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CASE REPORT

DECREASE OF CONSCIOUSNESS

SENIOR CLINICAL CLERKSHIP

By :
Ivandra Septiadi Tama Putra
04084821517036

Advisor :
dr. H. A. Rachman Toyo, Sp.S(K)

NEUROLOGY DEPARTMENT
MEDICAL FACULTY OF SRIWIJAYA UNIVERSITY
MOHAMMAD HOESIN GENERAL HOSPITAL
PALEMBANG
2016

CERTIFICATION PAGE
Case Report

DECREASE OF CONSCIOUSNESS

Presented by:

Ivandra Septiadi Tama Putra


04084821517036

Has been accepted as one of requirements in undergoing senior clinical clerkship period of 8th
August 2016 – 12th Sept 2016 in Neurology Department Medical Faculty Sriwijaya University
Mohammad Hoesin General Hospital Palembang.

Palembang, August 2016


Advisor,

Dr. H. A. Rachman Toyo, Sp.S(K)


FOREWORD

The authors offer our praise and gratitude to God for His blessings, mercy and grace
so that this case entitled "Decrease of consciousness" can be done well. This paper aims as
one of the requirements to fulfill the task in the Neurology Department of Dr. Mohammad
Hoesin General Hospital Palembang .
The authors would like to thank dr. H. A. Rachman Toyo, Sp.S(K) who has guided us
in finishing this paper.
We realize that this paper still has many shortcomings. Therefore, all criticism and
suggestions for improvement of this paper will be received gladly. Finally, we hope this paper
can provide many advantages to all people especially health care providers.

Palembang, August 2016

Author
CONTENTS

Cover ................................................................................................................ i

Certification Page ............................................................................................. ii

Foreword ........................................................................................................... iii

Contents ............................................................................................................ iv

Chapter I Patient’s Status ................................................................................. 1

Chapter II Resume ............................................................................................ 11

Chapter III Case Analysis ................................................................................. 14

Chapter IV Literature Review .......................................................................... 17

References ........................................................................................................ 33
CHAPTER I
STATUS OF THE PATIENT

IDENTIFICATION
Name : Mr. R
Age : 65 years old
Sex : Male
Occupation : Labor
Religion : Islam
Address : 36 Ilir, Gandus, Palembang City.
Admitted : Aug 5th 2016, 23:30
Medical Record : 898782/RI15016394

ANAMNESIS
Patient was admitted to Neurologic Department of Mohammad Hoesin General
Hospital because of decreasing level of consciousness which occur gradually.
+ 1 days before admission, the patient experiences difficulty in communicating
because he looked agitated and chaotic. He just lied on bed because he always felt sleepy. He
looked remain awake. Before decreasing level of consciousness, patient felt high fever,
shortness of breath and acute cough. There was no weakness in extremities. There was no
sensibility disturbance. There were no facial droop and dysarthria. This patient still can
express his thought with word, sentence and gesture. He also can understand the other’s
thought by word, sentence and gesture. There were no headache, nausea, vomit and seizure.
The patient was taken to medical practise and then referred to Mohammad Hoesin General
Hospital.
There was history of shortness of breath, acute cough, and high fever. There were no
history of hepatic disorder and renal disorder. There were no history of taking drugs given for
a long time and drink alcohol. There was no history of exposure the certain substance. There
was no history of head trauma. There were no history diabetes mellitus and heart disease. This
patient has hypertension since five years ago, but he never control regularly.
This is the first time that the patients suffers these complaints.
PHYSICAL EXAMINATION
PRESENT STATE
 Internal State
Heart : Heart : HR: 104 beats/min, regular murmur (-),
Conciousness : E3M5V3
gallop (-)
Nutrition : Sufficient
Lungs : Dullness on
Temperature : 38,5oC
percussion in right lung, vesiculer (+)
Pulse : 104 beats/min
decrease and moderate pitch of crackles in
Respiratory rate : 36 times/min
base of right lung, wheezing (-)
Blood pressure : 170/90 mmHg
Liver : No abnormality
Weight : 65 Kg
Spleen : No abnormality
Height : 170 Cm
Extremities : See neurological state
Genital : N/A

 Psychiatric state
Attitude : Cannot be assessed Facial Expression : No
Attention : Cannot be assessed Psychological contact : No

 Neurological state
Head
Shape : Normocephali Deformity : No
Size : Normal Fracture : No
Symetric : Yes Fracture pain : No
Hematome : No Vessel : No widening
Tumor : No Pulsation : No

Neck
Position : Straight Deformity : No
Torticolis : No Tumor : No
Nuchal Rigidity : No Vessels : No widening
CRANIAL NERVES Right Left
N.I: Olfactory Nerve Cannot be assessed Cannot be assessed
Smelling Cannot be assessed Cannot be assessed
Anosmia Cannot be assessed Cannot be assessed
Hyposmia Cannot be assessed Cannot be assessed
Parosmia
Right Left
N.II: Optical Nerve Cannot be assessed Cannot be assessed
Visual acuity V.O.D V.O.S
Visual Field

 Anopsia Cannot be assessed Cannot be assessed


 Hemianopsia Cannot be assessed Cannot be assessed
Oculi fundus
 Papil Edema Cannot be assessed Cannot be assessed
 Papil Athropy Cannot be assessed Cannot be assessed
 Retinal bleeding Cannot be assessed Cannot be assessed

