Prognosis of Anoxic-Ischemic Encephalopathy

  • James Fausto MD

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Introduction    Cardiac arrest, experienced by approximately 450,000 Americans annually, has a very poor survival rate (see Fast Fact #179).  Some patients who initially survive cardiopulmonary resuscitation remain comatose, demonstrating obvious impairments in consciousness and neurologic function.  This syndrome, called anoxic-ischemic encephalopathy (AIE, also known as ‘anoxic brain injury,’ or ‘hypoxic-ischemic coma’), can result in outcomes ranging from full recovery to permanent unconsciousness to death.  This Fast Fact discusses prognostic factors in adults with AIE after cardiac arrest. 

“Neurologic Outcome”    A challenge in interpreting the literature on AIE is the use of variable or imprecise definitions of a ‘poor neurologic outcome.’  The American Academy of Neurology practice parameter paper defines poor outcome as:  death, persistent unconsciousness (such as a vegetative state), or severe disability requiring full nursing care after 6 months (6).  This is the definition used in this Fast Fact.

Predictors of Neurologic Outcome     A review of the current literature reveals that data obtained by careful neurologic exam, electrophysiologic studies, and biochemical markers are most predictive of outcome (see below).   Other factors not strongly predictive of outcome include:  age, sex, cause of arrest, type of arrhythmia, total arrest time, duration of CPR, geographic location of arrest, elevated body temperature, elevated intracranial pressure, concurrent respiratory failure, and early brain imaging findings (3,6,7,8). 

Note:  the data below assume patients are not receiving medications which would significantly confound their neurologic examination such as high-dose barbiturates.  In all cases, specialist neurologic examination and input is advised. 

Strong Indicators of Poor Outcome (false positive rates of 0% based on current literature):

  • Absent pupillary light reflexes 24 hours after CPR, or 72 hours after CPR for those who initially had intact papillary light reflexes (3,6,7).  
  • Absent corneal reflexes 72 hours post-CPR (6,7).
  • Short-latency Somatosensory Evoked Potentials (SSEP, an electrophysiologic study):  bilateral absence of the N20 potentials on SSEP of the median nerve in AIE patients greater than 24 hours post-CPR (1,6,7,8).
  • Neuron-Specific Enolase (NSE, a blood test):  serum NSE > 33 mcg/L on day 1 to 3 (6,7,8).  While this biomarker is promising, it has not been studied in large trials, nor is the assay itself standardized, so its current clinical role remains undefined (7).

Moderate Predictors of Poor Outcomes (these all predict a poor outcome, but not as invariably as the above factors based on current literature):

  • Clinical exam findings: no spontaneous eye movements or absent oculocephalic reflexes at 72 hours post-arrest (3,6,7).  No, or extensor-only, motor response to painful stimuli at 72 hours also implies a very poor chance of recovery (3,6).
  • Electroencephalogram findings:  certain findings can be strongly associated with poor outcomes but are highly subject to institutional/technician variability.  Myoclonic status epilepticus within 1 day of cardiac arrest is the most predictive of a poor outcome (3,6,7,8). 

The Therapeutic Hypothermia Protocol    The majority of the evidence for prognosis in the comatose patient after CPR predates the widespread use of therapeutic hypothermia in patients after cardiac arrest. It remains unclear how this intervention will change prognostication.  While the above factors will likely still indicate poor prognosis, the timing of when the evaluations should be done, as well as if they will predict a uniformly poor outcome is uncertain.  One European study advises that patients have an initial neurological assessment as soon as possible, but that the second assessment occurs no earlier than 48-72 hours after the return of normal blood temperature and not 48-72 hours after the discontinuation of active cooling (2).  Zandbergen et al suggest that serum NSE >33 mcg/L occurring while hypothermic still consistently predicts poor outcomes accurately (8).  Initial data (4,8) on the predictive value of SSEPs in patients who underwent hypothermia confirmed that bilateral absent N20 responses is highly predictive of a poor outcome.  There has been a case report of an isolated patient with absent N20 responses who made a full recovery, highlighting the importance of ongoing investigation into the impact of the hypothermia protocol on the prognosis of AIE (4). 


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  2. Friberg,H.. Neurological prognostication after cardiac arrest. Scand J Trauma Resuscitation Emerg Med.  2008; 16:10.
  3. Levy DE, Caronna JJ, Singer BH, Lapinski RH, Frydman H, Pulm F. Predicting outcome from hypoxic-ischemic coma. JAMA. 1985; 253:1420-6.
  4. Leithner C, Ploner CJ, Hasper D, Storm C.  Does hypothermia influence the predictive value of bilateral absent N20 after cardiac arrest? Neurol. 2010; 74:965-969.
  5. Lloyd-Jones D, et al.  Heart disease and stroke statistics 2010 update:  a report from the American      Heart Association.  Circulation. 2010; 121:e46-e215.
  6. Wijdicks EFM, Hijdra A, Young GB, et al.  Practice parameter: prediction of outcome in comatose survivors after cardiopulmonary resuscitation (an evidence based review): report of the Quality Standards Subcommittee of American Academy of Neurology.  Neurol. 2006; 67:203-10.
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  8. Zandbergen EG, Hijdra A, Koelman JH, et al.  Prediction of poor outcome within the first 3     

days of postanoxic coma.  Neurol. 2006; 66:62-8.

Author Affiliation:   Montefiore Medical Center, Albert Einstein College of Medicine, Bronx, NY.

Version History:   Originally published October 2010; copy-edited August 2015 by Ann Helms MD.