Abstract
Postanoxic encephalopathy is the key determinant of death or disability after successful cardiopulmonary resuscitation. Animal studies have provided proof-of-principle evidence of efficacy of divergent classes of neuroprotective treatments to promote brain recovery. However, apart from targeted temperature management (TTM), neuroprotective treatments are not included in current care of patients with postanoxic encephalopathy after cardiac arrest. We aimed to review the clinical evidence of efficacy of neuroprotective strategies to improve recovery of comatose patients after cardiac arrest and to propose future directions. We performed a systematic search of the literature to identify prospective, comparative clinical trials on interventions to improve neurological outcome of comatose patients after cardiac arrest. We included 53 studies on 21 interventions. None showed unequivocal benefit. TTM at 33 or 36°C and adrenaline (epinephrine) are studied most, followed by xenon, erythropoietin, and calcium antagonists. Lack of efficacy is associated with heterogeneity of patient groups and limited specificity of outcome measures. Ongoing and future trials will benefit from systematic collection of measures of baseline encephalopathy and sufficiently powered predefined subgroup analyses. Outcome measurement should include comprehensive neuropsychological follow-up, to show treatment effects that are not detectable by gross measures of functional recovery. To enhance translation from animal models to patients, studies under experimental conditions should adhere to strict methodological and publication guidelines.
Highlights
Survival rates of out-of-hospital cardiac arrest have increased considerably over the past decades [1, 2]
We review the clinical evidence of efficacy of neuroprotective treatments in comatose patients after cardiac arrest
Several randomized controlled trials (RCT) on early application of extracorporeal life support in cardiac arrest are in progress [NCT03065647 [13], NCT01605409 [14], NCT02527031 [15], NCT01511666 [16], NCT03101787 [17]], no results are published yet
Summary
Survival rates of out-of-hospital cardiac arrest have increased considerably over the past decades [1, 2]. Of patients surviving up to hospital admission, more than three quarters initially remain comatose as a result of diffuse cerebral ischaemia [3, 4]. Comatose patients after circulatory arrest are treated on intensive care units to support airway, breathing, and circulation. Anoxic-ischemic encephalopathy is the key determinant of death and disability, with rates of in-hospital mortality or enduring neurologic impairment >50% [5]. Targeted temperature management (TTM) at 33 or 36◦C is applied as a therapeutic strategy in most hospitals to improve brain recovery, the clinical evidence supporting efficacy is complex and mechanisms of action are incompletely understood [6,7,8,9]
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