N.III: Occulomotorius
N.IV: Trochlearis
N.VI: Abducens Nerves Right Left
Diplopia Cannot be assessed Cannot be assessed
Eyes gap Cannot be assessed Cannot be assessed
Ptosis No No
Eyes position
 Strabismus No No
 Exophtalmus No No
 Enophtalmus No No
 Deviation conjugae No No
Eyes movement Cannot be assessed Cannot be assessed
Pupil
 Shape Round Round
 Size Ø 3mm Ø 3mm
 Isochor/anisochor Isochor Isochor
 Midriasis/miosis No No
Light reflex
 Direct Positive Positive
 Consensuil Positive Positive
 Accommodation Positive Positive
Argyl Robertson Cannot be assessed Cannot be assessed

N.V: Trigeminus Nerve


Motoric Right Left
 Biting Cannot be assessed Cannot be assessed
 Trismus Cannot be assessed Cannot be assessed
 Corneal reflex Cannot be assessed Cannot be assessed
Sensory
 Forehead Cannot be assessed Cannot be assessed
 Cheek Cannot be assessed Cannot be assessed
 Chin Cannot be assessed Cannot be assessed

N.VII: Facialis Nerve Right Left


Motoric
 Frowning Cannot be assessed Cannot be assessed
 Eyes closing Cannot be assessed Cannot be assessed
 Giggling Cannot be assessed Cannot be assessed
 Nasolabial fold Symmetric Symmetric
Facial shape
 Rest Symmetric Symmetric
 Speaking/whistling Cannot be assessed Cannot be assessed
Sensory
 2/3 anterior tounge Cannot be assessed Cannot be assessed
Autonomy
 Salivation Normal Normal
 Lacrimation Normal Normal
 Chvostek’s sign Normal Normal
N.VIII: Statoacusticus Nerve
Cochlearis Nerve Right Left
Whispering Cannot be assessed Cannot be assessed
Hour ticking N/A N/A
Weber test N/A N/A
Rinne test N/A N/A
Vestibularis Nerve
Nystagmus Cannot be assessed Cannot be assessed
Vertigo Cannot be assessed Cannot be assessed

N.IX: Glossopharingeus, and


N.X: Vagus Nerves
Pharyngeal arch Symmetric

Uvula Center

Swallowing disorder Cannot be assessed

Hoarsing/nasalising Cannot be assessed

Heart beat Normal

Reflex
 Vomiting Cannot be assessed
 Coughing Cannot be assessed
 Occulocardiac Cannot be assessed
 Caroticus sinus Cannot be assessed
Sensory
 1/3 posterior tounge Cannot be assessed

N.XI: Accessorius Nerve Right Left


Shoulder Raising Cannot be assessed Cannot be assessed
Head Twisting Cannot be assessed Cannot be assessed

N.XII: Hypoglossus Nerve Right Left


Tounge Deviation No No
Fasciculation No No
Papil Athrophy No No
Dysarthria Cannot be assessed Cannot be assessed
MOTORIC
ARM Right Left
Motion
No lateralization
Power
Tones Decrease Decrease
Physiological Reflex
 Biceps Decrease Decrease
 Triceps Decrease Decrease
 Radius Decrease Decrease
 Ulna Decrease Decrease
Pathological Reflex
 Hoffman Tromner - -
 Leri - -
 Meyer - -
 Trofik - -

LEG Right Left


Motion
No lateralization
Power
Tones Decrease Decrease
Clonus
 Thigh No No
 Foot No No
Physiological reflex
 KPR Decrease Decrease
 APR Decrease Decrease
Pathological reflex
 Babinsky Positive Positive
 Chaddock Negative Negative
 Oppenheim Negative Negative
 Gordon Negative Negative
 Schaeffer Negative Negative
 Rossolimo Negative Negative
 Mendel Bechterew Negative Negative
Abdominal skin reflex
 Upper Negative Negative
 Middle Negative Negative
 Lower Negative Negative
 Tropik Negative Negative

VERTEBRAL COLUMN
Kyphosis : No Tumor : No
Lordosis : No Meningocele : No
Gibbus : No Hematome : No
Deformity : No Tenderness : No

SENSORY
Cannot be assessed yet

MENINGEAL REFLEX
Right Left
Nuchal Rigidity No No
Kerniq No No
Lasseque No No
Brudzinsky
 Neck No No
 Cheek No No
 Symphisis No No
 Leg I No No
 Leg II No No

GAIT AND BALANCE


Gait Balance and Coordination
Ataxia : Can not be assessed Romberg : Can not be assessed
Hemiplegic : Can not be assessed Dysmetri : Can not be assessed
Scissor : Can not be assessed finger - finger : Can not be assessed
Propulsion : Can not be assessed finger nose : Can not be assessed
Histeric : Can not be assessed heel - heel : Can not be assessed
Limping : Can not be assessed Rebound phenomenon : Can not be
assessed
Steppage : Can not be assessed Dysdiadochokinesis : Can not be
assessed
Astasia-Abasia : Can not be assesed Trunk Ataxia : Can not be assessed
Limb Ataxia : Can not be assessed

ABNORMAL MOVEMENTS
Tremor : No
Chorea : No
Athetosis : No
Ballismus : No
Dystoni : No
Myoclonus : No

VEGETATIVE FUNCTION
Micturition : Catetherized
Defecation : No abnormality

LIMBIC FUNCTION
Motoric aphasia : No
Sensoric aphasia : No
Apraksia : No
Agraphia : No
Alexia : No
Nominal aphasia : No

