect of early application of prone positioning on outcomes in
patients with severe ARDS (PaO2/FiO2 ratio <150 mm Hg, FiO2 >0.6 and PEEP
>5 cm H2O) and found that early application of prolonged prone-positioning
in severe ARDS decreased 28-day and 90-day mortality than the supine
group.
• Lung recruitment maneuver: It is defined as sustained deep inflation of the
lung with the aim of opening up collapsed distal airway of the dependent
regions of lung. Usual method of performing recruitment maneuver is
sustained peak inflation pressure of 40 cm H2O for 40 seconds. But its result
on improved survival is questionable. It has to be done cautiously since it can
cause hemodynamic instability.
• High frequency oscillatory ventilation (HFOV)
• ECMO.
FLUID MANAGEMENT
There were two trials to indicate that pulmonary artery catheter was associated
with increased mortality. They were: Study to Understand Prognosis and
Preferences for Outcomes and Risks of Treatments (SUPPORT) and the Fluids
and Catheters Treatment Trial (FACTT). The conservative fluid management
is the current recommended fluid strategy because it improves central nervous
system function and lung function with reduced length of ICU stay.
NUTRITIONAL SUPPORT
Early enteral nutrition support with trophic calorie supplementation of 10 mL/hr
is the standard of care for ARDS patients. Omega-3 fatty acid and antioxidant
supplementation is not recommended since it has been found to increase
mortality.
BIBLIOGRAPHY
1. Claude Guérin, et al. Prone Positioning in Severe Acute Respiratory Distress Syndrome.
N Engl J Med. 2013;368:2159-68.
3. Rubenfeld GD, Herridge MS. Epidemiology and outcomes of acute lung injury. Chest.
2007;131:554-62.
4. Ryan A, Hearty A, Prichard R, Cunningham A, Rowley S, Reynolds J. Association
of hypoalbuminemia on the first postoperative day and complications following
esophagectomy. J Gastrointest Surg. 2007;11:1355-60.
5. The National Heart, Lung, and Blood Institute Acute Respiratory Distress Syndrome
(ARDS) Clinical Trials Network,: Efficacy and safety of corticosteroids for persistent
acute respiratory distress syndrome. N Engl J Med. 2006;354:1671.
6. Ventilation with lower tidal volumes as compared with traditional tidal volumes for
acute lung injury and the acute respiratory distress syndrome. The Acute Respiratory
Distress Syndrome Network. N Engl J Med. 2000;342:1301-8.
7. Wiedemann HP, Wheeler AP, Bernard GR, et al. Comparison of two fluid-management
strategies in acute lung injury. N Engl J Med. 2006;354:2564-75.
CHAPTER
27 Prem Kumar
ACUTE EXACERBATION OF CHRONIC

OBSTRUCTIVE PULMONARY DISEASE
INTRODUCTION
Chronic obstructive pulmonary disease (COPD) is a major cause of morbidity
and mortality among patients ending up with respiratory failure. Exacerbation
of COPD is also a common cause for intensive care unit (ICU) admission. Global
initiative for Chronic Obstructive Lung Disease (GOLD) defines COPD as a
disease state characterized by airflow limitation that is not fully reversible. It
includes chronic bronchitis and emphysema. Chronic bronchitis is associated
with obstruction of small airways which is common in smokers; emphysema is
associated with enlargement of air sacs, loss of elasticity, and closure of small
airways and small airway disease where there is narrowing of small bronchioles.
In this chapter, we will discuss about the risk factors, pathophysiology, diagnosis
and treatment of chronic obstructive lung disease and its exacerbation in
particular.
RISK FACTORS
• Cigarette smoking
• Respiratory infections—they are an important cause for exacerbation of
COPD
• Genetic— α1-antitrypsin deficiency
• Occupational exposure—coal mining, gold mining, and cotton textile dust.

Progressive expiratory airflow obstruction is the most common finding of COPD.
Due to some precipitating factors, inflammatory edema, glandular hypertrophy
and excessive secretion of mucus occurs which cause expiratory airway
obstruction which in turn occurs due to loss of distension forces on the airways
resulting in structural and functional narrowing of airway. Due to the risk factors
mentioned above, there is destruction of alveolar walls resulting in loss of elastic
recoil and expiratory airway obstruction.
Flow chart 27.1 Pathophysiology of acute exacerbation of COPD
The effects of severe airflow obstruction include:

• Ventilation maldistribution resulting in V/Q mismatch and impaired gas
exchange
• Increased work of breathing due to increased airway resistance
• Reduced minute ventilation due to reduced peak expiratory flow rate
• Air trapping resulting in dynamic hyperinflation.
DIAGNOSIS
Clinical Presentation
The cardinal symptoms of COPD are cough with sputum production and
exertional dyspnea. Patients with severe disease or exacerbation can have
expiratory wheeze, usage of accessory respiratory muscles and the classic tripod
sign. Cyanosis can be seen if hypoxemia is very severe. The traditional way of
classifying pink puffers for emphysema and blue bloaters for chronic bronchitis
has been challenged recently since the current literature points clinical features
towards the combination of pathophysiological changes of both chronic
bronchitis and emphysema. Signs of right heart failure can be present if there is
associated pulmonary hypertension.
Pulmonary Function Test (Fig. 27.1)

Pulmonary function test (PFT) shows obstructive pattern and there is reduction in
FEV1 and FEV1/FVC . There is increase in total lung capacity, functional residual
capacity, and residual volume when the severity of disease increases.
Chapter 27 Acute Exacerbation of Chronic Obstructive Pulmonary Disease 201
Fig. 27.1 Flow volume loops show decrease in the expiratory flow rate and the
expiratory curve is concave upward indicating obstructive pattern
Abbreviations: PEF, peak expiratory flow; PIF, peak inspiratory flow
Table 27.1 GOLD criteria for grading severity of COPD
GOLD stage—severity Spirometry

0–At risk Normal
I–Mild FEV1/FVC <0.7 and FEV1 ≥80% predicted
II–Moderate FEV1/FVC <0.7 and 50% ≤FEV1 <80% predicted
III–Severe FEV1/FVC <0.7 and 30% ≤FEV1 <50% predicted
IV–Very Severe FEV1/FVC <0.7 and FEV1<30% predicted
or
FEV1 <50% predicted with respiratory failure or signs of right
heart failure
Global initiative for chronic obstructive lung disease (GOLD) staging

for severity of the disease is shown in Table 27.1. Chest radiography shows
hyperlucency, bullae and flattening of diaphragm. Arterial blood gas analysis
depicts hypoxemia, hypercarbia and respiratory acidosis and aids in the
management.
Acute Exacerbation
By definition, exacerbation is worsening of cough/sputum production and
dyspnea which could be due to precipitating factors or increase in the severity
of the airflow obstruction and requires a change in regular medication. Sputum
production usually has a change in the character during exacerbation. Acute
exacerbation is one of the cause for respiratory failure thus, necessitating ICU
admission. Patients with moderate to severe obstruction tend to have more
exacerbations. During an exacerbation, precipitating factor should be identified
and based on the severity, treatment should be initiated.
Usual precipitating factor is a respiratory infection or an intercurrent illness.

Usually the respiratory infections are bacterial (Streptococcus pneumoniae,
haemophilus influenzae) or viral, postabdominal surgery.
CLINICAL ASSESSMENT
History: The current and the previous symptoms, history of previous exacerbations
and treatment, severity of breathlessness, fever.
Physical examination: Grading of dyspnea, cyanosis, signs of heart failure, use of
accessory muscles, central nervous system examination. Presence of wheezing
and paradoxical motion of abdomen.
Investigations: Chest radiography to view any patchy shadows, pneumothorax,
Kerley lines for pulmonary edema. Arterial blood gas analysis for detecting
hypoxemia, hypercarbia and respiratory acidosis.
Treatment (Table 27.2)

• Supplemental oxygen therapy
• Inhaled bronchodilators
• Corticosteroids
• Antibiotics.
Supplemental Oxygen Therapy

Usually exacerbations respond to oxygen therapy. Venturi face mask is advised
since it delivers known oxygen concentration. The concentration of 25–30%
is sufficient to maintain adequate oxygenation but at the cost of hypercarbia.
Hypercarbia can cause ventilation perfusion mismatch and worsen the patient.
Saturation of >90% is sufficient for COPD patients. The use of oxygen at higher
flow rate and concentration is not advised in patients with COPD in exacerbation.
Ventilation perfusion mismatching and impaired gas exchange results in
hypoxemia. Intrapulmonary shunting is minimal in COPD. Hence, COPD
patients respond to supplemental oxygen therapy with low flow rate (1–3 L/min),
if hypoxemia does not respond to oxygen therapy, then other causes need to
be suspected. Patients with hemodynamic instability and heart failure require
higher oxygen concentration, hence they require ventilator support.
Table 27.2 Dosages of various drugs useful in acute exacerbation of COPD
Drug Dose
Anticholinergic: Ipratropium bromide 17 µg/puff, 2–3 puffs every 6 hours
Inhaled β2 agonists: albuterol 90 µg/puff, 2 puffs every 4–6 hours
Azithromycin 500 mg followed by 250 mg daily for 5 days
Ciprofloxacin 500 mg every 12 hours for 7 days
Inhaled Bronchodilators
Bronchodilators offer symptomatic relief by reducing airway resistance but
these agents do not improve the lung function or do not prevent the progression
of the disease. Anticholinergic agents like Ipratropium bromide is preferred to
β2 agonists since it does not cause tachycardia. But β2 agonists have a more
rapid onset of action and improves symptoms abruptly. The combination of
anticholinergics and inhaled bronchodilators are effective in most of the patients
with exacerbation rather than sole therapy.
Corticosteroids
Glucocorticoids prevent relapses, reduces the length of ICU stay and improves
the postbronchodilator FEV1. According to current evidence, glucocorticoids
should not be used in high dose or for longer duration instead the recommended
dose is 30–40 mg of oral prednisolone or its equivalent for a period of 10–14 days.
Hyperglycemia and myopathy can be a complication in ICU patients.
Antibiotics
Patients with exacerbation are mostly infected with either bacterial or
viral infections. Usual bacterial pathogens are Streptococcus pneumoniae,
Haemophilus influenzae. Antibiotics can be chosen after culture sensitivity or
in case of severe infection, intravenous penicillin or cephalosporins along with
macrolides/respiratory fluoroquinolones can be started empirically. Antibiotics
given early have been found to reduce the incidence of intubation and mortality
according to recent studies.
Indications for mechanical ventilation are also the causes for ICU admission
too. Mechanical ventilation can be given by noninvasive positive-pressure
ventilation (NIPPV) or invasive mechanical ventilation through endotracheal
tube.
Indications for ICU Admission

• Acute onset of respiratory acidosis and hypercarbia
• Severe hypoxemia (PaO2 <40 mm Hg)
• Severe dyspnea culminating in respiratory failure
• Severe underlying disease not amenable for conservative management
without ICU admission.
Indications of Mechanical Ventilation

• Severe hypoxemia (PaO2 <40 mm Hg)
• Hypercarbia (PaCO2 >60 mm Hg)
• Severe respiratory acidosis (pH <7.2 )
• Severe dyspnea
• Clouding of consciousness
• Respiratory failure with hemodynamic instability.
Ventilation Strategy
• Reduce tidal volume to 8 mL/kg
• Keep low ventilator respiratory rate— less than 12 breaths/minute
• Prolong expiratory time—1:2.5–1:3.
Most of the current ventilator strategies for COPD advocate pressure
controlled ventilation initially with heavy sedation or paralysis to optimize gas
exchange and patient machine synchrony. Once the gas exchange is optimized
and the lung dynamics is near normalized, the patient is weaned from the
ventilator usually with CPAP or BiPAP or PSV. By increasing the peak inspiratory
flow rate, the inspiratory time is shortened hence reducing the work of breathing.
Dynamic hyperinflation occurs in COPD patients during mechanical ventilation
due to air trapping which in turn increases the work of breathing. Dynamic
hyperinflation can be expressed in terms of intrinsic PEEP or auto PEEP. Intrinsic
PEEP is the difference between the alveolar pressure and the proximal airway
pressure measured at the end of expiration.
Detecting Intrinsic PEEP

This occurs in case of increased respiratory rate, significant airway obstruction,
reduced expiratory time or inadequate inspiratory flow rate. Before measuring
intrinsic positive end-expiratory pressure (PEEP), the patient should be sedated
or paralyzed. It can be measured by visualizing the ventilator graphics and by
measuring plateau pressure or by measuring the intrinsic PEEP itself. Plateau
pressure can be measured by applying end-inspiratory pause and if it is more than
25 cm H2O, it indicates presence of intrinsic PEEP. Intrinsic PEEP is measured by
prolonged end-expiratory pause. If intrinsic PEEP exceeds 10 cm H2O, then it is
prudent to prolong the expiratory time or increase the inspiratory flow rate.
Application of External PEEP

Intrinsic PEEP can be overcome by applying external PEEP equivalent to or
slightly less than auto-PEEP. The level of PEEP necessary to overcome intrinsic
PEEP should be kept below 85% of measured intrinsic PEEP.
Weaning from Mechanical Ventilation

Pressure support ventilation or continuous positive airway pressure (CPAP) with
daily spontaneous breath trial is effective for weaning patients with COPD.
Parameters Indicating Weaning Success

• Simplified weaning index <9/minute
• CROP index ≥13 mL/breaths/minute
• Respiratory rate/tidal volume in liters (rapid shallow breathing index) <100
breaths/min/L.
Prognosis
BODE index is a useful predictor for survival in COPD patients.
B – Body mass index
O – Airflow obstruction
D – Severity of dyspnea
E – Exercise tolerance.
BIBLIOGRAPHY
1. Chang DW. Clinical application of mechanical ventilation, 3rd edn. India: Cengage
Learning, 2006.
2. Guerin C, Milic-Emili, Fournier G. Effect of PEEP on work of breathing in mechanically
ventilated COPD patients. Intensive Care Med. 2000;26:1207.
3. Marini JJ. Should PEEP be used in airflow obstruction? Am Rev Respir Dis. 1989;140:1.
4. Menitove SM, Goldring RM. Combined ventilator and bicarbonate strategy in the
management of status asthmaticus. Am J Med. 1983;74:898.
5. Pauwels RA, Buist AS, Calverley PM, et al. Global strategy for the diagnosis,
management, and prevention of chronic obstructive pulmonary disease. NHLBI/
WHO Global Initiative for Chronic Obstructive Lung Disease (GOLD) Workshop
summary. Am J Respir Crit Care Med. 2001;163:1256.
6. Pingleton SK. Nutritional support in the mechanically ventilated patient. Clin Chest
Med. 1988;9:101.
7. Smith TC, Marini JJ. Impact of PEEP on lung mechanics and work of breathing in
severe airflow obstruction. J Appl Physiol. 1988;65:1488.
8. Vitacca M, Vianello A, Colombo D, et al. Comparison of two methods for weaning
patients with chronic obstructive pulmonary disease requiring mechanical ventilation
for more than 15 days. Am J Respir Crit Care Med. 2001;164:225.
9. Wilkins RL, et al. Egan’s fundamentals of respiratory care, 8th edn. St. Louis, MO:
Mosby; 2003.
CHAPTER
28 Prem Kumar
ACUTE SEVERE ASTHMA
Asthma is an inflammatory disease of the airways characterized by reversible

airway obstruction which makes the airway more responsive than nonasthmatics
to various stimuli leading to airway wall thickening and edema which in turn leads
to excessive narrowing with subsequent airflow obstruction and symptomatic
wheezing and dyspnea. Most of the asthmatics have one or more exacerbations
in a year. Recently, the term status asthmaticus has been replaced by acute severe
asthma or exacerbation.
Upper respiratory tract virus infections such as rhinovirus, respiratory syncytial
virus, and coronavirus are the most common triggers of acute severe exacerbations.
Other triggers are beta blockers, certain foods. Exercise is a triggering factor in
children. Pathophysiology of acute severe asthma is given in Flow chart 28.1.
CLINICAL FEATURES
Cough, dyspnea, wheeze are cardinal symptoms. The symptoms may become
worse at night. The patient may experience chest tightness. The patients are
so breathless that they cannot speak a complete sentence. They may become
cyanotic due to severe hypoxemia. On physical examination, tachycardia,
tachypnea, accessory muscle use are all features of severe airway obstruction.
Expiratory wheeze is heard throughout the lung. Pulsus parodoxus occurs due
to large swings in intrathoracic pressure and there is accentuated fall in systolic
blood pressure during inspiration. All wheezing is not due to asthma. It can
be due to other causes like pulmonary edema, chronic obstructive pulmonary
disease (COPD), etc. Severe exacerbations can cause right ventricular strain,
acute reversible left ventricular dysfunction and myocardial ischemia. History
of coronary artery disease is important because the patient may be taking beta-
blockers and may be more prone for respiratory complications. The intensivist
should elicit history about the time of onset of the exacerbation and what
triggered the attack.
DIAGNOSIS
Pulmonary Function Tests

Clinical assessment of the severity of airflow obstruction is misleading, hence
objective assessment of airflow is required (Table 28.1). The PEFR and FEV1 have
Chapter 28 Acute Severe Asthma 207
Flow chart 28.1 Pathophysiology of acute severe asthma
Abbreviations: PEEP, positive end-expiratory pressure
Table 28.1 Objective assessment of obstruction after initial therapy
PEFR or FEV1 Interpretation

>70% predicted or >15% increase Good response
50–70% predicted or 10–15% increase Equivocal response
<50% predicted or <10% increase Poor response
Abbreviations: PEEP, positive end expiratory pressure; PEFR, peak expiratory flow rate
limitations in assessing airway function since both the parameters are sensitive to
obstruction of central airways and obstruction of small peripheral airways is less
reflected by these parameters. Peak flow measurement is deferred in patients with
severe exacerbation since it worsens bronchospasm. But in other patients without
severe exacerbations, PEFR or FEV1 predicts the requirement of hospitalization.
Table 28.2 Classification of severity of asthma exacerbation
Symptoms and Initial PEFR

signs (or FEV1) Clinical course
Mild Dyspnea only PEFR >70% Home therapy
with activity predicted Good relief with inhaled SABA may
need short course of oral corticosteroids
Moderate Dyspnea PEFR 40–69% Usually requires hospital visit
interferes with predicted Relief with frequent inhaled SABA
or limits usual Oral systemic corticosteroids; some
activity symptoms last for 1–2 days after
treatment is begun
Severe Dyspnea at rest; PEFR <40% May require hospitalization
interferes with predicted Partial relief from frequent inhaled SABA
conversation Oral systemic corticosteroids; some
symptoms last for >3 days after
treatment is begun
Adjunctive therapies are helpful
Life Too dyspneic PEFR <25% Requires hospitalization and ICU
threatening to speak; predicted Admission
perspiring Minimal or no relief from frequent
inhaled SABA
Intravenous corticosteroids
Adjunctive therapies are helpful
Abbreviations: SABA, short-acting beta-2 agonist; PEFR, peak expiratory flow rate
If the expiratory flow does not improve 60 minutes after initial therapy, then the
patient would required hospital admission. The normal range of PEFR is 500–
700 L/minute for men and 380–500 L/minute for women. Exacerbations are
characterized by decreases in expiratory airflow that can be documented and
quantified by simple measurement of lung function (spirometry or PEFR) (Table
28.2).
Risk Factors Associated with Mortality due to Asthma

• History of severe exacerbation with intubation and ventilatory support
• Use of >2 canisters of short-acting beta-2 agonist (SABA) per month
• Two or more hospitalizations in the past year
• Difficulty in recognizing the severity of worsening asthma
• Low socioeconomic status
• Drug abuse
• Patient with comorbid illness—chronic pulmonary disease, cardiovascular
disease.
Arterial Blood Gas Analysis

Arterial blood gases shows hypoxemia and reduced PCO2 due to hyperventilation
in mild-to-moderate exacerbation. A normal or rising PCO2 is an indication of
severe exacerbation and impending respiratory failure and requires immediate

monitoring and therapy. There can be compensatory hypocapnic metabolic
acidosis in response to acute respiratory alkalosis.
Chest X-ray
A chest roentgenogram may show pneumonia or pneumothorax.
MANAGEMENT (TABLE 28.3 AND FLOW CHART 28.2)

• Administer supplemental oxygen in moderate-to-severe exacerbations to
correct hypoxemia.
• Administer frequent SABA to reverse airflow obstruction.
• Administer oral corticosteroids to reduce airway inflammation in moderate
to severe exacerbations or in patients who have failure of response to SABA.
• Monitor response to treatment
– Repeated lung function measures (FEV1 or PEFR) after 1 hour is the
single best predictor of hospitalization.
– The presence of drowsiness is an indicator for impending respiratory
failure and patient requires ICU admission and ventilatory support.
• Consider adjunctive treatments with intravenous magnesium sulfate or
heliox, in severe exacerbations, if patients are unresponsive to the initial
therapy.
• Consider inhaled corticosteroids for preventing relapse.
• Review the inhaler technique.
Treatments not Recommended for Exacerbation of Asthma

• Antibiotics unless there is documented evidence of infection
• Mucolytics
• Methylxanthines
• Sedation.
Adjunctive Therapies
• Magnesium sulfate is useful only in severe exacerbations. It may increase
airflow rates by reducing airflow obstruction. Dose—2 g intravenously over
20 minutes
• Heliox
• Aminophylline—not recommended for exacerbations but can play some
role in refractory cases.
Noninvasive Ventilation
Studies have suggested the combination of noninvasive ventilation and
albuterol nebulization to be superior than SABA alone. The prerequisites and
contraindications are discussed in the chapter of noninvasive ventilation.
Continuous positive airway pressure (CPAP) or preferably bi-level positive airway
Table 28.3 Dosages of drugs used in exacerbation of asthma
Drug Dose Comments

Albuterol
Nebulizer solution
(0.63 mg/3 mL, 2.5–5 mg in 3 mL normal Only selective beta 2 agonists
1.25 mg/3 mL, saline every 15–20 minutes for are recommended
2.5 mg/3 mL, 3 doses, then 2.5–10 mg every For intubated patients, titrate to
5.0 mg/mL) 1–4 hours as needed physiologic effects
4–8 puffs every 20 minutes
MDI up to 4 hours, then every 1–4
(90 µg/puff) hours as needed
Levalbuterol
Nebulizer solution
(0.63 mg/3 mL, 1.25–2.5 mg every 20 minutes Levalbuterol administered in
1.25 mg/0.5 mL, for 3 doses, then 1.25–5 mg one-half the mg dose of albuterol
1.25 mg/3 mL) every 1–4 hours as needed provides comparable efficacy and
4–8 puffs every 20 minutes safety
MDI up to 4 hours, then every 1–4
(45 µg/puff) hours as needed
Ipratropium bromide Should not be used as first-line
Nebulizer solution 0.5 mg every 20 minutes for 3 therapy;
(0.25 mg/mL) doses, then as needed Should be added to
MDI 8 puffs every 20 minutes as SABA therapy for severe
(18 µg/puff) needed up to 3 hours exacerbations
Can mix in same nebulizer with
albuterol
Epinephrine 0.3–0.5 mg every 20 minutes
1:1,000 (1 mg/mL) for 3 doses
Given subcutaneously
Terbutaline 0.25 mg every 20 minutes for Terbutaline is preferred in
(1 mg/mL) 3 doses pregnancy if parenteral therapy
is indicated.
It is used with caution in
coronary artery disease
Methylprednisolone Total course of corticosteroids
Oral or IV 40–80 mg/day in 1 or 2 for asthma exacerbation may
divided doses until PEFR require 3–10 days
reaches 70% of predicted or Course <1 week, there is no
personal best need to taper the dose
Course >1 week, there is no
need to taper if the patient is on
inhaled steroids
Inhaled steroids can be started
anytime in the treatment of an
asthma exacerbation
Abbreviations: MDI, metered-dose inhaler; IV, intravenous; SABA, short-acting beta-2 agonist
Flow chart 28.2 Management of asthma exacerbation
Abbreviations: PEFR, peak expiratory flow rate; SABA, short-acting beta-2 agonist; PEF, peak expiratory flow
Table 28.4 Indications of endotracheal intubation and mechanical ventilation
• Progressive hypercapnia
• Obtunded mental status
• Silent chest
• Exhaustion of breathing—impending respiratory failure
• Hemodynamic instability
• Increased production of secretions
• Inability to protect airway
pressure (BiPAP) is started in asthmatic patients with exacerbations who require

noninvasive positive pressure ventilation (NIPPV). Start CPAP of 5–10 cm H2O
or BiPAP with inspiratory positive airway pressure (IPAP) of 8 cm H2O and titrate
according to need up to 15 cm H2O. expiratory positive airway pressure (EPAP) – 5
cm H2O. the pressures are adjusted so that the patient has respiratory rate below
25/minute, tidal volume >7 mL/kg and comfort.
Endotracheal Intubation and Mechanical Ventilation (Table 28.4)

Administration of a short- and rapid-acting intravenous benzodiazepine facilitates
intubation. Oral intubation is preferred rather than nasal since nasal polyps
and sinusitis are common in asthma and a larger endotracheal tube is placed
through oral route thus reducing the airway resistance. A large endotracheal tube
facilitates the option of therapeutic bronchoscopy later.
Initial Ventilator Settings

To avoid dynamic hyperinflation, the following settings are set in the ventilator:
• Tidal volume: 7–8 mL/kg
• Ventilator respiratory rate: 12–14/minute
• Inspiratory flow rate: 60 L/minute
• Minute ventilation: 7–8 L/minute
• PEEP: 5 cm H2O.
Either volume control or synchronized intermittent mandatory (SIMV) can
be used. Pressure-controlled ventilation (PCV) has the advantage of limiting the
peak inspiratory pressure. The current strategy for mechanical ventilation in
status asthmaticus is controlled hypoventilation with permissive hypercapnia.
This strategy does not establish a normal PaCO2 as long as the minute ventilation
and fraction of inspired oxygen maintain adequate tissue oxygenation, in other
words hypercapnia is accepted–permissive hypercapnia.
Dynamic Hyperinflation
To measure auto–PEEP, the patient ventilator asynchrony should be absent or
there should not be any patient effort. Single breath plateau pressure and auto–
PEEP can measure dynamic hyperinflation. Plateau pressure can be measured
by end-inspiratory hold maneuver. Auto–PEEP is obtained by measuring airway
opening pressure during an end-expiratory hold maneuver. Persistence of
expiratory flow at the start of inspiration also suggests auto–PEEP. Auto–PEEP

< 30 cm H2O can be tolerated.
Extubation Criteria
• No hypercapnia
• No significant dynamic hyperinflation
• Airway resistance <20 cm H2O
• PEEP <5 cm H2O
• Patient able to protect airway
• Mental status not obtunded
• No excessive secretions.
BIBLIOGRAPHY
1. Bellomo R, McLaughlin P, Tai E, et al. Asthma requiring mechanical ventilation: a low
morbidity approach. Chest. 1994;105:891.
2. Feihl F, Perret C. Permissive hypercapnia. Am J Respir Crit Care Med. 1994;150:1722.
3. Global Initiative for Asthma: NHLBI/WHO Workshop Report. Publication No. 95-
3659, Bethesda, MD, National Heart, Lung, and Blood Institute, 1995.
4. Global strategy for asthma management and prevention. NIH Publication 02-3659,
2002.
5. Hankinson J, Odencrantz J, Ferdan K. Spirometric reference values from a sample of
the general U.S. population. Am Rev Respir Crit Care Med. 1999;159:179-87.
6. Harrison BDW, Hart GJ, Ali NJ, et al. Need for intravenous hydrocortisone in addition
to oral prednisolone in patients admitted to hospital with severe asthma without
ventilatory failure. Lancet. 1986;1:181.
7. Manthous CA, Hall JB, Caputo MA, et al. Heliox improves pulsus paradoxus and peak
expiratory flow in nonintubated patients with severe asthma. Am J Respir Crit Care
Med. 1995;151:310.
8. National Asthma Education and Prevention Program. Expert Panel Report 2:
Guidelines for the Diagnosis and Management of Asthma. Publication No. 55-4051.
Bethesda, MD, National Institutes of Health, 1997.
9. National Asthma Education and Prevention Program Expert Panel Report. Guidelines
for the diagnosis and management of asthma. The Expert Panel Report 3, Summary
Report. 2007.
10. National Asthma Education and Prevention Program Expert Panel Report. Guidelines
for the diagnosis and management of asthma. Update on selected topics, 2002. NIH
Publication No. 02-5074,2003.
11. Ratto D, Alfaro C, Sipsey J, et al. Are intravenous corticosteroids required in status
asthmaticus? JAMA. 1988;260:527.
12. Wilmoth DF, Carpenter RM. Preventing complications of mechanical ventilation:
permissive hypercapnia. AACN Clin Issues. 1996;7:473.
CHAPTER
29 Prem Kumar, Marun Raj
DEEP VENOUS THROMBOSIS AND

PULMONARY EMBOLISM
Deep venous thrombosis (DVT) and pulmonary embolism (PE) are spectrum of
venous thromboembolism. DVT and PE can occur in any ICU patient and more
so in patients with risk factors. Hence, prophylaxis against DVT is more effective
in preventing mortality due to pulmonary embolism (Table 29.1).
Table 29.1 Risk factors associated with DVT and PE
Risk factors associated with venous thromboembolism

• Trauma Inherited conditions
• Prolonged Immobilization • Factor V Leiden deficiency
• Prolonged ventilation • Antiphospholipid antibody syndrome
• Previous history of DVT/PE • Heparin-induced thrombocytopenia
• Obesity • Anti-thrombin deficiency
• Coronary artery disease • Protein C, S deficiency
• Diabetes mellitus Major surgeries
• Congestive cardiac failure • Orthopedic surgeries—total knee replacement,
• Postpartum period total hip replacement
• Malignancy • Laparoscopic surgeries
• Age >40 • Vascular surgeries
• Central venous catheters • Major general surgery
• Hip or leg fracture

Most common sites of origin of pulmonary embolism are:
• Calf and popliteal veins of leg
• Pelvic veins
• Inferior vena cava.
CLINICAL FEATURES AND DIAGNOSIS

Most of the patients with PE have detectable DVT of legs. Most of the emboli
are asymptomatic and the clinical presentation depends on the size of emboli,
location, number of emboli (single/multiple) and the cardiorespiratory status
Chapter 29 Deep Venous Thrombosis and Pulmonary Embolism 215
Flow chart 29.1 Pathophysiology of venous thromboembolism
of the patient. Symptoms include breathlessness, leg pain, edema of limbs,

discoloration. Signs include dyspnea, tachypnea and tachycardia. Pain on
forced dorsiflexion of the foot (Homan’s sign) can be seen in DVT. Hemoptysis
and pleuritic chest pain is due to pulmonary infarction. Worsening of dyspnea
and hemodynamic instability can be due to right ventricular failure. Massive
pulmonary embolism can lead to circulatory collapse and cardiac arrest. More
than 50% obstruction of pulmonary circulation is required to cause increase
in mean pulmonary artery pressure. Other causes of embolism can be fat, air,
amniotic fluid, cement and bone fragment while reaming.
Noninvasive imaging is used in patients, where there is high clinical
suspicion of DVT or PE (Flow chart 29.2).
Electrocardiogram
The most common finding is sinus tachycardia and the more specific to PE is the
SIQ3T3 sign - S wave in lead I, a Q wave in lead III, and an inverted T wave in lead
III. Other findings are T-wave inversion in leads V1 to V4.
Lab Investigations
Plasma d-dimer is used to rule out DVT, as it has got high negative predictive
value. Serum troponin and plasma heart-type fatty acid–binding protein levels
can be elevated due to RV microinfarction. Elevated BNP or NT-BNP can also be
seen. D-dimer can be falsely elevated in severe systemic illness (Table 29.2).
Table 29.2 Features of different sizes of embolism
Pulmonary embolus Hypotension Echocardiography Prognosis

Small No No findings Excellent
Moderate-to-large No RV hypokinesia Borderline
Massive Yes RV failure Poor
Flow chart 29.2 Algorithms for PE and DVT diagnosis
Fig. 29.1 Loss of vein compressibility in DVT (Popliteal vessels)
Venous Ultrasonography
The primary criteria for diagnosing DVT is loss of vein compressibility. Other
diagnostic features are loss of phasic variability and loss of distal augmentation
(Fig. 29.1).
Fig. 29.2 Right pulmonary infarct due to pulmonary embolus
Chest X-ray
Usually, a normal chest X-ray is common in PE. Other findings are a peripheral
wedged-shaped density above the diaphragm (Hampton’s hump), focal oligemia
(Westermark’s sign), and an enlarged right descending pulmonary artery (Palla’s
sign).
CT–Chest
CT with contrast is the main imaging modality used for diagnosis of PE. Cardiac
chambers along with proximal and distal veins can be imaged for thrombus (Fig.
29.2).
MRI
Used along with gadolinium, it can detect DVT in cases where ultrasound is
equivocal. It is useful for detecting large proximal PE rather than distal PE.
V/Q Scan
It is used in patients who cannot tolerate intravenous contrast. High probability
is defined as two or more segmental perfusion defects in the presence of normal
ventilation.
Echocardiography
Although it is sensitive to detect only main pulmonary artery PE, it does help to
rule out other conditions (Figs 29.3 and 29.4).
Fig. 29.3 Pulmonary embolus present in pulmonary artery indicated by arrow
Fig. 29.4 Thrombus occupying the entire IVC
PREVENTION (TABLES 29.3 TO 29.6)

The following methods are used for prevention of thromboembolism:
• Intermittent pneumatic compression
• Compression stockings
• Administration of heparin—unfractionated or low molecular weight heparin
• Fondaparinux
• Warfarin.
Table 29.3 ACCP guidelines for prevention of thrombosis in nonsurgical patients
Clinical condition/situation Recommended prophylaxis

Hospitalized acutely ill medical patients
Risk for thrombosis LDUH or LMWH bid, or fondaparinux
Increased risk of thrombosis who Mechanical thromboprophylaxis with graduated
are bleeding or at high risk for major compression stockings or intermittent pneumatic
bleeding compression
Critically ill patients Routine ultrasound screening is not advised.
LMWH or LDUH thromboprophylaxis is
recommended.
Increased risk of thrombosis who Mechanical thromboprophylaxis with graduated
are bleeding or at high risk for major compression stockings or intermittent pneumatic
bleeding compression
Abbreviations: LDUH, low dose unfractionated heparin; LMWH, low molecular weight heparin; ACCP,
American College of Chest Physicians
Table 29.4 ACCP guidelines for prevention of thrombosis in nonorthopedic

surgical patients

Patients undergoing general, GI, urological,
gynecologic, bariatric, vascular, plastic, or
reconstructive surgery
Very low risk for VTE No pharmacologic or mechanical
prophylaxis.
Low risk for VTE Mechanical prophylaxis, preferably with
intermittent pneumatic compression (IPC)
Moderate risk for VTE with no high risk of LMWH, LDUH, or mechanical prophylaxis,
bleeding complications preferably with IPC
Moderate risk for VTE with high risk of Mechanical prophylaxis, preferably with
bleeding complications IPC
High risk for VTE with no high risk of LMWH or LDUH plus mechanical
bleeding complications prophylaxis with elastic stockings or IPC
High risk for VTE in patients who undergo Extended-duration pharmacologic
surgery for cancer with no high risk of prophylaxis (4 weeks) with LMWH
bleeding complications
High risk for VTE with high risk of bleeding Mechanical prophylaxis, preferably with
complications IPC
High risk for VTE in whom both LMWH and Low-dose aspirin, fondaparinux, or
unfractionated heparin are contraindicated mechanical prophylaxis, preferably with
or unavailable and who are not at high risk IPC
for major bleeding complications
Contd…
Contd…

Patients undergoing cardiac surgery
Uncomplicated postoperative course Mechanical prophylaxis, preferably with
optimally applied IPC or pharmacologic
prophylaxis
Hospital course prolonged by one or more Add pharmacologic prophylaxis with LDUH
nonhemorrhagic surgical complications or LMWH to mechanical prophylaxis
Patients undergoing thoracic surgery
Moderate risk for VTE who are not at high LDUH, LMWH, or mechanical prophylaxis
risk for perioperative bleeding with optimally applied IPC
High risk for VTE who are not at high risk LDUH, LMWH, plus mechanical
for perioperative bleeding prophylaxis with optimally applied IPC
High risk for major bleeding Mechanical prophylaxis with optimally
applied IPC.
Patients undergoing craniotomy
With no risk Mechanical prophylaxis with IPC.
Very high risk for VTE Mechanical prophylaxis with IPC plus
pharmacologic prophylaxis once adequate
hemostasis is established and the risk of
bleeding decreases.
Patients undergoing spinal surgery
No risk Mechanical prophylaxis with IPC,
unfractionated heparin, or LMWH
High risk for VTE (malignant disease or Mechanical prophylaxis with IPC plus
those undergoing surgery with combined pharmacologic prophylaxis once adequate
anterior-posterior approach) hemostasis is established and the risk of
bleeding decreases.
Patients with major trauma: Traumatic brain injury, acute spinal injury, and traumatic spine
injury
Major trauma with no risk LDUH, LMWH, or mechanical prophylaxis,
preferably with IPC.
High risk for VTE Add mechanical prophylaxis to
pharmacologic prophylaxis when not
contraindicated by lower extremity injury.
Major trauma patients in whom LMWH and Mechanical prophylaxis with IPC when not
LDUH are contraindicated contraindicated by lower-extremity injury.
Add pharmacologic prophylaxis with either
LMWH or LDUH when the risk of bleeding
diminishes or the contraindication to
heparin resolves.
Abbreviation: VTE, venous thromboembolism
Table 29.5 ACCP guidelines for prevention of thrombosis in

orthopedic surgical patients

Patients undergoing major orthopedic surgery: Total hip arthroplasty (THA), total knee
arthroplasty (TKA), hip fracture surgery (HFS)
Patients undergoing THA or TKA LMWH, fondaparinux, apixaban,
dabigatran, rivaroxaban, LDUH, adjusted-
dose VKA, aspirin, or an intermittent
pneumatic compression device (IPCD) for
minimum of 10–14 days
Patients undergoing HFS LMWH, fondaparinux, LDUH, adjusted-
dose VKA, aspirin, or an IPCD for
minimum of 10–14 days
Patients undergoing major orthopedic Start LMWH preferably in these patients
surgery (THA, TKA, HFS) and receiving and start LMWH ≥12 hour before
LMWH as thromboprophylaxis surgery or ≥12 hour after surgery. It is
recommended to use dual prophylaxis
with an antithrombotic agent and an IPCD
during the hospital stay
Thromboprophylaxis for patients Thromboprophylaxis for up to 35 days from
undergoing major orthopedic surgery in the day of surgery
the outpatient period
Patients undergoing major orthopedic IPCD
surgery and increased risk of bleeding
Abbreviations: VKA, vitamin K antagonist; IPCD, intermittent pneumatic compression device
Table 29.6 Dose of anticoagulants for prophylaxis of VTE
Drug Dose
Unfractionated heparin 80 units/kg bolus and 18 units/kg/hour infusion
Or bolus of 5,000 U every 8–12 hours
LMWH
Enoxaparin 1 mg/kg 12th hourly or 40 mg SC once daily or 12th hourly
Dalteparin 100 U/kg 12th hourly or 2500–5000 U SC once daily
Fondaparinux 2.5 mg SC once daily
Warfarin 5 mg initially and titrate the dose to get INR of 2.0–3.0
TREATMENT (FLOW CHART 29.3)

Flow chart 29.3 DVT treatment
Algorithm for PE Management

It is based on hemodynamic instability and right ventricular function.
Anticoagulation (Table 29.7)

Table 29.7 Dose of anticoagulants for treatment of VTE
Drug Dose aPTT

Unfractionated heparin 80 units/kg bolus and Maintain 2–3 times the
18 units/kg/hour infusion normal
LMWH
Enoxaparin 1 mg/kg SC 12th hourly Monitoring not required
Dalteparin 200 U/kg SC once a day
100 U/kg SC 12th hourly
FONDAPARINUX <50 kg—5 mg Monitoring not required
(Anti–Xa pentasaccharide) 50–100 kg—7.5 mg
>100 kg—10 mg
WARFARIN 5 mg initially INR titration to 2.0–3.0
(3–5 days of bridging with parenteral
anticoagulants is required)
New Oral Anticoagulants

• Rivaroxaban—Xa inhibitor
• Dabigatran—direct thrombin inhibitor.
Duration of Anticoagulation
• DVT restricted to calf veins or upper extremity, proximal leg DVT, or PE,
cancer patients with DVT/PE—3 to 6 months
• Idiopathic DVT/PE—2 to 3 months.
IVC Filters
Indications
• Presence of acute PE with contraindication to anticoagulation
• Recurrent venous thrombosis inspite of adequate anticoagulation.
In patients with acute PE who are treated with anticoagulants, use of an IVC
filter is not recommended.
Treatment of RV Dysfunction
• Intravenous fluid is administered judiciously in case of right ventricular
dysfunction.
• Dopamine/dobutamine are the first line vasopressors used in case of
hemodynamic instability.
Thrombolysis
• rtPA—100 mg over 2 hours. Contraindications are recent surgery, intracranial
disease. Indication is massive PE.
• Successful thrombolysis can reverse right heart failure and prevent
recurrence.
BIBLIOGRAPHY
1. Anderson FA Jr, Spencer FA. Risk factors for venous thromboembolism. Circulation.
2003;107(23 Suppl 1):I9.
2. Benotti JR, Dalen JE. The natural history of pulmonary embolism. Clin Chest Med.
1984;5:403.
3. Chastre J, Cornud F, Bouchama A, et al. Thrombosis as a complication of pulmonary-
artery catheterization via the internal jugular vein: prospective evaluation by
phlebography. N Engl J Med. 1982;306:278.
4. Cranley JJ, Canos AJ, Sull WJ. The diagnosis of deep venous thrombosis. Fallibility of
clinical symptoms and signs. Arch Surg. 1976;111:34.
5. Geerts WH, et al. Prevention of venous thromboembolism: American College of Chest
Physicians Evidence-based Clinical Practice Guidelines, 8th edn. Chest. 2008;133:
381S.
6. Guyatt GH, et al. Antithrombotic Therapy and Prevention of Thrombosis. American
College of Chest Physicians Evidence-based Clinical Practice Guidelines, 9th edn.
Chest. 2012;141(2)(Suppl):7S-47S.
7. Kucher N, Goldhaber SZ. Management of massive pulmonary embolism. Circulation.

2005;112:e28.
Principles of Internal Medicine, 18th edn. McGraw-Hill Publications; 2012.
9. McIntyre KM, Sasahara AA. The hemodynamic response to pulmonary embolism in
patients without prior cardiopulmonary disease. Am J Cardiol. 1971;28:288.
10. Paul M L. The ICU Book, 3rd edn. Lippincott Williams and Wilkins, 2007.
11. Torbicki A, et al. Guidelines on the diagnosis and management of acute pulmonary
embolism: The Task Force for the Diagnosis and Management of Acute Pulmonary
Embolism of the European Society of Cardiology (ESC). Eur Heart J. 2008;29:2276.
CHAPTER
30 Prem Kumar
OBSTRUCTIVE SLEEP APNEA AND OBESITY

HYPOVENTILATION SYNDROME
HISTORY
President Howard Taft stated, “I have lost that tendency to sleepiness which made
me think of the fat boy in Pickwick. My color is very much better and my ability
to work is greater’’. Joe the “Fat Boy,” the character in Dickens’s The Posthumous
Papers of the Pickwick Club, was from where the term “Pickwickian syndrome”
got derived.
INTRODUCTION
Obesity can be defined as a “disease” since it is physiologic dysfunction with
environmental, genetic, and endocrinologic causes. Common diseases associated
with obesity include insulin resistance, type 2 diabetes mellitus, obstructive
sleep apnea (OSA), obesity hypoventilation syndrome, coronary artery disease,
hypertension and osteoarthritis. The OSA is seen in increased incidence as an
etiology for intermittent functional upper airway obstruction. Obesity is a known
risk factor although OSA can occur in patients without obesity too (Tables 30.1
and 30.2).
Table 30.1 Levels of risk associated with increasing body mass index
Classification BMI (kg/m2) Risk of developing health problems

Underweight <18.5 Increased
Normal weight 18.5–24.9 Least
Overweight 25.0–29.9 Increased
Obese
Class 1 30.0–34.9 High
Class 2 35.0–39.9 Very high
Class 3 40.0–49.9 Extremely high
Superobese ≥50 Exceedingly high
Table 30.2 Waist circumference and risk
Waist circumference Body mass index (kg/m2)

Normal weight Overweight Obese class 1
<102 cm (♂) Least risk Increased risk High risk
<88 cm (♀)
≥102 cm (♂) Increased risk High risk Very high risk
≥88 cm (♀)
Spectrum of sleep disorders

Snoring→hypopnea→apnea→OSA→OHS.
OBSTRUCTIVE SLEEP APNEA

Obstructive sleep apnea (OSA) is a condition characterized by functional upper
airway obstruction which is associated with recurrent episodes of cessation of
breathing (apnea), reduction in airflow (hypopnea) during sleep resulting in
sleep deprivation and reduction in oxygen saturation inspite of respiratory effort.
• Apnea—no airflow >10 seconds
• Hypopnea—reduction in airflow >50% for 10 seconds and with at least 4%
reduction in SpO2 and arousal in EEG.
Causes of apnea can be either obstructive or central.
Diagnosis
Obstructive sleep apnea (OSA) can be suspected in patients having complaints of
snoring, apnea, daytime somnolence with exclusion of all other possible causes
which can cause or exacerbate OSA—adenotonsillar enlargement, macroglossia,
hypothyroidism, drug addiction with sedatives, opioids. Diagnosis is done with
polysomnography which calculates AHI (apnea/hypopnea index) which should
be >5 events/hour of sleep (Table 30.3).
AHI can be also calculated with the following formula:
AHI = Total number of apneas + hypopneas ÷ total sleep time × 60
Table 30.3 Recent classification for severity of obstructive sleep apnea
• Mild—AHI of 5–15 events/hour

• Moderate—AHI of 15–30 events/hour
• Severe—AHI of >30 events/hour
Oropharyngeal examination can be useful in patients with OSA. Modified

Mallampati score 3 or 4, macorglossia, retroganthia, tonsillar enlargement,
narrow oropharyngeal cavity can all point towards OSA. Large neck circumference
of 17 inches in men, >16 inches in women, or >60 cm in anyone is also a risk
factor.
Chapter 30 Obstructive Sleep Apnea and Obesity Hypoventilation Syndrome 227
Pathophysiology of OSA
Anatomic narrowing of upper airway plays a major role in the pathophysiology of
OSA. Apart from anatomic changes, there is decrease in respiratory center output
which causes loss of pharyngeal muscle tone during sleep casuing obstruction.
Frequent apneic episodes result in arousal, daytime somnolence, change in sleep
pattern (from deep sleep to wakeful ness indicated by the alpha pattern in EEG)
and sleep deprivation. Fall in oxygen saturation causes hypoxemia which causes
pulmonary vasoconstriction and on chronic stimulation may lead to pulmonary
hypertension and cardiac failure (cor pulmonale). 10% to 20% of patients with
OSA have chronic alveolar hypoventilation with elevation in PaCO2 and can also
develop cardiac arrhythmias. OSA plays an important role in metabolic syndrome.
Central Sleep Apnea

Recurrent episodes of apnea during sleep in the absence of respiratory effort.
Mostly, it is idiopathic but the most common cause of central sleep apnea (CSA)
in ICU is congestive cardiac failure, neuromuscular disorder, cardiac failure,
opioid sedation and brainstem disorder. CSA is due to loss of respiratory drive
to respiratory muscles. CPAP or adaptive support ventilation (ASV) is useful in
these patients.
OBESITY HYPOVENTILATION SYNDROME

Obesity hypoventilation syndrome (OHS) is also known by the name—pickwickian
syndrome. The diagnostic criteria for OHS developed by the American Academy
of sleep Medicine are given in Table 30.4. The OHS is associated with awake
chronic hypoxemia (PaO2 <65 mm Hg) without the presence of any other
cause (COPD, lung disease). These patients have impaired central ventilatory
drive. OHS patients have daytime hypercarbia which is absent in OSA. But the
diagnsosis of OHS in ICU is challenging because of other factors associated with
hypoxia and hypercarbia.
Table 30.4 Diagnostic criteria for obesity hypoventilation syndrome
• BMI>30 kg/m2
• Awake arterial hypercapnia (PaCO2 >45 mm Hg)
• Rule out other causes of hypoventilation
• Polysomnography reveals sleep hypoventilation with nocturnal hypercapnia with or
without obstructive apnea/hypopnea events
Obesity hypoventilation syndrome (OHS) is associated with daytime

hypercarbia with nocturnal increase in PaCO2 (>10 mm Hg from baseline).
Pulmonary function test and chest radiography are done to exclude COPD or any
other obstructive lung disease. FEV1/FVC ratio is normal in OHS whereas it is
reduced in obstructive lung disease. Electrocardiography and echocardiogram
can reveal features of right ventricular enlargement and pulmonary hypertension
(‘p’ pulmonale). Factors associated with hypoxemia in OHS are atelectasis,
alveolar hypoventilation, V/Q mismatch and pulmonary hypertension with heart
failure.
Treatment
Supplemental oxygen is ineffective in patients with OHS. BiPAP is started, if the
patient is intolerant to CPAP of ≥15 cm H2O, persistent hypoxemia inspite of
resolved obstruction, and if PaCO2 does not normalize after 3 months of therapy
with CPAP. Patients with type 2 respiratory failure should be considered for early
initiation of noninvasive ventilation. Early initiation of NIV will reduce the need
for intubation and invasive ventilation. NIV with facemask is preferred in ICU
patients rather than nasal mask.
Goals for NIV in OHS

• Improvement of signs and symptoms
• Improving PaO2
• Normalizing the nocturnal and daytime PaCO2 and pH
• Daytime PaCO2 of 40–50 mm Hg.
After achieving the goals, the patient can be transferred from ICU. Failure of
improvement with NIV should be considered as indication for invasive ventilation.
Failure of all strategies should point towards consultation with bariatric surgeon.
Indications of Tracheostomy in OHS

• It is considered as a last option in patients where all treatments have failed
• Daytime hypercapnia inspite of all treatments.
Tracheostomy can improve hypercapnia and nocturnal obstructive events.
Respiratory Stimulants
• Acetazolamide
• Medroxy progesterone.
Their role is questionable but may be used in combination with CPAP/BiPAP
(Flow chart 30.1).
Flow chart 30.1 Algorithm for management of OHS in an obese patient

Chapter 30 Obstructive Sleep Apnea and Obesity Hypoventilation Syndrome 229
Fig. 30.1 RAMP position for intubating a morbidly obese patient
Perioperative Management
It includes a careful preoperative assessment of airway and all other systems
involved with obesity. Large neck circumference (>17 inches in males, >15
inches in females) and increased amount of pretracheal soft tissue measured
ultrasonically were found to be positive predictors of difficult intubation with
laryngoscopy performed with patients in the sniffing position. Collins et al. did a
study on two different positions for intubation in obese patients. They found that
there was a favorable laryngoscopic view with RAMP position rather than sniffing
position (Fig. 30.1). Intubating these morbidly obese patients is challenging, and
hence an experienced anesthesiologist is required to intubate these patients.
Intubation using fiberoptic bronchoscopy is used, and if ventilation is difficult
to maintain, a proseal or intubating Laryngeal mask airway can be used as an
alternative. Postoperative management of airway is done with CPAP or BiPAP
machines in PACU with monitoring of EtCO2 and pulse oximetry to prevent
atelectasis and small airway closure.
BIBLIOGRAPHY
1. Alam K, Lewis JW, Stephens JN, et al. Obesity, metabolic syndrome and sleep apnoea:
All pro-inflammatory states. Obes Rev. 2007;8:119-27.
2. Al Dabal L, Bahammam AS. Obesity hypoventilation syndrome. Annals of Thoracic
Medicine 2009;4(2):41-9. doi:10.4103/1817-1737.49411.
3. Collins JS, Lemmens HJ, Brodsky JB, et al. Laryngoscopy and morbid obesity: A
comparison of the “sniff’’ and ‘‘ramped’’ positions. Obes Surg. 2004;14:1171-5.
4. Conway B, Rene A. Obesity as a disease: No lightweight matter. Obes Rev. 2004;5:
145-51.
5. Ezri T, Gewurtz G, Sessler DI, et al. Prediction of difficult laryngoscopy in obese
patients by ultrasound quantification of anterior neck soft tissue. Anaesthesia. 2003;
58:1111-4.
6. Guilleminault C. Clinical features and evaluation of obstructive sleep apnea. Kryger

MH, Roth T, Dement WC (Eds). Principles and Practice of Sleep Medicine, 2nd edn.
Philadelphia: WB Saunders; 1994.p 667.
7. Kushida CA, Chediak A, Berry RB, Brown LK, Gozal D, Iber C, et al. Clinical guidelines
for the manual titration of positive airway pressure in patients with obstructive sleep
apnea. J Clin Sleep Med. 2008;4(2):157-71.
8. Miller WP. Cardiac arrhythmias and conduction disturbances in the sleep apnea
syndrome. Am J Med. 1982;73:317.
9. Onal E, Lopata M, O’Connor T. Pathogenesis of apneas in hypersomnia: sleep apnea
syndrome. Am Rev Respir Dis. 1982;125:167.
10. Orr WC, Martin RJ. Obstructive sleep apnea associated with tonsillar hypertrophy in
adults. Arch Intern Med. 1981;141:990.
11. Rajagopal KR, Abbrecht PH, Derderian SS, et al. Obstructive sleep apnea in
hypothyroidism. Ann Intern Med. 1984;101:491.
12. Shepard JW Jr, Garrison MW, Grither DA, et al. Relationship of ventricular ectopy to
oxyhemoglobin desaturation in patients with obstructive sleep apnea. Chest. 1985;
88:335.
13. Walsh RE, Michaelson ED, Harkleroad LE, et al. Upper airway obstruction in obese
patients with sleep disturbance and somnolence. Ann Intern Med. 1972;76:185.
SECTION
9
APPROACH TO MECHANICAL
VENTILATION
Chapter 31 Basics of Mechanical Ventilation

Chapter 32 Initiation of Ventilation

Prem Kumar
Chapter 33 Modes of Ventilation

Prem Kumar
Chapter 34 Weaning from Mechanical

Ventilation
Prem Kumar
Chapter 35 Patient Ventilator Asynchrony

Prem Kumar
Chapter 36 Noninvasive Ventilation

CHAPTER
31 Prem Kumar, S Yuvaraj
BASICS OF MECHANICAL VENTILATION
Mechanical ventilation is a type of breathing in which an external machine

augments or controls the breathing of a patient when the ventilatory requirements
are not met. The goal of mechanical ventilation is to reduce the work of breathing
in the patient and to improve gas exchange.
There are two types of mechanical ventilation:
1. Negative pressure ventilation
2. Positive pressure ventilation.
Another classification of mechanical ventilation is:
• Noninvasive ventilation
• Invasive ventilation.
NEGATIVE PRESSURE VENTILATION

Till the mid 20th century, ventilators used for the patients were only negative
pressure ventilators popularly called as iron lung. Flow of oxygen was driven into
the patient’s lung by creating a subatmospheric pressure around the chest. But
it was difficult to nurse and access the patients especially when the patient was
hemodynamically unstable. Later negative pressure ventilators lost its popularity
and positive pressure ventilators replaced them.
POSITIVE PRESSURE VENTILATION

Positive-pressure ventilation is a type of ventilation where pressure above the
atmospheric pressure is driven either through a face mask or nasal mask (non-
invasive) or through an endotracheal tube (invasive). In an ICU, either non-
invasive or invasive ventilation is given according to the clinical conditions. On
delivery of the ventilation, airway pressure is more than the alveolar pressure.
VENTILATOR DESIGN
Current ventilators use bellows system using oxygen as driving gas. Recently
piston driven ventilators and microprocessor controlled pneumatic drive
mechanism are being used. The ventilators are designed to trigger, limit and cycle
the breath according to set parameters. Mode controller is either pneumatic-or
234 Section 9 Approach to Mechanical Ventilation
microprocessor-based system which enables the breath delivery according to

algorithm and feedback (closed loop) from the patient. Recently closed loop
system has become very popular since it allows continuous adjustment in
algorithms according to patient’s lung dynamics. Flow and pressure transducers
are installed in the ventilator which will act as sensors for breath effort. Humidifiers
also are part of the system which humidifies the gases delivered to the patient.
Ventilator circuit with known compliance is used.
NOMENCLATURES AND THEIR SIGNIFICANCE

Any mode of ventilation has four components (Table 31.1):
1. Breath type
2. Control
3. Phase variables
4. Conditional variable.
Table 31.1 Components of ventilation
Breath type Control variable Phase variables Conditional variable

• Mandatory • Pressure • Trigger • PEEP
• Assisted • Time • Limit
• Spontaneous-assisted • Flow • Cycling
• Volume • Expiration
BREATH TYPE (FIGS 31.1 TO 31.4)

Mandatory: The breath is initiated and terminated by the machine.
Assisted: The breath is initiated by the patient but terminated by the machine.
Spontaneous: The breath is initiated and terminated by the patient.
Fig. 31.1 Volume control mode with mandatory breaths

Chapter 31 Basics of Mechanical Ventilation 235
Fig. 31.2 SIMV (volume control) with pressure support showing assisted breaths
Fig. 31.3 Pressure support ventilation with spontaneous breaths
Fig. 31.4 Spontaneous and supported breaths in pressure waveform

Control
Usually volume or pressure controlled ventilation modes are seen in most
ventilators. Control indicates preset parameter which assures the set limit, e.g.
volume-controlled ventilation assures set tidal volume (Figs 31.5 and 31.6).
Trigger
It is a physical change that initiates a breath. Four types of trigger are—time,
pressure, flow, volume.
Fig. 31.5 Volume control ventilation shown by waveform (indicated by arrow)
Fig. 31.6 Pressure control ventilation shown by waveform (indicated by arrow)

Chapter 31 Basics of Mechanical Ventilation 237
Limit
After triggering is on, limit is the mechanism that provides a mode of ventilation
within a parameter such as time, pressure, volume, flow. Volume-limited breaths
are flow controlled. Pressure-limited ventilation are pressure controlled. Time
and volume control is seen infrequently.
Cycling
Cycling is defined as the transition point where there is change from inspiratory
phase to expiratory phase in a mechanically ventilated breath. It can be time
cycled which is most commonly seen in most pressure-controlled breaths. This
can be seen when inspiratory time lapses (Ti) in pressure-controlled ventilation.
It can also be:
Time cycled—seen in PCV
Pressure cycled—seen in intermittent mandatory breaths
Flow cycled—seen in PSV
Volume cycled—seen in volume assist modes.
Expiration
Expiration can be prolonged in conditions like COPD where air trapping is
common.
Effects of Positive Pressure Ventilation and PEEP

Lung dynamics—pressures in airways, alveoli are increased. Especially the peak
inspiratory pressure and mean airway pressure are related to tidal volume, peak
inspiratory flow rate and compliance. In lungs where compliance is decreased
(e.g. ARDS), higher peak inspiratory pressure (PIP) and PEEP is required to
ventilate the lung.
PEEP: It is an airway pressure strategy which increases the end-expiratory pressure
above the atmospheric pressure. PEEP increases mean airway pressure and
results in reduced cardiac output and increase in PEEP may cause hypotension.
It causes increase in PAP (pulmonary artery pressure) and hence increased
central venous pressure. The goal of PEEP in patients with airway obstruction is
to minimize inspiratory work.
Cardiovascular effects: Positive pressure ventilation causes increase in
intrathoracic pressure which in turn causes compression of great vessels and
ends in reduction of cardiac output. Positive pressure ventilation as such causes
fall in central venous pressure (CVP) due to reduced venous return.
BIBLIOGRAPHY
1. Chang DW. Clinical application of mechanical ventilation, 3rd edn. 2006.
2. Gay PC, Rodarte JR, Hubmayr RD. The effects of positive expiratory pressure on
isovolume flow and dynamic hyperinflation in patients receiving mechanical
ventilation. Am Rev Respir Dis. 1989;139:621.
3. Hill NS. Clinical applications of body ventilators. Chest. 1986;90:897.

4. Irwin RS, Rippe JM. Irwin and rippe’s intensive care medicine, 6th edn. Lippincott
Williams and Wilkins, 2008.
5. Petrof BJ, Legare M, Goldberg P, et al. Continuous positive airway pressure reduces
work of breathing and dyspnea during weaning from mechanical ventilation in severe
chronic obstructive pulmonary disease. Am Rev Respir Dis. 1990;141:281.
6. Tobin MJ, Jubran A, Laghi F. Patient-ventilator interaction. Am J Respir Crit Care Med.
2001;163:1059.
CHAPTER
32 Prem Kumar
INITIATION OF VENTILATION
Mechanical ventilation is indicated in patients who are not able to maintain the
ventilation or on loss of spontaneous ventilation. Mechanical ventilators either
give partial or complete support depending upon the condition and status of the
patient (Tables 32.1 and 32.2).
Table 32.1 Indications for initiation of mechanical ventilation
Indications
• Severe hypoxemia—PaO2 <50 mm Hg with FiO2 of >0.5
• PaCO2 >50 mm Hg
• Severe metabolic (lactic) acidosis pH <7.2
• SpO2 <85%
• Impending ventilatory failure as indicated by the following criteria:
– Tidal volume <5 mL/kg
– Respiratory rate >35/minute
– Vital capacity <10 mL/kg
– Minute ventilation >10 L/minute
– Maximal inspiratory pressure < –20 cm H2O
• Alveolar arterial gradient >450 mm Hg with 100% oxygen
• Head injury with GCS (Glassgow coma scale) <8
• Severe hemodynamic instability with hypoxemia
• Apnea due to other causes (e.g. Drug toxicity, myasthenia gravis)
• Vd/Vt ratio >0.6
Table 32.2 Types of respiratory failure—conditions which require mechanical

ventilation
Type 1 respiratory Type 2 respiratory Type 3 respiratory Type 4 respiratory

failure failure failure failure
Conditions with Obstructive lung Perioperative failure Occurs due to
increased shunting disease shock where there is
• ARDS • Asthma • Atelectasis decreased perfusion
• Pulmonary edema • COPD to respiratory
• Pneumonia muscles
• Intrapulmonary
shunting
Once mechanical ventilation is initiated, the goals of mechanical ventilation are:

• Reducing the work of breathing
• Improving the gas exchange
• Reversion of the pathological condition to normal
• Correction of lung dynamics
• Avoiding complications due to mechanical ventilation (e.g. barotrauma,
nosocomial pneumonia, oxygen toxicity).
INITIAL VENTILATOR SETTINGS

Initial ventilator settings should be based upon the patient’s status,
pathophysiology of the condition and its relation to the respiratory system. The
following ventilatory settings must be selected:
• Mode
• Tidal volume
• Inspired oxygen concentration (FiO2)
• Respiratory rate (mandatory)
• Inspiratory to expiratory ratio (I:E ratio) or inspiratory time (Ti)
• PEEP
• Trigger sensitivity
• Inspiratory flow pattern
• Pressure support
• Alarm settings.
Mode
The initial step in initiating ventilation is selection of mode and the decision
of selecting the mode depends on whether the patient requires total or partial
ventilatory support. Most of the ICU patients may require complete support
initially followed by partial support on weaning (Table 32.3).
But nowadays combined modes or dual control modes are available in
modern ventilators. (e.g. SIMV can be combined with pressure support which
fastens the weaning process).
Table 32.3 Traditional modes and its uses in ICU
Modes Comments
Assist control (A/C) mode/volume control Usually started with this mode for complete
(VCV) mode ventilatory support
Synchronized intermittent Can give partial or complete ventilatory
Mandatory ventilation (SIMV) support
Continuous positive airway pressure (CPAP)/ Gives partial support and can be used only
bilevel positive airway pressure (BiPAP)/ in spontaneously breathing patients
pressure support ventilation (PSV)
Chapter 32 Initiation of Ventilation 241
Tidal Volume
Initial tidal volume is usually 10–12 mL/kg based on the predicted body weight.
But in conditions like ARDS lower tidal volumes of 6 mL/kg is recommended
since lower tidal volume with higher respiratory rate is preferred to reduce the
lung injury caused by higher tidal volume. Reduced tidal volume is also used
in COPD patients with prolonged expiratory time to avoid air trapping. Tidal
volume is preferable to be guided with expired tidal volume and capnography
since the circuit compliance is another factor which has to be borne in mind
while calculating the tidal volume. This volume lost due to circuit compliance is
called circuit compression volume.
FiO2
The initial concentration can be set at 100% but after stabilizing the patient, the
least possible FiO2 (usually 0.3–0.4) to obtain better PaO2 (>90 mm Hg) is kept.
Higher concentration of oxygen can cause atelectasis, oxygen toxicity and further
increase the lung damage. It can be increased if other settings like PEEP and
pressure support does not improve oxygenation.
Respiratory Rate
The initial respiratory rate to attain normal PaCO2 is usually 10–12 breaths/
minute increased respiratory rates can be associated with air trapping causing
intrinsic PEEP. Once the patient is put on an initial ventilator setting, blood gas
analysis is done after 1 hour to titrate the respiratory rate and other settings to
optimize oxygenation and ventilation.
I:E Ratio
Usually, the normal I:E ratio kept in ventilator settings is 1:2–1:3. Expiratory phase
is prolonged in patients with COPD to avoid air trapping and thus to prevent
auto-PEEP. Auto-PEEP is an unintended end expiratory pressure which develops
due to inadequate alveolar air emptying resulting in air trapping. Inverse I:E
ratio is used in ARDS patients who have severe hypoxemia refractory to the usual
treatment. Inverse ventilation requires high sedation or paralysis. Increasing the
flow rate or reducing the tidal volume or reducing the respiratory rate or reducing
the inspiratory time (Ti%) will increase the I:E ratio or prolong the expiratory
phase.
PEEP
It is an airway pressure strategy which increases the end-expiratory pressure
above the atmospheric pressure. PEEP increases the functional residual capacity
by alveolar recruitment and improves the oxygenation and reduces the work
of breathing. It is also indicated for patients having refractory hypoxemia due
to intrapulmonary shunting. Usually, PEEP of 5 cm H2O is kept normally for
ventilated patients. In patients with ARDS (reduced lung compliance), higher
PEEP is required to improve oxygenation.
Trigger Sensitivity
The change required in the patient to deliver the ventilator breath is trigger
sensitivity. It is usually set at –2 cm H2O which means the patient just needs to
generate a pressure of –2 cm H2O at airway opening to initiate the ventilator
breath. Increasing the trigger (e.g. –4 cm H2O) means that the patient needs to
put more inspiratory effort to trigger the ventilator. It can be either pressure or
flow trigger.
Inspiratory Flow Pattern

It can be square flow pattern and sine wave pattern. Ascending and descending
flow patterns can be seen in patients with obstructive lung disease. Usually,
square flow pattern is used initially after keeping the setting in the ventilator.
Pressure Support
Nowadays modern ventilators have dual modes (e.g. SIMV with pressure support
[PS]). This pressure support augments the tidal volume in the spontaneous
breath which occurs in between the mandatory breaths thus reducing the work
of breathing and thereby fastening the weaning period.
Ventilator Alarms
Ventilator alarms are kept to avoid the hazards and complications due to ventilator
or due to the patient’s condition. The alarm setting parameters are the following:
• High and low airway pressure alarm
• High and low minute ventilation alarm
• Low-expiratory tidal volume alarm
• Apnea alarm
• High and low FiO2 alarm
• High respiratory rate alarm.
High and Low Airway Pressure Alarm

It is usually set at 40 cm H2O as empirical value in adults or 30 cm H2O in children.
But the usual way of setting the high pressure alarm is 10–15 cm H2O above the
peak-inspiratory pressure in the patient. In the same way, low pressure alarm is
set at 10–15 cm H2O below the peak-inspiratory pressure.
High and Low Minute Ventilation Alarm

The threshold limit for both high and low alarm is 10–15% above and below the
patients baseline minute ventilation.
Low-expired Tidal Volume Alarm

It is set at 100 mL below the average expired tidal volume in the patient.
Chapter 32 Initiation of Ventilation 243
Apnea Alarm
Apnea alarm should be set with 20 second delay and in most of the current
ventilators there is a back up mode in case if the apnea alarm is activated.
High and Low FiO2 Alarm

The threshold limit for FiO2 alarm is 5–10% above or below the analysed value in
the patient.
High Respiratory Rate Alarm

The alarm is usually kept 10–15 breaths above or below the observed the
respiratory rate (Flow charts 32.1 and 32.2).
Flow chart 32.1 Trouble shooting the ventilator alarms
Flow chart 32.2 Trouble shooting the PEEP alarms

BIBLIOGRAPHY
1. Chang DW. Clinical application of mechanical ventilation, 3rd edn. 2006.
2. Hill NS. Clinical applications of body ventilators. Chest. 1986;90:897.
3. Hubmayr RD, Gay PC, Tayyab M. Respiratory system mechanics in ventilated patients:
techniques and indications. Mayo Clin Proc. 1987;62:358.
4. Irwin RS, Rippe JM. Irwin and Rippe’s intensive care medicine, 6th edn. Lippincott
Williams and Wilkins; 2008.
5. MacIntyre N (Ed). Controversies in Mechanical Ventilation. Clinics in Chest Medicine.
Philadelphia: Elsevier Saunders; 2008.
6. Stroetz RW, Hubmayr RD. Patient-ventilator interactions. Monaldi Arch Chest Dis.
1998;53:331.
7. Tobin MJ, Jubran A, Laghi F. Patient-ventilator interaction. Am J Respir Crit Care Med.
2001;163:1059.
CHAPTER
33 Prem Kumar
MODES OF VENTILATION
There are different modes of ventilation with different operating characteristics

each having an advantage and disadvantage of its own. Hence choosing a mode of
ventilation is solely based on the clinical condition of the patient, lung dynamics
and goal of ventilation. Although newer modes of ventilation have come into
clinical practice, traditional modes of ventilation always find their importance in
day to day practice in ICU.
Basic modes of ventilation
• Volume-controlled ventilation (VCV)
• Assist control mode (A/C)
• Pressure-controlled ventilation (PCV)
• Synchronized intermittent mandatory ventilation (SIMV)
• Continuous positive airway pressure (CPAP)
• Bilevel positive airway pressure (BiPAP)
• Pressure support ventilation (PSV).
Newer modes of ventilation
• Pressure-regulated volume control (PRVC)
• Airway pressure release ventilation (APRV)
• Inverse ratio ventilation (IRV)
• Biphasic positive airway pressure (BIPAP)
• Adaptive support ventilation (ASV)
• Proportional assist ventilation (PAV)
• Neurally adjusted ventilatory assist (NAVA)
• Liquid ventilation
• High frequency ventilation.
BASIC MODES OF VENTILATION
Volume-controlled Ventilation/Assist Control

Volume control mode delivers breath irrespective of patient’s pattern of breathing
whereas assist control allows the patient to initiate the machine delivered breath
although the tidal volume is controlled by the machine. Nowadays volume
control mode is not present in most ICU ventilators because of ventilator patient
dyssynchrony caused by this mode and excessive need of sedation or paralysis
with neuromuscular muscle relaxants. It provides rest to the respiratory muscles.
Initial Settings
Respiratory rate, tidal volume, FiO2 are set in the ventilator and if the mode is
VCV, the tidal volume delivered is assured provided the patient is fully sedated or
paralysed. Most of the ventilators are volume-cycled. In assist control mode, the
patient’s inspiratory effort is detected by the demand valve in the ventilator and
the breath completed by the ventilator and the patient can inspire through the
ventilator demand valve. If the peak inspiratory pressure exceeds the safe limit,
then the remaining tidal volume above the PIP is not delivered. The assist control
mode will not allow the patient to take intermittent spontaneous breaths.
Advantages
• Patient receives assured tidal volume
• Offers complete ventilatory rest to respiratory muscles.
Disadvantages
• Patient ventilator dyssynchrony
• Respiratory alkalosis in case of spontaneous ventilation.
Indications
• It is used as an initial mode of ventilation in patients who are paralyzed or
patients with no spontaneous ventilation or postoperative patients who are
ventilated electively.
• To reduce the work of breathing
• Absent central respiratory drive (e.g. opioid overdose)
• Tetanus
• Assist control mode can be used in patients with intact respiratory drive who
needs complete respiratory support. If the patient does not trigger, then the
breath is time triggered.
• VCV characteristics—time-triggered , volume-cycled
• A/C—patient- or time-triggered, volume- or pressure-cycled
Waveforms —See Figure 33.1.
Pressure Control Ventilation

In PCV, the pressure-controlled breaths are time-triggered to the set respiratory
rate and after the mandatory breath is initiated, a plateau pressure is initiated
and maintained by the ventilator. The advantage of PCV is it can reduce the peak
inspiratory pressure since the mandatory breath is pressure limited and ensure
adequate ventilation and oxygenation. Hence, the incidence of barotrauma is
reduced.
Initial Settings
Pressure limit, respiratory rate, FiO2 is set but the tidal volume is not assured in
this mode. Another disadvantage is that it requires high sedation or paralysis.
Chapter 33 Modes of Ventilation 247
Fig. 33.1 Volume control mode with mandatory breaths
Advantages
It limits the peak inspiratory pressure and plateau pressure and minimizes lung
injury.
Disadvantages
• Tidal volume is not assured
• It requires high sedation or paralysis.
Indications
• Conditions which require a low airway pressure to maintain oxygenation
and ventilation (e.g. Severe ARDS)
• Lung damage prone patients (e.g. One lung ventilation)
PCV characteristics-time-triggered, pressure-limited, time-cycled
Waveforms —See Figure 33.2.
Synchronized Intermittent Mandatory Ventilation

It is a mode in which the ventilator delivers mandatory breaths during a
spontaneous inspiratory effort or is time-triggered in the absence of spontaneous
breath. Because of the synchronization, breath stacking is avoided. Breath stacking
is defined as the occurrence of spontaneous breath during a machine delivered
mandatory breath. Breath stacking occurs in intermittent mandatory ventilation
which can result in patient ventilator dyssynchrony which in turn would increase
the work of breathing. In SIMV, the demand valve opens in response to the patient’s
inspiratory effort. If at the time of mandatory breath, there is a spontaneous effort,
then the machine delivers an assisted breath. SIMV allows spontaneous breath
of any tidal volume in between the mandatory breaths. If SIMV has dual control
mode with pressure support, then the spontaneous breath is pressure-supported
allowing reduced work of breathing during spontaneous breathing and hastens
weaning.
Fig. 33.2 Pressure control mode with mandatory breaths
Initial Settings
Complete ventilatory support—keep usual respiratory rate of 10–12 breaths/
minute.
In case of partial ventilatory support, the respiratory rate is reduced
in decrements adjusted to the minute ventilation in accordance with the
spontaneous breaths.
Merits
• Facilitates weaning by supporting spontaneous breaths and reducing work
of breathing
• Reduces ventilation perfusion mismatch by reducing alveolar dead space
ventilation
• Reduces airway pressure
• Maintains respiratory muscle power.
Demerits
• It cannot completely control the I:E ratio in the presence of spontaneous
breaths
• High incidence of weaning failure.
Indications
• It is usually used as a weaning mode for patients who need partial ventilatory
support who are taken off from the control mode (volume or pressure).
SIMV characteristics: Type of breath-mandatory, spontaneous and assisted
breath, time or patient-triggered, volume-cycled.
Waveforms —See Figures 33.3 and 33.4.
Fig. 33.3 SIMV (pressure control ventilation) with pressure support shown by
waveform (indicated by arrow)
Fig. 33.4 SIMV (volume control) with pressure support showing assisted breaths
PRESSURE SUPPORT VENTILATION (FIG. 33.5)
Pressure-regulated Volume Control

It has different names in various ventilators like autoflow, adaptive pressure
ventilation. It is present in the Siemens ventilator. It is present as a dual control
mode with control mode and SIMV. PRVC gives volume support with the lowest
peak inspiratory pressure by altering flow rate and inspiratory time in response
to change in lung compliance and airway pressure. This mode prolongs the
inspiratory time to deliver the target volume to compensate for lower inspiratory
flow. The ventilator gives test breath. Certain ventilators have automode which
Fig. 33.5 Pressure support ventilation with spontaneous breaths
combines PRVC and volume support where in case of absence of spontaneous

ventilation, PRVC is initiated and if spontaneous effort is present, automode
switches to volume support.
Pressure change = tidal volume/compliance
In response to target pressure, the ventilator switches to pressure control
ventilation and assures tidal volume with least peak inspiratory pressure.
Initial Settings
Tidal volume, ventilator rate, trigger sensitivity, inspiratory time. It determines
lung dynamics by giving test breaths.
Indications
Useful in patients where adequate tidal volume is required with low peak
inspiratory pressure. (e.g. ARDS) but many studies have indicated that there is no
benefit with this mode compared with PCV.
PRVC characteristics—control or synchronized intermittent breath, time or
patient-triggered, volume-cycled.
Airway Pressure Release Ventilation

This is a mode of ventilation in which spontaneous ventilation are allowed like
CPAP maintaining a long period of high pressure followed by a short period of
low pressure where there is release of PEEP valve. The long period constitutes
the inspiratory phase and short phase constitutes the expiratory phase resulting
in an I:E ratio of 7-9:1. It resembles a pressure-controlled ventilation with inverse
I:E ratio. The only difference being that in APRV, the patient is allowed to breathe
spontaneously during any point of a mandatory breath. APRV mandatory breaths

are pressure limited. The patient’s tidal volume will vary according to the lung
dynamics and the pressure gradient.
Initial Settings
Phigh, Plow, Thigh, Tlow.
Advantages
• Decreases the frequency of opening and closing the alveoli, in other words
APRV maintains alveolar recruitment throughout the ventilatory cycle.
• Reduces lung injury due to the lower peak airway pressure generated by this
mode.
Disadvantage
Pneumothorax.
Indications
To improve oxygenation in patients with severe ARDS since it can provide partial
ventilatory support with lower peak airway pressure.
APRV characteristics—time-triggered, pressure-limited, time-cycled. Allows
spontaneous breathing during any point of mandatory breath.
Inverse Ratio Ventilation

There have been attempts in increasing the inspiratory time to increase
oxygenation in ARDS. Often an I:E ratio of 2:1–4:1 is used in IRV. Pressure
control ventilation is used in IRV. IRV improves oxygenation by reducing alveolar
dead space ventilation and intrapulmonary shunting. This improvement in
oxygenation is due to increase in mean airway pressure.
Initial Settings
Pressure preset, FiO2, I:E ratio.
Advantage
Improves oxygenation in ARDS.
Disadvantages
• Auto–PEEP due to shortened expiratory time
• Barotrauma
• Because of the prolonged the inspiratory duration, ventilation requires
sedation and peripheral muscle relaxants.
Indication
Acute respiratory distress syndrome (ARDS).
Biphasic Positive Airway Pressure

Biphasic positive airway pressure (BIPAP) can be described as pressure-
controlled ventilation with pressure support ventilation in a system allowing
time-cycled mandatory breaths and allows unrestricted spontaneous breathing
at any moment of the ventilatory cycle. It uses the same principle as APRV.
Baum et al. described biphasic positive airway pressure ventilation as a mode in
which spontaneous ventilation could be achieved at any point in the mechanical
ventilation cycle (inspiration or exhalation). This mode allows unrestricted
spontaneous breathing to reduce sedation and promote weaning. BIPAP and
APRV are conceptually the same, the main difference being that the time spent
in low pressure (Tlow) is less than 1.5 seconds for APRV. Otherwise, they have
identical characteristics, thus allowing any ventilator with the capability of
delivering APRV to deliver biphasic positive airway pressure, and vice versa.
Since it enables progressive transition from controlled to all levels of augmented
mechanical ventilation, BIPAP appears to be a suitable mode for the entire period
of mechanical ventilation of the patient.
Initial Settings
As with a pressure-controlled, time-cycled mode, the duration of each phase
(T(high), T(low)) as well as the corresponding pressure levels (P(high), P(low))
can be adjusted independently. BIPAP system delivers two different positive
pressure levels—an inspiratory positive airway pressure, or IPAP, and an
expiratory positive airway pressure, or EPAP. The difference between these two
pressure levels is commonly referred to as the pressure support.
Indications
• It can be used for both initiation of ventilation and weaning
• ARDS improves lung compliance, venous admixture, and arterial oxygen
tension without causing cardiovascular impairment in ARDS.
Advantages
• Improves oxygenation, reduces venous admixture.
• Recruits collapsed alveoli
• Hastens weaning since this mode allows spontaneous breathing at any point
of ventilatory cycle.
Liquid Ventilation
It is a technique where perfluorocarbons are used as oxygen delivery agents. The
solubility of oxygen and carbon dioxide is 20 times higher in PFC’s. the higher
solubility of oxygen with PFC’s increases the oxygen delivery to the lung.
There are two types of liquid ventilation:

1. Total
2. Partial
Total Liquid Ventilation

Only PFC is used as oxygen delivery agent, it requires special equipment. The
lungs are filled with PFC with a volume equal to FRC and a liquid ventilator is used
to generate tidal volume. CO2 clearance is achieved with a rate of 4–5 breaths/
minute. Distribution of PFC within the lungs is more uniform with total type.
Partial Type
PFC and gases like inhaled nitric oxide are used as oxygen delivery agents. Partial
liquid ventilation can be done with usual ventilator. Partial liquid ventilation
is also called PAGE (PFC-associated gas exchange). PFC may act as artificial
surfactant for neonatal respiratory distress syndrome (RDS) or as a lavage for
certain types of pulmonary dysfunction.
Indications
• Used in severe respiratory distress syndrome (hyaline membrane disease) in
neonates who do not meet the criteria for ECMO.
• Meconium aspiration syndrome with respiratory failure
• ARDS
• Nonventilatory indication—can be used as a medium for delivery of
antibiotics, anesthetic agents, vasoactive agents.
Advantages
• PFC is inert
• Keeps alveoli open at end expiration, increases functional residual capacity
and acts as PEEP.
• Improvement of oxygenation in acute lung injury
• Improvement in lung compliance
• Causes lavage effect by which the alveolar debris can be suctioned.
• Reduces the production of inflammatory cytokines
Disadvantages
• Equipment is costly especially with total liquid ventilation
• Pneumothorax
• Hemodynamic instability especially with total liquid ventilation.
High Frequency Ventilation

High frequency ventilation is a newer mode of ventilation where the ventilator
delivers small tidal volumes of high respiratory rates (>60 breaths/minute). 1 hz
equals 60 breaths/minute.
Types (Tables 33.1 and 33.2)

• High frequency positive pressure ventilation (HFPPV)
• High frequency jet ventilation (HFJV)
• High frequency oscillatory ventilation (HFOV).
Table 33.1 Frequencies of various types of high frequency ventilation
Type of ventilator Frequency

High frequency positive pressure ventilation (HFPPV) 60–150 breaths/minute
High frequency jet ventilation (HFJV) 100–150 breaths/minute
High frequency oscillatory ventilation (HFOV) 180–900 breaths/minute
Table 33.2 Differences between HFPPV and HFJV
HFPPV HFJV
Principle Tidal volume is delivered by High frequency jet ventilator delivers
convective air current high pressure pulsed gas to the patient
via an adaptor attached to ET tube
Clinical RDS patients who do not
A • Severe pulmonary hypoplasia
indications respond or worsening with • Severe restrictive lung disease
routine ventilation • Postpulmonary disease induced
pulmonary hypertension
Complications • Barotrauma • Necrotizing tracheobronchitis due
• Hemodynamic instability to lack of humidification
• Intracranial hemorrhage in • Hyperinflation due to gas trapping
neonates • Hemodynamic instability
These complications are due • Unpredictable tidal volume
to the increased mean airway delivery, hence PaO2 and PaCO2
pressure seen with this mode. should be monitored.
High Frequency Oscillatory Ventilation

This mode has been in use for neonates and children for hyaline membrane
disease and severe pulmonary disease but is recently in use for adult patients too
but with limited indications. High frequency oscillatory ventilation (HFOV) in
current literature is only indicated as a rescue therapy.
Principle
A piston pump produces oscillatory waves which deliver the gas to the lungs. The
oscillator attached to the ET tube assists both inspiration and expiration.
Indications
• Hyaline membrane disease—most common indication for HFOV. Usually
preterm neonates are considered for HFOV
• Congenital diaphragmatic hernia
• Pulmonary hypoplasia
• Failure of response to conventional ventilation in neonates
• Pulmonary hypertension
• Increasing FiO2 requirement, PIP >20 cm H2O, infants <1 kg
• For clinical use in adults, a trial of HFOV can be considered when:
– FiO2 >60%
– Mean airway pressure >20 cm H2O
– PEEP >15 cm H2O.
Advantages
• Allows decoupling of oxygenation and ventilation
• Humidification is not an issue unlike other types
• Better CO2 elimination
• Oxygenation is proportional to mean airway pressure and tidal volume
• Prevents release of inflammatory mediators in lung.
Disadvantages
• Requires high PEEP
• Hyperinflation and barotrauma
• Hemodynamic instability.
Closed Loop Ventilation

• Adaptive support ventilation (ASV)
• Proportional assist ventilation (PAV)
• Neurally adjusted ventilatory assist (NAVA).
Adaptive Support Ventilation

It a closed loop ventilation which changes the ventilatory parameters according to
patient’s breathing pattern. It alters the mandatory breaths and pressure support
level according to the feedback the ventilator gets from the lung dynamics of
the patient. This mode is present in Hamilton medical ventilator. The ventilator
gives a test breath and measures airway resistance (Paw), compliance and auto
–PEEP. Based on the above feedback gathered breath to breath, the ventilator
selects respiratory rate, tidal volume, inspiratory time, I:E ratio, pressure support
for mandatory and spontaneous breaths. In case there is no spontaneous effort,
the ventilator provides mandatory breaths according to the preselected values.
If there is spontaneous breaths, then the mandatory breath rate reduces and the
spontaneous breaths are supported with pressure support.
Initial Settings
Body weight (for calculation of dead space – 2.2 mL/kg), percentage of minute
volume (20–200% of predetermined setting). Predetermined setting of minute
volume in adults–100 mL/min/kg and children– 20 mL/min/kg (e.g. 120% means
120 mL/min/kg).
Advantages
• Since it employs lung protective strategies, it is useful in ARDS, COPD
patients in minimizing lung injury.
• Better patient ventilator synchrony
• Reduced need of sedation
• Reduced work of breathing and length of ICU stay.
ASV Characteristics
Mandatory breaths—pressure limited, time cycled, dual controlled (SIMV + PSV)
on breath by breath basis
Spontaneous breaths—PSV with variable pressure.
Proportional Assist Ventilation

Proportional assist ventilation (PAV) delivers gas with a feedback mechanism
which it gets on a breath-to-breath basis. This mode is available in puritan Bennett
ventilator. With the test breath, the ventilator calculates resistance, elastance
and auto–PEEP. With these calculations, the ventilator generates inspiratory
flow rate and volume and provides support in proportion to the pulmonary
characteristics and demand of the patient. In other words, PAV is a novel mode
of partial ventilatory support in which the ventilator generates an inspiratory
pressure in proportion to the respiratory effort of the patient. Unlike PSV where
the pressure support is constant, PAV alters pressure support according to the
patient’s demand. The respiratory drive has to be intact in this mode.
Initial Settings
Cycle (3 L/min), trigger, percent support (% of work of breathing). Percent support
usually started at 70% and decreased in intervals.
Indications
• Restrictive lung disease
• Improves ventilation and reduces the work of breathing in ventilator
dependent patients with COPD.
Advantages
• Patient ventilator synchrony
• Provides uniform breathing pattern.
Disadvantages
• Cannot be used in patients with reduced respiratory drive.
• PAV support will be inadequate to relieve the patient’s symptoms if the
elastance and resistance are overestimated, a positive feedback will develop
and the ventilator will continue to deliver flow and volume while the patient
stops inspiratory effort (the “run-away” phenomenon).
Characteristics
Assisted breaths, pressure- or flow-triggered, volume or flow cycling.
Neutrally Adjusted Ventilatory Assist

Neutrally adjusted ventilatory assist (NAVA) is a novel mode of ventilation
in which the system has the ability to measure the electrical activity of the
diaphragm and convert the ventilatory drive into ventilatory output. This is
called neuroventilatory coupling. Microprocessor-based technology obtains
signals and the signal from the diaphragm triggers the ventilator and assists the
patient’s inspiratory effort in proportion to the diaphragmatic electrical activity.
This ventilator support occurs within a breath and between breaths. This mode is
yet to come into clinical practice.
Prerequisites
• Intact diaphragmatic function
• Intact phrenic nerve
• Intact neuromuscular junction.
BIBLIOGRAPHY
1. Arnal JM, Wysocki M, Nafati C, Donati S, Granier I, Corno G, Durand-Gasselin J.
Automatic selection of breathing pattern using adaptive support ventilation. Intensive
Care Med. 2008;34(1):75-81.
2. Chang DW. Clinical application of mechanical ventilation, 3rd edn, 2006.
3. Derdak S. High-frequency oscillatory ventilation for acute respiratory distress
syndrome in adult patients. Crit Care Med. 2003;31(4 Suppl):S317-23.
4. Fedora M, Nekvasil R, Deda M, Klimovic, Dominik P. Partial liquid ventilation: first
experience in children with acute respiratory distress syndrome. Scripta Medica
(Brno). 2000;73(4):229-36.
5. Kaisers U, Kelly KP, Busch T. Liquid ventilation. New Concepts in Respiratory Function:
Br J Anaesth. 2003;91(1):143-51.
6. Kimless-Garber DB, Wolfson MR, Carlsson C, Shaffer TH. Halothane administration
during liquid ventilation. Respir Med. 1997;91:255-62.
7. Susan P. Mechanical ventilation. Physiological and clinical applications. Mosby
publications.
8. Thomas HS, Wolfson MR, Greens Pan JS. Liquid ventilation: Current status. Pediatr
Rev. 1999;20:134-42.
9. Valls I, Soler A, Wauer RR, Vallis-I-Soler A 2nd. European symposium on liquid
ventilation. Eur J Med Res. 2001;6(3):115-38.
10. Verbrugge SJ, Lachmann B. Partial liquid ventilation. Eur Respir J. 1997;10(9):1937-9.
11. Zelinka MA, Wolfson MR, Calligaro I, et al. A comparison of intratracheal and
intravenous administration of gentamicin during liquid ventilation. Eur J Pediatr.
1997;156: 401-4.
CHAPTER
34 Prem Kumar
WEANING FROM MECHANICAL

VENTILATION
DEFINITION OF WEANING
The process of gradual discontinuation of mechanical ventilatory support from
the patient (Flow chart 34.1).
WEANING CRITERIA
• Adequate oxygenation
– spO2 >92%,
– PaO2 >60 mm Hg with FiO2 of <0.4,
– PaCO2 <50 mm Hg
Flow chart 34.1 Weaning process
Abbreviations: NIV, noninvasive ventilation; SBT, spontaneous breath trial

Chapter 34 Weaning from Mechanical Ventilation 259
– P[A-a]O2 <350 mm Hg,

– PaO2/FiO2 >200 mm Hg
• Adequate ventilation
– Tolerates SBT for 1–2 hours,
– Vt (tidal volume) >5 mL/kg,
– Vital capacity >10 mL/kg
– RR <30/minute
– EtCO2 <50 mm Hg
– Minute ventilation <10 L/minute
• Lung dynamics and reserve
– Maximal inspiratory pressure > –25 cm H2O
– Static compliance > 30 mL/cm H2O
– Vd/Vt <0.6
– RSBI<100
– Qs/Qt (an indicator of pulmonary shunting) <20%
• Neuromuscular criteria
– P0.1 >5 cm H2O (indicator of neuromuscular inspiratory drive)
• Clinical criteria
– Hemodynamically stable
– Normal mental status
– Normotheramic
– No or minimal sedation.
Measuring Parameters for Weaning (Figs 34.1 to 34.3)
Fig. 34.1 Measurement of static compliance, resistance, plateau pressure

Fig. 34.2 Measurement of maximal inspiratory pressure (MIP)
Fig. 34.3 Measurement of P0.1
Weaning Indices
• Simplified weaning index <9/minute
• Compliance rate oxygenation and pressure index (CROP) >13 mL/breaths/
minute
• Rapid shallow breathing index (RSBI)—respiratory rate/tidal volume in liters
<100.
Among all these indices, rapid shallow breathing index is more accurate in
predicting weaning success. Patient is taken from the ventilator, and the expired
tidal volume and spontaneous respiratory rate is measured for 1 minute.
Simplified weaning index evaluates gas exchange and ventilator endurance.
CROP index indicates pulmonary gas exchange and the adequacy of respiratory
neuromuscular drive to the patient demand.
Weaning Techniques
• Synchronized intermittent mandatory ventilation (SIMV)
• Pressure support ventilation (PSV)
• Continuous positve airway pressure (CPAP) bilevel positive airway pressure
(BiPAP)
• T-tube trial.
Weaning Trial
When predictors of weaning are favorable, spontaneous breathing trial (SBT) is
indeed done with any of the above weaning modes.
Weaning Protocol of Synchronized Intermittent Mandatory Ventilation

(SIMV) (Flow chart 34.2)
Flow chart 34.2 Weaning protocol of SIMV
Weaning Protocol of PSV (Flow chart 34.3)
Flow chart 34.3 Weaning protocol of PSV

Weaning Protocol of T Tube

This is a traditional technique of weaning the patient. It is done in between
mechanical ventilation. Initially it is done for 5–10 minutes and later the duration
of T tube trial is increased to 30 minutes. But studies (Esteban, et al.) have found
that a single trial for a day is as effective as multiple trials and a single trial of
30 minutes duration with T tube is effective in identifying patients for safe
extubation. Though the technique of T tube weaning trial has become unpopular,
still it is being used by some intensivists.
Weaning with CPAP/BiPAP

Noninvasive/invasive ventilation with CPAP/BiPAP is used in patients with COPD
and type 2 respiratory failure and it has been shown that it facilitates extubation
and reduces the duration of mechanical ventilation. It can be done with either
face mask or through an endotracheal tube. The pressure support can be reduced
by 2–4 cm H2O over hours. Weaning with spontaneous breathing modes has
definitely a role in type 2 respiratory failure patients who have failed T tube trials.
Weaning Success
Effective spontaneous breathing without any ventilatory assistance for more than
24 hours.
Weaning Failure
• Abdominal distension causing increased work of breathing
• Subglottic stenosis, laryngeal edema
• Acute respiratory distress syndrome (ARDS)
• Respiratory muscle fatigue
• Poor neurological status
• Inadequate ability to protect airway
• Poor lung reserve and dynamics.
Extubation
A good clinician takes care of extubation in a meticulous way since the clinical
judgement should be correct in picking up the time of extubation to avoid post-
extubation respiratory distress.
Prerequisites for Extubation

• Head-end elevation by 30–60°
• Withholding enteral feeding for at least 4–6 hours
• Adequately suctioned upper airway and endotracheal tube
• Alveolar recruitment with AMBU bag (optional)
• Good airway reflexes
• Good respiratory drive
• No laryngeal edema identified by cuff leak test or ultrasound.
• Favorable weaning predictor tests.
Our Institutional Protocol for Extubation

• Give 1.5 mg/kg of 2% xylocard intravenously to abolish sympathetic stimulation.
• Give good oropharyngeal suction
• Deflate the cuff
• Occlude the tube
• Observe and hear whether patient can breath around the tube
• Introduce cook’s airway exchange catheter into the endotracheal tube
• Extubate the endotracheal tube with the airway exchange catheter (AEC) in
position
• Give O2 of 6 L/minute through AEC for 5–10 minute
• If SpO2 > 92%, AEC can be removed
• Place venturi mask and give O2 with 4–6 L/minute.
Indications for Paralyzing a Patient in Mechanical Ventilation

• Paralysis with muscle relaxants should be kept as a last option
• Weaning Failure
• Severe hemodynamic instability
• Neurosurgeries to prevent increased ICP
• Poor lung compliance
• Synchronization with modes of ventilation with inverse I:E ratio (e.g. APRV,
IRV).
BIBLIOGRAPHY
1. Adderley RJ, et al. When to extubate the croup patient: the “leak” test. Can J Anaesth.
1987;34(3(Pt 1)):304-6.
2. Deem S. Limited value of the cuff-leak test. Respir Care. 2005;50(12):1617-8.
3. Epstein SK, Ciubotaru RL. Independent effects of etiology of failure and time to
reintubation on outcome for patients failing extubation. Am J Respir Crit Care Med.
1998;158:489-93.
4. Esteban A, Alia I, Tobin MJ, et al. Effect of spontaneous breathing trial duration on
outcome of attempts to discontinue mechanical ventilation. Spanish Lung Failure
Collaborative Group. Am J Respir Crit Care Med. 1999;159:512.
5. Institute of Anesthesiology and Critical Care, Madras Medical College Institutional
Protocol for mechanical ventilation.
6. Meade M, Guyatt G, Cook D, et al. Predicting success in weaning from mechanical
ventilation. Chest. 2001;120(6 Suppl):400S-24S
7. Meade M, Guyatt G, Stinuff T, et al. Trials comparing alternative weaning modes and
discontinuation assessments. Chest. 2001;120(6 Suppl):425S-37S.
8. Nava S, Ceriana P. Causes of failure of noninvasive mechanical ventilation. Respir
Care. 2004;49(3):295-303.
9. Nava S, Gregoretti C, Fanfulla F, et al. Noninvasive ventilation to prevent respiratory
failure after extubation in high-risk patients. Crit Care Med. 2005;33:2465.
10. Tobin MJ, Jubran A. Principles and practice of mechanical ventilation. 2nd edn. New
York, NY: Mcgraw hill; 2006. pp.1185-1220.
11. Yang KL, Tobin MJ. A prospective study of indexes predicting the outcome of trials of
weaning from mechanical ventilation. N Engl J Med. 1991;324:1445.
CHAPTER
35 Prem Kumar
PATIENT VENTILATOR ASYNCHRONY
Patient ventilator asynchrony is a common problem in intensive care unit (ICU)

patients put on ventilator. The basic mechanism that causes patient ventilator
asynchrony is the mismatch between neural inspiratory and mechanical
inspiratory time. It is often undetected and improperly treated. Optimal mode
selection and settings, understanding patient’s clinical condition, lung dynamics
and ventilator graphics will prevent, detect and treat this condition thus, avoiding
the consequences of patient ventilator asynchrony such as increased work of
breathing and myocardial oxygen consumption. Other consequences of patient
ventilator asynchrony are increased duration of ICU stay, mechanical ventilation,
and increased incidence of weaning failure.
Patient ventilator interaction depends on four variables (Fig. 35.1 and Table 35.1):
1. Neural function (central)
2. Diaphragmatic contraction
3. Clinical condition or input
4. Respiratory mechanics of the lung and chest wall.
Let’s discuss the key features of patient ventilator asynchrony—variables
contributing to asynchrony, physiological effects, detection and treatment.
Fig. 35.1 Design features of an automated control system in ventilator
Table 35.1 Variables contributing to patient ventilator interaction
Patient variables Ventilator variables

• Respiratory drive • Triggering mechanism
• Ratio of inspiratory time to total breath cycle • Cycling
• Inspiratory flow demand (spontaneous) • Flow delivery
Chapter 35 Patient Ventilator Asynchrony 265
Flow chart 35.1 Causes of patient ventilator asynchrony
VARIABLES CONTRIBUTING TO ASYNCHRONY (FLOW CHART 35.1)

• Ventilatory requirement—flow and volume demand of the patient
• Ventilatory drive
• Patient’s inspiratory flow
• Ratio of inspiratory time to breath cycle duration
• Trigger mechanism
• Cycling criteria
• Gas delivery asynchrony.
Gas delivery asynchrony can occur when the flow, pressure and volume
delivered by the ventilator is inadequate to meet the demand of the patient. In
this perspective, pressure-limited ventilatory breaths will cause less asynchrony
since flow is adjusted to maintain constant pressure.
Inspiratory phase asynchrony is due to the ineffective triggering inspite of
patient’s inspiratory effort. Certain causes of ineffective triggering are intrinsic
positive end-expiratory pressure (PEEP), low elastance and increased airway
resistance. Administering external PEEP to a patient with auto-PEEP can reduce
the patient’s inspiratory effort to trigger the ventilator. Other interventions
which can be used for overcoming auto-PEEP are prolongation of expiratory
time, reducing respiratory rate, reducing tidal volume, administration of
bronchodilators. Increased application of pressure support can reduce the
respiratory drive and hence causing ineffective triggering.
Patient ventilator asynchrony can be prevented by having a continuous
interaction between the following parameters—trigger, cycling, ventilatory drive
of the patient, flow delivery, inspiratory flow demand, ratio of inspiratory time
to total breath duration. If these parameters constantly change itself according
to the demand of the patient based on the patient’s lung dynamic variables,
patient ventilator interaction would be better. For achieving this synchrony, there
has to be a closed loop system between the patient and ventilator. So based on
the patient variables, the ventilator alters the parameters for the demand of the
patient. Newer modes of ventilation like proportional assist ventilation, adaptive
support ventilation and neurally adjusted ventilatory assist are modes of closed
loop system.
One of the causes for patient ventilator asynchrony in assist control ventilation
(volume-cycled) is the set inspiratory flow rate in the post-trigger phase. For
pressure support ventilation, the initial pressure rise time, flow-threshold for
inspiratory cycling, pressure support level are factors which can influence patient
ventilator synchrony. Optimization of the patient ventilator can be obtained with
continuous matching of the following variables in the patient and the ventilator.
Continuous measurement of the following parameters and manual or
automated (preferable) adaptation of the ventilator to the changes in the patient’s
variable in the above variables or respiratory mechanics (e.g. compliance,
resistance, airway pressure, etc.) can reduce patient ventilator asynchrony.
Physiologic Effects of Patient Ventilator Asynchrony

• Effects of inadequate ventilatory support: Tachypnea due to increased
respiratory workload, agitation, paradoxical breathing, hypercarbia, use of
accessory muscles of respiration.
• Effects of excessive support: Delayed cycling causing inadequate expiratory
time causing dynamic hyperinflation resulting in auto–PEEP.
Diagnosis of Patient Ventilator Asynchrony (Figs 35.2 to 35.4)

Optimal synchrony is based on three factors:
1. Patient effort
2. Graphic waveforms of mechanical ventilator
3. Flow cycling.
Hence, in case of suspicion of patient ventilator asynchrony, the intensivist
has to observe the patient effort, tidal volume and ventilator waveform. It is best
done by putting the patient in pressure support ventilation (PSV) mode, and
based on signs of asynchrony, the flow cycle setting is adjusted so that excessive
pressure is avoided at end exhalation and triggering is optimal to avoid delayed,
ineffective and double triggering.
Premature cycling occurs when the ventilator terminates the breath while
the patient goes into a longer inspiratory period. During premature cycling, the
ventilator senses the second breath and results in stacking of breaths or double
Fig. 35.2 Patient ventilator asynchrony seen in square pattern. Dotted lines represent
normal pressure waveform. Arrow shows asynchrony
Chapter 35 Patient Ventilator Asynchrony 267
Fig. 35.3 Patient ventilator asynchrony seen in descending ramp pattern. Dotted lines
represent normal pressure waveform. Arrow shows asynchrony
Fig. 35.4 Patient ventilator asynchrony seen in descending ramp pattern. Arrow shows
Breath with inadequate flow rate (upper picture) and excessive patient trigger in pressure
waveform (lower picture)
triggering. The end result of this type of asynchrony is reduced tidal volume
and increased inspiratory load. Studies have indicated that higher flow cycling
percentages of peak inspiratory flow results in premature cycling.
Delayed cycling is defined as the presence of active expiratory effort before
the cycle criterion is met. This typically occurs in COPD. Delayed cycling results
in dynamic hyperinflation and intrinsic PEEP and hence increased respiratory
workload and delayed triggering.
Management of Patient Ventilator Asynchrony (Table 35.2)

Recent modes of ventilation like proportional assist ventilation, NAVA, adaptive
support ventilation reduces the incidence of patient ventilator asynchrony by
Table 35.2 Causes and management of patient ventilator asynchrony
Etiology Management
Delayed cycling—high resistance Decrease inspiratory time. Decrease tidal volume
and low elastic recoil (COPD) in case of CMV mode. Increase expiratory trigger
sensitivity in case of PSV mode
Ineffective triggering—poor Reduce trigger sensitivity
inspiratory effort, auto-PEEP Start interventions for reducing iPEEP –
application of external PEEP, reduce tidal volume,
prolong expiratory time
Delayed triggering—reduced trigger This is possible to be rectified only with new modes
sensitivity or increased trigger like NAVA. Increase trigger sensitivity
inspiratory time
Double triggering—increased venti- Decrease expiratory cycling criteria, decrease
latory demand, reduced inspiratory ventilatory demand by adjusting tidal volume and
time inspiratory time and flow
Autotriggering—leak in circuit, water Increase trigger sensitivity
in circuit, cardiac oscillations Avoid hyperventilation
Switch over from flow to pressure triggering
Abbreviations: COPD, chronic obstructive pulmonary disease; PEEP, positive end-expiratory pressure;
CMV, continuous mandatory ventilation; NAVA, neurally adjusted ventilatory assist
adapting itself to the ventilator demands of the patient like airway pressure, flow
and volume. NAVA has a technology of neuroventilatory coupling which senses
the neural activity in the diaphragm and starts triggering the ventilator. These
newer modes of ventilation are is discussed in detail under the chapter modes
of ventilation.
BIBLIOGRAPHY
1. Calderini E, Confalonieri M, Puccio PG, et al. Patient Ventilator asynchrony during
noninvasive ventilation: The role of the expiratory trigger. Intensive Care Med. 1999;
25:662-7.
2. Nilsestuen JO, Hargett KD. Using ventilator graphics to identify patient-ventilator
asynchrony. Respir Care. 2005;50(2):202-34.
3. Parthasarathy S, Jubran A, Tobin MJ. Cycling of inspiratory and expiratory muscle
groups with the ventilator in airflow limitation. Am J Respir Crit Care Med. 1998;158:
1471-8.
4. Prinianakis G, Kondili E, Georgopoulos D. Effects of the flow waveform method of
triggering and cycling on patient-ventilator interaction during pressure support.
Intensive Care Med. 2003;29(11):1950-9.
5. Ranieri VM, Grasso S, Fiore T, Giuliani R. Auto-positive end-expiratory pressure and
dynamic hyperinflation. Clin Chest Med. 1996;17:379-94.
6. Sassoon CS, Foster GT. Patient-ventilator asynchrony. Curr Opin Crit Care. 2001;7(1):
28-33.
7. Thille AW, Rodriguez P, Cabello B, et al. Patient-ventilator asynchrony during assisted
mechanical ventilation. Intensive Care Med. 2006;32:1515-22.
8. Tokioka H, Tanaka T, Ishizu T, Fukushima T, Iwaki T, Nakamura Y, Kosogabe Y. The
effect of breath termination criterion on breathing patterns and the work of breathing
during pressure support ventilation. Anesth Analg. 2001;92(1):161-5.
CHAPTER
36 Prem Kumar, S Yuvaraj
NONINVASIVE VENTILATION
DEFINITION
Noninvasive positive pressure ventilation (NIPPV) is a technique of assisting
ventilation without the use of endotracheal tube.
EQUIPMENT (INTERFACE)
Nasal, face mask, helmet, mouthpiece can be used for delivering NIPPV. These
interfaces should be tied on the back of the head or nape of neck with a strap for
tight fit to minimize leaks.
PROTOCOL FOR MANAGING PATIENTS PLANNED FOR NIPPV

• Evaluation: history, diagnosis, level of respiratory distress, see whether the
patient fulfils all the prerequisites for NIPPV.
• Monitoring:
Clinical parameters—patient comfort, consciousness level, chest wall
movement, patient ventilator asynchrony
Vitals—blood pressure, heart rate, ECG, respiratory rate, pulse oximetry.
Pulmonary gas exchange—arterial blood gas analysis.
Ventilatory parameters—expired tidal volume, lung dynamics measurements.
• Settings:
Contnuous positive airway pressure (CPAP)—set pressure support of 10–15
cm H2O and positive end-expiratory pressure (PEEP) of 5 cm H2O
BiPAP – Set IPAP of 10–15 cm H2O and expiratory psoitive airway pressure
(EPAP) of 5 cm H2O and titrate according to clinical condition. Alter flow rate,
sensitivity, and inspiratory time to optimize synchrony.
• Proper selection of patients for NIPPV would avoid failure of noninvasive
ventilation and unnecessary need for invasive ventilation. Patients with
hypoxic, hypercapnic or mixed respiratory failure, tachypnea and respiratory
distress are able candidates for NIPPV.
Prerequisites for Using NIPPV

• Patients able to maintain a patent airway
• Patients with ability to clear secretions
• Intact consciousness
• Tolerant to face mask
• No gastrointestinal bleeding or recent gastroesophageal surgery
• No recent facial trauma or burns
• No fixed upper airway obstruction.
Factors Associated with NIPPV Failure

• GCS <11
• Respiratory rate ≥ 30/minute
• Ph <7.25 at admission or 2 hours after therapy
• Severe hypercarbia (>80 mm Hg)
• APACHE II ≥9
• ARDS with SAPS (simplified acute physiology score) >34
• ARDS with failure of PaO2/FiO2 improvement over 175 after 1 hour of NIPPV
• Patient ventilator asynchrony
• Poor dentition
• Severe air leakage.
Noninvasive Ventilatory Modes

• Continuous positive airway pressure (CPAP)
• Bilevel positive airway pressure (BiPAP)
• Pressure support ventilation (PSV)
• Proportional assist ventilation (PAV).
Continuous Positive Airway Pressure

It delivers constant pressure in both cycles of respiration in a spontaneous
breathing patient. It does not deliver any mandatory breaths, hence can only be
used in a spontaneously breathing patient. This mode needs adequate alveolar
ventilation and respiratory drive. It can be administered by demand flow or
continuous flow system.
Initial Settings
• It is initially started with pressure support of 5–10 cm H2O and increased
in increments of 2–3 cm H2O according to patient comfort and blood gas
analysis
• It can be used for alveolar recruitment in ARDS (40 cm H2O PEEP for 40 sec).
Advantages
• It reduces the work of breathing by unloading inspiratory muscles and
improves dyspnea in COPD patients
• Increases functional residual capacity and improves oxygenation by reducing
intrapulmonary shunting
• Reduces left ventricular after load in cardiac failure patients thus improving
cardiac output and symptoms.
Chapter 36 Noninvasive Ventilation 271
Bilevel Positive Airway Pressure

Bilevel positive airway pressure (BiPAP) differs from CPAP in that it has 2 pressure
levels—IPAP (inspiratory positive airway pressure) and EPAP (expiratory positive
airway pressure). This mode delivers either mandatory breaths or patient
triggered spontaneous supported breaths. It has a spontaneous/timed mode.
IPAP improves ventilation by augmenting tidal volume and EPAP which is nothing
but the PEEP, increases oxygenation and relieves upper airway obstruction. The
difference between IPAP and EPAP is the pressure support which augments tidal
volume. The BiPAP device can be driven by air or supplemental oxygen which
can be added to the circuit to increase the FiO2.
Initial Settings
• Set the mode—spontaneous/timed
• Set IPAP of 10–15 cm H2O and EPAP of 5 cm H2O and titrate according to
clinical condition. Alter flow rate, sensitivity, and inspiratory time to optimize
synchrony.
• On weaning the patient, IPAP is reduced in decrements of 2–3 cm H2O until
5 cm H2O and EPAP to 5 cm H2O. When IPAP pressure equals EPAP, this
mode becomes like CPAP.
• Set IPAP maximum time 0.25 seconds longer than the inspiratory time of the
patient.
Pressure Support Ventilation

This mode is used to reduce the work of breathing and augment the tidal volume
of a spontaneous breathing patient. It applies a preset plateau pressure to the
patient’s airway throughout the duration of the spontaneous inspiratory effort.
The tidal volume varies with the patient’s flow demand and the ventilator cycles
to expiration when there is a reduction in the inspiratory flow.
Initial Settings
Pressure support—start with 8–10 cm H2O and increase till the expiratory tidal
volume is 7–8 mL/kg, spontaneous respiratory rate <25/minute and there is
patient comfort.
PEEP—start with 5 cm H2O and increase if PaO2 is reduced.
Advantages
• Augments the spontaneous tidal volume.
• Reduces the work of breathing.
PSV characteristics—spontaneous mode, pressure-limited, pressure-triggered,
flow-cycled.
Indications
• Asthma
• Acute exacerbation of COPD
• Cardiogenic pulmonary edema
• Negative pressure pulmonary edema (postobstructive)

• Pneumonia
• Type 1 respiratory failure
• Obstructive sleep apnea
• Trauma patients without contraindications for NIPPV
• Postoperative patients
• Facilitating weaning in mechanically ventilated patients.
ASTHMA
Noninvasive positive pressure ventilation (NIPPV) can be considered as an
alternative for patients who are at risk of endotracheal intubation since invasive
mechanical ventilation worsens lung dynamics by causing hyperinflation and
hence barotrauma.
Acute Exacerbation of COPD

NIPPV is the current first-line of therapy for COPD patients with type 2 respiratory
failure since it reduces the need for tracheal intubation and invasive ventilation,
reduces the length of ICU stay, improves gas exchange and hemodynamics,
reduces severity of dyspnea. Early institution of NIPPV has been found to reduce
complications. NIPPV with PSV and external PEEP reduces the work of breathing
and ameliorates the auto–PEEP level.
Cardiogenic Pulmonary Edema

Administration of positive pressure ventilation reduces the work of breathing and
left ventricular after load thus, maintaining cardiac output. It should be combined
with medical treatment for pulmonary edema. For cardiogenic pulmonary
edema, BiPAP has been found to produce better results than CPAP in terms of
dyspnea alleviation and gas exchange. Hence, early administration of NIPPV is
considered in patients with cardiogenic pulmonary edema.
Negative Pressure Pulmonary Edema (Postobstructive)

Postobstructive pulmonary edema after anesthesia is due to laryngospasm or due
to any cause of obstruction to the upper airway. Postairway obstruction causes
increase in the negative intrapleural pressure due to vigorous coughing against
closed airway which increases venous return and causes increased left ventricular
after load and increased transcapillary gradient which causes pulmonary edema.
This is usually treated by maintaining a patent airway and institution of positive
pressure ventilation.
PNEUMONIA
The definitive role of NIPPV has been found in patients with COPD with
community-acquired pneumonia.
Chapter 36 Noninvasive Ventilation 273
Type 1 Respiratory Failure

NIPPV has questionable role in patients with hypoxemic respiratory failure. But
there are studies which show that NIPPV reduces the work of breathing and the
incidence of endotracheal intubation. The role of NIPPV in hemodynamically
stable ARDS patients has been traditionally minimal. But recent studies showed
that NIPPV has improved dyspnea, gas exchange and lowered neuromuscular
drive when used for hemodynamically stable ARDS patients. A study by L’Her
et al. has shown that PSV combined with PEEP improved the lung dynamics and
pulmonary gas exchange in ARDS patients.
Obstructive Sleep Apnea

CPAP/BiPAP is effective in treating the respiratory and sleep problems associated
with OSA. It splints the upper airway by increasing the positive pressure thus,
overcoming the obstruction and hence, prevents alveolar collapse during sleep.
Goals for NIV in Obstructive Hypoventilation Syndrome

• Improvement of signs and symptoms
• Improving PaO2
• Normalizing the nocturnal and daytime PaCO2 and pH
• Daytime PaCO2 of 40–50 mm Hg.
Postoperative Patients
Atelectasis is common after thoracic and upper abdominal surgeries. This can
cause reduction in functional residual capacity, vital capacity and thus reduction
in PaO2. There is good evidence that early NIPPV improves gas exchange and
reduces the incidence of reintubation in postoperative patients.
BIBLIOGRAPHY
1. Bott J, Carroll MP, Conway JH, et al. Randomized controlled trial of nasal ventilation in
acute respiratory failure due to COPD. Lancet. 1993;341:1555-7.
2. Brochard L, Mancebo J, Wysocki M, Lofaso F, Conti G, Rauss A, et al. Noninvasive
ventilation for acute exacerbations of chronic obstructive pulmonary disease. N Engl
J Med. 1995;333:817-22.
3. Craig DB. Postoperative recovery of pulmonary function. Anesth Analg. 1981;60(1):
46-52.
4. Ferrer M, Valencia M, Nicolas JM, Bernadich O, Badia JR, Torres A. Early noninvasive
ventilation averts extubation failure in patients at risk: a randomized trial. Am J Respir
Crit Care Med. 2006;173:164-70.
5. Hines and Marschall. Stoelting’s Anesthesia and Co-Existing Disease, 5th edn.
Elsevier publications, 2008.
6. Jolliet P, Abajo B, Pasquina P, Chevrolet JC. Non-invasive pressure support ventilation
in severe community-acquired pneumonia. Intensive Care Med. 2001;27(5):812-21.
7. Katz JA, Marks JD. Inspiratory work with and without continuous positive airway
pressure in patients with acute respiratory failure. Anesthesiology. 1985;63(6):598-
607.
8. Lindner KH, Lotz P, Ahnefeld FW. Continuous positive airway pressure effect on
functional residual capacity, vital capacity and its subdivisions. Chest. 1987;92(1):66-
70.
9. Naughton MT, Benard DC, Liu PP, Rutherford R, Rankin F, Bradley TD. Effects of nasal
CPAP on sympathetic activity in patients with heart failure and central sleep apnea.
Am J Respir Crit Care Med. 1995;152:473-9.
10. Plant J, Owen J, Elliot M. Early use of non-invasive ventilation for acute exacerbations
of chronic obstructive pulmonary disease on general respiratory wards: a multicenter
randomized controlled trial. Lancet. 2000;355:1931-5.
11. Rocker GM, Mackenzie MG, Williams B, Logan PM. Noninvasive positive pressure
ventilation: successful outcome in patients with acute lung injury/ARDS. Chest.
1999;115:173-7.
SECTION
10
CARDIOVASCULAR DISEASES
IN ICU
Chapter 37 Cardiac Arrhythmias

Surendran GD
Chapter 38 Acute Heart Failure

Surendran GD
Chapter 39 Approach to Acute Myocardial

Infarction
Surendran GD
Chapter 40 Hypertensive Crisis

Surendran GD
Chapter 41 Cardiac Tamponade

Surendran GD
CHAPTER
37 Surendran GD
CARDIAC ARRHYTHMIAS
SUPRAVENTRICULAR ARRHYTHMIAS
Atrial Fibrillation
Atrial fibrillation (AF) is the most common sustained cardiac arrhythmia
encountered in clinical practice. It is a supraventricular arrhythmia characterized
by low-amplitude baseline oscillations (fibrillatory or ‘f’ waves) and an irregularly
irregular ventricular rhythm. It is due to disorganized atrial electrical activation
and uncoordinated atrial contraction. AF is associated with an increased risk of
stroke and heart failure.
Classification
• Paroxysmal—AF that terminates spontaneously within 7 days
• Persistent—AF that is present for >7 days but less than a year and requires
cardioversion
• Permanent—AF lasting greater than 1 year and refractory to cardioversion
Paroxysmal AF can be classified into vagotonic, adrenergic or mixed AF.
Lone AF refers to AF that occurs in patients younger than 60 years who do not
have hypertension or any evidence of structural heart disease.
Mechanism
There are two electrophysiologic mechanisms of AF:
1. Automatic, triggered, or micro-reentrant foci, so-called drivers, which fire at
rapid rates.
2. Multiple re-entrant circuits.
Etiology
The causes of AF can be broadly classified into cardiac and noncardiac causes.
Cardiac Causes
• Hypertensive heart disease
• Ischemic heart disease
278 Section 10 Cardiovascular Diseases in ICU
• Valvular heart disease (especially mitral valve)

• Cardiomyopathies
• Constrictive pericarditis
• Cardiac tumors and cardiac surgery
• Pericarditis, myocarditis
• Tachycardia-induced AF (Wolff-Parkinson-White syndrome).
Noncardiac Causes
• Severe pulmonary hypertension and pulmonary embolism
• Obesity and obstructive sleep apnea
• Excessive alcohol intake (holiday heart syndrome)
• Hyperthyroidism (the most common correctable cause).
Clinical Features
Signs and symptoms
The symptoms of AF vary widely. The most common symptom is palpitation,
other symptoms are fatigue, dyspnea, effort intolerance and lightheadedness.
Syncope is an uncommon symptom. Polyuria can occur because of the release of
atrial natriuretic peptide. Clinical examination should concentrate on identifying
AF and its causes as well the effects, viz. hemodynamic instability, signs of
peripheral thromboembolism, etc. The most important clinical finding of AF is
irregularly irregular pulse. Pulse deficit >10 is another notable finding and it is
due to short R-R intervals. Examination of JVP shows irregular pulsations with
absent ‘a’ waveforms. Variable intensity of S1 and associated murmurs are seen if
AF is associated with valvular heart disease.
Investigations
The various blood investigations to be done in a case of AF are thyroid function
tests, liver function tests, and renal function tests.
ECG
Low-amplitude baseline oscillations (fibrillatory or f waves) and an irregularly
irregular ventricular rhythm is diagnostic. The f waves have a rate of 300 to
600/min and are variable in amplitude, shape, and timing. The ventricular rate
is typically 100 to 160/min. In patients with Wolff-Parkinson-White syndrome,
the ventricular rate in AF can exceed 250/minute because of conduction over the
accessory pathway.
Echo
ECHO helps to diagnose any underlying structural heart disease.
Chest X-ray
Chest X-ray is done to diagnose underlying lung pathology or cardiac lesions (Fig.
37.1).
Chapter 37 Cardiac Arrhythmias 279
Fig. 37.1 Absent P waves with irregular RR interval indicating atrial fibrillation
Management
Patients who go to the emergency department because of AF generally have a
rapid ventricular rate. Control of the ventricular rate is most rapidly achieved with
intravenous diltiazem or esmolol. If the patient is hemodynamically unstable,
immediate transthoracic cardioversion is done.
Cardioversion should be preceded by transesophageal echocardiography to
rule out a left atrial thrombus, if:
• AF has been present for more than 48 hours, or
• The duration is unclear and the patient is not already receiving an
anticoagulant.
In hemodynamically stable patients, cardioversion is done for patients with
symptomatic AF who are seen with a first episode of AF or who have had long
intervals of sinus rhythm between previous episodes.
Early vs delayed cardioversion
Cardioversion
Pharmacologic vs electrical cardioversion
Early cardioversion
It is done if onset of AF <48 hours. The chances of thrombus formation and
recurrence is less here and anticoagulation is not needed.
Delayed cardioversion
It is done if duration of AF >48 hours. Similarly, one has to go for delayed
cardioversion only if TEE is unavailable or TTE shows LA thrombus.
Pharmacologic cardioversion
Although sedation is not required, the disadvantages of pharmacologic
cardioversion are that the efficacy is lower than electrical cardioversion and it is
very unlikely to be effective if the duration of AF >7 days.
Table 37.1 Dosages of common antiarrhythmic agents
Drug Loading Maintenance

Adenosine 6–12 mg (rapid bolus) –
Quinidine 6–10 mg/kg at 0.3–0.5 mg/kg per minute –
Digoxin 0.25 mg 2nd hourly until 1 mg total 0.125–0.25 mg/d
Ibutilide 1 mg over 10 minute if over 60 kg –
Amiodarone 15 mg/minute for 10 minute, 1 mg/minute for 6 hours 0.5–1 mg/minute
Lidocaine 1–3 mg/kg at 20–50 mg/minute 1–4 mg/minute
Procainamide 15 mg/kg over 60 minute 1–4 mg/minute
Diltiazem 0.25 mg/kg over 3–5 minute (max 20 mg) 5–15 mg/hour
Verapamil 5–10 mg over 3–5 minute 2.5–10 mg/hour
Esmolol 500 µg/kg over 1 minute 50 µg/kg/minute
Intravenous: Ibutilide, procainamide and amiodarone. Dosages of common anti-

arrhythmic agents is given in Table 37.1.
Oral: Propafenone (300–600 mg) and flecainide (100–200 mg).
Electrical cardioversion (Transthoracic)
Biphasic shock is preferred as it is more efficacious and produces less tissue
damage). To begin with, 150–200 J is given to begin and increased if required.
Ibutilide infusion preceding shock can reduce energy requirement and increases
efficacy.
Role of anticoagulation
If the AF duration >48 hours or unclear, anticoagulation should be given 3 weeks
prior to cardioversion and 4 weeks postcardioversion (electrical or chemical).
An alternative to 3 weeks of therapeutic anticoagulation before cardioversion
is anticoagulation with heparin and transesophageal echocardiography. If no
thrombi are seen, the patient can safely be cardioverted but requires 4 weeks of
therapeutic anticoagulation after cardioversion.
Long-term management
The two key components in the management of AF are rate control and rhythm
control.
Rate control
Rate-control strategy is preferable to a rhythm-control strategy in asymptomatic
or minimally symptomatic patients > 65 years. In younger patients and in patients
>65 years or older whose AF is symptomatic despite adequate heart rate control,
cardioversion can be tried. Drugs for rate control are digitalis, beta-blockers,
calcium channel antagonists, and amiodarone. Of these drugs, beta-blockers and
calcium channel antagonists are the 1st line drugs. Digitalis is ideal for patients
with heart failure and AF whereas amiodarone is appropriate choice if the other
agents are not tolerated or are ineffective. Antithrombotic therapy to prevent
thromboembolism is recommended for all patients with AF, except those with
lone AF or contraindications.
Special scenarios
• Postoperative atrial fibrillation: It is common after open heart surgery
(25–40%) and commonly occurs due to hypomagnesemia. Beta-blockers,
sotalol, and amiodarone reduce risk of AF.
• AF in Wolff-Parkinson-White syndrome: These patients have an accessory
pathway with a short refractory period and can experience a very rapid
ventricular rate during AF (>250 to 300 beats/minute) and can result in
loss of consciousness or precipitate ventricular fibrillation and cardiac
arrest. Transthoracic cardioversion is done if hemodynamically unstable.
If hemodynamically stable, intravenous procainamide may be preferable to
ibutilide because it blocks accessory pathway conduction.
Digitalis and calcium channel antagonists are contraindicated as they
selectively block conduction in the AV node and can result in increased
conduction through the accessory pathway. The preferred therapy is catheter
ablation of the accessory pathway.
• AF in heart failure: Rate-control drugs used are digitalis and beta-blockers
or amiodarone. Only amiodarone and dofetilide are the safe rhythm control
drugs.
• Acute myocardial infarction: Electrical cardioversion is recommended for
patients with hemodynamic compromise or ongoing ischemia or when
adequate rate control cannot be achieved with drug therapy. Intravenous
amiodarone or digitalis to slow the ventricular rate is recommended. If not
contraindicated, intravenous beta-blocker or nondihydropyridine CCBs are
recommended for rate control.
• Hyperthyroidism: Beta-blocker is first-line therapy. If a beta-blocker cannot
be used, verapamil or diltiazem should be used for rate control.
• Atrial fibrillation during pregnancy: For Rate control-Digoxin/beta-
blocker/nondihydropyridine CCB is given. If hemodynamically stable,
pharmacologic cardioversion with quinidine or procainamide and direct
electrical cardioversion is recommended in hemodynamically unstable
patients.
• AF in pulmonary disease: The primary therapy for is correction of hypoxemia
and acidosis. Verapamil or diltiazem is recommended for rate control.
Theophylline and beta-adrenergic agonists are avoided.
• AF in hypertrophic cardiomyopathy: Disopyramide plus a beta-blocker,
verapamil, or diltiazem (or ) amiodarone is given.
Atrial Flutter
It is a macrore-entrant atrial rhythm involving the cavotricuspid isthmus.
ECG Findings (Fig. 37.2)

The typical ECG findings are identically recurring, regular, sawtooth flutter waves
with uniform morphology due to fixed circuit, best seen in leads II, III, aVF, or
V1. Atrial rate is usually 250 to 350 beats/minute and ventricular rhythm will
be regular and have a fixed relationship with the flutter waves (except in case of
varying AV block).
Fig. 37.2 Flutter waves with tachycardia indicating atrial flutter
Treatment
Cardioversion with 50 J DC is the preferred treatment or intravenous ibutilide,
procainamide or amiodarone can also be given. Anticoagulation regimen is the
same as in AF. Catheter ablation is also very effective in recurrent cases.
Focal Atrial Tachycardias

Here the atrial rates vary from 150 to 200 beats/minute with a P-wave contour
different from that of the sinus P-wave with isoelectric intervals in between. It
occurs commonly in patients with significant structural heart disease and digitalis
toxicity. Beta-blocker or a calcium channel blocker class IA, IC, or III drugs can be
given. Catheter ablation indicated in incessant tachycardia.
Chaotic Atrial Tachycardia (Multifocal Atrial Tachycardia)

It is characterized by:
• Atrial rates between 100 and 130 beats/minute
• At least 3 different P-wave morphologies
• At least 3 different PR intervals
• Isoelectric line in between P waves.
ECG of multifocal atrial tachycardia is shown in Figures 37.3 and 37.4. Occurs
commonly in COPD and CCF. Management is directed primarily toward the
underlying disease.
Supraventricular Reentrant Tachycardias

It can be due to:
• Atrioventricular nodal reentrant tachycardia (AVNRT)
• Atrioventricular reentrant tachycardia (AVRT).
Atrioventricular Nodal Reentrant Tachycardia

Electrophysiology
A slow pathway with short refractory period and fast pathway with long refractory
period are present within the AV node. Premature atrial complex blocks
conduction in the fast pathway anterogradely, travels to the ventricle through the
slow pathway and returns to atrium via the fast pathway causing circus movement
and thereby precipitating tachycardia (Fig. 37.5).
Symptoms
Patients may complain of palpitations, dyspnea or rarely syncope.
Treatment
Vagal maneuvers (carotid sinus massage, the Valsalva and Müller maneuvers,
gagging, exposure of the face to ice water)
if fails

Adenosine 6 to 12 mg IV (given rapidly)
if fails

Verapamil 5 to 10 mg IV or diltiazem 0.25 to 0.35 mg/kg IV
if fails or in hemodynamic compromise

DC cardioversion
Fig. 37.3 Multifocal atrial tachycardia

Fig. 37.4 Multifocal atrial tachycardia showing P wave of different morphologies and
different PR intervals
Fig. 37.5 Atrioventricular nodal reentrant tachycardia
Atrioventricular Reentrant Tachycardia

Accessory pathways are fibers that connect the atrium or AV node to the ventricle
outside the normal AV nodal–His-Purkinje conduction system. When anterograde
conduction is present, it produces pre-excitation of the ventricle and delta waves.
If only retrograde conduction is present, there is neither pre-excitation nor delta
wave. AVRT without pre-excitation presents with narrow complex tachycardia
and is managed in the same way as AVNRT (Fig. 37.6).
Treatment
Vagal maneuvers and drugs such as intravenous adenosine, verapamil, or
diltiazem and beta-blockers (AV node blockade) can be given. These drugs
are contraindicated in SVT with pre-excitation. Instead, drugs that prolong the
refractory period in the accessory pathway should be used, such as class IA and
IC drugs.
Electrocardiographic clues that permit differentiation among the various SVTs
(Flow chart 37.1):
• P waves identical to sinus P waves and occur with a long RP interval and
a short PR interval are most likely caused by sinus nodal reentry, sinus
tachycardia, or an atrial tachycardia arising from the right atrium near the
sinus node.
Fig. 37.6 AVRT with left side accessory pathway
Flow chart 37.1 Diagnosis of narrow QRS complex tachycardia

• Retrograde (inverted in leads II, III, and aVF) P waves

Reentry involving the AV junction, either AV nodal reentry or
reciprocating tachycardia using a paraseptal accessory pathway.
• ST segment depression in narrow-complex tachycardia
AV reentrant tachycardia by an accessory pathway.
• Tachycardia without P waves
AV nodal reentry (retrograde P waves buried in the QRS complex)
• Tachycardia with an RP interval >90 ms
Accessory pathway.
VENTRICULAR ARRHYTHMIAS
Ventricular Premature Complex

Origin of premature ventricular beats which arise from sites distal from the
Purkinje fibers produces slow ventricular activation and a wide QRS complex
which is >140 ms in duration. Ventricular premature complexes (VPCs) are
common and increase with age and the presence of structural heart disease. VPC
can occur as bigeminy, trigeminy, couplets. Three or more consecutive VPCs
are termed as VT when the rate is >100 beats per minute (Fig. 37.7). VPCs are
associated with full compensatory pause. Treatment is based on the presence of
associated severe symptoms and structural heart disease. VPCs are benign and
need not be treated in the absence of structural heart disease.
Ventricular Tachycardia
Its origin is distal to the bifurcation of the His bundle. It can occur due to disorder
in impulse formation (enhanced automaticity or triggered activity) or conduction
(reentry). The QRS complex during VT may be uniform (monomorphic) or may
Fig. 37.7 Ventricular premature complex

