Outline the value of the following in determining prognosis for neurological recovery in an adult patient admitted to ICU, after successful cardiovascular resuscitation from an out-of-hospital cardiac arrest:

a)     Peri-arrest data

b)     Clinical examination

c)     Neuro-imaging

d)     Neurophysiology

e)     Biomarkers

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College Answer

a. Peri-arrest data:

Initial rhythm, bystander CPR, time to ROSC intuitively helpful and commonly considered, but have not been shown to correlate  with individual  outcome.   Co-morbidities  and pre- arrest performance status may determine overall survival.

b. Clinical Examination:

Unreliable  and of no predictive  value before 24 hours, clinical assessment  at ≥ 72 hours conventional
•    Appropriate     pre-conditions:    absence     of    sedation/relaxants,     adequate     CVS
resuscitation, normothermia, corrected biochemistry etc.
•    All data pertains to studies before the common use of therapeutic hypothermia, and the effect of this intervention  unknown.   May need longer than 72 hours to obtain reliable data from CNS examination in patients treated with induced hypothermia
•    GCS < 4, absent corneal response, absent pupillary response to light indicative of poor prognosis
•    myoclonus not sufficiently predictive to be reliable in isolation but myoclonic status epilepticus is a poor prognostic feature

c. Neuro-imaging:

•    CT may be performed early to exclude a CNS cause of arrest
•    CT  signs  of  poor  prognosis   include  qualitative   assessment,   and  quantitative assessment of white matter Houndsfield unit ratio.  Optimum timing not clear
•    MRI demonstration  of diffuse cortical lesions  or sub-cortical  lesions  is associated with poor outcome

d. Neurophysiology:

•    No neurophysiology study reliably predicts outcome at < 24 hours
•    EEG findings  of: diffuse suppression  to < 20 mV, burst suppression,  generalised seizures, diffuse periodic complexes indicate poor prognosis
•    EEG  shown  to  have  increased  false  positive  prediction  for  poor  outcome  after induced hypothermia
•    SSEP:  bilaterally  absent  cortical  responses  to  median  nerve  stimulation  seems highly accurate (0% False Positive Rate), not studied after induced hypothermia

e. Biomarkers:

•    Neurone specific enolase (NSE) most studied, some studies show 0% FPR for poor outcome, but cut-off levels vary, studies small

Discussion

With the exception of the "peri-arrest data" section, this question closely resembles Question 4 from the second paper of 2013.

The table from Question 4 is thus reproduced below, with the peri-arrest data section added, sans the confounding factors column. The whole peri-arrest data issue is better discussed in the chapter on prognostication of neurological recovery following a cardiac arrest.

Peri-arrest data:

Predictors of Poor Outcome in Comatose Survivors of Cardiac Arrest
Predictive sign or investigation Predictive utility Confounding factors
Absent pupillary reflex

 0% false positive rate at 72 hours, irrespective of cooling

  • Sedation
  • Hypothermia
  • Paralysis
  • Presence of shock
  • Metabolic derangements, eg. acidosis
Absent corneal reflex  0-15% false positive rate at 72 hours
Extensor motor response, or worse May be associated with poor outcomes
  • High false positive rate (~50%)
Myoclonic status epilepticus Persisting myoclonic status epilepticus has a 0% false positive rate within the first 24 hours
  • Interpreter-dependent
  • Findings may be subtle
  • Paralysis interferes with interpretation
Somatosensory evoked potentials:
absence of the N20 component
Absence of N20 predicts poor outcome with a0% false positive rate.

Presence of N20 does not rule out a poor outcome.

N20 responses may disappear on repeat testing.

N20 responses may reappear, but this does not suggest a good prognosis.

Burst suppression on EEG May be associated with poor outcome  Poor predicitive value; 
cannot be used for prognostication.
Absence of EEG reactivity Low false positive rate (0-5%) Confounded by sedation
Neuron-specific enolase NSE over 33μg/L at 1-3 days post CPR predicts poor outcome with a 0% false positive rate

NSE may be elevated for reasons other than brain injury; for instance, it may be secreted by neuroendocrine tumours

CT brain On CT, an inversed gray/white matter ratio in Hounsfield units was found in patients who failed to awaken after cardiac resuscitation. However, the predictive value of CT findings is not known

If performed too early, the CT may not demonstrate any findings.

The key features of the college answer one would be wise to remember include the following:

  • Arrest characteristics (eg. time to ROSC) do not correlate with individual outcome.
  • Clinical findings are unreliable within the first 24 hours.

References

References

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Bunch, T. Jared, et al. "Outcomes and in-hospital treatment of out-of-hospital cardiac arrest patients resuscitated from ventricular fibrillation by early defibrillation." Mayo Clinic Proceedings. Vol. 79. No. 5. Elsevier, 2004.

Levine, Robert L., Marvin A. Wayne, and Charles C. Miller. "End-tidal carbon dioxide and outcome of out-of-hospital cardiac arrest." New England Journal of Medicine 337.5 (1997): 301-306.

Rea, Thomas D., et al. "Temporal Trends in Sudden Cardiac Arrest A 25-Year Emergency Medical Services Perspective." Circulation 107.22 (2003): 2780-2785.

Carew, Heather T., Weiya Zhang, and Thomas D. Rea. "Chronic health conditions and survival after out-of-hospital ventricular fibrillation cardiac arrest." Heart 93.6 (2007): 728-731.

Goldberger, Zachary D., et al. "Duration of resuscitation efforts and survival after in-hospital cardiac arrest: an observational study." The Lancet (2012).

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Rogove, Herbert J., et al. "Old age does not negate good cerebral outcome after cardiopulmonary resuscitation: analyses from the brain resuscitation clinical trials."Critical care medicine 23.1 (1995): 18-25.

Levy, David E., et al. "Predicting outcome from hypoxic-ischemic coma." Jama253.10 (1985): 1420-1426.

Zandbergen, E. G. J., et al. "Prediction of poor outcome within the first 3 days of postanoxic coma." Neurology 66.1 (2006): 62-68.

Tapia, F. J., et al. "Neuron-specific enolase is produced by neuroendocrine tumours." The Lancet 317.8224 (1981): 808-811.

Torbey, Michel T., et al. "Quantitative analysis of the loss of distinction between gray and white matter in comatose patients after cardiac arrest." Stroke 31.9 (2000): 2163-2167.