LABORATORY FINDINGS
BLOOD
Hematology
- Hemoglobin  12,5 g/dL
- Eritrocyte  4,22 x 106/mm3
- Leukocyte  18,7 x 103/mm3
- Hematocrit  38%
- Trombocyte  273 x 103/uL
- Diff. Count  (0/0/83/9/8)
Blood Chemist
- Albumin  3,4 g/dL
- Glucose  173 mg/dL
Renal
- Ureum  49 mg/dL
- Creatinin  0,76 mg/dL
Electrolyte
- Ca  9,1 mg/dL
- P  4 mg/dL
- Mg  2,21 mEq/L
- Na  151 mEq/L
- K  3,6 mEq/L
- Cl  116 mmol/L
Blood Gas Analysis
- FiO2  60,0%
- Temperatum  37oC
- pH  7,453
- pCO2  43,8 mmHg
- pO2  93,2 mmHg
- SO2  95,8%
- Hct  24%
- Hb  8,1%
- Na+  147,5 mmol/L
- K+  3,23 mmol/L
- HCO3  31 mmol/L
- Total CO2  32,3 mmol/L
- BEecf  6,8 mmol/L
- BEb  7,1 mmo/L
- SBC  30,9 mmol/L
Conclussion :
 Leucoctye  Leucocytosis
 Diff count  shift to the left (acute infection)

CEREBRO SPINAL FLUID : N/A


Macroscopic
- Volume : N/A
- Colour : N/A
- Clarity : N/A
- Smell : N/A
- Density : N/A
- Sedimentation : N/A
- pH : N/A
Microscopic
- Leucocyte count : N/A
- PMN : N/A
- MN : N/A
- Blast Cell : N/A
- Nonne : N/A
- Pandy : N/A
- Protein : N/A
- Glucose : N/A
- Chloride : N/A
- Culture : N/A
RADIOLOGY EXAMINATION
Chest X-Ray (Aug, 5h 2016)

Conclussion : Consolidation in base of right lung  pneumonia

Head CT-Scan (Aug, 5th 2016) : Within normal limit.


CHAPTER II
RESUME

IDENTIFICATION
Name : Mr. R
Age : 65 years old
Sex : Male
Occupation : Labor
Address : 36 Ilir, Gandus, Palembang City.
Admitted : Aug 5th 2016, 23:30.

ANAMNESIS
Patient was admitted to Neurologic Department of Mohammad Hoesin General
Hospital because of decreasing level of consciousness which occur gradually.
+ 1 days before admission, the patient experiences difficulty in communicating
because he looked agitated and chaotic. He just lied on bed because he always felt sleepy. He
looked remain awake. Before decreasing level of consciousness, patient felt high fever,
shortness of breath and acute cough. There was no weakness in extremities. There was no
sensibility disturbance. There were no facial droop and dysarthria. This patient still can
express his thought with word, sentence and gesture. He also can understand the other’s
thought by word, sentence and gesture. There were no headache, nausea, vomit and seizure.
The patient was taken to medical practise and then referred to Mohammad Hoesin General
Hospital.
There was history of shortness of breath, acute cough, and high fever. There were no
history of hepatic disorder and renal disorder. There were no history of taking drugs given for
a long time and drink alcohol. There was no history of exposure the certain substance. There
was no history of head trauma. There were no history diabetes mellitus and heart disease. This
patient has hypertension since five years ago, but he never control regularly.
This is the first time that the patients suffers these complaints.

PHYSICAL EXAMINATION
Conciousness : E3M5V3
Temperature : 38,5oC
Pulse : 104 beats/min
Respiratory rate : 36 times/min
Blood pressure : 170/90 mmHg
Weight : 65 Kg
Height : 170 Cm

Neurologic Examination :
N III : Round pupil, isochor, light reflex +/+, diameter 3 mm
N VII : Nasolabialis fold is symmetric
N XII : Tongue deviation (-)

Motoric function Right arm Left arm Right leg Left leg

Movement No lateralization
Power
Tonus Decrease Decrease Decrease Decrease
Klonus - -
Physiological Decrease Decrease Decrease Decrease
reflex
Pathological (-) (-) Babinsky (+) Babinsky (+)
reflex

Sensory function : Cannot be assesed yet


Limbic function : Normal limit
Vegetative function : Catetherized
Meningeal signs : No
Abnormal movements : No
Gait dan balance : Cannot be assesed yet

DIAGNOSIS
Clinical diagnosis :
 Decreased level of consciousness
Topical diagnosis :
 Encephalon
Etiological diagnosis :
 Hypoxic-ischemic encephalopathy
(+) Additional diagnosis :
 Sepsis ec community acquired pneumonia
 Hypertension stage II

MANAGEMENT
Non-pharmacology :
 Head elevation 300
 O2 via NRM 10 litre/minute
 Liquid diet via NGT 1500 kkal
 Oral hygiene

Pharmacology :
 IVFD RL gtt xv/minute
 Inj. Ceftriaxon 2x1 gr IV
 Inj. Citicholin 2x250 mg IV
 Inj. Neurobion 1x5000 mcg IM
 Azitromisin 1x500 mg p.o
 Amlodipin 1x10 mg p.o
 Candesartan 1x8 mg p.o

PROGNOSIS
Quo ad vitam : dubia
Quo ad functionam : dubia
CHAPTER III
CASE ANALYSIS

