Critical Care Medicine Outline

CAGAYAN VALLEY MEDICAL CENTER
Department of Internal Medicine
CRITICAL CARE MEDICINE

SECTION 1 Respiratory Critical Care
293. Approach to the Patient with Critical Illness 1
294. Acute Respiratory Distress Syndrome 10
295. Mechanical Ventilatory Support 13
SECTION 2 Shock and Cardiac Arrest

296. Approach to the Patient with shock 20
297. Sepsis and Septic Shock 29
298. Cardiogenic Shock and Pulmonary Edema 39
299. Cardiovascular Collapse, Cardiac Arrest and Sudden Cardiac Death 48
SECTION 3 Neurologic Critical Care

300 Coma 57
301 Severe Acute Encephalopathies and Critical Care Weakness 59
302. Subarachnoid Hemorrhage 71
Presented by
Saint Paul University Philippines Clerks
ARAO, GINO
BANANG, MA. ANELY
CACHERO, AUMAR
DALUPING, DAPHNE
DELA CRUZ, DESIREE JOLLY
JWALA, MARY MERCY
PAMITTAN, KARLA IDA
PERALTA, AZIZA MELODY
RAJULABEEVI, AFRAH
SALVIO, SHARLENE MAE
TINIPAC, SMILEY
UNISTA, JONALYN
INTERNAL MEDICINE
PART 8 CRITICAL CARE MEDICINE
May 2021 SPUP School of Medicine
SECTION 1 RESPIRATORY CRITICAL CARE

293. APPROACH TO THE PATIENT WITH CRITICAL ILLNESS
ASSESSMENT OF ILLNESS SEVERITY
• In the ICU, illnesses are frequently categorized by degree of severity.
• Numerous severity-of-illness (SOI) scoring systems have been developed and validated over the past three decades.
• All existing SOI scoring systems are derived from patients who have already been admitted to the ICU.
• SOI scoring systems cannot be used to predict survival in individual patients.
• No established scoring systems that purport to direct clinicians’ decision-making regarding criteria for admission to an ICU
are available.
• Use of SOI scoring systems to direct therapy and clinical decision-making cannot be recommended. Instead, these tools
should be used as a source of important data to complement clinical bedside decision-making.
• The most commonly utilized scoring systems are:
o SOFA (Sequential Organ Failure Assessment)
o APACHE (Acute Physiology and Chronic Health Evaluation)
o SAPS (Simplified Acute Physiology Score) systems.
THE SOFA SCORING SYSTEM

• The SOFA scoring system is composed of scores from six organ systems
o Graded from 0 to 4 according to the degree of dysfunction
• The score accounts for clinical interventions; it can be measured repeatedly (i.e., each day), and rising scores correlate well
with increasing mortality.
• Patients with suspected infection can be predicted to have poor outcomes typical of sepsis if they have at least two of the
following clinical criteria:
o Respiratory rate >22
o Altered mental status
o Systolic blood pressure <100 mmHg
• Recently, a new bedside clinical score using two or more of the above clinical criteria has emerged and is termed quickSOFA
(qSOFA).
• qSOFA is intended to screen patients for ICU admission from out-of-hospital, emergency department, and hospital ward
settings.
THE APACHE II SCORING SYSTEM

• The APACHE II system is the most commonly used SOI scoring system in North America.
• Age, type of ICU admission (after elective surgery vs nonsurgical or after emergency surgery), chronic health problems, and
12 physiologic variables (the worst values for each in the first 24 h after ICU admission) are used to derive a score.
• The predicted hospital mortality rate is derived from a formula that takes into account the APACHE II score, the need for
emergency surgery, and a weighted, disease-specific diagnostic category
Jameson, L.J., Fauci, A., Kasper, D., Hauser, S., Longo, D., & Loscalzo, J. (2018). Harisson’s Principle s of Internal Medicine, 20th Edition (Vol.1&2) McGraw-Hill Education/ Medical.5
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THE SAPS SCORING SYSTEM

• The SAPS II score, used more frequently in Europe than in the United States, was derived in a manner similar to the APACHE
score.
• This score is not disease-specific but rather incorporates three underlying disease variables:
o AIDS, metastatic cancer, and hematologic malignancy.
• SAPS 3, which utilizes a 1-h rather than a 24-h window for measuring physiologic derangement scores, was developed in
2005.
INITIAL EVALUATION
• Shock, a common condition necessitating ICU admission or occurring in the course of critical care, is defined by the presence
of multisystem end-organ hypoperfusion.
• Clinical indicators include:
o Reduced mean arterial pressure (MAP), tachycardia, tachypnea, cool skin and extremities, acute altered mental
status, and oliguria.
§ Hypotension is usually, though not always, present.
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The end result of multiorgan hypoperfusion is

§
tissue hypoxia, often with accompanying lactic
acidosis.
• The initial assessment of a patient in shock should take only a few
minutes.
• It is important that aggressive resuscitation is instituted on the
basis of the initial assessment, particularly since early
resuscitation from septic and cardiogenic shock may improve
survival
• If the initial bedside assessment yields equivocal or confounding
data, more objective assessments such as
ultrasound/echocardiography may be useful.
• In spontaneously breathing patients, inferior vena cava collapse
seen on ultrasound predicts a fluid responsive state.
• Increasingly, ultrasound of the thorax and abdomen is used by
intensivists as an extension of the physical examination to assess
rapidly imputed filling volumes, adequacy of cardiac
performance, and for indices of other specific conditions (e.g.,
pericardial tamponade, pulmonary embolus, pulmonary edema,
pneumothorax).
• The goal of aggressive resuscitation is to reestablish adequate
tissue perfusion and thus to prevent or minimize end-organ
injury.
MECHANICAL VENTILATORY SUPPORT

• Mechanical ventilation may relieve the work of breathing and allow redistribution of a limited cardiac output to other vital
organs.
• Patients demonstrate respiratory distress by an inability to speak full sentences, accessory use of respiratory muscles,
paradoxical abdominal muscle activity, extreme tachypnea (>40 breaths/min), and decreasing respiratory rate despite an
increasing drive to breathe due to exhaustion.
• When patients with shock are treated with mechanical ventilation, a major goal is for the ventilator to assume all or the
majority of the work of breathing, facilitating a state of minimal respiratory muscle work.
• With the institution of mechanical ventilation for shock, further declines in MAP are frequently seen.
o The reasons include impeded venous return from positive-pressure ventilation, reduced endogenous catecholamine
secretion once the stress associated with respiratory failure abates, and the actions of drugs used to facilitate
endotracheal intubation(e.g., propofol, opiates).
• Patients with right heart dysfunction or preexiting pulmonary hypertension may also have diminished cardiac output related
to the increases in right ventricular afterload resulting from positive pressure ventilation.
• Accordingly, hypotension should be anticipated during and following endotracheal intubation.
o Many of these patients may be fluid responsive, IV volume administration should be considered.
RESPIRATORY FAILURE
• Respiratory failure is one of the most common reasons for ICU admission.
• In some ICUs, ≥75% of patients require mechanical ventilation during their stay.
• Respiratory failure can be categorized mechanistically on the basis of pathophysiologic derangements in respiratory function.
TYPE I: ACUTE HYPOXEMIC RESPIRATORY FAILURE

• This type of respiratory failure occurs with alveolar flooding and subsequent intrapulmonary shunt physiology.
• Alveolar flooding may be a consequence of pulmonary edema, lung injury, pneumonia, or alveolar hemorrhage.
• Pulmonary edema can be further categorized as occurring due to elevated pulmonary microvascular pressures, as seen in
heart failure and intravascular volume overload or ARDS (“low-pressure pulmonary edema,”).
• This syndrome is defined by acute onset (≤1 week) of bilateral opacities on chest imaging that are not fully explained by
cardiac failure or fluid overload and of shunt physiology requiring positive end-expiratory pressure (PEEP).
• Type I respiratory failure occurs in clinical settings such as sepsis, gastric aspiration, pneumonia, near-drowning, multiple
blood transfusions, and pancreatitis.
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• The mortality rate among patients with ARDS was traditionally very high (50–70%), although changes in patient care have
led to mortality rates closer to 30%
• It is well established that mechanical ventilation of patients with ARDS may propagate lung injury.
• In addition, a “fluid conservative” management strategy (maintaining a low central venous pressure [CVP] or pulmonary
capillary wedge pressure [PCWP]) is associated with fewer days of mechanical ventilation than a “fluid liberal” strategy
(maintaining a relatively high CVP or PCWP) in ARDS.
• There is growing interest in avoiding intubation in patients with ARDS by the use of a variety of devices, such as masks, high
flow oxygen delivery systems, and helmets for respiratory support; however, this is tempered by concern that higher tidal
volumes during spontaneous breathing with these devices could result in progression of preexisting lung injury.
TYPE II RESPIRATORY FAILURE

• This type of respiratory failure is a consequence of alveolar hypoventilation and results from the inability to eliminate carbon
dioxide effectively.
• Mechanisms are categorized by impaired central nervous system (CNS) drive to breathe, impaired strength with failure of
neuromuscular function in the respiratory system, and increased load(s) on the respiratory system.
• Reasons for diminished CNS drive to breathe include:
o drug overdose, brainstem injury, sleep-disordered breathing, and severe hypothyroidism.
• Reduced strength can be due to impaired neuromuscular transmission (e.g., myasthenia gravis, Guillain-Barre syndrome,
amyotrophic lateral sclerosis) or respiratory muscle weakness (e.g., myopathy, electrolyte derangements, fatigue).
• The overall load on the respiratory system can be subclassified into resistive loads (e.g., bronchospasm), loads due to reduced
lung compliance (e.g., alveolar edema, atelectasis, intrinsic positive end-expiratory pressure [auto-PEEP]), loads due to
reduced chest wall compliance (e.g., pneumothorax, pleural effusion, abdominal distention), and loads due to increased
minute ventilation requirements (e.g., pulmonary embolus with increased dead-space fraction, sepsis).
• The mainstays of therapy for type II respiratory failure are directed at reversing the underlying cause(s) of ventilatory failure.
• Noninvasive positive-pressure ventilation with a tight-fitting facial or nasal mask, with avoidance of endotracheal intubation,
often stabilizes these patients.
o This approach has been shown to be beneficial in treating patients with exacerbations of chronic obstructive
pulmonary disease.
o it has been tested less extensively in other kinds of respiratory failure but may be attempted nonetheless in the
absence of contraindications (hemodynamic instability, inability to protect the airway, respiratory arrest).
TYPE III RESPIRATORY FAILURE

• This form of respiratory failure results from lung atelectasis.
• Atelectasis occurs so commonly in the perioperative period, this form is also called perioperative respiratory failure.
• After general anesthesia, decreases in functional residual capacity lead to collapse of dependent lung units.
• Such atelectasis can be treated by frequent changes in position, chest physiotherapy, upright positioning, and control of
incisional and/or abdominal pain.
• Noninvasive positive-pressure ventilation may also be used to reverse regional atelectasis
TYPE IV RESPIRATORY FAILURE

• This form results from hypoperfusion of respiratory muscles in patients in shock.
• Normally, respiratory muscles consume <5% of total cardiac output and oxygen delivery.
• Patients in shock often experience respiratory distress due to pulmonary edema (e.g., in cardiogenic shock), lactic acidosis,
and anemia.
• In this setting, up to 40% of cardiac output may be distributed to the respiratory muscles.
• Intubation and mechanical ventilation can allow redistribution of the cardiac output away from the respiratory muscles and
back to vital organs while the shock is treated.
CARE OF THE MECHANICALLY VENTILATED PATIENT

• Whereas a thorough understanding of the pathophysiology of respiratory failure is essential for optimal patient care,
recognition of a patient’s readiness to be liberated from mechanical ventilation is likewise important.
• Accordingly, all intubated, mechanically ventilated patients should undergo daily screening of respiratory function.
• If oxygenation is stable (i.e., Pao2/FIo2 [partial pressure of oxygen/fraction of inspired oxygen] >200 and PEEP ≤5 cmH2O),
cough and airway reflexes are intact, and no vasopressor agents or sedatives are being administered, the patient has passed
the screening test and should undergo a spontaneous breathing trial.
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• This trial consists of a period of breathing through the endotracheal tube without ventilator support (continuous positive
airway pressure [CPAP] of 5 cmH2O with or without low level pressure support [e.g., 5 cmH2O] and an open T-piece breathing
system have all been validated) for 30–120 min.
• The spontaneous breathing trial is declared a failure and stopped if any of the following occur:
o Respiratory rate >35/min for >5 min
o O2 saturation <90%
o Heart rate >140/min or a 20% increase or decrease from baseline
o Systolic blood pressure <90 mmHg or >180 mmHg
o Increased anxiety or diaphoresis.
• If, at the end of the spontaneous breathing trial, none of the above events has occurred and the ratio of the respiratory rate
and tidal volume in liters (f/VT) is <105, the patient can be extubated.
• In patients in whom extubation fails may be associated with worse outcomes than are obtained with immediate reintubation.
• Mechanically ventilated patients frequently require sedatives and analgesics.
o Opiates are the mainstay of therapy for analgesia in mechanically ventilated patients.
• After adequate pain control has been ensured, additional indications for sedation include anxiolysis; treatment of subjective
dyspnea; reduction of autonomic hyperactivity, which may precipitate myocardial ischemia; and reduction of total O2
consumption (Vo2).
• Non-benzodiazepine sedatives are preferred since benzodiazepines are associated with worse patient outcomes.
• The neuromuscular blocking agent cisatracurium is occasionally used to facilitate mechanical ventilation in patients with
profound ventilator dyssynchrony despite optimal sedation, particularly in the setting of severe ARDS.
o Use of these agents may result in prolonged weakness (postparalytic syndrome)
• Amnesia can be achieved reliably with propofol and benzodiazepines such as lorazepam and midazolam.
• Since many of these critical patients have impaired hepatic and renal function, sedatives and opiates may accumulate when
given for prolonged periods.
o A nursing protocol–driven approach to sedation of mechanically ventilated patients or daily interruption of sedative
infusions paired with daily spontaneous breathing trials has been shown to prevent excessive drug accumulation
and shorten the duration of both mechanical ventilation and ICU stay.
MULTIORGAN SYSTEM FAILURE

• Multiorgan system failure, which is commonly associated with critical illness, is defined by:
o Simultaneous presence of physiologic dysfunction and/or failure of two or more organs.
o This syndrome occurs in the setting of severe sepsis, shock of any kind, severe inflammatory conditions such as
pancreatitis, and trauma.
• Although there is debate regarding specific definitions of organ failure, several general principles governing the syndrome of
multiorgan system failure apply.
o (1) organ failure, no matter how it is defined, must persist beyond 24 h.
o (2) mortality risk increases with the accrual of failing organs.
o (3) the prognosis worsens with increased duration of organ failure.
MONITORING IN THE ICU

• Monitoring of the respiratory and cardiovascular systems is undertaken frequently.
• Evaluation of respiratory gas exchange is routine in critical illness.
• The “gold standard” remains arterial bloodgas analysis:
o pH, Pao2, partial pressure of carbon dioxide (Pco2), and O2 saturation are measured directly.
o With arterial blood-gas analysis, the two main functions of the lung—oxygenation of arterial blood and elimination
of CO2—can be assessed directly.
• Although sampling of arterial blood is generally safe, it may be painful and cannot provide continuous information.
o In light of these limitations, noninvasive monitoring of respiratory function is often employed.
PULSE OXIMETRY
• The most commonly utilized noninvasive technique for monitoring respiratory function
• Pulse oximetry takes advantage of differences in the absorptive properties of oxygenated and deoxygenated hemoglobin.
• At wavelengths of 660 nm, oxyhemoglobin reflects light more effectively than does deoxyhemoglobin, whereas the reverse
is true in the infrared spectrum (940 nm).
• A pulse oximeter passes both wavelengths of light through a perfused digit such as a finger, and the relative intensity of
light transmission at these two wavelengths is recorded.
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• From this information, the relative percentage of oxyhemoglobin is derived.

• Since arterial pulsations produce phasic changes in the intensity of transmitted light, the pulse oximeter is designed to detect
only light of alternating intensity.
o This feature allows distinction of arterial and venous blood O2 saturations.
RESPIRATORY SYSTEM MECHANICS

• When volume-controlled modes of mechanical ventilation are used, accompanying airway pressures can easily be measured
as long as the patient is passive.
• The peak airway pressure is determined by two variables: airway resistance and respiratory system compliance.
• At the end of inspiration, inspiratory flow can be stopped transiently. This end-inspiratory pause (plateau pressure) is a
static measurement, affected only by respiratory system compliance and not by airway resistance.
• During volume-controlled ventilation, the difference between the peak (airway resistance + respiratory system compliance)
and plateau (respiratory system compliance only) airway pressures provides a quantitative assessment of airway resistance.
• Accordingly, during volume-controlled ventilation, patients with increases in airway resistance typically have increased peak
airway pressures as well as abnormally high gradients between peak and plateau airway pressures (typically >15 cmH2O) at
a constant inspiratory flow rate of 1 L/sec.
• The compliance of the respiratory system is defined by the change in volume of the respiratory system per unit change in
pressure.
• The respiratory system can be divided into two components:
o The lungs and the chest wall
• Respiratory system compliance is ~100 mL/cmH2O. (normal)
• Pathophysiologic processes such as:
o Pleural effusions, pneumothorax, and increased abdominal girth all reduce chest wall compliance.
• Lung compliance may be reduced by pneumonia, pulmonary edema, interstitial lung disease, or auto-PEEP.
• Accordingly, patients with abnormalities in compliance of the respiratory system (lungs and/or chest wall) typically have
elevated peak and plateau airway pressures but a normal gradient between these two pressures.
• Auto-PEEP occurs when there is insufficient time for emptying of alveoli before the next inspiratory cycle.
• Since the alveoli have not decompressed completely, alveolar pressure remains positive at the end of exhalation (functional
residual capacity).
• This phenomenon results most commonly from obstruction of distal airways in disease processes such as asthma and COPD.
• Auto-PEEP with resulting alveolar overdistention may result in diminished lung compliance, reflected by abnormally
increased plateau airway pressures.
• Modern mechanical ventilators allow breath-to-breath display of pressure and flow, permitting detection of problems such
as patient-ventilator dyssynchrony, airflow obstruction, and auto-PEEP
CIRCULATORY STATUS
• Oxygen delivery (Qo2) is a function of cardiac output and the content of O2 in the arterial blood (Cao2).
• The Cao2 is determined by the hemoglobin concentration, the arterial hemoglobin saturation, and dissolved O2 not bound
to hemoglobin.
• For normal adults:
• It is apparent that nearly all of the O2 delivered to tissues is bound to hemoglobin and that the dissolved O2 (Pao2)
contributes very little to O2 content in arterial blood or to O2 delivery.
• Normally, the content of O2 in mixed venous blood (C–vo2) is 15.76 mL/dL since the mixed venous blood is 75% saturated.
Therefore, the normal tissue extraction ratio for O2 is Cao2 – C–vo2/Cao2 ([21.16 – 15.76]/21.16) or ~25%.
• A pulmonary artery catheter allows measurements of O2 delivery and the O2 extraction ratio
PREVENTION OF COMPLICATIONS OF CRITICAL ILLNESS

SEPSIS IN THE CRITICAL CARE UNIT
• Sepsis, is defined as life-threatening organ dysfunction (i.e., an increase in Sequential Organ Failure Assessment [SOFA] of 2
points or more) caused by a dysregulated response to infection.
• Poor outcomes can be anticipated in patients with 2 or more of the following:
o respiratory rate >22 per min, altered mentation, systolic blood pressure <100 mmHg.
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NOSOCOMIAL INFECTIONS IN THE ICU

• Many therapeutic interventions in the ICU are invasive and predispose patients to infectious complications.
• These interventions include:
o endotracheal intubation, indwelling vascular catheters, transurethral bladder catheters, and other catheters placed
into sterile body cavities (e.g., tube thoracostomy, percutaneous intraabdominal drainage catheterization).
• The longer such devices remain in place, the more prone to these infections patients become.
• An important aspect of preventive care is the timely removal of invasive devices as soon as they are no longer needed.
• Multi-drug resistant organisms are commonplace in the ICU.
• Infection control is critical in the ICU, Care bundles, include:
o Frequent hand washing, are effective but underutilized strategies.
o Protective isolation of patients colonized or infected by drug-resistant organisms, are also commonly used.
DEEP-VENOUS THROMBOSIS (DVT)

• All ICU patients are at high risk for this complication because of their predilection for immobility.
• All should receive some form of prophylaxis against DVT.
• The most commonly employed forms of prophylaxis:
o Subcutaneous low-dose heparin injections and sequential compression devices for the lower extremities.
o Heparin prophylaxis may result in heparin-induced thrombocytopenia, another nosocomial complication in critically
ill patients.
o Low-molecular-weight heparins such as enoxaparin are more effective than unfractionated heparin for DVT
prophylaxis in high-risk patients (e.g., those undergoing orthopedic surgery) and are associated with a lower
incidence of heparin-induced thrombocytopenia.
o Fondaparinux, a selective factor Xa inhibitor, is even more effective than enoxaparin in high-risk orthopedic patients.
STRESS ULCERS
• Prophylaxis against stress ulcers is not necessary for all ICU patients. It should only be administered to high-risk patients,
such as those with coagulopathy or respiratory failure.
• Histamine receptor-2 antagonists are preferred over proton pump inhibitors because the latter are associated with increased
incidence of C. difficile colitis and pneumonia
NUTRITION AND GLYCEMIC CONTROL

• These are important issues that may be associated with respiratory failure, impaired wound healing, and dysfunctional
immune response in critically ill patients.
• Early enteral feeding is reasonable, with some data suggesting that permissive underfeeding of nonprotein calories is not
inferior to full goal feeding.
• Enteral feeding, if possible, is preferred over parenteral nutrition, which is associated with numerous complications, including:
o hyperglycemia, fatty liver, cholestasis, and sepsis.
• When parenteral feeding is necessary to supplement enteral nutrition, delaying this intervention until day 8 in the ICU results
in better recovery and fewer ICU-related complications.
• Tight glucose control is an area of controversy in critical care.
o Although one study showed a significant mortality benefit when glucose levels were aggressively normalized in a
large group of surgical ICU patients, other studies of both medical and surgical ICU patients suggested that tight
glucose control resulted in increased rates of mortality.
ICU-ACQUIRED WEAKNESS
• ICU-acquired weakness occurs frequently in patients who survive critical illness, particularly those with SIRS and/or sepsis.
• Both neuropathies and myopathies have been described, most commonly after ~1 week in the ICU.
• The mechanisms behind ICU-acquired weakness syndromes are poorly understood, they are known to present with
heterogeneous muscle pathophysiology.
• Intensive insulin therapy may reduce polyneuropathy in critical illness.
• Very early physical and occupational therapy in mechanically ventilated patients reportedly results in significant
improvements in functional independence at hospital discharge as well as in reduced durations of mechanical ventilation
and delirium.
ANEMIA
• Studies have shown that most ICU patients are anemic as a result of chronic inflammation.
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• Phlebotomy also contributes to ICU anemia.

• A large multicenter study involving patients in many different ICU settings challenged the conventional notion that a
hemoglobin level of 100 g/L (10 g/dL) is needed in critically ill patients, with similar outcomes noted in those whose
transfusion trigger was 7 g/dL.
o Red blood cell transfusion is associated with impairment of immune function and increased risk of infections as well
as of ARDS and volume overload, all of which may explain the findings in this study.
• A conservative transfusion strategy has shown similar outcomes in septic shock, postcardiac surgery, and post-hip surgery
patients.
• A conservative transfusion strategy has been shown to enhance survival among patients with active upper gastrointestinal
hemorrhage.
ACUTE KIDNEY FAILURE

• Acute kidney failure occurs in a significant percentage of critically ill patients.
• The most common underlying etiology is acute tubular necrosis, usually precipitated by hypoperfusion and/ or nephrotoxic
agents.
• No pharmacologic agents are available for prevention of kidney injury in critical illness.
• Studies have shown convincingly that neither low-dose dopamine, fenoldapam nor vasopressin are not effective in protecting
the kidneys from acute injury.
NEUROLOGIC DYSFUNCTION IN CRITICALLY ILL PATIENTS

DELIRIUM
• This state is defined by:
o (1) an acute onset of changes or fluctuations in mental status,
o (2) inattention,
o (3) disorganized thinking, and
o (4) an altered level of consciousness (i.e., a state other than alertness).
• Delirium is reported to occur in a wide range of mechanically ventilated ICU patients and can be detected by the Confusion
Assessment Method (CAM)-ICU or the Intensive Care Delirium Screening Checklist.
o These tools are used to ask patients to answer simple questions and perform simple tasks and can be used readily
at the bedside.
• The differential diagnosis of delirium in ICU patients is broad and includes infectious etiologies (including sepsis), medications
(particularly sedatives and analgesics), drug withdrawal, metabolic/ electrolyte derangements, intracranial pathology (e.g.,
stroke, intracranial hemorrhage), seizures, hypoxia, hypertensive crisis, shock, and vitamin deficiencies (particularly
thiamine).
• The etiology of a patient’s ICU delirium impacts the prognosis.
o Those with persistent ICU delirium not related to sedatives have increases in length of hospital stay, time on
mechanical ventilation, cognitive impairment at hospital discharge, and 6-month mortality rate.
o Interventions to reduce ICU delirium are limited.
o The sedative dexmedetomidine has been less strongly associated with ICU delirium than midazolam.
o In addition, very early physical and occupational therapy in mechanically ventilated patients has been demonstrated
to reduce delirium.
ANOXIC CEREBRAL INJURY

• This condition is common after cardiac arrest and often results in severe and permanent brain injury in survivors.
• Active cooling of patients after cardiac arrest is controversial, with some studies
• showing improved neurologic outcomes and others showing no such improvement.
• Patients suffering cardiac arrest should have a temperature targeted to no higher than 36°C.
STROKE
• Stroke is a common cause of neurologic critical illness.
• Hypertension must be managed carefully, since abrupt reductions in blood pressure may be associated with further brain
ischemia and injury.
• Acute ischemic stroke treated with tissue plasminogen activator (tPA) has an improved neurologic outcome when
treatment is given within 4.5 h of onset of symptoms.
• No benefit is seen when tPA therapy is given beyond 4.5 h after symptom onset.
• Heparin has not been convincingly shown to improve outcomes in patients with acute ischemic stroke.
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• Decompressive craniectomy is a surgical procedure that relieves increased intracranial pressure in the setting of space-
occupying brain lesions or brain swelling from stroke
o Available evidence suggests that this procedure may improve survival among select patients (≤55 years or age),
albeit at a cost of increased disability for some.
SUBARACHNOID HEMORRHAGE
• Subarachnoid hemorrhage may occur secondary to aneurysm rupture and is often complicated by cerebral vasospasm, re-
bleeding, and hydrocephalus.
• Vasospasm can be detected by either transcranial Doppler assessment or cerebral angiography
o It is typically treated with the calcium channel blocker nimodipine, aggressive IV fluid administration, and therapy
aimed at increasing blood pressure, typically with vasoactive drugs such as phenylephrine.
o The IV fluids and vasoactive drugs (hypertensive hypervolemic therapy) are used to overcome the cerebral
vasospasm.
o Early surgical clipping or endovascular coiling of aneurysms is advocated to prevent complications related to re-
bleeding.
• Hydrocephalus, typically heralded by a decreased level of consciousness, may require ventriculostomy drainage.
STATUS EPILEPTICUS
• Recurrent or relentless seizure activity is a medical emergency.
• Cessation of seizure activity is required to prevent irreversible neurologic injury.
• Lorazepam is the most effective benzodiazepine for treating status epilepticus and is the treatment of choice for controlling
seizures acutely.
• Phenytoin or fosphenytoin should be given concomitantly since lorazepam has a short half-life.
• Other drugs, such as gabapentin, carbamazepine, and phenobarbital, should be reserved for patients with contraindications
to phenytoin (e.g., allergy or pregnancy) or ongoing seizures despite phenytoin.
BRAIN DEATH
• Deaths of critically ill patients usually are attributable to irreversible cessation of circulatory and respiratory function.
• A diagnosis of death also may be established by irreversible cessation of all functions of the entire brain, including the
brainstem, even if circulatory and respiratory functions remain intact on artificial life support.
• Such a diagnosis requires demonstration of the absence of cerebral function (no response to any external stimulus) and
brainstem functions (e.g., unreactive pupils, lack of ocular movement in response to head turning or ice-water irrigation of
ear canals, positive apnea test [no drive to breathe]).
• Absence of brain function must have an established cause and be permanent without possibility of recovery; a sedative
effect, hypothermia, hypoxemia, neuromuscular paralysis, and severe hypotension must be ruled out.
• If there is uncertainty about the cause of coma, studies of cerebral blood flow and electroencephalography should be
performed.
WITHHOLDING OR WITHDRAWING CARE