Fig. 37.8 Monomorphic VT
Fig. 37.9 Polymorphic VT showing capture and fusion beats
vary from beat to beat (polymorphic). Algorithm for diagnosis of wide QRS
complex tachycardia is given in Flow chart 37.2.
ECG Findings (Figs 37.8 to 37.10)

• Occurrence of 3 or more consecutive VPCs whose duration is >120 ms, with
the ST-T vector pointing opposite the major QRS deflection.
• The RR interval is usually regular and rate ranges from 70 to 250 (depending
on VT type).
Duration of 30 seconds is taken for differentiating sustained and non-
sustained VT. Sustained VT requires termination of VT within 30 seconds
Flow chart 37.2 Diagnosis of wide QRS complex tachycardia
because of hemodynamic collapse or VT that is terminated by therapy from an

implantable defibrillator.
Supports SVT with Aberrancy

• Onset with premature P wave and RP interval ≤100 msec
• P and QRS rate and rhythm linked to suggest that ventricular activation
depends on atrial discharge
• Long-short cycle sequence and slowing or termination by vagal tone.
Fig. 37.10 Nonsustained VT with AV dissociation and capture beats
Supports VT
• Presence of Fusion beats, capture beats and AV dissociation—but not always
present
• P and QRS rate and rhythm linked to suggest that atrial activation depends
on ventricular discharge, e.g. 2:1 VA block
• “Compensatory” pause
• Left-axis deviation; QRS duration >140 msec.
Management
• VT without hemodynamic compromise—medical management.
• VT with hemodynamic compromise/unresponsive to medical treatment—
DC cardioversion.
Medical management
Intravenous administration of amiodarone, lidocaine or procainamide followed
by an infusion is used.
Amiodarone
Loading dose of 15 mg/minute is given over 10 minutes
Infusion of 1 mg/minute for 6 hours
Maintenance dose of 0.5 mg/minute for the next 18 hours

This can be continued for next few days as necessary. Hypotension does not
occur with newer preparations and can be used in renal and liver failure.
Long-term Prevention
ICD is the treatment of choice for patients who have survived cardiac arrest or
who have sustained VT resulting in hemodynamic compromise and poor LV
function. In patients who refuse an ICD, empiric amiodarone may be the next
best therapy.
Specific Types/Scenarios
VT in acute MI
• Acute phase (2–30 minute)—mainly occurs due to reentrant mechanisms/
increased automaticity.
• Delayed phase (30 minute–72 hours) due to abnormal automaticity in
surviving cells.
• Chronic phase (>72 hours) due to reentry.
VT in old MI
It is usually from scar tissue and is usually monomorphic. Polymorphic VT in MI
occurs in acute in active ischemia and requires no QT prolongation.
Treatment of sustained VT in MI
• 1st line in normal LV function—intravenous procainamide or sotalol
• 1st line in impaired LV function—intravenous amiodarone or lidocaine
• Peri-infarct polymorphic VT —more responsive to amiodarone.
Arrhythmogenic Right Ventricular Cardiomyopathy

It is an inherited disease that results in fibrofatty infiltration of predominantly the
right ventricle due to mutation in proteins of the desmosome and is manifested
by RVOT VT.
ECG
May show complete or incomplete RBBB and T wave inversion in V1 to V3.
Epsilon wave—Terminal notch in QRS.
Treatment
• ICDs are generally preferable to pharmacologic approaches.
• RF epicardial catheter ablation can be tried.
Catecholaminergic Polymorphic Ventricular Tachycardia

It occurs in the absence of overt structural heart disease and normal QT intervals
and presents with stress-induced VT that is often bidirectional. The treatment of
choice is beta-blockers and an ICD. Sympathectomy is effective in some cases.
Brugada Syndrome
Brugada syndrome presents as an idiopathic VF in which patient has RBBB and
ST-segment elevation in the anterior precordial leads without any evidence
of structural heart disease (Fig. 37.11). It occurs due to mutations in genes
responsible for the sodium channel (SCN5A) and calcium channel. Drug of
choice is quinidine. ICDs are required for treatment to prevent sudden death.
Fig. 37.11 Type 1 Brugada syndrome
Fig. 37.12 Torsades de Pointes
Torsades de Pointes
VT characterized by QRS complexes of changing amplitude that appear to
twist around the isoelectric line and occur at rates of 200 to 250/minute and QT
intervals generally >500 ms. Polymorphic VT in the absence of QT prolongation
is not considered as Torsades de Pointes (Fig. 37.12).
Causes
Congenital severe bradycardia, Congenital long QT syndrome, potassium
depletion, and use of QT-prolonging medications (such as class IA or III anti-
arrhythmic drugs).
Treatment
The precipitating cause of the long QT should be corrected. Intravenous
magnesium is the DOC followed by temporary ventricular or atrial pacing.
Isoprenaline, lidocaine, mexiletine or phenytoin can also be tried. Class IA, class
IC, and class III antiarrhythmic agents (e.g. amiodarone, dofetilide, sotalol) are
contraindicated.
Fig. 37.13 Ventricular fibrillation
Torsades de pointes resulting from congenital long-QT syndrome is treated

with beta-blocker, pacing, and ICDs. The other less common VTs are bidirectional
VT, bundle branch reentrant VT, fascicular VT and outflow VT.
Ventricular Flutter and Fibrillation

Ventricular flutter is manifested as a sine wave in appearance—regular large
oscillations occurring at a rate of 150 to 300/minute. VF is recognized by the
presence of irregular undulations of varying contour and amplitude (Fig. 37.13).
It is seen most commonly in association with coronary artery disease. Immediate
nonsynchronized DC electrical shock using 200–360 J is mandatory therapy
for VF.
Sinus Bradycardia
Here the sinus node discharges at a rate <60 beats/minute. Sinus bradycardia
needs treatment only when symptomatic or when associated with hemodynamic
compromise. It usually responds to atropine. If persistent, pacing should be done.
Sinus Pause or Sinus Arrest

Sinus pause or sinus arrest is recognized by a pause in the sinus rhythm. The P-P
interval of the pause is not a multiple of the basic P-P interval. Pacing is indicated
if the pause is >3 seconds.
Sinoatrial Exit Block

It is a benign condition where the sinus node fires normally but an impulse
formed within the sinus node fails to depolarize the atria or does so with delay.
The duration of the pause is a multiple of the basic P-P interval.
Table 37.2 Characteristics of Mobitz type I and II block
Mobitz type I (Wenckebach) Mobitz type II

It is characterized by progressive Occasional or repetitive sudden block of
lengthening of the conduction time until conduction of an impulse, without prior
an impulse is not conducted measurable lengthening of conduction time
Fig. 37.14 Prolonged interval indicating 1st degree heart block
Fig. 37.15 Progressive lengthening of PR interval followed by a dropped beat

indicating 2nd degree Mobitz type 1 AV block
AV Block
An AV block exists if the atrial impulse is conducted with delay or is not conducted
at all to the ventricle when the AV junction is not physiologically refractory. The
three types are:
1. First-degree heart block—PR interval is prolonged but all impulses are
conducted (Fig. 37.14).
2. Second-degree heart block occurs in two forms (Table 37.2):
i. Mobitz type I (Wenckebach) (Fig. 37.15)
ii. Mobitz type II (Fig. 37.16)
3. Third-degree block—No impulses are conducted (Fig. 37.17).
Fig. 37.16 Regular PR interval with intermittent nonconducting P wave

indicating Mobitz type 2 block
Fig. 37.17 Complete heart block in a patient with inferior wall myocardial infarction
When the block is at the AV nodal level, the escape complexes are narrow in
morphology and have rate of 40–60/minute. When it is below the AV level, the
escape complexes are broad and have a slow rate of about 40/minute.
AV block is quite common in inferior wall MI and is usually due to vagotonia
as well as Bezold Jarisch reflex and is usually transient. But high degree AV block
in anterior wall MI is usually associated with extensive myocardial damage and
pump failure and indicates poor prognosis.
Management
Intravenous atropine, isoprenaline. Pacing is done in significant cases.
BIBLIOGRAPHY
1. Barra SNC, Providência R, Paiva L, et al. A review on advanced atrioventricular block
in young or middle-aged adults. Pacing Clin Electrophysiol. 2012;35:1395.
2. Fuster V, Ryden LE, Cannom DS, et al. 2011 ACCF/AHA/HRS focused updates
incorporated into the ACC/AHA/ESC 2006 guidelines for the management of patients
with atrial fibrillation: A report of the American College of Cardiology Foundation/
American Heart Association Task Force on Practice Guidelines. Circulation. 2011;
123:e269.
3. Lee KW, Badhwar N, Scheinman MM. Supraventricular tachycardia—part I. Curr
Probl Cardiol. 2008;33:467.
4. Márquez MF, Bonny A, Hernández-Castillo E, et al. Long-term efficacy of low doses
of quinidine on malignant arrhythmias in Brugada syndrome with an implantable
cardioverter defibrillator: A case series and literature review. Heart Rhythm. 2012;9:
1955.
5. Nademanee K, Veerakul G, Chandanamattha P, et al. Prevention of ventricular
fibrillation episodes in Brugada syndrome by catheter ablation over the anterior right
ventricular outflow tract epicardium. Circulation. 2011;123:1270.
6. Narayan SM, Krummen DE, Shivkumar K, et al. Treatment of atrial fibrillation by the
ablation of localized sources: CONFIRM (Conventional Ablation for Atrial Fibrillation
with or without Focal Impulse and Rotor Modulation) trial. J Am Coll Cardiol. 2012;
60:628.
7. Pellegrini CN, Scheinman MM. Clinical management of ventricular tachycardia. Curr
Probl Cardiol. 2010;35:453.
8. Pflaumer A, Davis AM. Guidelines for the diagnosis and management of
catecholaminergic polymorphic ventricular tachycardia. Heart Lung Circ. 2012;21:96.
9. Prystowsky EN, Padanilam BJ, Joshi S, Fogel RI. Ventricular arrhythmias in the absence
of structural heart disease. J Am Coll Cardiol. 2012;59:1733.
10. Teh AW, Kistler PM, Kalman JM. Using the 12-lead ECG to localize the origin of
ventricular and atrial tachycardias: Part 1. Focal atrial tachycardia. J Cardiovasc
Electrophysiol. 2009;20:706.
CHAPTER
38 Surendran GD
ACUTE HEART FAILURE
DEFINITION
Acute heart failure is the term used to describe the rapid onset of signs and
symptoms of pulmonary congestion and/or peripheral hypoperfusion due to
cardiac and/or vascular dysfunction requiring hospital admission and immediate
treatment.
CLASSIFICATION
Simplified Classification Based on ESC Guidelines

• Decompensated heart failure: It is characterized by worsening signs and
symptoms of congestion on a background of chronic heart failure. It may
be acute, subacute or indolent. The cardiac output generally is preserved to
some extent, and they are hemodynamically stable.
• Acute hypertensive heart failure: In this type of heart failure, hypertension
can be the cause or the effect or both. It is usually acute in onset and the
patients have preserved ejection fraction.
• Cardiogenic shock: It is a condition characterized by reduction in cardiac
output resulting in tissue hypoxia which leads on to various functional and
structural disturbances in vital organs.
PATHOPHYSIOLOGY
Acute heart failure (AHF) is an extremely complex and heterogeneous syndrome
with varying presentation. In short, it occurs due to one or more of triggering
factors upon a previously normal or compensated heart disease or a chronically
failing heart that leads to interplay of myocardial/renal/vascular/neurohumoral
factors leading to symptomatic congestion and/or end-organ dysfunction (Flow
chart 38.1).
CLINICAL FEATURES
The symptoms of heart failure can generally be classified into:
• Those due to congestion
• Those due to hypoperfusion.
Chapter 38 Acute Heart Failure 297
Flow chart 38.1 Pathophysiology of acute heart failure
Symptoms
Dyspnea is the most common symptom and is present in 90% cases. Dyspnea
typically is present at rest or with minimal exertion. Patients also may present with
signs and symptoms related to systemic venous congestion such as peripheral
edema. In elderly patients, atypical manifestations such as fatigue, depression,
altered mental status or sleep disruptions can occur.
Signs
Despite advances in diagnostics technology and imaging, heart failure remains a
clinical diagnosis, and physical examination is of utmost importance.
• The JVP is elevated in cardiac failure. It reflects the right atrial pressure and
is an indirect measure of LV filling pressures and the single most useful
physical examination finding in the assessment of patients with AHF. S3
gallops generally indicate an ejection fraction of <30% (severe LV systolic
dysfunction).
• Rales or inspiratory crackles are the most common physical examination
finding but may not be heard in chronic failure due to pulmonary
hypertension and increased lymphatic drainage. Cool peripheries and
Peripheral edema (in about 65% cases) are common findings of acute heart
failure. Hypotension and low pulse pressure indicate poor outcomes.
BIOMARKERS
Natriuretic peptide testing in the diagnosis of acute dyspnea is currently the only
class I indication for a biomarker test in heart failure. NT-proBNP has similar
diagnostic value as BNP. BNP <30 rules out AHF; BNP > 100 confirms AHF.
Renal Function Tests

Blood urea nitrogen (BUN) is more directly related to the severity of AHF than
creatinine. It is proportional to neurohormonal activation in AHF.
Chest Radiography
Evidence of congestion is found in more than 80% of these patients.
Electrocardiography
It may show findings suggestive of ischemia, MI or arrhythmias.
Echocardiography
It is the single most useful test in the investigation of AHF. Echocardiography can
assess global systolic and diastolic function, regional wall motion abnormalities,
valvular function, hemodynamics including estimates of filling pressures and
cardiac output and pericardial disease.
Management
Emergency Care
This consists of rapidly relieving symptoms and identifying precipitating causes
and triggers and giving specific therapy to deal with them.
• Nasal O2 therapy: Indicated in patients with severe hypoxemia (SaO2 <90%)
• NIPPV: In patients with cardiogenic pulmonary edema, continuous positive
airway pressure (CPAP) or noninvasive intermittent positive-pressure
ventilation (NIPPV) helps alleviate symptoms, and reduces the need for
invasive ventilation and reduces mortality.
• Morphine: Morphine may be useful in patients with severe anxiety or
distress but should be avoided, especially in the presence of hypotension,
bradycardia, advanced atrioventricular block or CO2 retention.
• Loop diuretics: These drugs helps in relieving the volume overload and thus
provide immediate symptom relief. The intravenous route increases the
bioavailability and allows for rapid onset of action (typically within 30–60
minutes).
• Vasodilators play an important role in the initial therapy of patients with
pulmonary edema.
Management of Acute Heart Failure
Based on Initial Clinical Status

Drugs/Interventions Indications
• Intravenous bolus of loop diuretic Initially given in heart failure
• Oxygen During hypoxemia
• Intravenous opioid For reducing anxiety and distress
Based on Systolic Blood Pressure

• Add nonvasodilating inotrope SBP <85 mm Hg or shock
• No additional therapy SBP of 85–110 mm Hg
• Consider vasodilators (e.g. nitroglycerine) SBP >110 mm Hg
Systolic blood pressure (SBP): Based upon the response to treatment to the initial
treatment based on clinical status and systolic blood pressure, the follow-up
treatment is planned. If there is response to treatment by the above measures, the
above treatment is continued. If there is no response to the above treatment, the
patient is re-evaluated based on systolic blood pressure, oxygen saturation and
urine output.
Based on Re-evaluation of Patient’s Clinical Status

O2/NIV/Invasive mechanical ventilation Oxygen saturation (SaO2) <90%
Consider vasopressors/Nonvasodilating inotrope/right SBP <85 mm Hg
heart catheterization/Mechanical circulatory support
(e.g. IABP, ventricular assist device)
Diuretics consider low dose dopamine/right heart Urine output <20 mL/hour
catheterization/ultrafiltration
SPECIFIC THERAPIES FOR ACUTE HEART FAILURE
Diuretics
With significant volume overload (>5–10 liters) or diuretic resistance, a continuous
intravenous infusion can be considered (though DOSE trial showed no added
advantage). For diuretic resistance, thiazide-like diuretic that blocks the distal
tubule-intravenous chlorothiazide (500–1000 mg) or oral metolazone (2.5–10
mg) is given before the loop diuretic. If hypokalemia is a persistent problem,
potassium-sparing diuretic such as spironolactone or eplerenone should be
considered (Table 38.1).
VASODILATORS
Patients admitted with AHF and treated with diuretics plus vasodilators had
significantly better survival.
Classification
• Predominantly venous dilators (reduction in preload)
• Arterial dilators (decrease in afterload)
• Balanced vasodilators (combined effect).
Table 38.1 Therapeutic approaches for volume management in acute heart failure
Severity
of volume
overload Diuretic/device Dose (mg) Comments
Moderate Furosemide 20–40 mg Titrate dose according
or to clinical response
Torsemide 10–20 mg Monitor Na, K,
creatinine
Severe Furosemide 40–160 mg or Adjust ultrafiltration rate
or 5–40 mg/hour infusion to clinical response,
monitor for hypotension
Torsemide 20–100 mg or
ultrafiltration 5–20 mg/hour
200–500 mL/hour
Refractory to Add 25–50 mg twice daily Combination with loop
loop diuretics Hydrochlorothiazide 2.5–10 mg once daily diuretic may be better
or than very high dose of
Metolazone loop diuretics alone
Nitrates
They are potent venodilators and they decrease ventricular filling pressures and
cause improvement in pulmonary congestion, dyspnea and myocardial oxygen
demand at low doses. At higher doses, they act as arteriolar vasodilators also,
reducing afterload and increasing cardiac output. They are relatively selective
for epicardial coronary arteries resulting in increased coronary blood flow and
making them useful for patients with concomitant active myocardial ischemia.
The major limitation of organic nitrates is tolerance (develops within
24 hours). Headache is the most common adverse effect. The recent use of
PDE-5 inhibitors (sildenafil, tadalafil, and vardenafil) should be ruled out before
administration of nitrates as this deadly combination can lead to catastrophic
hypotension. Nitrates should be discontinued, if SBP is below 90 mm Hg.
Sodium Nitroprusside
Nitroprusside is a prodrug that is rapidly metabolized to nitric oxide and cyanide.
The cyanide metabolite causes nausea, abdominal discomfort and dysphoria.
Cyanide accumulation is seen mainly in hepatic dysfunction patients only. This
drug produces balanced reduction in afterload and preload. Because of very
short life (seconds to a few minutes), it is accurately titratable. Tapering the
dose is important as it can cause rebound hypertension. Sodium nitroprusside
is particularly effective in the setting of markedly elevated afterload (e.g.
hypertensive AHF) and moderate to severe mitral regurgitation. However, due to
coronary steal phenomenon not recommended in active myocardial ischemia.
Nesiritide
It is a recombinant human B-type [brain] natriuretic peptide. It produces potent
vasodilation and mild increases in cardiac output through cGMP-mediated
Table 38.2 Dosages of various vasodilators used for heart failure
Vasodilators Initial dose Infusion range Comments

Nitroglycerin; 20 μg/minute 40–200 μg/minute Hypotension
Glyceryl trinitrate
Isosorbide dinitrate 1 mg/hour 2–10 mg/hour Hypotension
Nitroprusside 0.3 μg/kg/ 0.3– 5 μg/kg/minute Caution in patients with
minute (usually <4 μg/kg/ active myocardial ischemia;
minute) can cause hypotension;
cyanide toxicity; thiocyanate
toxicity; light sensitivity
Nesiritide 2 μg /kg bolus 0.010–0.030 μg/kg/ –
with 0.01–0.03 minute
μg/kg/minute
infusion
vasodilation. Nesiritide causes hypotension in volume-depleted patients and so

used only in congestive patients (Table 38.2).
Inotropes and Inodilators

These are used in hypoperfusion when other interventions have failed.
Dobutamine
Dobutamine is an agonist of both beta 1- and beta 2-adrenergic receptors with
variable effects on the alpha-receptors. Tachyphylaxis may occur, if used for longer
than 24–48 hours. Concomitant beta-blocker therapy will result in competitive
antagonism and higher doses of dobutamine (10–20 μg/kg/minute) are required.
Mechanism
Beta-receptor stimulation results in increased inotropy and chronotropy. At low
doses, stimulation of beta 2- and alpha-receptors causes vasodilation, reduction
in afterload and indirect increases in cardiac output. However at higher doses,
vasoconstriction occurs.
Adverse Effects
Tachyarrhythmias and myocardial ischemia (contraindicated in active ischemia).
Dopamine
Dopamine is an agonist of both adrenergic and dopaminergic receptors and an
inhibitor of norepinephrine uptake. The effects of this drug varies with the dose.
• Low-dose dopamine (≤2 μg/kg/minute): Proposed to cause selective dilation
of renal, splanchnic and cerebral arteries but it is still an unsettled concept.
It can be tried but to be discontinued in case of no response.
• Intermediate-dose dopamine (2–10 μg/kg/minute): At this dose, it causes

increased inotropy but this effect depends on myocardial catecholamine
stores which unfortunately are often depleted in patients with advanced
heart failure. Hence, dopamine is a poor inotrope in patients with severe
systolic dysfunction.
• High-dose dopamine (10–20 μg/kg/minute): It causes peripheral and
pulmonary artery vasoconstriction, by alpha-1 agonism. This can lead to
end-organ ischemia and should be used cautiously.
Epinephrine
Epinephrine is a full beta-receptor agonist. Its increasing inotropic effect is
independent of myocardial catecholamine stores, and hence, is an useful agent
in the treatment of transplant recipients with denervated hearts.
Phosphodiesterase (PDE IIIa) Inhibitors (Milrinone, Enoximone)

These drugs have positive inotropic effect without causing tachycardia or
tachyphyaxis. Similarly, antagonism by beta-blockers is not a problem and can
be used with dobutamine for synergic effects. It causes significant peripheral
and pulmonary vasodilation and can be used in LV dysfunction with pulmonary
hypertension or in transplant recipients. However, caution is required in both
renal and hepatic insufficiency. Side effects these drugs include hypotension and
arrhythmias.
Levosimendan
It is a novel inodilator which acts by cardiac myofilament calcium sensitization
(inotropic) and activation of vascular smooth muscle potassium channels
(vasodilator). It significantly increase cardiac output, reduces PCWP and afterload
and decrease dyspnea. Hypotension and tachyarrhythmias are the common side
effects (Table 38.3).
OTHER DRUGS USED IN THE TREATMENT OF

ACUTE HEART FAILURE
Digoxin
Digoxin acts by increasing the myocardial contractility without increasing the
heart rate or decreasing the BP. Initial slow bolus 0.5 mg (rapid bolus causes
vasoconstriction) followed by 0.25 mg oral/intravenous 12 hours later as
maintenance is given. It has a narrow therapeutic window therapeutic window
and should be avoided in active ischemia, advanced renal failure and AV blocks.
Arginine Vasopressin Antagonists

These drugs are given only in symptomatic hyponatremia (as Vasopressin causes
hypervolemic hyponatremia of heart failure). Tolvaptan (oral) and conivaptan
(IV) are the available drugs but without improved long-term outcomes.
Table 38.3 Dosages of various inotropes used for heart failure—

milrinone dose to be altered
Inotropes Initial dose Maximal dose Comments

Dobutamine 1–2 μg/kg/minute 2–20 μg/kg/minute Inotropy
Dopamine 1–2 μg/kg/minute 2–4 μg/kg/minute Inotropy
Milrinone 25–75 μg/kg 0.10–0.75 μg/kg/ Inodilator
bolus over 10–20 minute
minute followed by
0.375–0.75 µg/kg/
minute
Enoximone 0.5–1 mg/kg 5–20 μg/kg/minute Inodilator
Levosimendan 12 μg/kg bolus over 0.1–0.2 μg/kg/minute Inodilator
10 minute followed
by infusion
Epinephrine 0.05–0.5 μg/kg/ For vasoconstriction
minute and inotropy.
Causes tachycardia,
arrhythmias and end-
organ hypoperfusion
Norepinephrine 0.2–1.0 μg/kg/minute For vasoconstriction
and inotropy, causes
reflex bradycardia,
cardiac arrhythmias
and end-organ
hypoperfusion
Calcium-channel Blockers
Calcium-channel blockers (CCBs) without significant myocardial depressant
effects, such as nicardipine and clevidipine, are useful in patients with AHF with
severe hypertension refractory to other therapies.
Istaroxime
It causes increased cytosolic calcium accumulation during systole, with
positive inotropic effects and rapid sequestration of cytosolic calcium into the
sarcoplasmic reticulum during diastole. Trials have shown that the addition of
istaroxime to standard therapy lowered PCWP and heart rate and increased SBP.
Nonpharmacologic Therapies
Ultrafiltration
Ultrafiltration involves removal of isotonic fluid, in a more effective way
potentially without the neurohormonal activation seen with diuretics. However,
derangement of renal function and high in-hospital mortality are associated with
this procedure.
Hypertonic Saline
Administration of hypertonic saline (HSS) (3%), along with high-dose furosemide
and sodium and fluid restriction, may be associated with greater diuretic and
clinical response as shown by the SMAC-HF study, however, further studies are
needed.
Novel Agents/Drugs Under Study

Serelaxin, Urodilatin [a modified version of pro–atrial natriuretic peptide (pro-
ANP)].
Ularitide, (a synthetically-produced urodilatin), Cenderitide (CD-NP),
Aliskiren (Direct renin inhibitor), Tezosentan (Endothelin receptor antagonists)
etc.
Cardiorenal Syndrome in Hospitalized Patients

It is defined as increase in serum creatinine above 0.3 mg/dL (or 25% decreases in
GFR) despite hemodynamic congestion. It should not be confused with changes
in renal function during successful decongestion therapy which is usually are
transient. ACE inhibitors and spironolactone should be stopped in this patient.
Higher doses of diuretics and vasodilators are used to treat this condition.
Criteria for Discharge

• Precipitating factors treated
• Volume status optimized
• Change over from intravenous diuretic to oral diuretic therapy
• Pharmacologic therapy optimized
• LV ejection fraction documented
• Counseling regarding risk factor modification done
• Discharge instructions and family education
• Review clinic visit scheduled.
BIBLIOGRAPHY
1. Binanay C, Califf RM, Hasselblad V, O’Connor CM, Shah MR, Sopko G, Stevenson
LW, Francis GS, Leier CV, Miller LW; ESCAPE investigators and ESCAPE study
coordinators. Evaluation study of congestive heart failure and pulmonary artery
catheterization effectiveness: the ESCAPE trial. JAMA. 2005;294(13):1625-33.
2. Dickstein, et al. 2008; Filippatos and Zannad 2007.
3. Dupont M, Mullens W, Finucan M, Taylor DO, Starling RC, Tang WH. Determinants
of dynamic changes in serum creatinine in acute decompensated heart failure:
the importance of blood pressure reduction during treatment. Eur J Heart Fail.
2013;15(4):433-40.
4. Felker GM, Lee KL, Bull DA, et al. Diuretic strategies in patients with acute
decompensated heart failure. N Engl J Med. 2011;364:797.
5. Gray A, Goodacre S, Newby DE, et al. Noninvasive ventilation in acute cardiogenic
pulmonary edema. N Engl J Med. 2008;359:142.
6. Hasenfuss G, Teerlink JR. Cardiac inotropes: Current agents and future directions. Eur
Heart J. 2011;32:1838.
7. Lee DS, Stitt A, Austin PC, et al. Prediction of heart failure mortality in emergent care:
A cohort study. Ann Intern Med. 2012;156:767.
8. Maisel AS, Krishnaswamy P, Nowak RM, et al. Rapid measurement of B-type natriuretic
peptide in the emergency diagnosis of heart failure. N Engl J Med. 2002;347:161.
9. McMurray JJ, Adamopoulos S, Anker SD, et al. ESC Guidelines for the diagnosis and
treatment of acute and chronic heart failure 2012: The Task Force for the Diagnosis
and Treatment of Acute and Chronic Heart Failure 2012 of the European Society of
Cardiology. Developed in collaboration with the Heart Failure Association (HFA) of
the ESC. Eur Heart J. 2012;33:1787.
10. Metra M, Teerlink JR, Voors AA, et al. Vasodilators in the treatment of acute heart
failure: What we know, what we don’t. Heart Fail Rev. 2009;14:299.
11. Pang PS, Cleland JG, Teerlink JR, et al. A proposal to standardize dyspnoea
measurement in clinical trials of acute heart failure syndromes: The need for a
uniform approach. Eur Heart J. 2008;29:816.
12. Park JH, Balmain S, Berry C, et al. Potentially detrimental cardiovascular effects of
oxygen in patients with chronic left ventricular systolic dysfunction. Heart. 2010;96:
533.
13. Vital FM, Saconato H, Ladeira MT, et al. Non-invasive positive pressure ventilation
(CPAP or bilevel NPPV) for cardiogenic pulmonary edema. Cochrane Database Syst
Rev. 2008;(3):CD005351.
14. West RL, Hernandez AF, O’Connor CM, et al. A review of dyspnea in acute heart failure
syndromes. Am Heart J. 2010;160:209.
15. Zile MR, Bennett TD, St John Sutton M, et al. Transition from chronic compensated
to acute decompensated heart failure: Pathophysiological insights obtained from
continuous monitoring of intracardiac pressures. Circulation. 2008;118:1433.
CHAPTER
39 Surendran GD
APPROACH TO ACUTE MYOCARDIAL

INFARCTION
DEFINITION
Acute myocardial infarction is a syndrome of myocardial ischemia with evidence
of myocardial necrosis on biochemical tests or electrocardiography or imaging.
UNIVERSAL DEFINITION OF MYOCARDIAL INFARCTION

There should be an evidence of myocardial necrosis in a clinical-setting consistent
with acute myocardial ischemia (Table 39.1).
Table 39.1 Universal definition of myocardial infarction
Detection of a rise and/or fall in cardiac biomarker values (preferably cTroponin), with at
least one of the following:
• Presence of ischemic symptoms
• Significant and new ST-T changes or new LBBB
• Presence of new pathologic Q waves on ECG
• Evidence of new regional wall motion abnormality or new loss of viable myocardium
in imaging
• Angiography demonstrating thrombus in coronary arteries
UNIVERSAL MYOCARDIAL INFARCTION CLASSIFICATION OF TYPE

Type 1: Spontaneous myocardial infarction related to atherosclerotic plaque
rupture.
Type 2: Myocardial infarction secondary to ischemic imbalance.
Type 3: Myocardial infarction resulting in death when biomarker values are
unavailable.
Type 4a: Myocardial infarction related to percutaneous coronary intervention.
Type 4b: Myocardial infarction related to stent thrombosis.
Type 5: Myocardial infarction related to coronary artery bypass grafting.
Chapter 39 Approach to Acute Myocardial Infarction 307
Pathophysiology (Flow chart 39.1)

Flow chart 39.1 Pathophysiology of acute MI
Table 39.2 Clinical features associated with myocardial dysfunction
• >15% myocardial involvement—Reduced EF

• >25% myocardial involvement—Clinical heart failure
• >40% myocardial involvement—Cardiogenic shock
CLINICAL FEATURES
Contrary to assumption that clinical examination is less important these days, it
is very important in deciding treatment strategy, risk stratification and follow-up
as well as identification of complications (Table 39.2 and Fig. 39.1).
Symptomatology (Table 39.3)

The precipitating factors are unusual heavy exercise (particularly in fatigued
or habitually inactive patients) and emotional stress. The peak incidence of
STEMI usually occurs in the morning due to circadian periodicity of increased
secretion of catecholamines and cortisol. The most common symptom is chest
discomfort resembling classic angina pectoris and it is of crushing, oppressing
or compressing in nature. Pain is felt predominantly retrosternal in location
with radiation to the ulnar aspect of left upper limb or jaw. It generally lasts for
more than 30 minutes, and is not relieved by rest or nitrates. Inferior wall MI can
present with nausea,vomiting and epigastric pain due to vagal reflex.
The patients can also present with atypical features such as symptoms of
heart failure, CNS symptoms, syncope, Psychosis and overwhelming weakness,
etc.
Fig. 39.1 Insufficiency of coronary flow may take place by any of

the above-mentioned mechanisms
Table 39.3 Causes of myocardial infarction without coronary atherosclerosis
• Arteritis
• Trauma (Physical/Radiation/Iatrogenic)
• Coronary mural thickening due to metabolic disease
• Luminal narrowing (Spasm/Dissection)
• Emboli to coronary arteries
• Congenital coronary artery anomalies
Signs
Patients are anxious and restless and describe their pain with a clenched fist
held against the sternum (Levine sign). Those presenting with failure may have
cold and clammy extremities. Small volume pulse is seen in LVF whereas brisk
upstroke is seen in mitral regurgitation or ventricular septal rupture. Inferior wall
MI patients usually have bradycardia and hypotension (due to Bezold Jarisch
reflex) whereas in anterior wall MI, tachycardia and hypertension are observed
as a result of excess sympathetic drive. JVP is elevated in patients with CCF and
RV-MI. On auscultation, S4 is almost always present but is less specific for MI
whereas the presence of S3 signifies severe LV dysfunction. Systolic murmur of
Table 39.4 Killip’s prognostic classification
Killip’s class
I No congestive heart failure
II Mild congestive heart failure, rales, S3, congestion on chest X-ray
III Pulmonary edema
IV Cardiogenic shock
Table 39.5 TIMI score for STEMI
Thrombolysis in myocardial infarction (TIMI) score for ST elevation

Acute myocardial infarction
• DM, history of HTN or history of angina (1 point)
• Systolic blood pressure less than 100 mm Hg (3 points)
• Heart rate greater than 100 (2 points)
• Killip’s class II–IV (2 points)
• Body weight less than 150 Ib or 67 kg (1 point)
• Anterior lead ST elevation or left BBB (1 point)
• Time to treat more than 4 hours (1 point)
Age
• ≥=75 years old (3 points)
• 65–75 years old (2 points)
• Less than 65 (0 points)
TIMI risk score predicts 30-day mortality after an MI

• 0 point: 0.8%
• 1 point: 1.6 %
• 2 points: 2.2%
• 3 points: 4.4%
• 4 points: 7.3%
• 5 points: 12%
• 6 points: 16%
• 7 points: 23%
• 8 points: 27%
• 9–14 points: 36%
Abbreviations: DM, diabetes mellilus; HTN, hypertension; BPM, beats per minute; BBB, bundle branch block
mitral regurgitation can be heard at the apex due to papillary muscle rupture or
dysfunction. Pericardial rubs are usually common on the 2nd or 3rd day are seen
usually at the left parasternal border and are usually triphasic (Tables 39.4 and
39.5).
Investigations
Even though the criteria for MI give importance to cardiac biomarkers, the
physician should NOT wait for the results to start treatment. Treatment should be
started as soon as possible based on history, clinical examination and ECG (Table
39.6 and Fig. 39.2).
Table 39.6 ECG criteria for STEMI
ST elevation
New ST elevation at the J point in two contiguous leads with the following criteria:
≥0.2 mV in men or ≥0.15 mV in women in V2–V3 and/or ≥0.1 mV in all leads (except
V2–V3)
Fig. 39.2 Anterior wall MI—ST elevation in anterior wall leads (V1–4)
Table 39.7 ECG criteria for acute MI in the presence of LBBB (Sgarbossa criteria)
Electrocardiographic criterion Points

Concordant ST segment elevation ≥1 mm in leads with a positive QRS complex 5
Concordant ST segment depression ≥1 mm in leads V1–V3 3
ST segment elevation ≥5 mm and discordant with the QRS complex 2
A score of ≥3 is more specific for acute MI
Posterior MI
Abnormal R wave in V1 (0.04 second in duration and/or R/S ratio ≥1 in the
absence of pre-excitation or RV hypertrophy) with ST depression in ≥2 precordial
leads (V1–V4).
ECG MANIFESTATIONS OF ISCHEMIA IN THE SETTING OF LBBB

New or presumably new LBBB at presentation previously considered as a STEMI
equivalent should not be considered diagnostic of acute myocardial infarction
(MI) in isolation. Following are the criteria for determining MI in the presence of
LBBB (Tables 39.7 and 39.8, Fig. 39.3)
Table 39.8 ECG changes associated with previous MI in the absence of LVH and
LBBB (based on ESC and ACC guidelines)
• Any Q wave in leads V2–V3 ≥0.02 sec or a QS complex in leads V2 and V3

• Q wave ≥0.03 sec and ≥0.1 mV deep or QS complex in leads I, II, aVL, aVF, or V4–
V5 in any 2 leads of a contiguous lead grouping (I, aVL; V1–V6; II, III, aVF)
• R wave ≥0.04 sec in V1–V2 and R/S ≥1 with a concordant positive T-wave in absence
of a conduction defect
Fig. 39.3 Inferior wall MI showing ST elevation in leads II, III, aVF
Fig. 39.4 Global ST depression and characteristic ST elevation of aVR suggests

critical LMCA lesion with high-risk of sudden cardiac arrest
Serum Markers of Cardiac Damage

Myocardial injury can be detected by the presence of circulating proteins released
from damaged myocardial cells. But they usually do not provide clues to the cause
of damage. For example, myocarditis and hence should always be interpreted in
the appropriate context (Fig. 39.4).
Cardiac Troponins (Troponin T and I)

They are the preferred biomarkers in MI. In patients with MI, troponins first begin
to rise by approximately 3 hours after the onset of chest pain and cTnI may persist
for 7–10 days after MI; whereas elevations in cTnT may persist for up to 10–14
days. Troponin T assays have greater uniformity in testing and are preferred. All
patients with suspected MI should undergo testing of Troponin T at admission
and 3–6 hours later. Further testing is needed only in doubtful cases.
CK-MB
It is considered to be less specific than troponin T and is of use only when troponin
T is not available and to detect reinfarction within 10 days.
Echocardiography
It is useful as a diagnostic tool when the clinical picture indicates an MI but ECG is
nondiagnostic. ECHO helps in evaluating the extent of jeopardized myocardium
as well as complications. In the Post-MI phase, it helps in viability testing for
revascularization (Flow chart 39.2).
Management
The central goal is to salvage the involved myocardium within the time window
by restoring perfusion by pharmacologic means or by catheter-based/surgical
therapy.
ANTIPLATELET THERAPY
Aspirin
The loading dose of Aspirin is 162–325 mg and it should be given to all patients.
Enteric-coated preparations should not be given for loading dose. Patient should
chew the drug for buccal absorption.
Clopidogrel
Despite inhibition of cyclo-oxygenase (COX) by aspirin, platelet activation
continues through thromboxane A2–independent pathways. So platelet P2Y12
receptor antagonists such as clopidogrel are given in all patients along with
aspirin with STEMI. The loading dose of clopidogrel is 300 mg. However in
patients planned for PCI, the loading dose of clopidogrel is 600 mg followed by
75 mg daily is given.
Prasugrel
The loading dose of prasugrel is 60 mg followed by 10 mg daily. Prasugrel should
not be given in patients with history of TIA or stroke.
Flow chart 39.2 Management of patient with STEMI
Abbreviation: FMC, first medical contact
Ticagrelor
The loading dose of Ticagrelor is 180 mg followed by 90 mg twice. When using
Ticagrelor, the recommended maintenance dose of Aspirin is 81 mg daily.
PAIN CONTROL
Morphine is the drug of choice as it decreases sympathetic overdrive in addition
to providing analgesia. It also reduces cardiac workload and produce peripheral
arterial and venous dilatation.
Nitrates
They enhance coronary blood flow by coronary vasodilation and also decrease
ventricular preload by venodilatation. They are contraindicated in those with
suspected right ventricular infarction or marked hypotension (e.g. systolic
pressure <90 mm Hg), especially if accompanied by bradycardia. If hypotension
and bradycardia occurs as a side effect, reversal can be done with intravenous
atropine. Long-acting preparations should be avoided in acute MI. They are useful
only in patients with persistent or recurrent angina, heart failure or hypertension
Beta-blockers
Beta-adrenergic blockade diminishes circulating levels of free-fatty acids and
thereby maintain the balance between myocardial oxygen supply and demand.
All patients without contraindication should receive oral beta-blockers within
the first 24 hours. They reduce the need for analgesics in many patients and
reduce infarct size and life-threatening arrhythmias. Beta-blockers are avoided
in hypotension (SBP<90 mm Hg), bradycardia, acute exacerbation of COPD and
AV block.
Dosage
• Metaprolol 5 mg IV is given thrice at 5 minute intervals.
• Oral metaprolol tartrate 25–50 mg 6th hourly for 2–3 days followed by 100 mg
bid.
ACE Inhibitors/ARB
ACE inhibitors reduce the rate of mortality from STEMI accompanied by
significant reductions in the development of heart failure. They also reduce the
incidence of ischemic events including recurrent infarction and the need for
coronary revascularization. They should be given to all STEMI patients within
24 hours even in the absence of heart failure unless contraindicated. ARBs are
equally effective in ACEI intolerant patients.
Aldosterone Antagonists
Eplerenone also reduces cardiovascular mortality.
Calcium-channel Blockers
They are not helpful in the acute phase of MI. Verapamil and Diltiazem can be
given to control rapid ventricular rate in MI with atrial fibrillation without LVF
when the rate is not adequately controlled by beta-blockers.
Magnesium
Patients with STEMI should have their serum magnesium measured on admission
as hypomagnesemia can cause arrhythmias.Magnesium correction is given only
if levels are below 2 mEq/L or if Torsades des Pointes is present.
Glucose Control
Blood glucose levels should be maintained <180 mg/dL while avoiding
hypoglycemia.
Table 39.9 Contraindications and cautions in the use of fibrinolytics for treating STEMI
Absolute contraindications
• Previous intracranial hemorrhage
• Known structural cerebral vascular disease
• Ischemic stroke within 3 months except acute ischemic stroke within 4.5 hours
• Intracranial or intraspinal surgery within 2 months
• Severe uncontrolled hypertension (unresponsive to emergency therapy)
• Active bleeding or bleeding diathesis
• Significant closed head or facial trauma with in 3 months
• For streptokinase, previous treatment within the previous 6 months
• Known malignant intracranial neoplasm (primary or metastatic)
• Suspected aortic dissection
Oxygen
Oxygen should be given only if hypoxemia is present as routine use increase SVR.
LIMITATIONS OF INFARCT SIZE

Time is myocardium is the key in the management of acute MI. Each 30-minute
delay from symptom to PCI increases risk for 1-year mortality by 8%. Various
trials have shown a trend toward a lower mortality rate in patients with STEMI,
especially if they were treated within 2 hours of the onset of symptoms even
before reaching hospital (Pre-hospital fibrinolysis). It is especially useful when
the anticipated transportation time is more than 60–90 minutes but needs expert
crew (Table 39.9).
Fibrinolysis
The maximal efficacy of fibrinolytics is achieved, if it is administered within 2–3
hours of MI. Between 6 and 12 hours, fibrinolysis does show reduction in mortality.
However, fibrinolytics after 12 hours show no mortality benefit. Nevertheless they
can be tried in patients <65 years with TW >12 hours with symptoms of ongoing
ischemia especially in large anterior wall infarcts.
Platelet rich thrombi are more resistant to fibrinolysis than are fibrin and
erythrocyte-rich thrombi and have an increased tendency for reocclusion
after initial successful reperfusion. In a PCI-capable facility, primary PCI is the
preferred mode of reperfusion therapy. If delay from first medical contact to
performing primary PCI is anticipated to exceed 120 minutes, fibrinolytic therapy
is indicated.
Fibrinolytics and Their Dosages
Alteplase
15 mg IV bolus followed by 0.75 mg/kg (up to 50 mg) IV over 30 minutes and
then 0.5 mg/kg (up to 35 mg) IV over 60 minutes. The maximum total dose is
100 mg for patients weighing more than 67 kg. This is the most common alteplase
infusion parameter used for AMI.
Tenecteplase
Tenecteplase is administered in a 30–50 mg IV bolus over 5 seconds. The dosage
is calculated on the basis of the patient’s weight as follows: <60 kg—30 mg, 60 to
69 kg—35 mg, 70 to 79 kg—40 mg, 80 to 89 kg—45 mg.
Streptokinase
1.5 million U in 100 mL of NS given IV over 60 minutes.
Reteplase
Two 10-U vials is first reconstituted with sterile water (10 mL) to 1 U/mL. The
adult dose of reteplase for AMI consists of 2 IV boluses of 10 units each; there is
no weight adjustment. The first 10 U IV bolus is given over 2 minutes; 30 minutes
later, a second 10 U IV bolus is given over 2 minutes. Administer normal saline
(NS) flush before and after each bolus.
PERCUTANEOUS CORONARY INTERVENTION
Primary PCI
When PCI is used as primary reperfusion therapy in patients with STEMI, it is
referred to as direct or primary PCI.
Rescue PCI
PCI done when fibrinolysis has failed to reperfuse the infarct vessel or a severe
stenosis is present in the infarct vessel, it is called rescue PCI. Routine delayed
angiography and PCI after successful fibrinolytic therapy may also be considered
and this is known as secondary PCI.
Advantages of PCI Over Fibrinolysis

Following are the conditions where only PCI can be considered and fibrinolysis is
contraindicated:
• Patients who present late, especially >12 hours after symptom onset
• Patients in cardiogenic shock
• Patients with increased risk for bleeding.
Referral to a PCI center can be superior to fibrinolysis, if the anticipated time
delay is <1–2 hours. But if not, it is always better to start fibrinolysis rather than
wasting precious time window in the process of transporting to a PCI facility
expecting better results.
Indications for Delayed Coronary Angiography with PCI

• Cardiogenic shock or acute severe HF that develops after initial evaluation
• Intermediate or high-risk findings on predischarge noninvasive ischemia
testing
• Spontaneous or easily provoked myocardial ischemia

• Failed reperfusion or reocclusion after fibrinolytic therapy
• Stable patients after successful fibrinolysis—before discharge and between
3 and 24 hour.
Anticoagulants
Benefits of Anticoagulation
• Establishing and maintaining patency of the infarct-related artery
• Prevent deep venous thrombosis and pulmonary embolism
• Prevent ventricular thrombus formation and cerebral embolization.
Unfractionated Heparin Dose (Table 39.10)

Bolus dose of 60 units/kg (maximum of 4000 units)
↓
Initial infusion at 12 units/kg/hour (maximum of 1000 units/hour for 48 hours)
Heparin should be given for at least 48 hours after fibrinolytic therapy.
aPTT to be maintained at 1.5–2 times control (≈50 to 70 seconds). Alternative
anticoagulant regimens are preferred, if administered for longer than 48 hours to
prevent heparin-induced thrombocytopenia.
Low-Molecular-Weight Heparin
They provide a stable, reliable anticoagulant effect, high bioavailability permitting
administration via the subcutaneous route, and a high anti-Xa–to–anti-IIa ratio
resulting in a marked decrement in thrombin generation. LMWH clearly reduced
recurrent MI but with a pattern of increased bleeding.
Parenteral Factor Xa Antagonists

Although Fondaparinux reduced the risk of death or reinfarction in patients
receiving fibrinolytic therapy, it also increased the risk of catheter thrombosis in
PCI group.
Table 39.10 Key points about the use of heparin
• Patients undergoing pharmacologic reperfusion therapy should receive anticoagulant

therapy for a minimum of 48 hours and preferably for the duration of hospitalization
after STEMI, up to 8 days
• Enoxaparin or fondaparinux is preferred when administration of an anticoagulant for
longer than 48 hours is planned
• In patients with history of heparin-induced thrombocytopenia, bivalirudin in conjunction
with streptokinase is the choice
• For patients planned for CABG, unfractionated heparin is preferred due to rapid
reversal.
Direct Thrombin Inhibitors

In patients undergoing fibrinolysis, direct thrombin inhibitors such as hirudin
or bivalirudin reduces the incidence of recurrent MI but with higher risk of
bleeding. When administered for a short period as an adjunct to primary PCI, it
reduced 30–day rate of major bleeding or major adverse cardiovascular events.
Nevertheless bivalirudin is associated with an increased early risk for stent
thrombosis.
Complications of Acute Myocardial Infarction

A search for complications of MI should always be done in patients with sudden
deterioration despite routine treatment. Complications of MI can be classified as:
• Mechanical
• Arrhythmic
• Embolic
• Inflammatory.
Mechanical Complications
The various mechanical complications of acute coronary syndrome are:
• Ventricular septal rupture (VSR)
• Acute mitral regurgitation (MR)
• Ventricular free wall rupture
• Ventricular pseudoaneurysm
• Ventricular aneurysm
• Cardiogenic shock
• LV and RV failure
• Dynamic LVOT obstruction.
Ventricular Septal Rupture

This complication is usually seen 2–5 days after MI. Elderly patients, female sex,
hypertension, first MI and delayed perfusion are the usual precipitating factors.
The patient presents with sudden worsening of clinical features and a new onset
pansystolic murmur is heard at left parasternal border.
Treatment
All VSR should be taken for surgical repair irrespective of the shunt fraction. IV
vasodilators (nitroprusside) and IABP can be used as bridge therapy for surgery.
Despite surgery, mortality is usually higher.
Acute Mitral Regurgitation

Mitral regurgitation occurs as a result of LV dilatation, papillary muscle ischemia
or rupture of papillary muscle. Clinically, it is diagnosed by the presence of
pansystolic murmur that radiates to axilla (in anterior rupture) and to the base
or parasternal region (in posterior rupture). It is more common in IWMI because
posterior papillary muscle has single blood supply by PDA whereas the anterior
muscle is supplied by both LAD and LCx.
Treatment
Surgical repair is the definitive treatment. Vasodilators (IV nitroprusside) and
respiratory support act as a bridge therapy to surgical repair.
Ventricular Free Wall Rupture

Although the incidence of ventricular free wall rupture is <1%, it has got a very
high mortality (>60%). It is more common in the first 5 days of MI. The patient
presents with sudden onset of chest pain with coughing or straining and leading
on to rapid hemodynamic compromise. Features of cardiac tamponade dominate
the clinical picture.
Treatment
In severe hemodynamic instability, pericardiocentesis can be done followed by
emergency thoracotomy with surgical repair.
Ventricular Pseudoaneurysm
It is more commonly seen in inferior wall MI. Ventriculography is the most
reliable method of diagnosis and surgical resection is the treatment of choice.
Ventricular Aneurysm
It is more common with anterior wall MI than with inferior wall MI or posterior
wall MI. Aneurysms can be acute or chronic. Acute aneurysms lead to severe
LV dysfunction and cardiogenic shock whereas chronic aneurysms are usually
clinically silent but may lodge mural thrombi and result in embolic manifestations.
Persistent ST elevation in ECG inspite of reperfusion and alleviation of pain is an
important finding.
Treatment
Management is with vasodilators, ACEI and IABP and surgical aneurysmectomy
in refractory cases. Anticoagulation needed for at least three months, if mural
thrombus is present. LV failure and cardiogenic shock has been dealt extensively
in acute heart failure management.
Intra-aortic Balloon Counterpulsation

It is used for the treatment of STEMI in three groups of patients:
1. Hemodynamically unstable patients and in whom support of the circulation
is required for the performance of cardiac catheterization and angiography.
2. Cardiogenic shock that is unresponsive to medical management.
3. Patients with refractory ischemia that is unresponsive to other treatments or
who are waiting for definitive revascularization.
Temporary mechanical support with left ventricular assist devices may
allow time for recovery of stunned or hibernating myocardium. Hemodynamic
improvement is greater with the percutaneous left ventricular assist device.
RV Failure
It is common in acute inferior wall MI or Inferoposterior MI. It is usually transient
and improves with reperfusion.
}
• Hypotension
• Dilated neck veins Classic triad of RV failure
• Clear lung fields
The combination of JVP >8 cm H2O and Kussmaul’s sign is sensitive and
specific. Cardiac auscultation may reveal RVS3 and RVS4. ECG shows ST elevation
in V4R and sometimes in V1 in addition to inferior lead changes.
Treatment
Rushing of IV fluids to maintain CVP >15 mm Hg is the mainstay of treatment.
If still not responsive, dobutamine infusion can be helpful. RV assist device is
indicated in resistant cases.
Dynamic LVOT Obstruction

It is a very uncommon complication seen in AWMI and occurs due to
compensatory hyperkinesias of inferobasal segments of LV leading to dynamic
LVOT obstruction. Eventhough these patients present with shock, they improve
with intravenous fluids and beta-blockers. However before giving fluids, this
condition should be confirmed by TTE.
Arrhythmic Complications
The various arrhythmias associated with ventricular premature complex,
ventricular tachycardia, VF, atrial fibrillation, PSVT, sinus bradycardia, junctional
rhythm and AV block.
Embolic Complications
Embolic complications are more common in large AWMI (10%). Embolism
mostly occur in the first 2 weeks after MI and TTE is the test of choice to find out
LV mural thrombus.
Inflammatory Complications
Early
Pericarditis
Late
Early Pericarditis
Early pericarditis usually occurs 1–3 days after MI and is more common with
trans mural MI. Patients presents with pain which is worse in supine position and
relieved by bending forwards and the pain also radiates to the trapezius ridge
(pathognomonic). Triphasic rub may also be heard.
ECG findings (has to be differentiated from MI)

• ST segment elevation (generalized) with concavity upwards
• PR segment depression
• T wave inversion is seen only after ST becomes isoelectric.
This typical picture is usually not seen in MI.
Treatment
Aspirin 650 mg QID is the first-line drug for pericarditis. Nonsteroidal anti-
inflammatory drugs (NSAIDs) and corticosteroids are to be avoided in acute MI
as it interferes with myocardial healing.
Late Pericarditis (Dressler’s Syndrome)

It usually occurs 1–8 weeks after MI and is due to autoimmune reaction to necrotic
tissue. The patient presents with fever and leukocytosis and raised ESR. Steroids
and NSAIDs can be used if it occurs 4 weeks after MI.
BIBLIOGRAPHY
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for acute myocardial infarction. N Engl J Med. 2009;360:2705.
3. Dracup K, McKinley S, Riegel B, et al. A randomized clinical trial to reduce patient
prehospital delay to treatment in acute coronary syndrome. Circ Cardiovasc Qual
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4. Falk E, Nakano M, Bentzon JF, et al. Update on acute coronary syndromes: The
pathologists’ view. Eur Heart J. 2013;34:719.
5. Mehta RH, Starr AZ, Lopes RD, et al. Incidence of and outcomes associated with
ventricular tachycardia or fibrillation in patients undergoing primary percutaneous
coronary intervention. JAMA. 2009;301:1779.
6. Nabel EG, Braunwald E. A tale of coronary artery disease and myocardial infarction. N
Engl J Med. 2012;366:54.
7. Oldgren J, Wallentin L, Afzal R, et al. Effects of fondaparinux in patients with ST-
segment elevation acute myocardial infarction not receiving reperfusion treatment.
Eur Heart J. 2008;29:315.
8. O’Gara PT, Kushner FG, Ascheim DD, et al. 2013 ACCF/AHA guideline for the
management of ST-elevation myocardial infarction: A report of the American College
of Cardiology Foundation/American Heart Association Task Force on Practice
Guidelines. Circulation. 2013;127:e362.
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of Cardiology Foundation/American Heart Association Task Force on Practice
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infarction. J Am Coll Cardiol. 2012;60:1581.
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elevation acute myocardial infarction. J Thromb Haemost. 2009;7:14.
CHAPTER
40 Surendran GD
HYPERTENSIVE CRISIS
DEFINITION
Hypertensive crises are a heterogeneous group of disorders characterized by
severe hypertension and acute target organ damage. Severe hypertension is
defined as systolic BP >180 mm Hg and diastolic BP >120 mm Hg.
HYPERTENSIVE EMERGENCY
(PREVIOUSLY MALIGNANT HYPERTENSION)
Hypertensive emergency is defined as severe hypertension with evidence of
acute target organ damage, manifested by a variety of symptoms and typically
BP is > 220/130 mm Hg. Severe hypertension with chronic target organ damage
without acute manifestations does not constitute an emergency. Hypertensive
emergency needs ICU admission and immediate lowering of BP with intravenous
antihypertensive (Table 40.1).
Table 40.1 Definition of hypertensive emergency
Severe hypertension (>180/120) plus any of the following:

• Hypertensive encephalopathy
• Acute stroke, intracranial hemorrhage, cerebral infarction
• Acute congestive heart failure
• Acute coronary syndrome
• Acute renal insufficiency
• Acute aortic dissection
• Eclampsia
• Retinopathy, papilledema
• Postoperative bleeding from vascular suture lines
• Postcoronary artery bypass grafting (CABG)
Chapter 40 Hypertensive Crisis 323
HYPERTENSIVE URGENCY
Hypertensive urgency is defined as severe hypertension without acute end organ
damage. BP can be lowered over a period of days to weeks. Patients can be treated
on an outpatient basis with oral medications. BP in this scenario can be as high as
220/130 mm Hg but without target organ damage. They require follow-up within
24–72 hours.
There is no absolute BP cut-off value to differentiate HT emergency from
urgency. It is the presence or absence of acute target organ damage which
differentiates the two scenarios.
Pseudo Emergencies
These are acute rises in blood pressure due to a physiologic factor leading
to a massive sympathetic drive. For example, pain, hypoxia, hypercarbia,
hypoglycemia, anxiety, etc. Usually, it does not need medications to lower BP.
Pathophysiology
Autoregulation is the cornerstone in the pathogenesis as well as management.
The vital organs possess autoregulatory mechanisms to maintain constant blood
flow despite fluctuations in BP. This protects them from both hypoperfusion and
hyperperfusion, both of which can be detrimental.
In normotensives and patients with adequately controlled BP, the range
of autoregulation is mean arterial pressure of 60–120 mm Hg. So even a slight
increase beyond this level will lead to target organ damage. But in chronic
hypertensive patients arteriolar smooth muscle hypertrophy prevents direct
transmission of pressure to the tissues and autoregulation is shifted to higher
levels. Hence, these patients tolerate elevated BP without target organ damage.
Elevated levels of circulating catecholamine’s cause arteriolar fibrinoid
necrosis and endothelial damage which releases vasoactive amines and leads to
a vicious cycle which results in hypertensive emergency.
Precipitating Factors of Hypertensive Crisis

• Undiagnosed or poorly controlled essential hypertension
• Nonadherence to drug regimen
• Renovascular disease/renal parenchymal disease
• Actue CNS insults, e.g. stroke
• Drug-induced, e.g. sympathomimetic, nonsteroidal anti-inflammatory
drugs (NSAIDs)
• Collagen vascular diseases, e.g. scleroderma
• Pre-eclampsia
• Phenochromocytoma
• Obstructive sleep apnea.
Diagnosis
History: Symptomatology suggestive of target organ damage such as dyspnea,
chest pain, headache, confusion, altered sensorium, vomiting, oliguria,
hematuria, visual disturbances should be elicited. History of hypertension, its

precipitating factors and treatment history should be obtained
Physical examination: BP measurement should be taken at 15–20 minute intervals
from both upper and lower extremities. A thorough examination should be done
for vascular bruits especially renal bruits and all pulses should be checked.
Presence of S3 and S4, murmurs, pulmonary edema and any focal deficits should
be searched for meticulously.
INVESTIGATIONS
Blood Tests
• Complete blood count and peripheral smear
• Urea, creatinine and electrolytes: For renal failure and endocrine
abnormalities
• Urine routine analysis: Hematuria and proteinurea indicate glomerular
damage
• Cardiac enzymes: Slightly elevated in hypertensive crisis.
Evaluation of secondary causes of hypertension is usually done after the crisis
settles down except measurement of renin, aldosterone and metanephrenine
levels in clinically relevant scenarios as most antihypertensives alter these values
once therapy is started.
Electrocardiography (ECG)
Left ventricular hypertrophy (LVH) indicates chronic hypertension, ST segment
and T wave changes may indicate changes secondary to LVH or ischemia/
infarction.
Chest X-ray
May show cardiomegaly, pulmonary edema or enlarged aortic shadow suggestive
of aortic aneurysm or discussion.
CT/MRI Brain
It is done to rule out stroke in cases presenting with altered sensoruim.
Management
Hypertensive emergencies are treated in ICU and the goal is to minimize or
reverse end organ damage. While reducing the BP, one should keep in mind that
mean arterial pressure (MAP) should not be lowered more than 25% of baseline
blood pressure. However, this does not apply to all situations and an aggressive
BP lowering should be done in the following three conditions.
1. Aortic dissection
2. Acute pulmonary edema
3. Postoperative bleeding.
The various drugs used in the management of hypertensive crisis are:
Sodium Nitroprusside
It is the drug of choice in many conditions as it has a rapid onset of action, rapid
reversal and predictable homodynamic response. It decreases both afterload and
preload. It does not raise intracranial pressure (ICP) unlike nitroglycerin (NTG)
and hence can be safely given in neurologic conditions.
However, this causes cyanide and thiocyanate toxicity in patients with liver
and renal failure. Similarly, it should be avoided in acute coronary syndrome as it
can cause coronary steal phenomenon.
Labetolol
It is an α + β-blocker with β to α blocking ratio of 7:1. It has a rapid onset of action
(<5 min) and the effects also last longer (1–3 hours). Heart rate, SVR and MAP all
fall. All contraindications to β-blockers apply to labetalol also.
Nitroglycerin
It is primarily a venodilator with some degree of after load reduction as well. It
is the best drug in acute coronary syndromes due to favorable redistribution of
coronary blood flow and dilation of epicardial coronary arteries. Not situated in
raised ICP as it increases cerebral blood flow.
Other drugs
• Urapidil: New central sympatholytic which acts on central serotinogergic
pathways and also as a peripheral and adrenergic blocker.
• Fenoldopam: It is a selective peripheral dopamine-1-receptor agonist. It
is primarily an arterial vasodilator with rapid action. It is highly useful in
the intraoperative period especially for renal transplantation and in renal
insufficiency.
• Nicardipine: It is a dihydropyridine calcium-channel blockers (CCB). Useful
in postoperative setting and neurologic crisis (does not raise ICP) but
contraindicated in acute coronary syndrome. It is given as a continous IV
infusion.
• Clevidipine: It is a short acting CCB without reflex tachycardia.
• Enalaprilat: It is a short acting intravenous angiotensin-converting-enzyme
inhibiter (ACEI) that is preferred especially in scleroderma renal crisis.
• Intravenous hydralazine: Its use should be limited to pre-eclampsia and
eclampsia. It is contraindicated in active ischemia and raised intracranial
pressure (ICP).
Once BP is controlled adequately, switch over to oral again. At least two anti-
hypertensive drugs are started.
Management of Specific Hypertensive Crises

• Hypertensive crisis with encephalopathy: This can manifest into two forms.
1. Diffuse cerebral edema and encephalopathy: This manifests as altered
sensorium, irritability and rarely seizures. It reverses completely once
BP is lowered. Nitroprusside is the preferred agent in this setting.
2. Posterior reversible leukoencephalopathy syndrome: It is usually seen in

post cardiac transplant recipients on cyclosporine or tacrolimus. MRI is
required for the diagnosis and it resolves completely with BP lowering.
• Ischemic stroke: Elevated blood pressure protects the peri-ischemic areas
which are already maximally dilated from hypoperfusion. Hence, blood
pressure should not be lowered unless it is >220/120 mm Hg or when
thrombolytic therapy is considered (require BP <185/110 mm Hg) as it may
increase the extension of the infarct. Infarct, reducing BP by 15% in the first
24 hours is sufficient
• Hemorrhagic stroke: Labetolol is the preferred drug in this setting and lowering
SBP <140 mm Hg has showed better results than usual recommended goal of
180 mm Hg
• Advanced retinopathy: This is usually associated with BP >220/130 mm Hg
with evidence of multiple end-organ damage and Grade III or IV retinopathy.
The prognosis of these cases is poor and hence examining the fundus is of
utmost importance in HT crisis.
• Aortic dissection: BP should be lowered immediately in type A dissection as
it requires immediate surgery. Type B requires antihypertensives to decrease
shear force on vessel wall. Sodium nitroprusside with intravenous metoprolol
is the treatment of choice.
• Acute cardiogenic pulmonary edema (due to hypertension): Here pulmonary
edema is not due to volume over load but due to acute pressure overload
and afterload mismatch. Hence, instead of overzealous treatment with
intravenous loop diuretics (which may actually worsen the picture),
treatment to reduce afterload should be given and IV nitrates are the
treatment of choice. Once BP is lowered, pulmonary edema will be reduced.
• Myocardial ischemia: Elevated BP can induce demand supply mismatch and
also rupture coronary plaques. Intravenous nitroglycerin is the treatment of
choice.
Other Special Scenarios

Post-CABG: Nitroglycerine is the drug of choice.
Postoperative bleeding: Nitroprusside/Nicardipine/Labetolol can be used.
Pregnancy
• Magnesium prevents progression from pre-eclampsia to eclampsia.
• Labetolol is the drug of choice to lower the BP.
Pheochromocytoma: Phentolamine is the drug of choice.
Hypertensive Urgencies
These are usually seen in chronic hypertensives who are nonadherent to
treatment. They present with severe SHT but without acute target organ
damage. Here the goal is to reduce blood pressure over days without causing
hypoperfusion. Outpatient treatment with oral agents is enough.
The various drugs available for treatment are:

• Captopril: It is the fastest acting oral ACE inhibitor (acts within 15–30 min)
and can be given safely. It is started with 6.25 mg and gradually increased to
12.5 mg/25 mg TID.
• Nifedipine: Long acting can be given (30 mg daily with up titration).
• Labetdilol: It is also an effective agent (Start with 100 mg BID with up titration
according to response).
BIBLIOGRAPHY
Raven; 2009.
2. Irwin RS, Rippe JM, Irwin Rippe’s. Intensive Care Medicine, 6th edn. Lippincott:
Williams and Wilkins Publications; 2008.
3. Longo DL, Kasper DL, Jameson JL, Fauci AS, Stephen LH, Loscalzo J. Harrison’s
principles of internal medicine, 18th edn McGraw Hill Publications; 2012.
4. Paul NL. The intensive care unit manual, 2nd edn PA: Elsevier Publications; 2014.
CHAPTER
41 Surendran GD
CARDIAC TAMPONADE
DEFINITION
Accumulation of large amount of fluid in the pericardial space leading on to
compromised ventricular function, ultimately resulting in reduction of circulation
is known as pericardial tamponade.
Cardiac tamponade comprises a continuum ranging from mild (pericardial
pressure <10 mm Hg) to severe (pericardial pressure >15–20 mm Hg). This
condition is characterized by equal elevation of atrial and pericardial pressures, an
exaggerated inspiratory decrease in arterial systolic pressure (pulsus paradoxus),
and arterial hypotension.
PATHOPHYSIOLOGY
Although pericardial tamponade is usually caused by large effusions (>500 mL),
sometimes rapidly accumulating small effusion of about 100–150 mL can also
cause tamponade. The high pericardial pressure impedes the filling of the right
side of the heart; effects on the left side of the heart are largely secondary to
underfilling. Pericardial pressure and right atrial pressure are elevated above
normal and are equal to each other.
PRECIPITATING FACTORS
Drugs (cyclosporine, anticoagulants, thrombolytics), recent cardiac surgery,
indwelling instrumentation, blunt chest trauma, malignancies, connective tissue
disease, renal failure and septicemia, etc.
CLINICAL FEATURES
The most common symptom of tamponade is dyspnea, which is usually relieved
by sitting forward. Pericardial pain may be seen in some patients. Patients with
tamponade almost always appear uncomfortable, with signs reflecting varying
degrees of reduced cardiac output and shock, including tachypnea, diaphoresis,
cool extremities, cyanosis and depressed sensorium.
Chapter 41 Cardiac Tamponade 329
BECKS TRIAD (USEFUL CLUE FOR DIAGNOSIS OF TAMPONADE)

• Hypotension
• Elevated jugular venous pressure (JVP)
• Muffled heart sounds.
The other signs of tamponade are tachycardia, hypotension with reduced
pulse pressure (late stages), Kussmauls sign, pulsus paradoxus, Loss of ‘y’descent
in JVP and clear lungs
DIFFERENTIAL DIAGNOSIS
The differential diagnoses of tamponade are:
• Myocardial failure
• Right-sided heart failure due to pulmonary embolus or pulmonary
hypertension
• Right ventricular MI.
INVESTIGATIONS
Electrocardiography
The characteristic ECG changes of pericardial tamponade are reduced voltage
and electrical alternans. Reduced voltage is nonspecific as it is seen in other
conditions like emphysema, pneumothorax, etc. Electrical alternans is highly
specific but relatively insensitive for large effusions.
Chest X-ray
In moderate to large effusions, the cardiac silhouette is enlarged giving a
rounded, flask like appearance. Lateral views may reveal pericardial fat sign.
The lungs are oligemic.
M Mode/2D Echocardiogram
Early diastolic collapse of the anterior RV free wall is the most specific finding
whereas late diastolic RA collapse is the more sensitive finding. Rarely, left
ventricular collapse and left atrial collapse occur with loculated effusions after
cardiac surgery. The cardiac chambers are small in tamponade and the heart may
swing anteroposteriorly within the effusion.
Doppler Echocardiography
Tricuspid flow increases and mitral flow decreases during inspiration (reverse in
expiration). Decrease in transmitral E velocity >25% on inspiration and decrease
in tricuspid E velocity >40% on expiration is noted.
Cardiac Catheterization
It helps in confirmation of the diagnosis and quantification of the hemodynamic
compromise. RA pressure and intrapericardial pressures are elevated and are
almost identical to each other. Pulmonary capillary wedge pressure (PC-WP),
pulmonary artery (PA) diastolic pressure and RV mid diastolic pressure is also
elevated. LV systolic and aortic pressures are normal.
Cardiac catheterization also helps in detecting other cardiac abnormalties
(cardiomyopathies, coronary artery disease (CAD), etc.) and hemodynamic
abnormalties (LV faiure, pulmonary hypertension (PHT), etc.).
Coronary angiography, LV/RV angiography and CT are the other available
tests.
MANAGEMENT
Not all patients with echocardiographic signs of tamponade require pericardio
centesis. In case of low pressure tamponade (seen in hemodialysis and when
diuretics are administered to patients with effusions), peicardiocentesis is not
needed whereas hyperacute tamponade (usually resulting from cardiac trauma)
necessitates immediate pericardiocentesis. Majority of patients falls between
these two extremes and will require pericardial drainage.
Pericardiocentesis
Needle pericardiocentesis is usually done by the subxiphoid approach with
continuous monitoring. As soon as fluid is drained a J-tipped guidewire is inserted
and a drainage catheter is introduced. After rapid aspiration of about 100–150
mL to rapidly reduce symptoms, a pig-tail catheter is left in situ for continuous
drainage.
Drainage of the pericardial fluid using a catheter minimizes trauma,
allows measurement of pericardial pressure and instillation of drugs into the
pericardium, and helps prevent re-accumulation of pericardial fluid. Extended
(3 ± 2 days) catheter drainage is associated with a trend toward lower recurrence.
Drainage should continue until the volume of the aspirated volume is less than
25 mL/d.
Surgical Drainage
Open surgical drainage offers several advantages, including complete drainage,
access to pericardial tissue for histopathologic and microbiologic diagnoses,
the ability to drain loculated effusions and the absence of traumatic injury
resulting from blind placement of a needle into the pericardial sac. The collected
pericardial fluid should be sent for necessary investigations.
Recurrent Effusions
Recurrent effusions may be treated by repeat pericardiocentesis, sclerotherapy
with tetracycline, surgical creation of a pericardial window or pericardiectomy.
Chapter 41 Cardiac Tamponade 331
Pleuropericardial window is usually created in patients with malignant effusions.

Pericardiectomy may be required for recurrent effusions in dialysis patients.
BIBLIOGRAPHY
1. Chen EP, Miller JI. Modern approaches and use of surgical treatment for pericardial
disease.
2. Fejka M, Dixon SR, Safian RD, et al. Diagnosis, management, and clinical outcome of
cardiac tamponade complicating percutaneous coronary intervention. Am J Cardiol.
2002;90:1183-6.
3. Hoit BD. Pericarditis. In: Antman E (Ed). Cardiovascular Therapeutics, 2nd edn.
Philadelphia, PA: WB Saunders; 2002.pp.1113-22.
4. Sagrista-Sauleda J, Angel J, Sambola A, et al. Low-pressure cardiac tamponade: clinical
and hemodynamic profile. Circulation. 2006;114:945-52.
5. Tsang TS, Seward JB, Barnes ME, et al. Outcomes of primary and secondary treatment
of pericardial effusion in patients with malignancy. Mayo Clin Proc. 2000;75:248-53.
6. Tsang TS, Barnes ME, Gersh BJ, et al. Outcomes of clinically significant idiopathic
pericardial effusion requiring intervention. Am J Cardiol. 2003;91:704-7.
SECTION
11
RENAL AND ELECTROLYTE
DISTURBANCES IN ICU
Chapter 42 Acute Kidney Injury

Jenu Santhosh, Prem Kumar
Chapter 43 Renal Replacement Therapy

G Ninoo George
Chapter 44 Hyponatremia
TA Naufal Rizwan
Chapter 45 Potassium
Prem Kumar, Sushma Vijay Pingale
Chapter 46 Calcium
TA Naufal Rizwan
Chapter 47 Phosphorus
TA Naufal Rizwan
Chapter 48 Magnesium
TA Naufal Rizwan
CHAPTER
42 Jenu Santhosh, Prem Kumar
ACUTE KIDNEY INJURY
INTRODUCTION
Kidneys receive major cardiac output (25%). Renal cortex receives almost 90%
of the total renal blood flow. Local myogenic reflex maintains the renal blood
flow and filtration, viz. increasing perfusion pressure causes contraction of the
afferent arteriole causing reduction in filtration pressure. Low pressure dilates the
afferent arteriole and constricts the efferent arteriole thus maintaining filtration.
Acute kidney injury (AKI) occurs in 20% of patients with sepsis and 50% of those
with septic shock.
CHARACTERISTICS
Acute kidney injury (AKI) is characterized by the sudden deterioration of kidney
function resulting in the retention of nitrogenous and other waste products
usually cleared by the kidneys (Table 42.1).
CATEGORIES
Prerenal Azotemia
It is the most common type of AKI. Most common causes are hypovolemia
causing reduced renal perfusion, reduced cardiac output, nephrotoxic drugs
like NSAIDs which leads to rise in creatinine and blood urea nitrogen levels.
This condition is reversible if the cause is corrected but if it gets prolonged, it
may lead to acute tubular necrosis. Failure of renal autoregulation occurs when
the systolic blood pressure falls below 80 mm Hg or when the mean arterial
blood pressure falls below 60 mm Hg. ACE inhibitors and angiotensin receptor
blockers (ARBs) reduce efferent arteriolar vasoconstriction which is a cause of
concern in pre-existing renal disease patients, bilateral renal artery stenosis since
efferent arteriolar vasoconstriction is required to maintain GFR due to low renal
perfusion. Another risk for the development of prerenal azotemia is cirrhosis of
liver where renal perfusion is reduced inspite of volume overload—hepatorenal
syndrome.
336 Section 11 Renal and Electrolyte Disturbances in ICU
Table 42.1 Etiology of acute kidney injury
Causes
• G enetic (ACE genetic polymorphism)
• Hemodynamic changes:
– Hypotension
– Sepsis—even though it is a condition with hyperdynamic circulatory state, still there
is renal hypoperfusion because the efferent arteriole dilates more than afferent
arteriole causing loss of filtration pressure
• N onhemodynamic changes:
– Medications, contrast agents, cytokines, immunological agents
– Apoptosis/necrosis
• Type of resuscitation fluid:
– Hyperoncotic solutions (dextran, starch)
• Prerenal:

– Reduced effective circulating volume—CCF, liver failure, drug induced
(vasodilators, sepsis, anesthetic agents)
– Hypovolemia
– Reduced cardiac output
– Failure of renal autoregulation—NSAIDs, ACEI/ARB, cyclosporine
• P
ostrenal:
– Remember block in catheter always in a case with sudden drop in urine output with
no other hemodynamic changes.
– Increased intra-abdominal pressure—reduced cardiac output, reduced renal
blood flow, renal vein compression are the pathologic mechanisms behind this
type of renal injury.
• T ropical problems:
– Scrub typhus
– Falciparum malaria
– Enteric fever
– Dengue
– Mixed malaria
– Leptospirosis
– Undifferentiated acute febrile illness
– Others (spotted fever, vivax, hantavirus infection)
Abbreviations: NSAID, nonsteroidal anti inflammatory drugs; ACEI, angiotensin converting enzyme
inhibitor; ARB, angiotensin receptor blocker
Intrinsic Acute Kidney Injury

Most common causes are ischemia, sepsis, drug induced. Outer medulla is more
prone for damage during ischemia. Pathophysiology is persistent glomerular
vasoconstriction in response to ischemia, endothelial and vascular smooth
muscle damage, and tubular obstruction causing reduced GFR. Ischemia can be
a cause of AKI in postoperative patients also especially in patients who undergo
major surgeries of prolonged duration with prolonged intraoperative hypotension
and major blood loss. (e.g. Cardiothoracic surgery with cardiopulmonary bypass,
aortic cross clamping for vascular procedures, abdominal procedures). Risk
factors for postoperative AKI are diabetes mellitus, pre-existing renal disease,
heart failure, contrast agents.
Postrenal AKI
This occurs due to partial or complete obstruction either one or both the ureters
or with bladder neck obstruction due to benign prostatic hyperplasia causing
Chapter 42 Acute Kidney Injury 337
retrograde increase in hydrostatic pressure due to backflow which in turn causes

reduced glomerular filtration. Causes are obstruction of ureters by calculi, blood
clots or stricture or an obstructed Foley’s catheter can sometimes be a cause.
Effects of decreased renal function in critically ill
• Electrolyte disturbances
• Volume overload
• Acidosis
• Decreased immunity
• Increased infection
• Dysregulated inflammatory response
• Altered half-life of medications
• Immune, endocrine, cardiovascular, pulmonary, hematological, CNS,
neuromuscular dysfunction (Tables 42.2 and 42.3).
DIAGNOSIS
Current Definition of AKI

• Rise of serum creatinine by at least 0.3 mg/dL or 50% more than the baseline
within a 24–48 hours period.
• Reduction in urine output to 0.5 mL/kg/hour for longer than 6 hours.
Table 42.2 Differences between prerenal azotemia and acute kidney injury
Prerenal azotemia Acute kidney injury

BUN/creatinine ratio above 20 FeNa typically >1%
FeNa <1% Urine sediment often contains granular
Urine sodium concentration <10 mEq per L casts, renal tubular epithelial cell casts
Urine specific gravity >1.018 Urine osmolality <500 mosm/kg
Urine osmolality >500 mosm/kg
Urine sediment shows hyaline casts
Abbreviations: FeNa, fractional excretion of sodium; BUN, blood urea nitrogen
Table 42.3 RIFLE criteria for acute renal dysfunction
Category GFR Urine output

Risk Increased creatinine × 1.5 or UO < 0.5 mL/kg/hour × High sensitivity
GFR decrease >25% 6 hour
Injury Increased creatinine × 2 or UO < 0.5 mL/kg/hour ×
GFR decrease >50% 12 hour
Failure Increased creatinine × 3 or UO < 0.3 mL/kg/hour × High specificity
GFR decrease >75% 24 hour or anuria ×
12 hours
Loss Persistent ARF = complete loss of function > 4 weeks High specificity
ESRD End-stage disease
Abbreviations: RIFLE, risk, injury, failure, loss ESRD; ESRD, end stage renal disease; UO, urine output;
GFR, glomerular filtration rate
• Acute kidney damage can be differentiated from history, physical

examination, serum creatinine and radiologic studies. Serial rise of serum
creatinine is an indicator of AKI.
MARKERS FOR RENAL DYSFUNCTION IN AKI
Urine Output
It is more of a marker for renal blood flow than for solute clearance. It is not an
ideal marker for renal dysfunction since oliguria may be seen with intact tubular
function and elevated vasopressin whereas normal urine output may be seen
with injured tubules (nonoliguric renal failure) but with poor urine quality
(inadequate waste removal).
Serum Creatinine
It is an amino acid formed from skeletal muscle. It is freely filtered and not
reabsorbed or metabolized by the kidney. There are certain pitfalls in its
measurement.
• The amount of creatinine depends upon age, sex, diet, muscle mass, and
muscle disease. It takes time to accumulate. Hence, it does not detect renal
dysfunction in real time.
• 10% to 40% of creatinine is cleared by tubular secretion. Hence, it can mask
significant fall in GFR
• Drugs can alter the values (blood taken through the intravenous line where
N-acetylcysteine (NAC) is administered will show low creatinine values if
estimated by enzymatic method).
Serum Urea
Levels are altered by various factors like volume status (increased levels in volume
depletion) catabolic state, GI bleed, steroid use, metabolic acidosis (causes
muscle proteolysis) and liver disease (decreased synthesis).
Urine Abnormalities
Only situation where it is used is systemic vasculitis or glomerulonephritis where
presence of dysmorphic RBCs and casts is useful diagnostically therapeutically
and prognostically.
New Biomarkers
Plasma panel—Neutrophil gelatinase-associated lipocalcin (NGAL), cystatin C
Urine panel—NGAL, cystatin C, IL-18, KIM- 1.
Cystatin C
Presence in urine detects and quantifies renal tubular injury. Serum levels
are more sensitive to early and mild changes in kidney function than serum
creatinine.
NGAL
It is one of the earliest protein released from kidneys after renal injury and is
detectable in blood and urine. It rises within 1–3 hours of insult and peaks at 6
hours (for creatinine only 3rd day). It is been identified as a powerful predictor
of AKI.
IL-18
Urine level increases at 6 hours and peak at 12 hours after insult.
KIM-1
It is specific for nephrotoxic and ischemic renal injury. Rises only after 12–24
hours after the insult.
Prevention
• Hydration and volume expansion
– Intravenous route is preferred route to oral route in preventing AKI
– Use isotonic to hypotonic fluids (avoid hydroxy ethyl starch (HES) and
other high molecular weight preparations).
• Maintain perfusion pressure
– Target pressure is individualized. Maintain higher mean arterial pressure
(MAP) in chronic hypertensives who become hypotensive.
– Keep PaO2 >60 mm Hg and hemoglobin 8–10 gm%
– Use vasopressors only after volume repletion. This is because if vascular
volume is low, and vasopressors are used they reduce renal perfusion
in the process of maintaining MAP. The recommended MAP is 60–65
mm Hg.
– Nor adrenaline may be used. This is useful in septic shock as it constricts
efferent arteriole preferably.
– Look for intra-abdominal hypertension.
• Avoid nephrotoxic substances
– Use single daily dose of aminoglycosides if they cannot be avoided.
– Use minimal volume of nonionic, iso-osmolar contrast with adequate
isotonic fluids to prevent contrast nephropathy.
– Avoid NSAIDs, antibiotics with nephrotoxicity and ACE inhibitors.
Pharmacological
• Furosemide: They do not prevent kidney injury but may produce harm. They
may be needed in volume overloaded patients with renal failure, if there is no
adequate response they should be stopped.
• Dopamine agonists: They have been tried as renoprotective agents but there
is no evidence to prove its effectivity.
• Natriuretic peptides: ANP has been tried in AKI. Studies demonstrated that
there is no reduction in mortality rates either in low dose or high dose group.
But low dose ANP (50 ng/kg/min) reduced the need for RRT.
• Calcium channel blockers: There is no benefit with calcium channel blockers.

• Adenosine antagonists: Theophylline needs further study for usage in AKI.
• Contrast nephropathy: It is defined as rise in creatinine > 0.5 mg% or > 25%
above baseline after exposure to contrast. Contrast nephropathy leads to
a rise in serum creatinine within 24–48 hours, peak within 3–5 days, and
resolves within 5–7 days. Adequate hydration with 0.45% normal saline at
1 mL/kg/hour for 12 hours, use of N-acetylcysteine (NAC) and the choice of
contrast agent may prevent contrast nephropathy. Standard dosage of NAC-
600 mg intravenously before the procedure and 600 mg orally twice daily for
48 hours after the procedure.
• Mannitol: Its use in prevention of oliguric renal failure is not well established.
Its use may be even detrimental.
If there is no response inspite of maintaining adequate MAP, PaO2 and
hemoglobin (8–10 gm %), the patient is said to have established intrinsic
renal failure.
Treatment for Established Renal Failure

• Volume resuscitation and use of vasopressors to optimize systemic and renal
hemodynamics.
• Elimination of nephrotoxic agents
• Initiation of renal replacement therapy when indicated
• Correct electrolytes and acid base abnormalities (hyponatremia, hyper
kalemia, metabolic acidosis, hypocalcemia, hyperphosphatemia)
• Adjust drug doses
• Nutritional support—Sufficient protein and calorie intake is given to avoid
negative nitrogen balance
• Infection control
• Discontinue magnesium containing antacids to avoid hypermagnesemia.
• Rhabdomyolysis is treated with aggressive fluid resuscitation. Alkaline
solutions like sodium bicarbonate can be beneficial in preventing tubular
injury. In case of reduced urine flow, diuretics can be used after volume
repletion.
• Postrenal AKI is treated by relieving the obstruction by suprapubic
cystostomy in case of bladder neck obstruction, percutaneous nephrostomy
or ureteral stent placement in case of ureteral obstruction. After relieving the
obstruction, diuresis can persist for few days.
Indications of Dialysis in AKI

• Volume overload despite diuretic therapy
• Hyperkalemia
• Acidosis refractory to medical therapy
• Creatinine clearance or estimated glomerular filtration rate (GFR) <10 mL/
min/1.73 m2
• BUN >100 mg/dL in patients without clinical signs of recovery of kidney
function
• Bleeding diathesis
• Presence of uremic symptoms (asterixis, encephalopathy, pericardial rub or

effusion, uremic bleeding).
Complications of AKI
• Hyperkalemia
• Volume overload
• Electrolyte disturbances— hyponatremia, hypocalcemia, hyperphosphatemia
• Uremia
• Altered drug metabolism.
BIBLIOGRAPHY
1. Allgren RL, Marbury TC, Rahman SN, et al. Anaritide in acute tubular necrosis. N Engl
J Med. 1997;336:828.
2. Battle DC, Arruda JAL, Kurtzman NA. Hyperkalemic distal renal tubular acidosis
associated with obstructive uropathy. N Engl J Med. 1981;304:373.
3. Berisa F, Beaman M, Adu D, et al. Prognostic factors in acute renal failure following
aortic aneurysm surgery. QJM. 1990;76:689.
4. Carcoana OV, Hines RL. Is renal dose dopamine protective or therapeutic? Yes. Crit
Care Clin. 1996;12:677.
5. Coca SG, et al. Biomarkers for the diagnosis and risk stratification of acute kidney
injury: a systematic review. Kidney Int. 2008;73:1008.
6. Corwin HL, Sprague SM, DeLaria GA, et al. Acute renal failure associated with cardiac
operations. A case-control study: nutrition in acute renal failure. J Thorac Cardiovasc
Surg Crit Care Clin. 1987;3:155.
7. Dan LL, Dennis LK, Jameson JL, et al. Harrison’s principles of internal medicine, 18th
edn. McGraw Hill publications; 2012.
8. Heyman SN, Brezis M, Reubinoff CA, et al. Acute renal failure with selective medullary
injury in the rat. J Clin Invest. 1988;82:401.
9. Hines & Marschall. Stoelting’s Anesthesia and Co-Existing Disease, 5th edn. Elsevier
publications; 2008.
10. Hricik DE, Browning PJ, Kopelman R, et al. Captopril-induced functional renal
insufficiency in patients with bilateral renal-artery stenoses or renal-artery stenosis in
a solitary kidney. N Engl J Med. 1983;308:373.
11. Irwin RS, Rippe JM. Irwin and Rippe’s Intensive Care Medicine. 6th edn. Lippincott
Williams & Wilkins publications; 2008.
12. Rahman SN, Kim GE, Mathew AS, et al. Effects of atrial natriuretic peptide in clinical
acute renal failure. Kidney Int. 1994;45:1731.
13. Ronco C. Continuous renal replacement therapies for the treatment of acute renal
failure in intensive care patients. Clin Nephrol. 1993;40:187.
14. Rose BD. Acute renal failure. In: Rose BD (ed): Pathophysiology of Renal Disease. New
York: McGraw-Hill; 1981.p.55.
CHAPTER
43 G Ninoo George
RENAL REPLACEMENT THERAPY
INTRODUCTION
Acute kidney injury (AKI) is extremely common in critically ill patients. The
incidence of AKI in critically ill patients is increasing due to various factors
like increasing patient age, multiple comorbidities, use of nephrotoxic agents,
invasive vascular procedures using iodinated contrast agents, etc. Not only is the
incidence increasing, so also is the severity of AKI, often necessitating the need
for renal replacement therapy.
Kidney is one of the few vital organs whose physiological function can be
replaced using extracorporeal treatment. Renal replacement therapy (RRT) refers
to any modality that can replace the function of the kidney using artificial means.
To qualify as renal replacement, the treatment should be able to control fluid
balance, electrolyte balance and acid-base balance. To this date, we have three
forms of RRT, viz. hemodialysis, peritoneal dialysis and renal transplantation.
Different modalities of renal replacement therapy is given in Table 43.1 and
terminologies used in AKI is given in Table 43.2. Of these, renal transplantation
Table 43.1 Different modalities of renal replacement therapy
Modalities of renal replacement therapy in current clinical practice:

• Intermittent
– Intermittent hemodialysis (IHD)
– Sustained low efficiency dialysis (SLED); extended daily dialysis (EDD)
• Continuous
– Peritoneal dialysis (PD)
– Continuous renal replacement therapy (CRRT)
– slow continuous ultrafiltration (SCUF)
– CAVH/CVVH
– CAVHD/CVVHD
– CAVHDF/CVVHDF
Abbreviations: CAVH, continuous arteriovenous hemofiltration; CVVH, continuous venovenous
hemofiltration; CAVHD, continuous arteriovenous hemodiafiltration; CVVHD, continuous venovenous
hemodiafiltration; CAVHDF, continuous arteriovenous hemodiafiltration; CVVHDF, continuous
venovenous hemodiafiltration
Chapter 43 Renal Replacement Therapy 343
Table 43.2 Terminologies used in AKI
• C: Continuous
• I: Intermittent
• AV: Arteriovenous (here the driving force for blood to move around the circuit is heart)
• VV: Venovenous (here the driving force is external pump)
• HF: Hemofiltration (fluid removal)
• HD: Hemodialysis (solute removal)
• HDF: Hemodiafiltration (fluid and solute removal)
• Detoxification: Hemoperfusion/hemodialysis
• SCUF: Slow continuous ultrafiltration
• SCD: Slow continuous dialysis
• SLED: Slow low efficiency dialysis.
is practiced only in chronic kidney disease and therefore will not be discussed
further.
Indications of Renal Replacement Therapy

The classical indications of RRT in the ICU are:
• Refractory fluid overload
• Refractory hyperkalemia
• Uremic complications.
Apart from these classical indications, there are several other situations
where renal replacement therapy can be beneficial. These include different types
of poisonings (methanol, lithium, etc.), removal of cytokines by hemofiltration in
sepsis, refractory hypercalcemia, refractory congestive cardiac failure, etc.
ACCESS
Safe and secure access to the patient’s blood is of paramount importance in
hemodialysis. For this, several types of dialysis catheters are available. The
catheters currently used in practice have two lumens of the venovenous type.
Arterial access is not required in acute hemodialysis since most machines have a
blood pump that can suck blood out of the venous system.
The most common site of insertion of the dialysis catheter is the right internal
jugular vein. The next preferred site is left internal jugular vein, followed by the
femoral vein. The use of subclavian vein for dialysis access should be avoided as
much as possible for the risk of creating central vein stenosis, which precludes
future creation of AV fistula on that side of the upper limb, if need arises in future.
The use of femoral vein carries the highest risk of infection among the various
dialysis access sites and hence the dialysis catheter should not be kept for more
than 1 week in the femoral site. On the other hand, the internal jugular dialysis
catheter can be kept for a maximum of 4 weeks without high risk of infection.
Notwithstanding this, any unnecessary prolongation of dialysis catheter carries
risk of infection, sepsis and thrombosis.
In peritoneal dialysis (PD), various acute and chronic type PD catheters are
available. The PD catheters are inserted in the infraumbilical position directed to
one of the iliac fossae.
HEMODIALYSIS VERSUS PERITONEAL DIALYSIS

Acute PD is not commonly practised nowadays in most countries due to risk of
peritonitis and lack of efficacy compared to HD. However in resource-constrained
settings where HD facility is lacking, acute PD can be life-saving. On the other
hand, chronic PD using Tenckhoff silicone catheters are as effective as chronic
HD and are commonly practised worldwide. However, chronic PD is not suitable
for acute usage in the ICU. Thus, in the ICU, the preferred modality is HD rather
than PD. If at all, acute PD is practised, it has to be carried out in strict aseptic
precautions and the catheter should not be kept in situ for more than 5 days due
to increased risk of infection.
INTERMITTENT HEMODIALYSIS VERSUS SLOW LOW EFFICIENCY

DIALYSIS
In patients who are hemodynamically unstable, conventional intermittent HD
can cause further hemodynamic instability. Therefore, in patients who are on
inotropic support, sustained low-efficiency dialysis called SLED is preferred. In
this modality, the blood pump speed is reduced to around 100 mL/minute and
dialysate flow is reduced to around 300 mL/minute and carried out for extended
periods of time ranging from 6 to 12 hours.
SLOW LOW EFFICIENCY DIALYSIS VERSUS CONTINUOUS RENAL

REPLACEMENT THERAPY
In hemodynamically unstable patients, another modality of dialysis called
continuous renal replacement therapy (CRRT) is gaining popularity, especially
in affluent countries like US, Australia and Europe. CRRT is of various types like
CAVHD, CAVHF, CAVHDF, CVVHD, CVVHF and CVVHDF. Of these, CVVHD,
CVVHF and CVVHDF are commonly practised. CRRT is carried out almost 18–24
hours daily using commercially available dialysate and replacement solutions.
CRRT carries several advantages over SLED like better hemodynamic stability,
lack of sudden fluctuations in fluid balance, better nutritional support, lack of fluid
restrictions and better recovery of AKI. However, there is no mortality advantage
over SLED and it is quite expensive. Thus in resource constrained settings, SLED
is commonly used, whereas in affordable patients with hemodynamic instability,
CRRT is preferred.
ADVERSE EFFECTS OF RENAL REPLACEMENT THERAPY

The RRT is an invasive therapeutic modality and therefore can produce various
complications. Some of the most commonly encountered complications are
given in Table 43.3.
Chapter 43 Renal Replacement Therapy 345
Table 43.3 Complications of RRT
Access-related Dialysis-related
Catheter-induced sepsis Intradialytic hypotension
Catheter-induced thrombosis Sudden changes in electrolyte balance
Catheter displacement Risks of anticoagulation, etc.
Poor catheter flow (fibrin sheath)
CONCLUSION
Renal replacement therapy is a life-saving therapeutic modality in critically ill
patients. CRRT and SLED are suitable modalities in hemodynamically unstable
patients, whereas intermittent HD is preferred in other patients. In resource-
constrained settings where HD facilities do not exist, PD can be life-saving.
BIBLIOGRAPHY
1. Abraham G, Varughese S, Mathew M, Vijayan M. A review of acute and chronic
peritoneal dialysis in developing countries. Clin Kidney J. 2015;8(3):310-7.
2. Ansari N. Peritoneal dialysis in renal replacement therapy for patients with acute
kidney injury. Int J Nephrol. 2011.pp.739-94.
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Nephrol. 2006;17(11):3132-8.
4. Ghahramani N, Shadrou S, Hollenbeak C. A systematic review of continuous renal
replacement therapy and intermittent haemodialysis in management of patients with
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5. Kellum JA. Renal replacement therapy in critically ill patients with acute renal
failure: does a greater dose improve survival? Nature Clinical Practice Nephrology.
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7. Mehta RL. Continuous renal replacement therapy in the critically ill patient. Kidney
International. 2005;67:781-95.
8. Ostermann M, Dickie H, Barrett NA. Renal replacement therapy in critically ill patients
with acute kidney injury—when to start. Nephrol Dial Transplant. 2012;27(6):2242-8.
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patients. Nephrol Dial Transplant. 2001;16(Suppl 5):67-72.
CHAPTER
44 TA Naufal Rizwan
HYPONATREMIA
Hyponatremia is a condition where the serum sodium is less than 135 mEq/L.
It usually results from retention of water secondary to impairment in free water
excretion. When the serum sodium falls slowly over a period of days or weeks, our
body compensates by extruding solutes into the extracellular space. However, in
case of rapid fall in sodium, compensatory mechanisms do not occur resulting in
various complications.
CAUSES
Most cases of hyponatremia are associated with low osmolality. However, in some
patients the osmolality may not be low, indicating the presence of significant
concentration of other osmotically active solutes in the plasma. Etiology of
hyponatremia based on urine sodium level is given in Table 44.1.
Table 44.1 Etiology of hyponatremia based on urine sodium level
Urine sodium level Etiology

>20 mEq/L • Renal causes of hypovolemic hyponatremia
• SIADH, renal failure, postoperative states, hypothyroidism, pain
<10 mEq/L • GI and skin causes of hypovolemic hyponatremia
• Hypervolemic causes like CCF, cirrhosis, nephrotic syndrome
(except CRF)
Abbreviations: SIADH, syndrome of inappropriae antidiuretic hormone; GI, gastrointestinal; CCF,
congestive cardiac failure; CRF, chronic renal failure
Chapter 44 Hyponatremia 347
PSEUDOHYPONATREMIA
• Increased plasma osmolality (>290 mOsm/kg)
– Hyperglycemia, mannitol, glycerol
• Normal plasma osmolality (275–290 mOsm/kg)
– Hyperlipidemia, hyperproteinemia, post-TURP.
TRUE HYPONATREMIA (< 275 mOsm/KG)

• Hypovolemic
– Renal loss (diuretics, salt wasting nephropathy, hypoaldosteronism)
– GI loss (vomiting, diarrhea, tube drainage, fistula)
– Skin loss (sweating, burns, cystic fibrosis)
• Euvolemic
– Syndrome of inappropriate antidiuretic hormone (SIADH), postopera-
tive states (TURP), pain (due to AVP release)
– Hypothyroidism, glucocorticoid deficiency, primary polydipsia
• Hypervolemic
– Congestive cardiac failure (CCF), nephrotic syndrome, cirrhosis liver,
chronic renal failure.
Clinical Features
The symptoms of hyponatremia not only correlates with the serum sodium
concentration, but also with the rapidity of onset. Hence, acute hyponatremia is
more dangerous than the chronic one. The clinical features are predominantly
neurologic and these include nausea, vomiting, confusion, difficulty in
concentration, lethargy, agitation, headache, etc. Seizures, stupor and coma usually
occur only when plasma sodium is <120 mEq/L or when it decreases rapidly.
In addition to the neurologic findings, patient may also have muscle
weakness, muscle cramps, rhabdomyolysis, signs of hypovolemia (dry mucous
membrane, tachycardia) or hypervolemia (pedal edema, ascites, etc.).
Investigations
• Serum sodium
• Serum osmolality
• Urine sodium level
• Urine osmolality
– In most cases of hyponatremia, urine osmolality is >200 mOsm/kg
– One important exception is primary polydipsia where it is <100 mOsm/kg.
Treatment
Treatment of hyponatremia depends on:
• Symptoms
• Volume status of the patient
• Acute or chronic.
Cardinal Rules of Correction of Hyponatremia

• In asymptomatic hyponatremia, the serum sodium should not be raised by
more than 0.5–1 mEq/L/hour and in the first 24 hours, the rise should not be
more than 12 mEq/L
• In acute or severe symptomatic hyponatremia, it can be increased by
1–2 meq/L/hour for first 4 hours but again not more than 12 mEq/L in the
first 24 hours.
ASYMPTOMATIC HYPONATREMIA
The objective should be to find out the underlying cause and correction of the
same.
• Hypovolemic hyponatremia
– Normal saline should be infused.
• Hypervolemic hyponatremia
– Salt and water restriction + Loop diuretics
– Water restriction should be less than the urine output
– Vasopressin antagonists (conivaptan, tolvaptan) can also be tried.
• Euvolemic hyponatremia
– Water restriction + treatment of the underlying cause
– Vasopressin antagonists (conivaptan, tolvaptan) can also be tried.
SYMPTOMATIC HYPONATREMIA
In case of symptomatic hyponatremia, rapid correction (but not more than
12 mEq/L in the first 24 hours) using hypertonic saline (3% or 5%) can be done.
Steps in Correcting Hyponatremia

Step 1: Expected Change in Sodium
Infusate sodium concentration–serum sodium
concentration
Expected change in Na =
Total body water + 1
Total body water is 0.6 × body weight (men) and 0.5 × body weight (women)
For example, in a 50 kg man with a serum sodium of 120 mmol/L, and if
corrected with 3% Nacl,
513–120
The expected change in sodium = = 12.68
30 + 1
This means 1 liter of 3% Nacl will produce 12.68 mmol/L change in serum
sodium level.
Step 2 : Liters Infusate and Hours to Correct (Table 44.2)

Liters infusate = Target sodium–Serum sodium
Expected change in sodium per liter infusate
135–120
In the previous example, the liters infusate = = 1.18
12.68
Table 44.2 Sodium level in various infusate
Infusate Sodium level (mmol/L)

5% NaCl 855
3% NaCl 513
0.9% NaCl 154
Ringer lactate 130
0.45% NaCl 77
Hours to correct = (Target sodium–serum sodium) × 0.5

i.e. (135–120) × 0.5 = 30 hours.
Step 3: Rate of Infusion

Liters infusate
Rate of infusion (mL/hr) = × 1000
Hours to correct
1.18 × 1000
i.e. = 39.4 mL/hour
30
So, the final answer is, 3% Nacl should be given at a rate of 39.4 mL/hour for a
period of 30 hours for correcting the hyponatremia in this patient.
OSMOTIC DEMYELINATION SYNDROME

This syndrome is seen as a result of rapid correction of hyponatremia. It occurs
due to sudden osmotic shrinkage of brain cells and is more commonly seen in
correction of chronic hyponatremia since their brain volume has returned to
near normal as a result of osmotic adaptive mechanisms. It is characterized by
dysphasia, spastic quadriparesis, pseudobulbar palsy, mutism, delirium, coma,
etc. The risk of osmotic demyelination syndrome (ODS) is high in alcoholics,
malnutrition and hypokalemia. There is no specific treatment for this condition.
HYPERNATREMIA
It is a condition where the serum sodium is greater than 145 mEq/L. More
commonly, it is the result of combined water and electrolyte deficit, with losses
of water in excess of sodium. Persons with diminished thirst (elderly) and
diminished access to fluids are at the highest risk of developing hypernatremia.
Causes
The causes of hypernatremia are classified as follows.
Hypovolemic
• Renal losses
– Osmotic diuresis secondary to hyperglycemia, urea, mannitol
– Postobstructive diuresis
• Gastrointestinal losses
– Diarrhea
• Skin losses
– Fever, exercise, severe burns, heat exposure.
Euvolemic
It occurs due to diabetes insipidus (DI) and the three types of DI are:
1. Central
• Tumor, hydrocephalus, ACA occlusion, trauma, inflammation
2. Nephrogenic
• Genetic—mutations in aquaporins channels
• Acquired—Hypokalemia, hypercalcemia, lithium, ifosfamide, antivirals
3. Gestational
• Due to reduced circulating AVP.
Hypervolemic
• Administration of hypertonic saline, sodium bicarbonate
• Primary hyperaldosteronism.
Clinical Features
The symptoms are seen predominantly in acute hypernatremia. Most of the
symptoms are neurologic and these include confusion, lethargy, altered mental
status, stupor and deep coma. They occur as a result of sudden shrinkage of
brain cells. Patients with acute hypernatremia are also at risk of developing
various vascular complications like parenchymal hemorrhage, Subarachnoid
hemorrhage and subdural hematomas. Rhabdomyolysis is another complication
which occurs due to osmotic damage of the muscle membranes.
Investigations
• Serum sodium
• Serum osmolality
• Urine osmolality
– If >800 mOsm/kg and low urine volume—GI loss and insensible water
loss
– If >800 mOsm/day and adequate urine volume—diuretics, osmotic
diuresis
• Serum AVP and the response to DDAVP—to differentiate central from
nephrogenic DI
• Urine electrolytes and urine volume.
Treatment
The therapeutic goals are to:
• Stop the ongoing water loss
• Correct the water deficit.
Step 1: Calculate the Water Deficit

Plasma Na+ concentration–140
Water deficit = × Total body water
140
In hypernatremia, the total body water is 50% of weight in men and 40% in
women.
For example, in a 60 kg man with a plasma sodium of 160 mmol/L,
160–140
Water deficit = × 30 = 4.28 liters.
140
Step 2: Correction of Water Deficit

Half of the water deficit can be corrected in the first 24 hours (in case of acute
hypernatremia) and the remaining half over the next 24–48 hours. The rate of
sodium fall should not be more than 0.5 mmol/L/hour and definitely should not
be more than 12 mmol/L in the first 24 hours. Rapid correction of hypernatremia
can result in swelling of the brain cells leading to seizures and permanent
neurologic damage.
The safest route of administration of water is by mouth or via a nasogastric
tube. Alternatively, 5% D or ½ NS can also be given intravenously.
MANAGEMENT OF DIABETES INSIPIDUS
Central Diabetes Insipidus (DI)

• Desmopressin—intranasal or 4 µg/day IV or SC in divided doses
• Low salt diet + low dose thiazides diuretics.
Partial Central DI
• Chlorpropamide, clofibrate, carbamazepine
These drugs stimulate AVP secretion or its action on kidney.
• NSAIDs—they impair prostaglandin synthesis and potentiate AVP action.
Nephrogenic DI
• Treatment of underlying disorder and removal of offending drug
• Low salt diet + low dose thiazides diuretics
• NSAIDs and amiloride.
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CHAPTER
45 Prem Kumar, Sushma Vijay Pingale
POTASSIUM
The human body, in normal condition, contains total body potassium of

approximately 50 mEq/kg. Majority of the potassium is intracellular and only
2% of the total potassium stores are found extracellularly. This extracellular
potassium reflects the balance between potassium intake and excretion.
POTASSIUM BALANCE IN HEALTH AND DISEASE

Average daily dietary [K+] intake in adults is 80 mEq/day out of which 70 mEq is
excreted in urine and remaining 10 mEq through the stools. The cell membrane
Na+ K+ ATPase regulates the extracellular K+ concentration. Na+ K+ ATPase pump
actively transports sodium out of, and potassium into, most cells. The activity of
this pump is enhanced by insulin and catecholamines, thereby causing a decrease
in plasma potassium levels.
In acidosis, extracellular H+ ions enter cells and this movement results in the
intracellular K+ ions moving out to maintain the electrical balance. This causes an
increase in plasma potassium levels. The reverse effect is seen in alkalosis where
the extracellular K+ ions move into the cells to balance the movement of H+ ions
out of cells. This results in decrease in plasma potassium levels. The plasma K+
concentration changes approximately 0.6 mEq/L per 0.1 U in arterial pH (range
0.2–1.2 mEq/L).
The normal serum potassium levels are 3.5–5.5 mEq/L.
HYPOKALEMIA
Hypokalemia is defined as a serum potassium concentration less than 3.5 mEq/L.
The relationship between changes in total body potassium and changes in serum
potassium is curvilinear and hence plasma potassium concentration correlates
poorly with the total potassium deficit. A decrease in plasma [K+] from 4 mEq/L
to 3 mEq/L usually represents a 100–200 mEq deficit, whereas plasma [K+] below
3 mEq/L can represent a deficit anywhere between 200 mEq and 400 mEq.
Causes
Hypokalemia can arise due to excessive loss through renal, gastrointestinal route
or due to transcellular shifts and rarely due to inadequate intake (Table 45.1).
Table 45.1 Causes of hypokalemia
Transcellular shift
• Metabolic alkalosis
• Hypokalemic periodic paralysis
• Insulin administration
• Head injury
• β-2 agonists
• Hypothermia
Decreased intake
Gastrointestinal loss
• Severe diarrhea
• Nasogastric suctioning
• Intestinal fistulas
Renal loss
• Diuretic administration
• Osmotic diuresis
• Salt wasting nephropathies
• Renal tubular acidosis
Renal Loss
The most common cause for excessive renal loss of potassium is either diuretic
therapy or increased mineralocorticoid activity. The other causes are renal
tubular acidosis, ketoacidosis, hypomagnesemia, salt wasting nephropathies
and drugs. The urinary Cl- concentration is high (>25 mEq/L) in renal cause
of hypokalemia and low (<15 mEq/L) in extrarenal cause (nasogastric suction,
alkalosis) of hypokalemia.
Gastrointestinal Loss
The main gastrointestinal (GI) causes of loss of potassium are diarrhea and
nasogastric suction. The normal stool volume is approximately 200 mL and
contains 75 mEq/L of K+. But in diarrhea, the daily volume of stool can rise up
to 10 liters. Thus, significant amount of potassium is lost in severe diarrhea
and hence can result in hypokalemia if not replenished adequately. The other
GI causes are fistulae, laxative abuse, villous adenomas and pancreatic tumors
secreting vasoactive intestinal peptide.
Transcellular Shifts
The movement of potassium from extracellular compartment to intracellular
compartment is seen in alkalosis, hypokalemic periodic paralysis, beta-2 agonists
and insulin therapy and in hypothermia.
Clinical Features
Mild hypokalemia (K+ 2.5–3.5 mEq/L) is often asymptomatic and may manifest
only in the form of ECG changes like flattening and inversion of T wave, ST
depression, prominent U waves (>1 mm in height) and prolongation of the
Chapter 45 Potassium 355
QT interval. Cardiac toxicity may be manifested by serious arrhythmias due

to hyperpolarization of the myocardial cell membrane, leading to a prolonged
refractory period and increased susceptibility to reentrant arrhythmias. Severe
hypokalemia (K+ <2.5 mEq/L) results in skeletal muscle weakness especially
the quadriceps, muscle cramps, tetany and ileus. Polyuria due to stimulation of
thirst and resistance to the action of ADH are the primary renal manifestations of
hypokalemia. Severe hypokalemia can also result in rhabdomyolysis.
Management
The first step in management of hypokalemia is to treat any condition that
promotes transcellular potassium shifts (e.g. alkalosis, hypothermia etc.).
If the cause of hypokalemia is potassium depletion then potassium replacement
should be done. Oral or intravenous potassium chloride generally is the preferred
treatment for hypokalemia.
Oral route for replacement is generally safest (60–80 mEq/d) and preferred
in mild hypokalemia. Oral potassium chloride can be given in crystalline form
(salt substitutes), as liquid, or in a slow-release tablet or capsule. Salt substitutes
contain 50 to 65 mEq per teaspoon. They are safe, cheap and better tolerated
than the other preparations. The liquid preparations of potassium chloride are
often unpalatable, and the slow-release preparations can, in rare cases, cause
ulcerative or stenotic lesions in the gastrointestinal tract as a result of the local
accumulation of high concentrations of potassium.
Severe hypokalemia should be managed by intravenous replacement with
potassium chloride, which is available as a concentrated solution in ampoules
containing 10, 20, 30, and 40 mEq of potassium. These solutions are extremely
hyperosmotic (2 mEq/L solution has an osmolality of 4000 mOsm/L H2O) and
hence must be diluted. The maximum rate of intravenous potassium replacement
should not exceed 20 mEq/hour. The infusion should be given through a central
vein because of the irritating properties of the hyperosmotic potassium solutions.
Life-threatening arrhythmias where serum K+ is <1.5 mEq/L may necessitate
an infusion rate of up to 40 mEq/l. In such cases infusion through a central
line can pose a theoretical risk of transient hyperkalemia in the right heart
chambers, which can predispose to a sudden cardiac standstill and hence must
be avoided. Femoral line or 2 large bore peripheral venous lines are preferred in
such circumstances. Intravenous replacement should generally not exceed 240
mEq/d. ECG monitoring should be done in patients with significant ECG changes
and monitoring of muscle strength in patients with muscle weakness during the
replacement therapy. Replacement of the potassium deficit usually requires
several days. When hypokalemia is refractory to replacement with potassium
chloride, then magnesium levels should be assessed and a magnesium deficiency
if observed should be corrected.
HYPERKALEMIA
Hyperkalemia is defined as serum potassium level >5.5 mEq/L. It is a common
electrolyte abnormality in intensive care unit (ICU) patients (e.g. renal failure).
The most common cause of hyperkalemia is reduced renal excretion of K+. Other
causes are given in Table 45.2.
Table 45.2 Causes of hyperkalemia
• Transcellular shift: Metabolic acidosis, burns, prolonged immobilization, tumor lysis,

neuromuscular disease, arginine, hyperosmolality
• Acute or chronic renal failure
• Adrenal insufficiency: Addison’s disease, infections (tuberculosis, human
immunodeficiency virus (HIV), heparin, congenital adrenal hyperplasia
• Hyporeninemic hypoaldosteronism: Diabetes, tubulointerstitial disease
• Hyperkalemic periodic paralysis
• Drug-induced: Succinylcholine, digoxin, nonsteroidal anti-inflammatory drugs (NSAIDs),
β-blockers, cyclosporine, angiotensin-converting-enzyme (ACE) inhibitors, angiotensin
receptor blocke (ARB), rennin inhibitor, spironolactone, amiloride.
• Congestive heart failure
• Hypovolemia
• Pseudohyperkalemia
Pseudohyperkalemia
It is increase in serum K+ due to the release of K+ during or after venipuncture,
thrombocytosis, erythrocytosis, leukocytosis. There is elevation in measured
plasma potassium concentration due to potassium movement out of the cells
during or after the blood specimen has been drawn.
Metabolic Acidosis
Buffering of excess hydrogen ions in the cells causes transcellular shift of
potassium to extracellular fluid to maintain electroneutrality.
Renal Disease
Hyperkalemia occurs due to impaired intake of K+ into cells, reduced Na+/K+
ATPase activity, high potassium intake, hypoaldosteronism.
Critical Illness
Hypoaldosteronism due to reduced adrenal production occurs in critically ill
patients.
Clinical Features
Resting membrane potential depends on potassium. Hyperkalemia causes partial
depolarization of the cell membrane, decrease in the membrane excitability and
affects the repolarization phase of cardiac action potential resulting in impaired
cardiac conduction, weakness of the muscles, hence hyperkalemia causes cardiac
conduction disturbances. Cardiac arrhythmias associated with hyperkalemia are
peaked T waves (earliest sign), widening of PR interval and QRS complexes, loss of
p wave, sine wave pattern, ventricular tachycardia, ventricular fibrillation, heart
block, asystole. Electrocardiogram (ECG) findings associated with hyperkalemia
is based on serum potassium level—tall peaked T waves (5.5–6.5 mEq/L), loss of
Chapter 45 Potassium 357
P waves (6.5–7.5 mEq/L), widened QRS complex (7–8 mEq/L), and ultimately to
a sine wave pattern (8 mEq/L). Neuromuscular manifestations are paresthesias,
weakness and paralysis of respiratory muscles. Hyperkalemia causes reduction
in the excretion of acid load which causes metabolic acidosis (retention of NH4+ ).
Diagnosis
History, physical examination should be focus on diet, medications, blood
pressure, history of renal failure, volume status. Laboratory investigations
include serum sodium, potassium, magnesium, calcium, urea, creatinine, serum
osmolality, complete blood count, and urinary pH.
Table 45.3 Treatment of hyperkalemia
Management Comment
10 mL of 10% calcium gluconate (3–4 mL Calcium raises the action potential
of calcium chloride) intravenously over 2 to threshold and reduces excitability without
3 minutes Onset starts in 1–3 minutes and change in the resting membrane potential
lasts for 30–60 minutes Can be repeated (RMP). Calcium reverses the depolarization
blockade caused by hyperkalemia by
restoring the difference between the resting
and threshold potentials
10 units of IV regular insulin along with 50 Rapid transcellular shift of K+ into cells.
mL of 50% dextrose. Onset starts in 10–20 Administering glucose for hyperkalemia
min, peaks at 30–60 minutes, and lasts 4 has the risk of worsening hyperkalemia due
to 6 hours. This is followed by infusion of to the osmotic effect of hypertonic glucose
10% dextrose at 50 to 75 mL/hour to avoid
hypoglykemia. Hyperkalemia with glucose
concentrations >200–250 mg/dL, insulin
should be administered without glucose
Inhaled β2-agonists—inhaled albuterol of It should be used along with insulin. Renal
10–20 mg inhaled over 10 minutes, onset failure patients are resistant to the effects of
starts in 30 minutes, peaks at about 90 β2-agonists. Hyperglycemia, tachycardia
minutes, and lasts for 2–6 hours are adverse effects
Soda bicarbonate (40–80 mEq) As such it has no therapeutic effect
for hyperkalemia. Can be used for
hyperkalemia along with severe metabolic
acidosis
Potassium excretion—loop and thiazide Can be given in hypervolemic patients with
diuretics preserved renal function
Potassium removal—dialysis Most effective method to reduce potassium
Potassium binders—sodium polystyrene Sodium polystyrene sulfonate (Kayexalate)
sulfonate. Dose is 15–30 g in 50 mL of 33% is a cation exchange resin that enhances
sorbitol to avoid constipation K+ excretion in gastrointestinal tract
and increases the fecal excretion of
K+. Full effect can take up to 24 hours.
Complication of kayexalate is intestinal
necrosis
Management (Table 45.3)

The first initial step in managing hyperkalemia is whether the patient needs
emergency treatment or not. Once the patient develops cardiac manifestations
due to hyperkalemia or when serum K+ is >6.5 mEq/L, it is a medical emergency
and requires immediate treatment. Management requires ICU admission,
continuous cardiac monitoring.
BIBLIOGRAPHY
1. Adrogue H, Madias N. Changes in plasma potassium concentration during acute
acid-base disturbances. Am J Med. 1981;71:456.
2. Allon M, Copkney C. Albuterol and insulin for treatment of hyperkalemia in
hemodialysis patients. Kidney Int. 1990;38:869.
3. Allon M. Hyperkalemia in end-stage renal disease: mechanisms and management. J
Am Soc Nephrol. 1995;6:1134.
4. Charytan D, Goldfarb DS. Indications for hospitalization of patients with hyperkalemia.
Arch Intern Med. 2000;160:1605.
5. Don B, Schambelan M. Hyperkalemia in acute glomerulonephritis due to transient
hyporeninemic hypoaldosteronism. Kidney Int. 1990;38:1159.
6. Don BR, Sebastian A, Cheitlin M, et al. Pseudohyperkalemia caused by fist clenching
during phlebotomy. N Engl J Med. 1990;322:1290-2.
7. Emmett M, Hootkins RE, Fine KD, et al. Effect of three laxatives and a cation exchange
resin on fecal sodium and potassium excretion. Gastroenterology. 1995;108:752.
8. Evans KJ, Greenberg A. Hyperkalemia: A review. J Intensive Care Med. 2005;20:272-
90.
9. Kunin A, Surawicz B, Sims E. Decrease in serum potassium concentration and
appearance of cardiac arrhythmias during infusion of potassium with glucose in
potassium-depleted patients. N Engl J Med. 1962;266:228.
10. Longo DL, Kasper DL, Jameson JL. et al. Harrison’s principles of internal medicine.
18th edn. McGraw Hill publications. 2012.
11. Oster JR, Singer I, Fishman LM. Heparin-induced aldosterone suppression and
hyperkalemia. Am J Med. 1995;98:575.
12. Sterns RH, et al. Ion-exchange resins for the treatment of hyperkalemia: Are they safe
and effective? J Am Soc Nephrol. 2010;21:733.
13. Whang R, Whang D, Ryan M. Refractory potassium depletion. A consequence of
magnesium deficiency. Arch Intern Med. 1992;152:40.
CHAPTER
46 TA Naufal Rizwan
CALCIUM
CALCIUM METABOLISM
The adult human body contains approximately 1100 g of calcium, of which
approximately 99% is located in the bones. The normal serum calcium level is
8.9–10.1 mg/dL, of which 50% is free ionized calcium, 40% is bound to proteins
and remaining 10% is combined with various anions. The extracellular calcium
level is maintained in a narrow range by various feedback mechanisms that
operate between the parathyroid glands, kidney, intestine and bone.
Functions of Calcium
• Excitation contraction coupling in all muscles
• Neurotransmitter release at nerve terminals
• Coagulation cascade
• Complement cascade
• Cofactor for numerous enzymes
• Bone and teeth formation
• Salivary and aldosterone secretion.
HYPOCALCEMIA
Hypocalcemia is said to be present if:
Total corrected calcium is <2.1 mmol/L (<8.4 mg/dL)

and/or
Ionized Calcium is <1.2–1.3 mmol/L (4.8–5.2 mg/dL)
(Conversion: 1 mmol/L = 4 mg/dL)
Corrected calcium (mg/dL): Measured total calcium (mg/dL) + 0.8 (4.4–serum
albumin{g/dL})
Hypocalcemia is an electrolyte abnormality commonly seen in intensive care

unit (ICU) patients. Hypoalbuminemia is one of the most common cause of
hypocalcemia in ICU. Other common cause is renal failure.
Causes (Table 46.1)

Table 46.1 Causes of hypocalcemia based on the parathyroid hormone levels
• Low parathyroid hormone levels

– Parathyroid agenesis: Isolated/Digeorge syndrome (patient also has cleft lip/palate,
congenital heart diseases)
– Parathyroid destruction: Surgical/radiation/infiltrative diseases/autoimmune diseases
– Parathyroid dysfunction: Hypomagnesemia
• High parathyroid hormone levels
– Vitamin D deficiency or impaired 1,25(OH)2 production/action: Nutritional/Renal
insufficiency/vit D resistance
– Parathyroid hormone resistance syndromes: Pseudohypoparathyroidism/PTH
receptor mutations
– Drugs: Calcium chelators/bisphosphonates/phenytoin/ketoconazole
– Miscellaneous causes: Acute pancreatitis/acute rhabdomyolysis/osteoblastic
metastases
Clinical Features
The clinical features of hypocalcemia vary from being asymptomatic (in mild and
chronic) to life-threatening complications (in severe). The clinical features are
predominantly neuromuscular and cardiopulmonary.
Cardiopulmonary Manifestations
The cardiopulmonary manifestations of hypocalcemia are wheezing, stridor
due to laryngeal spasm, bradycardia, dysphagia, arrhythmias, etc. Negative
chronotropy and reduced myocardial contractility may lead to hypotension,
angina and heart failure.
Neuromuscular Manifestations
Focal numbness and paresthesias of the fingers, toes and perioral regions are the
usual symptoms in moderate to severe hypocalcemia. Seizures and carpopedal
spasm are seen in severe hypocalcemia. Irritability, confusion, hallucinations,
dementia and extrapyramidal manifestations are the other manifestations of
hypocalcemia.
CHVOSTEK’S SIGN
Gentle tapping of the facial nerve, just 2 cm anterior to the tragus of the ear, results
in twitching of the circumoral muscles.
TROUSSEAU SIGN
Carpal spasm induced by keeping the inflated blood pressure cuff 20 mm Hg
above the systolic BP for 3 minutes.
The other manifestations of hypocalcemia include dystonias, papilloedema,
choreathetosis, hemiballismus and oculogyric crisis.
Chapter 46 Calcium 361
Investigations
• Serum calcium (ionized), magnesium, phosphate
• Serum albumin to rule out factitious hypocalcemia
• Serum PTH level
• Liver function tests
• Vitamin D metabolites
• ECG–QT prolongation in hypocalcemia
• Skeletal X-ray—to rule out rickets, osteomalacia, osteoblastic metastases,
etc.
Treatment
The treatment depends on the severity of hypocalcemia, rapidity at which it
develops and the presence of complications. Hypomagnesemia, if associated,
should be corrected.
Severe Symptomatic Hypocalcemia

10 mL of 10% calcium gluconate (90 mg) given IV over 5 minutes.
(diluted in 50 mL of 5% dextrose or 0.9% Nacl)
↓ If hypocalcemia still persists
10 ampoules of calcium gluconate in 1 L of 5% dextrose or 0.9% Nacl
(administered over 24 h).
Chronic Hypocalcemia (Mostly Seen with Hypoparathyroidism)

Calcium supplements (1000–1500 mg/d elemental calcium in divided doses) and
either vitamin D2 or D3 (25,000–100,000 U daily) or calcitriol [1,25(OH)2D, 0.25–2
g/d] should be given. Nutritional vitamin D deficiency is treated with low doses
of vitamin D (50,000 U, 2–3 times per week for several months) while vitamin
D deficiency due to malabsorption require much higher doses (100,000 U/d or
more).
HYPERCALCEMIA
Hypercalcemia is a condition where the serum calcium level is >10.5 mg/dL.
More than 90% of cases are due to primary hyperparathyroidism and malignancy.
Excess calcium ingestion can also cause hypercalcemia as in the case of milk-
alkali syndrome. Causes are given in Table 46.2
Clinical Features
The clinical features of hypercalcemia depend on the serum level of calcium
and the rapidity of the development of hypercalcemia. The symptoms are
predominantly renal, neuropsychiatric and gastrointestinal. Mild hypercalcemia
(10.5–11.5 mg/dL) is usually asymptomatic whereas severe hypercalcemia
(>12 mg/dL) produces serious symptoms.
Table 46.2 Causes of hypercalcemia
• Increased PTH production

– Parathyroid adenoma (most common), parathyroid hyperplasia, carcinoma, renal
insufficiency
• Malignancy
– Due to increased PTHrP in many solid tumors
– Lytic skeletal metastases
• Increased 1,25(OH)2D production
– Granulomatous diseases (Tuberculosis, sarcoidosis)
– Lymphoma, Vitamin D intoxication
• Endocrine causes
– Acromegaly, adrenal insufficiency, pheochromocytoma, thyrotoxicosis
• Medications
– Thiazides, vitamin A, antiestrogens, lithium
• Miscellaneous
– Milk-alkali syndrome, immobilization, TPN
Abbreviations: PTH, parathyroid hormone; TPN, total parenteral nutrition
Neuropsychiatric
Impaired concentration, lethargy, personality changes, stupor, depression, coma,
etc.
Gastrointestinal
Nausea, vomiting, anorexia, constipation, peptic ulcer, pancreatitis.
Renal
Polyuria, hematuria, nephrolithiasis,renal colic, AKI, etc.
DIAGNOSTIC WORKUP
Blood Investigations
Serum Albumin
Since ionized calcium estimation is influenced by numerous artifacts and
collection methods, measurement of total calcium is a better option. However, it
has to be corrected (as previously explained) based on the serum albumin level.
Serum PTH, Serum Phosphorus

Elevated PTH and calcium with low phosphorus—primary hyperparathyroidism.
PTHrP
Elevated in malignancy.
Urine Calcium
Hypocalciuria is <100 mg/d—seen in milk-alkali syndrome, thiazide diuretic use,
and familial hypocalciuric hypercalcemia.
Hypercalciuria is >300 mg/d—malignancy or those receiving oral active
vitamin D therapy.
Chest X-ray
May be helpful in malignancy, sarcoidosis and tuberculosis.
ECG
ECG changes include shortened QT interval, AV block, idioventricular rhythm, etc.
Treatment
The treatment of hypercalcemia depends on the underlying cause. Mild
hypercalcemia usually do not require any treatment. The various treatment
options available for the management of hypercalcemia are as follows:
Hydration
Hypercalcemia invariably produces dehydration. Hence, volume expansion
should be the initial line of management. 4–6 L of IV saline may be required to
restore the volume status. Care should be taken when restoring the volume in
patients with congestive cardiac failure (CCF) and renal failure.
Diuretics
Loop diuretics (Furosemide) are the diuretics of choice. However, they should be
given only after dehydration is corrected. Thiazides worsen hypercalcemia and
are contraindicated.
Bisphosphonates
Although they are safe, effective and normalizes calcium level in more than
70% of cases, they require 48–72 hours before reaching full therapeutic effect.
They act by inhibiting the calcium resorption from bone which is the cause of
hypercalcemia in malignancy and severe hyperparathyroidism. The commonly
used bisphosphonates are:
• Zoledronic acid (4 mg intravenously over 30 min)
• Pamidronate (60–90 mg intravenously over 2–4 h)
• Etidronate (7.5 mg/kg day for 3–7 consecutive days).
Steroids
Steroids are the preferred therapy in 1,25 (OH)2 D-mediated hypercalcemia
as they reduce the levels of 1,25 (OH)2D. The commonly used steroids are
IV hydrocortisone (100–300 mg/d) or oral prednisone (40–60 mg daily) for

3–7 days.
Other drugs such as ketoconazole, chloroquine, and hydroxychloroquine
may also decrease 1,25 (OH)2D production and are used occasionally.
Other Drugs
The other drugs used rarely in the management of hypercalcemia are calcitonin,
gallium nitrate, plicamycin, IV phosphate (can cause serious tissue damage) and
calcimimetic agent cinacalcet hydrochloride (a new agent that suppresses PTH).
Calcitonin
Calcitonin reduces calcium resorption from bone by inhibiting osteoclasts
and increases renal excretion of calcium, sodium, potassium, magnesium, and
phosphate. Advantages of calcitonin are its rapid onset, effect within 24 hours,
analgesic effect, and low toxicity. It can be used safely in patients with renal
failure. Dose is 8 IU per kg every 6 hours for 5 days.
Gallium Nitrate
Gallium nitrate inhibits resorption of bone and causes hypocalcemia. Dose is 200
mg/BSA for 5 days by continuous IV infusion. Adverse effect is renal toxicity and
should not be used in patients with hypotension. It should not be coadministered
with aminoglycosides within 48 hours before or after treatment with gallium
nitrate. Adequate urine output is maintained during therapy. It is given in patients
where calcitonin and bisphosphonate therapy have failed.
Dialysis
It is rarely required.
BIBLIOGRAPHY
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bisphosphonate refractory hypercalcemia of malignancy. BMJ Case Rep. 2014;2014.
2. Bastepe M, Juppner H. Pseudohypoparathyroidism and mechanisms of resistance
toward multiple hormones: molecular evidence to clinical presentation. J Clin
Endocrinol Metab. 2003;88:4055-8.
3. Bech A, de Boer H. Denosumab for tumor-induced hypercalcemia complicated by
renal failure. Ann Intern Med. 2012;156:906.
4. Binstock ML, Mundy GR. Effect of calcitonin and glucocorticoids in combination on
the hypercalemia of malignancy. Ann Intern Med. 1980;93:269-72.
5. Burkhardt E, Kistler HJ. Hypercalciämie bei hospitalisierten Patienten. Schweiz Med
Wschr. 1981;111:2017 -23.
6. Chernow B, Zaloga G, McFadden E, et al. Hypocalcemia in critically ill patients. Crit
Care Med. 1982;10:848.
7. Cicci JD, Buie L, Bates J, van Deventer H. Denosumab for the management of
hypercalcemia of malignancy in patients with multiple myeloma and renal
dysfunction. Clin Lymphoma Myeloma Leuk. 2014;14:e207.
8. Connor TB, Rosen BL, Blaustein MP, et al. Hypocalcemia precipitating congestive
heart failure. N Engl J Med. 1982;307(14):869-72.
9. Connor TB, Rosen BL, Blaustein MP, et al. Hypocalcemia precipitating congestive
heart failure. N Engl J Med. 1982;307:869.
10. Davenport A, Goel S, Mackenzie JC. Treatment of hypercalcemia with pamidronate in

patients with end stage renal failure. Scand J Urol Nephrol. 1993;27:447.
11. Dietzek A, Connelly K, Cotugno M, et al. Denosumab in hypercalcemia of malignancy:
a case series. J Oncol Pharm Pract. 2015;21:143.
12. Gennari C. Calcium and vitamin D nutrition and bone disease of the elderly. Public
Health Nutrition. 1988;4(2B):547-59.
13. Halterman JS, Smith SA. Hypocalcemia and stridor: an unusual presentation of
vitamin D-deficient rickets, J Emerge Med. 1998;16(1):41-3.
14. Hasling C, Charles P, Mosekilde L. Etidronate disodium in the management of
malignancy-related hypercalcemia. Am J Med. 1987;82(Suppl 2A):51.
15. Hastbacka J, Pettila V. Prevalence and predictive value of ionized hypocalcemia
among critically ill patients. Acta Anaesthesiol Scand. 2003;47:1264-9.
16. Henrich D, Hoffmann M, Uppenkamp M, Bergner R. Ibandronate for the treatment
of hypercalcemia or nephrocalcinosis in patients with multiple myeloma and acute
renal failure: Case reports. Acta Haematol. 2006;116:165.
17. Hu MI, Glezerman IG, Leboulleux S, et al. Denosumab for treatment of hypercalcemia
of malignancy. J Clin Endocrinol Metab. 2014;99:3144.
18. Karuppiah D, Thanabalasingham G, Shine B, et al. Refractory hypercalcaemia
secondary to parathyroid carcinoma: response to high-dose denosumab. Eur J
Endocrinol. 2014;171:K1.
19. Lienhardt A, Bai M, Lagarde JP, Rigaud M, Zhang Z, Jiang Y, et al. Activating mutations
of the calcium-sensing receptor: management of hypocalcemia. J Clin Endocrinol
Metab. 2001;86:5313-23.
20. Marx SJ. Familial hypocalciuric hypercalcemia. Primer on the metabolic bone disease
and disorders of mineral metabolism, In: Favus MJ (Ed). Philadelphia, Lippincott
Williams & Wilkins. 1999.pp.195-8.
21. Marx SJ. Hyperparathyroid and hypoparathyroid disorders. N Engl J Med. 2000;343:
1863-75.
22. Minambres I, Chico A, Perez A. Severe hypocalcemia due to vitamin D deficiency
after extended Roux-en-Y gastric bypass. Journal of Obesity. 2011;2011 (Article ID
141024):3.
23. Mosekilde L. Vitamin D and the elderly. Clin Endocrin. 2005;62(3):265-81.
24. Mundy GR, Guise TA. Hypercalcemia of malignancy. Am J Med. 1997;103:134-5.
25. Noto H, Heller H. Vitamin D deficiency as an ignored cause of hypocalcemia in acute
illness: report of 2 cases and review of the literature. The Open Endocrinology Journal.
2009;3:1-4.
26. Slomp J, van der Voort PH, Gerritsen RT, Berk JA, Bakker AJ. Albumin-adjusted calcium
is not suitable for diagnosis of hyper- and hypocalcemia in the critically ill. Crit Care
Med. 2003;31:1389-93.
27. Trimarchi H, Lombi F, Forrester M, et al. Disodium pamidronate for treating severe
hypercalcemia in a hemodialysis patient. Nat Clin Pract Nephrol. 2006;2:459.
28. Warrell RP Jr, Israel R, Frisone M, et al. Gallium nitrate for acute treatment of cancer-
related hypercalcemia. Ann Intern Med. 1988;108:669.
29. Wisneski LA. Salmon calcitonin in the acute management of hypercalcemia. Calcif
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in the critically ill. Am J Kidney Dis. 2001;37:689.
CHAPTER
47 TA Naufal Rizwan
PHOSPHORUS
INTRODUCTION
The normal serum level of phosphate is 2.5–4.5 mg/dL. About 85% of total body
phosphorus is present in the bone with extracellular fluid (ECF) and intracellular
fluid (ICF) concentrations almost the same. Serum phosphate levels vary by as
much as 50% on a normal day and hence, the estimation should be ideally done
in the basal, fasting state.
METABOLISM
The small intestine and the kidneys play a major role in maintaining the
phosphate level. The phosphate absorption from the small intestine is increased
by 1, 25(OH)2D whereas the absorption is decreased by calcium salts, aluminum
hydroxide (present in antacids) and sevelamer hydrochloride.
The proximal tubule is the principal site of renal phosphate reabsorption.
Parathyroid hormone (PTH) and FGF23 (new hormone) impairs the phosphate
reabsorption. Similarly, the presence of hypocalcemia, hypomagnesemia
and volume expansion reduces the reabsorption whereas volume depletion
increases it.
HYPOPHOSPHATEMIA
Hypophosphatemia can be acute or chronic. Although the causes can be inherited
or acquired, the three principal mechanisms that can cause low phosphate
levels are increased renal phosphate excretion, diminished intestinal phosphate
absorption and redistribution.
Increased Renal Phosphate Excretion
PTH/PTHrP Dependent
Primary hyperparathyroidism, secondary hyperparathyroidism (Vit D deficiency,
calcium starvation), hypercalcemia of malignancy (PTHrP) and familial
hypocalciuric hypercalcemia.
Chapter 47 Phosphorus 367
PTH/PTHrP Independent
Genetic causes
X-linked hypophosphatemic (XLH) rickets, autosomal dominant hypopho
sphatemic rickets (ADHR), Dent disease, Fanconi’s syndrome, Wilson disease,
etc.
Acquired causes
Tumor-induced osteomalacia (TIO), alcoholism, hyperaldosteronism,
uncontrolled DM, hypomagnesemia, drugs (acetazolamide, diuretics, cisplatin,
calcitonin, steroids, estrogens) and toxins (alcohol, lead).
Impaired Intestinal Phosphate Absorption

Aluminum containing antacids and sevalamer.
Redistribution of ECF Phosphate into Cells

IV glucose, insulin therapy for diabetic ketoacidosis (DKA) or prolonged
hyperglycemia, catecholamines (epinephrine, dopamine), Gram-negative sepsis,
respiratory alkalosis, leukemic blast crisis, etc.
Accelerated Net Bone Formation

Following parathyroidectomy,treatment of vitamin D deficiency, Pagets disease,
etc
Clinical Features
Symptoms of hypophosphatemia are nonspecific and highly dependent on
cause, duration and severity.
Mild Hypophosphatemia (2–2.5 mg/dL)

It is usually asymptomatic although some patients complain of weakness.
Chronic hypophosphatemia also tends to be less severe with the predominant
complaints being proximal muscle weakness, pseudofractures and bone pain in
adults. In children, they manifest as short stature and rickets.
Severe Hypophosphatemia (<2 mg/dL)

The clinical features of severe hypophosphatemia are as follows.
• Neuromuscular: Weakness, lethargy, confusion, hallucinations, disorienta-
tion, dysarthria, dysphagia, anisocoria, nystagmus, ataxia, cerebellar tremor,
hyperreflexia, sensory deficits, paraesthesia, impaired bladder control, sei-
zures, coma and death.
• Cardiorespiratory: Cardiac dysfunction, ventricular arrhythmias and respira-
tory failure.
• Rhabdomyolysis: Occurs as a result of adenosine triphosphate (ATP)

depletion and altered membrane integrity. It is more common in acute
alcohol withdrawal patient.
• Hematological (due to ATP depletion): Hemolysis, diminished leukocyte
chemotaxis, platelet dysfunction and impaired phagocytosis.
Investigations
Biochemistry
• Serum phosphate, magnesium, calcium and potassium level
• Arterial blood gas analysis, urinalysis, serum uric acid.
Radiology
X-ray, bone densitometry, Technetium Tc99 sestamibi scan (in selected cases).
Treatment
The various treatment options available for treating hypophosphatemia are:
• Dietary phosphate
• Oral phosphate preparations
• IV phosphate.
Mild-to-Moderate Hypophosphatemia
Oral phosphate supplements are useful, especially in the genetic disorders
of phosphate wasting and oncogenic osteomalacia. It is given as sodium or
potassium phosphorus preparations and the usual dose is 2–3 g/day. The side
effects include osmotic diarrhea, volume overload and hyperkalemia.
Severe Hypophosphatemia
Presence of severe hypophosphatemia (<2 mg/dL) and neuromuscular and
cardiorespiratory manifestations warrants the need of IV phosphate supple
mentation. Intravenous phosphate is given as sodium or potassium phosphate.
The initial dose is 1–3 mmol/h given for 6 hours. If hypocalcemia is present, it has
to be corrected first before correcting the phosphate level. IV phosphate should
be given cautiously in patients with renal failure or metabolic alkalosis.
Other Measures
Calcimimetic Drugs (Cinacalcet)
These drugs act by activating the calcium sensing receptor on parathyroid gland
cells and thus, reducing the PTH release. The dose of cinacalcet is 30 mg PO qid
initially.
Vitamin D Preparations
It acts by increasing the intestinal and renal absorption of phosphate. They
are highly useful in hypophosphatemia occurring as a result of secondary
hypoparathyroidism (due to vitamin D deficiency). The various formulations
available are:
• Ergocalciferol (vitamin D2) at doses of 10000–80000 U/day
• Calcitriol (active vitamin D3) at doses 0.25 µg/d PO
• Paracalcitol—vitamin D analog.
Surgery
It is useful in patients with primary hypoparathyroidism and tumor-induced
osteomalacia.
HYPERPHOSPHATEMIA
Hyperphosphatemia is a condition where the serum phosphate level is greater
than 5.5 mg/dL. It is a major cause of secondary hyperparathyroidism, especially
in chronic renal insufficiency, as it stimulates the production of parathyroid
hormone (PTH). Etiology of hyperphosphatemia is given in Table 47.1.
Clinical Features
The signs and symptoms of hyperphosphatemia are due to the following factors.
• Acute effects of hypocalcemia
• Deposition of abnormal calcium phosphate complexes in various tissues
• Hyperphosphatemia-induced resistance to PTH.
Neuromuscular
Altered mental status, delirium, seizures, coma, muscle cramps, paraesthesias,
Chvostek sign, Trousseau sign, tetany.
Table 47.1 Causes of hyperphosphatemia
The causes can be broadly classified as follows.