A man, 65 years old, was admitted to Neurologic Department of Mohammad Hoesin


General Hospital because of decreased level of consciousness which occur gradually. This
patient experienced difficulty in communicating with his family because he looked agitated
and confussed. He just lied on bed because he always felt sleepy. He also felt difficult to wake
up. From the chief complaint, we can think many differential diagnosis. Because, there are
many causes of decreasing level of consciousness. They are known as CIMENTED
(Cardiovascular, Infection, Metabolic, Electrolyte, Neoplasm, Trauma, Epilepsy, Drugs).
Cardiovascular as a cause of decreasing level of consciousness means that the
inadequate blood flow to cerebral. The reduction of cerebral blood flow lead to hypoxemia
condition (deprivated oxygen level in brain tissue). Hypoxemia condition can be caused by
several factors such as cerebrovascular disease, cardiovascular disease and pulmonary
disease. From history, there were no neurologic deficit such as the weakness in extremities,
sensibility disturbance, facial droop and dysarthria. There were no headache, seizure, nausea
and vomit. This patient can still express his thought and understand someone’s thought with
words, sentences and gestures. It indicated that we can exclude the cerebrovascular disease.
About cardiovascular disease, this patient didn’t feel specific pain such as pressure, squeezing
or a burning sensation across the precordium and radiate to neck, shoulder, jaw, back and
either arm. There were also no history of heart disease. So, we also can exclude
cardiovascular disease.
But, from history, around two days before admission, this patient experienced acute
cough, high fever and shortness of breath. High fever indicated that there was infection. Acute
cough and shortness of breath means that the origin of disturbance is from respiration system.
Acute cough, high fever and shortness of breath leads to bacterial pneumonia. This disease is
supported by pulmonary physical examination. From physical examination, we got decreasing
fremitus on palpation, dullness on percussion and decreasing intensity of vesicular breath
sound with moderate rales/crackles in base of lung on auscultation. So, pulmonary disease
lead to hypoxemia condition lead to neurologic disturbance can not be excluded.
Infection or inflammation of the brain also can lead to gradually decrease in level of
consciousness, e.g encephalitis. But, the clinical manifestation of encephalitis such as high
fever, severe headache, nausea, vomiting and myalgia. Encephalitis usually associate with
meningitis so from physical examination, there are neck pain, stiffness, or positive of
meningeal sign. Those things did not be founded in this case. Metabolic as a cause of
decreasing leve of consciousness means that metabolic disturbance which is cause by
systemic disease such hepatic disease, renal disease or hypo-hyperglycemia because of
diabetes mellitus. From history, there were no hepatic disease which can lead to hepatic
encephalopathy, renal disease which can lead to uremic encephalopathy and diabetes mellitus
which can lead to ketoacidosis diabeticum that can disturb the level of consciousness. It is
also supported by laboratory examination which indicate that there were no abnormality in
hepatic function, kidney function and blood glucose level. So, encephalitis or other infection
of the brain and metabolic disturbance can be excluded as a cause of this decreasing level of
consciousness.
Electrolyte as a cause of decreasing level of consciousness means that there was
disturbance in sodium or potassium electrolyte. But, from laboratory examination, the sodium
and potassium are in normal limit. Neoplasm of the brain or known as space-occupying lesion
is usually due to malignancy but it can be caused by other pathology such as an abscess or a
haematoma. The effect of the tumour in brain can increase intracranial pressure which
manifest as headache, vomit, or posture-ralted headace. The headache usually becomes
progressively sever and followed with nonfocal neurological symptoms such as blackout and
change in personality and memory. Those things did not be founded in this case. From
additional examination such as head CT-Scan, there was no mass or tumour which can seen in
the result. So, electrolyte and neoplasm as the cause of decreasing level of consciousness in
this case can be excluded. Trauma, Epilepsy, and Drugs also can be excluded because there
were no history of exposure with certain substances, head trauma and seizure.
Therefore, the causes of gradually decrease in level of consciousness was pulmonary
disease which indicate to pneumonia. Pneumonia is an infection of the lungs that is caused by
bacteria, viruses, fungi or parasites. It is characterized primarily by inflammation of the
alveoli in the lungs. The infection can starts in the lungs and then migrate into the
bloodstream. It is known as a blood infection or blood poisoning or sepsis. From physical
examination, this patient already fulfilled the criteria of sepsis such as tachypnea (>24
times/minute), tachycardia (>90 beats/minute), hyperthermia (>38,50 C) and leukocytosis
(>12.000/mm3).
Sepsis can lead to inadequate blood supply to the brain due to systemic hypoxemia. It
makes reduction of cerebral blood flow which is known as brain hypoxia. In adult, CBF is
maintained at a constant level which is known as the cerebral autoregulation. But, after the
compensatory fail, the CBF falls below critical level and the brain injury secondary to
diminished blood supply and a lack of sufficient oxygen occurs. At the cellular level, this
leads to neuronal injury in hypoxic-ischemic encephalopathy. The manifestation vary
depending on hypoxic-ischemia encephalopathy severity. The predominant presenting clinical
features of HIE are alteration of consciousness such happen in this case. The patient may
lethargic, somnolen or stupor. A complete neurologic assessment is still essential. The
neurologic examination should be taken in the context of ongoing systemic processes. From
motoric examination, muscle tone may be slightly decrease with significant hypotonia. It also
happen to physiologic reflex. In severe HIE, behavioral abnormalities, disturbance of ocular
motion, seizure can happen. And this condition may lead to death. From neurologic
examination, we found that decreased muscle tone (hypotonia), decreased physiologic reflex
and there were pathologic reflex in both of legs. Additional examination also show that there
are leukocytosis and acute infection which indicate that it can be a real sign of pneumonia
which can lead to sepsis. So, we diagnose this patient with decreased level of consciousness
because of hypoxic-ischemic encephalopathy where this HIE happen because of sepsis that
came from bacterial pneumonia.
The treatment of this disease is nonpharmacology and pharmacology. From
nonpharmacology, we give oxygen via non rebreathing mask due to hypoxic condition and
make the elevation of head. Liquid diet is given because of the altered of consciousness so it
can prevent from aspiration. From pharmacology, we give broad spectrum antibiotics such as
ceftriaxone and azithromycin due to systemic infection because of sepsis which came from
bacterial pneumonia. Amlodipin and candesartan are given due to hypertension stage II which
happen in this patient. And citicholin and neurobion are given to nourish nerve cell. In
addition, it should be given the information to the family about the patient's current condition
and treatment to be performed.
CHAPTER IV
LITERATURE REVIEW