• Withholding or withdrawal of care occurs commonly in the ICU setting.
• The Task Force on Ethics of the Society of Critical Care Medicine reported that it is ethically sound to withhold or withdraw
care if a patient or the patient’s surrogate makes such a request or if the physician judges that the goals of therapy are not
achievable.
• Since all medical treatments are justified by their expected benefits, the loss of such an expectation justifies the act of
withdrawing or withholding such treatment; these two actions are judged to be fundamentally similar.
• An underlying stipulation derived from this report is that an informed patient should have his or her wishes respected with
regard to life-sustaining therapy.
o Implicit in this stipulation is the need to ensure that patients are thoroughly and accurately informed regarding the
plausibility and expected results of various therapies.
• The act of informing patients and/or surrogate decision-makers is the responsibility of the physician and other health care
providers.
• If a patient or surrogate desires therapy deemed futile by the treating physician, the physician is not obligated ethically to
provide such treatment.
• Arrangements may be made to transfer the patient’s care to another care provider.
• Whether the decision to withdraw life support should be initiated by the physician or left to surrogate decisionmakers alone
is not clear.
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• Critical care providers should meet regularly with patients and/or surrogates to discuss prognosis when the withholding or
withdrawal of care is being considered.
• After a consensus among caregivers has been reached, this information should be relayed to the patient and/or surrogate
decision-maker.
• If a decision to withhold or withdraw life-sustaining care for a patient has been made, aggressive attention to analgesia and
anxiolysis is needed.
294. ACUTE RESPIRATORY DISTRESS SYNDROME

• it is a clinical syndrome of severe dyspnea of rapid onset,
hypoxemia, and diffuse pulmonary infiltrates leading to
respiratory failure.
• is caused by diffuse lung injury from many underlying
medical and surgical disorders.
• It can be direct or indirect lung injury.
Categories of ARDS based on the degrees of hypoxemia
Epidemiology
• The annual incidence of ARDS is estimated to be as high as 60 cases/100,000 population.
• Approximately 10% of all intensive care unit (ICU) admissions involve patients with ARDS.
Etiology
• Most cases (>80%) are caused by a relatively small number of clinical disorders: pneumonia and sepsis (~40–60%), followed
in incidence by aspiration of gastric contents, trauma, multiple transfusions, and drug overdose.
• Among patients with trauma, the most frequently reported surgical conditions in ARDS are pulmonary contusion, multiple
bone fractures, and chest wall trauma/flail chest, whereas head trauma, near-drowning, toxic inhalation, and burns are rare
causes.
• The risks of developing ARDS are increased in patients with more than one predisposing medical or surgical condition.
• Other risk factors: These include older age, chronic alcohol abuse, metabolic acidosis, pancreatitis, and severity of critical
illness.
Clinical Course
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Pathophysiology
Exudative Phase • alveolar capillary endothelial cells and type I pneumocytes (alveolar epithelial cells) are injured, with
consequent loss of the normally tight alveolar barrier to fluid and macromolecules.
• Pro-inflammatory cytokines and lipid mediators are increased in this acute phase, leading to the
recruitment of leukocytes (especiallyneutrophils) into the pulmonary interstitium and alveoli.
• Condensed plasma proteins aggregate in the air spaces with cellular debris and dysfunctional
pulmonary surfactant to form hyaline membrane whorls.
• Pulmonary vascular injury due to vascular obliteration by microthrombi and fibrocellular
proliferation.
• Alveolar edema predominantly involves dependent portions of the lung with diminished aeration.
• Encompasses the first 7 days of illness after exposure to a precipitating ARDS risk factor.
• Laboratory values are generally nonspecific and are primarily indicative of underlying clinical
disorders.
• The chestradiograph usually reveals opacities consistent with pulmonary edema and often involves
at least three-quarters of the lung fields. the chest x-ray in ARDS. But it may not demonstrate
cardiomegaly, pleural effusions, or pulmonaryvascular redistribution as is often present in pure
cardiogenic pulmonary edema.
Proliferative Phase • This phase usually lasts from day 7 to day 21.
• Histologic findings: the first signs of resolution are often evident in this phase, with the initiation of
lung repair, the organization of alveolar exudates, and a shift from neutrophil- to lymphocyte-
predominant pulmonary infiltrates.
• As part of the reparative process, type II pneumocytes proliferate along alveolar basement
membranes. These specialized epithelial cells synthesize new pulmonary surfactant and differentiate
into type I pneumocytes.
Fibrotic Phase • While many patients with ARDS recover lung function 3–4 weeks after the initial pulmonary injury,
some enter a fibrotic phase that may require long-term support on mechanical ventilators and/or
supplemental oxygen.
• Histologic findings: the alveolar edemaand inflammatory exudates of earlier phases convert to
extensive alveolar-duct and interstitial fibrosis. Marked disruption of acinar architecture leads to
emphysema-like changes, with large bullae.
• Intimal fibroproliferation in the pulmonary microcirculation causes
• progressive vascular occlusion and pulmonary hypertension.
• Patients in this late phase experience a substantial burden of excess morbidity.
Treatment
General principles:
1. Recognition and treatment of underlying medical and surgical disorders (e.g., pneumonia, sepsis, aspiration, trauma)
2. Minimization of unnecessary procedures and their complications;
3. Standardized “bundled care” approaches for ICU patients, including prophylaxis against venous thromboembolism,
gastrointestinal bleeding, aspiration, excessive sedation, prolonged mechanical ventilation, and central venous catheter
infections
4. Prompt recognition of nosocomial infections
5. Provision of adequate nutrition via the enteral route when feasible.
Minimizing ventilator-induced lung injury

• Volutrauma from repeated alveolar overdistention from excess tidal volume
• Atelectrauma from recurrent alveolar collapse.
• ARDS is a heterogeneous disorder, principally involving dependent portions of the lung with relative sparing of other regions.
Because compliance differs in affected versus more “normal” areas of the lung, attempts to fully inflate the consolidated
lung may lead to overdistention of and injury to the more normal areas.
• The mortality rate was significantly lower in the low VT patients (31%) than in the conventional VT patients (40%).
Minimizing Aledtrauma by Prevention of Alveolar Collapse

• In ARDS, the presence of alveolar and interstitial fluid and the loss of surfactant can lead to a marked reduction of lung
compliance.
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• Without an increase in end-expiratory pressure, significant alveolar collapse can occur at end-expiration, with consequent
impairment of oxygenation.
• Positive end-expiratory pressure (PEEP) is adjusted to minimize Fio2 (inspired O2 percentage) and provide adequate Pao2
(arterial partial pressure of O2) without causing alveolar overdistention.
Prone Positioning
• A recent trial demonstrated a significant reduction in 28-day mortality with prone positioning (32.8 to 16%) for patients with
severe ARDS (Pao2/Fio2 <150 mm Hg).
• Understanding that this maneuver requires a critical-care team that is experienced in “proning,” as repositioning critically ill
patients can be hazardous, leading to accidental endotracheal extubation, loss of central venous catheters, and orthopedic
injury.
Recruitment maneuvers
• transiently increase PEEP to high levels to “recruit” atelectatic lung can increase oxygenation, but a mortality benefit has not
been established.
Alternate modes of mechanical ventilation,

• such as airway pressure release ventilation and high frequency oscillatory ventilation, have not been proven beneficial over
standard modes of ventilation in ARDS management and in many cases require specialized expertise at the bedside.
Lung-replacement therapy with extracorporeal membrane oxygenation (ECMO)

• Shown to improve mortality for patients with ARDS in the United Kingdom who were referred to an ECMO center (though
only 75% of referred patients received ECMO) and thus may have utility in select adult patients with severe ARDS as a rescue
therapy.
Fluid Management
• Increased pulmonary vascular permeability leading to interstitial and alveolar edema fluid rich in protein is a central feature
of ARDS.
• Impaired vascular integrity augments the normal increase in extravascular lung water that occurs with increasing left atrial
pressure. Maintaining a low left atrial filling pressure minimizes pulmonary edema and prevents further decrements in
arterial oxygenation and lung compliance; improves pulmonary mechanics; shortens ICU stay and the duration of mechanical
ventilation.
• Aggressive attempts to reduce left atrial filling pressures with fluid restriction and diuretics should be an important aspect
of ARDS management, limited only by hypotension and hypoperfusion of critical organs such as the kidneys.
Neuromuscular Blockade
• In severe ARDS, sedation alone can be inadequate for the patient ventilator synchrony required for lung-protective
ventilation.
• In a multicenter, randomized, placebo-controlled trial of early neuromuscular blockade (with cisatracurium besylate) for 48
h, patients with severe ARDS had increased survival and ventilator-free days without increasing ICU-acquired paresis.
Prognosis
Mortality
• In the recent report from the Large Observational Study to Understand the Global Impact of Severe Acute Respiratory Failure
(LUNG SAFE) trial, hospital mortality estimates for ARDS range from 34.9% for mild ARDS, 40.3% for moderate ARDS, and
46.1% with severe ARDS.
• Of interest, mortality in ARDS is largely attributable to nonpulmonary causes, with sepsis and nonpulmonary organ failure
accounting for >80% of deaths.
• The major risk factors for ARDS mortality are nonpulmonary.
• Advanced age is an important risk factor. Patients aged >75 years have a substantially higher mortality risk (~60%) than those
<45 (~20%).
• Other risk factors include preexisting organ dysfunction from chronic medical illness—in particular, chronic liver disease,
cirrhosis, chronic alcohol abuse and chronic immunosuppression.
• Patients with ARDS arising from direct lung injury (including pneumonia, pulmonary contusion, and aspiration are nearly
twice as likely to die as those with indirect causes of lung injury, while surgical and trauma patients with ARDS—especially
those without direct lung injury—generally have a higher survival rate than other ARDS patients.
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Functional Recovery in ARDS Survivors

• While it is common for patients with ARDS to experience prolonged respiratory failure and remain dependent on mechanical
ventilation for survival, it is a testament to the resolving powers of the lung that the majority of patients who survive regain
nearly normal lung function.
• Patients usually recover maximal lung function within 6 months.
• One year after endotracheal extubation, more than one-third of ARDS survivors have normal spirometry values and diffusion
capacity.
• Recovery of lung function is strongly associated with the extent of lung injury in early ARDS.
• Low static respiratory compliance, high levels of required PEEP, longer durations of mechanical ventilation, and high lung
injury scores are all associated with less recovery of pulmonary function.
• When physical function is assessed 5 years after ARDS, exercise limitation and decreased physical quality of life are often
documented despite normal or nearly normal pulmonary function.
295. MECHANICAL VENTILATORY

MECHANICAL VENTILATORY SUPPORT
• Mechanical ventilation (MV) is used to assist or replace spontaneous breathing.
• It is implemented with special devices that can support ventilatory function and improve oxygenation through the application
of high-oxygen-content gas and positive pressure.
• The primary indication for initiation of MV is respiratory failure, of which there are two basic types:
o Hypoxemic- hypoxemic, which is present when arterial O2 saturation < 90 % occurs despite increase inspired oxygen
fraction and usually results from ventilation- perfusion mismatch
o Hypercarbic- characterized by elevated arterial carbon dioxide partial pressure (PCO2 ) values (usually >50 mmHg)
resulting from conditions that decrease minute ventilation or increase physiologic dead space such that alveolar
ventilation is inadequate to meet metabolic demands. When respiratory failure is chronic, neither of the two types
is obligatorily treated with MV, but when it is acute, MV may be lifesaving.
INDICATIONS
• Acute respiratory failure with hypoxemia- most common reasons for instituting MV
o acute respiratory distress syndrome, heart failure with pulmonary edema, pneumonia, sepsis, complications of
surgery and trauma), which accounts for ~65% of all ventilated cases, and hypercarbic ventilatory failure—e.g., due
to coma (15%), exacerbations of chronic obstructive pulmonary disease (COPD; 13%), and neuromuscular diseases
(5%).
• The primary objectives of MV are to decrease the work of breathing, thus avoiding respiratory muscle fatigue, and to reverse
life-threatening hypoxemia and progressive respiratory acidosis. In some cases, MV is used as an adjunct to other forms of
therapy.
• For example, it is used to reduce cerebral blood flow in patients with increased intracranial pressure. MV also is used
frequently in conjunction with endotracheal intubation for airway protection to prevent aspiration of gastric contents in
otherwise unstable patients during gastric lavage for suspected drug overdose or during gastrointestinal endoscopy. In
critically ill patients, intubation and MV may be indicated before the performance of essential diagnostic or therapeutic
studies if it appears that respiratory failure may occur during those maneuvers.
TYPES OF MECHANICAL VENTILATION

1. Noninvasive Ventilation
o NIV has gained acceptance because it is effective in certain conditions, such as acute or chronic respiratory failure,
and is associated with fewer complications—namely, pneumonia and tracheolaryngeal trauma.
o NIV usually is provided with a tight-fitting face mask, a nasal mask similar to that used for treatment of sleep apnea
and in some cases with the use of a helmet or a hood.
o NIV has proved highly effective in patients with respiratory failure arising from exacerbations of COPD.
o It is most frequently implemented as bilevel positive airway pressure ventilation or pressure-support ventilation
(PSV). Both modes, which apply a preset positive pressure during inspiration and a lower pressure during expiration,
are well tolerated by a conscious patient and optimize patient-ventilator synchrony.
o The major limitation to the widespread application of NIV has been patient intolerance: the interface required for
NIV can cause both physical and psychological discomfort. In addition, NIV has had limited success in patients with
acute hypoxemic respiratory failure, for whom endotracheal intubation and conventional MV remain the ventilatory
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method of choice. The most important group of patients who benefit from a trial of NIV are those with COPD
exacerbations and respiratory acidosis (pH 7.35)
o NIV is not better than conventional treatment that includes controlled oxygen delivery and pharmacotherapy for
exacerbations of COPD (systemic glucocorticoids, bronchodilators, and, if needed, antibiotics).
o NIV is not useful in the majority of cases of respiratory failure and is contraindicated in patients with the conditions
listed in Table 295-1.
o NIV can delay lifesaving ventilatory support in those cases and, in fact, can actually result in aspiration or
hypoventilation. Once NIV is initiated, patients should be monitored; a reduction in respiratory frequency and a
decrease in the use of accessory muscles (scalene, sternomastoid, and intercostals) are good clinical indicators of
therapeutic benefit.
o Arterial blood gases should be determined at least within hours of the initiation of therapy to ensure that NIV is
having the desired effect. Lack of benefit within that time frame should alert the physician to the possible need for
conventional MV.
2. Conventional MV
• Conventional MV is implemented once a cuffed tube is inserted into the trachea to allow conditioned gas (warmed,
oxygenated, and humidified) to be delivered to the airways and lungs at pressures above atmospheric pressure.
Care should be taken during intubation to avoid brain-damaging hypoxia.
• In most cases, the administration of mild sedation may facilitate the procedure. Opiates and benzodiazepines are
good choices but can have a deleterious effect on hemodynamics in patients with depressed cardiac function or low
systemic vascular resistance.
o Morphine can promote histamine release from tissue mast cells and may worsen bronchospasm in patients
with asthma; fentanyl, sufentanil, and alfentanil are acceptable alternatives.
o Ketamine may increase systemic arterial pressure and has been associated with hallucinatory responses.
o The shorter-acting agents—etomidate and propofol—have been used for both induction and maintenance
of anesthesia in ventilated patients because they have fewer adverse hemodynamic effects, but both are
significantly more expensive than older agents.
• Great care must be taken to avoid the use of neuromuscular paralysis during intubation of patients with renal failure, tumor
lysis syndrome, crush injuries, medical conditions associated with elevated serum potassium levels, and muscular dystrophy
syndromes; in particular, the use of agents whose mechanism of action includes depolarization at the neuromuscular
junction, such as succinylcholine chloride, must be avoided
PRINCIPLES OF MV
• Once the patient has been intubated, the basic goals of MV are to optimize oxygenation while avoiding ventilator-induced
lung injury due to overstretch and collapse/re-recruitment. This concept, known as the “protective ventilatory strategy” (see
below and Fig. 295-1) is supported by evidence linking high airway pressures and volumes and overstretching of the lung as
well as collapse/re-recruitment to poor clinical outcomes (barotrauma and volume trauma).
• Although normalization of pH through elimination of CO2 is desirable, the risk of lung damage associated with the large
volume and high pressures needed to achieve this goal has led to the acceptance of permissive hypercapnia. This condition
is well tolerated when care is taken to avoid excess acidosis by pH buffering
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MODES OF VENTILATION
• Mode refers to the manner in which ventilator breaths are triggered, cycled, and limited. The trigger, either an inspiratory
effort or a time-based signal, defines what the ventilator senses to initiate an assisted breath.
• Cycle refers to the factors that determine the end of inspiration. For example, in volume-cycled ventilation, inspiration ends
when a specific tidal volume is delivered. Other types of cycling include pressure cycling and time cycling.
• The limiting factors are operator-specified values, such as airway pressure, that are monitored by transducers internal to
the ventilator circuit throughout the respiratory cycle; if the specified values are exceeded, inspiratory flow is terminated,
and the ventilator circuit is vented to atmospheric pressure or the specified pressure at the end of expiration (positive end-
expiratory pressure, or PEEP).
• Most patients are ventilated with assist-control ventilation (ACMV), intermittent mandatory ventilation (IMV), or PSV, with
the latter two modes often used simultaneously
ü Assist-Control Ventilation
o most widely used mode of ventilation. In this mode, an inspiratory cycle is initiated either by the patient’s
inspiratory effort or, if none is detected within a specified time window, by a timer signal within the
ventilator.
o Every breath delivered, whether patient- or timer-triggered, consists of the operator-specified tidal volume.
o Ventilatory rate is determined either by the patient or by the operator-specified backup rate, whichever is
of higher frequency.
o ACMV is commonly used for initiation of MV because it ensures a backup minute ventilation in the absence
of an intact respiratory drive and allows for synchronization of the ventilator cycle with the patient’s
inspiratory effort.
o Problems can arise when ACMV is used in patients with tachypnea due to nonrespiratory or nonmetabolic
factors, such as anxiety, pain, and airway irritation.
o Respiratory alkalemia may develop and trigger myoclonus or seizures. Dynamic hyperinflation leading to
increased intrathoracic pressures (so-called auto-PEEP) may occur if the patient’s respiratory mechanics
are such that inadequate time is available for complete exhalation between inspiratory cycles.
o Auto-PEEP can limit venous return, decrease cardiac output, and increase airway pressures, predisposing
to barotrauma.
ü Intermittent Mandatory Ventilation
o With this mode, the operator sets the number of mandatory breaths of fixed volume to be delivered by
the ventilator; between those breaths, the patient can breathe spontaneously. In the most frequently used
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synchronized mode (SIMV), mandatory breaths are delivered in synchrony with the patient’s inspiratory
efforts at a frequency determined by the operator.
o If the patient fails to initiate a breath, the ventilator delivers a fixedtidal-volume breath and resets the
internal timer for the next inspiratory cycle.
o SIMV differs from ACMV in that only a preset number of breaths are ventilator-assisted. SIMV allows
patients with an intact respiratory drive to exercise inspiratory muscles between assisted breaths; thus it
is useful for both supporting and weaning intubated patients.
o SIMV may be difficult to use in patients with tachypnea because they may attempt to exhale during the
ventilator-programmed inspiratory cycle.
o Consequently, the airway pressure may exceed the inspiratory pressure limit, the ventilator-assisted
breath will be aborted, and minute volume may drop below that programmed by the operator.
o In this setting, if the tachypnea represents a response to respiratory or metabolic acidosis, a change in
ACMV will increase minute ventilation and help normalize the pH while the underlying process is further
evaluated and treated.
ü Pressure-Support Ventilation
o This form of ventilation is patient-triggered, flow-cycled, and pressure-limited. It provides graded
assistance and differs from the other two modes in that the operator sets the pressure level (rather than
the volume) to augment every spontaneous respiratory effort.
o The level of pressure is adjusted by observing the patient’s respiratory frequency.
o During PSV, the inspiration is terminated when inspiratory airflow falls below a certain level; in most
ventilators, this flow rate cannot be adjusted by the operator. With PSV, patients receive ventilator
assistance only when the ventilator detects an inspiratory effort.
o PSV is often used in combination with SIMV to ensure volume-cycled backup for patients whose respiratory
drive is depressed. PSV is well tolerated by most patients who are being weaned from MV; PSV parameters
can be set to provide full ventilatory support and can be withdrawn to load the respiratory muscles
gradually.
Other Modes of Ventilation

• There are other modes of ventilation, each with its own acronym and each with specific modifications of the manner and
duration in which pressure is applied to the airway and lungs and of the interaction between the mechanical assistance
provided by the ventilator and the patient’s respiratory effort.
• Although their use in acute respiratory failure is limited, the following modes have been used with varying levels of
enthusiasm and adoption.
ü PRESSURE-CONTROL VENTILATION (PCV)
o this form of ventilation is time-triggered, time-cycled, and pressure-limited. A specified pressure is imposed
at the airway opening throughout inspiration. Since the inspiratory pressure is specified by the operator,
tidal volume and inspiratory flow rate are dependent, rather than independent, variables and are not
operator-specified.
o PCV is the preferred mode of ventilation for patients in whom it is desirable to regulate peak airway
pressures, such as those with preexisting barotrauma, and for post– thoracic surgery patients, in whom the
shear forces across a fresh suture line should be limited.
ü INVERSE-RATIO VENTILATION (IRV)

o This mode is a variant of PCV that incorporates the use of a prolonged inspiratory time with the appropriate
shortening of the expiratory time. IRV has been used in patients with severe hypoxemic respiratory failure.
o This approach increases mean distending pressures without increasing peak airway pressures. It is thought
to work in conjunction with PEEP to open collapsed alveoli and improve oxygenation. However, no clinical-
trial data have shown that IRV improves outcomes.
ü CONTINUOUS POSITIVE AIRWAY PRESSURE (CPAP)
o CPAP is not a true support mode of ventilation because all ventilation occurs through the patient’s
spontaneous efforts. The ventilator provides fresh gas to the breathing circuit with each inspiration and sets
the circuit to a constant, operator-specified pressure.
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CPAP is used to assess extubation potential in patients who have been effectively weaned and who require
o
little ventilatory support and in patients with intact respiratory system function who require an
endotracheal tube for airway protection.
ü Nonconventional Ventilatory Strategies
o Several nonconventional strategies have been evaluated for their ability to improve gas exchange and
survival rates in severe hypoxemic respiratory failure.
o These strategies include high-frequency oscillatory ventilation (HFOV), airway pressure release ventilation
(APRV), partial liquid ventilation (PLV) using perfluorocarbons and the administration of nitric oxide gas
delivered through the airways.
o Although case reports and small uncontrolled cohort studies have shown benefit, randomized controlled
trials have failed to demonstrate consistent improvements in outcome with these strategies.
o Some “salvage” techniques have gained acceptance given recent positive clinical outcomes.
o A randomized trial of extracorporeal membrane oxygenation (ECMO) documented positive outcomes,
although older studies had failed to document positive results. However, with the popularity of venous-
venous access, and encouraging reports in small series and uncontrolled trials, the use of ECMO has
increased world-wide. Guidelines for ECMO centers have been published, and if considered in patients with
severe respiratory failure refractory to conventional therapy, the patient should be referred to a center
familiar with the procedure. The second of these techniques, prone positioning, should be available in all
units caring for these patients.
o The design of new ventilator modes reflects attempts to improve patient-ventilator synchrony—a major
practical issue during MV—by allowing patients to trigger the ventilator with their own effort while also
incorporating flow algorithms that terminate the cycles once certain preset criteria are reached; this
approach has greatly improved patient comfort.
PROTECTIVE VENTILATORY STRATEGY

• Whichever mode of MV is used in acute respiratory failure, the evidence from several important controlled trials indicates
that a protective ventilation approach guided by the following principles is safe and offers the best chance of a good outcome:
o (1) Set a target tidal volume close to 6 mL/kg of ideal body weight.
o (2) Prevent plateau pressure (static pressure in the airway at the end of inspiration) exceeding 30 cm H2 O.
o (3) Use the lowest possible fraction of inspired oxygen (Fio2 ) to keep the Sao2 at ≥90%.
o (4) Adjust the PEEP to maintain alveolar patency while preventing overdistention and closure/reopening.
• With the application of these techniques, the mortality rate among patients with acute hypoxemic respiratory failure has
decreased to ~30% from close to 50% a decade ago.
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PATIENT MANAGEMENT
• Once the patient’s gas exchange has been stabilized, definitive therapy for the underlying process responsible for respiratory
failure is continued.
• Subsequent modifications in ventilator therapy must be provided in parallel with changes in the patient’s clinical status.
• As improvement in respiratory function is noted, the first priority is to reduce the level of mechanical ventilatory support.
• Patients on full ventilatory support should be monitored frequently, with the goal of switching to a mode that allows for
weaning as soon as possible.
• Protocols and guidelines that can be applied by paramedical personnel when physicians are not readily available have proved
to be of value in shortening ventilator and intensive care unit (ICU) time, with very good outcomes.
• Patients whose condition continues to deteriorate after ventilatory support is initiated may require increased O2 , PEEP, or
one of the alternative modes of ventilation
GENERAL SUPPORT DURING VENTILATION