• Impaired renal phosphate excretion
– Renal failure
– Hypoparathyroidism
- Autoimmune, postsurgical, postradiation
– Parathyroid suppression
- Vitamin D intoxication, milk-alkali syndrome, sarcoidosis, hypomagnesemia
• Massive ECF phosphate loads
– Excessive exogenous phosphate administration (oral, intravenous)
– Extensive cellular injury (crush injuries, hyperthermia, rhabdomyolysis, etc.)
– Transcellular shifts (metabolic acidosis and respiratory acidosis)
• Excessive intake of phosphate (uncommon cause)
– Excessive intake of laxatives and enemas containing phosphate
Abbreviation: ECF, extracellular fluid
Cardiovascular
Hypotension, heart failure, prolonged QT interval, arrhythmias.
Metastatic Calcification
• Vascular calcification (capillaries, small arterioles)
• Aortic valve calcification
• Nephrocalcinosis
• Calciphylaxis (calcific uremic arteriolopathy)—can cause gangrene and
ulcers.
Investigations
• Serum phosphate, calcium, potassium, magnesium
• Blood urea nitrogen (BUN) and serum creatinine
• ECG changes of hypocalcemia like prolonged QT interval may be present
• Radiographs may show evidence of metastatic calcification (e.g., basal
ganglia).
Treatment
The various treatment options available are:
• Volume expansion—This enhances renal phosphate clearance
• Hypocalcemia correction (described in detail under hypocalcemia)
• Oral phosphate binders.
They act by decreasing the gastrointestinal absorption of phosphorus.
Binders containing calcium may cause hypercalcemia and similarly, binders
containing aluminum are contraindicated in renal failure because of aluminium
toxicity.
The commonly used phosphate binders are:
Sevelamer Hydrochloride
It does not affect calcium and has been found to decrease the incidence of
vascular calcium deposition in patients with renal failure. The dose is 2.4–4.8 g
PO divided tid with meals.
Lanthanum Carbonate
It is a noncalcium, nonaluminum phosphate binder. It is highly useful in ESRD
patients. The dose is 250–500 mg PO tid as chewable tabs.
Binders-containing Aluminum
Antacids containing aluminum can also be used as a phosphate binder but it
is avoided in renal failure patients because of the risk of developing aluminum
toxicity.
Hemodialysis
It is indicated for refractory cases and for patients with renal failure.
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Dis. 2001;37:1267-76.
3. Ben-Dov IZ, Galitzer H, Lavi-Moshayoff V. The parathyroid is a target organ for FGF23
in rats. J Clin Invest. 2007;117:4003-8.
4. Berndt TJ, Schiavi S, Kumar R. Phosphatonins and the regulation of phosphorus
homeostasis. Am J Physiol Renal Physiol. 2005;289:F1170-82.
5. Cozzolino M, Pasho S, Fallabrino G. Pathogenesis of secondary hyperparathyroidism.
Int J Artif Organs. 2009;32:75-80.
6. De Boer IH, Rue TC, Kestenbaum B. Serum phosphorus concentrations in the third
National Health and Nutrition Examination Survey (NHANES III). Am J Kidney Dis.
2009;53:399-407.
7. Dhingra R, Sullivan LM, Fox CS. Relations of serum phosphorus and calcium levels
to the incidence of cardiovascular disease in the community. Arch Intern Med.
2007;167:879-85.
8. DiMeglio LA, White KE, Econs MJ. Disorders of phosphate metabolism. Endocrinol
Metab Clin North Am. 2000;29:591-609.
9. Faroqui S, Levi M, Soleimani M, Amlal H. Estrogen downregulates the proximal
tubule type IIa sodium phosphate cotransporter causing phosphate wasting and
hypophosphatemia. Kidney Int. 2008;73:1141-50.
10. Gaasbeek A, Meinders AE. Hypophosphatemia: an update on its etiology and
treatment. Am J Med. 2005;118:1094-101.
11. Knochel JP. The clinical status of hypophosphatemia: an update. N Engl J Med.
1985;313:447-9.
12. Knochel JP. The pathophysiology and clinical characteristics of severe hypophos
phatemia. Arch Intern Med. 1977;137:203-20.
13. Krajisnik T, Olauson H, Mirza MA. Parathyroid Klotho and FGF-receptor 1 expression
decline with renal function in hyperparathyroid patients with chronic kidney disease
and kidney transplant recipients. Kidney Int. 2010;78:1024-32.
14. Moe SM. Disorders involving calcium, phosphorus, and magnesium. Prim Care. 2008;
35:215-37:v–vi.
15. Murer H, Hernando N, Forster I, Biber J. Proximal tubular phosphate reabsorption:
molecular mechanisms. Physiol Rev. 2000;80:1373-409.
16. Roman-Garcia P, Carrillo-Lopez N, Cannata-Andia JB. Pathogenesis of bone and
mineral related disorders in chronic kidney disease: Key role of hyperphosphatemia. J
Ren Care. 2009;35(Suppl 1):34-8.
17. Shimizu Y, Tada Y, Yamauchi M. Hypophosphatemia induced by intravenous
administration of saccharated ferric oxide: another form of FGF23-related
hypophosphatemia. Bone. 2009;45:814-6.
18. Takeda E, Taketani Y, Sawada N. The regulation and function of phosphate in the
human body. Biofactors. 2004;21:345-55.
19. Tenenhouse H. Phosphate transport: molecular basis, regulation and pathophysiology.
J Steroid Biochem Mol Biol. 2007;103:572-7.
20. Wolf M. Fibroblast growth factor 23 and the future of phosphorus management. Curr
Opin Nephrol Hypertens. 2009;18:463-8.
CHAPTER
48 TA Naufal Rizwan
MAGNESIUM
HYPOMAGNESEMIA
Magnesium is an important divalent cation. It plays a major role in cellular
function, replication and energy metabolism by acting as a cofactor in various
enzymes, nucleic acids and transporters. Around 50% of the total body magnesium
is in the bones. Among the extraskeletal magnesium, only 1% is confined to the
extracellular fluid (ECF) whereas the remaining 99% extraskeletal magnesium is
present within the cells (Table 48.1).
The normal level of magnesium is 1.7–2.4 mg/dL (1.5–2 mEq/L). Intestinal
absorption of magnesium is stimulated by 1,25(OH)2 and regulation of serum
magnesium concentration is achieved mainly through renal reabsorption
(predominantly in cTAL).
Clinical Features
The clinical features of hypomagnesemia are predominantly neuromuscular and
cardiovascular. Severity of symptoms, at times, may not correlate with the serum
magnesium level.
Table 48.1 Causes of hypomagnesemia
Extrarenal causes Renal causes

• Impaired intestinal absorption: Malabsorption • Genetic causes: Magnesium
syndromes, proton pumpinhibition (PPI) drugs, wasting syndromes, Barter’s
vit D deficiency, TRPM6 mutations (Hypomag- syndrome, Gitelman’s syndrome
nesemia with secondary hypocalcemia seen) • A cquired causes: ATN,
• Increased intestinal losses: Vomiting, diarrhea, tubulointerstitial disease, renal
fistulas, intestinal drainage transplantation
• Cutaneous losses: Intense exertion, burns • D rugs: Diuretics, cisplatin,
• Redistribution aminoglycosides, amphotericin B,
– To bone: Postparathyroidectomy, cyclosporine
Osteoblastic metastases, treatment of vit D • O thers: SIADH,
deficiency DM, hypercalcemia,
– Intracellular: Recovery from DKA, correction hyperaldosteronism,
of respiratory acidosis hyperthyroidism
Chapter 48 Magnesium 373
Neuromuscular
Symptoms and signs of neuromuscular irritability such as tremors, muscle
twitching, muscle weakness, vertigo, frank tetany, Trousseau’s and Chvostek’s
signs are seen in hypomagnesemic patients. Seizures (sometimes triggered by
loud noises) and vertical nystagmus are also present. Depression, psychosis and
irritability are some of the psychiatric manifestations of this disorder.
Cardiovascular
Patients with hypomagnesemia are more prone to develop cardiac arrhythmias
such as supraventricular tachycardias and ventricular arrhythmias (like
monomorphic VT, torsades de pointes, VF, etc). ECG abnormalities of hypo
magnesemia are prolonged PR or QT intervals, ST straightening and T-inversion.
Electrolyte Homeostasis
Hypokalemia and hypocalcemia are commonly associated with hypomagnesemia
Skeletal System
Increased osteoclastic activity coupled with decreased osteoblastic activity
results in increased skeletal fragility and impaired skeletal growth.
Treatment
Mild Cases
In mild and asymptomatic cases, oral salts are preferred. The various oral
formulations available are Magnesium chloride, hydroxide, oxide, etc. They are
usually given at 40–60 meq/d in divided doses. Large doses can produce diarrhea.
Severe Cases
In severe cases, intravenous route is the preferred route of administration for
magnesium. Both MgCl2 and MgSO4 can be given. However, the sulfate ions in
MgSO4 can bind with calcium, thereby worsening hypocalcemia. The usual
dose is 100 mEq/d given as a continuous infusion (1g contains 8 mEq). The dose
should be reduced to 75% in case of reduced GFR. Intracellular Mg store takes
longer time to replenish, so magnesium administration should continue for 1–2
days even after the serum Mg level is normalized. Intramuscular route should be
avoided.
Serum magnesium should be monitored at 12–24 hours intervals as excessive
administration of magnesium can result in hypermagnesemia, which is detected
by facial flushing, loss of deep tendon reflexes, hypotension and atrioventricular
block. In patients with inappropriate renal magnesium wasting, potassium
sparing diuretics such as amiloride and triamterene should be given. They act by
blocking the distal tubule epithelial sodium channel.
HYPERMAGNESEMIA
Hypermagnesemia is a condition where the serum magnesium level is greater
than 2.5 mg/dL. It is a rare electrolyte abnormality as the kidneys are highly
effective in excreting excess magnesium. Intestinal pathology like paralytic ileus,
obstruction and perforation can cause prolonged retention of even normal
amount of Mg containing cathartics resulting in hypermagnesemia.
Clinical Features
The most prominent clinical features are vasodilation and neuromuscular
blockade. The signs and symptoms vary according to the level of serum
magnesium. Platelet clumping and delayed thrombin formation are seen at
higher levels of serum magnesium (Tables 48.2 and 48.3).
Investigations
• Serum magnesium, potassium and calcium
• Serum BUN and creatinine
• Serum CPK and urine myoglobin if rhabdomyolysis is suspected
• ABG, thyroid function test
• ECG—Intraventricular conduction delay, PR, QRS and QT-prolongation.
Treatment
The various treatment options available are:
Table 48.2 Causes of hypermagnesemia
• Impaired magnesium excretion: Renal failure, familial hypocalciuric hypercalcaemia

• Excessive intake: Mg-containing vitamins, cathartics, antacids and IV Mg infusions
• Endocrine causes: Adrenal insufficiency, hypothyroidism
• Rapid mobilization from soft tissues: Trauma, burns, shock, sepsis
Table 48.3 Clinical manifestations of hypermagnesemia based on

serum magnesium level
Serum magnesium Clinical features

2.5–4 mg/dL Nausea, vomiting, skin flushing, weakness, sedation
4–5.5 mg/dL Disappearance of deep tendon reflexes and increase in PR
and QRS duration
5.5–7.5 mg/dL Hypotension, vasodilation and respiratory depression
7.5–10 mg/dL Arrhythmias and intraventricular conduction block
Greater than 10 mg/dL Asystole, heart block, respiratory failure, coma
Chapter 48 Magnesium 375
Hydration and Diuretics

Vigorous IV hydration should be done using Ringer lactate or normal saline.
Careful monitoring of the cardiovascular function is a must. Following hydration,
loop diuretics (such as furosemide) should be given to increase the excretion of
magnesium.
Calcium
IV calcium gluconate, given at a dose of 100–200 mg over 1–2 hours, offers
temporary benefit by antagonizing the neuromuscular and cardiovascular
toxicity of hypermagnesemia.
Hemodialysis
It is the treatment of choice in patients with severe hypermagnesemia and in
patients with renal failure.
BIBLIOGRAPHY
1. Ali A, Walentik C, Mantych GJ, et al. Iatrogenic acute hypermagnesemia after total
parenteral nutrition infusion mimicking septic shock syndrome: two case reports.
Pediatrics. 2003;112:e70-e2.
2. Bairaktari E, Kalaitzidis R. Hypomagnesemia in alcoholic patients. Alcohol Clin Exp
Res. 1998;22:134.
3. Birrer RB, Shallash AJ, Totten V. Hypermagnesemia-induced fatality following epsom
salt gargles, Journal of Emergency Medicine. 2002;22(2):185-8.
4. Cao Z, Bideau R, Valdes RJ, et al. Acute hypermagnesemia and respiratory arrest
following infusion of MgSO4 for tocolysis. Clin Chim Acta. 1999;285:191-3.
5. Chernow B, Bamberger S, Stoiko M, et al. Hypomagnesemia in patients in post
operative intensive care. Chest. 1989;95:391-7.
6. Cohen L, Laor. A correlation between bone magnesium concentration and magnesium
retention in the intravenous magnesium load test. Magnes Res. 1990;3:271-4.
7. Dai LJ, Quamme GA. Intracellular Mg2+ and magnesium depletion in isolated renal
thick ascending limb cells, Journal of Clinical Investigation. 1991;88(4):1255-64.
8. Deheinzelin D, Negri EM, Tucci MR, et al. Hypomagnesemia in critically ill cancer
patients: A prospective study of predictive factors. Braz J Med Biol Res. 2000;33:1443-
8.
9. Escuela MP, Guerra M, Anon JM, et al. Total and ionized serum magnesium in critically
ill patients. Intensive Care Med. 2005;31:151-6.
10. Huey CG, Chan KM, Wong ET, et al. Los Angeles County-University of Southern
California Medical Center clinical pathology case conference: extreme hyper
magnesemia in a neonate. Clin Chem. 1995;41:615-8.
11. Jhang WK, Lee YJ, Kim AY, Park JS, Park SY. Severe hypermagnesemia presenting with
abnormal electrocardiographic findings similar to those of hyperkalemia in a child
undergoing peritoneal dialysis, Korean Journal of Pediatrics. 2013;56(7):308-11.
12. Kroll MH, Elin RJ. Relationships between magnesium and protein concentrations in
serum. Clin Chem. 1985;31:244-6.
13. Lote CJ, Thewles A, Wood JA, et al. The hypomagnesemic action of FK506: urinary
excretion of magnesium and calcium and the role of parathyroid hormone. Clin Sci
(Lond). 2000;99:285-92.
14. Mathers TW, Beckstrand RL. Oral magnesium supplementation in adults with
coronary heart disease or coronary heart disease risk. J Am Acad Nurse Pract. 2009;
21:651-7.
15. Quamme GA. Renal magnesium handling: new insights in understanding old
problems. Kidney Int. 1997;52:1180-95.
16. Ryzen E, Wagers PW, Singer FR, Rude RK. Magnesium deficiency in a medical ICU
population. Crit Care Med. 1985;13:19-21.
17. Schelling JR. Fatal hypermagnesemia. Clin Nephrol. 2000;53:61.
18. Spiegel DM. Magnesium in chronic kidney disease: unanswered questions. Blood
Purif. 2011;31:172-6.
19. Walser M. Ion association VI. Interactions between calcium, magnesium, inorganic
phosphate, citrate and protein in normal human plasma. J Clin Invest, 1961;40:723-
30.
20. Wong ET, Rude RK, Singer FR, Shaw ST Jr. A high prevalence of hypomagnesemia and
hypermagnesemia in hospitalized patients. Am J Clin Pathol. 1983;79:348-52.
SECTION
12
GASTROINTESTINAL DISEASES
IN ICU
Chapter 49 Upper Gastrointestinal Bleeding

TA Naufal Rizwan
Chapter 50 Lower Gastrointestinal Bleeding

TA Naufal Rizwan
Chapter 51 Acute Pancreatitis

TA Naufal Rizwan
Chapter 52 Acute Liver Failure

TA Naufal Rizwan
Chapter 53 Abdominal Infections in ICU

TA Naufal Rizwan
CHAPTER
49 TA Naufal Rizwan
UPPER GASTROINTESTINAL BLEEDING
Acute gastrointestinal bleeding is a common problem necessitating admission

in ICU. Due to advent of noninvasive methods of treatment, the mortality has
reduced. Upper gastrointestinal bleeding usually presents as hematemesis or
melena. Vomiting of blood is known as hematemesis. It may be either bright red
or brown coffee grounds material. Passage of black tarry stools is called melena,
which can develop with as little as 50 mL blood loss. Rarely, if the upper gastro-
intestinal bleeding is severe, it can also manifest as hematochezia (Table 49.1).
PEPTIC ULCER
This is the most common cause for UGI bleed, accounting for nearly 50% of all
cases. However, the incidence has declined in the recent past, possibly due to
the better management of H. pylori infection and prophylaxis with proton pump
inhibitors in high-risk patients.
VARICEAL BLEED
This accounts for 10–20% of all UGI bleed. Esophageal varices are more common
than the gastric or duodenal varices.
Table 49.1 Causes of upper GI bleeding
• Peptic ulcers of esophagus, stomach and duodenum

• Esophagogastric (Mallory-Weiss) mucosal tear
• Esophageal rupture (Boerhaave’s syndrome)
• Inflammation and erosions (esophagitis, gastritis, duodenitis)
• Varices of esophagus, stomach or duodenum
• Neoplasm (carcinoma, lymphoma, leiomyoma, leiomyosarcoma, polyps)
• Hemobilia
• Vascular-enteric fistula (usually from aortic aneurysm or graft)
• Vascular anomalies
380 Section 12 Gastrointestinal Diseases in ICU
MALLORY-WEISS TEAR
It is a nontransmural tear at the gastroesophageal junction, occuring as a result
of vomiting, retching or vigorous coughing. It is commonly associated with heavy
alcohol use. About 5% of UGI bleeding is due to Mallory-Weiss tear.
BOERHAAVE’S SYNDROME
Spontaneous rupture at the gastroesophageal junction as a result of forceful
vomiting or retching is called as Boerhaave syndrome.
VASCULAR ANOMALIES
• Angioectasias (angiodysplasias): These are aberrant submucosal vessels,
which are 1–10 mm in size caused by chronic obstruction of submucosal
veins.
• Telangiectasias: These are small, cherry red lesions caused by dilation of
venules. They are also seen in CREST syndrome.
• Dieulafoy lesion: This is an aberrant, large submucosal artery situated mostly
in the proximal stomach.
Risk factors associated with mortality in upper GI bleeding:

• Age >60 years
• Shock on admission
• Incidence of rebleeding in 3 days
• Failure to clear red nasogastric aspirate.
MANAGEMENT
Because patients vary in the severity of bleeding, the orderly sequence of history
taking, physical examination, diagnostic evaluation, and treatment may have to
be altered to meet the immediate demands.
History
• Ingestion of gastric mucosal irritants: The recent ingestion of aspirin, other
nonsteroidal anti-inflammatory drugs, or alcohol raises the possibility that
erosive gastritis or other mucosal injury has developed. Aspirin not only
causes direct mucosal injury, but also interferes with platelet adhesion and
worsens the prognosis of acutely bleeding patients.
• Associated medical conditions: The number of associated medical conditions
directly increases the risk of mortality in acute gastrointestinal bleeding.
Mortality in patients with no accompanying medical conditions is about 1%,
whereas the risk of dying in patients with four or more associated illnesses is
more than 70%.
Chapter 49 Upper Gastrointestinal Bleeding 381
Hemodynamic Assessment
Coolness of the extremities and pallor of the conjunctivae, mucous membranes, and
nail beds may be evident as a result of blood loss and peripheral vasoconstriction.
The presence of postural signs (when the patient sits up from a supine position, the
pulse rate increases more than 20 beats per minute and the systolic blood pressure
drops more than 10 mm Hg) indicate that blood loss has exceeded 1 L.
• SBP <100 mm Hg and HR >100–Severe acute blood loss
• SBP >100 mm Hg and HR >100–Moderate acute blood loss
• SBP >100 mm Hg and HR <100–Minor blood loss
Fluid, Electrolyte, and Blood Replacement

• Large-bore intravenous catheter should be inserted promptly into a
peripheral vein. Blood can be drawn at this time for laboratory studies. If the
bleeding is profuse, two or more intravenous catheters may be required. In
case a peripheral vein is not available, venous access should be established
via a jugular, subclavian, or femoral vein.
• Infusion of fluids: Normal saline is infused rapidly until blood for transfusion
is available. If the patient is bleeding profusely and blood for transfusion is
not yet available, saline should be infused even if the patient has ascites and
edema. If bleeding is less severe, hypotonic sodium solutions may be infused
until blood for transfusion arrives.
Blood Replacement
• Packed cells should be transfused to maintain Hb > 7 g/dL. One unit of FFP
should be given for each 5 units of packed RBC transfused. Platelets should
be transfused if platelet count is <50000/mm3. In uremic patients with active
bleeding, desmopressin (DDAVP) may be given (3 doses, 0.3 µ/kg IV, twice
daily).
• A central venous pressure catheter or Swan-Ganz catheter may be
necessary to evaluate the effects of volume replacement and the need for
continued infusion of blood, particularly in elderly patients or patients with
cardiovascular disease. Urine output should be monitored to know about the
perfusion of vital organs.
Nasogastric Intubation and Gastric Lavage

A nasogastric (NG) tube should be passed in all patients with acute gastrointestinal
bleeding unless the source is obviously the lower gastrointestinal tract. If the
aspirate is clear, NG tube can be removed.
Benefits of NG Intubation
It helps to document the presence of blood and to monitor the rate of bleeding.
It can also be used for gastric lavage and to decompress the stomach, thus
facilitating hemostasis.
Disadvantages of NG Intubation
In addition to causing discomfort to the patient, it also causes irritation of the
esophageal and gastric mucosae, creating mucosal artifacts and aggravating
existing lesions. NG intubation also predisposes to gastroesophageal reflux and
pulmonary aspiration.
PHARMACOLOGIC THERAPY
• Proton pump inhibitors
If high, IV PPI—Pantoprazole or esomeprazole 80 mg IV bolus followed
by 8 mg/h continuous infusion for 72 hours—Rebleeding risk.
If low, oral PPI—esomeprazole or pantoprazole 40 mg OD or bid
• Octreotide: It is indicated in UGI bleed, related to liver disease or portal
hypertension. The usual dose is 100 µg IV bolus followed by 50–100 µ/hour
continuous infusion. Terlipressin may also be used instead of octreotide.
• Nonselective beta-blockers: Beta-blockers are indicated to reduce the risk of
variceal rebleeding.
– Propranolol: Starting dose 20 mg BID—maintenance dose 40 mg BID
– Nadolol: Starting dose 40 mg OD—maintenance dose 80 mg OD.
ENDOSCOPY
Once the hemostasis is achieved, endoscopy should be done to identify the
source of bleeding and to know the risk of rebleeding. It can also be used to
render endoscopic therapy.
The choice of various treatment options available in endoscopy are:
• Thermocoagulation
• Laser photocoagulation
• Banding
• Sclerotherapy
• Endoclip application
• Endoscopic injection of epinephrine (1:10000).
SPECIFIC CONDITIONS
Endoscopic Therapy for Peptic Ulcer

Indication
The ulcer with a nonbleeding visible vessel as it has got a 50% chance of rebleeding
or continued bleeding.
Endoscopic treatment options available are:

• Endoscopic therapy with thermocoagulation (bipolar or heater probes)
• Endoscopic clips
• Endoscopic injection of epinephrine
Chapter 49 Upper Gastrointestinal Bleeding 383
Endoscopic Therapy for Varices

• Endoscopic banding: This is the endoscopic treatment of choice for variceal
bleed. The advantages of this procedure are less complications and less
rebleeding compared to sclerotherapy.
However, repeat sessions are required at every 2–4 weeks intervals until
the varices are obliterated or reduced to small sizes.
• Sclerotherapy: Sclerotherapy is a procedure in which sclerosants
(ethanolamine, tetradecyl sulfate) are injected into the variceal trunks. It is
indicated in whom the visualization for banding is difficult. The complications
of sclerotherapy are esophageal ulceration, stricture and perforation.
Nonendoscopic Treatment Options for Varices

Apart from endoscopy, the various other treatment options available for varices
are:
• Balloon tube tamponade
• Transvenous intrahepatic portosystemic shunts
• Surgical portosystemic shunts.
Balloon Tube Tamponade (Sengstaken-Blakemore or Minnesota Tube)

The triple-lumen Sengstaken-Blakemore (SB) tube is representative of several
tubes that can compress gastroesophageal varices by balloon tamponade. One
lumen is used to evacuate the stomach. The second and third lumens lead to the
gastric and esophageal balloons, respectively.
Indications: Balloon tamponade is indicated only in variceal bleeding that is not
controlled by pharmacological or endoscopic measures. It should be used only as
a temporary procedure.
Complications
• Esophageal ulceration,
• Aspiration
• Airway obstruction.
Transvenous Intrahepatic Portosystemic Shunts (TIPSS)

It is a procedure in which an expandible wire mesh stent is passed into the liver
parenchyma through a catheter inserted in the jugular vein, thus creating a
portosystemic shunt between hepatic vein and portal vein.
Indications
• Bleeding from gastric varices and portal hypertensive gastropathy (Banding
cannot be done for gastric varices)
• Recurrent esophageal variceal bleed, not responding to endoscopic
techniques.
Complications
stent stenosis }
Stent thrombosis Hence, periodic monitoring with Doppler
ultrasonography or hepatic venography is required.
Surgical Portosystemic Shunts

With the advent of TIPSS, surgical portosystemic shunts are rarely performed.
BIBLIOGRAPHY
1. Al-Dhahab H, Barkun A. The acute management of nonvariceal upper gastrointestinal
bleeding. Ulcers Vol. 2012, Article ID 361425.
2. Avunduk, Canan. Manual of Gastroenterology: Diagnosis and Therapy, 4th edn.
3. Baradarian R, Ramdhaney S, Chapalamadugu R, et al. Early intensive resuscitation of
patients with upper gastrointestinal bleeding decreases mortality. Am J Gastroenterol.
2004;99:619.
4. Branicki FJ, Boey J, Fok PJ, et al. Bleeding duodenal ulcer: a prospective evaluation of
risk factors for rebleeding and death. Ann Surg. 1989;211:411.
5. Huang ES, Karsan S, Kanwal F, et al. Impact of nasogastric lavage on outcomes in
acute GI bleeding. Gastrointest Endosc. 2011;74:971.
6. Hwang JH, Fisher DA, Ben-Menachem T, et al. The role of endoscopy in the
management of acute non-variceal upper GI bleeding. Gastrointest Endosc. 2012;
75:1132.
7. Laine L, Jensen DM. Management of patients with ulcer bleeding. Am J Gastroenterol.
2012;107:345.
8. Leontiadis G, Barkun A. Commentary: what is the optimal PPI dosing following
endoscopic haemostasis in acute ulcer bleeding? Alimentary Pharmacology &
Therapeutics. 2012;35(11):1351-2.
9. Leontiadis GI, Howden CW. The role of proton pump inhibitors in the management of
upper gastrointestinal bleeding. Gastroenterol Clin North Am. 2009;38:199-213.
10. Leontiadis GI, Sharma VK, Howden CW. Proton pump inhibitor treatment for acute
peptic ulcer bleeding. Cochrane Database of Systematic Reviews, no. 1, p. CD002094,
2006.
11. Longo DL, Fauci AS, Kasper DL, et al. Principles of Internal Medicine, 18th edn.
12. Papadakis MA, McPhee SJ, Rabow MW. Current Medical Diagnosis & Treatment 2015,
54th edn.
13. Ramsoekh D, van Leerdam ME, Rauws EA, et al. Outcome of peptic ulcer bleeding,
nonsteroidal anti-inflammatory drug use, and Helicobacter pylori infection. Clin
Gastroenterol Hepatol. 2005;3:859-64.
14. Sung JJ, Barkun A, Kuipers EJ. Peptic Ulcer Bleed Study Group. Intravenous
esomeprazole for prevention of recurrent peptic ulcer bleeding: a randomized trial.
Ann Intern Med. 2009;150:455-64.
15. Upper GI bleeding–associated mortality: Challenges to improving a resistant outcome.
Am J Gastroenterol. 2010;105:90-2.
16. Vergara M, Calvet X, Gisbert JP. Epinephrine injection versus epinephrine injection
and a second endoscopic method in high-risk bleeding ulcers. Cochrane Database
Syst Rev. 2007;18:CD005584.
CHAPTER
50 TA Naufal Rizwan
LOWER GASTROINTESTINAL BLEEDING
Bleeding that arises from a source below the ligament of Treitz is known as lower
gastrointestinal bleed. In about 95% of cases, it is from the small intestine or the
colon. Spontaneous cessation of bleeding occurs in more than 2/3rd of patients.
ETIOLOGY
• Hemorrhoids
• Anal fissure
• Inflammatory bowel disease (proctitis or colitis)
• Neoplasm (carcinoma or polyps)
• Diverticulosis
• Ischemic enteritis or colitis
• Angiodysplasia
• Antibiotic-associated colitis
• Radiation colitis
• Amyloidosis
• Meckel’s diverticulum
• Vascular-enteric fistula
Diverticulosis
It is the most common cause for lower gastrointestinal bleed, accounting for
nearly one half of all the cases. The risk is increased in patients using NSAIDs.
However, bleeding stops spontaneously in about 80% of cases.
Anorectal Disease
The common anorectal diseases producing lower gastrointestinal bleed are
fissure in ano, hemorrhoids and rectal ulcers. It usually presents as small amounts
of bright red blood seen in the toilet bowl.
Angioectasias
They are flat, red lesions (2–10 mm) with ectatic peripheral vessels radiating from
a central vessel. They are commonly seen in patients over 70 years of age and
usually manifest as painless bleeding melena or hematochezia.
Neoplasms
Both benign polyps and carcinomas present as lower GI bleed in the form of
hematochezia or occult blood.
Inflammatory Bowel Disease

In addition to hematochezia or occult blood loss, patients with inflammatory
bowel disease also present with diarrhea, constipation and abdominal pain.
INVESTIGATIONS
The most important thing in a lower GI bleed is to rule out the upper GI source of
bleeding. If the aspirate from the nasogastric tube has coffee ground appearance,
it indicates UGI bleed. The other specific investigations available are:
Anoscopy and Sigmoidoscopy

If the bleeding is not severe, anoscopy and sigmoidoscopy should be performed
initially to rule out anorectal diseases, inflammatory bowel diseases, etc.
Colonoscopy
In case of large volume bleeding, colonoscopy becomes the preferred
investigation. Before doing the colonoscopy, bowel should always be purged to
remove the blood clots.
Nuclear Scintigraphy (Technetium-labeled Red Blood Cell)

The advantages of doing a radionuclide scan are to localize the source of bleeding
and to know if angiography is required or not.
Arteriography
Angiograms are usually done only when the Technetium scans are positive
for active, significant bleeding. However, when the bleeding is very severe
causing hemodynamic compromise, it should be performed without attempt at
colonoscopy or scintigraphy.
Push Enteroscopy and Capsule Endoscopy

These help in localizing the small intestinal source of bleeding.
TREATMENT
Hemodynamic Assessment
Hemodynamic assessment is the first step in the management of lower
gastrointestinal bleed. Coolness of the extremities and pallor of the conjunctivae,
Chapter 50 Lower Gastrointestinal Bleeding 387
mucous membranes and nail beds may be evident as a result of blood loss and
peripheral vasoconstriction.
• Systolic BP (SBP) <100 mm Hg and HR (Heart rate) >100–severe acute blood
loss
• SBP >100 mm Hg and HR >100–moderate acute blood loss
• SBP >100 mm Hg and HR <100–minor blood loss.
Volume Resuscitation
Large-bore intravenous catheter should be inserted promptly into a peripheral
vein. Blood loss should be adequately managed by infusion of fluids and blood
replacement. Urine output should be monitored to know about the perfusion of
vital organs.
SPECIFIC MEASURES
The treatment options available are:
• Colonoscopy
• Intra-arterial embolization
• Surgical treatment.
Colonoscopy
Various modalities of treatment that can be done with the help of colonoscopy are:
• Epinephrine injection
• Cautery (bipolar or heater probe)
• Application of endoclips or bands
Intra-arterial Embolization
It is a procedure in which an autologous clot or small pieces of gelatin sponge
are injected into the artery, thereby occluding the bleeding vessel and achieving
hemostasis. However, this can be done only if the bleeding vessel is identified.
Complications like ischemic colitis occur in a minority of patients.
Surgical Treatment
With the advent of colonoscopic and angiographic procedures, the need for
surgical treatment has greatly come down. However, if the bleeding is severe
(requiring more than 6 units of blood in 24 hours) as in the case of diverticulosis
and angiodysplasia, surgery is indicated.
BIBLIOGRAPHY
1. Arroja B, Cremers I, Ramos R, Cardoso C, Rego AC, Caldeira A, et al. Acute lower
gastrointestinal bleeding management in Portugal: a multicentric prospective 1-year
survey. Eur J Gastroenterol Hepatol. 2011;23:317-22.
Lippincott William & Wilkin; 2008.
3. Brackman MR, Gushchin VV, Smith L, Demory M, Kirkpatrick JR, Stahl T. Acute lower
gastroenteric bleeding retrospective analysis (the ALGEBRA study): an analysis of
the triage, management and outcomes of patients with acute lower gastrointestinal
bleeding. Am Surg. 2003;69:145-9.
4. Chaudhry V, Hyser MJ, Gracias VH, Gau FC. Colonoscopy: the initial test for acute
lower gastrointestinal bleeding. Am J Surg. 1998;64:723-8.
5. Dutta G, Panda M. Case Report: An uncommon cause of lower gastrointestinal
bleeding: a case report. Cases Journal. 2008;1:235.
6. D’Othée BJ, Surapaneni P, Rabkin D, Nasser I, Clouse M. Microcoil embolization for
acute lower gastrointestinal bleeding. Cardiovasc Intervent Radiol. 2006;29(1):49-58.
7. Gayer C, Chino A, Lucas C, Tokioka S, Yamasaki T, Edelman DA, et al. Acute lower
gastrointestinal bleeding in 1112 patients admitted to an urban emergency medical
center. Surgery. 2009;146:600-6 discussion 606-7.
8. Green BT, Rockey DC, Portwood G, Tarnasky PR, Guarisco S, Branch MS, et al.
Urgent colonoscopy for evaluation and management of acute lower gastrointestinal
hemorrhage: a randomized controlled trial. Am J Gastroenterol. 2005;100:2395-402.
9. Hreinsson, Gumundsson JP, Kalaitzakis S, Björnsson E, Einar S. Lower gastrointestinal
bleeding: incidence, etiology, and outcomes in a population-based setting. European
Journal of Gastroenterology & Hepatology. 2013;25(1):37-43.
10. Koh DC, Luchtefeld MA, Kim DG, et al. Efficacy of transarterial embolization as
definitive treatment in lower gastrointestinal bleeding. Colorectal Dis. 2009;11(1):53-
9.
11. Lanas A, et al. Time trends and impact of upper and lower gastrointestinal bleeding
and perforation in clinical practice. Am J Gastroenterol. 2009;104:1633-41.
12. Longo DL, Fauci AS, Kasper DL, et al. Harrison’s Principles of Internal Medicine, 18
ed. McGraw-Hill; 2012.
13. Makela JT, Kiviniemi H, Laitinen S, Kairaluoma MI. Diagnosis and treatment of acute
lower gastrointestinal bleeding. Scand J Gastroenterol. 1993;28:1062-6.
14. Navuluri R, Kang L, Patel J, Ha T. Acute lower gastrointestinal bleeding; Semin
Intervent Radiol. 2012;29(3):178-86.
15. Papadakis MA, McPhee SJ, Rabow MW. Current medical diagnosis & treatment, 54th
edn., 2015.
CHAPTER
51 TA Naufal Rizwan
ACUTE PANCREATITIS
GENERAL CONSIDERATIONS
Acute inflammation of the pancreas is known as acute pancreatitis. Gall-stones
and alcohol account for the majority of the cases. It can range from a mild, self-
limiting disorder to a more serious necrotic pancreatitis.
ETIOLOGY
It is given in Table 51.1.
Table 51.1 Causes of acute pancreatitis
Common causes:
• Gallstones
• Alcohol
• Hypertriglyceridemia
• ERCP
• Postoperative
• Trauma
Uncommon causes:
• Vasculitis, connective tissue disorders
• Infections (Mumps, coxsackie virus, CMV)
• Pancreas divisum, cystic fibrosis, renal failure
• Pancreatic cancer, hypercalcemia
Drugs:
• Azathioprine
• Sulfonamides
• Estrogens
• Valproic acid
• Tetracyclines, pentamidine, thiazides, furosemide
PATHOGENESIS
The pathogenesis largely remains unclear. The postulated mechanisms are:
• Autodigestion: Toxins, infections, increased intracellular calcium lead onto
the activation of the pancreatic proteases that, in turn, results in the digestion
of pancreatic and peripancreatic tissues.
• Pancreatic ductular hypertension due to the obstruction of the pancreatic

drainage at the level of ampulla.
CLINICAL FEATURES
Abdominal pain is the most common presenting symptom. It can be mild
or severe, mostly located in the epigastrium and periumbilical region with
occasional radiation to the back and chest. The pain is characteristically reduced
when the patient sits with the trunk flexed and knees drawn up. Nausea, vomiting
and abdominal distension may also be present. Low-grade fever, hypotension and
tachycardia are seen in more severe disease. Jaundice is seen if the underlying
etiology is a gallstone.
Abdominal examination may reveal epigastric tenderness, guarding, and
reduced bowel sounds. The signs of severe necrotizing pancreatitis are Grey
Turners sign (blue-red-purple or green-brown discoloration of the flanks due
to tissue metabolism of hemoglobin) and Cullen’s sign (Faint blue discoloration
around the umbilicus due to hemoperitoneum).
INVESTIGATIONS
Elevated Serum Amylase and Lipase

More than threefold elevation of serum amylase and lipase is almost diagnostic
of acute pancreatitis, if the other causes are ruled out. There is no correlation
between the severity of pancreatitis and the degree of elevation of these enzymes.
Serum amylase returns to baseline values in 3–5 days whereas lipase may remain
elevated even up to 2 weeks (Table 51.2).
Table 51.2 Markers of severity of acute pancreatitis
Markers of severity within 24 hours

• SIRS
• Hemoconcentration (Hct>44%)
• BISAP
(B) Blood urea nitrogen >22 mg%
(I) Impaired mental status
(S) SIRS
(A) Age >60 years
(P) Pleural effusion
• Organ failure
– Cardiovascular: BP <90 mm Hg, Heart rate >130
– Pulmonary: PAO2 <60 mm Hg
– Serum Creatinine >2.0 mgs%
Markers of severity during hospitalization
• Persistent organ failure
• Pancreatic necrosis
• Hospital-acquired infection
Chapter 51 Acute Pancreatitis 391
Nonpancreatic Causes for Increased Serum Amylase

• Upper gastrointestinal perforation
• Biliary peritonitis
• Intestinal infarction
• Macroamylasemia.
Other Blood Investigations

• Leukocytosis
• Hematocrit >44% (hemoconcentration)
• BUN >22 mg/dL (loss of plasma into peritoneal cavity)
• Hyperglycemia (↓ insulin and ↑ glucagon, glucocorticoids)
• Hypocalcemia (saponification of calcium by fatty acids in fat necrosis areas)
• Hyperbilirubinemia, increased SGOT, SGPT, ALP—seen in 10% patients
• Hypertriglyceridemia—seen in 5–10% patients
• Elevated serum LDH (>500 U/dL)—carries a poor prognosis
• Hypoxemia (PO2 <60 mm Hg)—may herald the onset of ARDS.
RADIOLOGY
• Chest X-ray—to rule out gastrointestinal perforation
• X-ray abdomen—may show gall stones and pancreatic calcification
• USG Abdomen—helps in detection of gallstones and demonstration of
pancreatic swelling and necrosis.
• CT abdomen—helps in assessing the severity of acute pancreatitis and
evaluating the complications (Table 51.3).
Table 51.3 CT severity index
Grade Findings Score

A Normal pancreas 0
B • Enlarged pancreas with irregular contour 1
• No peripancreatic inflammation
C Peripancreatic inflammation present 2
D Intrapancreatic or extrapancreatic fluid collections 3
E Two or more collections or gas in pancreas 4
Necrosis % Score
0 0
<33% 2
33–50% 4
>50% 6
CT severity index equals unenhanced CT score plus necrosis score
Maximum = 10 ≥6 = severe disease
• Perforated viscous
• Acute cholecystitis
• Acute intestinal obstruction
• Mesenteric ischemia
• Myocardial infarction
• Dissecting aortic aneurysm
• Diabetic ketoacidosis
• Pneumonia
Ranson’s criteria and APACHE II are not very useful as they are cumbersome,
require large data and do not have acceptable predictive values.
MANAGEMENT
General Measures
Patient should be kept nil per oral and enteral nutrition is supported by either
nasogastric or nasojejunal tubes. Patients with pancreatitis have severe
abdominal pain and this is relieved by giving analgesics. There is no role for
prophylactic antibiotics. However if the patient appears septic, antibiotics may
be started awaiting culture reports. If the cultures are negative, antibiotics should
be discontinued. Other drugs that have been found to be useful are octreotide
(somatostatin analogue) and gabexate mesylate (antiprotease).
Specific Measures
Necrosectomy
It is indicated in necrotizing pancreatitis with ongoing signs of pancreatic
infection such as fever, leukocytosis, etc. The various techniques available for
necrosectomy are endoscopic, retroperitoneal and percutaneous catheter (Table
51.4).
Table 51.4 Complications of acute pancreatitis
Local
• Pancreatic necrosis
• Pancreatic abscess
• Pancreatic pseudocyst
• Pancreatic ascites
• Thrombosis of blood vessels (splenic and portal vein)
• Obstructive jaundice
Systemic
• Renal: Oliguria, renal vessel thrombosis
• Cardiovascular: Hypotension, pericardial effusion
• Pulmonary: Pleural effusion, pneumonitis, ARDS
• CNS: Psychosis, fat embolism
• Others: Purtscher’s retinopathy (sudden blindness), DIC
Chapter 51 Acute Pancreatitis 393
ERCP
• Urgent ERCP—done in acute biliary peritonitis associated with cholangitis
or organ failure
• Elective ERCP—done in recurrent biliary obstruction
• ERCP with sphincterotomy—done in pancreatic duct disruptions.
BIBLIOGRAPHY
1. Akeda K, Takada T, Kawarada Y, et al. JPN guidelines for the management of acute
pancreatitis: medical management of acute pancreatitis. J Hepatobiliary Pancreat
Surg. 2006;13:42-7.
Lippincott Williams & Wilkin; 2008.
3. Cruz-Santamaría DM, Taxonera C, Giner M. Update on pathogenesis and clinical
management of acute pancreatitis. World J Gastrointest Pathophysiol. 2012;3(3):60-
70.
4. David C, Whitcomb. Acute pancreatitis. N Engl J Med. 2006;354:2142-50.
5. Dellinger EP, Tellado JM, Soto NE, et al. Early antibiotic treatment for severe acute
necrotizing pancreatitis: a randomized, double-blind, placebo-controlled study. Ann
Surg. 2007;245:674-83.
6. Eatock FC, Chong P, Menezes N, et al. A randomized study of early nasogastric versus
nasojejunal feeding in severe acute pancreatitis. Am J Gastroenterol. 2005;100:432-9.
7. Johnson CD, Besselink MG, Carter R. Acute pancreatitis. BMJ. 2014;349.
8. Longo DL, Kasper DL, Jameson JL, et al. Harrison’s principles of internal medicine,
18th edn. McGraw Hill publications; 2012.
9. Olsch UR, Nitsche R, Ludtke R, et al. Early ERCP and papillotomy compared with
conservative treatment for acute biliary pancreatitis (The German Study Group on
Acute Biliary Pancreatitis). N Engl J Med. 1997;336:237-42.
10. Papachristou GI, Muddana V, Yadav D, et al. Comparison of BISAP, Ranson’s, APACHE-
II, and CTSI scores in predicting organ failure, complications, and mortality in acute
pancreatitis. Am J Gastroenterol. 2010;105:435-41.
11. Papadakis MA, McPhee SJ, Rabow MW. Current medical diagnosis & treatment. 54th
edition. 2015.
12. Petrov MS, Shanbhag S, Chakraborty M, et al. Organ failure and infection of
pancreatic necrosis as determinants of mortality in patients with acute pancreatitis.
Gastroenterology. 2010;139:813-20.
13. Singh VK, Bollen TL, Wu BU, et al. An assessment of the severity of interstitial
pancreatitis. Clin Gastroenterol Hepatol. 2011;9:1098-103.
14. Steer ML, Perides G. Pathogenesis: How does acute pancreatitis develop? In:
Domínguez-Muñoz E, (Ed). Clinical pancreatology for practicing gastroenterologists
and surgeons. Oxford: Blackwell Publishing Ltd; 2005.pp.10-26.
15. Talukdar R, Vege SS. Classification of the severity of acute pancreatitis. Am J
Gastroenterol. 2011;106:1169-70.
16. Van Santvoort HC, Bakker OJ, Bollen TL, et al. A conservative and minimally invasive
approach to necrotizing pancreatitis improves outcome. Gastroenterology. 2011;
141:1254-63.
CHAPTER
52 TA Naufal Rizwan
ACUTE LIVER FAILURE
INTRODUCTION
Fulminant hepatic failure (FHF), acute hepatic failure and fulminant hepatitis all
refer to acute severe impairment of liver function accompanied by encephalopathy
and coma in patients who have had liver disease for less than 8 weeks.
CLASSIFICATION
The classification of acute liver failure is based on the time interval between the
development of jaundice and hepatic encephalopathy. There are two types of
classification available for acute liver failure (Tables 52.1 and 52.2).
Table 52.1 First classification
Stage Time from jaundice to hepatic encephalopathy
Hyper acute <7 days
Acute 8–28 days
Subacute 29 days–12 weeks
Table 52.2 Second classification

Stage Time from jaundice to hepatic encephalopathy
Fulminant <2 weeks
Subfulminant >2 weeks
CAUSES OF ACUTE LIVER FAILURE (TABLE 52.3)

Table 52.3 Etiology of acute liver failure
Infective Ischemic
Hepatitis virus A, B, C, D, E Ischemic hepatitis
Herpes simplex Acute Budd-Chiari syndrome
CMV Surgical shock
Drug reactions and toxins Metabolic
Acetaminophen (paracetamol) overdose Wilsons disease
Antidepressants Reyes syndrome
Halothane Fatty liver of pregnancy
Isoniazid, rifampicin
Non-steroidal anti-inflammatory drugs
Mushroom poisoning
Chapter 52 Acute Liver Failure 395
Viral Hepatitis
The most common cause for acute liver failure worldwide is acute viral hepatitis,
Hepatitis A infection being the most common. Infection with hepatitis B virus,
herpes simplex virus (HSV) and rarely hepatitis C virus (HCV) may also lead
to FHF. Fulminant liver failure due to HSV and CMV responds to acyclovir and
ganciclovir, respectively.
Acetaminophen Poisoning
The characteristic picture is of very high serum aspartate transaminase levels,
usually accompanied by a lower level of alanine transaminase. N-acetyl cysteine,
if administered within 15 hours, prevents the development of fulminant hepatic
failure in the majority of cases.
PATHOPHYSIOLOGY
Acute liver failure is characterized by liver cell death which can occur due to
apoptosis or necrosis.
CLINICAL FEATURES
Although acute liver failure patients have nonspecific symptoms such as nausea,
malaise and vomiting in the earlier stages, they rapidly develop jaundice and
hepatic encephalopathy, which can lead on to coma.
ASSOCIATIONS OF ACUTE HEPATIC FAILURE

Following are associated with acute hepatic failure:
• Hepatic encephalopathy
• Cerebral edema
• Coagulopathy
• Electrolyte and metabolic disturbances
• Infections
• Renal complications
• Pulmonary complications.
Hepatic Encephalopathy
Neuropsychiatric manifestations occurring secondary to liver dysfunction is
known as hepatic encephalopathy. Although the exact mechanism of hepatic
encephalopathy is still not fully known, the postulated mechanism is as follows:
Table 52.4 Hepatic encephalopathy scale
Grade Neurologic status

0 No abnormality detected
1 Mild lack of awareness, shortened attention span
2 Lethargy, disorientation in time, clear personality change
3 Very drowsy but responsive to stimuli, confused, gross disorientation in time or
space
4 Comatose, unresponsive to painful stimuli with or without abnormal movements
(decorticate or decerebrate posturing)
Clinical Features (Table 52.4)

The onset of encephalopathy is often sudden and the affected patients are usually
agitated and they exhibit violent behavior. They are restless with a few patients
showing personality changes too. Delusions, delirium and mania are also noted
in majority of the patients. Other features of acute liver failure include nightmares,
seizures, flapping tremor and fetor hepaticus.
Cerebral Edema
Cerebral edema with subsequent raised intracranial tension is the most common
cause of death in patients with acute liver failure.
Mechanism
• Cytotoxic hypothesis:
• Vasogenic hypothesis: Cerebral edema occurs due to changes in cerebral

blood flow and blood brain barrier.
Clinical Features
The clinical features of cerebral edema include systolic hypertension, bradycardia
and dysconjugate eye movements. Increased muscle tone and myoclonus are
also seen in a few patients. Patients with cerebral edema exhibit decerebrate
posturing and slow oculovestibular reflexes. The pupillary reaction is usually
sluggish; however, papilloedema is uncommon.
Coagulopathy
Coagulopathy predisposes to bleeding, which if severe (involving the GIT and
brain can even lead on to death. The reasons for coagulopathy in acute liver
failure are depletion of clotting factors (except factor VIII all others are produced
by the liver), increased fibrinolytic activity and diminished platelet function.
Infections
More than 90% of patients with acute liver failure have clinical or bacteriological
evidence of infection. Most of the infections are respiratory and caused by Gram
+ve organisms. Fungal infections are also common. Poor host defences, poor
respiratory effort, suppressed protective mechanisms like cough reflex and
the presence of endotracheal tubes, venous lines and urinary catheters are the
predisposing factors for infections.
Metabolic and Electrolyte Disturbances

The common metabolic abnormalities seen in acute liver failure are hypokalemia,
hypophosphatemia, hypocalcemia and hypomagnesemia. Hypoglycemia is seen
due to increased insulin levels and diminished gluconeogenesis. Respiratory
alkalosis due to hyperventilation and respiratory acidosis due to elevated ICP and
respiratory depression are also noted.
Renal Abnormalities
Renal failure is common in fulminant hepatic failure and the causes are hepato-
renal syndrome (functional renal failure occurring secondary to liver failure),
acute tubular necrosis and sepsis.
Pulmonary Complications
The various pulmonary complications associated with acute liver failure are
atelectasis, ARDS and pulmonary edema.
Investigations of acute liver failure
• Hemoglobin, platelets, WBC, prothrombin time, blood group

• Blood glucose, liver function tests, renal function tests, electrolytes
• Microbiology, viral markers for hepatitis, blood culture-aerobic and anaerobic,
sputum, urine, stool culture
• ABG
• Chest X-ray, ECG, EEG, USG abdomen, CT abdomen, CT brain
• Plasma FDP, hepatic scan, liver biopsy
PROGNOSIS
Prognosis in acute hepatic failure depends on the age of the patient, cause of the
acute liver failure, clinical course, occurrence of secondary complications, and
duration and severity of the coma.
Prothrombin time greater than 100 seconds regardless of the stage of
encephalopathy or the presence of any three of the following findings indicates
a poor prognosis in FHF caused by viral hepatitis or drug toxicity excluding
acetaminophen toxicity:
• Arterial pH <7.3
• Age <10 or >40 years
• Jaundice >7 days before the onset of encephalopathy
• Prothrombin time >50 seconds
• Serum bilirubin >18 mg/DL.
Causes of Death in Fulminant Hepatic Failure

• Neurologic complications (67%),
• Gastrointestinal hemorrhage (13%)
• Bacterial infection and sepsis (13%)
• Hemodynamic complications (8%).
TREATMENT
General Measures
Vitals like blood pressure, pulse rate and respiratory rate should be monitored.
Nasogastric tube, urinary catheter and intravenous catheter should be placed. For
patients who are in respiratory distress, endotracheal intubation and ventilation
should be considered. Blood samples for various investigations must be sent
periodically.
Specific Measures
Hepatic Encephalopathy
Hepatic encephalopathy is managed by protein-restricted diet, phosphate
enema twice daily, lactulose 30 mL twice or thrice daily and oral antibiotics
(Metronidazole, rifaximin). Sedatives should be avoided.
Cerebral Edema
The foremost thing in the management of cerebral edema is measurement of
ICP using epidural, subdural or extradural catheters. Osmotic diuretics like IV
mannitol (20%) should be used to reduce the edema. In resistant cases, surgical
decompression like craniectomy should be performed.
Hypoglycemia and Electrolyte Abormalities

Hypoglycemia is corrected by giving 100 mL of 50% glucose followed by
continuous infusion of 5% or 10% dextrose. The other electrolyte abnormalities
like hypokalemia and hypocalcemia should also be corrected appropriately
Renal Failure
Continuous arteriovenous or venovenous hemofiltration is the preferred option
if serum creatinine is >4.5 mg/d. It is better to avoid intermittent hemodialysis.
Respiratory Failure
Intubation and ventilation required to maintain normal blood gases and prevent
aspiration.
Hypotension
Hypotension is usually corrected with albumin and crystalloid. In cases not
responding to the above, vasopressors are added.
Infection
Frequent cultures should be sent to determine the bacterial growth. Prophylactic
antibiotics are usually not indicated. However, if the cultures are positive, specific
antibiotics and antifungals must be added later.
Bleeding
Gastrointestinal bleeding is managed by H2 blocker, proton pump inhibitors,
sucralfate and transfusion of fresh frozen plasma and platelets. Arterial puncture
is usually avoided.
• Artificial liver support
MARS—Molecular adsorbent recirculating system
This uses an albumin impregnated dialysis membrane and a dialysate
containing 5% human albumin. The dialysate is perfused over charcoal
and resin adsorbents and finally dialyzed to remove water-soluble toxins
including ammonia.
• Bioartificial liver support
Here, bioreactors containing viable hepatocytes in culture are used.
The various bioartificial liver support systems are:

• ‘Bioartificial Liver’ (BAL)
• ‘Extracorporeal Liver Assist Device’ (ELAD)
• ‘Berlin Extracorporeal Liver Support System’ (BELS).
LIVER TRANSPLANTATION
Liver transplantation may be a lifesaving procedure for patients with acute liver
failure and delay in implementing this therapy can be fatal.
In most centers, worsening hepatic encephalopathy, clinical evidence of
cerebral edema, and increasing prolongation of the prothrombin time after
24 to 48 hours of intensive medical treatment are used as the key factors for
recommending liver transplantation.
King’s College Hospital criteria for liver transplantation in

acute liver failure
Acetaminophen (paracetamol)
• pH <7.30 (irrespective of grade of encephalopathy)
or
• Prothrombin time >100s (INR >7), and
• Serum creatinine > 300 mmol/L in patients with grade III or IV encephalopathy
Nonacetaminophen patients
• Prothrombin time >100s (INR >7) (irrespective of grade of encephalopathy)
or
Any three of the following variables (irrespective of grade of encephalopathy)
• Age <10 or >40 years
• E tiology: Non-A–E hepatitis, ‘viral’ hepatitis no agent identified, halothane hepatitis,
idiosyncratic drug reaction
• Duration of jaundice before onset of encephalopathy >7 days
• Prothrombin time >50s (INR >3.5)
• Serum bilirubin >300 µmol/L
Contraindications
The contraindications for liver transplantation are:
• Active ongoing infection
• ARDS
• Fixed dilated pupils for prolonged periods of time (1 hour or more)
• Cerebral perfusion pressure <40 mm Hg or ICP >35 mm Hg for >1 hour.
The outcome of liver transplantation also depends on graft quality, because
grafts from incompatible blood groups, steatotic grafts, or partial or reduced-size
grafts do not produce favorable results.
Auxiliary Liver Transplantation

It is a procedure in which the native liver, which is left in place, may recover if
a transplanted auxiliary liver provides temporary support. The advantage over
conventional transplantation is the temporary need for immunosuppression.
BIBLIOGRAPHY
1. Agarwal B, Wright G, Gatt A, et al. Evaluation of coagulation abnormalities in acute
liver failure. J Hepatol. 2012;57:780.
Lippincott William & Wilkin.
3. Bernal W, Hyyrylainen A, Gera A, et al. Lessons from look-back in acute liver failure?
A single centre experience of 3300 patients. J Hepatol. 2013;59:74-80.
4. Bernal W, Wendon J. Acute liver failure. N Engl J Med. 2013;369:2525-34.
5. Caraceni P, van Thiel DH. Acute liver failure. Lancet. 1995;345:163.
6. Chai P, Samuel D. Etiology and prognosis of fulminant hepatitis in adults. Liver
Transpl. 2008;14(Suppl 2):S67-S79.
7. Dooley JS, Lok A, Burroughs AK, Heathcote J. Sherlock’s Diseases of the Liver and
Biliary System, 12th edn.
8. Lee WM, Recent Developments in acute liver failure. Best Pract Res Clin Gastroenterol.
2012;26(1):3-16.
9. Lee WM. Etiologies of acute liver failure. Semin Liver Dis. 2008;28:142.
18th edn. McGraw Hill publications; 2012.
11. Mochida S, Takikawa Y, Nakayama N, et al. Diagnostic criteria of acute liver failure: A
report by the Intractable Hepato-biliary Diseases Study Group of Japan. Hepatol Res.
2011;41:805.
12. Papadakis MA, McPhee SJ, Rabow MW. Current Medical Diagnosis & Treatment, 54th
edn. 2015.
13. Richardson P, O’Grady J. Diseases of the liver: Acute liver disease. The Pharmaceutical
Journal. 2009.
14. Schiff ER, Maddrey WC, Sorrell MF. Schiff’s Diseases of the Liver, 11th Edition.
15. Stravitz RT, Kramer DJ. Management of acute liver failure. Nat Rev Gastroenterol
Hepatol. 2009;6:542-53.
CHAPTER
53 TA Naufal Rizwan
ABDOMINAL INFECTIONS IN ICU
INTRODUCTION
It is broadly defined as the inflammation of the peritoneum secondary to
microorganisms, resulting in purulence in the peritoneal cavity. They are the
second most common cause of severe sepsis in the ICU and their mortality rate
is very high. Most of them are associated with an inflammation or perforation
process of the gastrointestinal tract.
CLASSIFICATION
Uncomplicated IAI (Intra-abdominal Infection)

Inflammation confined to the GIT without anatomic disruption—peritoneum
not involved.
Complicated IAI (Table 53.1)

Anatomic disruption present—Inflammation involves the peritoneal space too.
Localized Peritonitis
Manifest as an abscess with tissue debris, bacteria, inflammatory cells and
exudative fluid contained in a fibrous capsule.
Chapter 53 Abdominal Infections in ICU 403
Table 53.1 Organisms according to source

Source Expected organism
Primary peritonitis Young healthy female cirrhotic Streptococcus enteric gram
CAPD negatives Staphylococcus
aureus
Secondary peritonitis Stomach and duodenum Lactobacillus, Streptococcus
Biliary system E. coli, Klebsiella,
Enterococcus
Small Intestine E.coli, Klebsiella,
Lactobacillus, Enterococci,
Streptococci, Diptheroids
Distal ileum and colon Bacteroides fragilis,
Clostridium spp. E.coli,
Klebsiella, Enterobacter spp.
Tertiary peritonitis Immunocompromised Enterococcus, Candida,
Enterobacter
Staphylococcus epidermidis
Primary Peritonitis
Here, gut wall is intact (so bacteria reach via translocation across the intact gut
wall) and infection is predominantly monomicrobial.
Secondary Peritonitis
In secondary peritonitis, gut wall is not intact—perforation, laceration or necrotic
segment of the GI tract are present and infection is usually polymicrobial.
Tertiary Peritonitis
It is an infection that is persistent or recurrent at least 48 hours after appropriate
management of primary or secondary peritonitis. They are usually seen in
immunocompromised patients.
PATHOPHYSIOLOGY
Pathophysiology of abdominal infections are shown in Figure 53.1.
CLINICAL FEATURES
The clinical features depend on whether the intra-abdominal infection is
complicated or not and also on the type of peritonitis. Fever, nausea, vomiting
and abdominal pain (increased by coughing or sneezing) are the usual presenting
complaints. Examination of the abdomen shows guarding, rigidity, abdominal
tenderness and rebound tenderness. Patient lies motionless with flexed knees.
Bowel sounds are usually sluggish or absent and jaundice may be present.
Tachycardia, tachypnea and oliguria are seen if the patient develops sepsis.
Fig. 53.1 Pathophysiology of abdominal infections
INVESTIGATIONS
• Complete blood count, electrolytes, blood sugar
• Urea, creatinine, liver function tests
• ABG, serum lactate
• X-ray abdomen
• USG abdomen, CT abdomen
• Peritoneal fluid analysis—useful in spontaneous bacterial peritonitis
• Blood culture
MANAGEMENT
The three key components in the management of intra-abdominal infections are:
1. Resuscitation
2. Source control
3. Antimicrobial treatment.
Resuscitation
Patients with IAI have volume depletion as a result of vomiting, diarrhea, fever,
diminished oral intake and third space loss (due to ileus). Intravenous fluids,
blood replacement and vasopressors are required to restore the volume. Target
for volume replacement should be to achieve a mean arterial pressure (MAP) >
65 mm Hg and a central venous pressure (CVP) of 12–15 mm Hg within the first
6 hours.
Source Control
Elimination or control of the source of infection is critical in the management
of the infection. The various procedures available for controlling the source of
infection are:
• Drainage

• Debridement }
Temporary procedures
• Establishing bowel continuity
Drainage
The two types of drainage procedures available are percutaneous and open
drainage.
1. Percutaneous drainage: It is usually done under imaging guidance. It is less
invasive and more affordable. It is useful in patients who are poor surgical
candidates. However, in cases of frank bowel perforation or if there is a
significant amount of necrotic tissue present, percutaneous drainage will not
be of use.
2. Open drainage: It is indicated if generalized peritonitis or bowel necrosis is
present.
Debridement
It is a procedure wherein foreign bodies, fecal matter, hematoma, and infected or
necrotic tissues are removed.
Establishing Bowel Continuity

It is a definitive procedure in which both the anatomy and the function of
the gastrointestinal tract is restored. Single stage procedures with primary
anastomoses are the treatment of choice. The type of procedure depends on the
underlying surgical illness.
Antimicrobial Treatment (Table 53.2)

Although surgery is the mainstay of treatment in complicated IAI, systemic
antibiotics have got its own merits. They play a great role in the prevention as
well as treatment of the infection, in addition to reducing the complications. The
choice of antimicrobial regimen and duration of treatment is guided by patient
risk, which in this context, is intended to describe the risk for failure of treatment.
The conditions associated with high risk of treatment failure are health care-
associated infections, APACHE II score >15, advanced age, organ dysfunction,
immunosuppression and malignancy.
Table 53.2 Empirical management of abdominal infections
Risk of the patient Treatment

High-risk patients Piperacillin/tazobactam 3.375 g IV q6h
(or)
Cefepime 2 gm IV bid + Metronidazole 500 mg IV every 6 hours
Low-risk patients Tigecycline 100 mg IV stat followed by 50 mg IV every 12 hours
(or)
Ceftriaxone 1–2 gm IV od + Metronidazole 500 mg IV q6h
If Enterococcus is suspected, vancomycin should be added. In case of

vancomycin resistant enterococci, Daptomycin/linezolid/tigecycline should be
used. Micafungin is added if fungal cultures are positive.
DURATION OF TREATMENT
The usual duration of treatment is 5–7 days. Once patients are able to tolerate oral
intake, antibiotic therapy can be transitioned to oral dosing for the remainder
of their treatment. The commonly used oral antibiotics are either amoxycillin-
clavulanic acid or metronidazole with moxifloxacin/ciprofloxacin.
GI Colonization
Gastrointestinal tract is one of the major sources of sepsis due to the translocation
of pathogenic bacteria and this gets precipitated by the administration of
antibiotics and acid suppressants. The use of antibiotics which are nonabsorbable
can prevent colonization and recently selective decontamination is also useful
for this purpose.
Acalculous Cholecystitis
Though it is uncommon in ICU, still it typically develops in critically ill patients.
It is an acute inflammation of the gallbladder which occurs without gallstones.
Risk Factors
• Sepsis
• Major abdominal surgery
• Multiple trauma
• Patients on parenteral nutrition with extensive burns
• Prolonged illness with multiple organ system failure.
Pathophysiology
Since the etiology is unknown, it is thought to be due to gallbladder distention
with bile stasis and ischemia. There is edema of the serosa and muscular layers,
with patchy thrombosis of arterioles and venules.
Clinical Features and Diagnosis

In the conscious patient, right upper quadrant pain and tenderness, fever,
and leukocytosis are present. In the unconscious patient, fever, leukocytosis
and elevated alkaline phospatase are all features requiring further evaluation.
Ultrasonography is the diagnostic imaging of choice and it can demonstrate
abscess, biliary sludge, fluid collection around the gallbladder, distended
gallbladder with thickened wall, biliary sludge, pericholecystic fluid, and the
presence or absence of abscess formation. CT scan can also be done in case if
inconclusive with ultrasound but there is strong suspicion of the diagnosis.
Management
Acalculous cholecystitis requires immediate intervention to prevent gall-
bladder rupture. Percutaneous cholecystostomy by ultrasound or CT guidance
is the treatment of choice for these patients since most of these patients are
hemodynamically unstable. In case of an inconclusive diagnosis, percutaneous
cholecystostomy is done both for diagnosis and treatment. If patients don’t
improve with cholecystostomy, open cholecystectomy is done after the patient
is stabilized.
BIBLIOGRAPHY
1. Barie PS, Hydo LJ, Eachempati SR. Longitudinal outcomes of intra-abdominal
infection complicated by critical illness. Surg Infect (Larchmt). 2004;5(4):365-73.
2. Ben-Ami R, Rodriguez-Bano J, Arsian H, et al. A multinational survey of risk factors
for infection with extended-spectrum β-lactamase-producing Enterobacteriaceae in
nonhospitalized patients. Clin Infect Dis. 2009;49:682-90.
3. Evans HL, Raymond DP, Pelletier SJ, et al. Diagnosis of intra-abdominal infection in
the critically ill patient. Curr Opin Crit Care. 2001;7(2):117-21.
4. Leaper D. Nosocomial infection. Br J Surg. 2004;91(5):526-7.
5. Lopez N, Kobayashi L, Coimbra R. A Comprehensive review of abdominal infections.
World J Emerg Surg. 2011;6:7.
6. Mazuski JE, Sawyer RG, Nathens AB, et al. The Surgical Infection Society guidelines on
antimicrobial therapy for intra-abdominal infections: an executive summary. Surgical
Infection Society, 3rd edn. 2002.pp.161-74.
7. Menichetti F, Sganga G. Definition and classification of intra-abdominal infections.
J Chemother. 2009;21(Suppl 1):3-4.
8. Pieracci FM, Barie PS. Management of severe sepsis of abdominal origin. Scand J Surg.
2007;96(3):184-96.
9. Sartelli M, Catena F, Ansaloni L, Coccolini F. Complicated intra-abdominal infections
worldwide: the definitive data of the CIAOW study. World Journal of Emergency
Surgery. 2014;9:37.
10. Solomkin JS, Mazuski JE, Baron EJ, et al. Guidelines for the selection of anti-infective
agents for complicated intra-abdominal infections. Clin Infect Dis. 2003;37:997-1005.
11. Solomkin JS, Mazuski JE, Bradley JS, et al. Diagnosis and management of complicated
intra-abdominal infection in adults and children: guidelines by the Surgical Infection
Society and the Infectious Diseases Society of America. Surg Infect (Larchmt). 2010,
11(1):79-109.
12. Solomkin JS, Mazuski JE, Bradley JS, Rodvold KA. Diagnosis and management of
complicated intra-abdominal infection in adults and children: Guidelines by the
Surgical Infection Society and the Infectious Diseases Society of America; Oxford
Journals, Medicine & Health, Clinical Infectious Diseases. 2010;50(2):133-64.
13. Swenson BR, Metzger R, Hedrick TL, et al. Choosing antibiotics for intra-abdominal
infections: what do we mean by “high risk”? Surg Infect (Larchmt). 2009;10:29-39.
14. T Herzog, AM Chromik, W UhL. Treatment of complicated intra-abdominal infections
in the era of multidrug resistant bacteria. European Journal of Medical Research.
2010;15:525-32.
SECTION
13
HEMATOLOGICAL DISORDERS
IN INTENSIVE CARE UNIT
Chapter 54 Hemolytic Anemia and Sickle

Cell Crisis
Vinoj
Chapter 55 Disseminated Intravascular

Coagulation and Heparin-induced
Thrombocytopenia
Vinoj
Chapter 56 Immune Thrombocytopenic

Purpura
Vinoj
CHAPTER
54 Vinoj
HEMOLYTIC ANEMIA AND SICKLE

CELL CRISIS
HEMOLYTIC ANEMIA
Hemolytic anemia is a group of blood disorders where the lifespan of red blood
cells is reduced to less than 120 days. Hemolysis can occur extravascularly or
intravascularly among which extravascular hemolysis is the most common,
which occurs due to RBC deformability. Intravascular hemolysis occurs due
to mechanical trauma to RBC or due to complement fixation or toxic factors
against RBC. The principal clinical manifestations of hemolytic anemia are
anemia and jaundice. Along with these features splenomegaly is specifically
seen in extravascular hemolysis due to hyperplasia of phagocytes. Whereas
hemoglobinemia, hemoglobinuria, hemosideremia are more commonly seen
in intravascular hemolysis. Hemolytic anemias can be episodical or continuous.
The hemolytic anemias can be classified into intrinsic RBC defect or due to
external factor.
Intrinsic RBC Defect

• Inherited genetic defect
• Membrane disorders
– Hereditary spherocytosis
– Hereditary elliptocytosis
• Enzyme deficiency
– HMP shunt—G6PD deficiency
– Glutathione synthetase deficiency
– Glycolytic—pyruvate kinase deficiency
– Hexokinase deficiency
• Hemoglobinopathies
– Sickle cell anemia
– Thalassemia
– Unstable hemoglobinemia
– Methemoglobinemia
• Membrane lipid abnormalities
– Abetalipoproteinemia
• Acquired genetic defect
• Paroxysmal nocturnal hemoglobinuria
412 Section 13 Hematological Disorders in Intensive Care Unit
Extrinsic Factors
• Immune-mediated destruction
– Hemolytic disease of newborn
– Transfusion reactions
– Drug-induced—dapsone, nalidixic acid, nitrofurantoin, primaquine,
sulfonamides, penicillins, cephalosporins, procainamide, a methyl
dopa, NSAIDs.
– Autoimmune disorders.
• Mechanical trauma
– HUS/TTP
– DIC
– Defective cardiac valves
– Repetitive physical trauma like Marathon running, etc.
• Infections
– Malaria
– Babesiosis.
• Toxic injury
– Clostridial sepsis
– Snake venom
– Lead poisoning.
• Sequestration
• Hypersplenism.
Diagnosis
Hemolytic anemia can be severe in ICU due to various causes such as aplastic
crisis in patient with chronic hemolytic anemia, DIC, sepsis with bacteria releasing
hemolytic toxin, autoimmune cause. Hemolytic anemia should be suspected in
case of failure of rise in hematocrit in spite of blood transfusion, increased LDH
and raised indirect bilirubin, hemoglobinuria. Patients are pale, jaundiced, have
hepatosplenomegaly due to extramedullary erythropoiesis. Haptoglobin binds
free intravascular hemoglobin and is cleared through the liver, resulting in a low
serum haptoglobin level. Differences between intravascular and extravascular
hemolysis is shown in Table 54.1.
Table 54.1 Differences between intravascular and extravascular hemolysis
Intravascular Extravascular
Investigation hemolysis hemolysis
Hemoglobin/hematocrit ↓ ↓
Lactate dehydrogenase ↑ ↑
Indirect bilirubin ↑ ↑
Reticulocyte count ↑ ↑
Osmotic fragility - Present
Coombs’ test (direct antiglobulin test) Positive Positive
DIC screen (includes FDP, D dimer and others) Positive Positive
Flow cytometry CD55, CD59 Positive Negative
Chapter 54 Hemolytic Anemia and Sickle Cell Crisis 413
Complications
Anemia, jaundice, acute kidney injury, acute lung injury, acute heart failure,
shock, DIC, thromboembolic episodes, electrolyte disturbances, predispose
infections, aplastic crisis, iron overload are common in patients with hemolytic
anemias since they are on frequent red cell transfusions. Iron overload can cause
liver and cardiac dysfunction.
Treatment
Folic acid supplementation is given for all patients with hemolytic anemia
at a dose of 5 mg for acute hemolytic crisis and 1 mg for chronic hemolytic
anemia. Packed red cells transfusion may be needed during exacerbation
and hemodynamic instability. Post-splenectomy patients are more prone for
infections, hence in case of suspected infections, antibiotics should be started.
Iron chelating agents like parenteral deferoxamine remove 10–20 mg/day or oral
deferasirox. In patients with chronic hemolytic anemia who has aplastic crisis
due to parvovirus infection will require red cell transfusion support for a week.
Serial reticulocyte count can be done to monitor recovery.
SICKLE CELL CRISIS

Sickle cell anemia is an autosomal recessive disorder in which abnormal
hemoglobin leads to chronic hemolytic anemia. A single DNA base change leads
to amino acid substitution of valine for glutamine in sixth position on beta globin
chain.
Pathophysiology
HbS on deoxygenation polymerizes reversibly to form gelatinous polymers
that stiffen the RBC membrane, increase viscosity and cause dehydration due
to ionic leak. These changes produce sickle-shaped cell that loses the ability to
traverse the small capillaries. These altered sticky cells abnormally adhere to the
endothelium of venues and cause microvascular obstruction leading to tissue
ischemia, acute pain, and end-organ damage.
Clinical Manifestation
Patients with sickle cell crisis present with hemolytic anemia, reticulocytosis
and granulocytosis also occur. Patients are pale, jaundiced and can have
hepatosplenomegaly. Vaso-occlusion can be triggered by fever, changes in
temperature, hypoxia or infections. This causes ischemia in musculoskeletal and
connective structures which is manifested by acute pain, tenderness, fever, and
tachycardia. When these occur recurrently, it is called as painful crises. Pain can
last for a few hours to weeks. Repeated crises requiring hospitalization (>3 per
year) is associated with decreased survival in adult life. Acute chest syndrome
is due to in situ sickling in lung which, in turn, causes chest pain, tachypnea,
fever, cough, arterial oxygen desaturation. Bone ischemia can occur due to
aseptic necrosis of femoral and humeral heads. Other manifestations are chronic
arthropathy, salmonella osteomyelitis, hand-foot syndrome—painful infarcts of

digits and dactylitis, retinal hemorrhage, neovascularization and detachments,
renal papillary necrosis—isosthenuria, stroke, increased susceptibility to
pneumococcal infection—autosplenectomy, priapism.
Lab Findings
Hematocrit 15–30%, granulocytosis, sickle cells constituting 5–50% RBC,
reticulcytosis, Howel jolly bodies, hemoglobin electrophoresis—HbS 85–98% of
Hb, reactive thrombocytosis, rise in indirect bilirubin levels.
Management of Crisis
Acute painful crisis is managed with vigorous hydration and evaluation of the
precipitating cause and analgesia with patient controlled analgesia (PCA). PCA
is given with morphine. Morphine is given at a dose of 0.1–0.15 mg/kg every 3–4
hour for severe pain. Skeletal pain is treated with Ketorolac 30–60 mg initially
followed by 15–30 mg every 6–8 hour. Short-term pain relief can be given with
nitrous oxide but it has the adverse effect of causing diffusion hypoxia, hence
should be given only after consultation with anesthesiologist. It is given along
with oxygen to prevent hypoxia. NSAIDs are given for arthropathy.
Mainstay of treating sickle cell anemia is administration of hydroxyurea.
Hydroxyurea is indicated for patients with repeated episodes of acute chest
syndrome or with more than three crises per year requiring hospital admission.
It increases fetal Hb and causes suppression of the granulocyte and reticulocyte
count (WBC and reticulocytes play a major role in the pathogenesis of crisis). It
is given at a dose of 10–30 mg/kg per day and dose is titrated to keep white cell
count between 5000 and 8000/µL. Hydroxyurea improves survival. Azacytidine
and decitabine can also be used for this purpose but there is increased incidence
of complications. Bone marrow transplantation is the most effective way to treat
sickle cell anemia but more commonly used in children.
Acute chest syndrome is an emergency which requires ICU admission.
Oxygen therapy is given to treat hypoxemia and steps are taken to evaluate and
treat pneumonia and pulmonary embolism since they are common in sickle
cell crisis. Red cell transfusion is given to maintain Hb >10 g/dL and exchange
transfusion is done in case of arterial desaturation. Complications like pulmonary
hypertension, cardiomyopathy, and renal failure are causes of mortality in sickle
cell disease patients.
BIBLIOGRAPHY
1. Colledge NR, Walker BR, Ralston S, Davidson S. Davidson’s Principles and Practice of
Medicine, 22nd edn. Edinburgh. Churchill Livingstone/Elsevier. 2005.
2. Dacie J. The Hemolytic Anemias. London: Churchill Livingstone; 1985-95.
3. Johnson CS. The acute chest syndrome. Hematol Oncol Clin North Am. 2005;19:857-
79.
4. Longo DL, Kasper DL, Jameson JL, Fauci AS, et al. Harrison’s principles of internal
medicine, 18th edn. McGraw Hill publications; 2012.
Chapter 54 Hemolytic Anemia and Sickle Cell Crisis 415
5. Ohene-Frempong K. Indications for red cell transfusion in sickle cell disease. Sem
Hematol. 2001;38[Suppl 1]:5-13.
6. Steinberg MH. Management of sickle cell disease. N Engl J Med. 1999;340:1021-30.
7. Steinberg MH. Pathophysiologically based drug treatment of sickle cell disease.
Trends Pharmacol Sci. 2006;27:204.
8. Switzer JA, et al. Pathophysiology and treatment of stroke in sickle-cell disease:
Present and future. Lancet Neurol. 2006;5:501.
9. Vichinsky Ep, Neumayr Ld, Earles An, Williams R, Lennette Et, Dean D, et al. Causes
and outcomes of the acute chest syndrome. In: Sickle cell disease. N Engl J Med.
2000;342(25):1855-65.
10. Yale Sh, Nagib N, Guthrie T. Acute chest syndrome. In: Sickle cell disease. Crucial
considerations in adolescents and adults. Postgraduate Medicine. 2000;107(1):215-
8,221-2.
CHAPTER
55 Vinoj
DISSEMINATED INTRAVASCULAR
COAGULATION AND HEPARIN-INDUCED
THROMBOCYTOPENIA
DISSEMINATED INTRAVASCULAR COAGULATION

Disseminated intravascular coagulation (DIC) is a syndrome where there is
inappropriate thrombin activation leading to excessive blood protease activity
resulting in widespread intravascular fibrin formation which overcomes
anticoagulant mechanisms. Causes of DIC is given in Table 55.1.
Pathophysiology
The activation of thrombin leads to the following:
• Fibrinogen conversion to fibrin
• Platelet activation and consumption
• Factors V and VIII activation
• Protein C activation
• Endothelial cell activation
• Fibrinolysis.
Table 55.1 Causes of DIC
Common clinical causes of disseminated intravascular coagulation

• Infections—bacterial, viral, mycotic
• Trauma
• Tissue injury—fat embolism, rhabdomyolysis, extensive burns
• Immunological disorders—acute hemolytic transfusion reaction, organ or tissue
transplant rejection, Graft-versus-host disease
• Obstetric complications—Abruptio placenta, amniotic-fluid embolism, septic abortion,
intrauterine death
• Snakebite, insect bite
• Liver disease—fatty liver of pregnancy, cirrhosis, fulminate hepatic failure
• Carcinomas
• Massive transfusion
• Severe shock
• ARDS
• Drugs—warfarin, fibrinolytic agents, prothrombin concentrate, aprotinin
Chapter 55 Disseminated Intravascular Coagulation and Heparin-induced… 417
Uncontrolled thrombin activation leads to consumption of coagulation

factors and platelets along with fibrin deposition in microcirculation. This
causes red cell damage, hemolysis and organ damage due to ischemia.
Secondary fibrinolysis leads to release of D-dimer. Diffuse bleeding occurs due to
consumption of coagulation factors and thrombocytopenia.
Clinical Features
The patients with DIC can have varied spectrum of clinical manifestations from
thrombosis to bleeding according to the imbalance of hemostasis present in the
patient. Patients can be asymptomatic with laboratory evidence of DIC but no
bleeding or thrombosis which is usually seen in carcinomas or sepsis. Bleeding
can occur from venipuncture sites or from GIT, liver, lung, can present with
petechiae, ecchymosis. Bleeding is due to a combination of coagulation factor
depletion, platelet dysfunction, thrombocytopenia, and excessive fibrinolysis.
These patients may present with diffuse bleeding from multiple sites. Thrombosis
can occur due to activation of clotting process leading to venous thrombosis.
Lab Findings
It is based on the finding the cause of DIC. Platelet count, RBC count, coagulation
profile—aPTT, PT, thrombin time (TT) and markers of fibrin degradation
products (FDPs) and analysis of the bloodsmear. These investigations should be
repeated every 8 hours. In DIC, PT/aPTT are prolonged. Thrombocytopenia is
present with the elevated FDP levels. FDP level is the most sensitive test for DIC.
The D-dimer test is more specific for detection of fibrin and it indicates that the
cross-linked fibrin is dissolved by plasmin. Levels of AT-III and plasminogen are
reduced.
Treatment
Treatment of the underlying cause is the primary mode of management and
management of complications is based in the result of coagulation tests. Most of
the patients with DIC are critically ill and hence they may need respiratory and
hemodynamic support.
Patients with thrombocytopenia and reduced coagulation factors require
replacement therapy with FFP or cryoprecipitate or platelets. PT is a good
indicator for assessing severity of clotting factors consumption. In case of low
fibrinogen level or fibrinolysis, 10 U of cryoprecipitate is given for every 2–3 U
of FFP to correct the hemostasis. In case of severe thrombocytopenia, platelet
transfusion is done at a dose of 1–2 units for every 10 kg body weight.
Heparin, antifibrinolytics, AT-III can be given to control coagulation.
Continuous heparin infusion at a dose of 5–10 U/kg/hour can be given for patients
with known thrombosis or with carcinomas known to cause thrombosis. Heparin
is also given for patients with intrauterine fetal death although these agents have
not been to improve mortality. Antifibrinolytic drugs like epsilon-aminocaproic
acid (EACA), or tranexamic acid prevents fibrin degradation by plasmin which
in turn may reduce bleeding episodes in patients with DIC and hyperfibrinolysis
although there is always a risk of thrombosis. Purpura fulminans associated with

acquired protein C deficiency can be treated with protein C.
HEPARIN-INDUCED THROMBOCYTOPENIA
Heparin-induced thrombocytopenia (HIT) is caused by antibodies directed
against antigens on platelet factor 4. IgG antibodies mediate this process by
binding to heparin-PF4 and Fc receptors. This causes generation of platelet
microparticles which are prothrombotic due to binding of clotting factors and
thrombin.
Type I — it is reversible and has effects on the pulmonary vasculature.
Type II—progressive and severe thrombocytopenia associated with
thrombosis mostly fatal.
Clinical Features
Heparin-induced thrombocytopenia (HIT) is more common in females and
patients who are in unfractionated heparin than low-molecular-weight heparin.
Patients have thrombocytopenia and it usually begins 3–14 days after commencing
heparin infusion or it can occur within hours in a patient previously exposed to
heparin. It is unusual for the platelet count to fall below 1,00,000/µL and 50%
decrease of platelet count from the baseline value should raise the suspicion of
HIT. It is more common in post surgery patients. HIT is associated with arterial or
venous thrombosis but more commonly venous thrombosis.
Investigations
Heparin-induced thrombocytopenia (HIT) can be diagnosed by enzyme-linked
immunosorbent assay (ELISA) for antibodies against heparin-PF4 complex.
More specific test is serotonin release assay.
Management
Heparin should be discontinued and an alternative anticoagulant should
be initiated to prevent or to treat thrombosis. Alternative anticoagulants are
lepirudin, argatroban, bivalirudin, or fondaparinux. Platelet transfusions are not
indicated and should be avoided since it may even initiate or worsen thrombosis.
Patients with HIT have to be treated with parenteral anticoagulants till the platelet
count returns to normal after which warfarin can be started. In case of patients
with HIT who require urgent surgery may receive heparin once platelet activation
has been blocked with antiplatelet drugs like aspirin or ticlopidine. LMWHs can
be tested in the laboratory using serotonin release before patient administration
although they also can cause HIT.
Platelet Dysfunction
Critically ill patients develop platelet dysfunction due to uremia or it is drug-
induced. Clinical manifestations are bleeding. Qualitative platelet dysfunction
Chapter 55 Disseminated Intravascular Coagulation and Heparin-induced… 419
can be treated with desmopressin 0.3 μg/kg IV every 12 hours which increases von
Willebrand’s Factor (vWF) levels and improves platelet aggregation. Conjugated
estrogens 0.6 mg/kg IV every day for 5 days are also effective but peak action
takes several days. Dialysis is the treatment of choice for patients with platelet
dysfunction resulting in bleeding.
BIBLIOGRAPHY
Medicine, 22nd edn. Edinburgh: Churchill Livingstone/Elsevier; 2005.
2. Levi M, Cate HT. Disseminated intravascular coagulation. N Engl J Med. 1999;341:586.
3. Levi M. Disseminated intravascular coagulation: what’s new. Crit Care Clin.
2005;21:449.
5. Osterud B, Bjorklid E. The tissue factor pathway in disseminated intravascular
coagulation. Semin Thromb Hemost. 2001;27:605.
6. Pixley RA, De La Cadena R, Page JD, et al. The contact system contributes to
hypotension but not disseminated intravascular coagulation in lethal bacteremia. J
Clin Invest. 1993;91:61.
7. Wada H. Disseminated intravascular coagulation. Clinica Chimica Acta. 2004;344:13.
8. Warkentin TE, Kelton JB. A 14-year study of heparin-induced thrombocytopenia. Am
J Med. 1996;101:502.
9. Warkentin TE, Levine MN, Hirsh J, et al. Heparin-induced thrombocytopenia in
patients treated with low-molecular-weight heparin or unfractionated heparin. N Eng
J Med. 1995;332:1330.
10. Weiner CP. The obstetric patient and disseminated intravascular coagulation. Clin
Perinatol. 1986;13:705.
CHAPTER
56 Vinoj
IMMUNE THROMBOCYTOPENIC PURPURA
Immune thrombocytopenia (ITP) is an autoimmune-mediated hematological

disorder affecting platelets. Here the immune system produces antibodies
directed against platelet antigens, resulting in platelet destruction and
suppression of platelet production in the bone marrow. ITP is estimated to affect
approximately 3.3/100,000 adults per year and 6.4/100,000 children/year. The
incidence of ITP increases with age and, among adults between the ages of 18
and 65 years, is slightly higher in women than in men.
PATHOGENESIS
Evidence is now convincing that the syndrome of ITP is caused by platelet
destruction as the result of an immunologic process. Platelet survival is greatly
shortened and thrombocytopenia in ITP appears to result from the action of a
platelet antibody. The responsible factor is an immunoglobulin of the IgG class
that is species specific. As acute ITP associated with antecedent viral infection,
a viral antigen-antibody complex, may be responsible for platelet sensitization
and destruction in ITP. Spleen also is important in ITP as a site of production of
platelet antibodies. In chronic ITP, an immunoglobulin has been demonstrated
on the surface of the megakaryocytes producing impaired thrombopoises.
Patients with ITP can develop additional antibodies to other tissues and organs.
For example, thyroid tissue.
CLASSIFICATION OF IMMUNE THROMBOCYTOPENIC PURPURA

Immune thrombocytopenia purpura (ITP) is defined as isolated thrombocyt
openia (platelet count < 100 × 109/L) with no associated causes or disorders.
Traditionally, ITP has been classified as:
• Acute: Sudden onset, lasting less than 6 months
• Chronic: Persisting more than 6 months
• Refractory: Persistently low platelet counts despite appropriate treatment or
splenectomy.
Chapter 56 Immune Thrombocytopenic Purpura 421
CLINICAL FEATURES
Immune thrombocytopenia purpura (ITP) is a diagnosis of exclusion and history
is elicited for any drug intake and infection (HIV and hepatitis C). Isolated
thrombocytopenia is present.
Acute ITP
Acute ITP occurs most frequently in children 2–6 years, it rarely affects adults and
has no gender predilection. The onset of the disorder usually is sudden. A history
of infection preceding the onset of bleeding may be present. Acute ITP usually is
self-limited. Spontaneous remissions occur in as many as 90% of patients. The
duration of the disease ranges from a few days to a few months.
Chronic ITP
Chronic ITP affects persons of all ages, but it is relatively more common between
puberty and 50 years of age. It occurs more frequently in women than in men, a
ratio of approximately 3:1 has been found. The onset of the chronic form of the
disorder usually is insidious. Patients usually have a fluctuating clinical course.
Episodes of bleeding may last a few days or a few weeks, and may be intermittent
or even cyclic. Spontaneous remissions are uncommon.
Bleeding Manifestations
• Petechiae or purpura
• Unusual or easy bruising
• Persistent bleeding symptoms from cuts or other injuries
• Mucosal bleeding
• Frequent or heavy nasal bleeding
• Hemorrhage from any site (usually gingival or menorrhagia in women).
LABORATORY FINDING
Blood
• Isolated thrombocytopenia is the essential abnormality
• Abnormalities in platelet size and morphologic appearance are common
• Prolonged bleeding time
• Absent or deficient clot retraction
• A positive reaction to the tourniquet test
• Deficient prothrombin consumption.
Prothrombin time, partial thromboplastin time, and coagulation time, are normal
in patients with uncomplicated thrombocytopenia.
The Marrow
Increased marrow megakaryocytes with a shift to younger, less polyploid
megakaryocytes and fewer mature, platelet-producing megakaryocytes has been
commonly reported.
Tests for Platelet Antibodies

Assays of PAIgG represent the first sensitive and reproducible method for
demonstrating antibodies in ITP.
TREATMENT
1st Line Therapy

Corticosteroids
Corticosteroids are the standard initial treatment for patients with ITP.
Corticosteroids prevent the destruction of platelets by macrophages within the
spleen and liver thereby increasing platelet levels. The first-line treatment option
is prednisone 0.5–2 mg/kg/day until the platelet count increases to over 30–50
× 109/L. Corticosteroids are usually prescribed as a short-term treatment (3–4
weeks). On stopping treatment, dose should always be tapered.
Immunoglobulins
Immunoglobulins are used to desensitize the immune system. Usually a dose of
1 g/kg body weight is given for 2–3 days. IVIg is indicated for patients at high risk
of bleeding or before surgery to increase platelet counts. The response to IVIg is
rapid but generally transient lasting between 2 and 4 weeks. Repeat infusions of
IVIg at regular intervals can be done to maintain the platelet count at a safe level.
Concomitant use with corticosteroids can attenuate the response.
2nd Line Therapy
Immunosuppressants
In patients with severe symptomatic ITP, more intensive immunosuppression
may be required. Azathioprine response rates can be slow and patients should
receive continuous treatment for at least 4 months before being considered
unresponsive. Cyclosporin A can be used alone or in combination with
prednisone. Mycophenolate mofetil is an antiproliferative immunosuppressant
that has been used in a limited manner.
Corticosteroid-sparing Agents
Danazol is an attenuated androgen originally developed to treat endometriosis.
The response rate is around 60%, with older patients appearing to respond better.
Chapter 56 Immune Thrombocytopenic Purpura 423
Dapsone has anti-inflammatory and immunomodulatory effects. Response rates

of around 50% have been reported. Dapsone may be particularly useful in elderly
patients or if splenectomy is contraindicated.
Monoclonal Antibodies
Rituximab is a chimeric monoclonal antibody that binds to the CD20 surface
antigen present on B-cells and acts as an immunosuppressant. Rituximab is
widely used even though it is not indicated for ITP and the optimal dose has not
been established.
Splenectomy
Splenectomy is indicated for patients who are refractory or intolerant to
corticosteroids and have severe thrombocytopenia, bleeding or both. It is
recommended to wait at least 6 months from diagnosis before performing a
splenectomy in case of spontaneous remission.
Thrombopoietin Receptor Agonists

Thrombopoietin receptor agonists mimic the action of the body’s endogenous
thrombopoietin to stimulate the production of platelets in bone marrow. Unlike
other available therapies they are not immunosuppressive. Two thrombopoietin
receptor agonists are currently available—eltrombopag, a daily oral medication,
and romiplostim, a once-weekly subcutaneous injection. Both are indicated
for adult splenectomized patients who have ITP refractory to other treatments
such as corticosteroids and immunoglobulins, and as second-line therapy for
nonsplenectomized patients in whom surgery is contraindicated. A response
(increase in platelet count) is usually seen within 1–2 weeks of treatment initiation
in both splenectomized and nonsplenectomized patients. If there is no response
to the highest dose after 4 weeks, the patient can be considered unresponsive.
Vinca Alkaloids
Vinca alkaloids, such as vincristine and vinblastine, are used in cancer to inhibit
tumor cell growth. In ITP, vinca alkaloids may inhibit phagocytic cell function
through binding to platelet microtubules, which may help localize treatment to
the platelet-destroying phagocytic cells.
EMERGENCY TREATMENT OF ACUTE BLEEDING

In patients with severe bleeding, in addition to conventional critical care measures,
appropriate treatment includes platelet transfusions, high-dose parenteral
glucocorticoids, and IVIg. Platelet transfusions may produce some increase in
platelet numbers in many patients, often diminish bleeding for a time, and can
be effective in the management of serious complications, e.g. subarachnoid
hemorrhage. They should be reserved for such life-threatening emergencies or
for the immediate preoperative treatment of patients with serious hemorrhage
before splenectomy. Dose of intravenous immunoglobulin is 1 g/kg/day for 2–3

days. Methylprednisolone is given at a dose of 1 g/day for 3 days.
BIBLIOGRAPHY
1. Arnold DM, et al. Systematic review: efficacy and safety of rituximab for adults with
idiopathic thrombocytopenic purpura. Ann Intern Med. 2007;146(1):25-33.
2. British Committee for Standards in Haematology General Haematology Task Force.
Guidelines for the investigation and management of idiopathic thrombocytopenic
purpura in adults, children and in pregnancy. Br J Haematol. 2003;120(4):574-96.
3. Bussel JB, et al. Eltrombopag for the treatment of chronic idiopathic thrombocytopenic
purpura. N Engl J Med. 2007;357(22):2237-47.
4. Civetta JM, Taylor RW, Kirby RR. Critical care, 4th edn. Philadelphia: Lippincott-
Raven; 2009.
5. Dutta TK, et al. Dapsone in treatment of chronic idiopathic thrombocytopenic
purpura in adults. J Assoc Physicians India. 2001;49:421-5.
6. Kaushansky K. Thrombopoietin. N Engl J Med. 1998;339(11):746-54.
7. Kuter DJ, et al. Efficacy of romiplostim in patients with chronic immune thrombo
cytopenic purpura: a double-blind randomized controlled trial. Lancet. 2008;371
(9610):395-403.
9. Maloisel F, et al. Danazol therapy in patients with chronic idiopathic thrombocytopenic
purpura: long-term results. Am J Med. 2004;116(9):590-4.
10. Provan D. Characteristics of immune thrombocytopenic purpura: a guide for clinical
practice. Eur J Haematol. 2009;82(Suppl 71):8-12.
11. Provan D, et al. International consensus report on the investigation and management
of primary immune thrombocytopenia, Blood, 2009.
SECTION
14
ENDOCRINE DISORDERS IN
INTENSIVE CARE UNIT
Chapter 57 Diabetic Ketoacidosis

Chapter 58 Hyperosmolar Hyperglycemic State

Vinoj, Ninoo George
Chapter 59 Diabetes Insipidus

Vinoj, Ninoo George
Chapter 60 Syndrome of Inappropriate

Secretion of Antidiuretic Hormone
Vinoj, Ninoo George
Chapter 61 Thyroid Emergencies

Vinoj, Ninoo George
Chapter 62 Adrenal Emergencies

Vinoj, Ninoo George
CHAPTER
57 Vinoj, G Ninoo George
DIABETIC KETOACIDOSIS
Diabetic ketoacidosis (DKA) is a life-threatening metabolic disorder resulting

from decreased effective circulating insulin, insulin resistance and increased
production of counter-regulatory hormones. The frequency of DKA ranges
from 16% to 80% of children newly diagnosed with diabetes, depending
on geographic location. It is the leading cause of morbidity and is the most
common cause of diabetes-related deaths in children and adolescents with type
1 diabetes. Mortality is predominantly due to cerebral edema. While it occurs
predominantly in type 1 diabetic patients at the time of diagnosis, it can also
happen in type 2 diabetes when medications are inadequately managed. DKA
and HHS (hyperosmolar hyperglycemic hyperosmolar state) are present along
a spectrum of hyperglycemia, with or without ketosis. DKA constitutes a triad of
hyperglycemia, ketonemia and high anion gap metabolic acidosis which is given
in Figure 57.1.
It is characterized by
Fig. 57.1 Triad of diabetic ketoacidosis
Laboratory parameters observed in diabetic ketoacidosis are as follows. Blood

glucose concentration is usually around 250–600 mg/dL, plasma ketones are >3
mmol/L, serum bicarbonate is <15 mEq/L and arterial pH is in the range of 6.8
– 7.3 with increased anion gap. DKA and HHS are differentiated by the following
parameters (Table 57.1).
428 Section 14 Endocrine Disorders in Intensive Care Unit
Table 57.1 DKA and HHS should be differentiated based on lab parameters
DKA HHS
Glucose, mmol/L (mg/dL) 13.9–33.3 (250–600) 33.3–66.6 (600–1200)
Osmolality (mOsm/mL) 300–320 330 -380
Plasma ketones ++++ +/–
Arterial pH 6.8–7.3 >7.3
Arterial PCO2, mm Hg 20–30 Normal
Anion gap [Na–(Cl + HCO3)] ↑ Normal to mild ↑
Serum bicarbonate, mEq/L <15 mEq/L Normal to mild ↓
Creatinine Mild ↑ Moderate ↑
Sodium, mEq/L 125–135 135–145
Potassium Normal to ↑ Normal
Abbreviations: DKA, diabetic ketoacidosis, HHS, hyperosmolar hyperglycemic
PRECIPITATING FACTORS
Several factors are known to precipitate ketoacidosis. The predominant ones are
as follows.
• Inadequate insulin therapy
• New onset diabetes (20–25%)
• Infections (30–45%)
• Cerebrovascular accident, myocardial infarction, acute pancreatitis
• Drugs: Clozapine, olanzapine (atypical antipsychotics)
• Trauma, surgery
• Pregnancy.
BASIC PATHOPHYSIOLOGY OF DIABETIC KETOACIDOSIS

(FLOW CHART 57.1)
• Absolute or relative insulin deficiency
• Increased counter regulatory hormones
• Decreased insulin/glucagon ratio promotes
– Gluconeogenesis
– Glycogenolysis
– Ketone body formation
- b-hydroxybutyrate is the major constituent
- Acetone produces the fruity breath odor
- Acetoacetate is commonly detected by sodium nitroprusside test.
CLINICAL FEATURES
Symptoms
• ausea, vomiting (induced by β hydroxybutyrate)
N
• Thirst/polyuria
Chapter 57 Diabetic Ketoacidosis 429
Flow chart 57.1 Pathogenesis of diabetic ketoacidosis
• bdominal pain
A
• Shortness of breath.
Signs
• achycardia
T
• Dehydration/hypotension
• Tachypnea/respiratory distress/Kussmaul’s respiration
• Acetone smell breath
• Abdominal tenderness
• Lethargy/loss of consciousness.
MANAGEMENT GOALS
ASSESSMENT AND MONITORING

• Find out the factors which precipitated the event
• Measure capillary glucose every 1–2 hour during treatment
• Serum electrolytes: K+, Na+, Mg+, Cl–, bicarbonate, phosphate and anion gap
every 4 hours for the first 24 hours.
• Acid base status: pH , HCO3–, PCO2, β hydroxybutyrate
• Renal function: Creatinine, Urine Output
• Monitor blood pressure, pulse, respirations, mental status, fluid intake and
output every 1–4 hour.
FLUID REPLACEMENT
• Average fluid loss will be around 3–5 L
– 3 L extracellular—replace with saline
– 3 L intracellular—replace with dextrose
• Administer 2–3 L of 0.9% saline over first 1–3 hours (15–20 mL/kg/hour)
• Switch over to 0.45% saline at 250–500 mL/hour (when hemodynamic
stability and adequate urine output are achieved).
• Change to 5% glucose in 0.45% saline when plasma glucose reaches 200 mg/
dL.
INSULIN THERAPY
Short-acting regular insulin is preferred. Administer bolus dose of 0.1 U/kg IV.
Start insulin infusion 0.1 U/kg/hour and increase the dose to 2-3 times if there
is no response in 2–3 hours. If the initial serum potassium is <3.3 mmol/L (3.3
mEq/L), do not administer insulin until the potassium is corrected. If the initial
serum potassium is >5.2 mmol/L (5.2 mEq/L), do not supplement K+ until the
potassium is corrected. IV insulin should be continued until the acidosis resolves
(when serum bicarbonate is >18 mEq/L). Once acidosis resolves, taper the dose
of insulin to 0.5 U/kg/hour. Hyperglycemia usually improves at a rate of 75–100
mg/dL. Plasma glucose should be maintained at 150–200 mg/dL complications
of DKA are given in detail in Table 57.2.
ELECTROLYTE CORRECTION
Replace potassium of 10 mEq/hour when plasma K+ <5.0–5.2 mEq/L (or 20–30
mEq/L of infusion fluid) and ECG is normal, and there is documented normal
urine flow and normal creatinine. Administer 40–80 mEq/h when plasma K+ < 3.5
mEq/L or if bicarbonate is given. The goal is to maintain the serum potassium at
>3.5 mmol/L (3.5 mEq/L).
Despite a bicarbonate deficit bicarbonate replacement is not usually
necessary. However, in case of severe acidosis where arterial pH <6.9, sodium
bicarbonate of 50 mEq/L is added in 200 mL of sterile water with 10 mEq/L KCl
per hour for 2 hours until the pH is >7.0. Phosphate replacement is beneficial
when serum phosphate is <1 mg/dL. Hypomagnesemia may develop during
Chapter 57 Diabetic Ketoacidosis 431
Table 57.2 Complications of DKA
Cerebral edema
It is the leading cause of mortality in children and is caused due to idiogenic osmoles
which stabilizes brain cells from shrinking while DKA is developing
Hypokalemia
• Precipitated by failing to correct the potassium deficit
• This is caused by rehydration and insulin therapy which not only corrects acidosis but
also facilitates potassium reentry into the cell
Hypoglycemia
Due to inadequate monitoring
Acute pulmonary edema
Due to excessive fluid therapy
Other complications
Cortical vein thrombosis, myocardial infarction, acute gastric dilatation, erosive gastritis,
late hypoglycemia, respiratory distress, infections, hypophosphatemia
Abbreviations: DKA, diabetic ketoacidosis
therapy and which may require supplementation. Patient is shifted to long-acting

insulin once the patient is started on oral diet.
BIBLIOGRAPHY
1. American Diabetes Association. Clinical practice recommendations, 2002. Diabetes
Care. 2002;25(Suppl)1:S1-147.
2. Atkin SH, et al. Fingerstick glucose determination in shock. Ann Intern Med. 1991;
114(12):1020-4.
Medicine, 22nd edn. Edinburgh: Churchill Livingstone/Elsevier publications.
4. Emergency Nurses Association. Medical emergencies. In: ENPC provider manual,
2nd edn. Park Ridge (IL): The Association. 1999.p.273-301.
5. Jabbour SA, Miller JL. Uncontrolled diabetes mellitus. Clin Lab Med. 2001;21(1):99-
110.
6. Kearney T, et al. Diabetic and endocrine emergencies. Postgrad Med J. 2007;83(976):79-
86.
7. Kitabchi AE, et al. Hyperglycemic crises in adult patients with diabetes. Diabetes Care.
2009;32:1335.
Principles of Internal Medicine. McGraw Hill publications; 2012(18).
9. National Center for Chronic Disease Prevention and Health Promotion. Diabetic
ketoacidosis. In: Diabetes surveillance, Atlanta (GA): Centers for Disease Control and
Prevention; 1999.
10. Westphal SA. The occurrence of diabetic ketoacidosis in noninsulin-dependent
diabetes and newly diagnosed diabetic adults. Am J Med. 1996;101(1):19-24.
CHAPTER
HYPEROSMOLAR HYPERGLYCEMIC STATE
Hyperosmolar hyperglycemic state (HHS) is a life-threatening emergency

manifested by marked elevation of blood glucose, hyperosmolarity, and little
or no ketosis. It is reported in all age groups, but it most frequently affects older
patients with type 2 diabetes. The hallmark of hyperosmolar hyperglycemic
state is profound dehydration, marked hyperglycemia, and often some degree of
neurologic impairment with mild or no ketosis. The mortality rate of hyperosmolar
hyperglycemic state ranges from 10% to 50%. Precipitating factors of HHS is given
in Table 58.1.
PATHOPHYSIOLOGY
The initiating event in hyperosmolar hyperglycemic state is glucosuric diuresis.
Glucosuria impairs the concentrating capacity of the kidney, further exacerbating
water loss. Under normal conditions, the kidneys act as a safety valve to eliminate
glucose above a certain threshold and prevent further accumulation. However,
decreased intravascular volume or underlying renal disease decreases the
glomerular filtration rate, causing the glucose level to increase. The loss of more
water than sodium leads to hyperosmolarity. Although insulin is present, it is not
adequate to reduce blood glucose levels, particularly in the presence of significant
insulin resistance.
Table 58.1 Precipitating factors in hyperosmolar hyperglycemic state
• Coexisting diseases
– Acute myocardial infarction
– Cerebrovascular accident
– Cushing’s syndrome
– Hyperthermia/Hypothermia
– Pancreatitis
– Renal failure
• Infection
• Medications like calcium channel blocker, chlorpromazine, glucocorticoids, phenytoin
• Noncompliance
• Substance abuse
• Undiagnosed diabetes
Chapter 58 Hyperosmolar Hyperglycemic State 433
CLINICAL FEATURES
Patients typically present with weakness, visual disturbance, or leg cramps.
Nausea and vomiting may occur, but are much less frequent than in patients
with diabetic ketoacidosis. Eventually, patients develop neurologic symptoms of
lethargy, confusion, hemiparesis or seizures. Physical findings reveal profound
dehydration that is manifested by poor tissue turgor, dry buccal mucosa
membranes; soft, sunken eyeballs; cool extremities; and a rapid, thready pulse.
A low-grade fever often is present. Abdominal distention may occur because of
gastroparesis induced by hypertonicity. Various changes in mental status may
manifest, ranging from complete lucidity to disorientation to lethargy to coma.
Laboratory Findings
Typical laboratory findings in hyperosmolar hyperglycemic state include blood
glucose levels greater than 600 mg per dL, serum osmolarity greater than 320
mOsm/kg, pH levels greater than 7.30, and mild or absent ketonemia. DKA and
HHS are differentiated by the following parameters (Table 58.2).
Management
• IV 0.9% saline
• Correction of any hypokalemia
• IV insulin (as long as serum K is ≥3.3 mEq/L)
Fluid loss is more pronounced in HHS than DKA. Treatment is 0.9% saline
solution 1–3 liter intravenously over the first 2–3 hours, then at 1 L/hour to raise
blood pressure and improve circulation and urine output. If the serum sodium
>150 mmol/L (150 mEq/L), 0.45% saline should be used. It can be replaced by
0.45% saline when blood pressure becomes normal and plasma glucose reaches
300 mg/dL. The rate of infusion of IV fluids should be adjusted depending on
blood pressure, cardiac status, and the balance between fluid input and output.
Table 58.2 Diabetic ketoacidosis (DKA) and hyperosmolar hyperglycemia state

(HHS) should be differentiated based on lab parameters
DKA HHS
Glucose, mmol/L (mg/dL) 13.9–33.3 (250–600) 33.3–66.6 (600–1200)
Osmolality (mOsm/mL) 300–320 330–380
Plasma ketones ++++ +/–
Arterial pH 6.8–7.3 >7.3
Arterial PCO2, mm Hg 20–30 Normal
Anion gap [Na – (Cl + HCO3)] ↑ Normal to mild ↑
Serum bicarbonate, mEq/L <15 mEq/L Normal to mild ↓
Creatinine Mild ↑ Moderate ↑
Sodium, mEq/L 125–135 135–145
Potassium Normal to ↑ Normal
The average water deficit in HHS patients is 8–10 liters and fluid infusion should
be done over 1–2 days at 200–300 mL/hour. Insulin is given at 0.1 U/kg IV bolus
followed by a 0.1 unit/kg/hour infusion after the first liter of saline has been
infused.
Hydration alone can sometimes precipitously decrease plasma glucose,
so insulin dose may need to be reduced. A too-quick reduction in osmolality
can lead to cerebral edema. Once plasma glucose reaches 300 mg/dL, insulin
infusion should be reduced to basal levels (1–2 units/h) until rehydration is
complete and the patient is able to eat. Target plasma glucose is between 250
and 300 mg/dL. Addition of 5% dextrose infusion may occasionally be needed to
avoid hypoglycemia. After recovery from the acute episode, patients are usually
switched to adjusted doses of subcutaneous insulin. Most patients can resume
using oral hypoglycemic drugs once their condition is stable.
Potassium replacement is similar to DKA

• 40 mEq/h for serum K <3.3 mEq/L
• 20 to 30 mEq/h for serum K between 3.3 and 4.9 mEq/L
• None for serum K ≥5 mEq/L.
BIBLIOGRAPHY
1. American Diabetes Association. Clinical practice recommendations. Diabetes Care
2002;25(Suppl 1):S1–147.
Medicine, 22nd edn. Edinburgh: Churchill Livingstone/Elsevier publications.
3. Emergency Nurses Association. Medical emergencies. In: ENPC provider manual.
2nd edn. Park Ridge (IL): The Association; 1999.pp.273–301.
4. Kearney T, et al. Diabetic and endocrine emergencies. Postgrad Med J. 2007;83(976):
79–86.
5. Kitabchi AE, et al. Hyperglycemic crises in adult patients with diabetes. Diabetes Care.
2009;32:1335.
Principles of Internal Medicine. 18th edn. McGraw Hill publications; 2012.
CHAPTER
DIABETES INSIPIDUS
Diabetes insipidus is a rare syndrome characterized by the excretion of abnormal

large volumes of dilute urine (polyuria) and a concomitant increase in fluid
intake (polydipsia). Types of diabetes insipidus is given in Table 59.1.
VASOPRESSIN: NEURAL HORMONE

• Synthesis of the arginine vasopressin (AVP) and oxytocin precursors occurs
in the cell bodies of magnocellular neurosecretory neurons within the
supraoptic nucleus and paraventricular nucleus of the hypothalamus
• They migrate along the axons and get stored in secretory granules within the
terminals of the magnocellular neurons in the posterior pituitary
• Vasopressin exerts its antidiuretic effect via V2 receptors in kidney and
involves insertion of protein water channels called aquaporin.
• Vasopressin-responsive water channel in the collecting ducts is aquaporin-2
Table 59.1 Types of diabetes insipidus
Type of DI Causes Underlying mechanism
Nephrogenic diabetes Lack of renal sensitivity to

Acquired or genetic
insipidus circulating AVP
Excessive fluid intake despite

Compulsive/habitual
Primary polydipsia normal AVP levels and
excessive intake of fluids
sensitivity to the hormone
Lack of AVP due to increased
Gestational diabetes metabolism of vasopressin by
Pregnancy
insipidus the enzyme vasopressinase,
produced by the placenta
Central diabetes
Disease, trauma, genetic
insipidus (pituitary/ Lack of production of AVP
mutation
neurohypophyseal/cranial)
ETIOLOGY
Nephrogenic Diabetic Insipidus

Nephrogenic diabetes insipidus (NDI), which can be congenital or acquired,
results from failure of the kidney to respond to vasopressin.
Congenital Nephrogenic DI
• X-linked (90-95%) caused by mutation of V2 receptor gene (AVPR2) is located
at chromosome region Xq28
• Autosomal dominant or autosomal recessive present in 5–10 % of patients
caused by mutation of Aquaporin 2 gene (AQP2) located at chromosome
region 12q13
• Sporadic nephrogenic DI with mental retardation and intracerebral
calcification
Acquired Nephrogenic DI
• Acquired metabolic abnormalities—Hypokalemia, hypercalcemia
• Drugs—lithium, amphotericin b, diphenylhydantoin, foscarnet, cidofovir
• Medullary Damage—chronic pyelonephritis, cystinosis, sickle cell disease
chronic renal failure, obstructive nephropathy, infiltrative disease (leukemia,
lymphoma, amyloidosis).
Central Diabetic Insipidus

Central diabetes insipidus is caused due to decreased vasopressin production.
Acquired
• Idiopathic
• Tumors—Craniopharyngioma, germinoma, hypothalamic metastases
(especially breast carcinoma), hypothalamic glioma, large pituitary tumors
with suprasellar extension, lymphoma
• Intracranial surgery
• Head injury
• Granulomata — sarcoidosis, tuberculosis (TB), wegener’s, histiocytosis
• Infections—encephalitis, meningitis, cerebral abscess
• Vascular disorders—hemorrhage/thrombosis, aneurysms, sickle cell
disease, sheehans syndrome (postpartum pituitary necrosis)
• Postradiotherapy.
Inherited
• Autosomal recessive combination of diabetes insipidus, diabetes mellitus,
optic atrophy, deafness (DIDMOAD)—Wolfram syndrome
• Autosomal dominant mutations of vasopressin gene.
Chapter 59 Diabetes Insipidus 437
Gestational Diabetes Insipidus

This condition results from degradation of vasopressin by placental
vasopressinase. Gestational diabetes insipidus may be associated with increased
complications of pregnancy, including pre-eclampsia. Treatment for most cases
of gestational diabetes insipidus is with the synthetic hormone desmopressin.
Primary Polydipsia (Dipsogenic Diabetes Insipidus)

It is caused by a primary defect in osmoregulation of thirst. Dipsogenic diabetes
insipidus has been reported in tuberculous meningitis, multiple sclerosis, and
neurosarcoidosis.
Clinical Manifestations of Diabetes Insipidus

The most common symptom in people with diabetes insipidus is passing large
volumes of urine (Polyuria). This usually means that there is a need to go to the
toilet frequently, often during the night, which results in disturbed sleep. Bladder
control usually remains normal.
Large losses of water from the body results in a great increase in thirst
(Polydipsia), to make up for the lost fluid. Therefore in individuals with diabetes
insipidus, thirst becomes the regulator of water balance in the body. A person
with diabetes insipidus may drink 6–20 liters of water per day, although in partial
diabetes insipidus the amounts may be less.
Other signs may include needing to get up at night to urinate (nocturia) and
bed-wetting (enuresis). Patient may also present with:
• Hypernatremic dehydration
• Anorexia, constipation
• Hyperthermia and lack of sweating
• Symptoms of underlying cause
Infants and young children who have diabetes insipidus may have the
following signs and symptoms:
• Unexplained fussiness or inconsolable crying
• Unusually wet diapers
• Fever, vomiting or diarrhea
• Dry skin with cool extremities
• Delayed growth
• Weight loss.
Lab Investigations
• Biochemistry
– Plasma glucose, urea and electrolytes
– Plasma and urine osmolality
• Water deprivation test and response to desmopressin (Table 59.2). The patient
is deprived of fluids for up to 8 hours or 5% loss of body weight, following
which desmopressin (DDAVP) 2 µg (IM) is given. Plasma vasopressin levels
and osmolality in response to infusion of 5% hypertonic saline at 0.05 mL/
kg/minute for two hours may be measured in cases of diagnostic difficulty.
Table 59.2 Classification of causes of diabetes insipidus (DI) on basis of water

deprivation and DDAVP response
Urine osmolality after fluid Urine osmolality after

deprivation (mOsm/kg) DDAVP (mOsm/kg) Likely diagnosis
<300 >800 Central DI
<300 <300 Nephrogenic DI
>800 >800 Primary/psychogenic polydipsia

<300 >800 Partial central DI or nephrogenic
DI or primary/psychogenic
polydipsia or diuretic abuse
• A therapeutic trial of low-dose desmopressin is another option, with careful

monitoring of plasma osmolality or serum sodium. Central DI patients
improve, and those with nephrogenic DI are unaffected. Those with
psychogenic polydipsia develop hyponatremia and may stop drinking.
• MRI of the pituitary, hypothalamus and surrounding tissues, including the
pineal gland, may be contributory in helping to determine the underlying
cause.
• Renal tract ultrasound or intravenous pyelogram (IVP) may be used to assess
for obstructive complications caused by the high urinary back-pressure.
Treatment of Central Diabetes Insipidus

• Since the primary problem is hormone deficiency, physiological replacement
with desmopressin is usually effective. Criteria for desmopressin adminis
tration is given in Table 59.3.
• Desmopressin (DDAVP) acts on the distal tubules and collecting ducts of
the kidney to increase water reabsorption, as a long-acting analog of anti-
diuretic hormone (ADH).
Available Formulations
• Intranasal solution—100 µg/mL
• Intranasal spray (10 µg/spray)
• Parenteral (IM/IM)—4 µg/mL used rarely
• Oral—200 µg/tablet (roughly 10 µg intranasal dose is approximately
equivalent to 200 µg orally).
Table 59.3 Criteria for desmopressin administration
Desmopressin should be administered only after the below criteria are fulfilled:
• Serum sodium is >145 mmol/L
• Urine output exceeds 4 mL/kg/hr (calculated 6 hourly)
• Urine specific gravity is 1.005 or less (dilute urine output)
Chapter 59 Diabetes Insipidus 439
Administration—Principles
• Under 2 years, dose is usually 2–5 µg intranasally
• ≥2 years, dose is similar to adult dose (5–10 µg /day)
• Dosage effect is based on all or nothing principle—in general, the dose
determines the duration of action and not the degree of response
• Oral dose has slower onset/offset of action, therefore not useful in acute
situation
• Nasal administration is operator dependent—also need to consider
effectiveness, if problems with nasal mucosa such as intercurrent upper
respiratory infection, hayfever, etc.
• Careful fluid balance needs to be maintained to prevent fluid overload/
hyponatremia.
Mild cases of DI (urine output 3-4 liters/24 hours) can be managed by
ingestion of water to quench thirst. It is essential to avoid chronic overdosage
with desmopressin since it will cause hyponatremia.
Long-term Management
Because of the risk of hyponatremia, occasional (1 to 3 monthly) measurements
of serum sodium are advised. Some endocrinologists recommend skipping
desmopressin administration for one day each week to avoid the development
of hyponatremia.
Treatment of Nephrogenic Diabetes Insipidus

If daily urine volume is < 4 liters for 24 hours and the patient is not suffering
from severe dehydration, then definitive therapy is not always necessary.
It is essential to drink water and to drink enough to satiate their thirst. Any
metabolic disturbance is corrected and in case of any suspicion of any drug
causing the condition, it should be stopped. High-dose DDAVP can be used with
success in mild-to-moderate cases of nephrogenic DI. Combination treatment
with a thiazide diuretic and/or amiloride in combination with prostaglandin
synthesis inhibitor and low-sodium diet may be effective in reducing polyuria
and polydipsia. Patients with nephrogenic DI undergoing surgery need careful
multidisciplinary management with close attention to fluid regimens and
DDAVP administration. Patients with genetic causes or severe nephrogenic DI
may need to practice clean, intermittent catheterization to reduce urinary tract
back-pressure complications.
COMPLICATIONS
DDAVP can worsen myocardial ischemia in susceptible patients. There may
be a need for nitrates/other antianginal medications. Patients with genetic
causes of nephrogenic DI are prone to bladder dysfunction and hydroureter/
hydronephrosis if the condition is undiagnosed or untreated for an appreciable
period of time.
BIBLIOGRAPHY
1. Bichet D. Vasopressin receptor mutations in nephrogenic diabetes insipidus. Semin
Nephrol. 2008;28:245.
2. Cooperman M. Diabetes insipidus. http:// emedicine.medscape.com/article/117648.
Updated June 17, 2011. Accessed January 9, 2012.
3. Loh JA, et al. Disorders of water and salt metabolism associated with pituitary disease.
Endocrinol Metab Clin North Am. 2008;37(1):213–34.
4. Makaryus AN, et al. Diabetes insipidus: diagnosis and treatment of a complex disease.
Cleve Clin J Med. 2006;73(1):65–71.
5. Sands JM, Layton HE. Urine concentrating mechanism and its regulation. In: Seldin
DW, Giebisch G (Eds). The Kidney: Physiology and Pathophysiology, 3rd edn.
Philadelphia: Lippincott Williams and Wilkins; 2000.pp.1175-216.
6. Zerbe RL, Robertson GL. A comparison of plasma vasopressin measurements
with a standard indirect test in the differential diagnosis of polyuria. N Engl J Med.
1981;305:1539-46.
CHAPTER
SYNDROME OF INAPPROPRIATE
SECRETION OF ANTIDIURETIC HORMONE
INTRODUCTION
The syndrome of inappropriate secretion of antidiuretic hormone (SIADH) is
a disorder of impaired water excretion caused by the inability to suppress the
secretion of antidiuretic hormone (ADH). It is one of the most common causes
of hyponatremia in critically-ill patients. It is commonly under-diagnosed and
often mismanaged due to poor understanding of its pathophysiology. SIADH
is one of the medical conditions where the treatment, if inappropriate, can
be more damaging than the disease itself. However, if diagnosed and treated
appropriately, the condition is easily reversible and one can avoid unnecessary
disease or treatment-related morbidity and mortality.
PATHOPHYSIOLOGY
The knee-jerk reaction of many physicians on seeing hyponatremia in a patient
is to initiate normal saline, with the presumption that hyponatremia always
occurs due to loss of sodium from the body. While this is true in depletional
hyponatremia (e.g. diarrhea), in most other cases of hyponatremia, this concept
is fundamentally wrong. It is imperative to understand that hyponatremia is
more of a disorder of water metabolism than sodium metabolism, with ADH
being a key-player in initiation and maintenance of hyponatremia. Hence, any
disturbance in ADH secretion will manifest itself as changes in serum sodium
concentration.
Before moving into the pathophysiology of SIADH, let us understand normal
water metabolism in our body. Water metabolism in humans is synonymous with
ADH metabolism. The prime function of ADH is to maintain serum osmolality in
the normal range of 285–295 mOsm/kg.
Serum osmolality >295 mOsm/kg causes stimulation of thirst and ADH
release (ADH acts on the kidney leading to conservation of water, which reflects
in production of concentrated urine). When serum osmolality <285 mOsm/kg,
ADH secretion stops, thereby leading to production of dilute urine. This dilute
urine excretes the excess free water restoring serum osmolality to normal.
Majority of cases of hyponatremia (>99%) which are clinically encountered
are of the hypoosmolar type, since serum sodium is the principal determinant
of serum osmolality. So extrapolating from our previous discussion, when

hyponatremia occurs (i.e. serum osmolality <285 mOsm/kg), ADH secretion
should stop and urine should become dilute. If this compensation occurs, then
the water gain will be excreted and serum sodium (i.e. serum osmolality) will be
restored to normal.
Apart from serum osmolality, another major stimulus for ADH release is
effective arterial blood volume (EABV). When a person becomes volume depleted
(e.g. diarrhea, dehydration, etc.) or EABV is low (e.g. CCF, cirrhosis, nephrotic
syndrome), irrespective of his serum osmolality. ADH will be released (because
the body is programmed in such a way to think that effective circulating blood
volume is more important than serum osmolality).
From Table 60.1, one can understand that in any type of hyponatremia, ADH
is elevated. Volume status should be identified in case of ↑ADH. If patient has
effective volume depletion, then ADH is getting released appropriately. If patient
does not have effective volume depletion, then ADH is released inappropriately
as in SIADH (Flow chart 60.1).
Causes of SIADH
The usual causes of SIADH are malignancies, pulmonary and neurologic diseases.
However, even severe pain, nausea and stress can lead to inappropriate ADH
release. Postoperative patient suffering from pain, nausea and stress is prone to
SIADH supported by the fact that they are put on intravenous dextrose infusions
for nutritional support. The various causes of SIADH are summarized in Table 60.2.
Table 60.1 Differential diagnosis of SIADH
S. Serum osmolality
No. Cause and sodium ADH level
1. Depletional Serum osmolality ADH elevated
Hyponatremia low
(Diarrhea, Serum sodium low Although according to serum osmolality,
vomiting, ADH should be suppressed, but since
burns, renal patient is volume depleted, ADH will
loss, etc.) be released. Thus, there is water gain
causing hyponatremia in these conditions
2. Hypervolemic Serum osmolality ADH elevated
hyponatremia low
(CCF, cirrhosis, Serum sodium low Although patient is fluid overloaded, but
nephrotic) since patient’s EABV is depleted, ADH
will be released. Thus, there is water gain
causing hyponatremia in these conditions
3. SIADH Serum osmolality ADH elevated
(nausea, pain, low
stress, CNS, Serum sodium low There is no physiologic stimulus for
pulmonary ADH release like osmolality or volume
disorders, etc.) depletion. However, due to certain
nonphysiologic stimulus, ADH is
inappropriately released leading to water
gain and hyponatremia
Chapter 60 Syndrome of Inappropriate Secretion of Antidiuretic Hormone 443
Flow chart 60.1 Pathogenesis of hyponatremia
Table 60.2 Causes of SIADH
Pulmonary
Carcinomas disorders Nervous system disorders Other
Bronchogenic Bacterial and Encephalitis (viral or AIDS - HIV
and duodenal viral pneumonia bacterial)
carcinoma
Carcinoma of Tuberculosis Meningitis (viral, bacterial, Idiopathic (elderly)
the pancreas tuberculous, and fungal)
Gastric Pulmonary Head trauma Prolonged exercise
carcinoma abscess
Thymoma Positive pressure Brain abscess an tumors
ventilation
Carcinoma of Asthma Subarachnoid hemorrhage
the bladder or subdural hematoma
Lymphoma Mesothelioma Cerebellar and cerebral
atrophy
Ewing’s sarcoma Cystic fibrosis Cavernous sinus thrombosis
Carcinoma of Pneumothorax Guillain–Barré syndrome

the prostate
Carcinoma of Acute intermittent porphyria
the ureter
Oropharyngeal
carcinoma
Table 60.3 Diagnostic criteria of SIADH
Diagnostic criteria of SIADH

• Hyponatremia <135 mmol/liter together with decreased effective serum osmolality
< 275 mOsm/kg
• Urinary osmolality >100 mOsm/kg
• Absence of heart, kidney and liver disease
• Urinary sodium concentration >40 mmol/liter, unless taking diuretics or on a severe
salt restriction
• Normal adrenal and thyroid function
• Failure to correct hyponatremia by infusion of 0.9% NaCl
• Successful correction of hyponatremia by fluid restriction/vaptans
Clinical Features of SIADH

The clinical features of SIADH are secondary to the effects of hyponatremia. Thus
the symptoms can vary from giddiness, gait disturbance, frequent falls, memory
disturbance and cognitive defects in mild hyponatremia to altered sensorium,
drowsiness, seizures and coma in extreme cases. More importantly, one should
try to find out the presence of any underlying condition like malignancy, lung or
neurologic diseases, which adds credence to the diagnosis of SIADH.
Diagnosis of SIADH (Table 60.3)

A rare differential diagnosis is cerebral salt-wasting syndrome. Its laboratory
parameters resemble SIADH, although the spot urinary sodium concentration is
usually much greater than 30–40 mmol/liter, sometimes exceeding 150 mmol/
liter. Clinically, patients with cerebral salt-wasting syndrome cannot be subjected
to fluid restriction since it would lead to hypovolemia and hypotension and they
may require infusion of 0.9% or 3% NaCl to maintain blood pressure.
In clinical practice, the distinction between euvolemia and hypovolemia
is difficult, thereby in such situations it would be helpful to infuse 0.9% NaCl of
about 500–1000 mL over 12 hours and observe any alterations of serum sodium
and the urinary sodium. In euvolemic SIADH, serum sodium will not change
appreciably in response to 0.9% NaCl, but the urinary sodium will increase.
Conversely, in hypovolemic hyponatremia the saline infusion will improve the
serum sodium, leaving the urinary sodium more or less unchanged. A different
type of clinical problem may arise from the combined occurrence of two etiologies
of hyponatremia at the same time (Flow chart 60.2).
Treatment of SIADH
Various modalities have been tried in the treatment of SIADH. A brief discussion
of the various modalities is mentioned here.
Free Water Restriction

Since the primary pathology in SIADH in retention of free water. Free water
restriction is of prime importance to prevent further worsening of hyponatremia
Flow chart 60.2 Differential diagnosis of hyponatremia
and may in some instances to correct hyponatremia. The normal osmolar load
of a person’s diet that needs to be excreted in urine daily is ~ 600 mOsm. Free
water intake from oral intake and intravenous fluids should generally be < 1–1.5
liters/day and total intake of all liquids should be at least 500 mL less than urinary
output. Thus, the amount of free water restriction that needs to be done depends
on the urine osmolality. If the urine osmolality is very high (say more than 600
mOsm/L), then free water restriction less than 500 mL daily is required.
Increasing Osmolar Load in Diet

If the osmolar load is increased in the diet, then more free water is required to
excrete the load, thus increasing free water clearance. This was previously one of
the mainstays of treatment before vaptans became available. One can increase
the osmolar load in diet by using salt tablets, urea, protein, etc. Urea in dosages
of 10–40 g/day results in osmotic diuresis and enhanced water excretion. The
drawback of urea is its taste; not all patients will accept it.
Overcoming ADH Action

Demeclocycline, an antibiotic (600–1200 mg/day), and lithium carbonate,
an antidepressant (600–900 mg/day), may both cause nephrogenic diabetes
insipidus, thus overcoming the action of ADH. This effect has been used to treat
the hyponatremia of SIADH. However, nephrogenic diabetes insipidus takes 2–4
days to come about, does not occur in all patients receiving these agents, may be
associated with renal toxicity (in the case of lithium), and corrects hyponatremia
rather slowly by 2–4 mmol/liter/day. These drugs are not currently used very
often to correct hyponatremia.
Role of Vaptans
The recent introduction of parenteral (conivaptan) and orally available (tolvaptan)
antagonists to the renal V-2 vasopressin receptor—collectively called vaptans—
has been considered a breakthrough. Conivaptan was originally developed as
an oral preparation but is now available on the market as intravenous parenteral
conivaptan. Eligible patients are treated in hospital. An initial loading dose of 20
mg over 30 minutes is recommended. This is followed by a continuous infusion
at a rate of 20 mg/day for up to 4 days. In a study by Velez et al. this regimen
increased the serum sodium from 121.7 to 129.2 mmol/liter within the first
24 hour of treatment. Lower serum sodium, lower blood urea nitrogen, and higher
estimated glomerular filtration rate (eGFR) at baseline were correlated with a
larger absolute increase in serum sodium at 24 hour. The following adverse events
have been noted—infusion site reactions, including thrombophlebitis, postural
hypotension, hypotension, mild-to-moderate increases in blood urea nitrogen or
creatinine, and significantly increased thirst. Four of 42 patients corrected their
hyponatremia too fast (Zeltser et al. 2007). No osmotic demyelination was noted.
Tolvaptan is available as a tablet, usually taken once a day in the morning. The
recommended dosage for SIADH is 15–30 mg/day. Patients receiving tolvaptan
should discontinue any previous fluid restriction and drink fluids freely though
not excessively. The treatment should be initiated under close supervision by
the hospital (as an outpatient or an inpatient). When given in this way, tolvaptan
increased serum sodium from approximately 128–136 mmol/liter within 4 days
in one study.
When vaptans are used, it is critical to monitor levels for the first 24 hour–
exclude a too rapid correction rate. Any fluid restriction should be discontinued
and drinking encouraged. Any increase in serum sodium of >6 mmol/liter by
6th hour of treatment is likely to result in a rise of >10 mmol/liter at 24 hours. In
such cases, water should be given orally or intravenously [(by infusion, e.g. of 5%
dextrose in water (D5W)] at hour 6 of treatment to slow the rate of correction. There
is the possibility of a too rapid correction rate in cases of severe hyponatremia
(<<120 mmol/liter) and in those with a high eGFR at baseline. It may not be
always necessary to continue treatment until a serum sodium concentration of
136 mmol/liter or higher has been achieved; in some patients, symptoms will
disappear at a serum sodium concentration of 130 mmol/liter.
Use of Hypertonic Saline

One of the common errors in clinical practice is to initiate normal saline (0.9%) for
SIADH. This is potentially dangerous and can lead to worsening of hyponatremia.
However, with use of 3% saline, hyponatremia can be corrected in SIADH. One
method to calculate the rate of correction is provided by the Adrogué–Madias
formula (see formula ). The formula calculates the change in the serum sodium
concentration that is expected to result from an infusion of saline solution.
By comparing this total change in the serum sodium with the desired rate of
correction per hour, it is then possible to derive the hourly infusion rate. The
formula may underestimate the change in serum sodium actually achieved and
this applies to severe hyponatremia (<120 mmol/liter) in particular. Therefore, it
is advisable to follow the actual serum sodium closely, for example, every 3 hour
when infusing various concentrations of saline.
Volinf [(Nainf + Kinf ) – NaSerum]
∆Na Serum =
TBW + VolInf
where
NaSerum = Calculated change in serum sodium
Volinf = Volume of infused saline
Nainf = Sodium concentration of saline infusion
TBW = Total body water (approx 50% of body weight in women, 60% of
body weight in men)
Risk of Osmotic Demyelination Syndrome

Osmotic demyelination syndrome is a pathological condition that occurs due to
over-rapid correction of serum sodium. A correction rate of <8–10 mmol/L per
day should be strictly followed while treating SIADH. Causes of over-correction
include sudden amelioration of stimulus of ADH release, use of loop diuretics,
simultaneous correction of potassium, etc. To avoid risk of over-correction, close
monitoring of sodium every 4 hours is mandatory especially while correcting
severe hyponatremia.
BIBLIOGRAPHY
1. Adrogué HJ, Madias NE. Hyponatremia. N Engl J Med. 2000;342:1581-9.
2. Annane D, Decaux G, Smith N. Efficacy and safety of oral conivaptan, a vasopressin-
receptor antagonist, evaluated in a randomized, controlled trial in patients with
euvolemic or hypervolemic hyponatremia. Am J Med Sci. 2009;337:28-36.
3. Berl T, Quittnat-Pelletier F, Verbalis G, Schrier RW, Bichet DG, Ouyang J, et al. Oral
tolvaptan is safe and effective in chronic hyponatremia. J Am Soc Nephrol. 2010;21:
705–12.
4. Berl T. The Adrogué–Madias formula revisited. Clin J Am Soc Nephrol. 2007;2:1098-9.
5. Decaux G, Waterlot Y, Genette F, Mockel J. Treatment of the syndrome of inappropriate
secretion of antidiuretic hormone with furosemide. N Engl J Med. 1981;304:329-30.
6. Decaux G. Is asymptomatic hyponatremia really asymptomatic? Am J Med. 2006;119(7
Suppl 1):S79-82.
7. Ellison DH, Berl T. The syndrome of inappropriate antidiuresis. N Engl J Med.

