Hypoxic ischemic encephalopathy, neurocritical care, prognostic factors regarding brain death

1. HYPOXIC ISCHEMIC
ENCEPHALOPATHY
PRECEPTOR
DR MAMTA BHUSHAN SINGH
PRESENTER:
DR SUCHARITA RAY

2. Case vignette
A 62yr old man hypertensive while arguing with his son suddenly complained
of dizziness and collapsed. He was taken to the hospital within 20 minutes and
on the way became unresponsive to his sons frantic attempts at
communication.
Emergency Evaluation: Cyanosed and pulseless. CPR started immediately. ECG:
V Fib requiring a 200-joule biphasic shock followed by CPR and then finally a
360 joule biphasic shock with conversion to a wide-complex rhythm at 120
bpm.
The BP was 120/70 mm Hg. Estimated time from collapse to return of
spontaneous circulation (ROSC) was 15 minutes. He was intubated and then
transported to the emergency department (ED) of a local hospital.

3. Clinical Examination
General Examination: Unremarkable
Neurologic examination: No response to verbal stimulation and no eye opening
to noxious stimulation.
He had reactive pupils, trace corneal reflexes, weakly present horizontal
oculocephalic reflexes, no gag reflex, and a weak cough reflex.
Upon noxious stimulation, he had extensor posturing of the arms and triple
flexion in legs.
The Glasgow Coma Scale (GCS) score was 4. (E1V1M2)

4. The Big Questions…
What is the likely diagnosis ?
How to best treat this condition?
Based on the diagnosis does the neurologic examination exclude the
possibility of a good Outcome ?

5. The First Big Question…
What is the likely diagnosis ?

6. WHAT IS HYPOXIC ISCHEMIC
ENCEPHALOPATHY
• Hypoxic-ischemic encephalopathy (HIE) is a syndrome of acute global brain
injury resulting from critical reduction or loss of blood flow and/or supply of
oxygen and nutrients.
• Some of the terms used to describe this clinical syndrome include:
• Anoxic encephalopathy
• Post-cardiac arrest syndrome*
• Term is used to indicate that the phase of resuscitation has ended with
resumption of spontaneous circulation and the complex changes that occur
secondary to it

7. Mechanism of hypoxia/ischemia Causes
Cardiac arrest followed by respiratory
depression
Massive blood loss, septic/traumatic shock,
and heart disease, such as AMI or ventricular
arrhythmia
Respiratory failure followed by cardiac arrest
with poor inspired oxygen
Tracheal compression/obstruction, drowning,
strangulation, aspiration of gastric content, or
during GA if the inspired gas is oxygen poor
Respiratory muscles weakness Guillain-barré syndrome, amyotrophic lateral
sclerosis, myasthenia gravis) or central
nervous system injury (mainly spinal cord
injury)
Reduced oxygen carriage by the blood Carbon monoxide poisoning
Histotoxicity Cyanide poisoning.
Ropper AH, Brown RH. 2014. Adams and Victor’s principles of neurology, Mc Graw Hill
CAUSES OF HYPOXIC ISCHEMIC ENCEPHALOPATHY

8. Q: IS HYPOXIA ALONE SUFFICIENT FOR CAUSING BRAIN NECROSIS?
ANSWER: FALSE
Unlike ischemia and hypoglycemia, hypoxia alone is rarely responsible for brain necrosis
Study subjects: Physiologically monitored Wistar rats subjected to hypoxia alone (PaO2 =
25 mm Hg) at maintained blood pressure (30 mm Hg) versus Ischemia alone (unilateral
carotid ligation) via unilateral carotid ligation and each of the parameters graded with the
other kept constant.
Hypoxia alone, with normal BP for 15 minutes: No necrosis
Ischemia alone caused necrosis in 4 of 12 rats, despite PaO2 > 100 mm Hg.
Miyamoto et al. Neurology; 2000 Jan 25;54(2):362-71

9. WHAT FACTORS TO KEEP IN MIND IN A CASE OF HYPOXIA/ISCHEMIA:
•The event causing the cut off of oxygen/blood supply
•The rate at which the disruption of blood/oxygen supply takes place
•Previous comorbid factors
•Compensatory mechanisms if any
THE INHERENT PROPERTY OF THE
OXYGEN CARRYING MECHANISM