• Patients for whom MV has been initiated usually require sedation and analgesia to maintain an acceptable level of comfort.
Often, this treatment consists of a combination of a benzodiazepine and an opiate administered intravenously.
• Medications commonly used for this purpose include lorazepam, midazolam, diazepam, morphine, and fentanyl.
o Oversedation must be avoided in the ICU because most studies show that daily interruption of sedation in patients
with improved ventilatory status results in a shorter time on the ventilator and a shorter ICU stay.
• Immobilized patients receiving mechanical ventilatory support are at risk for deep venous thrombosis and decubitus ulcers.
o Venous thrombosis should be prevented with the use of subcutaneous heparin and/ or pneumatic compression
boots.
o Fractionated low-molecular-weight heparin appears to be equally effective for this purpose.
o To help prevent decubitus ulcers, frequent changes in body position and the use of soft mattress overlays and air
mattresses are employed.
o Early mobilization is recommended for patients on MV, since this approach is associated with better outcomes.
• Prophylaxis against diffuse gastrointestinal mucosal injury is indicated for patients undergoing MV. Histamine-receptor (H2
-receptor) antagonists, antacids, and cytoprotective agents such as sucralfate have all been used and appear to be effective.
• Nutritional support by enteral feeding through either a nasogastric or an orogastric tube should be initiated and maintained
whenever possible.
o Delayed gastric emptying is common in critically ill patients taking sedative medications but often responds to
promotility agents such as metoclopramide.
o Parenteral nutrition is an alternative to enteral nutrition in patients with severe gastrointestinal pathology who
need prolonged MV.
COMPLICATIONS OF MECHANICAL VENTILATION

• Endotracheal intubation and MV have direct and indirect effects on the lung and upper airways, the cardiovascular and the
gastrointestinal system.
• Pulmonary complications include barotrauma, nosocomial pneumonia, oxygen toxicity, tracheal stenosis, and
deconditioning of respiratory muscles.
• Barotrauma and volutrauma overdistend and disrupt lung tissue; may be clinically manifest by pneumomediastinum,
interstitial and subcutaneous emphysema, or pneumothorax; and can result in the liberation of cytokines from
overdistended tissues, further promoting tissue injury.
• Clinically significant pneumothorax requires tube thoracostomy.
• Intubated patients are at high risk for ventilator-associated pneumonia as a result of aspiration from the upper airways
through small leaks around the endotracheal tube cuff;
o the most common organisms responsible for this condition are Pseudomonas aeruginosa, enteric gram-negative
rods, and Staphylococcus aureus.
o Given the high associated mortality rates, when suspected, early initiation of empirical antibiotics directed against
likely pathogens is recommended.
• Hypotension resulting from elevated intrathoracic pressures with decreased venous return is almost always responsive to
intravascular volume repletion.
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• In patients who are judged to have respiratory failure on the basis of alveolar edema but in whom the cardiac or pulmonary
origin of the edema is unclear, hemodynamic monitoring with a pulmonary arterial catheter may be of value in helping to
clarify the cause of the edema.
• Gastrointestinal effects of positive-pressure ventilation include stress ulceration and mild to moderate cholestasis
WEANING FROM MECHANICAL VENTILATION

Decision to Wean
• It is important to consider discontinuation of MV once the underlying respiratory disease begins to reverse.
• Although the predictive capacities of multiple clinical and physiologic variables have been explored, the consensus from a
ventilatory weaning task force cites the following conditions as indicating amenability to weaning:
o Lung injury is stable or resolving;
o gas exchange is adequate, with low PEEP (<8cmH2O) and FIo2 (<0.5)
o hemodynamic variables are stable, the patient is no longer using vasopressors
o the patient is capable of initiating spontaneous breaths. A “wean screen” based on these variables should be done
at least daily.
• If the patient is deemed capable of beginning to wean, the recommendation is to perform a spontaneous breathing trial
(SBT), whose value is supported by several randomized trials (Fig. 295-2).
o The SBT involves an integrated patient assessment during spontaneous breathing with little or no ventilatory
support.
o The SBT is usually implemented with a T-piece using 1–5 cmH2 O CPAP with 5–7 cmH2 O or PSV from the ventilator
to offset resistance from the endotracheal tube. Once it is determined that the patient can breathe spontaneously,
a decision must be made about the removal of the artificial airway, which should be undertaken only when it is
concluded that the patient has the ability to protect the airway, is able to cough and clear secretions, and is alert
enough to follow commands. In addition, other factors must be taken into account, such as the possible difficulty
of replacing the tube if that maneuver is required.
• If upper airway difficulty is suspected, an evaluation using a “cuff-leak” test (assessing the presence of air movement around
a deflated endotracheal tube cuff) is supported by current evidence.
• If the “cuff-leak test” suggests a risk of post-extubation stridor, the administration of systemic corticosteroids should be
considered prior to extubation.
• Despite all precautions, ~10–15% of extubated patients require reintubation.
• Several studies suggest that NIV can be used to obviate reintubation, particularly in patients with ventilator failure secondary
to COPD exacerbation or congestive heart failure; in this setting, earlier extubation with the use of prophylactic NIV has
yielded good results.
Prolonged MV and Tracheostomy

• From 5 to 13% of patients undergoing MV will go on to require prolonged MV (>21 days). In these instances, critical care
personnel must decide whether and when to perform a tracheostomy.
• This decision is individualized and is based on the risk and benefits of tracheostomy and prolonged intubation as well as the
patient’s preferences and expected outcomes.
• A tracheostomy is thought to be more comfortable, to require less sedation, and to provide a more secure airway and may
also reduce weaning time. However, tracheostomy carries the risk of complications, which occur in 5–40% of these
procedures and include bleeding, cardiopulmonary arrest, hypoxia, structural damage, pneumothorax, pneumomediastinum,
and wound infection.
• In patients with long-term tracheostomy, complex complications include tracheal stenosis, granulation, and erosion of the
innominate artery.
• In general, if a patient needs MV for >10–14 days, a tracheostomy, planned under optimal conditions, is indicated. Whether
it is completed at the bedside or as an operative procedure depends on local resources and experience.
• Some 5–10% of patients are deemed unable to wean in the ICU. These patients may benefit from transfer to special units
where a multidisciplinary approach, including nutrition optimization, physical therapy with rehabilitation, and slower
weaning methods (including SIMV with PSV), results in successful weaning rates of up to 30%.
• Unfortunately, close to 2% of ventilated patients may ultimately become dependent on ventilatory support to maintain life.
Most of these patients remain in chronic care institutions, although some with strong social, economic, and family support
may live a relatively fulfilling life with at-home ventilation.
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SECTION 2 SHOCK and CARDIAC ARREST

296. APPROACH TO THE PATIENT WITH SHOCK
Objectives:
• Discuss the initial assessment utilizing the history, physical examination, and initial diagnostic testing to confirm the presence of
shock and determine the type of shock causing the organ dysfunction.
• Discuss key principles of initial therapy with the aim of reducing the high morbidity and mortality associated with shock.
Shock
• The clinical condition of organ dysfunction resulting from an imbalance between cellular oxygen supply and demand.
• Life-threatening condition common in the intensive care unit (ICU).
• Results from multitude of heterogeneous disease processes that can lead to shock.
• Reversible Shock (Organ dysfunction seen in early shock is reversible with restoration of adequate oxygen supply) à Irrreversible
phase à Death from multisystem organ dysfunction (MSOF).
• The clinician must:
o Identify the patient with shock promptly
o Make a preliminary assessment of the type of shock present
o Initiate therapy to prevent irreversible organ dysfunction and death
PATHOPHYSIOLOGY OF SHOCK
• The cellular oxygen imbalance of shock is most commonly related to impaired oxygen delivery in the setting of circulatory failure.
• Shock can also develop during states of:
o increased oxygen consumption: Cyanide poisoning à uncoupling of oxidative phosphorylation
o or impaired oxygen utilization.
• In the setting of insufficient oxygen supply, the cell is no longer able to support aerobic metabolism.
o With adequate oxygen, the cell metabolizes glucose to pyruvate à enters the mitochondria à ATP is generated via
oxidative phosphorylation.
o Without sufficient oxygen supply, the cell is forced into anaerobic metabolism à pyruvate is metabolized to lactate with
much less ATP generation (per mole of glucose).
o Maintenance of the homeostatic environment of the cell is dependent on an adequate supply of ATP.
§ ATP-dependent ion pumping systems (Na+/K+ ATPase) consume 20–80% of the cell’s energy.
o Inadequate oxygen delivery and subsequent decreased ATP disrupt the cell’s ability to maintain osmotic, ionic, and
intracellular pH homeostasis. Influx of calcium can lead to activation of calcium-dependent phospholipases and proteases,
causing cellular swelling and death. In addition to direct cell death, cellular hypoxia can cause damage at the organ system
level via leakage of the intracellular contents into the extracellular space activating inflammatory cascades and altering the
microvascular circulation.
DETERMINANTS OF OXYGEN DELIVERY

• Disease processes affecting any of the components of oxygen delivery have the potential to lead to the development of shock.
• The two major components of DO2 are cardiac output (CO) and arterial oxygen content (CaO2):
DO =CO×CaO 22
• The two components of CO are heart rate (HR) and stroke volume (SV)
DO2 =(HR×SV)×CaO2
• The major determinants of SV are preload, afterload (systemic vascular resistance, SVR), and cardiac contractility.
SV α (Preload × contractility)/SVR
o Preload refers to the myocardial fiber length before contraction (the ventricular end-diastolic volume).
o Contractility refers to the ability of the ventricle to contract independent of preload and afterload.
o The SVR represents the afterload, or the force against which the ventricle must contract.
• The CaO2 is composed of oxygen carried by convection with hemoglobin and oxygen dissolved in blood, given as
CaO2 = (Hb × 1.39 × SaO2) + (PaO2 × 0.03)
• A disease process that affects these variables (HR, preload, contractility, SVR, SaO2, or Hb) has the potential to reduce oxygen
delivery and cause cellular hypoxia.
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CLASSIFICATION OF SHOCK
• The four major shock types are distributive, cardiogenic, hypovolemic, and obstructive.
• Use the history, physical examination, and laboratory testing to

determine the type of shock present and promptly begin appropriate initial
therapy to restore oxygen delivery.
Distributive Shock
• The condition of reduced oxygen delivery where the primary physiologic disturbance is a reduction in SVR.
• It is unique among the types of shock in that there is a compensatory increase in CO.
• The central venous pressure (CVP) and pulmonary capillary wedge pressure (PCWP) are usually reduced.
• Sepsis
o Most common type of distributive shock
o Redefined as the dysregulated host response to infection resulting in life-threatening organ dysfunction.
• Septic Shock
o Sepsis accompanied by persistent hypotension requiring vasopressor support.
• Other processes that are manifest as cellular hypoxia related to a primary reduction of SVR include:
o Pancreatitis
o Severe burns
o Liver failure.
• Anaphylaxis
o Predominantly an IgE-mediated allergic reaction that can rapidly develop after exposure to an allergen (food, medication,
or insect bite)
o Profound distributive type of shock possibly mediated through histamine release.
o There is evidence of both venous and arterial vasodilation.
o Extravasation of up to 35% of the circulating blood volume within 10 min.
• Patients with severe brain or spinal cord injury may have a reduction of SVR related to disruption of the autonomic pathways
that regulate vascular tone.
o There is pooling of blood in the venous system with a resulting decreased venous return and decreased CO.
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• Adrenal insufficiency may be related to chronic steroid use, metastatic malignancy, adrenal hemorrhage, infection (tuberculosis,
HIV), autoimmune adrenalitis, or amyloidosis.
o In conditions of stress (such as infection or surgery), the deficit may become apparent with an inability to increase cortisol
leading to vasodilation as well as aldosterone deficiency-mediated hypovolemia.
Cardiogenic Shock
• Characterized by reduced oxygen delivery related to a reduction in CO owing to a primary cardiac problem.
• There is usually a compensatory increase in SVR.
• When the cardiac process (e.g., myocardial infarction):
o Affects the left ventricle (LV), there will be elevation of the PCWP
o Affects the right ventricle (RV), the CVP will be elevated.
• The CO (and accordingly the DO2) can be reduced by alterations in the SV or HR.
• SV may be reduced by:
o Processes that affect myocardial contractility (myocardial infarction, ischemic cardiomyopathies, and primary myocarditis)
o Mechanical valvular disease (acute mitral insufficiency or aortic insufficiency).
• Both bradyarrhythmias and tachyarrhythmias (from either an atrial or ventricular source) may have associated hemodynamic
consequence with a reduction in CO.
Hypovolemic Shock
• Encompasses disease processes that reduce CO (and oxygen delivery) via a reduction in preload.
• Characterized by an elevated SVR and low CVP and PCWP related to decreased intravascular volume.
• Caused be any process causing a reduction in intravascular volume
• Most commonly is related to hemorrhage,
o External (secondary to trauma)
o Internal (most commonly upper or lower gastrointestinal [GI]) bleeding.
• Non-hemorrhagic processes
o GI illnesses causing profound emesis or diarrhea
o Renal losses (osmotic diuresis associated with diabetic ketoacidosis or diabetes insipidus)
o Skin loss (severe burns, inflammatory conditions such as Stevens-Johnson).
Obstructive Shock
• Also characterized by a reduction in oxygen delivery related to reduced CO
• Etiology of the reduced CO is an extracardiac processes impairing blood flow.
• Processes that can impede venous return to the heart and reduce CO include:
o Tension pneumothorax (PTX)
o Cardiac tamponade
o Restrictive pericarditis
• Similarly processes that obstruct cardiac outflow:
o pulmonary embolism (right heart)
o aortic dissection (left heart)
Mixed Shock
• Patient presenting with more than one type of shock.
• The initial physiologic disturbance leading to reduced perfusion and cellular hypoxia in sepsis is distributive shock. In this setting,
a sepsis-induced cardiomyopathy can develop, which reduces myocardial contractility, thus producing a cardiogenic component
to what now would be described as a mixed type of shock.
Undifferentiated Shock
• Shock type and specific disease process are not apparent.
• Classify a patient with one of the types of shock outlined above so that proper therapy can be initiated to restore tissue perfusion
and oxygen delivery.
• Seen most commonly is dependent upon the clinical area of practice.
• Medical ICU: Distributive shock related to sepsis.
• Cardiac ICU: Cardiogenic or obstructive types of shock.
• Emergency department: Mix of patients with trauma patients presenting with hypovolemic shock and septic patients having a
distributive pathophysiology.
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STAGES OF SHOCK
1. Compensated shock (preshock)
o The body utilizes a variety of physiologic responses to counteract the initial insult and attempts to reestablish the
adequate perfusion and oxygen delivery.
o no overt signs of organ dysfunction
o Laboratory evaluation may demonstrate mild organ dysfunction (i.e., elevated creatinine or troponin) or a mild elevation
of lactate.
o Compensatory responses
§ Reduction in SVR = compensatory rise in HR (and CO)
§ Early hemorrhagic volume loss = compensatory increase in SVR
2. Shock (decompensated shock)
o Host compensatory responses are overwhelmed à patient transitions into true shock with evidence organ dysfunction
o Appropriate interventions to restore perfusion and oxygen delivery during these initial two phases of shock can reverse
the organ dysfunction
3. Irreversible shock.
o Organ dysfunction is permanent and often the patient progresses to MSOF.
EVALUATION OF THE PATIENT WITH SHOCK

• The first aim is confirmation of the presence of shock.
o High clinical suspicion for this condition.
o The possibility of shock should be considered all patients presenting with new organ dysfunction.
• Key Principles in the Treatment of Shock
o Recognize shock early
o Assess for type of shock present
o Initiate therapy simultaneous with the evaluation into the etiology of shock
o Restoration of oxygen delivery is the aim of the therapy
o Identify etiologies of shock which require additional life-saving interventions.
• A second aim of the initial assessment (history, physical examination, and diagnostic testing) is to identify either a specific shock
etiology or to determine the type of shock present.
History
• Concise, focused history
• If the patient is unable to provide a history, ancillary information from anyone accompanying the patient should be obtained,
and a brief chart review should be performed.
• Be attentive to any details indicating new organ dysfunction.
o The most easily identified new organ dysfunction from the history is the presence of a newly altered mental status or
decrease in renal function (oliguria).
o In some cases, the type of shock (and the specific disease process) is apparent from the history.
Distributive shock from sepsis Fever and a history revealing of a focal site of infection
Patient with a preexisting immune dysfunction or medication-induced neutropenia
may present with hypoperfusion and new organ dysfunction
Anaphylactic distributive shock Onset of hives, dyspnea, and new facial edema after exposure to common allergens
Cardiogenic shock Onset of exertional chest discomfort

Palpitations with syncope or presyncope (significant arrhythmia)
Patient with extensive cardiac disease
Hypovolemic shock History of trauma (blunt or penetrating) or GI bleed (hematemesis, melena, or bright
red blood per rectum
Obstructive type shock Patient with hypertension and tearing chest or back pain (aortic dissection)
Acute onset chest pain with dyspnea in the setting of immobility and or underlying
malignancy d/t pulmonary embolism
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Physical Examination
• Two questions to answer
o Is shock present (either in compensated stage prior to overt evidence of organ dysfunction or decompensated indicated by
the presence of new organ dysfunction)?
o What type of shock is present (distributive, cardiogenic, hypovolemic, or obstructive)?
• The physical examination findings present during the compensated phase of shock tend to be nonspecific.
o Elevation of the HR (with the body’s attempt to increase CO)
o Tachypnea (to compensate for the developing metabolic acidosis).
o While nonspecific, the clinician should recognize these findings early as they may herald the development of end-organ
dysfunction if perfusion and oxygen delivery are not restored.
• Shock is most commonly seen in the setting of circulatory failure
o Manifest as hypotension (a mean arterial pressure [MAP] of <60 mmHg)
o Patients may have underlying conditions that cause longstanding low blood pressure without any evidence of organ
dysfunction.
o Patients with underlying hypertension may develop organ dysfunction at higher blood pressures.
• The physical examination can confirm the presence of shock prior to the return of laboratory testing.
• The central nervous system (CNS), kidney, and skin are the organ systems most easily assessed for evidence of organ dysfunction.
o These organ systems are considered the “windows” through which we can identify organ dysfunction.
Decreased oxygen delivery to the brain Confusion and encephalopathy.

o Early stage of shock: body will redirect blood flow to the CNS to
maintain adequate perfusion.
o Patient with shock and altered mental status, all the usual
compensatory mechanisms have been outstripped.
o New encephalopathy: Decompensated shock.
Renal function Evaluate the patient’s urine output since the time of presentation
o Urinary catheter should be placed for accurate hourly assessment of
urine output.
o In patients with normal baseline renal function, oliguria (<0.5 mL/kg
per h) may indicate shock.
Skin Decreased capillary refill and cold and clammy skin are signs of
hypoperfusion and shock
• Many components of the examination provide insight into hemodynamics and assist in elucidating the type of shock present.
• Evaluation of jugular venous pressure (JVP) and peripheral edema can provide insight into right-sided cardiac pressures.
• Pulmonary auscultation can identify signs of left-sided cardiac dysfunction. The physical examination may be used to
differentiate shock with high CO (distributive) from that with low CO (cardiogenic shock, hypovolemic shock, and obstructive
shock).
High Cardiac Output (Distributive) Low Cardiac Output
Warm peripheral extremities Cool extremities
Brisk capillary refill (<2 s) Delayed poor capillary refill
Bounding pulses Weak pulses
Patients with chronic heart failure do not present with the classical findings of acute
heart failure.
Cardiogenic Shock Hypovolemic Shock

Increased intravascular filling pressure Intravascular volume depletion
JVP may be elevated (with right-sided

failure) Reduced (JVP <8 cm)
S3 gallop
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Type of Shock Physical Findings
Distributive (Septic) Site of an untreated infection (cellulitis, abscess, infected pressure injury, or focal)
Cardiogenic Brady- or tachyarrhythmia
Hypovolemic Large ecchymosis may indicate a significant bleed related to trauma or spontaneous
retroperitoneal bleeding
Rectal examination may reveal GI hemorrhage
Obstructive Cardiac Tamponade: Pulsus paradox and elevated JVP
PTX: Paucity of breath sounds over the affected side, deviation of the trachea away from
the affected side, or subcutaneous emphysema.
• The shock index (SI) is defined as the HR/systolic blood pressure (SBP) with a normal SI being 0.5–0.7.
o An elevated SI (>0.9): More sensitive indicator of transfusion requirement and of patients with critical bleeding among
those with hypovolemic (hemorrhagic) shock than either HR or BP alone.
o The SI may also identify patients at risk for postintubation hypotension.
• The quick Sequential Organ Failure Assessment (qSOFA) score is a rapid assessment scale that assigns a point for:
o SBP <100
o Respiratory rate >22
o Altered mental status (Glasgow Coma Scale <15).
* A qSOFA ≥2 (with a concern for infection) is associated with a significantly greater risk of death or prolonged ICU stay.
* The Third International Consensus Definition of Sepsis has recommended the use of the qSOFA to identify the most acutely ill subset
of patients with sepsis (longer length of stay, increased need for ICU admission, and higher in-hospital mortality).
Diagnostic Testing
• Laboratory evaluation should be initiated promptly in all
patients with suspected shock.
o Dual aim:
§ Assess the extent of end-organ dysfunction
§ Gain insight into the possible etiology of shock
Blood Tests . Blood urea nitrogen (BUN), creatinine, Provide an assessment of the extent of end-organ dysfunction related
and transaminases to shock
Urine electrolytes with subsequent calculation of the May indicate states of hypovolemia or decreased effective circulating
fractional excretion of sodium (FENa) or fractional volume
excretion of urea (FEUrea)
Elevation of alkaline phosphatase Suggest biliary obstruction and may thereby identify a source of
infection in patients with distributive shock
Elevation of cardiac enzymes Indicate a primary cardiac problem with myocyte damage related to
ischemia, myocarditis, or a pulmonary embolism
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Elevation of the white blood cell count May raise suspicion for an infective process
Not diagnostic
Accompanying left shift may improve the sensitivity of this measure
Venous blood gas (VBG) Extent of acidosis may be determined
+
ABG If there is accompanying hypoxemia
Urinalysis and urine sediment Evaluate for pyuria
Blood cultures, urine cultures, and sputum cultures
Radiographic evaluation Seek sources of infection suggested by the history and physical
examination.
Lactate measurement Diagnosis, risk stratification, andtreatment of shock
Increased lactate (hyperlactemia) and lactic acidosis (hyperlactemia

and pH <7.35) are common in shock
• Lactate product of anaerobic glucose metabolism

o In glycolysis
§ The enzyme phosphofuctokinase metabolizes glucose to pyruvate
Aerobic Condition/ Normal Condition Cellular Hypoxia/ Reduced Oxygen Delivery
Pyruvate is then converted (in the The Krebs (tricarboxylic acid) cycle cannot oxidize the pyruvate, and
mitochondria) to acetyl CoA and thus, the pyruvate is converted to lactate by the enzyme lactate
enters the Krebs cycle with resulting dehydrogenase.
ATP generation through oxidative
phosphorylation.
Lactate is produced from skeletal The amount of lactate produced from these tissues increases (and
muscle, brain, skin, and intestine other tissue can begin to produce lactate).
o There is evidence that elevated lactate correlates with a worse outcome
ECG
• The electrocardiogram (ECG) is an essential part of the evaluation of the patient with shock.
• There may be a bradycardia or tachy- cardic arrhythmia causing a reduction in CO.
• ST segment elevation myocardial infarction may be identified.
• The presence of the S1 Q3 T3 pattern would raise concerns for pulmonary embolism.
• Reduced voltage in the presence of electrical alternans raises the possibility of pericardial tamponade.
Echocardiography
• Increasingly used as an essential tool to help categorize shock, and it provides an assessment that is both rapid and noninvasive.
• The bedside echocardiogam performed by the ICU team does not replace a formal examination performed by the
echocardiography service.
• Transthoracic echocardiography (TTE)
o The basic echocardiographic assessment for the shock patient utilizing both the two- dimensional (2D) and M mode.
• Standardized, focused echocardiography protocols such as the RACE protocol (rapid assessment for cardiac echocardiography)
o Facilitate the assessment of cardiac function.
o It focuses the examination on LV function, RV function, and pericardium.
o It also can assess volume
• The 2D mode can evaluate LV size, wall thickness, and ventricular function.
o Ventricular size and thickness can suggest longer standing cardiac processes.
o Evaluation of LV function through estimation of left ventricular ejection fraction (LVEF), and can identify shock with globally
reduced LV function or regional wall motion abnormalities.
o Assessment of RV function also examines RV size and wall thickness (to identify conditions such as elevated pulmonary
pressures or suggest pulmonary embolism), and also evaluate the patient for pericardial tamponade.
o Used to assess valve function, including acute processes, such as mitral valve rupture.
§ Assessment of valvular function is often a process that requires a higher skilled practitioner.
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INITIAL TREATMENT OF SHOCK

• Key principle in shock management is to initiate
treatment for circulatory shock simultaneous
with efforts to elucidate shock etiology
• If the initial history, physical examination, and
laboratory evaluation have identified the shock
type or the specific etiology, then therapy is
directed to reverse the underlying physiologic
abnormality causing the hypoperfusion and
reduced oxygen delivery.
• The development of shock is a medical emergency, and optimal therapy involves the involvement of a multidisciplinary team to
allow the evaluation and initiation of therapy to begin simultaneously.
• Patients must be treated in a setting where adequate resources are available to support frequent reassessments and invasive
monitoring.
• Most patients with shock should be cared for in an ICU setting.
• A key early consideration is to ensure adequate intravenous access
o Placement of a peripheral venous catheter (16G or 18G)
§ Provide initial access for the aggressive volume resuscitation (Distributive or hypovolemic shock)
§ Permit prompt antibiotic administration (Distributive shock with sepsis)
o Placement of a central venous catheter (CVC)
§ For patients with ongoing hypotension despite adequate volume resuscitation
§ Indicated to provide therapy with vasopressors and inotropes.
§ Provide a mechanism for hemodynamic monitoring (CVP)
§ Means to obtain central venous oxygen saturations (ScvO2).
• The ScvO2 is a surrogate of mixed venous oxygen saturation thus provides insight into the adequacy of oxygen
delivery
§Central venous access using a sheath will provide an access point for placement of a Swan Ganz catheter if more
detailed assessment of hemodynamic measurements are required (PCWP, CO, and SVR).
o Intraosseous device
§ Patient presents critically ill or in the midst of cardiopulmonary arrest
o Placement of an arterial line
§ Allows for intravascular measurement of blood pressure and continuous determination of MAP.
§ Provide insight into the adequacy of volume resuscitation through the measurement of systolic or pulse pressure
variation.
§ Provide access for determination of arterial oxygen tension, which is helpful since peripheral oximetry measurements
(SpO2) can be unreliable in states of tissue hypoperfusion.
§ Facilitates repeated measures of acid base status or lactate to assess the impact of treatment.
• All patients with shock should have a urinary catheter placed to permit hourly assessment of renal function as another potential
indication of the adequacy of resuscitation.
Volume Resuscitation
• Initial volume resuscitation has the aim of restoring tissue perfusion and is crucial to optimal shock therapy.
• The physiologic goal of volume resuscitation is to move the patient to the nonpreload-dependent portion of the Starling curve.
• Most patients with any of the four shock types will benefit from an increase in intravascular volume.
o For patients with distributive shock, the need for early aggressive volume replacement is well established.
• The “usual care” arms of some studies received early initial volume resuscitation.
• Suspected septic shock, a minimum of 30 mL/kg is recommended
• Need for volume resuscitation is most apparent for patients with distributive or hypovolemic shock
• Patients with cardiogenic shock may benefit by cautious volume replacement.
o There should be a careful assessment of volume status prior to volume administration.
• Volume replacement therapy should be given as a bolus with a predefined endpoint to assess the effect of the volume
resuscitation.
• Crystalloid: Most commonly used to begin volume resuscitation
• In patients with hypovolemic shock due to ongoing hemorrhage, volume replacement with packed red blood cells is warranted.
o If hemoglobin content is <7 g/dL in order to optimize oxygen delivery.
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• In cases of massive transfusion: Platelets and fresh frozen plasma should be provided to offset the dilution of these components
during volume replacement.
• Assessment of intravascular volume status (and the adequacy of volume resuscitation) begins with the physical examination.
• The passive leg raise (PLR) test
o Can predict responsiveness to additional intravenous fluid (IVF) by providing the patient with an endogenous volume bolus.
o While the patient is resting in a semi- recumbent position at a 45-degree angle, the bed is placed in trendelenburg such
that the patient’s head becomes horizontal and the legs are extended at a 45-degree angle.
o There is then an immediate (within 1 min) assessment of changes in CO (or pulse pressure variation as a surrogate).
o If the shock patient is mechanically ventilated there is the option of looking at changes in SV variation (or pulse pressure
variation) during the respiratory cycle to assess volume responsiveness.
§ A >12% SV variation suggests a volume-responsive state. This measurement requires that the patient be in a volume
cycle mode of ventilation, without breath-to-breath variations in intrathoracic pressure and without arrhythmias.
§ A final caveat to the use of these parameters to assess volume status is that these studies are performed on patients
being ventilated with tidal volumes larger than currently used to minimize ventilator-induced lung injury.
• Use of echocardiography to assist in determination of intravascular fluid status, with a variety of static and dynamic variables
that the trained operator can assess.
o Parameters to assess adequacy of volume resuscitation are inferior vena cava (IVC) diameter and IVC collapse.
o Alternatively, serial assessments of LV function can be performed while volume is being administered.
• Placement of a pulmonary artery catheter (PAC) is another tool for assessment of volume status. This more invasive measure
involves placement of the PAC into the central venous circulation and through the right heart.
• Ports in the PAC (Swan Ganz catheter) allow for direct measurement of CVP, pulmonary artery (PA), and PCWPs. The PCWP is
used as a surrogate for LA pressure.
• The need for continued volume replacement must be frequently reassessed. As the patient continues to receive treatment for
shock, the initial proper strategy regarding volume management may change in light of development of processes that
independently require a different volume management strategy.
• For patients who initially present with shock but then develop failure related to acute respiratory distress syndrome (ARDS) or
renal failure, it may be reasonable to begin volume removal.
Vasopressor and Inotropic Support