4.1. Definition
Encephalopathy (encephalo= brain + pathy= disorder) is a broad term used to describe
abnormal brain function or brain structure. The abnormality may be transient, recurrent, or
permanent. Encephalopathy does not refer to a single disease, but rather to a syndrome of
global brain dysfunction.1 On clinical examination, patients with encephalopathy are often
lethargic, confused, or agitated, typically without obvious focal localizing neurologic
features.2 Hypoxic-ischemic encephalopathy (HIE) is one of the most frequent and dramatic
urgency found in neurological brain diseases of adults. This is a neuro-vascular and neuro-
metabolic syndrome, caused by a shortage of supply of oxygen and glucose or their
metabolism in the brain.3

4.2. Etiology
Hypoxic-ischemic encephalopathy has several causes. The causes often related to heart
failure and circulation and of the lungs and respiration. They are:3
a. Heart failure followed by respiratory depression secondary to massive blood loss,
septic or traumatic shock, and heart disease, such as myocardial infarction or
ventricular arrhythmia.
b. Respiratory failure followed by cardiac arrest as a result of low oxygen intake (in
tracheal compression or obstruction, drowning, strangulation, aspiration of gastric
content, or during general anesthesia if the inspired gas is poor in oxygen),
respiratory muscles weakness in neurological diseases (Guillain-Barré syndrome,
amyotrophic lateral sclerosis, myasthenia gravis) or central nervous system injury
(mainly spinal cord injury).
c. Reduced oxygen carriage by the blood in carbon monoxide poisoning.
d. Histotoxicity in cyanide poisoning.

4.3. Pathophysiology
The various causes of HIE share an overall common pathophysiologic mechanism
where the global brain injury is a result of lack of oxygen and glucose supply. Brain injury
results from a sudden reduction or cessation of blood flow that is followed by hypoxemia as
respiratory failure sets in. In HIE, the neuronal injury mediated by oxygen deprivation,
resulting in a decrease of adenosine-triphosphate (ATP) production with resulting cellular
energy starvation as well as loss of cellular integrity. This process results in uncontrolled
glutamate release, which leads to injury from excitotoxicity mediated principally through
NMDA receptors. As part of this cascade of cellular injury, inhibitory neurotransmitters that
normally minimize glutamate excitotoxicity such as GABA and glycine, are decreased as
well. NMDA mediated glutamate excitotoxicity creates an intracellular calcium influx that
activates a number of second messengers that amplify cellular injury by increasing the
calcium permeability and increasing glutamate release leading to a vicious cycle.3,4
This complex chain of events from circulatory arrest to intracellular calcium overload
occurs rapidly, and results in the activation of neuronal nitric oxide synthase. Oxygen free
radical species are also responsible for cellular injury by direct DNA fragmentation, protein
oxidation, lipid peroxidation and disruption of the mitochondrial respiratory chain. Reactive
oxygen species are released by calcium mediated mitochondrial disruption and as well as
during reperfusion when renewed oxygen supplies act as a substrate for enzymatic oxidative
reactions. Oxidative stress leads to further inflammation and injury through complement
activation and subsequent degradation, cytokine production (IL-1, IL-6, IL-8 and TNF-α),
expression of leukocyte adhesion molecules and microvascular dysfunction.3,4,5
Secondary brain injury is a delayed phenomenon, and is mediated by cerebral edema
with resulting elevations in intracranial pressure, non-convulsive seizures and blood brain
barrier disruption. Cytotoxic edema is a result of excitotoxicity and ionic pump failure, as
well as cellular water shift across cell membranes with impaired aquaporin function. Matrix
metalloproteases are implicated in blood-brain barrier disruption. Oxidative DNA damage
resulting from reperfusion induces both necrotic and apoptotic processes in the brain at the
cellular level, such as DNA fragmentation as well as negative intracellular signaling events
such as NAD depletion, p53 activation, and intramitochondrial processes.3,4,5

4.4. Clinical Manifestation


Encephalopathy describes abnormal brain function due to problems with the brain
tissue. Encephalopathy can present a very broad spectrum of symptoms that range from mild,
such as some memory loss or subtle personality changes, to severe, such as dementia,
seizures, coma, or death. In general, encephalopathy is manifested by an altered mental state
that is sometimes accompanied by physical manifestations (for example, poor coordination of
limb movements). Symptoms of encephalopathy can be generalized causing decreased level
of consciousness from minimal lethargy to coma. Encephalopathy can cause abnormal
thought processes including confusion, poor memory, hallucinations, and even psychotic
thinking. The symptoms may be evident because the parts of the body that the brain controls
may not work appropriately. There may be incoordination and difficulty walking (ataxia) or
there may be abnormalities with vision and eye movement.3,6

4.5. Diagnose
There are no tests or procedures specific for the diagnosis of HIE. Diagnostic work-up
using laboratory tests, neuro-electrophysiologic studies and neuroimaging are needed to help
establish the etiology of HIE, stage the severity of injury, help define prognosis and rule out
other pathologies that may present similarly to HIE. Biomarkers of brain tissue injury such as
neuron-specific enolase (NSE) for neurons, protein s100 for astrocytes, neurofilament heavy
chain (NfH) protein among others are generally elevated in serum or CSF during the acute
phase. These biomarkers may be used to define the severity of injury and some may be useful
as adjuncts in prognostication. Early head CT may be normal, but subsequent tests or MRI
may demonstrate areas of brain tissue injury in areas with selective vulnerability, diffuse
cerebral edema, loss of gray white matter differentiation among other findings that are
indicative of HIE. 7,8
The typical findings related to HIE on neuroimaging [head CT or MRI] may be noted
early but requires a few days to define the full extent of injury. Emergent neuroimaging at the
time of presentation of alteration in level of consciousness is important to rule-out other
causes of acute brain injury, which may require specific interventions, such as subarachnoid
hemorrhage, intracranial hemorrhage and acute ischemic stroke. Considering that seizures
may be common and can occur early in the post-resuscitation period, early EEG is important
in diagnosis and management of seizures.3