2007;356: 2064-72.
8. Gross P. Clinical management of SIADH. Ther Adv Endocrinol Metab. 2012;3(2):61-
73.
9. Schrier RW, Gross P, Gheorghiade M, Berl T, Verbalis JG, Czerwiec FS, et al. Tolvaptan,
a selective oral vasopressin V2-receptor antagonist, for hyponatremia. N Engl J Med.
2006;355:2099–12.
10. Velez JCQ, Dopson SJ, Sanders DS, Delay TA, Arthur JM. Intravenous conivaptan for
the treatment of hyponatremia caused by the syndrome of inappropriate secretion
of antidiuretic hormone in hospitalized patients: a single-centre experience. Nephrol
Dial Transplant. 2010;25:1524–31.
CHAPTER
THYROID EMERGENCIES
INTRODUCTION
Thyroid emergencies are rare, life-threatening conditions resulting from either
severe deficiency of thyroid hormones (myxedema coma) or, by contrast,
decompensated thyrotoxicosis with the increased action of thyroxine (T4) and
triiodothyronine (T3) exceeding metabolic demands of the organism (thyrotoxic
storm). Another emergency condition is the thyroid ophthalmopathy.
The understanding of the pathogenesis of these conditions, appropriate
recognition of the clinical signs and symptoms, and their prompt and accurate
diagnosis and treatment are crucial in optimizing survival.
THYROID STORM
It is a dreaded fortunately rare complication of a very common disorder. It is a
life-threatening exacerbation of hyperthyroidism. It is also called thyrotoxic
crisis. It has a mortality rate up to 30%. The mortality is mainly due to cardiac
failure, arrhythmia or hyperthermia.
Clinical Features
The clinical diagnosis is based on the identification of signs and symptoms
that suggest decompensation of several organ systems. Some of these cardinal
manifestations include fever out of proportion to an apparent infection and
dramatic diaphoresis.
The other key components of thyrotoxic storm include tachycardia out
of proportion to the fever, and gastrointestinal dysfunction, which can include
nausea, vomiting, diarrhea and, in severe cases, jaundice. As the storm progresses,
symptoms of central nervous system dysfunction simulating an encephalopathic
picture will appear, which may include increasing agitation and emotional
lability, confusion, paranoia, psychosis, and coma. In older patients, thyrotoxic
storm may present as so-called masked or apathetic thyrotoxicosis.
Precipitating Factors
• Stroke
• Injection
• Trauma
• Diabetic ketoacidosis
• Surgery especially on the thyroid
• Radioiodine therapy.
Scoring (Table 61.1)

• >45 = Highly suggestive of thyroid storm
• 25–44 = Suggestive of impending storm
• <25 = Unlikely to represent storm.
Table 61.1 Burch and Wartofsky diagnostic criteria
Diagnostic parameters Scoring points

Thermoregulatory dysfunction
Temperature °F (°C)
• 99–99.9 (37.2-37.7) 5
• 100–100.9 (37.8–38.2) 10
• 101–101.9 (38.3–38.8) 15
• 102–102.9 (38.9–39.2) 20
• 103–103.9 (39.3–39.9) 25
• >/= 104.0 (>/= 40.0) 30
Central nervous system effects
• Absent 0
• Mild (agitation) 10
• Moderate (delirium, psychosis, extreme lethargy) 20
• Severe (seizures, coma) 30
Gastrointestinal-hepatic dysfunction
• Absent 0
• Moderate (diarrhea, nausea/vomiting, abdominal pain) 10
• Severe (unexplained jaundice) 20
Cardiovascular dysfunction
Tachycardia (beats/minute)
• 90–109 5
• 101–119 10
• 120–129 15
• 130–139 20
• >/= 140 25
Congestive heart failure
• Absent 0
• Mild (pedal edema) 5
• Moderate (bibasilar crepitations) 10
• Severe (pulmonary edema) 15
Atrial fibrillation
• Absent 0
• Present 10
Precipitating event
• Absent 0
• Present 10
Chapter 61 Thyroid Emergencies 451
Management
Requires a multifaceted approach:
1. Intensive monitoring and supportive care
2. Identification and treatment of the precipitating cause
3. Measures-reducing thyroid hormone synthesis.
The mainstay of treatment is to ward-off the hyperthyroidism. This requires
administration of antithyroid drugs, SSKI (5% Super Saturated Potassium Iodide),
beta-blocker—propranolol, steroids.
Pharmacologic Therapy
• Propylthiouracil is the drug of choice. It inhibits thyroid hormone synthesis
by inhibiting thyroid peroxidase enzyme as well as blocks peripheral
conversion of T3 to T4. A loading dose of 600 mg is given IV followed by 200–
300 mg 6th hourly via oral or through nasogastric tube or rectally.
• One hour after the loading dose of propylthiouracil give 5% Super Saturated
Potassium Iodide (SSKI) 6th hourly which blocks thyroid hormone synthesis
via the Wolff-Chaikoff effect. Iopanoic acid or sodium iodide may be used as
an alternative.
• Next drug to be given is the non selective β-blocker propranolol which acts by
inhibiting the peripheral conversion of T4 to T3. It controls the tachycardia.
A dose of 40–60 mg per oral 4th hourly or 2 mg IV 4th hourly can be given.
• Other supporting measures include dexamethasone 2 mg IV 6th hourly.
Antibiotics, if infection is present, cooling, administration of O2 and IV fluids.
Thyroid Ophthalmopathy
Severe thyroid ophthalmopathy with optic nerve involvement or chemosis
resulting in corneal damage is a medical emergency. A short-term high-dose
steroid is the treatment of choice.
• Prednisolone 40–80 mg daily can be combined with cyclosporine. Dose
should be tapered by 5 mg every 2 weeks.
• Pulse therapy with IV methyl prednisolone of 500–1000 mg in 250 mL normal
saline infused over 2 hour daily for 1 week followed by oral regimen.
• In case of failure of medical management, orbital decompression can be
tried.
MYXEDEMA COMA
It is an uncommon but life-threatening form of untreated hypothyroidism with
physiological decompensation. This complication occurs following cessation of
thyroid replacement medication due to poor compliance or in an undiagnosed
patient. The most common presentation of the syndrome is in hospitalized
elderly women with long-standing hypothyroidism, with 80% of cases occurring
in women older than 60 years. However, myxedema coma occurs in younger
patients as well (Table 61.2).
Table 61.2 Precipitating factors of myxedema coma
Precipitating factors
• Hypothermia
• Congestive cardiac failure
• Cerebrovascular accidents
• Myocardial infarction
• Infection
– Pneumonia
– Urinary tract infection
– Cellulitis
– Sepsis
• Drugs
– Amiodarone
– Lithium
– Respiratory depressants—sedatives, antidepressants, anesthetic agents
PATHOGENESIS
Hypoventilation, leading to hypoxia and hypercapnia, plays a major role in
pathogenesis. Hypoglycemia and dilutional hyponatremia also contribute to the
development of myxedema coma. Hypothermia produces cardiac depression
which results in diminished cardiac output and that causes a reflex peripheral
vasoconstriction. This leads to a mild diastolic hypertension and diminished blood
volume.
Clinical Features (Fig. 61.1)

Hypothermia (often profound to 26.7°C and unconsciousness constitute two
of the cardinal features of myxedema coma. Of importance is the coincident
infection may be masked by hypothyroidism, with a patient presenting as afebrile
despite an underlying severe infection. Although coma is the predominant clinical
presentation, a history of disorientation, depression, paranoia, or hallucinations
(myxedema madness) may often be elicited.
The neurologic findings may also include cerebellar signs (poorly coordinated
purposeful movements of the hands and feet, ataxia, adiadochokinesia),
poor memory and recall, or even frank amnesia, and abnormal findings on
electroencephalography (low amplitude and a decreased rate of α-wave activity).
Status epilepticus has been also described and up to 25% of patients may experience
seizures possibly related to hyponatremia, hypoglycemia, or hypoxemia.
Diagnosis
• Serum T4 and intracellular T3 levels will be low
• Serum TSH level is high
• Serum TSH level is low in central hypothyroidism which is a very rare entity
• Other investigations
– Serum electrolytes
Chapter 61 Thyroid Emergencies 453
Fig. 61.1 Clinical manifestations of myxedema coma
– ECG
– Central venous pressure monitoring
– Arterial blood gas analysis
Treatment Goals (Fig. 61.2)
Fig. 61.2 Management modalities of myxedema coma

General Measures in Management

• Airway protection from aspiration in patients with poor consciousness level
should be given utmost priority.
• It is better to avoid sedatives.
• Correction of hyponatremia.
• It may be prudent to administer 3% sodium chloride along with furosemide
so that serum sodium may be elevated by 3–4 mEq/L to tide over the
immediate crisis.
Hormone Replacement
• Thyroid hormone therapy is the backbone of treatment of patients with
myxedema coma.
• At present, oral and intravenous T4 and T3 are used.
• T4 (levothyroxine) therapy provides steady, smooth and slow onset action. It
avoids major peaks and troughs in the body. It is also easily available. It can be
given as a single bolus of 500 µg. Though repeat dose is not required for few days,
it is usually continued at a dose of 50–100 µg/day. T4 level rises acutely to levels
above normal and slowly get converted to T3. If IV preparation is not available,
levothyroxine can be given through nasogastric tube by the same initial dose.
• Advantages of liothyronine (T3) therapy:
– Early onset of action
– Beneficial effect on neuropsychiatric symptoms.
– Dose = T3 is given at a dose of 10–20 µg bolus either IV or through nasogastric
tube followed by 10 µg which is given after 24 hours and thereafter 10 µg
every 4 hourly for the next few days till patient is able to take orally.
– Liothyronine in excessive can cause arrhythmias.
• Another option is to combine levothyroxine 200 µg and liothyronine 25 µg as
single bolus dose IV followed by daily treatment with levothyroxine 50–100
µg/day and liothyronine 10 µg/8th hourly.
Predictors of Mortality
• Hypotension, bradycardia at presentation.
• Need for mechanical ventilation
• Hypothermia unresponsiveness to treatment
• Sepsis
• Low Glasgow coma score (GCS), high APACHE II and sequential organ
failure assessment (SOFA) score>6.
BIBLIOGRAPHY
Medicine, 22nd edn. Edinburgh: Churchill Livingstone/Elsevier.
Principles of Internal Medicine, 18th edn. McGraw Hill Publications; 2012.
3. Wartofsky L. Myxoedema coma, endocrinology metabolism. Clinics of North America,
2006;35:687-98.
4. Yamamoto T, Fukuyama J, Fujiyoshi A. Factors associated with mortality of myxedema
coma: report of eight cases and literature survey. Thyroid. 1999;9(12):1167-74.
Chapter 62 Adrenal Emergencies 455
CHAPTER
ADRENAL EMERGENCIES
ADRENAL CRISIS
Glucocorticoids (mainly cortisol) and mineralocorticoids (mainly aldosterone)
are important for life and its production by the adrenal glands is especially
important at times when the body experiences intense ‘stress’, such as surgery,
trauma or serious infection. If the adrenal glands cannot produce enough cortisol,
the body might not be able to cope with this kind of major stress, which can be
life-threatening.
• This situation is called adrenal crisis and is a medical emergency.
• Any patient with unexplained hypotension in the intensive care unit, think of
Adrenal crisis.
It is also known as Addisonian crisis or acute adrenal insufficiency.
Pathophysiology
The basic pathology is insufficient levels of cortisol and aldosterone. Crisis occurs
when the physiological demand for the hormones exceeds the ability of adrenal
glands to produce cortisol. This scenario usually occurs in a patient with chronic
adrenal insufficiency when subjected to an intercurrent stress or illness.
Etiology of Adrenal Insufficiency

Adrenal insufficiency arises if the adrenal glands are destroyed, absent or cannot
function. Failure of the adrenal glands themselves is called primary adrenal
insufficiency or Addison’s disease (most common) (Table 62.1).
Serum ACTH level is used to differentiate between primary and secondary
adrenal insufficiency.
PRIMARY (↑ ACTH)
Addison’s disease is most often caused by autoimmune disease where the body’s
immune system mounts an attack against its own adrenal cells. However, it can
also be caused by infection, most importantly by tuberculosis.
Sometimes both adrenal glands are surgically removed for various reasons.
This is called a bilateral adrenalectomy and is another cause of primary adrenal
Table 62.1 Etiology of adrenal insufficiency—primary and secondary causes
Primary causes
Addison’s disease
• Common causes
– Autoimmune
– Sepsis
– Hemorrhage secondary to trauma
– Tuberculosis
– HIV/AIDS
– Metastatic carcinoma
– Bilateral adrenalectomy
– Drug induced
– Critical illness
• Rare causes
– Lymphoma
– Intra-adrenal hemorrhage (Waterhouse Friedrichsen syndrome following meningo-
coccal septicemia)
– Amyloidosis
– Hemochromatosis
Corticosteroid biosynthetic enzyme defects
• Congenital adrenal hyperplasia
• Drugs
– Metyrapone
– Ketoconazole
– Etomidate
Secondary (↓ ACTH)
Withdrawal of suppressive glucocorticoid therapy
Hypothalamic or pituitary disease
insufficiency. Suppression of HPA axis can occur only after 5 days of treatment
with glucocorticoids. Patients who were on glucocorticoids for at least 1 month
and patients who discontinued glucocorticoids within the last year are candidates
who have the highest risk for adrenal suppression.
Loss of the pituitary gland ability to produce ACTH is most often caused by
a tumor in that area. Secondary adrenal insufficiency results due to the loss of
production and control of ACTH by pituitary gland.
Precipitating Factors
• Gastrointestinal infection
• Fever
• Surgery
• Burns
• General anesthesia
Table 62.2 Clinical manifestations of adrenal insufficiency
Signs and symptoms caused by glucocorticoid deficiency

Fatigue, weight loss, joint pain, myalgia
Fever, anemia, lymphocytosis, eosinophilia
Hypoglycemia, hyponatremia
Hypotension especially postural
Signs and symptoms caused by mineralocorticoid deficiency
Abdominal pain, nausea, vomiting
Dizziness
Salt craving
Low blood pressure, postural hypotension
Increased serum creatinine (due to volume depletion)
Hyponatremia
Hyperkalemia
Clinical Features
Clinical signs and symptoms of adrenal insufficiency usually develop gradually
and can include severe fatigue and weakness, loss of weight, increased
pigmentation of the skin, faintness and low blood pressure, often with a particular
drop in blood pressure shortly after standing up (postural hypotension). Other
symptoms include nausea, vomiting, salt craving and painful muscles and joints.
Hyperpigmentation occurs due to excess of pro-opiomelanocortin (POMC)-
derived peptides (Table 62.2).
Investigations
• Fasting blood sugar
• ACTH stimulation test: To establish the diagnosis of adrenal insufficiency
with confidence, a short synacthen test (SST) needs to be performed. This
test is also known as an ACTH stimulation test or a cosyntropin test. The
short synacthen test measures the ability of the adrenal glands to produce
cortisol in response to ACTH, the pituitary hormone that regulates adrenal
cortisol production. When carrying out this test, a baseline blood sample
is drawn before injecting a dose of ACTH, followed by drawing of a second
blood sample 30–60 minutes after the ACTH injection. If the adrenal
glands are healthy, cortisol production in the second sample will exceed
commonly 500–550 nmol/L. By contrast, failing adrenal glands will not be
able to produce this amount of cortisol. The term critical illness-related
corticosteroid insufficiency is used for considering adrenal function.
• Serum cortisol level: Serum-free cortisol <10 µg/dL is used as a threshold for
glucocorticoid therapy.
• Serum sodium and potassium estimation.
Treatment Goals
Volume Correction
• IV normal saline 500–100 mL for adults, 10–20 mL/kg for child.
• In severe hyponatremia (<125 mmol/L), avoid increase of plasma sodium
>10 mmol/L/day to prevent pontine demyelination.
• Fludrocortisone is not required during the acute phase of treatment.
Glucocorticoids Replacement for Primary Insufficiency

• IV hydrocortisone succinate 100 mg stat
• Continue parenteral hydrocortisone 50–100 mg IV over 24 hours and after
initial stabilization of the patient, hydrocortisone is decreased by 50% each
day.
• Maintenance dose of hydrocortisone is 20–30 mg/day.
• According to current SSC guidelines, recommendation for use of steroids
in sepsis is that intravenous hydrocortisone not routinely used to treat
patients with septic shock if hemodynamic stability is achieved with fluids
and vasopressors. If this is not possible, intravenous hydrocortisone is
used as a continuous infusion of 200 mg/day. Corticosteroids should not
be administered for the treatment of sepsis in the absence of shock and
ACTH stimulation test is done to identify patients who require steroids.
Hydrocortisone is tapered when vasopressors are not required.
• Perioperative replacement—For minor surgeries, a single supplemental dose
of 25 mg of hydrocortisone or its equivalent is given. For major surgeries,
dose of glucocorticoids is increased from 50 to 75 mg/day of hydrocortisone
or its equivalent up to 2 days.
Correction of Metabolic Abnormalities

• Acute hypoglycemia—IV 10% glucose
• Correction of hyperkalemia
– Stabilize cell membrane potential
- IV calcium gluconate (10 mL of 10% solution)
– Shift K+ into cells
- Inhaled β2 agonist, e.g. Salbutamol
- IV glucose (50 mL of 50% solution) and 5U insulin
- Intravenous sodium bicarbonate
– Remove K+ from body
- IV furosemide and normal saline
- Ion exchange resin orally or rectally
- Dialysis
Treatment of Underlying Cause

• Consider acute infection.
• Consider adrenal or pituitary pathology.
BIBLIOGRAPHY
1. Arlt W, Allolio B. Adrenal insufficiency. Lancet. 2003;361:1881-93.
2. Arlt W, et al. Dehydroepiandrosterone replacement in women with adrenal
insufficiency. New England Medical Journal. 2003;341(14):1013-20.
Medicine, 22nd edn. Edinburgh, Churchill Livingstone/Elsevier publications.
18th ed. McGraw Hill publications; 2012.
5. Guinot M, Duclos M, Idres N, Souberbielle Jc, Megret A, Bouc Y. Value of basal serum
cortisol to detect corticosteroid-induced adrenal insufficiency. In: Elite Cyclists.
European Journal Applied Physiology. 2007;99:205-16.
6. Gurnell EM, et al. Long-term replacement. In: Primary adrenal insufficiency: A
randomized, controlled trial. The Journal of Clinical Endocrinology & Metabolism.
2008;93(2):400-09.
7. Hahner S, Allolio B. Management of adrenal insufficiency. In different clinical settings.
Expert Opinions in Pharmacotherapy. 2005;6(14):2407-17.
SECTION
15 OBSTETRIC EMERGENCIES
Chapter 63 Obstetric Hemorrhage

Prem Kumar
Chapter 64 Hypertensive Disorders of Pregnancy

Prem Kumar
Chapter 65 Acute Fatty Liver of Pregnancy

Prem Kumar
Chapter 66 Amniotic Fluid Embolism

Prem Kumar
CHAPTER
63 Prem Kumar
OBSTETRIC HEMORRHAGE
Obstetric hemorrhage still remains a major cause of maternal morbidity and

mortality. In fact, postpartum hemorrhage is still the leading cause of death in
developing countries. There is a normal physiologic blood loss at the time of
delivery. In an average vaginal delivery, the patient loses on an average of 300
to 500 mL and it is 1,000 to 1,500 mL with cesarean section. The increased blood
volume in pregnant patients compensates this loss. In case of severe hemorrhage,
medical and surgical intervention is needed. The obstetrician, intensivist and
the anesthesiologist is involved in most of the obstetric emergencies related to
hemorrhage.
CAUSES OF OBSTETRIC HEMORRHAGE

Antepartum hemorrhage Postpartum hemorrhage
Abruption of placenta Atonicity of uterus
Placenta previa Retained placenta
Vasa previa Placenta accreta
Rupture of uterus Uterine inversion
Genital trauma
CLASSIFICATION
It is shown in Table 63.1
Table 63.1 Classification of blood loss in obstetric hemorrhage
Blood low Clinical features Severity

<15% Minimal on none
15–25% Tachycardia (<100/min) mild hypotension Mild
25–35% Tachycardia (>100/min), hypotension, oliguria, Moderate
confused, tachypnea
>35% Tachycardia (>120/min), severe hypotension, anuria, Severe
tachypnea, obtunded consciousness
464 Section 15 Obstetric Emergencies
ANTEPARTUM HEMORRHAGE
Most of the causes of antepartum hemorrhage is due to either abruption of placenta
or placenta previa. These causes of placental hemorrhage produce more adverse
effects on the fetus than the mother. First and second trimester conditions such
as spontaneous abortion and ectopic pregnancy can lead to blood loss and if it is
significant, then the patient is monitored in the ICU continuous hemodynamic
monitoring. Fluid management and blood transfusion is required to prevent
hypovolemic shock. Third trimester bleeding causes are usually placental (e.g.
Placenta previa, abruption of placenta).
Placenta Previa
Placenta previa is when the placenta covers the cervical os. It can be total or
partial. Total type—placenta covers the entire cervical os. Partial type—placenta
covers a part of cervical os. They present with painless vaginal bleeding. The
absence of abdominal pain and abnormal uterine tone distinguishes placenta
previa from placental abruption. Diagnosis is usually made with ultrasound.
Vaginal examinations are best avoided. Once the condition is diagnosed, bedrest
and monitoring of mother and fetus is done. Expectant management mandates
access to a higher center with 24-hour obstetric and anesthesia services and a
neonatal intensive care unit.
Criteria for Terminating Expectant Management

• Patient has active labor
• Gestational age reaches 37 weeks
• Fetus attains lung maturity
• Presence of excessive bleeding occurs.
Tocolytic therapy is not advised for patients with anticipated placental
abruption or uncontrolled hemorrhage. If the patient is taken for cesarean
section, at least 4 packed red cells are kept on table and 2 wide bore cannulas
are started preinduction with anticipation of severe intraoperative hemorrhage.
Anesthesia can be quite challenging in these patients, hence a senior person
should be available to manage these cases. Sometimes, the patient may have
placental abnormalities (accreta abutting the myometrium, increta invading
partially into the myometrium, and percreta invading through the myometrium).
These conditions may require hysterectomy during cesarean section in case of
uncontrolled bleeding.
Abruption of Placenta
Placental abruption is premature separation of placenta from the uterine
wall usually from the decidua basalis. Clinical features are vaginal bleeding or
concealed bleeding within the uterus, abdominal tenderness and increased
uterine activity. The risk of abruption is fetal hypoxia and it can lead to fetal
distress or intrauterine death. Abruption also causes a decrease in the placental
surface available for exchange of oxygen and hence fetal distress. Abruption is
Chapter 63 Obstetric Hemorrhage 465
the most common cause of disseminated intravascular coagulation (DIC) in

pregnancy.
Common Complications Associated with Placental Abruption

• Hypovolemic shock
• Coagulopathy
• Fetal distress or death
• Acute renal failure.
Diagnosis is by clinical presentation and ultrasound which may show the
presence of retroplacental hematoma. Fetal heart rate monitoring and maternal
hemodynamics should be monitored. Wide bore cannula is started and blood
sent for cross-matching. Hemoglobin and coagulation studies are done. Initial
management is done with fluid therapy and blood transfusion. The presence of
fetal blood in maternal circulation is found by Kleihauer-Betke test.
Criteria for Conservative Management

• Maternal hemodynamics stable
• Fetus stable
• Abruption not severe
• Mother not at term.
If bleeding does not arrest during delivery, considering the risk of the
mother’s life, uterine artery ligation or hysterectomy may be necessary. If there is
coagulopathy, fresh frozen plasma or cryoprecipitate may be required.
Vasa Previa
Velamentous insertion of the cord where fetal vessels traverse the fetal
membranes ahead of the fetal presenting part is called vasa previa. Membrane
rupture can be associated with fetal vessel rupture leading to fetal demise. This
condition is associated with high fetal mortality (50–70%). The treatment of vasa
previa is directed solely toward ensuring fetal survival. Ruptured vasa previa is
an obstetric emergency which needs immediate delivery by cesarean section.
Attention should be given for neonatal volume replacement during resuscitation.
POSTPARTUM HEMORRHAGE
Postpartum hemorrhage (PPH) is defined as blood loss more than 500 mL in
vaginal delivery, and it is more than 1,000 mL with cesarean section. Though this
definition is arbitrary, still this can be used as a guide for management.
• Primary PPH—occurs first 24 hours after delivery
• Secondary PPH—occurs between 24 hours and 6 weeks postpartum.
The most common cause of PPH is uterine atony and it occurs in the
immediate postpartum period. Other causes are retained placenta, coagulopathy,
genital trauma (lacerations of the cervix and vagina). Delayed hemorrhage occurs
due to retained placenta. Soft uterus and vaginal bleeding are clinical features of
uterine atony. In case of uterine atony, bimanual compression, uterine massage
Table 63.2 Pharmacologic therapy for uterine atony
Drug Dose Adverse effects

Oxytocin 20–60 IU/L intravenous Hypotension, cardiac arrhythmias
infusion
Methylergonovine 0.2 mg intramuscular Contraindicated in cardiac disease
and hypertension since it causes
arteriolar constriction and causes
rise in blood pressure
15-methylprostaglandin 250 µg intramuscular Bronchoconstriction, contraindicated
F2α or intramyometrially in pulmonary hypertension
and uterotonic agents are given. Blood typing and cross-matching should be done
along with complete blood count and coagulation studies. The goal of treatment
is early restoration of blood pressure and hematocrit. Placenta accreta is defined
as an abnormally adherent placenta. There are three types:
1. Placenta accreta vera—adherence to the myometrium without invasion of or
passage through uterine muscle.
2. Placenta increta—invasion of the myometrium.
3. Placenta percreta—invasion of the uterine serosa or other pelvic structures.
Role of Intensivist or Anesthesiologist in Uterine Atony (Table 63.2)

• Wide-bore cannula
• Supplemental oxygen
• Adequate fluid resuscitation based on hemodynamics
• Administration of uterotonic agents.
Management of Severe Blood Loss (Flow chart 63.1)

• Cross-match blood
• Warm the blood if the infusion rate is higher (>100 mL/min) or if there is
massive blood transfusion.
• Give 6–8 units of fresh frozen plasma for every 10 units of packed red cells
• Give 10 units of platelets if platelet count is <50,000 mm3
• Consider recombinant factor VIIa. Dose—60–100 µg/kg
• Add cryoprecipitate to replace fibrinogen.
Flow chart 63.1 Management options in PPH
Chapter 63 Obstetric Hemorrhage
467
BIBLIOGRAPHY
1. Brenner WE, Edelmar DA, Hendricks CA. Characteristics of patients with placenta
previa and results of expectant management. Am J Obstet Gynecol. 1978;132:180.
2. Clark S. Placenta previa accreta and prior cesarean section. Obstet Gynecol.
1985;66:89.
3. Ferguson JE II, Bourgesis FJ, Underwood P. B-Lynch suture for postpartum
hemorrhage. Obstet Gynecol. 2000;95:1020.
4. Hurd WW, Meodornik M, Hertzberg V, et al. Selective management of abruptio
placentae: a prospective study. Obstet Gynecol. 1983;61:467.
5. Pais SO, Glickman M, Schwartz, et al. Embolization of pelvic arteries for control of
postpartum hemorrhage. Obstet Gynecol.1980;53:754.
6. Pozaic S. Hemorrhagic complications in pregnancy. In: Harvey CJ (Ed). Critical Care
Obstetrical Nursing. Gaithersburg, Md: Aspen Publications; 1991;115-46.
7. Pritchard JA, Rowland RC. Blood volume changes in pregnancy and the puerperium.
Am J Obstet Gynecol. 1964;88:391.
8. Schwartz PE. The surgical approach to severe postpartum hemorrhage. In: Bereowitz
RL (Ed). Critical Care of the Obstetric Patient. New York: Churchill Livingstone;
1983.p.285.
9. Ueland K. Maternal cardiovascular dynamics. VII. Intrapartum blood volume changes.
Am J Obstet Gynecol. 1976;126:671-7.
CHAPTER
64 Prem Kumar
HYPERTENSIVE DISORDERS OF
PREGNANCY
Hypertension is the most common medical disorder in pregnancy. It is one of

the major causes for maternal morbidity and mortality. In this chapter, we will be
discussing pre-eclampsia and eclampsia in detail. These patients are referred to
ICU for uncontrolled hypertension, seizures, pulmonary edema, coagulopathy,
renal failure or cerebral complications.
CLASSIFICATION OF HYPERTENSIVE DISORDERS IN PREGNANCY

• Gestational hypertension
• Pre-eclampsia—mild, severe
• Chronic hypertension
• Chronic hypertension with superimposed pre-eclampsia.
DEFINITIONS
• Pre-eclampsia—new onset of hypertension and proteinuria after 20 weeks of
gestation.
• Eclampsia—occurrence of new onset seizure in a pregnant woman with pre-
eclampsia not attributable to other causes.
PRE-ECLAMPSIA
Risk Factors
• Nulliparity
• Multiple gestation
• Hydatidiform mole
• Obesity
• History of pre-eclampsia in previous pregnancy
• Advanced maternal age
• History of placental abruption
• History of pre existing hypertension.
Flow chart 64.1 Pathogenesis of pre-eclampsia
Pathogenesis (Flow chart 64.1)

• Failure of trophoblastic invasion into spiral arteries resulting in change only
in the decidual segments. The myometrial segments remain constricted and
are hyper-responsive to stimuli.
• Angiotensin 1 receptor antibodies may release oxygen radicals and block
trophoblastic invasion.
Clinical Features
Women present with hypertension and early onset have worse outcome. The
condition usually regresses after delivery usually within 2 days. Features of severe
pre-eclampsia is given in Table 64.1.
Diagnostic Criteria
• A sustained systolic blood pressure of at least 140 mm Hg, or a sustained
diastolic blood pressure of at least 90 mm Hg, that occurs after 20 weeks’
gestation in a woman with previously normal blood pressure.
• Proteinuria of ≥300 mg in a 24-hour urine collection.
Table 64.1 Features of severe pre-eclampsia
• Blood pressure: ≥160/110 mm Hg

• Proteinuria: ≥5 g in a 24-hour urine
• Oliguria: Urine output <500 mL in 24 hours
• Cerebral or visual disturbances: Headache, blurred vision, or altered consciousness
• Pulmonary edema
• Epigastric or right upper quadrant pain
• Impaired liver function
• Signs of HELLP syndrome
• Fetal growth restriction
• Pharyngolaryngeal edema
Hemoconcentration is an indicator of disease severity. Increased serum uric acid level
is found in pre-eclampsia.
Abbreviation: HELLP syndrome, hemolysis, elevated liver enzyme levels, and low platelet level syndrome
Chapter 64 Hypertensive Disorders of Pregnancy 471
Management
Lab Investigations
• Complete blood count, liver function test, platelet count, 24-hour urine
protein, serum creatinine.
• Doppler ultrasound to estimate the blood flow velocity of uteroplacental
circulation.
• Nonstress test.
Treatment
• The ultimate treatment of pre-eclampsia is delivery of the placenta and the
fetus.
• The goals of management are control of blood pressure, maintenance of
placental perfusion, prevention of seizures, prevention of complications.
Most of these cases are managed in the ICU till 72 hours after delivery.
• Prophylactic steroids are administered if the gestation is less than 34 weeks
(betamethasone, 12 mg intramuscularly [IM] every 24 hours for two doses or
dexamethasone, 6 mg IM every 12 hours for four doses).
• Monitoring with ECG, noninvasive blood pressure, SpO2, urine output is
done.
Antihypertensive Therapy (Table 64.2)

The goal of antihypertensive therapy is to reduce maternal complications (e.g.
placental abruption, cerebral hemorrhage, congestive cardiac failure). The goal
Table 64.2 Drugs used for PIH
Onset of Points of special

Drug Dose action Adverse effects mention
Hydralazine 5 mg IV followed 10–20 Tachycardia, Drug of choice
by 5–10 mg minutes headache, for severe pre-
every 20 minutes Duration— neonatal eclampsia
to a maximum of 6–8 hours thrombocytopenia
40 mg
Labetalol 20–40 mg IV 5–10 Contraindicated Now considered as
every 10 minutes minutes in patients 1st line therapy
to a maximum of with asthma,
220 mg congestive
cardiac failure
Sodium 0.25–5 µg/kg/ 0.5–1 Fetal cyanide Used as a bridge to
nitroprusside min IV minutes toxicity delivery
Nifedipine 10 mg orally and Headache, Hypotension and
repeated after flushing, risk of potentiation of
30 minutes if PPH neuromuscular
required blockade in patients
taking magnesium
sulfate
Abbreviations: PIH, pregnancy-induced hypertension; PPH, postpartum hemorrhage
of therapy is to lower the mean arterial pressure by not more than 15–25% and
with a target diastolic pressure of 100–105 mm Hg or the systolic blood pressure
should be reduced by 20–30 mm Hg and diastolic pressure by 10–15 mm Hg.
Most commonly used antihypertensives are hydralazine, labetalol, sodium
nitroprusside and nifedipine.
Other Agents
• Nitroglycerine
• Diazoxide
• Ketanserin
• Magnesium
• Nimodipine
• Methyldopa—only for mild cases.
Seizure Prophylaxis
Anticonvulsants are given to prevent seizures in pre-eclampsia and prevent
recurrent seizures in eclampsia. Magnesium sulfate is the drug of choice. Current
literature implies that seizures are not due to cerebral vasospasm but due to
abrupt sustained blood pressure elevation causing cerebral vasodilation and
cerebral edema. There is still controversy about the use of magnesium sulfate
in pre-eclampsia. Still it is been started for severe pre-eclampsia by many
obstetricians and intensivists.
Magnesium Sulfate
Mechanism of action—not clearly understood. Proposed mechanisms are
antagonism of calcium at membrane causing reduction in cerebral vasospasm,
inhibits platelet aggregation and causes vasodilatation by release of prostacyclin
from the vascular endothelium, blocks NMDA receptors. The infusion is
initiated with the onset of labor and continued till 24 hours postpartum. Serum
concentration and adverse effects of magnesium is given in Table 64.3.
Actions
• Anticonvulsant effect
• Antihypertensive effect
• Tocolytic effect.
Dosage Regimens
• Loading dose: 4–6 g given over 20–30 minutes
• Maintenance infusion: 1–2 g/hour.
Pharmacokinetics
It is eliminated by kidneys. Half life is 4 hours in patients with normal renal function.
Table 64.3 Serum concentration and adverse effects of magnesium
Serum concentration of magnesium Interpretation

1.7–2.4 mg/dL Normal serum concentration
5–9 mg/dL Therapeutic concentration
12 mg/dL Lost patellar reflexes
15–20 mg/dL Respiratory depression
>25 mg/dL Cardiac arrest
Cardiac Effects of Hypermagnesemia

• Prolonged PR and QT interval causing A-V block if serum concentration
>18 mg/dL
• Cardiac arrest if serum concentration >25 mg/dL.
Magnesium toxicity may be reversed with the administration of IV calcium
(10 mL of a 10% solution of calcium gluconate given slowly IV over 10 minutes).
Complications of Severe Pre-eclampsia

• Reversible cerebral edema, stroke
• Renal failure—most cases are prerenal or intrarenal and it resolves completely
after delivery. Bilateral renal cortical necrosis is a serious rare complication
• Pulmonary edema—usually occurs postpartum
• HELLP syndrome
• Placental abruption.
HELLP SYNDROME
HELLP syndrome is a high risk variant of severe pre-eclampsia characterised by
hepatic, renal and cerebral complications. This is associated with high maternal
mortality. Hemolysis is the hallmark of HELLP syndrome. Other findings are
periportal hepatic necrosis and hemorrhage, DIC, abruption of placenta,
pulmonary edema, and renal failure. Predominantly it occurs in the postpartum
period.
Diagnostic Criteria
• Hemolysis—serum bilirubin >1.2 mg/dL, peripheral smear showing features
of hemolysis.
• Elevated liver enzymes—lactate dehydrogenase >600 IU/L, SGOT >70 IU/L
• Platelet count <1,00,000/mm3.
Clinical Features
• Nausea and vomiting
• Epigastric pain
• Hypertension
• Headache.
Diagnosis
Complete blood count, platelet count, liver function test. In case of hepatic
bleeding, ultrasonography and CT scan is useful for diagnosis.
Management
The diagnosis of HELLP syndrome is considered an indication for immediate
delivery. The treatment is same as that of severe pre-eclampsia-controlling
hypertension, correcting coagulation abnormalities. The use of high dose
corticosteroid (dexamethasone 10 mg 6th hourly) has been found to raise platelet
count. Hepatic hemorrhage without rupture with hemodynamic stability can be
managed conservatively. In case of rupture of subscapular hematoma of liver
which is a life-threatening complication of HELLP syndrome, the patient presents
with hypovolemic shock. The condition is a surgical emergency, hence it requires
fluid and blood resuscitation with emergency laparotomy.
ECLAMPSIA
It is defined as new onset seizure during pregnancy or postpartum period in a
woman who has clinical features of pre-eclampsia without previous seizure
disorder. Seizures can occur in intrapartum period or within 48 hours after
delivery. Eclampsia is associated with high maternal and perinatal mortality.
Complications which can occur in mother are cerebrovascular event, pulmonary
aspiration, cardiac arrest.
Management
The goals of management of eclampsia are ABCs of resuscitation. Protect the
airway by giving jaw thrust and oxygen, breathing is supported by bag and mask
ventilation with oxygen. Circulation is supported by IV access and blood pressure
monitoring. Termination and prevention of seizures by magnesium sulfate is done.
If seizure is not controlled with magnesium, diazepam 5–10 mg is given. If there
are refractory seizures, patient is given thiopentone sodium and succinylcholine
and the patient is intubated and given ventilatory support. Antihypertensive
therapy is given with intravenous labetalol or hydralazine. Delivery of the fetus is
considered once the mother is stabilized preferably by vaginal route.
BIBLIOGRAPHY
1. American College of Obstetricians and Gynecologists. Diagnosis and Management of
Preeclampsia and Eclampsia. ACOG Practice Bulletin No. 33, January 2002. Obstet
Gynecol. 2002;99:159-67.
2. Chestnut DH. Chestnut’s Obstetric Anesthesia: Principles and Practice, 4th edn.
Philadelphia: Elsevier Publishers; 2009.
3. Lucas MJ, Leveno KJ, Cunningham FG. A comparison of magnesium sulfate with
phenytoin for the prevention of eclampsia. N Engl J Med. 1995;333:201.
4. Mabie W, Gonzalez AR, Sibas BM, et al. A comprehensive trial of labetalol and
hydralizene in the acute management of severe hypertension complicating pregnancy.
Obstet Gynecol. 1987;70:328.
5. Report on the National High Blood Pressure Education Program Working Group on
High Blood Pressure in Pregnancy. Am J Obstet Gynecol. 2000;183:S1-22.
6. Sibai B. Diagnosis, prevention, and management of eclampsia. Obstet Gynecol. 2005;
105:402.
7. The Magpie Trial Collaborative Group: Do women with pre-eclampsia, and their
babies, benefit from magnesium sulfate? The Magpie Trial: a randomized placebo-
controlled trial. Lancet. 2002;359:1877.
8. Witlin AG, Sibai B. Magnesium sulfate therapy in preeclampsia and eclampsia. Obstet
Gynecol. 1998;92:883.
9. Working Group Report on High Blood Pressure in Pregnancy. Washington, DC,
National Institutes of Health, 2000.
CHAPTER
65 Prem Kumar
ACUTE FATTY LIVER OF PREGNANCY
Acute fatty liver of pregnancy (AFLP) is an uncommon disorder of pregnancy.

Incidence is 1 in 1,00,000 pregnancies. It is characterized by impaired hepatic
function leading to liver failure.
PATHOPHYSIOLOGY
• Acute fatty liver of pregnancy is common in women with multiple gestation.
More than 50% of cases are associated with pre-eclampsia.
• There is documented evidence of the presence of AFLP in mothers whose
fetus had long chain hydroxyacyl coenzyme dehydrogenase deficiency.
• Another study showed that mitochondrial dysfunction in fetal liver as another
etiology. But none of these evidences have proved to be the causative factor
for AFLP, still the etiology for AFLP is unknown.
CLINICAL PRESENTATION
Diagnosis of AFLP is considered in a woman of late gestation presenting with
impaired hepatic function. They may complain of vomiting, gastrointestinal
bleeding and right upper abdominal pain. Patients may have jaundice, headache
and malaise.
LAB INVESTIGATIONS
Elevated liver enzymes, prolonged prothrombin time and reduced antithrombin
III level. Hypoglycemia is common and it occurs due to impaired glycogenolysis.
Fatty infiltration can be seen in ultrasonography. Patients may end up with
hepatorenal syndrome.
DIFFERENTIAL DIAGNOSIS (TABLE 65.1)

Acute fatty liver of pregnancy has to be differentiated from viral hepatitis,
intrahepatic cholestasis and HELLP syndrome.
Chapter 65 Acute Fatty Liver of Pregnancy 477
Table 65.1 Differential diagnosis of acute fatty liver of pregnancy
Serum bilirubin Liver enzymes

Disorder (mg/dL) (IU/L) Specific features
AFLP <5 <500 Fatty infiltration
Hypoglycemia
Hepatorenal syndrome
Intrahepatic <5 <300 Pruritus, dilated canaliculi
cholestasis
Viral hepatitis >5 >1000 Jaundice
HELLP syndrome <5 >500 Hemolysis
Thrombocytopenia
Abbreviations: AFLP, acute fatty liver of pregnancy; HELLP, hemolysis, elevated liver enzymes and low
platelets
COMPLICATIONS
• Profound hypoglycemia
• Acute renal failure
• DIC
• Hepatic encephalopathy
• Hepatic rupture
• Coagulopathy
• Fetal effects—uteroplacental insufficiency leading to fetal distress.
MANAGEMENT
Acute fatty liver of pregnancy is a medical emergency and the mainstay is
supportive treatment. Goals of the management are:
• Maintaining oxygenation
• Maintaining renal and neurological function
• Correction of metabolic disorders and electrolyte disturbances
• Correction of hypoglycemia
• Correction of coagulation abnormalities
• Delivery of the fetus once the mother is stabilized.
Intravenous infusion with 10% dextrose is given to prevent hypoglycemia
and blood glucose level maintained >60 mg/dL. In case there is hepatic
encephalopathy, low protein diet and enteral lactulose is given to reduce serum
ammonia level. AFLP is a reversible form of peripartum liver failure hence
all forms of invasive treatment should be planned carefully. Orthotopic liver
transplantation can be considered for patients who have no signs of recovery
even after 72 hours of postpartum period.
BIBLIOGRAPHY
1. Amon E, Allen SR, Petrie RH, Belew JE. Acute fatty liver of pregnancy associated with
pre-eclampsia: management of hepatic failure with postpartum liver transplantation.
Am J Perinatol. 1991;8:278-9.
2. Castro MA, Fassett MJ, Reynolds TB, et al. Reversible peripartum liver failure: a new
perspective on the diagnosis, treatment, and cause of acute fatty liver of pregnancy,
based on 28 consecutive cases. Am J Obstet Gynecol. 1999;181:389-95.
3. Davidson KM, Simpson LL, Knox TA, D’Alton ME. Acute fatty liver of pregnancy in
triplet gestation. Obstet Gynecol. 1998;91:806-8.
4. Franco J, Newcomer J, Adams M, Saeian K. Auxiliary liver transplant in acute fatty liver
of pregnancy. Obstet Gynecol. 2000;95:1042.
5. Haemmerli UP. Jaundice during pregnancy: with special emphasis on recurrent
jaundice during pregnancy and its differential diagnosis. Acta Med Scand. 1966;
4444:1-111.
6. Kaplan MM. Acute fatty liver of pregnancy. N Engl J Med. 1985;313:367-70.
7. Rinaldo P, Treem WR, Riely CA. Liver disease in pregnancy. N Engl J Med. 1997;
336:377-8.
CHAPTER
66 Prem Kumar
AMNIOTIC FLUID EMBOLISM
Amniotic fluid embolism (AFE) is a devastating condition which is largely

unpreventable without any cause. It is a diagnosis of exclusion and the maternal
mortality rate is very high (30–80%). Most of these deaths occur in the first few
hours. The incidence is 1 in 80,000 deliveries.
PATHOPHYSIOLOGY
• Some studies have suggested that leukotrienes are responsible for the
pathological features of AFE.
• Immune-mediated complement activation is another hypothesis.
• Disturbance of the clotting mechanism by released trophoblast has been
suggested by some investigators.
• Amniotic fluid contains prostaglandin, leukotrienes, fetal debris which can
get released into maternal circulation through uterine veins or placental
abruption. These factors causes complement activation and pulmonary
vasoconstriction resulting in pulmonary hypertension.
• This syndrome or pathophysiology more likely resembles anaphylaxis.
Hence, AFE constituting hemodynamic instability, coagulopathy and
hypoxia is suggested by many as anaphylactoid syndrome of pregnancy.
• There is a biphasic response to the effects of AFE—early and second phase.
• Early phase constitutes pulmonary vasoconstriction and pulmonary
hypertension resulting in right heart failure. This phase occurs within 30
minutes.
• Second phase consists of left ventricular failure resulting in pulmonary
edema.
CLINICAL FEATURES
The diagnosis of AFE is that of exclusion. Patients present with breathlessness,
cyanosis, sudden hemodynamic collapse, seizures during labor or cesarean
section or even in the postpartum period. Coagulopathy is also another feature
of AFE in patients who survive the insult. There has been an increased incidence
of AFE in patients where pharmacologic induction of labor was done or when
membranes are ruptured artificially.
LAB INVESTIGATIONS
• Maternal plasma concentration of zinc coproporphyrin which is a component
of meconium is thought to be a sensitive test for diagnosing AFE.
• Monoclonal antibody test for detection of fetal mucin in maternal circulation.
MANAGEMENT
• Supportive management is the mainstay in the management of AFE.
• Start CPR if required. The use of perimortem cesarean section has resulted in
maternal and neonatal survival.
• Resuscitative measures should be aggressive by starting a wide bore IV
cannula for rapid infusion of fluids, inotropic support is given if required.
• Pulmonary artery catheterization is useful in these patients to measure
the pulmonary artery occlusion pressure and in diagnosing left ventricular
failure and hence is used as a guide for fluid and inotropic support.
• Most of these patients would require tracheal intubation and ventilatory
support.
• Blood component therapy is given to manage the coagulopathy.
• Neurological assessment is done frequently since the patient may have
neurologic sequelae.
BIBLIOGRAPHY
1. Clark SL, Hankins GDV, Dudley DA, et al. Amniotic fluid embolism: Analysis of the
national registry. Am J Obstet Gynecol. 1995;172:1158-69.
2. Clark SL. New concepts of amniotic fluid embolism: A review. Obstet Gynecol Surv.
1990;45:360-8.
3. Davies S. Amniotic fluid embolism and isolated disseminated intravascular
coagulation. Can J Anaesth. 1999;46:456.
4. Gilbert WM, Danielson B. Amniotic fluid embolism: decreased mortality in a
population-based study. Obstet Gynecol. 1999;93973-77.
5. Gilmore DA, Wakins J, Secrest J, et al. Anaphylactoid syndrome of pregnancy: a review
of the literature with latest management and outcome data. AANA J. 2003;71:120.
6. Kobayashi H, Ohi H, Terao T. A simple, noninvasive, sensitive method for diagnosis of
amniotic fluid embolism by monoclonal antibody TKH-2 that recognizes NeuAcα2–
6GalNAc. Am J Obstet Gynecol. 1993;168:848-53.
7. Lee W, Gensberg KA, Cotton DB, et al. Squamous and trophoblastic cells in the
maternal pulmonary circulation identified by invasive hemodynamic monitoring
during the postpartum period. Am J Obstet Gynecol. 1986;155:159.
8. Margarson MP. Delayed amniotic fluid embolism following cesarean section under
spinal anaesthesia. Anaesthesia. 1995;50:804-6.
9. Quinn A, Barrett T. Delayed onset of coagulopathy following amniotic fluid embolism:
Two case reports. Internat J Obstet Anesth. 1993;2:177-80.
10. Stehr SN, Liebich I, Kamin G, Koch T, Litz RJ. Closing the gap between decision and
delivery: amniotic fluid embolism with severe cardiopulmonary and haemostatic
complications with a good outcome. Resuscitation. 2007;74:377-81.
SECTION
16
NEUROLOGICAL DISORDERS IN
INTENSIVE CARE UNIT
Chapter 67 Cerebrovascular Diseases

TA Naufal Rizwan
Chapter 68 Status Epilepticus

TA Naufal Rizwan
Chapter 69 Meningitis and Encephalitis

TA Naufal Rizwan
Chapter 70 Alcohol Withdrawal Syndrome

TA Naufal Rizwan
Chapter 71 Delirium in ICU

TA Naufal Rizwan
CHAPTER
67 TA Naufal Rizwan
CEREBROVASCULAR DISEASES
Cerebrovascular diseases comprises heterogeneous group of disorders that

herald their presence by producing symptoms and signs resulting from either
ischemia or hemorrhage within central nervous system (CNS) (Fig. 67.1).
Fig. 67.1 Classification of cerebrovascular disease

Abbreviation: TIA, transient ischemic attack
TRANSIENT ISCHEMIC ATTACK
Definition
It is characterized by an acute loss of focal cerebral or monocular function with
symptoms lasting <24 hours and which is thought to be due to inadequate cerebral
or ocular blood supply as a result of low blood flow, thrombosis or embolism
associated with disease of the arteries, heart or blood.
Features of Transient Ischemic Attacks

Transient ischemic attacks (TIA) is sudden in onset. The symptoms are maximal
at onset and resolve within 24 hours. Brain imaging may or may not show a
relevant focal ischemic lesion in the brain.
Management of Transient Ischemic Attacks

Patients with TIA or those with stroke, who have made a good immediate recovery,
should be assessed and investigated for cause as soon as possible. Patients likely
to have a diagnosis of TIA should be prescribed aspirin 300 mg daily immediately
and risk factors for cerebrovascular disease such as severe hypertension should
be treated appropriately.
484 Section 16 Neurological Disorders in Intensive Care Unit
STROKE
Definition
A clinical syndrome characterized by an acute loss of focal cerebral function due
to a vascular event with symptoms lasting >24 hours or leading to death.
Types
• Hemorrhagic stroke: Spontaneous hemorrhage into the brain substance.
• Ischemic stroke: Inadequate blood supply to a part of the brain as a result
of low blood flow, thrombosis or embolism associated with diseases of the
blood vessels, heart or blood.
ISCHEMIC STROKE (80%)
Pathophysiology
Around 80% of ischemic strokes occur in the carotid or anterior circulation and
20% occur in vertebrobasilar or posterior circulation.
Large Artery Atherosclerotic Disease

Atherosclerosis mainly affects larger extracranial or intracranial vessels. The
mechanism is mainly artery to artery embolization or in situ thrombosis in areas
of preexisting arterial stenosis.
Small Vessel or Penetrating Artery Disease (Lacunes)

Long standing hypertension induces changes in the small penetrating vessels
of brain in the form of medial hypertrophy and fibrinoid necrosis leading to
occlusion. Lacunes are small ischemic infarcts from 0.5 mm to 15 mm in the deep
region of brain or brainstem caused by lipohyalinosis of penetrating arteries of
brain.
Embolic Stroke (Box 67.1)

Box 67.1: Risk factors for cardioembolism
• Acute myocardial infarction, dilated cardiomyopathy and left ventricular aneurysm
• Cardiac arrhythmias, atrial fibrillation
• Valvular heart disease (calcific or rheumatic)
• Infective endocarditis, prosthetic heart valves
• Intracardiac tumors (atrial myxoma, rhabdomyoma)
• Traumatic cerebrovascular disease, radiation-induced vasculopathy
• Moyamoya disease, fibromuscular dysplasia, vasculitis
• Antithrombin III deficiency, protein C or S deficiency
• Factor V leiden mutation, prothrombin mutation
• Afibrinogenemia/hypofibrinogenemia/plasminogen activators deficiency
Chapter 67 Cerebrovascular Diseases 485
CLINICAL FEATURES
Focal Neurological and Ocular Symptoms
Motor Symptoms
The predominant motor symptoms include weakness or clumsiness of one side
of the body, in whole or in part (hemiparesis, monoparesis and sometimes only
the hand). Some patients may develop also simultaneous bilateral weakness and
difficulty in swallowing.
Speech/Language Disturbances
Patients have difficulty in understanding or expressing spoken language
(aphasia, dysarthria). They may also have difficulty in reading (dyslexia), writing
(dysgraphia) and calculating (dyscalculia).
Sensory Symptoms
Altered feeling on one side of the body, in whole or in part.
Visual Symptoms
The visual symptoms seen in stroke are loss of vision in one eye (in whole or in
part) or loss of vision in half or quarter of the visual field. Bilateral blindness and
double vision (diplopia) are also seen in some patients.
Vestibular Symptoms
Patient may experience disturbances in balance, giddiness, etc.
Behavioral/Cognitive Symptoms
Difficulty in dressing, combing hair, cleaning teeth, geographical disorientation
(visuospatial–perceptual dysfunction) and forgetfulness.
Nonfocal Neurological Symptoms

• Generalized weakness and/or sensory disturbance
• Light-headedness, faintness
• ‘Blackouts’ with altered or loss of consciousness with or without impaired
vision in eyes
• Incontinence of urine or feces
• Confusion, ringing in the ears (tinnitus).
HEMORRHAGIC STROKE
Pathophysiology
Intracerebral and Cerebellar Hemorrhage
Hemorrhagic stroke is mostly due to rupture of microaneurysms (Charcot
Bouchard aneurysms). They are usually massive and often fatal. The common
sites of bleed are basal ganglia, pons, cerebellum and subcortical white matter. In
normotensive patients, particularly over 60 years, lobar intracerebral hemorrhage
occurs in the frontal, temporal, parietal or occipital cortex.
Subarachnoid Hemorrhage
The common causes for subarachnoid hemorrhage are:
• Saccular (berry) aneurysms (70%)
• Arteriovenous malformation (AVM) 10%
• No arterial lesion found in 15% of cases.
Subdural and Extradural Hemorrhage/Hematoma

Mostly traumatic.
CLINICAL FEATURES OF HEMORRHAGIC STROKE

Hemorrhagic stroke is usually a sudden, dramatic event. Intense headache usually
described as “worst headache of my life”. Seizures may be present. Headache
with loss of consciousness along with photophobia, phonophobia, nuchal
rigidity should alert the possibility of subarachnoid hemorrage (SAH). Loss of
consciousness is common with major lobar hemorrhages. Focal neurological
signs like contralateral hemiparesis, hemisensory loss suggesting basal ganglia
hemorrhage are common.
Assessment of Acute Stroke

Brain imaging (CT brain) should be taken as soon as possible in all patients, at
least within 24 hours of onset. This is very important, especially in a patient who
has the following:
• On anticoagulants
• Known bleeding tendency
• Unexplained progressive or fluctuating symptoms
• Papilledema
• Neck stiffness or fever.
If the underlying pathology is uncertain or the diagnosis of stroke is in doubt
even after the CT scan, magnetic resonance imaging (MRI) should be considered.
Early Interventions
Blood glucose, arterial oxygen concentration, hydration and temperature should
be maintained within normal limits. Blood pressure should only be lowered in
the acute phase where there are likely to be complications from hypertension,
e.g. hypertensive encephalopathy, aortic aneurysm or acute kidney injury or if
systolic BP >210 mm Hg in ischemic stroke and >180 mm Hg in hemorrhagic
stroke. Aspirin (300 mg) orally or rectally should be given as soon as possible after
the onset of stroke symptoms if a hemorrhagic stroke is ruled out. Patients should
also be mobilized as soon as possible.
Thrombolytics in Ischemic Stroke

Intravenous recombinant tissue plasminogen activator (tPA) alteplase (0.9 mg/
kg to a 90 mg max; 10% as a bolus, then the remainder over 60 minutes) is given
in patients with confirmed ischemic stroke within 3 hours of onset symptoms.
Contraindications for thrombolytic therapy is given in Box 67.2.
Table 67.2 Contraindications for thrombolytic therapy

• Sustained BP >185/110 mm Hg despite treatment
• Platelets <100,000; HCT <25%
• Use of heparin within 48 hours and prolonged PTT, or elevated INR
• Rapidly improving symptoms/minor stroke symptoms
• Prior stroke or head injury within 3 months; prior intracranial hemorrhage
• Major surgery in preceding 14 days/gastrointestinal bleeding in preceding 21 days
• Recent myocardial infarction
• Coma or stupor
MANAGEMENT OF CEREBRAL EDEMA

Five to ten percent of patients develop cerebral edema leading to obtundation or
brain herniation. Edema peaks on the 2nd or 3rd day but can cause mass effect
for approximately 10 days. Larger the infarct, greater the significance of clinical
edema. Water restriction and IV mannitol (1.5 to 2 g/kg IV over 30 minutes) may
be used to raise the serum osmolarity.
Rehabilitation
All patients should be referred to a specialist rehabilitation team involving treating
doctor, physiotherapist, speech therapist, psychologist (to assess depression).
All members of the healthcare team should work together with the patient,
caregiver and family using a shared philosophy and common goals. The team
should promote integrating the practice of skills gained in therapy into the
patient’s daily routine in a consistent manner.
General Management
Patients with dysphagia should be managed by a trained specialist and receive
advice on safe swallowing techniques. Nutritional and hydration support should
be considered for any patient with malnutrition or difficulties in feeding. Bowel

and bladder function should be monitored and actively managed. The patient’s
cognitive status should be considered when planning and delivering treatment.
Secondary Prevention
Advice on lifestyle factors.
Blood Pressure Control

High blood pressure persisting for over two weeks should be treated (non-
diabetics <140/85 mm Hg; diabetics <130/80 mm Hg). The drugs preferred are
Thiazide diuretics (indapamide or bendrofluazide) or an angiotensin-converting
enzyme (ACE) inhibitor (e.g. perindopril or ramipril) or preferably combination
of both, unless there are contraindications.
For Ischemic Stroke/TIA
Antiplatelets
Aspirin (75–300 mg) daily or clopidogrel or a combination of low dose aspirin and
dipyridamole modified release (MR). For aspirin intolerant patients, clopidogrel
(75 mg daily or dipyridamole MR 200 mg twice daily) should be used.
Anticoagulants
Anticoagulation should be started in every patient with persistent or paroxysmal
atrial fibrillation (valvular or nonvalvular) unless contraindicated. Anticoagulants
should not be started until brain imaging has excluded hemorrhage, and usually
not until 14 days have passed from the onset of an ischemic stroke.
Statins
Treatment with a statin (e.g. 40 mg simvastatin) should be given to patients
with ischemic stroke or TIA unless contraindicated. Any patient with a carotid
artery territory stroke, without severe disability, should be considered for carotid
endarterectomy. Carotid endarterectomy should be performed as soon as the
patient is fit for surgery.
BIBLIOGRAPHY
1. Adams RJ, Albers G, Alberts MJ. Update to the AHA/ASA recommendations for the
prevention of stroke in patients with stroke and transient ischemic attack. Stroke.
2008;39:1647-52.
2. Allan H Ropper, Martin A Samuels, Joshua Klein. Adams and Victor’s Principles of
Neurology, 10th edition.
3. Amarenco P, Labreuche J, Lavallee P, Touboul PJ. Statins in stroke prevention and
carotid atherosclerosis: systematic review and up-to-date meta-analysis. Stroke.
2004;35:2902-9.
4. Asaithambi G, Tong X, George MG, Tsai AW, Peacock JM, Luepker RV, Lakshminarayan
K. Acute stroke reperfusion therapy trends in the expanded treatment window era.
J Stroke Cerebrovasc Dis. 2014;23(9):2316-21.
5. Berkhemer OA, Puck SS, Fransen, Beumer D, Lucie A van den Berg, Hester FL, Albert
JY, Wouter JS. A randomized trial of intra-arterial treatment for acute ischemic stroke.
N Engl J Med. 2015;372:11-20.
6. Campbell BCV, Mitchell PJ, Kleinig TJ, et al. Endovascular therapy for ischemic stroke
with perfusion-imaging selection. N Engl J Med. 2015;372:1009-18.
7. Chaturvedi S, Bruno A, Feasby T. Carotid endarterectomy—an evidence-based
review: report of the Therapeutics and Technology Assessment Subcommittee of the
American Academy of Neurology. Neurology. 2005;65:794-801.
8. Kato Y, Hayashi T, Tanahashi N, Kobayashi S, Cardioembolic Stroke is the Most Serious
Problem in the Aging Society: Japan Standard Stroke Registry Study; Japan Standard
Stroke Registry Study Group.
9. Lewis PR, Timothy AP. Merritt’s Neurology, 12th edition.
principles of internal medicine, 18th edition. McGraw Hill Publications; 2012.
11. Maxine AP, Stephen J, Michael WR. Current Medical Diagnosis & Treatment, 54th
edition, 2015.
12. Nassief A, Marsh JD. Statin therapy for stroke prevention. Stroke. 2008;39.
13. Toby B. Cumming, Marshall RS, Ronald ML. Stroke, cognitive deficits, and
rehabilitation: still an incomplete picture. Int J Stroke. 2013;8(1).
14. Tong X, George MG, Yang Q, Gillespie C. Predictors of in-hospital death and
symptomatic intracranial hemorrhage in patients with acute ischemic stroke treated
with thrombolytic therapy: Paul Coverdell Acute Stroke Registry 2008-2012. Int J
Stroke. 2014;9(6):728-34.
15. Zhang Y, Reilly KH, Tong W. Blood pressure and clinical outcome among patients with
acute stroke in inner Mongolia, China. J Hypertens. 2008;26:1446-52.
CHAPTER
68 TA Naufal Rizwan
STATUS EPILEPTICUS
DEFINITION
Status epilepticus is characterized by continuous seizures or repetitive seizures
with the patient not regaining consciousness in between the seizure episodes (in
repetitive seizures) and that usually lasts for >15–30 minutes.
ETIOLOGY
• Anticonvulsants drug withdrawal or noncompliance
• CNS infections
• Trauma
• Brain tumors
• Metabolic derangements.
TYPES
At a simplified level, status may be classified into generalized convulsive status
epilepticus, nonconvulsive status epilepticus (including complex partial and
absence status), and simple partial status.
CONVULSIVE
Generalized tonic clonic movements seen.
Chapter 68 Status Epilepticus 491
Nonconvulsive (Including Complex Partial and Absence Status)

Here there are no tonic clonic movements. The typical picture is of a twilight state
with varying degrees of confusion. The usual automatisms of complex partial
seizures may or may not be seen.
SIMPLE PARTIAL STATUS EPILEPTICUS

It is probably even rarer and commonly takes a somatomotor form.
COMPLICATIONS
The complications of status epilepticus are:
• Acidosis
• Hyperthermia, hypotension
• Renal failure (due to myoglobinuria)
• Cardiorespiratory dysfunction
• Neurological sequelae-epileptic encephalopathy (Usually in seizures lasting
>30 minute).
INVESTIGATIONS
• Blood tests for metabolic parameters
• Imaging of the brain
• Electroencephalogram (EEG)—measures the electrical activity of the cortex
• MEG (Magnetoencephalography)—measures the magnetic fields generated
by the cortical activity-done in interictal period.
Importance of EEG
The importance of EEG lies in the fact that it is the only way of diagnosing
nonconvulsive status epilepticus. It is also helpful in generalized convulsive
status epilepticus patients who are paralyzed with neuromuscular blockade for
airway protection. Similarly if the patient remains comatose for a long time even
after the seizure stopped, EEG must be done to detect ongoing seizures.
TREATMENT
General Measures
Airway maintenance is of great importance as it may prevent cerebral hypoxia
as well as aspiration pneumonitis. Any underlying metabolic derangements, if
present, must be appropriately corrected. Care must be taken to prevent injuries
to the patient.
Specific Measures
• Inj. lorazepam (0.1–0.2 mg/kg) or Inj. diazepam (0.2 mg/kg)
(given intravenously (IV) over 2 minutes)
If no improvement

Repeat the above dose after 5 minute.
If no improvement

• Inj. phenytoin (18–20 mg/kg IV) at 50 mg/minute
Or
Inj. fosphenytoin (18–20 mg/kg IV) at 150 mg/minute
Seizures continuing
• Inj. phenytoin (7–10 mg/kg IV) at 50 mg/minute

Or
Inj. fosphenytoin (7–10 mg/kg IV) at 150 mg/minute
Seizures continuing
• Inj. sodium valproate 25 mg/kg IV

Seizures continuing
• Inj. phenobarbitol 20 mg/kg IV at 60 mg/minute

Seizures continuing
• Inj. phenobarbitol 10 mg/kg IV at 60 mg/minute

Seizures continuing
• Intubation and ventilatory support– IV anesthesia

– Inj. midazolam 0.2 mg IV stat followed by 0.1–0.2 mg/kg/hour
– Inj. propofol 1–2 mg/kg IV stat followed by 2–10 mg/kg/hour
Advantages of Fosphenytoin Over Phenytoin

• Can be mixed with all common intravenous solutions
• Less reactions at the infusion site
• Can be administered at a faster rate (150 mg/min).
BIBLIOGRAPHY
1. Beran RG. An alternative perspective on the management of status epilepticus.
Epilepsy Behav. 2008;12(3):349-53.
2. Chapman MG, Smith M, Hirsch NP. Status epilepticus. Anaesthesia. 2001;56:648-59.
3. Chen JWY, Wasterlain CG. Status epilepticus: pathophysiology and management in
adults. Lancet Neurol. 2006;5(3):246-56.
Chapter 68 Status Epilepticus 493
4. Cherian A, Thomas SV. Status epilepticus. Ann Indian Acad Neurol. 2009;12(3):
140-53.
5. Husain AM, Horn GJ, Jacobson MP. Non-convulsive status epilepticus: Usefulness of
clinical features in selecting patients for urgent EEG. J Neurol Neurosurg Psychiatry.
2003;74:189-91.
Principles of Internal Medicine. 18th edition McGraw Hill Publications; 2012.
7. Lothman E. The biochemical basis and pathophysiology of status epilepticus.
Neurology. 2003;40:13-23.
8. Maxine AP, Stephen JM, Michael WR. Current Medical Diagnosis and Treatment.
5th edition 2015. pp.168-70.
9. Meierkord H, Boon P, Engelsen B, Gocke K, Shorvon S, Tinuper P, Holtkamp M. EFNS
guideline on the management of status epilepticus. Eur J Neurol. 2006;13(5):445-50.
10. Misra UK, Kalita J, Patel R. Sodium valproate versus phenytoin in status epilepticus: A
pilot study. Neurology. 2006;67:340-2.
11. Mark M, Heinrich M. Fundamentals of neurology. 2006. pp.161-71.
12. John PB, Daniel HL. Status epilepticus in adults. The Lancet Neurology. 2015;14(6):
615-24.
13. Rossetti AO, Lowenstein DH. Management of refractory status epilepticus in adults:
still more questions than answers. Lancet Neurol. 2011;10(10):922-30.
14. Seif-Eddeine H, Treiman DM. Problems and controversies in status epilepticus: a
review and recommendations. Expert Rev Neurother. 2011;11(12):1747-58.
15. Towne AR, Waterhouse EJ, Boggs JG, Garnett LK, Brown AJ, Smith JR, Jr, et al.
Prevalence of nonconvulsive status epilepticus in comatose patients. Neurology.
2000;54:340-5.
16. Ulate-Campas, Caughlin F, Gainza-Lein M, Sanches IF, Pearl PL, et al. Automated
seizure detection systems and their effectiveness for each type of seizure. Euro J
Epilepsy. 2016. pp.88-101.
CHAPTER
69 TA Naufal Rizwan
MENINGITIS AND ENCEPHALITIS
DEFINITION
Infection of the meninges (generally the arachnoid and piamater) and the
subarachnoid space is known as meningitis. If the inflammation also involves the
brain parenchyma, it is called meningoencephalitis.
CLASSIFICATION
Acute, subacute, and chronic.
ACUTE BACTERIAL MENINGITIS

Causes of acute bacterial meningitis is given in Table 69.1.
Routes of Spread
• Hematogenous spread (infected thrombi, bacteria)
• Direct extension from the adjacent septic foci (ear, paranasal sinuses)
• Iatrogenic (spinal surgery, cerebral surgery, etc.).
Table 69.1 Common causes of acute bacterial meningitis
Organisms
The common causes of acute bacterial meningitis and their risk factors are:
• Streptococcus pneumoniae—otitis, sinusitis, alcoholism, postsplenectomy and diabetes
• Neisseria meningitidis—complement deficiencies
• Group B streptococcus (S. agalactiae)—Neonates and older age groups
• Listeria monocytogenes—neonates, pregnancy, older persons
• S. aureus and CoNS—neurosurgical procedures
• Gram-negative bacilli (Klebsiella, E. coli, Proteus)—cirrhosis, alcoholism, diabetes
• Haemophilus influenzae—children
Abbreviation: CoNS, coagulase
Chapter 69 Meningitis and Encephalitis 495
PATHOGENESIS (FLOW CHART 69.1 )

Flow chart 69.1 Pathogenesis of bacterial meningitis
Abbreviations: LPS, Lipopolysaccharide; TNF, tumor necrosis factor; IL, interleukin; ICP, intracranial pressure.
These cytokines and chemokines produce the following consequences:

• Alters the blood brain barrier leading to vasogenic edema
• Stimulate the production of reactive oxygen and nitrogen species, resulting
in cell death
• Stimulate the adherence of neutrophils to vascular endothelial cells, thus
producing cytotoxic edema, cell injury and cell death
• Helps in the formation of subarachnoid exudates which in turn obstructs the
flow of cerebrospinal fluid resulting in obstructive hydrocephalus
• Infiltration of the blood vessels (vasculitis) which will in turn result in
cerebral ischemia, infarction, cortical vein thrombosis, etc.
CLINICAL FEATURES
Classic Triad
• Headache
• Fever
• Neck stiffness (Nuchal rigidity).
The other symptoms and signs of meningitis are nausea, vomiting,
photophobia, irritability, lethargy, confusion, stupor or coma. Seizures are seen
in around 30% cases and may be due to ischemia, hypoxia or cerebral edema.
Hypotension (in severe cases), tachycardia and tachypnea are also seen in some
patients. On examination, the deep tendon reflexes are depressed. Kernig sign
and Brudzinski sign are present. Petechiae, purpura or ecchymoses (mostly in
lower half of body) are seen in meningococcal meningitis. Cranial nerve palsies
and focal neurologic signs are uncommon and usually do not develop until
several days after the onset of the infection.
Features of Raised ICP

Features of increased ICP are deteriorating or reduced level of consciousness,
papilledema, dilated and poorly reactive pupils, sixth nerve palsies, decerebrate
posturing and the Cushing reflex (bradycardia, hypertension and irregular
respiration).
INVESTIGATIONS
CSF Analysis
Lumbar puncture and cerebrospinal fluid (CSF) analysis is the most important
investigation in the management of meningitis. It should be done in all the
patients unless contraindicated because of increased intracranial tension.
Antibiotics given within 4 hours before obtaining the cerebrospinal fluid probably
do not affect the CSF culture results.
Latex agglutination: May be positive in patients with meningitis due to
S. pneumoniae, N. meningitidis, H. influenzae type b, E. coli, group B streptococci.
Limulus lysates: Positive in cases of gram-negative meningitis.
PCR, CIE, ELISA, RIA-costly but highly effective.
• Complete blood count—leucocytosis present
• Blood culture is positive in about 50% cases
• Culture of the oropharynx, nasopharynx and petechial skin rash in selected
cases
• Urine routine
• Liver function tests and renal function tests
• Serum electrolytes and blood glucose CSF for analysis (Table 69.2).
IMAGING
Before doing a lumbar puncture, imaging of the brain is mandatory in the
following conditions:
• Recent head trauma
Table 69.2 Cerebrospinal fluid findings in acute bacterial meningitis
• Opening pressure >180 mm H2O

• White blood cells—10–10,000/mm3; neutrophils predominate (later mononuclear
cells)
• Red blood cells—absent in nontraumatic tap
• Glucose <40 mg/dL
• CSF/serum glucose <0.4
• Protein >45 mg/dL (usually between 100 mg/dL and 500 mg/dL)
• Lactic acid and LDH increased
• Gram’s stain is positive in >60% cases
• Culture is positive in >80% cases
Abbreviations: CSF, cerebrospinal fluid; LDH, lactate dehydrogenase
• Immunocompromised patients
• Presence of papilledema and focal neurological signs
• Known CNS neoplasms.
The radiological investigations to be done in a case of meningitis are X-ray
chest (may disclose an abscess or pneumonitis), X-ray of paranasal sinuses, CT
brain and MRI brain.
• Viral meningitis
• Tuberculous, leptospiral and fungal meningitis
• Chemical meningitis (following lumbar puncture, spinal anesthesia, etc.)
• Sarcoid meningitis.
In case of recurrent meningitis, the following disorders must be considered:
• BehÇet disease (recurrent oropharyngeal ulcers, uveitis, orchitis and
meningitis)
• Mollaret meningitis (recurrent fever and headache—HSV-induced)
• Vogt-Koyanagi-Harada syndrome (Meningitis with iridocyclitis and depig-
mentation of the hair and skin)
• Carcinomatous and lymphomatous meningitis.
TREATMENT
Antibiotics
As bacterial meningitis is a medical emergency, antibiotics should be started
within 60 minutes of a patient’s arrival in the emergency room. Empirical
antimicrobial therapy is initiated in patients with suspected bacterial meningitis
(before the results of CSF Gram’s stain and culture) as per the following
recommendations (Tables 69.3 and 69.4).
ANTIBIOTICS BASED ON ORGANISMS

Once the CSF culture reports come, antibiotics can be changed based on the
organisms as follows (Tables 69.5 and 69.6).
Table 69.3 Empirical antimicrobial therapy
Age of patient Antimicrobial therapy

• 0–4 weeks Cefotaxime plus ampicillin
• 4–12 weeks Third-generation cephalosporin plus ampicillin
• 3 months–18 years Third-generation cephalosporin plus vancomycin
• 18–50 years Third-generation cephalosporin plus vancomycin
• >50 years Third-generation cephalosporin plus vancomycin plus ampicillin
Table 69.4 Empirical antimicrobial therapy for special conditions
Special conditions
• Immunocompromised Vancomycin plus ampicillin and ceftazidime
• Basilar skull fracture Third-generation cephalosporin plus vancomycin
• Head trauma/neurosurgery Vancomycin plus ceftazidime
• CSF shunt Vancomycin plus ceftazidime
For severe penicillin allergy, consider vancomycin and chloramphenicol (for meningococcus)
and trimethoprim/sulfamethoxazole (for Listeria).
Abbreviation: CSF, cerebrospinal fluid
Table 69.5 Choice of antibiotics based on organism
Organism Antibiotic
Haemophilus influenzae
B-lactamase-negative Ampicillin or Third-generation cephalosporins or
chloramphenicol
B-lactamase-positive Third-generation cephalosporins or chloramphenicol or
cefepime
Neisseria meningitidis Penicillin G or ampicillin or Third-generation
cephalosporins or chloramphenicol
Streptococcus pneumoniae
Penicillin MIC <0.1 g/mL Penicillin G or ampicillin or Third-generation cephalosporins,
Chloramphenicol or vancomycin plus rifampin
Penicillin MIC 0.1–1.0 g/mL Third-generation cephalosporins or vancomycin or
meropenem
Penicillin MIC >2.0 g/mL Vancomycin plus third-generation cephalosporins or
meropenem
Enterobacteriaceae Third-generation cephalosporins or meropenem or fluoro-
quinolone or trimethoprim/sulfamethoxazole or cefepime
Pseudomonas aeruginosa Ceftazidime or cefepime or meropenem or
fluoroquinolone or piperacillin
Listeria monocytogenes Ampicillin or penicillin G or Trimethoprim/
sulfamethoxazole
Streptococcus agalactiae Ampicillin or penicillin G or third-generation cephalosporins
or vancomycin
Staphylococcus aureus
Methicillin-sensitive Nafcillin or oxacillin or vancomycin
Methicillin-resistant Vancomycin or linezolid, quinupristin-dalfopristin, daptomycin
Staphylococcus epidermidis Vancomycin
Abbreviation: MIC, minimum inhibitory concentration
The usual duration of antibiotics is between 10 and 14 days. Prolongation of

fever or the late appearance of drowsiness, hemiparesis or seizures should raise
the suspicion of subdural effusion, mastoiditis, sinus thrombosis, cortical vein
thrombosis or brain abscess; all require that therapy be continued for a longer period.
Table 69.6 Antibiotics dosage
Antimicrobial agent Adult

Ampicillin 12 g/day, q4h
Cefepime 6 g/day, q8h
Cefotaxime 12 g/day, q4h
Ceftriaxone 4 g/day, q12h
Ceftazidime 6 g/day, q8h
Gentamicin 7.5 (mg/kg)/day, q8h
Meropenem 3 g/day, q8h
Metronidazole 1500–2000 mg/day, q6h
Penicillin G G 20–24 million U/d, q4h
Vancomycin 2 g/day, q12h
Corticosteroids
Corticosteroids have been found to be effective in the management of acute
bacterial meningitis. The incidence of seizures and coma were reduced in patients
who received corticosteroids. However, there was no change in the incidence of
neurologic sequelae such as hearing loss. The usual dose of dexamethasone is
10 mg IV q6h for 4 days. The first dose of steroid should ideally be given 20 minutes
prior or at least along with the first dose of antibiotics.
Other Measures
Head-end elevation, hyperventilation, mannitol and other neurosurgical
interventions are adopted if cerebral edema is present. Anticonvulsants should
be added if seizures occur.
Prognosis
The poor prognostic factors for acute bacterial meningitis are onset of seizures
within 24 hours of admission, diminished level of consciousness, infancy, old
age, presence of comorbid conditions and increased intracranial tension.
Sequelae
The neurological sequelae of acute bacterial meningitis are diminished
intelligence, memory disturbances, seizures, hearing loss and gait disturbances.
VIRAL MENINGITIS
Etiology
The common viruses responsible for acute meningitis are enteroviruses
(echoviruses, coxsackieviruses), herpes simplex, Varicella zoster, Epstein-Barr
virus, HIV and arthropod-borne viruses.
Routes of Entry
• Respiratory passages—e.g. measles, mumps, VZV
• Gastrointestinal route—e.g. enteroviruses
• Genital route—e.g. HSV
• Inoculation by mosquitoes or animal bites—e.g. rabies.
Clinical Features
The symptoms of viral meningitis are more or less similar to the acute bacterial
meningitis described above but with reduced severity. However, the presence of
seizures, focal neurologic signs, stupor and coma are highly uncommon in viral
meningitis and their presence usually indicates viral encephalitis or another CNS
infectious process.
INVESTIGATIONS
CSF Analysis
The usual CSF picture in acute viral meningitis is as follows:
• Opening pressure—normal or mildly elevated
• Glucose—normal
• Protein—normal or slightly elevated (20–80 mg/dL)
• Cell count 25–500/mm3 with lymphocytic pleocytosis.
Exceptions
In some cases of meningitis due to mumps, CSF glucose may be reduced.
Similarly, neutrophilic predominance is seen in meningitis due to ECHO virus
infection.
Other Investigations
Apart from the routine investigations mentioned in the management of acute
bacterial meningitis, other important investigations are:
• Serologic studies: Helps in documenting the antibodies and is useful in
arboviruses like West nile virus.
• PCR amplification of viral nucleic acid: This test is costly but highly sensitive
and is very useful in CMV, EBV, VZV, HHV-6, etc.
• Viral culture: It has poor sensitivity and not routinely done.
• Partially treated bacterial meningitis
• Mycobacterial/fungal meningitis
• Neoplastic and noninfectious meningitis.
Treatment
General measures like maintaining the fluid and electrolyte balance should
be taken care. Analgesics, antipyretics and antiemetics should be given for
appropriate patients. Antivirals are usually indicated only in severe viral
meningitis.
For Severe HSV, EBV, VZV

Acyclovir IV 20–30 mg/day in 3 divided doses followed by oral acyclovir 800 mg
5 times/day or famciclovir 500 mg tid or valacyclovir 1000 mg tid for 1–2 weeks.
For less severe patients, oral drugs alone are sufficient.
For HIV Meningitis

HAART should be given. Pleconaril is a newer drug that can be used for enteroviral
meningitis.
Prognosis
The prognosis is an excellent with neurologic sequelae reported in only a very
few cases.
TUBERCULAR MENINGITIS
Etiology
Mycobacterium tuberculosis.
Pathogenesis
Tubercles are formed in the brain parenchyma due to the hematogenous spread
of the tubercle bacilli during the primary infection. These tubercles later enlarge,
become caseous and may discharge the bacilli and antigens into the subarachnoid
space producing meningitis.
Clinical Features
Prodromal Stage (2 weeks–2 months)

Low-grade fever, headache, night sweats, neck stiffness, loss of appetite, loss of
weight, lethargy, vomiting, abdominal pain, etc.
Later Stage
Stupor, focal neurologic signs, seizures, cranial nerve palsies and hydrocephalus.
Table 69.7 Lab investigations
• CSF analysis
– Elevated CSF opening pressure
– Increased protein (10–500 mg/dL)
– Decreased glucose (20–40 mg/dL)
– Cell count—10–500 cells/µL with lymphocytic pleocytosis
– Presence of a cob web-like clot
– AFB smear in CSF is positive in only around 30% cases
– CSF culture positive in around 50% cases
– PCR for detection of mycobacterial DNA is positive in about 75% of patients
• Other investigations
– X-ray chest, tuberculin tests—to detect the primary source
– CT or MRI brain
Abbreviations: CSF, cerebrospinal fluid; AFB, acid-fast bacilli; PCR, polymerase chain reaction; DNA,
deoxyribonuceleic acid; CT, computed tomography; MRI, magnetic resonance imaging
Sequelae
Minor or major sequelae occur in about 25% of the patients who recover. These
include deafness, convulsive seizures, blindness, hemiplegia, paraplegia and
intellectual impairment.
Investigations
It is given in Table 69.7.
Treatment
Antituberculous Therapy
}
Isoniazid 300 mg/day and rifampicin 10 mg/kg/day
+
Pyrazinamide 30 mg/kg/day and ethambutol 25 mg/kg/day for 9–12 months
in divided doses
+
Pyridoxine 50 mg/day
Steroids
Dexamethasone is indicated if evidence of hydrocephalus is present.
FUNGAL MENINGITIS
Organisms: Cryptococcal neoformans, Histoplasma capsulatum, C. immitis, etc.
They are acquired by the inhalation of fungal spores.
Investigations
• CSF analysis: Increased protein, reduced glucose and lymphocytic pleocytosis
• PCR.
Treatment
• Cryptococcus neoformans
Amphotericin B (0.7 mg/kg/day IV) + flucytosine 100 mg/kg/day for 2 weeks
↓
Flucanozole PO 400 mg/day for 2 months
↓
Fluconazole PO 200 mg/day for 12 months
• Histoplasma capsulatum
Amphotericin B (0.7 mg/kg/day IV) for 4 weeks
↓
Itraconazole PO 200 mg/day for 6 months.
VIRAL ENCEPHALITIS
Definition
Inflammation of the brain parenchyma is called as encephalitis. Encephalitis is
usually associated with meningitis (Meningoencephalitis), spinal cord or nerve
roots (encephalomyelitis, encephalomyeloradiculitis).
Etiology
Herpes simplex virus, VZV, EBV, arthropod-borne virus, CMV, enterovirus, etc.
Clinical Features
The clinical features of acute viral encephalitis are fever, confusion, behavioral
changes, personality changes and hallucinations, etc. Some patients may also
have focal neurologic signs like aphasia, ataxia, involuntary movements and
cranial nerve deficits. Seizures, weakness, diabetes insipidus and SIADH are also
seen in some patients.
Investigations
CSF Analysis
CSF picture in viral encephalitis is similar to viral meningitis with:
• Mildly increased protein
• Normal glucose
• Lymphocytic pleocytosis
• PCR-highly sensitive for CMV, EBV, HHV-6, enteroviruses
• Culture—poor sensitive
• Serology—IgM antibodies—west nile virus.
MRI, CT, EEG

Presence of focal findings is highly suggestive of HSV encephalitis. Examples of
focal findings include:
• Increased signal intensity in the frontotemporal region on MRI
• Focal areas of mass effect and contrast enhancement on CT
• Periodic focal temporal lobe spikes on EEG.
Brain Biopsy
Brain biopsy is indicated in patients in whom PCR fail to lead to a specific
diagnosis, if focal abnormalities are present in MRI and if there is no response to
treatment with antivirals.
TREATMENT
General Measures
Monitoring of vitals like respiration, blood pressure and ICP should be done. Fluid
and electrolyte balance should be maintained. Antipyretics and anticonvulsants
are given for appropriate patients. Precautions should be taken to prevent the
development of DVT, pressure sores and aspiration pneumonia.
Specific Measures (Table 69.8)

Table 69.8 Pharmacologic management of viral encephalitis
For HSV, EBV, VZV

• IV Acyclovir 10 mg/kg tid (in 100 mL NS over 1 hour) for 2–3 weeks
• Side effects: Elevated urea, creatinine; thrombocytopenia, vomiting, diarrhea
For CMV
• Ganciclovir
– Induction therapy—ganciclovir 5 mg/kg bid (over 1 hour) for 2–3 weeks
– Maintenance therapy—ganciclovir 5 mg/kg od (over 1 hour) for an indefinite
period
– Side effects of ganciclovir: Granulocytopenia, thrombocytopenia, etc.
• Foscarnet
– Induction therapy—foscarnet 60 mg/kg tid (over 1 hour) for 2–3 weeks
– Maintenance therapy—foscarnet 60–120 mg/kg od (over 1 hour)
– Side effects: Renal impairment, hypocalcemia
Other newer drugs for viral encephalitis
• Cidofovir 5 mg/kg IV weekly once for 2 weeks, then biweekly for 2 or more doses
• Intravenous ribavarin 15–25 mg/kg/day
Abbreviations: HSV, herpes simplex virus; EBV, Espstein-Barr virus; VZV, varicella zoster virus; CMV,
cytomegalovirus
Sequelae
The sequelae of acute viral encephalitis include movement disorders, weakness,
seizure disorder and cognitive impairment.
BIBLIOGRAPHY
1. Abdulkareem M Al Bekairy, Shmeylan Al Harbi, Abdulmalik M Alkatheri, Saleh Al
Dekhail, Lolowa Al Swaidan, Nabil Khalidi. Bacterial meningitis: An update review.
Afr. J. Pharm. Pharmacol. 2018(18).pp.469-78.
2. Baringer JR. Herpes simplex virus encephalitis. In: Davis LE, Kennedy PGE (Eds).
Infectious diseases of the nervous system, 1st edition, Butterworth-Heinemann; 2002.
pp.139-64.
3. Broued MC, Tunked AR, Van de Break D. Epidemiology, diagnosis, and antimicrobial
treatment of acute bacterial meningitis. Clin Microbiol. Rev. 2010;23(3):467-92.
4. Dorothee H, Nguyen DB, Nguyen T, Mai H, et al. Intensified antituberculosis therapy
in adults with tuberculous meningitis. N Engl J Med. 2016;374:124-34.
5. Galimi R. “Extrapulmonary Tuberculosis: Tuberculous Meningitis New Developments,”
European Review for Medical and Pharmacological Sciences. 2011;15(4).pp. 365-86.
6. Haldar S, Sharma N, Gupta VK, Tyagi JS. “Efficient Diagnosis of Tuberculous
Meningitis by Detection of Mycobacterium tuberculosis DNA in Cerebrospinal Fluid
Filtrates Using PCR.” J Med Micro. 2009;58(5).pp.616-24.
7. Kennedy PGE. Viral encephalitis-causes, differential diagnosis and management.
Neurol Neurosurg Psychiatry. 2004;75:i10-i15.
8. Lamelas A, Harris SR, Roltgen K, et al. Emergence of a new epidemic Neisseria
meningitidis serogroup A Clone in the African meningitis belt: high-resolution picture
of genomic changes that mediate immune evasion, MBio. 2014;5:e01974–e0201.
Principles of Internal Medicine, 18th edition, McGraw Hill Publications; 2012.
10. Mei-Ling Sharon Tai. Tuberculous Meningitis: Diagnostic and Radiological Features,
Pathogenesis and Biomarkers; NM. 2013;4(2).
11. Mustapha MM, Lee HH. Insights into seasonal dynamics of bacterial meningitis; The
Lancet Global Health. 2016;4(6):e345-16.
12. Mustapha MM, Marsh JW, Krauland MG, et al. Genomic epidemiology of hypervirulent
serogroup W, ST-11 Neisseria meningitidis. EBioMedicine. 2015;2:1447-55.
13. Olaf Hoffman, Weber RJ. Pathophysiology and Treatment of Bacterial Meningitis.
Ther Adv Neurol Disord. 2009;2(6):1-7.
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of bacterial meningitis: a time-series analysis. Lancet Glob Health. 2016;4: e370-e7.
15. Papadakis MA, Mcphee SJ, Rasovo MW. Current Medical Diagnosis and Treatment,
54th edition, 2015.
16. Sili U, Kaya A. Herpes simplex virus encephalitis: Clinical manifestations, diagnosis
and outcome in 106 adult patients Mert. 2014;60(2):112-8.
17. Van de Beek, D. Progress and challenges in bacterial meningitis. Lancet. 2012;380:
1623-4.
CHAPTER
70 TA Naufal Rizwan
ALCOHOL WITHDRAWAL SYNDROME
Symptoms that occur in established alcoholics when they are starved of alcohol
for more than a few hours are known as alcohol withdrawal syndrome. It is usually
seen in a binge or periodic drinker rather than the steady drinker. It is also called
as alcohol abstinence syndrome.
SYMPTOMS
Symptoms of alcohol withdrawal syndrome are tabulated in Table 70.1.
Table 70.1 Symptoms of alcohol withdrawal syndrome
Early Late
• Tremulousness Delirium tremens
• Hallucinosis
• Seizures
Tremulousness
This is the most common withdrawal symptom. The patients usually describe it
as ‘jitters’ or ‘shakes’. Initially tremulousness begins in the morning and once the
patient takes alcohol, the symptoms disappear. However, the symptoms return
on successive mornings with increasing severity. Generalized tremor is the
most important feature of this illness. This tremor is more when the patient is in
emotional stress and is mild when he/she is in quiet surroundings. The tremor
may even interfere with his speech and eating. The other associated symptoms
are facial flushing, over alertness, easy startling, nausea, vomiting, abdominal
pain, etc. The patients may also have tachycardia, tachypnea and systolic
hypertension.
Hallucinosis
Hallucinosis is a disturbance of perception and is seen in around 25% of alcohol
withdrawal patients. The most common hallucinations are visual, although
auditory, olfactory or tactile hallucinations are noted in a few patients. Visual
hallucinations, if present, usually involve the persons or animals.
Chapter 70 Alcohol Withdrawal Syndrome 507
“Alcoholic Mania” (Also Called as Hallucinatory Insanity of Drunkards)

It is a special type of alcoholic psychosis, consisting of more or less pure auditory
hallucinosis, prominent at the night time. Most auditory hallucinations are
human voices, belonging to their friends or relatives. Ringing, buzzing or clicking
sounds are also noted in some patients. These hallucinations appear so real to the
patient that he may even call the police or commit suicide if the hallucinations
are threatening. Following treatment, the patient realizes the voices were indeed
imaginary.
Seizures (Rum Fits or Whiskey Fits)

Seizures are usually seen 8–48 hours after the cessation of alcohol. Most of them
are GTCS and usually 2–6 episodes are seen in a day. More than 25% of patients
with seizures go on to develop delirium tremens. Focal seizures and status
epilepticus are uncommon with alcohol withdrawal.
DELIRIUM TREMENS
Delirium tremens is an acute organic psychosis that usually manifests 2–3 days
after the last alcohol drink. Delirium tremens is the most dangerous alcohol
withdrawal symptom. It may follow withdrawal seizures either before the postictal
period has cleared or after 1 or 2 asymptomatic days. It is usually seen in a patient
who has been admitted for some other illness, accident or operation.
Clinical Features
Patients with delirium tremens are confused, agitated and restless. They may
exhibit sleeplessness, tremors and sensory hyperacuity. Visual hallucinations
(often snakes) and delusions are also seen in some patients. Signs and symptoms
of autonomic hyperactivity like fever, diaphoresis, dehydration, tachycardia,
arrhythmias and dilated pupils are present.
Pathogenesis
The exact pathogenesis of alcohol withdrawal symptoms is still unclear. However,
the increase of excitatory neurotransmitters (Glutamate) and a decrease in
inhibitory neurotransmitters (GABA) plays an important role in the pathogenesis
of this disorder. Hypomagnesemia and increased arterial pH also contribute to
the disorder.
Investigations
• Blood investigations—complete blood count, liver function tests, renal
function tests
• ABG analysis, serum electrolytes (potassium, calcium, magnesium)
• CSF study
• CT brain, MRI brain
• EEG.
Management
Management of Withdrawal Symptoms

• Benzodiazepines (drug of choice): Benzodiazepines like diazepam, lorazepam
and chlordiazepoxide are the usual drugs used in the management of
delirium tremens.
– Oral (mild withdrawal symptoms): Diazepam 20 mg/day, decreasing at
5 mg/day
– IV (moderate to severe symptoms): Lorazepam 2 mg/diazepam 10 mg
slow IV repeated at 30 minute intervals until the patient is calm
• Beta-blockers: Atenolol 50 mg od or bid—to reduce the autonomic symptoms
• Alpha-2 agonists: Clonidine 5 µg/kg orally every 2 hours—for cardiovascular
withdrawal symptoms
• Carbamazepine—400–800 mg daily orally may also be given
• Thiamine 100 mg/d and other vitamin supplements
• Phenytoin has no role in preventing seizures during alcoholic withdrawal
• If hallucinations are the only symptoms, antipsychotics like haloperidol or
phenothiazines may be considered (these drugs can increase the risk of
seizures).
MANAGEMENT OF DELIRIUM TREMENS

Treatment of the patient with delirium tremens can be difficult, and the condition
is likely to run a course of 3–5 days regardless of the therapy employed.
• Parenteral benzodiazepines: Diazepam, 10 mg IV, or lorazepam 2 mg IV or
IM, repeated every 15 minutes until calming. Maintenance doses are given
every 2–4 hourly depending on the patients response
• Dehydration—corrected by IV fluids
• Hyperthermia—corrected by cooling mattresses or evaporative cooling
• Hypotension—corrected by IV fluids and vasopressors
• Infections—treated by antibiotics
• Hypoglycemia—corrected by 25% dextrose
• Correction of electrolyte abnormalities
• Thiamine 100 mg IV od, pyridoxine 100 mg/day, folic acid 1 mg/day.
BIBLIOGRAPHY
1. Amato L, Minozzi S, Vecchi S, Davoli M. Benzodiazepines for alcohol withdrawal.
Cochrane Database Syst Rev. 2010; CD005063.
2. Bayard M, Mcintyre J, Hill KR, Woodside JJ. Alcohol withdrawal Syndrome. Am Fam
Physician. 2004;69(6):1443-1450.
3. Benjamin J Sadock, Virginia Alcott Sadock and Pedro Ruiz. Kaplan and Sadock’s
Comprehensive Textbook of Psychiatry, 9th edition.
4. Dennis DL, Kasper DL, Jameson JL, Fauci AS, Hauser SL, Loscalzo J. Harrison’s
Principles of Internal Medicine, 18th edition. McGraw Hill Publications; 2012.
5. Esel E. Neurobiology of alcohol withdrawal: inhibitory and excitatory neurotrans
mitters. Turkish J Psychiatry. 2006; 17(2):129-37.
6. Ferguson JA, Suelzer CJ, Eckert GJ, et al. Risk factors for delirium tremens development.
J Gen Intern Med. 1996;11:410.
Chapter 70 Alcohol Withdrawal Syndrome 509
7. Hall W, Zador D. The alcohol withdrawal syndrome. Lancet. 1997;349(9069):1897-

1900.
8. Kosten TR, O’Connor PG. Management of drug and alcohol withdrawal. N Engl J Med.
2003;348:1786.
9. Malcolm R, Myrick H, Roberts J, Wang W, Anton RF, Ballenger JC. The effects of
carbamazepine and lorazepam on single versus multiple previous alcohol withdrawals
in an outpatient randomized trial. J Gen Intern Med. 2002;17:349-55.
10. Mayo-Smith MF. Pharmacological management of alcohol withdrawal. A meta-
analysis and evidence-based practice guideline. American Society of Addiction
Medicine Working Group on Pharmacological Management of Alcohol Withdrawal.
JAMA. 1997;278:144-51.
11. McKeon A, Frye MA, Delanty N. The alcohol withdrawal syndrome. J Neurol
Neurosurg Psychiatry. 2008;79:854-62.
12. McKinley MG. Alcohol withdrawal syndrome overlooked and mismanaged? Crit Care
Nurs. 2005; 25(3):40-9.
13. Papadakis MA, Mcphee SJ, Raboue MW. Current Medical Diagnosis & Treatment,
54th edition; 2015.
14. Ropper AH, Samuels MA, Klein J. Adams and Victor’s Principles of Neurology,
10th edition.
15. Rowland LP, Pedley TA. Merritt’s Neurology, 12th edition.
16. Wright T, Myrick H, Henderson S, Peters H, Malcolm R. Risk factors for delirium
tremens: a retrospective chart review. Am J Addict. 2006;16:213-9.
CHAPTER
71 TA Naufal Rizwan
DELIRIUM IN INTENSIVE CARE UNIT
DEFINITION
Delirium is an acute confusional state characterized by the presence of
hallucinations, delusions, illusions along with psychomotor and autonomic
overactivity.
CLINICAL FEATURES
The symptoms of delirium usually develop over a period of 2–3 days. The earliest
symptoms are impaired concentration and restlessness. The other associated
features are disruption of the sleep-wake cycle, drowsiness, incoherence,
irritability and inattention. Emotional lability, impairment of language and
memory are also present. In some patients, autonomic disturbances like tremors,
tachycardia, sweating, dilated pupils, facial flushing is seen. These symptoms
usually disappear in 2–3 days, although in exceptional cases they may persist for
several weeks, and recovery is usually complete.
TERMINAL DELIRIUM
Delirium occurring at the end of life. It is usually due to multiple medical causes
and may even be unrecognized.
Sundowning
Mild-to-moderate delirium occurring at the night, mostly seen in patients with
pre-existing dementia, is called as sundowning.
Etiology
Non-neurologic Causes
• Pneumonia, enteric fever, malaria, etc.
• Septicemia and bacteremia (septic encephalopathy)
• Postoperative states
• Endocrine causes—Increased thyroid and cortisol levels.
Chapter 71 Delirium in Intensive Care Unit 511
Neurologic Causes
• Vascular, neoplastic or other diseases involving the temporal lobes and
brainstem
• Concussion and contusion (traumatic delirium)
• Meningitis, encephalitis
• Subarachnoid hemorrhage.
Toxic/Withdrawal States
• Alcohol and drugs withdrawal
• Drug intoxications—cocaine, amphetamine, opiates, benzodiazepines, etc.
• Postconvulsive delirium.
Pathology and Pathophysiology

It has been found that certain specific areas of the brain are responsible for some
of the symptoms that are seen in delirium. For example, temporal lobes play a role
in auditory and olfactory hallucinations while the midbrain and hypothalamus
are concerned with visual hallucinations and autonomic symptoms of delirium,
respectively.
The postulated mechanisms of delirium are:
• Delirium seen in withdrawal states: Some drugs have a depressant action on
certain parts of the brain. Withdrawal of these drugs may result in overactivity
of those parts of the brain, resulting in delirium.
• Delirium seen in infections: It is due to the direct toxic effect of the infections
on the brain.
Delirium has to be differentiated from:
• Acute confusional state with psychomotor underactivity
• Beclouded dementia
• Acute confusional state secondary to focal cerebral disease.
Investigations
The investigations that are needed to be done in a patient with delirium depend
on the following three different scenarios of presentation:
1. Patient is afebrile and no focal neurologic signs
• Endogenous metabolic disorders: Glucose, urea, creatinine, electrolytes,
ABG, thyroid tests, LFT, autoantibody screen, cardiac enzymes, etc.
• Exogenous toxic state: Toxicologic screening of blood and urine.
2. Patient is febrile or signs of meningeal irritation present
• Systemic infection: CBC, chest X-ray, urine routine, urine and blood
culture
• Meningitis and encephalitis: Lumbar puncture.
3. Focal neurologic signs or seizures present CT or mri scan, eeg.
Treatment
Four key steps in the management of delirium include:
1. Identifying the cause
2. Controlling the behavior
3. Preventing complications
4. Supporting functional needs.
General Measures
Identifying the underlying medical cause and withdrawal of all the offending drugs
must be carried out. Proper environment is mandatory in the management of
delirium such as a room with adequate natural lighting will reduce the incidence
of ‘sun downing’. A family member or a nurse should be with the patient at all
times preferably. An agitated patient should not be tied to the bed, rather he
should be allowed to walk about the room as this may reduce his excitement and
fright. Warm baths, mentally stimulating activities and frequent reorientation to
the surroundings have been found to be effective in reducing the delirium. The
physician should explain every procedure (including simple ones like recording
the temperature) to the patient as this will allay the fear and reduce the risk of
hallucination.
Specific Measures (Medications)

Most of the delirious patients can be managed by the general measures described
above. However, medications are required in some patients. The two indications
for medication in delirious states are behavioral control (e.g. pulling out IV lines)
and subjective distress (e.g. pronounced fear due to hallucinations). Haloperidol,
quetiapine and risperidone are the commonly used drugs. Benzodiazepines
(diazepam or lorazepam) are useful in alcohol withdrawal syndrome.
Electroconvulsive Therapy
It has been used as a last resort for delirious patients with severe agitation who
are not responsive to pharmacotherapy, such as high doses of IV haloperidol.
BIBLIOGRAPHY
1. Barr J, Fraser GL, Puntillo K, et al. Clinical Practice guidelines for the management of
pain, agitation, and delirium in adult patients in the intensive care unit. Critical Care
Medicine. 2012
2. Cavallazzi R, Mohamed Saad, Paul E Marik. Delirium in the ICU. An overview. Annals
of Intensive Care. 2012,2:49.
3. Dan LL, Dennis LK, Larry J, Anthony SF, Stephen LH, Joseph L. Harrison’s Principles
of Internal Medicine. 18th edition 2012. pp.515-6.
4. Dubois MJ, Bergeron N, Dumont M, Dial S, Skrobik Y. Delirium in an intensive care
unit: a study of risk factors. Intensive Care Med. 2001;27(8):1297-304.
5. Immers HE, Schuurmans MJ, van de Bijl JJ. Recognition of delirium in ICU patients:
a diagnostic study of the NEECHAM confusion scale in ICU patients. BMC Nurs. 2005;
4:7.
Chapter 71 Delirium in Intensive Care Unit 513
6. Jeremy SP, Ryan DH, Li W, Benjamin H, Michael NY, et al. Delirium in survivors of cardiac
arrest treated with mild therapeutic hypothermia. Am J Crit Care.2016;25(4):e81-e9.
7. Mark VB, Peter P, Lisette S. Assessment of delirium in ICU patients. Neth J Crit Care.
2010;14(1).
8. Maxine AP, Stephen JM, Michael WR. Delirium. Current Medical Diagnosis and
Treatment. 54th edition 2015.pp.64-5.
9. Ouimet S, Kavanagh BP, Gottfried SB, Skrobik Y. Incidence, risk factors and
consequences of ICU delirium.Intensive Care Med. 2007;33(1):66-73.
10. Peterson JF, Pun BT, Dittus RS, Thomason JW, Jackson JC, Shintani AK, Ely EW.
Delirium and its motoric subtypes: study of 614 critically ill patients. Am Geriatr Soc.
2006,54(3):479-84.
11. Reade MC, Finger S. Sedation and delirium in the intensive care unit. N Engl J Med.
2014;370:444-54.
12. Roberts B, Rickard CM, Rajbhandari D, Turner G, Clarke J, et al. Multicentre study
of delirium in ICU patients using a simple screening tool. Aust Crit Care. 2005;18(1):
8-14.
13. Ryosuke T, Yasutaka O. A clinical perspective of sepsis-associated delirium. Journal of
Intensive Care. 2016;4:18.
14. Sadock BJ, Sadock VA, Ruiz P. Kaplan and Sadock’s Comprehensive Textbook of
Psychiatry, 9th edition Wolters Kluwer; 2009.
15. van Eijk MMJ, Slooter AJC. Delirium in intensive care unit patients. Semin Cardoithorac
Vasc Anesth. 2010;14:141-47.
SECTION
17 NEUROMUSCULAR DISORDERS
Chapter 72 Guillain-Barré Syndrome

TA Naufal Rizwan
Chapter 73 Myasthenia Gravis

TA Naufal Rizwan
Chapter 74 Periodic Paralysis

TA Naufal Rizwan
Chapter 75 Critical Illness Polyneuropathy

TA Naufal Rizwan
CHAPTER
72 TA Naufal Rizwan
GUILLAIN-BARRÉ SYNDROME
GENERAL CONSIDERATIONS
Guillain-Barré syndrome (GBS) is an acute or subacute polyradiculoneuropathy
that is autoimmune in nature. Males are frequently affected and adults are at
higher risk than children. Subtypes of Guillain-Barré syndrome is given in Table
72.1.
ETIOLOGY
In more than 2/3rd of cases, it usually occur 2–3 weeks following an acute
respiratory or gastrointestinal infection. Organisms commonly associated with
GBS are Campylobacter jejuni, CMV, EBV, human herpes virus, Mycoplasma
pneumoniae and HIV. GBS is also frequently seen in patients suffering from SLE
and non-Hodgkins lymphoma.
PATHOGENESIS
The exact mechanism still remains unclear. However, various evidences show that
autoimmunity play an important role in the pathogenesis of GBS. Gangliosides,
which are glycosphingolipids are involved in cell-cell interaction and regulation
of growth. In GBS, antibodies are directed against these gangliosides resulting in
nerve conduction block. Both humoral and cell-mediated immunity contribute
to the pathogenesis of the disease.
Table 72.1 Subtypes of Guillain-Barré syndrome
Subtype Features Electrodiagnosis

Acute inflammatory demyelinating Rapid recovery Demyelinating
polyneuropathy (AIDP) Anti-GM1 antibodies
Acute motor axonal neuropathy Rapid recovery Axonal
(AMAN) Anti-GD1a antibodies
Acute motor sensory axonal Slow recovery Axonal
neuropathy (AMSAN)
Miller-Fisher syndrome (MFS) Ataxia, areflexia, ophthalmoplegia Demyelinating
anti-GQ1b antibodies
518 Section 17 Neuromuscular Disorders
CLINICAL FEATURES
The symptoms of Guillain-Barré syndrome are predominantly motor in nature,
although sensory and autonomic involvement is noted in some patients.
Motor
The most characteristic feature of GBS is symmetrical weakness, which often
begin in the legs and then later involve the upper limbs (ascending paralysis).
Weakness evolves over hours to few days and leg weakness is more than the arm.
Deep tendon reflexes are absent.
Sensory
In early GBS, tingling sensation in the legs and pain in the shoulder may be
present. Proprioception is greatly affected whereas pain and temperature are
usually intact.
Cranial Nerves
Bilateral LMN facial palsy, which is asymmetric, is seen in 50% cases. Lower
cranial nerves (9–12) involvement, though not very common, can result in bulbar
weakness. Rarely 3, 4, 6 nerves are affected.
Autonomic Involvement
Autonomic involvement is manifested by facial flushing, sweating and postural
hypotension. In serious cases, patient can also develop cardiac arrhythmias,
bladder dysfunction and pulmonary dysfunction.
Findings which Help in Diagnosis
Clinical
• Progressive, symmetric motor weakness that usually ceases by 4 weeks
• Hyporeflexia or areflexia
• Cranial nerve involvement (most common-facial nerve)
• Mild-to-moderate sensory signs
• Autonomic involvement—tachycardia, postural hypotension, etc.
• Recovery starts in 2–4 weeks
• Preceding GI or respiratory infection.
Laboratory
The CSF albumino cytological dissociation [(Elevated CSF protein 1–10 g/L (100–
1000 mg/dL) without accompanying pleocytosis)].
Chapter 72 Guillain-Barré Syndrome 519
Electrodiagnostic
• Nerve conduction velocity slowing or conduction block (80%)
• Absence of H and F responses
• NCV normal in about 20% patients.
Findings Reducing the Possibility of GBS

• Asymmetric weakness
• Severe bladder/bowel involvement
• Definite sensory level
• CSF mononuclear cells >50/mm3.
Infections
• Diphtheria, Lyme disease, tick-borne diseases
• Poliomyelitis, CMV.
Noninfectious
• Botulism
• Vasculitis
• OPC poisoning, arsenic poisoning
• Myasthenia gravis
• Porphyria.
Treatment
General Measures
The general measures include analgesics for pain, frequent turning to prevent
pressure sores and exercises to prevent joint contractures.
Specific Measures
Steroids have no role in the treatment of GBS. The various treatment options
available are:
• IVIg-administered at a dose of 400 mg/kg/day for 5 days—this neutralizes
the GBS autoantibodies
• Plasmapheresis—40–50 mL/kg plasma exchange, 4–5 times a week.
Treatment is usually not indicated if the patient has reached the plateau
phase, unless the motor weakness is very severe. With the above treatment, most
patients show improvement at the end of first week. Severe GBS presenting with
bulbar dysfunction may require intubation and mechanical ventilation.
Prognosis
Full recovery is seen in 80–85% of patients, although persisting areflexia may be
present. Recovery is delayed and incomplete in GBS with axonal damage. About
5% of patients develop one or more relapses; such cases are designated as chronic
inflammatory demyelinating polyneuropathy (CIDP). Advanced age, delay in the
onset of treatment and severe GBS indicate poor prognosis.
BIBLIOGRAPHY
1. Bianca van den Berg, Christa Walgaard, Judith Drenthen, Christiaan Fokke, Bart
C Jacobs, Pieter A van Doorn. Guillain–Barré syndrome: pathogenesis, diagnosis,
treatment and prognosis. Nature Reviews Neurology. 2014;10:469-82.
2. Colls BM. “Guillain-Barré syndrome and hyponatraemia.” Internal Medicine Journal;
2004.p.218.
3. Dan LL, Dennis LK, Larry J, Anthony SF, Stephen LH, Joseph L. Harrison’s Principles
of Internal Medicine, 18th edn; 2012.pp.515-30.
4. Hadden RD, et al. Preceding infections, immune factors, and outcome in Guillain–
Barré syndrome. Neurology. 2001;56:758-65.
5. Hiraga A, et al. Recovery patterns and long term prognosis for axonal Guillain–Barré
syndrome. J Neurol Neurosurg. Psychiatry. 2005;76:719-22.
6. Hugh JW, Bart CJ, Pieter AV. Guillain-Barrés yndrome. Lancet. 2016;388:717-27.
7. Hughes RA, et al. Immunotherapy for Guillain–Barré syndrome: a systematic review.
Brain. 2007;130:2245-57.
8. Inés GS, Irene SG, Francisco JR, Javier A. Guillain-Barré Syndrome: Natural history and
prognostic factors: a retrospective review of 106 cases. BMC Neurology. 2013;13:95.
9. Kaida K, Kusunoki S. Antibodies to gangliosides and ganglioside complexes in
Guillain–Barré syndrome and Fisher syndrome: mini-review. J Neuroimmunol. 2010;
223:5-12.
10. Kuwabara S, Yuki N Axonal. Guillain–Barré syndrome: concepts and controversies.
Lancet Neurol. 2013;12:1180-8.
11. Mark M, Heinrich M. Fundamentals of Neurology. 1st edn; 2006. pp.173-4.
12. Maxine AP, Stephen JM, Michael WR Delirium. Current Medical Diagnosis and
Treatment, 54th edn; 2015.pp.1023-6.
13. Nobuhiro Yuki, et al. Guillain–Barré Syndrome. N Engl J Med. 2012;366:2294-304.
14. Udaya Seneviratne. Guillain-Barré syndrome; Postgrad Med J. 2000;76:774-82.
CHAPTER
73 TA Naufal Rizwan
MYASTHENIA GRAVIS
Myasthenia gravis is a neuromuscular junction disorder characterized by

fluctuating weakness of certain voluntary muscles. Weakness during continued
activity and improvement following rest and anticholinesterases are the
important features of this disease.
ETIOLOGY
Although exact etiology still remains unclear, autoimmune mechanisms play an
important role in the disease process. This is supported by the presence of thymic
abnormalities in most of the myasthenia patients.
PATHOGENESIS
Normal
Myasthenia Gravis
In myasthenia gravis, repeated activity reduces the release of ACh at the
neuromuscular (NM) junction (presynaptic rundown). Also, there is destruction
of the ACh receptor by the anti-AChR antibodies.
Box 73.1: Drugs causing exacerbation of myasthenia gravis

Beta-Blockers: Atenolol
Antibiotics: Macrolides, quinolones, etc.
Quinine derivatives: Chloroquine, mefloquine, etc.
Muscle relaxants: Pancuronium, vecuronium, etc.
Relationship between Thymus Gland and Myasthenia Gravis

About 75% of myasthenia gravies (MG) patients have hyperplastic thymus and
10% have thymomas. Myoid cells (muscle-like cells) in the thymus have AChRs
on their surface and may act as an autoantigen, eliciting autoimmune response.
CLINICAL FEATURES
Myasthenia gravis affects women more than the men. Peak incidence in women is
in their 20s and in men in their 30s. The two cardinal features of MG are weakness
and fatigability. Weakness increases on repeated usage and is relieved by rest
and drugs. Drugs causing exacerbation of myasthenia gravis is given in Box 73.1.
Infections can lead to increased weakness resulting in crisis.
Eye Signs and Symptoms

Involvement of the eyes is one of the most characteristic and early manifestations
of MG.
Ptosis
It occurs due to weakness of levator palpebrae superiors. It can be unilateral or
bilateral. Fluctuating ptosis is also seen in some patients. Sunlight worsens the
ptosis and ice pack over the eyes relieves it.
Diplopia
It is due to involvement of other extraocular muscles.
Lid twitch sign

Twitching of the upper eyelid that appears a moment after the patient moves the
eyes from a downward to the primary position.
Other Signs and Symptoms

• Snarling expression—involvement of facial muscles results in the natural
smile being transformed in to snarl
• Mushy speech—weakness of the tongue
• Myasthenic hand—weakness of the distal extremity muscles
• Weakness of neck muscles result in difficulty in holding up the head
• Chewing, especially tough food like meat, becomes difficult.
In more than 2/3rd of patients, weakness becomes generalized involving
the limb muscles. Limb weakness is often proximal and asymmetric. In severe
Chapter 73 Myasthenia Gravis 523
Table 73.1 Difference between myasthenia gravis and LEMS
Myasthenia gravis LEMS

Type Postsynaptic disorder Presynaptic disorder
Antibodies against ACh Receptor P/Q-type calcium channels
Predominant involvement Extraocular muscles Proximal muscles of lower limbs
Deep tendon reflexes Preserved Depressed or absent
Repetitive nerve stimulation Decremental Incremental response
(Higher rates-50 HZ) response
cases, weakness of the diaphragm, abdominal muscles, intercostals and even the
external sphincters of the bladder and bowel can occur.
Ocular Myasthenia Gravis
If weakness remains restricted to the ocular muscles for 3 years, it is likely that it
will not become generalized and these patients are said to have ocular MG.
Not seen in myasthenia gravis
• Deep Tendon reflexes are not altered
• Pain is seldom an important complaint
• Demonstrable sensory loss is never seen
• Muscle atrophy is usually not seen.
• Lambert-Eaton myasthenic syndrome (LEMS) (Table 73.1)
• Botulism
• Neurasthenia
• Hyperthyroidism
• Congenital myasthenic syndromes (genetic abnormality).
Disorders Associated with MG

Rheumatoid arthritis, systemic lupus crythematosus (SLE), Graves’ disease,
thymoma, Hashimotos thyroiditis, etc.
INVESTIGATIONS
Antibodies Assay
• Anti-ACh receptor antibodies: These are the most important antibodies
and are seen in 85% of generalized MG and 50% of ocular MG patients.
However, the absence of these antibodies does not rule out MG. Similarly,
no correlation has been found between the antibody level and severity of the
disease. The antibody level decrease with the treatment and exacerbations
increase it.
• Anti-musk (muscle specific kinase) antibodies: These are seen in around 40%
generalized MG patients, in whom AChR antibody is negative. They are not
seen in AChR antibody positive or ocular MG patients.
Electrodiagnostic Testing
Prerequisites
Anti-AChE medications should be stopped at least 6 hours before the test. Weak
muscles or proximal muscles should be tested preferably. Electric shock should
be delivered at a rate of 2–3/second and muscle action potentials recorded.
Impression
Normal persons: Repetitive nerve stimulation does not change the evoked
responses.
Myasthenia gravis: Rapid reduction of >10–15% in the amplitude of the evoked
responses.
Anticholinesterase Test
Edrophonium (Tensilon) 2 mg IV given—if weakness improves, it is suggestive
of MG. Edrophonium is preferred because it is both short as well as rapid acting.
Since edrophonium can produce side effects such as nausea, diarrhea, salivation,
etc. atropine should be kept ready. Neostigmine 15 PO can also be used for the
test.
Imaging
• CT or MRI of the brain to rule out intracranial lesions in ocular or cranial MG
• CT mediastinum to rule out thymoma.
TREATMENT
Various treatment options available are as follows:
• Anticholinesterase medications
• Immunosuppressive agents
• Intravenous immunoglobulin (IVIg)
• Plasmapheresis
• Thymectomy.
Anticholinesterase Medications
Pyridostigmine is the most commonly used drug and the usual dose is 30–60 mg
given 3–4 times daily. Action starts in 15 minutes and last up to 3–4 hours. Nausea,
salivation and diarrhea are the common side effects which can be managed with
atropine/diphenoxylate or loperamide.
Glucocorticoids
Prednisolone
Other Immunosuppressive Drugs

• Azathioprine: The usual starting dose is 50 mg/d which is then gradually
increased to 2–3 mg/kg. However, beneficial effect is seen only after 3–6
months. Idiosyncratic reactions such as flulike symptoms, bonemarrow
suppression are seen in 10% of patients. Allopurinol should not be used to
treat hyperuricemia in patients receiving azathioprine.
• Mycophenolate mofetil: This drug acts by inhibiting the purine synthesis of
the denovo pathway. The dose is 1–1.5 g, given twice a day. Beneficial effect
is seen only after many months. The adverse effects are rare with a very small
risk of malignancy.
• Calcineurin inhibitors: The calcineurin inhibitors used in the treatment of
MG are Cylosporine (4–5 mg/kg/d) and Tacrolimus (0.07–0.1 mg/kg/d).
Nephrotoxicity and hypertension are important adverse effects.
• Cyclophosphamide: Indicated in MG refractory to other treatment.
• Rituximab: It is an antibody against CD20 B cells and is preferably used in
MG with anti-MuSK (muscle-specific tyrosine kinase) antibody.
Plasmapheresis
It is a procedure where the pathogenic antibodies are mechanically removed from
the blood. Usually, 5 exchanges are done over 2 weeks period (3–4 L /exchange).
It is used as a temporary procedure in serious patients.
IV Immunoglobulin
The usual dose of IVIg is 400 mg/kg/d given for 5 days. It should not be used as a
long-term management. Mild side effects like headache, fluid overload are noted
in some patients.
Thymectomy
Following thymectomy, improvement is seen in up to 85% patients. Removal
of thymoma, if present, also reduces the risk of local tumor spread. All patients
with generalized MG, between puberty and 55 years of age, should undergo
thymectomy (even if thymoma is not present).
EVALUATING THE EFFECTIVENESS OF TREATMENT