• Initiated if intravascular volume status has been optimized with volume resuscitation but hypotension and inadequate tissue
perfusion persist
• The use of vasopressors and inotropes must be tailored to the primary physiologic disturbance.
Distributive Shock Norepinephrine is the first o Potent α1 (vasoconstriction )and β1 adrenergic effects (positive inotropic
choice vasopressor and chronotropic effects)
• Aim is to
increase the
SVR.
High dose epinephrine o Similar profile (at lower doses the β effects predominate)
o Associated with tachyarrhythmia, myocardial ischemia, decreased
splanchnic blood flow, pulmonary hypertension, and acidosis. Vasopressin
deficiency may be present
Vasopressin o Acts on the vasopressin receptor to reverse vasodilation and redistribute
flow to the splanchnic circulation
o Second agent for hypotension in septic shock
Dopamine o Does not have a role as a first line agent in distributive shock
o Increase in adverse events (arrhythmia)
Cardiogenic shock Dobutamine o First line agent
o Synthetic catecholamine with primarily β-mediated effects and minimal α
adrenergic effects
o β1 effect: Increased inotropy
o β2 effect: vasodilation with decreased afterload
o It can be used with norepinephrine in patients with mixed distributive and
cardiogenic shock.
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OXYGENATION AND VENTILATION SUPPORT

• In addition to the cellular hypoxia caused by the circulatory failure, patients with shock may present with hypoxemia.
Distributive shock Hypoxemia may be related to a primary pulmonary process (pneumonia in a patient with septic shock)
Cardiogenic or Hypoxemia may be related to LV dysfunction and elevations of PCWP
Obstructive shock
• For patients with all types of shock, there can be development of ARDS and subsequent V/Qmismatch and shunt.
o Supplemental oxygen should be initiated and titrated to maintain SpO2 of 92–95%.
o This may require intubation and initiation of mechanical ventilation.
§ Should be provided promptly so as to minimize the duration of tissue hypoxia if the patient requires.
• Patients with shock may have high minute ventilatory needs to compensate for metabolic acidosis.
• As shock progresses, they may not be able to maintain adequate respiratory compensation, which may be a second indication
to initiate mechanical ventilator support.
o If mechanical support is initiated, it is important to provide ventilation with lung-protective strategies focused on low tidal
volume ventilation and optimization of positive end-expiratory pressure to minimize ventilator-induced lung injury.
o There should be daily sedation cessation to assess underlying neurologic function and minimize time on mechanical
ventilation.
Antibiotic Administration
• Sepsis and septic shock are the most common cause of shock.
• For patients presenting with undifferentiated shock, if the diagnosis of septic shock is being entertained then broad spectrum
antibiotics should be administered after obtaining appropriate cultures.
• For patients with sepsis, every hour delay in antibiotic administration is associated with an increase in mortality.
• While it is ideal to initiate antibiotics after appropriate cultures, the inability to obtain cultures should not delay the start of
treatment.
• When sepsis is excluded as a cause of shock, an important aspect of antibiotic stewardship is to stop all antibiotics.
Specific Causes of Shock Requiring Tailored Intervention

Patients with distributive shock secondary Require removal of the inciting allergen, administration of epinephrine, and vascular
to anaphylaxis support with intravenous fluid resuscitation and vasopressors
Adrenal insufficiency Requires replacement with intravenous stress dose steroids
Cardiogenic shock patients with arrhythmia May require treatment as outlined in advanced cardiac life support algorithms or
placement of an artificial pacemaker
Acute ischemic events Consideration must be given to revascularization and temporary mechanical
supportive measures
Valve dysfunction Emergency surgery may be considered
Hypovolemic shock due to hemorrhage Surgical intervention: Trauma
Endoscopic or Interventional Radiology: GI source of blood loss
Tension PTX Necessitate immediate decompression
Proximal pulmonary embolism Evaluation for thrombolytic therapy or surgical removal of the clot
Dissection of the ascending aorta may require surgical intervention
297. SEPSIS AND SEPTIC SHOCK

DEFINITION
- Hippocrates
o rotting flesh and festering wounds
- Galen
o laudable event required for wound healing
- Semmelweis, Pasteur, and others
o 19th century
o germ theory
o “blood poisoning”
o due to pathogen invasion and spread in the bloodstream of the host
- Bone and colleagues
o proposed that the host, not the germ, was responsible for the pathogenesis of sepsis
o systemic inflammatory response to infection
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- Severe Sepsis
o sepsis complicated by acute organ dysfunction
- Septic Shock
o subset of sepsis cases that were complicated by hypotension despite adequate fluid resuscitation along with perfusion
abnormalities
- Sepsis Definitions Task Force in 2016
o proposed the Third International Consensus Definitions
- Sepsis: dysregulated host response to infection that leads to acute organ dysfunction
- Septic Shock: subset of sepsis cases in which underlying circulatory and cellular/metabolic abnormalities are profound enough
to substantially increase mortality risk
ETIOLOGY
Sepsis: community-acquired and hospital-acquired infections
1. Pneumonia - most common source (1/2 of cases)
2. Intraabdominal and genitourinary infections
Blood cultures – positive (1/3 of cases); many cases - culture negative at all sites
Most common gram-positive isolates: S. aureus and S. pneumoniae
Most common gram-negative isolates: E. coli, Klebsiella species, and P. aeruginosa
Positive isolates in patients on ICUs:
o gram-negative bacteria (62%)
o gram positive bacteria (47%)
o fungi (19%)
Common risk factors for increased risk of infection:
o chronic diseases (e.g., HIV infection, chronic obstructive pulmonary disease, cancers)
o immunosuppression
Risk factors for progression from infection to organ dysfunction may include:
o underlying health status,
o preexisting organ function
o timeliness of treatment.
Incidence of sepsis is influenced by:
o Age
o Sex
o Race/ethnicity
o “highest at the extremes of age; higher in males than in females; higher in blacks than in whites”
EPIDEMIOLOGY
o 2 million cases of sepsis occur annually
o Shock: present in ~30% of cases; 230,000 cases in a recent systematic review
o Septic shock: 19 per 1000 hospitalized encounters
o Incidences of sepsis and septic shock increasing with almost 50% in the past decade
PATHOGENESIS
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o Sepsis: result of an excessive inflammatory host response (SIRS)

o Infection: triggers a much more complex, variable, and prolonged host response
o Specific response of each patient depends on:
§ pathogen (load and virulence)
§ host (genetic composition and comorbidity)
§ with different responses at local and systemic levels
o Proinflammatory reactions:
§ directed at eliminating pathogens
§ responsible for “collateral” tissue damage in sepsis
o Anti-inflammatory responses:
§ implicated in the enhanced susceptibility to secondary infections that occurs later in the course
o These mechanisms can be characterized as an interplay between two “fitness costs”:
§ direct damage to organs by the pathogen
§ damage to organs stemming from the host’s immune response
Initiation of Inflammation
o Pathogens activate immune cells by an interaction with pattern recognition receptors:
o 4 main classes are prominent:
1. Toll-like receptors (TLRs) - up to 10 TLRs have been identified in humans
2. RIG-I-like receptors
3. C-type lectin receptors
4. NOD-like receptors (inflammasomes)
o Pathogen-associated molecular patterns (PAMPs)
§ structures conserved across microbial species
§ receptors result in upregulation of inflammatory gene transcription and initiation of innate immunity
§ Lipid A moiety of lipopolysaccharide (LPS or endotoxin)
§ attaches to the LPS-binding protein on the surface of monocytes, macrophages, and neutrophils
§ transferred to and signals via TLR4 to produce and release cytokines such as tumor necrosis factor that
grow the signal and alert other cells and tissues
o Damage-associated molecular patterns (DAMPs)
§ receptors also sense DAMPs
§ endogenous molecules released from injured cells
§ high-mobility group protein B1
§ S100 proteins
§ extracellular RNA, DNA, and histones
§ release during sterile injuries such as those incurred during trauma gives rise to the concept that the pathogenesis
of multiple-organ failure may be similar in sepsis and noninfectious critical illness
o In addition to activating the proinflammatory cytokines, the inflammatory responses implicated in the pathogenesis of
sepsis also activate the complement system, platelet-activating factor, arachidonic acid metabolites, and nitric oxide.
Coagulation Abnormalities
o Sepsis is commonly associated with coagulation disorders and frequently leads to disseminated intravascular coagulation
o Abnormalities in coagulation
§ isolate invading microorganisms
§ prevent the spread of infection and inflammation to other tissues and organs
o Excess fibrin deposition
§ driven by coagulation via tissue factor
§ a transmembrane glycoprotein expressed by various cell types
§ impaired anticoagulant mechanisms
§ including the protein C system and antithrombin
§ compromised fibrin removal due to depression of the fibrinolytic system
o Coagulation and other proteases further enhance inflammation via protease-activated receptors
o Endothelial predominance
§ E.g. meningococcemia
§ common and deadly
Organ Dysfunction
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o impaired tissue oxygenation plays a key role

o Factors contributing to reduced oxygen delivery in sepsis and septic shock:
§ Hypotension
§ Reduced red-cell deformability
§ Microvascular thrombosis
o Inflammation can cause dysfunction of the vascular endothelium, accompanied by cell death and loss of barrier integrity,
giving rise to subcutaneous and body-cavity edema
o Excessive and uncontrolled release of nitric oxide causes:
§ vasomotor collapse
§ opening of arteriovenous shunts
§ pathologic shunting of oxygenated blood from susceptible tissues
o Mitochondrial damage due to oxidative stress and other mechanisms impairs cellular oxygen utilization
o Slowing of oxidative metabolism, in parallel with impaired oxygen delivery, reduces cellular O2 extraction
o With severe or prolonged insult, ATP levels fall beneath a critical threshold, bioenergetic failure ensues, toxic reactive oxygen
species are released, and apoptosis leads to irreversible cell death and organ failure
Anti-Inflammatory Mechanisms
o Phagocytes: switch to an anti-inflammatory phenotype that promotes tissue repair
o Regulatory T cells and myeloid-derived suppressor cells: reduce inflammation
o Neuroinflammatory reflex
§ sensory input is relayed through the afferent vagus nerve to the brainstem, from which the efferent vagus nerve
activates the splenic nerve in the celiac plexus, with consequent norepinephrine release in the spleen and
acetylcholine secretion by a subset of CD4+ T cells
o Acetylcholine release targets α7 cholinergic receptors on macrophages, reducing proinflammatory cytokine release
§ disruption by vagotomy renders animals more vulnerable to endotoxin shock
§ while stimulation of the efferent vagus nerve or α7 cholinergic receptors attenuates systemic inflammation in
experimental sepsis
Immune Suppression
o Patients who remain dependent on intensive care occasionally demonstrate evidence of a suppressed immune system
§ may have ongoing infectious foci despite antimicrobial therapy or may experience the reactivation of latent viruses
o Reduced responsiveness of blood leukocytes to pathogens in patients with sepsis
§ strong functional impairments of splenocytes harvested from ICU patients who died of sepsis
o Immune suppression was evident in the lungs and spleen
§ both organs - expression of ligands for T cell–inhibitory receptors on parenchymal cells were increased
o Enhanced apoptotic cell death
§ B cells, CD4+ T cells, and follicular dendritic cells
§ has been implicated in sepsis associated immune suppression and death
o Secondary infections
§ developed in 14% of patients
§ associated genomic response at the time of infection was consistent with immune suppression, including impaired
glycolysis and cellular gluconeogenesis
§ most common secondary infections:
§ catheter-related bloodstream infections
§ ventilator-associated infections
§ abdominal infections
APPROACH TO THE PATIENT

“Is this patient septic?”
o Consensus criteria for sepsis and septic shock agree on core diagnostic elements, including suspected or documented
infection accompanied by acute, life-threatening organ dysfunction
o Primary physiologic manifestations of organ dysfunction can be assessed quickly at the bedside with a six-organ framework,
yielding the SOFA score.
o General manifestations of shock:
§ arterial hypotension with evidence of tissue hypoperfusion (e.g., oliguria, altered mental status, poor peripheral
perfusion, or hyperlactemia)
CLINICAL MANIFESTATIONS
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o Specific clinical manifestations are quite variable

o Depending on:
§ the initial site of infection
§ the offending pathogen
§ the pattern of acute organ dysfunction
§ the underlying health of the patient
§ the delay before initiation of treatment
o Signs of both infection and organ dysfunction may be subtle
o Once sepsis has been established and the inciting infection is assumed to be under control, the temperature and white blood
cell (WBC) count often return to normal. However, organ dysfunction typically persists.
CARDIORESPIRATORY - most commonly affected organ systems in sepsis (respiratory and cardiovascular systems)
FAILURE
- Acute respiratory distress syndrome (ARDS)
o Respiratory o defined as hypoxemia and bilateral infiltrates of noncardiac origin that arise within 7 days of
compromise the suspected infection
o classified by Berlin criteria
§ mild (PaO2/FiO2, 201–300 mmHg)
§ moderate (101–200 mmHg)
§ severe (≤100 mmHg)
o A common competing diagnosis is hydrostatic edema secondary to cardiac failure or volume
overload
o Cardiac failure:
§ traditionally identified by elevated pulmonary capillary wedge measurements from
a pulmonary artery catheter (>18 mmHg)
§ can be objectively evaluated on the basis of clinical judgment or focused
echocardiography
- Hypotension
o cause can be frank hypovolemia
o maldistribution of blood flow
o Cardiovascular o intravascular volume due to
compromise o diffuse capillary leakage, reduced systemic vascular resistance, or depressed myocardial
function
o After adequate volume expansion, hypotension frequently persists, requiring the use of
vasopressors
o Early shock:
§ volume status is reduced
§ systemic vascular resistance may be quite high with low cardiac output
§ after volume repletion: may rapidly change to low systemic vascular resistance and
high cardiac output
KIDNEY INJURY - Acute kidney injury (AKI)
o documented in >50% of septic patients
o increasing the risk of in-hospital death by six- to-eightfold
o manifests as oliguria, azotemia, and rising serum creatinine levels and frequently requires
dialysis
o may occur in up to 25% of patients in the absence of overt hypotension
o Current mechanistic work suggests that a combination of diffuse microcirculatory blood flow
abnormalities, inflammation, and cellular bioenergetic responses to injury contribute to
sepsis-induced AKI beyond just organ ischemia
NEUROLOGIC - Coma or Delirium
COMPLICATIONS o Imaging studies: no focal lesions
o Electroencephalographic findings: consistent with nonfocal encephalopathy
- Sepsis-associated delirium
o considered a diffuse cerebral dysfunction caused by the inflammatory response to infection
without evidence of a primary central nervous system infection.
o Consensus guidelines recommend delirium screening with valid and reliable tools such as the
Confusion Assessment Method for the Intensive Care Unit (CAM-ICU) and the Intensive
Care Delirium Screening Checklist (ICDSC)
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- Critical-illness polyneuropathy and myopathy are also common in patients with a prolonged course
- Survivors of sepsis - neurologic complications can be severe
o moderate to severe cognitive impairment increased by 10.6 percentage points among
patients who survived severe sepsis (odds ratio, 3.34; 95% confidence interval [CI], 1.53–
7.25) over that among survivors of nonsepsis hospitalizations
o Many of these limitations persisted for up to 8 years
ADDITIONAL - Ileus
MANIFESTATIONS - Elevated aminotransferase levels
- Altered glycemic control
- Thrombocytopenia and Disseminated intravascular coagulation
- Adrenal dysfunction
o related more to reversible dysfunction of the hypothalamic–pituitary axis or tissue
glucocorticoid resistance than to direct damage to the adrenal gland
- Sick euthyroid syndrome
DIAGNOSIS
Laboratory and Physiologic Findings
- Tachycardia (heart rate, >90 beats per min)
o was present in >50% of encounters
- Most common accompanying abnormalities:
o tachypnea (respiratory rate, >20 breaths per min)
o hypotension (systolic blood pressure, ≤100 mmHg)
o hypoxia (SaO2, ≤90%)
- Leukocytosis (WBC count, >12,000/μL)
o fewer than 1/3 of patients
- Leukopenia (WBC count, <4000/μL)
o fewer than 5%
- Features that may identify acute organ dysfunction:
o platelet count
o total bilirubin
o serum lactate level
§ measured in only a small minority of at-risk encounters
- Metabolic acidosis with anion gap
o may be detected, as respiratory muscle fatigue occurs in sepsis-associated respiratory failure
- Less common findings:
o serum hypoalbuminemia
o troponin elevation
o hypoglycemia
o hypofibrinogenemia
Diagnostic Criteria
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sepsis = f (threat to life/organ dysfunction/dysregulated host response/infection)
o sepsis – dependent variable which in turn is a function of four independent variables linked in a causal
pathway, with—from left to right—one conditional upon the other
- Sepsis Definitions Task Force recommended that, once infection is suspected, clinicians consider whether it has caused organ
dysfunction by determining a SOFA score
- SOFA score
o ranges from 0 to 24 points, with up to 4 points accrued across six organ systems
o widely studied in the ICU among patients with infection, sepsis, and shock
o with ≥2 new SOFA points, the infected patient is considered septic and may be at ≥10% risk of in-hospital death
o requires multiple laboratory tests and may be costly to measure repeatedly
- quick SOFA (qSOFA) score
o proposed as a clinical prompt to identify patients at high risk of sepsis outside the ICU, whether on the medical ward or
in the emergency department
o ranges from 0 to 3 points, with 1 point each for systolic hypotension (≤100 mmHg), tachypnea (≥22 breaths/min), or
altered mentation
o qSOFA score of ≥2 points has a predictive value for sepsis similar to that of more complicated measures of organ
dysfunction
o undergoing broader evaluation in other cohorts, in low-and middle-income settings, and in algorithms linked to clinical
decision-making
o Recent work has also shown that, although SIRS criteria may be fulfilled in sepsis, they sometimes are not and do not
meaningfully contribute to the identification of patients with suspected infection who are at greater risk of a poor
course, ICU admission, or death—outcomes more common among patients with sepsis than among those without
- For clarity, criteria are proposed for septic shock that include:
o (1) sepsis plus
o (2) the need for vasopressor therapy to elevate mean arterial pressure to ≥65 mmHg, with
o (3) a serum lactate concentration >2.0 mmol/L after adequate fluid resuscitation
- Arterial lactate
o long-studied marker of tissue hypoperfusion, and hyperlactemia and delayed lactate clearance are associated with a
greater incidence of organ failure and death in sepsis
o In a study of >1200 patients with suspected infection, 262 (24%) of 1081 patients exhibited an elevated lactate
concentration (≥2.5 mmol/L) even in the setting of normal systolic blood pressure (>90 mmHg) and were at elevated risk
of 28-day in-hospital mortality.
o Lactic acidosis may occur in:
§ the presence of alcohol intoxication
§ liver disease
§ diabetes mellitus
§ administration of total parenteral nutrition
§ antiretroviral treatment
o elevated lactate concentration may simply be the manifestation of impaired clearance
o These factors may confound the use of lactate as a stand-alone biomarker for the diagnosis of sepsis; thus it should be
used in the context of other markers of infection and organ dysfunction
TREATMENT
Initial management of infection:
- forming a probable diagnosis
- obtaining samples for culture
- initiating empirical antimicrobial therapy
- achieving source control
Appropriate choice for empirical antibiotic therapy depends on:
- suspected site of infection
- location of infection onset
- patient’s medical history
- local microbial susceptibility patterns
Antibiotic delays may be deadly
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- Every 1-h delay among patients with sepsis, a 3–7% increase in the odds of in-hospital death
- Empirical antifungal therapy should be administered only to septic patients at high risk for invasive candidiasis
2 BUNDLES OF CARE
Initial Management Management Bundle
Bundle
to be completed within 3 to be completed within 6 h
h of presentation 1. an intravenous
1. early fluid bolus
administration 2. treatment with
of appropriate vasopressors for
broad-spectrum persistent
antibiotics hypotension or
2. collection of shock
blood for 3. re-measurement
culture before of serum lactate
antibiotic levels
administration
3. measurement
of serum lactate
levels
Other elements:
- cardiorespiratory
resuscitation and
mitigation of the
immediate threats
of uncontrolled
infection
- Early resuscitation
requires a
structured approach
including the
administration of IV
fluids and
vasopressors, with
oxygen therapy and
mechanical
ventilation to
support injured
organs
SUBSEQUENT TREATMENT OF SEPSIS AND SEPTIC SHOCK
• Monitoring
- Pulmonary Artery Catheter (PAC)
o aka continuous ScvO2 catheter
o invasive devices
o estimate cardiac output and measure mixed venous oxygen saturation, among other parameters, to refine the etiology
of shock and potentially influence patient outcomes
o no longer recommended for routine use
- Arterial Pulse Contour Analysis (PCA) or focused echocardiography
o Noninvasive monitoring tools
o continuous estimates of parameters such as cardiac output, beat-to-beat stroke volume, and pulse pressure variation
o along with passive leg-raise maneuvers or inferior vena cava collapsibility on ultrasound, can help determine a patient’s
volume responsiveness but require that a variety of clinical conditions be met (e.g., patient on mechanical ventilation,
sinus rhythm)
• Support of Organ Function

- primary goal of organ support: to improve delivery of oxygen to the tissues as quickly as possible
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- may require administration of IV fluids or vasopressors, blood transfusions, or ventilatory support

