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. 1. Introduction For decades, research efforts in subarachnoid hemorrhage (SAH) have focused on vasospasm and delayed ischemic neurological deficits. However, brain injury at the time of aneurysm rupture is a significant predictor of functional outcome. Indeed, poor admission neurological status (Hunt-Hess or World Federation of Neurological Surgeons Score), which reflects acute brain injury, is a larger contributor to death or severe disability than delayed cerebral ischemia [1, 2]. However, the mechanism of early brain injury after aneurysm rupture remains elusive and no current therapies are available. One possible mechanism of acute injury was described in a small case series of 6 patients with observed recurrent aneurysm rupture either during transcranial Doppler (TCD) or during craniotomy with open skull but intact dura. The investigators report a spike in intracranial pressure (ICP) that developed over 1 minute and then 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]. This study examined aneurysm rebleeding and does not provide direct
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