10. Situation Amount Clinical consequence
Normal brain blood supply 55 ml/min/ 100 g None
Normal brain oxygen supply 4 mg/min/100 g
Acute drop in blood flow 25 ml/min/ 100 g Slowing of the EEG
And syncope or impaired
consciousnessDrop in oxygen saturation <2mg/min/100gm
Refractory shock, post cardiac
arrest, cyanide poisoning
12 to 15 ml/min / 100 g Electrocerebral silence, coma, and
cessation of most neuronal
metabolic and synaptic functions
8 to 10 ml/min/ 100 g. Neuronal death
Oxygen supply< 1 mg/min/100 g
Ropper AH, Brown RH. 2014. Adams and Victor’s principles of neurology, Mc Graw Hill
THRESHOLDS FOR BRAIN TISSUE FOR ISCHEMIA/HYPOXIA

11. PATHOPHYSIOLOGY

12. SEVERE
INJURY
LESS
SEVERE
INJURY
Lai M, Yang S. Perinatal Hypoxic-Ischemic Encephalopathy J Biomed Biotechnology; 2011

13. The Molecular Pathway: Interweaving apoptosis and necroptosis pathways after
HI insult.
Thornton C. Role of mitochondria in apoptotic and necroptotic cell death in the developing brain, Clin Chim Acta (2015); Still in press

14. Post–Cardiac Arrest Syndrome: Pathophysiology, Neurologic Manifestations, and
Potential Treatments
Syndrome Pathophysiology Clinical Manifestation Potential
Rx
Post cardiac Impaired cerebrovasc Coma Therapeutic hypothermia
Arrest brain autoregulation Seizures Early hemodynamic
Injury Cerebral edema Myoclonus optimization
Postischemic Cog. Dysfunction Airway protection and
neurodegeneration Persistent veg state mechanical ventilation
Sec. Parkinsonism Seizure control
Cortical stroke Controlled reoxygenation
Spinal stroke (SaO2 94% to 96%)
Brain death Supportive care
Neumar et al Post–Cardiac Arrest Syndrome. ILCOR Consensus statement. 2453. Circulation. 2008;118:2452–2483.

15. Atypical Posthypoxic neurologic sequelae
•Progressive Extrapyramidal syndrome
•Korsakoff syndrome
•Parkinsonian syndrome with cognitive impairment (mc due to CO poisoning),
•Choreoathetosis
•Cerebellar ataxia
•Intention (action) myoclonus,
•Seizures.
•With prominent ischemia is prominent, two main syndromes are seen, visual agnosia
(Balint syndrome and cortical blindness) and “man in the barrel” syndrome (severe
bilateral arm weakness)
Commichau C. (2006). Hypoxic-Ischemic encephalopathy, in Neurological therapeutics principles and
practice, Noseworthy JH. 528-537

16. Background and methods:
4.5-year prospective observational study
Study period: January 2009 till August 2013
An aetiology study group examined 302 episodes of IHCA.
The purpose was to investigate the causes and cause-related survival in patients
who had inhospital cardiac arrest (IHCA).
To evaluate whether these causes were recognised by the ETs.
D. Bergum et al. Causes of in-hospital cardiac arrest – Incidences and rate of recognition. Resuscitation 87 (2015) 63–68

17. RESULTS OF THE STUDY:
•Cause of IHCA reliably determined in 258 (85%) episodes
•The cause was correctly recognised by the ET in 198 of 302 episodes (66%).
•Cardiac causes were (156, 60%) and hypoxic causes (51, 20%) were present.
•The cause-related survival was 30% for cardiac aetiology and 37% for hypoxic
aetiology.
D. Bergum et al. Causes of in-hospital cardiac arrest – Incidences and rate of recognition. Resuscitation 87 (2015) 63–68

18. Caronna and Finklestein. Neurological syndromes after cardiac arrest. Stroke. 1978; 9:517-520

19. J J Caronna and S Finklestein. Neurological syndromes after cardiac arrest. Stroke. 1978;9:517-520
Signs indicating a favorable prognosis:
1> Spontaneous roving horizontal eye
movements at 12 to 24 hours
2> Speech and comprehension within the
first 48 hours
3> Purposive movement of limbs at any
time
EEG does not have a role in the
diagnosis/prognosis or therapy during
any phase of HIE