Crystalloids Colloid solutions
- 0.9% normal saline (widely used in the US) - Albumin
- Ringer’s lactate - Dextran
- Hartmann’s solution - Gelatins
- Plasma-Lyte - Hydroxyethyl starch
- In general, crystalloids are recommended on the - Most widely used fluids in critically ill patients, with variability
basis of strong evidence as first-line fluids for across ICUs and countries
sepsis resuscitation, with specific caveats - A clinician’s choice among colloids is influenced by availability,
- their use is guided by resolution of hypotension, cost, and the desire to minimize interstitial edema
oliguria, altered mentation, and hyperlactemia
Vasopressors
- recommended when circulating fluid volume is adequate to maintain perfusion of vital organs
- norepinephrine, epinephrine, dopamine, and phenylephrine
- Dopamine: arrhythmias were significantly greater
- Norepinephrine: first-choice vasopressor in septic shock
- Vasopressin: levels of the endogenous hormone may be low in septic shock and the administration can reduce the
norepinephrine dose
o Consensus guidelines suggest adding vasopressin (up to 0.03 U/min) in patients without a contraindication to
norepinephrine, with the intent of raising mean arterial pressure or decreasing the norepinephrine dose
o Indications: when tachyarrhythmias from dopamine or norepinephrine, limb ischemia from vasopressin, or other
adverse effects dictate
- Transfusion of red blood cells to high thresholds (>10 g/dL) had been suggested as part of EGDT in septic shock
o Scandinavian TRISS trial demonstrated that a lower threshold (7 g/dL) resulted in 90-day mortality rates similar to those
with a higher threshold (9 g/dL) and reduced transfusions by almost 50%
- Indications for mechanical ventilatory support:
o Significant hypoxemia (PaO2, <60 mmHg; or SaO2, <90%)
o Hypoventilation (rising PaCO2)
o Increased work of breathing
o Inadequate or unsustainable compensation for metabolic acidosis (pH <7.20)
- Endotracheal intubation: protects the airway, and positive pressure breathing allows oxygen delivery to metabolically active
organs in favor of inspiratory muscles of breathing and the diaphragm
o patients should be closely monitored for vasodilatory effects of sedating medications or compromised cardiac output
due to increased intrathoracic pressure, both of which may cause hemodynamic collapse
• Adjuncts
- designed to interrupt the initial cytokine cascade (e.g., anti-LPS or anti-proinflammatory cytokine strategies)
- interfere with dysregulated coagulation (e.g., antithrombin or activated protein C)
- Recombinant activated protein C (aPC)
o one of the first agents approved by the US FDA
o most widely used
o no longer recommended in the care of sepsis or septic shock
- Many adjunctive treatments in sepsis and septic shock target changes in the innate immune response and coagulation cascade
- Specific adjuncts like glucocorticoids in septic shock have continued to be widely used.
- IV hydrocortisone
o International clinical practice guidelines against its use to treat septic shock if adequate fluid resuscitation and
vasopressor therapy are able to restore hemodynamic stability
o if not, the guidelines suggest the administration of IV hydrocortisone at a dose of 200 mg per day (weak
recommendation, low quality of evidence)
- IV immunoglobulin
o may be associated with potential benefit, but significant questions remain and such treatment is not part of routine
practice
PROGNOSIS
- Infection
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o primary risk factor for sepsis and septic shock

o the fifth leading cause of years of productive life lost because of premature death
- >1/2 of sepsis cases require ICU admission, representing 10% of all ICU admissions
- mortality rate from sepsis and septic shock is now closer to 20%
- Patients who survive to hospital discharge after sepsis remain at increased risk of death in the following months and years
o Those who survive often suffer from impaired physical or neurocognitive dysfunction, mood disorders, and low quality
of life
o Among survivors, the rate of hospital readmission within 90 days after sepsis exceeds 40%
PREVENTION
- Factors contributing to the steady burden of sepsis cases:
o the aging of the population
o the overuse of inappropriate antibiotics
o the rising incidence of resistant microorganisms
o the use of indwelling devices and catheters
- Number of cases could be reduced by:
o avoiding unnecessary antibiotic use
o limiting use of indwelling devices and catheters
o minimizing immune suppression when it is not needed
o increasing adherence to infection control programs at hospitals and clinics
298. CARDIOGENIC SHOCK & PULMONARY EDEMA
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• Cardiogenic shock (CS) and pulmonary edema are

life-threatening high acuity conditions that
require treatment as medical emergencies, usually
in an intensive care unit (ICU) or cardiac intensive
care unit (CICU).
• The most common joint etiology is severe left
ventricular (LV) dysfunction from myocardial
infarction (MI) that leads to pulmonary congestion
and/or systemic hypoperfusion.
CARDIOGENIC SHOCK
• CS is a low cardiac output state resulting in life-
threatening end-organ hypoperfusion and
hypoxia.
• The clinical presentation is typically characterized
by persistent hypotension (<90 mmHg systolic
blood pressure [BP]) unresponsive to volume
replacement and is accompanied by clinical
features of peripheral hypoperfusion, such as
elevated arterial lactate (>2 mmol/L).
• Objective hemodynamic parameters such as
cardiac index or pulmonary capillary wedge
pressure can help confirm the diagnosis, but are
not mandatory.
• The in-hospital mortality rates range from 40 to
60%, depending on shock severity and the
associated underlying cause.
Acute MI with LV dysfunction remains the most
frequent cause of CS with other causes.
• Circulatory failure based on cardiac dysfunction
may be caused by primary myocardial failure, most
commonly secondary to acute MI and less frequently by cardiomyopathy or myocarditis, cardiac tamponade, arrhythmias or
critical valvular heart disease.
Incidence
• The incidence of CS complicating acute MI has decreased to 5–10%, largely due to increasing use of early mechanical
reperfusion therapy for acute MI.
• Shock is more common with ST-elevation MI (STEMI) than with non-STEMI.
LV failure accounts for ~80% of cases of CS complicating acute MI.
Acute severe mitral regurgitation (MR), ventricular septal rupture (VSR), predominant right ventricular (RV) failure, and free
wall rupture or tamponade account for the remainder.
• A recently recognized uncommon cause of transient CS is the Takotsubo syndrome.
Pathophysiology
• A profound depression of myocardial contractility results in a deleterious spiral of reduced cardiac output, low blood pressure,
and ongoing myocardial ischemia, followed by further contractility reduction.
• This vicious cycle usually leads to death if not interrupted.
• CS can result in both acute and subacute derangements to the entire circulatory system. Hypoperfusion of vital organs and
extremities remains a clinical hallmark. Although ineffective stroke volume is the inciting event, inadequate circulatory
compensation also may contribute to shock. Initial peripheral vasoconstriction may improve coronary and peripheral
perfusion at the cost of increased afterload.
• However, over the course of CS systemic inflammation response triggered by acute cardiac injury often induces pathologic
vasodilatation.
• Inflammatory cytokines, endothelial and inducible nitric oxide synthase may augment NO production, accompanied by
peroxynitrite, which has a negative inotropic effect and is cardiotoxic. Lactic acidosis and hypoxemia contribute to the vicious
circle, as severe acidosis reduces the efficacy of endogenous and exogenous catecholamines.
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• During ICU support bleeding and/or transfusions may trigger inflammation and are usually associated with higher mortality.
Patient Profile
• In patients with MI, older age, prior MI, diabetes mellitus, anterior MI location, and multivessel coronary artery disease with
extensive coronary artery stenoses are associated with an increased risk of CS.
• Shock associated with a first inferior MI should prompt a search for a mechanical cause or RV involvement.
• CS may rarely occur in the absence of significant stenosis, as seen in Takotsubo syndrome or fulminant myocarditis.
Timing
• Shock is present on admission in approximately one quarter of MI patients who develop CS; one-quarter develop it rapidly
thereafter, within 6 h of MI onset, and another quarter develop shock later on the first day.
• Later onset of CS may be due to reinfarction, marked infarct expansion, or mechanical complications.
Diagnosis
• For these unstable patients, supportive therapy must be initiated simultaneously with diagnostic evaluation.
• A focused history and physical examination should be performed along with an electrocardiogram (ECG), chest X-ray, arterial
blood gas (ABG) analysis, lactate measurement, and blood specimens to the laboratory.
• Initial echocardiography is an invaluable tool to elucidate the underlying cause of CS.
CLINICAL FINDINGS
• Most patients initially are dyspneic, appear pale, apprehensive, and diaphoretic, and mental status may be altered.
• The pulse is typically weak and rapid or occasionally severe bradycardia due to high-grade heart block may be present.
• BP is typically reduced (<90 mmHg; or catecholamines required to maintain blood pressure (>90 mmHg), but occasionally BP
may be maintained by very high systemic vascular resistance.
• Tachypnea and jugular venous distention may be present. Typically there is a weak apical pulse and soft S1, and an S3 gallop
may be audible.
• Acute, severe MR and VSR usually are associated with characteristic systolic murmurs
Crackles are audible in most patients with LV failure.
• Oliguria/anuria is common.
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• Often CS patients require early mechanical ventilation (~80%) for management of acute hypoxemia, increased work of
breathing, and hemodynamic instability; catecholamines often are required to maintain adequate blood pressure.
LABORATORY FINDINGS
• The white blood cell count and C-reactive protein typically are elevated.
• Renal function often is progressively impaired. Newer renal function markers such as Cystatin C or Neutrophil gelatinase-
associated lipocalin (NGAL) do not add prognostic information over creatinine.
• Hepatic transaminases are elevated due to liver hypoperfusion in ~20% of patients and may be very high.
• The arterial lactate level is usually elevated to >2 mmol/L.
• ABGs usually demonstrate hypoxemia and anion gap metabolic acidosis.
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• Glucose levels at admission are often elevated, a strong independent predictor for mortality. Cardiac markers, creatine kinase
and its MB fraction, and troponins I and T are typically markedly elevated in acute MI.
ELECTROCARDIOGRAM
• In acute MI with CS, Q waves and/or ST elevation in multiple leads or left bundle branch block are usually present.
Approximately one-half of MIs with CS are anterior infarctions.
• Global ischemia due to severe left main stenosis usually is accompanied by aVR lead ST segment elevation and ST depressions
in multiple leads.
CHEST ROENTGENOGRAM
• The chest x-ray typically shows pulmonary vascular congestion and often pulmonary edema, but may be normal in up to a
third of patients.
• The heart size is usually normal when CS results from a first MI, but may be enlarged when it occurs in a patient with a
previous MI.
ECHOCARDIOGRAM
• An echocardiogram should be obtained
promptly in patients with suspected/confirmed
CS to help define its etiology.
• Echocardiography is able to delineate the extent
of infarction/myocardium in jeopardy and the
presence of mechanical complications such as
VSR, MR, or cardiac tamponade.
• Furthermore, valvular obstruction or
insufficiency, dynamic LV outflow tract
obstruction, proximal aortic dissection with
aortic regurgitation or tamponade may be seen,
or indirect evidence for pulmonary embolism
may be obtained.
PULMONARY ARTERY CATHETERIZATION

• The use of pulmonary artery catheter (PAC)
hemodynamic monitoring is declining because
clinical trials have shown no mortality benefit.
• However, hemodynamic data provided by a PAC
can confirm the presence and severity of CS,
involvement of the right ventricle, left-to-right
shunting, pulmonary artery pressures and trans-
pulmonary gradient, and the pulmonary and
systemic vascular resistance.
• It can help in recognition of acute MR,
decreased left atrial filling pressure, and
secondary occult sepsis and to exclude left-to-
right shunts.
• Equalization of diastolic pressures suggests
cardiac tamponade, but echocardiogram is
more definitive.
• The detailed hemodynamic profile can be used to individualize and monitor therapy and to provide prognostic information,
such as cardiac index and cardiac power, can be obtained.
• The use of a PAC is currently recommended by the American Heart Association for potential utilization in cases of diagnostic
or CS management uncertainty or in patients with severe CS who are unresponsive to initial therapy.
ADVANCED HEMODYNAMIC MONITORING

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• Recently new central venous catheter systems linked to computer-based algorithms provide continuous monitoring of a
variety of derived hemodynamic parameters, including cardiac output, stroke volume, stroke volume variation, and systemic
vascular resistance.
• When combined with a femoral arterial catheter, calculated extravascular lung water and pulmonary permeability index can
be monitored.
• The information allows for more rational therapy and assessment, but has not yet shown improved clinical outcomes in
patients with shock or pulmonary edema.
CARDIAC CATHETERIZATION AND CORONARY ANGIOGRAPHY

• The definition of the coronary anatomy provides useful information and is immediately indicated in all patients with CS
complicating MI for further reperfusion treatment.
• Furthermore, cardiac catheterization should also be considered for resuscitated cardiac arrest survivors without ST-segment
elevation because ~70% of these patients have relevant coronary artery disease.
TREATMENT
ACUTE MYOCARDIAL INFARCTION
GENERAL MEASURES
• In addition to the usual treatment of acute MI, initial therapy is aimed at maintaining adequate systemic and coronary
perfusion by raising the blood pressure with vasopressors and adjusting volume status to a level that ensures optimum LV
filling pressure.
• There is some interpatient variability, but generally adequate perfusion occurs with a mean arterial BP of 60–65 mmHg or
a systolic BP ~90 mmHg.
• Hypoxemia and acidosis need to be corrected; up to 90% of patients require ventilatory support, decreasing the stress from
increased work of breathing. Moderate glucose control (≤180 mg/dL or 10.0 mmol/L) should be a goal and hypoglycemia
must be avoided.
• Negative ionotropic agents should be discontinued.
• Bradyarrhythmias may require transvenous pacing.Recurrent ventricular tachycardia or rapid atrial fibrillation may require
immediate treatment.
REPERFUSION-REVASCULARIZATION
• Rapid revascularization of the infarct-related artery is the only evidence-based treatment strategy for mortality reduction in
CS and forms the mainstay therapeutic intervention for CS due to MI.
• In the SHOCK Trial 132 lives were saved per 1000 patients treated with early revascularization with percutaneous coronary
intervention (PCI) or coronary artery bypass graft (CABG) compared with initial medical therapy.
• Outcome benefit correlates strongly with the time between symptom onset and reperfusion.
• In general, PCI with drug-eluting stents of the infarct-related artery is the preferred reperfusion strategy.
• Approximately 80% of CS patients present with multivessel coronary artery disease.
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• The recent CULPRIT-SHOCK randomized trial showed that culprit lesion only PCI with possible staged revascularization led to
a reduction in 30-day mortality or renal replacement therapy in comparison to immediate multivessel PCI. This reduction in
the primary study endpoint was mainly driven by a 30-day mortality reduction.
• Currently, vascular access for diagnostic angiography and PIC via the radial artery is preferred when feasible over femoral
arterial access due to its greater safety.
• CABG is currently performed in only 5% of cases mainly if coronary anatomy is not amenable to PCI.
VASOPRESSORS AND INOTROPES

• Inotropic agents are theoretically appealing in CS treatment. However, current evidence is scarce.
• Vasoactive medications are often used in the management of patients with CS and all have important disadvantages,
including increase in myocardial O2 consumption, afterload, lethal arrhythmias, and possible myocardial cell death.
As a consequence, catecholamines should be used in the lowest possible doses for the shortest possible time. Despite their
frequent use, little clinical outcome data proves their benefit or is available to guide the initial selection of vasoactive
therapies in patients with CS.
• No vasopressor has been demonstrated to change outcome in large clinical trials.
• Norepinephrine is reasonable as the first line vasopressor based on randomized trials compared to dopamine.
Norepinephrine was associated with fewer adverse events, including arrhythmias, compared to dopamine in a randomized
trial of patients with several etiologies of circulatory shock and with improved survival in a pre-specified subgroup of CS
patients. Norepinephrine dosing is usually begun at 2 to 4 μg/min and titrated upward based on blood pressure.
• Dopamine’s hemodynamic effects vary depending upon dose and there is interpatient variability in responses. Low doses
stimulate renal dopaminergic receptors and with increasing dosage there is stimulation of first β-adrenergic receptors and
then a adrenergic receptors. Dopamine should be avoided as first-line therapy for MI with CS based on hemodynamic and
proarrhythmogenic effects.
Dobutamine is a synthetic sympathomimetic amine with positive inotropic action and minimal positive chronotropic activity
at low doses (2.5 μg/kg per min), but moderate chronotropic activity at higher doses. Its vasodilating activity often precludes
its use when a vasoconstrictor effect is required.
• Levosimendan may also be appealing despite a lack of randomized data, but was not beneficial for organ dysfunction in
sepsis.
MECHANICAL CIRCULATORY SUPPORT

• The most commonly used mechanical circulatory support (MCS) device has been the intraaortic balloon pump (IABP),
which is inserted into the aorta via the femoral artery and provides passive hemodynamic support.
• However, routine IABP use in conjunction with early revascularization (predominantly with PCI) did not reduce either 30-day
or 12-month mortality in the IABP-SHOCK II trial.
• IABP also had no benefit on secondary endpoints (arterial lactate, catecholamine doses, renal function, or intensive care
severity of illness unit scores).
• IABP is no longer recommended for CS with LV failure.
Active MCS devices to support the left, right, or both ventricles can be placed percutaneously or surgically.
• Temporary percutaneous MCS can be used as bridge to recovery, to surgically implanted devices, to heart transplantation,
or as a temporizing measure when the neurologic status is uncertain.
• Percutaneous MCS including the TandemHeart, Impella devices, and also venoarterial extracorporeal membrane
oxygenation (VA-ECMO) have been used in patients not responding to standard treatment (catecholamines, fluids, and IABP)
and also as a first-line treatment.
• Active percutaneous MCS results in better hemodynamic support compared to IABP.
• However, the appropriate role of MCS is uncertain as a positive impact on clinical outcomes or mortality has not yet been
demonstrated in trials or metaanalyses.
Surgically implanted devices can support the circulation as bridging therapy for cardiac transplant candidates or as
destination therapy. Assist devices should be used selectively in suitable patients based on decisions by a multidisciplinary
team with expertise in the selection, implantation, and management of MCS devices.
PROGNOSIS
• The expected death rates for patients with MI complicated by CS range widely based on age, severity of hemodynamic
abnormalities, severity of clinical hypoperfusion (arterial lactate, renal function), and performance of early revascularization.
• The recently introduced IABP-SHOCK II score predicts prognosis based on six readily available variables: age >73 years; prior
stroke; glucose at admission >10.6 mmol/L (191 mg/dL); creatinine at admission >132.6 μmol/L (1.5 mg/dL); thrombolysis
in myocardial infarction flow grade after PCI <3; and arterial blood lactate at admission >5 mmol/L.
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• It also may help guide treatment strategies.
SHOCK SECONDARY TO RIGHT VENTRICULAR INFARCTION

• Persistent CS due to predominant RV failure accounts for only 5% of CS complicating MI. It often results from proximal right
coronary artery occlusion. The salient features are relatively high right atrial pressures, RV dilation and dysfunction, and
only mildly or moderately depressed LV function. High right-sided pressures may be absent without volume loading.
However, CS often has overlap combinations of both RV and LV ischemia, given a shared septum and the effect of ventricular
interdependence on RV function. Management of isolated RV CS includes fluid administration to optimize right atrial
pressure (10–15 mmHg); avoidance of excess fluids, which shift the interventricular septum into the LV; catecholamines;
early reestablishment of infarct-artery flow; and MCS.
MITRAL REGURGITATION
• Acute severe MR due to papillary muscle dysfunction and/or rupture may complicate MI and result in CS and/or pulmonary
edema. This complication most often occurs on the first day, with a second peak several days later.
• The diagnosis is confirmed by echocardiography. Afterload reduction with IABP and, if tolerated, vasodilators to reduce
pulmonary edema, is recommended as a bridge to surgery or interventional treatment.
• Mitral valve repair or reconstruction is the definitive therapy and should be performed early in the course in suitable
candidates.
• Other options include percutaneous edge-to-edge repair which has been successful in small case series.
VENTRICULAR SEPTAL RUPTURE

• VSR complicating MI is a relatively rare event associated with very high mortality if CS is present (>80%).
• The incidence of infarct-related VSR without reperfusion was 1–2% but has decreased to 0.2% in the era of reperfusion. VSR
occurs a median of 24 h after infarction, but may occur up to 2 weeks later.
• Echocardiography demonstrates shunting of blood from the left to the right ventricle and may visualize the opening in the
interventricular septum.
• Current guidelines recommend immediate surgical VSR closure, irrespective of the patient’s hemodynamic status, to avoid
further hemodynamic deterioration. IABP support as bridge to surgery is recommended. Given high mortality, suboptimal
surgical results and many patients not being eligible for surgery, interventional percutaneous VSR umbrella device closure
has been developed. Results of interventional VSR closure suggest a similar outcome as surgery. How to close the VSR should
be based on a heart team decision.
FREE WALL RUPTURE

• Myocardial rupture is a dramatic complication of MI that is most likely to occur during the first week after the onset of
symptoms. The clinical presentation typically is a sudden loss of pulse, blood pressure, and consciousness but sinus rhythm
on ECG (pulseless electrical activity) due to cardiac tamponade.
• Free wall rupture may also result in CS due to subacute tamponade when the pericardium temporarily seals the rupture sites.
Definitive surgical repair is required.
ACUTE FULMINANT MYOCARDITIS

• Myocarditis can mimic acute MI with ST abnormalities or bundle branch block on the ECG and marked elevation of cardiac
markers. Acute myocarditis causes CS in a small proportion of cases.
• These patients are typically younger than those with CS due to acute MI and often do not have typical ischemic chest pain.
Echocardiography usually shows global LV dysfunction.
• Initial management is the same as for CS complicating acute MI but does not involve revascularization.
• Endomyocardial biopsy is recommended to determine the diagnosis and need for immunosuppressives for entities such as
giant cell myocarditis. Refractory CS can be managed with MCS.
PULMONARY EDEMA
Diagnosis
• Acute pulmonary edema usually presents with the rapid onset of dyspnea at rest, tachypnea, tachycardia, and severe
hypoxemia. Crackles and wheezing due to alveolar flooding and airway compression from peribronchial cuffing may be
audible. Release of endogenous catecholamines often causes hypertension. It is often difficult to distinguish between
cardiogenic and noncardiogenic causes of acute pulmonary edema. Echocardiography may identify systolic and diastolic
ventricular dysfunction and valvular lesions. Electrocardiographic ST elevation and evolving Q waves are usually diagnostic
of acute MI and should prompt immediate instituition of MI protocols and coronary artery revascularization therapy. Brain
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natriuretic peptide levels, when substantially elevated, support heart failure as the etiology of acute dyspnea with pulmonary
edema.
• The use of a Swan-Ganz catheter permits measurement of pulmonary capillary wedge pressure (PCWP) and helps
differentiate high-pressure (cardiogenic) from normal-pressure (non-cardiogenic) causes of pulmonary edema. PAC is
indicated when the etiology of the pulmonary edema is uncertain, when edema is refractory to therapy, or when it is
accompanied by hypotension. Data derived from use of a catheter often alter the treatment plan, but no impact on mortality
rates has been demonstrated.
Treatment
• The treatment of pulmonary edema depends on the specific etiology.
As an acute, life-threatening condition, a number of measures must be applied immediately to support the circulation, gas
exchange, and lung mechanics.
• Simultaneously, conditions that frequently complicate pulmonary edema, such as infection, acidemia, anemia, and acute
kidney dysfunction, must be corrected.
SUPPORT OF OXYGENATION AND VENTILATION

• Patients with acute cardiogenic pulmonary edema generally have an identifiable cause of acute LV failure—such as
arrhythmia, ischemia/infarction, or myocardial decompensation that may be rapidly treated, with improvement in gas
exchange.
• In contrast, non-cardiogenic edema usually resolves much less quickly, and most patients require mechanical ventilation.
Oxygen Therapy Support of oxygenation is essential to ensure adequate O2 delivery to peripheral tissues, including the heart.
Generally the goal is O2 saturation of ≥92%, but very high saturation (>98%) may be detrimental.
Positive-Pressure Ventilation Pulmonary edema increases the work of breathing and the O2 requirements of this work, imposing a
significant physiologic stress on the heart. When oxygenation or ventilation is not adequate in spite of supplemental O2, positive-
pressure ventilation by face or nasal mask or by endotracheal intubation should be initiated. Noninvasive ventilation can rest the
respiratory muscles, improve oxygenation and cardiac function, and reduce the need for intubation. In refractory cases, mechanical
ventilation can relieve the work of breathing more completely than can noninvasive ventilation. Mechanical ventilation with positive
end-expiratory pressure can have multiple beneficial effects on pulmonary edema, as it:
(1) decreases both preload and afterload, thereby improving cardiac function;
(2) redistributes lung water from the intraalveolar to the extraalveolar space, where the fluid interferes less with gas
exchange
(3) (3) increases lung volume to avoid atelectasis.
Renal Replacement Therapy For pulmonary edema patients with refractory volume overload, metabolic acidosis (pH <7.15–7.25),
hypoxemia, and/or persistent hyperkalemia, renal replacement therapy should be considered. For patients who are hypotensive or
requiring ionotropic support, continuous renal replacement therapy usually is better tolerated than intermittent hemodialysis.
REDUCTION OF PRELOAD
• In most forms of pulmonary edema, the quantity of extravascular lung water is determined by a combination of the
pulmonary capillary pressures (PCWP), the pulmonary vascular permeability, and the intravascular volume status.
Diuretics
• The “loop diuretics” furosemide, bumetanide, and torasemide are effective in most forms of pulmonary edema, even in the
presence of hypoalbuminemia, hyponatremia, or hypochloremia.
• Furosemide is also a venodilator that rapidly reduces preload before any diuresis occurs, and is the diuretic of choice. The
initial dose of furosemide should be ≤0.5 mg/kg, but a higher dose (1 mg/kg) is required in patients with renal insufficiency,
chronic diuretic use, or hypervolemia or after failure of a lower dose. Combinations of diuretics and/or continuous infusion
are helpful to achieve the desired degree of diuresis in selected patients.
Nitrates
• Nitroglycerin and isosorbide dinitrate act predominantly as venodilators but have coronary vasodilating properties as well.
Their onset is rapid and they are effectively administered by a variety of routes.
• Sublingual nitroglycerin (0.4 mg × 3 every 5 min) is first-line therapy for acute cardiogenic pulmonary edema.
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• If pulmonary edema persists in the absence of hypotension, sublingual may be followed by IV nitroglycerin, commencing at
5–10 μg/min. IV nitroprusside (0.1–5 μg/kg per min) is a potent venous and arterial vasodilator. It is useful for patients with
pulmonary edema and hypertension, but is not recommended in states of reduced coronary artery perfusion.
• It requires close monitoring and titration using an arterial catheter for continuous blood pressure measurement.
Morphine
• Given in 2- to 4-mg IV boluses, morphine is a transient venodilator that reduces preload while relieving dyspnea and anxiety.
• These effects can diminish stress, catecholamine levels, tachycardia, and ventricular afterload in patients with pulmonary
edema and systemic hypertension. However, some registry trials showed increased mortality by use of morphine.
Angiotensin-Converting Enzyme (ACE) Inhibitors

• ACE inhibitors reduce both afterload and preload and are recommended for hypertensive patients.
• A low dose of a short-acting agent may be initiated and followed by increasing oral doses.
• In acute MI with heart failure, ACE inhibitors reduce short- and long-term mortality rates. The optimal starting point of ACE
inhibitors has not been tested so far.
Other Preload-Reducing Agents

• IV recombinant brain natriuretic peptide (nesiritide) is a potent vasodilator with diuretic properties and is effective in the
treatment of cardiogenic pulmonary edema.
• It should be reserved for refractory patients and is not recommended in the setting of ischemia or MI.
Physical Methods
• In nonhypotensive patients, venous return can be reduced by use of the sitting position with the legs dangling along the side
of the bed.
Inotropic and Inodilator Drugs

• The sympathomimetic amines dopamine and dobutamine (see above) are potent inotropic agents.
• The bipyridine phosphodiesterase-3 inhibitors (inodilators), such as milrinone (50 μg/kg followed by 0.25–0.75 μg/kg per
min), stimulate myocardial contractility while promoting peripheral and pulmonary vasodilation.
• Inodilators may be helpful in selected patients with cardiogenic pulmonary edema and severe LV dysfunction, but there is
little published clinical data.
Digitalis Glycosides
• Once a mainstay of treatment because of their positive inotropic action, digitalis glycosides are rarely used at present.
• However, they may be useful for control of ventricular rate in patients with rapid ventricular response to atrial fibrillation or
flutter and LV dysfunction with pulmonary edema, because they do not have the negative inotropic effects of other drugs
that inhibit atrioventricular nodal conduction.
Intraaortic Balloon Counterpulsation

• IABP may be helpful in rare instances of acute MR from infective endocarditis, but is not typically used for pulmonary edema
with CS.
Treatment of Tachyarrhythmias and Atrioventricular Resynchronization

• Sinus tachycardia or atrial fibrillation can result from elevated left atrial pressure and sympathetic stimulation. Tachycardia
itself can limit LV filling time and raise left atrial pressure further.
• Although relief of pulmonary congestion will slow the sinus rate or ventricular response in atrial fibrillation, a primary
tachyarrhythmia may require cardioversion.
• In patients with reduced LV function and without atrial contraction or with lack of synchronized atrioventricular contraction,
placement of an atrioventricular sequential pacemaker should be considered.
Reduction in Pulmonary Vascular Permeability

• At present, no clinical therapies have been demonstrated as clinically effective to reduce the “leakiness” of the pulmonary
capillaries.
Stimulation of Alveolar Fluid Clearance

• A variety of drugs and cellular therapies can stimulate alveolar epithelial ion transport and upregulate the clearance of
alveolar solute and water, but this strategy has not been proven beneficial in clinical trials thus far.
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SPECIAL CONSIDERATIONS
Risk of Iatrogenic Cardiogenic Shock
• In the treatment of pulmonary edema, vasodilators lower blood pressure, and their use, particularly in combination, may
lead to hypotension, coronary artery hypoperfusion, and shock.
• In general, patients with a hypertensive response to pulmonary edema tolerate and benefit from these medications. In
normotensive patients, low doses of single agents should be instituted sequentially, as needed.
Acute Coronary Syndromes

• Acute STEMI complicated by pulmonary edema is associated with in-hospital mortality rates of 20–40%. After immediate
stabilization, coronary artery blood flow must be reestablished rapidly.
• Early primary PCI is the method of choice; alternatively, a fibrinolytic agent should be administered. Early coronary
angiography and revascularization by PCI or CABG also are indicated for patients with non-ST elevation acute coronary
syndrome.
Extracorporeal Membrane Oxygenation (ECMO)

