What is the prognosis of a coma following cardiac arrest?

Prognosis of Coma After Cardiac Arrest

The prognosis of coma following cardiac arrest is poor overall, with many patients dying, remaining permanently unresponsive, or unable to perform independent activities, though accurate prognostication requires a multimodal approach and should not be attempted before 72 hours after return of spontaneous circulation. 1

Timing of Prognostication

• No clinical neurological signs or diagnostic studies reliably predict poor outcome during the first 24 hours after return of spontaneous circulation (ROSC) 1
• Neurologic prognosis remains uncertain before at least 72 hours after ROSC 1
• Decisions to limit or withdraw life-sustaining treatment should never rely on a single prognostication element 1

Clinical Examination Findings

Most Reliable Predictors (in patients not treated with hypothermia)

• Absence of both pupillary light and corneal reflexes at 72 hours predicts poor outcome with high reliability (false-positive rate [FPR] 0%, 95% CI 0-9%) 1
• Bilateral absence of N20 cortical response to median nerve somatosensory evoked potentials (SSEPs) after 24 hours predicts poor outcome with high reliability (FPR 0%, 95% CI 0-3%) 1

Less Reliable Predictors

• Absence of vestibulo-ocular reflexes at 24 hours (FPR 0%, 95% CI 0-14%) 1
• Glasgow Coma Scale (GCS) score ≤5 at 72 hours (FPR 0%, 95% CI 0-6%) 1
• Motor response with GCS motor score ≤2 at 72 hours has a FPR of 5% (95% CI 2-9%) 1

Electrophysiological Studies

• EEG findings within 24 hours after ROSC are not reliable predictors of outcome 1
• In normothermic patients without confounders, the following EEG patterns are associated with poor outcome (FPR 3%, 95% CI 0.9-11%): 1
  • Generalized suppression to <20 μV
  • Burst-suppression pattern with generalized epileptic activity
  • Diffuse periodic complexes on a flat background
• Continuous/reactive EEG background strongly predicts good recovery 2
• One week after cardiac arrest, specific EEG findings may be useful for predicting poor outcomes 1

Impact of Therapeutic Hypothermia

• Therapeutic hypothermia alters prognostic accuracy of traditional parameters 2
• Hypothermia delays recovery of motor responses and may render clinical evaluation unreliable 2
• The prognostic accuracy of malignant EEG patterns appears less reliable in patients treated with hypothermia 1
• Status epilepticus in post-ROSC patients treated with hypothermia has an FPR of 7-11.5% for predicting poor outcome 1

Biomarkers

• Serum biomarkers alone should not be used to predict poor outcomes 1
• Therapeutic hypothermia alters the predictive value of serum markers like neuron-specific enolase (NSE) and S-100B 2
• Good recovery can occur despite NSE levels >33 μg/l, thus this cut-off should not be used to guide therapy 2

Neuroimaging

• MRI and CT are the most studied neuroimaging modalities 1
• Extensive cortical and subcortical lesions on MRI are associated with poor neurological outcome 1
• Diffusion MRI may help predict long-term neurological sequelae 2
• Despite potential, neuroimaging has not yet been proven as an independently accurate modality for prediction of outcome 1

Long-term Outcomes

• Shorter coma duration is associated with better functional outcomes at discharge 3
• However, among survivors to discharge, coma duration does not appear to affect long-term survival 3

Recommended Multimodal Approach

1. Wait at least 72 hours after ROSC before making definitive prognostic assessments 1
2. Ensure absence of confounding factors (sedatives, hypotension, hypothermia, neuromuscular blockade, seizures, hypoxemia) 1
3. Perform thorough neurological examination focusing on brainstem reflexes 1
4. Obtain electrophysiological studies (EEG and SSEPs) 1, 2
5. Consider neuroimaging (MRI or CT) 1
6. Interpret biomarkers cautiously, especially in patients treated with hypothermia 1, 2

Emerging Treatments

• Research on neuroprotective strategies is ongoing, with recent trials investigating:
  • Intranasal orexin-A showing potential to enhance arousal from coma and decrease neuroinflammation in animal models 4
  • Intravenous acyl-ghrelin showing potential efficacy in improving neurological outcomes in a phase 2 clinical trial 5

Common Pitfalls in Prognostication

• Making prognostic decisions too early (<72 hours after ROSC) 1
• Relying on a single prognostic element rather than a multimodal approach 1
• Not accounting for the effects of therapeutic hypothermia on traditional prognostic parameters 2
• Using biomarkers as sole predictors of outcome 1
• Not considering confounding factors that may affect clinical examination findings 1