20. PARADIGM SHIFT

21. THE MOST ISCHEMIA SUSCEPTIBLE AREAS OF THE BRAIN:
1.The cortical projection neurons
2.The posterior cingulate cortex/precuneus
3.Medial prefrontal cortex
4.Bilateral temporoparietal junctions [collectively termed Default Mode
Network
5.Cerebellar Purkinje cells
6.CA-1 area of the hippocampus
J J Caronna and S Finklestein. Neurological syndromes after cardiac arrest. Stroke. 1978; 9:517-520

22. NEUROIMAGING OF HYPOXIC ISCHEMIC ENCEPHALOPATHY
1.The white matter of the brain is susceptible to hypoxic-ischemic events and
may be involved, even when the insult is systemic and generalized.
2.Thus a leukoencephalopathy can be the end result of long-standing
hypertension or a single hypotensive episode, e.g. perinatal hypoxia.
3.The changes can occur in the setting of global hypoxia in the presence of
focal or global ischemia.
4.The changes vary according to age and severity and are not specific
Gutierrez LG: CT and MR in non-neonatal hypoxic-ischemic encephalopathy: radiological findings with pathophysiological
correlations. Neuroradiology 2010, 52:949–976

23. NEUROIMAGING OF HYPOXIC ISCHEMIC ENCEPHALOPATHY
•What structures does a HIE involve in neuroimaging ?
Severe global hypoxic-ischemic injury in this population primarily affects
the gray matter structures:
• Basal ganglia
• Thalami
• Cerebral cortex (in particular the sensorimotor and visual cortices,
although involvement is often diffuse)
• Cerebellum
• Hippocampi
Gutierrez LG: CT and MR in non-neonatal hypoxic-ischemic encephalopathy: radiological findings with pathophysiological
correlations. Neuroradiology 2010, 52:949–976

24. NEUROIMAGING OF HYPOXIC ISCHEMIC ENCEPHALOPATHY
•Why the grey matter is preferentially involved in hypoxic damage ?
The gray matter contains most of the dendrites where postsynaptic glutamate
receptors are located. Hence early to be involved in the excitotoxicity.
It is also more metabolically active than white matter
•Why is cerebellum more affected in older but spared in children?
The relative immaturity of Purkinje cells (which are normally exquisitely
sensitive to ischaemic damage) in neonates somehow protects the cerebellar
cortex
Gutierrez LG: CT and MR in non-neonatal hypoxic-ischemic encephalopathy: radiological findings with pathophysiological
correlations. Neuroradiology 2010, 52:949–976

25. NEUROIMAGING FEATURES OF HYPOXIC-ISCHEMIC
ENCEPHALOPATHY• Diffuse oedema with effacement of the CSF-containing spaces
• Decreased cortical gray matter attenuation with loss of normal gray-white
differentiation
• Decreased bilateral basal ganglia attenuation
• Reversal Sign: Reversal of the normal CT attenuation of grey and white
matter, demonstrated within the first 24 hours.
•White Cerebellum Sign: Diffuse oedema and hypoattenuation of the
cerebral hemispheres with sparing of the cerebellum and brainstem,
resulting in apparent high attenuation of the cerebellum and brainstem
relative to the cerebral hemispheres
Gutierrez LG: CT and MR in non-neonatal hypoxic-ischemic encephalopathy: radiological findings with pathophysiological
correlations. Neuroradiology 2010, 52:949–976

26. • Linear hyperdensity outlining the cortex as well as linear cortical
enhancement (later and less evident signs), corresponding to Cortical Laminar
Necrosis
• Falx cerebri and tentorium cerebelli can appear hyperdense to ischaemic
brain parenchyma and is one of the causes of pseudo-subarachnoid
hemorrhage
* Both the reversal sign and the white cerebellum sign indicate severe injury
and a poor neurologic outcome
Radiographic features
Gutierrez LG: CT and MR in non-neonatal hypoxic-ischemic encephalopathy: radiological findings with pathophysiological
correlations. Neuroradiology 2010, 52:949–976

27. NCCT Head:
Bilateral hyperdense caudate and
putamina and subtle increased
cortical density

28. 1.Severe grey matter necrosis.
2.Reversal of normal white/grey
matter density.
NCCT Head performed 40 minute down time following cardiac arrest.