• For patients with acute, severe non-cardiogenic edema with a potential rapidly reversible cause, ECMO may be considered
in highly selected patients as a temporizing supportive measure to achieve adequate gas exchange with current survival to
discharge rates of 50–60%.
• Usually venovenous ECMO is used in this setting. ECMO can function as a bridge to transplantation or other interventions.
Unusual Types of Edema

• Specific etiologies of pulmonary edema may require particular therapy.
• Re-expansion pulmonary edema can develop after removal of long-standing pleural space air or fluid.
o These patients may develop hypotension or oliguria with pulmonary edema resulting from rapid fluid shifts into the
lung.
Diuretics and preload reduction are contraindicated, and intravascular volume repletion often is needed while
supporting oxygenation and gas exchange.
• High-altitude pulmonary edema often can be prevented by use of dexamethasone, calcium channel–blocking drugs, or
long-acting, inhaled β-adrenergic agonists.
o Treatment includes descent from altitude, bed rest, oxygen, and, if feasible, inhaled nitric oxide; nifedipine may also
be effective.
o For pulmonary edema resulting from upper airway obstruction, recognition of the obstructing cause is key, because
treatment then is to relieve or bypass the obstruction.
CHAPTER 299: CARDIOVASCULAR COLLAPSE, CARDIAC ARREST, AND SUDDEN CARDIAC DEATH
OVERVIEW AND DEFINITIONS
Cardiovascular collapse
• Severe hypotension from acute dysfunction of the heart or peripheral vasculature causing hypotension with resulting
cerebral hypoperfusion and loss of consciousness that can be the result of a cardiac arrhythmia, severe myocardial or
valvular dysfunction, loss of vascular tone, and/or acute disruption of venous return.
• When an effective circulation is restored spontaneously, patients present with Syncope
• If spontaneous resolution does not occur, then Cardiac Arrest occurs
• If resuscitation attempts are unsuccessful or not initiated, ultimately resulting in Death
Etiologies for cardiovascular collapse

• Benign conditions
o Vasovagal syncope
• Life-threatening conditions:
o Ventricular tachyarrhythmias
o Severe bradycardia
o Severely depressed myocardial contractility
§ Massive acute MI
§ Pulmonary embolus
o Catastrophic events interfering with cardiac function
§ Myocardial rupture with cardiac tamponade
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§ Papillary muscle rupture with torrential mitral regurgitation
Sudden cardiac arrest (SCA)

• Abrupt loss of cardiac function resulting in complete cardiovascular collapse
• Due either to an acute life-threatening cardiac arrhythmia or abrupt loss of myocardial pump function that requires
emergency medical intervention for restoration of effective circulation.
• Most SCAs occur outside the hospital,
o < 10% of these victims survive to be discharged from the hospital despite undergoing attempted resuscitation by
emergency medical services (EMS)
o Those that die prior to hospital admission, a cardiovascular cause for the arrest is often presumed based upon the
absence of evidence for a traumatic or other non-cardiac cause at the time of the arrest.
Sudden cardiac death (SCD)

• Death is classified as SCD if the patient does not survive an SCA
• Deaths that occur during hospitalization or within 30 days after resuscitated cardiac arrest are usually counted as SCDs in
epidemiologic studies.
• Includes a broader category of unexplained rapid deaths thought to be due to cardiac causes where resuscitation was not
attempted.
• In epidemiologic studies, SCD is usually defined as an unexpected death without obvious extra-cardiac cause that occurs in
association with a witnessed rapid collapse or within 1 h of the onset of symptoms.
o based on the presumption that rapid deaths are often due to an arrhythmia
• Definitive information necessary to establish the cause of death is usually not available.
• In unwitnessed cases, the definition is often further expanded to include unexpected deaths where the subject was
documented to be well when last observed within the preceding 24 h
o This expanded definition further decreases the certainty that the death was due to an arrhythmia or cardiac causes.
EPIDEMIOLOGY
DEMOGRAPHICS
• SCA and SCD are major public health problems that account for 15% of all deaths and comprise 50% of all cardiac deaths.
• Although cardiac pathology, particularly coronary heart disease (CHD), underlies the majority of SCD, up to two-thirds of all
SCD occur as the first clinical expression of previously undiagnosed heart disease.
• SCD rates have declined but not as steeply as rates for CHD in general.
• Age, gender, race, and geographic region all influence the incidence of SCD.
• SCD is rare in individuals of younger than 35 years of age (1–3 per 100,000 per year),
• SCD increases markedly with age
o Incidence of coronary artery disease (CAD), heart failure (HF), and other predisposing conditions also increase.
o The proportion of deaths that are due to SCD decreases markedly with age as other causes of death increase.
• Women have a lower incidence of SCD and SCA than men
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o Women are more likely to present with pulseless electrical activity (PEA) and to have their SCD occur at home as
compared to men.
• Black as opposed to white Americans have higher rates of SCD, are more likely to have unwitnessed arrests, to be found with
PEA, and have worse rates of survival.
• Socioeconomic disparities, with resuscitation being less likely in low-income neighborhoods, is likely a contributing factor
• Alternatively, individuals of Hispanic ethnicity appear to have lower rates of SCD, despite having a higher prevalence of
cardiac risk factors.
• Incidence of SCD may be relatively low among Asian populations as well, both within the United States and globally.
RISK FACTORS
• Preexisting CHD and HF
o Are the most prevalent predisposing cardiac conditions and are associated with four- to tenfold increases in SCD
risk
• Overt structural heart disease and/or a certain types of inherited arrhythmia syndromes
• Genetics
o A history of SCD among a first-degree relative is associated with an increased risk for SCD, and with the occurrence
of ventricular fibrillation (VF) during acute MI, but is not associated with an increased risk for acute MI.
• Obstructive sleep apnea and seizure disorders
o Due to hypoxia and/or suffocation-induced cardiac arrest
• Atrial fibrillation
o Partly, but not entirely, accounted for by its association with underlying heart disease
• Chronic kidney disease
o Annualized SCD rates approaching 5.5% in patients undergoing dialysis
o Electrolyte shifts and LVH, which are common in this population, have been suggested to play a role
• Dietary influences
o Individuals with higher intakes of polyunsaturated fatty acids, particularly n-3 fatty acids, and other components of
a Mediterranean-style diet have lower SCD risks in observational studies, possibly due to antiarrhythmic effects of
dietary components.
o Low levels of alcohol intake may be beneficial, but heavy intake (>3 drinks/day) appears to elevate risk.
• Shares many of the same risk factors with CHD and HF, including:
Hypertension Hypertension and resultant left ventricular hypertrophy (LVH) appear to be

particularly important markers of SCD risk in blacks, in whom the prevalence of
these conditions is greater.
Diabetes Strong risk factor for SCD even in patients with established CHD
Hypercholesterolemia, Serum cholesterol appears to be more strongly related to SCD at younger ages,
Obesity and the benefits of cholesterol lowering on SCD incidence have not been firmly
established.
Smoking Smoking markedly elevates risk, and smoking cessation lowers risk particularly
among individuals who have not yet developed overt CHD.
PRECIPITATING FACTORS
• SCD and cardiac arrest peaks in the morning hours and again in the later afternoon
• SCA arrests
o More likely to occur in certain locations: notable clustering around train stations, airports, and other public places
where there is significant population transit
• SCD rates
o Rates are highest during winter in the northern hemisphere and summer in the southern hemisphere
o Seasonal variability may be related to temperature and light exposure
o Acutely peak during disasters such as earthquakes and terrorist attacks
o Higher in urban areas and individuals that live near major roadways are at elevated SCD risk
o Acute elevation in SCD risk that occurs during or shortly after bouts of vigorous exertion, and men appear to be
more susceptible. Habitual exercise and training lowers this acute risk, but does not appear to eliminate it entirely.
• Exertion-associated SCDs
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o Majority of such deaths actually occur in the general “non-athlete” population

o Precipitating factor: heightened autonomic tone, which can promote ischemia and has direct pro-arrhythmia and
electrophysiologic actions that lower the threshold for VF.
CAUSES OF SUDDEN CARDIAC DEATH

UNDERLYING HEART DISEASE
• SCD is most commonly associated with underlying CAD
o ~70–75% of SCDs in white men are due to CAD,
o 40–50% of SCDs in women and blacks.
o Lower in Asian ethnicities
• Non-ischemic cardiomyopathies are the 2nd most frequent cause of SCD
o Hypertrophic
o Dilated
o Infiltrative
• Other less common causes include:
o Valvular heart disease
o Myocarditis
o Myocardial hypertrophy (often from hypertension)
o Rare primary electrical heart diseases such as the long QT and Brugada syndrome.
• On average, 5–10% of SCA victims do not have a significant cardiac abnormality at the time of autopsy or after extensive
premortem cardiac evaluation, and this also varies by gender and race.
CARDIAC RHYTHMS AND SUDDEN DEATH

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• The initial rhythm found when EMS arrive at the scene of an out-of hospital cardiac arrest is an important indication of the
potential cause of the arrest and of the prognosis
• PEA or asystole: most common
• The rhythm at the time of EMS arrival may not reflect the rhythm that initially precipitated the SCA because:
o Vast majority of cardiac arrests are not monitored at the time of collapse
o Arrhythmias are inherently unstable once hemodynamic collapse occurs
o VF and primary bradycardias can degenerate quickly into asystole
• VF remains a common initial rhythm.
o VF as an initial rhythm still predominates in public locations or in other situations when there is a short time between
collapse and arrival of EMS
o Decrease in VF incidence
ü Decreases in underlying CHD incidence
ü Increased used of beta blockers in CHD
ü Implantable cardioverter defibrillators (ICD) in high-risk patients
• Increase of PEA incidence over the past several years
ü Aging of the population
ü Increased prevalence of end-stage cardiovascular disease
ü Other severe comorbidities
o Older, sicker patients may be more likely to have arrests in the home and to have acute precipitants leading to PEA
(i.e., respiratory, metabolic, vascular), and/or be less likely to sustain VF up to the point of EMS arrival.
DISEASE SPECIFIC MECHANISMS

• Acute MI or transient ischemia that leads to polymorphic VT and VF
o Most common cause
• Other primary mechanisms include:
o Severe bradyarrhythmias such as heart block with a slow escape rhythm
o PEA due to a massive MI or associated myocardial rupture.
• Areas of ventricular scar from prior infarcts increase the predisposition to reentrant VT, which often degenerates to VF
o Once patients have suffered a MI, their risk of SCD elevates up to tenfold, with the highest absolute rates in the first
30 days after MI.
• The mechanisms underlying SCD vary at different time points after MI
o Non-arrhythmic causes such as myocardial rupture and/or extensive reinfarction predominating early: within the
first 1–2 months
o Ischemic polymorphic VT and/or scar-related ventricular arrhythmias prevailing: Later
o VT and sudden death: occur years after an initial MI
Cardiomyopathies and Other Forms of Structural Heart Disease

• Scar-mediated reentrant VT
o Can also occur in a host of nonischemic cardiomyopathies in which replacement fibrosis and/or inflammatory
ventricular infiltrates occur
• CHD surgical scars
o Created during corrective surgery
o Such as those performed to correct ventricular septal defects in tetralogy of Fallot, can also serve as the substrate
for ventricular re-entry.
• Other common predisposing processes
o LVH, ventricular stretch due to fluid overload, and cardiomyocyte dysfunction can result in electrical heterogeneity
and other electrophysiologic changes that predispose to ventricular arrhythmias
§ Ion channel alterations that prolong action potential duration, impair cellular calcium handling, and
diminished cellular coupling.
§ These processes occur in a wide variety of diseases associated with depressed ventricular function and/or
hypertrophy, including CAD, valvular heart disease, myocarditis, and non-ischemic cardiomyopathies.
Absence of Structural Heart Disease
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Ventricular Fibrillation Due to an inherited ion channel abnormality, as in the long QT and Brugada syndromes
Rapid atrial fibrillation Associated with the Wolff-Parkinson-White syndrome
Polymorphic VT Due to drugs that prolong the QT interval (Drug toxicities)
PEA Due to Pulmonary emboli, exsanguination, or the terminal phase of respiratory arrest
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MANAGEMENT OF CARDIAC ARREST

• Out-of-hospital chain of survival
1. Initial evaluation and recognition of the SCA
2. Rapid initiation of cardiopulmonary resuscitation (CPR) with an emphasis on chest compressions
3. Defibrillation as quickly as possible usually with an automatic external defibrillation applied by the lay rescuer or EMT
4. Basic and advanced EMS; and
5. Advanced life support and postcardiac arrest care
• Achieve the return of spontaneous circulation
o Initial goal of resuscitation
• Success is related to:
ü Time between collapse and initiation of resuscitation decreasing markedly after 5 min,
ü Rhythm at the time of EMT arrival, being best for VT (25–30%), worse for VF and poor for PEA and asystole (<5%)
o Determined by the clinical state and comorbidities of the victim prior to the arrest:
worse for those with severe disease, such as cardiogenic shock, prior to arrest.
INITIAL EVALUATION AND INITIATION OF CPR
• Response: The rescuer should check for a response from the victim, shout for help, and call or ask someone else to call their
local emergency number (e.g., 911)
o Ideally on a cell phone that can be placed on speaker mode at the patient’s side such that the responding dispatcher
can provide instructions and queries to the rescuer.
• Airway: Consideration of aspiration or airway obstruction is important
o If suspected, a Heimlich maneuver may dislodge the obstructing body.
• Pulse: A trained healthcare provider would also check for a pulse
o Taking no longer than 10 sec so as not to delay initiation of chest compressions
• Breathing: Assess breathing
o Gasping respirations and brief seizure activity are common during SCA and may be misinterpreted as breathing and
responsiveness.
• Chest compressions: should be initiated without delay
o Administered at a rate of 100–120/min depressing the sternum by 5 cm (2 in.)
o Allow full chest recoil between compressions.
o Chest compressions generate forward cardiac output with sequential filling and emptying of the cardiac chambers,
with competent valves maintaining forward direction of flow.
o Interruption of chest compressions should be minimized to reduce end organ ischemia.
• Ventilation: Ventilation may be administered
o Trained rescuer is present: Two breaths for every 30 compressions
o For lay rescuers without training: chest compressions alone (“hands only CPR”) are more likely to be effectively
applied and of similar benefit.
o If a second rescuer is present: they should be sent to seek out an automatic external defibrillator (AED), which
are now widely available in many public areas.
RHYTHM-BASED MANAGEMENT
• The rapidity with which defibrillation/cardioversion is achieved is an important predictor of outcome.
• Defibrillator: most often an AED, should be applied as soon as available.
1. Once patches are applied to the chest, a brief pause in chest compressions is required to allow the AED to record
the rhythm.
2. An AED will advise a shock if the recorded rhythm meets criteria for VF or VT.
3. Chest compressions are continued while the defibrillator is being charged.
4. As soon as a diagnosis of VF or VT is established, a biphasic waveform shock of 150–200 J should be delivered.
5. Chest compressions are resumed immediately and continue for 2 min until the next rhythm check.
6. If VT/VF is still present, a second maximal energy shock is delivered.
o This sequence is continued until personnel to administer advanced life support are available, or return of
spontaneous circulation is achieved.
• Electrocardiogram (ECG) rhythm strips: produced by the AED should be retrieved
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o The initial rhythm can be an important consideration in determining the cause of the arrest and to guide further
therapy and evaluation if resuscitation is successful.
• When Advanced Cardiac Life Support is available:
o An intravenous or intraosseous line is established for administration of medication
o Consideration given to placement of an advanced airway (endotracheal tube or supraglottic airway device).
o Epinephrine 1 mg every 3–5 min may be administered intravenously or intraosseously.
• Arterial blood gas analysis
o Confirmation that acidosis and hypoxia are adequately addressed
o Done when circulation is not restored or the patient is less than fully conscious despite return of circulation
o If metabolic acidosis persists after successful defibrillation and with adequate ventilation, 1 meq/kg NaHCO3 may
be administered.
• The cardiac rhythm guides resuscitation when monitoring is available.
o VT is treated with external shocks
ü Synchronized to the QRS when VT is monomorphic, and
ü Asynchronous shocks for polymorphic VT or VF
o If VT/VF recurs after one or more shocks
ü Amiodarone 300 mg can be administered as a bolus via intravenous or intraosseous route in the hope that
arrhythmia recurrence will be prevented after the next shock, followed by a 150 mg bolus if the arrhythmia
recurs.
o If Amiodarone fails
ü Lidocaine can be administered.
• Consideration of etiology should also guide therapy
Etiology Therapy
Recurrent VT/VF due to ongoing Emergent coronary angiography and revascularization
myocardial ischemia or infarction
QT prolongation causing the polymorphic Administration of magnesium
VT torsades des pointes
Hyperkalemia Respond to administration of calcium, while other measures are
implemented to reduce serum K.
PEA/asystole CPR, ventilation, and administration of epinephrine
Causes of PEA/asystole that require specific therapy:
airway obstruction hypoxia, hypovolemia, acidosis, hyperkalemia,
hypothermia, toxins, cardiac tamponade, tension pneumothorax,
pulmonary embolism, and MI
Opiate overdose Administration of Naloxone
POSTCARDIAC ARREST ACUTE MANAGEMENT

• Following restoration of effective circulation, the possibility of acute MI should be immediately assessed.
o Emergent coronary angiography with percutaneous angioplasty and stenting.
• Angiography should also be considered if an acute coronary syndrome is suspected, even if ST segment elevation is absent
• Decisions regarding which patients without ST segment elevation should undergo urgent angiography are complex
o Consider hemodynamic or electrical instability, evidence of ongoing ischemia, comorbidities, and overall prognosis
are taken into consideration.
• Hemodynamic instability is often present following resuscitation and further ischemic end organ damage is a major
consideration.
• Optimizing ventilation with consideration of acidosis, hypoxemia, and electrolyte abnormalities is important.
• Maintaining systolic BP at >90 mmHg, mean BP >65 mmHg is desirable and may require administration of vasopressors and
adjustment of volume status.
• Potentially treatable reversible causes including hyperkalemia, severe hypokalemia, and drug toxicity with QT prolongation
causing torsades des pointes should be identified and treated
• After stable spontaneous circulation is achieved, brain injury due to ischemia and reperfusion is a major determinant of
survival and accounts for over two-thirds of deaths.
o The probability of successful neurologic recovery decreases rapidly with time between collapse and restoration of
circulation and is <30 % at 5 mins in the absence of bystander CPR.
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o The time between collapse and restoration of circulation is generally imprecise

• Therapeutic hypothermia (targeted temperature management)
o Improve the likelihood of survival and neurologic recovery in patients who present with shockable (VT or VF)
rhythms
o Recommended for all cardiac arrest patients who remain comatose, regardless of presenting rhythm, who have lack
of purposeful response to verbal commands following return of spontaneous circulation
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SECTION 3 NEUROLOGIC CRITICAL CARE

300. COMA
• Coma is among the most common neurologic emergencies encountered in general medicine and requires an organized
approach
• The vegetative state signifies an awake-appearing but nonresponsive state often in a patient who has emerged from coma.
In the vegetative state, the eyelids may open periodically, giving the appearance of wakefulness
• Akinetic mutism refers to a partially or fully awake state in which the patient is able to form impressions and think, as
demonstrated by later recounting of events, but remains virtually immobile and mute. The condition results from damage in
the regions of the medial thalamic nuclei or the frontal lobes (particularly lesions situated deeply or on the orbitofrontal
surfaces) or from extreme hydrocephalus
THE ANATOMY AND PHYSIOLOGY OF COMA

• Almost all instances of coma can be traced to either:
o widespread abnormalities of the cerebral hemispheres
or to
o reduced activity of a special thalamocortical alerting
system termed the reticular activating system (RAS)
which is diffusely located in the brainstem.
• Coma Due to Cerebral Mass Lesions and Herniation
Syndromes
o In the most common form of herniation, brain tissue is
displaced from the supratentorial to the infratentorial
compartment through the tentorial opening; this is
referred to as transtentorial herniation.
o Uncal transtentorial herniation refers specifically to impaction of the anterior medial temporal gyrus (the uncus) into the
tentorial opening just anterior to and adjacent to the midbrain.
o Lateral displacement of the midbrain may compress the opposite cerebral peduncle against the tentorial edge, producing
a Babinski sign and hemiparesis contralateral to the hemiparesis that resulted from the mass (the Kernohan-Woltman sign)
o Central transtentorial herniation denotes a symmetric downward movement of the thalamic structures through the tentorial
opening with compression of the upper midbrain.
o Other forms of herniation include transfalcial herniation (displacement of the cingulate gyrus under the falx and across the
midline, and foraminal herniation (downward forcing of the cerebellar tonsils into the foramen magnum, which causes early
compression of the medulla, respiratory arrest, and death.
o In cases of acutely enlarging masses, horizontal displacement of the pineal gland (often calcified in adults) of 3–5 mm is
generally associated with drowsiness, 6–8 mm with stupor, and >9 mm with coma
• Coma Due to Metabolic Disorders and Toxins
o Many systemic metabolic abnormalities cause coma by interrupting the delivery of energy substrates (e.g., oxygen,
glucose) or by altering neuronal excitability (drugs and alcohol, anesthesia, and epilepsy).
o These are some of the most common causes of coma in large case series.
o The metabolic abnormalities that produce coma may, in milder forms, induce an acute confusional state.
o Thus, in metabolic encephalopathies, clouded consciousness and coma are in a continuum.
• Epileptic Coma
o Generalized electrical seizures are associated with coma, even in the absence of motor convulsions (nonconvulsive
status epilepticus).
o The postictal state produces continuous, generalized slowing of the background EEG activity similar to that of metabolic
encephalopathies.
o It typically lasts for a few minutes, but in some cases can be prolonged for hours or even rarely for days
• Coma Due to Widespread Damage to the Cerebral Hemispheres
o This category, comprising a number of unrelated disorders, results from extensive bilateral structural cerebral damage
that simulates a metabolic disorder.
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o Hypoxia-ischemia is perhaps the best characterized and one in which it is not possible initially to distinguish the acute
reversible effects of oxygen deprivation of the brain from the subsequent effects of anoxic neuronal damage.
o Diffuse white matter damage from cranial trauma or inflammatory demyelinating diseases can cause a similar coma
syndrome.

HISTORY
• The cause of coma may be immediately evident as in cases of trauma, cardiac arrest, or observed drug ingestion.
GENERAL PHYSICAL EXAMINATION

• Fever suggests a systemic infection, bacterial meningitis, encephalitis, heat stroke, neuroleptic malignant syndrome,
malignant hyperthermia due to anesthetics, or anticholinergic drug intoxication
• The funduscopic examination can detect increased intracranial pressure (ICP) (papilledema), subarachnoid hemorrhage
(subhyaloid hemorrhages), and hypertensive encephalopathy (exudates, hemorrhages, vessel-crossing changes,
papilledema).
• Cutaneous petechiae suggest thrombotic thrombocytopenic purpura, meningococcemia, or a bleeding diathesis associated
with an intracerebral hemorrhage.
• Cyanosis and reddish or anemic skin coloration are other indications of an underlying systemic disease or carbon monoxide
as responsible for the coma
NEUROLOGIC EXAMINATION
• The patient should first be observed without intervention by the examiner.
• Tossing about in the bed, reaching up toward the face, crossing legs, yawning, swallowing, coughing, or moaning reflect a
drowsy state that is close to normal awakeness.
• Lack of restless movements on one side or an outturned leg suggests hemiplegia. Subtle, intermittent twitching movements
of a foot, finger, or facial muscle may be the only sign of seizures.
LEVEL OF AROUSAL
• Tickling the nostrils with a cotton wisp is a moderate stimulus to arousal—all but deeply stuporous and comatose patients
will move the head away and arouse to some degree.
• An even greater degree of responsiveness is present if the patient uses his hand to remove an offending stimulus.
• Pressure on the knuckles or bony prominences and pinprick stimulation are humane forms of noxious stimuli; pinching the
skin causes unsightly ecchymoses and is generally not necessary but may be useful in eliciting abduction withdrawal
movements of the limbs
BRAINSTEM REFLEXES
• The most important brainstem reflexes that are examined are pupillary size and reaction to light, spontaneous and elicited
eye movements, corneal responses, and the respiratory pattern.
Pupillary Signs
o Pupillary reactions are examined with a bright, diffuse light.
o Reactive and round pupils of midsize (2.5–5 mm) essentially exclude upper midbrain damage, either primary or
secondary to compression
Respiratory Patterns
o These are of less localizing value in comparison to other brainstem signs.
o Shallow, slow, but regular breathing suggests metabolic or drug depression.
o Cheyne-Stokes respiration in its typical cyclic form, ending with a brief apneic period, signifies bihemisphere damage or
metabolic suppression and commonly accompanies light coma
LABORATORYSTUDIESAND IMAGING
• The studies that are most useful in the diagnosis of coma are chemical-toxicologic analysis of blood and urine, cranial CT or
MRI, EEG, and CSF examination.
• Arterial blood gas analysis is helpful in patients with lung disease and acid-base disorders
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• The EEG provides clues in metabolic or drug-induced states but is rarely diagnostic.
DIFFERENTIAL DIAGNOSIS OF COMA

• The causes of coma can be divided into three broad categories: cases without focal neurologic signs (e.g., metabolic and toxic
encephalopathies); cases with prominent focal signs (e.g., stroke, cerebral hemorrhage); and meningitis syndromes,
characterized by fever or stiff neck and an excess of cells in the spinal fluid (e.g., bacterial meningitis, subarachnoid
hemorrhage, encephalitis).
• Causes of sudden coma include drug ingestion, cerebral hemorrhage, trauma, cardiac arrest, epilepsy, and basilar artery
occlusion.
• Coma that appears sub acutely is usually related to a preexisting medical or neurologic problem or, less often, to secondary
brain swelling surrounding a mass such as tumor or cerebral infarction.
BRAIN DEATH
• This is a state of irreversible cessation of all cerebral and brainstem function with preservation of cardiac activity and
maintenance of respiratory and somatic function by artificial means.
• Brain death is the only type of brain damage recognized as morally, ethically, and legally equivalent to death.
• Some period of observation, usually 6–24 h, is recommended, during which the clinical signs of brain death are sustained.
• It is advisable to delay clinical testing for at least 24 h if a cardiac arrest has caused brain death or if the inciting disease is not
known
TREATMENT OF COMA
• The immediate goal in a comatose patient is prevention of further nervous system damage. Hypotension, hypoglycemia,
hypercalcemia, hypoxia, hypercapnia, and hyperthermia should be corrected rapidly.
• An oropharyngeal airway is adequate to keep the pharynx open in a drowsy patient who is breathing normally.
• Tracheal intubation is indicated if there is apnea, upper airway obstruction, hypoventilation, or emesis, or if the patient is at
risk for aspiration. Mechanical ventilation is required if there is hypoventilation or a need to induce hypocapnia in order to
lower ICP
301. SEVERE ACUTE ENCEPHALOPATHIES AND CRITICAL CARE WEAKNESS

• Life-threatening neurologic illness
• Neurologic critical care focuses on preservation of neurologic tissue and prevention of secondary brain injury caused by
ischemia, hemorrhage, edema, herniation, and elevated intracranial pressure (ICP).
• Encephalopathy
o general term describing brain dysfunction that is diffuse, global, or multi-focal. Severe acute encephalopathies
represent a group of various disorders due to different neurological or systemic etiologies, but that share the common
themes of primary and secondary brain injury.
PATHOPHYSIOLOGY
Brain Edema
» Brain Edema Swelling, or edema, of brain tissue occurs with many types of brain injury.
» 2 principal types of Edema
1. Vasogenic edema
▪ Refers to the influx of fluid and solutes into the brain through an incompetent blood-brain barrier (BBB).
▪ The BBB may be compromised in ischemia, trauma, infection, and metabolic derangements, and typically
develops rapidly following injury.
2. Cytotoxic edema
▪ Results from cellular swelling, membrane breakdown, and ultimately cell death.
» Clinically significant brain edema - usually a combination of vasogenic and cytotoxic components.
» Edema can lead to:
▪ Increased ICP → ischemia of impaired perfusion
▪ Tissue shifts and brain displacement or herniation from focal processes → injury by mechanical distention and
compression
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Ischemic Cascade and Cellular Injury

• Inadequate delivery of oxygen and glucose → ischemic cascade
is initiated
• Release of glutamate (excitatory amino acids) → influx of
calcium and sodium ions → disrupt cellular homeostasis
• ↑ intracellular calcium → activate proteases and lipases →
lipid peroxidation and free radical–mediated cell membrane
injury → Cytotoxic edema → necrotic cell death and tissue
infarction occur
• This pathway to irreversible cell death is common to ischemic
stroke, global cerebral ischemia, and traumatic brain injury.
• Penumbra
o Areas of ischemic brain tissue that have not yet undergone
irreversible infarction, potentially salvageable if ischemia can
be reversed.
o Systemic hypotension and hypoxia → further reduce
substrate delivery to vulnerable brain tissue → fever,
seizures, and hyperglycemia → can increase cellular
metabolism → outstripping compensatory processes.
o These events are known as secondary brain insults because
they lead to exacerbation of the primary brain injury.
o Fundamental goals of management are prevention,
identification, and treatment of secondary brain insults.
• Apoptosis
o Alternative pathway of cellular injury
o This programmed cell death may occur in ischemic stroke,
global cerebral ischemia, traumatic brain injury, and possibly
intracerebral hemorrhage.
o Apoptotic cell death occurs without cerebral edema and
therefore is often not seen on brain imaging.
Cerebral Perfusion and Autoregulation

• Brain tissue requires constant perfusion in order to ensure
adequate delivery of substrate.
• Cerebral perfusion pressure (CPP)
o Mean systemic arterial pressure (MAP) minus the ICP
o Provides the driving force for circulation across the capillary
beds of the brain.
• Autoregulation
o Physiologic response whereby cerebral blood flow (CBF) is
regulated via alterations in cerebrovascular resistance to
maintain perfusion over wide physiologic changes such as
neuronal activation or changes in hemodynamic function.
o If systemic blood pressure drops → vasodilation of
arterioles in the brain → cerebral perfusion is preserved
o Prevent hyperperfusion → arteriolar vasoconstriction at
high systemic pressures → fairly constant perfusion across a
wide range of systemic blood pressures. (Fig. 301-1)
o At extreme MAP or CPP (high or low), flow becomes directly
related to perfusion pressure.
o Autoregulatory changes occur in the microcirculation
mediated by vessels below the resolution
• Cerebral blood flow (CBF)
o Strongly influenced by pH and Paco2
o ↑CBF - hypercapnia and acidosis
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o ↓CBF - hypocapnia and alkalosis because of pH related changes in cerebral vascular resistance.
o Basis for the use of hyperventilation to lower ICP, and effect on ICP is mediated through a decrease in both CBF and
intracranial blood volume.
o Cerebral autoregulation is a complex process critical to the normal homeostatic functioning of the brain, and this
process may be disordered focally and unpredictably in disease states such as traumatic brain injury and severe focal
cerebral ischemia.