4.6. Treatment
Emergent Medical Stabilization
After a successful resuscitation with return of spontaneous circulation per ACLS
guidelines, patients who remain unresponsive and are presumed to have HIE, should be
rapidly evaluated for therapeutic hypothermia and ongoing care. If not yet done, the
airway should be definitively secured with endotracheal intubation and mechanical
ventilation should be instituted. All patients should have a 12-lead ECG performed
immediately after resuscitation. Hemodynamic stability has to be maintained and
consideration for cardiac reperfusion interventions must be undertaken in all appropriate
patients. Patient should be kept NPO and enteral access should be obtained via
orogastric tube, and gastric contents emptied and the tube should be placed on low
intermittent suction. Urinary catheters should be inserted in all patients for close
monitoring of urinary output. 3,4,5
After adequate peripheral intravenous access, central venous access should be
considered. The indications for central access are for administration of vasopressors,
additional access, hemodynamic monitoring and endovascular temperature management
when available and applicable. Arterial access should also be obtained expeditiously to
enable hemodynamic monitoring and serial arterial blood gas measurements. Finally
patients should have an initial emergency cranial computed tomography to rule out
complicating conditions with potential to alter immediate management such as
subarachnoid or intraparenchymal hemorrhage, ischemic stroke and cerebral herniation
or conditions that may affect the use of antiplatelet agents of anticoagulants should there
be a concomitant myocardial infarction.3,5

Therapeutic Hypothermia
Since the development of modern CPR techniques in the 1950s, numerous
pharmacological trials with putative neuropotective effects have failed to improve
survival and quality of life of patients resuscitated from cardiac arrest. In 2002, two
randomized clinical trials showed therapeutic hypothermia of 32-34°C for 12-24 hours
provided to comatose survivors of cardiac arrest improved both survival and quality of
life of survivors. Therapeutic hypothermia has demonstrated a robust benefit with a
number needed to treat (NNT) of six. While these two landmark studies focused on out
of hospital cardiac arrest with VT/VF as initial rhythms, subsequent studies showed
likely survival and quality of life benefits for victims of cardiac arrest with initial
rhythms of asystole or PEA with TH. While no prospective randomized controlled trial
has been undertaken to show that benefit of TH in patients with PEA and asystole,
existing studies have also shown that TH is not harmful either. At this time we would
recommend cooling all comatose cardiac arrest victims regardless of presenting ECG
rhythm in accordance to the ILCOR guidelines (AHA class I recommendation for out of
hospital arrest with VT/VF as the initial rhythm, and IIB for those with PEA and
asystole as initial rhythm). Despite its benefits to CA survivors, some considerations
need to be noted for the possible adverse effects of TH. The clinical trials showed non-
significant occurrence of adverse events between TH and control group. Nonetheless,
the more common adverse conditions to be vigilant for include pneumonia, sepsis,
bleeding, electrolyte abnormalities, cardiac arrhythmias and dysglycemia. Establishing
treatment protocols of care for induction and maintenance of hypothermia and
rewarming, as well as tracking and correction of potential adverse events have enhance
the delivery of care and contributed to the success of the TH.
There are many methods to induce hypothermia, ranging from physical surface cooling
on the (ice packs, cold baths, special pads, helmets, etc), intravenous infusions of
chilled fluids, endovascular devices, intraperitoneal, and endonasal cooling systems.
Some evidence favors tighter control of temperature to 32°C, and automated closed-
loop systems (endovascular or surface) are ideal to maintain target temperature in TH.
In general the main determinants of the ability to cool patients regardless of the method,
are the initial ambient and patient temperatures, body surface area, age and the level of
impairment of the endogenous thermoregulatory mechanisms. With regards to the
timing of induction of TH, it is generally accepted that prompt initiation of hypothermia
and achievement of target temperature is optimal. 9,10,11
Clinical evidence in humans undergoing intra-arrest therapeutic hypothermia (IATH) is
limited, but has been shown to be both safe and feasible, and in one study it showed
improvements in ROSC, survival to hospital discharge and neurologic outcomes. The
duration of the maintenance phase of TH is another area that is not well studied or fully
understood. In the original 2002 trials, the European study maintained hypothermia for
24 hours, whereas the Australian study did so for 12 hours. There are ongoing studies
looking to address the question of the optimal duration of TH. There are additional
unanswered questions pertaining the ideal rate of rewarming, which is usually 0.5°C per
hour. The optimal duration of TH and the most appropriate method and rate of
rewarming are still in need of clarification.3