• Range of eye movements
• Forced vital capacity
• Time taken for the ptosis to develop following an upward gaze
• Forward arm abduction time (for 5 min).
MYASTHENIC CRISIS
Definition
Exacerbation of weakness in a myasthenic patient which is serious enough to
endanger the life is known as myasthenic crisis.
Causes
Infection (most common cause) and excessive anticholinesterase drugs
(cholinergic drugs).
Treatment
• Antibiotic therapy
• Respiratory assistance
• Fluid and electrolyte balance to be maintained
• Plasmapheresis or IVIg
• Stop AChE drugs if their excessive use is the cause for crisis.
BIBLIOGRAPHY
Neurology, 10th edn.
2. Andrew G Engel, Michael Benatar. Myasthenia gravis and myasthenic disorders.
Neurology. 2013;81(1)99.
3. Annapurni Jayam Trouth, Alok Dabi, Noha Solieman, Mohankumar Kurukumbi,
Janaki Kalyanam. Myasthenia gravis: A review. Autoimmune Dis. 2012; 2012:874680.
4. Barth D, Nabavi Nouri M, Ng E, Nwe P, Bril V. Comparison of IVIg and PLEX in patients
with myasthenia gravis. Neurology. 2011;76(23)2017-23.
5. Batocchi AP, Evoli A, Schino CD, Tonali P. Therapeutic apheresis in myasthenia gravis.
Therapeutic Apheresis. 2000;4(4):275-9.
6. Chaudhry V, Cornblath DR, Griffin JW, O’Brien R, Drachman DB. Mycophenolate
mofetil: a safe and promising immunosuppressant in neuromuscular diseases.
Neurology. 2001;56(1):94-6.
Joseph Loscalzo. Harrison’s Principles of Internal Medicine, 18th edn. 2012. McGraw
Hill publications.
8. Gold R, Schneider-Gold C. Current and future standards in treatment of myasthenia

gravis. Neurotherapeutics. 2008;5(4):535-41.
9. Hellmann MA, Mosberg-Galili R, Lotan I, Steiner I. Maintenance IVIg therapy in
myasthenia gravis does not affect disease activity. 2014;338(Issues 1-2):39-42.
10. Keesey JC. Clinical evaluation and management of myasthenia gravis. Muscle and
Nerve. 2004;29(4):484-505.
11. Lewis P Rowland, Timothy A Pedley. Merritt’s Neurology, 12th edn.
12. Maxine A Papadakis, Stephen J McPhee, Michael W Rabow. Current Medical Diagnosis
and Treatment, 54th edn. 2015.
13. Pascuzzi RM. The edrophonium test, Seminars in Neurology. 2003;23(1):83-8.
14. Pescovitz MD. Rituximab, an anti-CD20 monoclonal antibody: history and mecha
nism of action. American Journal of Transplantation. 2006;6(5):859-66.
15. Vern C Juel, Janice M Massey. Myasthenia gravis. Orphanet Journal of Rare Diseases.
2007;2:44.
CHAPTER
74 TA Naufal Rizwan
PERIODIC PARALYSIS
Familial periodic paralysis comprises diseases characterized by recurrent

episodes of limb weakness. The three main types are:
1. Hypokalemic periodic paralysis (HypoKPP)
2. Hyperkalemic periodic paralysis (HyperKPP)
3. Anderson’s syndrome or periodic paralysis with cardiac arrhythmia.
HYPOKALEMIC PERIODIC PARALYSIS

This disorder occurs due to a mutation in the CALCL1A3 or SCN4A.
Types
HypoKPP Type 1 (90%)

It is the most common type and it is inherited as an autosomal dominant disorder.
It occurs due to mutation in the skeletal muscle calcium channel gene CALCL1A3.
HypoKPP Type 2 (10%)

It is due to mutations in the voltage-sensitive sodium channel gene (SCN4A).
Clinical features
Diet rich in carbohydrate and sodium, and rest following prolonged exercise
are the usual predisposing factors for hypokalemic periodic paralysis. Weakness
affects the proximal muscles more than the distal muscles. Ocular and bulbar
muscles are less commonly involved while the respiratory muscles are usually
spared. Weakness usually resolves in 24–48 hours. Only in severe attacks, tendon
and cutaneous reflexes are absent. Cutaneous sensation is not disturbed.
Repeated attacks of HypoKPP have been found to occur in patients with
hyperthyroidism. However, the paralytic attacks cease when the thyroid disorder
has been successfully treated.
Complications
Immediate: Life-threatening cardiac arrhythmias-due to hypokalemia.
Delayed: Severe proximal weakness.
Chapter 74 Periodic Paralysis 529
Investigations
• Documentation of low potassium and increased sodium level during attacks.
• Interattack muscle biopsies show the presence of single or multiple centrally
placed vacuoles or tubular aggregates.
• Motor conduction studies may demonstrate reduced amplitudes.
• EMG may show electrical silence in severely weak muscles. In between
attacks, EMG and NCS are usually normal.
Treatment
During attacks: Oral KCl 0.2–0.4 mmol/kg every 30 minutes until serum potassium
becomes normal. However, if patient has vomiting or diarrhea or cannot take oral
potassium, it should be given as intravenous infusion (preferably in mannitol
since dextrose containing solution are contraindicated).
Prophylactic treatment:
• Acetazolamide 125–1000 mg/d in divided doses (only in hypoKPP type 1)
Although acetazolamide paradoxically lowers the potassium level, this
is offset by the beneficial effect of metabolic acidosis
• Triamterene or spironolactone 25–100 mg/d
• Low carbohydrate, low sodium diet.
HYPERKALEMIC PERIODIC PARALYSIS

This disorder occurs due to a mutation in sodium channel SCN4A gene.
Description
Weakness is usually mild, often affects the proximal muscles and usually lasts less
than 4 hours. Attacks are precipitated by rest following exercise and fasting.
Investigations
Serum potassium: Potassium values are usually elevated, although in a significant
proportion of cases, it is within normal limits.
Nerve conduction study: Reduced motor amplitudes.
EMG: Myotonic discharges during and between attacks.
Muscle biopsy: Vacuoles that are smaller, less numerous, and more peripheral
compared to the hypokalemic form or tubular aggregates are seen.
Treatment
• Acetazolamide 125–1000 mg/d in divided doses.
• Calcium gluconate

Glucose and insulin }
Reduces the potassium level
• Thiazides or fludrocortisone.
Potassium-aggravated Myotonia
It is a variant of hyperkalemic periodic paralysis in which weakness is not seen,
instead myotonia is present.
ANDERSON’S SYNDROME
Five diagnostic criteria for Anderson’s syndrome are:
1. Dysmorphism
2. Periodic paralysis
3. Potassium sensitivity
4. Myotonia (usually mild)
5. Cardiac arrhythmia.
Spontaneous attacks have been associated with high, low, or normal
potassium levels.
BIBLIOGRAPHY
Neurology, 10th edn.
2. Bendahhou S, Cummins TR, Tawil R, Waxman SG, Ptacek LJ. Activation and
inactivation of the voltage-gated sodium channel: role of segment S5 revealed by a
novel hyperkalaemic periodic paralysis mutation. J Neurosci. 1999b;19:4762-71.
3. Benjamin R Soule, Nicole L Simone. Hypokalemic periodic paralysis: a case report
and review of the literature. Cases Journal. 2008;1:256.
Joseph Loscalzo. Harrison’s Principles of Internal Medicine. 18th edn. 2012. McGraw
Hill publications.
5. Donaldson MR, Jensen JL, Tristani-Firouzi M, Tawil R, Bendahhou S, Suarez WA, et al.
PIP2 binding residues of Kir 2.1 are common targets of mutations causing Andersen
syndrome. Neurology. 2003;60:1811-6.
6. Haider Abbas, Nikhil Kothari, Jaishri Bogra. Hypokalemic periodic paralysis. Natl J
Maxillofac Surg. 2012;3(2):220-1.
7. Heine R, Pika U, Lehmann-Horn F. A novel SCN4A mutation causing myotonia
aggravated by cold and potassium. Hum Mol Genet. 1993;2:1349-53.
8. Jurkat-Rott K, Lerche H, Lehmann-Horn F. Skeletal muscle channelopathies. J Neurol.
2002;249(11):1493-1502.
9. Lewis P Rowland, Timothy A Pedley. Merritt’s Neurology,12th edition.
10. Maxine A Papadakis, Stephen J McPhee, Michael W Rabow. Current Medical Diagnosis
and Treatment, 54th edn. 2015.
11. Okinaka S, Shizume K, Iino S, Watanabe A, Irie M, Noguchi A, The association of
periodic paralysis and hyperthyroidism in Japan.J Clin Endocrinol Metab. 1957;
17(12):1454-9.
12. Periodic Paralyses Treatment and Management: Naganand Sripathi, MD; Nicholas
Lorenzo, MD, CPE.
13. Phillip Wong. Hypokalemic thyrotoxic periodic paralysis: Case Reports; CJEM. 2003;
5(5):353-5.
14. Sushil K Ahlawat, Anita Sachdev. Hypokalaemic paralysis. Postgrad Med J. 1999;75:193-7.
CHAPTER
75 TA Naufal Rizwan
CRITICAL ILLNESS POLYNEUROPATHY
Critical illness polyneuropathy (CIP) is a sensorimotor polyneuropathy which is

characterized by flaccid weakness and sensory loss and is seen in patients who
are critically ill. It was first described by Bolton and colleagues in 1984.
PREDISPOSING FACTORS
It is seen in critically-ill patients who are suffering from sepsis and multiorgan
failure. Although the exact incidence is not known, it has been estimated that
more than 50% of patients in ICU with sepsis/systemic inflammatory response
syndrome (SIRS) develop CIP. Additional risk factors for developing CIP are
female gender, high blood sugar, low serum albumin, immobility, multi-
organ dysfunction, renal failure, renal replacement therapy, duration of organ
dysfunction and ICU stay, low albumin and central neurologic failure.
PATHOLOGY
Critical illness polyneuropathy is primarily a distal axonopathy in which distal
degeneration of both motor and sensory axons occur without any inflammation.
The underlying cause of the axonal degeneration may relate to a lack of vascular
autoregulation and increased microvascular permeability resulting in endoneural
edema and capillary occlusion.
PATHOGENESIS
Although the exact pathogenesis is still unclear, microcirculatory changes have
been postulated to be the leading factor involved in the disease process (Flow
chart 75.1).
CLINICAL FEATURES
Critical illness polyneuropathy often overlaps with critical illness myopathy. The
clinical features of CIP are:
• Tetraparesis or tetraplegia is the hallmark of this disease. Weakness is
generalized, flaccid, symmetric and progressive. Lower limbs are involved
Flow chart 75.1 Pathogenesis of critical illness polyneuropathy
more commonly than the upper limbs. Weakness of the distal muscles
is more than the proximal muscles. Phrenic nerve, if involved, can result
in respiratory difficulties. In fact, most of the times, CPI is identified only
when the patient is unable to be successfully weaned from the mechanical
ventilator.
• Deep tendon reflexes are diminished or lost. Abnormalities of the touch,
pain, temperature and vibration sensation (which is more in the distal parts)
is also noted in patients with CPI.
Screening
Initial screening for CIP/CIM may be performed using the Medical Research
Council (MRC) score. The MRC score involves assessing strength in 3 muscle
groups in the right and left sides of both the upper and lower extremities. Each
muscle tested is given a score of 0–5, giving a total possible score of 60. An
MRC score less than 48 is suggestive of CIP/CIM. However, it can be done only
in patients who are awake and cooperative, which unfortunately is not usually
seen in ICU patients. Also, the screening tool is nonspecific, because it does
not identify the cause a person’s muscle weakness. If weakness is detected, this
evaluation should be done repeatedly. In the case of weakness being persistent,
nerve conduction study should be performed.
Diagnosis
Nerve conduction study is the best diagnostic test to confirm critical illness
polyneuropathy. Electrophysiological studies show reduction or absence of
both compound muscle and sensory nerve action potentials, fibrillations and
loss of motor unit potentials with a maximal effort. Significant slowing of nerve
conduction or nerve conduction blocks are not seen and if present, the possibility
of Guillain-Barré syndrome should be considered. The presence of tissue edema,
inadequate voluntary contraction and electrical interference often makes this
test difficult to perform.
Chapter 75 Critical Illness Polyneuropathy 533
The differential diagnosis for CIP are Guillain-Barré syndrome, acute porphyria,
botulism, prolonged effect of nondepolarizing neuromuscular blocking agents
and myasthenic crisis.
TREATMENT
No specific treatment is available. Supportive treatment includes proper
attention to the pulmonary hygiene and prevention of bed sores, deep vein
thrombosis, skin breakdown and compressive neuropathies. Hyperglycemia
and hypoalbuminemia should be corrected. Intensive insulin therapy is found
beneficial in the management of CIP. Insulin itself has some potential beneficial
effects, including anti-inflammatory effects, endothelial protection, improvement
of dyslipidmia and is also an anabolic hormone.
Rehabilitation is another important component in the management of CIP.
The various physiotherapy options available are exercises, early mobilization
and percutaneous neuromuscular electrical stimulation (NMES). NMES is a
method to induce skeletal muscle growth as well as to enhance capacity for
patients who are not able to perform active exercises preventing loss of muscle
mass. Since patient cooperation is not required, it is considered an alternative
for active exercises. NMES has been found to increase muscle strength, regional
vascularization (helps in pressure sores) and tissue healing. Recovery from
critical illness polyneuropathy takes months to years and is often incomplete.
BIBLIOGRAPHY
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14. Stevens RD, Dowdy DW, Michaels RK, Mendez–Tellez PA, Pronovost PJ, Needham
DM. Nueromuscular dysfunction acquired in critical care illness. Int Care Med.
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15. Tepper M, Rakic S, Haas JA, Woittiez AJ. Incidence and onset of critical illness
polyneuropathy in patients with septic shock. Neth J Med. 2000;56:211-4.
16. Witt NJ, Zochodne DW, Bolton CF, Grand Maison F, Wells G, Young GB, et al. Peripheral
nerve function in sepsis and multiple organ failure. Chest. 1991;99:176-84.
SECTION
18
APPROACH TO A TRAUMA
PATIENT
Chapter 76 Advanced Trauma Life Support

Prem Kumar
Chapter 77 Open Fractures

K Gunalan
Chapter 78 Pelvic Fractures

K Gunalan
Chapter 79 Fat Embolism Syndrome

Chapter 80 Abdominal Trauma

Marun Raj
Chapter 81 Vascular Trauma of Extremities

Marun Raj
Chapter 82 Traumatic Head Injury

Sushma Vijay Pingale,
V Thanga Thirupathi Rajan
Chapter 83 Thoracic Trauma

Sushma Vijay Pingale, Marun Raj
CHAPTER
76 Prem Kumar
ADVANCED TRAUMA LIFE SUPPORT
INTRODUCTION
The advanced trauma life support (ATLS) guidelines recommend that any
trauma evaluation should first include a “primary survey” which includes the
identification and treatment of life and limb threatening injuries beginning with
the treatment of the injury which requires immediate attention (Table 76.1). The
focus should be on urgent problems which should be captured in the “golden
hour”. Once these urgent needs are taken care of, a meticulous “secondary survey”
is done with further diagnostic studies to reduce the incidence of missed injuries.
Faster the diagnosis, faster the initiation of treatment and better the outcome.
ATLS emphasizes the ABCDE mnemonic: airway, breathing, circulation,
disability, and exposure.
AIRWAY
Verifying for an open airway is of prime importance since hypoxia is the immediate
threat to the patient if airway is involved in trauma. Causes of airway obstruction
Table 76.1 Primary survey
Airway Breathing Circulation Disability Exposure

Diagnosis Auscultation Pulse oximetry, • Vital signs, • GCS score, • Full physical
ABG, chest e-FAST, typing neurological examination,
X-ray and cross examination, • Detailed
matching, • Cervical history,
• Coagulation spine films, other lab
parameters, CT-brain studies to
• Complete support
blood count, diagnosis.
pelvic X-ray
Manage- Triple • M echanical • IV access • Cervical • Removal of
ment maneuver, ventilation • F luid infusion collar clothes and
oxygen, • Intercostal • Pressure on • Emergency thorough
intubation drainage wounds surgery, ICP examination
• O-ve blood monitoring • Surgery
Thoracotomy • Detailed
• Surgery review
• Pelvic binder
538 Section 18 Approach to a Trauma Patient
in trauma patients is given in Table 76.2. Hypoxia can lead to permanent brain
damage and if airway is not protected, patient may end up in death due to hypoxia
in 5–10 minutes.
The airway is best managed by endotracheal intubation in comatose
patients. Rapid sequence induction is done with thiopentone (3–5 mg/kg),
fentanyl (3–5 µg/kg) followed by a short acting neuromuscular blocking agent
like succinylcholine (1–2 mg/kg). Succinylcholine can increase the intracranial
pressure transiently but its use will lead to faster intubation, its benefits may
outweigh its risks. Hence, one must weigh the use of succinylcholine in each
individual situation based on the acuity of CNS injury, the anticipated speed
with which intubation should be accomplished, and the likelihood that hypoxia
will develop. Alternative to succinylcholine are rocuronium (0.9–1.2 mg/kg). But
rocuronium has longer duration of action compared to succinylcholine. The use
of thiopentone may result in hypotension in volume depleted patients hence
etomidate would be a better choice in these patients. The patient should be
adequately preoxygenated by giving 100% oxygen for 5 minutes or 4 vital capacity
breaths if it is an emergency. The patient should be intubated in neutral head
position with a manual-in line cervical spine immobilization in case of suspected
cervical spine injury which is discussed in the chapter under airway management.
Indications of endotracheal intubation in trauma patients is given in Table 76.3.
The placement of the endotracheal tube should be confirmed by auscultation
in prehospital setup and by a capnometer in hospital setup. The endotracheal
tube not only helps in establishing good oxygenation and ventilation but also
protects against aspiration. When oral intubation is difficult, as seen in severe
maxillofacial trauma or difficult airway, then urgent surgical airway should be
established by a cricothyrotomy or tracheostomy.
Table 76.2 Causes of airway obstruction in trauma patients
Causes of airway obstruction or inadequate ventilation in trauma patients

• Hemorrhage in the upper airway
• Poor consciousness (GCS <8) leading to airway obstruction due to tongue
• Aspiration of gastric contents
• Cervical spine injury
• Pneumothorax
• Direct injury to tracheobronchial tree
• Shock
• Traumatic brain injury
Table 76.3 Indications of endotracheal intubation in trauma patients
Acute airway obstruction

• Traumatic airway injury
• Burns causing smoke inhalation
• Laryngeal edema
• Laryngospasm
– Head injury with GCS ≤8
– Cardiac arrest
– Trauma patients with respiratory failure
– Risk of aspiration (bleeding, vomiting)
Chapter 76 Advanced Trauma Life Support 539
BREATHING
Breathing if found to be shallow and inadequate mandates mechanical
ventilation. Injuries which must be made out are tension pneumothorax, flail
chest, pulmonary contusion. Inspect the head and neck, look for symmetrical chest
movements, subcutaneous emphysema, tracheal deviation or use of accessory
muscles of respiration. Surgical or interventional procedure may be required
and has high priority if it is the cause of cardiac arrest (e.g. Cricothroidotomy,
tracheostomy for upper airway obstruction, tube thoracostomy, or open
thoracotomy).
CIRCULATION
Hemorrhage is the next priority in any trauma patient since it can be fatal if it
is ongoing and untreated. Prompt identification and assessment of hemorrhage,
identifying the cause of hemodynamic instability and faster initiation of
management while resuscitation is ongoing will improve the outcome in a trauma
patient presenting with hypovolemic shock. Assessment of shock includes an early
phase which focuses on the diagnosis of the common sites of bleeding followed
by immediate intervention in ED or OT if the condition requires immediate
intervention. This is followed by a late phase which begins after hemostasis is
achieved until restoration of the normal physiology. The sites of bleeding in a
trauma patient are assessed by FAST scan which is discussed in detail under the
chapter role of ultrasound in critical care. In case of active hemorrhage requiring
surgical intervention, damage control surgery is done for anatomic control of
hemorrhage. Goals of early and late resuscitation is given in Table 76.4.
Resuscitation of hemorrhage is based upon three goals:
1. Restoration of blood volume
2. Restoration of peripheral vascular resistance
3. Restoration of tissue perfusion.
Resuscitation of hemorrhagic shock is divided into two phases:
1. Early phase—ongoing active bleeding
2. Late phase—all the sources of bleeding are controlled.
Table 76.4 Goals of early and late resuscitation
Goals of early resuscitation Goals of late resuscitation

Systolic blood pressure of 80–90 mm Hg Systolic blood pressure >100 mm Hg
Normal coagulation parameters Normal coagulation parameters
Hematocrit of 25–30% Hematocrit of >25%
Platelet count >50,000/mm3 Maintain normal body temperature
Maintain core temperature >35°C Maintain normal electrolytes, urine output
Prevent worsening of acidosis and increase Reverse systemic acidosis and document
in lactate the trend of serum lactate
Adequate analgesia Optimize cardiac output
Early Resuscitation
Administration of fluids is the mainstay of management in early phase. The
goal of resuscitation is to restore cardiac output and blood pressure. Initial
administration of 20 mL/kg of warmed isotonic crystalloids is recommended by
guidelines. Isotonic crystalloids (ringer lactate, normal saline, Plasma-Lyte A)
are administered and any visible hemorrhage is controlled with direct pressure.
Current evidence recommends the application of hypotensive resuscitation [or
damage control resuscitation (DCR)] in patients with hemorrhagic shock with
active bleeding where the source of bleeding is unknown and the definitive
control of bleeding is not done although this approach has not been shown
to improve mortality. DCR is a strategy combining hemostatic resuscitation,
permissive hypotension and damage control surgery. Goals of this strategy are
initial stabilization of the patient, reducing metabolic acidosis, hypothermia,
hypocalcemia and coagulopathy. This hypotensive resuscitation strategy reduces
transfusion requirement and severe postoperative coagulopathy in trauma
patients with hemorrhagic shock. Mean arterial pressure of 65 mm Hg is the goal
for this resuscitation.
Aggressive fluid resuscitation can cause increased blood pressure thereby
leading onto increased bleeding, dilutional anemia resulting in reduced tissue
perfusion, reduced clotting factors, immune suppression, hypothermia,
electrolyte disturbances. Blood sample is sent for grouping, cross-matching,
complete blood count, lactate. Blood gas analysis is also done.
Late Resuscitation
It starts after control of bleeding by surgery or by other methods. The goal of
late resuscitation is to restore tissue perfusion along with vital organ support.
Prolonged tissue and organ hypoperfusion can lead onto multiorgan failure.
Resuscitation Fluids
Isotonic Crystalloids
Initial fluid of choice for trauma patients with hemorrhagic shock are isotonic
crystalloids (ringer lactate, normal saline, Plasma-Lyte A). Advantages —they are
cost-effective, nonallergic, noninfectious, can be administered with medications,
easy for administration and can be easily warmed to room temperature.
Disadvantages are absence of coagulation capacity, reduced half-life in the
intravascular compartment, absence of O2 carrying capacity, can trigger cellular
apoptosis due to reperfusion injury.
Hypertonic Saline
It is not recommended for routine use in trauma patients but the advantage
of hypertonic saline is its faster ability to restore intravascular volume than
crystalloids. It can be used for fluid resuscitation in war conditions. It can be
used as an osmotic agent in patients with traumatic brain injury with raised
intracranial pressure.
Colloids
Colloids though has the theoretical advantage of rapidly restoring intravascular
volume than crystalloids, it has been found by studies that colloids have no better
advantage over crystalloids in terms of tissue perfusion and mortality. It can be
used when the IV access is limited. Disadvantages are the lack of O2 carrying
capacity and clotting.
Packed RBCs
They are the most important blood component for the treatment of traumatic
hemorrhagic shock. Advantages are O2 carrying capacity, better expansion of
intravascular volume compared to other fluids. In case of emergency when
there is no time for cross-matching, O negative blood is given. Disadvantages are
transfusion reactions, infections, hypothermia, etc.
Plasma
It may be required in conditions when there is expected massive transfusion
or in patients with coagulopathy. Plasma requires blood typing and not cross-
matching.
Platelets
Current evidence recommends the administration of PRBC: Fresh frozen plasma:
platelets in a ratio of 1:1:1 in patients with massive blood loss. This approach
has been shown to improve survival due its impact on the early intervention in
preventing trauma-induced coagulopathy. Platelet transfusion is indicated for
coagulopathic patients with active bleeding. Platelets should not be administered
through warmers or rapid infusors since it can adhere to the surfaces of these
devices.
MASSIVE TRANSFUSION
Definition
Transfusion of blood more than patient’s blood volume in 24 hours or transfusion
of >10% blood volume in <10 minutes or >50% of blood volume in 4 hours in an
adult.
Massive transfusion can occur in clinical scenarios like trauma, surgical
complications, ruptured aortic aneurysm, etc. mortality is high after massive
transfusion due to acidosis, coagulopathy, etc.
Criteria for Activation of Massive Transfusion Protocol

(Flow chart 76.1)
• Major surgical bleeding
• Severe trauma of thorax, abdomen or long bones resulting in severe blood
loss
Flow chart 76.1 Massive transfusion protocol (MTP)
• Actual or anticipated transfusion of 4 units of packed RBCs in <4 hours

• Unstable hemodynamics with active ongoing bleeding.
Goals of Massive Transfusion Protocol (Table 76.5)

Optimization of tissue perfusion, oxygenation and cardiac output are goals of
massive transfusion protocol (MTP). Lab studies are done every 30–60 minutes
to monitor the electrolyte, coagulation, metabolic and acid base status. Complete
blood count, serum-ionized calcium, ABG, coagulation studies are done every
hour to monitor status.
COMPLICATIONS
Hypocalcemia due to citrate, hypothermia, hyperkalemia due to release of
potassium on cell lysis, metabolic alkalosis occurs due to conversion of citrate to
lactate and in turn to bicarbonate. Other complications are ARDS, DIC. The most
common cause of bleeding following massive blood transfusion is dilutional
thrombocytopenia.
Table 76.5 Goals of resuscitation in MTP
• pH >7.2
• Base excess < –5
• Serum lactate <4 mmol/L
• Platelet count >50,000/mm3
• Coagulation studies—PT/aPTT <1.5 times the normal, INR ≤1.5, serum fibrinogen
>100 mg/dL
• Serum ionized calcium >1.1 mmol/L
• Core temperature >35°C
Disability
Level of consciousness is assessed using AVPU scale—alert, voice, pain,
unresponsiveness (GCS, pupil size, reaction to light, equality). If required,
intubate the patient, start intravenous mannitol 1 g/kg in case of increased ICP
and prepare to shift the patient for CT-brain and cervical spine film. If the patient
is hemodynamically unstable, stabilize the patient and shift for imaging. Put
cervical collar in case of suspected cervical spine injury, push for emergency
surgery in case of any need for surgical intervention.
Exposure
Complete physical examination is done after undressing the patient. Prevent
hypothermia by removing the source causing hypothermia. Lab investigations
are done for support of diagnosis followed by complete review of the patient.
Secondary Survey
Once the primary survey is over and the primary resuscitation efforts are over
along with optimization of vital function, secondary survey is started with head to
toe evaluation. Complete history and physical examination including neurological
examination are done to review the patient. Vital signs are reevaluated, lab studies
and imaging are done to confirm the clinical diagnosis. Additional studies which
can be done after stabilization of the patient to diagnose the suspected condition
are CT-chest, abdomen, spine, angiography, bronchoscopy, esophagoscopy,
urography, etc. Patients with trauma are frequently reevaluated with monitoring
of vital signs, ABG, central venous pressure, pulse oximetry, urine output. Pain
relief is given with regional nerve blocks and IV opioids.
Head trauma, thoracic trauma and abdominal trauma are discussed in detail
in their respective chapters.
BIBLIOGRAPHY
1. Advanced Trauma Life Support Course for Physicians. The American College of
Surgeons; 1993.
2. Crosby ET. Tracheal intubation in the cervical spine-injured patient-Editorial. Can J
Anaesth. 1992;39(2):105-9.
3. Doyle JA, Davis DP, Hoyt DB. The use of hypertonic saline in the treatment of traumatic
brain injury. J Trauma. 2001;50:367-83.
4. Dutton RP, McCunn M, Hyder M, et al. Factor VIIa for correction of traumatic
coagulopathy. J Trauma. 2004;57:709-18.
5. Majernick TG, Bieniek R, Houston JB, et al. Cervical spine movement during
orotracheal intubation. Ann Emerg Med. 1986;15:417-20.
6. Podolsky S, Baraff LJ, Simon RR, Hoffman JR, Larmon B, Ablon W. Efficacy of cervical
spine immobilization methods. J Trauma. 1983;23(6):461-5.
7. Rhee P, Burris D, Kaufmann C, et al. Lactated Ringer’s solution resuscitation causes
neutrophil activation after hemorrhagic shock. J Trauma. 1998;44:313-9.
8. Sellick BA. Cricoid pressure to control regurgitation of stomach contents during
induction of anaesthesia. Lancet. 1961;2:404-6.
9. Stern SA, Dronen SC, Birrer P, et al. Effect of blood pressure on hemorrhage volume
and survival in a near-fatal hemorrhage model incorporating a vascular injury. Ann
Emerg Med. 1993;22:155-63.
10. Velanovich V. Crystalloid versus colloid fluid resuscitation: A meta-analysis of
mortality. Surgery. 1989;105:65-71.
CHAPTER
77 K Gunalan
OPEN FRACTURES
INTRODUCTION
Open fractures are usually the result of high-energy trauma and should alert the
treating physician to the possibility of associated injuries. Therefore, detailed
evaluation and appropriate resuscitation of the patient is necessary. The
neurovascular status of the injured extremity should be carefully assessed, and
the development of compartment syndrome should not be overlooked. The soft-
tissue injury should be evaluated to determine the size and location of the wound,
the degree of muscle damage, and the presence of contamination.
CLASSIFICATION
The Gustilo and Anderson classification system (Table 77.1) which was
subsequently modified by Gustilo et al. is used widely to grade open fractures.
In this system, type I indicates a puncture wound of ≤1 cm with minimal
contamination or muscle crushing. Type II indicates a laceration of >1 cm in length
with moderate soft-tissue damage and crushing; bone coverage is adequate and
comminution is minimal. A type-IIIA open fracture involves extensive soft-tissue
damage, often due to a high-energy injury with a severe crushing component.
Massively contaminated wounds and severely comminuted or segmental
fractures are included in this subtype. Soft-tissue coverage of the bone is adequate.
Type IIIB indicates extensive soft-tissue damage with periosteal stripping and
bone exposure, usually with severe contamination and bone comminution. A
type-IIIC fracture is associated with an arterial injury requiring repair.
Table 77.1 Gustilo open fracture classification
Type Definition
I Open fracture with clean wound and wound <1 cm in length
II Open fracture with extensive soft tissue damage and crushing. Wound is >1 cm
IIIA Open fracture with extensive soft tissue damage and crushing. Fractures are
severely comminuted or segmental and wounds are contaminated. May require
vascular repair
IIIB Open fractures with extensive soft-tissue damage with periosteal stripping and bone
exposure, usually with severe contamination and bone comminution
IIIC Open fractures associated with arterial injury requiring repair
ANTIBIOTIC COVER
As most open fractures are contaminated with microorganisms, antibiotics are
used not for prophylaxis but rather to treat wound contamination. To prevent
a clinical infection, immediate antibiotic administration, wound debridement,
soft-tissue coverage, and fracture stabilization are necessary.
The results of cultures of post-debridement specimens and sensitivity testing
may help in the selection of the best agents for subsequent procedures. The
antibiotic therapy should target both the gram-positive and the gram-negative
pathogens contaminating the wound. A commonly used regimen consists of a
first-generation cephalosporin (e.g. cefazolin), which is active against gram-
positive organisms, combined with an aminoglycoside (e.g. gentamicin or
amikacin), which is active against gram-negative organisms. Substitutes for
aminoglycosides include quinolones, third-generation cephalosporins, or other
antibiotics with gram-negative coverage.
Clostridial myonecrosis (gas gangrene) is of particular concern when an
injury is contaminated with anaerobic organisms (e.g. farm injuries) or when
there is vascular injury that may create conditions of ischemia and low oxygen
tension. Therefore, in such cases, ampicillin or penicillin should be added to the
antibiotic regimen to provide coverage against anaerobes.
Antibiotic administration should be started promptly, as a delay of more than
three hours has been shown to increase the risk of infection. The recommended
duration of therapy is three days. An additional three days of administration
of antibiotics—selected on the basis of the results of initial cultures—is
recommended for subsequent surgical procedures, such as wound coverage and
bone-grafting.
Local antibiotic delivery must be considered when extensive contamination
is present. This is commonly done with an “antibiotic bead-pouch” construct
formed with antibiotic powder and polymethylmethacrylate (PMMA) cement.
SURGICAL DEBRIDEMENT AND IRRIGATION

The timing of initial surgical intervention has wide variance within the literature.
Historically, the 6-hour rule has been employed as the time limit within which
an open fracture should be taken to the operating room for initial debridement.
Open fractures should be taken to the operating room in an urgent manner using
appropriate surgical judgment. There are certain scenarios when emergency
debridement may be needed. These may include Type III injuries with vascular
injury and/or gross fecal or soil contamination. Wound is dressed and splinted,
the covering should not be lifted until the patient is delivered to the operating
room as this practice can increase the infection rate.
Perhaps the most important aspect in the treatment of open fractures is the
initial surgical intervention with irrigation and meticulous debridement of the
injury zone. This initial debridement should include a sequential evaluation of
skin, fat, fascia, muscle, and bone. One of the most important assessments in the
debridement process is vascularity to the affected tissues.
Irrigation, along with debridement, is absolutely crucial in the management
of open fractures, the removal of contaminating debris and the decrease of
Chapter 77 Open Fractures 547
potentially infective bacterial loads. A popular protocol for lavage is usage of 3 L

for a Type I open fracture, 6 L for a Type II open fracture, and 9 L for a Type III open
fracture. Surgeons should favor using a low-to-medium pressure lavage device as
higher-pressure devices have been associated with added tissue or bone damage.
WOUND CLOSURE
Options for wound closure in the treatment of open fractures include primary
closure of the skin, split-thickness skin-grafting, and the use of either free or
local muscle flaps. Historically, surgeons have opted to delay closure because
of the perceived risks of clostridial infections and gas gangrene. This concern is
certainly present in the grossly contaminated open fracture. Current treatment
strategies correctly emphasize the importance of debridement and irrigation,
and adhering to these principles has allowed surgeons to consider earlier closure
and immediate primary closure in some cases when certain criteria are met.
Recommendation is toward primary closure of Type I, Type II, and a few selected
Type IIIA fractures. The most important factors in our decision-making process is
the adequacy of the initial debridement and the degree of wound contamination.
SKELETAL FIXATION (FIGS 77.1 TO 77.5)

Early stabilization of open fractures provides many benefits to the injured patient.
It protects the soft tissues around the zone of injury by preventing further damage
from mobile fracture fragments. It also restores length, alignment, and rotation—
all vital principles of fracture fixation. This restoration of length also helps decrease
Fig. 77.1 Open tibial shaft fracture

Fig. 77.2 External fixation done for open tibial fracture
Fig. 77.3 Mangled lower extremity

Chapter 77 Open Fractures 549
Fig. 77.4 Extensive degloving injury
Fig. 77.5 Postdebridement and external fixation
soft tissue dead spaces and has been shown in studies to decrease the rates of
infection in open fractures. The surgeon has many choices when deciding on
fixation constructs—skeletal traction, external fixation, and intramedullary nails
and plates. The choice of fixation involves the bone fractured and the fracture
location (intra-articular, metaphyseal, diaphyseal), the extent of the soft-tissue
injury and the degree of contamination, and the physiologic status of the patient.
External fixation is a valuable tool in the surgeon’s arsenal for acute open
fracture management. Indications for external fixation are grossly contaminated
open fractures with extensive soft-tissue compromise, the Type IIIA-C injuries,
and when immediate fixation is needed for physiologically unstable patients.
This later indication involves the damage control concept of orthopedic trauma.
Plate fixation is generally indicated for open upper extremity fractures and
periarticular fractures where reconstruction of the articular surface is paramount.
Current plating technology and less-invasive techniques are lowering these rates
and providing patients with good to excellent results.
Intramedullary nail fixation remains the mainstay of treatment for most
open tibial shaft fractures and for selected femoral fractures. Prophylactic bone
grafting can also be used in the early treatment of open fractures. The literature
has several examples of studies pertaining to immediate or early prophylactic
bone grafting, and this practice has reported to shorten the time to fracture union
and reduce the rate of delayed union.
BIBLIOGRAPHY
1. Brumback RJ, Jones AL. Interobserver agreement in the classification of open
fractures of the tibia: The results of a survey of two hundred and forty-five orthopaedic
surgeons. J Bone Joint Surg Am. 1994;76:1162-6.
2. Buchholz RW, Court-Brown CM, Heckman JD, Tornet P. Rockwood and green textbook
of orthopaedics, 7th edition. Philadelphia: Lippincott, Williams & Wilkins; 2010.
3. Canale ST, Beaty JH. Campbell textbook of orthopaedics, 12th edition. Philadelphia:
Mosby; 2013.
4. Court-Brown CM, McQueen MM, Quaba AA. Management of open fractures. St Louis;
London: Mosby; M Dunitz; 1996.
5. Court-Brown CM, Rimmer S, Prakash U, McQueen MM. The epidemiology of open
long bone fractures. Injury. 1998;29:529-34.
6. Gustilo RB, Anderson JT. Prevention of infection in the treatment of one thousand
and twenty-five open fractures of long bones: Retrospective and prospective analyses.
J Bone Joint Surg Am. 1976;58:453-8.
7. Gustilo RB, Gruninger RP, Davis T. Classification of type III (severe) open fractures
relative to treatment and results. Orthopedics. 1987;10:1781-8.
8. Gustilo RB, Mendoza RM, Williams DN. Problems in the management of type III
(severe) open fractures: A new classification of type III open fractures. J Trauma.
1984;24:742-6.
9. Information about Orthopaedic Patients and Conditions - AAOS. 2008. (4/8/2008)
10. Johansen K, Daines M, Howey T, Helfet D, Hansen ST. Jr Objective criteria accurately
predict amputation following lower extremity trauma. J Trauma. 1990;30:568–72.
11. Praemer A, Furner S, Rice DP. Musculoskeletal conditions in the United States. Park
Ridge, Ill: American Academy of Orthopaedic Surgeons; 1992.
12. Rajasekaran S. Early versus delayed closure of open fractures. Injury. 2007;38:890-5.
13. Sharma S, Devgan A, Marya KM, Rathee N. Critical evaluation of mangled extremity
severity scoring system in Indian patients. Injury. 2003;34:493-6.
14. Tscherne H, Oestern HJ. A new classification of soft-tissue damage in open and closed
fractures. Unfallheilkunde. 1982;85:111-5.
CHAPTER
78 K Gunalan
PELVIC FRACTURES
INTRODUCTION
Fractures of the pelvic ring comprise about 2% of all fractures (Fig. 78.1), but the
incidence is increasing due to increasing numbers of high-speed vehicular crashes
and suicide attempts. Parameters predicting mortality are age, injury severity
score (ISS) and the existence of severe hemorrhage. Exsanguinating hemorrhage is
the major cause of death in the first 24 hours after trauma. Immediate recognition
of hemorrhagic shock and effective control of bleeding must be pivotal in every
resuscitation effort. Appropriate recognition and management of serious pelvic
fractures is also integral to resuscitative strategy.
Fig. 78.1 Pelvic ring disruption

Management of these potentially lethal injuries requires expedited

stabilization by a multidisciplinary team of trained personnel with a defined
treatment protocol. Multidisciplinary clinical-pathway and coordinated
joint decision-making improves patient survival. The understanding of these
potentially fatal injuries are progressing and early management of pelvic ring
injuries are evolving.
ADVANCED TRAUMA LIFE SUPPORT

Upon arrival in the emergency department, patients should be resuscitated
according to the guidelines of the Advanced Trauma Life Support. The primary
survey emphasizes immediate assessment of the airway and breathing
while maintaining cervical spine precautions. Attention is then focused on
the cardiovascular system. Quickly identifying the site of hemorrhage in a
hemodynamically unstable patient is both critical and time-dependent. Volume
resuscitation is generally begun after intravenous (IV) access has been established
and it is only an adjunct to aggressive hemorrhage control.
If the patient shows signs of hypovolemia, a thorough and systematic search
must be initiated to identify the source of bleeding. Plain radiographs of the
chest (CXR) and pelvis are obtained at this stage. Optimally, this is followed by
an evaluation for intra-abdominal bleeding, through either diagnostic peritoneal
lavage (DPL) or, increasingly by focused assessment with sonography for trauma
(FAST) exam.
HEMODYNAMIC STATUS
Hypovolemia should be carefully evaluated and hemorrhagic shock should be
diagnosed and graded promptly. Specific attention should be paid for assessing
the pulse, respiratory rate and tissue perfusion. Tachycardia and cool peripheries
are early indicators, and a narrowed pulse pressure may suggest significant blood
loss. In the early resuscitative phase, clinical signs and symptoms, along with
measurement of hourly urine output, continue to be the most practical indicators
of systemic perfusion.
FRACTURE STABILITY
If pelvic radiographs reveal obvious radiological instability of the ring, aggressive
physical examination with compression and distraction will not provide
additional information on injury severity, but rather could potentially cause
further injury or aggravate bleeding. In hemodynamically unstable patients
with no obvious site of hemorrhage, careful clinical examination of the pelvis
is mandatory even when radiographs look normal. Physical examination of the
pelvis should include thorough inspection of the flanks, lower abdomen, groin,
perineum and buttocks to detect any wounds or bruises. The genitals and rectum
should be inspected carefully to detect any blood at the urethral meatus. In the
presence of signs suggestive of a genitourinary injury, insertion of a urinary
catheter should be avoided, and a retrograde urethrogram is performed.
Chapter 78 Pelvic Fractures 553
Orthopedic assessment should also note any clinical deformity of the

pelvis, limb-length discrepancy or malrotation. In patients who are both
hemodynamically and mechanically unstable, and in whom the major bleeding
is thought to be related to the pelvic fracture, external stabilization of the pelvis
becomes the first priority. Because the main sources of bleeding are most
frequently the presacral venous plexus and fractured bony surfaces, external
stabilization decreases the hemorrhage by reducing the volume of the pelvic
basin and approximating the fracture ends.
PNEUMATIC ANTISHOCK GARMENT

The pneumatic antishock garment (PASG) can be helpful for immediate
mechanical stabilization at an accident scene. The PASG may provide an initial
redistribution of blood from the limb to the trunk and restrict the expansion of a
pelvic hematoma. It impedes access to limbs and abdomen, making assessment
of the patient in the emergency room more difficult. Currently, the role of PASG
and MAST is limited.
PELVIC BINDERS
Circumferential pelvic binders or sheets are gradually replacing anterior external
fixation (AEF) as the method of choice of immediate external stabilization, and
currently they are part of the ATLS protocol. These binders are noninvasive,
simple to apply, inexpensive and can be applied at a prehospital stage. To perform
this method of stabilization, either an ordinary broad sheet can be tied at the level
of the greater trochanter, or a commercial pelvic binder can be used. It must be
positioned appropriately or be moveable when required, to provide access to
the entire abdomen and groin. Safe, noninvasive method seems to be a logical
first resuscitative step with a serious pelvic fracture, to provide early hemorrhage
control before considering invasive methods.
ANTERIOR EXTERNAL FIXATOR (FIGS 78.2 AND 78.3)

Immediate anterior external fixator (AEF) of an unstable pelvic injury has been the
mainstay of acute stabilization for the past few decades. Skeletal stabilization of
pelvic injury should be viewed as part of resuscitation rather than reconstruction.
The anterior fixator is thought to contribute to hemostasis by maintaining a
reduced pelvic volume, allowing tamponade, and by decreasing bony motion at
the fracture site, allowing clots to stabilize. The pelvic fractures most amenable
to this form of treatment are the open book fracture, and the unstable shear type
when combined with longitudinal traction. Lateral compression injuries incur
fewer benefits from this method. Its judicious use before laparotomy can both
reduce further bleeding and prevent hypotension from decompression of the
tamponade effect upon opening the abdominal wall.
The application of AEF requires training and can be difficult to accomplish in
the trauma room. It is hard to maintain a sterile environment, and contamination
of the pin tracts can jeopardize definitive care of pelvic fractures.
Fig. 78.2 Anterior external fixation
A B
Figs 78.3A and B Anterior external fixator and symphyseal plating
ACUTE FRACTURE FIXATION

The patient undergoes a laparotomy to deal with visceral injuries, symphyseal
disruption and medial ramus fractures should be plated at the same time.
Because neither blood loss nor operative time are greatly increased, combining
these repairs decreases the risk of complications in a patient who is already
compromised.
Percutaneous pelvic fixation techniques allow for acute and definitive
treatment of anterior and posterior pelvic ring injuries, without extensive
dissection. Accurate early pelvic stabilization diminishes pain and hemorrhage,
provides better patient nursing and comfort, and allows early mobilization.
ANGIOGRAPHY
Interventional angiographic procedures are increasingly being used as
adjuncts to hemorrhage control in cases of solid-organ trauma. Although the
Chapter 78 Pelvic Fractures 555
source of bleeding is non-arterial in most cases, arterial injury can account for
hemodynamic instability in 10–20% of patients.
Patients who remain hemodynamically labile after external stabilization
and other resuscitative measures but have no major intraperitoneal bleeding
are potential candidates for pelvic angiography. Other indications for pelvic
angiography include the incidental discovery of an arterial “blush” in a contrast
CT scan in an apparently stable patient, and as a last-ditch effort in thermally
stable patients who remain in shock after exploratory laparotomy and surgical
control of all other sources of bleeding.
In practice, angiography has some drawbacks. It is time-consuming
and currently requires transfer of a severely injured, unstable patient to the
angiography suite, which may hamper resuscitative efforts.
PELVIC PACKING
The rationale behind pelvic packing derives from the fact that the major source of
hemorrhage from pelvic ring injury is venous. This technique seems particularly
applicable to patients with multiple hemorrhagic sources, both intra- and
retroperitoneal, whose visceral injuries mandated a laparotomy as the first
operative resuscitative measure.
OPEN PELVIC FRACTURES (FIG. 78.4)

Open fractures of the pelvis by definition communicate with the rectum, the
vagina, or the outside environment by disruption of the skin. An open pelvic
fracture prompts recommendations for colostomy to prevent soft-tissue sepsis
Fig. 78.4 Internal fixation after primary stabilization

in an expanded perineum. In addition to hemorrhage control and stabilization

of the pelvic ring, meticulous debridement of the wound and administration of
broad-spectrum antibiotics are required. In open pelvic fractures with continuing
hemorrhage, packing can be life-saving.
BIBLIOGRAPHY
1. American College of Surgeons, committee on trauma. Advanced trauma life support
for doctors: student course manual, 7th Edition. Chicago: American College of
Surgeons; 2004.
2. Bode PJ, Niezen RA, van Vugt AB, Schipper J. Abdominal ultrasound as a reliable
indicator for conclusive laparotomy in blunt abdominal trauma. J Trauma. 1993;34:
27-31.
3. Bottlang M, Krieg JC. Introducing the pelvic sling: pelvic fracture stabilization made
simple. JEMS. 2003;28:84-93.
4. Buchholz RW, Court-Brown CM, Heckman JD, Tornet P. Rockwood and green textbook
of orthopaedics, 7th edition. Philadelphia: Lippincott, Williams and Wilkins; 2010.
5. Canale ST, Beaty JH. Campbell textbook of orthopaedics, 12th edition. Philadelphia:
Mosby; 2013.
6. Demetriades D, Karaiskakis M, Toutouzas K, et al. Pelvic fractures: epidemiology and
predictors of associated abdominal injuries and outcomes. J Am Coll Surg. 2002;195:
1-10.
7. Giannoudis PV, Pape HC. Damage control orthopaedics in unstable pelvic ring
injuries. Injury. 2004;35:671-7.
8. Hamill J, Holden A, Paice R, Civil I. Pelvic fracture pattern predicts pelvic arterial
haemorrhage. Aust NZJ Surg. 2000;70:338-43.
9. Hildebrand F, Giannoudis PV, van Griensven M, Chawda M, Pape HC. Pathophysiologic
changes and effects of hypothermia on outcome in elective surgery and trauma
patients. Am J Surg. 2004;187:363-71.
10. Mattox KL. Introduction, background, and future projections of damage control
surgery. Surg Clin North Am. 1997;77:753-9.
11. Niwa T, Takebayashi S, Igari H, et al. The value of plain radiographs in the prediction
of outcome in pelvic fractures treated with embolisation therapy. Br J Radiol. 2000;
73:945-50.
12. Ramzy AI, Murphy D, Long W. The pelvic sheet wrap: initial management of unstable
fractures. JEMS. 2003;28:68-78.
13. Schurink GW, Bode PJ, van Luijt PA, van Vugt AB. The value of physical examination in
the diagnosis of patients with blunt abdominal trauma: a retrospective study. Injury.
1997;28:261-5.
14. Shapiro MB, Jenkins DH, Schwab CW, Rotondo MF. Damage control: collective
review. J Trauma. 2000;49:969-78.
15. Tile M. Acute pelvic fractures. I: causation and classification. J Am Acad Orthop Surg.
1996;4:143-51.
16. Tile M. Acute pelvic fractures. II: principles of management. J Am Acad Orthop Surg.
1996;4:152-61.
CHAPTER
79 Sushma Vijay Pingale
FAT EMBOLISM SYNDROME
Fat embolism syndrome (FES) is the term used to describe the intravascular
appearance of fat globules along with a specific cluster of respiratory,
dermatologic, and neurologic symptoms and signs. It is less common but a
potentially fatal event carrying a mortality rate of 10–15%.
ETIOLOGY
• Long bone fractures—especially femur and tibia
• Acute pancreatitis
• Parenteral infusion of lipids
• Cardiopulmonary bypass
• Liposuction.
PATHOGENESIS
It has been proposed that fracture of long bones causes disruption of fat cells
and release of shower of fat globules and bone marrow debris. These fat globules
enter the circulation through tears in the medullary vessels of the fractured
bones. The fat globules are then said to exert toxic effects on the capillary walls
and the alveolar membrane and cause the release of vasoactive amines and
prostaglandins and lead to a generalized proinflammatory response, eventually
leading to microvascular occlusions by platelets and fibrin in various beds and
interstitial leakage of protein and neutrophil rich fluids. This may result in acute
respiratory distress syndrome (ARDS). They also damage the capillaries of
cerebral circulation causing cerebral edema.
CLINICAL FEATURES
Fat embolism syndrome typically presents 24–72 hours after fracture of long
bones or after bone manipulation. It presents in the form of triad of hypoxemia,
confusion and petechiae. The patient has tachycardia and may develop fever
and refractory hypoxemia. A peculiar petechial rash is seen on the upper torso
or head and neck and conjunctiva is almost pathognomonic of FES. Fat globules
may be found in the retina, urine or sputum. The patient may be acutely agitated,
confused, stuporous or comatose and a focal neurological deficit may also be
present.
DIAGNOSIS
Although there is no definitive test to diagnose fat embolism the laboratory tests
provide a data supportive towards diagnosis. Thrombocytopenia and prolonged
clotting time is commonly observed. Cryostat test can detect fat globules in
clotted blood that has been rapidly frozen. The serum lipase is elevated in 50%
of patients with fat embolism syndrome but returns to normal within 24 hours of
injury and thus does not have any relation with the severity of the disease. X-ray
chest may show diffuse pulmonary infiltrates. The ECG will show ischemic ST
segment changes and right-sided heart strain pattern. The Arterial blood gas
analysis will show that the ratio of partial arterial oxygen pressure and fraction of
inspired oxygen (PaO2/FiO2) is less than 40. CT and MRI scans shows nonspecific
findings. Biopsy of skin lesions may help by revealing fat globules on staining.
Based on the Gurd criteria (Table 79.1) which can be used for diagnosis, the
presence of any one major criteria plus four minor criteria and evidence of fat
macroglobulinemia is required for the diagnosis of FES. Fat embolism syndrome
can be diagnosed by Schonfeld index (Table 79.2). Score >5 is required for
diagnosis of fat embolism syndrome. According to recent studies, the presence of
fat globules does not correlate with the severity of FES.
Table 79.1 Gurd criteria for diagnosis of fat embolism syndrome
Major features (at least one)

• Respiratory insufficiency
• Cerebral involvement
• Petechial rash
Minor features (at least four)
• Pyrexia
• Tachycardia
• Retinal changes
• Jaundice
• Renal changes
Laboratory features
• Fat microglobulinemia (required)
• Anemia
• Thrombocytopenia
Table 79.2 Schonfeld fat embolism syndrome index
Sign Score
Petechial rash 5
Diffuse alveolar infiltrates 4
Hypoxemia PaO2<70 mm Hg, FiO2 100% 3
Confusion 1
Fever >38°C (>100.4°F) 1
Heart rate >120 beats/minute 1
Respiratory rate >30 1
Abbreviations: PaO2, arterial oxygenation; FiO2, inspired oxygen concentration
Chapter 79 Fat Embolism Syndrome 559
MANAGEMENT
The management can be described as prophylactic and supportive. Early
stabilization of fractures has shown to bring down the incidence of ARDS and
FES. Prophylactic methylprednisolone (6 mg per kg IV in 6 doses) after trauma
has been shown to reduce the incidence of fat embolism to as low as 2.5%
but recent studies has questioned its role. Finally if FES does develop, then
supplementation of oxygen via mask or continuous positive airway pressure or
mechanical ventilation as appropriate is necessary.
BIBLIOGRAPHY
1. Babalis GA, Yiannakopoulos CK, Karliaftis K, et al. Prevention of post-traumatic
hypoxemia in isolated lower limb long bone fractures with a minimal prophylactic
dose of corticosteroids. Inj Int J Care Injured. 2004;35:309-17.
2. Behrman SW, Fabian TC, Kudsk KA, et al. Improved outcome with femur fractures:
early vs delayed fixation. J Trauma. 1990;30:792-8.
3. Bulger EM, Smith DG, Maier RV, et al. Fat embolism syndrome: a 10 year review. Arch
Surg. 1997;132:435-9.
4. Edward Morgan G, Jr, Maged S Mikhail, Michael J Murray. Clinical Anesthesiology, 5th
edn. McGraw-Hill Publications; 2007.
5. Gurd AR, Wilson RI. The fat embolism syndrome. J Bone Joint Surg Br. 1974;56:408-16.
6. Irwin, Richard S Rippe, James M. Irwin and Rippe’s Intensive Care Medicine, 6th Edn.
Lippincott Williams & Wilkins; 2008.
7. Robinson CM. Current concepts of respiratory insufficiency syndromes after fracture.
J Bone Joint Surg Br. 2001;83B:781-9.
8. Ronald D Miller. Miller’s Anesthesia, 7th edn. 2009. Elsevier Publications, 2009.
9. Schonfeld SA, Ploysongsang Y, DiLisio R, et al. Fat embolism prophylaxis with corti
costeroids: a prospective study in high risk patients. Ann Int Med. 1983;99:438-43.
CHAPTER
80 Marun Raj
ABDOMINAL TRAUMA
INTRODUCTION
The nature of wound is the same whether made by accidents, war and of course
by surgeon’s knife, but they differ only in degree. The way in which a wound is
sustained will frequently determine the amount of damage to the tissues, some of
which, concealed from superficial view, can be inferred from the injury. Factors
contributing to blunt trauma in motor vehicle accidents are steering wheel which
leads onto organ injuries like liver, stomach, diaphragm, and seat belt injury leads
on to mesenteric tear or avulsion, rupture of small bowel or colon and iliac artery
or abdominal aortic thrombosis. Shoulder harness usually leads onto rupture of
upper abdominal viscera, and air bag is notorious to produce cardiac rupture and
blunt injury to visceral organs.
MECHANISM OF INJURY
• Direct compression from blunt injury leads onto crush, or sheer injury
to abdominal viscera and in fact, any organ can be injured, though most
commonly injured are solid visceral organs and bowel.
• Shock waves that radiate from the point of impact leads on to injury to hollow
organs like small and large bowel and diaphragm.
• High speed deceleration injuries may produce differential movements of
fixed (DJ flexure and ileocecal junction) and nonfixed structures, ends up in
unpredictable injuries disproportionate to intensity of injuries.
Commonly affected organs are solid organs followed by bowel, and the least
involved ones are arteries and veins. Spleen is the most commonly involved solid
organ in blunt abdominal trauma which accounts for 40–45% and grading of
splenic injury is given in Table 80.1, and the next commonly affected solid organ
is liver, which accounts for 35–40%. The hollow visceral organs, especially small
bowel accounts for around 10% of injuries due to their nonattachment and blood
vessels account for less than 5% of injuries.
DIAGNOSTIC PRINCIPLES IN GENERAL

The most important part of the abdominal trauma is history taking regarding
the mode of injury, which most of the time clinches the diagnosis, and predicts
the organ involved in the injury. It is not uncommon for a driver or front-seat
Chapter 80 Abdominal Trauma 561
Table 80.1 Grading of splenic injury
Grade Injury description

1 Hematoma—subscapular <10% surface area
Laceration—capsular tear <1 cm parenchymal depth
2 Hematoma—subcapsular 10–50% surface area, intraparenchymal < 5 cm
diameter
Laceration—parenchymal depth of 1–3 cm without involvement of vessel
3 Hematoma—subcapsular >50% surface area or with expansion
Ruptured subcapsular or parenchymal hematoma. Intraparenchymal hematoma
>5 cm
Laceration—parenchymal depth of >3 cm or involvement of vessels
4 Laceration of segmental or hilar vessels producing >25% of splenic vascular
compromise
5 Completely shattered spleen—Hilar vascular injury with complete splenic
vascular compromise
passenger to sustain a chain of injuries one or the other side ending up in scalp
laceration or hematoma, fractured lower or upper limb, lacerated chest wall. It
is not even difficult to imagine that the abdomen had been similarly struck and
a careful examination will reveal signs of injury that otherwise might have been
missed. Side-swipe injury also should arouse the suspicion of intra-abdominal
damage, even if they are no external signs visible. Apart from the above facts, the
features that suggest intra-abdominal injury are those of peritoneal irritation,
abdominal distension and hypovolemia out of proportion to external blood loss.
Vomiting is usually a late occurrence, but the patients who had been
vomiting frequently and inexplicably should raise the suspicion of abdominal
injury (intraperitoneal or retroperitoneal visceral rupture). Bowel sounds are
infrequently of value as silent abdomen raises the suspicion of visceral injury, but
can occur in the setting of hypotension also. There are some special signs which
may help in diagnosing the intra-abdominal injuries.
Grey-Turner Sign
It is the bluish discoloration of lower flanks, lower back, associated with
retroperitoneal bleeding of pancreas, kidney, or pelvic fracture.
Cullen Sign
Bluish discoloration around umbilicus, which indicates peritoneal bleeding,
often pancreatic hemorrhage.
Kehr Sign
Left shoulder pain while supine, caused by diaphragmatic irritation (splenic
injury, free air, intra-abdominal bleeding).
Balance Sign
Dull percussion in left upper quadrant area indicates splenic injury.
LAB INVESTIGATIONS
X-rays
Plain X-ray films taken in erect posture is more useful than supine film, though
lateral decubitus may be preferred for those who are unconscious, or could not
stand due to multiple associated injuries. Gas under the diaphragm though
confirms visceral perforation, it may not happen for all cases, and tiny visceral
punctures may go unnoticed. More help is likely to come from observing signs
of injury to the bony structures on the sides of abdomen like chest, pelvis and
lumbar spines. These injuries may confirm the energy of impact and direct the
attention to nearby structures. Loss of psoas shadow may be helpful in diagnosing
retroperitoneal collection.
Ultrasonogram
Focused assessment with sonography for trauma (FAST) is gaining momentum
in case of intra-abdominal injuries. The four quadrants methods include
perihepatic, perisplenic, pelvis and pericardium, which are screened rapidly to
rule out injuries and they are very useful in mass casualties to triage the patients,
which not only saves the patients but also the resources and manpower.
Computerized Tomography Scan

Contrast-enhanced CT scan has now replaced almost all the investigatory methods
in diagnosing intra-abdominal injuries and if available, it can be swiftly done with
a high degree of accuracy without interpretation error. Even in advanced centers
CT has replaced angiography and scintigraphy in the assessment of both solid
and visceral injuries.
DIAGNOSTIC PERITONEAL LAVAGE
Indications
• Equivocal signs on physical examination
• Unconscious patient with suspicion of intra-abdominal pathology.
Procedure for Diagnostic Peritoneal Lavage

• Bladder should be empty and if needed insert a nasogastric tube
• Midline incision is done 3 cm below umbilicus and of 3 cm length
• Peritoneum grasped with forceps and purse string sutures applied
• Peritoneum is opened with careful observation
• Peritoneal dialysis catheter or 8–10 fr catheter inserted into pelvis as the
purse string is tightened
• One liter of NS infusion done in few minutes

• Patient is log rolled and the empty bottle is brought down
• Fluid is taken for analysis.
Interpretation of Diagnostic Peritoneal Lavage

• Laparotomy is indicated under the following criteria:
– >10 mL of blood/bile/vegetable fiber/feculent fluid
– RBC >100000/mm3
– WBC >500/mm3
– Amylase >175 IU/dL
• Doubtful injury: RBC—50000–100000/mm3, WBC—100–500/mm3
• Nonoperative conservative management is done if RBC <50000/mm3, WBC
<100/mm3.
Limitations of Diagnostic Peritoneal Lavage

• Time consuming and dependent on skill of surgeon and the lab technician
• Relatively contraindicated in patients with previous exploratory laparotomy,
pregnancy, obesity
• Retroperitoneal hemorrhage can be missed.
ANGIOGRAPHY
Conventional angiogram is indicated mainly in case of retroperitoneal injuries,
though CT angiogram has almost replaced the indication. Angiogram can be
done if planned for any adjunct procedure in same sitting, otherwise its role is
limited nowadays.
PREOPERATIVE MANAGEMENT
Its mandatory to get an adequate large bore vascular access for volume
replacement to stabilize the circulation. Adequate volume of blood and
blood products should be available in case, if there is suspicion of abdominal
hemorrhage. Aim is to push the patient into the operating table as early as possible
without any delay with packed red cells on table. Even with new techniques of
anesthesia, the presence of solid food or fluid in stomach is still at risk during
induction of anesthesia. If the stomach contains much fluid, there exists the risk
of regurgitation into the pharynx, trachea and lungs, which occurs between the
moment of loss of cough reflux, which follows induction of anesthesia, and the
insertion of an endotracheal tube. It is reasonable, if the condition of the patient
needs it to insert a nasogastric tube to aspirate fluid from the stomach but it is of
little use to aspirate solid food and nasogastric tube cannot prevent aspiration
even after the gastric contents are aspirated. It is best removed before induction
as it is capable of keeping the cardiac and esophageal sphincters open and may
cause aspiration during induction of anesthesia. Rapid sequence induction (RSI)
along with cricoid pressure is done by the anesthesiologist to prevent aspiration
during induction. Nasogastric tube is reinserted after endotracheal intubation
to empty the stomach before the end of surgery. All patients should have
bladder catheterized to empty the bladder and for monitoring of urine output
during intraoperative and postoperative period. Prophylactic antibiotics are
administered according to the protocol of the institution before induction and
should be continued in the postoperative period.
DAMAGE CONTROL SURGERY

• Triad of coagulopathy, acidosis and hypothermia leads to poor outcome
• Goal is to minimize operative time
• Control bleeding rapidly
• Expedite primary repair or resection with stapling device OR ligate bowel
with umbilical tape or equivalent.
• Close only skin or alternatively implant plastic prosthesis to cover the wound.
• Re-explore after 48–72 hours (after stabilizing physiology of the patient).
ABDOMINAL COMPARTMENT SYNDROME

Abdominal compartment syndrome (ACS) has been defined as the
“cardiovascular, pulmonary, renal, splanchnic, abdominal wall and intracranial
disturbances resulting from elevated intra-abdominal pressures”. Normal intra-
abdominal pressure ranges from 0 to 5 mm Hg and intra-abdominal hypertension
is defined as intra-abdominal pressure (IAP) at or above 12 mm Hg. IAP above 20
mm Hg leads onto organ dysfunction/failure. IAP >25 mm Hg requires immediate
decompression. Actually abdominal perfusion pressure (APP) is nothing but the
intra-abdominal pressure subtracted from mean arterial pressure (APP = MAP
– IAP) and it reflects actual gut perfusion better than IAP alone, and optimizing
APP to >50–60 mm Hg should probably be primary endpoint, which is more
sensitive and specific.
Clinical Features
Clinical features are given in Table 80.2.
Table 80.2 Clinical manifestations of various systems
Cardiovascular system Hypotension

Reduced venous return
Reduced cardiac output
Central nervous system Increased intracranial pressure
Respiratory system Dyspnea, tachypnea due to increased intrathoracic pressure
↓ PaO2
↓ or ↑ PaCO2
Gastrointestinal system ↓ Splanchnic perfusion
Bacterial translocation
Anastomotic leak
Renal system ↓ Renal blood flow
↓ GFR
↓ Urine output
Abdominal wall Delayed wound healing
1 mm Hg = 1.36 cm H2O
1 cm H2O = 0.74 mm Hg
Fig. 80.1 Measurement of intra-abdominal pressure
Measurement of Intra-abdominal Pressure (Fig. 80.1)

It can be measured intragastrically, intracolonically, intravesically. Among these,
intravesical method is the most common method.
Procedure
50 mL of sterile saline is instilled into the bladder through the aspiration port of
the Foleys catheter with the drainage tube clamped. A 18-gauge needle attached
to a pressure transducer is then inserted in the aspiration port and the pressure
is measured, the transducer should be zeroed at the level of pubic symphysis.
Another simple method of measuring bladder pressure is via the fluid column
in a Foley catheter. This requires disconnection of the Foley to instill saline and
careful bending of the Foley to ensure correct measurement.
Treatment
Abdominal compartment syndrome with IAP >25 mm Hg is a surgical emergency
which requires immediate decompression. Principles of decompression
fasciotomy are:
• Avoid primary closure of the abdomen
• Fascia should not be closed
• Skin edges are not sutured
• Laparostomy
• Closure is done with silo (plastic) bag
• Vacuum-assisted closure.
BIBLIOGRAPHY
1. American College of Surgeons Committee on Trauma. Abdominal Trauma. In: ATLS
Student Course Manual, 8th edn. American College of Surgeons; 2008.
2. Christiano JG, Tummers M, Kennedy A. Clinical significance of isolated intraperitoneal
fluid on computed tomography in pediatric blunt abdominal trauma. J Pediatr Surg.
2009;44(6):1242-8.
3. DeMars JJ, Bubrick MP, Hitchcock CR. Duodenal perforation in blunt abdominal
trauma. Surgery. 1979;86(4):632-8.
4. Gifford RR, Sr, Hymes AC. Duodenal rupture after blunt abdominal trauma. Minn
Med. 1980;63(2):83-7.
5. Holmes JF, Offerman SR, Chang CH, Randel BE, Hahn DD, Frankovsky MJ, et al.
Performance of helical computed tomography without oral contrast for the detection
of gastrointestinal injuries. Ann Emerg Med. 2004;43(1):120-8.
6. Mokka RE, Kairaluoma MI, Huttunen R, Larmi TK. Retroperitoneal injuries of the
duodenum caused by blunt abdominal trauma. Ann Chir Gynaecol. 1976;65(1):33-7.
7. Palomar J, Polanco E, Frentz G. Rupture of the bladder following blunt trauma: a plea
for routine peritoneotomy in patients with extraperitoneal rupture. J Trauma. 1980;
20(3):239-41.
8. Roman E, Silva YJ, Lucas C. Management of blunt duodenal injury. Surg Gynecol
Obstet. 1971;132(1):7-14.
9. Shanmuganathan K. Multidetector row CT imaging of blunt abdominal trauma.
Semin Ultrasound CT MR. 2004;25(2):180-204.
10. Talbot WA, Shuck JM. Retroperitoneal duodenal injury due to blunt abdominal
trauma. Am J Surg. 1975;130(6):659-66.
CHAPTER
81 Marun Raj
VASCULAR TRAUMA OF EXTREMITIES
INTRODUCTION
In today’s competitive world, extremity vascular trauma presents a huge problem
due to the morbidity and mortality, it carries inspite of huge advancement made
in the field of medicine. Since most of the time (Golden Hour) period is wasted
while shifting patient to tertiary care centers.
HISTORICAL PERSPECTIVE
The standard of care of all extremity vascular injuries during the World War
I and II were only ligation of affected arteries with subsequent amputations as
the surest way of avoiding death. Although, the vascular repair techniques had
been to some extent established by this period, the unsanitary conditions which
prevailed, lack of timely transportation, absence of effective anesthesia methods,
antibiotics and effective blood banking made the surgeons life who were taking
care of those patients a nightmare to manage these cases on a large scale.
The report by the Debakey and Simone of 2470 vascular injuries during
the World War II which involved ligation of popliteal arteries resulted in a
huge amputation of nearly 72% of cases, the highest of any extremity vessels in
the literature. Even in those limbs salvaged, arterial ligation led to significant
problems with functional and neurological disability. Injured arteries were first
repaired on a large scale in Korean war and the limb amputation rate was only
29% and similar results were also reported in Vietnam war which was 27%. D ‘Sa
et al. reported 66 cases of vascular injuries from Ireland with a mere amputation
rate of 12% for arterial injuries and 8% for venous injuries. S’Fier et al. reported
amputation rate of 14% overall from the hostilities in Lebanon in the year 1980.
These reports clearly demonstrated the effectiveness of vascular repair in saving
the limbs and also the life of so many young patients with good quality of life.
EPIDEMIOLOGY
The exact incidence of injury to the extremity vessels are difficult to quantify as
the site of injury, mechanisms of injury (whether penetrating trauma and blunt
injury) and ethnic differences vary. To give an example 12% of arterial injuries
among survivors in World War I were due to popliteal artery injuries and 20% of
Table 81.1 Clinical features of vascular injuries
Hard signs
• Active hemorrhage
• Absent or diminished distal pulses
• Presence of bruit or thrill
• Hemorrhage, expanding or pulsatile hematoma
• Distal ischemia—classical 6Ps (Pain, Paresthesia, Pallor, Poikilothermia, Pulselessness
and Paralysis)
Soft signs
• Proximity of injury to major vessel
• Presence of neurological deficits
• Transient hypotension
• Stable hematoma
those in Korean war were due to femoropopliteal segment. Over the post-years,
the civilian sector has provided the bulk of experience with these injuries, in which
setting blunt mechanisms amount for 19% of all extremity arterial injuries and
have an incidence of 5.6 per 1000 cases of penetrating trauma and 1.6 per 1000
cases of blunt trauma. The exact incidence of trauma cases in Indian continent
widely varies from one area to others and no exact data available as of now.
CLINICAL PRESENTATION (TABLE 81.1)

Most cases of extremity vascular injuries present with obvious clinical
manifestations, generally called as Hard sings of vascular injury. It is widely agreed
that, in the settings of uncomplicated penetrating trauma to the lower extremity,
the presence of any one or more hard signs mandate immediate intervention,
either surgical or endovascular.
The clinical picture in this circumstance answers only two questions
necessary to make a surgical decision, namely whether a significant vascular
injury exists, which it does, with a probability approaching 100%, and where it
does, the wounds demonstrate. Any further imaging or diagnostic test is therefore,
unnecessary, superfluous, costly and potentially dangerous considering the
adverse impact of delay on outcome. Most limb-threatening complications of
delayed diagnosis of extremity vascular injury are the result of overlooking hard
signs, rather than an absence of signs, on initial evaluation.
NONINVASIVE IMAGING
Noninvasive studies have recently seen an increase in the armamentarium of
vascular injuries diagnosis. Central to the debate surrounding the role of non-
invasive studies in penetrating extremity injuries is whether the immediate cost
reduction of little or no diagnostic testing beyond physical examination and
observation is outweighed by the long-term expense and medicolegal exposure
associated with vascular injuries that have been missed. Noninvasive vascular
studies include Duplex ultrasonography and angiography.
Chapter 81 Vascular Trauma of Extremities 569
Duplex Ultrasonography
Duplex ultrasound has the advantage of being rapidly available, less costly, non-
invasive and documenting arterial injury by measuring the arterial pressure
index, which is the ratio of systolic pressure distal to an injured extremity, to that
in an uninjured extremity. Accuracy of this study mainly depends on operator
and may vary from 80% to 95%. Its major limitations are operator dependability
and failure to recognize intimal flaps and small pseudoaneurysms.
Angiography
Computerized tomography and magnetic resonance angiography have picked
up the momentum during the last decade. Even though these modalities are not
available widely, it has the advantages, compared with other modalities of being
noninvasive, and imaging multiple organs in a single test and more objective
and less operator dependent. The major drawbacks are that nonavailability,
intravascular contrast in case of CT angiogram and presence of orthopedic
instrumentation or pacemakers in case of MR studies.
INVASIVE STUDIES
Contrast arteriography by puncturing the vessels directly may be indicated to
confirm or exclude extremity vascular injuries sometimes, even in the presence of
hard signs, when the physical examination is not sufficiently reliable to allow for
a therapeutic decision. Blunt trauma and complex trauma to the lower extremity,
which cause extensive bone and soft tissue injury, may manifest hard signs that
do not arise from vascular injury at all but from soft tissue and bone bleeding,
direct nerve damage, and so on.
Arteriography is recommended here to exclude arterial injury and thus,
prevent a high rate of unnecessary surgical exploration in these already
compromised limbs. Imaging is also of value in shotgun wounds because of
multiple possible sites of injury that may be missed on surgical exploration.
Arteriography should be used liberally in elderly patients with chronic vascular
insufficiency following extremity trauma because pulse deficit and ischemia may
not be related to an acute vascular injury. In these circumstances, arteriography
should be performed by direct hand-injection of contrast percutaneous into the
femoral artery at the groin in the trauma center or opening room by the surgeon
to save time, and with acceptable accuracy.
Imaging for vascular injury is generally unnecessary in the absence of hard
signs following extremity trauma. Extremity wounds that place vessels at risk
and yet do not manifest hard signs have long posed a diagnostic dilemma; many
studies have shown that vascular injuries do still occur in this setting in 10–25%
of these cases. These injuries include penetrating trauma in proximity to the
major extremity vessels and any high-risk blunt trauma such as, lower extremity
crush, distal femur, proximal tibia and supracondylar fracture humerus. In the
past, routine surgical exploration or arteriography was recommended in patients
with these asymptomatic extremity injuries to avoid any missed extremity
trauma, with its known limb-threatening consequences. More recently, several
studies have provided compelling evidence that most of the asymptomatic
vascular injuries that occur in this setting are nonocclusive, have a benign and
self-limited natural history with a high rate of spontaneous resolution, do not
require surgical repair, and therefore do not require the considerable expenses
and resources necessary for detection. The minimal reported missed injury rate
when clinical management of injured extremities are decided entirely from the
physical examination alone is comparable to that of arteriography and surgical
exploration but is far less expensive and invasive.
MANAGEMENT OF EXTREMITY TRAUMA

The management of any trauma can be classified as prehospital, emergency
room and operative room care.
Prehospital Care
Time is the most precious commodity for patients with open major vascular
injuries. The concepts of “scoop and run” should be applied whenever possible.
No time should be made to resuscitate or place intravenous lines in the field
which unnecessarily delays the treatment. The only prehospital care should be
control of any external bleeding by direct pressure and administration of oxygen
by mask or nasal cannula.
Emergency Room Care

The initial assessment and management should follow the standard advanced
trauma life support protocol irrespective of site of injury. Intravenous lines
should be inserted always in the upper limb and in case of upper limb injuries,
lower limb should be considered. The patient should be placed in Trendelenburg
position to prevent air embolism in case of major upper limb and supraclavicular
venous injuries. External bleeding should be controlled by direct pressure over
the wound whenever possible; however, sometime bleeding behind the bony
prominence, may cause troublesome bleeding which may not be controlled by
external pressure alone. A Foley’s catheter in such situation passed through open
wound if any may control bleeding. Initial evaluation of patients should be done
by advance trauma life support team once the patient reaches hospital.
Operative Room Management
Subclavian and Axillary Vessels (Figs 81.1 and 81.2)

The anatomical knowledge is very critical for surgical exposure of any vessel in
the body. Surgical exposures, especially in the presence of active bleeding, can
be very difficult and may challenge the skills of any experienced vascular surgeon
also. The patient is placed in supine position with the arm abducted at 30° and the
head turned to the opposite side. The incision starts at sternoclavicular junction,
extends over the medial half of the clavicle; for proximal subclavian injuries trap
door incision involves median clavicular incision, an upper median sternotomy
and an anterior left thoracotomy through the third or fourth intercostal space.
A B
Figs 81.1A and B Stab injury in the supraclavicular area leading to subclavian
artery injury which was repaired using great saphenous vein conduit
A B
Figs 81.2A and B Accidental shotgun injury to axillary artery and X-ray showing
two pellets in axilla
For distal axillary vascular injuries, the incision is started below the middle of the
clavicle and extends into the deltopectoral groove. There are different choices of
vessel reconstruction ranging from direct end-to-end anastomosis to interposition
grafts, either in the form of autologous vein graft or synthetic graft which depends
on many factors. Venous injuries should be repaired only if it can be performed
by simple suturing without producing severe stenosis and without the use of any
complex reconstructive techniques, which not only delays the procedure time but
also severely affect the overall outcome. Ligation of the vein is very well tolerated
by almost all patients, and there is no evidence that complex reconstruction
reduces the probability of development of compartment syndrome. Following
ligation, the patient often develops transient edema that subsides within a few
days of limb elevation and compression bandage. In patients with arterial injury
and prolonged limb ischemia, especially in the presence of associated venous
trauma, perioperative administration of mannitol may prevent the development
of compartment syndrome and avoid the need for fasciotomy, though mannitol
should be used in caution in case of hypotension.
Brachial and Upper Radial and Ulnar Vessel Injuries (Figs 81.3 and 81.4)
The brachial and upper forearm arterial injuries are quite common in children,
who usually fall on outstretched hand. The brachial and upper forearm vessel
injuries are almost always associated with bony injuries, which needs to be
managed comprehensively by a team of orthopedic and vascular surgeons.
One needs high index of suspicion and expertise to diagnose and make surgical
intervention decision since the size of vessels are small and sometimes surgical
exposure would produce more catastrophic vessel spasm. The usual incision
made is lazy S, where the upper end of the incision starts approximately 4–5 cm
above and lateral to elbow crease and ends below and medial to the crease. Upper
limb fasciotomy as a routine does not warranted considering the muscle mass
and ample collaterals and close monitoring and fasciotomy on demand avoids
unnecessary fasciotomy.
Lower Radial and Ulnar Vessel Injuries

Radial and ulnar vessels injuries are most common in crush and cut injuries.
These injuries are usually associated with involvement of median and/or ulnar
nerves also. Most injuries need interposition vein graft considering the nature of
injury and size of injured vessel. Primary nerve repair should always be done as
most of these injuries may not be life-threatening even if the repair takes some
more time.
Femoral Vessel Injury (Figs 81.5A and B)

In patients with proximal injuries to the femoral vessels, it is often wise to
initially expose the distal common iliac vessels through separate incision above
the inguinal ligament and to obtain proximal vascular control before entering
the femoral region. Once proximal control is obtained, one can safely explore
Fig. 81.3 Severe upper limb injury who presented in 3 hours of injury underwent suc-
cessful repair of brachial artery with skeletal stabilization
Fig. 81.4 Radial and ulnar artery injury
A B
Figs 81.5A and B Penetrating trauma involving both common femoral artery
which was lacerated with thrombus in situ
the femoral arteries through vertical groin incision, extending along the medial
border of sartorius muscle and exposing the injury in a detailed manner. Bleeding
from the femoral region may sometimes be challenging especially with combined
arterial and venous injuries. Venous bleeding can be more difficult to manage,
more often can be controlled by direct pressure from the source of bleeding.
Blind clamping is strongly discouraged because damage to femoral nerve and
numerous collateral may adversely affect the outcome of vascular repair.
Popliteal Vessel Injury (Fig. 81.6)

Distal superficial femoral and proximal popliteal vessel injuries is managed by
the longitudinal incision made over the medial border of sartorius muscle from
mid-thigh to above knee level in supine position. Proximal popliteal vessels
need incision of adductor hiatus tendon. Placing the patient in prone position is
generally discouraged as the isolated mid-popliteal vessel injuries are rare. Distal
popliteal and tibioperoneal trunk injuries can be managed by placing the patient
Fig. 81.6 Penetrating trauma causing popliteal injury
in supine position and making incision in the below knee medial aspect, just
above the anterior border of medial gastrocnemius.
Tibial Vessel Injury

Involvement of both tibial arteries, even in both bone fractures of lower limb
are very rare. Most of the time nonsurgical management of tibial injuries are
recommended for isolated single tibial artery with good collateralization by other
tibial artery. Anterior tibial vessel control is done by putting longitudinal incision
made in the anterior compartment and posterior tibial vessel control just below
the medial border of tibial bone.
COMPARTMENT SYNDROME
Compartment pressure is usually elevated in combined arterial and venous
injuries, prolonged ischemia of more than six hours, complex and multiple
extremity fractures, combined vascular and bone or soft tissue injury and
thrombosed arterial and venous repair which leads to compartment syndrome.
This is characterized by a compromise in capillary perfusion, and ultimately
necrosis of muscle and nerves. Ischemic tissue damage gives rise to the classic
manifestations of pain out of proportion to injury, and worsened by passive
stretch, sensorimotor deficits and tenseness of the extremities. Prompt treatment
is necessary when these findings are present, but tissue loss is usually established
at this point. Palpable pulses do not rule out this condition, and absent pulses
always should be attributed to vascular injury and not compartment syndrome.
Fasciotomy is the definitive treatment, involving complete incision and
decompression of skin and investing fascia of each of the compartment of
extremities (Figs 81.7A and B). It is generally agreed that prophylactic fasciotomy,
which is done before the development of symptoms and tissue loss in
asymptomatic patients with high-risk injuries and findings mentioned earlier, is
A B
Figs 81.7A and B Patient presented with tibial condyle fracture with compartment
syndrome blebs and successfully underwent four compartment fasciotomy
far preferable to therapeutic fasciotomy done after the development of symptoms

and signs of tissue loss. Careful serial examination of injured extremities at high
risk for compartment syndrome is a valid option, but such observation must
include serial measurements of compartment pressure due to the insensitivity
and unreliability of physical findings. Any pressure measurement of more than
25 mm Hg mandates immediate fasciotomy.
BIBLIOGRAPHY
1. Agarwal N, Shah PM, Clauss RH, et al. Experience with 115 civilian venous injuries.
J Trauma. 1982;22;827-32.
2. Anderson RJ, Hobson RW II, Lee BC, et al. Reduced dependency in angiography for
penetrating extremity trauma. J Trauma. 1990;30:1059-65.
3. Attebery LR, Dennis JW, Russo-Alesi F, et al. Changing patterns of arterial injuries
associated with fractures and dislocations. J Am Coll Surg. 1986;183:377-83.
4. Bermudez KM, Knudson MM, Nelken NA, et al. Long-term results of lower extremity
venous injuries. Arch Surg. 1997;132:963-8.
5. Biffl WL, Moore EE, Burch JM. Femoral arterial graft failure caused by secondary
abdominal compartment syndrome. J Trauma. 2001;50:740-2.
6. Bigger IA. Treatment of traumatic aneurysms and arteriovenous fistula. Arch Surg.
1944;49:170-82.
7. Bynoe RP, Miles WS, Bell RM, et al. Noninvasive diagnosis of vascular trauma by
duplex ultrasonography. J Vas Surg. 1991;14:346-52.
8. Degiannis E Levy RD, Potokar T, et al. Penetrating injuries of axillary artery. Aust NZ J
Surg. 1995;65:327-30.
9. Demetrios, et al. Subclavian and axillary vascular injuries. Surg Clinics of North
America. 2001;81:1357-65.
10. Eddy, et al. Femoral vessel injuries and its management. Surg. Clinics of North
America. 2002;82:49-65.
11. Marin ML, Veith FJ, Panetta TF, et al. Transluminally placed endovascular graft repair
for arterial trauma. Vasc Surg. 1994;20:466-73.
12. Menzoian JO. A comprehensive approach to extremity vascular trauma. Arch Surg.
1985;120:801-7.
13. Moniz MP, Ombrellaro MP, Stevens SL, et al. Concomitant orthopaedic and vascular
injuries as predictor for limb loss in blunt lower extremity trauma. Am Surg. 1997;63(1):
24-8.
14. Old W, Oswaks R. Clavicular excision in management of vascular trauma. Am Surg.
1984;50:286-9.
CHAPTER
82 Sushma Vijay Pingale,

V Thanga Thirupathi Rajan
TRAUMATIC HEAD INJURY
INTRODUCTION
Head injury is one of the leading cause of morbidity and mortality across all
ages and amongst all types of injuries. The trauma to the central nervous system
consists of both the primary injury, in which tissue is disrupted by mechanical
force, and a secondary injury which is a cascade of processes that occurs hours or
days after the primary injury and further damages the brain parenchyma.
PRIMARY INJURY
The primary injury which occurs at the moment of impact can be in the form of
a hematoma, contusion or diffuse axonal injury. The primary injury can only be
modified by the trauma prevention programs.
The hematoma can be subdural, extradural or intracranial. Subdural
hematoma is the most common focal intracranial lesion seen in 24% of severe
traumatic brain injury (TBI) patients with a 50% mortality rate. It is defined as
the presence of blood between the duramater and the arachnoid mater. The
accumulation of blood could arise from rupture of the bridging veins or the
cortical arteries. It spreads over the cerebral convexity but the extension into
contralateral hemisphere is prevented by the dural reflections of the falx cerebri.
Subdural hematoma (SDH) can be classified as acute, subacute or chronic. The
acute hematomas appear bright white on the CT whereas the subacute lesions
are isodense with brain tissue and the chronic hematomas are hypodense (Fig.
82.1). All acute subdural hematomas with a thickness greater than 10 mm or
a midline shift greater than 5 mm should be surgically evacuated promptly.
Factors which predict the outcome in patients with SDH are age of the patient,
time from injury to treatment, presence of pupillary abnormalities, GCS/motor
score on admission, immediate coma or lucid interval, CT findings (thickness of
hematoma, extent of midline shift, and the presence of underlying brain swelling)
postoperative intracranial pressure and the type of surgery.
The extradural hematoma (EDH) is defined as the collection of blood
between the inner table of skull and the dura. It occurs as a result of tear in the
middle meningeal artery or one of its branches (Fig. 82.2). Extradural hematomas
are more common in the temporal or parietal regions and carry a mortality rate of
15–20%. They appear as hyperdense mass lesions on CT having a classic biconvex
or lenticular shape and a smooth inner border because they strip the dura from
Chapter 82 Traumatic Head Injury 577
Fig. 82.1 Subdural hematoma with midline shift
Fig. 82.2 Extradural hematoma showing the biconvex shape
the inner table of the skull as they enlarge. But unlike subdural hematomas, their
spread is limited by the suture lines of the skull where the dura is very adherent.
The indication for surgical evacuation is EDH greater than 30 cm3. The factors
predicting outcome in patients with EDH are same as those mentioned above for
SDH.
Intracranial hematoma is the hemorrhage within the brain tissue and is seen
after a very severe TBI. Duret’s hemorrhage is one of the type of intraparenchymal
A B C
Figs 82.3A to C Subarachnoid hemorrhage
Fig. 82.4 Left-sided contusion
hemorrhage in which the bleeding is seen within the base of pons or midbrain
and almost results in death or vegetative state.
Studies have shown that traumatic subarachnoid hemorrhage (SAH) is seen
in up to 60% of admissions for TBI. It is associated with vasospasm in 20% of
patients which can aggravate the secondary injury (Figs 82.3A to C). Prolongation
of QTc interval is also commonly found in patients with traumatic SAH. Use of
nimodipine has level 1 evidence from randomized control trials in management of
predominantly traumatic SAH. Nimodipine, when administered prophylactically
from diagnosis for 21 days, offers modest improvement in outcome and incidence
of ischemic deficit.
Contusions are common after TBI and are seen most commonly in the
inferior frontal cortex and the anterior temporal lobes where the surface of the
inner table of the skull is very irregular. They may not be visible in the initial
CT scan. They evolve over time and may appear as small areas of punctate
hyperdensities (hemorrhages) with surrounding hypodensity (edema) given in
Figure 82.4. Generally small contusions are asymptomatic or may present with
headache. Larger contusions especially if present in frontal lobes may cause an
increase in the intracranial pressure and patient may land up in coma. Focal
neurological symptoms may be evident if the contusion is located in an eloquent
Table 82.1 Grading of diffuse axonal injury (DAI)
Clinical grading of DAI

• Mild DAI—duration of coma is between 6 and 24 hours
• Moderate DAI—duration of coma is for >24 hours but without presence of decerebrate
posturing as the best motor response on nociceptive stimulation.
• Severe DAI—duration of coma is for >24 hours and with presence of decerebrate
posturing as a motor response on nociceptive stimulation.
MRI grading of DAI
• Grade 1—small scattered lesions on the white matter of cerebral hemisphere
• Grade 2—grade 1 plus focal lesions on the corpus callosum
• Grade 3—grade 1 and 2 plus additional focal lesions on the brainstem.
area of the brain, such as the motor or speech areas. The contusions located in
temporal area if enlarged can result in uncal herniation. Because of this risk of
enlargement (20–30%) during the first 24–48 hours, continuous monitoring
of their size by serial CT scans is recommended. If an enlargement is noticed,
unilateral frontal or temporal contusion evacuation can be done to provide space
for the expanding brain without the risk of any significant neuro deficit.
Diffuse axonal injury (DAI) refers to laceration or punctate contusions at the
interface between the gray and the white matter. Grading of DAI is given in Table
82.1. Traumatic coma of greater than 6 hours is usually attributed to DAI and
less than 6 hours is considered as concussion. It is a common cause of persistent
vegetative state or prolonged coma.
SECONDARY INJURY
The primary insult to the brain tissue initiates a series of secondary injury
processes which further aggravate the injury to the brain. These processes
manifest in the form of raised intracranial pressure and alteration in the cerebral
blood flow.
Studies have described a typical phasic cerebral blood flow pattern which
consists of early cerebral hypoperfusion followed by hyperemia followed in the
later phase by occurrence of post-traumatic vasospasm. The occurrence and
degree of hyperperfusion within 12 hours after traumatic head injury has shown
to closely correlate with mortality. The vasospasm sets in 4–5 days of injury.
These alterations in cerebral blood flow have been correlated with a decrease of
saturation of hemoglobin in the bulb of IJV (Jugular venous O2 saturation) and
studies have shown that jugular bulb venous oxygen saturation (SjVO2) below
50% was associated with a poor neurologic outcome.
The normal resting intracranial pressure (ICP) is less than 10 mm Hg. It
is determined by the volume of CSF, blood and the brain tissue in the cranial
vault as indicated by Monro Kelly doctrine. The brain has its own mechanisms
to maintain the normal intracranial pressure like altering the blood volume,
increasing the CSF absorption and the compressible texture of the brain tissue.
When these compensatory buffering mechanisms have been exhausted, the
intracranial pressure starts rising leading to intracranial hypertension which if left
uncorrected may approximate the mean arterial pressure leading to impediment
of the blood supply to the brain. Intracranial hypertension develops in 50% of

comatose patients following severe TBI. It is defined as sustained intracranial
pressure greater than 20 mm Hg. Studies have found that mortality and morbidity
increased significantly when the intracranial pressure persistently remains above
this threshold. The early immediate increase in brain water seen after trauma is
probably vasogenic in origin also called as vasogenic edema whereas that in the
later postinjury period is cellular in origin called as cellular edema.
Management of Traumatic Brain Injury

As discussed above, the primary brain injury cannot be prevented after the
trauma but by preventing hypoxemia, hypotension, hypercarbia and intracranial
hypertension one can largely limit the secondary injury and improve the outcome.
Thus, the aim of management of TBI should be to prevent the secondary injury by
effective management of the above parameters.
The traumatic brain injury is classified clinically by the Glasgow coma scale
as given below (Table 82.2). Best score —15 points and worst score—3 points. CT
scan categories for head injury is given in Table 82.3.
The recent ATLS guidelines recommend that any trauma evaluation should
first include a “primary survey” that includes simultaneous efforts to identify and
treat life- and limb-threatening injuries, beginning with the most immediate. The
focus should be on urgent problems which should be captured in the “golden
hour”. Once these urgent needs are taken care of, a meticulous “secondary
survey” and further diagnostic studies designed to reduce the incidence of
missed injuries should follow. ATLS emphasizes the ABCDE mnemonic—airway,
breathing, circulation, disability, and exposure.
Table 82.2 Glasgow coma scale
Eye-opening response 4 = Spontaneous

3 = To speech
2 = To pain
1 = None
Verbal response 5 = Oriented to name
4 = Confused
3 = Inappropriate speech
2 = Incomprehensible sounds
1 = None
Motor response 6 = Follows commands
5 = Localizes to painful stimuli
4 = Withdraws from painful stimuli
3 = Abnormal flexion (decorticate posturing)
2 = Abnormal extension (decerebrate posturing)
1 = None
Severity of GCS Score Need of CT - brain Management

Mild 14, 15 Yes Observation
Moderate 9–13 Yes Observation in ICU
Severe 3–8 Yes Mechanical ventilation with ICP monitoring
Table 82.3 Marshall scale: CT scan categories for head injury
Category Definition
Diffuse injury I No visible intracranial pathologic process
Diffuse injury II Cisterns with midline shift of 0–5 mm are present ± lesion
densities present; no high or mixed density lesions at ≥25 mL
Diffuse injury III Cisterns compressed or absent, with midline shift of 0–5 mm;
no high or mixed density lesions of ≥25 mL
Diffuse injury IV Midline shift of >5 mm; no high or mixed density lesion of ≥25 mL
Evacuated mass Any lesion surgically evacuated
lesion (V)
Nonevacuated mass High or mixed density lesion of ≥25 mL; not surgically evacuated
lesion (VI)
Airway
The airway is best managed by endotracheal intubation in comatose patients.
Rapid sequence induction with thiopentone (3–5 mg/kg) or fentanyl (3–5 µg/kg)
followed by a short acting neuromuscular blocking agent like succinylcholine
(1–2 mg/kg) should be done. Succinylcholine can increase the intracranial
pressure transiently but its use will lead to faster intubation, its benefits may
outweigh its risks. Hence, one must weigh the use of succinylcholine in each
individual situation based on the acuity of CNS injury, the anticipated speed
with which intubation can be accomplished, and the likelihood that hypoxia
will develop. Alternatives to succinylcholine are rocuronium (0.9–1.2 mg/kg)
and vecuronium (0.1–0.2 mg/kg). But both these agents have longer duration
of action as compared to succinylcholine. The use of thiopentone may result
in hypotension in volume depleted patients hence etomidate would be a better
choice in these patients. The patient should be adequately preoxygenated by
giving 100% oxygen for 5 minutes or 4 vital capacity breaths if possible. The
patient should be intubated in neutral head position with a manual-in line
cervical spine immobilization which is discussed in the chapter under airway
management. The placement of the endotracheal tube should be confirmed by
auscultation in prehospital setup and by a capnometer and X-ray in hospital
setup. The endotracheal tube not only helps in establishing good oxygenation
and ventilation but also protects against aspiration. When oral intubation is
difficult, as seen in severe maxillofacial trauma or difficult airway, then urgent
surgical airway should be established by a cricothyrotomy or tracheostomy.
Breathing
Breathing if found shallow and inadequate mandates mechanical ventilation and
the rate should be kept at 10–12 breaths per minute in adults so as to maintain
an end tidal concentration of carbon dioxide of around 35 mm Hg. Prophylactic
hyperventilation (PaCO2 < 25 mm Hg), especially during the first 24 hours of
injury is not recommended now because hyperventilation reduces the ICP by
causing cerebral vasoconstriction which further reduces the blood flow to an
already ischemic injured brain. Without ICP monitoring, hyperventilation is

indicated only if rapid deterioration of neurologic status is seen.
Circulation
The guidelines for management of severe traumatic brain injury recommend that
a systolic blood pressure <90 mm Hg and PaO2 <60 mm Hg should be avoided
or rapidly corrected. The traumatic coma data bank (TCDB) studies have shown
that a single prehospital observation of hypotension (SBP <90 mm Hg) was
among the five most powerful predictors of outcome after TBI. A single episode of
hypotension was found to increase the morbidity and double the mortality when
compared with groups that did not have hypotension. Hypoxia coupled with
hypotension increased the mortality from severe TBI by three fold.
The guidelines for management of severe traumatic brain injury recommend
that the cerebral perfusion pressure (CPP) should be targeted in the range of
50–70 mm Hg. The CPP is calculated as
CPP = MAP – ICP
(MAP is mean arterial pressure, ICP is intracranial pressure)
The patients in whom autoregulation is intact do well with higher CPP
whereas those with impaired autoregulation are better managed with a CPP in
the range of 50–60 mm Hg with more emphasis on the acute management of ICP.
Isotonic crystalloids (normal saline, lactated Ringer’s solution, Plasma-Lyte
A) are the recommended resuscitative fluids which should be infused through
large bore IV cannulas to achieve normotension (early goal of systolic BP 90–100
mm Hg). Hypertonic saline is more preferred as an osmotic agent for reducing
ICP rather than resuscitation because studies have not found any benefit over
crystalloids for resuscitating trauma victims.
Intracranial Hypertension
Once airway, breathing and circulation are taken care of, the next step is to assess
the patient’s neurological status and disability by noting the GCS and doing CT
scan of head from C2 vertebra to the vertex. The medical conditions that increase
the intracranial pressure, e.g. fever, seizures, agitation and jugular venous outflow
obstruction should be treated.
Measures taken to decrease the intracranial pressure include:
• Head end elevation by 30–40 degrees avoiding excessive neck flexion.
• Anticonvulsant prophylaxis with phenytoin is recommended for post-
traumatic seizures only for first seven days in patients with TBI. Beyond
that, its use is not recommended and any late post-traumatic seizures (after
7 days) should be managed in accordance with the treatment regimen for
new onset seizure disorder.
• Sedation with a narcotic and paralysis with a neuromuscular blocker like
vecuronium should be done after securing the airway in a patient who is
agitated or posturing. Morphine or fentanyl can be used in small doses. Before
giving narcotic, the patient should be made normovolemic so as to avoid
narcotic-induced hypotension. Oxygen saturation should be monitored by
using a pulse oximeter.
• Intermittent CSF drainage (1–2 mL) can be tried by placing a ventricular

catheter to decrease the ICP when it is higher than the therapeutic goal of
20 mm Hg if above methods fail. This asserts the role of ventriculostomy and
intracranial pressure monitoring.
Clinical symptoms such as headache, nausea, and vomiting which are
said to be clinical markers of raised ICP are impossible to elicit in comatose
patients. CT scan findings of midline shift and compressed basal cisterns
are predictive of raised ICP, but intracranial hypertension can occur without
these findings. Hence, it is difficult to reliably determine intracranial
hypertension using these parameters. These limitations make direct
monitoring of ICP necessary.
Indications for ICP monitoring
– Patients with GCS of 8 or less after resuscitation and an abnormal CT
scan.
– Patients with GCS of 8 or less and a normal CT but adverse features
such as age over 40 years, systolic blood pressure of 90 mm Hg or less, or
unilateral or bilateral motor posturing.
The only contraindication for ICP monitoring in these cases is severe
coagulopathy. Placement of the ventriculostomy catheter is the gold
standard for measurement of ICP in TBI patients. The ventricular catheter
is positioned with its tip in the frontal horn of the lateral ventricle and is
coupled by fluid-filled tubing to an external strain gauge transducer and is
found to give most accurate readings and is very cost-effective. It can be reset
to zero and can be recalibrated in situ. The ventriculostomy ICP monitor also
helps in the treatment of an increased ICP by intermittent drainage of the
cerebrospinal fluid.
The other transducers used for ICP monitoring are the microsensor
transducer and the fiberoptic transducer which can also be placed in
ventricular catheter and provide similar benefits but at a higher cost. The
other ICP monitors are the parenchymal ICP monitors which cannot be
recalibrated and the epidural, subdural and the subarachnoid fluid coupled
or pneumatic monitors which are less accurate.
Observation of the trends in the ICP recordings have a prognostic
significance (e.g. Lundberg “A” or the “plateau” ICP wave which indicate
critical cerebral compliance and impending herniation). The brain trauma
foundation guidelines for management of severe traumatic brain injury
recommend an upper threshold of 20–25 mm Hg for the intracranial pressure.
The complications of ICP monitoring are infection (6%), hemorrhage,
malfunction, obstruction or malposition. Studies have shown that keeping
the ventricular catheter in situ for more than 5 days increases the risk of
ventriculitis and hence is not recommended.
• The hyperosmolar therapy with mannitol or hypertonic saline (3% or 7.5%)
can be tried if the above measures are not enough to decrease the ICP.
Mannitol is an osmotic diuretic which acts promptly on infusion
by expanding the plasma, reducing the hematocrit and increasing the
deformability of erythrocytes thereby decreasing the blood viscosity and
causing an increase in the cerebral blood flow and cerebral oxygen delivery.
Its effect on decreasing the ICP starts within minutes and is most marked
in patients with low CPP. The osmotic effect is delayed for 15–30 minutes
and persists for a variable period of 90 minutes to ≥6 hours depending on

the clinical condition. It is given as IV rapid infusion of 0.25–1 gm/kg and
it will maximally decrease the ICP within 10 minutes of administration.
Intermittent bolus infusion is preferred over continuous because the later
may result in extravasation of the drug into the brain tissue causing a reverse
osmotic gradient and an increase in the edema and ICP. Serum osmolality
and the sodium levels should be monitored frequently during mannitol
administration to minimize the risk of acute tubular necrosis and renal
failure. It is contraindicated when the serum osmolality is >320 mosm/L and
the serum sodium is >160 mEq/L and hypovolemia.
Hypertonic saline acts by osmotically mobilizing the water across the
intact blood brain barrier and thereby decreasing the cerebral water content.
It also dehydrates endothelial cells and erythrocytes, leading to an increase
in the diameter of the vessels and deformability of erythrocytes leading to
plasma volume expansion with improved blood flow. Dose is 0.1–1 mL/
kg/hour administered on a sliding scale. The major complication is central
pontine myelinolysis if it is given to patients with preexisting chronic
hyponatremia. It may induce or aggravate pulmonary edema in patients
with underlying cardiac or pulmonary problems. Hence, it is usually tried in
patients whose ICP is refractory to mannitol therapy.
• Hyperventilation as a means to decrease the ICP is indicated only when
there is rapid deterioration of patient’s neurological status. As mentioned
earlier it should be avoided or used cautiously in the first 24–48 hours since
it causes cerebral vasoconstriction in the areas which are CO2 responsive
and further decreases the blood supply to the brain whose blood supply is
already compromised due to injury. If hyperventilation is used, the brain
PO2 and jugular venous oxygen saturation should be monitored to detect any
cerebral ischemia that may ensue due to the therapy. If the brain tissue PO2
is <10 mm Hg, the risk of ischemia increases.
• The definitive treatment for a surgical mass lesion causing significant midline
shift is urgent craniotomy and evacuation of the mass. Indications for surgery
in traumatic brain injury is given in Table 82.4.
Mass effect on CT scan is defined as distortion, dislocation, or obliteration of
the fourth ventricle; compression or loss of visualization of the basal cisterns,
or the presence of obstructive hydrocephalus.
• Barbiturate therapy: Barbiturates decrease the cerebral metabolic demand
and the blood flow. High-dose barbiturate therapy may help in decreasing
the ICP when all the medical and surgical treatment modalities have
failed. Pentothal sodium is the preferred drug. It is given in a loading IV
dose of 10–15 mg/kg over 1–2 hours followed by a maintenance infusion of
1 mg/kg/hour. The dose can be increased till ICP decreases or MAP begins
to fall. Studies have shown that one in four patients treated with barbiturate
will develop hypotension hence the risk benefit ratio has to be considered.
Normovolemia should be ensured before starting barbiturate therapy. It is
not recommended as a prophylactic measure for ICP management.
• Hypothermia: This therapy consists of decreasing the body temperature to
32–33°C as soon as possible after injury and maintenance of that temperature
at least for the next 24–48 hours. This is achieved by using surface cooling
Table 82.4 Indications for surgery in traumatic brain injury
• An acute SDH with a thickness >10 mm or a midline shift >5 mm on CT regardless
of the patient’s GCS score
• SDH <10 mm thick and midline shift <5 mm with GCS score <9
• An extradural hematoma (EDH) >30 cm3 regardless of the patient’s GCS
• Patients with GCS scores of 6 to 8 with frontal or temporal contusions >20 cm3 in
volume with midline shift of at least 5 mm and/or cisternal compression on CT scan,
and patients with any lesion >50 cm3 in volume
• If the GCS score decreases between the time of injury and hospital admission by 2 or
more points and/or the patient presents with asymmetric or fixed and dilated pupils
and/or the ICP exceeds 20 mm Hg
• Patients with parenchymal mass lesions and signs of progressive neurologic
deterioration referable to the lesion, medically refractory intracranial hypertension, or
signs of mass effect on CT scan
• Patients with posterior fossa mass lesions having mass effect on CT scan or with
neurologic dysfunction or deterioration referable to the lesion
• Patients with open (compound) cranial fractures depressed greater than the thickness
of the cranium should undergo operative intervention to prevent infection
techniques. Studies have shown that hypothermia maintained for more than
48 hours decreases the mortality and improves the Glasgow coma score. It
has been thought to significantly decrease the ICP.
Mild (GCS 14,15) and moderate (GCS 9–13) brain injuries usually manifest
in the form of loss of consciousness at the time of injury to the head and some
amount of retrograde amnesia. They are generally referred to as concussions and
do not have any significant intracranial pathology. Mild injury patients can be
kept under standard observation and if they are found to be completely normal
neurologically after 1–2 hours, they can be discharged with a companion and with
instructions to revert back to hospital if they develop any symptoms. Moderate
injury patients need ICU admission and serial evaluation.
General Care of TBI Patients

While managing patients with TBI one has to keep in mind that the recovery may
take a long time and hence the other issues of the patient’s body also should be
attended. This includes starting enteral nutrition as soon as possible or parenteral
nutrition if enteral is not possible. The resting metabolic expenditure increase
by 140% in a nonparalysed patient and is 100% in paralysed patient with severe
TBI. Hence, while calculating the caloric requirement, this has to be taken note of
and at least 15% of the caloric requirements should consist of protein especially
branched chain amino acids.
Deep venous thrombosis prophylaxis should be started with sequential
compression devices. Low dose heparin is effective but carries a risk of intracranial
bleed in TBI patients.
Short course of antibiotics can be given during intubation to prevent
pneumonia but the long-term prophylactic use of antibiotics is not recommended.
Generally, antibiotics should be given only when infection develops.
Physiotherapy and Rehabilitation

Physiotherapy plays a major role in getting the TBI patient back to lead their
normal or near normal life. It should be started within the first few days after
injury, by a trained physiotherapist. Initially passive range of exercises should
be started. Gradually the patient should be made to sit. Studies have shown that
early sitting in comatose patient helps in the early recovery of consciousness.
BIBLIOGRAPHY
1. ATLS for Doctors. Student Manual, 7th edition. Chicago, American College of
Surgeons; 2004.
2. Barzo P, Marmarou A, Fatouros P, et al. Biphasic pathophysiological response of
vasogenic and cellular edema in traumatic brain swelling. Acta Neurochir Suppl
(Wien). 1997;70:119-22.
3. Barzo P, Marmarou A, Fatouros P, et al. Contribution of vasogenic and cellular edema
to traumatic brain swelling measured by diffusion-weighted imaging. J Neurosurg.
1997;87:900-7.
4. Brain Trauma Foundation: Guidelines for the management of severe head injury. US
Brain Trauma Foundation, 2007.
5. Bullock RM, Chesnut R, Ghajar J, et al. Guidelines for the surgical management of
traumatic brain injury. Neurosurgery. 2006;58(3 Suppl):S1-S62.
6. Chesnut RM, Marshall LF, Klauber MR, et al. The role of secondary brain injury in
determining outcome from severe head injury. J Trauma. 1993;34:216-22.
7. Collier BR, Miller SL, Kramer GS, et al. Traumatic subarachnoid hemorrhage and QTc
prolongation. J Neurosurg Anesthesiol. 2004;16:196-200.
8. Dorhout Mees SM, Rinkel G, Feigin V, et al. Calcium antagonists for aneurysmal
subarachnoid haemorrhage. Cochrane Database Syst Rev. 2007;(3):CD000277.
9. Doyle JA, Davis DP, Hoyt DB. The use of hypertonic saline in the treatment of traumatic
brain injury. J Trauma. 2001;50:367-83.
10. Eisenberg HM, Frankowski RF, Contant CF, et al. High-dose barbiturate control of
elevated intracranial pressure in patients with severe head injury. J Neurosurg. 1988;
69:15-23.
11. Foulkes M, Eisenberg HM, Jane JA, et al. The Traumatic Coma Data Bank: design,
methods, and baseline characteristics. J Neurosurg. 1991;75(Suppl):S8-S13.
12. Gennarelli TA, Spielman GM, Langfitt TW, et al. Influence of the type of intracranial
lesion on outcome from severe head injury: a multicenter study using a new
classification system. J Neurosurg. 1982;56:26-32.
13. Hlatky R, Contant CF, Diaz-Marchan P, et al. Significance of a reduced cerebral blood
flow during the first 12 hours after traumatic brain injury. Neurocrit Care. 2004;1:
69-83.
14. Irwin Rippe RS, James M. Intensive Care Medicine, 6th edition. Lippincott Williams
and Wilkins; 2008.
15. Jones NR, Molloy CJ, Kloeden CN, et al. Extradural haematoma: Trends in outcome
over 35 years. Br J Neurosurg. 1993;7:465-71.
16. Lundberg N, Troupp H, Lorin H. Continuous recording of the ventricular fluid
pressure in patients with severe acute traumatic brain damage. A preliminary report.
J Neurosurg. 1965;22:581-90.
17. Marshall LF, Marshall SB, Klauber MR, et al. A new classification of head injury based
on computerized tomography. J Neurosurg. 1991;75:S14-S20.
18. Martin NA, Patwardhan RV, Alexander MJ, et al. Characterization of cerebral
hemodynamic phases following severe head trauma: hypoperfusion, hyperemia, and
vasospasm. J Neurosurg. 1997;87:9-19.
19. Massaro F, Lanotte M, Faccani G, et al. One hundred and twenty-seven cases of
acute subdural haematoma operated on. Correlation between CT scan findings and
outcome. Acta Neurochir (Wien). 1996;138:185-91.
20. Mattioli C, Beretta L, Gerevini S, et al. Traumatic subarachnoid hemorrhage on the
computerized tomography scan obtained at admission: A multicenter assessment of
the accuracy of diagnosis and the potential impact on patient outcome. J Neurosurg.
2003;98:37-42.
21. Miller RD. Miller’s Anesthesia, 7th edition. Elsevier Publications; 2009.
22. Muizelaar JP, Marmarou A, Ward JD, et al. Adverse effects of prolonged hyperventi
lation in patients with severe head injury: a randomized clinical trial. J Neurosurg.
1991;75:731-9.
23. Narayan RK, Kishore PRS, Becker DP, et al. Intracranial pressure: to monitor or not to
monitor? A review of our experience with severe head injury. J Neurosurg. 1982;56:
650-9.
24. Servadei F. Prognostic factors in severely head injured adult patients with acute
subdural haematomas. Acta Neurochir (Wien). 1997;139:279-85.
25. Tempkin NR, Dikmen SS, Wilensky AJ, et al. A randomized, double-blind study of
phenytoin for the prevention of post-traumatic seizures. NEJM. 1990;323:497-502.
26. Zumkeller M, Behrmann R, Heissler HE, et al. Computed tomographic criteria and
survival rate for patients with acute subdural hematoma. Neurosurgery. 1996;39:
708-12.
CHAPTER
83 Sushma Vijay Pingale, Marun Raj
THORACIC TRAUMA
Thoracic trauma is one of the leading cause of trauma-related deaths. The major
potentially life-threatening injuries in thoracic trauma are given in the Table 83.1.
INJURY TO CHEST WALL

Rib fractures by themselves are not very harmful but they are accompanied by
more severe injuries like pulmonary contusion which are more of a concern. The
age of the patient and the location of the rib fracture are other major determinants
of the morbidity and mortality associated with rib fracture. Studies have shown
that elderly patients with rib fractures have twice the mortality of younger patients
with similar injuries. The left-sided fractured ribs are generally associated with
splenic injuries and the right-sided rib fractures are associated with injury to the
liver. The first rib may be associated with injury to the subclavian artery.
The number of fractured ribs also has significant bearing on the outcome as
shown by the study of Flagel et al. The overall mortality rate for patients with rib
fractures is around 10% and is said to increase with each additional rib fracture
independent of age.
Flail Chest
It is a condition defined as the fracture of at least four consecutive ribs in two or
more places in a parallel vertical orientation. It results in an incompetent segment
of chest wall which causes paradoxical movement of the rib cage. As the patient
inspires, the negative pressure that is generated is dissipated by the movement
of the flail segment inwards while the remainder of the thoracic cage moves
outward during inspiration. The associated lung injury may further contribute to
Table 83.1 Life-threatening injuries in thoracic trauma
• Injury to chest wall—Rib fractures and flail chest

• Injury to pleura—Pneumothorax and hemothorax
• Injury to lung parenchyma—Contusion and tracheobronchial injury
• Injury to heart—Cardiac contusion, rupture and valvular injury
• Injury to aorta
• Injury to esophagus
Chapter 83 Thoracic Trauma 589
hypoxia by causing a mismatch in the ventilation and perfusion. The mainstay of

treatment in this type of injury is to support the ventilation and give excellent pain
relief in the form of epidural analgesia. Positive pressure ventilation is the gold
standard as it forces the flail segment to rise and fall normally with inspiration.
Epidural anesthesia abolishes the pain associated with the multiple rib fractures
and thereby avoids the splinting and hypoventilation associated with it and hence
become one of the major treatment for such injuries. Intercostal nerve block can
also be tried whenever epidural analgesia is not feasible.
INJURY TO PLEURA
The pleural space is the potential space between the parietal and visceral pleura.
An injury to any of these pleurae can result in air or blood accumulating in this
space which can compress the lung parenchyma and cause collapse of the lung.
Pneumothorax
Pneumothorax is a condition in which there is presence of free air in the pleural
space resulting in partial or total lung collapse. It can occur due to disruption of
parietal pleura or visceral pleura. It can be spontaneous (due to rupture of some
bulla) or traumatic. A traumatic pneumothorax can arise as a result of a blunt or
penetrating trauma.
Clinical Features
Pneumothorax is identified by chest pain and dyspnea, sinus tachycardia,
decreased breath sounds and expansion of chest wall on the affected side. If the
patient is hemodynamically stable, a chest radiograph can be obtained in the
upright position which is diagnostic in most of the cases. X-ray in the supine
position may show anterolateral air which typically increases the radiolucency at
the costophrenic sulcus creating the “deep sulcus sign”. Small pneumothoraces
which are not visible on plain radiographs can be picked up by the CT scan of
thorax (Figs 83.1A and B).
A B
Figs 83.1A and B (A) X-ray—bilateral pneumothorax and (B) CT scan—
left-sided massive pneumothorax
A B
Figs 83.2A and B Right-sided tension pneumothorax shifting the
mediastinum to the left side
Tension pneumothorax is a life-threatening condition in which there is

progressive accumulation of trapped air in the pleural space which increases the
intrapleural pressure causing total collapse of the lung on the affected side and
shift of the mediastinum to the opposite side thus jeopardising the cardiac output
(Figs 83.2A and B). It is a clinical diagnosis and if not decompressed immediately,
it can cause complete hemodynamic collapse. Emergency decompression with a
14- or 16-gauge catheter in the midclavicular line of the second intercostal space
may be lifesaving while preparations for chest tube insertion are being made.
Hemothorax is defined as the accumulation of blood in the pleural space.
The source of the blood may be bleeding anywhere in the chest cavity including
the chest wall, lung parenchyma, heart, major thoracic vessels or diaphragm.
Patients with hemothorax present with tachycardia, tachypnea, decreased breath
sounds and chest wall movement and dullness to percussion on the affected side.
In case of massive hemothorax they may also present with shock.
Massive hemothorax is one in which there is accumulation of more than
1500 mL of blood in the pleural space. It is more common on the left side and is
usually due to aortic rupture in a blunt trauma or pulmonary hilar or major vessel
injury due to a penetrating trauma.
Small hemothoraces (<15% of the volume of hemithorax) may not be
visible on X-ray because the blunting of the costophrenic angle in a radiograph
requires accumulation of 200–250 mL of blood. CT scan is useful in such occult
hemothorax.
Treatment of Pneumothorax and Hemothorax

Tube thoracostomy is the definitive treatment for most pneumothoraces as well
as hemothorax. The fifth intercostal space in the mid-axillary line on the affected
side is the preferred site for the tube placement and the optimal position is
posterior to facilitate dependent drainage of blood and the tube is directed to the
apex of the pleural cavity. Tube size preferred in adults is generally 36 Fr. A chest
radiograph should always be taken after doing a tube thoracostomy.
In case of an open pneumothorax (caused when a penetrating chest injury
opens the pleural space to the atmosphere) a sterile occlusive dressing covering
three sides of the wound is done so as to allow it to function as a one way valve
allowing air to escape during expiration and occlude during negative pressure
inspiration. A chest tube is inserted under aseptic precautions at a site away
from the site of injury to treat any possible tension pneumothorax that may
Table 83.2 Indications for exploration in thoracic injury
• Caked hemothorax (high volume output initially followed by an abrupt decrease in

the volume)
• Drainage of more than 1500 mL of blood on insertion of chest tube
• Continuous hemorrhage of more than 200 mL/hour for three consecutive hours
• Large air leak with inadequate ventilation or persistent collapse of lung
• Esophageal perforation
arise. Oxygen should be supplemented and the airway and breathing should be
controlled if required.
A moderate-sized hemothorax (500–1500 mL) which stops bleeding
immediately after the insertion of chest tube can be managed conservatively
with a closed drainage system. The removal of tube should be done only after
the pneumothorax and air/blood leak has resolved completely. Indications for
exploration in thoracic injury is given in Table 83.2.
INJURY TO LUNG
Pulmonary contusion is a common problem in a majority of patients sustaining
major chest trauma. It may result due to direct blunt trauma, shearing at gas
liquid interface or the transmission of a shock wave. The pathophysiological
changes are hemorrhage and interstitial edema. A flail chest is associated with
pulmonary contusion in approximately three fourths of thoracic trauma cases
and this doubles the morbidity and mortality. The patient will be tachypnoeic
with increased work of breathing, will have hypoxia and hypercarbia commonly.
A chest radiograph may not show any signs up to 6 hours of injury and hence
CT scan is useful during the early phase of injury. Treatment is supportive and
includes supplementation of oxygen, pulmonary toileting (through nasotracheal
suction, chest physiotherapy or postural drainage or bronchoscopy) and adequate
pain relief. The intravenous fluids are given judiciously since hypervolemia may
exacerbate the fluid extravasation into the alveolar space and thus worsen the
parenchyma consolidation. The degree of pulmonary dysfunction usually peaks at
72 hours and generally resolves within 7 days in the absence of associated infection.
Tracheobronchial injury though uncommon should be suspected in the
presence of cervical subcutaneous emphysema, pneumomediastinum or
pneumothorax with a persistent air leak. A bronchoscopy is diagnostic. More
than 80% of tracheobronchial injury due to blunt trauma is located within 2.5 cm
of the carina. Oral intubation may be required in patients who have respiratory
difficulty. Injury to the trachea can be primarily repaired or converted to a
tracheostomy if necessary for airway control. When a major bronchus is injured,
lobectomy is advocated with closure of the bronchial stump debrided back to
healthy tissue.
INJURY TO HEART
Blunt cardiac injuries can result from motor vehicle crashes or due to any trauma
to the chest. The injury may result in cardiac contusion, rupture or valvular injury.
Generally the cardiac contusion is not considered serious if the ECG and the
serum troponin levels are normal at the time of presentation and 8 hours later.
But if the ECG and the troponin levels are abnormal then the patient needs good
cardiac monitoring as it may lead to cardiogenic shock resistant to ionotropic
support. Then alternatives like the intra-aortic balloon counterpulsation may be
required.
Cardiac rupture can present as cardiac tamponade. Hypotension is seen in
the absence of overt blood loss. Ultrasonography may show hemopericardium.
Creation of a pericardial window in the operating room can be both diagnostic
and therapeutic. Traumatic valve insufficiency, depending on the severity and
the valve involved may necessitate early surgical treatment.
INJURY TO AORTA
Though not uncommon for the civilian population to have thoracic vascular
injuries, most of the injuries are treatable if the patient present within the golden
hours. Medical fraternity needs further training in these aspect since most of the
time these injuries are easily missed due to inadequacy of the expertise available
and the need for tertiary care setup to deal all these injuries.
Evaluation of the Chest Injuries

Patients admitted to emergency department with life-threatening chest traumatic
injuries need several things to be performed in a swift manner without wasting
time.
• Evaluation of the patient clinically to rule out the possibility of pericardial
tamponade, pneumothorax or cardiorespiratory compromise and any
dangerous extrathoracic injuries.
• Respiratory failure and airway obstruction are managed by immediate
endotracheal intubation, assisted ventilation if necessary and tracheo
bronchial suction.
• A central venous catheter is inserted into jugular vein to accurately assess
the volume requirement and at the same time to replace the volume in swift
manner without producing compromise although a wide bore peripheral
cannula is better than central venous cannula for rapid infusion of fluids and
blood products.
• Chest X-ray taken in erect posture if possible reveals many factors including
rib fractures, pleural effusion, diaphragmatic position and mid line shift
if any.
Once the above said stages of clinical evaluation are over and the patient is
stabilized, then triage can be completed. In triage, it is essential to distinguish
those patients with airway obstruction, pericardial tamponade and tension
pneumothorax, since the delay in treatment in order to take investigations or
imaging is hazardous. Next step is grouping the patients with injuries such
as traumatic rupture of aorta or massive hemothorax, where intervention by
exploratory thoracolaparotomy is urgent but is preceded by rapid investigation.
The last group compromises the majority of trauma victims who at most
need minor intervention and in hospital observation. The classification of

chest injuries by triage is further classified based on the anatomy of the lesion
involved:
• Chest wall and diaphragm
• Intrathoracic viscera.
Traumatic Rupture of Aorta

Following a deceleration injury, the aorta may rupture at the isthmus just
distal to the origin of the left subclavian artery. The intima and media rupture
circumferentially but the adventitia remains intact and the patient will survive
until the adventitia ruptures, which may occur at any time. There are usually no
specific clinical sings that point directly at the lesion, but its presence is always
looked for whenever there is a history of a severe fall or motor-vehicle accident.
On chest X-ray, the superior mediastinum is broadened and sometimes in
anteroposterior view, mediastinum may look widened. Hence in that case,
clinical presentation helps in diagnosing the condition. Venous hemorrhage is
a source of mediastinal hematoma and will radiographically mimic a rupture.
Other radiographic signs of great importance are loss of aortic knuckle, rightward
displacement of the trachea and the esophagus and a left hemothorax. Injury to
the thoracic skeleton is a marker for the severity of the deceleration and therefore
the likelihood of rupture. The diagnosis must be confirmed by CT of the thorax or
angiography of the thoracic aorta. The aortic rupture is then repaired through a fifth
interspace thoracotomy with cross-clamp control gained proximally across the
arch between left common carotid and subclavian arteries and distally opposite
the pulmonary veins. Distal perfusion during cross-clamping is maintained with
a heparinized shunt running from aortic arch to distal descending thoracic aorta
or femoro-femoral bypass. The rupture is repaired with an interposition Dacron
of PTFE synthetic graft.
Dissection of Aorta
Aneurysm results from a transverse split through the aortic intima into the media.
From the entry point the aneurysm tunnels through the media and creates a
double lumen aorta. The true lumen bounded by normal aortic wall and the
dissection flap of intima and media and a false lumen bounded by the dissection
flap centrally and the residual media and adventitia externally. When a dissection
occurs, the patient experiences sudden-onset central chest pain radiating to the
back. There may not be any abnormality on physical examination, but evidence
of branch artery damage such as neurological signs, aortic incompetence and
diminished peripheral pulses with leg symptoms. CT angiogram has almost
replaced the conventional angiogram nowadays. Type A dissection is treated
with prosthetic replacement of the ascending aorta with or without aortic valve
resuspension and coronary artery bypass grafting. Acute type B dissection are
mostly managed medically and chronic type 2 with complications need surgical
replacement of aorta.
INJURY TO ESOPHAGUS
Esophageal perforation is more common iatrogenically during endoscopy. Patient
complains of pain. There may be presence of fever, crepitus and subcutaneous
or mediastinal air. A plain radiograph of chest may show subcutaneous
emphysema. Contrast studies are confirmatory and also point to the exact site of
perforation. When the perforation is small, conservative approach consisting of
broad spectrum intravenous antibiotics and keeping the patient nil by mouth is
helpful. Nasogastric tube is avoided and surgery is indicated when there is a free
communication of the leak with either the peritoneal or thoracic cavities or in
case of presence of mediastinal abscess.
BIBLIOGRAPHY
1. Avery EE, Morch ET, Benson DW. Critically crushed chest: a new method of treatment
with continuous mechanical hyperventilation to produce alkalotic apnea and internal
pneumatic stabilization. J Thorac Cardiovasc Surg. 1956;32:291-311.
2. Bulger EM, Arneson MA, Mock CN, et al. Rib fractures in the elderly. J Trauma. 2000;
48:1040-7.
3. Clark GC, Schecter WP, Trunkey DD. Variables affecting outcome in blunt chest
trauma: flail chest vs pulmonary contusion. J Trauma. 1988;28:298-304.
4. Flagel BT, Luchette FA, Reed RL, et al. Half-a-dozen ribs: the breakpoint for mortality.
Surgery. 2005;138:717-25.
5. Gupta A, Jamshidi M, Rubin JR. Traumatic first rib fracture: is angiography necessary?
A review of 730 cases. Cardiovasc Surg. 1997;5:48-53.
6. Irwin RS, Rippe JM. Irwin and Rippe’s Intensive Care Medicine, 6th edition Lippincott
Williams and Wilkins; 2008.
7. Lynn RB, Iyengar K. Traumatic rupture of the bronchus. Chest. 1972;61:81-3.
8. Miller RD. Miller’s Anesthesia. 7th edition. Elsevier Publications; 2009.
9. Sherwood SF, Hartsock RL. Thoracic injuries. In: McQuillian KA, Von Rueden KT,
Hartstock RL, et al. (Eds): Trauma Nursing from Resuscitation through Rehabilitation.
3rd edition. Philadelphia, Saunders; 2002. pp. 543-90.
10. Shweik E, Klen J, Wood GC, et al. Assessing the true risk of abdominal solid organ
injury in hospitalized rib fracture patients. J Trauma. 2001;50:684-8.
11. Velmahos GC, Karaiskakis M, Salim A, et al. Normal electrocardiography and serum
troponin I levels preclude the presence of clinically significant blunt cardiac injury.
J Trauma. 2003;54(1):45-51.
12. Yamamoto L, Schroeder C, Morley D, et al. Thoracic trauma: the deadly dozen. Crit
Care Nurs Q. 2005;28(1):22-40.
SECTION
19 ULTRASONOGRAPHY
Chapter 84 Role of Ultrasound in Critical Care

Prem Kumar
CHAPTER
84 Prem Kumar
ROLE OF ULTRASOUND IN
CRITICAL CARE
INTRODUCTION
Ultrasound is a recently introduced technology in the field of anesthesiology,
critical care and emergency room. The growing concern for procedures to
be performed in real time, reducing complications, aiding diagnosis and
interventions has made ultrasound to be one of the best modality in critical care.
Ultrasound has become the gold standard for bedside diagnosis, hemodynamic
assessment and for guidance in performing interventions in real time in critically
ill patients (Fig. 84.1).
Fig. 84.1 Portable ultrasound machine

598 Section 19 Ultrasonography
PHYSICS OF ULTRASOUND
Ultrasound is high frequency sound waves with frequency >20 KHz (human ears
can hear sound frequencies between 20 Hz and 20 KHz). Medical ultrasound has
a frequency of 2.5 MHz–15 MHz. It allows noninvasive imaging of tissues in real
time based on reflection and scattering. This is based on a phenomenon called
piezoelectric effect where there is mechanical deformation in response to an
electric field applied to lead zirconate titanate. The term piezoelectric means
pressure electric effect. By incorporating piezoelectric elements into transducer,
it converts electric energy into mechanical oscillations thereby acting both as
transmitter and receiver.
Terminologies to be understood in ultrasound physics:
• Acoustic velocity
• Acoustic impedance
• Axial and lateral resolution
• Attenuation coefficient.
Acoustic velocity is the speed at which sound wave travels through a medium
which is equal to frequency times the wavelength. Acoustic impedance is the
degree of impedance a sound wave undergoes while it travels through a medium.
There are two types of spatial resolution—axial and lateral. The minimal distance
of the superior and inferior planes along the axis of the beam is axial resolution.
The ultrasound wave undergoes various characteristics as it travels through the
tissues—reflection, scattering and absorption.
There are 2 properties in ultrasound which determines the selection of
probe—wavelength and frequency. Wavelength is the distance between two areas
of maximal rarefaction and penetration of the ultrasound wave is proportional to
wavelength. Frequency is the number of wavelengths that pass per unit time. It is
measured as cycles per second and the unit is hertz (Hz). Higher the frequency,
better the resolution but the lower the penetration and vice versa in case of lower
frequency.
Imaging Modes
A-mode
The transducer emits ultrasound wave into medium and a single dimensional
image is generated as a series of vertical peaks which corresponds to the depth of
the tissues. This mode does not provide information about the spatial relationship
of the structures, hence it is a basic mode for imaging the structures.
B-mode
This mode produces a 2 dimensional image due to a linear array of many
piezoelectric crystals in the transducer. This mode produces dots of different
brightness based on the amplitude of a series of A scans. Intensity of gray scale
indicates the strength of echogenicity and the side to side and upward downward
distance in the display reflects the real distances in the tissue. Since this mode
Chapter 84 Role of Ultrasound in Critical Care 599
provides cross-sectional image, this mode is commonly used in regional

anesthesia and critical care.
M-mode
This mode produces a single beam with a motion signal where structural
movement like heart valve can be visualized in a waveform manner. This mode is
used for cardiac valve imaging and fetal cardiac imaging.
Doppler
This is superimposed on a B mode image in which the color depends on whether
blood flow direction is towards the transducer or away from it. Red and blue color
indicates the direction and velocity of blood flow where red color indicates the
flow away from the probe and blue color indicates the flow towards the probe.
Selection of Ultrasound Transducer

Frequency is the main element of transducers and they are also described by their
array (e.g. linear) configuration. Based on frequency, transducers are classified
into high, mid and low frequency transducers (Table 84.1 and Fig. 84.2).
Table 84.1 Transducers and its indications
High frequency (>10 MHz) Suited to visualize structures within 3 cm from the skin surface.
Good to visualize superficial structures (e.g. internal jugular
vein, nerve blocks)
Mid frequency (5–10 MHz) Suited for structures within 3–6 cm from skin surface. Used
for nerve blocks, deeper vascular structures
Low frequency (<5 MHz) Used for visualizing deeper structures (e.g. IVC collapsibility)
Fig. 84.2 Transducers—linear array and curvilinear

ULTRASOUND IMAGE CHARACTERISTICS

Any image obtained on the screen can be controlled by depth and gain. The
intensity of the returned ultrasound waves is depicted by the brightness on the
screen (echogenicity). Strong reflection of a structure back to the transducer is
portrayed as white color on screen (hyperechoic or echogenic). Less reflection of
the structure which shows dark image on the screen is depicted as hypoechoic.
Bone, pleura are seen as hyperechoic and nerves, fluids, muscle tissues are seen
as hypoechoic (Table 84.2).
Transducer Movements (Figs 84.3 to 84.7)

• Sliding
• Tilting
• Rotating
• Angling
• Compression.
Before starting to scan, the orientation of the transducer is confirmed in
relation to the image on the screen. The U symbol in the top left screen corner
represents the palpable prominence on one side of the transducer. Transducer
position on the screen is confirmed by placing the finger on one side of the
transducer to note a change in the image of the screen. It is better to always orient
Table 84.2 Ultrasound appearance of various structures
Structure Appearance
Artery Hypoechoic, pulsatile, noncompressible. Doppler shows pulsatile flow
Vein Hypoechoic, nonpulsatile, compressible. Valsalva effect, Doppler shows
continuous flow
Bone Hyperechoic
Tendon Hyperechoic with anisotropy—bright lines longitudinally or bright dots at
right angles fibrillary pattern
Nerves Variable hypo- or hyperechoic with anisotropy fascicular pattern
Muscle Hypoechoic with multiple hyperechoic lines
A B
Figs 84.3A and B Sliding
A B C
Figs 84.4A to C Angling
Fig. 84.5 Compression
A B
Figs 84.6A and B Rotation
ourselves that the left and right side of the screen image corresponds to the left
and right side of the structure of interest in the patient.
Imaging (Figs 84.8A and B)