29. Severe hypoxic ischemic
encephalopathy with multifocal
infarctions
(including midbrain, bilateral
thalamic, multifocal supratentorial
cortical)

30. Recent resuscitation from CPR:
Cerebral Oedema leading to decreased
parenchyma attenuation
and engorgement and dilatation of the
superficial venous structures due
an increased intracranial pressure
Huang BY, Castillo M. Hypoxic-ischemic brain injury: imaging findings from birth to adulthood. Radiographics. 28 (2): 417-39,2009

31. Cortical layers 3, 4, and 5 have
higher metabolic demands and
hence lead to cortical laminar
necrosis.
The gyriform high attenuation
(likely caused by local
hemorrhage) is believed to be
caused by the accumulation of
denatured proteins in dying cells
It does not represent presence of
hemorrhage.

32. Low density of caudate head
and lentiform nucleus.
This vagrant was found unconscious on the street, bottle of alcohol in hand.
Huang BY, Castillo M. Hypoxic-ischemic brain injury: imaging findings
from birth to adulthood. Radiographics. 28 (2): 417-39,2009

33. White cerebellum sign (Reversal sign or dense cerebellum sign)
Diffuse decrease in density of the
supratentorial brain parenchyma,
with relatively increased
attenuation of the thalami,
brainstem and cerebellum.
This sign indicates irreversible brain
damage and has a very poor
prognosis
Theories proposed for this sign :
1.Raised intracranial pressure
causes partial venous obstruction
resulting in distension of deep
medullary veins.
2.Preferential flow to posterior
circulation.
3.Transtentorial herniation partially
relieving the increased intracranial
pressure, and thus increase
perfusion of central structures.
It is associated with :
1.severe head trauma
2.birth asphyxia
3.Drowning
4.status epilepticus
5.bacterial meningitis
6.Encephalitis
7.post-cardiac arrest hypoxia
Chavhan GB. Twenty classic signs in neuroradiology: A
pictorial essay. Indian J Radiol Imaging. 19 (2): 135-45.

34. Cranial CT after cardiac arrest demonstrating watershed infarction between the anterior and
middle and between the middle and posterior cerebral arteries

35. NEUROPATHOLOGY OF VEGETATIVE STATE AFTER AN ACUTE BRAIN INSULT
Adams JH. The neuropathology of the vegetative state after an acute brain insult. Brain 123, 1327–1338, 2000.
(A) Gross specimen demonstrating watershed infarcts (B) Low magnification view of the cerebral cortex

36. NEUROPATHOLOGY OF VEGETATIVE STATE AFTER AN
ACUTE BRAIN INSULT
Adams JH. The neuropathology of the vegetative state after an acute brain insult. Brain 123, 1327–1338, 2000.
(B) Area of necrosis involves layers II to V of cortex (C) Pyknotic and eosinophilic cerebral cortex

37. SEQUENCE EARLY LATE
T1WI Subtle swelling of grey matter structures
Laminar cortical necrosis after 2 weeks
Cortical necrosis,Passive
ventricular enlargement
(Ventriculomegaly,) PVWM
volume loss, PV cavitation,
thin callosum
T2WI T2 signal in PVWM (edema, ischemia, or
infarction), focal T2 signal (hemorrhagic
necrosis)
Residual Basal Ganglia
hyperintensity, Gliosis,
thalamic scarring, PV cysts
Demyelination
DWI Normal before 24 h of life. 1st
24 hours,
cerebellar hemispheres, basal ganglia, or
cerebral cortex , perirolandic and occipital
cortices).
ADC normalizes within 10-12
days. Pseudonormalization of
DWI
MRI CHANGES IN HIE

38. 35-year-old patient who had experienced an
ischemic event several weeks earlier.
Axial T1-weightedMR image:
Bilateral serpiginous high signal intensity in the
cortex of the occipital lobes (greater on the left
side),
A finding that is compatible with cortical
necrosis
Huang BY, Castillo M. Hypoxic-ischemic brain injury: imaging findings from birth to adulthood. Radiographics.28 (2): 417-39, 2009

39. MRI findings. FLAIR images (a) High signal intensity areas in bilateral periventricular white matter and
pallidal nuclei. DWI imaging (b) show similar high signal intensity in the PWM, with diffuse low signal
intensity in the ADC map (c). Follow up one month later shows resolution