Severe Brain Dysfunction
• Stabilize basic respiratory, cardiac, and hemodynamic parameters.
• Significant barriers to neurologic assessment include endotracheal intubation and the use of sedative or paralytic agents to
facilitate procedures.
• Impaired level of consciousness is common in critically ill patients thus determine the cause of dysfunction
▪ Diffuse process (usually metabolic)
Ex: Metabolic encephalopathies related to organ failure, drug overdose, or hypoxia-ischemia.
▪ Focal process (usually structural)
Ex: Ischemic and hemorrhagic stroke and traumatic brain injury, especially with intracranial
hematomas.
• These two categories of disorders have fundamentally different causes, treatments, and prognoses, the initial focus is on
making this distinction rapidly and accurately.
• Minor focal deficits may be present in metabolic encephalopathies. However, the finding of prominent focal signs such as
pupillary asymmetry, hemiparesis, gaze palsy, or visual field deficit should suggest the possibility of a structural lesion.
• Neuroimaging
− All patients with a decreased level of consciousness associated with focal findings
− All patients with coma of unknown etiology
− May reveal evidence of edema and mass effect.
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− Any suggestion of trauma should alert the possibility of cervical spine injury and prompt an imaging evaluation using
CT or MRI.
▪ Computed tomography (CT) scanning
− Most appropriate initial study because it can be performed quickly in critically ill patients
− Demonstrates hemorrhage, hydrocephalus, and intracranial tissue shifts well.
▪ Magnetic resonance imaging (MRI)
− More specific information in acute ischemic stroke (diffusion-weighted imaging [DWI]).
▪ CT or MRI angiography or venography may suggest arterial occlusion or cerebral venous thrombosis
▪ Noncontrast CT scan of the brain may reveal a hyperdense basilar artery indicating thrombus in the vessel, and
subsequent CT or MR angiography can assess basilar artery patency. Acute brainstem ischemia due to basilar artery
thrombosis may cause brief episodes of spontaneous extensor posturing superficially resembling generalized seizures.
Coma of sudden onset, accompanied by these movements and cranial nerve abnormalities, necessitates emergency
imaging.
• Other diagnostic tools:

▪ Electroencephalography (EEG)
− EEG of metabolic encephalopathy is generalized slowing.
− Help exclude inapparent seizures, especially non-convulsive status epilepticus.
− Untreated continuous or frequently recurrent seizures may cause neuronal injury, making the diagnosis and
treatment of seizures crucial in this patient group.
▪ Lumbar puncture (LP)

− May be necessary to exclude infectious or inflammatory processes, and an elevated opening pressure may be an
important clue to cerebral venous sinus thrombosis.
− Coma or profound encephalopathy - perform a neuroimaging study prior to LP.
− Bacterial meningitis is suspected - LP performed first or antibiotics may be empirically administered before the
diagnostic studies are completed.
− EEG and LP are most useful when the mechanism of the altered level of consciousness is uncertain; they are not
routinely performed for diagnosis in clear-cut cases of stroke or traumatic brain injury.
▪ Laboratory assessment
− Critically ill patients - include assessment of sodium and calcium,, glucose, renal and hepatic function, complete
blood count, and coagulation.
− Serum or urine toxicology screens should be performed in patients with encephalopathy of unknown cause.
• Monitoring of ICP
− Important in primary neurologic disorders, such as stroke or traumatic brain injury, who are at significant risk for
secondary brain injury due to elevated ICP and decreased CPP.
− Included are patients with the following:
▫ Severe traumatic brain injury (Glasgow Coma Scale
[GCS] score ≤8)
▫ Large tissue shifts from supratentorial ischemic or
hemorrhagic stroke
▫ Hydrocephalus from subarachnoid hemorrhage (SAH),
intraventricular hemorrhage, or posterior fossa stroke
▫ Fulminant hepatic failure - elevated ICP may be
treated with barbiturates or, eventually, liver
transplantation.
− Ventriculostomy is preferable to ICP monitoring devices that
are placed in the brain parenchyma, because it allows CSF
drainage as a method of treating elevated ICP.
− However, parenchymal ICP monitoring is most appropriate
for patients with diffuse edema and small ventricles (which
may make ventriculostomy placement more difficult) or any
degree of coagulopathy (in which ventriculostomy carries a
higher risk of hemorrhagic complications) (Fig 301-2).
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TREATMENT OF ELEVATED ICP

• Elevated ICP may occur in head trauma, intracerebral hemorrhage,
SAH with hydrocephalus, and fulminant hepatic failure. By the time
elevated ICP occurs, intracranial compliance is severely impaired
so any small increase in the volume of CSF, intravascular blood,
edema, or a mass lesion may result in a significant increase in ICP
and a decrease in cerebral perfusion. This is a fundamental
mechanism of secondary ischemic brain injury that requires
immediate attention.
• In general, ICP should be maintained at <20 mmHg and CPP should
be maintained at ≥60 mmHg.
• Interventions to lower ICP are based on the underlying mechanism
responsible for the elevated ICP
• For example:
o In hydrocephalus from SAH, the principal cause of
elevated ICP is impairment of CSF drainage, ventricular
drainage of CSF is likely to be sufficient and most
appropriate.
o In head trauma and stroke, cytotoxic edema may be
most responsible, and the use of osmotic agents such as
mannitol or hypertonic saline becomes an appropriate
early step.
• As elevated ICP may cause tissue ischemia, and, if cerebral
autoregulation is intact, the resulting vasodilation can lead to a
cycle of worsening ischemia. Paradoxically, administration of vasopressor agents to increase mean arterial pressure may
actually lower ICP by improving perfusion, thereby allowing autoregulatory vasoconstriction as ischemia is relieved and
ultimately decreasing intracranial blood volume.
• Early signs of elevated ICP - drowsiness and diminished level of consciousness.
• Hypotonic IV fluids should be avoided
• Elevation of the head of the bed is recommended.
• Observed for risk of aspiration and compromise of the airway as the level of alertness declines.
• Coma and unilateral pupillary changes - late signs and require immediate intervention.
• Intubation and hyperventilation - emergent treatment of elevated ICP causing vasoconstriction and reduces cerebral blood
volume.
• Hyperventilation is best administered only for short periods of time until a more definitive treatment can be instituted to
avoid provoking or worsening cerebral ischemia. The effects of hyperventilation on ICP are short-lived, often lasting only for
several hours because of the buffering capacity of the cerebral interstitium, and rebound elevations of ICP may accompany
abrupt discontinuation of hyperventilation.
• As the level of consciousness declines to coma, if a ventriculostomy device is in place, direct drainage of CSF to reduce ICP
is possible.
• High-dose barbiturates, decompressive hemi-craniectomy, and hypothermia are sometimes used for refractory elevations
of ICP, although these have significant side effects and only decompressive hemicraniectomy.
SECONDARY BRAIN INSULTS

• Primary brain injuries (trauma or stroke) are at risk for ongoing secondary ischemic brain injury.
• Secondary brain injury
− can be a major determinant of a poor outcome
− Most secondary brain injury is mediated through other clinical events that exacerbate the ischemic cascade already
initiated by the primary brain injury. Although elevated ICP may lead to secondary ischemia.
− Episodes of secondary brain insults are usually not associated with apparent neurologic worsening. Rather, they lead
to cumulative injury limiting eventual recovery, higher mortality rate or worsened long-term functional outcome.
− Close monitoring of vital signs is important, as is early intervention to prevent secondary ischemia.
− Avoiding hypotension and hypoxia is critical, as SBP <90 mmHg as short as 10 min in duration have been shown to
adversely influence outcome after traumatic brain injury.
− Stroke or head trauma who do not require ICP monitoring, close attention to adequate cerebral perfusion is
warranted.
− Hypoxia (O2Sat <90%) with hypotension - also leads to secondary brain injury.
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− Fever and hyperglycemia - worsen experimental ischemia and have been associated with worsened clinical outcome after
stroke and head trauma.
− Fever - Aggressive control is the goal of normothermia but difficult to achieve with antipyretic medications and cooling
blankets. Intravascular temperature control devices for the management of refractory fever is under investigation.
− Hyperglycemia - IV insulin infusion for control to better regulation of serum glucose levels than SC insulin. Goal is to
maintain serum glucose level at <10.0 mmol/L (<180 mg/dL), although episodes of hypoglycemia appear equally
detrimental and the optimal targets remain uncertain.
− New cerebral monitoring tools to continuously evaluate brain tissue oxygen tension, CBF, and metabolism (via
microdialysis) may further improve the management of secondary brain injury.
CRITICAL CARE DISORDERS OF THE CNS

HYPOXIC-ISCHEMIC ENCEPHALOPATHY
• occurs from lack of delivery of oxygen to the brain because of extreme hypotension (hypoxia-ischemia) or hypoxia due to
respiratory failure.
• Causes
o myocardial infarction,
o cardiac arrest,
o shock,
o asphyxiation,
o paralysis of respiration,
o carbon monoxide or cyanide poisonining
• sometimes termed histotoxic hypoxia because they cause a direct impairment of the respiratory chain.
Clinical Manifestations
• Mild degrees of pure hypoxia,
o occur at high altitudes
o cause impaired judgment, inattentiveness, motor incoordination, and, at times, euphoria.
o The brain is more tolerant to pure hypoxia than it is to hypoxia-ischemia.
• hypoxia-ischemia
o occurs with circulatory arrest
o consciousness is lost within seconds.
o If circulation is restored within 3–5 min, full recovery may occur, but if hypoxia-ischemia lasts beyond 3–5 min, some
degree of permanent cerebral damage often results.
o some patients make a relatively full recovery after even 8–10 min of global cerebral ischemia.
• Clinical examination at different time points after a hypoxic-ischemic insult (especially cardiac arrest) is useful in assessing
prognosis for long-term neurologic outcome.
• The prognosis is better for patients with intact brainstem function, as indicated by normal pupillary light responses and intact
oculocephalic (doll’s eyes), oculovestibular (caloric), and corneal reflexes.
o Absence of these reflexes and the presence of persistently dilated pupils that do not react to light are grave prognostic
signs.
o A low likelihood of a favorable outcome from hypoxic-ischemic coma is strongly suggested by an absent pupillary light
reflex or extensor or absent motor response to pain on day 3 following the injury, excluding patients with metabolic
disturbances and those treated with high-dose barbiturates or hypothermia, which confound interpretation of these signs.
o Electrophysiologically, the bilateral absence of the N20 component of the somatosensory evoked potential (SSEP) in the
first several days also conveys a poor prognosis.
§ the presence of a burst-suppression pattern of myoclonic status epilepticus on EEG or a nonreactive EEG is
associated with a low likelihood of good functional outcome.
o very elevated serum level (>33 μg/L) of the biochemical marker neuron-specific enolase (NSE) within the first 3 days is
indicative of brain damage after resuscitation from cardiac arrest and predicts a poor outcome.
• prognostication after cardiac arrest encourage the use of a multimodal approach that includes these diagnostic tests, along
with CT or MRI neuroimaging, in conjunction with clinical neurological assessment.
• administration of mild hypothermia after cardiac arrest may affect the time points when clinical and electrophysiologic
predictors become reliable in identifying patients with a very low likelihood of clinically meaningful recovery.
• sufficient time from injury is important to ensure accuracy of prognostic assessment.
• Long-term consequences of hypoxic-ischemic encephalopathy
persistent coma or a vegetative state, dementia, visual agnosia, parkinsonism, choreoathetosis, cerebellar ataxia, myoclonus,
seizures, and an amnestic state, which may be a consequence of selective damage to the hippocampus.
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Pathology
• Principal histologic findings are extensive multifocal or diffuse laminar cortical necrosis, with frequent involvement of the
hippocampus.
• Hippocampal CA1 neurons are vulnerable to even brief episodes of hypoxia-ischemia, perhaps explaining why selective
persistent memory deficits may occur after brief cardiac arrest.
• Scattered small areas of infarction or neuronal loss may be present in the basal ganglia, hypothalamus, or brainstem.
• extensive bilateral thalamic scarring may affect pathways that mediate arousal àpersistent vegetative state.
• watershed infarcts, occurs at the distal territories between the major cerebral arteries and can cause cognitive deficits,
including visual agnosia, and weakness that is greater in proximal than in distal muscle groups.
Diagnosis
• Diagnosis is based on the history of a hypoxic-ischemic event such
as cardiac arrest. Blood pressure <70 mmHg systolic or Pao2 <40
mmHg is usually necessary.
• Carbon monoxide intoxication can be confirmed by measurement
of carboxyhemoglobin and is suggested by a cherry red color of
the venous blood and skin, although the latter is an inconsistent
clinical finding.
TREATMENT
Hypoxic-Ischemic Encephalopathy
• Treatment should be directed at restoration of normal cardiore-
spiratory function.
ü securing a clear airway,
ü ensuring adequate oxygenation and ventilation,
ü restoring cerebral perfusion, whether by cardiopulmonary resuscitation, fluid, pressors, or cardiac pacing.
• Hypothermia may target the neuronal cell injury cascade and has substantial neuroprotective properties in experimental
models of brain injury.
• Potential complications of hypothermia include coagulopathy and an increased risk of infection. Current guidelines
recommend TTM for cardiac arrest patients who have no meaningful response to verbal commands after return of
spontaneous circulation, with temperature maintained constant between 32 and 36°C for at least 24 h.
• Severe carbon monoxide intoxication may be treated with hyperbaric oxygen. Anticonvulsants may be needed to control
seizures, although these are not usually given prophylactically.
• Posthypoxic myoclonus may respond to oral administration of clonazepam at doses of 1.5–10 mg daily or valproate at doses
of 300–1200 mg daily in divided doses. Myoclonic status epilepticus within 24 h after a primary circulatory arrest generally
portends a very poor prognosis, even if seizures are controlled.
• Carbon monoxide and cyanide intoxication can also cause a delayed encephalopathy.
• Little clinical impairment is evident when the patient first regains consciousness, but a parkinsonian syndrome characterized
by akinesia and rigidity without tremor may develop.
• Symptoms can worsen over months, accompanied by increasing evidence of damage in the basal ganglia as seen on both CT
and MRI.
POSTCARDIAC BYPASS BRAIN INJURY

• CNS injuries following open heart or coronary artery bypass grafting (CABG) surgery are common and include acute
encephalopathy, stroke, and a chronic syndrome of cognitive impairment.
• Pathogenesis
ü Hypoperfusion and
o neurologic complications from cerebral hypoperfusion or focal ischemia from carotid or focal intracranial stenoses
in the setting of regional hypoperfusion.
ü Embolic disease
o Embolic disease is likely the predominant mechanism of cerebral injury during cardiac surgery as evidenced by
diffusion-weighted MRI and intraoperative transcranial Doppler ultrasound studies.
o Thrombus in the heart itself as well as atheromas in the aortic arch can become dislodged during cardiac surgeries,
releasing a shower of particulate matter into the cerebral circulation.
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o Cross-clamping of the aorta, manipulation of the heart, extracorporeal circulation techniques (“bypass”),
arrhythmias such as atrial fibrillation, and introduction of air through suctioning have all been implicated as potential
sources of emboli.
o single large embolus leads to an isolated large-vessel stroke that presents with obvious clinical focal deficits.
o When there is a high burden of very small emboli, an acute encephalopathy can occur postoperatively, presenting
as either a hyperactive or hypoactive confusional state, the latter of which is frequently and incorrectly ascribed to
depression or a sedative-induced delirium.
o When the burden of microemboli is lower, no acute syndrome is recognized, but the patient may suffer a chronic
cognitive deficit.
o Postoperative infarcts in the border zones between vascular territories commonly are blamed on systemic
hypotension, but can also result from embolic disease.
METABOLIC ENCEPHALOPATHIES
• Altered mental states, variously described as confusion, delirium, disorientation, and encephalopathy, are present in many
patients with severe illness in an intensive care unit (ICU).
ü Older patients:
o vulnerable to delirium, a confusional state characterized by disordered perception, frequent hallucinations,
delusions, and sleep disturbance.
o often attributed to medication effects, sleep deprivation, pain, and anxiety.
• The presence of delirium is associated with worsened outcome in critically ill patients
ü cause of delirium is often multifactorial, resulting from organ dysfunction, sepsis, and especially the use of medications
given to treat pain, agitation, or anxiety.
ü Critically ill patients are often treated with a variety of sedative and analgesic medications, including opiates,
benzodiazepines, neuroleptics, and sedative-anesthetic medications, such as propofol.
ü patients requiring sedation: use of the centrally acting α2 agonist dexmedetomidine may reduce delirium and shorten
the duration of mechanical ventilation compared to the use of benzodiazepines such as lorazepam or midazolam.
ü The presence of family members in the ICU may also help to calm and orient agitated patients, and in severe cases, low
doses of neuroleptics (e.g., haloperidol 0.5–1 mg) can be useful.
• In the ICU setting, several metabolic causes of an altered level of consciousness predominate.
ü Hypercarbic encephalopathy can present with headache, confusion, stupor, or coma.
ü Hypoventilation syndrome occurs most frequently in patients with a history of chronic CO2 retention who are receiving
oxygen therapy for emphysema or chronic pulmonary disease
ü The elevated Paco2 leading to CO2 narcosis may have a direct anesthetic effect, and cerebral vasodilation from increased
Paco2 can lead to increased ICP.
ü Hepatic encephalopathy is suggested by asterixis and can occur in chronic liver failure or acute fulminant hepatic failure.
ü Both hyperglycemia and hypoglycemia can cause encephalopathy, as can hypernatremia and hyponatremia.
ü Confusion, impairment of eye movements, and gait ataxia are the hallmarks of acute Wernicke’s disease.
SEPSIS-ASSOCIATED ENCEPHALOPATHY
Pathogenesis
• In patients with sepsis, the systemic response to infectious agents leads to the release of circulating inflammatory mediators
that appear to contribute to encephalopathy.
• Critical illness, in association with the systemic inflammatory response syndrome (SIRS), can lead to multisystem organ
failure.
ü occur in the setting of apparent sepsis, severe burns, or trauma, even without clear identification of an infectious agent.
• the encephalopathy is not simply the result of metabolic derangements of multiorgan failure. The cytokines tumor necrosis
factor, interleukin (IL)-1, IL-2, and IL-6 are thought to play a role in this syndrome.
Diagnosis
Sepsis-associated encephalopathy
• diffuse dysfunction of the brain without prominent focal findings.
• Confusion, disorientation, agitation, and fluctuations in level of alertness are typical.
• In hemodynamic compromise, the decrease in level of alertness can be more prominent, at times resulting in coma.
• Hyperreflexia and frontal release signs such as a grasp or snout reflex can be seen.
• Abnormal movements such as myoclonus, tremor, or asterixis can occur.
• Occur in the majority of patients with sepsis and multisystem organ failure.
• Diagnosis is often difficult because of the multiple potential causes of neurologic dysfunction in critically ill patients and
requires exclusion of structural, metabolic, toxic, and infectious (e.g., meningitis or encephalitis) causes.
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• mortality rate of patients with sepsis-associated encephalopathy severe enough to produce coma approaches 50%,
• Patients dying from severe sepsis or septic shock may have elevated levels of the serum brain injury biomarker S-100β and
neuropathologic findings of neuronal apoptosis and cerebral ischemic injury.
• long-term cognitive dysfunction clinically similar to dementia is being increasingly recognized in some survivors, especially in
older patients.
OSMOTIC DEMYELINATION SYNDROME (CENTRAL PONTINE MYELINOLYSIS)

• quadriplegia and pseudobulbar palsy although less severe presentations may occur.
• Predisposing factors
o severe underlying medical illness or nutritional deficiency;
o most cases are associated with rapid correction of hyponatremia or with hyperosmolar states and clinical symptoms are
usually identified a few days after sodium correction.
o Previously termed central pontine myelinolysis,
• pathology
o demyelination without inflammation in the base of the pons, with relative sparing of axons and nerve cells.
o MRI is useful in establishing the diagnosis and may also identify partial forms that present as confusion, dysarthria, and/or
disturbances of conjugate gaze without quadriplegia. Occasional cases present with lesions outside of the brainstem.
• Therapeutic guidelines for the restoration of severe hyponatremia should aim for gradual correction, i.e., by ≤10 mmol/L (10
meq/L) within 24 h and 20 mmol/L (20 meq/L) within 48 h.
WERNICKE’S DISEASE
• Wernicke’s disease is a common and preventable disorder due to a deficiency of thiamine.
• alcoholics account for most cases
• patients with malnutrition due to hyperemesis, starvation, renal dialysis, cancer, HIV/AIDS, or rarely gastric surgery are also at
risk.
• characteristic clinical triad is ophthalmoplegia, ataxia, and global confusion.
• Most patients are profoundly disoriented, indifferent, and inattentive, although rarely they have an agitated delirium related
to ethanol withdrawal
• Ocular motor abnormalities include horizontal nystagmus on lateral gaze, lateral rectus palsy (usually bilateral), conjugate gaze
palsies, and rarely ptosis.
• Gait ataxia probably results from a combination of polyneuropathy, cerebellar involvement, and vestibular paresis.
• The pupils are usually spared, but they may become miotic with advanced disease.
• usually associated with other manifestations of nutritional disease, such as polyneuropathy.
• amblyopia or myelopathy occurs.
• Tachycardia and postural hypotension may be related to impaired function of the autonomic nervous system or to the
coexistence of cardiovascular beriberi.
• Patients who recover show improvement in ocular palsies within hours after the administration of thiamine, but horizontal
nystagmus may persist.
• Ataxia improves more slowly than the ocular motor abnormalities.
• Approximately half recover incompletely and are left with a slow, shuffling, wide-based gait and an inability to tandem walk.
• Apathy, drowsiness, and confusion improve more gradually.
• Korsakoff’s psychosis
ü As these symptoms recede, an amnestic state with impairment in recent memory and learning may become more
apparent
ü frequently persistent; the residual mental state is characterized by gaps in memory, confabulation, and disordered
temporal sequencing.
Pathology
• Periventricular lesions surround the third ventricle, aqueduct, and fourth ventricle, with
petechial hemorrhages in occasional acute cases and atrophy of the mammillary bodies
in most chronic cases.
• There is frequently endothelial proliferation, demyelination, and some neuronal loss.
• These changes may be detected by MRI
• The amnestic defect is related to lesions in the dorsal medial nuclei of the thalamus.
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Pathogenesis
• Thiamine is a cofactor of several enzymes, including transketolase, pyruvate dehydrogenase, and α-ketoglutarate dehydro-
genase.
• Thiamine deficiency produces a diffuse decrease in cerebral glucose utilization and results in mitochondrial damage.
• Glutamate accumulates due to impairment of α-ketoglutarate dehydrogenase activity and, in combination with the energy
deficiency, may result in excitotoxic cell damage.
TREATMENT
• Wernicke’s disease is a medical emergency and requires immediate administration of thiamine, in a dose of 100 mg either IV
or IM.
• The dose should be given daily until the patient resumes a normal diet and should be begun prior to treatment with IV
glucose solutions.
ü Larger doses, 100 mg four times a day or more, have been advocated by some.
ü Glucose infusions may precipitate Wernicke’s disease in a previously unaffected patient or cause a rapid worsening of
an early form of the disease. For this reason, thiamine should be administered to all alcoholic patients requiring
parenteral glucose.
HYPERPERFUSION DISORDERS (POSTERIOR REVERSIBLE ENCEPHALOPATHY SYNDROME)

