Clinical Trials in Cardiac Arrest and Subarachnoid Hemorrhage: Lessons from the Past and Ideas for the Future

Jennifer A Frontera

doi:10.1155/2013/263974

Abstract

Introduction. Elevated intracranial pressure that occurs at the time of cerebral aneurysm rupture can lead to inadequate cerebral blood flow, which may mimic the brain injury cascade that occurs after cardiac arrest. Insights from clinical trials in cardiac arrest may provide direction for future early brain injury research after subarachnoid hemorrhage (SAH). Methods. A search of PubMed from 1980 to 2012 and clinicaltrials.gov was conducted to identify published and ongoing randomized clinical trials in aneurysmal SAH and cardiac arrest patients. Only English, adult, human studies with primary or secondary mortality or neurological outcomes were included. Results. A total of 142 trials (82 SAH, 60 cardiac arrest) met the review criteria (103 published, 39 ongoing). The majority of both published and ongoing SAH trials focus on delayed secondary insults after SAH (70%), while 100% of cardiac arrest trials tested interventions within the first few hours of ictus. No SAH trials addressing treatment of early brain injury were identified. Twenty-nine percent of SAH and 13% of cardiac arrest trials showed outcome benefit, though there is no overlap mechanistically. Conclusions. Clinical trials in SAH assessing acute brain injury are warranted and successful interventions identified by the cardiac arrest literature may be reasonable targets of the study.

Highlights

Elevated intracranial pressure that occurs at the time of cerebral aneurysm rupture can lead to inadequate cerebral blood flow, which may mimic the brain injury cascade that occurs after cardiac arrest
30% (17/57) of studies showed a positive impact on delayed cerebral ischemia, infarction, angiographic or transcranial Doppler (TCD) vasospasm, though there was incomplete overlap with the Statins and cerebral blood flow in subarachnoid hemorrhage (SAH)
With the exception of aneurysm repair and aneurysm rebleeding trials, the vast majority of SAH trials focus on the delayed cerebral ischemia period

Summary

Introduction

Research efforts in subarachnoid hemorrhage (SAH) have focused on vasospasm and delayed ischemic neurological deficits. The investigators report a spike in intracranial pressure (ICP) that developed over 1 minute and declined over several minutes This abrupt increase in ICP approached levels near mean arterial pressure and led to a concomitant drop in cerebral blood flow resulting in circulatory arrest, as documented by TCD [61]. Inadequate cerebral blood flow is frequently evidenced clinically by the transient loss of consciousness that occurs at SAH ictus. This mechanism of global transient circulatory arrest has been described in animal models of SAH at the time of initial hemorrhage [62, 63] and mimics the anoxic/hypoxic ischemic mechanism incurred by cardiac arrest. In this paper, published and ongoing clinical trials in cardiac arrest are compared to those in aneurysmal SAH to identify overlapping or complementary approaches to treatment as well as new avenues for potential research

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