Question 4

Describe the clinical signs and investigations available to predict poor neurological outcome in comatose survivors of cardiac arrest.
Include in your answer the factors that may confound the interpretation of these signs and investigations.

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College Answer

Observations and Investigations:

Clinical Signs:

  • Absent brain stem reflexes.
  • Myoclonic status epilepticus within the first 24 hours.
  • (Generalised and repetitive myoclonus is strongly associated with poor outcome, with a reported false positive rate of 0%. Conversely, single seizures and sporadic myoclonus, do not accurately predict poor outcome.)
  • Absence of pupillary responses – within days 1 to 3 after CPR.
  • Absent corneal responses - within days 1 to 3 after CPR.
  • Absent or extensor motor responses – after 3 days post CPR.


EEG patterns of generalised suppression, burst suppression, or generalised periodic complexes are strongly associated with poor outcome, but the prognostic accuracy is not considered as high as SSEP.

Bilateral absence of N20 component of SSEP with median nerve stimulation within 1-3 days post CPR is strongly associated with poor outcome.


Serum neuron-specific enolase levels > 33mg/L at days 1-3 strongly associated with poor outcome.

(S100, CSF CKBB are not considered accurate enough for prognostication.)


Imaging may reveal catastrophic intracerebral cause for the arrest.

(Diffuse swelling on CT scan is common, but predictive power not known, role of MRI/PET also unclear.)

Confounding Factors:

Induced Hypothermia – majority of studies carried out before induced hypothermia widely used. Evidence that cooling may alter interpretation of these results, but to what extent remains unclear

Time of assessment: Period of at least 72 hours post CPR recommended. Unclear how hypothermia effects this.

CT scan done too early may not show changes

Sedatives / neuro- muscular blockers 
Metabolic derangements 
Presence of shock

Organ failure

Role of “self-fulfilling prophecy” in interpreting studies

Salient points

  • Absent brainstem reflexes
  • Extensor motor response
  • EEG
  • Myoclonic status epilepticus
  • SSEP
  • Neuron-specific enolase
  • CT brain (oedema)


This question would benefit from a tabulated answer.

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.

As far as cardiac arrest goes, a  2006 review of the evidence has been published in Neurology by the American Academy of Neurology. It outlines the main factors which influence neurological outcome after cardiac arrest. This 2006 statement has to some extent been superceded by the most recent ERC/ESICM statement (Sandroni et al, 2014). More detail on this topic has been summarised in the chapter on prognostication of neurological recovery following cardiac arrest.