Shivering
Another important consideration when treating with hypothermia is the management
and prevention of shivering. Shivering is a centrally mediated thermoregulatory
response that normally sets in at 35.5°C, and is usually overcome below 34°C.
However, these reference temperatures apply to healthy individuals, and may not be the
same in all CA patients. The absence of shivering after induction of hypothermia, or
spontaneous hypothermia prior to induction of hypothermia has been associated with
worse outcomes, it is possible that damage to the hypothalamus impairing
thermoregulation may be a marker for more severe injury. On the other hand, the
presence of shivering is known to increase body temperature which has been shown to
worsen brain injury and negative impact outcome.
A clinical scale to quantify and assess shivering has been developed and can be used to
suppress shivering in a stepwise fashion. When securing the airway, we would suggest
the use of a non-depolarizing neuromuscular blocking (NMB) agent with no histamine
release potential and short to intermediate duration to facilitate induction of
hypothermia by inhibiting shivering. There has been a shift from continuous infusion of
NMB to intermittent bolus dosing, to control shivering. Concomitant sedation is
necessary with the use of NMB agents. Along with prevent shivering and thereby
facilitating induction of hypothermia, sedation and analgesia also plays an important
role in optimizing ventilator synchrony and minimizing endogenous stress induced by
catecholamine surges.
There is great variability in the practice and methods for both sedation and analgesia in
TH for the PCAS, and this is due to the lack of clear evidence pointing to the choice of
ideal agents. Options for sedation include: fentanyl or remifentanyl infusions; propofol
infusions can be added if necessary to achieve adequate sedoanalgesia that is quickly
titratable, and has favorable context-sensitive half-life profiles. There is also some
experience with the use of benzodiazepines such as midazolam or lorazepam.
Dexmedetomidine is another promising agent as it has little propensity for respiratory
depression and sedation, found in brain injured patients to have superior cognitive
impairment profile, has some potential neuroprotective properties and decreases
shivering. Additionally an initial 4-6gr load of intravenous magnesium sulphate to
achieve serum magnesium levels of 3-4mg/dL, is recommended to correct potential
hypomagnesemia and to facilitate hypothermia by decreasing shivering as part of the
initial stabilization and induction of hypothermia. There are a variety of interventions to
control shivering and in the absence of high quality studies, practitioners need to
individualize treatment based on patient response and medical conditions. The use of
meperidine has also been advocated to aid in controlling shivering, but concerns
regarding the accumulation of metabolites and their impact on seizure threshold make
this a less appealing agent. Buspirone has been shown to be effective and is a favored
adjunct in the management of shivering as is the use of skin counter-warming
measures.3,10
Seizure and Myoclonus Management
In HIE secondary to cardiac arrest the incidence of non-convulsive status epilepticus
(NCSE) is estimated to be as high as 24%, and is associated with worse outcomes.
Therefore, neuromonitoring with continuous surface EEG should be considered
standard of care. It is important to recognize that the presence of NCES in this patient
population should be viewed as an opportunity to aggressively treat this condition in
hopes to modify the natural history of the condition instead of succumbing to self-
fulfilling prophecies of poor outcomes and therapeutic nihilism. There is insufficient
evidence to recommend prophylactic use of antiepileptic drugs at this time, at the same
time the evidence for choosing a particular agent in the treatment of NCSE or status
epilepticus in general. We would recommend the use of less sedating agents and/or
those with short half lives (midazolam, levetiracetam, phosphenytoin or valproic acid)
to avoid clouding the neurologic evaluation and neuroprognostication once the patient
has been rewarmed and adequate time for observation is provided. In those with status
epilepticus, existing management guidelines may enhance delivery of care and improve
patient outcome. Acute post hypoxic myoclonus (PHM) occurs in about 30% of CA
patients with HIE, and can be divided into status myoclonus and multifocal myoclonus.
Though little evidence exists regarding the optimal therapy for PHM, subcortical
myoclonus usually responds best to clonazepam. Propofol, though not an antiepileptic
drug per se, does suppress myoclonic as well as electrographic activity but longer term
control after weaning of propofol is problematic; whereas valproate, phenytoin,
phenobarbital or other benzodiazepines seem to be less effective.3

ICP Management
Cerebral edema is thought to play a major role in the pathophysiology of brain injury
following cardiac arrest. Cerebral edema seems to be apparent on the initial cranial CT
in approximately 30% of patients following cardiac arrest. Therapeutic hypothermia has
an effect in decreasing cerebral edema; however additional measures such as
osmotherapy and barbiturate coma have not been well studied and at this time are not
recommended for routine use. In case of cerebral herniation, the use of hypertonic saline
and osmotherapy in an attempt to reverse herniation is indicated.3
General Intensive Care Management
Hemodynamic Management
Goal directed hemodynamic parameters for PCAS victims undergoing therapeutic
hypothermia should generally include euvolemia and a mean arterial pressure (MAP) of
60 or systolic pressure [SBP] of 90 mmHg to maintain organ perfusion; however a
MAP of 70-100 mmHg may be considered in particularly to augment cerebral perfusion
pressure (CPP) in cases of cerebral edema and elevated intracranial hypertension.
However, these goals must always be individualized and depend on the availability of
monitoring equipment. A multimodal approach to the assessment of intravascular
volume with dynamic indices of volume, fluid responsiveness and organ perfusion
including focused bedside ultrasonography, as well as invasive measurements of
continuous cardiac output, stroke volume variation, pulse pressure variation, global end-
diastolic volume and other hemodynamic variables. However, early and thoughtful
consideration should be given to mechanical support via intraaortic balloon
counterpulsation, cardiopulmonary bypass, ventricular assist devices or an
extracorporeal circulatory support systems.3

Mechanical Ventilation
In the management of HIE, mechanical ventilation should be aimed at maintaining
tissue normoxia and normocapnea. Arterial oxygen concentration or saturation goals
have not been studied rigorously, but there seems to be some indication that
supranormal values may be counterproductive. Current guidelines for post resuscitation
care suggest discontinuation of 100% FiO2 once ROSC is achieved, and that oxygen
delivery be titrated to maintain an arterial oxygen saturation of 94-98% as soon as
possible in the post resuscitation phase, as hyperoxia seems to have detrimental effects.
Normocapnea with PCO2 values between 40-45 mmHg and end-tidal CO2 values of
35-40 mmHg, should be targeted. Hyperventilation can decrease cardiac output via
increased intrathoracic pressure, potential decreases in cerebral blood flow and a
decrease in seizure threshold. Though low tidal volume lung protective ventilation
strategies are standard of care for patients with ARDS and acute lung injury, we also
recommend ventilation with tidal volumes of 6mL/Kg of ideal body weight in patients
without evidence of ARDS. It is recommended that continuous pulse oxymetry and end-
tidal carbon dioxide be monitored, with frequent correlation to measured arterial blood
gas measurements. Both techniques have been used extensively in the setting of
resuscitation, however transcutaneous pulse oxymetry can be potentially confounded in
a linear fashion by increasing hypothermia, and both oxymetry and capnography can be
further affected by poor perfusion states.3