Short-axis view: Imaging is a cross-sectional view of the structure with the
transducer kept at right angle to the direction of the structure of interest.
A B
Figs 84.7A and B Tilting
A B
Figs 84.8A and B Ultrasound image of internal jugular vein—short axis view and
long axis view
Long-axis view: Probe and target structure are aligned in a way or kept parallel so
that the image of the structure is in longitudinal axis.
NEEDLE ORIENTATION
When needles are introduced into the field, they are depicted as being in plane or
out of plane based on whether the needle is in or out of the plane of the ultrasound
beam (Figs 84.9 and 84.10).
In plane imaging—needle is introduced to the target structure in the same plane
of the ultrasound beam, hence the needle can be seen in its entire length. So the
needle tip can be seen and positioned precisely in the area of interest.
Out of plane imaging—needle is introduced to the target structure perpendicular
to the ultrasound beam, hence the needle can be seen as a bright spot on the
screen. Disadvantage is this method does not indicate the needle tip position.
Fig. 84.9 Needle orientation—in plane
Fig. 84.10 Needle orientation—out of plane
Clinical Uses of Ultrasound in ICU (Table 84.3)

• Diagnosis and assessment—thoracic, cerebral, abdominal, vascular, ocular
structures. RUSH protocol is done for diagnosing the cause of shock (Tables
84.4 and 84.5, Fig. 84.11). e-FAST (Focused Assessment with Sonography
for Trauma) protocol is done for patients coming to emergency room with
trauma (Figs 84.12A to F). Aortic view can be seen in Figures 84.13A to D.
• Echocardiography—diagnosis and assessment of volumes
• Procedural—central venous catheterization, regional nerve blocks, etc.
PULMONARY EMBOLISM
The echocardiographic findings suggestive of pulmonary embolism are RV
dilation, impairment of the RV free wall contraction, paradoxical septal wall
motion, or dilation of the right pulmonary artery, in a patient with hemodynamic
instability/collapse.
Table 84.3 Uses of ultrasound in critical care
Site Findings Diagnosis

Abdomen Free fluid Intraperitoneal fluid/blood
Abdominal aorta >3 cm Abdominal aortic aneurysm
Thorax Lung sliding sign (absence) Pneumothorax
(Figs 84.18, 84.20 to 84.22)
Comet tail artifacts (absence) Pleural effusion
Echo-free space between visceral
and parietal pleura Pulmonary edema
A, B lines (Fig. 84.19)
Vascular Compressibility of common femoral Deep venous thrombosis
(lower limb) vein and popliteal vein (Figs 84.14
and 84.15).
Echocardiography Assessment of left ventricular (LV) Myocardial ischemia/
(TTE) and right ventricular (RV) function/ infarction
Regional wall motion abnormalities
Assessment of the pericardial space Pericardial effusion
Dilated right ventricle, right atrium Pulmonary embolism
Underfilled ventricles, IVC diameter Hypovolemia
and collapsibility on respiration
(Figs 84.16A and B) Cardiac arrest
Ventricular activity
Transcranial Flow velocity, pulsatile index Cerebral vasospasm,
Doppler cerebral artery obstruction
Ocular Optic sheath diameter >5 mm Increased intracranial
pressure
Table 84.4 RUSH protocol
RUSH Hypovolemic Cardiogenic Obstructive shock Distributive shock

exam shock shock
Pump Underfilled Dilated Pericardial effusion Hypercontractile heart
ventricles ventricles dilated RV (early sepsis) hypocon-
Hypercontractile heart tractile heart (late sepsis)
Tank Flat IVC Distended Distended IVC Normal/small IVC nor-
Peritoneal IVC Absent lung mal/small IJV
fluid pleural RWMA Sliding Pleural fluid (empyema)
fluid Comet tail artifacts Peritoneal fluid (perito-
nitis)
Pipes Aortic Normal DVT Normal
dissection
Table 84.5 Stepwise approach in RUSH protocol
Step no. 1 Step no. 2 Step no. 3

Pump Pericardial effusion: Left ventricular contractility: Right ventricular strain:
• Effusion? Normal or reduced? • Increased size of
• Signs of tamponade? RV?
• Diastolic collapse • Septal displacement
of RV from right to left
Tank Inferior vena cava: E-FAST exam: Tension pneumothorax:
Size, collapsibility based • Free fluid abd/pelvis? Absent lung sliding?
on inspiration. • Free fluid thoracic cavity? Absent comet tails?
• Pulm edema: Lung rockets?
Pipes Abdominal aorta Femoral or popliteal
aneurysm: vein DVT?
Abdominal aorta >3 cm Compressible?
A B C
Figs 84.11A to C RUSH protocol: (A) Parasternal view; (B) Subxiphoid view;
(C) Apical view
A B C
D E
Figs 84.12A to F e-FAST (Focused Assessment with Sonography for Trauma) protocol:
(A) Subxiphoid view; (B) Perihepatic and hepatorenal view; (C) Perisplenic view;
(D) Pelvic view; (E) Pleural view
A B
C D
Figs 84.13A to D Probe positions for aortic view. (A) Suprasternal; (B) Parasternal;
(C) Epigastric; (D) Supraumbilical
Fig. 84.14 Common femoral vein for DVT
Bedside Lung Ultrasound in Emergency Protocol for

Acute Respiratory Failure
Bedside lung ultrasound in emergency (BLUE) protocol is a fast protocol which
requires less than minutes for an expert and little longer for a novice. The purpose
of BLUE protocol is that it allows diagnosis of acute respiratory failure based on
the venous analysis (Flow chart 84.1). Pulmonary edema, pulmonary embolism,
Fig. 84.15 Popliteal vein for DVT
A B
Figs 84.16A and B Ultrasound-guided IVC imaging showing collapsibility in the
second image
pneumonia, chronic obstructive pulmonary disease, asthma, and pneumothorax

yield specific profiles in this protocol.
BLUE-points: Two hands are placed on the chest with the upper hand touching
the clavicle, thumbs excluded which correspond to the location of the lung. This
allows three standardized points to be defined. The upper-BLUE-point is at the
middle of the upper hand. The lower-BLUE-point is at the middle of the lower
palm. The PLAPS (posterolateral alveolar or pleural syndromes) point is defined
by the intersection of a horizontal line at the level of the lower BLUE-point;
a vertical line at the posterior axillary line (Figs 84.17A and B).
Cardiac Arrest Ultrasound Exam

Protocol for Cardiac Arrest
Cardiac arrest ultrasound exam (CAUSE). This protocol helps in identifying the
cause of pulseless electrical activity or asystole and guides the management
(Flow chart 84.2).
Flow chart 84.1 Algorithm showing the bedside lung ultrasound

in emergency protocol for lung ultrasound
A B
Figs 84.17A and B BLUE and PLAPS points
Fluid Administration Limited by Lung Sonography Protocol

Fluid administration limited by lung sonography (FALLS). This protocol is mainly
used for hemodynamic assessment of circulatory failure using lung ultrasound.
This protocol identifies causes based on lung ultrasound for circulatory failure.
Secure European System for Applications in a Multi-vendor Environment

(SESAME) Protocol
This is done for identifying the causes of cardiac arrest.
PROCEDURAL USES OF ULTRASOUND

• Central vein catheterization: It is used for both central and peripheral vein
catheterization. NICE guidelines recommend the use of ultrasound for
catheterization of central veins.
Flow chart 84.2 Algorithm showing the cardiac arrest ultrasound

exam protocol for cardiac arrest
Abbreviations: RV, right ventricle; LV, left ventricle; RA, right atrium; PE, pulmonary embolus
Fig. 84.18 B-mode showing the bat sign and lung sliding sign
Fig. 84.19 Normal lung image by M-mode showing A-lines

which are reverberation artifacts
Fig. 84.20 Sea shore sign in M–mode (normal lung sliding with respiration)
Fig. 84.21 Bar code sign indicating pneumothorax
Fig. 84.22 Lung point indicating the transition between normal lung and pneumothorax
• Percutaneous tracheostomy: To determine the site of puncture and to identify

aberrant vessels (Fig. 84.23).
• Thoracentesis: Done with ultrasound guidance for all pleural procedures
(e.g. Needle thoracotomy or intercostal drainage for pneumothorax, draining
pleural effusion).
Fig. 84.23 Ultrasound image showing trachea for percutaneous tracheostomy
Fig. 84.24 Ultrasound image for intercostal nerve block for analgesia in chest injury
• Regional nerve blocks: It is the gold standard for performing peripheral nerve
blocks for patients with trauma for pain relief and to reduce the inflammatory
process (Fig. 84.24).
BIBLIOGRAPHY
1. Hendrickson RG, Dean AJ, Costantino TG. A novel use of ultrasound in pulseless
electrical activity: the diagnosis of an acute abdominal aortic aneurysm rupture.
J Emerg Med. 2001;21:141-4.
2. Hernandez C, et al. CAUSE: Cardiac arrest ultra-sound exam—A better approach to
managing patients in primary non-arrhythmogenic cardiac arrest. Resuscitation.
2008;76:198-206.
3. Joyner CR, Herman RJ, Reid JM. Reflected ultrasound in the detection and localisation
of pleural effusion. JAMA. 1967;200:399-402.
4. Kirkpatrick AW, Sirois M, Laupland KB, Liu D, Rowan K, Ball CG, et al. Hand-held
thoracic sonography for detecting post-traumatic pneumothoraces: the Extended
Focused Assessment with Sonography for Trauma (EFAST). J Trauma. 2004;57(2):
288-95.
5. Legome E, Pancu D. Future applications for emergency ultrasound. Emerg Med Clin
North Am. 2004;22:817-27.
6. Lichtenstein D, Menu Y. A bedside ultrasound sign ruling out pneumothorax in the
critically ill: lung sliding. Chest. 1995;108:1345-8.
7. Lichtenstein D, Mezière G, Biderman P, Gepner A, Barré O. The comet-tail artifact:
an ultrasound sign of alveolar-interstitial syndrome. Am J Respir Crit Care Med. 1997;
156:1640-6.
8. Lichtenstein D, Mezière G, Biderman P, Gepner A. The comet-tail artefact an
ultrasound sign ruling out pneumothorax. Intensive Care Med. 1999;25:383-8.
9. Lichtenstein D, Mezière G, Lagoueyte JF, Biderman P, Goldstein I, Gepner A. A-lines
and B-lines: lung ultrasound as a bedside tool for predicting pulmonary artery
occlusion pressure in the critically ill. Chest. 2009;136:1014-20.
10. Lichtenstein D, Mezière G. The BLUE-points: three standardized points used in the
BLUE-protocol for ultrasound assessment of the lung in acute respiratory failure. Crit
Ultrasound J. 2011;3:109-10.
11. Lichtenstein D. FALLS-protocol. In Whole Body Ultrasonography in the Critically Ill.
Edited by. Heidelberg, Berlin, New York: Springer-Verlag; 2010.pp.223-41.
12. Lichtenstein DA. Lung ultrasound in the critically ill. Lichtenstein Annals of Intensive
Care. 2014;4:1.
13. Lyon M, Blaivas M, Brannam L. Sonographic measurement of the inferior vena cava as
a marker of blood loss. Am J Emerg Med. 2005;23:45-50.
14. Mayo PH, Goltz HR, Tafreshi M, Doelken P. Safety of ultrasound-guided thoracentesis
in patients receiving mechanical ventilation. Chest. 2004;125(3):1059-62.
15. Miller RD. Miller’s Anesthesia. 7th edition. Elsevier Publications; 2009.
16. Miniati M, Monti S, Pratali L, et al. Value of transthoracic echocardiography in the
diagnosis of pulmonary embolism: results of a prospective study in unselected
patients. Am J Med. 2001;110(7):528-35.
17. Salen P, Melniker L, Chooljian C, et al. Does the presence or absence of sonographically
identified cardiac activity predict resuscitation outcomes of cardiac arrest patients?
Am J Emerg Med. 2005;23:459-62.
18. Slasky BS, Auerbach D, Skolnick ML. Value of portable real-time ultrasound in the
intensive care unit. Crit Care Med. 1983;11:160-4.
19. Vignon P, Chastagner C, Berkane V, Chardac E, Francois B, Normand S, Bonnivard M,
Clavel M, Pichon N, Preux PM, Maubon A, Gastinne H. Quantitative assessment of
pleural effusion in critically ill patients by means of ultrasonography. Crit Care Med.
2005;33:1757-63.
20. Volpicelli G, El Barbary M, Blaivas M, Lichtenstein D, Mathis G, Kirkpatrick AW,
Melniker L, Gargani L, Noble VE, Via G, Dean A, Tsung JW, Soldati G, Copetti R,
Bouhemad B, Reissig A, Agricola E, Rouby JJ, Arbelot C, Liteplo A, Sargsyan A, Silva
F, Hoppmann R, Breitkreutz R, Seibel A, Neri L, Storti E, Petrovic T. International
evidence-based recommendations for point-of-care lung ultrasound. Intensive Care
Med. 2012;38:577-91.
SECTION
20 ACID-BASE DISORDERS
Chapter 85 Basics of Acid-Base Balance

Chapter 86 Metabolic and Respiratory Acid-

Base Disorders
Chapter 87 Interpretation of Acid-Base

Disorder
CHAPTER
BASICS OF ACID-BASE BALANCE
Acid-base disturbances are one of the most common disorders seen in the
critically-ill patients. The normal blood pH is 7.35–7.45. Any value less than 7.35
is acidosis and more than 7.45 is alkalosis. Maintenance of blood pH at 7.40 is
necessary to stabilize intracellular pH at 7.20, which is very important chemical
condition for optimal cell physiology.
BASIC CONCEPTS AND TERMINOLOGIES

pH is defined in terms of [H+]. The hydrogen ion concentration [H+] in the extra-
cellular fluid is calculated as
[H+] nEq/L = 24 × (PCO2/HCO3)
Normal arterial PCO2 = 40
Therefore [H+] = 24 × 40/24
= 40 nEq/L.
Since the [H+] ion concentration is measured in nEq which is very minute
(nEq is one millionth of a mEq), the [H+] ion concentration is routinely expressed
in terms of pH which is defined as the negative logarithm to the base 10 of the [H+]
ion concentration in nEq/L. Thus, a normal [H+] of 40 nEq/L will correspond to
a pH of 7.40.
Normal arterial pH = – log (40 × 109)
= 7.40
An increase in [H+] concentration will decrease the pH and vice versa because
the pH is negative logarithm of the [H+]. [H+] ion concentration between 16 and
160 nEq/L (i.e. pH of 6.8–7.8) is compatible with life.
An acid as defined by Arrhenius is a compound that contains hydrogen and
reacts with water to form hydrogen ions. A strong acid is a substance that readily
and almost irreversibly gives up an H+ and increases [H+] concentration.
HA [H+] + [A–]
Ka[HA] = [H+] + [A–]
Where Ka is a dissociation constant.
Strong acids have high dissociation constant.
A weak acid is a substance which reversibly donates H+ and tends to have less
of an effect on [H+]. Biological compounds are either weak acids or weak bases.
618 Section 20 Acid-Base Disorders
HA [H+] + [A–]
Ka[HA] = [H+][A–]
[H+] = Ka[HA]/[A–]
The negative logarithm of this equation is called as the Henderson-
Hasselbalch equation.
pH = pka + log([A–]/[HA])
Where pka is the negative logarithm of the dissociation constant pKa. Thus
Henderson-Hasselbalch equation enables the calculation of pH.
Base is defined as a compound that produces hydroxide ions in water.
A strong base avidly binds H+ and decreases [H+]. A weak base reversibly binds H+.
Actual Bicarbonate
Actual bicarbonate is the bicarbonate concentration in the plasma measured in
mEq or mmoles/L. It is estimated from the carbon dioxide content of blood by
the Van Slyke apparatus or from a nomogram by the Astrup technique. It cannot
be estimated directly.
Standard Bicarbonate
Standard bicarbonate is the bicarbonate content in the plasma of blood which
has been equilibrated at a PCO2 of 40 mm Hg as also with oxygen so as to saturate
it with oxygen. It is the mobile, most active and rapidly reacting fraction of the
total buffer potential. It is a measure of nonrespiratory bicarbonate and its rate of
excretion and retention is governed by the kidneys. Normal standard bicarbonate
denotes metabolic equilibrium. A decrease in standard bicarbonate indicates
metabolic acidosis whereas an increase in its concentration indicates metabolic
alkalosis.
Base Excess
Base excess is defined as the amount of strong acid or base that must be added
for blood pH to return to 7.40 and PaCO2 to return to 40 mm Hg at full oxygen
saturation and 37°C.
It defines the presence in blood of excess or deficit of base, and represents the
metabolic component of an acid-base disturbance. It adjusts for non-carbonic
buffering in the blood and requires measurement of hemoglobin concentration
for its estimation. A positive base excess denotes metabolic alkalosis and a
negative value indicates metabolic acidosis.
Indications for Arterial Blood Gas Analysis

The arterial blood gas analysis is one of the best tools to assess the disturbances in
ventilatory and metabolic homeostasis. PaCO2 is the best index for assessment of
alveolar ventilation and PaO2 is the best index for assessment of the oxygenation.
The bicarbonate levels help in assessing the nature of the disturbance. Thus,
the arterial blood gas analysis helps in assessing the alveolar ventilation, the
Chapter 85 Basics of Acid-Base Balance 619
oxygenation, the oxygen carrying capacity of the blood and the degree of
compensation. Conditions such as shock, exacerbation of chronic obstructed
pulmonary disease, diabetic ketoacidosis mandate arterial blood gas analysis,
and hence the critical care guidelines mandate availability of 24 hours arterial
blood gas analysis.
Arterial blood gas analysis also helps in assessing a patient’s response
to therapeutic intervention like ventilator management, weaning, etc. Some
circulatory interventions can also be based on the arterial blood gas analysis.
Lastly, the arterial blood gas analysis also enjoys a role preoperatively in assessing
a patient for surgical evaluation, e.g. in the pulmonary resection.
Some arterial blood gas analyzers also provide information about the
hemoglobin and serum electrolytes and this can be of great value in deciding the
treatment in the critically ill patients especially when the laboratory data will take
time.
Regulation of the Acid-Base Balance

The metabolic homeostasis is maintained by excreting all the acids produced by
the body. These acids can be classified as respiratory (volatile) and metabolic
(fixed) acids. Carbon dioxide is called as respiratory volatile acid because it can be
excreted via the lungs. It is produced as an end product of complete oxidation of
carbohydrate and fatty acids. Daily basal carbon dioxide production is estimated
to be between 12000 and 13000 mmoles/day. It can be calculated as follows:
In a resting adult, oxygen consumption is 250 mL/minute and carbon dioxide
production is 200 mL/minute (respiratory quotient: 0.8)
Daily CO2 production = 0.2 × 60 × 24 liter/day.
If we divide it by 22.4 liters/mole, we get 12857 mmoles/day.
An increase in the metabolic activity will increase the carbon dioxide
production.
The fixed acids, also called as metabolic acids are produced due to incomplete
metabolism of carbohydrate, fats (ketones) and protein (sulphate, phosphate) and
are usually referred to by their anion (lactate, phosphate, sulphate, acetoacetate
or beta-hydroxy butyrate). They are called fixed because they are not excreted
by the lungs and they are referred to as anions inspite of being acids because the
dissociation of the acid must have produced one hydrogen ion for every anion
so the amount of anions present accurately reflects the number of hydrogen ions
that must have been produced in the original dissociation. Daily production
of hydrogen ions in an adult is approximately 70 to 100 mmoles/day, and it is
excreted by the kidney. This excludes lactate since majority of lactate produced is
metabolized and not excreted so there is no net lactate requiring excretion from
the body. Buffering mechanisms is given in Table 85.1.
Table 85.1 Buffering mechanisms
The body defends itself against the acid-base perturbations by three compensatory mechanisms:
1. Chemical buffering (Immediate)
2. Respiratory compensation (whenever possible)
3. Renal compensation (Slower but effective)
Chemical Buffering
A buffer is a solution of two or more chemicals that minimizes changes in pH in
response to the addition of an acid or base. Ideally, a buffer has a pka that is equal
to the pH and an ideal body buffer should have a pka between 6.8 and 7.2 .
Physiologically important buffers in human body are bicarbonate (H2CO3/
HCO3), hemoglobin (HbH/Hb–) other intracellular proteins, phosphates (H2PO4–/
HPO42–) and ammonia (NH+3/NH4+). By far bicarbonate is the most important of all
in the extracellular fluid compartment. Buffering by plasma bicarbonate is almost
immediate whereas that due to interstitial bicarbonate requires 15–20 minutes.
It is the most important extracellular fluid buffer for metabolic acids but not for
respiratory acid-base disturbances and changes in bicarbonate concentration do
not reflect the severity of respiratory acidosis.
H2O + CO2 → H2CO3 → HCO3– + H+
When we look at this reaction from the angle of the role of bicarbonate as a
buffer one can say that when H+ enters tissue fluids:
H+ + HCO3– → H2CO3 → CO2 + H2O
The CO2 is rapidly washed out by lungs and thus a rapid control of H+ ion
at the cost of depletion of [HCO3–] is produced. The Henderson–Hasselbalch
equation for the bicarbonate carbonic acid reaction illustrates the role played by
this reaction in regulating acid-base balance.
pH = pk + log HCO3/H2CO3
= 6.1 + log HCO3/H2CO3. pk for HCO3 is 6.1
= 6.1 + log HCO3/0.03 × PCO2
0.03 is the solubility of CO2 in plasma and PCO2 the partial pressure of CO2
in plasma. If instead of pH one considers the H+ ion concentration, then a more
simplified and practical derivation of the Henderson-Hasselbalch equation for
the bicarbonate buffer is as follows:
[H+] = 24 × PCO2/ [HCO3–]
Thus, substituting the normal values
[H+] = 24 × 40/24
= 40 nmol/liter
Below 7.40, [H+] increases 1.25 nEq/L for each 0.01 decrease in pH, above
7.40, [H+] decreases 0.8 nEq/L for each 0.01 increase in pH.
Hemoglobin
Hemoglobin is the most important noncarbonic buffer in extracellular fluid.
It is rich in histidine which is an effective buffer from pH 5.7 to 7.7 (pka 6.8). It is
capable of buffering both carbonic (CO2) and noncarbonic (volatile) acids. This
is in contrast to the bicarbonate buffer which is capable of buffering only the
metabolic acids.
Deoxygenated hemoglobin is a strong base. The CO2, which easily crosses
the erythrocyte membrane, combines with H2O in the erythrocyte under the
Chapter 85 Basics of Acid-Base Balance 621
influence of carbonic anhydrase to form H2CO3. This H2CO3 ionizes to H+ and

HCO3–. The hydrogen ions bind to the histidine residues on deoxyhemoglobin
(Haldane effect) and HCO3– is actively pumped from cells. To maintain the
electroneutrality, the chloride moves inward (Chloride shift). Thus, there would
be huge increase in the pH of venous blood, if hemoglobin did not bind H+ ions
produced by metabolism. Hemoglobin can also directly buffer CO2 by forming
carbaminohemoglobin.
Respiratory Compensation
The respiratory compensation means the alterations that occur in the pH
secondary to the changes in ventilation. These changes in alveolar ventilation are
mediated by chemoreceptors within the brainstem which sense the changes in
the pH of the cerebrospinal fluid. Every 1 mm Hg increase in PaCO2 increases
the minute ventilation by 1–4 L/minute. A decrease in plasma bicarbonate
concentration by 1 mEq/L triggers an increase in the alveolar ventilation and
decrease in PaCO2 by 1–1.5 mm Hg below 40 mm Hg. On the contrary, an increase
in arterial blood pH depresses the respiratory center. The resulting decrease in
alveolar ventilation tends to elevate PaCO2 and restore arterial pH towards
normal. But the response is less predictable in this case and if hypoxemia ensues
due to the progressive hypoventilation then eventually the oxygen sensitive
chemoreceptors are activated which stimulate ventilation and thus limit the
pulmonary compensatory response.
For every 1 mEq/L increase in bicarbonate concentration the PaCO2 is found
to be increased by 0.25–1 mm Hg.
Renal Compensation
Renal compensation begins to appear slowly in 6–12 hours and is fully developed
over 2–3 days. The kidneys regulate plasma bicarbonate concentration through
three main processes:
1. Reabsorption of HCO3– when there is accumulation of H+ ions in the Blood:
80–90% of HCO3– is reabsorbed in the proximal tubule. The remainder is
reabsorbed by the distal nephron which secretes H+ to defend systemic pH.
This reabsorption of bicarbonate greatly depends on the PaCO2.
In respiratory acidosis, the carbon dioxide (CO2) present in the renal tubular
cells combines with water (H2O) in the presence of carbonic anhydrase to
form carbonic acid (H2CO3). This H2CO3 dissociates rapidly into H+ and HCO3.
The HCO3– ion enters the peritubular capillary and thus into the circulation.
The H+ ion is secreted into the renal tubule where it reacts with the filtered
HCO3– to form H2CO3. This H2CO3 again dissociates into H2O and CO2 in the
presence of luminal carbonic anhydrase. The CO2 thus formed reenters the
renal tubular cell to replace the CO2 which was consumed originally.
↑ PaCO2→↑ HCO3– reabsorption →↑ HCO3– levels.
↓ PaCO2 →↓ HCO3– reabsorption →↓ plasma HCO3– levels.
In metabolic acidosis, chloride is preferentially excreted by the kidney and
it reabsorbs HCO3– when there is accumulation of H+ ions in the blood along
with excretion of titratable acid and NH4 to counter for the increase of H+ ions
in the blood.
2. Excretion of titratable acid and increased formation of ammonia:
Once the filtered bicarbonate is reabsorbed completely, the H+ ion coming
into the tubular lumen is buffered by HPO4– ion which combines with it and
forms H2PO4– which is excreted in the urine. Once the phosphate buffer is
also consumed, the ammonia produced during acidosis acts as the next
important buffer. The ammonia which is formed in the mitochondria of
proximal tubular cells by deamination of glutamine passively crosses the
luminal membrane of the cell and enters the tubular fluid. Here it buffers the
H+ by combining with it and forming NH4+ which is then excreted in the urine.
3. Increased bicarbonate excretion in the urine when there is primary increase in
plasma bicarbonate
BIBLIOGRAPHY
1. Androgue HJ, Madias N. Management of life-threatening acid-base disorders. Part 2.
N Engl J Med. 1998;338:107-11.
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Hosp Practice; 1974. pp. 157.
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6. Kraut JA, Madias NE. Approach to patients with acid-base disorders. Respir Care.
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11. Udwadia FE. Principles of Critical Care, 2nd edn. Oxford Publications.
CHAPTER
METABOLIC AND RESPIRATORY ACID-BASE

DISORDERS
METABOLIC ACIDOSIS (TABLE 86.1)

When the acidosis is due to a decrease in bicarbonate, it is called as metabolic
acidosis. Metabolic acidosis is divided into two groups:
1. Normal anion gap metabolic acidosis
2. High anion gap metabolic acidosis.
Normal Anion Gap Acidosis

The anion gap is nothing but the difference between the measured cations (Na+)
and the measured anions (Cl– and HCO3–)
Table 86.1 Causes of metabolic acidosis
High anion gap

Overproduction of acid Diabetic ketoacidosis
Lactic acidosis type A (Hypoxia, Shock) or
Type B (Biguanides)
Starvation
Exogenous acid Salicylates

Methanol
Ethylene glycol
Reduced excretion Renal failure

Normal anion gap
Bicarbonate loss Extrarenal
Diarrhea
Biliary/Pancreatic fistula
Ileostomy
Ureterosigmoidostomy
Renal
Renal tubular acidosis
Carbonic anhydrase inhibitors
Addition of acid HCL, NH4CL,

(with chloride) Arginine or lysine hydrochloride
Anion gap = Na+ – (Cl + HCO3–)

Therefore Na+ + unmeasured cations = (Cl + HCO3–) + unmeasured anions
Therefore, Na+ – (Cl + HCO3–) = unmeasured anions – unmeasured cations
The basis of the anion gap is that the concentration of positively charged
cations should equal the concentration of negatively charged anions in order to
maintain the electrochemical balance.
The unmeasured anions are proteins, organic acids, phosphates and
sulphates. The unmeasured cations are potassium (K+), calcium (Ca2+) and
magnesium (Mg++). Thus, the anion gap is an estimate of the relative increase
in the number of unmeasured anions and helps in determining whether the
metabolic acidosis is due to accumulation of nonvolatile acids (e.g. lactic acid) or
a net loss of bicarbonate (e.g. diarrhea).
The normal value of the anion gap is 7 ± 4 mEq/L (range is 3 to 11 mEq/L)
in accordance with the newer automated systems which measure the serum
electrolytes more accurately.
Metabolic acidosis with a normal anion gap is also called as hyperchloremic
acidosis. The loss of bicarbonate in the metabolic acidosis which can be either
via stools or intestinal fistulas results in replacement of chloride for the lost
bicarbonate to preserve electroneutrality. This replacement of bicarbonate by
chloride causes a hyperchloremic acidosis.
The interpretation of the anion gap is altered in presence of hypoalbuminemia.
Serum albumin constitutes about half of the unmeasured anion pool. Hence, a
decrease in albumin by 50% in absence of any derangement in serum electrolytes
and bicarbonate will decrease the anion gap by 5-6 mEq/L. Thus, the anion gap
has to be adjusted in hypoalbuminemic patients. This can be calculated as:
Adjusted anion gap = Observed anion gap + 2.5 × [4.5 – measured albumin (g/dL)]
4.5 is the normal albumin concentration in g/dL.
High Anion Gap Acidosis

High anion gap is caused due to the addition of a fixed acid into the extracellular
space. The acid dissociates to produce H+ ions and anions. The hydrogen
ions are neutralized by combining with HCO3– ions to form carbonic acid. The
ensuing increase in the unmeasured anions increases the anion gap. Thus, as the
bicarbonate decreases the anion gap increases as can be seen from the equation:
Anion gap = Na – (Cl + HCO3–)
The causes of high anion gap acidosis are given in Table 86.1. Some conditions
like diabetic ketoacidosis are associated with a high anion gap as well as normal
anion gap metabolic acidosis. The identification of the normal anion gap acidosis
can be made by comparing the change in anion gap to the change in the plasma
bicarbonate concentration. This is called as the delta gap.
Delta gap = Change in anion gap – change in bicarbonate
If the delta gap is significantly positive (> +6), a metabolic alkalosis is
usually present because the rise in anion gap is more than the fall in bicarbonate
concentration. On the contrary, a significantly negative delta gap value (<–6)
Chapter 86 Metabolic and Respiratory Acid-Base Disorders 625
suggests hyperchloremic acidosis because the rise in anion gap is less than the
fall in bicarbonate.
Measured anion gap – Normal anion gap
Delta ratio =
Normal [HCO3–] – Measured [HCO3–]
This ratio is also called as the gap-gap. In the presence of a high anion gap
metabolic acidosis, a gap ratio of <1 indicates that a normal anion gap metabolic
acidosis coexists. Whereas a gap ratio of >1 indicates that a metabolic alkalosis
coexists.
Compensation for Metabolic Acidosis

The primary change in metabolic acidosis is a decrease in bicarbonate and
increase in H+. Therefore, the pH decreases which stimulates the respiratory
center in the brainstem causing a fall in PaCO2 which is given by the formula:
Expected PaCO2 = [1.5 × HCO3–] + 8
Range of ± 2
Clinical Features of Metabolic Acidosis

Acidosis is associated with alterations in transcellular ion pumps and increased
ionized calcium. These changes are particularly detrimental to the cardiovascular
system and result in vasodilation and diminished muscular performance
(particularly myocardial), and arrhythmias as the pH decreases to <7.2. The
oxyhemoglobin dissociation curve shifts rightward to increase the oxygen
delivery to the tissues. Rapid-onset metabolic acidosis may be associated with
profound hypotension, cardiac arrhythmias, and death.
The breathing is a typical Kussmaul’s breathing in which there is an increase
in tidal volume instead of respiratory rate. The manifestation of acidosis in
various organs is given Table 86.2.
Table 86.2 Manifestations of metabolic acidosis on various systems
Central nervous system

• Obtundation
• Coma
Respiratory system
• Respiratory muscle fatigue
• Hyperventilation
• Breathlessness
Cardiovascular system
• ↓ CO, blood pressure, response to catecholamines
• ↑ potential for ventricular fibrillation
• Impaired myocardial contractility
Metabolism
• Hyperkalemia
• Insulin resistance
Management of Metabolic Acidosis

The management of metabolic acidosis mainly consists of treatment of the cause
and supporting the circulation and breathing, if it is severely compromised.
Whenever a respiratory acidosis coexists, then it is important to first correct the
respiratory acidosis.
• In diabetic ketoacidosis, the management of the acidosis is focused on
correction of the hyperglycemia and volume depletion by giving insulin and
IV fluids. Infection, if any present should be treated by starting antibiotics.
The detailed management of DKA is discussed in detail under chapter 57.
• Lactic acidosis: The normal lactate levels are ≤2 mEq/L. While treating
lactic acidosis one needs to keep in mind the causes of increased lactic acid
e.g. shock, hypoxia especially when associated with a low cardiac output,
severe uncorrected anemia (Hb <5 g/dL) which is not compensated for
by a hyperdynamic circulation, marked liver cell dysfunction, thiamine
deficiency, D lactic acid acidosis (which is seen following small bowel
resection or jejunoileostomy) and usage of drugs like epinephrine or sodium
nitroprusside. The major crux of the treatment should be to improve tissue
perfusion first and then treat the cause.
The use of sodium bicarbonate is restricted nowadays to correct a pH of
7.25 or less and when bicarbonate is <10 mmol/L. The formula for calculation
of sodium bicarbonate dose for severe lactic acidosis is:
NaHCO3 = 0.3 × body weight × base deficit
One half of the calculated amount is given as an intravenous bolus and
the remaining deficit is corrected over next 4–6 hours.
The problem with sodium bicarbonate treatment is the production
of undesirable effects which include hyperosmolarity, fluid overload,
hypokalemia, hypocalcemia and increased serum lactate levels. Hence,
it should be avoided in lactic acidosis. The standard sodium bicarbonate
solutions contain a PCO2 of 200 mm Hg which can produce increased CO2
load in patients with respiratory acidosis. Carbicarb is an alternative buffer
solution which contains sodium bicarbonate and disodium carbonate in
equal proportion. It has a PCO2 of 3 mm Hg which is much lower than the
standard bicarbonate solution.
• Alcoholic ketoacidosis: The treatment consists of infusion of dextrose
containing solutions. The glucose helps retard hepatic ketone production,
while the infused volume promotes the renal clearance of ketones.
• Ethylene glycol poisoning: Inhibition of alcoholic dehydrogenase by using
fomepizole is recommended. The dose of Fomepizole is 15 mg/kg IV as an
initial dose, then 10 mg/kg every 12 hours for 48 hours, then 15 mg/kg every
12 hours until the plasma ethylene glycol level is 25 mEq/L or lower.
Metabolic Alkalosis
Metabolic alkalosis is defined as a primary increase in plasma [HCO3–]. It is
classified as chloride sensitive and chloride resistant metabolic alkalosis. Causes
of metabolic alkalosis are given in Table 86.3.
Table 86.3 Causes of metabolic alkalosis
Chloride-responsive (urine chloride <20 mmol/L)

Loss of acid
• Vomiting
• Nasogastric suction
Gastrocolic fistula
Chloride depletion
• Diarrhea
• Diuretics
Excessive alkali
• NaHCO3 administration
• Antacid abuse
Chloride-resistant (urine chloride >20 mmol /L )
• Primary or secondary hyperaldosteronism
• Cushing’s syndrome
• Severe hypokalemia
• Carbenoxolone
Chloride Sensitive Metabolic Alkalosis

The basic cause for this type of alkalosis is depletion of extracellular volume and
chloride. The common causes are vomiting, nasogastric suction and diuretic
use. In vomiting or nasogastric suction about 50–100 mEq/L of H+ ions present in
the gastric juice are lost along with water, Cl–, Na+ and K+. Loop diuretics inhibit
Na+K+2Cl– symport whereas thiazides inhibit Na+Cl– symport. Thus, Cl– and K+
are lost via the urine along with Na+ and water. The Cl– that is not reabsorbed
is replaced by bicarbonate. This enhanced bicarbonate reabsorption leads to or
maintains the alkalosis. The increased loss of K+ in the urine leads to an increase
in H+ ion secretion into the distal tubules in an attempt to reabsorb K+ at the cost
of H+. Mg2+ is also lost in the urine during diuresis and this further enhances K+
loss. The ensuing volume depletion stimulates aldosterone release which in turn
stimulates H+ and K+ secretion in order to retain Na+ and further exaggerates the
alkalosis. The urinary Cl– concentration in a chloride sensitive metabolic alkalosis
is low (<15 mEq/L).
Chloride-resistant Metabolic Alkalosis

The genesis of chloride-resistant metabolic alkalosis is due to an increased
mineralocorticoid activity or severe potassium depletion. The Na+ H+ K+ transport
system in the distal tubules is responsive to aldosterone, which promotes the
reabsorption of Na+ and the secretion of H+ and K+. This type of metabolic alkalosis
is usually associated with volume expansion rather than volume depletion.
Urinary chloride concentration is >25 mEq/L.
Compensation for Metabolic Alkalosis

The compensatory response for metabolic alkalosis is an increase in the PaCO2.
But this is limited by the hypoxemia which ensues due to hypoventilation (in
order to raise the PaCO2). The expected increase in PaCO2 is given by the formula:
Table 86.4 Manifestations of metabolic alkalosis on various systems
Central nervous system

• Lethargy, delirium
• Seizures
• Tetany
Respiratory system
• Arterial hypoxemia
• Hypoventilation
• ↑PaCO2
Cardiovascular system
• ↓Coronary perfusion
• Arterial vasoconstriction
• Potential for cardiac arrhythmias
Metabolism
↓K+, Ca+, PO4, Mg2+
PaCO2 = (0.7 × HCO3–) + 20

Range ± 2.
Clinical Features of Metabolic Alkalosis

Metabolic alkalosis is silent most of the times. Severe alkalosis (pH >7.6) can
result in seizures, mental obtundation, cardiac dysfunction, arrhythmias and
hypoventilation. The oxygen dissociation curve is shifted to the left causing
a decrease in oxygen delivery to the tissues. The manifestations of metabolic
alkalosis in various organs are given in Table 86.4.
Treatment of Metabolic Alkalosis

Most common type of metabolic alkalosis in the critically ill patients in the ICU
is the chloride sensitive one and hence infusion of normal saline to correct the
volume and chloride deficit is the mainstay of treatment.
The volume of isotonic saline (0.9%) needed can be determined by estimating
the chloride (Cl) deficit, as shown here:
Chloride deficit (mEq) = 0.2 × weight (kg) × (normal Cl – Actual Cl)

The factor 0.2 represents the extracellular volume as a fraction of body weight.
Volume of saline to be infused = Chloride deficit/154
154 is the mEq of chloride present in 1L of normal saline. The hypokalemia
should be corrected by infusion of potassium chloride (20–40 mEq in dextrose).
Hypokalemia, if left uncorrected can perpetuate the alkalosis. Magnesium
deficiency, if present should also be corrected.
The aim of treatment in the chloride resistant metabolic alkalosis is to treat
the underlying cause of mineralocorticoid excess and correct the K+ deficit. It
responds to drugs such as acetazolamide which blocks HCO3– reabsorption in the
kidneys by inhibiting the carbonic anhydrase enzyme. The dose is 5–10 mg/kg IV.
Use of Hydrochloric Acid in Metabolic Alkalosis

This is reserved for patients with severe alkalemia (pH >7.5) when other treatment
fails.
H+ deficit (mEq) = 0.5 × weight (kg) × (actual HCO3 – desired HCO3)

Volume (L) of 0.1NHCl = H+ deficit/100
Volume (L) of 0.25 NHCl = H+ deficit/250
Infusion rate = 0.2 mEq/kg/ hour.
0.1 NH4Cl which contains 100 mEq of H+ per liter is the best option and is
given through a central line. Ammonium chloride and arginine chloride can also
be given but are less safe. Extravasation can cause tissue necrosis.
Respiratory Acidosis
Respiratory acidosis is defined as an acidosis associated with and caused by
an elevation of the PaCO2 (Table 86.5). The causes, types and clinical features
and treatment of respiratory acidosis are discussed in detail in the chapter on
respiratory failure.
The compensatory response to acute (6–12 hour) elevations in PaCO2 is
limited and is primarily provided by hemoglobin and the exchange of extracellular
H+ for Na+ and K+ from bone and the intracellular fluid compartment. As such the
bicarbonate response is very limited in the acute respiratory acidosis being just
an increase of 1 mEq/L for 10 mm Hg increase in PaCO2 above 40 mm Hg. If a
respiratory alteration persists, however, renal mechanisms increase or decrease
serum HCO3– in a direction that pushes the H+ back toward normal.
After the renal compensation sets in, the compensatory increase in
bicarbonate for the chronic respiratory acidosis is 4 mEq/L mm Hg per 10 mm Hg
increase in PaCO2 above 40 mm Hg.
Thus, after renal compensation occurs, the ΔH+/ΔPCO2 ratio is also
altered. The ΔH+/ΔPCO2 is calculated as the change in H+ from baseline (i.e. 40
nanoequivalents/liter) divided by the change in PaCO2 from baseline (i.e. 40
mm Hg). This alteration represents the chronic state. A ratio of 0.8 implies an
acute respiratory acidosis. A ratio of 0.3 implies a chronic (and compensated)
respiratory acidosis. The ΔH+/ΔPCO2 ratio between 0.3 and 0.8 corresponds to
an acute-on-chronic respiratory acidosis (as often occurs with an exacerbation of
chronic obstructive pulmonary disease).
Table 86.5 Causes of respiratory acidosis
• Drug-induced respiratory depression

• Status asthmaticus
• Upper airway obstruction
• Restriction of ventilation (rib fractures/flail chest)
• Disorders of neuromuscular function—GBS, myasthenia gravis
• Permissive hypercapnia
• Malignant hyperthermia
Table 86.6 Causes of respiratory alkalosis
• Iatrogenic (mechanical hyperventilation)

• Arterial hypoxemia causing hyperventilation
• Central nervous system injury
• Liver disease
• Pregnancy
• Aspirin overdose
Management
Respiratory acidosis is treated by correcting the condition responsible for
hypoventilation and mechanical ventilation may be needed when there is marked
increase in PaCO2. Rapid reduction of chronically increased PaCO2 levels by
mechanical ventilation reduces the CO2 stores more than the decrease in HCO3
concentration thus producing metabolic alkalosis. Hence, it is better to reduce PaCO2
slowly to permit sufficient time for renal tubular elimination of bicarbonate.
Respiratory Alkalosis
Respiratory alkalosis is defined as an alkalosis caused by a primary decrease in
PaCO2 (Table 86.6). The main cause for respiratory alkalosis is hyperventilation
which results in the washout of carbon dioxide. The causes are described in the
chapter on respiratory failure.
The compensation for acute decrease in PaCO2 is a decrease in Plasma
[HCO3–] by 2 mEq/L for each 10 mm Hg acute decrease in PaCO2 below 40 mm Hg.
The distinction between acute and chronic respiratory alkalosis is not always
made, because the compensatory response to chronic respiratory alkalosis is
quite variable: plasma [HCO3–] generally decreases by 4 mEq/L for each 10 mm Hg
decrease in PaCO2 below 40 mm Hg.
BIBLIOGRAPHY
N Engl J Med. 1998;338:107-11.
2. Bear RA, Gribik M. Assessing acid-base imbalances through laboratory parameters.
Hosp Practice; 1974. p. 157.
1998;26:1807-10.
4. Ganong WF. Review of Medical Physiology, 21st edn. 2003. McGraw-Hill publications.
5. Butterworth IV JF, Mackey DC, Wasnick JD. Morgan & Mikhail’s Clinical Anesthesiology,
5th edn. McGraw-Hill publications; 2007.
6. Irwin RS, Rippe JM Irwin and Rippe’s. Intensive Care Medicine, 6th edn. Lippincott
Williams & Wilkins; 2008.
7. Kraut JA, Madias NE. Approach to patients with acid–base disorders. Respir Care.
2001;46:392. [PMID: 11262558].
Medicine (Baltimore). 1980;59(3):161-87.
9. Paul ML. The ICU Book, 3rd edn. Lippincott Williams & Wilkins; 2007.
10. Ronald D Miller. Miller’s Anesthesia, 7th ed. Elsevier Publications; 2009.
11. Udwadia FE. Principles of critical care, 2nd ed. Oxford Publications.
CHAPTER
INTERPRETATION OF ACID-BASE DISORDER
The acid-base disorders can be classified as acidosis and alkalosis. Acidosis is

an abnormal state leading to an increase in the acid in the body. Acidemia is a
condition where the pH of the arterial blood falls below 7.35. The alkalosis is an
abnormal state leading to a fall in acid or an increase in the alkali in the body.
Alkalemia is a condition where the pH of the arterial blood is above 7.45.
Both acidosis and alkalosis can further be divided into respiratory and
metabolic depending on the etiology. As we have already seen:
[H+] (nEq/L) = 24 × PCO2/HCO3–
Thus, to keep the pH within the normal limits, the PCO2/HCO3– ratio has
to be kept constant. Therefore, if there is an increase in PCO2 as in respiratory
acidosis, then it should be accompanied by a compensatory increase in HCO3–
so that the pH remains constant. Similarly if there is a change in HCO3– as in the
metabolic disorders, then the PCO2 also should change in the same direction as
the bicarbonate. The initial change in the PCO2 or HCO3– is termed as the primary
acid-base disorder and the change that follows the primary disorder in an effort
to neutralize the pH is called as the compensatory change.
One needs to keep in mind that the compensatory changes do not correct
the acid-base disturbances (Table 87.1). They only limit the change in the pH
caused by the primary disorder. If the compensatory change is more or less than
expected, then by definition a mixed acid-base disorder exists.
STEPWISE APPROACH FOR INTERPRETATION OF ABG

• Step 1: Look at the pH (is it acidemia or alkalemia?)
• Step 2: Look at the PaCO2 is the change in PaCO2 consistent with a respiratory
disorder?
• Step 3: If step 2 shows that the change in PaCO2 is not consistent with a
respiratory disorder, then look at the HCO3 and see whether it indicates a
metabolic disorder
• Step 4: Make a tentative primary diagnosis
• Step 5: Refer to the Table 87.2 and compare the change in PaCO2 and HCO3
and judge whether there is a compensatory response, and whether it is
adequate (partial or complete). If the compensatory response is more or less
than expected, then it indicates that a mixed acid-base disorder exists.
Table 87.1 Acid-Base disorders and its compensation
Primary disorder pH HCO3– PaCO2 Compensation

Metabolic acidosis ↓ ↓↓ Hyperventilation
↓PaCO2
Metabolic alkalosis ↑ ↑↑ Hypoventilation
↑ PaCO2
Respiratory acidosis ↓ ↑↑ Renal retention
of HCO3
Respiratory alkalosis ↑ ↓↓ Renal elimination of
HCO3
Table 87.2 Compensatory response in acid-base imbalances
Disorder Response Expected compensation

Respiratory acidosis
Acute ↑HCO3 1 mEq/L for every 10 mm Hg increase in
PaCO2 above 40 mm Hg
4 mEq/L for every 10 mm Hg increase in

Chronic ↑HCO3 PaCO2 above 40 mm Hg
Respiratory alkalosis
Acute ↓HCO3 2 mEq/L for every 10 mm Hg decrease in
PaCO2 below 40 mm Hg
4 mEq/L for every 10 mm Hg decrease in

Chronic ↓HCO3 PaCO2 below 40 mm Hg
Metabolic acidosis ↓PaCO2 (1.5 × HCO3) + 8
Metabolic alkalosis ↑PaCO2 (0.7× HCO3) + 20
• Step 6: In case of metabolic acidosis, calculate the anion gap to classify

whether it is high anion gap or normal anion gap acidosis.
• Step 7: In case of metabolic alkalosis, measure the urinary chloride
concentration to see whether it is chloride sensitive or resistant type.
ARTERIAL BLOOD GAS EXERCISES

1. A 40-year-old moderately dehydrated man was admitted with 3 days
history of acute severe diarrhea.
Electrolyte results (in mmol/L): Na+ 136, K+ 3.0, Cl– 110, HCO3– 15, Anion gap
11.
pH 7.31
pCO2 32 mm Hg
pO2 90 mm Hg
HCO3 15 mmol/L
Chapter 87 Interpretation of Acid-Base Disorder 633
Interpretation
• Step 1: pH is 7.31, so it is acidemia.
• Step 2: The PaCO2 is 32, i.e. it has decreased (normal-40 mm Hg). This is not
consistent with the change in pH because if the pH is acidotic, then the PCO2
should increase to call it as a respiratory acidosis.
• Step 3: The HCO3 is 15, i.e. it has decreased (normal-24 mm Hg). This is
consistent with the change in pH as it suggests a metabolic component to
the acidosis.
• Step 4: Thus, the primary diagnosis is metabolic acidosis.
• Step 5: As per the Table 87.1 in case of metabolic acidosis, the PaCO2 should
also decrease as a compensatory response to the decrease in HCO3 and it is
given by the formula:
Expected PaCO2 = (1.5 × HCO3) + 8
= (1.5 × 15) + 8
= 30.5
The actual value of PaCO2 given is 32 which is close to (±2). Hence, the
compensation is adequate.
• Step 6: Since this is metabolic acidosis, we need to calculate the anion gap to
find out whether it is high or normal anion gap acidosis.
Anion gap = Na+ – (Cl– + HCO3)
= 136 – (110 + 15)
= 11.
ABG Diagnosis = Normal Anion Gap Metabolic Acidosis

2. A 50-year-old male patient with chronic renal failure was on treatment
with tablet furosemide for the past 3 years. Now the patient presents to
the emergency room with profound weakness and areflexia. His oral
intake had been poor for a few days.
Her Sr electrolytes Na+ 145, K+ 3.5, Cl– 86, bicarbonate 45
pH = 7.58
pCO2 = 49 mm Hg
pO2 = 85 mm Hg
HCO3– 44 mmol/L
Urinary chloride = 10 mEq/L
Interpretation
• Step 1: pH is 7.58 so it is alkalemia.
• Step 2: PaCO2 is 49, i.e. it has increased. This is not consistent with the change
in pH because the PaCO2 should be decreased to call it alkalosis due to a
respiratory cause.
• Step 3: The HCO3 is 44, i.e. it has increased. This is consistent with the change
in pH and suggests a metabolic cause for the alkalemia.
• Step 4: Thus, the primary diagnosis is metabolic alkalosis.
• Step 5: In metabolic alkalosis, the compensatory change should be an
increase in HCO3 and this is given by the formula:
Expected PaCO2 = (0.7 × HCO3) + 20
= (0.7 × 44) + 20
= 50.8
The actual value of PaCO2 is 49 which is close to the expected PaCO2 and
hence the compensation is adequate.
• Step 6: Urinary chloride is 10 mEq/L, so this is chloride sensitive metabolic
alkalosis.
ABG Diagnosis = Chloride Sensitive Metabolic Alkalosis

3. A healthy 30-year-old woman undergoes elective lap appendicectomy
under general anesthesia. She has no significant past medical history.
Preoperative urea and electrolytes were all within the reference range.
pH = 7.20
pCO2 = 70 mm Hg
pO2 = 75 mm Hg
HCO3 = 27 mmol/L.
Interpretation
• Step 1: pH is 7.20 so it is acidemia.
• Step 2: The PaCO2 is 70, i.e. it has increased. This is consistent with the change
in pH because if the pH is acidotic, then the PCO2 should increase to call it as
a respiratory acidosis.
• Step 3: The HCO3 is 27, i.e. it has increased.
• Step 4: Thus, the primary diagnosis is acute respiratory acidosis.
• Step 5: As per Table 87.1 in case of acute respiratory acidosis, the HCO3 should
also increase as a compensatory response to the increase in PaCO2 and it is
given by the formula:
Expected HCO3 = 1 mEq/L for every 10 mm Hg increase in PaCO2 above
40 mm Hg.
The expected HCO3 for 70 mm Hg of PaCO2 will be 24 + 3 = 27 mm Hg.
Hence, it is adequate (actual HCO3 = 27 mEq/L).
ABG Diagnosis = Acute Respiratory Acidosis with Fully Compensated

Metabolic Alkalosis
4. A 10-year-old malnourished boy presents with a one-day history of
productive cough, fever and increasing dyspnea. In the ER, the chest
X-ray shows hilar opacities. His oxygen saturation is 85% on room air.
An arterial blood gas is obtained and it reveals a
• pH–7.55
• PCO2–30
• PO2–60
• HCO3–22
Chapter 87 Interpretation of Acid-Base Disorder 635
Interpretation
• Step 1: pH is 7.55 so it is alkalemia.
• Step 2: The PaCO2 is 30, i.e. it has decreased. This is consistent with the
change in pH because if the pH is alkalotic, then the PaCO2 should decrease
to call it as a respiratory alkalosis.
• Step 3: The HCO3 is 22, i.e. it has decreased.
• Step 4: Thus the primary diagnosis is acute respiratory alkalosis.
• Step 5: As per the Table 87.2 in case of acute respiratory alkalosis the HCO3
should also decrease as a compensatory response to the decrease in PaCO2
and it is given by the formula:
Expected HCO3 = 2 mEq/L for every 10 mm Hg decrease in PaCO2 below 40
mm Hg.
The expected HCO3 for 30 mm Hg of PaCO2 will be 24 – 2 = 22 mm Hg. Hence,
it is adequate (actual HCO3 – 22 mEq/L).
ABG Diagnosis = Acute Respiratory Alkalosis with Fully

Compensated Metabolic Acidosis
5. A 50-year-old man with COPD presented with dyspnea, fever. He was on
a thiazide diuretic for 10 months following a previous admission with
congestive cardiac failure.
Arterial blood results:
pH 7.4
pCO2 50 mm Hg
pO2 75 mm Hg
HCO3 32 mmol/L
K+ 2.5 mmol/L
Interpretation
• Step 1: The pH is 7.4 so it is normal but looking at the clinical scenario, one
should keep a suspicion of an acid-base disturbance in this patient.
• Step 2: The PaCO2 is 50, i.e. it has increased suggesting respiratory acidosis.
This is expected since the patient is having COPD.
• Step 3: The HCO3 is 32, i.e. it has increased suggesting metabolic alkalosis.
• Step 4: Thus in any acid-base disturbance, the pH can approach the normal
value but not the median value of 7.4, it that occurs, it indicates the presence
of a 2 primary acid-base disorders. Hence, the diagnosis is respiratory
acidosis with acute exacerbation along with metabolic alkalosis.
• Step 5: Respiratory acidosis with a pCO2 of 50 mm Hg would predict a [HCO3]
of about 28 mmol/L at maximal compensation. The actual value is much
higher than this so a metabolic alkalosis must also be present indicating a
mixed acid-base disorder.
ABG Diagnosis = Mixed Respiratory Acidosis and Metabolic Alkalosis

BIBLIOGRAPHY
N Engl J Med. 1998;338:107-11.
2. Bear, RA, Gribik, M. Assessing acid-base imbalances through laboratory parameters.
Hospital Practice. 1974;9:157
1998;26:1807-10.
4. Ganong WF. Review of Medical Physiology. 21st edn. McGraw-Hill publications; 2003.
5. Irwin RS, Rippe JM. Irwin and Rippe’s Intensive Care Medicine, 6th Edn Lippincott
Williams & Wilkins, 2008.
6. Kraut JA, Madias NE. Approach to patients with acid–base disorders. Respir Care.
2001;46:392. [PMID: 11262558].
7. Miller RD. Miller’s Anesthesia, 7th edn. Elsevier Publications; 2009.
8. Morgan GE, Jr, MS Mikhail, Murray MJ. Clinical Anesthesiology, 5th edn. McGraw-Hill
publications; 2007.
Medicine. 1980;59:161-87.
10. Paul ML. The ICU Book, 3rd edn. Lippincott Williams & Wilkins; 2007.
11. Udwadia FE. Principles of Critical Care, 2nd edn. Oxford Publications.
SECTION
21 NUTRITIONAL SUPPORT
Chapter 88 Nutrition and Metabolism in

Critically Ill Patients
Chapter 89 Enteral and Parenteral Nutrition

CHAPTER
NUTRITION AND METABOLISM IN

CRITICALLY ILL PATIENTS
Good nutrition is an important prerequisite for a healthy body and more so

for a body that is fighting a critical illness. The principles of management of
nutrition in the critically ill patients have undergone a sea change over a period
of time as mankind has explored the various biochemical and pathophysiological
changes that take place in the human body in an illness. In order to manage the
nutrition of patients in the intensive care unit, one needs to first understand these
biochemical and pathophysiological changes that occur during a disease.
PATHOPHYSIOLOGY OF NUTRITION IN ILLNESS

Human body, when normal, has a perfect balance of anabolism and catabolism
depending on the food intake. Stress in any form, i.e. surgery, trauma or infection
disrupts this balance and results in an increase in the catabolic response also
called as “autocannibalism”. The extent and duration of this catabolic response is
largely determined by the magnitude of the injury. This stress response basically
comprises the release of several catecholamines and catabolic hormones like
glucagon, growth hormone and cortisol. These hormones act synergistically
and promote increased glucose production via the gluconeogenesis. The
main substrates for gluconeogenesis are glycerol (from lipolysis), alanine
(from proteolysis) and lactate (from wound). These changes are associated
with a decrease in insulin sensitivity, which in turn, is the result of decreased
phosphorylation of the insulin receptor and second messenger. This post-
receptor defect hinders cellular glucose uptake. The unremitting gluconeogenesis
causes hyperglycemia which despite an increase in insulin level, does not help in
providing the glucose to the cells. The cytokines interleukin -1(IL-1), interleukin
-6, (IL-6) and tumor necrosis factor (TNF) may directly or indirectly enhance
these hyperglycemic responses.
The insulin levels in the serum are normal or elevated but cannot prevent
the ensuing hyperglycemia because the ability to decrease blood glucose
concentration per insulin concentration is markedly diminished. This large
amount of glucose is then presented to noninsulin-mediated glucose uptake
pathway because of which the overall uptake of glucose is maintained. This
640 Section 21 Nutritional Support
hyperglycemia also ensures a steady supply of glucose to cells like the immune
cells and the wound inflammatory cells which are predominantly glucose
dependent.
Thus, the limited uptake of glucose in cells due to insulin resistance causes
a decrease in glucose oxidation pathway and an increase in lipid oxidation
pathway and breakdown of proteins mainly the skeletal proteins. There is
increased synthesis of acute phase proteins in stress occurring simultaneously
with decrease in the synthesis of binding proteins like albumin, transthyretin,
retinol-binding protein and transferrin. The decrease in concentration of these
binding proteins increases the plasma concentration of free hormones like the
cortisol and thus the vicious cycle of autocannibalism continues.
NUTRITIONAL ASSESSMENT
The aim of nutritional assessment is to identify the type and degree of malnutrition
and direct the treatment towards correcting it. The nutritional assessment in the
critically ill patients in the intensive care unit can be done based on the following:
• Patient’s history
• Clinical examination
• Anthropometric measurements
• Laboratory data.
History
The history taking should include asking about the patient’s nutritional intake
before becoming ill because studies have found that a history of weight loss of
10% over the previous 12 months is an indicator of protein-calorie malnutrition
resulting mainly due to inadequate caloric intake. Weight loss of 20–30% suggests
moderate protein calorie malnutrition and weight loss of more than 30% suggests
severe calorie malnutrition. A history relating to the medical and surgical illnesses
with specific reference to conditions which could impair ingestion, digestion or
absorption of nutrients should be sought.
Clinical Examination
Physical examination should include observation of the general appearance
of the patient with emphasis on evidence of temporal, upper body and upper
extremity wasting of skeletal muscle mass.
Anthropometric Measurements
The anthropometric parameters which should be measured include the height
and the body weight. However, the weight may be a misleading factor in the
critically ill patients because it is often related to alterations in the hydration status
of the patient. The other indices are measurements of triceps skin-fold thickness
and mid-arm muscle circumference which are found to be reasonably accurate
even in the presence of edema since the excess of body water accumulates to a
lesser extent in the upper extremity.
Chapter 88 Nutrition and Metabolism in Critically Ill Patients 641
Laboratory Examination
The laboratory data needed to assess nutrition includes complete blood count
to know the hematopoietic function, the renal function tests, the liver function
tests and serum electrolytes. Apart from these, the investigations which need to
be done are the total serum proteins, serum albumin levels, serum transferrin,
thyroxine-binding prealbumin, retinol-binding protein, fibronectin and the
24 hours urinary urea nitrogen excretion and determination of nitrogen balance.
The half-life of serum albumin is 20 days. The serum albumin levels, following
nutritional repletion may not rise significantly before 4–5 weeks. Moreover,
the serum albumin levels may fall after rapid intravenous fluid infusion, after
decreased synthesis due to liver dysfunction or due to increased loss through big
wounds, burns or renal dysfunction. Hence, it is not an ideal marker to reflect
acute responses to nutritional therapy. It can be used as a good prognostic marker
of a patient’s chronic nutritional state.
The 24 hours urinary urea nitrogen excretion evaluates the somatic protein
breakdown. Two thirds of the N2 derived from this protein breakdown is excreted
in the urine. Protein is 16% nitrogen hence each gram of urinary nitrogen
represents 6.25 grams of degraded protein.
Thus, the total body nitrogen balance can be calculated as follows:
Protein intake (g) – (24 hours urinary urea

Nitrogen excretion + 4)
Nitrogen balance (g) =
6.25
The factor 4 represents the daily nitrogen loss (in grams) in feces and other
losses. The goal of nitrogen balance is to maintain a positive balance of 4–6
grams. The above equation holds true as long as the major source of nitrogen
loss is urine. In patients on enteral feeds having diarrhea or extensive weeping
wounds or in renal insufficiency, this equation may not give a correct estimate.
Improvement in nitrogen balance suggests that nutritional support is adequate
or the catabolism has decreased.
Nutritional Requirements
The aims of calculating the nutritional requirement and support are:
• To provide enough energy to promote anabolic functions and at the same
time avoid any caloric overload.
• To prevent oxidative cellular injury.
• To favorably modulate the immune response.
The basic principle in treating any underlying protein malnutrition also
is to give caloric food first and treatment of stresses that lead to the severe
autocannibalism. In general, most patients do well with a caloric support of 25
kcal/kg ideal body weight per day. The patients with renal failure, liver failure,
congestive cardiac failure, burns, etc. need specific requirements and are
discussed later in the chapter. The ASPEN (American Society of Parenteral and
Enteral Nutrition) guidelines suggest that if the patient is obese, then the adjusted
body weight should be used in the calculation.
The human body derives its energy from combustion of the three carbon-
based organic fuels namely carbohydrate, proteins and lipids. The energy yield
per gram of lipid is 9 kcal/g, per gram of protein is 4 kcal/g and per gram of glucose
is 3.7 kcal/g. The body’s energy expenditure, the total body oxygen consumption
(VO2) and the carbon dioxide production (VCO2) are the summation of the
combustion of these three substrates.
The respiratory quotient (RQ) is the ratio of VCO2 to VO2.

RQ = VCO2/VO2
The daily energy expenditure can be calculated by two ways:
1. Harris–Benedict equation
2. Indirect calorimetry.
Harris–Benedict Equation
The daily or the basal energy expenditure (BEE) is the heat production of basal
metabolism in the resting and fasted state. The resting energy expenditure (REE)
is the heat production of basal metabolism in the resting state. It is equivalent to
BEE plus the thermal effect of food.
The Harris–Benedict (HB) equation determines the BEE based on sex, body
weight (kg) and height (cm) (Table 88.1).
These are the calculations for healthy adults. Stress and illness increase the
catabolism and hence the caloric requirement increases. The Calvin long’s stress
factors are hence applied to these equations to take into account the increased
caloric requirement due to the catabolism.
Studies which have compared the predicted and actual energy expenditure
in critically ill patients have shown that the predictive equations with the
multiplication factor for the degree of stress overestimate daily energy needs by
20–60% (Table 88.2).
Table 88.1 Harris–Benedict equation
Men
BEE (kcal/24 hr) = 66.5 + (13.7 × weight) + (5 × height) – (6.8 × age)
Women
BEE (kcal/24 hr) = 66.5 + (9.6 × weight) + (1.7 × height) – (4.7 × age)
Table 88.2 Calculation of calorie requirement
Thus, the caloric requirement is calculated as:

• 1.3 × HB for sepsis or uncomplicated major surgery
• 1.5 × HB for complicated sepsis (with organ failure) and burns less than 20%
• 2 × HB for burns more than 20%.
Table 88.3 Calculation of resting energy expenditure (REE)
REE (kcal/min) = 3.94 (VO2) + 1.1(VCO2)

REE (kcal/day) = REE × 1440
Indirect Calorimetry
Indirect calorimetry is the technique by which one measures the metabolic
energy expenditure of the body indirectly by measuring the whole body VO2
and VCO2 (Table 88.3). It is based on the principle that the use of energy
involves the consumption of oxygen (VO2) and the production of carbon dioxide
(VCO2), nitrogen wastes and water and when matter is converted to heat by the
body, measurement of VO2 and VCO2 indirectly reflects the metabolic energy
expenditure.
Specialized apparatus called metabolic carts are used to measure the
exchange of oxygen and carbon dioxide across the lungs, i.e. they measure the
oxygen concentration of inhaled oxygen and the carbon dioxide concentration
of exhaled gas. It can be used at the bedside and can easily be connected to the
ventilator tubings to measure the VO2 and VCO2.
The VO2 and VCO2 are measured for 30 minutes and this data is then
used to calculate REE for a 24 hours period. The REE calculates the metabolic
requirement at rest. Critically ill patients, whose body is constantly in a state
of catabolism, requires much more daily expenditure than REE calculated by
indirect calorimetry, hence the requirements have to be increased by 10 to 15%.
The limitations of indirect calorimetry are that it is expensive, time consuming
and unreliable at high fraction of inspired oxygen (>60%). Thus, it is reserved for
selected patients who need careful rotation of daily energy intake.
Thus, although there are various ways to calculate the caloric requirements,
the current guidelines for nutrition in critical care recommend an average intake
of 25–35 kcal/kg ideal body weight per day. Out of this, 40–60% calories should be
provided by carbohydrate, 20–30% by fat and 15–25% by proteins. Carbohydrates
and proteins provide 4 kcal/g and fats provide 9 kcal/g.
Carbohydrate Requirements
Carbohydrates are the main energy-giving fuel for our body. Glucose forms the
main substrate for many pathways generating energy in human body. The tissues
which are completely dependent on glucose are the red blood cells, the immune
cells, the transparent tissues of the eyes, renal medulla and the muscle during
anaerobic contraction. Tissues like brain are strongly but not totally dependent on
glucose. Brain can also utilize ketones and lactate when the availability of glucose
is low. All the other remaining tissues in the body are not directly dependent
on glucose. The rate of normal endogenous glucose production of the human
body is 2–3 g/kg/day. In order to maintain the normoglycemia, the exogenous
intake should at least correspond to the endogenous rate of glucose production.
Approximately, 60% of non-protein energy should be supplied as glucose with an
intake of 3–3.5 g/kg/day. Patients who are at increased risk of hyperglycemia for
example, patients with diabetes mellitus, sepsis, steroid therapy, should initially
be given carbohydrate at the rate of 1–2 g/kg/day and then treated depending on
the blood sugar levels.
The main concern while giving carbohydrate as a part of nutrition in the
critically ill patients is the blood glucose levels. Hyperglycemia increases the
morbidity and mortality in the critically ill patients whereas acute hypoglycemia
can result in sudden death especially in patients who are on sedation in the ICU.
The multicenter Normoglycemia in Intensive Care Evaluation and Surviving
Using Glucose Algorithm Regulation (NICE-SUGAR) trial found that patients
in the ICU, who were treated with insulin to achieve a target blood glucose of
81–108 mg/dL, had greater mortality and more hypoglycemia (6.8% versus 0.5%)
than the patients who were treated to a target level of less than 180 mg/dL. Thus,
achieving a target blood glucose level of less than 180 mg/dL is preferable over
tight control.
A study done by McCowen et al. demonstrated that giving hypocaloric total
parenteral nutrition was not effective in preventing hyperglycemia and infectious
complications and provision of total parenteral nutrition to a goal of 25 kcal/kg
was not associated with more hyperglycemia or infections than the hypocaloric
diet. They found that a regimen of 1.5 g/kg of protein in conjunction with 25 kcal/
kg provided significant nutritional benefits in terms of nitrogen balance.
Lipids
Lipids provide the maximum energy as compared to the other organic fuels.
Linoleic acid is the only dietary fatty acid which is considered essential. Linoleic
acid should form 4% of the total caloric intake and at least 0.5% of the dietary fatty
acids. A deficient intake of linoleic acid produces a clinical disorder characterized
by a scaly dermopathy, cardiac dysfunction, neutropenia, thrombocytopenia
and increased susceptibility to infection. It can be prevented by oral intake of
10–15 mL/day of safflower oil or by the use of IV lipid emulsions.
Proteins
Critically ill patients in the ICU can lose 16% of total body proteins in the first
21 days with most (67%) of this coming from the skeletal muscle. In a study
described by Martindale et al., the thigh muscle biopsy samples of 63 critically
ill patients who were in ICU for more than 7 days and ventilated for more
than 48 hours, showed that 29% of the tissue had been lost in 10 days in these
hyperdynamic patients. Thus, supplementing amino acids is important to
increase protein synthesis and maintain muscle mass.
On an average a protein intake of 0.75–1 g/kg/day is sufficient for most
patients in ICU. Protein requirements are higher in patients with severe burns,
trauma or fulminant tetanus and may be up to 2.5 g/kg/day. The nitrogen
balance studies can help adjust the protein intake. A rising blood urea nitrogen
exceeding 100 mg/dL or an increase in serum ammonia level are indications to
decrease the protein administration. Adding resistance exercise to the protein
supplement regimen can have additional benefits including increasing nutrient
uptake in muscles and other tissues, decreasing inflammation and lowering the
insulin resistance.
Micronutrients
Vitamins
Amongst the micronutrients, there are 12 essential vitamins which need to be
supplemented. These are vitamin A, vitamin B12, vitamin C, vitamin D, vitamin E,
vitamin K, vitamin B1 (thiamine), vitamin B2 (riboflavin), vitamin B6 (pyridoxine),
pantothenic acid, biotin and folate. The requirements of vitamins are very high in
the hypermetabolic seriously ill patients.
Thiamine deficiency is frequently observed in the ICU and deserves a
special mention. Thiamine deficiency can manifest as cardiac dysfunction (Beri
Beri disease), peripheral neuropathy, metabolic encephalopathy (Wernicke’s
encephalopathy) or lactic acidosis. All these disorders are quite common in the
ICU patients and hence a high index of suspicion towards thiamine deficiency
should be kept in mind while treating such patients.
Trace Elements
The trace elements which should be supplemented are iron, zinc, manganese,
molybdenum, copper, chromium, selenium, iodine and cobalt. In general, the
enteral feeds of 1000–1500 mL will have these vitamins and minerals in adequate
amount according to the required daily allowance. They need to be supplemented
in enteral feeds less than 1000 mL and in total parenteral nutrition. As regards the
fluid intake, in general, patients should receive 25 mL of fluid per kg actual dry
body weight to avoid dehydration.
BIBLIOGRAPHY
1. Apostolakos MJ, Papadakos PJ. The Intensive Care Manual. McGraw-Hill publications;
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2. Bankhead R, et al. Enteral nutrition practice recommendations. Journal of Parenteral,
and Enteral Nutrition. 2009;33(2):122-67.
3. Bolder U, Ebener C. Working group for developing the guidelines for parenteral
nutrition of the German Association for Nutritional Medicine. Ger Med Sci. 2009,7:
Doc 23.
4. Brunicardi FC. Schwartz’s Principles of Surgery, 8th edn. McGraw-Hill publications;
2004.
5. Carrol Rees Parrish. The Hitchhiker’s Guide to Parenteral Nutrition Management for
Adult Patients. Practical Gastroenterology. July 2006.
6. Dhaliwal, et al. The Canadian critical care nutrition guidelines in 2013: an update on
current recommendations and implementation strategies. Nutrient Clin Pract. 2014;
29(1):29-43.
7. Driscoll DF, Blackburn GL. Total parenteral nutrition 1990: a review of its current
status in hospitalized patients. The need for patient-specific feeding. Drugs. 1990;
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8. Fink MP, Abraham E, Vincent JL, Kochanek PM. Textbook of Critical care, 5th edn.
Elsevier Saunders publications.
9. Giner M, Laviano A, Meguid MM, et al. In 1995 a correlation between malnutrition
and poor outcome in critically ill still exists. Nutrition. 1996;12:23-9.
10. Irwin JM, Rippe RS. Irwin and Rippe’s Intensive Care Medicine. 6th edn. Lippincott
Williams & Wilkins publications; 2008.
11. KC, Friel C, Sternberg J, Chan S, Forse RA, Burke PA, Bistrian BR. Hypocaloric total
parenteral nutrition: effectiveness in prevention of hyperglycemia and infectious
complications—a randomized clinical trial. Crit Care Med. 2000;28(11):3606-11.
12. Marino PL. The ICU Book, 3rd edn. Lippincott Williams & Wilkins; 2007.
13. Miller RD. Miller’s Anesthesia, 7th edn. Elsevier Publications 2009.
14. Monk DN, et al. Ann Surg. 1996;223(4):395-405.
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16. Udwadia FE. Principles of critical care, 2nd edn Oxford Publications.
CHAPTER
ENTERAL AND PARENTERAL NUTRITION
TIMING OF NUTRITIONAL SUPPORT

A study done by Giner et al. has shown that nutritional therapy considerably
reduces morbidity and mortality in the critically ill patients. The European Society
of Parenteral and Enteral Nutrition (ESPEN) guidelines on EN5 state that ‘‘The
insufficient provision of nutrients is likely to result in undernutrition within 8–12
days following surgery and/or ICU admission. In order to prevent undernutrition
and related adverse effects, all ICU patients who are not expected to be on a full
oral diet within three days should receive EN’’.
The European (ESPEN) and Canadian Society for Clinical Nutrition (CSCN)
clinical guidelines recommend the initiation of EN within 24 hours or 24–48
hours, respectively, after admission to ICU. The guidelines also recommend that
if the enteral route is contraindicated then the parenteral mode should be used
and the parenteral nutrition should also ideally be initiated within 24–48 hours.
But before starting nutritional therapy, one needs to keep in mind that in an acute,
hypercatabolic critical illness, stabilization of hemodynamics, and correction of
the fluid and electrolytes and acid-base disturbances should take precedence
over the nutritional therapy. Nutritional requirement in specific conditions are
discussed in this chapter.
ROUTES FOR GIVING NUTRITIONAL SUPPORT

There are two routes through which the nutritional support can be given—
enteral and parenteral. Enteral route means through the gastrointestinal tract
and parenteral means through intravenous route. So far the enteral route is
considered the most physiological route and hence is the preferred one.
Enteral Nutrition
Nutrition provided through the gastrointestinal tract via a tube, catheter, or stoma
that delivers nutrients distal to the oral cavity is called as enteral nutrition.
Enteral route for giving nutritional support is indicated when swallowing is
inadequate or impossible but gastrointestinal function is otherwise intact. For
example, patients who have an oropharyngeal lesion, esophageal lesion, burns
or a neurological disorder, where swallowing and the upper GI tract are affected
and patients on ventilatory support are the candidates in whom the enteral route
is preferred.
Reasons for using enteral route as the preferred route for giving nutrients are:
• The enteral route maintains the structural and functional integrity of the gut.
• Complete bowel rest will lead to progressive atrophy and disruption of the
intestinal mucosa. This is because the bowel mucosa gets its nutrients from
those present in the bowel lumen. The amino acid glutamine is thought to
play an important role in this process as it is considered as the principal
metabolic fuel for intraepithelial cells.
• The mucosal disruption that may ensue due to lack of nutrition may lead
to translocation of enteric pathogens across the bowel mucosa and into
the systemic circulation. This potential to prevent sepsis of bowel origin is
considered as one of the foremost reasons for preferring enteral route over
the parenteral one.
Studies have suggested that giving enteral feeds in shock increased oxygen
demand in a segment of the bowel that was poorly perfused, hence stabilizing
the patient hemodynamically is a prerequisite to starting enteral nutrition.
Enteral nutrition can be given via an infusion into the stomach, duodenum or the
jejunum via the nasogastric tubes, nasoduodenal tubes or the nasojejunal tubes.
The tubes can be passed beyond the pylorus under fluoroscopic guidance.
The feeding tubes that are currently favored are narrower (8 to 10 French)
and more flexible than standard nasogastric tubes are longer in length and
come with a stylet for insertion. Care has to be taken during their insertion since
they may enter the larynx and the respiratory tract if the cough response of the
patient is not strong. The tip of the tube is radiopaque. The gold standard for
the confirmation of the tube placement is a properly obtained and interpreted
radiograph which visualizes the entire course of the tube. The auscultatory
method can neither distinguish between gastric and small bowel placement
nor can it detect the placement of the tip of the tube in the esophagus. Hence, a
radiograph is mandatory before starting the feeds. Another method to assess the
tube placement is measuring the pH of the specimen aspirated from the tube. If
the pH of the aspirate is less than 5.0, then the tube is most likely placed in the
stomach. However, if the gastric pH is more than 6.0, then the pH method is of no
benefit in predicting tube location in the gastrointestinal tract.
The other problem with the tubes is that they can get misplaced during the
course of the feeds (Table 89.1). To confirm their correct positioning, daily bedside
methods like determining whether the external length of the tubing has changed
since the time of the confirmatory radiograph, observing for negative pressure
Table 89.1 Contraindications for nutritional support through enteral route
• Generalized suppurative peritonitis

• Bowel ileus or obstruction
• Enterocutaneous fistulas with an output of more than 500 mL/day
• Acute fulminant necrotizing pancreatitis
• Severe shock
Chapter 89 Enteral and Parenteral Nutrition 649
while attempting to withdraw fluid from the feeding tube, observing for changes
in residual volumes and measuring pH of the aspirate obtained from the tip of
the tube have to be followed. An acute increase in the gastric residual volume
may indicate the displacement of the tube from the small bowel into the stomach.
An increase in the negative pressure is more likely to be felt while aspirating the
fluid from the small bowel than from a gastric tube. If the external length of the
tube has increased significantly then displacement should be suspected and a
radiograph should be obtained to ascertain the tube position.
Apart from the nasally inserted tubes, procedures like the percutaneous
endoscopic gastrostomy and jejunostomy can also be done to give the enteral
feeds. In patients who are at risk of aspiration due to reflux and the patients who
require feeding for a longer time (>4 weeks) direct placement of percutaneous
gastric or jejunal tube is recommended.
Starting the Enteral Feeds

The American Society for Parenteral and Enteral Nutrition (ASPEN) guidelines
recommend that the enteral feeds should be started postoperatively in surgical
patients without waiting for flatus or bowel movement. These feedings can be
initiated within 24–48 hours. Percutaneous endoscopic gastrostomy tube may be
utilized for feedings within 2 hours in adults and 6 hours in infants and children.
The test infusion comprising volume of normal saline equivalent to the
desired hourly feeding volume should be infused into the stomach for one hour
to check for the safety. The tube should then be clamped for half an hour and
then the aspirate is measured. If the gastric residual volume is <50%, then the
feeding can be started safely.
The initiation and advancement of the enteral nutrition regimens should be
based on the patient’s demographics, enteral route (gastric versus small bowel),
nutrition requirements and the GI status. For the initial feeding regimen, full
strength isotonic formulas are preferred. The ‘starter regimens’ which begin
with dilute formulas and slow infusion rates and then gradual increase in the
concentration and the infusion rate over a few days, are preferred for small bowel
(duodenum and jejunum) who have a limited reservoir function. Starter regimens
are not necessary for gastric feedings because the stomach has a good reservoir
capacity and the gastric secretions can dilute the full feedings and reduce the
osmotic load associated with them.
The enteral feeds can be given as intermittent bolus feedings or continuous
infusions. Bolus feedings are defined as formula delivered by gravity via a syringe
over approximately 15 minutes. These are usually tolerated when infused into
the stomach. The ASPEN guidelines recommend that the feedings may be
initiated with full strength formula 3–8 times per day with increases of 60–120 mL
every 8–12 hours as tolerated up to the goal volume. The feeds can be given by
continuous infusions over a period of 16 hours. The chances of aspiration and
diarrhea are found to be less by this technique and also result in good weight gain
and positive nitrogen balance. The feeding tubes should be flushed with 30 mL
of water every 4 hours during continuous feeding or before and after intermittent
feedings.
Table 89.2 Classification of enteral feeds
The enteral feeds are classified on the basis of nature of nutrients or the ease of absorption
into the following types:
• L iquidized or blenderized food: These are the liquidized versions of the food we eat.
For example, rice, boiled vegetables, curd, milk, fruit juice, etc.
• L actose-free formulas: These formulas are indicated in patients with a normal
gastrointestinal tract but who are intolerant to lactose. For example, Sustacal HC 1.5
kcal/mL, Isocal 1 kcal/mL, HCN 2 kcal/mL.
• C hemically derived formulas: These formulas contain protein in the hydrolysated
form. These are indicated in patients whose ability to absorb nutrients is impaired. For
example, vital HN.
• E lemental formulas: These contain amino acids. These are often used in patients with
limited absorptive capacity. They are well-absorbed from jejunum hence often used for
jejunal feeds. For example, Vivonex 1 kcal/mL.
Nursing a Patient on Enteral Feeds

The backrest of the patient’s bed should be elevated to a minimum 30°
and preferably to 45° for all patients receiving the enteral feeds if there
is no contraindication. The gastric residual volume should be checked every
4 hours during the first 48 hours in gastric route-fed patients. If the gastric
residual volume is more than 250 mL after a second gastric residual check then
a prokinetic agent should be considered. If gastric stony occurs then the gastric
feeds need to be withheld. If the gastric residual volumes are consistently more
than 500 mL then the placement of the feeding tube below the ligament of Treitz
should be considered. The fluid and electrolytes and other metabolic parameters
based on the patient’s clinical situation should be monitored regularly.
Most of the enteral formulas provide 14–20% of calories as protein and
contain medium or long chain triglycerides (Table 89.2).
Complications of Enteral Feeding

Gastric retention, aspiration pneumonia, diarrhea and tube blockage are the
main complications that can be encountered during enteral feeding. Head
elevation by 30°–45° degrees, small bowel feeds, use of prokinetic agents, less use
of narcotics and using feeding protocols in which the residual gastric volume is
monitored, are some of the ways by which gastric retention and aspiration can
be prevented. To tackle diarrhea reduction of feeds by half, avoidance of bolus
feeding and lactose in the feeding and avoidance of sorbitol-containing liquid
medicines can be tried. Supplementation of amino acids containing formula
feeds is recommended. To prevent tube blockage flushing the tube before and
after the feeds, filling with water and plugging them when not in use should be
done.
Parenteral Nutrition
The nutrition given through the intravenous route is called as parenteral
nutrition. Parenteral nutrition is associated with an increased risk of infectious
complications, especially line infection, and increased cost unlike enteral
nutrition.
Indications
• Enteral nutrition is not feasible (short bowel syndrome, enterocutaneous
fistulas with a large leak >500 mL, severe diarrhea, complete bowel
obstruction, active GI bleeding, pseudo-obstruction with intolerance to
food)
• Target caloric requirement cannot be achieved via enteral feeding alone (in
this case, parenteral nutrition is given as a supplement to enteral nutrition)
• Relative indications include nonhealing moderate-output enteric-cutaneous
fistulas, acute radiation enteritis, marked abdominal distention and ileus
due to intra-abdominal sepsis, chylothorax unresponsive to a medium-chain
triglyceride diet.
Access for the Parenteral Nutrition

The parenteral nutrition is usually given through a central vein (long term) or
a peripheral vein (short term). The major limitation in using the peripheral
vein for parenteral nutrition is the development of thrombophlebitis due to the
high osmolality of the nutrient solutions (osmolality >900 mOsm/L). Centrally
administered parenteral nutrition can cover all nutritional needs as vessel
tolerance to hyperosmolar solutions is usually not a limitation. The central veins
preferred are the internal jugular and the subclavian vein. They can be cannulated
using single or triple lumen catheters and these catheters can be kept for 10–12
days provided strict asepsis is maintained while handling them. Most peripheral
vein catheters last about 48–72 hours from the time of insertion. Peripherally
inserted central venous catheters (PICC) last longer and can be used to provide
hypertonic parenteral nutrition mixtures.
Parenteral Nutrition Solutions

Carbohydrates
Carbohydrates are usually provided in amounts of up to 60% of total kcal/day.
Dextrose solutions in the concentration of 10, 20 and 50 percentage constitute the
carbohydrate content of parenteral nutrition.
Proteins
These are mainly supplied in the form of amino acid solutions. The standard
amino acid solutions contain approximately 50% essential amino acids and 50%
nonessential amino acids. The protein content of these amino acids can be arrived
at by multiplying the nitrogen content in grams by 6.2. The metabolism of essential
amino acids causes less increase in the blood urea nitrogen concentration than
the metabolism of nonessential amino acids. This is because the nitrogen present
in essential amino acids is partially recycled for the production of nonessential
amino acids. It is for this reason that the essential amino acids are preferred
in renal failure. The amino acids preferred in patients with hepatic failure are
those containing a high concentration of branched chain aminoacids (leucine,
isoleucine, valine). Glutamine should be supplemented in parenteral nutrition
in the form of glutamic acid because it is the main metabolic fuel for intestinal
epithelial cells and is instrumental in maintaining the functional integrity of the

bowel mucosa.
Lipids
Intravenous fat emulsions provide 20–30% of daily kcals. The main source of
fatty acids in the lipid emulsions are the vegetable oils (safflower or soybean oil).
They contain 50–65% of linoleic acid and 4–9% of linolenic acid. They are available
in strength of 10% and 20%. The 10% emulsions provide 1 kcal/mL approximately
and the 20% emulsions provide 2 kcal/mL. They are made isotonic by addition of
glycerol.
Vitamins and Electrolytes
Vitamins A, B, C and D, and electrolytes—sodium, chloride, potassium and
magnesium and few trace elements are also added to the parenteral nutrition
formulas to combat their deficiency.
Formulations and Administration

The parenteral nutrition formulations are available as three-in-one (dextrose,
amino acid, lipids) or two-in-one packs (dextrose and amino acids). The lipid
emulsions are to be infused separately when the two-in-one packs are used.
The example of three-in-one formula is Vitrimix which provides 1000 kcals in
1000 mL of solution. It contains 75 grams of dextrose,7 grams of nitrogen and 20%
of lipids in 250 mL. Its osmolality is 960 mosm/L.
The example of two-in-one formula is Aminomix which provides 1000 kcals
and contains 200 grams of dextrose and 8.2 grams of nitrogen (Table 89.3).
Monitoring
Estimation of complete hemogram, serum electrolytes, blood glucose, urea,
creatinine, blood NPN, liver function tests, serum proteins, calcium, phosphorus
and arterial blood gas should be done before starting the TPN and followed up
at least once or twice a week. The blood glucose and serum electrolytes need
frequent monitoring. The blood glucose should be maintained between 120 and
180 mg/dL.
Complications of Total Parenteral Nutrition

• Hyperglycemia (due to the use of high concentration of dextrose-containing
solutions)
• Hypoglycemia (due to sudden stoppage of dextrose infusion)
• Hypophosphatemia
• Hypomagnesemia
• Hepatic steatosis
• Thrombophlebitis
• Catheter-related sepsis.
Table 89.3 Nutrition in specific conditions
Diagnosis Caloric Proteins Special points

requirement
Acute renal failure 25 kcal /kg/day 0.5 g/kg/day Restrict fluid to <1/day, if urine
(not on dialysis) output is low
Acute renal failure 25 kcal /kg/day 1.5 g/kg/day Loss of 6–12 g of amino acids
(on dialysis) and 25–30 g of glucose during a
six-hour session of hemodialysis
should be replenished
Hepatic failure (no 25 cal/kg/day 1 g/kg/day Branch chain amino acids
encephalopathy) preferred
Hepatic failure 25 kcal/kg/day 0.3 g/kg/day Branched chain amino acids
(encephalopathy) improve encephalopathy and
should be given
Respiratory failure 25 kcal/kg/day 1.2 g/kg/day – Restrict carbohydrates (to
(COPD) ↓CO2 production)
– Give carbohydrate and fat in
ratio of 40:60
Respiratory failure 25 kcal/kg/day 1.2 g/kg/day Reduce fats and give
(ARDS) carbohydrate and fat in ratio
of 65:35 (since lipid emulsion
interferes with gas exchange)
Cardiac failure 25 kcal/kg/day 1 g/kg/day Restrict salt and water
(start with half
caloric requirement
initially)
Severe burns 30–35 kcal/kg/ 1.5–2.5 g/ Protein intake should
day kg/day be increased to combat
hypoalbuminemia
Multiple trauma 25 kcal/kg/day 1.2–1.5 g/ Immune enhancing formulas
kg/day (glutamine, arginine, omega
3 fatty acids and antioxidant
vitamins) should be tried
REFEEDING SYNDROME
The body of a nutritionally depleted patient, i.e. one who has lost ≥10% of body
weight over ≤6 months gets adapted to the minimal nutrient intake. Refeeding
such patients must be done gradually with caution as their metabolic system
may not be able to tolerate the overload. To start with a balanced diet comprising
carbohydrates, fats and proteins at intakes less than the REE should be given
and then gradually increased over 10 days. The patients will be in negative N2
balance initially and hence protein intake has to be increased gradually to help
in rebuilding of the muscle tissue. This should be accompanied by exercise.
Phosphate which is an important component of tissue membranes, enzymes
and nucleosides is utilized as new tissues are being formed and hence can result
in hypophosphatemia. Hypophosphatemia leads to weakness of major muscle
and glucose intolerance also known as refeeding syndrome. Muscle weakness
may also be exacerbated if there is coexistent hypokalemia, hypocalcemia and

hypomagnesemia. Thus serum phosphate, calcium, magnesium, potassium
levels apart from serum electrolytes should be monitored daily and their
replacement should be done promptly. Fluid overload should be avoided.
BIBLIOGRAPHY
1. Apostolakos MJ, Papadakos PJ. The Intensive Care Manual. McGraw-Hill publications;
2001.
2. Bankhead R, et al. Enteral nutrition practice recommendations. Journal of Parenteral,
and Enteral Nutrition. 2009;33(2):122-67.
3. Bolder U, Ebener C. Working group for developing the guidelines for parenteral
nutrition of the German Association for Nutritional Medicine. Ger Med Sci. 2009,7:
Doc 23.
4. Brunicardi FC. Schwartz’s Principles of Surgery, 8th edn. McGraw-Hill publications;
2004.
5. Carrol Rees Parrish. The Hitchhiker’s Guide to Parenteral Nutrition Management for
Adult Patients. Practical Gastroenterology. July 2006.
6. Dhaliwal, et al. The Canadian critical care nutrition guidelines in 2013: an update on
current recommendations and implementation strategies. Nutrient Clin Pract. 2014;
29(1):29-43.
7. Driscoll DF, Blackburn GL. Total parenteral nutrition 1990: a review of its current
status in hospitalized patients. The need for patient-specific feeding. Drugs. 1990;
40:346-63.
8. Fink MP, Abraham E, Vincent JL, Kochanek PM. Textbook of Critical care, 5th edn.
Elsevier Saunders publications.
9. Giner M, Laviano A, Meguid MM, et al. In 1995 a correlation between malnutrition
and poor outcome in critically ill still exists. Nutrition. 1996;12:23-9.
10. Irwin JM, Rippe RS. Irwin and Rippe’s Intensive Care Medicine. 6th Edition. Lippincott
Williams & Wilkins Publications; 2008.
11. KC, Friel C, Sternberg J, Chan S, Forse RA, Burke PA, Bistrian BR. Hypocaloric total
parenteral nutrition: effectiveness in prevention of hyperglycemia and infectious
complications—a randomized clinical trial. Crit Care Med. 2000;28(11):3606-11.
12. Marino PL. The ICU Book, 3rd edn. Lippincott Williams & Wilkins; 2007.
13. Miller RD. Miller’s Anesthesia, 7th edn. Elsevier publications. 2009.
14. Monk DN, et al. Ann Surg. 1996;223(4):395-405.
15. Singer P, et al. ESPEN Guidelines on Parenteral Nutrition: Intensive Care. Clinical
Nutrition, 2009(28);387-400.
16. Udwadia FE. Principles of critical care, 2nd edn. Oxford publications.
SECTION
22
SEDATION AND ANALGESIA
IN ICU
Chapter 90 Sedation and Analgesia for

Critical Care Patients
Prem Kumar
Chapter 91 Patient-controlled Analgesia

Prem Kumar
CHAPTER
90 Prem Kumar
SEDATION AND ANALGESIA FOR

CRITICAL CARE PATIENTS
Pain and agitation is one of the major problems in ICU patients and can be a
major cause of morbidity. Patients with acute postoperative pain are inadequately
treated because of the fear of complication, arbitrary management of among
intensivists, lack of availability of proper assessment and management protocols.
Pain is subjective, hence questionnaire related to pain assessment is asked and is
supplemented with objective scales. Inadequate pain relief is the most common
cause of agitation in ICU patients. Recent studies demonstrate that inadequate
treatment of acute pain can evolve into chronic pain. Proper staff education is
vital to the success of pain management. Appropriate sedation reduces the
duration of mechanical ventilation and ICU stay.
There are three dimensions for pain:
1. Sensory—discriminative
2. Affective—motivational
3. Cognitive—evaluative.
ISSUES TO BE ADDRESSED FOR MANAGEMENT OF

PAIN AND SEDATION IN ICU
• Define the cause of agitation and pain
• Associated comorbid conditions?
• Hepatic and renal function for metabolism?
• Options of using regional/intravenous analgesia according to the status of
the patient
• Choosing a relevant pain scale for the patient.
PAIN AND SEDATION CONSIDERATIONS

• Inadequately treated severe pain can lead to a change in the response of the
neural tissue to painful stimuli—this phenomenon is called neuroplasticity.
This can lead to chronic pain in the future which can debilitate the patient.
• Stress response to pain can cause release of catecholamines, pro-
inflammatory cytokines, acute phase reactants, cortisol. Activation of renin-
angiotensin system (RAS), coagulation disturbances and altered immune
response is one of the major causes for morbidity and mortality.
658 Section 22 Sedation and Analgesia in ICU
• Because of anxiety and the other psychological disturbances, patient may

end up with post-traumatic stress disorder.
• Making out the cause of pain is vital to its management. Pharmacological
management is based on patient assessment, response to treatment,
maintenance of adequate drug level. Frequent evaluation and modification
of pain approaches and drug dosages are done.
• One more important point to stress is the importance of using regional
analgesia with local anesthetics and opioids for pain control since it reduces
the stress response of pain.
• Analgesia and sedation required in keeping the patient calm and comfortable
but arousable is what is recommended in recent literature since this reduces
the duration of mechanical ventilation and ICU stay.
• Daily sedation interruption (sedation holiday) leads to better outcome in
ICU patients. Interrupted doses are preferred than continuous infusions.
Spontaneous breath trials are done during the time of sedation holiday.
ASSESSMENT OF PAIN (TABLES 90.1 AND 90.2)

• It is mainly subjective assessment by way of different pain questionnaire
• Objective pain scales are used to supplement subjective assessment.
• Objective signs like tachycardia, tachypnea, hypotension and grimacing can
be used for assessing pain. But these are not reliable since they can be caused
by other factors too.
• Patients who are at risk for undertreated pain are infants, patients with
difficulty in communication like language alteration, developmental
retardation, and psychiatric disease.
• Assessment of pain can be done with unidimensional and multidimensional
pain questionnaires.
• Unidimensional: Visual analog scale, numeric rating scale, verbal descriptor
scale, Wong-Baker FACES pain scale.
• Multidimensional–McGill pain questionnaire, memorial pain assessment
card (MPAC), brief pain inventory–short form (BPI-SF).
Table 90.1 Clinical evaluation of pain
• Location of pain
• Severity of pain: Visual, verbal, or numeric analog scales
• Feel of the pain: Somatic or visceral or neuropathic or breakthrough pain
– Neuropathic pain occurs due to injury of the peripheral nervous system and is
due to dysfunction of the sodium channels and NMDA receptor
– Breakthrough pain: It is an episodic increase in pain with a background of
adequately controlled pain. It can occur due to some precipitating factor or just
before the administration of regular analgesic dose.
– Incident pain: It is a form of breakthrough pain which occurs due to movement
or during change of dressing.
• History of analgesic intake and other drugs which may influence its effect
• Frequency of pain
• Timing of pain
• Precipitating factors
Chapter 90 Sedation and Analgesia for Critical Care Patients 659
Table 90.2 Differences between somatic and visceral pain
Somatic pain Visceral pain

• an be superficial or deep
C • It is due to some disease process or
• Superficial pain is due to nociceptive abnormality in the function of internal
input arising from skin, subcutaneous organ or its superficial structure
tissues, and mucous membranes (parietal pleura, pericardium, and
• Deep pain arises from muscles, peritoneum)
tendons, joints, or bones • It is associated with nausea,
• Superficial pain is sharp, pricking, well vomiting, sweating, and changes in
localized hemodynamics
• Deep pain is dull aching, less well
localized
PAIN SCALES
• Visual analog scale (VAS)
• Numeric rating scale (NRS)
• Wong-Baker FACES pain scale
• Verbal descriptor scale
• McGill pain questionnaire.
Visual Analog Scale
The VAS is a continuous scale comprised of usually 10 cm in length, anchored by

2 verbal descriptors, one for each symptom extreme. The scale reads 0—no pain
and 10—worst possible pain. This is the most common scale used by intensivist’s
for pain assessment.
Numeric Rating Scale
Numeric rating scale (NRS) is an 11 point scale and can be used verbally and
the NRS scale increases as the intensity of pain increases. A NRS or VS ≤3 is an
indication that the patient has adequate analgesia.
Wong-Baker FACES Pain Scale

Faces Pain scale comment
Happy, no hurt
Hurts a little bit
Hurts little more
Hurts even more
Hurts whole lot
Hurts worst
Verbal Descriptor Scale
Short-form McGill Pain Questionnaire (Tables 90.3 and 90.4)

It includes 5 measures:
1. Pain location (sensory dimension).
2. Pain intensity (sensory dimension).
Table 90.3 Short-form McGill pain questionnaire (SF-MPQ)
Quality of pain None Mild Moderate Severe

Throbbing
Shooting
Stabbing
Sharp
Cramping
Gnawing
Hot burning
Aching
Heavy
Tender
Splitting
Tiring—
exhausting
Sickening
Fearful
Punishing-cruel
No pain............................................................................................................... worst possible pain
Table 90.4 Present pain intensity (PPI)
0 No pain
1 Mild
2 Discomforting
3 Distressing
4 Horrible
5 Excruciating
3. Pain quality (sensory, affective, and cognitive dimensions).

4. Pain pattern (sensory dimension).
5. Alleviating and aggravating factors (behavioral dimension).
The original McGill pain questionnaire had descriptors divided into four
major groups: sensory (S), 1–10; affective (A), 11–15; evaluative (E), 16; and
miscellaneous (M), 17–20. The sum of the values is the pain rating index (PRI). In
the short-form McGill pain questionnaire, Descriptors l–11 represent the sensory
dimension of pain experience and 12–15 represent the affective dimension. Each
descriptor is ranked on an intensity scale of 0 = none, 1 = mild, 2 = moderate,
3 = severe.
Scales Used for Sedation Assessment in ICU

• Richmond agitation sedation scale
• Ramsay sedation score.
Scale Used for Assessing Delirium in ICU

Confusion assessment method for the intensive care unit (CAM-ICU).
Management of Pain and Sedation (Flow charts 90.1 and 90.2)

Opioids and benzodiazepines remains the mainstay of sedation and analgesia
management in ICU. Recently dexmedetomidine has gained popularity due its
pharmacokinetic and pharmacodynamic profile and there are studies where it
has been used in ventilated patients for 7 days but still FDA approval for its use is
limited to 24 hours. The advantage of dexmedetomidine is the lack of respiratory
depression. Wherever possible, regional analgesia should be supplemented with
sedative agents.
Flow chart 90.1 Managing pain and sedation in ICU
Abbreviations: TENS, Transcutaneous electrical nerve stimulation; NSAIDs, Nonsteroidal anti-

inflammatory drugs
Flow chart 90.2 Algorithm for pain/sedation/delirium management in ICU
Options of Regional Analgesia

• In case of nonventilated awake postoperative patients—Intravenous patient
controlled analgesia (PCA) or patient controlled epidural analgesia (PCEA)
is used (Table 90.5).
• Epidural analgesia
• Continuous peripheral nerve catheter based analgesia.
Table 90.5 Drugs used for pain and sedation in ICU
Drug Dose Metabolism Comments

NSAIDs and • Diclofenac 75 mg Paracetamol— • Cautiously used in
acetaminophen 12th hourly IM or liver hepatic and renal
slow IV disease, asthma
• Ketorolac 1 mg/kg NSAIDs—Liver • Cause GI
6th hourly IM or slow and kidney disturbances
IV • Interaction with
• Paracetamol ACE inhibitors, ARB,
15–20 mg/kg 6th diuretics
hourly IV
Opioids • Respiratory
depression
Morphine 1.1–0.2 mg/kg IV 6th Liver and • Histamine release
hourly or kidney • Reduce morphine
Fentanyl 2–5 mg/hr in case of dose by 50% in case
infusion. of renal failure
Tramadol 1–2 µg/kg IV every • Tramadol may
30– 60 minutes or precipitate serotonin
1–5 µg/kg/hr syndrome in patients
50–100 mg 12th taking SSRI
hourly
Ketamine 1 mg/kg IV or 5 µg/kg/ Liver • Should be
min for sedation and combined with
analgesia. Duration glycopyrrolate and
of action = 15–20 benzodiazepines.
minutes • Causes
hypertension,
tachycardia,
increased ICT, IOP
Propofol Loading dose of 0.5–1 Liver and lung • Dose >4 mg/kg/
mg/kg followed by hr for >48 hours
50– 200 µg/kg/min IV can cause propofol
infusion syndrome
(metabolic acidosis,
hemoglobinuria)
• Hypotension,
bradycardia
Contd…
Contd…
Drug Dose Metabolism Comments

Benzodiazepines Midazolam Liver. • Can cause
50–100 µg/kg IV every Midazolam hypotension in
15–90 min or 1–3 mg requires minor patients with
or reduction of hypovolemia
0.05–0.1 mg/kg/hr dose in renal • Can cause
disease but respiratory
Lorazepam lorazepam depression
0.02–0.06 mg/kg every does not • Midazolam is most
2–5 hours or common BZD used
0.01–0.1 mg/kg/hr for sedation for short
term
• Lorazepam is used if
prolonged sedation
is required
Haloperidol 2–10 mg IV every • Prolonged QT
20–30 minutes interval, torsades de
pointes, neuroleptic
malignant
• Due to its delayed
onset, it has to
be combined with
benzodiazepine
Dexmedetomidine FDA approved sedation Liver • Highly selective α2
is limited to 24 hours. agonist
Loading dose = 1 µg/ • Advantage of
kg over 10 minutes having anxiolysis,
followed by Infusion sedation, analgesia,
dose = 0.4–0.7 µg/ sympatholysis with
kg/hr an arousable
patient
• Hypotension,
biphasic heart rate
response
• Hypertension can
occur with rapid
administration
Anesthetic Isoflurane or Liver • Certain studies
conserving device sevoflurane have compared
(AnaConDa) its efficacy with
intravenous
sedatives but this
device is yet to get
FDA approval
Table 90.6 Ramsay sedation scale
Score Description
1 Anxious and agitated or restless, or both
2 Cooperative, orientated, and tranquil
3 Drowsy, but responds to commands
4 Asleep, brisk response to light glabellar tap or loud auditory stimulus
5 Asleep, sluggish response to light glabellar tap or loud auditory stimulus
6 Asleep and unarousable
Ramsay sedation scale (RSS) and Richmond agitation sedation scale

(RASS) is primarily used for measuring sedation in ICU patients on mechanical
ventilation and is primarily used to measure the level of sedation rather than
agitation (Tables 90.6 and 90.7). Agitation is measured by confusion assessment
method for the intensive care unit (CAM–ICU) method (Table 90.8).
Table 90.7 Richmond agitation sedation scale
Score Label Description

+4 Combative Combative, violent, immediate danger to staff
+3 Very agitated Pulls to remove tubes or catheters; aggressive
+2 Agitated Frequent non-purposeful movement, fights ventilator
+1 Restless Anxious, apprehensive, movements not aggressive
0 Alert and calm Spontaneously pays attention to caregiver
–1 Drowsy Not fully alert, but has sustained awakening to voice
(eye opening and contact >10 sec)
–2 Light sedation Briefly awakens to voice (eyes open and contact <10 sec)
–3 Moderate sedation Movement or eye opening to voice (no eye contact)
–4 Deep sedation No response to voice, but movement or eye opening
to physical stimulation
–5 Unarousable No response to voice or physical stimulation
Table 90.8 Confusion assessment method for the intensive care unit
Features and descriptions Absent Present

I. Acute onset or fluctuating course
A. Is there evidence of an acute change in mental status from the baseline?
B. O
r, did the (abnormal) behavior fluctual during the past 24 hours, that is, tend to
come and go or increase and decrease in severity as evidenced by fluctuations on
the Richmond agitation sedation scale (RASS) or the Glasgow coma scale?
II. Inattention
Did the patient have difficulty focusing attention as evidenced by a score of <8
correct answers on either the visual or auditory components of the attention screening
examination (ASE)?
Contd…
Contd…
III. Disorganized thinking

Is there evidence of disorganized or incoherent thinking as evidenced by incorrect
answers to 3 or more of the 4 questions and inability to follow the commands?
Questions
1. Will a stone float on water?
2. Are there fish in the sea?
3. Does 1 pound weigh more than 2 pounds?
4. Can you use a hammer to pound a nail?
Commands
1. Are you having unclear thinking?
2. Hold up this many fingers. (Examiner holds 2 fingers in front of the patient.)
3. Now do the same thing with the other hand (without holding the 2 fingers in front
of the patient)
(If the patient is already extubated from the ventilator, determine whether the
patient’s thinking is disorganized or incoherent, such as rambling or irrelevant
conversation, unclear or illogical flow of ideas, or unpredictable switching from
subject to subject.)
IV. Altered level of consciousness
Is the patient’s level of consciousness anything other than alert, such as being vigilant
or lethargic or in a stupor, or coma?
Alert: Spontaneously fully aware of environment and interacts appropriately
Vigilant: Hyperalert
Lethargic: Drowsy but easily aroused, unaware of some elements in the environment
or not spontaneously interacting with the interviewer; becomes fully aware and
appropriately interactive when prodded minimally
Stupor: Difficult to arouse, unaware of some or all elements in the environment or
not spontaneously interacting with the interviewer;becomes incompletely aware when
prodded strongly; can be aroused only by vigorous and repeated stimuli and as soon
as the stimulus ceases, stuporous subject lapses back into unresponsive state
Coma: Unarousable, unaware of all elements in the environment with no spontaneous
interaction or awareness of the interviewer so that the interview is impossible even with
maximal prodding
Overall CAM-ICU Assessment (Features 1 and 2 and either Feature 3 or 4 ):yes…No…
Regional Analgesia Techniques

• Epidural analgesia
• Continuous peripheral nerve catheter analgesia.
Epidural Analgesia (Table 90.9)

The advantages of analgesia is reduced incidence of systemic adverse effects like
respiratory depression, improvement of pulmonary function in patients who have
been done upper abdominal and thoracic surgery, preservation of gastrointestinal
function and reduced release of stress hormones due to surgery and trauma thus
reducing the inflammatory response and morbidity and mortality.
Table 90.9 Dose for epidural analgesia
Timing of injection Dose

Initial dose 10–15 mL of a 0.25%–0.125% solution of 0.5% bupivacaine
or
10–15 mL of a 0.1%–0.2% solution of ropivacaine
Continuous infusion 0.0625 or 0.125% bupivacaine at 5–15 mL/hr
or
0.2% ropivacaine at 5–15 mL/hr
Indications
• Thoracic and upper abdominal surgery
• Orthopedic procedures
• Penetrating or blunt thoracic trauma ± rib fracture.
American society of regional anesthesia (ASRA) guidelines should be
followed for patients who are on anticoagulants. In case of sepsis, epidural
analgesia is better avoided due to the risk of infection and hypotension. Either
intermittent or continuous analgesia can be given for epidural analgesia.
Continuous Peripheral Nerve Catheter Analgesia

• Peripheral nerve block can be done both for upper and lower extremities
with ultrasound or peripheral nerve stimulation.
• It can be used for pain relief in both trauma and post surgery.
BIBLIOGRAPHY
1. Anand KJ, Hickey PR. Halothane-morphine combined with high dose sufentanil for
anesthesia and postoperative analgesia in neonatal cardiac surgery. N Engl J Med.
1992;326:1.
2. Banning A, Sjögren P, Henriken H. Pain causes in 200 patients referred to a
multidisciplinary cancer pain clinic. Pain. 1991;45:45.
3. Burckhardt CS, Jones KD. Adult measures of pain: The McGill Pain Questionnaire
(MPQ), Rheumatoid Arthritis Pain Scale (RAPS), Short-Form McGill Pain
Questionnaire (SF-MPQ), Verbal Descriptive Scale (VDS), Visual Analog Scale (VAS),
and West Haven-Yale Multidisciplinary Pain Inventory (WHYMPI). Arthritis Rheum.
2003;49:S96-104.
4. Burton JH, Miner J. Emergency sedation and pain management, 1st edn. 2008.
Canmbridge university publications.
5. Cohen S, Christo P, Moroz L. Pain management in trauma patients. Am J Phys Med
Rehabil. 2004;83(2):142.
6. Dickenson AH. Spinal pharmacology of pain. Br J Anaesth. 1995;75:193.
7. Elliott K, Minami N, Kolesnikov Y, et al. The NMDA receptor antagonists, LY274614
and MK-801, and the nitric oxide synthase inhibitor, NG-nitro-L-arginine, attenuate
analgesic tolerance to the mu opioid morphine but not to the kappa opioids. Pain.
1994;56:69.
8. Hedderich R, Ness TJ. Analgesia for trauma and burns. Crit Care Clin. 1999;15:167.
9. Huskisson EC. Measurement of pain. Lancet. 1974;2:1127-31.
10. Jacob E, Puntillo K. Variability of analgesic practices for hospitalized children on
different pediatric specialty units. J Pain Symptom Manage. 2000;20:59.
11. Jensen MP, Karoly P, Braver S. The measurement of clinical pain intensity: a
comparison of six methods. Pain. 1986;27:117-26.
12. Melzack R. The McGill Pain Questionnaire: Major properties and scoring methods.
Pain. 1975;1:277-99.
13. Monitoring sedation status over time in ICU patients: Reliability and validity of the
Richmond agitation-sedation scale (RASS). JAMA. 2003;289(22):2983-91.
14. Schreiber S, Galai-Gat T. Uncontrolled pain following physical injury as the core-
trauma in post-traumatic stress disorder. Pain. 1993;54:107.
15. Whipple JK, Lewis KS, Quebberman EJ, et al. Analysis of pain management in critically
ill patients. Pharmacotherapy. 1995;15:592.
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288:1765.
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surgical patients. Anesthesiology. 1987;66:729.
CHAPTER
91 Prem Kumar
PATIENT-CONTROLLED ANALGESIA
Patient-controlled analgesia (PCA) is an effective way of administering pain relief

for acute pain. It can be given either through intravenous route (PCA) or epidural
route (PCEA) or peripheral nerve blockade. The advantage of PCA is its efficacy
because the administration is controlled by the patient and thus resulting in more
patient satisfaction, better analgesia, reduced complications compared with
other modes of analgesia. In this chapter, we will discuss the various methods of
PCA, drugs used, and its merits and demerits.
PRE-REQUISITES
• Awake, nonventilated patients.
• Should be educated enough before surgery to understand the method of
administration and its adverse effects in patients used for postoperative pain
relief. Both the patient and the relatives must be taught about the device.
• Strict adherence to operation by the patient and not by proxy.
MECHANICS ABOUT THE DEVICE

Patient-controlled analgesia works on the principle of electronic infusion pump
with a button which should be pressed by the patient when the patient senses pain.
To reduce the incidence of adverse effects due to overdose, the device is enabled
with a feature called lockout interval where the infusion pump is disabled for a
time irrespective of operation of the pain button. This lockout interval differs for
different agents and it is determined by the peak effect of the drug. (e.g. lockout
interval of morphine is 10–20 min).
HOW TO WRITE AN ORDER FOR PCA?