40. Delayed White Matter Injury (Postanoxic Leukoencephalopathy)
•Uncommon syndrome of delayed white matter injury, 2-3% patients of HIE.
•Usually occurs weeks after a hypoxic-ischemic event e.g CO poisoning.
•Period of relative clinical stability/improvement, followed by an acute
neurologic decline with delirium, personality changes, intellectual impairment,
movement disorders, or, rarely, seizures
•May even show steady decline without a lucid interval
•Approximately 75% of patients have complete or near-complete recovery over
the next 6–12 months.
•In the remaining patients, there may be residual dementia.
•Rarely, the condition may progress to paresis, a vegetative state, or death

41. Immediate period after causative insult:
No WM Abnormalities on conventional imaging
Period of delayed neurologic decline:
DWI: Diffuse confluent areas of restricted diffusion throughout the cerebral
white matter
T2WI: Corresponding hyperintensity on T2-weighted images is also seen.
Postanoxic Leukoencephalopathy Neuroimaging
Roychowdhury S. Postanoxic encephalopathy: Review of MR findings. J Comput Assist Tomogr 1998;22:992–94

42. Postanoxic Leukoencephalopathy Neuroimaging
Postanoxic leukoencephalopathy in an adult patient who had experienced respiratory arrest 2
weeks earlier. (a, b) Axial T2-weighted (a) and diffusion-weighted (b) MR images show diffuse
white matter hyperintensity.(c) On the corresponding ADC map, the white matter is hypointense,
a finding that indicates restricted diffusion.

43. ILCOR Levels of evidence for prognostic studies.
LOE P1: Inception (prospective) cohort studies (or meta-analyses of
inception cohort studies), or validation studies of a clinical decision rule (CDR)
LOE P2: Follow-up of untreated control groups in randomized controlled trials
(or meta-analyses of follow-up studies), or derivation studies of a CDR, or
validation studies of a CDR using a split-sample
LOE P3 Retrospective cohort studies
LOE P4 Case series
LOE P5 Studies not directly related to the specific patient/population (e.g.
different patient/population, animal and mechanical models)

44. SUMMARY OF EVIDENCE FOR NCCT
HEAD
D.K. Hahn et al. Quality of evidence in studies evaluating neuroimaging for neurologic prognostication in adult patients resuscitated from
cardiac arrest.Resuscitation 85 (2014) 165– 172; 167

45. SUMMARY OF EVIDENCE FOR MRI
BRAIN
D.K. Hahn et al. Quality of evidence in studies evaluating neuroimaging for neurologic prognostication in adult patients resuscitated from
cardiac arrest.Resuscitation 85 (2014) 165– 172; 167

46. CONCLUSIONS FROM THE STUDY
• There is insufficient scientific evidence to support or refute the use of
neuroimaging
• There is an abundance of data in the current literature,
• The majority of these studies are limited by their design.
• These limitations include:
• Retrospective design,
• Small cohort size,
• Lack of control for confounders
• Early withdrawal of care,
• Lack of blinding
• Lack of comparison with standard clinical methods of prognostication
D.K. Hahn et al. Quality of evidence in studies evaluating neuroimaging for neurologic prognostication in adult patients resuscitated from
cardiac arrest.Resuscitation 85 (2014) 165– 172; 167

47. Biochemical markers (NSE, S-100, IL-8) as predictors of neurological
outcome in patients after cardiac arrest and return of spontaneous
circulation
BIOMARKERS THAT HAVE BEEN STUDIED SO FAR:
1.Brain creatine phosphokinase (CPK BB)
2.Glutamate transaminase
3.Lactate dehydrogenase
4.Pyruvate (Serum/CSF)
THE THREE PROMISING BIOMARKERS STUDIED:
Neuron-specific enolase (NSE)
Protein soluble in 100% ammonium sulfate (S-100)
Interleukin-8 (IL-8)

48. Konstantinos A. Biochemical markers (NSE, S-100, IL-8) as predictors of neurological outcome in patients after CA AND ROSC.
Resuscitation (2007) 75, 219—228

49. Konstantinos A. Biochemical markers (NSE, S-100, IL-8) as predictors of neurological outcome in patients after CA AND ROSC.
Resuscitation (2007) 75, 219—228

51. The Big Question…
What is the likely diagnosis ?
How to best treat this condition?

52. Salazar-Reyes H, Varon J: Hypoxic tissue damage and the protective effects of therapeutic
hypothermia. Crit Care & Shock 2005;8:28-31.