Temperature Modulation
After maintaining TH of 32-34°C for 24 hours, active, controlled rewarming at a rate of
0.25-0.5°C per hour is recommended until a core temperature of 36-37°C is achieved.
Rewarming, the therapeutic temperature management system should remain in place for
a further 48-72 hours to ensure normothermia, protecting the brain from the detrimental
effects of hyperthermia. Rebound pyrexia is a common phenomenon occurring in about
40% of patients post therapeutic hypothermia only temperatures >38.7°C appear to be
associated with worse neurologic outcomes in patients who survive to discharge. The
mechanism for this common presentation of fever after therapeutic hypothermia is not
well understood, however several factor are thought to contribute to its presence: altered
thermoregulation from damage to thalamic structures, rebound hyperthermia, infection
and pro-inflammatory states all are likely contributors.3,8

Renal, Endocrine, Hematologic and Gastrointestinal Management


Therapeutic hypothermia induces important changes in metabolism and homeostasis,
resulting in changes to urine output [cold diuresis] with alterations in potassium,
magnesium and phosphate. The importance of control over potassium and magnesium
levels is related to their importance in cardiac conduction and role in arrhythmogenesis;
potassium levels of >4 mEq/L and magnesium levels >2.0 mEq/L should be maintained,
with levels in the 3-4 mEq/L range to reduce shivering being preferred. Serum sodium
concentrations should be maintained in the normal range whenever possible, however in
cases of cerebral edema, elevated intracranial pressure and herniation, increased sodium
goals must be individualized. Hypotonic intravenous fluids should be avoided.
Normoglycemia should be maintained with insulin infusions to avoid potential for
erratic absorption of subcutaneous insulin with changes in temperature as well as the
fluctuations of glycemia across the phases of therapeutic hypothermia. Hypothermia
decreases insulin secretion and sensitivity and great care must be taken to avoid
hypoglycemia during rewarming as insulin sensitivity increases to baseline. There is no
evidence that ultratight glycemic control improves outcomes, on the contrary
hyperglycemia has been implicated with worse outcomes and increased mortality.
Current guidelines suggest maintaining blood glucose levels between 144-180 mg/dL as
well as aggressively treating levels below 80 mg/dL.3
Patients undergoing TH post cardiac arrest should receive stress ulcer prophylaxis, as
they are at high risk for developing significant gastrointestinal bleeding due to ischemia,
hypoperfusion, physiologic stress and coagulopathy. There is no clear evidence
regarding optimal hemoglobin or hematocrit goals, nor transfusion thresholds for
resuscitated cardiac arrest victims with HIE. The literature on transfusion and
hemoglobin goals in Neurocrit Care lacks adequate large prospective studies. Though
much controversy remains on this subject, patients with acute coronary syndromes and
cerebral ischemia in particular should be carefully evaluated in terms of risk-benefit,
and consideration may be given to transfuse to a goal hematocrit >30% pending
definitive prospective data. It must be noted that the most recent systematic literature
reviews and transfusion guidelines specifically state that a restrictive transfusions
cannot be recommended in high risk patients. DVT prophylaxis is indicated with
graduated compression stockings, pneumatic compression devices and appropriately
weight-based subcutaneous heparin administration.3

4.7. Prognosis
The prognosis for a patient with encephalopathy depends on the initial causes and, in
general, the length of time it takes to reverse, stop, or inhibit those causes. Consequently, the
prognosis varies from patient to patient and ranges from complete recovery to a poor
prognosis that often leads to permanent brain damage or death. A long delay or multiple
delays in treatment can lead to a poor prognosis with extensive brain damage, coma, or death.
Although the symptoms and time frame vary widely from patient to patient and according to
the initial causes of encephalopathy, the prognosis of each case usually depends upon the
extent and rapidity with which the underlying cause is treated. The doctor or team of doctors
treating the underlying cause of encephalopathy can offer the best information on the
individual's prognosis.1

4.8. Prevention
Many cases of encephalopathy can be prevented. The key to prevention is to stop or
limit the chance of developing any of the multitudes of causes of encephalopathy. If
encephalopathy develops, the quicker the underlying cause is treated, the more likely that
severe encephalopathy can be prevented. Methods for prevention of encephalopathy are about
as numerous as the underlying causes; however, some cases of encephalopathy may not be
preventable (for example, congenital and accidental traumatic encephalopathy).1
REFERENCES

1. Medicine Net. 2015. Encephalopathy.


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Neurology (pg. 283-294). Springer, USA.
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Encephalopathy in Adults. Neurocritical Care Society Review Course.
4. Vintila, Corina Roman-Filip, and C. Rociu. 2010. Hypoxic-Ischemic Encephalopathy in
Adult. Acta Medica Transilvanica. 2(3):189-192.
5. Garrido, Mireia Moragas and Jordi Gascon Bayarri. 2012. Hypoxic Encephalopathy.
In:Radu Tanasescu (Editor). Miscellanea on Encephalopathies – A Second Look (pg.
149-166). InTech, Rijeka, Croatia.
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weighted imaging after cardiac arrest. Ann Neurol 2009;65(4):394–402.
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