• Loading (bolus) dose (if required)
• Demand dose
• Lockout interval
• Background infusion (if any)
• 1 and 4 hour limit
Chapter 91 Patient-controlled Analgesia 671
Information to be Gathered While Using PCA Pump

• Drug name
• Dose
• Concentration
• Amount of drug administered
• Number of successful and unsuccessful doses
• Breakthrough analgesics administered.
Advantages of PCA
• Superior analgesia compared with other methods
• More patient satisfaction
• Reduced complications
• Minimal effect of pharmacokinetic and pharmacodynamic variability
• Less requirement of nursing care
• Improved respiratory function.
Disadvantages
• Cost
• Possibility of operation error
• Device malfunction (rare)
• No difference found in the hospital or ICU stay compared with other methods
• Higher incidence of pruritus.
Key Points About PCA

• Optimal demand dose should be chosen since it differs for every patient.
Inadequate dose can cause inadequate analgesia and excessive demand
dose results in respiratory depression. Dosages of drugs used for PCA and
patient-controlled epidural analgesia (PCEA) is given in Tables 91.1 and 91.2.
• With the exclusion of background infusion, the incidence of respiratory
depression is less since respiratory depression is common only with the use
of background infusion. Patients who have opioid tolerance like patients
on chronic malignant or non-malignant pain with persistence of pain even
after usual or incremental PCA dose is one of the indication for background
infusion.
• Standard institution guidelines, documentation and monitoring are required
to avoid adverse effects.
• Factors associated with respiratory depression are old age, associated
pulmonary disease, background infusion, concomitant administration of
sedatives.
• Management of side effects of opioid administration like nausea and
vomiting is done by prescribing serotonin or dopamine antagonists. Pruritus
is treated by diphenhydramine and in case of excessive sedation, opioid is
changed.
• Multimodal analgesic approach can reduce the complications associated
with most of the drugs.
Table 91.1 Patient-controlled analgesia dose for intravenous opioids in adults
Drug Continuous Demand dose

concentration infusion (PCA bolus) Lockout interval 4 hour limit
Morphine 1–2 mg/hr 1–2 mg 5–10 minutes 30 mg or
(1 mg/mL) equivalent/hr
Fentanyl 0–50 µg/hr 20–50 µg 5–10 minutes –
(10 µg/mL)
Buprenorphine – 30–100 µg 10–20 minutes –
(30 µg/mL)
Tramadol 0–20 mg/hr 10–20 mg 5–10 minutes –
Table 91.2 Patient-controlled epidural analgesia dose in adults
Continuous Demand dose

Drug concentration infusion (PCA bolus) Lockout interval Maximum limit
Thoracic surgery
0.0625%–0.125% 3–4 mL/hr 2–3 mL 10–15 minutes –
bupivacaine + 5
µg/mL fentanyl
0.1%–0.2% 3–4 mL/hr 2–3 mL 10–20 minutes –
ropivacaine + 5
µg/mL fentanyl
Abdominal and
lower extremity
surgery
0.0625%–0.125% 4–6 mL/hr 3–4 mL 10–15 minutes –
bupivacaine + 2
µg/mL fentanyl
0.1%–0.2% 3–5 mL/hr 2–5 mL 10–20 minutes –
ropivacaine + 2
µg/mL fentanyl
Labor analgesia
0.0625%–0.125% 4–6 mL/hr 3–4 mL 10–15 minutes 25 mL/hr
bupivacaine + 2
µg/mL fentanyl
0.1%–0.2% 4–6 mL/hr 3–4 mL 10–15 minutes 30 mL/hr
ropivacaine + 2
µg/mL fentanyl
Much of the complications associated with epidural and intravenous route

like hypotension, bradycardia and the adverse effects of opioids can be reduced
by the use of continuous peripheral nerve blockade infusions.
Advantages of Peripheral Nerve Block Infusions (Table 91.3)

• Effective for postoperative pain management
• Superior to opioid analgesia
Chapter 91 Patient-controlled Analgesia 673
Table 91.3 Patient-controlled analgesia for peripheral nerve blockade
Drug Continuous Demand dose

Type of block concentration infusion (PCA bolus) Lockout interval
Interscalene 0.125%–0.25% 5–8 mL/hr 2–4 mL 15–20 minutes
block bupivacaine or
0.2% ropivacaine
Femoral block 0.125%–0.25% 5–10 mL/hr – –
bupivacaine or
0.2% ropivacaine
Popliteal 0.125%–0.25% – 5–10 mL 30–60 minutes
sciatic block bupivacaine or
0.2% ropivacaine
Paravertebral 0.125%–0.25% 0.2 mL/kg/hr – –
block bupivacaine or
0.2% ropivacaine
• Reduced incidence of infection

• Reduced incidence of neurological complications
• Facilitates discharge in day care surgery with greater patient satisfaction.
BIBLIOGRAPHY
1. Camu F, Van Aken H, Bovill JG. Postoperative analgesic effects of three demand-dose
sizes of fentanyl administered by patient-controlled analgesia. Anesth Analg. 1998;
87:890.
2. Dawson PJ, Libreri FC, Jones DJ, et al. The efficacy of adding a continuous intravenous
morphine infusion to patient-controlled analgesia (PCA) in abdominal surgery.
Anaesth Intensive Care. 1995;23:453.
3. Etches RC. Respiratory depression associated with patient-controlled analgesia:
A review of eight cases. Can J Anaesth. 1994;41:125.
4. Hudcova J, McNicol E, Quah C, et al. Patient controlled opioid analgesia versus
conventional opioid analgesia for postoperative pain. Cochrane Database Syst Rev.
2006;4:CD003348.
5. Looi-Lyons LC, Chung FF, Chan VW, et al. Respiratory depression: An adverse
outcome during patient-controlled analgesia therapy. J Clin Anesth. 1996;8:151.
6. Macintyre PE. Safety and efficacy of patient-controlled analgesia. Br J Anaesth. 2001;
87:36.
7. Paech MJ. Patient controlled epidural analgesia in obstetrics. Int J Obstet Anesth.
1996;5:115-25.
SECTION
23 AIRWAY MANAGEMENT IN ICU
Chapter 92 Rapid Sequence Induction

Prem Kumar
Chapter 93 Endotracheal Intubation in

Critical Care
Prem Kumar,
Dianitta Devapriya Veronica
Chapter 94 Tracheostomy
A Meenakshi Sundaram
CHAPTER
92 Prem Kumar
RAPID SEQUENCE INDUCTION
Rapid sequence induction (RSI) is an airway management technique to secure the

airway with tracheal intubation as fast as possible to reduce the risk of pulmonary
aspiration and hypoxemia. The risk of pulmonary aspiration is high in patients
who had recent food intake and comes to the emergency department or intensive
care unit (ICU) due to various causes (e.g. head injury) for airway management.
Hence, RSI is done to reduce the incidence of pulmonary aspiration during
endotracheal intubation.
ESSENTIAL COMPONENTS OF RAPID SEQUENCE INDUCTION (TABLE 92.1)

• Preoxygenation
• Administration of rapidly acting intravenous anesthetic agents (e.g.
thiopentone)
Table 92.1 Technique of rapid sequence induction
Preoxygenation with 100% O2 for 3 minutes
Apply cricoid pressure of 10 (Newtons) when patient is awake
Administer intravenous anesthetic agent (e.g. Thiopentone 3–5 mg/kg)
Cricoid pressure increased to 30 N as patient losses consciousness
Administer succinylcholine 2 mg/kg
Omit bag and mask ventilation
Maintaining cricoid pressure, laryngoscopy and orotracheal intubation is done and

cricoid pressure maintained until endotracheal tube cuff is inflated
678 Section 23 Airway Management in ICU
• Rapid acting neuromuscular blocking agents—most commonly used is

succinylcholine
• Application of Sellick’s maneuver (cricoid pressure)
• Omission of bag and mask ventilation during RSI to prevent gastric distension.
In case of hemodynamically unstable patients, ketamine (1–2 mg/kg) or
etomidate (0.2–0.3 mg/kg) can be given. Before the cricoid pressure is released,
the cuff of endotracheal tube is inflated, bilateral air entry checked over both sides
and end tidal carbon dioxide (EtCO2) confirmation is also done. In patients with
cardiac arrest, the technique is modified such that intravenous anesthetic agent
or muscle relaxant is not administered. 10 N (Newtons) approximately equals 1
kg or equal to the pressure which causes pain on application of pressure to nasal
bridge.
INDICATIONS OF RAPID SEQUENCE INDUCTION

• Full stomach patients
• Emergency surgery
• Traumatic head injury with Glasgow coma scale ≤ 8
• Emergency intubations.
CRICOID PRESSURE
The principle behind application of cricoid pressure is that it causes compression
of tracheal and esophageal lumen and thus preventing passive regurgitation of
stomach contents. Positioning is head up position since it has been shown to
reduce rise of intragastric pressure thus reducing the risk of passive regurgitation.
Cricoid pressure can reduce the lower esophageal sphincter tone, cause
difficulty in laryngoscope insertion, reduce the view of larynx, causes difficulty
in introducing the endotracheal tube and produces impediment to application
of external laryngeal manipulation by the assistant to improve laryngeal view
during intubation. If there is vomiting during application of cricoid pressure,
there is chance of esophageal rupture. In that case, low cricoid pressure can be
given to prevent esophageal rupture. Though the application of cricoid pressure
is controversial on the basis of its impediment to intubation and laryngoscopy,
still because of ethical issues, studies could not be done to validate its value.
According to current literature, its use in emergency department and ICU is still
practiced. There is a practice of inserting nasogastric tube before induction to
empty the stomach contents although pulmonary aspiration can still occur
even after emptying the stomach with nasogastric tube. To prevent aspiration
pneumonitis, drugs like H2 receptor antagonists, proton pump inhibitors can
be given increase the pH. This can be prescribed if there is some time before
intubation like obstetric patients, patients with risk of gastroesophaseal reflux
disease (GERD). In patients with trauma and suspected cervical spine injury, RSI
with manual inline stabilization is done for endotracheal intubation.
In case of desaturation, cricoid pressure is released on the basis of risk benefit
ratio, bag and mask ventilation is done. Failed intubation plan should be borne in
mind with all the necessary equipment kept ready prior to induction in patients
who are performed RSI. Laryngeal mask airway, combitube are all alternative
Chapter 92 Rapid Sequence Induction 679
devices useful in failed intubation during RSI. Succinylcholine dose can be

lowered (0.25–1 mg/kg) in critically ill patients since the recovery of spontaneous
ventilation from lower doses is also faster. In patients with anticipated difficult
intubation, obese patients, hemodynamically unstable patients, the usual dose of
1–2 mg/kg is recommended.
ALTERNATIVE TO SUCCINYLCHOLINE–ROCURONIUM?
In patients where there are contraindications to the use of succinylcholine such
as burns, muscular dystrophies, hyperkalemia, open globe injury, massive soft
tissue injuries, rocuronium is the best alternative since it has short onset of action.
Rocuronium, 0.9–1.2 mg/kg is the only nondepolarizing muscle relaxant with
short onset of action (60–90 seconds). Disadvantage is its long duration of action
and the possibility of failed intubation which may end up in airway catastrophe.
BIBLIOGRAPHY
1. Henderson JJ, Popat MT, Latto IP, et al. Difficult Airway Society guidelines for
management of the unanticipated difficult intubation. Anaesthesia. 2004;59:675-94.
2. Hocking G, Roberts FL, Thew ME. Airway obstruction with cricoid pressure and lateral
tilt. Anaesthesia. 2001;56:825-8.
3. Maltby JR, Beriault MT. Science, pseudoscience and Sellick. Can J Anaesth. 2002;
49:443-7.
4. Mellin-Olsen J, Fasting S, Gisvold SE. Routine preoperative gastric emptying is seldom
indicated. A study of 85,594 anaesthetics with special focus on aspiration pneumonia.
Acta Anaesthesiol Scand. 1996;40:1184-8.
5. Neelakanta G, Chikyarappa A. A review of patients with pulmonary aspiration of
gastric contents during anesthesia reported to the Departmental Quality Assurance
Committee. J Clin Anesth. 2006;18:102-7.
6. Smith KJ, Dobranowski J, Yip G, et al. Cricoid pressure displaces the esophagus: An
observational study using magnetic resonance imaging. Anesthesiology. 2003;99:
60-4.
CHAPTER
93 Prem Kumar,
Dianitta Devapriya Veronica
ENDOTRACHEAL INTUBATION
IN CRITICAL CARE
Endotracheal (ET) intubation is one of the common procedures done in intensive

care unit (ICU). The purpose of intubation is to ensure optimal oxygenation and
ventilation in critically ill patients. Usually endotracheal intubation is done in
patients where noninvasive methods of securing airway has failed and in patients
who require immediate airway management due to life-threatening risk factors
(e.g. upper airway obstruction). This chapter discusses the basic anatomy,
indications, preintubation fast-track airway assessment, techniques of airway
management, difficult airway management and complications.
BASIC ANATOMY
The nasopharynx is important with respect to airway. The base of the skull
forms the roof of the nasopharynx, and the soft palate forms the floor. Hence,
the enlargement of adenoids can cause obstruction of upper airway and can get
injured during nasal intubation. In the same way, tonsillar enlargement can cause
impediment in viewing the larynx during laryngoscopy. Larynx is related superiorly
by the hypopharynx and inferiorly continues with the trachea (Fig. 93.1).
The larynx consists of articulating cartilages—thyroid, cricoid, arytenoids,
epiglottic, corniculate and cuneiform cartilages. The cricoid cartilage completely
encircles the airway and is attached to the first tracheal ring by the cricotracheal
ligament. In case of securing the airway by performing a needle cricothyrotomy,
the cricoid cartilage is palpated and the cricotracheal ligament is pierced. The
true vocal cords and space between them is called glottis. All muscles of larynx
are supplied by the recurrent laryngeal nerve except the cricothyroid which is
supplied by the external branch of the superior laryngeal nerve. Glottis is the
narrowest region of the upper airway in an adult whereas cricoid region is the
narrowest in children. The carina is located at T4 level and the angulation of right
main bronchus is less acute than the right making the right side more prone for
endobronchial intubation (Table 93.1).
FAST-TRACK EVALUATION AND AIRWAY ASSESSMENT

BEFORE INTUBATION
In case of emergency, where the need for intubation is immediate, a fast-track
evaluation of the patient and the airway is done to avoid catastrophe. In the
Chapter 93 Endotracheal Intubation in Critical Care 681
Fig. 93.1 Laryngeal view on direct laryngoscopy
Table 93.1 Indications of endotracheal intubation
• Acute airway obstruction

– Traumatic airway injury
– Infection—epiglottitis, laryngotracheobronchitis, retropharyngeal abscess
– Burns causing smoke inhalation
– Laryngeal edema
– Laryngospasm
• Head injury with GCS ≤8
• Drug poisoning
• Respiratory failure—causes of types 1 and 2
– Acute respiratory distress syndrome
– Pulmonary edema
– Obesity hypoventilation syndrome
– Neuromuscular disorders—Guillain Barré syndrome
– Atelectasis
• Cerebrovascular accident
• Cardiac arrest
• Patients who require pulmonary toileting
period of evaluation, the technique of intubation with the least possible trauma
is planned.
The following are examined before induction:
• Head
• Upper airway
• Cervical spine
• Temporomandibular joint
• Dentition.
A faster way of assessing airway before induction is done. An evaluation to do
that is LEMON assessment of airway (Table 93.2).
Table 93.2 LEMON airway assessment
L—Look
E—Evaluate
M—Mallampatti class
O—Obstruction
N—Neck mobility
L—Look for external anatomic features suggestive of difficult airway
E—Evaluate interincisor distance, hyomental distance, distance between thyroid cartilage and floor of mouth
Interincisor distance—should accommodate 3 fingers

Hyomental distance—should accommodate 3 fingers
Thyroid cartilage to floor of mouth distance—should accommodate 2 fingers
M—Mallampati class
Mallampatti class is done to assess the oropharyngeal view. It should be done with the
patient sitting in upright position with protrusion of tongue and without phonation. It has
4 grades. Grade 3 and 4 indicate difficult airway.
Grade 1—faucial pillars, uvula, soft palate, hard palate visible
Grade 2—uvula, soft palate, hard palate visible
Grade 3—base of uvula or none, soft palate, hard palate visible
Grade 4—only hard palate visible
O—Obstruction
Conditions causing obstruction in the airway (e.g. epiglottitis) should be assessed.
N—Neck mobility
Look for adequate neck flexion and extension. Patients with cervical spine collar will have difficulty in
intubation. Normal flexion is 15–25 degree and extension is 75–85 degrees.
ADJUNCTS FOR AIRWAY MANAGEMENT

• Face mask (Fig. 93.2)
• Triple maneuver—head tilt, chin lift, jaw thrust
• Airway—oropharyngeal, nasopharyngeal (Fig. 93.3)
• Bag and mask ventilation
• Laryngeal mask airway (Fig. 93.4)
• Endotracheal tubes.
In this chapter, we will discuss the techniques with respect to endotracheal
intubation (Fig. 93.5).
Equipment Required for Endotracheal Intubation (Fig. 93.6)

• Mask with bag and valve device (Fig. 93.7)
• Oral and nasal airways
• Laryngoscope with different blades—straight and curved (Fig. 93.8)
• ET tubes of various sizes (Table 93.3)
• Stylet, bougies (Fig. 93.9)
• Tape to fix ET tube (Fig. 93.10)
Fig. 93.2 Anatomical transparent silicone face mask
Fig. 93.3 Oropharyngeal airway
• Suction
• Magill forceps (Fig. 93.11)
• Syringe for cuff inflation
• Poppits pillow
• Difficult airway cart
Fig. 93.4 Laryngeal mask airway (LMA)
Fig. 93.5 Position of intubation

Fig. 93.6 Airway equipment required in ICU for airway management
Fig. 93.7 Mask with bag and valve device (adult and pediatric)
Fig. 93.8 Laryngoscope with various size blades
Table 93.3 ET tube size for different ages
Age Internal diameter in millimeter (mm)

Preterm neonate 2.5
Full term 3.0
≤6 years Age/3 + 3.5
7 years and more Age/4 + 4.5
Adult females 7.0–8.0 mm
Adult males 8.0–9.0 mm
Fig. 93.9 Gum elastic bougie for aiding intubation

Fig. 93.10 Endotracheal tubes of various sizes
Fig. 93.11 Magill’s forceps
INTUBATION TECHNIQUES
• General anesthesia with rapid sequence induction
• Local anesthesia
• Awake intubation with flexible fiberoptic bronchoscopy
Most of the patients who require intubation in ED or ICU are patients
who have depressed consciousness with poor GCS. In patients who are prone
for aspiration, rapid sequence induction is done. In awake and alert patients,
sedation with anesthetic agents may be required. In patients who require awake
Table 93.4 Drugs used for endotracheal intubation
Drug Dose Adverse effects Comments

Propofol 1–2 mg/kg Hypotension, Can be used in all patients
propofol infusion who are hemodynamically
syndrome stable
Thiopentone 3–5 mg/kg Hypotension, Reduces intracranial tension
precipitates by reducing cerebral blood
porphyria flow. Hence preferred in
traumatic brain injury
Ketamine 0.5–2 mg/kg Hypertension, Used in hemodynamically
increased ICT unstable patients
Etomidate 0.2–0.3 mg/kg Adrenocortical Can be used in hypotension
suppression
Midazolam 0.02–0.5 mg/kg Hypotension
Muscle relaxants
Succinylcholine 1–2 mg/kg Hyperkalemia, Duration can be prolonged
increased ICT, in liver disease. Used for
phase 2 block rapid sequence induction.
Rocuronium 0.9–1.2 mg/kg Can be used as
an alternative for
succinylcholine in patients
with contraindications for
succinylcholine
intubation, lignocaine is given topically to anesthetize the upper airway (Table

93.4). In cases of emergency, orotracheal intubation is done and is preferred by
most intensivists. But nasotracheal intubation can be done if the intubation is not
an emergency and there are no contraindications for it. Nasotracheal intubation
has the advantage of having better patient tolerability and lesser incidence of
tube kink due to biting by the patient. The intensivist/anesthesiologist who does
the intubation should have the standard monitoring—electrocardiogram (ECG),
noninvasive blood pressure, pulse oximetry, and capnography.
In emergency, intubation is done with rapid sequence induction (RSI). RSI is
discussed in detail in the next chapter.
MANAGEMENT OF DIFFICULT AIRWAY

American Society of Anesthesiologists (ASA) definition for difficult airway is the
clinical situation where conventionally trained anesthesiologist experiences
difficulty with mask ventilation, tracheal intubation or both (Flow chart 93.1).
It can be either anticipated (e.g. orofacial trauma) or unanticipated. In patients
with anticipated difficult airway, awake intubation through various techniques
can be used like direct laryngoscopy after topical anesthesia, intubating LMA,
blind nasal intubation, retrograde intubation, rigid bronchoscopy, lighted
stylet, flexible fiberoptic bronchoscope or surgical airway. Among these, flexible
fiberoptic bronchoscopy is the commonly used technique among awake
intubations.
Flow Chart 93.1 Difficult airway algorithm for unanticipated difficult airway
Suspected Cervical Spine Injury

A trauma patient is always considered to have full stomach and is at risk for
aspiration during induction. The causes of pulmonary aspiration are recent
intake of food or liquid, delayed gastric emptying due to trauma-induced
stress response, swallowed blood from oral or nasal injuries. It is imperative to
administer nonparticulate antacids to a trauma patient before induction if there
is possibility of delay for intubation and the patient is alert with good airway
reflexes. The usual practice is that all blunt trauma victims are considered to have
cervical spine involvement unless proved otherwise. The airway management
in these patients requires attention since the usual laryngoscopy would cause
Fig. 93.12 Manual in-line axial stabilization (MIAS)

for suspected cervical spine injury
movement of cervical joint and thus cause worsening of cervical injury. Thus,
the management in these patients requires manual in-line axial stabilization to
prevent worsening of cervical injury. This technique requires 4 personnel trained
in the procedure. One person to perform mask ventilation, one person to provide
in-line cervical stabilization, one person to give cricoid pressure, one person to
administer drugs (Fig. 93.12). If cervical collar is present, it should be removed
since it will interfere with laryngoscopy. Video laryngoscopes like bullard or
glidescope can be useful in these scenarios. Flexible fiberoptic bronchoscope
can be used for cooperative patients who are devoid of oropharyngeal bleeding,
airway bleeding and secretions and rapid hypoxemia.
CARE OF ENDOTRACHEAL TUBE IN ICU

Securing the ET tube is of prime importance and it is secured with an adhesive
tape fixed to the cheeks. In case of burns patient, a strap is tied to the back of
neck. Adequate suctioning of the ET tube with a separate suction catheter is
done according to need in patients with ET tube to prevent blockade. Suctioning
is done along with ventilation through the suction port to avoid hypoxemia
(closed ventilation suctioning). In case of nonavailability of closed ventilation
system, high FiO2 is kept for few minutes before suctioning. Complications like
hypertension, hypoxemia, cardiac arrhythmias, mucosal damage, and increased
ICT can occur during suctioning. Suction catheters are usually 45–50 cm in length
and to avoid obstruction of the ET tube, the outer diameter of the suction catheter
should be less than half the size of the internal diameter of the endotracheal
tube. The practice of instilling normal saline into the airway before suctioning
to aid secretion removal is not recommended. Cuff pressures are monitored
with manometers and maintained between 15 and 25 mm Hg. Complications of
endotracheal intubation is given in Table 93.5.
Table 93.5 Complications of endotracheal intubation
Cardiac complications
• Tachycardia
• Hypertension
• Bradycardia due to vagal stimulation
During intubation
• Dental injury
• Injury to oral cavity, trachea, larynx
• Arytenoid cartilage dislocation
• Bleeding
• Aspiration
• Spinal cord injury
• Hypoxemia
Sore throat
Vocal cord injury—edema
Hypoglossal nerve injury
Laryngitis
Complications due to ET tube
• Blocking of ET tube due to secretions
• Kinking
• Endobronchial intubation
• Tracheal stenosis
Since the ET tube bypasses the natural orifices, humidification is required

in patients where invasive mechanical ventilation is done. There are two devices
which can be used for humidification in ventilated patients:
1. Heated water bath humidifier—external active source of heat and water is
given.
2. Heat and moisture exchanger filter (HMEF): It passively retains the heat
and humidity, leaving the trachea during expiration and recycles it during
the next inspiration. HMEFs are also known as hygroscopic condenser
humidifiers. HMEFs are nowadays combined with bacterial filters to prevent
infection. Disadvantage is increased resistance which can cause increased
work of breathing.
BIBLIOGRAPHY
1. ATLS for Doctors. Student Manual, 7th edn. Chicago, American College of Surgeons,
2004.
2. Cooper RM, Pacey JA, Bishop MJ, et al. Early clinical experience with a new video
laryngoscope (GlideScope) in 728 patients. Can J Anaesth. 2005;52:191-8.
3. Ehrhart IC, Hofman WF, Loveland SR. Effects of endotracheal suction versus apnea
during interruption of intermittent or continuous positive pressure ventilation. Crit
Care Med. 1981;9:464.
4. Harold Ellis, Stanley Feldman, William harrop Griffith. Anatomy for anaesthetists, 8th
edn. Denmark: Blackwell Publications; 2004.
5. Hurni J-M, Feihl F, Lazor R, et al. Safety of combined heat and moisture exchanger
filters in long-term mechanical ventilation. Chest. 1997;111:686.
6. Landa JF, Kwoka MA, Chapman GA, et al. Effects of suctioning on mucociliary
transport. Chest. 1980;77:202.
7. Majernick TG, Bieniek R, Houston JB, et al. Cervical spine movement during
orotracheal intubation. Ann Emerg Med. 1986;15:417-20.
8. Murphy MF, Walls RM. Manual of Emergency Airway Management. Chicago;
Lippincott Williams and Wilkins; 2000.
9. Rau JL. Airway management. In: Wilkins RL, Stoller JK, Scanlan CL (Eds). Egan’s
Fundamentals of Respiratory Care, 8th edn, St. Louis: Mosby; 2003.p.627.
10. Sackner MA, Landa JF, Greeneltch N, et al. Pathogenesis and prevention of
tracheobronchial damage with suction procedures. Chest. 1973;64:284.
11. Shim C, Fine N, Fernandez R, et al. Cardiac arrhythmias resulting from tracheal
suctioning. Ann Intern Med. 1969;71:1149.
12. Snell RS, Katz J. Clinical Anatomy for Anesthesiologists. Norwalk, CT, Appleton and
Lange, 1988.
13. Turkstra TP, Craen RA, Pelz DM, et al. Cervical spine motion: A fluoroscopic
comparison during intubation with lighted stylet, Glide Scope, and Macintosh
laryngoscope. Anesth Analg. 2005;101:910-5.
14. Wahlen BM, Gercek E. Three-dimensional cervical spine movement during
intubation using the Macintosh and Bullard laryngoscopes, the Bonfils fibrescope and
the intubating laryngeal mask airway. Eur J Anaesthesiol. 2004;21:907-13.
CHAPTER
94 A Meenakshi Sundaram
TRACHEOSTOMY
Tracheostomy is a common procedure done for many medical conditions. It is

one of the most common procedures done in intensive care units.
Tracheotomy: Operative procedure that creates an opening in the trachea.
Tracheostomy: Creation of permanent or semi-permanent opening in the trachea.
Based on the need for tracheostomy, it is broadly classified as:
• Emergency tracheostomy
• Elective tracheostomy.
EMERGENCY TRACHEOSTOMY
Most basic and gold standard procedure in emergency room for upper airway
obstruction is tracheostomy. It is employed when airway obstruction is complete
or almost complete and there is an urgent need to establish the airway where
intubation or laryngotomy are either not possible or feasible in such cases.
Indications
Upper airway obstruction due to:
• Foreign body
• Trauma: External injury of larynx and trachea, trauma due to endoscopies,
especially in infants and children, fractures of mandible or maxillofacial
injuries.
• Infections: Acute laryngotracheobronchitis, acute epiglottitis, diphtheria,
Ludwig’s angina, peritonsillar, retropharyngeal or parapharyngeal abscess,
tongue abscess.
• Laryngeal edema: Due to steam, irritant fumes or gases, allergy (angioneurotic
or drug sensitivity), radiation.
• Bilateral abductor paralysis
• Congenital anomalies: Laryngeal web, cysts, tracheoesophageal fistula,
bilateral choanal atresia
• Malignancies: Benign and malignant neoplasms of larynx, pharynx, upper
trachea, tongue and thyroid.
Prerequisites for Emergency Tracheostomy

• Nonmetallic tracheostomy tube with vent for connecting the ventilator
• Retractors, cricoid hook, tracheal dilator, artery forceps curved and straight
• 2% lignocaine with adrenaline suction, good lighting.
Technique for Emergency Tracheostomy

Whenever possible, endotracheal intubation should be done before tracheostomy.
This is specially important in infants and children. Positioning is supine position
with a pillow under the shoulders for neck extension. Usually anesthesia is not
required for these patients since most of them are either unconscious or it is
emergency. In conscious patients, infiltration is done with 2% lignocaine with
adrenaline or in some patients, general anesthesia with intubation may be
necessary before performing tracheostomy.
Steps of Tracheostomy
• Incision (vertical or horizontal) is made 1 cm below the cricoid cartilage or
halfway between cricoid and sternal notch.
• Retractors are placed, the skin is retracted, and the strap muscles are
visualized in the midline. The muscles are divided along the raphe, then
retracted laterally.
• The thyroid isthmus lies in the field of the dissection. Typically, the isthmus
is 5–10 mm in its vertical dimension, mobilize it away from the trachea
and retract it, then using syringe loaded with 4% lignocaine, the lumen is
punctured and the syringe is aspirated to visualize air bubbles to confirm the
position and 0.5 cc of lignocaine is injected into trachea to reduce the cough
reflex and then place the tracheal incision in the second or third tracheal
ring.
• Tracheostomy tube of appropriate size is introduced after dilating the stoma
with tracheal dilator.
• The position of tube is confirmed by connecting to ambu bag and auscultating
the chest.
• The tube is fixed and secured around the neck.
• The tube cuff inflated at a cuff pressure of 20–25 mm Hg.
• Skin incision should not be sutured or packed tightly as it may lead to
development of subcutaneous emphysema.
• Gauze dressing is placed between the skin and flange of the tube around the
stoma.
ELECTIVE TRACHEOSTOMY
This is a well-planned procedure done in various settings (Table 94.1).
Types of Elective Tracheostomy

It is of two types
1. Therapeutic: To relieve respiratory obstruction, remove tracheobronchial
secretions or give assisted ventilation.
Chapter 94 Tracheostomy 695
Table 94.1 Indications of elective tracheostomy
• Major head and neck surgery (often temporary airway)

• Bypassing upper airway obstruction
• Chronic ventilator dependency
• Relieving OSA
• Eliminating pulmonary dead space
• Management of secretions, including aspiration:
– Inability to cough
- Coma of any cause, e.g. head injuries, cerebrovascular accidents, narcotic
overdose
- Paralysis of respiratory muscles, e.g. spinal injuries, polio, Guillain-Barré
syndrome, myasthenia gravis
- Spasm of respiratory muscles, tetanus, eclampsia, strychnine poisoning
– Painful cough
Chest injuries, multiple rib fractures, pneumonia
– Aspiration of pharyngeal secretions
Bulbar polio, polyneuritis, bilateral laryngeal paralysis
Fig. 94.1 Types of tracheostomy
2. Prophylactic: To guard against anticipated respiratory obstruction or

aspiration of blood or pharyngeal secretions such as in extensive surgery of
tongue, floor of mouth, mandibular resection or laryngofissure.
TYPES OF TRACHEOSTOMY (FIG. 94.1)
High Tracheostomy
It is done above the level of thyroid isthmus. Perichondritis of the cricoid cartilage
and subglottic stenosis are complications of high tracheostomy. Only indication is
carcinoma of larynx because in such cases, total larynx anyway would ultimately
be removed and a fresh tracheostome made in a clean lower area.
Mid-tracheostomy
This is the preferred one. It is done through the 2nd or 3rd ring and would entail
division of the thyroid isthmus or its retraction upwards or downwards to expose
this part of trachea.
Lower Tracheostomy
It is done below the level of isthmus. Trachea is deep at this level and close to
several large vessels and also there are difficulties with tracheostomy tube which
impinge on suprasternal notch.
Tracheostomy Tubes
An ideal tracheostomy tube should be flexible enough to reduce tissue damage,
increase patient comfort and rigid enough to maintain airway. A tracheostomy is
arc-shaped which is called as Jackson curve.
Parts of a Tracheostomy tube

• Outer cannula: This forms the main body of the tube that passes into the
trachea. The inner diameter of outer tube mostly forms the stated size of the
tube.
• Inner cannula: This can be inserted into the outer tube and can be removed
for cleaning purpose.
This tube is longer and narrower than outer tube. It secured in place by
locking it with outer tube (Figs 94.2 and 94.3) (Tables 94.2 and 94.3).
Table 94.2 Types of tracheostomy tubes
• Single lumen tubes

• Double lumen tubes
• Uncuffed tubes
• Cuffed tubes
• Fenestrated tubes
• Adjustable flange tubes.
Table 94.3 Different features of tracheostomy tubes
Manufacturer Material Inner tube Cuffed tube Speaking valve

Portex Polyurethane No Both Yes
Shiley PVC Yes Both Yes
Tracoe Polyurethane Yes Both Yes
Bivona Silicone No Cuffed No
Moore Silastic No Uncuffed No
Negus Silver Yes Uncuffed Yes
CRICOTHYROIDOTOMY/MINITRACHEOSTOMY
It is a procedure of creating a communication between airway and skin through
cricothyroid membrane.
Tracheostomy Tubes
A B
Fig. 94.2A and B Metal Fuller’s tracheostomy tube
A B
Figs 94.3A and B Portex cuffed tracheostomy tube
Types
• Needle cricothyroidotomy
• Open
• Percutaneous.
Advantages of minitracheostomy
• Simplicity
• Relatively bloodless field
• Minimal training required
• Avoids hyperextension of neck in patients with cervical injury.
Cricothyroidotomy in Children
The clear cutoff age for doing cricothyroidotomy in children is unclear. It is
commonly agreed that it is not usually done in children below 12 years. In
young children, membrane is more smaller, larynx is funnel-shaped, rostral and
compliant and hence there are more chances of subglottic stenosis.
Anatomy
Neck kept in neutral or extended position, the thyroid prominence is palpated.
The next big prominence just below it is cricoid cartilage. Just one finger above
cricoid cartilage is a depression, which is cricothyroid membrane.
Surgical anatomy: Entry point is the cricothyroid membrane in the midline below
the level of the vocal cords. The tube enters through the skin, subcutaneous fat,
middle cricothyroid ligament of cricothyroid membrane and subglottic larynx
mucosa.
Needle cricothyroidotomy: Needle size of 12 or 14 gauge is used. It is done only
when there no other options for securing the airway in emergency situations.
Surgical Steps
• Position the patient with the neck extended and exposed.
• Identify the landmarks, thyroid cartilage, cricoid cartilage, cricothyroid
membrane.
• Prepare a sterile field
• Inject 2% lidocaine with 1 in 1,00,000 epinephrine into skin and through the
cricothyroid membrane into airway to anesthetize and suppress cough reflex
• Fix the thyroid cartilage with 1st and 3rd fingers of non-dominant hand and
freely palpate with 2nd finger the cricothyoid membrane.
• With the dominant hand, insert the 14-gauge intravenous cannula attached
to syringe with normal saline directing it caudally at 45°.
• As the needle is advanced, apply negative pressure. Air bubbles will enter
the fluid-filled syringe as the needle enters the membrane and enters the
trachea.
• Advance the cannula and remove the needle.
• Apply jet ventilation at 15 L/minute.
• Auscultate for breath sounds and monitor with pulse oximetry.
Potential Advantages of Tracheostomy Over Tracheal Intubation

• Lesser sedation needed for tube acceptance
• More patient comfort with regard to oral hygiene, mobilization and phonation
• Reduced risk of laryngeal damage due to prolonged intubation
• Reduced airway resistance and respiratory effort
• Shorter duration of weaning from mechanical ventilation
• More effective cough
• Shorter ICU stay.
Percutaneous Dilational Tracheostomy

Percutaneous dilational tracheostomy (PDT) usually requires general anesthesia.
Neuromuscular blockers may be needed.
Instruments Required
• PDT-kit.
• Laryngoscope, intubation tray, equipment for difficult airway should be kept
ready.
• Optional: Fiberoptic bronchoscope.
• Optional: Ultrasound.
Technique
• Patient positioning with neck extended, pillow under the shoulders.
• Direct laryngoscopy done after retracting the ET tube such that the cuff is just
beneath the vocal cords and difficult airway assessed.
• The cricoid and thyroid cartilage are marked. The optimal site of tracheo
stomy is below the lower border of cricoid cartilage corresponding to
second and tracheal cartilage. More proximal placement raises the chance
of subglottic stenosis whereas more distal placement raises the chances of
erosion of great vessels in mediastinum.
• After sterile preparation, local infiltration given along with adrenaline.
• A 8–12 mm horizontal incision made at chosen level. Smaller incision is
made to reduce the amount of bleeding, chance of infection and keeping a
tight-fitting stoma.
• Introduction of guidewire: The cuff of tracheal tube is deflated and trachea is
punctured in midline and guidewire is introduced. Clinical confirmation of
intratracheal placement is done.
• Stomal dilation with one or more dilators possibly with dilating forceps.
• Choice of tracheal cannula is done by clinical judgement.
Rule of Thumb for Selecting the Cannula

• Use adjustable flange for patients with deep seated trachea.
• Use tube wire for patients with chances of tube kinking (short neck, obesity,
caudally placed stoma).
Tracheostomy Care
• Humidification: After the procedure, the normal physiology of the respiratory
tract is altered. Humidifiers are used for patients on tracheostomy tubes for
humidification.
Types of humidifiers:
– Hot-water humidifier
– Cold-water humidifier
– Heat and moisture exchanger
– Nebulization
• Suctioning: Every tracheostomy patient needs adequate suctioning at

appropriate timing for avoiding block by secretions. Things required for
suctioning are suction unit, suction catheter, O2 through t-piece.
Suctioning Technique
Explain the procedure if patient is conscious. The appropriate size catheter is
introduced with the suction kept off. Once the depth needed is reached, suction
unit is switched on and the airway suctioned with oxygen being given through the
tube. Suctioning is done at frequent intervals to avoid block by secretions.
BIBLIOGRAPHY
1. Claudia Russell, Basil Matta. Tracheostomy: A Multiprofessional Handbook. 1st
Edition, Cambridge University Press.
2. Fagan J. Cricothyroidotomy and Needle cricothyroidotomy, 1st edn. University of
Cape Town.
3. Gleeson, Scott Brown’s otorhinolaryngology, Head and Neck surgery, 7th edn.
Butterworth-Heinemann.
4. Paul W Flint, Bruce H Haughey, Valerie J Lund, John K Niparko, Mark A Richardson,
K Thomas Robbins, J Regan Thomas. Cummings otolaryngology Head and neck
surgery, 6th edn. Elsevier Publications.
SECTION
24 TRANSFUSION PRACTICE IN ICU
Chapter 95 Blood Transfusion: Components

and Indications
Prem Kumar
Chapter 96 Complications of Blood Transfusion

Prem Kumar
CHAPTER
95 Prem Kumar
BLOOD TRANSFUSION: COMPONENTS

AND INDICATIONS
Blood transfusion therapy is one of the important interventions done in critically

ill patients to increase hematocrit, correct coagulation abnormalities and optimize
oxygen delivery. Since blood components are associated with adverse effects
due its use, its use is restricted to specific indications. In critical care, anemia,
thrombocytopenia and coagulation abnormalities are all frequent indications for
use of blood component therapy. In this chapter, we will discuss the method of
blood component separation and indications of blood components.
COMPONENT SEPARATION (FLOW CHART 95.1)

Various blood components separated from whole blood are:
• Packed red cells
• Platelets
• Fresh frozen plasma
• Cryoprecipitate
Flow chart 95.1 Blood component separation

704 Section 24 Transfusion Practice in ICU
Table 95.1 Preservatives used in packed red cells
Citrate—anticoagulant
Phosphate—buffer
Dextrose—red cell energy source
Adenine—it allows RBCs to resynthesize adenosine triphosphate (ATP), thus extending the
storage time from 21 days to 35 days
Packed Red Cells

Packed red cells are obtained by removing plasma from whole blood. Usual
volume of packed red cells is 350 mL which is stored at 1–6°C. The hematocrit
value is 40% in whole blood and 70% in packed red cells. Whole blood was used
in the past decade for volume expansion and increasing O2 carrying capacity
but according to recent guidelines, packed red cells can be used for most of
the indications related to whole blood with respect to blood loss, anemia.
Whole blood can be used in severe hemorrhage. Solutions recommended for
administering reconstituted packed red cells are 5% dextrose in half normal
saline, 5% dextrose in 0.9% saline, 0.9% saline with a pH of 7.4. Citrate phosphate
dextrose adenine (CPDA-1) is an anticoagulant preservative added with blood.
Other preservatives that can be used are adsol, optisol. Hypothermia slows the
rate of glycolysis (Table 95.1).
Compatibility
In case of emergency where the patient sustains massive blood loss, it is
permissible to transfuse O-ve packed red cells but the sample should be sent for
grouping before transfusion. But with modern technology, it is possible to obtain
ABO compatibility within 5 minutes and cross matching within 30 minutes.
Storage
On storage, intracellular release of potassium occurs, RBC’s metabolize glucose
to lactate, hydrogen ions accumulate, and plasma pH decreases and many
intensivists believe that prolonged storage is less effective in O2 carrying capacity
than the fresh one. The storage temperatures of 1–6°C stimulates sodium-
potassium pump and hence the RBC loses potassium and gain sodium. Osmotic
fragility increases thus resulting in lysis and there is progressive decrease in RBC
concentrations of ATP and 2,3-DPG. To avoid such complications, storage of
blood in an electrostatic field of 500–3000 V decreases hemolysis and reduces the
decrease in pH.
Other guidelines from various societies—American Society of Anesthesio
logists task force, the British Committee for Standards in Haematology have
recommended that transfusion is generally not indicated when the hemoglobin
concentration is above 10 g/dL but is indicated when it is less than 6–7 g/dL.
They have not mentioned a specific transfusion trigger. But according to recently
published guidelines (Table 95.2), they recommend a restrictive blood transfusion
strategy that is when the hemoglobin level is <7 g/dL for adult trauma and critical
care patients, with the exception of patients with acute myocardial ischemia.
Chapter 95 Blood Transfusion: Components and Indications 705
Table 95.2 Indications of packed red cells
The AABB (American Association of Blood Banks) recommends a restrictive transfusion

strategy.
• Red cell transfusion should be considered at hemoglobin concentrations of ≤7 g/dL
in adult and pediatric intensive care unit patients. Patients should be hemodynamically
stable– class 1 recommendation.
• In postoperative surgical patients, transfusion should be considered at a hemoglobin
concentration of ≤8 g/dL or when there are symptoms (orthostatic hypotension or
tachycardia unresponsive to fluid resuscitation, chest pain, congestive heart failure)—
class 2 recommendation
• In cardiovascular disease, red cell transfusion is considered when hemoglobin is
≤8 g/dL but the evidence is less for its strong recommendation although it can be
considered.
Other indications
• Symptomatic anemia
• Prophylaxis in life-threatening anemia
• Hemorrhage—to restore the O2 carrying capacity
• Exchange transfusion
• Sickle cell disease
• Severe parasitic infection (malaria, babesiosis)
• Severe methemoglobinemia
• Severe hyperbilirubinemia of newborn
Dosage and Administration

ABO group of RBC products must be compatible with ABO group of recipient,
red cells should be serologically compatible with the patient. After therapy, 1 unit
of packed red cells raise the hemoglobin by approximately 1 g/dL or hematocrit
of 3%. This principle holds good only in a patient weighing 70–80 kg. The rate
of transfusion is approximately over 15 minutes and transfusion is completed
within 4 hours. As a general guide, transfusing a volume of 4 mL/kg will typically
give an Hb increase of 1 g/dL. In patients with minor blood loss but ongoing, Hb
should be regularly monitored, after every 2–3 units of red cells. Pediatric red cell
transfusions should be prescribed in milliliters. It may take up to 24 hours for
equilibration of intravascular volume after transfusion.
Processing of RBC’s
• Leukocyte reduction—decrease the risk of febrile nonhemolytic transfusion
reactions, infections and HLA alloimmunization
• Washing is done for removal for residual plasma—decrease the risk of
anaphylactic reactions.
• Irradiation—prevents transfusion associated graft-versus-host disease
(TA-GVHD).
Platelets
Platelet concentrates are obtained by differential centrifugation from freshly
drawn blood or from donors from whom large amount of platelets are obtained
by platelet pheresis techniques. Indications of platelet transfusion is given in
Table 95.3 Indications of platelet transfusion
Hospitalized adult patients with therapy-induced hypoproliferative thrombocytopenia

• Prophylactic transfusion in adults with platelet count of ≤10 × 109/L to reduce the risk
for spontaneous bleeding
• Transfusion up to a single apheresis unit or equivalent. Greater doses are not more
effective, and lower doses equal to one half of standard apheresis unit are equally effective
Adult patients having minor invasive procedures
• Prophylactic platelet transfusion for patients having elective central venous catheter
placement with a preprocedure platelet count of 20 × 109 cells/L
• Prophylactic platelet transfusion for patients having elective diagnostic lumbar puncture
with a preprocedure platelet count of 50 × 109 cells/L
Adult patients having major elective noneuraxial surgery
• Prophylactic platelet transfusion for patients having major elective nonneuraxial surgery
with a preprocedure platelet count of 50 × 109 cells/L
• Platelet transfusion is considered for patients on CPB (cardiopulmonary bypass) who
exhibit perioperative bleeding with perioperative bleeding with thrombocytopenia and
platelet dysfunction
• Routine prophylactic administration of platelets are not recommended in patients on CPB
Adult patients receiving antiplatelet therapy who have intracranial hemorrhage (traumatic
or spontaneous)
• There is no specific recommendation for or against platelet transfusion for patients
receiving antiplatelet therapy who have intracranial hemorrhage
Patients who are not bleeding or having invasive procedures or surgery
• Prophylactic platelet transfusion is done to patients with a platelet count below 10×109
per liter who are not bleeding or having invasive procedures or surgery, and who do
not have any of the following conditions (chronic bone marrow failure, autoimmune
thrombocytopenia, heparin‑induced thrombocytopenia, thrombotic thrombocytopenic
purpura.)
Table 95.3. Platelets play an important role in the initial phase of hemostasis
where platelets adhere by von Willebrand factor (vWF) and adhesive proteins to
the subendothelium. Platelets are the only blood component that is stored under
room temperature and can be stored for 5 days according to current guidelines.
It is stored under room temperature since platelets lose shape and release
their granular contents when refrigerated. Bacterial contamination is common
because of its storage under room temperature and still higher if kept at 20–24°C.
Sepsis from a bacterially contaminated platelet transfusion is the most frequent
infectious complication from any blood product. Any patient who develops fever
within 6 hours of platelet transfusion, sepsis from platelets should be considered.
Platelets are responsible for allergic and nonhemolytic febrile reactions.
Different Types of Platelet Processing

• Apheresis (collecting more platelets from one donor to avoid pooling of
platelets from multiple donors)
• Leukocyte—depleted platelets
• Ultraviolet B–irradiated platelets
Whenever possible, ABO compatible platelets should be administered. Up
to 8 units of platelets, each from a separate donor can be pooled into a single
bag for transfusion and all units should be from the same ABO type. The usual
adult dose is 1 unit/15 kg of body weight. In case of prophylactic transfusions,
Chapter 95 Blood Transfusion: Components and Indications 707
4–6 units of pooled random donor platelets are used. 1 unit of platelet transfusion
increases platelet count by 7000–10,000/mm3 in a patient with 70 kg weight when
checked 1 hour after transfusion. The raise of platelet count may vary according
to associated illness like sepsis, splenomegaly.
Fresh Frozen Plasma

1 unit of fresh frozen plasma (FFP) is the plasma obtained from 1 unit of whole
blood and it contains all plasma proteins. Factors 5 and 8 reduces on storage.
It should be frozen within 8 hours of collection and may provided as frozen or
thawed. 1 unit contains 250 mL and ABO compatibility is done. The administration
of both red cells and FFP is not recommended except in few situations like
massive blood transfusion. It has high-risk of infection like hepatitis B, hepatitis
C, and HIV. Indications of FFP is given in Table 95.4
Dosage
Fresh frozen plasma is given at a volume of 10–15 mL/kg except for reversal
of warfarin where 5–8 mL/kg is sufficient. Usually doses are given to achieve
a minimum of 30% of coagulation factors concentration. 1 unit of FFP raises
coagulation factors by 2–3%.
Cryoprecipitate
Cryoprecipitate is prepared from plasma and it contains fibrinogen, von Willebrand
factor, factor VIII, factor XIII, and fibronectin. Cryoprecipitate is the only adequate
fibrinogen concentrate available for transfusion. It is given ABO compatible.
Indications
• Fibrinogen deficiency
• Disseminated intravascular coagulations (DIC).
Table 95.4 Indications of FFP as recommended by American Society

of Anesthesiologists (ASA) task force
• Replacement of isolated coagulation factor deficiency

• Antithrombin III deficiency
• Reversal of warfarin
• Treatment of thrombotic thrombocytopenia purpura
• Treatment of immunodeficiencies
• Massive blood transfusion
Practice guidelines for use of FFP as recommended by American Association of Blood
Banks (AABB)
• Plasma transfusion is to be considered for patients requiring massive transfusion
• Recommendation is not for or against transfusion of plasma for patients undergoing
surgery in the absence of massive transfusion.
• Indicated for warfarin anticoagulation–related intracranial hemorrhage
• Not indicated for acute pancreatitis, organophosphate poisoning, coagulopathy,
associated with acetaminophen overdose, intracranial hemorrhage after severe closed
head injury in patients without coagulopathy, nonsurgical noncardiac patients in the
intensive care unit
• Can be given for von Willebrand disease or hemophilia A if they do not

respond to DDAVP and recombinant preparations are not available.
Otherwise cryoprecipitate is usually not recommended for these conditions.
• Renal failure associated platelet dysfunction not responding to DDAVP.
Dosage and Administration

• 1 bag will increase fibrinogen concentration by 7–8 mg/dL in a 70 kg patient.
• In case of use in von Willebrand disease or hemophilia, the usual dose is
1 bag per 10 kg of body weight.
• Cryoprecipitate should be administered rapidly and through a filter and the
rate of administration should be at least 200 mL/hour, and infusion should
be completed within 6 hours of thawing.
• Fibrin glue can be prepared from cryoprecipitate for local hemostasis.
BIBLIOGRAPHY
1. British Committee for Standards in Haematology (BCSH) Guideline on the
Administration of Blood Components. August 2012.
2. Carson JL, Terrin ML, Noveck H, Sanders DW, Chaitman BR, Rhoads GG, et al. FOCUS
Investigators. Liberal or restrictive transfusion in high-risk patients after hip surgery.
N Engl J Med. 2011;365:2453-62.
3. Dunne WM, Case LK, Isgriggs L. In-house validation of the BACTEC 9240 blood
culture system for detection of bacterial contamination in platelet concentrates.
Transfusion. 2005;45:1138-42.
4. He´bert PC, Wells G, Blajchman MA, Marshall J, Martin C, Pagliarello G, et al.
A multicenter, randomized, controlled clinical trial of transfusion requirements in
critical care. Transfusion Requirements in Critical Care Investigators, Canadian
Critical Care Trials Group. N Engl J Med. 1999;340:409-17.
5. Jeffrey L Carson, et al. Red blood cell transfusion: A clinical practice guideline from
the AABB. Ann Intern Med. 2012;157:49-58.
6. Lacroix J, He´bert PC, Hutchison JS, Hume HA, Tucci M, Ducruet T, et al. TRIPICU
Investigators. Transfusion strategies for patients in pediatric intensive care units.
N Engl J Med. 2007;356:1609-19.
7. Moore GL, Peck CC, Sohmer PR, et al. Some properties of blood stored in CPDA-1
solution. Transfusion. 1981;21:135.
8. Napolitano LM, Kurek S, Luchette FA, Anderson GL, Bard MR, Bromberg W, et al.
EAST Practice Management Workgroup. Clinical practice guideline: red blood cell
transfusion in adult trauma and critical care. J Trauma. 2009;67:1439-42.
9. Nishiyama T, Hayashi D. Electrostatic field can preserve red blood cells in stored
blood preparations. J Anesth. 2007;21:42-6.
10. Richard M Kaufman, et al. Platelet Transfusion: A clinical practice guideline from the
AABB. Ann Intern Med. 2015;162:205-13.
11. Roback, et al. Evidence-Based Practice Guidelines For Plasma Transfusion.
Transfusion. 2010;50:1227-39.
12. Slichter SJ. Principles of platelet transfusion therapy, In: Hoffman R, Benz EJ, Shattil
SJ, et al (Eds): Hematology Basic Principles and Practice. New York, Churchill-
Livingstone; 1991.pp.1610-22.
13. Valeri CR. Measurement of viable ADSOL-preserved human red cells. N Engl J Med.
1985;312:377.
14. Weigert AL, Schafer AL. Uremic bleeding: pathogenesis and therapy. Am J Med Sci.
1998;316:94-104.
CHAPTER
96 Prem Kumar
COMPLICATIONS OF BLOOD TRANSFUSION
Complications due to transfusion can cause infections, anaphylactic reactions,

electrolyte disturbances, coagulation abnormalities and acid-base disturbances.
Adverse reactions due to transfusion occur in spite of checks. In this chapter,
we will discuss the various complications due to blood component therapy
(Table 96.1).
ADVERSE REACTIONS TO TRANSFUSION

Adverse reactions can occur with mild symptoms and signs in the background
of severe reactions. In the event of an adverse reaction, transfusion should be
immediately stopped and reported to the blood bank.
Certain reactions can be reduced or prevented by filtering, irradiating or

washing blood components. The incidence of viral infections has come down due
to screening although the transfusion reactions and bacterial sepsis continue.
Transfusion Reactions (Table 96.2)
Febrile Nonhemolytic Transfusion Reaction

It is the most common common transfusion reaction occurring after transfusion
of component containing cellular elements. This occurs due to sensitization of
antigens on donor leukocytes, HLA antigens and cytokines; and it usually occurs
within 1 hour of completion of the transfusion. Leukodepletion will reduce the
incidence of these reactions.
Table 96.1 Complication of blood transfusion
Types of complication Comments

Infectious Hepatitis B
Hepatitis C
HIV–1, –2
CMV
Human T-lymphotropic virus (HTLV-II)
Malaria
Babesiosis
West Nile virus
Uncommon infections—syphilis, Chagas’ disease, variant
Creutzfeldt-Jakob disease, parvovirus B19, and severe adult
respiratory syndrome (SARS)
Transfusion reactions Febrile nonhemolytic transfusion reaction
Delayed hemolytic reaction
Transfusion-related acute lung injury (TRALI)
Acute hemolytic reaction
Anaphylactic
Other reactions RBC allosensitization
HLA allosensitization
Graft-versus-host disease (GVHD)
Table 96.2 Types of reactions
Immune mediated Nonimmune mediated

Acute hemolytic transfusion reactions Hypothermia
Delayed hemolytic transfusion reactions Iron toxicity
Febrile nonhemolytic transfusion reactions Electrolyte disturbances
Anaphylactic reactions Hypotension
Allergic reactions Immunomodulation
Graft-versus-host disease (GVHD)
Transfusion-related acute lung injury
(TRALI)
Post-transfusion purpura
Alloimmunization
Acute Hemolytic Transfusion Reactions

Immunemediated hemolysis occurs when the recipient has preformed
antibodies and among these, ABO isoagglutinins are the reason for most of
these reactions. Clinical features include chills, fever, chest and flank pain,
flushing, nausea, hemoglobinemia, hemoglobinuria, hypotension, tachypnea,
tachycardia. Lab investigations include measurement of serum haptoglobin,
lactate dehydrogenase (LDH), and indirect bilirubin levels which are indicative
of hemolysis. Coagulation studies are also done. Error of patient identification
and mislabelling are all causes of reaction and in the blood bank, direct Coombs
test is done. Immune complex resulting from the reaction can cause renal
dysfunction and RBC lysis which, in turn, releases tissue factor which may initiate
DIC. Management of acute hemolytic transfusion reactions is given in Table 96.3.
Chapter 96 Complications of Blood Transfusion 711
Table 96.3 Management of acute hemolytic transfusion reactions
• T erminate the transfusion immediately

• Maintain urine output of 0.5–1 mL/kg/hour by administering IV fluids and diuretics
(furosemide 20–40 mg, mannitol 0.5 g/kg over 10–20 minutes)
• Alkalinization of urine is done by administering bicarbonate of 40–70 mEq. Goal is to
raise urine pH to 8
• Do coagulation studies, serum and urine hemoglobin concentration
• Send the blood bag to blood bank for investigation where direct antiglobulin test is
done. Also to send patient blood and urine.
Delayed Hemolytic Reaction

It can occur due to patients who are previously sensitized to RBC alloantigens
with low antibody levels resulting in negative alloantibody screen. Usually the
alloantibodies are detected in the circulation after 1–2 weeks post-transfusion. No
specific treatment is required for patients where these reactions have occurred.
Anaphylactic and Allergic Reactions

It can occur even with a few milliliter of blood component. Clinical features are
dyspnea, bronchospasm, vomiting, hemodynamic instability, respiratory failure.
Management includes immediate termination of the transfusion, epinephrine
0.5–1 mL of 1:1000 subcutaneously. Steroids may be required. Patients who have
an event of anaphylactic or allergic reactions to any blood component should
be tested for IgA deficiency. Plasma proteins can cause urticarial lesions and it
can be treated by diphenhydramine 50 mg orally or intramuscularly. It can be
prevented by administering diphenhydramine before transfusion. Washing of
cellular components to remove residual plasma can reduce the incidence of this
complication.
Transfusion-related acute lung injury
Transfusion-related acute lung injury (TRALI)—Acute respiratory distress, either
1–2 hours after transfusion or within 6 hours of transfusing the patient and
presents as noncardiogenic pulmonary edema. Clinical features include fever,
dyspnea, fluid in the endotracheal tube, severe hypoxia, bilateral interstitial
infiltrates on chest X-ray. There is absence of left atrial hypertension. TRALI
usually results from the transfusion of plasma although any blood product can
cause it. Pathophysiology is that the anti-HLA antibodies in the donor plasma
binds the recipient leukocytes and gets aggregated in the pulmonary vessels and
causes increased capillary permeability causing pulmonary edema. Management
is mainly supportive and the patient usually recovers within 4–5 days. TRALI is
the leading cause of transfusion-related death.
Graft versus host disease
It is a complication of allogeneic stem cell transplantation where the donor
T lymphocytes recognize the recipient HLA antigens and initiate immune
response. Clinical features include fever, diarrhea, cutaneous eruption,
leukopenia, thrombocytopenia and liver function abnormalities. Irradiation of
blood component can reduce the incidence of this complication. Sepsis is the
cause of death in GVHD.
Nonimmunologic Reactions
ODC Curve
Shift of ODC curve to the left can occur when there is decrease in 2,3 DPG and
thus causing more affinity of oxygen to hemoglobin thus resulting in reduced O2
delivery.
Citrate Intoxication and Hyperkalemia

Citrate toxicity occurs due to binding of calcium by citrate and thus causing
hypocalcemia. Clinical features of hypocalcemia include narrow pulse pressure,
hypotension but the incidence is rare. It can occur in a few situations such as liver
disease, massive blood transfusion, pediatric patients, during liver transplant and
hypothermia.
On prolonged storage of blood, RBC lysis can cause intracellular release of
potassium and it can be as high as 20 mEq/L in blood stored for more than 2
weeks. It requires more than 120 mL/minute for the occurrence of hyperkalemia
which can occur only in massive blood transfusion. Hence, rapid infusion
rate is a risk factor for hyperkalemia although still it is very rare. Management
is administration of 10% calcium gluconate, beta 2-agonists and insulin with
dextrose.
Hypothermia
Administration of blood stored at 4°C and frozen plasma without warmers can
cause of hypothermia resulting in cardiac arrhythmias. Increased warming of
blood can cause RBC lysis. The practice of warming blood in warm water before
administration should be avoided.
Acid-base Disturbances
The pH of the stored blood is acidic because of the addition of preservative which
is acidic hence the pH of blood reduces over prolonged storage. Acidosis is both
metabolic and respiratory, respiratory acidosis is due to the plastic bag from which
the CO2 doesn’t have a way for diffusion although this becomes insignificant after
transfusion because of ventilation by the patient. But on massive transfusion,
citrate gets converted to bicarbonate thus causing metabolic alkalosis.
Coagulation Abnormalities
In case of trauma, coagulation cascade is initiated and may cause consumption
coagulopathy. It is due to the volume of blood given and the duration of
hypotension which determines the coagulopathy. On massive transfusion,
the most common cause of bleeding is due to dilutional thrombocytopenia
rather than DIC. Other causes of bleeding include low factor 5 and 8, hemolytic
transfusion reaction, DIC-like syndrome. Low fibrinogen level suggests DIC-like
syndrome.
Chapter 96 Complications of Blood Transfusion 713
Table 96.4 Lab investigations for diagnosing various transfusion-related infections
Virus Lab test

Hepatitis B Hepatitis B surface antigen (HbsAg)
Hepatitis C Antibodies to HCV and HCV RNA
HIV Antibodies to HIV–1, HIV–1 p24 antigen, and
HIV RNA using NAT
Cytomegalovirus Antibody to CMV
Human T-lymphotropic virus (HTLV) Antibody to HTLV-I and -II
Infectious complications
It can be viral or bacterial. Viral infections cause morbidity and mortality.
Other than the viruses mentioned above in Table 96.4, lab tests for screening
other agents like parasites (malaria, dengue, etc.) are done according to the
geographical incidence and local infection epidemiology.
Bacterial contamination
Usually, bacterial contamination occurs due to platelet since they are stored
at room temperature. The risk of bacterial overgrowth is more with single unit
platelet than apheresis product. Patients infected with bacteria can develop
rapid onset (usually within minutes of transfusion) of fever and chills which
differentiates bacterial contamination from febrile nonhemolytic transfusion
reaction. The end result of bacterial contamination is sepsis. Coagulase-
negative staphylococci, Gram-negative organisms are common. Management
is immediate termination of the transfusion, reporting to blood bank, broad
spectrum antibiotics, supportive treatment and the blood is sent for culture.
Though packed RBC and FFP are not commonly contaminated with bacteria
because of the storage temperature of 1–6°C, still gram-negative organisms like
Pseudomonas, Escherichia, Serratia, Acinetobacter can contaminate the blood
component.
MASSIVE BLOOD TRANSFUSION
Definition
Transfusion of blood more than patient’s blood volume in 24 hours or transfusion
of >10% blood volume in <10 minutes or >50% of blood volume in 4 hours in an
adult. Massive transfusion is given in detail in Chapter 76.
Complications
Hypocalcemia due to citrate, hypothermia, hyperkalemia due to release of
potassium on cell lysis, metabolic alkalosis due to citrate conversion to lactate
and, in turn, to bicarbonate, ARDS, DIC. The most common cause of bleeding
following massive blood transfusion is dilutional thrombocytopenia.
BIBLIOGRAPHY
1. Brohi K, Cohen MJ, Ganter MT, et al. Acute traumatic coagulopathy: Initiated by
hypoperfusion. Ann Surg. 2007;245:812-8.
2. Brubaker DB. Clinical significance of white cell antibodies in febrile nonhemolytic
transfusion reactions. Transfusion. 1990;30:733-7.
3. Cohen ND, Muñoz A, Reitz BA, et al. Transmission of retroviruses by transfusion of
screened blood in patients undergoing cardiac surgery. N Engl J Med. 1989;320:1173.
4. Heddle NM, Kelton JG. Febrile nonhemolytic transfusion reactions. In: Popovsky MA
(Ed): Transfusion Reactions, 2nd edn. Bethesda, MD, AABB Press; 2001.pp.55-62.
5. Kleinman S, Caulfield T, Chan P, et al. Toward an understanding of transfusion-related
acute lung injury: statement of a consensus panel. Transfusion. 2004;44:774-89.
6. Linko K, Tigerstedt I. Hyperpotassemia during massive blood transfusions. Acta
Anaesthesiol Scand. 1984;28:220.
7. Miller RD, Robbins TO, Tong MJ, et al. Coagulation defects associated with massive
blood transfusions. Ann Surg. 1971;174:794.
8. Miller RD. Complications of massive blood transfusions. Anesthesiology. 1973;39:82.
9. Parshuram CS, Jaffe AR. Prospective study of potassium-associated acute transfusion
events in pediatric intensive care. Pediatr Crit Care Med. 2003;4:65-8.
10. Toy P, Popovsky MA, Abraham E, et al. Transfusion-related acute lung injury:
definition and review. Crit Care Med. 2005;33:721-6.
11. Zhou L, Giacherio D, Cooling L, Davenport RD. Use of B-natriuretic peptide as a
diagnostic marker in the differential diagnosis of transfusion-associated circulatory
overload. Transfusion. 2005;45:1056-63.
SECTION
25 FLUID MANAGEMENT
Chapter 97 Perioperative Fluid Balance

Prem Kumar
Chapter 98 Fluid Resuscitation

Prem Kumar
CHAPTER
97 Prem Kumar
PERIOPERATIVE FLUID BALANCE
Understanding fluid balance is vital to the fluid management in perioperative and

critically ill patients admitted in ICU. This chapter deals with the basic physiology
and assessment of fluid balance.
BASIC PHYSIOLOGY OF FLUID BALANCE
Fluid Compartments (Fig. 97.1 and Table 97.1)

Total body water (TBW) constitutes approximately 60% of body weight.
The ions present in ECF are sodium (Na+), chloride (Cl–), bicarbonate (HCO3–)
and relatively little contribution from potassium (K+), magnesium (Mg2+), and
Fig. 97.1 Fluid compartments
Table 97.1 Composition of various fluid compartments
Interstitial space Intracellular

Ion Plasma (mOsm/L) (mOsm/L) (mOsm/L)
Na+ 142 139 14
K+ 4 4 140
Cl–
108 108 4
HCO3– 24 28 10
HPO4 H2PO4– –
2 2 11
Mg +
0.8 0.7 20
Protein 1.2 0.2 4
Total osmolality 301 300 301
718 Section 25 Fluid Management
plasma proteins (albumin). The ions present in ICF are potassium (K+), magnesium
(Mg2+) and phosphates (PO42+). Potassium maintains electroneutrality.
Osmolality is defined as the number of osmoles which determines the osmotic
pressure and is expressed in milliosmoles per kg of water (mOsm/kg). Osmosis
is the net diffusion of water across a selectively permeable membrane from a
region of high water concentration to one that has lower water concentration.
The pressure required to drive this migration is called osmotic pressure. The
osmolal concentration of a solution is called osmolality when the concentration
is expressed as osmoles per kilogram of water and it is called osmolarity when it
is expressed as osmoles per liter of solution.
Water distribution across compartments depends mainly on Na+ and K+
content of each compartment, hence the effective osmolality of each compartment
is determined mainly by the osmotic effect of Na+ and K+ acting across the cell
membrane. Cell membrane is highly permeable to water but less permeable to
sodium and chloride. So water moves across the cell membrane rapidly, so that
the intracellular fluid remains isotonic with the extracellular fluid.
The primary site of exchange of water between interstitial and intravascular
space are the post capillary venules and capillaries. Diffusion is also another
mechanism involved in the exchange of ions. Net filtration of water and ions are
determined by starling’s law which is dependent upon hydrostatic and oncotic
pressure.
Net filtration = Kf x (Pc – Pif – pc + pif)

where,
Kf is the capillary filtration coefficient
Pc is the capillary hydrostatic pressure,
Pif is the interstitial fluid hydrostatic pressure,
pc is the capillary plasma colloid osmotic pressure,
pif is the interstitial fluid colloid osmotic pressure.
Therefore, fluid homeostasis is critical in any perioperative patient since there

are fluctuations in both water and solute balance. Preservation of blood volume
by autoregulation at various systems (especially cellular level and kidneys) thus
maintaining normal circulatory volume and adequate cardiac output is the key
for tissue perfusion. Both volume regulation and regulation of osmolality plays
important role in fluid homeostasis.
Normal Exchange of Fluid and Electrolytes

Normally a person consumes about 1.5–2 liters of water per day. But the daily water
loss is approximately 1 liter in urine, 500 mL as insensible loss (skin and respiratory
system) and 250 mL in stools. In critically ill patients, conditions causing increased
basal metabolic rate and metabolism like fever, hyperventilation, sepsis, etc. can
increase the insensible water loss. Increased sweating can cause loss of water and
electrolytes. Electrolyte homeostasis is maintained by kidneys.
Chapter 97 Perioperative Fluid Balance 719
Table 97.2 Conditions with reduced and normal extracellular volume
Reduced ECF volume Normal ECF volume

1. Hemorrhage—trauma, blood loss 1. Cardiac failure
2. Renal loss of sodium—use of diuretics, diabetes 2. Pulmonary embolism
insipidus, hypoaldosteronism 3. Valvular heart disease
3. Extrarenal loss of sodium—GI loss, third space loss,
respiratory loss
Regulation of Fluid Balance

Effective circulatory volume is based on the regulation of sodium balance and is
dependent on renin angiotensin aldosterone system (RAAS), sympathetic activity,
natriuresis by atrial natriuretic peptide and vasopressin. Sympathetic activation
causes release of catecholamines and regulates vascular resistance and cardiac
output. Reduced renal perfusion causes activation of RAAS, and angiotensin
causes vasoconstriction and Na+ retention by secreting aldosterone. Fluid
balance in the perioperative period requires knowledge about the negative fluid
balance caused by fasting, third space loss, blood loss calculation and allowable
blood loss, vasodilatation caused by anesthetic agents. Fluid management in
perioperative period requires calculation of the volume, choosing the type of
fluid according to the fluid and electrolyte requirement.
Disturbances in Fluid Balance

Surgical patients have fluid disturbances in the intraoperative and postoperative
period, and deficits in the extracellular volume is most commonly seen
(Table 97.2). It can be acute and chronic. Acute volume deficit is associated with
tachycardia, hypotension, oliguria, azotemia. Chronic volume deficits cause
decrease in skin turgor, weight loss, ileus. Volume deficits cause elevation in
blood urea nitrogen levels, hemoconcentration, low urine sodium (< 20 mEq/L),
urine osmolality > serum osmolality. Sodium level cannot be taken as a reliable
marker to reflect volume status since it can be high, normal or even low during
hypovolemia. Common cause of extracellular fluid loss in perioperative surgical
patients are loss of gastrointestinal fluids (nasogastric suction, vomiting, diarrhea,
or fistula), burns, intra-abdominal infections, peritonitis, soft tissue injuries,
burns, prolonged surgery, intestinal obstruction (Table 97.3).
Assessment of Fluid Balance

A feasible and a rational approach has to be formulated according to the resources
available. Based upon this, the following approach is useful for assessment of
fluid balance in perioperative period:
• History
• Clinical assessment
• Monitoring and diagnosing the cause of fluid imbalance.
Table 97.3 Electrolyte composition of GI fluids and sources of losses

in the perioperative period
Source of loss Na+ K+ HCO3– Cl–

Gastric fluid (e.g. vomiting) 50–80 5–15 – 100–120
Duodenum (e.g. fistula) 130–140 5–10 10–40 70–100
Pancreatic fluid (e.g. fistula) 120–140 5–10 90–100 50–90
Biliary (e.g. fistula) 130–150 5–10 30–50 80–110
Ileal (e.g. fistula) 100–130 5–10 20–40 80–100
Colon (obstruction, colostomy, diarrhea) 50–70 20–40 20–40 30–50
Sweat (e.g. hypermetabolism) 20–50 5–10 – 40–60
History
1. Comorbid illness
2. Hydration and volume status of the preoperative period.
3.
4.
Clinical assessment is done in terms of hemodynamics—heart rate,

blood pressure. Tissue and organ perfusion in terms of urine output, intact
consciousness, mental function and capillary refilling time.
Chapter 97 Perioperative Fluid Balance 721
Monitoring can be done both by routine monitors or in case of critically ill

patients, advanced hemodynamic monitoring is done to indirectly know the
intravascular volume status with cardiac filling, heart function, and end-organ
perfusion (lactate). In patients with hypovolemia, anesthetic drugs and stress
response secondary to surgery and pain cause derangements in blood pressure
and heart rate. Invasive beat to beat blood pressure monitoring, central venous
pressure, cardiac filling pressures with transesophageal echocardiography, mixed
venous oxygen tension (SvO2), pulmonary artery catheterization are all done to
know the static hemodynamic parameters. Pulse pressure variation, stroke volume
variation are all dynamic parameters done for hemodynamic assessment. In the
past, fluid boluses were given as challenge to see the hemodynamic response and
management is done thereafter according to the response but nowadays fluid
challenge is said to be obsolete and dynamic tests with volume challenge without
administering fluids are done with PLRT (passive leg raising test). It is clear
from studies that incorrect and improper fluid management results in increased
morbidity and mortality.
BIBLIOGRAPHY
1. F Charles Brunicardi. Schwartz›s Principles of Surgery, 8th edn. McGraw-Hill
publications; 2004
2. Ganong WF. Review of Medical Physiology, 21st edn. McGraw-Hill publications; 2003.
3. Guyton and Hall. Textbook of Medical Physiology, 11th edn. 2006. Elsevier
publications.
4. Lobo DN, Macafee DA, Allison SP. How perioperative fluid balance influences
postoperative outcomes. Best Pract Res Clin Anaesthesiol. 2006;20:439-55.
5. Miller RD. Miller’s Anesthesia, 7th edn. Elsevier publications; 2009.
6. Starling EH. On the absorption of fluids from the connective tissue spaces. J Physiol.
1896;19:312-26.
7. Taylor AE. Capillary fluid filtration: Starling forces and lymph flow. Circ Res. 1981;
49:557-75.
CHAPTER
98 Prem Kumar
FLUID RESUSCITATION
Fluid management is vital in both postoperative and critically ill patients in ICU
since fluid homeostasis are required to maintain adequate tissue and organ
perfusion. The aim of fluid therapy in postoperative and critically ill patients is
to maintain an effective circulatory volume to produce adequate cardiac output
while avoiding fluid overload. Maintaining an optimal fluid balance is quite
challenging since it is difficult to measure the end points of optimal fluid balance.
In this chapter, we will discuss the principles of fluid therapy in postoperative
and critically ill patients along with details of crystalloids and colloids and fluid
management for various specific conditions.
FLUID MANAGEMENT IN PERIOPERATIVE PATIENTS

Perioperative patients require maintenance fluids to replace the ongoing losses
of water and electrolytes under normal physiological conditions. Apart from this,
replacement fluid therapy is given for deficits resulting from bleeding, third space
loss, GI loss, sweating and loss associated with open surgical site.
Maintenance Fluid Therapy

Maintenance fluid therapy is administered to replace the ongoing losses of water
and electrolytes under normal physiologic conditions and is calculated based on
the standard ongoing loss in an adult weighing 70 kg which is 30–35 mL/kg/day.
Maintenance fluid is calculated according to the 4–2–1 rule till the patient is
fasting (Table 98.1).
Table 98.1 4–2–1 rule
For the 1st 10 kg 4 mL/kg/hr

For the next 10 kg (11–20 kg) Add 2 mL/kg/hr
For weight >20 kg Add 1 mL/kg/hr
Maintenance fluid is administered with isotonic crystalloids with the

calculated volume of fluids. For example, maintenance fluid requirement for a
60 kg patient is calculated here: 40 mL/hr + 20 mL/hr + 40 mL/hr = 100 mL/hr.
Chapter 98 Fluid Resuscitation 723
For the 1st 10 kg 4 mL/kg/hr–40 mL/hr

For the next 10 kg (11–20 kg) Add 2 mL/kg/hr–20 mL/hr
For weight >20 kg Add 1 mL/kg/hr–40 mL/hr
Replacement Fluid Therapy (Table 98.3)

The purpose of administering replacement fluids in the perioperative period is
correcting the current existing deficit along with ongoing water and electrolyte
loss. It is usually given for deficits resulting from bleeding, third space loss, GI
loss, sweating and loss associated with open surgical site. Total fluid deficit due to
the former enumerated causes can’t be calculated like maintenance fluid, hence
the fluid therapy is arbitrarily done by clinical assessment (hemodynamics, pulse
volume, capillary refilling), measured fluid loss, and plasma Na+ which is not a
reliable estimate for intravascular volume although it can estimate water balance.
The choice of fluid administered for this purpose is based on the clinical
condition or scenario causing the loss, volume of fluid lost and electrolyte
disturbance. The Table 98.2 depicts the choice of fluid for various clinical
scenarios.
Table 98.2 Choice of fluid in certain clinical conditions
Clinical condition causing loss Choice of fluid

Blood loss Replace 1 mL of blood loss with 3 mL of balanced, isotonic
crystalloid solution or 1 mL of colloid solution/blood
Third space loss, bile, pancreas, Replace with balanced isotonic crystalloid solutions
and small bowel losses
Gastric and colonic losses Replace with 5% dextrose and ½ normal saline with
30 mEq KCl/L
Profuse sweating (e.g. fever) Replace with 5% dextrose and ¼ normal saline with
5 mEq KCl/L
Table 98.3 Key elements in the fluid management of perioperative patients
Preoperative period Intraoperative period Postoperative period

• P reoperative • F luid management • C orrection of volume deficit in the
evaluation of includes preoperative and intraoperative
volume status calculation of period
and electrolyte loss with respect • Correction of ongoing loss, third
abnormality and its to blood loss, space loss along with maintenance
correction anesthetic therapy
• Third space loss drugs causing • All specific GI loss should be replaced
should be corrected vasodilatation, with the appropriate fluid
preoperatively in third space loss, • Initial fluid of choice is isotonic
patients having ongoing loss crystalloids followed by dextrose with
burns, intestinal • Correction of half normal saline in the 2nd or the
obstruction, and third space 3rd postoperative day in case there is
severe soft tissue loss secondary contraindication for enteral nutrition
injuries to abdominal • In case of difficulty in ascertaining
• Administration of surgeries where the volume deficit, advanced hemo
maintenance fluids bowel is exposed dynamic monitors are used to guide
with 4–2–1 rule fluid therapy
Fig. 98.1 Classification of intravenous fluids
Fluid resuscitation is guided by the reversal of signs of volume deficit like

return of hemodynamics to normal, maintenance of adequate urine output
(0.5–1 mL/kg/hour), and correction of base deficit. In conditions where patients
do not respond or fail to get corrected of their volume deficit (e.g. renal failure,
cardiac failure), they require advanced hemodynamic monitoring in the
intraoperative and postoperative period.
Intravenous Fluids
Intravenous fluids are broadly classified into crystalloids and colloids (Fig. 98.1).
The choice of fluid administered depends on the electrolyte abnormality and
the volume status. Crystalloids are aqueous solutions of inorganic and small
organic molecules with or without glucose. Colloids are homogeneous non-
crystalline substances containing large molecules especially proteins or large
glucose polymers. Depending upon the concentration of solute and osmolality,
crystalloids can be divided into isotonic, hypotonic, and hypertonic solutions
but colloids with the capacity of containing large molecules remain in the
intravascular space for a long time and maintain plasma colloid on cotic pressure
than crystalloids and hence act as volume expanders.
Crystalloids
Crystalloids can be classified into balanced and unbalanced solutions. Crystalloids
are nontoxic, cost-effective and generally safe since there is no incidence of allergic
reactions. Balanced solutions contain physiologic electrolyte composition and
buffers resembling plasma unlike unbalanced solutions. Isotonic crystalloids are
preferred in perioperative period and ICU. Disadvantage of isotonic crystalloids
is its reduced ability to stay longer in the intravascular space since sodium is the
predominant ion present in most of the isotonic crystalloids and Na+ equilibrates
over the whole ECF compartment and only ¼th of the administered crystalloid
solution remains intravascular. Hence, in case of replacement of blood loss with
isotonic crystalloids, 1: 3–4 times the volume of crystalloids has to be replaced
for the intravascular blood loss. The intravascular half-life of crystalloids is
20–30 minutes. The choice of the fluid is based upon the electrolyte composition
especially Na+, K+, and Cl– and its buffering capacity. Hypertonic 3% saline is
administered in the treatment of severe symptomatic hyponatremia. 3% to
7.5% saline can be given for resuscitation of patients in hypovolemic shock but
should be administered slowly through a central vein catheter. Along with
colloids, hypertonic saline can be used for severe hemorrhage—this concept is
called small volume resuscitation. In cases of severe hyponatremia, plasma Na+
concentration should be corrected slowly at a rate <10 mEq/L/day to avoid central
pontine myelinolysis. Rate of correction should not exceed 15 mEq/L/day.
Complications due to administration of crystalloids: Normal saline causes non
anion gap hyperchloremic metabolic acidosis on administration of large volumes.
Other isotonic crystalloids like ringer lactate contains lactate which gets converted
to HCO3– which may result in metabolic alkalosis and since it contains potassium,
it should be cautiously used in patients with renal disease or in patients prone for
hyperkalemia. Ringer lactate should not be coadministered with blood products
or certain drugs like thiopentone since the presence of calcium in ringer lactate
will precipitate these agents. In spite of administering 2–3 liters of crystalloids,
if there is poor response of hemodynamics, colloids are added. Composition of
various crystalloids is given in Table 98.4.
Colloids
Colloids are homogeneous noncrystalline substances containing large
molecules especially proteins or large glucose polymers. Colloids remain in the
Table 98.4 Composition of various crystalloids
Glucose
Fluid Na+ K+ Cl– (g/L) Buffers Ca2+ Mg2+ pH Osmolality
Normal 154 154 6.0 308
saline (NS)
Ringer 130 4 109 Lactate 28 3 6.5 274
lactate (RL)
Plasmalyte 140 5 98 Acetate 27 3 7.4 294
Gluconate 23
5% Dextrose 50 4.5 252
10% Dextrose 100 505
50% Dextrose 500 2530
5% Dextrose 77 77 50 5.0 406

with ½ NS
5% dextrose
with ¼ NS
3% Hypertonic 513 513 1026
saline
7.5% Hyper 1284 1284 6.0 2568
tonic saline
Table 98.5 Composition of various colloids
Colloid Sodium (meq/L) Molecular Weight Osmolality

Albumin 5% 130–150 70,000 300
Albumin 25% 130–150 70,000 1500
Hetastarch 154 4,50,000 310
Dextran 40 154 40,000 308
Dextran 70 154 70,000 308
intravascular space for a long time than crystalloids because of its large molecular
weight. Its intravascular half-life is 3–6 hours. Colloids can be used for patients
with hemorrhagic shock in case of delay in arrival of blood and in patients
where hypovolemia is present with severe hypoalbuminemia (e.g. burns).
Most of the colloids are manufactured in isotonic electrolyte solutions. Almost
all the colloids interfere with blood typing and cross matching. Blood-derived
colloids are albumin, synthetic colloids are dextran, hydroxyethyl starch, gelatin.
Composition of various colloids is given in Table 98.5.
Human Albumin
It is the purified form of human plasma and is available as 5% and 25%.
Albumin has been used in the past for patients with hypovolemic shock, burns
or hypoalbuminemia but according to recent studies, it is shown that albumin
administration for such indications have not improved the outcome compared
with crystalloids, hence considering the cost of albumin, its use is restricted only
to specific indications. It use has been shown to maintain the plasma oncotic
pressure for distribution of fluids. The incidence of allergic reactions is less
compared with other colloids.
Dextran
It is synthesized from sucrose and it comes in 2 formulations—Dextran 40 and
70. Dextran molecules <50 KD are eliminated by the kidneys and the specific
indication is improving the microcirculation by reducing blood viscosity
and improving rheology. Useful for increasing perfusion of microvascular
anastomoses in perioperative period. Maximal daily dose is 1.5 g/kg. Dextran
induces dose dependent hyperfibrinolysis and decrease in vWF and associated
factor VIII (VIII:c) which can cause bleeding. It has to be cautiously used in
renal failure. Dextran 70 is used for volume expansion and Dextran 40 is used for
improving microcirculation. It can cause anaphylactic reactions.
Gelatin
Gelatin is produced by degradation of bovine collagen. The molecular weight of
gelatin is 30 kD with a concentration of 3.5–5.5%. Gelatin is excreted unchanged
by the kidneys and by the reticuloendothelial system. It requires higher volume
for adequate volume expansion. Hemostasis can be impaired by gelatin which
causes impairment in fibrin polymerization and dysfunction of coagulation

factors. They have increased risk of transmitting prion diseases and gelatin has
the highest incidence of anaphylactic reactions among all the colloids.
Hydroxyethyl Starch (HES)

Hydroxyethyl starches are modified polysaccharides similar to glycogen and
derived from amylopectin and cleaved by amylase. Various preparations of
starch are hetastarch, tetrastarch, pentastarch and available as 3% and 6%
solution. Small molecules are rapidly excreted by kidneys and large molecules
are hydrolyzed by α-amylase before elimination. Plasma half-life increases with
increase in molecular weight. HES is nonantigenic and anaphylactic reactions are
less.
BIBLIOGRAPHY
1. Alderson P, Bunn F, Lefebvre C, et al. Human albumin solution for resuscitation and
volume expansion in critically ill patients. Cochrane Database Syst Rev. 2004;(4):
CD001208.
2. de Jonge E, Levi M. Effects of different plasma substitutes on blood coagulation:
A comparative review. Crit Care Med. 2001;29:1261-7.
3. Dubick MA, Bruttig SP, Wade CE. Issues of concern regarding the use of hypertonic/
hyperoncotic fluid resuscitation of hemorrhagic hypotension. Shock. 2006;25:321-8.
4. F Charles Brunicardi. Schwartz’s Principles of Surgery, 8th edn. 2004. McGraw-Hill
Publications.
5. Finfer S, Bellomo R, Boyce N, et al. A comparison of albumin and saline for fluid
resuscitation in the intensive care unit. N Engl J Med. 2004;350:2247-56.
6. Goldwasser P, Feldman J. Association of serum albumin and mortality risk. J Clin
Epidemiol. 1997;50:693-703.
7. Guyton, Hall. Textbook of Medical Physiology, 11th edn. Elsevier publications; 2006.
8. Jacob M, Chappell D, Rehm M. Clinical update: Perioperative fluid management.
Lancet. 2007;369:1984-6.
9. Laxenaire MC, Charpentier C, Feldman L. Anaphylactoid reactions to colloid plasma
substitutes: incidence, risk factors, mechanisms. A French multicenter prospective
study. Ann Fr Anesth Reanim. 1994;13:301-10.
10. Niemi TT, Suojaranta-Ylinen RT, Kukkonen SI, Kuitunen AH. Gelatin and hydroxyethyl
starch, but not albumin, impair hemostasis after cardiac surgery. Anesth Analg. 2006;
102:998-1006.
11. Roberts JS, Bratton SL. Colloid volume expanders: Problems, pitfalls, and possibilities.
Drugs. 1998;55:621.
12. Ronald D Miller. Miller’s Anesthesia, 7th edn. Elsevier publications; 2009.
13. Waters JH, Gottlieb A, Schoenwald P, et al. Normal saline versus lactated Ringer›s
solution for intraoperative fluid management in patients undergoing abdominal
aortic aneurysm repair: An outcome study. Anesth Analg. 2001;93:817-22.
SECTION
26
CARDIOPULMONARY
RESUSCITATION
Chapter 99 Basic Life Support

Prem Kumar
Chapter 100 Advanced Cardiac Life Support

Prem Kumar
Chapter 101 Cardiac Arrest in Special

Situations
Prem Kumar
CHAPTER
99 Prem Kumar
BASIC LIFE SUPPORT
INTRODUCTION
Basic life support (BLS) is the cornerstone for resuscitating a patient with
sudden cardiac arrest and stroke. It constitutes 4 things—early recognition
of cardiac arrest, activation of emergency response system (ERS), early CPR
cardiopulmonary resuscitation (CPR), and rapid defibrillation. If resuscitation
is done outside the hospital, paramedical personnel use automated external
defibrillator (AED) for BLS. AED’s are present in most of the public places in
order to resuscitate a patient with sudden cardiac arrest. AED correctly assesses
heart rhythm, allowing the rescuer who is not trained with cardiac arrhythmias to
correctly defibrillate the patient. This chapter deals with the basic life support as
recommended by American Heart Association 2010 guidelines.
Sudden cardiac arrest can be:
• In or out of hospital
• Witnessed or unwitnessed
• Cardiac or noncardiac cause.
Recognizing cardiac arrest is difficult for a lay person, hence if a lay person
sees a person unresponsive, the lay person should immediately activate the ERS
and start CPR. The reason for poor survival in patients with sudden cardiac arrest
is the delay to start CPR. Hence, early chest compression is the critical component
of CPR and it should not be delayed. Recommendation is to push hard and push
fast for chest compressions but insertion of advanced airway and defibrillation
should not delay or interrupt compressions. Rapid defibrillation is the best
predictor of successful resuscitation following VF/VT-induced sudden cardiac
arrest. The reduction in the duration between cardiac arrest and defibrillation
has improved survival in patients sustaining cardiac arrest both in and out of
hospital. Adult chain of survival is given in Table 99.1
Key changes from 2005 to 2010 AHA recommendations:
• Early recognition of cardiac arrest which is based on unresponsiveness and
absence of normal breathing.
• Look, listen and feel has been removed from algorithm
• Encouraging chest compression only CPR
• Change of BLS sequence from ABC to CAB
732 Section 26 Cardiopulmonary Resuscitation
Table 99.1 Adult chain of survival
The adult chain of survival is the universal strategy followed for successful resuscitation
and follow-up of postcardiac arrest. The following are the links for the chain of survival:
• Early recognition of cardiac arrest and activation of the emergency response system
• Early CPR emphasizing chest compressions
• Rapid defibrillation
• Effective advanced life support
• Integrated postcardiac arrest care
• De-emphasis for pulse check is recommended for healthcare providers.

Healthcare providers should not check pulse for >10 seconds and lay person
is not advised to check pulse.
• More importance is given to high quality CPR [compressions of adequate
rate (at least 100/min) and depth (at least 5 cm)], allowing full chest recoil
between compressions, minimizing interruptions in chest compressions
and avoiding excessive ventilation).
PHYSIOLOGY OF CARDIOPULMONARY RESUSCITATION

There are two mechanisms of cardiac output associated with chest compressions:
1. Cardiac pump mechanism
2. Thoracic pump mechanism.
Cardiac Pump Mechanism

Cardiac pump mechanism is based on the mechanism that chest compression
causes ejection of blood from the ventricles due to compression between the
sternum and vertebral column. On performing echocardiography during CPR,
there was reduction in ventricular volumes on the LV and RV, closure of mitral
and tricuspid valves and ejection of blood into great vessels indicating the cardiac
pump mechanism.
Thoracic Pump Mechanism

Chest compression produces increase in intrathoracic pressure which equalizes
the intravascular pressure within the thorax. There is venous collapse at the
thoracic inlet and the arterial system being resistant to collapse transmits blood
into extrathoracic vessels. The arteriovenous difference thus allows forward blood
flow into the extrathoracic vessels. During increase in intrathoracic pressure,
pulmonary valve is closed, mitral and aortic valves are open during chest
compression indicating the thoracic pump mechanism. Vigorous cough causes
increased intrathoracic pressure and it sustains consciousness during VF/VT
cardiac arrest and increases forward blood flow-cough CPR.
Chapter 99 Basic Life Support 733
ADULT BASIC LIFE SUPPORT SEQUENCE (FLOW CHART 99.1)
Immediate Recognition and Activation of

the Emergency Response System
If an unresponsive patient is seen, the bystander has to tap the patient for his
responsiveness and if the patient is unresponsive, ERS is activated and if the
patient does not have normal breathing or gasping, the patient is considered to
have cardiac arrest and CPR is started immediately. Pulse should not be checked
by the lay rescuer before starting CPR. In case of healthcare provider, he should
not check the pulse for more than 10 seconds (Fig. 99.1 and Flow chart 99.2),
Flow chart 99.1 Adult basic life support sequence
Fig. 99.1 Rescuer specific cardiopulmonary resuscitation strategies

Flow chart 99.2 Adult basic life support for healthcare providers
Early defibrillation is the best predictor for survival in patients sustaining cardiac
arrest. When more than 1 rescuer is present, one rescuer should start chest
compression and the other one should activate the ERS and get an AED as soon
as possible. Once the AED arrives, AED is turned on and the AED prompts are
followed.
SEQUENCE OF ADULT BASIC LIFE SUPPORT SKILLS

Chest compression should be given with the patient kept on a firm surface. Hence,
it is better to keep a back board on the bed before chest compression in order to
give high quality CPR though there is limited evidence of its use. Rescuer should
keep the heel of one hand on the middle of the patient’s chest which corresponds
to the lower half of sternum and other heel of the other hand is kept on the top of
Table 99.2 Early cardiopulmonary resuscitation
Chest compressions Rescue breaths

• Chest compressions are done by • Lay rescuer can give only chest
application of compression over the compressions in case of hesitation to
lower-half of sternum give mouth to mouth rescue breaths
• Compressions increase cardiac output • Trained rescuer can deliver rescue
by direct compression of the heart and breaths by mouth to mouth or bag
increasing intrathoracic pressure mask to provide ventilation and
• Compression rate should be atleast oxygenation
100/min and the depth should be • Deliver each rescue breath over
atleast 5 cm with minimal interruption 1 second
during compressions • Sufficient tidal volume to produce
• Compression-ventilation ratio of 30:2 visible chest rise is given on delivering
is recommended for adults rescue breaths
the first and it should be overlapped and parallel. Compressions are given at a rate
of 30:2 with at least 100/minute and depth of at least 5 cm and the chest should
be allowed to recoil completely after compression (Table 99.2). Incomplete recoil
during CPR is associated with increased intrathoracic pressure which causes
decreased coronary, myocardial and cerebral perfusion. The compression rate
refers to the speed of compressions, not the actual number of compressions
delivered per minute. The number of chest compressions delivered per minute
is an important determinant of return of spontaneous circulation (ROSC) and
intact neurological status. After 1 minute of CPR, fatigue is common and after
2 minutes or 5 cycles of CPR, switching of compressors is done. Interruptions
should not exceed for >10 seconds.
Once the advanced airway is in place, chest compressions are given
continuously without interruptions and breaths are given at a rate of 8–10/minute
(1 breath every 6–8 seconds).
AIRWAY MANAGEMENT (TABLE 99.3)

Head tilt–chin lift maneuver is done to open up the airway, and in case of
suspected cervical spine injury, jaw thrust is given instead of head tilt–chin lift.
It has been shown from studies that the cardiac output is approximately 25–30%
of normal and hence oxygen uptake and carbon dioxide delivery to the lungs
are also reduced and hence a low tidal volume of approximately 6–7 mL/kg
(500–600 mL) is sufficient for effective oxygenation and ventilation during CPR.
Excessive ventilation is deleterious since it increases intrathoracic pressure and
impedes the venous return to the heart and causes reduced cardiac output.
The routine use of cricoid pressure is not recommended since it was found to
impede ventilation and delay the placement of advanced airway.
Special Situations
• Acute coronary syndromes
• Drowning
• Stroke
Table 99.3 Methods of ventilation
Mode of ventilation Comments

Mouth-to-mouth Open the victim’s airway, pinch the victim’s nose, and create an
breathing airtight mouth-to-mouth seal
Take a regular breath and give 1 breath over 1 second
Mouth-to-barrier Can be used in case of hesitation to do mouth-to-mouth breathing
device breathing
Mouth-to-nose and Mouth-to-nose ventilation is given if ventilation through the
mouth-to-stoma patient’s mouth is not possible and mouth to stoma rescue breaths
ventilation is given in case of a patient with tracheal stoma
Bag and mask Bag and mask device with an oxygen reservoir and oxygen
inlet is used to allow delivery of high oxygen concentrations.
Disadvantage is gastric insufflation
Bag and mask ventilation is done when there are ≥2 rescuers.
The rescuer should use an adult reservoir (1–2 L) bag to deliver
approximately 600 mL tidal volume and oxygen is supplemented
with FiO2 >40% with minimum flow rate of 10–12 L/minute
Supraglottic airway Recommended devices are LMA, esophageal-tracheal
combitube and the King airway device. Acceptable alternative to
bag and mask ventilation.
Endotracheal tube Usual standard of airway in ICU but it needs more expertize and
should be done by professionals for in hospital cardiac arrest.
• Foreign body obstruction

• Hypothermia.
Acute Coronary Syndromes

Early recognition, diagnosis and treatment of acute coronary syndrome improves
the survival in these group of patients. The classic symptoms are chest discomfort,
shortness of breath, sweating, nausea, and lightheadedness and the symptoms
last more than 15 minutes. Immediate advice to chew aspirin (160–325 mg) is
given. If the patient has a STEMI on ECG, it is better to immediately shift the
patient for PCI and the survival is improved if the transport is <30 minutes and
initial contact to balloon time is <90 minutes. Oxygen supplementation is given
and nitroglycerine can be given for patients with chest discomfort and suspected
ACS provided the patient is hemodynamically stable and does not have inferior
wall or right ventricular infarction. Intravenous morphine is administered for
persistent chest pain.
Drowning
The most important consequence of submersion is hypoxia, hence in drowning
victims the guidelines recommends individualization of the sequence according
to the presumed cause. CPR is done in ABC sequence in drowning victims
owing to the hypoxic nature of the arrest. Prompt initiation of rescue breathing
increases the victim’s chance of survival. When the victim is taken from the water,
the rescuer should open the airway, check for breathing and in case there is no
breathing, 2 rescue breaths should be given. Chest compressions are given after
rescue breaths. Chest compressions are difficult to perform in water and the
maneuvers of relieving foreign body obstruction is not recommended and in fact
causes more complications and delay in CPR. The most important determinant
of outcome is the duration and severity of hypoxia.
Stroke
Early recognition, activation of EMS, immediate shifting to a tertiary center, and
early administration of fibrinolytic therapy (within a few hours) to indicated
patients improves outcome. Clinical features include sudden numbness or
weakness of the face, arm, or leg, especially on one side of the body; trouble
speaking or understanding; sudden trouble seeing in one or both eyes; loss of
balance or severe headache, dizziness.
Foreign-body Airway Obstruction

Most of the cases of obstruction occurs in children while playing or eating and is
usually witnessed and immediate intervention has very good outcome. Foreign
bodies can cause either mild or severe obstruction. Usually it is either witnessed
or the patient clutches the neck showing the classic choking sign. In case of mild
obstruction, allow the patient to cough. In case of severe obstruction, attempts are
done to relieve the obstruction. Signs of severe obstruction are difficult respiration,
silent cough, stridor and an unresponsive victim. In case of responsive adults and
children ≥1 year of age, back blows, chest thrusts and abdominal thrusts were all
proved to be effective. Abdominal thrusts are recommended for children <1 year
since it may cause injury. For obese patients and pregnant patients, chest thrusts
should be given since it is difficult to encircle the hands around the abdomen. In
case of an unresponsive victim, the rescuer should carefully place the patient on
the ground, activate the EMS and start CPR. Chest thrusts can be done and the
rescuer should look for an object in the victim’s mouth each time when he opens
the airway and remove the foreign body if found. Finger sweep can be done but is
harmful to the rescuer and not recommended.
Hypothermia
Cardiopulmonary resuscitation is immediately started if the patient is found
unresponsive and to prevent further heat loss, the victim’s wet clothes are
removed. The victim is insulated from cold and also ventilated with warm
humidified oxygen. The victim is immediately shifted to a hospital as fast as
possible. In case of VF/VT, patient is delivered shocks. Passive warming can be
used in out of hospital cardiac arrest.
Monitoring Cardiopulmonary Resuscitation

Chest compression rate, depth, ventilation rate, chest recoil and end tidal CO2
were used to guide CPR performance but still real-time CPR prompting and
feedback technology such as visual and auditory prompting devices can improve
the quality of CPR. Partial pressure of end-tidal carbon dioxide (Petco2) is useful in
the confirmation of placement of ET tubes in the trachea and also for monitoring
the quality of CPR. It should be >10 mm Hg for a high quality CPR. In cases of low
pulmonary blood flow, Petco2 is not reliable to differentiate between esophageal
and tracheal intubation. In that case, esophageal detector device is useful. The
rapid increase in Petco2 can be used as an evidence of return of spontaneous
circulation.
BIBLIOGRAPHY
1. Berg RA, et al. Adult Basic Life Support: 2010 American Heart Association Guidelines
for Cardiopulmonary Resuscitation and Emergency Cardiovascular Care. Circulation.
2010;122:S685-S705.
2. Berg RA, Kern KB, Hilwig RW, Berg MD, Sanders AB, Otto CW, et al. Assisted
ventilation does not improve outcome in a porcine model of single-rescuer bystander
cardiopulmonary resuscitation. Circulation. 1997;95:1635-41.
3. Christenson J, Andrusiek D, Everson-Stewart S, Kudenchuk P, Hostler D, Powell J,
Callaway CW, Bishop D, Vaillancourt C, et al. Chest compression fraction determines
survival in patients with out-of-hospital ventricular fibrillation. Circulation.
2009;120:1241-7.
4. Deshmukh HG, Weil MH, Gudipati CV, et al. Mechanism of blood flow generated
by precordial compression during CPR. I. Studies on closed chest precordial
compression. Chest. 1989;95:1092.
5. Le May MR, So DY, Dionne R, Glover CA, Froeschl MP, Wells GA, Davies RF, Sherrard
HL, Maloney J, et al. A citywide protocol for primary PCI in ST-segment elevation
myocardial infarction. N Engl J Med. 2008;358:231-40.
6. Redberg RF, Tucker KJ, Cohen TJ, et al. Physiology of blood flow during cardiopulmo
nary resuscitation. A transesophageal echocardiographic study. Circulation. 1993;
88:534.
7. Redding JS. The choking controversy: critique of evidence on the Heimlich maneuver.
Crit Care Med. 1979;7:475-9.
8. Rumball CJ, MacDonald D. The PTL, Combitube, laryngeal mask, and oral airway:
a randomized prehospital comparative study of ventilatory device effectiveness
and cost-effectiveness in 470 cases of cardiorespiratory arrest. Prehosp Emerg Care.
1997;1:1-10.
9. Sasson C, Rogers MA, Dahl J, et al. Predictors of survival from out-of-hospital cardiac
arrest: a systematic review and metaanalysis. Circ Cardiovasc Qual Outcomes.
2010;3:63-81.
10. Soroudi A, Shipp HE, Stepanski BM, Ray LU, Murrin PA, Chan TC, et al. Adult foreign
body airway obstruction in the prehospital setting. Prehosp Emerg Care. 2007;11:25-9.
11. Valenzuela TD, Roe DJ, Cretin S, et al. Estimating effectiveness of cardiac arrest
interventions: a logistic regression survival model. Circulation. 1997;96:3308-13.
12. Von Goedecke A, Bowden K, Wenzel V, et al. Effects of decreasing inspiratory times
during simulated bag-valve-mask ventilation. Resuscitation. 2005;64:321-5.
CHAPTER
100 Prem Kumar
ADVANCED CARDIAC LIFE SUPPORT
INTRODUCTION
As a follow on from basic life support, almost all patients necessarily require
advanced cardiac life support (ACLS) for interventional follow-up care.
ACLS requires training and expertise and it is done in hospital by intensivists,
anesthesiologists, and physicians. ACLS is a required skill in ICU, ED, and
operation theaters. Latest ACLS training is one of the important predictors for
proper management of patients with cardiac arrest. Interventions are aimed
at preventing cardiac arrest, treating cardiac arrest and improving outcome in
patients who achieve return of spontaneous circulation (ROSC) after cardiac
arrest (Table 100.1).
Key changes from 2005 to 2010 AHA recommendations:
• High quality cardiopulmonary resuscitation (CPR) is emphasized for cardiac
arrest (Chest compressions of at least 100/minute and 5 cm, allowing
complete chest recoil after each chest compression, minimizing interruptions
between chest compressions and avoiding excessive ventilation).
• Increased emphasis is given for physiologic monitoring to improve
quality of CPR and to detect ROSC. Continuous waveform capnography
is recommended for confirming endotracheal tube placement and for
monitoring CPR quality. If PETCO <10 mm Hg, improve the quality of CPR.
2
Table 100.1 Interventions for prearrest/cardiac arrest/after return

of spontanceous circulation
Interventions for
preventing cardiac arrest
Airway management
Ventilation support } For respiratory failure
Treatment of bradyarrhythmias and tachyarrhythmias
Interventions for treatment Immediate recognition of cardiac arrest
of cardiac arrest Activation of ERS
Early CPR
Rapid defibrillation
Advanced airway management
Physiologic monitoring
After ROSC Postcardiac arrest care for improved survival and
neurological outcome
• Atropine is not recommended for routine use in the management of PEA/

asystole.
• Chronotropic drug infusions are recommended as alternative to pacing in
unstable symptomatic bradycardia.
• Adenosine is used in the initial management of stable undifferentiated
regular monomorphic wide-complex tachycardia.
ADJUNCTS FOR AIRWAY MANAGEMENT

The purpose of ventilation in cardiac arrest patients is to maintain adequate
oxygenation and to eliminate CO2. Both systemic and pulmonary perfusion
are reduced in patients with cardiac arrest, hence less than normal minute
ventilation is sufficient for maintaining ventilation perfusion ratio. 100% O2 can
be used when available.
The airway adjuncts that can be used for resuscitation of patients with cardiac
arrest are:
• Oropharyngeal airway
• Nasopharyngeal airway
• Supraglottic airway devices—Laryngeal mask airway, laryngeal tube,
combitube (esophageal-tracheal tube)
• Endotracheal tube.
Oropharyngeal airways are useful as an aid in delivering ventilation with bag
and mask and for avoiding tongue fall in unconscious patients. Nasopharyngeal
airways are useful in patients where there is airway obstruction with the patient
clenching the jaw. In patients who have known or suspected basal skull fracture or
severe coagulopathy, nasopharyngeal airway is avoided. Although the timing of
advanced airway is not specific, studies have shown that advanced airway secured
within 5 minutes improves survival although it was not associated with improved
ROSC. In achieving airway control, a backup strategy for ventilation should be on
mind. Once the advanced airway is placed, confirmation of placement is done by
bilateral auscultation, visible chest rise and by capnography.
Insertion of supraglottic airway device does not require interruption of chest
compressions or laryngoscope for visualization of cords unlike endotracheal
intubation. During CPR, supraglottic airway is a reasonable alternative to bag
and mask ventilation and endotracheal intubation. Esophageal-tracheal tube has
advantage of less risk of aspiration, and more reliable ventilation compared with
bag and mask ventilation. Laryngeal tube is more compact and less complicated
for insertion than combitube. Laryngeal mask airway gives a reliable means of
ventilation than the face mask but the disadvantage of LMA is that LMA does not
offer full protection against aspiration.
Endotracheal intubation should be done by only trained personnel since it
causes delay and interruptions during chest compressions. Frequent training is
required for those who perform endotracheal intubation. Continuous waveform
capnography is recommended as the most reliable method of confirming and
monitoring correct placement of an endotracheal tube. Other devices used for
confirming placement are exhaled CO2 detectors and esophageal detector device
(EDD). EDD can be used if capnography is not available. After placement of an
advanced airway, the compressor should continue chest compressions without
Chapter 100 Advanced Cardiac Life Support 741
pauses for ventilation. Ventilation rate should be given at a rate of 1 breath

every 6–8 seconds (8–10 breaths/minute) and both the compressor and the
ventilator should switch roles every 2 minutes. During intubation, interruption
of chest compression should not exceed more than 10 seconds. Indications for
endotracheal intubation are absence of protective airway reflexes and inability to
ventilate the patient using bag and mask. Advantages of ET tube is that it provides
a route for delivery of high O2 concentration, protects airway form aspiration,
facilitates delivery of selected tidal volume, alternative route of drug delivery for
some drugs, most reliable airway among all airway devices. ET tube should be
secured with a tape and continuously monitored with capnography. Automatic
transport ventilators can be used if available. Suction devices can be either
installed or portable and is used for clearing respiratory secretions. The installed
suction unit should provide airflow of >40 L/minute at the end of the delivery
tube and a vacuum of >300 mm Hg when the tube is clamped.
MANAGEMENT OF ADULT CARDIAC ARREST

Cardiac arrest can be due to four rhythms (Table 100.2):
1. Ventricular fibrillation (VF)
2. Pulseless ventricular tachycardia (VT)
3. Pulseless electrical activity (PEA)
4. Asystole.
Survival of patients with cardiac arrest rests with high quality CPR and
rapid defibrillation within minutes of cardiac arrest and integrated postcardiac
arrest care. Diagnosing and treating the underlying cause of cardiac arrest is the
cornerstone of managing cardiac arrest (Flow chart 100.1 and Fig. 100.1). Apart
from CPR, defibrillation is the only therapy which increases survival in patients
having VF/VT. If the patient achieves ROSC, postcardiac arrest care is started
immediately to prevent cardiac arrest and for improved neurological function.
Cardiopulmonary Resuscitation Quality

• Push hard (≥2 inches [5 cm]) and fast (≥100/min) and allow complete chest
recoil
• Minimize interruptions in compressions
Table 100.2 Definition of cardiac arrest rhythms
Rhythm Definition
VF Disorganized electrical activity with lack of generation of significant forward
blood flow
VT Organized electrical activity of ventricular myocardium with lack of generation
of significant forward blood flow
PEA Group of organized electrical rhythms with lack of mechanical ventricular
activity or mechanical ventricular activity that is insufficient to generate a
clinically detectable pulse
Asystole Absence of detectable ventricular electrical activity with or without atrial
electrical activity
Flow chart 100.1 Algorithm for management of adult cardiac arrest
• Avoid excessive ventilation

• Rotate compressor every 2 minutes
• If there is no advanced airway, compression–ventilation ratio of 30:2 is given
Fig. 100.1 Rhythm-based management of cardiac arrest
• Quantitative waveform capnography

If Petco2 <10 mm Hg, attempt to improve CPR quality
• Intra-arterial pressure.
If relaxation phase (diastolic) pressure <20 mm Hg, attempt to improve CPR
quality.
Return of Spontaneous Circulation (ROSC)

• Pulse and blood pressure
• Abrupt sustained increase in Petco2 (typically ≥40 mm Hg)
• Spontaneous arterial pressure waves with intra-arterial monitoring.
Shock Energy
• Biphasic: Manufacture recommendation (e.g. initial dose of 120–200 J); if
unknown, use maximum available. Second and subsequent doses should be
equivalent, and higher doses may be considered.
• Monophasic: 360 J.
Drug Therapy
• Epinephrine IV/IO dose: 1 mg every 3–5 minutes
• Vasopressin IV/IO dose: 40 units can replace first or second dose of
epinephrine
• Amiodarone IV/IO dose: First dose: 300 mg bolus. Second dose: 150 mg.
Advanced Airway
• Supraglottic advanced airway or endotracheal intubation
• Waveform capnography to confirm and monitor ET tube placement
• 8–10 breaths per minute continuous chest compressions.
Reversible Causes
• Hypovolemia • Tension pneumothorax
• Hypoxia • Tamponade, cardiac
• Hydrogen ion (acidosis) • Toxins
• Hypo-/hyperkalemia • Thrombosis, pulmonary
• Hypothermia • Thrombosis, coronary
Defibrillation
If VF/VT terminated by a shock recur later, subsequent shocks are delivered at the
previously successful energy level. Doing CPR while a defibrillator is made ready
for use is strongly recommended for all patients in cardiac arrest.
Drug Therapy (Tables 100.3 and 100.4)

A vasopressor can be given when there is persistent VF/pulseless VT after at
least 1 shock and 2-minute CPR period. The goal of administering vasopressor in
VF/VT is to increase myocardial blood flow during CPR and achieve ROSC. Though
the optimal timing of vasopressor is not well established, usually it is given when
a shock fails to generate a perfusing rhythm as to increase the myocardial blood
flow before the next shock but vasopressors could theoretically cause deleterious
effects if the patient is given vasopressor after achieving ROSC. Amiodarone can be
considered when VF/VT is unresponsive to CPR, defibrillation, and vasopressor
therapy. Lignocaine is an alternative to amiodarone. Magnesium sulfate is used
for torsades de pointes (Polymorphic VT with prolonged QT interval).
The goal of administering vasopressor in PEA/asystole is increasing
myocardial and cerebral blood flow. The use of atropine for PEA/asystole is not
Table 100.3 Role of medications in cardiac arrest
Drug Comments
Epinephrine α adrenergic stimulation increase coronary and cerebral perfusion
pressure.
β stimulation is controversial since it can increase myocardial work and
reduce subendocardial perfusion.
Dose: 1 mg dose of IV/IO epinephrine every 3–5 minutes for adults.
Vasopressin • Nonadrenergic peripheral vasoconstrictor
• It causes coronary and renal vasoconstriction
• Studies have not shown any advantage over epinephrine
Dose: Vasopressin 40 units IV/IO may replace either the first or second
dose of epinephrine.
Atropine Routine use of atropine for PEA/asystole is not recommended.
Amiodarone • Has action on sodium, potassium, and calcium channels
• It has α and β adrenergic blocking properties
• Given for VF/VT unresponsive to shock, CPR and vasopressor
Dose: Initial dose of 300 mg IV/IO followed by 1 dose of 150 mg IV/IO.
Lignocaine Lignocaine can be considered if amiodarone is not available.
Dose: Initial dose is 1–1.5 mg/kg IV. If VF/pulseless VT persist, additional
doses of 0.5–0.75 mg/kg IV administered at 5–10 minute intervals to a
maximum dose of 3 mg/kg.
Magnesium Indicated in torsades de pointes.
sulfate Dose: 1–2 g diluted in 10 mL of 5% dextrose.
Calcium Routine administration of calcium is not recommended.
Soda Routine administration is not recommended. Bicarbonate can be beneficial
bicarbonate to patients with pre-existing severe metabolic acidosis, hyperkalemia, or
tricyclic antidepressant overdose.
Dose: 1 mEq/kg
Table 100.4 Doses and details of drugs and cardioversion/defibrillation
Synchronized cardioversion
Initial recommended doses
• Narrow regular: 50–100 J
• Narrow irregular: 120–200 J biphasic or 200 J monophasic
• Wide regular: 100 J
• Wide irregular: Defibrillation dose (NOT synchronized)
Adenosine IV dose
First dose: 6 mg rapid IV push; follow with normal saline flush
Second dose: 12 mg if required
Antiarrhythmic infusions for stable wide—QRS tachycardia
• Procainamide IV dose: 20–50 mg/minute until arrhythmia gets suppressed,
hypotension ensues, QRS duration increases >50%, or maximum dose 17 mg/kg is
given. Maintenance infusion: 1–4 mg/minute Avoid if there is prolonged QT or CHF.
• A miodarone IV dose: First dose: 150 mg over 10 minutes. Repeat as needed if VT
recurs.
Follow by maintenance infusion of 1 mg/min for first 6 hours.
• Sotalol IV dose: 100 mg (1.5 mg/kg) over 5 minutes. Avoid if prolonged QT.
recommended since it does not have any therapeutic benefit. The reversible
causes of cardiac arrest should be identified and corrected.
Return of Spontaneous Circulation after Cardiac Arrest

If ROSC occurs after resuscitation, postcardiac arrest care is started and
identification along with treatment of the precipitating causes of cardiac arrest
is done to prevent recurrent arrest. Importance is given for the diagnosis and
treatment of causes like hypoxemia, hypotension and STEMI. Therapeutic
hypothermia is initiated if the patient is comatose.
Monitoring Cardiopulmonary Resuscitation

Chest compression rate, depth, ventilation rate, chest recoil and end tidal CO2 were
used to guide CPR performance but still real-time CPR prompting and feedback
technology such as visual and auditory prompting devices can improve the quality
of CPR. Partial pressure of end-tidal CO2 (Petco2) is useful in the confirmation of
placement of ET tubes in the trachea and also for monitoring the quality of CPR.
It should be >10 mm Hg for high quality CPR. Normal Petco2 = 35–40 mm Hg and
if ventilation is constant, Petco2 correlates with cardiac output. Persistent low
Petco2 values (<10 mm Hg) during CPR in intubated patients are an indication
that the ROSC is unlikely. In cases of low pulmonary blood flow, Petco2 is not
reliable to differentiate between esophageal and tracheal intubation. In that case,
esophageal detector device is useful. The rapid increase in Petco2 can be used
as an evidence of return of spontaneous circulation. Arterial relaxation (diastolic
pressure) should be >20 mm Hg since this is close to aortic relaxation pressures
during CPR. Changes in central venous oxygen saturation (ScvO2)reflect changes
in oxygen delivery by means of changes in cardiac output. ScvO2 monitoring is
an indicator of cardiac output and oxygen delivery during CPR. Pulse oximetry
and arterial blood gas analysis is not reliable. Echocardiography can be used
in the diagnosis of treatable causes like pericardial tamponade and help in the
diagnosis and treatment.
Access for Delivering Parenteral Medications

• Peripheral venous drug administration is done along with 20 mL bolus of
intravenous fluid to facilitate drug delivery into central circulation.
• IO access is done in case of difficulty in achieving IV access.
• Central venous line either internal jugular or subclavian vein can be
cannulated during cardiac arrest. Advantage is shorter drug circulation time
and can be used for monitoring ScvO2. Disadvantage is that it interrupts CPR.
• If IV or IO access cannot be established, lignocaine, epinephrine, vasopressin
can be administered by endotracheal route during cardiac arrest but the
absorption is slow. The usual dose administered via ET tube is 2–2.5 times
the recommended IV dose. The drug is diluted with 5–10 mL of sterile water
or normal saline and administered.
Flow chart 100.2 Algorithm for management of bradycardia
Other Therapies and its use in Cardiac Arrest

Empirical fibrinolytic therapy can be considered in patients who have or is
presumed to have cardiac arrest due to pulmonary embolism. Electrical pacing is
not routinely used for patients with cardiac arrest due to any rhythm.
Precordial Thump
Precordial thump can be considered for termination of witnessed monitored
unstable ventricular tachyarrhythmias when a defibrillator is not immediately
ready for use but that should not delay CPR and shock.
Algorithm for the management of bradycardia (Flow chart 100.2) and

tachycardia (Flow chart 100.3) is given below. Etiology of narrow and wide QRS
complex tachycardia is given in Table 100.5.
Flow chart 100.3 Algorithm for management of tachycardia
Table 100.5 Causes of narrow and wide QRS complex tachycardia

Narrow–QRS-complex (SVT) tachycardias (QRS Wide–QRS-complex tachycardias (QRS
< 0.12 second), in order of frequency ≥ 0.12 second)
• Sinus tachycardia • Ventricular tachycardia (VT) and
• Atrial fibrillation ventricular fibrillation (VF)
• Atrial flutter • SVT with aberrancy
• AV nodal reentry • Pre-excited tachycardias [Wolff-
• Accessory pathway—mediated tachycardia Parkinson-White (WPW) syndrome]
• Atrial tachycardia (including automatic and • Ventricular paced rhythms
re-entry forms)
• Multifocal atrial tachycardia (MAT)
• Junctional tachycardia (rare in adults)
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CHAPTER
101 Prem Kumar
CARDIAC ARREST IN SPECIAL SITUATIONS
INTRODUCTION
Cardiac arrest occurring during special situations requires certain changes in
the resuscitation. This chapter deals with the following special conditions—
anaphylaxis, pregnancy, pulmonary embolism, morbid obesity, trauma, hypo
thermia, asthma, electrolyte disturbances, drowning, electric shock/lightening
strike, percutaneous coronary intervention (PCI), cardiac tamponade, cardiac
surgery.
ANAPHYLAXIS
Anaphylaxis is a severe, life-threatening, generalized or systemic hypersensitivity
reaction involving IgG and IgE. It is characterized by rapidly developing, life-
threatening problems involving the airway, breathing and circulation.
Basic Life Support Modifications

• Airway should be secured rapidly and should not be delayed because of
anticipated risk of developing oropharyngeal or laryngeal edema.
• Intramuscular adrenaline should be given on the anterolateral aspect of the
middle third of thigh since it gives high peak blood concentration. Absorption
and achieving plasma drug concentration of subcutaneous adrenaline is
slower than intramuscular route especially in patients with shock.
• Adrenaline should be administered in all patients with signs of systemic
allergic reactions like hypotension, airway swelling, or difficulty breathing
and the dose of adrenaline is 0.2–0.5 mg IM of 1:1000 concentration. It is
repeated every 5–10 minutes in case of lack of clinical improvement. For
basic life support, adrenaline is given though auto injectors. In patients
with anaphylactic cardiac arrest, the use of adrenaline autoinjector is
recommended if it is available.
Advanced Cardiac Life Support Modifications

• Potential for difficult airway is present in patients who develop airway
symptoms, hence a plan for advanced airway management including
surgical airway is recommended.
Chapter 101 Cardiac Arrest in Special Situations 751
• In patients not responding to vasopressors, aggressive fluid resuscitation

with isotonic crystalloids is given to raise the blood pressure.
• If an intravenous line is in place, intravenous adrenaline is a reasonable
alternative to IM route for patients with anaphylactic shock.
• If patients are not in cardiac arrest but in anaphylactic shock, IV adrenaline
is given at a dose of 50–100 µg/kg but hemodynamic monitoring should be
done. Infusion of IV adrenaline (5–15 µg/min) can be used as an alternative
to bolus dose in patients who are not in cardiac arrest.
• Alternative vasopressors like vasopressin, norepinephrine, methoxamine,
and metaraminol can be considered in patients with cardiac arrest due to
anaphylaxis who does not respond to adrenaline.
• Antihistamines, inhaled β-2 agonists and corticosteroids can be considered
in patients in cardiac arrest.
PREGNANCY
Although pregnant patients are predominantly young, still their outcome is poor
after cardiac arrest. There are 2 potential patients in the resuscitation of pregnant
patient—mother and fetus. The best chance for fetal survival is the survival of the
mother. The rescuers should be aware of the physiological changes in pregnant
patient.
Key Interventions to Prevent Arrest

• Place the patient in full left lateral position to relieve the aortocaval
compression produced by the uterus.
• Give 100% O2 and to establish IV line above the diaphragm.
• Systolic blood pressure of <100 mm Hg or <80% of baseline is defined as
maternal hypotension and should be treated with crystalloids or colloids and
vasopressors (ephedrine).

• Manual left uterine displacement in the supine position is done to relieve
the aortocaval compression. Manual uterine displacement is done by 2 hand
technique from the left side of the patient or 1 hand technique from the right
side of the patient.
• If the former technique is not successful and a wedge is available, a left lateral
tilt of 30o is given using a wedge to support the thorax and the pelvis.
• Airway management is difficult in pregnant patients owing to the left lateral
tilt and also the altered upper airway anatomy with reduced pulmonary
reserve (↓ FRC and ↑ O2 demand). Therefore, the risk of desaturation
and aspiration is higher. Hence, optimal use of bag mask ventilation with
suctioning along with preparation for advanced airway placement is critical
in the airway management of a pregnant patient with cardiac arrest.
• Tidal volume can be reduced owing to reduced lung capacity.
• Chest compression should be done slightly higher on the sternum than the
usual position to adjust for the elevation of diaphragm.

• Because of the altered upper airway anatomy, there is a risk of failed
intubation in pregnant patients which can also be a cause of morbidity and
mortality during anesthesia, hence a difficult airway cart should be kept
ready and difficult airway management should be done in case of difficult
airway.
• Bag and mask ventilation with 100% O2 should be done before intubation.
• Dosages of various drugs used for cardiac arrest in pregnant patients are the
same dose that is used for any adult cardiac arrest patient.
• Defibrillation should be given at the recommended ACLS defibrillation doses.
Cardioversion and defibrillation on the external chest are safe at all stages of
pregnancy except for a small risk of causing fetal cardiac arrhythmias. In case
there are fetal monitors during defibrillation, it has to be removed before
administering shock.
• Causes of cardiac arrest specific to pregnancy should be aware of—cardiac
disease (most common)—especially myocardial infarction and aortic
dissection, hypertensive disorders (pre-eclampsia/eclampsia), magnesium
sulphate toxicity, amniotic fluid embolism, massive pulmonary embolism,
anesthesia.
• In case of cardiac arrest in a pregnant patient, a team for doing emergency
cesarean delivery should be ready. In case of >24 weeks of gestation, the
survival rate of the infant is better when the infant is delivered not more than
5 minutes after cardiac arrest of the mother. Hence, regardless of the viability
of the fetus, emergency cesarean section can be considered at 4 minutes after
onset of cardiac arrest if there is no ROSC.
• If therapeutic hypothermia is instituted, the fetus is continuously monitored
for bradycardia.
Pulmonary Embolism
• Cardiac arrest caused by pulmonary embolism (PE) mostly presents as PEA.
• In patients with cardiac arrest due to presumed or known PE, it is reasonable
to administer fibrinolytics. Surgical embolectomy can also be done. Patients
without known PE should not be given fibrinolytic therapy.
Morbid Obesity
• Airway management is quite challenging and changes in the thorax make
resuscitation efforts difficult.
• There are no modifications to standard BLS and ACLS.
TRAUMA
Common causes of cardiac arrest in trauma patients are hypoxia, hypovolemia,
diminished cardiac output secondary to pneumothorax or pericardial tamponade,
and hypothermia.

• Cervical spine should be stabilized, jaw thrust should be given instead of
head tilt and chin lift to open the airway.
• Any visible hemorrhage is compressed and if the victim is unresponsive,
standard BLS is initiated.

• In case of inadequate bag mask ventilation, advanced airway is placed while
maintaining cervical spine stabilization. If insertion of advanced airway is
not possible, cricothyroidotomy is considered.
• Identification of reversible causes is the cornerstone of resuscitation in
trauma victims along with cardiopulmonary resuscitation (CPR).
• Unilateral reduction in breath sounds should raise suspicion of pneumo
thorax, hemothorax and diaphragmatic rupture.
• Resuscitative thoracotomy can be done in selected patients.
• Commotio cordis is VF triggered by a blow to the anterior chest during cardiac
repolarization. It usually happens in young persons involved in sports where
a sudden blow to the anterior chest by a ball causes VF. Rapid defibrillation is
critical in these patients.
HYPOTHERMIA
• Severe hypothermia (<30°C) is associated with interference of critical
functions of the body especially cardiac system (cardiac arrhythmias).
• Prevent heat loss by removing wet garments and passive rewarming is done
for patients with mild hypothermia (>34°C).
• External warming is done for victims with moderate hypothermia (30–34°C).
• Core rewarming is used for victims with severe hypothermia. Even external
rewarming is effective in these victims.
• Core rewarming techniques are warm water lavage of thoracic cavity and
with partial cardiopulmonary bypass. Warm IV fluids and warm humidified
O2 can be used.
• Warming techniques should not delay airway management and insertion of
intravenous cannula.

• Detection of pulse is difficult in hypothermic patients
• Rewarming should be done along with BLS.

• In patients with cardiac arrest due to hypothermia, aggressive active core
rewarming techniques is the primary therapeutic modality.
• It is reasonable to administer vasopressors to patients with hypothermia
induced cardiac arrest.
• After ROSC, patients should be warmed with a goal of 32–34°C.

• Patients should not be considered dead before warming has been provided.
ASTHMA
• There are no BLS modifications.
• ACLS modifications—Autopositive end-expiratory pressure (PEEP) produce
adverse effects on the coronary perfusion. Ventilation strategy of low
respiratory rate and tidal volume is followed to prevent the effects of auto-
PEEP. During resuscitation of asthmatic patients with cardiac arrest, brief
disconnection of bag mask ventilation or ventilator is done to prevent air
trapping. In case of ventilation difficulty in asthmatic patients with cardiac
arrest, tension pneumothorax should be suspected.
Electrolyte Disturbances
Electrolyte disturbances are associated with cardiac arrhythmias and interfere
with resuscitative efforts and hemodynamic recovery.
Potassium
Potassium disturbances are associated with life-threatening events. Severe
hyperkalemia is defined as K+ concentration >6.5 mmol/L and can cause cardiac
arrhythmias and cardiac arrest. Renal failure and drug-induced toxicity are
common causes. The first sign is the presence of peaked T waves in ECG and
as serum potassium rises, flattened or absent P waves, prolonged PR interval,
widened QRS complex, and sine wave pattern appear on ECG. Untreated or very
high potassium levels may cause ventricular arrhythmias and asystolic cardiac
arrest.

Management of severe hyperkalemia is aimed at antagonizing the effects of
potassium on excitable cell membrane. Treatment is given to shift potassium into
cells and removing potassium from the intravascular compartment.
The priorities of treatment for hyperkalemia are:
• Stabilizing the myocardial cell membrane with 10% calcium gluconate
15–30 mL IV over 2–5 minutes or 10% calcium chloride 5–10 mL IV over
2–5 minutes.
• Shifting K+ into cells by glucose with insulin. 50 mL of 50% dextrose and
10 U of regular insulin IV are given over 15–30 minutes, nebulized albuterol
10–20 mg in 4 mL of normal saline over 15 minutes.
• In case of severe metabolic acidosis with hyperkalemia, sodium bicarbonate
of 50 meq IV is given over 5 minutes.
• Promoting K+ excretion by IV furosemide 40–80 mg, kayexalate 15–50 g with
sorbitol orally or rectally, dialysis.
In case of hypokalemia, U waves, T-wave flattening, ventricular arrhythmias

are common. They may deteriorate faster if hypokalemia becomes severe and may
end up in PEA and asystole. Bolus administration of IV potassium for suspected
hypokalemia-induced cardiac arrest is not recommended.
Magnesium
• Hypermagnesemia: Administration of 10% calcium gluconate 15–30 mL IV
over 2–5 minutes or 10% calcium chloride 5–10 mL IV over 2–5 minutes may
be considered during cardiac arrest associated with hypermagnesemia
• Hypomagnesemia: It is associated with polymorphic ventricular tachy
cardia (torsades de pointes). IV magnesium 1–2 g of MgSO4 bolus IV is
recommended.
DROWNING
The most important consequence of submersion is hypoxia, hence in drowning
victims, the guidelines recommend individualization of the sequence according
to the presumed cause. CPR is done in ABC sequence in drowning victims
owing to the hypoxic nature of the arrest. Prompt initiation of rescue breathing
increases the victim’s chance of survival. When the victim is taken from the water,
the rescuer should open the airway, check for breathing and in case there is no
breathing, 2 rescue breaths should be given. Chest compressions are given after
rescue breaths. Chest compressions are difficult to perform in water and the
maneuvers of relieving foreign body obstruction is not recommended and in fact
causes more complications and delay in CPR. The most important determinant
of outcome is the duration and severity of hypoxia.
Electric Shock/Lightening Strike

Electric shock and lightning strike cause direct effects of current on the heart
and brain, cell membranes, and vascular smooth muscle thus causing cardiac
arrest due to VF or asystole. Alternating current flows through the heart during
the relative refractory period and can cause VF. Lightening causes massive
direct current shock simultaneously depolarizing the whole myocardium and
causes thoracic muscle spasm causing respiratory arrest. Lightening causes
catecholamine release, prolongation of QT interval, myocardial necrosis, and
intracranial hemorrhages.

• The rescuer should make himself safe on the scene of cardiac arrest before
rescuing the victim. Once the rescuer keeps the victim in a safe place, he can
start resuscitative efforts.
• Associated cervical spine injury can occur, hence spinal stabilization is done.
Removing the clothes, belt can avoid further thermal damage.

• Early intubation is done in view of the extensive burns caused by injury.
• For patients with ROSC, rapid IV fluid administration is done to counteract
distributive shock. Maintaining diuresis is important to prevent acute kidney
injury due to extensive tissue injury.
PERCUTANEOUS CORONARY INTERVENTION

There is always a risk of cardiac arrest during percutaneous coronary intervention
(PCI), and standard CPR techniques are followed in case of cardiac arrest.
Mechanical chest compression devices can be used for resuscitation. Emergency
cardiopulmonary bypass can be used, cough CPR can be used as a temporary
measure to maintain blood pressure and consciousness during initial phase of
ventricular arrhythmias. Intracoronary verapamil has been used but its use is not
validated.
CARDIAC TAMPONADE
Increasing fluid and pressure compromises atrial and ventricular filling thus
reducing stroke volume and cardiac output leading to hypotension and cardiac
arrest. Rapid pericardiocentesis guided by echocardiography is the most
effective method to relieve tamponade in a nonarrest setting. If there is no
echocardiography, emergency pericardiocentesis without echocardiography
guidance can be done. Thoracotomy can be done for trauma-induced pericardial
tamponade to remove blood clots.
CARDIAC SURGERY
Common causes of cardiac arrest are ventricular fibrillation, hypovolemia,
cardiac tamponade, tension pneumothorax. Resternotomy is done in a well
equipped ICU. Though there are reports of damage to heart due to external chest
compressions, chest compressions should not be withheld if resternotomy is not
done. Cardiopulmonary bypass may be started in patients who fail to respond to
usual resuscitative measures.
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Cardiac arrest in pregnancy: increasing use of perimortem caesarean section due to
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vasopressin: two case reports. Int Arch Allergy Immunol. 2004;134:260-1.
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defibrillation energy requirements? Br J Anaesth. 2001;87:237-9.
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pregnancy: case report and review of the literature. Acad Emerg Med. 1999;6:1072-4.
12. Rees GA, Willis BA. Resuscitation in late pregnancy. Anaesthesia. 1988;43:347-9.
13. Rees SG, Thurlow JA, Gardner IC, et al. Maternal cardiovascular consequences of
positioning after spinal anaesthesia for caesarean section: left 15 degree table tilt vs
left lateral. Anaesthesia. 2002;57:15-20.
14. Sheikh A, Shehata YA, Brown SG, et al. Adrenaline (epinephrine) for the treatment
of anaphylaxis with and without shock. Cochrane Database Syst Rev. 2008;No.
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subcutaneous injection. J Allergy Clin Immunol. 2001;108:871-3.
17. Vanden Hoek TL, et al. Part 12: cardiac arrest in special situations: 2010 American
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18. Vasdev GM, Harrison BA, Keegan MT, et al. Management of the difficult and failed
airway in obstetric anesthesia. J Anesth. 2008;22:38-48.
19. Yilmaz R, Yuksekbas O, Erkol Z, et al. Postmortem findings after anaphylactic reactions
to drugs in Turkey. Am J Forensic Med Pathol. 2009;30:346-9.
20. Yunginger JW, Sweeney KG, Sturner WQ, Giannandrea LA, Teigland JD, Bray M,
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1988;260:1450-2.
SECTION
27 BRAIN DEATH
Chapter 102 Care of a Brain Dead Patient

Sumathy, Prem Kumar,
Deepalakshmi
CHAPTER
102 Sumathy, Prem Kumar, Deepalakshmi
CARE OF A BRAIN DEAD PATIENT
The concept of brain death was first introduced by Mollaret et al. Determination
of brain death requires the confirmation of irreversible cessation of all functions
of the brain which includes also the brainstem. The term irreversible cessation
of brain function refers that none of the treatment can be expected to reasonably
change the condition. Although testing of the brain function can be done, it is
determined clinically by loss of consciousness, loss of brainstem responses,
apnea. As the concept of brain death grew, the idea of organ harvesting from
brain dead patients for organ transplantation came into practice, hence critical
care management of potential organ donors is crucial in maximizing the number
and the quality of transplanted organs.
Following are the duties of the critical care physician are:
• Early identification of brain death
• Brain death certification
• The responsibility to offer the patient’s family the opportunity to donate
organs/tissues
• Obligation to unknown recipients to provide the best possible organs and
tissue.
DEFINITION
Brain death is defined as the irreversible loss of all the functions of the brain
including the brainstem due to total necrosis of the cerebral neurons following
loss of blood flow and oxygenation when the proximate cause is known.
PHYSIOLOGY OF BRAIN DEATH
Central Nervous System

Brain death is the total irreversible loss of all functions of brain excluding the
spinal cord. Brain stem reflexes such as pupillary, oculocephalic, oculovestibular,
and pharyngeal reflexes are absent and they are tested to confirm brain death.
762 Section 27 Brain Death
Respiratory System
Respiratory center is located in medulla oblongata. In brain death patients, there
is loss of spontaneous respiration even when the PaCO2 rises up to 60 mm Hg.
Mechanical stimulation of carina to cause cough reflex can be used for detecting
residual functioning of the medullary respiratory neurons.
Cardiovascular System
Vasomotor center is in pons and medulla. Increased intracranial tension due
to intracranial bleed or any cause can cause hypertension and bradycardia.
Transtentorial herniation can cause pressure over the pons and cause Cushing’s
response. This causes ischemia of vasomotor centers of brain and causes central
autonomic dysfunction leading to catecholamine surge causing hypertension,
tachycardia, and increased myocardial contractility. Over hours after brain death,
autonomic surge decreases and catecholamines decrease causing hemodynamic
instability due to reduced sympathetic outflow, cardiac output, and systemic
vascular resistance. If autonomic reflexes are intact in brain death patients,
surgical stimulation can lead to hypertension and tachycardia. This is the reason
why general anesthesia should be used for brain death organ donors.
Temperature Regulation
Body temperature is regulated in hypothalamus. The neural communication
between temperature regulating center and peripheral tissues is lost in brain
death patients. Hence, patients with brain death tend to be hypothermic.
Hypothalamopituitary Function
Hypothalamic and anterior pituitary functions are preserved for a certain period
of time after the onset of brain death. Thyroid-stimulating hormone, prolactin,
growth hormone, and luteinizing hormone are all found at a normal level in brain
death patients. The levels of vasopressin, T3, T4 are decreased.
Immune System
Though the immune system is intact, response to stimulation is suppressed and
there is increased level of proinflammatory mediators, such as cytokines (IL-1β,
IL-6, TNF-α) which is responsible for the failure rate of organ transplantation.
Privileging
Each hospital should establish a process for identifying the privileging physicians
to make brain death determination. The legal and expert guidelines for organ
transplantation in India are given by Transplantation of Human Organs and Tissues
Rules, 2014. The guidelines can be accessed in the website - http://notto.nic.in/.
According to the Transplantation of Human Organs Rules, 1995 (THO Rules)
of the Tamil Nadu Government, the following four doctors are authorized to
certify brain death.
Chapter 102 Care of a Brain Dead Patient 763
Table 102.1 Guidelines for determining brain death
Prerequisites
• Clinical or neuroimaging evidence of an acute central nervous system condition that
is compatible with the clinical diagnosis of brain death
• There should not be severe electrolyte, acid-base, or endocrine disturbance that
would confound the clinical diagnosis of brain death
• No drug intoxication or poisoning
• Core temperature ≥32°C (90°F)
• Doctor No: 1-RMP

(Registered medical practitioner): In charge of the hospital in which brainstem
death has occurred.
Who is RMP?: RMO, ARMO, Duty RMO or the RMP in charge of the hospital
• Doctor No: 2-RMP - (Physicians, surgeons, intensivists) nominated from the
panel of names approved by the appropriate authority (Director of medical
and rural health services)
• Doctor No: 3-(Neurologist or neurosurgeon) nominated from the panel of
names approved by the appropriate authority
• Doctor No: 4-RMP - Treating the aforesaid person.
Notification
Hospitals should make reasonable efforts to notify the next of kin or person
closest to the individual that the process of evaluating brain death has begun.
Reasonable Accommodation
Hospitals must establish written procedures for the reasonable accommodation
of the individual’s religious or moral objections to use of the brain death standards
to determine death when such an objection has been expressed by the patient
prior to the loss of decision making capacity, or by the next of the kin or other
person closest to the individual.
Responsibilities of the Physician Determining Brain Death

The diagnosis of brain death is primarily clinical. No other tests are required if the
full clinical examination, including each of two assessments of brainstem reflexes
and the apnea test is conclusively performed. Prerequisites for diagnosing brain
death is given in Table 102.1.
STEPS FOR DETERMINING BRAIN DEATH

• Evaluate the irreversibility and potential causes of coma
• Initiate the hospital policy for notifying the next of kin
• Conduct and document the first clinical assessment of brainstem reflexes
• Observe the individual during a defined waiting period for any clinical
inconsistencies with the diagnosis of brain death
• Conduct and document the clinical assessment of brainstem reflexes
• Perform and document the apnea test
• Perform confirmatory test, if needed
• If the individuals religious or moral objection to the brain death standard is
known, implement hospital policies for reasonable accommodation
• Certify brain death
• Withdraw cardiorespiratory support in accordance with hospital policies,
including those for organ donation.
DIAGNOSTIC CRITERIA FOR THE CLINICAL DIAGNOSIS

OF BRAIN DEATH
The three prime findings in brain death are following:
1. Coma or unresponsiveness
2. Absence of brainstem reflexes
3. Apnea.
Coma or Unresponsiveness
Absence of cerebral motor response to pain in all extremities is tested by applying
supraorbital pressure. The patient should be in coma and have GCS ≤3. Spinal
motor responses (i.e. the Lazarus sign) may occur spontaneously during apnea
testing.
Absence of Brainstem Reflexes

Absence of pupillary response to light, absence of oculocephalic reflex, absence
of corneal, pharyngeal and tracheal reflexes are all features consistent in patients
with brainstem death. Oculovestibular reflex is tested by irrigation of cold water
which shows no deviation of eyes to irrigation in each ear with 50 mL of cold water.
Pharyngeal and tracheal reflex is tested by stimulation of the posterior pharynx
with tongue blade or by bronchial suctioning. The criteria of the American
Academy of Neurology for brain death include light reflex, oculocephalic reflex,
caloric (vestibular) test, corneal reflex, jaw reflex, pharyngeal reflex, and cough
reflex.
Tests for the function of cranial nerves of the brainstem:

• Absence of pupillary light response (II, III)
• Absence of corneal reflexes (V, VII)
• No facial response to painful stimuli in the face, trunk or limbs (V, VII)
• Absence of gag reflex (IX)
• Absence of cough reflex (X)
• Absence of nystagmus with instillation of 30–50 mL of ice cold water
into the EAC (external auditory canal)—oculovestibular testing (VIII)
(Flow chart 102.1).
Flow chart 102.1 Oculovestibular testing
Abbreviations: EAC, external auditory canal; CSF, cerebrospinal fluid.
Apnea Test
The apnea test is performed after the clinical examination of brainstem reflexes.
Prerequisites:
• Core temperature >36.5°C/97.7°F
• Systolic blood pressure ≥90 mm Hg
• Euvolemia: Positive fluid balance in the previous 6 hours
• Normal PaCO2: PaCO2 ≥ 40 mm Hg
• Normal PaO2: Preoxygenate to obtain arterial PaO2 ≥200 mm Hg
Procedure of the apnea testing:
• Preoxygenate the patient with 100% O2 for 10 minutes
• Do a baseline ABG
• Connect a pulse oximeter
• Disconnect the ventilator
• Deliver 100% O2 by administering 6 L/minute into the trachea by placing a
cannula at the level of carina
• Look closely for respiratory movements (abdominal or chest excursions that
produce adequate tidal volumes)
• Measure arterial PaO2, PaCO2, and pH by taking ABG sample after
approximately 8 minutes and reconnect the ventilator.
Table 102.2 Apnea test interpretations
Apnea test positive supports Diagnosis of brain death Negative test

• Patient remains apneic, without any respiratory • Presence of respiratory efforts
movements • Test should be repeated
• PaCO2 ≥60 mm Hg (20 mm Hg ↑ in PaCO2 Indeterminate test
over the baseline)
PaCO2 <60 mm Hg/PaCO2 ↑ is
<20 mm Hg over baseline
Abort the test and immediately take a ABG sample if:

• The systolic BP becomes <90 mm Hg
• Arterial desaturation
• Cardiac arrhythmias.
If PaCO2 is ≥60 mm Hg or PaCO2 increase is ≥20 mm Hg over baseline PaCO2,
the apnea test result is positive. If PaCO2 is < 60 mm Hg or PaCO2 increase is
<20 mm Hg over baseline PaCO2, the result is indeterminate, and an additional
confirmatory test can be considered (Table 102.2).
Two clinical examinations followed by apnea testing separated by 6 hours
are required for establishing the diagnosis of brain death. Confirmatory tests
in the determination of brain death are not always mandatory, but they may be
required especially if there is a confusing clinical presentation.
Confirmatory Tests for Brain Death

Confirmatory tests to record the loss of bioelectrical activity of the brain or the
cerebral circulatory arrest are not always mandatory for adults, but it is commonly
done for children < 1 year to confirm brain death.
• Cerebral angiography
• Electroencephalography
• Cerebral scintigraphy
• Transcranial Doppler ultrasonography.
Electroencephalography (EEG) and evoked potential
EEG is the most commonly used test to confirm brain death. Isoelectric EEG is a
reliable finding for brain death. Electrocerebral inactivity (ECI) or electrocerebral
silence (ECS) is defined as absence of electroencephalographic activity above 2
µV/mm when recorded from scalp electrode. But EEG can be altered by anesthetic
agents and sedatives leading to false positive results. Unlike EEG, somatosensory
evoked potentials (SSEP) and brainstem auditory evoked potentials (BAEP) are
minimally affected by drugs, hence can be used for diagnosis of brain death.
Cerebral blood flow
Absence of cerebral circulation can indicate irreversible brain damage. This can
be done by 4 vessel angiography, CT and MRI angiography, transcranial Doppler
ultrasonography.
MANAGEMENT OF HEARTBEATING BRAIN DEATH ORGAN DONOR

The standards of medical management of the potential organ donor should be
the same as those of any brain-injured patient until the irreversibility of injury is
confirmed. The patient must be medically suitable for organ donation. The criteria
for suitability may change from time to time and according to circumstances.
General Medical Criteria

• Age—up to 75 years
• Irreversible loss of brain function
• Has been maintained on ventilator with intact circulation
• Has no malignancy except primary brain/skin malignancy
• Has no major untreated sepsis
• No major significant system specific disease (e.g. cardiac, pulmonary, liver)
• No significant infectious disease
• Cause of death not due to massive poisoning with potential for transplant
organ dysfunction (cyanide, carbon monoxide, etc.).
Exclusion Criteria for Organ Donation

• HIV
• Hepatitis B and C positive donors (Refer to transplant co-coordinator for
individual assessment)
• Any malignancy other than primary skin/CNS lesion
• Treatment with human pituitary growth hormone and other hormones of
pituitary origin
• Untreated bacterial, viral, fungal infection
• Creutzfeld–Jacobs’s disease, family history of dementia.
Obtaining Consent for Organ Donation

After explanation of the illness, brain injury and the concept of brain death,
the coordinator and intensivist should get consent for organ donation from the
family members.
• Contact local organ-procurement organization (OPO)
• In conjunction with OPO, obtain verbal consent to perform noninvasive
blood testing (blood sampling, ECG, radiology studies) to determine
suitability for organ donation
• Establish diagnosis of brain death
• After brain death has been declared and in conjunction with OPO, obtain
written family consent for donation.
Investigations
• Before 1st apnea test—blood grouping and typing, complete blood count,
liver function test, renal function test
• After getting consent—HIV, Hbs Ag, anti–HCV, CMV, VDRL
• Kidney donor—HLA typing, ultrasound kidney
• Liver—USG
• Heart—12 lead ECG, echocardiography if donor is >50 years, coronary
angiogram
• Lung—chest X-ray, ABG, bronchoscopy.
Table 102.3 Two clinical phases of brain death
1st phase 2nd phase

Hypertension and tachycardia due to • Catecholamine depletion/↓ Sympathetic drive
autonomic surge. • Volume depletion due to diuretics mannitol,
This is treated by: furosemide is used in the Rx of cerebral
• SNP—0.5–5 µg/kg/minute edema
• Esmolol—100–500 µg/kg bolus • Continuous blood loss from injuries
followed by 100–300 µg/kg/minute • Insensible fluid loss
• Diabetes insipidus
• Metabolic/endocrine abnormalities
• Hypothermia
• Myocardial dysfunction
Abbreviation: SNP, sodium nitroprusside
Clinical Management of the Organ Donor

Severe brain injury and brain death create a variety of extracerebral organ
manifestations including autonomic storm, neuroendocrine hormone
deficiencies, systemic inflammatory response syndrome (SIRS), neurogenic
pulmonary edema (NPE), myocardial stunning, electrolyte and immunologic
derangements (Table 102.3).
The challenge of ICU physician is maintaining adequate organ perfusion and
metabolism. Maximal ICU management strategies should be employed to bring
out improved outcomes. The outcomes are the following:
• Larger number of organs transplanted
• Longer recipient survival times
• Improved organ function following transplantation.
MANAGEMENT OF 2ND PHASE
Management of Cardiovascular System
Monitoring
• Central venous monitoring is recommended for patients with brain death
• PA catheter is not routinely placed in brain death patients but inserted
for the following indications—ejection fraction ≤40% and patient on high
vasopressor support.
Management of Hypotension
• Rapid replacement of blood volume by infusing crystalloids/colloids with
titration of CVP to 8–10 mm Hg with goal of systolic blood pressure >100 mm Hg,
MAP = 60–70 mm Hg and heart rate <100/minute.
• In case of inotrope/vasopressor support,
– Dopamine - <10 µg/kg/minute.
– Dobutamine - <10 µg/kg/minute.
– There has been a recent trend towards use of vasopressin for circulatory
support. Dose is 0.5–4 units/hour (0.01-0.04 U/min).
– Second line agents are noradrenaline, adrenaline, and phenylephrine.
• In case of monitoring with pulmonary artery is present, targets are PCWP =
12–14 mm Hg, cardiac index - >2.4 L/min/m2, SVR = 800–1200 dynes/sec/cm–5
• Bradyarrhythmias can occur in brain death patients since heart is denervated
and hence it is resistant to atropine. Dopamine or small doses of adrenaline
50–100 µg is given for treating it.
MANAGEMENT OF RESPIRATORY SYSTEM

The concerns related to respiratory system in brain death patients:
• Lung injury (Release of proinflammatory cytokines)
• Aspiration
• Pulmonary contusion/pneumonia
• Volutrauma/barotrauma
• Pulmonary embolism
• V/Q mismatch
• Neurogenic pulmonary edema.
Neurogenic pulmonary edema occurs due to intense vasoconstriction
(α-receptor stimulation) thus, leading to shifting of fluid from peripheral to
central circulation thus, causing increase in left atrial pressure and pulmonary
capillary pressure leading to pulmonary edema.
Interventions for Pulmonary Stability

• Aggressive pulmonary care—Repositioning (every 2 hours); Chest
physiotherapy and suctioning; Oral hygiene.
• Careful fluid management—CVP-guided fluid therapy to avoid pulmonary
edema.
• Ventilation strategies
}
FiO2 titrated to keep O2 saturation ≥95%
PaO2 ≥80 mm Hg Goals of ventilation
pH—7.35–7.45
PaCO2—35–45 mm Hg
PEEP—5 cm H2O
TV—6–8 mL/kg
PIP—<30 cm H2O.
• Intervention of the inflammatory process.
Methylprednisolone—15 mg/kg plays an important role in diminishing the
systemic inflammatory response and it improves oxygenation.
• It has been recommended that bronchoscopy should be undertaken in
every lung organ donor for therapeutic bronchial toileting and for isolation
of potential pathogens. Antimicrobial therapy should be tailored to
bronchial wash Gram stain or culture results. Empirical antibiotics are not
recommended.
MANAGEMENT OF ENDOCRINE SYSTEM
HPA Axis Dysfunction
Anterior Hypothalamic: Pituitary Endocrine Function

It was demonstrated from studies that T3 and T4 were reduced in brain death
patients, hence the deficiencies are managed by supplementation with intravenous
T3 of 4 µg bolus followed by 3 µg/hour infusion. This causes improved myocardial
contractility and increased cardiac output. Adrenal insufficiency also occurs in
brain death patients and this is the cause for reduced stress response during
hypotension and can also cause organ failure. This is managed by administering
methylprednisolone—15 mg/kg/day.
Posterior Hypothalamic Pituitary Deficiency