53. TREATMENT OF A CASE OF HYPOXIC ISCHEMIC ENCEPHALOPATHY
Emergent Medical Stabilization
Therapeutic Hypothermia
Seizure and Myoclonus Management
ICP Management
General Intensive Care Management
PROGNOSTICATION
© 2013 Neurocritical Care Society Review Course

54. EMERGENT MEDICAL STABILIZATION
 Securing Airway
IV Access-preferably Central Venous Access
NPO, orogastric tube with low intermittent suction
Urinary Catherter with Strict I/O Monitoring
Monitoring of vitals, administration of vasopressors if required
Ruling out concomitant other pathologies like SAH, CVA etc
© 2013 Neurocritical Care Society Review Course

55. Strategies for Improving Survival After In-Hospital Cardiac Arrest in the United States:
2013 Consensus Recommendations
by Laurie J. Morrison, Robert W. Neumar, Janice L. Zimmerman, Mark S. Link, L.
Kristin Newby, Paul W. McMullan, Terry Vanden Hoek, Colleen C. Halverson, Lynn
Doering, Mary Ann Peberdy, and Dana P. Edelson
Circulation
Volume 127(14):1538-1563
April 9, 2013
Copyright © American Heart Association, Inc. All rights reserved.

56. Strategies for Improving Survival After In-Hospital Cardiac Arrest in the United States:
2013 Consensus Recommendations
Copyright © American Heart Association, Inc.

57. Seizure and Myoclonus Management
 Incidence of non-convulsive status epilepticus can be as high as 24% which
signifies a worse prognosis
 Continuous VEEG monitoring for the same is standard of care
 Insufficient evidence to recommend prophylactic use of antiepileptics
 Less sedating agents and/or those with short half lives (midazolam,
levetiracetam, phosphenytoin or valproic acid) to avoid clouding the
neurologic evaluation and neuroprognostication
 Acute post hypoxic myoclonus (PHM) occurs in about 30%:
 Status myoclonus
 Multifocal myoclonus.
 Subcortical myoclonus: Rx with clonazepam. Propofol, may also be useful
though longer term control after weaning is problematic
Copyright © American Heart Association, Inc.

58. Patel R, Jha S. Intravenous valproate in post-anoxic myoclonic status epilepticus: A report of ten patients.
Neurol India 2004;52:394-6
Intravenous valproate in post-anoxic myoclonic
status epilepticus: A report of ten patients
• Study of the efficacy of intravenous VP in 10 patients who developed MSE
following anoxic cerebral injury in the peri- and postoperative (within 24-48
hours) period.
• MSE was terminated with iv VP alone in 6 patients and the time duration
for the termination of MSE was between 2-10 hours.
• An additional infusion of a second AED, I/V diazepam/lorazepam, one each
was required in 2 patients to terminate MSE.
• The time taken for the termination of MSE was 26 and 38 hours.
Limitation: Continuous EEG monitoring was not done and serum valproate
levels were not measured.

59. Therapeutic Hypothermia

60. • Therapeutic hypothermia has demonstrated a robust benefit with a number
needed to treat (NNT) of six.
• Survival benefit for out of hospital cardiac arrest with VT/VF as initial rhythms or
asystole or PEA
• 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.
• The duration of the method in the original 2002 European study
maintained hypothermia for 24 hours and Australian study was for 12
hours.
Copyright © American Heart Association, Inc.

61. ICP Management
•Cerebral edema apparent on the initial cranial CT in approximately 30% of
patients following cardiac arrest
•In case of cerebral herniation, the use of hypertonic saline and osmotherapy in
an attempt to reverse herniation is indicated
Copyright © American Heart Association, Inc.

