Question 4

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.

Electrophysiological:

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.

Biochemical:

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.)

Radiological:

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)

Discussion

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.

Wijdicks, E. F. M., et al. "Practice Parameter: Prediction of outcome in comatose survivors after cardiopulmonary resuscitation (an evidence-based review) Report of the Quality Standards Subcommittee of the American Academy of Neurology."Neurology 67.2 (2006): 203-210.

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.