Diabetes insipidus (DI)
90% of donors have low or undetectable vasopressin (ADH) levels resulting in
diabetes insipidus which can be diagnosed by:
• Urine output—>500 mL/hour
• Serum Na—>155 mEq/L
• Urine specific gravity—>1.005
• Serum osmolality—>305 mOsm/L.
Treatment
• Volume replacement (with hypotonic saline or 5% dextrose in water)
• DI in isolation can be treated with a continuous infusion of vasopressin or
intermittent DDAVP.
• Vasopressin infusion should be the first choice if hemodynamic support with
vasopressin is required or combined hormonal therapy is indicated.
Desmopressin (DDAVP)
It’s a highly selective V2 receptor activity with long half life and has diuretic action with
minimal vasopressor activity. Dose is loading—8 ng/kg, infusion—4 ng/kg /hour.
Arginine vasopressin
In contrast to desmopressin, this has vasopressor activity. Therefore, administration
of vasopressin treats diabetes insipidus as well as lowers the vasopressor requirement
for the donor. Dose is 1 U bolus followed by infusion of 0.01–0.04 U/minute.
QUADRUPLE HORMONAL REPLACEMENT THERAPY (Table 102.4)

The Cardiac Work Group of the Crystal City Conference led by United Network
for Organ Sharing (UNOS) recommended donor management protocol which
includes four-drug hormonal resuscitation (T3, vasopressin, methylprednisolone,
and insulin). It is given to patients who are hemodynamically unstable or with
LV ejection fraction of <45%. Procurement and transplantation Network
(OPTN)/UNOS did studies based on hormonal treatment of brain-dead donors
(T3/T4, methylprednisolone, and arginine vasopressin) and they found better
survival of organs in recipients and increased organ transplants.
Table 102.4 Quadruple hormonal replacement therapy for brain death patients
• T3: 4 µg bolus followed by 3 µg/hour infusion

• Vasopressin: 1 U bolus followed by infusion of 0.01–0.04 U/minute
• Methylprednisolone: 15 mg/kg/day
• Insulin: Glycemic control with insulin infusion titrated to blood glucose target of
6–8 mmol /L
Renal System
Maintain systolic blood pressure >80–90 mm Hg to maintain renal perfusion.
Hepatic System
Depletion of liver glycogen occurs in 12 hours following brain death. Hence,
administration of glucose and insulin may improve glycogen storage as well as
improve glycemic control. If there is hypernatremia, it can cause accumulation of
idiogenic osmoles within the liver and leads to graft dysfunction. Totsuka et al.,
has demonstrated that correcting donor sodium levels to <155 mmol/L decreases
the incidence of liver allograft loss.
Hypothermia
In brain death patients, there is loss of neural connection between the
temperature-regulating center and peripheral body tissues, hence there is
hypothermia. Hypothermia is deleterious since it can cause cardiac arrhythmias,
myocardial depression, shift of oxygen dissociation curve (ODC) curve to left
side and coagulopathies. Interventions which can be done to maintain core
temperature are warm IV fluids, warm blankets, humidified gases, thyroid
hormone replacement and external warming devices.
Hematology
A hemoglobin target of 9–10 g/dL is the most appropriate to optimize cardiopulmo
nary function in the face of hemodynamic instability. The lowest hemoglobin
limit allowable for ICU management of stable donors is 7 g/dL. Coagulopathy
can be due to release of thromboplastin, hypothermia and dilutional effect.
BIBLIOGRAPHY
1. Act and rules under Transplant of Human Organs Act (THOA) - http://notto.nic.in/.
2. Amado JA, Lopez-Espadas F, Vazquez-Barquero A, et al. Blood levels of cytokines
in brain-dead patients: Relationship with circulating hormones and acute-phase
reactants. Metabolism. 1995;44:812.
3. Harms J, Isemer FE, Kolenda H. Hormonal alteration and pituitary function during
course of brainstem death in potential organ donors. Transplant Proc. 1991;23:2614.
4. Mollaret P, Goulon M. Le coma dépassé (mémoire préliminaire). Rev Neurol (Paris).
1959;101:3.
5. Novitzky D, Cooper DK, Rosendale JD, et al. Hormonal therapy of the brain-dead
organ donor: experimental and clinical studies. Transplantation. 2006;82:1396.
6. Practice parameters for determining brain death in adults: report of the Quality
Standards Subcommittee of the American Academy of Neurology. Neurology. 1995;
45:1012.
7. Ropper AH. Unusual spontaneous movements in brain dead patients. Neurology.
1984;34:1089.
8. Schrader H, Krogness K, Aakvaag A, et al. Changes of pituitary hormones in brain
death. Acta Neurochir (Wien). 1980;52:239.
9. Sugimoto T, Sakano T, Kinoshita Y, et al. Morphological and functional alterations of
the hypothalamic-pituitary system in brain death with long term bodily living. Acta
Neurochir (Wien). 1992;115:31.
10. Walker AE, Diamond EL, Moseley J. The neuropathological findings in irreversible
coma: a critique of the “respirator brain”. J Neuropathol Exp Neurol. 1975;34:295.
11. Wijdicks EF. The diagnosis of brain death. N Engl J Med. 2001;344:1215.
12. Young PJ, Matta BF. Anaesthesia for organ donation in the brainstem dead—why
bother? Anaesthesia. 2000;55:105.
13. Zaroff JG, Rosengard BR, Armstrong WF, et al. Consensus conference report:
maximizing the use of organs recovered from the cadaver donor: Cardiac recommen
dations. Circulation. 2002;106:836.
SECTION
28 MEDICAL ETHICS
Chapter 103 Ethics in Critical Care

Prem Kumar
CHAPTER
103 Prem Kumar
ETHICS IN CRITICAL CARE
Medical ethics is a code of conduct that deals with moral values and choices
resulting in the best course of action for patients suffering from medical conditions.
Medical ethics relates the relationship between health care personnel and
patients and is not limited to doctors alone. Ethics primarily deals with the human
behavior (differentiation between the right and the wrong). Intensivists should
make moral and ethical reasoning along with the patient and the kith and kin
for end-of-life care with relevance to prognosis. Although it can be philosophical
and based on religion and cultural backgrounds, the decision of the patient and
relationship between the patient and intensivist–patient relationship is vital in
the decision making towards end-of-life care. There can be differences in opinion
regarding what is best for the patient between the patient and intensivist. Fair
allocation of nursing care and resources with respect to critical care irrespective
of the patient’s financial condition, medical condition and prognosis should be
done.
Intensive care is one of the costlier branches in medical care since it involves
many health care providers, equipment and technology. Hence, it is important
for the public, government and critical care expert panel to determine the budget
which should be allocated for health in terms of critical care thus providing
equitable access of medical care for all citizens. Ethical issues arise when there
is clash of values. Resolving the ethical issues of intensive care is quite difficult
and depends on the discussion of healthcare committee and the recognition of
values.
END-OF-LIFE CARE
Over time, intensive care has become more costly, and bearing the economic
burden is still more painful for patients and relatives in developing countries like
India. Hence, it is clear that we need a comprehensive national initiative to bridge
the gap between the problem and the patient. Although the practice of intensive
care has become more systematic and standardized in India in the past decade,
the biggest challenge for intensivists is the balance between financial burden of
the patient and the provision of prolonged life support in patients where there is
minimal chance of recovery/survival. The intensivist does not have the right to
withhold life support against the will of the patient or the relatives.
In certain countries of the western world, there are laws for end-of-life care
where the intensivist can withhold life support with the consent of the patient
776 Section 28 Medical Ethics
which is many times not possible or usually the kith and kin. In India, there is
lack of a national end-of-life care (EOLC) policy. Indian association of palliative
care (IAPC) has drafted consensus guidelines for end-of-life and palliative care
in intensive care.
According to the guidelines, the steps involved in providing good end-of-life care
are:
• Recognize the dying process
• End-of-life decision making process
• Initiation of EOLC/EOLC pathway
• Process of EOLC
• Scope of palliative care in EOLC
• After-death care
• Medical care review meeting
• Bereavement support.
The six principles of Gold Standards Framework include:
1. Identification of patients needing EOLC
2. Assessment of needs
3. Planning of EOLC
4. Provision of the EOLC
5. Ongoing assessment of the process of EOLC
6. Reflection on and improvisation of the EOLC process.
End-of-life care decision making process (Flow chart 103.1)
Once the decision to withdraw life support is taken, the whole process of decision
making to withdraw life support, consent of the patient or relatives, the rationale
and the method of withdrawing support is documented. According to studies,
people of India preferred to die at their homes rather than in hospitals. In Indian
set up, the most relevant option is palliative care at home.
Flow chart 103.1 End-of-life care decision making process

Chapter 103 Ethics in Critical Care 777
BIBLIOGRAPHY
1. Chapman L, Ellershaw J. Care in the last hours and days of life. Medicine (Baltimore).
2011;39:674-7.
2. End-of-life Care Strategy. Department of Health Publication. London; 2008.
3. Jayaram R, Ramakrishnan N. Cost of intensive care in India. Indian J Crit Care Med.
2008;12:55-61.
4. Macaden SC, Salins N, Muckaden M, Kulkarni P, Joad A, Nirabhawane V, et al. IAPC
Consensus Position Statement on End-of-life Care Policy for the dying. Indian J Palliat
Care. 2014;20:171-81.
5. Macaden SC. Moving toward a national policy on palliative and end-of-life care.
Indian J Palliat Care. 2011;17Suppl:S42-4.
6. Mani RK, Amin P, Chawla R, Divatia J, Kapadia F, Khilnani P, et al. Guidelines for end-
of-life and palliative care in Indian intensive care units’ ISCCM consensus ethical
position statement. Indian J Crit Care Med. 2012;16:166-81.
APPENDICES
Appendix 1 Normal Biochemical Values
Appendix 2 Clinical Scores, Indices and

Equations
Appendix 3 Drugs, Dosages and Side Effects
Appendix 4 ICU Rounds

APPENDIX
1
NORMAL BIOCHEMICAL VALUES
REFERENCE VALUES FOR LABORATORY TESTS

Blood analytes
Lipid profile Conventional unit SI unit
Total cholesterol Desirable <200 mg/dL <5.17 mmol/L
Borderline high 200–239 mg/dL 5.17–6.18 mmol/L
High >240 mg/dL >6.21 mmol/L
LDL cholesterol Optimal <100 mg/dL <2.59 mmol/L
Near optimal 100–129 mg/dL 2.59–3.34 mmol/L
Borderline high 130–159 mg/dL 3.36–4.11 mmol/L
High 160–189 mg/dL 4.14–4.89 mmol/L
Very high >190 mg/dL >4.91 mmol/L
HDL cholesterol Desirable 30–75 mg/dL 0.75–1.95 mmol/L
Low <40 mg/dL <1.03 mmol/L
High >60 mg/dL >1.55 mmol/L
Triglycerides Desirable 30–200 mg/dL 0.34–2.26 mmol/L
Glucose
Fasting Normal–Adult 75–110 mg/dL 4.2–6.1 mmol/L
Neonate 30–60 mg/dL 1.7–3.3 mmol/L
Newborn 40–80 mg/dL 2.2–4.5 mmol/L
Child 60–100 mg/dL 3.3–5.6 mmol/L
Impaired glucose 111–125 mg/dL 6.2–6.9 mmol/L
tolerance (adult)
Diabetes mellitus >125 mg/dL >7.0 mmol/L
(adult)
2 hours post-prandial Normal (adult) 70–120 mg/dL 3.9–6.7 mmol/L
Glycated hemoglobin 4–6% 0.04–0.06 Hb
(HbA1c) fraction
Aceto-acetate 0.2–1.0 mg/dL 20–99 μmol/L
Lactic acid 5–12 mg/dL 0.5–1.2 mmol/L
Contd…
782 Appendices
Contd…
Iron hemostasis parameters

Iron 41–141 μg/dL 7–25 μmol/L
Ferritin Male 29–248 ng/mL 29–248 μg/L
Female 10–150 ng/mL 10–150 μg/L
Transferrin 200–400 mg/dL 2.0–4.0 g/L
Liver function test
Total protein Newborn 4.6–7.0 g/dL 46–70 g/L
>2 years 6.0–8.0 g/dL 60–80 g/L
Adult 6.7–8.6 g/dL 67–86 g/L
Albumin Male 4.0–5.0 g/dL 40–50 g/L
Female 4.1–5.3 g/dL 41–53 g/L
Globulin 2.0–3.5 g/dL 20–35 g/L
Bilirubin
Total 0.3–1.3 mg/dL 5.1–22 μmol/L
Direct
0.1–0.4 mg/dL 1.7–6.8 μmol/L
Indirect
0.2–0.9 mg/dL 3.4–15.2 μmol/L
Prothrombin time 12.7–15.4 s 12.7–15.4 s
Ceruloplasmin 25–63 mg/dL 250–630 mg/L
Markers of liver cell injury
Alanine 7–41 U/L 0.12–0.70 μkat/L
aminotransferase
(SGPT)
Aspartate amino 12–38 U/L 0.2–0.65 μkat/L
transferase (SGOT)
Markers of cholestasis
Alkaline phosphatase 33–96 U/L 0.56–1.63 μkat/L
(ALP)
Gamma glutamyl 9–58 U/L 0.15–0.99 μkat/L
transferse (GGT)
Ammonia 19–60 μg/dL 11–35 μmol/L
Kidney function test
Creatinine Newborn 0.3–1.0 mg/dL 27–88 μmol/L
Infant 0.2–0.4 mg/dL 18–35 μmol/L
Child 0.3–0.7 mg/dL 27–62 μmol/L
Adolescent 0.5–1.0 mg/dL 44–88 μmol/L
Male 0.6–1.2 mg/dL 53–106 μmol/L
Female 0.5–0.9 mg/dL 44–80 μmol/L
Contd…
Appendix 1 Normal Biochemical Values 783
Contd…
Urea 15–40 mg/dL 5.4–14.3 mmol/L

Blood urea nitrogen 7–20 mg/dL 2.5–7.1 mmol/L
Creatinine clearance 91–130 mL/min 1.5–2.2 mL/s
Inulin clearance Male 124 ± 25.8 mL/min 2.1 ± 0.4 mL/s
Female 119 ± 12.8 mL/min 2.0 ± 0.2 mL/s
Uric acid Male 3.1–7.0 mg/dL 0.18–0.41 μmol/L
Female 2.5–5.6 mg/dL 0.15–0.33 μmol/L
Thyroid function test
TSH Adult 0.34–4.25 μIU/mL 0.34–4.25 mIU/L
Pregnancy 0.3–5.2 μIU/mL 0.3–5.2 mIU/L
Cord blood 2.3–13.2 μIU/mL 2.3–13.2 mIU/L
Children 0.7–6.4 μIU/mL 0.7–6.4 mIU/L
Newborn screening <20 μIU/mL <20 mIU/L
(Whole blood heel
puncture)
T4 Cord blood 7.4–13.1 μg/dL 95–168 nmol/L
1–5 years 7.3–15.0 μg/dL 94–194 nmol/L
5–10 years 6.4–13.3 μg/dL 83–172 nmol/L
10–15 years 5.6–11.7 μg/dL 72–151 nmol/L
Male 4.6–10.5 μg/dL 59–135 nmol/L
Female 5.5–11.0 μg/dL 65–138 nmol/L
Free T4 Newborn 2.2–5.3 ng/dL 28.4–68.4 pmol/L
Children 0.8–2.0 ng/dL 10.3–25.8 pmol/L
Adult 0.8–2.7 ng/dL 10.3–34.7 pmol/L
Pregnancy 0.5–1.6 ng/dL 6.4–20.6 pmol/L
T3 Cord blood 5–141 ng/dL 0.08–2.17 nmol/L
Adult 77–135 ng/dL 1.2–2.1 nmol/L
Pregnancy 80–260 ng/dL 1.25–4.00 nmol/L
Free T3 Cord blood 1.5–3.91 pg/mL 0.2–6.0 pmol/L
Pregnancy 2.0–3.8 pg/mL 3.1–5.9 pmol/L
Children and adult 2.4–4.2 pg/mL 3.7–6.5 pmol/L
Arterial blood gas analysis
pH 7.35–7.45 7.35–7.45
Bicarbonate 22–30 mEq/L 22–30 mmol/L
pCO2 32–45 mm/Hg 4.3–6.0 kpa
pO2 72–104 mm/Hg 9.6–13.8 kpa
Anion gap 7–16 mEq/L 7–16 mmol/L
Osmolality 275–295 275–295
mOsmol/kg mOsmol/kg
Contd…
784 Appendices
Contd…
Electrolytes
Sodium 136–146 mEq/L 136–146 mmol/L
Potassium 3.5–5.0 mEq/L 3.5–5.0 mmol/L
Chloride 102–109 mEq/L 102–109 mmol/L
Calcium Total 8.7–10.2 mg/dL 2.2–2.6 mmol/L
Ionized 4.5–5.3 mg/dL 1.12–1.32 mmol/L
Phosphorus 2.5–4.3 mg/dL 0.81–1.4 mmol/L
Magnesium 1.5–2.3 mg/dL 0.62–0.95 mmol/L
Lead <10 μg/dL <0.5 μmol/L
Mercury 0.6–59 μg/L 3.0–294 nmol/L
Arsenic 2–23 μg/L 0.03–031 μmol/L
Cadmium <5.0 μg/L <44.5 nmol/L
Zinc 75–120 μg/dL 11.5–18.5 μmol/L
Cardiac markers
Creatine kinase (CK) Total–Male 51–294 U/L 0.87–5.0 μkat/L
Female 39–238 U/L 0.66–4.0 μkat/L
CPK-MB 0.0–5.5 ng/mL 0.0–5.5 μg/L
Troponins Troponin I 0.0–0.08 ng/mL 0.0–0.08 μg/L
Troponin T 0.0–0.01 ng/mL 0.0–0.01 μg/L
Lactate 115–221 U/L 2.0–3.8 μkat/L
dehydrogenase (LDH)
Myoglobin Male 19–92 μg/L 19–92 μg/L
Female 12–76 μg/L 12–76 μg/L
Pancreatic function test
Amylase 20–96 U/L 0.34–1.6 μkat/L
Lipase 3–43 U/L 0.51–0.43 μkat/L
Insulin 2–20 μU/mL 14.35–143.5
pmol/L
C-peptide 0.5–2.0 ng/mL 0.17–0.66 nmol/L
Gastric function test
Gastrin <100 pg/mL <100 ng/mL
Glucagon 20–100 pg/mL 20–100 ng/L
OPC poisoning
Cholinesterase 5–12 U/mL 5–12 kU/L
Pseudocholinesterase 8–18 IU/mL
Contd…
Contd…
Urine analysis
Specific gravity 1.001–1.035 1.001–1.035
Acidity 20–40 mEq/d 20–40 mmol/d
pH 5.0–9.0 5.0–9.0
Urea 10–20 g/d 0.43–0.71 mol/d
Creatinine Male 14–26 mg/kg/d 124–230 μmol/kg/d
Female 11–20 mg/kg/d 97–177 μmol/kg/d
Uric acid 250–800 mg/d 1.49–4.76 mmol/d
Glucose 50–300 mg/d 0.3–1.7 mmol/d
Total protein <150 mg/d <0.15 g/d
Albumin Normal 0–30 mg/d 0.0–0.03 g/d
Microalbuminuria 30–300 mg/d 0.03–0.30 g/d
Macroalbuminuria >300 mg/d >0.3 g/d
Ammonia 30–50 mEq/d 30–50 mmol/d
Amylase 4–400 U/L
Calcium <300 mg/d <7.5 mmol/d
Phosphate 400–1300 mg/d 12.9–42.0 mmol/d
Sodium 100–260 mEq/d 100–260 mmol/d
Chloride 110–250 mEq/d 110–250 mmol/d
5-Hydroxy indole 2–9 mg/d 10–47 μmol/d
acetic acid (5–HIAA)
Vannilyl mandelic acid 1.4–6.5 mg/d 7–33 μmol/d
(VMA)
CSF analysis
Osmolarity 292–297 mOsmol/L 292–297 mmol/kg
H2O
Volume 150 mL
CSF pressure 50–180 mm H2O
pH 7.31–7.34 7.31–7.34
pCO2 45–49 mm Hg 6–7 kpa
Glucose 40–70 mg/dL 2.22–3.89 mmol/L
Protein (lumbar) 15–50 mg/dL 0.15–0.5 g/L
Lactate 10–20 mg/dL 1–2 mmol/L
Ammonia 25–80 μg/dL 15–47 μmol/L
Red blood cells nil nil
Leukocytes 0–5 mononuclear 0–5 mononuclear
cells/mm3 cells/μL
Contd…
786 Appendices
Contd…
Electrolytes Sodium 135–145 mEq/L 135–145 mmol/L

Potassium 2.7–3.9 mEq/L 2.7–3.9 mmol/L
Calcium 2.1–3.0 mEq/L 1.0–1.5 mmol/L
Chloride 116–122 mEq/L 116–122 mmol/L
Magnesium 2.0–2.5 mEq/L 1.0–1.2 mmol/L
Hormones
Adreno- Newborn 10–185 pg/mL 2.2 – 41pmol/L
corticotrophic
Adult <120 pg/mL <26 pmol/L
hormone (ACTH)
Aldosterone Adult–Supine 3–16 ng/dL 0.08–0.44 nmol/L
Upright 7–30 ng/dL 0.19–0.83 nmol/L
Androstenedione Child <5 ng/dL 0.2 nmol/L
Adults–Male 75–205 ng/dL 2.6–7.2 nmol/L
Female 82–275 ng/dL 3.0–9.6 nmol/L
Antidiuretic hormone 270–280 <1.5 ng/L <1.4 pmol/L
(ADH) mOsm/kg
280–285 <2.5 ng/L <2.3 pmol/L
mOsm/kg
285–290 1–5 ng/L 0.9–4.6 pmol/L
mOsm/kg
290–294 2–7 ng/L 1.9–6.5 pmol/L
mOsm/kg
295–300 4–12 ng/L 3.7–11.1 pmol/L
mOsm/kg
Catecholamines
Epinephrine Adults–Supine <50 pg/mL <273 pmol/L
(30 min)
Sitting (15 min) <60 pg/mL <328 pmol/L
Standing (30 min) <90 pg/mL <491 pmol/L
Norepinephrine Adults–Supine 110–410 pg/mL 650–2423 pmol/L
(30 min)
Sitting (15 min) 120–680 pg/mL 709–4019 pmol/L
Standing (30 min) 125–700 pg/mL 739–4137 pmol/L
Dopamine Adult (all positions) <87 pg/mL <475 pmol/L
Chorionic Male and non- <5.0 mIU/mL <5.0 IU/L
gonadotropin pregnant female
Pregnancy 5–15000 mIU/mL 5–15000 IU/L
(depends on
weeks)
Trophoblastic >100,000 mIU/mL >100,000 IU/L
disorders
Contd…
Contd…
Cortisol–total Cord blood 5–17 μg/dL 138–469 nmol/L

Infant 2–11 μg/dL 55–304 nmol/L
Child 3–21 μg/dL 83–580 nmol/L
Adult 5–23 μg/dL 138–635 nmol/L
Cortisol–free 0.6–1.6 μg/dL 17–44 nmol/L
Dehydro- Male 180–1250 ng/dL 6.25–43.4 nmol/L
epiandrosterone
11-Deoxy cortisol Cord blood 295–554 ng/dL 9–16 nmol/L
Adult 20–158 ng/dL 0.6–4.6 nmol/L
Dihydrotestosterone Child <3 ng/dL <0.10 nmol/L
Male 30–85 ng/dL 1.03–2.92 nmol/L
Estradiol Male 10–50 pg/mL 37–184 pmol/L
Female 20–450 pg/mL 73–1652 pmol/L
Postmenopausal <21 pg/mL <74 pmol/L
Estriol–free Male and <2.0 ng/mL <6.9 nmol/L
nonpregnant
female
Pregnancy 0.30–28.9 ng/mL 1.04–100.3 nmol/L
Estriol–Total Pregnancy 38–460 ng/mL 132–1596 nmol/L
Male 1.0–11.0 μg/day 3.5–38.2 nmol/day
Female 0–60.0 μg/day 0–38.2 nmol/day
Postmenopausal 0–11.0 μg/day 0–38.2 nmol/day
Estrone Male 15–65 pg/mL 55–240 pmol/L
Female 15–250 pg/mL 55–925 pmol/L
Postmenopausal 15–55 pg/mL 55–204 pmol/L
Follicular-stimulating Male 1.4–15.4 mIU/mL 1.4–15.4 IU/L
hormone
Female 1.4 – 92 mIU/mL 1.4–92 IU/L
Postmenopausal 19.3–100. 6 mIU/mL 19.3–100.6 IU/L
Growth hormone Basal 2–5 ng/mL 2–5 μg/L
Insulin tolerance >10 ng/mL >10 μg/L
test
Contd…
788 Appendices
Contd…
17-Hydroxy Male 27–199 ng/dL 0.8–6.0 nmol/L

progesterone
Pregnancy 200–1200 ng/dL 6.0–36.0 nmol/L
Post ACTH <320 ng/dL <9.6 nmol/L
Post-menopausal <70 ng/dL <2.1 nmol/L
Insulin 2–25 μIU/mL 12–250 pmol/L
Insulin-like growth 135–449 ng/mL 135–449 μg/L
factor 1
Insulin-like growth 288–736 ng/mL 288–736 μg/L
factor 2
Luteinizing hormone Male 1.2–7.8 mIU/mL 1.2–7.8 IU/L
Female–Follicular 1.7–15.0 mIU/mL 1.7–15.0 IU/L
Midcycle peak 21.9–56.6 mIU/mL 21.9–56.6 IU/L
Luteal phase 0.6–16.3 mIU/mL 0.6–16.3 IU/L
Post-menopausal 14.2–52.3 mIU/mL 14.2–52.3 IU/L
Parathormone 10–65 pg/mL 10–65 ng/L
Parathormone-related <1.4 pmol/L <1.4 pmol/L
peptide (PTHRP)
Proinsulin 1.1–6.9 pmol/L 1.1–6.9 pmol/L
Prolactin Male 3.0–14.7 ng/mL 3.0–14.7 μg/L
Female 3.8–23.0 ng/mL 3.8–23.0 μg/L
Pregnancy 95–473 ng/mL 95–473 μg/L
Testosterone–total Male 50–210 pg/mL 174–729 pmol/L
Female 1.0–8.5 pg/mL 3.5–29.5 pmol/L
Testosterone–free Male 260–1000 ng/dL 9–34.72 nmol/L
APPENDIX
2
CLINICAL SCORES, INDICES AND EQUATIONS
APACHE II SCORING SYSTEM

APACHE II Score=Acute Physiology Score + Age Points + Chronic Health Points
+4 +3 +2 +1 0 +1 +2 +3 +4
Rectal ≥ 41 39– 38– 36– 34– 32– 30– <29.9
temperature 40.9 38.9 38.4 35.9 33.9 31.9
(0°C)
MAP (mm Hg) >160 130– 110– 70–109 50– <49
159 129 69
HR >180 140– 110– 70–109 55– 40–54 <39
(beats/min) 179 139 69
RR (beats/min) >50 35–49 25–34 12–24 10 6–9 <5
–11
O2 delivery >500 350– 200– <200
(mL/min) 499 349
PaO2 (mm/ >70 61– 55–60 <55
Hg) 70
pH >7.7 7.6– 7.5 – 7.3 – 7.25– 7.15 – <7.15
7.69 7.59 7.49 7.3 7.2
Na >180 160– 155– 150– 130 120– 111– <110
179 159 154 –149 129 119
K >7 6–6.9 5.5 – 3.5 – 3–3.4 2.5 <2.5
1.9 5.4 –2.9
Cr >3.5 2–3.4 1.5– 0.6 – <0.6
1.9 1.4
Hct >60 50– 46– 30– 20– <20
59.9 49.9 45.9 29.9
WBC count >40 20– 15– 3–14.9 1–2.9 <1
39.9 19.9
790 Appendices
Age Points
<44 0
45–54 2
55–64 3
65–74 5
>75 6
History of severe organ insufficiency Points

Nonoperative patients 5
Emergency postoperative patients 5
Elective postoperative patients 2
MODS SCORING SYSTEM
Variable 0 1 2 3 4
PaO2/FiO2 >300 226–300 151–225 76–150 ≤5
Platelet count (103/mm3) >120 80–120 50–80 21–50 ≤20
Bilirubin (mg/dL) ≤1.2 1.2–3.5 3.5–7.0 7.0–14 ≥14
HR X CVP/MAP ≤10 10.1–15 15.1–20 20.1–30 >30
Glasgow Coma Scale 15 13–14 10–12 7–9 ≤6
score
Creatinine (mg/dL) ≤1.1 1.1–2.3 2.3–4 4.0–5.7 5.7
Abbreviations: HR, heart rate; CVP, central venous pressure; MAP, mean arterial pressure
SOFA SCORING SYSTEM
Variable 1 2 3 4
PaO2 (mm Hg) <400 ± <300 ± MV <200 + MV < 100 + MV
MV
Platelet count (103/ <150 <100 <50 <20
mm3)
Cardiovascular MAP <70 Dopa/ Dopa >5 μg/kg/ Dopa >15 μg/
system mm Hg dobutamine min, adr/NA kg min, adr/NA
≤5 μg/kg ≤0.1 μg/min >0.1 μg/min
min
Glasgow Coma 13–15 10–12 6–9 <6
Scale
Bilirubin (mg/dL) 1.2–1.9 2–5.9 6–11.9 >12
Cr (mg/dL) or 1.2–1.9 2–3.4 3.5–4.9 or >5 or
Urine output <500 mL/day <200 mL/day
Abbreviations: MV, mechanical ventilation; MAP, mean arterial pressure; NA, noradrenaline
Appendix 2 Clinical Scores, Indices and Equations 791
GOLD CRITERIA FOR GRADING SEVERITY OF COPD
GOLD stage–severity Spirometry

0 – At risk Normal
I – Mild FEV1/FVC <0.7 and FEV1 ≥80% predicted
II – Moderate FEV1/FVC <0.7 and 50% ≤FEV1 <80% predicted
III – Severe FEV1/FVC <0.7 and 30% ≤FEV1 <50% predicted
IV – Very severe FEV1/FVC <0.7 and FEV1<30% predicted
or
FEV1 <50% predicted with respiratory failure or signs of right
heart failure
LEVELS OF RISK ASSOCIATED WITH INCREASING BODY MASS INDEX
Classification BMI (kg/m2) Risk of developing health problems

Underweight <18.5 Increased
Normal weight 18.5–24.9 Least
Overweight 25.0–29.9 Increased
Obese
Class 1 30.0–34.9 High
Class 2 35.0–39.9 Very high
Class 3 40.0–49.9 Extremely high
Superobese ≥50 Exceedingly high
WAIST CIRCUMFERENCE AND RISK
Waist Circumference Body Mass Index (kg/m2)

Normal Weight Overweight Obese Class 1
< 102 cm (♂) Least risk Increased risk High risk
< 88 cm (♀)
≥ 102 cm (♂) Increased risk High risk Very high risk
Nitrogen balance (g) = protein intake (g) – (24 hours urinary urea nitrogen
excretion + 4) 6.25
The respiratory quotient (RQ) is the ratio of VCO2 to VO2.
RQ = VCO2/VO2
Harris Benedict equation:

• Men: BEE (kcal/24 hr) = 66.5 + (13.7 × weight) + (5 × height) – (6.8 × age)
• Women: BEE (kcal/24 hr) = 66.5 + (9.6 × weight) + (1.7 × height) – (4.7 × age)
792 Appendices
Calculation of REE:
• REE (kcal/min) = 3.94 (VO2) + 1.1(VCO2)
• REE (kcal/day) = REE × 1440
SF-MPQ (SHORT FORM–MCGILL PAIN QUESTIONNAIRE)
Quality of pain None Mild Moderate Severe

Throbbing
Shooting
Stabbing
Sharp
Cramping
Gnawing
Hot burning
Aching
Heavy
Tender
Splitting
Tiring–exhausting
Sickening
Fearful
Punishing-cruel
No pain ...................................................................................worst possible pain
Table 1 Present pain intensity (PPI)
0 No pain
1 Mild
2 Discomforting
3 Distressing
4 Horrible
5 Excruciating
RAMSAY SEDATION SCALE (RSS)
Score Description
1 Anxious and agitated or restless, or both
2 Cooperative, orientated, and tranquil
3 Drowsy, but responds to commands
4 Asleep, brisk response to light glabellar tap or loud auditory stimulus
5 Asleep, sluggish response to light glabellar tap or loud auditory stimulus
6 Asleep and unarousable
RICHMOND AGITATION SEDATION SCALE (RASS)
Score Label Description

+4 Combative Combative, violent, immediate danger to staff
+3 Very agitated Pulls to remove tubes or catheters; aggressive
+2 Agitated Frequent non-purposeful movement, fights ventilator
+1 Restless Anxious, apprehensive, movements not aggressive
0 Alert and calm Spontaneously pays attention to caregiver
–1 Drowsy Not fully alert, but has sustained awakening to voice
(eye opening and contact >10 sec)
–2 Light sedation Briefly awakens to voice (eyes open and contact <10 sec)
–3 Moderate sedation Movement or eye opening to voice (no eye contact)
–4 Deep sedation No response to voice, but movement or eye opening to
physical stimulation
–5 Unarousable No response to voice or physical stimulation
Oxygen Saturation at Various Chambers and Vessels

Sampling chamber or vessel Oxygen saturation (in %)
SVC 70
IVC 80
RA 75
RV 75
Pulmonary artery 75
794 Appendices
Parameters Measured by Pulmonary Artery (PA) Catheter

Variable Normal range (Units)


Derived Parameters Obtained with Data from PA Catheter

Body surface area (BSA) Weight(kg) 0.425
× height
(cm) 0.725 × 0.007184
Arterial oxygen content (CaO2) SaO2 × Hb × 1.39 + 180 mL liter–1
PaO2 (mm Hg) × 0.003
Mixed venous oxygen content SvO2 × Hb × 1.39 + 130 mL liter–1
(CVO2) PvO2 (mm Hg) × 0.003
Oxygen delivery (DO2) Ǭ × CaO2 800–1000 mL min –1
Oxygen consumption (VO2) Ǭ/(Cao2/CvO2) 180–300 mL min–1
Oxygen delivery index (DO2I) DO2/BSA 500–650 mL min–1 m–2
Oxygen consumption (VO2 I) VO2/ BSA 100–180 mL min–1 m–2
Cardiac index (CI) Ǭ/BSA 2.5–4.0 liter min–1 m–2
Left ventricular stroke work index CI × (MAP – PAOP) × 40–60 g m–1 m–2
(LVSWI) 0.0136
Systemic vascular resistance (SVR) (MAP – CVP) × 80/Ǭ 900–1200 dyn s cm–5 m–2
Systemic vascular resistance (MPA – CPA) × 80/CI 1500–2500 dyn s cm–5
index (SVRI) m–2
Mean pulmonary artery pressure [PASP + (2 × PADP)]/3 10–20 mm Hg
(mPAP)
Right ventricular stroke work Cl × (MPAP – CVP) × 6–12 g m–1 m–2
index (RVSWI) 0.0136
Pulmonary Vascular resistance (MPAP – PAOP) × 80/Ǭ 50–150 dyn s cm–5 m–2
(PVR)
Pulmonary vascular resistance (MPAP – PAOP) × 80/CI 250–350 dyn s cm –1 m–2
index (PVRI)
Ǭ, cardiac output
Grading of Diffuse Axonal Injury (DAI)

Clinical grading of DAI
1. Mild DAI—duration of coma is between 6 and 24 hours.
2. Moderate DAI—duration of coma is for >24 hours but without presence of
decerebrate posturing as the best motor response on nociceptive stimulation.
3. Severe DAI—duration of coma is for >24 hours and with presence of decerebrate
posturing as a motor response on nociceptive stimulation.
MRI grading of DAI
1. Grade 1—small scattered lesions on the white matter of cerebral hemisphere
2. Grade 2—grade 1 plus focal lesions on the corpus callosum
3. Grade 3—grade 1 and 2 plus additional focal lesions on the brainstem.
Glasgow Coma Scale
Eye-opening response 4 = Spontaneous

3 = To speech
2 = To pain
1 = None
Verbal response 5 = Oriented to name
4 = Confused
3 = Inappropriate speech
2 = Incomprehensible sounds
1 = None
Motor response 6 = Follows commands
5 = Localizes to painful stimuli
4 = Withdraws from painful stimuli
3 = Abnormal flexion (decorticate posturing)
2 = Abnormal extension (decerebrate posturing)
1 = None
Severity of GCS Score Need of CT–Brain Management

Mild 14, 15 Yes Observation
Moderate 9–13 Yes Observation in ICU
Severe 3–8 Yes Mechanical ventilation with ICP
monitoring
796 Appendices
Marshall Scale: CT Scan Categories for Head Injury

Category Definition
Diffuse injury I No visible intracranial pathologic process
Diffuse injury II Cisterns with midline shift of 0–5 mm are present
± lesion densities present; no high or mixed density
lesions at ≥ 25 mL
Diffuse injury III Cisterns compressed or absent, with midline shift of
0–5 mm; no high or mixed density lesions of ≥ 25 mL
Diffuse injury IV Midline shift of >5 mm; no high or mixed density lesion
of ≥ 25 mL
Evacuated mass lesion (V) Any lesion surgically evacuated
Nonevacuated mass lesion (VI) High or mixed density lesion of ≥ 25 mL; not surgically
evacuated
Differences Between Pre-renal Azotemia and Acute Kidney Injury

Pre-renal azotemia Acute kidney injury
BUN/creatinine ratio above 20 FeNa typically >1%
FeNa <1% Urine sediment often contains granular
Urine sodium concentration < 10 mEq per L casts, renal tubular epithelial cell casts.
Urine specific gravity >1.018 Urine osmolality < 500 mOsm/kg
Urine osmolality >500 mOsm/kg
Urine sediment shows hyaline casts
Table 2 RIFLE criteria for acute renal dysfunction
Category GFR Urine output

Risk Increased creatinine × 1.5 UO < 0.5 mL/kg/hr × 6 hr High sensitivity
or GFR decrease >25%
Injury Increased creatinine × 2 or UO < 0.5 mL/kg/hr × 12 hr
GFR decrease >50%
Failure Increased creatinine × 3 or UO < 0.3 mL/kg/hr × 24 hr High
GFR decrease >75% or anuria × 12 hrs specificity
Loss Persistent ARF = complete loss of function > 4 weeks High
specificity
ESRD End stage disease
APPENDIX
3
DRUGS, DOSAGES AND SIDE EFFECTS
CARDIOVASCULAR SYSTEM
Maintenance
S.No. Drugs Loading dose dose Adverse effects
Acute 1 Anti-platelets
myocardial
Clopidogrel 75 mg PO Nausea, vomiting, diarrhea,
infarction
Daily bleeding, thrombotic throm-
bocytopenic purpura
2 Beta-blockers
Metoprolol 5 mg IV X 3 50–200 mg Bradycardia,
Dose PO q 12 hypotension, fatigue,
bronchospasm, heart
Esmolol 500 mg/kg 50–300 mg/
block depression, sexual
kg/minute
dysfunction
3 Direct thrombin inhibitors
Argatroban 350 mg/kg 25 mg/kg/ Bleeding and hypersensi-
minute tivity reactions
Bivalirudin 1 mg/kg 2.5 mg/kg/hr
4 Fibrinolytics
Alteplase 15 mg 0.75 mg/kg Mild hypotension, bleed-
(50 mg ) x ing
30 minute
0.5 mg/kg
(35 mg ) x 60
minute
100 mg over
90 minute
Reteplase 10 mg IV 10 mg IV
after 30
Tenectaplase ≤60 kg– 30
minute of
mg
first dose
61–70
kg–35 mg
71–80
kg–40 mg
Contd…
798 Appendices
Contd…
Maintenance
81– 90
kg–45 mg
≥90 kg–50
mg
Streptoki- 1.5 million
nase units over
2 hrs
5 Gp IIb/IIIa inhibitors
Abciximab 0.25 mg/kg 0.125 mg/ Thrombocytopenia,
kg/minute bleeding
Eptifibitide 180 mg/kg 2 mg/kg/
minute
Tirofiban 0.4 mg/kg/ 0.1 mg/kg/
min x 30 min minute
6 Low molecular weight heparins
Enoxaparin 1 mg/kg SC
q12h
Dalteparin 120 U/kg SC
q12h
7 Nitrates
Nitroglycerin 10–200 mg/ Headache, flushing,
min dizziness, hypotension,
tachycardia
Isosorbide 5–40 mg PO
dinitrate TID
Isosorbide 30–120 mg
mono nitrate PO daily
8 NSAIDs
Aspirin 160–325 Bleeding, dyspepsia,
mg/D– PO gastritis. Tinnitus, ana-
phylaxis
9 Opioids
Morphine 2–4 mg IV Constipation, dyspepsia,
q5 minute nausea, drowsiness,
respiratory depression,
hypotension, pruritis
10 Unfractioned 60 U/kg/hr 12 U /kg/hr Bleeding, type 1 and type
heparin 2 heparin-induced throm-
bocytopenia, bleeding,
hyperkalemia
Contd…
Appendix 3 Drugs, Dosages and Side Effects 799
Contd…
Maintenance
Anti 1 Adenosine 6 mg (repeat Flushing, headache,
arrhyth- 12 mg if first nervousness, anxiety
mics and dose is not
conduction effective)
abnormali-
2 Amiodarone 300 mg 1 mg/min Bradycardia, hypoten-
ties
x 6 hr sion, nausea, heart
0.5 mg/ block, pulmonary fibrosis,
minute for blue gray discoloration,
≥18 hour optic neuropathy
3 Atropine 1 mg IV q Dry eyes, dry mouth ,
3–5 minute urinary retention, tachy-
cardia
4 Calcium channel blockers
Diltiazem 0.25 mg/kg 5–15 mg/hr Bradycardia, hypoten-
sion, constipation, head-
Verapamil 5 mg 5–15 mg/hr
ache, flushing edema,
heart block and heart
failure
5 Epinephrine 1 mg IV q Tachycardia , hyperten-
3–5 minute sion
6 Lidocaine 1–1.5 mg/kg 1–4 mg/ Confusion, drowsiness,
minute slurred speech, psychosis,
muscle twitch, bradycar-
dia, seizure
7 Procaina- 15–18 mg/ 1–6 mg/kg Diarrhea, nausea, vomit-
mide kg ing, torsade de pointes
8 Vasopressin 40 units IV Bradycardia, precipitates
angina, congestion,
rhinitis, epistaxis, fluid
retention, hyponatremia
Congestive 1 Angiotensin-converting enzyme (ACE) inhibitors
heart
failure Captopril 6.25 – 50 Cough, hyperkalemia,
mg PO TID hypotension, renal insuf-
ficiency, anaphylaxis,
angioneurotic edema
Lisinopril 2.5–40 mg
PO BID
Enalapril 2.5–10 mg
PO BID
Ramipril 1.25–5 mg
PO BID
2 Aldosterone receptor blockers
Spironolac- 12.5–50 mg Hyperkalemia, gyneco-
tone PO mastia, hyponatremia
Eplerenone 25–50 mg
PO
Contd…
800 Appendices
Contd…
Maintenance
3 Digoxin 10–15 mg/ 0.125–0.5 Bradycardia, arrhyth-
kg ( 50 % in mg/day mias, heart block, visual
initial dose, disturbances, mental
and 25 % at disturbances
6–12 hrs x 2)
4 Loop diuretics
Furosemide 20–80 mg/ Hypokalemia, hy-
day IV or pomagnesemia,
PO IN 2 – 3 hypocalcemia, ortho-
divided dose static hypotension,
azotemia,ototoxicity
Torasemide 10 – 20 mg
IV /PO daily
Bumetanide 0.5 – 2 mg/
day in 1 –2
doses
5 Nesiritide 2 mg/kg 0.01–0.03 Hypotension, increased
mg/ kg/min serum creatinine
Hyper- 1 Angiotensin-converting enzyme (ACE) inhibitors
tensive
Enalaprilat 1.25 – 5 mg Hypotension,
emergen-
IV q6h hyperkalemia, renal
cies
insufficiency, anaphylaxis,
angiodema
2 Beta and alpha adrenergic blocker
Labetalol 20 – 40 mg 0.5–2 mg/ Nausea, vomiting,
minute if hypotension,
needed bradycardia, heart block,
bronchoconstriction
Nicardipine 3 – 15 mg/hr Hypotension,
tachycardia, flushing,
peripheral edema
4 Central sympatholytics
Clonidine 0.1 – 0.3 mg Drowsiness,
PO BID–TID dizziness,hypotension,
bradycardia, dry mouth
5 Vasodilators
Hydralazine 10 – 40 mg Hypotension,
(arteriolar ) IV q4–q6 tachycardia, flushing,
h Or headache, lupus like
10 – 75 mg syndrome, peripheral
PO TID – neuropathy
QID
Nitroprus- 0.25 – 3 mg/ Nausea, vomiting,
side (arte- kg/min hypotension, tachycardia,
riolar and (max 10 mg/ thiocyanate and cyanide
venous) kg/min) toxicity, muscle spasm
RESPIRATORY SYSTEM
Loading Maintenance
S.No. Drugs dose dose Adverse effects
Acute respiratory 1 Anticholinergics
distress
syndrome Ipratropium 2–4 puffs Dry mucus
(ARDS)/ BID to QID membranes,
asthma, chronic tachycardia
obstructive 2 Beta agonists
pulmonary
Albuterol 2–4 puffs Tachycardia,
disease (COPD)
BID to QID insomnia, irritability,
nervousness, tremor,
Levalbuterol 0.63–0.125
hyperglycemia,
mg TID
hypokalemia
3 Corticosteroids
Methyl 2 mg/kg Short term
predniso- in divided Hyperglycemia,
lone doses mood changes,
insomnia,
gastrointestinal (GI)
irritation, increased
appetite
Long term
osteoporosis, acne,
thin skin, muscle
wasting,cataracts,
infection, HPA axis
suppression
Pulmonary 1 Anticoagulants
hypertension
Warfarin Target INR Bleeding, skin
necrosis, purple toe
syndrome
Diltiazem Up to 720 Peripheral
mg/day edema, flushing,
headache, dizziness,
Nifedipine Up to 240
hypotension,
mg/day
gingival hyperplasia,
increased
cardiovascular events
3 Endothelin antagonist
Bosentan 62.5 mg 125 mg PO Headache, flushing,
PO BID x 1 BID hypotension,
month hepatotoxicity
anemia
4 PDE – 5 inhibitors
Sildenafil 20 mg PO Headache, flushing,
TID hypotension,
dyspepsia, vision
changes
Contd…
802 Appendices
Contd…
Loading Maintenance
Nitric oxide 5–40 PPM Hypotension,
methemoglobinemia,
elevated nitrogen
dioxide
5 Prostacyclins
Epopros- 2–50 ng/ Jaw pain, nausea,
tenol kg/min IV headache, flushing,
5000– hypotension, infusion
20000 site pain
ng/mL
continuous
nebulization
Treprostinil 10–150
ng/kg/min
iloprost 2.5–5 mg
inhaled
6–9 times
daily
Shock 1 Corticosteroids
Hydrocorti- 200–300 Short-term

sone mg/day in hyperglycemia, mood
3 to 4 changes, insomnia,
divided GI irritation,
doses increased appetite,
osteoporosis,acne,
thin skin, muscle
wasting,cataract,
infection, HPA axis
suppression
2 Drotrecogin 24 mg/kg/ Bleeding
alpha hr x 96 hrs
3 Inotropes/ vasopresors
Norepi- 0.02–3 mg/ Hyperglycemia, tissue
nephrine kg/minute hypoxia, tachycardia,
arrhythmias,
myocardial ischemia,
tissue necrosis
Epinephrine 0.01–0.1 Hyperglycemia,
mg/kg/ tachycardia,
minute arrhythmias,
splanchnic and renal
hypoxia
Phenyle- 0.5–10 mg/ Tachycardia, reduced
phrine kg/minute cardiac output,
necrosis
Contd…
Contd…
Loading Maintenance
Dopamine 5–20 Tachycardia
mg/kg/min
Vasopressin 0.01–0.04 Reduced cardiac
U/minute output, myocardial
ischemia, hepato-
splanchnic
hypoperfusion,
thrombocytopenia,
hyponatremia
Dobutamine 2.5–20 mg/ Tachycardia,
kg/minute arrhythmia
4 Mineralocorticoids
Fludrocorti- 50–100 mg Hypertension,

sone PO q24h edema,
hypernatremia,
hypokalemia
5 Mixed dilators
Milrinone 50 mg/kg 0.25–0.75 Hypotension,
mg/kg/minute thrombocytopenia,
arrhythmia
6 Thrombolytics
Alteplase 100 mg IV Bleeding
over 2 hrs
ELECTROLYTE IMBALANCE
Loading Maintenance
Hyperkalemia Albuterol 10–20 mg Tachycardia,
nebulized insomnia, irritability,
over 30–60 nervousness, tremor,
minute hyperglycemia,
hypokalemia
Calcium 1 g IV over Hypercalcemia,
gluconate 2 minute constipation,
arrhythmias, phlebitis
Regular 10–20 U IV Hypoglycemia,
human (~ 1 U allergy, edema, local
insulin FOR 4–5 g reactions
dextrose)
Sodium bi- 1 mEq/ Hypoglycemia,
carbonate kg/IV hypokalemia, weight
gain, local skin
reactions
Contd…
804 Appendices
Contd…
Loading Maintenance
Hypercalcemia 1 Calcitonin 4 U/kg (up Facial flushing,
to 8 U/kg) nausea, vomiting,
allergic reactions
2 Bisphosphonates
Pamidro- 60–90 mg Fever, fatigue,
nate IV thromboplebitis,
bone, joint and
muscle pain
Zoledronic 4 mg IV
acid
Hypophos- Phosphate salts
phatemia
Potassium 0.08–0.16 Hyperphosphatemia,
phosphate mmol/kg IV hypocalcemia,
Sodium over 6 hr hypomagnesemia,
phosphate hyperkalemia,
hypernatremia,
diarrhea
ENDOCRINE DISORDERS
Loading Maintenance
Adrenal 1 Corticosteroids
insufficiency
Hydrocorti- 100 mg IV Short-term
sone q8h Hyperglycemia, mood
changes, insomnia,
Dexametha- 10 mg
GI irritation,
sone IV prior
increased appetite
to ACTH
Long-term
stimulation
Osteoporosis,acne,
test
thin skin, muscle
wasting,cataracts,
infection, HPA axis
suppression
Fludrocorti- 50–200 mg Hypertension, edema,
sone PO q24h hypernatremia,
hypokalemia
Hyperthyroidism 1 Thio urea drugs
Propylthi- 300–600 50–300 Rash, fever,
ouracil mg/day in mg/day arthralgias,
3 divided leukopenia,
doses q8h agranulocytosis,
aplastic anemia,
hepatotoxicity, lupus
like syndrome, hypo-
prothrombinemia,
polymyositis
Contd…
Contd…
Loading Maintenance
Methima- 30–60 5–30 mg/day
zole mg/day in
divided dose
q8h
2 Beta 10–40 mg Bradycardia,
blockers PO q6h hypotension, fatigue,
bronchospasm,heart
block depression,
sexual dysfunction,
dyslipidemia, altered
glucose metabolism
cold extremities
3 SS 1–2 drops Metallic taste,
potassium PO q12h nausea, stomach
iodide upset,salivary
gland swelling,
hypersensitivity
reactions
Hypothyroidism 1 Thyroid 50–100 m 100 mg IV Symptoms of
hormones IV q6–q8 x q24 hr hyperthyroidism
Levothyrox- 24 hr
ine
Temperature 1 Acetami- 325–1,000 Hepatotoxicity
control nophen mg PO q4–
q6 PRN
2 Bromocrip- 2–205 mg Headache, dizziness,
tine PO TID nausea, diarrhea,
hypotension, nasal
congestion
3 Dantrolene 1–2.5 mg/ Drowsiness, dizziness,
kg IV diarrhea, vomiting,
(may repeat hepatotoxicity, muscle
q5–q10 min weakness
up to 10
mg/kg
4 NSAIDs
Ibuprofen 200–800 Gastric irritation,
mg PO q3– nausea, gastric ulcer,
q6 h PRN acute renal failure
Ketorolac 15–30 mg
IM or
10 mg PO
PRN
806 Appendices
GASTROINTESTINAL DISORDERS
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S. No. Drugs dose dose Adverse effects
Proton pump inhibitors
1 Pantopra- 20–40 mg 8 mg/hr x 72 Headache, dizzi-
zole PO q12– hrs ness, somnolence,
q24 h diarrhea, constipa-
80 mg IV tion, nausea
bolus
Omepra- 20–40 mg
zole PO q12–
q24 h
Lansopra- 30–60 mg
zole PO q12–
q24 h
Esomepra- 20–40 mg
zole PO q24 h
2 Octreotide 25–50 mg IV 25–50 mg/hr Diarrhea,
bolus infusion flatulence, nausea,
abdominal cramps,
bradycardia,
arrhythmia,
conduction
abnormalities,
hypothyroidism,
cholelithiasis
HEPATIC DYSFUNCTION
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1 Lactulose 20–30 g Diarrhea, flatulence,
(30–45 mL) nausea
PO q2h
2 Neomycin 500–2000 Nausea, vomiting,
mg PO q6– diarrhea, irritation,
q12 soreness of mouth
or rectal area,
nephrotoxicity,
neurotoxicity
3 Nonspecific
Beta Bradycardia,
blockers hypotension, fatigue,
bronchospasm,heart
Propranolol 20–80 mg
block depression,
PO q12h
sexual dysfunction,
Nadolol 20–80 mg dyslipidemia, altered
PO q12h glucose metabolism,
cold extremities
4 Rifaximin 400 mg PO Headache
TID
HEMATOPOIETIC DISORDERS
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1 DDAVP 0.3 mg/kg Facial flushing,
hyponatremia,
hypotension,
tachycardia,
thrombosis
2 Direct thrombin inhibitors
Lepirudin 0.1–0.15 Bleeding, allergic
mg/kg/hr reactions
Argatroban 2 mg/kg/
min
3 Phytonadi- 1–10 mg Anaphylaxis,
one q24h hypotension
4 Warfarin 1–5 mg/day Bleeding, skin
necrosis, purple toe
syndrome
CENTRAL NERVOUS SYSTEM

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Status 1 Benzodiazepines
epilepticus
Lorazepam 0.1 mg/kg Central nervous sys-
at 2 mg/min tem (CNS) depres-
up to 8 mg sion, paradoxical
excitation, hypoten-
Midazolam 0.2 mg/kg 0.75–10 mg/
sion, respiratory
kg/minute
depression
2 Hydantoin 20 mg Hypotension, brady-
FOS phenytoin cardia, phlebitis,
phenytoin eq/kg/IV/IM gingival hyperplasia,
folic acid deficiency,
hirsutism, acne,
vitamin D deficiency,
osteomalacia
3 Levetri- 500–1000 Somnolence,
acetam mg IV/PO nausea, vomitng,
q12h behavioral
disturbances
4 Barbiturate 20 mg/kg IV Sedation, nystag-
Phenobar- mus, ataxia, nausea,
bitol vomiting, hypoten-
sion, bradycardia,
respiratory depress-
sion, rash , bone
marrow suppression
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808 Appendices
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5 Phenytoin 20 mg/kg IV 5–7 mg/kg/ Nystagmus, diplo-
day pia, ataxia, sedation,
lethargy, behavioral
changes, coma,
seizures, idiosyn-
cratic reactions like
rash, bone marrow
suppression, Steven–
Johnson syndrome,
hepatitis
6 Propofol 30–250 mg/ Hypotension, brady-
kg/min cardia, CNS depres-
sion hypertriglyceri-
demia, pancreatitis,
propofol infusion
syndrome
7 Valproate 1000–2500 Somnolence,
mg/day IV/ diplopia, nausea,
PO in 2–4 diarrhea, hepato-
divided dose toxicity, pancreatitis,
thrombocytopenia,
hyperammonemia,
rash
Elevated ICT 1 Hypertonic 30–50 mL Hypernatremia,
saline q3–q6h hyperchloremia
2 Mannitol 1–1.5 g/ 0.25–1 g/kg Hypotension, acute
kg/IV q3 –q6 renal failure, fluid
and electrolyte
imbalances
Stroke 1 Alteplase 0.9 mg/kg Bleeding
(ischemic IV (10 % as
stroke) initial bolus)
2 Factor VII 1.2–4.8 Hypertension,
(hemor- mg IV thrombosis
rhagic
stroke)
Butyroph- 2–80 mg CNS depression,
Delirium enones IV/PO q6h orthostatic
Haloperidol hypotension, QT
prolongation, extra-
pyramidal side
effects, neuroloptic
malignant syndrome
Sedation 1 Benzodiaz-
epines
Lorazepam 2–4 mg 0.5–4 mg /hr CNS depression, par-
adoxical excitation,
hypotension, respira-
tory depression
Contd…
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Midazolem 1–5 mg 1–10 mg /hr
Propofol 25–100 mg/ Hypotension,
kg/minute bradycardia, CNS
depression hyper-
triglyceridemia,
pancreatitis,
propofol infusion
syndrome
2 Dexme- 0.2–0.7 mg/ Hypotension,
detomidine kg/hr bradycardia
INFECTIOUS DISEASES
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Antibacterial 1 Aminoglycosides
drugs Amikacin 8 mg/kg IV Nephrotoxicity,
12 h ototoxicity
Or
15 mg/kg
Gentamicin 3 mg/kg 2 mg/kg IV
q8 h or
5–7 mg/kg
Anti-staphy-
lococcal
2 Penicillins
Nafcillin 2 g IV q4– Diarrhea, nausea,
q6 vomiting, rash
Oxacillin 2 g IV q4– anaphylaxis, neutro
q6 h penia, thrombo-
cytopenia, acute
interstitial nephritis,
hepatotoxicity
3 Beta lactam/lactamase inhibitors
Amoxicillin/ 875 mg PO Anaphylaxis, seizure,
clavulanate BID hemolytic anemia,
Ampicillin/ 1.5–3 g IV neutropenia,
sulbactam q6h thrombocytopenia,
Clostridium difficile
Piperacillin/ 3.375–4.5 colitis, cholestatic
tozabactam g IV q6h jaundice, drug fever
Ticarcillin/ 3.1g IV q4–
clavulanate q6 h
4 Carbapenems
Imipenem 500 mg– Diarrhea, nausea,
1 g IV vomiting, anaphy-
q6–q8 h laxis, seizures, drug
fever, C. difficile colitis
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810 Appendices
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Meropenam 1 g IV q8h
Ertapenam 1 g IV q 24 h
5 Cephalosporins
Cefazolin 1–2 g IV Diarrhea, nausea,
q8 h vomiting, rash
Cefoxitin 1–2 g IV anaphylaxis, seizure,
q4–q8h hemolytic anemia,
neutropenia,
Ceftriaxone 1–2 g IV thrombocytopenia,
q12–q24 h drug fever
Cefepime 500 mg–
2 g IV
q8–q12 h
6 Clindamycin 600–900 Nausea, vomiting,
mg IV q8h diarrhea, rash,
abdominal pain,
C. difficile colitis
7 Tetracyclins
Ciprofloxa- 500–750 Nausea, vomiting,
cin mg PO BID diarrhea, photo-
or sensitivity, rash,
400 mg IV anaphylaxis, QT
q8–q12 h prolongation, joint
toxicity in children,
tendon rupture
Levofloxa- 500–750 CNS stimulation,
cin mg IV/ dizziness, som-
PO q24 8h nolance
Moxifloxacin 400 mg IV/
PO q24 h
Gemifloxa- 320 mg PO
cin q24 h
8 Glycopeptides
Vancomycin 15 mg/kg IV Red man syndrome,
q12 h ototoxicity, nephro-
toxicity, thrombocy-
topenia
9 Glycylcyclines
Tigecycline 100 mg IV 50 mg IV Nausea, vomiting,
q12 h diarrhea
10 Ketolides
Telithromy- 800 mg PO Nausea, vomiting,
cin q24 h diarrhea, acute
hepatic failure, QT
prolongation
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11 Lipopeptides
Daptomycin 4–6 mg/kg Constipation,
IV q24 h diarrhea, vomiting,
myopathy, anemia
12 Macrolides
Erythromy- 250–500 Nausea, vomiting,
cin mg PO QID diarrhea, abnormal
Or taste, QT prolonga-
0.5–1.0 g IV tion, cholestasis
q6h
Azithromycin 250–500
mg IV/
PO daily
Clarithro- 250–500
mycin mg
PO BID
13 Metronida- 500 mg IV/ Nausea, vomiting,
zole PO q8h metallic taste, disul-
firam like reaction,
seizure, peripheral
neuropathy
14 Oxazolidinediones
Linezolid 600 mg IV/ Diarrhea, peripheral
PO q12 h and optic neuropa-
thy, myelosuppres-
sion, lactic acidosis
15 Penicillins
Ampicillin 2–3 g IV Diarrhea, nausea,
q4–q6 h vomiting, rash
Aqueous 2–4 million anaphylaxis, seizure,
penicillin g U IV q4h hemolytic anemia,
neutropenia, throm-
bocytopenia, drug
fever
16 Streptogramin
Quinu- 7.5 mg/kg Arthralgia, myalgia,
pristin/ IV q8h inflammation, pain
dalfopristin edema at infusion
site, hyperbilirubine-
mia
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812 Appendices
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17 Tetracyclins
Tetracyclin 250–500 Photosensitivity,
mg diarrhea, tooth
PO q6 h discoloration,
bone and growth
retardation, renal
tubular necrosis,
dizziness, vertigo,
pseudotumor
cerebri
Doxycyclin 100 mg IV/
PO q12 h
Minocyclin 200 mg PO 100 mg
PO q12 h
18 Trimetho- 5 mg/kg Rash, nausea,
prim/ IV q8h vomiting, diarrhea,
sulfameth- myelosuppression,
oxazole Stevens–Johnson
syndrome, hyper-
kalemia, aseptic
meningitis, hepatic
necrosis
Antifungal 1 Amphotericin B
drugs Ampho- 0.3–1.5 Infusion-related
tericin B mg/kg reactions,
deoxycho- q24 h hypokalemia,
late hypomagnesemia,
nephrotoxicity,
acute liver failure,
myelosuppression
2 Azoles
Fluconazole 100–80 mg Nausea, vomiting,
PO/IV daily diarrhea, rash,
visual disturbances,
phototoxicity,
hepatic failure,
CVS toxicity,
hypertension,
edema
Itraconazole 200 mg IV/
PO q24 h
Voricona- 4 mg/kg IV
zole q12 h
Or
200 mg PO
BID
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3 Echinocandins
Caspo- 70 mg IV 50 mg IV Hepatotoxicity, rash,
fungin q24 h flushing, itching
Micafungin 50–150 mg
IV q24 h
4 Flucytosine 25–37.5 Nausea, vomiting,
mg/kg diarrhea, rash,
PO q6 h myelosuppression,
hepatotoxicity, con-
fusion, hallucina-
tion, sedation
Toxicology 1 Activated 25–100 g Vomiting, con-
charcoal stipation, fecal
discoloration, bowel
obstructions
2 Benzodi- 0.2–0.5 mg Withdrawal symp-
azepine IV q1 minute toms (sweating,
poisoning (up to 5 mg) agitation, hyperten-
Flumazenil sion, tachycardia,
nausea, vomit-
ing, CVS events,
seizures)
3 Iron
chelating 1 g IV 500 mg IV q4 Urine–orange dis-
agent h x 2 doses coloration, hypoten-
Deferoxam- sion, tachycardia,
ine erythema, urticaria,
anaphylaxis, res-
piratory distress
syndrome
4 Methyl
alcohol 15 mg/kg IV 10 mg/kg IV No specific side
poisoning q12 h x 4 effects
Fomepizole doses
15 mg/kg IV
q12 h until
methanol
level <20
5 Morphine 0.4–2 mg IV Withdrawal symp-
poisoning q2 min (up toms (sweating,
Naloxone to 10 mg) agitation, hyperten-
sion, tachycardia,
nausea, vomit-
ing, CVS events,
seizures, pulmonary
edema)
Contd…
814 Appendices
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6 Paracetamol Oral Oral Nausea, vomiting,
poisoning 140 mg/kg 70 mg/kg q4 unpleasant odor,
N–acetyl IV h x 17 doses anaphylatic
cysteine 150 mg/kg IV reactions
1.5 mg/kg/hr
x 4hr
Then
6.25 mg/kg/
hr x 16 hr
Pregnancy 1 Hydralazine 10–40 mg Hypotension, flush-
IV q4–q6 h ing, tachycardia,
Or headache, drug-
10–75 mg induced lupus like
PO TID– syndrome, periph-
QID eral neuropathy
2 Labetalol 100–800 Hypotension, brady-
mg PO q cardia, nausea,
8–q12 vomiting, heart
(max 2.4 g/ block, broncho-
day) constriction
3 Magnesium 4–6 g IV 2 g/hr Hypermagnesemia,

sulfate over 15 –20 infusion diarrhea
minute
4 Phenytoin 20 mg/kg IV 5–7 mg/kg/ Nystagmus,
day diplopia, ataxia,
sedation, lethargy,
behavioral changes,
coma, seizures, idi-
osyncratic reactions
like rash, bone mar-
row suppression,
Steven–Johnson
syndrome, hepatitis,
gingival hyperplasia,
folic acid deficiency,
hirsutism, acne,
vitamin D deficiency,
osteomalacia
APPENDIX
4
ICU ROUNDS
ESSENTIAL DATA AND ASSESSMENT FOR

MANAGEMENT OF CRITICALLY ILL PATIENTS
History
• Review the ICU chart or progress notes
• Review the overnight events
• Review medication.
Physical Examination
• Focussed examination on all systems
• Mental status
• Sedation status (Ramsay sedation score)
• Degree of pain (Visual analogue score).
External Device Data

• Review ventilator settings
• Assess the patency of catheters and tubes
• Review all infusions.
Laboratory Data
• Complete blood count
• Tests of specific interest to the patient
• ABG.
Imaging Data
• Chest X-ray
• CT/MRI
• Angiogram.
INDEX
Page numbers followed by f refer to figure, fc refer to flow chart, and t refer to table.
A antagonists 340
Abciximab 798 Adrenal crisis 455
Abdomen 73, 604 pathophysiology 455
Abdominal compartment syndrome 564, Adrenal emergencies 455
565 Adrenal insufficiency 457t
Abdominal infections etiology of 456t
management of 405t primary 455
pathophysiology of 403, 404f causes, etiology of 456t
Abdominal trauma 560 secondary causes, etiology of 456t
mechanism of injury 560 signs of 457
Abdominal wall 564 symptoms of 457
Acalculous cholecystitis 406, 407 Adrenocorticotropic hormone 72
Acetaminophen 152, 400, 664, 805 stimulation test 457
poisoning 160, 395 Adult basic life support
treatment 160 sequence 733, 733fc
toxicity 160t skills 734
Acid, overproduction of 623 Adult cardiac arrest, management of 741,
Acid-base 742fc
balance Adult chain of survival 732t
basics of 617 Advanced airway 744
regulation of 619 Advanced cardiac life support 73, 739
disorder 615, 632t modifications 750, 752, 753, 754, 756
interpretation of 631 Advanced trauma life support 73, 537,
disturbances 712 552
imbalances 632t Afibrinogenemia 484
Acquired nephrogenic diabetes insipidus Air embolism 33, 78, 79
436 Air-conditioning system 6
Activated charcoal 151 Airflow obstruction 205
Active myocardial ischemia 300 Airway 537
Acute coronary syndrome, mechanical assessment before intubation 680
complications of 318 disorders 187
Acute exacerbation, pathophysiology equipment 685f
of 200fc management 181, 675, 685f, 735
Acute kidney injury adjuncts for 682, 740
dialysis in 340 of difficult 688
etiology of 336t obstruction
intrinsic 336 acute 538, 681
Acute liver failure, etiology of 394t causes of 538
Addison’s disease 455, 456 in trauma patients, causes of 538t
Adenosine 280, 799 pressure alarm
818 ICU Manual
high 242 Angioectasias 385

low 242 Angiography 83, 554, 563, 569
pressure release ventilation 250 Angioplasty 27
Albumin 726, 782, 785 Angiotensin
Albuterol 210, 801, 803 converting enzyme inhibitor 336
Alcohol receptor blocker 335, 336
withdrawal syndrome 506 Angiotensin-converting enzyme
symptoms of 506, 506t inhibitors 799, 800
Alcoholic ketoacidosis 626 Anion gap acidosis, high 624
Alcoholic mania 507 Anorectal disease 385
Aldosterone 786 Antepartum hemorrhage 464
antagonists 314 Anterior external fixator 553, 554f
receptor blockers 799 Antibiotic 128t, 203
Alkalosis management 197 based on organisms 497
Allergic reactions 711 cover 546
Alpha adrenergic blocker 800 dosage 499t
Alteplase 315, 797, 808 prescription, principles of 127
Alveolar principles of 127
hemorrhage 188 resistance, prevent 131
oxygen 9, 10 Antibiotic-associated colitis 385
American College of Chest Physicians Anticholinergic 202, 801
219 Anticholinesterase
American Society of Parenteral and drugs 526
Enteral Nutrition 641 medications 524
Amikacin 546, 809 test 524
Aminoglycoside 546, 809 Anticoagulants 328, 488
Amiodarone 280, 291, 745, 799 Anticoagulation, benefits of 317
Ammonia 782, 785 Antidepressants 159
Amniotic fluid embolism 79, 80, 479 treatment 160
diagnosis of 479 Antidiuretic hormone 72, 441, 786
management 480 Antidotes, specific 152t
pathophysiology 479 Antihistamine 144
Amoxicillin 809 Antihypertensive therapy 471
Amphotericin B 812 Anti-inflammatory response syndrome,
deoxycholate 812 compensatory 116
Ampicillin 499, 809, 811 Antimalarial drugs, dosages of 136t
Amylase 785 Antimicrobial
Anal fissure 385 therapy 121
Analgesia treatment 405
adequate 539 Anti-musk antibodies 524
patient-controlled 670 Antiplatelet 488, 797
pump, patient-controlled 671 therapy 312
techniques, regional 667 Anti-staphylococcal 809
Anaphylactic reaction 710, 711 Antithrombin III deficiency 484
causes of 140 Antivenom 166
diagnosing 142t indications of 167t
Anaphylaxis 140, 750 Anuria 463
management of 143fc Aorta
Anatomical transparent silicone face dissection of 593
mask 683f injury to 592
Anderson’s syndrome 530 Aortic counter pulsation 84
Androstenedione 786 Aortic dissection 324, 326
Anemia 13, 135, 413 acute 322
Anesthetic conserving device 665 Aortic regurgitation 49, 81
Angiodysplasia 385 Apnea alarm 243
Index 819
Apnea test 765 Atrial fibrillation 277, 450

interpretations 766t classification 277
Aprotinin 416 clinical features 278
Aqueous penicillin g 811 etiology 277
Argatroban 797, 807 mechanism 277
Arginine vasopressin 435 postoperative 281
antagonists 302 Atrial flutter 281, 282f
Arrhythmia 66, 81, 449 treatment 282
Arrhythmic complications 320 Atrial pressure, right 78
Arrhythmogenic right ventricular Atrioventricular nodal reentrant
cardiomyopathy 290 tachycardia 283, 284f
Arsenic 784 Atrioventricular reentrant tachycardia
Arterial blood 9 284
gas treatment 284
analysis 208, 618 Atropine 745, 799
exercises 632 Auditory canal, external 765
Arterial hypoxemia causing Autoimmune disease, caused by 455
hyperventilation 630 Automated control system in ventilator
Arterial oxygen 10 264f
content 48, 56, 794 Automated external defibrillator 731
Arterial oxygenation 89, 558 Auxiliary liver transplantation 400
Arterial pH 428, 433 Axillary artery 17, 18
Arterial pressure injury to 571f
mean 53, 65, 89, 120 Axillary vessels 570
monitoring, recent advances in 21 Azathioprine 389, 525
waveforms 19f Azithromycin 202, 811
Arterial systolic pressure 328 Azoles 812
Arterial waveform 19
dampening of 22f
phases of 20f B
Arteriography 386 Bacterial contamination 713
Arteriovenous Bacterial meningitis
hemodiafiltration, continuous 342 acute 494, 496t
hemofiltration, continuous 342 causes of acute 494t
Artery 600 Balance sign 562
atherosclerotic disease, large 484 Balloon
Ascending paralysis 518 counterpulsation, intra-aortic 319
Aspiration 188 pump, intra-aortic 84
pneumonitis 193 tube tamponade 383
Aspirin 149, 312, 798 Barbiturate phenobarbitol 807
overdose 630 Barbiturate therapy 584
Associations of acute hepatic failure 395 Barometric pressure 9
Asthma 206, 272, 754
Basic life support 731
acute severe 206
modifications 750, 751, 753, 755
dosages of drugs in exacerbation of
Bat sign 609f
210t
Beats per minute 309
exacerbation 209
Behçet disease 497
classification of 208t
Benzodiazepines 58, 152, 665, 807, 808
management of 211fc
Beri-beri disease 645
severity of 208t
Beta-agonists 801
pathophysiology of acute severe 207fc
Beta-blocker 161, 314, 508, 797, 800, 805
Asymptomatic hyponatremia 348
dosage 314
Asynchrony
Beta-lactamase, extended-spectrum 132
signs of 266
Bezold Jarisch reflex 294
variables contributing to 265
Atracurium 140 Bicarbonate loss 623
820 ICU Manual
Bicarbonate Brainstem reflexes, absence of 764

actual 618 Breakthrough pain 658
therapy 124 Breath
Bilevel positive airway pressure 240, 245, mandatory 234f
271 type 234
Bilirubin 782 Breathing 181, 539, 581
Binders-containing aluminum 370 type of 233
Bioartificial liver support 399 Bromocriptine 805
systems 400 Bronchogenic carcinoma 443
Biochemical values, normal 781 Brugada syndrome 290
Biphasic positive airway pressure 252 type 1 291f
Bisphosphonates 804 Budd-Chiari syndrome, acute 394
Bivalirudin 797 Buffering mechanisms 619t
Bladder, carcinoma of 443 Bumetanide 800
Bleeding Bundle branch block 309
emergency treatment of acute 423 Buprenorphine 672
intra-abdominal 561 Burch and Wartofsky diagnostic criteria
postoperative 322, 324 450t
Blenderized food 650 Burn 171, 442
Blood 421 assessment 174
component causing inhalational injury 193
administration 123 center referral criteria 180t
separation 703fc chemical 183
investigations 362, 391 classification 173
loss 73, 723 depth of 174f, 176t
in obstetric hemorrhage, evaluation of 173
classification of 463t injury
management of severe 466 classification 173
pressure 73, 470 types of 173
control 488 management of 180
replacement 381 pathophysiology of 175fc
stream infection 97 patient
catheter-related 40, 99 perioperative care of 182
tests 324 priorities in managing 181t
transfusion severe 653
complication of 709, 710t
urea nitrogen 298, 337, 783
Blunt chest trauma 328
C
Blunt trauma, high-risk 569 Cadmium 784
Body mass index 205 Calcimimetic drugs 368
Boerhaave’s syndrome 379, 380 Calcineurin inhibitors 525
Bone 359, 600 Calcitonin 364, 804
formation, accelerated net 367 Calcium 359, 375, 745, 784, 785
Bosentan 801 channel blockers 340, 799, 800, 801
Bowel losses, small 723 functions of 359
Brachial artery 17, 18 gluconate 530, 803
Brachial ulnar injuries 572 metabolism 359
Bradycardia, management of 747fc Calcium-channel blockers 303, 314
Brain dead patient, care of 761 Calorie requirement, calculation of 642t
Brain death 759, 763t Calorimetry, indirect 643
clinical phases of 768t Candida 100
confirmatory tests for 766 Capillary refill test 73
diagnosis of 764 Capsule endoscopy 386
patients 771t Captopril 327, 799
physiology of 761 Carbamate 153t
steps for determining 763 poisoning 153
Index 821
Carbapenems 809 manifestations 360

Carbohydrate 651 resuscitation 729, 731, 753
requirements 643 early 735t
Carbon dioxide physiology of 732
analysis, end tidal 3 quality 741
production of 643 Cardiorenal syndrome 304
Carbon monoxide 152, 183 Cardiothoracic surgery 336
poisoning 183 Cardiovascular
management of 183 diseases 275
Carcinoma 385 dysfunction 450
Cardiac abnormalties 330 effects 237
Cardiac arrest 607, 609fc, 681, 739t, 746, system 115, 174, 564, 625, 628, 762,
747 790, 797
causes of 752 management of 768
in special situations 750 Carotid artery, internal 33
rhythm 741t Carotid sinus massage 283
based management of 743f Catecholaminergic polymorphic
role of medications in 745t ventricular tachycardia 290
Cardiac arrhythmia 33, 277, 356, 484, 530 Caterpillars 162
Cardiac catheterization 330 treatment 163
Cardiac causes 277 Catheter
Cardiac complications 691 management of 40
Cardiac damage, serum markers of 311 protocol for 40
Cardiac dysfunction 645 tip position, confirming 40
Cardiac effects of hypermagnesemia 473 Catheter-associated of urinary tract
Cardiac enzymes 324 infection, prevention of 105
Cardiac failure 449, 653 Catheterizing right
Cardiac index 48, 56, 794 femoral vein, technique of 37f
Cardiac output 78 internal jugular vein, technique
high 13 of 30f, 32f
measuring 47 subclavian vein, technique of 34f, 35f
reduced 13 Catheter-related bloodstream infections,
Cardiac perforation 33 prevention of 105
Cardiac pump mechanism 732 Cavernous sinus thrombosis 443
Cardiac surgery 220, 756 Cefazolin 499, 546, 810
Cardiac tamponade 79, 80, 328, 756 Cefotaxime 499
management 330 Cefoxitin 810
pathophysiology 328 Ceftazidime 499
Cardiac troponins 312 Ceftriaxone 499, 810
Cardinal symptoms 206 Central arteries, waveform of 20f
Cardioembolism, risk factors for 484 Central diabetes insipidus 351, 435, 436
Cardiogenic pulmonary edema 272 treatment of 438
acute 326 Central nervous system 73, 174, 564, 625,
Cardiogenic shock 44, 65, 81, 82, 84, 296 628, 761, 807
causes of 81 effects 450
characteristics 81 injury 630
etiology of 81t Central sleep apnea 227
high-risk patients for 82 Central sympatholytics 800
invasive procedures in 84 Central vein catheterization 608
management of 84, 85 Central venous
pathogenesis of 82, 82fc catheterization 27, 27t, 214
Cardiomyopathy 414 monitoring, waveforms of 54f
Cardiopulmonary pressure 3, 27, 47, 52, 55, 89, 120, 237,
arrest 27 404
bypass 336, 557 monitoring 27, 53
822 ICU Manual
Cephalosporins 810 Coma 135, 149, 764

Cerebellar hemorrhage 486 Common antiarrhythmic agents, dosages
Cerebral of 280t
blood flow 766 Common femoral vein 606f
disturbance 470 Common organisms causing nosocomial
edema 396, 399, 431, 557 infections 99t, 100t
management of 487 Common-facial nerve 518
embolization 19 Compartment syndrome 574, 575f
infarction 322 management of 165t
Cerebrospinal fluid 496, 496t, 498, 765 Congenital
analysis 496, 500 adrenal hyperplasia 456
Cerebrovascular anomalies 693
accident 432, 452, 681 nephrogenic diabetes insipidus 436
diseases 483 Congestive cardiac failure 214, 346, 452
Ceruloplasmin 782 Congestive heart failure 450
Cervical spine injury 689, 690f acute 322
Chaotic atrial tachycardia 282 Connective tissue disease 328
Chemical buffering 620 Contusion, left-sided 578f
Chemically derived formulas 650 Copper 152
Chest Cor pulmonale, acute 81
injury Coral snake bite 166
analgesia in 612f treatment 166
evaluation of 592 Coronary artery disease 81, 214, 225
wall 187 Coronary atherosclerosis 308t
injury to 588 Coronary syndrome, acute 322, 736
Chlorhexidine 40 Corrosive poisoning 157
Chloride 784, 785 Corticosteroid 203, 801, 802, 804
Cholesterol, total 781 biosynthetic enzyme defects 456
Cholinergic drugs 526 sparing agents 422
Cholinergic symptoms 154 Cough 206
Chorionic gonadotropin 786 Cranial nerve 518
Chvostek’s sign 360 dysfunction 167
Cigarette smoking 199 of brainstem, function of 764
Cinacalcet 368 palsies 495
Ciprofloxacin 202, 810 Creatine kinase 784
Citrate intoxication 712 Creatinine 324, 428, 433, 785
Clarithromycin 811 Creative phosphokinase 135
Clavulanate 809 Cricoid pressure 678
Cleistanthus collinus 155 Cricothyroidotomy 539, 696
Clevidipine 325 in children 698
Clindamycin 810 Critical care patients
Clonidine 800 analgesia for 657
Clopidogrel 312, 797 sedation for 657
Clostridial myonecrosis 546 Critical illness polyneuropathy 531
Clostridium difficile 100 pathogenesis of 531, 532fc
Coagulation abnormalities 712 pathology 531
Coagulopathy 397 treatment 533
patients with 27 Critically ill patient 9
Cobra bite 167 physiology of 7
treatment 168 Crotalinae bites 163
Cobra venom 167 Crush injuries 369
Coexisting diseases 432 Cryoprecipitate 707
Colitis 385 Crystalloids 68t, 724
Colloids 541, 725 complications of 725
composition of 726t composition of 725t
Colonic losses 723 Cullen sign 561
Index 823
Cushing’s response 762 severe 354

Cushing’s syndrome 432 Diastolic dysfunction increases end-
Cyclophosphamide 525 diastolic volume 55f
Cyclosporine 328 Diastolic runoff 20
Cystatin C 338 Dicrotic notch 20
Cytomegalovirus 504, 713 Diffuse alveolar infiltrates 558
Cytotoxic hypothesis 396 Diffuse axonal injury, grading of 579t, 795
Digoxin 152, 280, 302, 800
Dihydrotestosterone 787
D Diltiazem 280, 799, 801
Dalfopristin 811 Diphenhydramine 144
Dalteparin 221, 222, 798 Diplopia 522
Damage control surgery 564 Dipsogenic diabetes insipidus 437
Dantrolene 805 Direct thrombin inhibitors 318, 797, 807
Daptomycin 811 Disseminated intravascular coagulation
Decompensated heart failure 296 135, 416
Deep vein thrombosis causes of 416t
prophylaxis 124 pathophysiology 416
treatment 222fc Diuretics 299, 375
Deep venous thrombosis 214 Dizziness 457
Dehydroepiandrosterone 787 Dobutamine 69, 301, 303, 803
Delirium 510 adverse effects 301
symptoms of 510 Dofetilide 291
tremens 507 Dopamine 69, 301, 303, 786, 803
management 508 agonists 339
management of 507, 508 low-dose 301
Dengue 137, 336 Doppler echocardiography 329
hemorrhagic fever 138 Dorsalis pedis artery 17
management of 138 Doxycyclin 812
Depletional hyponatremia 442 Dressler’s syndrome 321
Desmopressin administration 438t Drotrecogin alfa 802
Dexamethasone 804 Drowning 736, 755
Dexmedetomidine 665 Drug causing exacerbation 522
Dextran 726 Drug overdose 159
Dextrose 725 Drug poisoning 681
Diabetes Drug resistance, mechanisms of 98
insipidus 435, 437 Drug therapy 744
causes of 438t Drug, dosages of 797
classification of 438t Drug, side effects of 797
complications 439 Drugs in acute exacerbation, dosages of
management of 351 202t
partial central 351 Duodenal carcinoma 443
types of 435t Duodenum 720
mellitus 109, 214, 225, 309, 336, 436 Duplex ultrasonography 569
undiagnosed 432 Dynamic hyperinflation 212
Diabetic ketoacidosis 427, 428, 431, 433t, Dyspnea 206, 215, 297
626 severity of 205
basic pathophysiology of 428
complications of 431t
pathogenesis of 429fc E
triad of 427f Echocardiography 312
Diagnostic peritoneal lavage 562 Eclampsia 322, 474
interpretation of 563 management 474
Dialysis 653 Elapid bite 166
Diarrhea 404, 441, 442, 624 treatment 166
824 ICU Manual
Elective tracheostomy 694 Enteric fever 336, 510

types of 694 Enteric gram-negative bacilli 102
Electric injury 183 Enterobacter 100
Electric shock 755 Enterobacteriaceae 498
Electroconvulsive therapy 512 Envenomation 147, 162
Electrolyte 381, 652, 786 Enzyme-linked immunosorbent assay
abormalities 399 418
correction 430 Epidural analgesia 667
disturbance 333, 397, 754 dose for 668t
homeostasis 373 Epinephrine 69, 210, 302, 303, 745, 786,
normal exchange of 718 799, 802
Elevated liver enzyme levels 470 in anaphylaxis, role of 144
Elevated serum amylase 390 Eplerenone 799
Embolic complications 320 Epoprostenol 802
Embolic stroke 484 Epsilon-aminocaproic acid 417
Embolism, sizes of 215t Epstein-Barr virus 499, 504
Emergency response system 731 Eptifibatide 798
Emergency room care 570 Ertapenam 810
Emergency tracheostomy 693 Erythromycin 811
prerequisites for 694 Esmolol 280, 797
technique for 694 Esomeprazole 806
Emergency transvenous pacemakers 27 Esophageal
Empirical antibiotic therapy 130t detector device 740
on infection site 130 Doppler 52
Empirical antimicrobial therapy 497t, Esophagus, injury to 594
498t Estradiol 787
Enalapril 799 Estrogens 389
Enalaprilat 325, 800 Ethics in critical care 775
Encephalitis 494 Ethylene glycol
End-diastolic pressure 20 methanol 152
Endocrine poisoning 626
causes 510 Etomidate 688
disorders 425, 804 European Society of Parenteral and
system 174 Enteral Nutrition guidelines 647
system, management of 770 Euvolemic hyponatremia 348
End-of-life care 775 Ewing’s sarcoma 443
decision making process 776fc Exercise tolerance 205
Endoscopy 382 Exogenous acid 623
Endothelin antagonist 801 Extensive degloving injury 549f
Endotracheal intubation 212, 212t, 681t, External fixation 549f
682 Extracellular fluid 369
basic anatomy 680 Extradural hemorrhage 486
complications of 691t Extradural hematoma 576, 577f
drug for 688t Extrarenal causes 372
in critical care 680 Extravascular hemolysis 412t
in trauma patients 538t Extremity trauma, management of 570
Endotracheal tube 687f Eye 174
care of 690 signs 522
Enoxaparin 221, 222, 798 symptoms 522
Enoximone 303 Eye-opening response 580
Enteral feeding, complications of 650
Enteral feeds 650
classification of 650t
F
starting 649 Facial nerve 360
Enteral nutrition 647 Facial palsy 518
Index 825
Falciparum malaria 336 Focal neurological symptoms 485

Familial periodic paralysis 528 Follicular-stimulating hormone 787
Fast-flush test 21 Fondaparinux 221
effects of 22f Foreign-body airway obstruction 737
Fat Fosphenytoin over phenytoin, advantages
embolism 79, 80, 188 of 492
embolism syndrome 193, 557 Fossa tumors, posterior 27
diagnosis of 558t Fracture
etiology 557 classification, open 545
management 559 fixation, acute 554
pathogenesis 557 open 545
Fatty liver of pregnancy 394 stability 552
acute 476, 477, 477t Free water restriction 444
complications, acute 477 Fresh frozen plasma 703, 707
management, acute 477 Fulminant hepatic failure 394
pathophysiology, acute 476 causes of death in 398
Febrile nonhemolytic transfusion Fungal meningitis 502
reaction 709, 710 Furosemide 339, 389, 800
Femoral artery 17, 18, 573f Fusion beats 287f
Femoral block 673
Femoral vein 27, 29
anatomy of right 29f
G
cannulation 36 Gallium nitrate 364
technique 36 Gas gangrene 546
right 39f Gastric
Femoral vessel injury 572 carcinoma 443
Femoro-femoral bypass 593 fluid 720
Fenoldopam 325 lavage 151, 381
Fentanyl 664, 672 losses 723
Fever 404, 495 mucosal irritants, ingestion of 380
Fibrinolysis 315 Gastroesophageal reflux disease 678
Fibrinolytic 315, 797 Gastrointestinal
agents 416 bleeding 399, 452
dosages 315 diseases 377
Flail chest 588, 629 disorders 806
Fluconazole 812 loss 350, 354
Fludrocortisone 803, 804 system 174, 564
Fluid 381 Gastrointestinal-hepatic dysfunction 450
balance Gelatin 726
assessment of 719 Gemifloxacin 810
basic physiology of 717 Gentamicin 499, 546, 809
disturbances in 719 Gestational diabetes insipidus 435, 437
regulation of 719 Glasgow Coma Scale 580t, 790, 795
calculation in burns, formulas for 181t Globulin 782
compartments 717, 717f Glomerular filtration rate 337
composition of 717t Glucocorticoids 197, 455, 525
management 68, 197, 715 replacement 458
normal exchange of 718 Glucose 428, 433, 530, 785
replacement 430 control 314
responsiveness, dynamic parameters Glycemic control 124
of 58 Glyceryl trinitrate 301
resuscitation 182, 722 Glycopeptides 810
therapy, replacement 723 Glycylcyclines 810
Flutter waves 282f Graft disease 705, 711
Focal atrial tachycardias 282 Gram-negative organisms 546
826 ICU Manual
Great saphenous vein 571f Hemodynamic assessment 381, 386

Grey-Turner sign 561 Hemodynamic monitoring 51
Growth hormone 787 parameters of 52t
Guillain-Barré syndrome 187, 188, 443, Hemodynamic status 552
517, 533 Hemodynamic support 122
etiology 517 Hemodynamic variations 65t
pathogenesis 517 Hemoglobin 620
subtypes of 517t Hemoglobinuria 135
symptoms of 518 Hemolysis 470
Gum elastic bougie for aiding intubation Hemolytic anemia 411-413
686f complications 413
Gustilo open fracture classification 545t diagnosis 412
treatment 413
H Hemolytic reaction, delayed 711
Haemophilus influenzae 102, 202, 203, Hemolytic transfusion reactions
498 acute 710
Hagen-Poiseuille formula 24 delayed 710
Hallucinatory insanity of drunkards 507 management of acute 710, 711t
Hallucinosis 506 Hemorrhage 539
Haloperidol 665 resuscitation of 539
Hampton’s hump 217 Hemorrhagic shock
Harris-Benedict equation 642, 642t pathophysiology of 72fc
HDL cholesterol 781 resuscitation of 539
Head injury 354 Hemorrhagic stroke 326, 484, 486
Headache 495 Hemorrhoids 385
Healthcare providers, adult basic life Hemothorax, treatment of 590
support for 734fc Heparin 317t
Heart 66 Heparin-induced thrombocytopenia 416,
catheterization, left 83 418
chambers, right 43 Hepatic encephalopathy 394, 395, 398
failure 281 scale 396t
acute 296, 300t, 413 Hepatic failure
acute hypertensive 296 acute 160
classification, acute 296 encephalopathy 653
clinical features, acute 296 no encephalopathy 653
dosages of inotropes for 303t Hepatic hemorrhage 474
dosages of vasodilators for 301t Hepatic system 771
management of acute 298 Hepatitis
pathophysiology, acute 296, 297f B 394, 713
signs, acute 297 C 394, 713
symptoms of 296, 307
virus
symptoms, acute 297
A 394
therapy for acute 299
B 394
treatment of acute 302
C 394
injury to 591
rate 89 D 394
Heartbeating brain death organ donor, E 394
management of 766 Hepatorenal syndrome 335
HELLP syndrome 470, 473, 476 Hepatotoxic 150
diagnosis of 474 Herpes simplex 394, 499
Hematological disorders 409 virus 504
Hematology 174, 771 Hip fracture 214
Hematopoietic disorders 807 Histoplasma capsulatum 502
Hemodialysis 344, 371, 375 Hormone replacement 454
acute 27 Host disease 705, 711
Index 827
Human Hypertonic saline 26, 304, 540, 808

albumin 726 use of 447
immunodeficiency virus 713 Hyperventilation 584
insulin, regular 803 Hypervolemic hyponatremia 348, 442
T-lymphotropic virus 713 Hypnotics treatment 159
Humidifiers, types of 699 Hypocalcemia 340, 359, 360
Hydralazine 471, 800, 814 causes of 360, 360t
arteriolar 800 chronic 361
Hydration 339, 375 Hypofibrinogenemia 484
Hydrochloric acid in metabolic alkalosis Hypoglycemia 135, 150, 399, 431
629 Hypokalemia 150, 353, 431
Hydrocortisone 802, 804 causes of 353, 354t
Hydroxyethyl starch 727 management of 355
Hypercalcemia 361, 389 treatment for 355
bisphosphonates, treatment of 363 Hypokalemic periodic paralysis 354, 528
causes of 362t types 528
diuretics, treatment of 363 Hypomagnesemia 372, 373
hydration, treatment of 363 causes of 372t
steroids, treatment of 363 treatment 373
treatment of 363 mild cases 373
Hypercapnic respiratory failure 187 severe cases 373
Hyperkalemia 340, 355, 457, 712 Hyponatremia 340, 346-348, 352, 457
causes of 355, 356t causes 346
correction of 458 diagnosis of 445fc
treatment for 754, 357t etiology of 346, 346t
Hyperkalemic periodic paralysis 529 pathogenesis of 443fc
treatment 529 steps in correcting 348
Hypermagnesemia 374, 374t, 755 symptoms of 347
causes of 374t treatment of 347
treatment 374 Hypophosphatemia
Hypermetabolic phase 182t mild 367
Hypernatremia 349 mild-to-moderate 368
causes 349 severe 367, 368
Hyperosmolar hyperglycemic state 432, Hypotension 66, 135, 215, 399, 463
432t management of 768
pathophysiology 432 mild 463
Hyperphosphatemia 340, 369 postural 457
causes of 369t severe 463
signs of 369 Hypothalamic-pituitary
symptoms of 369 adrenal axis dysfunction 770
Hypertension 225, 309, 326 deficiency, posterior 770
severe 322 Hypothalamopituitary function 762
Hypertensive crisis 322 Hypothermia 13, 354, 432, 452, 584, 712,
precipitating factors of 323 737, 753, 771
with encephalopathy 325 Hypoventilation syndrome 225
Hypertensive disorders Hypovolemia 84
in pregnancy, classification of 469 Hypovolemic hyponatremia 348
of pregnancy 469 Hypovolemic shock 65, 71, 465
Hypertensive emergency 322t, 324 etiology 71
Hypertensive encephalopathy 322 management 73
Hypertensive urgencies 323, 326 pathophysiology 71
Hyperthermia 369, 423, 449 Hypoxemia, severe 203, 239
malignant 13, 629 Hypoxemic respiratory failure 187
Hyperthyroidism 281 Hypoxia 13
828 ICU Manual
I Interleukin 88, 116, 495

Ibuprofen 805 Intermediate syndrome 154
Ibutilide 280 Intermediate-dose dopamine 302
Imipenem 809 Intermittent hemodialysis 344
Immune Intermittent pneumatic compression
disorders 95 device 221
system 762 Intermittent porphyria, acute 443
thrombocytopenia 420 Internal fixation 555f
thrombocytopenic purpura 420 Internal jugular vein 27, 28, 30, 46
acute 421 anatomy of right 28f
chronic 421 left 38f
classification of 420 Interscalene block 673
pathogenesis 420 Interstitium 10
treatment 422 Intestinal absorption, impaired 372
Immunoglobulins 123, 422 Intestinal fistulas 354
Immunosuppressants 422 Intestinal losses, increased 372
Immunosuppressive drugs 525 Intestinal phosphate absorption,
Inappropriate antidiuretic hormone, impaired 367
syndrome of 346, 347 Intestine 359
Inappropriate secretion of antidiuretic Intra-abdominal
hormone, syndrome of 441 infection, complicated 402
Indian Society of Critical Care Medicine 4 pressure, measurement of 565, 565f
Infection 95, 397, 399, 432 Intra-arterial embolization 387
abdominal 402 Intracardiac tumors 484
catheter-related 40 Intracerebral hemorrhage 486
causes of 128 Intracranial
classification, abdominal 402 hemorrhage 322
focus of primary 129 hypertension 582
intra-abdominal 402
pressure 495, 579
management, abdominal 404
Intravascular hemolysis 412t
of meninges 494
Intravenous 210
site 130t
atropine 294
Infectious complications 713
fluids 724
Infective endocarditis 484
Inflammatory bowel disease 385, 386 classification of 724f
Inflammatory complications 320 hydralazine 325
Inflammatory demyelinating immunoglobulin 424
polyneuropathy opioid 298
acute 517 Inulin clearance 783
chronic 520 Invasive arterial blood pressure 52
Inflammatory disease 206 monitoring 53
Inhaled bronchodilators 203 Invasive blood pressure 53
Initial ventilator settings 195, 212, 240 Ipratropium 801
Injury bromide 202
secondary 579 Iron 149, 152, 782
severity score 551 Ischemia, manifestations of 310
Inotropes 122 Ischemic enteritis 385
Inspiratory flow pattern 242 Ischemic hepatitis 394
Insulin 530, 788 Ischemic stroke 326, 484, 488, 808
administration 354 pathophysiology 484
therapy 430 Isosorbide dinitrate 301, 798
Insulin-like growth factor 788 Isosorbide mononitrate 798
Intensive care unit 1, 3, 193, 359 Isotonic crystalloids 540
Intercostal nerve block 612f Istaroxime 303
Interferon 116 Itraconazole 812
Index 829
J Levothyroxine 805
Jaundice 135, 394, 413 Lid twitch sign 522
Jugular vein Lidocaine 280, 799
external 32 Lightening strike 755
right internal 38f Lignocaine 745
Linezolid 811
Lipase 390
K Lipids 644, 652
Kehr sign 561 parenteral infusion of 557
Kerosene poisoning 157 Lipopeptides 811
Ketamine 664, 688 Lipopolysaccharide 495
Ketolides 810 Liposuction 557
Ketorolac 805 Liquid ventilation 252
Kidney 66, 359 total 253
function test 782 Liquidized food 650
injury Lisinopril 799
acute 335, 337, 337t, 338, 342, 413, Listeria monocytogenes 498
796 Liver 66
categories, acute 335 disease 338, 630
complications of acute 341 failure
diagnosis, acute 337 acute 394, 395
Killip’s prognostic classification 309t causes of acute 394
Klebsiella 100 classification, acute 394
Knee-jerk reaction 441 investigations of acute 398
prognosis, acute 398
L treatment, acute 398
transplantation 400
Labetalol 325, 471, 800, 814
Long bone fracture 73, 557
Labetdilol 327
Loop diuretic 298, 800
Lactate dehydrogenase 496, 710, 784
intravenous bolus of 298
Lactic acid 781
Lorazepam 807, 808
Lactose-free formulas 650
Low blood pressure 457
Lambert-Eaton myasthenic syndrome
Low dose unfractionated heparin 219
523
Low minute ventilation alarm 242
Language disturbances 485
Lower gastrointestinal bleeding 385
Lansoprazole 806
Lower limb 604
Lanthanum carbonate 370
Lower radial injuries 572
Laryngeal mask airway 684f
Low-expired tidal volume alarm 242
Laryngoscope 686f
LDL cholesterol 781 Low-molecular-weight heparin 317
Lead 784 Lung
Left ventricle 78 disease
Left ventricular failure 81 chronic obstructive 199
Leg severe 27
fracture 214 dynamics 237, 259
raising test, passive 59 infection 188
Lepidoptera 162 injury to 591
Lepirudin 807 acute 193, 413
Leukocyte reduction 705 direct 193
Leukoencephalopathy syndrome, indirect 193
posterior reversible 326 parenchymal diseases 187
Levalbuterol 210, 801 recruitment maneuver 197
Levetriacetam 807 sliding sign 609f
Levine sign 308 sonography protocol 608
Levofloxacin 810 Luteinizing hormone 788
Levosimendan 302, 303 Lymphoma 443
830 ICU Manual
M chloride sensitive 627, 634

Macrolides 811 chloride-resistant 627
Magill’s forceps 687f compensation for 627
Magnesium 314, 372, 755, 784 fully compensated 634
adverse effects of 473t treatment of 628
sulfate 209, 472, 745, 814 Metabolic
actions 472 disorder 623
dosage regimens 472 disturbance 397
pharmacokinetics 472 Metabolism 625, 628
Maintain perfusion pressure 339 in critically ill patients 639
Maintenance fluid therapy 722 Metal fuller’s tracheostomy tube 697f
Malaria 510 Metastatic calcification 370
diagnosis, severe 134 Metered-dose inhaler 210
in pregnancy, severe 137 Methemoglobinia 152
management, severe 134 Methicillin-resistant Staphylococcus
manifestations of severe 135t aureus 132
mixed 336 Methimazole 805
severe 134 Methylprednisolone 210, 424, 801
Mallory-Weiss tear 380 Metronidazole 398, 499, 811
Managing hemorrhagic shock 74 Microcirculation 10
Mannitol 808 Micronutrients 645
Mask with bag and valve device 685f Midazolam 688, 807
Massive blood transfusion 713 Mid-tracheostomy 695
complications 713 Miller-Fisher syndrome 517
Massive pneumothorax, left-sided 589f Milrinone 69, 303, 803
Massive transfusion 541 Mineralocorticoid deficiency
protocol 542fc signs caused by 457
goals of 542 symptoms caused by 457
Maximal inspiratory pressure 260f Mineralocorticoids 803
MDR gram-negative bacteria 132t Minitracheostomy 696
Mechanical hyperventilation 630 advantages of 697
Mechanical ventilation 123, 191, 191t, Minnesota tube 383
203, 212, 212t Minocyclin 812
basics of 233 Mitochondria 9
initiation of 239t Mitochondrial level 11
paralyzing patient in 263 Mitral regurgitation 49
weaning from 258 acute 318
Meckel’s diverticulum 385 treatment, acute 319
Medical ethics 773 Mitral stenosis 49, 81
Meningitis 494 Mivacurium 140
signs of 495 Molecular weight heparin, low 219, 798
symptoms of 495 Mollaret meningitis 497
Mental status 73 Monitoring cardiopulmonary
Mercury 784 resuscitation 737, 746
Meropenem 499, 810 Monoclonal antibodies 423
Metabolic abnormalities 458 Morbid obesity 752
Metabolic acidosis 135, 150, 338, 340, Morphine 298, 664, 672, 798
356, 369, 623, 625, 625t, 632 Mortality to asthma 208
causes of 623t Moths 162
compensation for 625 Motor axonal neuropathy, acute 517
fully compensated 635 Motor response 580
management of 626 Motor sensory axonal neuropathy, acute
Metabolic alkalosis 354, 626, 628, 628t, 517
632 Motor symptoms 485
causes of 627t Moxifloxacin 810
Index 831
Moyamoya disease 484 Needle orientation 603f

Mucosal tonometry 52, 53 Negative pressure
Müller maneuvers 283 pulmonary edema 272
Multidrug resistant 132 ventilation 233
pathogen 131 Neisseria meningitidis 498
Multifocal atrial tachycardia 282, 283f, Neoplasm 385, 386
284f Nephrogenic diabetes insipidus 351, 435,
Multiple organ dysfunction syndrome 87, 436
88fc treatment of 439
etiology 87 Nephropathy, contrast 340
pathophysiology of 87, 88fc Nephrotoxic substances, avoid 339
Multiple organ failure 116 Nerve 600
Multiple trauma 653 blocks, regional 612
Muscle 600 conduction study 529
biopsy 529 Nesiritide 300, 301, 800
proteolysis, causes 338 Neural hormone 435
relaxants 688 Neurally adjusted ventilatory assist 268
specific kinase 524 Neurologic causes 511
weakness 135 Neurological disorders 481
Muscle-like cells 522 Neurological examination 149
Myasthenia gravis 521, 522, 629 Neuromuscular blockade 124
etiology 521 Neuromuscular disorders 187, 515
pathogenesis 521 Neuromuscular drugs 187
treatment 524 Neuromuscular electrical stimulation 533
Myasthenic crisis 526, 533 Neuromuscular function, disorders of
causes 526 629
treatment 526 Neuromuscular irritability
Mycobacterium tuberculosis 501 signs of 373
Mycophenolate mofetil 422, 525 symptoms of 373
Myocardial dysfunction 307t Nicardipine 325, 800
Myocardial infarction 306, 306t, 452 Nicotinic symptoms 154
acute 81, 281, 306, 432, 484, 797 Nifedipine 327, 471, 801
causes of 308t Nitrates 300, 313, 798
complications of acute 318 Nitric oxide 88, 802
pathophysiology, acute 307, 307fc Nitrogen balance 641
Myocardial ischemia 326 Nitroglycerin 301, 325, 798
Myoglobin 784 Nitroprusside 301
Myoid cells 522 Noncardiac causes 278
Myotonia 530 Noncardiogenic pulmonary edema 135
Myxedema coma 449, 451, 452t, 453f Nonendoscopic treatment options for
management modalities of 453f varices 383
Nonfocal neurological symptoms 485
Nonimmune-mediated reactions, causes
N of 140
Nafcillin 809 Nonimmunologic reactions 712
Nasal O2 therapy 298 Noninvasive positive pressure ventilation
Nasogastric intubation 381 190, 269
benefits of 381 Noninvasive ventilation 189, 209, 258,
disadvantages of 382 269
Nasogastric suctioning 354 Noninvasive ventilatory modes 270
Natriuretic peptide 339 Non-neurologic causes 510
testing 297 Nonpancreatic causes 391
Nausea 457 Nonpharmacologic therapies 303
Nebulizer solution 210 Nonsteroidal anti-inflammatory drugs
Neck stiffness 495 321, 336, 662
Needle cricothyroidotomy 698 Nonventilator therapy 189
832 ICU Manual
Norepinephrine 69, 85, 303, 786, 802 Oral anticoagulants, new 223
Normal anion gap Organ donation 767
acidosis 623 obtaining consent for 767
metabolic acidosis 633 Organ donor 768
Nosocomial diarrhea 99 Organ failure, sequence of 88fc
Nosocomial infection, causes of 97 Organochlorine 155
Nosocomial infections 97 compounds 155
Nosocomial pneumonia 98, 99, 130 and pyrethroids 155t
Novel agents 304 Organophosphorus 152, 153
Nuchal rigidity 495 compounds 153, 153t
Nuclear scintigraphy 386 Oropharyngeal
Numeric rating scale 659 airway 683f
Nutrition 125, 639 carcinoma 443
enteral 647 lesion 647
in illness, pathophysiology of 639 Orthopedic surgery 221
in specific conditions 653t Orthotopic liver transplantation 160t
parenteral 647 Oscillatory ventilation, high frequency
Nutritional assessment 640 254
Nutritional requirements 641 Osmolar load in diet, increasing 445
Nutritional support 197, 637, 648t Osmotic demyelination syndrome 349
routes for giving 647 Osmotic diuresis 354
timing of 647 Osteoarthritis 225
Oxacillin 809
Oxazolidinediones 811
O Oxygen 298, 315
O2 exchange, measures of 13 cascade 9, 12f
Obesity 214 steps of 9
hypoventilation syndrome 225, 227, concentration, inspired 558
227t consumption 48, 56, 794
Obstetric content 10
emergencies 461 delivery 10, 48, 56, 794
hemorrhage 463 index 48, 56, 794
causes of 463 dissociation curve 11f
classification 463 dynamics, indices of 11
Obstructive hypoventilation syndrome indices, regional 12
273 inspired 9
Obstructive shock 65, 77, 80t concentration of 89
causes 77 saturation 3, 47
mechanism of 77t transport 9
pathophysiology 77 Oxygenation, adequate 258
pathophysiology of 78fc
Obstructive sleep apnea 225, 226, 273
classification for severity of 226t P
diagnosis 226 Packed cell volume 135
Obtunded consciousness 463 Packed red cells 704, 704t, 705t
Octreotide 806 Pain
Ocular myasthenia gravis 523 abdominal 390, 457
Ocular symptoms 485 algorithm for 663fc
Oculovestibular testing 765fc and sedation, management of 657,
Oduvanthalai poisoning 156 662, 662fc
Oliguria 463, 470 assessment of 658
Omeprazole 806 clinical evaluation of 658t
Operative room management 570 control 313
Opioids 160, 798 drugs for 664t
cause sedation 160 feel of 658
Optic atrophy 436 incident 658
Index 833
intensity, present 661t, 792 Pelvic packing 555

location of 658 Pelvic ring disruption 551f
quality of 661 Pelvis 73
scales 659 Penetrating artery disease 484
severity of 658 Penetrating trauma causing popliteal
somatic 659t injury 574f
visceral 659t Penicillin 809, 811
Palla’s sign 217 G 499
Pamidronate 804 Pentamidine 389
Pancreas 723 Peptic ulcer 379
carcinoma of 443 endoscopic therapy for 382
Pancreatic cancer 389 Percutaneous coronary intervention 316,
Pancreatic fluid 720 750, 756
Pancreatitis 432 Percutaneous dilational tracheostomy
acute 389, 557 699
causes of acute 389t Percutaneous pelvic fixation techniques
etiology, acute 389 554
severity of acute 390t Percutaneous tracheostomy 611
Pancuronium 140 Pericardial pressure 328
Pantoprazole 806 Pericardiocentesis 330
Paracetamol 149, 400 Pericarditis
poisoning 814 early 320
Parathormone 788 late 321
Parathormone-related peptide 788 Periodic paralysis 528, 530
Parathyroid Perioperative fluid balance 717
agenesis 360 Perioperative patients, management of
destruction 360 723t
dysfunction 360 Peripheral arterial catheterization 17
glands 359 Peripheral arteries, waveform of 20f
hormone Peripheral circulation 66
levels 360t Peripheral nerve
levels, low 360 block infusions, advantages of 672
production of 369 catheter analgesia 668
resistance syndromes 360 Peripheral venous
Paravertebral block 673 cannulation, steps of 25f
Parenteral benzodiazepines 508 catheter 24
Parenteral nutrition 650, 651 Peripherally inserted central venous
solutions 651 catheters 36, 651
total 27, 33, 125, 354 Peritoneal dialysis 344
Patient ventilator asynchrony 264, 266f Peritoneal lavage
causes of 265fc, 268t limitations of diagnostic 563
management of 267, 268t procedure for diagnostic 562
physiologic effects of 266 Peritonitis
Patient-controlled analgesia localized 402
advantages of 671 primary 403
disadvantages of 671 secondary 403
Peak expiratory flow 201, 211 Permissive hypercapnia 629
rate 207, 208, 211 Phenylephrine 69, 802
Peak inspiratory Phenytoin 808, 814
flow 201 Phosphate 785
pressure 237 salts 804
Pelvic binders 553 Phosphodiesterase inhibitors 302
circumferential 553 enoximone 302
Pelvic fractures 551 milrinone 302
open 555 Phosphorus 784
834 ICU Manual
Physician determining brain death 763 Postcoronary artery bypass grafting 322
Physics of ultrasound 598 Postpartum hemorrhage 465, 471
Physiological disturbances 173 Postrenal acute kidney injury 336
Physiotherapy 586 Potassium 353, 428, 433, 754, 784
Phytonadione 807 balance in
Piperacillin 809 disease 353
Pit viper bites 163 health 353
Pituitary endocrine function 770 phosphate 804
Placenta sensitivity 530
abruption of 464 Potassium-aggravated myotonia 530
previa 464 Prasugrel 312
Placental abruption, complications with 465 Precipitate ketoacidosis 428
Plasma 541 Precipitating event 450
ketones 428, 433 Precordial thump 747
osmolality Prednisolone 525
increased 347 Pre-eclampsia 469
normal 347 complications of severe 473
Plasmalyte 725 pathogenesis of 470fc
Plasmapheresis 525 severe 470t
Plasminogen activators deficiency 484 Pregnancy 751
Plateau pressure 259f Pregnancy-induced hypertension 471
Platelet 541, 705 Prerenal azotemia 335, 337, 337t, 796
antibodies, tests for 422 Pressure control
count 539 mode with mandatory breaths 248f
dysfunction 418 ventilation 236f, 246, 249f, 250f
level syndrome, low 470 Pressure support 242, 249f
processing, types of 706 ventilation 235f, 240, 245, 249, 266,
transfusion 706t 271
Pleura, injury to 589 Pressure waveform, supported breaths
Pneumatic antishock garment 553 in 235f
Pneumonia 193, 239, 272, 510 Pressure-controlled ventilation 245
Pneumothorax 33, 589, 611f Pressure-regulated volume control 249
bar code sign indicating 611f Presurgery antibiotic prophylaxis 132
bilateral 589f Procainamide 280, 799
low-risk of 27 Proinsulin 788
treatment of 590 Prolactin 788
Poisoning 147, 153 Prophylactic treatment 529
general principles of 149 Propofol 664, 688, 808
Polydipsia, primary 435, 437 Proportional assist ventilation 256
Polyneuropathy, delayed 154 Propylthiouracil 804
Polyps 385 Prostacyclins 802
Popliteal sciatic block 673 Prostate, carcinoma of 443
Popliteal vein 607f Protein 644, 651
Popliteal vessel 216f C 484
injury 573 recombinant activated 123
Porphyria, acute 533 total 785
Portable ultrasound machine 597f Proteinuria 470
Portex cuffed tracheostomy tube 697f Prothrombin concentrate 416
Portosystemic shunts, surgical 384 Prothrombin time 782
Positive airway pressure 209, 240, 245, Proton pump inhibitors 382, 806
269, 270 Proximal injectate lumen 44
Positive end expiratory pressure 49, 207, Pseudo emergency 323
265, 268 pathophysiology 323
Positive pressure ventilation 233 Pseudohyperkalemia 356
effects of 237 Pseudohyponatremia 347
Index 835
Pseudomonas aeruginosa 100, 103, 498 diagnosis of

Ptosis 522 narrow 285fc
Pulmonary arterial hypertension 49 wide 288fc
Pulmonary artery 218f Quadruple hormonal replacement
catheter therapy 770, 771t
lumens 44 Quinidine 280
parameters measured by 794 Quinupristin 811
placement of 44, 46f
catheterization 27, 43, 43f, 46, 83
diastolic pressure 47, 55
R
occlusion pressure 47, 49, 55 Radial artery 17, 18
pressure 237 injury 573f
mean 47, 48, 55, 56, 794 Radiation colitis 385
monitoring 3 Radioallergosorbent test 142
systolic pressure 47, 55 Ramipril 799
wedge pressure 74 Ramsay sedation scale 666t, 793
Pulmonary capillary wedge pressure 65 Rapid sequence induction 677, 678
Pulmonary complications 397 technique of 677t
Pulmonary contusion 193 Rapid shallow breathing index 260
Pulmonary disease, chronic obstructive Reactions, types of 710t
188, 199, 268 Reactive oxygen species 88, 116
Pulmonary edema 84, 188, 239, 606 Recent cardiac surgery 328
acute 324, 431 Refeeding syndrome 653
Pulmonary embolism 79-81, 188, 214, Regional analgesia, options of 664
603, 606, 752 Rehabilitation 487, 586
Pulmonary function test 200, 206 Rehabilitative phase 183
Pulmonary hypertension 414 Renal abnormalities 397
Pulmonary hypoplasia 255 Renal causes 372
Pulmonary infarct, right 217f Renal compensation 621
Pulmonary infarction 215 Renal disease 356
score, clinical 102t end stage 337
Pulmonary O2 transfer, indices of 11 pre-existing 336
Pulmonary stability, interventions for 769 Renal disturbances 333
Pulmonary vascular resistance 56, 72, Renal dysfunction 338
78, 794 acute 337t
index 56 Renal failure 135, 328, 355, 399, 414, 432
Pulmonary veno-occlusive disease 49 acute 653
Pulse 73 causes of 359
contour analysis 53 chronic 346
index contour continuous cardiac treatment for established 340
output 52 Renal function
oximetry 52 effects of decreased 337
pressure 73 tests 298
variation 3, 17, 21, 52, 59 Renal insufficiency, acute 322
Pulsus paradoxus 328 Renal loss 354, 442
Pupils 149 Renal parenchymal disease 323
Push enteroscopy 386 Renal phosphate excretion 369
Pyrethroid 155 Renal replacement therapy 5, 124, 342,
poisoning 155 342t, 343, 344
adverse effects of 344
complications of 345t
Q Renal system 174, 564, 771
QRS complex tachycardia Renal tubular acidosis 354
causes of Renin-angiotensin
narrow 748t aldosterone system 72, 719
wide 748t system 657
836 ICU Manual
Renovascular disease 323 S

Reptile bites 163 Salbutamol 458
Respiratory acid-base disorder 623 Saline, normal 725
Respiratory acidosis 369, 629, 630, 632 Salt wasting nephropathies 354
acute 634 Schonfeld fat embolism syndrome index
causes of 629t 558t
Respiratory alkalosis 630, 632 Scorpionidae 162
acute 635 Scorpions 162
causes of 630t treatment 162
Respiratory care 189 Scrub typhus 336
Respiratory compensation 621 Sedation, drugs for 664t
Respiratory depression, drug-induced Sedatives treatment 159
629 Seizure
Respiratory diseases 185 prophylaxis 472
Respiratory distress 135 rum fits 507
syndrome, acute 123, 135, 188, 193, whiskey fits 507
557 Seldinger’s technique 18
Respiratory failure 166, 187, 190fc, 273, Selenium 123
399, 653, 681 Sellick’s maneuver 74, 678
acute 187, 606 Sengstaken-Blakemore tube 383
causes of acute 187t Sensory symptoms 485
etiology of 188t Sepsis 115, 117
types of 188t, 239t criteria for 118t
Respiratory infections 199 diagnosis of 120
Respiratory rate 241 intra-abdominal 99, 130
alarm, high 243 management of severe 118
Respiratory stimulants 228 screening of 120
Respiratory system 174, 564, 625, 628, severe 117
718, 762 spectrum of 116f
management of 769 Sepsis-induced hypotension 115
Resting energy expenditure 643t Septic encephalopathy 510
Resuscitation fluid 540 Septic shock 115
type of 336 management of 118
Resuscitative phase, early 180 pathogenesis of 115, 116fc
Reteplase 316, 797 resuscitation in 119t
Retinopathy Serum
advanced 326 albumin 362
papilledema 322 amylase, increased 391
Reversible causes 744 bicarbonate 428, 433
Reyes syndrome 394 concentration 473t
Rhabdomyolysis 368, 369 of magnesium 473
Rib fractures 629 cortisol level 457
Richmond agitation sedation scale 666t, creatinine 338
793 magnesium 373, 374
Rifaximin 398 level 374t
Right ventricle end diastolic osmolality 442
pressure 47, 55, 78 parathyroid hormone 362
volume 78 phosphorus 362
Right ventricular potassium 529
dysfunction, treatment of 223 urea 338
stroke work index 56, 794 Sevelamer hydrochloride 370
systolic pressure 47, 55 Severe organ insufficiency 91
Rocuronium 140, 679 Shock 27, 63, 66t, 413
Rodenticide poisoning 156 classification of 65, 73t
Rush protocol 604t, 605t degrees of 73t
Index 837
diagnosis of 67fc circulation 739t

distributive 65 return of 743, 746
energy 744 Square wave test 21
etiology of obstructive 77t Standard bicarbonate 618
inotropes for 69t Staphylococcus aureus 98, 100, 498
management 66 Static compliance, measurement of 259f
types of 65t Statins 488
vasopressors for 69t Status asthmaticus 629
Short-acting beta-2 agonist 208, 210, 211 Status epilepticus 490
Sibson’s fascia 28 complications 491
Sickle cell etiology 490
anemia 413 treatment 491
crisis 411, 413 types 490
management of 414 STEMI, management of patient with
pathophysiology 413 313fc
Sildenafil 801 Stenotrophomonas maltophilia 100
Sinoatrial exit block 292 Streptococcus agalactiae 498
Sinus Streptococcus pneumoniae 102, 121, 202,
arrest 292 203, 498
bradycardia 292 Streptogramin 811
pause 292 Streptokinase 316
Skeletal fixation 547 Stress ulcer prophylaxis 125
Skin 66, 718 Stroke 484, 737
layers of 174f acute 322
losses 350 assessment of acute 486
Slow low efficiency dialysis 344 index 56
Snake bite 164 types 484
first aid measures for 164t volume 48, 56, 794
history of 166 variation 3, 21, 52, 59
manifestations of 164fc Subarachnoid hemorrhage 486, 578, 578f
Soda bicarbonate 357, 745 Subclavian artery injury 571f
Sodium 428, 433, 784, 785 Subclavian vein 27, 28
bicarbonate 803 anatomy of right 29f
channel 290 cannulation 33
expected change in 348 right 39f
fractional excretion of 337 Subclavian vessels 570
level in infusate 349t Subdural hematoma 486, 576
nitroprusside 300, 325, 471 with midline shift 577f
phosphate 804 Substance abuse 432
Somatic pain 659 Succinylcholine 140, 679
Sonography for trauma 605f Suctioning technique 700
Sotalol 291 Sulbactam 809
Specific hypertensive crises, management Sulfamethoxazole 812
of 325 Sulfonamides 389
Speech disturbances 485 Superficial burns 177f
Spinal injury, acute 220 Supplemental oxygen therapy 202
Spinal surgery 220 Supraventricular arrhythmias 277
Spironolactone 799 Supraventricular reentrant tachycardias
Splenectomy 423 282
Splenic injury, grading of 561t Surgical-wound infections 99
Spontaneous Surviving sepsis campaign bundles 121t
attacks 530 Symphyseal plating 554f
breath 235f, 250f Symptomatic hypocalcemia, severe 361
trial 258 Symptomatic hyponatremia 348
breathing patients 58 Synchronized cardioversion 745
838 ICU Manual
Synchronized intermittent mandatory Thrombolytic therapy 487t

ventilation 245, 247 Thrombolytics 328, 803
Syndrome of inappropriate antidiuretic in ischemic stroke 487
hormone Thrombopoietin receptor agonists 423
causes of 442, 443t Thromboxane 88
diagnosis of 442t, 444 Thrombus in situ 573f
diagnostic criteria of 444t Thumb for selecting cannula, rule of 699
Systemic arterial pressure, cyclical Thymoma 443
variation of 59fc Thyroid
Systemic inflammatory response emergencies 449
syndrome 72, 116, 175 hormone 805
Systemic vascular resistance 48, 56, 65, severe deficiency of 449
794 therapy 454
index 48, 56, 794 ophthalmopathy 451
Systolic storm 13, 449
blood pressure 299, 539 Tibial artery, posterior 17
decline 20 Tibial condyle fracture 575f
peak 20 Tibial fracture
pressure variation 17, 21, 52, 58 open 548f
upstroke 20 shaft, open 547f
Tibial vessel injury 574
Ticagrelor 313
T Ticarcillin 809
Tachycardia 66, 215, 282f, 450, 463 Tigecycline 810
management of 748fc Tirofiban 798
Tachypnea 215 Tissue
Technetium-labeled red blood cell 386 oxygenation 12
Telithromycin 810 adequacy of 12
Temperature regulation 762 impaired 13
Tendon 600 Tonic clonic movements 490
Tenecteplase 316, 797 Torasemide 800
Tension pneumothorax 590 Torsades de pointes 291, 291f
right-sided 590f causes 291
Terbutaline 210 treatment 291
Terminal delirium 510 Total parenteral nutrition, complications
etiology 510 of 652
sundowning 510 Toxic states 511
Testosterone Tazobactam 809
free 788 Trace elements 645
total 788 Trachea for percutaneous tracheostomy
Tetracyclin 389, 810, 812 612f
Thermoregulatory dysfunction 450 Tracheostomy 693
Thevetia peruviana 155 care 699
Thiazides 389 high 695
Thiourea drugs 804 lower 696
Thiopentone 187, 688 steps of 694
Thoracic bioimpedance plethysmography tube 696, 696t, 697
51, 52 parts of 696
Thoracic injury, exploration in 591t types of 696t
Thoracic pump mechanism 732 types of 695, 695f
Thoracic surgery 220 Tracheotomy 693
Thoracic trauma 588 Tramadol 664
life-threatening injuries in 588t Transcellular shifts 354
Thorax 73, 604 Transcutaneous Doppler ultrasonography
Thromboembolism, prevention of 218 52
Index 839
Transcutaneous electrical nerve Upper gastrointestinal bleeding 379

stimulation 662 causes of 379t
Transducer movements 600 Upper limb injury, severe 572f
Transferrin 782 Upper radial injuries 572
Transfusion Urapidil 325
adverse reactions to 709 Urea 324, 783
of blood 541 Ureter, carcinoma of 443
reactions 709, 710 Uric acid 783, 785
Transfusion-related Urinary
acute lung injury 711 catheter 75
infections 713t use of 109
Transient ischemic attack 483 drainage bag colonization 109
management of 483 tract infection 97, 99, 108, 109, 109t
Transthoracic echocardiography 5, 52 Urine
Transvenous abnormalities 338
cardiac pacing 27 calcium 363
intrahepatic portosystemic shunts 383 output 337, 338
pacing 5 routine analysis 324
Trauma 214, 752 sodium level 346t
patient 535 Urosepsis, treatment of 113
Traumatic airway injury 538 Uterine atony, pharmacologic therapy
Traumatic brain injury 220 for 466t
management of 580
severe 582
severe 576
V
surgery in 585t Vagal maneuvers 283
Traumatic cerebrovascular disease 484 Valproate 808
Traumatic head injury 576 Valproic acid 389
Traumatic rupture of aorta 593 Valsalva maneuvers 283
Traumatic spine injury 220 Valvular heart disease 81, 484
Treprostinil 802 Vancomycin 499, 810
Triglycerides 781 Vaptans, role of 446
Trimethoprim 812 Variceal bleed 379
Troponins 784 Varicella zoster 499
Troubleshooting virus 504
PEEP alarms 243fc Varices, endoscopic therapy for 383
ventilator alarms 243fc Vasa previa 465
Trousseau sign 360 Vascular anomaly 380
treatment 361 Vascular injury 568t
True hyponatremia 347 Vascular trauma of extremities 567
Tubercular meningitis 501 Vascular-enteric fistula 379, 385
Tumor necrosis factor 72, 88, 116, 495, Vasodilators 299, 800
639 classification 299
Vasopressin 69, 745, 799, 803
Vasopressors 85, 122
U Vecuronium 140
Ulnar artery 17 Vein 600
injury 573f compressibility, loss of 216f
Ulnar vessel injuries 572 Vena cava, superior 28
Ultrasound in critical care, role of 597 Venous oxygen
Ultrasound transducer, selection of 599 content, mixed 48, 56, 794
Unanticipated difficult airway 689fc tension, mixed 13
Unfractionated heparin 221, 222, 798 saturation, mixed 14, 57
dose 317 Venous thromboembolism 220
Upper airway obstruction 629 pathophysiology of 215fc
840 ICU Manual
Venous ultrasonography 216 Vipers 163

Venovenous hemodiafiltration, Viral
continuous 342 encephalitis 503
Venovenous hemofiltration, continuous pharmacologic management of
342 504t
Ventilation hepatitis 395, 476
adaptive support 227, 255 meningitis 499
adequate 259 Visceral pain 659
alarm, high minute 242 Visual
basic modes of 245 analog scale 659
closed loop 255 disturbance 470
components of 234t symptoms 485
continuous mandatory 268 Vitamin 645, 652
high frequency 253 D
initiation of 239 deficiency 360
inverse ratio 251 preparations 369
methods of 736t K antagonist 221
modes of 245 Vogt-Koyanagi-Harada syndrome 497
restriction of 629 Volume control mode with mandatory
strategy 204 breaths 247f
system 6 Volume-controlled ventilation 236f, 245
types of high frequency 254t Vomiting 404, 442, 457
Ventilator Voriconazole 812
alarms 242
asynchrony, diagnosis of patient 266
design 233
W
interaction 264t Waist circumference and risk 226t, 791
Ventilator-associated pneumonia 97 Warfarin 221, 416, 801, 807
Ventricle, right 78 Water deficit
Ventricular aneurysm 319 calculate 351
treatment 319 correction of 351
Ventricular arrhythmias 286 Water vapor pressure 9
Ventricular fibrillation 292f Weaning process 258fc
Ventricular flutter and fibrillation 292 Wernicke’s encephalopathy 645
Ventricular free wall rupture 319 Westermark’s sign 217
treatment 319 Wheeze 206
Ventricular premature complex 286, 286f Wilsons disease 394
Ventricular pseudoaneurysm 319 Withdrawal states 511
Ventricular septal Withdrawal symptoms, management of
defect 81 508
rupture 318 Wolff-Chaikoff effect 451
treatment 318 Wolff-Parkinson-White syndrome 281
Ventricular tachycardia 286 Wolfram syndrome 436
Verapamil 280, 799 Wong-Baker faces pain scale 660
Verbal Wound
descriptor scale 660 closure 547
response 580 management phase 182
Vessel, small 484
Vestibular symptoms 485 Z
Vinca alkaloids 423
Zinc 784
Viperidae 163
Zoledronic acid 804

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ICU

G Ninoo George Marun Raj

The Health Sciences Publishers

© Digital Version 2018, Jaypee Brothers Medical Publishers

Inquiries for bulk sales may be solicited at: jaypee@jaypeebrothers.com

A Meenakshi Sundaram MS DNB Sumathy MD

Critical care medicine is relatively new but increasingly important medical

SECTION 2: Physiology of Critically Ill Patient

SECTION 3: Vascular Access and Hemodynamic Monitoring

SECTION 5: Infection and Immune Disorders in ICU

17. Tropical Infections 134

SECTION 6: Poisoning and Envenomation

SECTION 8: Respiratory Diseases in ICU

27. Acute Exacerbation of Chronic Obstructive Pulmonary Disease 199

SECTION 9: Approach to Mechanical Ventilation

SECTION 10: Cardiovascular Diseases in ICU

38. Acute Heart Failure 296

SECTION 11: Renal and Electrolyte Disturbances in ICU

46. Calcium 359

SECTION 12: Gastrointestinal Diseases in ICU

SECTION 13: Hematological Disorders in ICU

56. Immune Thrombocytopenic Purpura 420

SECTION 14: Endocrine Disorders in ICU

SECTION 15: Obstetric Emergencies

66. Amniotic Fluid Embolism 479

SECTION 16: Neurological Disorders in ICU

SECTION 17: Neuromuscular Disorders

75. Critical Illness Polyneuropathy 531

SECTION 18: Approach to a Trauma Patient

SECTION 19: Ultrasonography

SECTION 20: Acid-Base Disorders

SECTION 21: Nutritional Support

SECTION 22: Sedation and Analgesia in ICU

SECTION 23: Airway Management in ICU

93. Endotracheal Intubation in Critical Care 680

SECTION 24: Transfusion Practice in ICU

SECTION 25: Fluid Management

SECTION 26: Cardiopulmonary Resuscitation

SECTION 27: Brain Death

SECTION 28: Medical Ethics

SECTION 29: Appendices

1 INTENSIVE CARE UNIT

Chapter 1 Setting Up an ICU

Intensive care unit (ICU) is a specified area in a hospital designed to manage

INDIAN SOCIETY OF CRITICAL CARE MEDICINE (ISCCM) PROVIDE

Level I (Table 1.1)

Level II (Table 1.2)

Table 1.2 ICU bed and space recommendations

ICU bed 1 to 4 per 100 hospital beds

Heating, Ventilation and Air-conditioning (HVAC) System of ICU

Chapter 2 Critically Ill Patient and Oxygenation

CRITICALLY ILL PATIENT AND

Microcirculation and Interstitium

Fig. 2.1 Oxygen dissociation curve

where CaO2=Content of O2 in arterial blood = 20 mL, CvO2=Content of O2 in

Indices of Pulmonary O2 Transfer

Indices of Oxygen Dynamics

Fig. 2.2 Oxygen cascade

Regional Oxygen Indices

Mixed Venous O2 Tension (SvO2)

Table 2.1 Causes of increased and decreased SvO2

Causes of ↑ SvO2 Causes of ↓ SvO2

ScvO2 (Mixed Venous O2 Saturation)

Chapter 1 Setting Up an ICU

Chapter 2 Critically Ill Patient and Oxygenation

Chapter 3 Peripheral Arterial Catheterization

Chapter 4 Peripheral Venous Catheterization

Chapter 5 Central Venous Catheterization

Chapter 6 Pulmonary Artery Catheterization

Chapter 7 Hemodynamic Monitoring