62. General Intensive Care Management
Hemodynamic Management: MAP of 60 or SBP of 90 mmHg to maintain
organ perfusion; however a MAP of 70-100 mmHg may be considered to
augment cerebral perfusion pressure (CPP) in cases of cerebral edema and
elevated intracranial hypertension.
Mechanical Ventilation:
Discontinue 100% FiO2 once ROSC is achieved
Arterial oxygen saturation of 94-98% soon as possible post resuscitation
* Hyperoxia seems to have detrimental effects
Normocapnea with PCO2 between 40-45 mmHg and ETCO2 35-40 mmHg
Copyright © American Heart Association, Inc.

63. Association between arterial hyperoxia following resuscitation from cardiac
arrest and in-hospital mortality.
Objective: Postresuscitation hyperoxia is associated with increased mortality.
Design, Setting, and Patients Multicenter cohort study: Project IMPACT database of
intensive care units (ICUs) at 120 US hospitals (2001 - 2005)
Main Outcome Measure In-hospital mortality.
Inclusion criteria:
Age > 17 years, nontraumatic cardiac arrest,
CPR within 24 hours prior to ICU arrival
ABG within 24 hours following ICU arrival.
Patients were divided into 3 groups hypoxia, hyperoxia and normoxia based on
predefined parameters J H Kilgannon et al. (Reprinted) JAMA, June 2, 2010—Vol 303, No. 21 2165

64. Results Of 6326 patients, 1156 had hyperoxia (18%), 3999 had hypoxia (63%),
and 1171 had normoxia (19%).
The hyperoxia group had significantly higher inhospital mortality (732/1156 [63%;
95% confidence interval {CI}, 60%-66%])
Normoxia group (532/1171 [45%; 95% CI, 43%-48%];
Hypoxia group (2297/3999 [57%; 95% CI, 56%-59%]
Controlling for confounders (age, preadmission functional status, comorbid
conditions, vital signs, and other physiological indices), hyperoxia exposure had an
odds ratio for death of 1.8 (95% CI, 1.5-2.2).
Conclusion Among patients admitted to the ICU following resuscitation from cardiac
arrest, arterial hyperoxia was independently associated with increased in-hospital
mortality compared with either hypoxia or normoxia.
J H Kilgannon et al. (Reprinted) JAMA, June 2, 2010—Vol 303, No. 21 2165

65. OTHER PROMISING STRATEGIES !!!

66. The Big Questions…
What is the likely diagnosis ?
How to best treat this condition?
Based on the diagnosis does the neurologic examination exclude the
possibility of a good Outcome ?

67. Outcome of coma by etiology
Death Persistent vegetative state Good recovery
Hypoxic-Ischemic 58 20 8
Toxic-Metabolic 47 6 25
Cerebrovascular 74 7 3
Total 61 12 10
Adapted from Bates D.The prognosis of medical coma. J Neurol Neurosurg Psychiatry. 2001;71(Suppl 1): i20–3.

68. Cardiac arrest survivors treated with or without mild therapeutic hypothermia:
performance status and quality of life assessment
•To determine long-term neurological and psychological status in cardiac arrest survivors
•To compare neuropsychological outcomes between patients treated with mild therapeutic
hypothermia (MTH) vs patients who did not undergo hypothermia treatment
•Single-center, retrospective, observational study on 28 post-cardiac arrest adult vs 37
control group patients, hospitalized at the same center following cardiac arrest in the
preceding years and fulfilling criteria for induced hypothermia but not given it.

69. Results: No statistically significant differences in physical functioning found between
groups either at the end of hospital treatment or at long-term follow-up (DRS: p = 0.11;
Barthel Index: p = 0.83).
In long-term follow-up, MTH patients showed higher vitality (p = 0.02) and reported fewer
complaints on role limitations due to emotional problems (p = 0.04) compared to the
control group.
No significant differences were shown between study groups in terms of physical
capacity and independent functioning.
Conclusion: To conclude, in long-term follow-up, MTH patients showed higher vitality and
reported fewer complaints on role limitations due to emotional problems compared to
the control group. This suggest that MTH helps to preserve global brain function in cardiac
arrest survivors. However, the results can be biased by a small sample size and variable
observation periods.