• hyperperfusion likely due to endothelial dysfunction
ü hypertensive encephalopathy, eclampsia, postcarotid endarterectomy syndrome, and toxicity from calcineurin-inhibitor
and other medications
• Vasogenic edema
ü the primary process leading to neurologic dysfunction
ü two mechanisms:
o exceeding the cerebral autoregulatory threshold
leading to increased CBF TABLE 301-3 Common Etiologies of Posterior Reversible
o capillary leakage into the interstitium, or direct Encephalopathy Syndrome
impairment of the BBB • Disorders in which increased capillary pressure
• posterior portions of the brain: predilection may be due to a dominates the pathophysiology
lower threshold for autoregulatory breakthrough in the • Hypertensive encephalopathy, including secondary
posterior circulation or a vasculopathy that is more common causes such as renovascular hypertension,
in these blood vessels. pheochromocytoma, cocaine use, etc.
• divided into those caused primarily by increased pressure • Postcarotid endarterectomy syndrome
and those due to endothelial dysfunction from a toxic or • Preeclampsia/eclampsia
autoimmune etiology • Disorders in which endothelial dysfunction dominates
• Clinical presentation the pathophysiology
ü prominent headaches, • Calcineurin-inhibitor toxicity (e.g. cyclosporine,
o no specific characteristics, range from mild to tacrolimus)
severe, and may be accompanied by alterations in • Chemotherapeutic agent toxicity (e.g., cytarabine,
consciousness ranging from confusion to coma azathioprine, 5-fluorouracil, cisplatin, methotrexate,
ü seizures, tumor necrosis factor α antagonists)
o multiple types depending on the severity and • HELLP syndrome (hemolysis, elevated liver enzyme
location of the edema levels, low platelet count)
o Nonconvulsive seizures: a low threshold for • Hemolytic-uremic syndrome (HUS)
obtaining an electroencephalogram (EEG) in
these patients should be maintained
ü focal neurologic
o cortical visual loss, given the tendency of the process to involve the
occipital lobes.
o occur depending on the area affected
o the rapidity of rise is the most important risk factor.
• MRI classically exhibits the high T2 signal of edema primarily in the posterior occipital
lobes, not respecting any single vascular territory
• CT is less sensitive but may show posterior reversible encephalopathy syndrome
(PRES): a pattern of patchy hypodensity in the involved territory.
ü not always reversible or limited just to the posterior brain regions.
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ü Vessel imaging may demonstrate narrowing of the cerebral vasculature, especially in the posterior circulation; whether
this noninflammatory vasculopathy is a primary cause of the edema or occurs as a secondary phenomenon remains
unclear.
ü ancillary studies such as CSF analysis often yield nonspecific results.
ü cyclosporine, can cause this syndrome even at low doses or after years of treatment. Therefore, normal serum levels of
these medications do not exclude them as inciting agents.
• Treatment
ü judicious lowering of the blood pressure with IV agents such as labetalol or nicardipine
o If the blood pressure is very elevated, lower the MAP by ~20% initially, as further lowering of the pressure may cause
secondary ischemia and possibly infarction as pressure drops below the lower range of the patient’s autoregulatory
capability.
ü removal of the offending medication,
ü treatment of an underlying medical condition such as eclampsia.
o Seizures must be identified and controlled, often necessitating continuous EEG monitoring.
o Anticonvulsants are effective when seizure activity is identified, but in the special case of eclampsia, there is
evidence to support the use of magnesium sulfate for seizure control.
POST-SOLID ORGAN TRANSPLANT BRAIN INJURY

• Immunosuppressive medications are administered in high doses to patients after solid organ transplant, and many of these
compounds have well-described neurologic complications.
• calcineurin inhibitors
ü headache, seizures, or focal neurologic deficits
ü This neurotoxicity occurs mainly with cyclosporine and tacrolimus and can present even in the setting of normal serum
drug levels.
ü Treatment primarily involves lowering the drug dosage or discontinuing the drug.
ü Sirolimus has very few recorded cases of neurotoxicity and may be a reasonable alternative for some patients.
• OKT3-associated akinetic mutism
• Methotrexate: leukoencephalopathy, especially when it is administered intrathecally or with concurrent radiotherapy.
• Cerebrovascular complications of solid organ transplant are often first recognized in the immediate postoperative period.
• Border zone territory infarctions can occur, especially in the setting of systemic hypotension during cardiac transplant surgery.
• Embolic infarctions classically complicate cardiac transplantation, but all solid organ transplant procedures place patients at
risk for systemic emboli.
• When cerebral embolization accompanies renal or liver transplantation surgery, a careful search for right-to-left shunting
should include evaluation of the heart with agitated saline echocardiography (i.e., “bubble study”), as well as looking for
intrapulmonary shunting.
• Renal and some cardiac transplant patients often have advanced atherosclerosis, providing a risk for stroke.
• Imaging with CT or MRI should be done when cerebrovascular complications are suspected to confirm the diagnosis and to
exclude intracerebral hemorrhage, which most often occurs in the setting of coagulopathy secondary to liver failure or after
cardiac bypass procedures.
• Given that patients with solid organ transplants are chronically immunosuppressed, infections are a common concern
ü In any transplant patient with new CNS signs or symptoms such as seizure, confusion, or focal deficit, the diagnosis of a
CNS infection should be considered and evaluated through imaging (usually MRI) and possibly lumbar puncture.
ü first month posttransplant,
o bacterial organisms associated with surgical procedures and indwelling catheters.
ü second month posttransplant,
o opportunistic infections of the CNS become more common, including Nocardia and Toxoplasma species as well as
fungal infections such as aspergillosis.
o Viral infections that can affect the brain of the immunosuppressed patient, such as herpes simplex virus,
cytomegalovirus, human herpesvirus type 6 (HHV-6), and varicella, also become more common after the first month
posttransplant.
ü Beyond 6 months
o at risk for these opportunistic bacterial, fungal, and viral infections but can also suffer late CNS infectious
complications such as progressive multifocal leukoencephalopathy (PML) associated with JC virus, and Epstein-Barr
virus–driven clonal expansions of B cells resulting in posttransplant lymphoproliferative disorder or CNS lymphoma.
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CRITICAL CARE DISORDERS OF THE PERIPHERAL NERVOUS SYSTEM (PNS)

• Critical illness with disorders of the PNS arises in two contexts:
(1) primary neurologic diseases that require critical care interventions such as intubation and mechanical ventilation,
(2) secondary PNS manifestations of systemic critical illness, often involving multisystem organ failure.
• The former include acute polyneuropathies such as Guillain-Barré syndrome, neuromuscular junction disorders including
myasthenia gravis and botulism, and primary muscle disorders such as polymyositis. The latter result either from the
systemic disease itself or as a consequence of interventions and as a group are often referred to as ICU acquired weakness
(ICUAW).
• General principles of respiratory evaluation in patients with PNS involvement, regardless of cause,
ü assessment of pulmonary mechanics, such as maximal inspiratory force (MIF) and vital capacity (VC),
ü evaluation of strength of bulbar muscles.
ü endotracheal intubation should be considered when the MIF falls to below –25 cmH2O or the VC is <1 L.
o severe palatal weakness may require endotracheal intubation in order to prevent acute upper airway obstruction
or recurrent aspiration.
ü Arterial blood gases and oxygen saturation from pulse oximetry are used to follow patients with potential respiratory
compromise from PNS dysfunction.
ü intubation and mechanical ventilation should be undertaken based on clinical assessment rather than waiting until
oxygen saturation drops or CO2 retention develops from hypoventilation. Noninvasive mechanical ventilation may be
considered initially in lieu of endotracheal intubation in myasthenia gravis but is generally insufficient in patients with
severe bulbar weakness or ventilatory failure with hypercarbia.
NEUROPATHY
• dysfunction of the PNS is also quite common.
• It is typically present in patients with prolonged critical illnesses lasting several weeks and involving sepsis; clinical suspicion is
aroused when there is failure to wean from mechanical ventilation despite improvement of the underlying sepsis and critical
illness.
• Critical illness polyneuropathy
ü the most common PNS complication related to critical illness;
ü it is seen in the setting of prolonged critical illness, sepsis, and multisystem organ failure.
ü Neurologic findings include diffuse weakness, decreased reflexes, and distal sensory loss.
ü Electrophysiologic: diffuse, symmetric, distal axonal sensorimotor neuropathy,
ü pathologic studies: confirmed axonal degeneration.
ü The circulating factors such as cytokines, which are associated with sepsis and SIRS, are thought to play a role.
ü 70% of patients with the sepsis syndrome have some degree of neuropathy, although far fewer have a clinical syndrome
profound enough to cause severe respiratory muscle weakness requiring prolonged mechanical ventilation or resulting
in failure to wean.
ü Aggressive glycemic control with insulin infusions appears to decrease the risk of critical illness polyneuropathy.
ü Treatment is otherwise supportive, with specific intervention directed at treating the underlying illness. Although
spontaneous recovery is usually seen, the time course may extend over weeks to months and necessitate long-term
ventilatory support and care even after the underlying critical illness has resolved.
DISORDERS OF NEUROMUSCULAR TRANSMISSION

• A defect in neuromuscular transmission may be a source of weakness in critically ill patients.
• Botulism may be acquired by ingesting botulinum toxin from improperly stored food or may arise from an anaerobic abscess
from Clostridium botulinum (wound botulism).
ü Infants can present with generalized weakness from gut-derived Clostridium infection, especially if they are fed honey.
ü Diplopia and dysphagia are early signs of food-borne botulism.
ü Treatment is mostly supportive, although use of antitoxin early in the course may limit the duration of the neuromuscular
blockade.
ü General ICU care: focused care to avoid ulcer formation at pressure points, deep venous thromboprophylaxis, and
infection prevention.
ü Public health officers should be rapidly informed when the diagnosis is made to prevent further exposure to others from
the tainted food or source of wound botulism (such as injection drug use).
• Undiagnosed myasthenia gravis may be a consideration in weak ICU patients; however, persistent weakness secondary to
impaired neuromuscular junction transmission is almost always due to administration of drugs.
ü impair neuromuscular transmission: these include antibiotics, especially aminoglycosides, and beta-blocking agents.
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ü In the ICU, the nondepolarizing neuromuscular blocking agents (nd-NMBAs), also known as muscle relaxants, are most
commonly responsible
o pancuronium, vecuronium, rocuronium, and cisatracurium.
o often used to facilitate mechanical ventilation or other critical care procedures, but with prolonged use persistent
neuromuscular blockade may result in weakness even after discontinuation of these agents hours or days earlier.
o Risk factors for this prolonged action of neuromuscular blocking agents include female sex, metabolic acidosis, and
renal failure.
o In general, the lowest dose of neuromuscular blocking agent should be used to achieve the desired result and, when
these agents are used in the ICU, a peripheral nerve stimulator should be used to monitor neuromuscular junction
function.
MYOPATHY
• Critically ill patients, especially those with sepsis, frequently develop muscle weakness and wasting, often in the face of
seemingly adequate nutritional support.
• Critical illness myopathy
ü describes several different discrete muscle disorders that may occur in critically ill patients.
ü catabolic myopathy may develop as a result of multiple factors, including elevated cortisol and catecholamine release
and other circulating factors induced by the SIRS.
• cachectic myopathy,
ü serum creatine kinase levels and electromyography (EMG) are normal.
ü Muscle biopsy shows type II fiber atrophy.
ü Panfascicular muscle fiber necrosis may also occur in the setting of profound sepsis.
• acute necrotizing intensive care myopathy
ü characterized clinically by weakness progressing to a profound level over just a few days.
ü associated elevations in serum creatine kinase and urine myoglobin.
ü Both EMG and muscle biopsy may be normal initially but eventually show abnormal spontaneous activity and
panfascicular necrosis with an accompanying inflammatory reaction.
ü Acute rhabdomyolysis can occur from alcohol ingestion or from compartment syndromes.
• thick-filament myopathy
ü occur in the setting of glucocorticoid and nd-NMBA use.
o This muscle disorder is not due to prolonged action of nd-NMBAs at the neuromuscular junction but, rather, is an
actual myopathy with muscle damage; it has occasionally been described with high-dose glucocorticoid use or sepsis
alone.
ü most often recognized when a patient fails to wean from mechanical ventilation despite resolution of the primary
pulmonary process.
ü Pathologically, there may be loss of thick (myosin) filaments
ü has a good prognosis.
ü the myopathy invariably improves and most patients return to normal, because this syndrome is a result of true muscle
damage, not just prolonged blockade at the neuromuscular junction, this process may take weeks or months, and
tracheotomy with prolonged ventilatory support may be necessary.
ü Some patients do have residual long-term weakness, with atrophy and fatigue limiting ambulation.
ü At present, it is unclear how to prevent this myopathic complication, except by avoiding use of nd-NMBAs, a strategy not
always possible.
ü Monitoring with a peripheral nerve stimulator can help to avoid the overuse of these agents. However, this is more likely
to prevent the complication of prolonged neuromuscular junction blockade than it is to prevent this myopathy.
302. SUBARACHNOID HEMORRHAGE

• Renders the brain critically ill from both primary and secondary brain insults.
Rupture of a saccular aneurysm - the most common cause of SAH excluding head trauma
Other causes:
• bleeding from a vascular malformation (arteriovenous malformation or dural arteriovenous fistula)
• extension into the subarachnoid space from a primary intracerebral hemorrhage.
SACCULAR (“BERRY”) ANEURYSM

• 25,000–30,000 cases per year.
• If the patient survives but the aneurysm is not obliterated, the rate of rebleeding is about 20% in the first 2 weeks, 30% in the
first month, and about 3% per year afterward.
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• Giant aneurysms, those >2.5 cm in diameter, occur at the same sites as small aneurysms and account for 5% of cases.
• The three most common locations:
o terminal internal carotid artery
o middle cerebral artery (MCA) bifurcation
o top of the basilar artery.
PATHOPHYSIOLOGY
• Saccular aneurysms occur at the bifurcations of the large- to medium-sized intracranial arteries; rupture is into the
subarachnoid space in the basal cisterns and sometimes into the parenchyma of the adjacent brain.
• As an aneurysm develops, it typically forms a neck with a dome. The length of the neck and the size of the dome vary greatly
and are important factors in planning neurosurgical obliteration or endovascular embolization.
• The arterial internal elastic lamina disappears at the base of the neck. The media thins, and connective tissue replaces smooth-
muscle cells. At the site of rupture (most often the dome), the wall thins, and the tear that allows bleeding is often ≤0.5 mm
long.
• Aneurysm size and site are important in predicting risk of rupture. Those >7 mm in diameter and those at the top of the basilar
artery and at the origin of the posterior communicating artery are at greater risk of rupture.
CLINICAL MANIFESTATIONS
• Asymptomatic - most unruptured intracranial aneurysms
• Symptoms are usually due to:
o rupture and resultant SAH,
o mass effect on cranial nerves or brain parenchyma.
Sudden rise of intracranial pressure (ICP)
• may account for the sudden transient loss of consciousness that occurs in nearly half of patients.
Excruciating headache
• brief moment may precede the sudden loss of consciousness but most patients first complain of headache upon regaining
consciousness.
• “the worst headache of my life”;
• usually generalized, often with neck stiffness, and vomiting
Loss of consciousness
• for several days - In 10% of cases if aneurysmal bleeding is severe enough
Hemiparesis, aphasia, and mental slowness (abulia)
• deficits when a hematoma is large enough to produce mass effect.
Third cranial nerve palsy
• particularly when associated with pupillary dilation, loss of ipsilateral (but retained contralateral) light reflex, and focal pain
above or behind the eye, may occur with an expanding aneurysm at the junction of the posterior communicating artery and
the internal carotid artery.
Sixth nerve palsy
• may indicate an aneurysm in the cavernous sinus, and visual
field defects can occur with an expanding supraclinoid
carotid or anterior cerebral artery (ACA) aneurysm.
Occipital and posterior cervical pain
• may signal a posterior inferior cerebellar artery or anterior
inferior cerebellar artery aneurysm
Pain in or behind the eye and in the low temple
• can occur with an expanding MCA aneurysm.
Thunderclap headache
• a variant of migraine that simulates an SAH.
Sentinel bleeds
• leaks of blood into the subarachnoid space when aneurysms
undergo small ruptures
The initial clinical manifestations of SAH can be graded using the Hunt-Hess or World Federation of Neurosurgical Societies
classification schemes (Table 302-1). For ruptured aneurysms, prognosis for good outcomes falls as the grade increases. For example,
it is unusual for a Hunt-Hess grade 1 patient to die if the aneurysm is treated, but the mortality rate for grade 4 and 5 patients may be
as high as 60%.
Delayed Neurologic Deficits
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• Four major causes

1. Rerupture
o incidence of rerupture of an untreated aneurysm in the first month following SAH is ~30%, with the peak in the first 7
days.
o associated with a 50% mortality rate and poor outcome. Early treatment eliminates this risk.
2. Hydrocephalus
o can cause stupor and coma and can be mitigated by placement of an external ventricular drain.
o is differentiated from cerebral vasospasm with a CT scan, CT angiogram, transcranial Doppler (TCD) ultrasound, or
conventional x-ray angiography.
o May clear spontaneously or require temporary ventricular drainage.
o Chronic hydrocephalus may develop weeks to months after SAH and manifest as gait difficulty, incontinence, or
impaired mentation.
3. Delayed cerebral ischemia

o Vasospasm is the narrowing of the arteries at the base of the brain following SAH and this may cause symptomatic
ischemia and infarction in ~30% of patients and is the major cause of delayed morbidity and death.
o Signs of DCI appear 4–14 days after the hemorrhage, most often at 7 days.
a. Vasospasm is believed to result from direct effects of clotted blood and its breakdown products on the arteries within the
subarachnoid space. In general, the more blood that surrounds the arteries, the greater the chance of symptomatic
vasospasm. All of these focal symptoms may present abruptly, fluctuate, or develop over a few days. In most cases, focal
spasm is preceded by a decline in mental status.
b. Vasospasm can be detected reliably with conventional x-ray angiography, but this procedure is invasive and carries the
risk of stroke and other complications. TCD ultrasound is based on the principle that the velocity of blood flow within an
artery will rise as the lumen diameter is narrowed. By directing the probe along the MCA and proximal ACA, carotid terminus,
and vertebral and basilar arteries on a daily or every-other-day basis, vasospasm can be reliably detected and treatments
initiated to prevent cerebral ischemia. CT angiography is another method that can detect vasospasm.
c. Severe cerebral edema in patients with infarction from vasospasm may increase the ICP enough to reduce cerebral
perfusion pressure. Treatment may include mannitol, hyperventilation, and for intractable cases hemicraniectomy;
moderate hypothermia may have a role as well.
4. Hyponatremia.
o may be profound and can develop quickly in the first 2 weeks following SAH.
o There is both natriuresis and volume depletion with SAH, so that patients become both hyponatremic and
hypovolemic.
o Both atrial natriuretic peptide and brain natriuretic peptide have a role in producing this “cerebral salt-wasting
syndrome.”
o Typically, it clears over the course of 1–2 weeks and, in the setting of SAH, should not be treated with free-water
restriction as this may increase the risk of stroke
LABORATORY EVALUATION AND IMAGING

Blood in the cerebrospinal fluid (CSF) - hallmark of aneurysmal rupture
High-quality noncontrast CT scan
o obtained within 72 h.
o More than 95% of cases have enough blood to be visualized
o The extent and location of subarachnoid blood can help locate the underlying aneurysm, identify the cause of any neurologic
deficit, and predict the occurrence of vasospasm
Lumbar puncture
o should be performed to establish the presence of subarachnoid blood if the scan fails to establish the diagnosis of SAH and
no mass lesion or obstructive hydrocephalus is found
o Lysis of the red blood cells and subsequent conversion of hemoglobin to bilirubin stains the spinal fluid yellow within 6–12
h.
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o This xanthochromic spinal fluid peaks in intensity at 48 h and lasts for 1–4 weeks, depending on the amount of subarachnoid
blood..
Four-vessel conventional x-ray angiography

o generally performed to localize and define the anatomic details of the aneurysm and to determine if other unruptured
aneurysms exist once the diagnosis of hemorrhage from a ruptured saccular aneurysm is suspected, (both carotids and both
vertebrals)
CT angiography
o alternative method for locating the aneurysm and may be sufficient to plan definitive therapy.
Electrolytes
o Close monitoring (daily or twice daily) is important because hyponatremia can occur precipitously during the first 2 weeks
following SAH
Electrocardiogram (ECG)
o frequently shows ST-segment and T-wave changes similar to those associated with cardiac ischemia.
o A prolonged QRS complex, increased QT interval, and prominent “peaked” or deeply inverted symmetric T waves are usually
secondary to the intracranial hemorrhage.
Echocardiography
o reveals a pattern of regional wall motion abnormalities that follow the distribution of sympathetic nerves rather than the
major coronary arteries, with relative sparing of the ventricular wall apex. The sympathetic nerves themselves appear to be
injured by direct toxicity from the excessive catecholamine release.
TREATMENT
Early aneurysm repair
o prevents rerupture and allows the safe application of techniques to improve blood flow (e.g., induced hypertension) should
vasospasm and DCI develop.
Surgical repair
o involves placing a metal clip across the aneurysm neck, thereby immediately eliminating the risk of rebleeding. This approach
requires craniotomy and brain retraction, which is associated with neurologic morbidity.
Endovascular techniques
o involve placing platinum coils, or other embolic material, within the aneurysm via a catheter that is passed from the femoral
artery. The aneurysm is packed tightly to enhance thrombosis and over time is walled off from the circulation
Medical management focuses on:

ü protecting the airway
ü managing blood pressure before and after aneurysm treatment
ü preventing rebleeding prior to treatment
ü managing vasospasm and DCI
ü treating hydrocephalus
ü treating hyponatremia
ü limiting secondary brain insults
ü preventing pulmonary embolus (PE).
• Intracranial hypertension following aneurysmal rupture occurs secondary to

o subarachnoid blood, parenchymal hematoma, acute hydrocephalus, or loss of vascular autoregulation.
Ventriculostomy
o Patients who are stuporous should undergo emergent ventriculostomy to measure ICP and to treat high ICP in order to
prevent cerebral ischemia.
o High ICP refractory to treatment is a poor prognostic sign.
o If the patient has a depressed level of consciousness, ICP should be measured and the cerebral perfusion pressure targeted
to 60–70 mmHg.
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• If headache or neck pain is severe, mild sedation and analgesia are prescribed.
• Adequate hydration is necessary to avoid a decrease in blood volume predisposing to brain ischemia.
Anticonvulsants
o sometimes given as prophylactic therapy because a seizure could theoretically promote rebleeding.
Glucocorticoids
o may help reduce the head and neck ache caused by the irritative effect of the subarachnoid blood.
Antifibrinolytic agents
o not routinely prescribed but may be considered in patients in whom aneurysm treatment cannot proceed immediately. They
are associated with a reduced incidence of aneurysmal rerupture but may also increase the risk of DCI and deep-vein
thrombosis (DVT).
DCI due to vasospasm

o remains the leading cause of morbidity and mortality following aneurysmal SAH.
o Treatment with the calcium channel antagonist nimodipine (60 mg PO every 4 h) improves outcome. Nimodipine can cause
significant hypotension in some patients, which may worsen cerebral ischemia in patients with vasospasm.
Phenylephrine or norepinephrine
o Symptomatic cerebral vasospasm can also be treated by increasing the cerebral perfusion pressure by raising mean arterial
pressure through plasma volume expansion and the judicious use of IV vasopressor agents
o Raised perfusion pressure has been associated with clinical improvement in many patients, but high arterial pressure may
promote rebleeding in unprotected aneurysms.
Intra-arterial vasodilators and percutaneous transluminal angioplasty

o are considered if DCI due to vasospasm persists despite optimal medical therapy
o Vasodilatation by direct angioplasty appears to be permanent, allowing hypertensive therapy to be tapered sooner.
Pneumatic compression stockings

o to prevent pulmonary embolism.
Unfractionated heparin
o administered subcutaneously for DVT prophylaxis can be initiated within 1–2 days following endovascular treatment or
craniotomy with surgical clipping and is a useful adjunct to pneumatic compression stockings.
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Critical Care Medicine Outline

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CAGAYAN VALLEY MEDICAL CENTER

Department of Internal Medicine

CRITICAL CARE MEDICINE

SECTION 2 Shock and Cardiac Arrest

SECTION 3 Neurologic Critical Care

SECTION 1 RESPIRATORY CRITICAL CARE

THE SOFA SCORING SYSTEM

THE APACHE II SCORING SYSTEM

THE SAPS SCORING SYSTEM

The end result of multiorgan hypoperfusion is

MECHANICAL VENTILATORY SUPPORT

TYPE I: ACUTE HYPOXEMIC RESPIRATORY FAILURE

TYPE II RESPIRATORY FAILURE

TYPE III RESPIRATORY FAILURE

TYPE IV RESPIRATORY FAILURE

CARE OF THE MECHANICALLY VENTILATED PATIENT

MULTIORGAN SYSTEM FAILURE

MONITORING IN THE ICU

• From this information, the relative percentage of oxyhemoglobin is derived.

RESPIRATORY SYSTEM MECHANICS

PREVENTION OF COMPLICATIONS OF CRITICAL ILLNESS

NOSOCOMIAL INFECTIONS IN THE ICU

DEEP-VENOUS THROMBOSIS (DVT)

NUTRITION AND GLYCEMIC CONTROL

• Phlebotomy also contributes to ICU anemia.

ACUTE KIDNEY FAILURE

NEUROLOGIC DYSFUNCTION IN CRITICALLY ILL PATIENTS

ANOXIC CEREBRAL INJURY

WITHHOLDING OR WITHDRAWING CARE

294. ACUTE RESPIRATORY DISTRESS SYNDROME

Categories of ARDS based on the degrees of hypoxemia

Minimizing ventilator-induced lung injury

Minimizing Aledtrauma by Prevention of Alveolar Collapse

Alternate modes of mechanical ventilation,

Lung-replacement therapy with extracorporeal membrane oxygenation (ECMO)

Functional Recovery in ARDS Survivors

295. MECHANICAL VENTILATORY

TYPES OF MECHANICAL VENTILATION

Other Modes of Ventilation

ü INVERSE-RATIO VENTILATION (IRV)

PROTECTIVE VENTILATORY STRATEGY

GENERAL SUPPORT DURING VENTILATION

COMPLICATIONS OF MECHANICAL VENTILATION

WEANING FROM MECHANICAL VENTILATION

Prolonged MV and Tracheostomy

SECTION 2 SHOCK and CARDIAC ARREST

DETERMINANTS OF OXYGEN DELIVERY

• Use the history, physical examination, and laboratory testing to

EVALUATION OF THE PATIENT WITH SHOCK

Cardiogenic shock Onset of exertional chest discomfort

Decreased oxygen delivery to the brain Confusion and encephalopathy.

Cardiogenic Shock Hypovolemic Shock

JVP may be elevated (with right-sided

Type of Shock Physical Findings

Cardiogenic Brady- or tachyarrhythmia

Rectal examination may reveal GI hemorrhage

Obstructive Cardiac Tamponade: Pulsus paradox and elevated JVP

Increased lactate (hyperlactemia) and lactic acidosis (hyperlactemia

• Lactate product of anaerobic glucose metabolism

INITIAL TREATMENT OF SHOCK

Vasopressor and Inotropic Support

OXYGENATION AND VENTILATION SUPPORT

Specific Causes of Shock Requiring Tailored Intervention

297. SEPSIS AND SEPTIC SHOCK

o Sepsis: result of an excessive inflammatory host response (SIRS)

o impaired tissue oxygenation plays a key role

APPROACH TO THE PATIENT