Neuroprognostication after Cardiac Arrest

Neuroprognostication after Cardiac Arrest

A 30 year old man suffered a 30 minute cardiorespiratory arrest secondary to an asthma attack. He was resuscitated, had his severe bronchospasm managed and he was treated with therapeutic hypothermia at 33 degrees. Once rewarmed, his neurology was assessed over several days. He was ventilated on a spontaneous mode, but his pupils remained fixed and dilated and there was no higher motor function seen. A CT brain was consistent with severe hypoxic ischaemic injury. After discussion with the family, treatment was withdrawn.

How reliable is neuroprognostication after cardiac arrest? What modalities are tested? Is there a difference in patients treated with therapeutic hypothermia?

David Garry

Despite advances in resuscitation and intensive care, survival from cardiac arrest is poor (1,2). The treatment for patients with post cardiac arrest return of spontaneous circulation can be lengthy, expensive, and difficult for the family as well as the patient. Prognostication can be a valuable tool to help guide decision making.

Existing data suggests that physical findings at 72 hours post arrest are reliable enough to help guide clinical practice (3,4,5). Booth et al (4) performed a meta-analysis of approximately 2000 post cardiac arrest patients in 2004. They found that patients who lack pupil and corneal responses at 24 hours, and motor response at 72 hours have an “extremely small chance for neurological recovery”. The results of this meta-analysis are reflected in the American Academy of Neurology guidelines, who state that “absent pupil and corneal reflex, and motor response on day 3 is predictive of poor outcome with a false positive rate of 0%”. The Intensive Care Society states that “absent pupil or corneal reflexes within days 1 to 3 after CPR, or absent or extensor motor responses 3 days after cardiac arrest reliably predict a poor outcome in the normothermic patient”.

The treatment of patients successfully resuscitated after cardiac arrest changed in 2002 after 2 landmark papers (6,7) showing benefit from a short period of therapeutic hypothermia. Hypothermia can impact on pharmacokinetics, pharmacodynamics and underlying physiology. This has led to uncertainty on the ability to use the above data for neuroprognostication. Several studies have since been published looking at neuroprognostication in patients treated with therapeutic hypothermia. Al Thenayan et al (8) (retrospective chart review of 37 adults) found that absent pupillary and corneal reflexes on day 3 are consistent with poor outcome, but the motor response was unreliable. Friberg and Rundgren (9) (87 adult patients) found that 50 patients regained consciousness within 72 hours of normothermia. Of the 37 that did not, 8 made a late recovery, and all had a positive profile with electroencephalography (EEG), somatosensory evoked potentials (SSEP) and neuron-specific enolase (NSE). Based on these results they advised that bedside neurological exam should not be performed until 72 hours after normothermia, and supplemented by at least one other prognostic tool. Rittenberger et al(10) performed a retrospective study of 272 patients, 59% of whom were treated with therapeutic hypothermia. They found that absence of pupil or corneal reflexes at 72 hours excluded survival. A Glasgow Coma Scale motor score less than or equal to 2 at 72 hours showed a 14% survival (to hospital discharge)

Other modalities are available for prognostication in post cardiac arrest patients. Head CTs are sometimes performed, but there is insufficient evidence to define lesions that predict poor outcome with precision (a small study of 25 patients showed that loss of grey/white differentiation predicts poor outcome). NSE can be used as a marker of ischaemic brain damage. A study of 45 patients (11) found a significantly elevated level of blood NSE in the 34 patients who had an unfavourable outcome as compared to the group with a favourable outcome. Caution is required though, as NSE is also present in RBCs and platelets. SSEPs are frequently used in the USA. Bilateral absence of the N20 response at 72 hours in the absence of therapeutic hypothermia has been shown to accurately predict poor prognosis (12) and is minimally influenced by drugs and metabolic derangements. EEG is sometimes used, with generalised suppression to <20 microvolts, burst suppression pattern with generalised epileptiform activity, or generalised period complexes on a flat background strongly, but not invariably, associated with poor outcome. Hypothermia decreases the voltage, but otherwise should not affect the EEG pattern.

Lessons learnt
Clinical examination offers a reliable method for neuroprognostication with absent pupil or corneal reflexes within days 1 to 3 after CPR, or absent or extensor motor responses 3 days after cardiac arrest reliably predicting a poor outcome. These clinical signs seem less reliable however in patients treated with therapeutic hypothermia. Other modalities are available, but none of them are sensitive or specific enough to merit universal adoption. Neuroprognostication is a useful tool that can help guide clinical decisions as part of the overall clinical picture.

1 Rea TD, Eisenberg MS, Sinibaldi G, et al: Incidence of EMS-treated out-of-hospital cardiac arrest in the United States. Resuscitation 2004; 63:17–24
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3 Edgren E, Hedstrand U, Kelsey S, et al: Assessment of neurological prognosis in comatose survivors of cardiac arrest. BRCT I Study Group. Lancet 1994; 343:1055–1059
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8 Al Thenayan E, Savard M, Sharpe M, et al: Predictors of poor neurologic outcome after induced mild hypothermia following cardiac arrest. Neurology 2008; 71:1535–1537
9 Friberg H, Rundgren M: Prediction of out- come after cardiac arrest and induced hypo- thermia. Abstr. Circulation 2008; 118:S823
10 Rittenberger JC, Sangl J, Wheeler M, et al: Association between clinical examination and outcome after cardiac arrest. Resuscita- tion 2010; 81:1128 –1132
11 Tatiana H Rech et al. Serum neuron-specific enolase as early predictor of outcome after in-hospital cardiac arrest: a cohort study. Critical Care Forum 2006.
12 Wijdicks EF, Hijdra A, Young GB, et al. Quality Standards Subcommittee of the American Academy of Neurology. 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. 2006;67:203–210


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