70. Majority of studies done have so far predicted an outcome no better than a
vegetative state or severe disability with total dependency at 3 to 6 months after
arrest (a Glasgow Outcome Scale score of 3 or less)
Vegetative state= wakefulness
but no evidence of conscious
awareness.
Wijdicks EFM et al Practice parameters: prediction of outcome in comatose survivors after CPR. Neurology 2006; 67:203-10

71. Decision Algorithm for Use in Outcome Prediction for Comatose Survivors of Cardiac Arrest
Wijdicks EFM et al Practice parameters. Neurology 2006; 67:203-10

72. NEUROPROGNOSTICATION IN PATIENTS OF HYPOXIC ISCHEMIC
ENCEPHALOPATHY:
Use of therapeutic hypothermia as a treatment modality
Use of sedatives and analgesics
Organ failure and shock
Phenomenon of self fulfilling prophecy
Prognostication not the same for different causative etiologies.
No good evidence from well-designed studies to support early
prognostication (< 72 hours) in cardiac arrest survivors treated with
TH.
Wijdicks EFM et al Practice parameters: prediction of outcome in comatose survivors after CPR. Neurology 2006; 67:203-10

73. NEUROPROGNOSTICATION IN PATIENTS OF HYPOXIC ISCHEMIC
ENCEPHALOPATHY:
Neuroprognostication is vital and yet one of the most controversial topics in post
resuscitation care.
To date there is no adequate paradigm to prognosticate HIE treated with TH
Prognostication parameters exist for HIE without TH as a intervention as far
back as 2006 by AAN.
Traditional prognostication parameters:
Brainstem reflexes
Motor responses
Myoclonus
Wijdicks EFM et al Practice parameters: prediction of outcome in comatose survivors after CPR. Neurology 2006; 67:203-10

74. Objectives:
•Review and update of the evidence on predictors of poor outcome in adult
comatose survivors of cardiac arrest
•Patients may be either treated or not treated with controlled temperature
•Identification of gaps in knowledge and suggestion of a reliable
prognostication strategy.
C. Sandroni et al. Prognostication in comatose survivors of cardiac arrest. Resuscitation 85 (2014) 1779–
89

75. C. Sandroni et al. Prognostication in comatose survivors of cardiac arrest. Resuscitation 85 (2014) 1779–
Methods:
Systematic Review of a total of 73 studies
Predictors were based on the following:
1.Clinical examination
2.Electrophysiology
3.Biomarkers and
4.Imaging

76. C. Sandroni et al. Prognostication in comatose survivors of cardiac arrest. Resuscitation 85 (2014) 1779–89
Results and conclusions:
•The quality of evidence was low or very low for almost all studies
•In patients who are comatose with absent or extensor responses at ≥72 h from
arrest, either treated or not treated with controlled temperature
•Bilateral absence of either pupillary and corneal reflexes or N20 wave of short-
latency somatosensory evoked potentials were identified as the most robust
predictors.

77. C. Sandroni et al. Prognostication in comatose survivors of cardiac arrest. Resuscitation 85 (2014) 1779–89
USEFUL BUT LESS ROBUST PREDICTORS:
•Early status myoclonus
•Elevated values of neuron specific enolase at 48–72 h from arrest
•Unreactive malignant EEG patterns after rewarming
•Presence of diffuse signs of postanoxic injury on either CT or MRI.
* Prolonged observation and repeated assessments should be considered when
results of initial assessment are inconclusive.

78. NEUROPROGNOSTICATION IN PATIENTS OF HYPOXIC ISCHEMIC ENCEPHALOPATHY:
Recent parameters incorporated in prognostication of HIE:
Somatosensory evoked potentials [SSEP]
Neuron specific enolase (NSE)
Neuroimaging

79. • Large unmet gap in knowledge, attitude and practice in patients with in hospital
or out of hospital cardiac arrest
• At our level accurate diagnosis should be achieved at the earliest and aggressive
management should be pursued in triaged patients
• Efforts must be placed on creating new hospital protocols that emphasize the
importance of achieving mild hypothermia within the first hours after
cardiopulmonary arrest, as well as detecting and promptly treating any kind of
seizure
• Neuroprognostication should take into account not only clinical signs but also
laboratory parameters
TAKE HOME MESSAGE

81. DURATION OF HYPOXIA CLINICAL SIGNS
•Up to 1 minute Unconsciousness, convulsions,
Miosis, abolished pupillary reflex
•After 2 minutes Mydriasis, the abolition of corneal
reflex
•After 5 minutes Cerebral cortex suffering irreversible
damage
•After 15 minutes Irreversible damage at brain stem
and the spinal cord