Definition of Delayed Cerebral Ischemia After Aneurysmal Subarachnoid Hemorrhage as an Outcome Event in Clinical Trials and Observational Studies

Abstract

Background and Purpose-In clinical trials and observational studies there is considerable inconsistency in the use of definitions to describe delayed cerebral ischemia (DCI) after aneurysmal subarachnoid hemorrhage. A major cause for this inconsistency is the combining of radiographic evidence of vasospasm with clinical features of cerebral ischemia, although multiple factors may contribute to DCI. The second issue is the variability and overlap of terms used to describe each phenomenon. This makes comparisons among studies difficult. Methods-An international ad hoc panel of experts involved in subarachnoid hemorrhage research developed and proposed a definition of DCI to be used as an outcome measure in clinical trials and observational studies. We used a consensus-building approach. Results-It is proposed that in observational studies and clinical trials aiming to investigate strategies to prevent DCI, the 2 main outcome measures should be: (1) cerebral infarction identified on CT or MRI or proven at autopsy, after exclusion of procedure-related infarctions; and (2)

Lower incidence of cerebral infarction correlates with improved functional outcome after aneurysmal subarachnoid hemorrhage

“…Microthromboembolism, cortical spreading ischemia, delayed effects of acute SAH-induced brain injury, and impaired cerebral autoregulation have been suggested to have a role in clinical outcome (Vergouwen et al, 2008;Dreier et al, 2009;Yundt et al, 1998). Since cerebral infarction is the ultimate outcome of DCI, it has been suggested that cerebral infarction is a better outcome measure in observational studies and clinical trials than vasospasm (Vergouwen et al, 2010). The findings of the present study support this suggestion.…”

“…The findings of the present study support this suggestion. Obviously, the main outcome measure in such studies should be functional outcome (Vergouwen et al, 2010).…”

“…Although several drugs were identified that successfully prevent vasospasm, no effects on clinical outcome were observed (Macdonald et al, 2008;Etminan et al, 2011). It has been proposed that cerebral infarction and functional outcome, and not vasospasm, should be the main outcome measures in clinical trials and observational studies (Vergouwen et al, 2010). The aim of the present study was to investigate if a lower incidence of cerebral infarction after SAH correlates with better functional outcomes.…”

“…Hypodensities on CT imaging resulting from ventricular catheter or intraparenchymal hematoma should not be regarded as cerebral infarctions from DCI' (Vergouwen et al, 2010). Poor clinical outcome was defined as severe disability, vegetative state or death, as defined by the investigators of the individual studies, either measured with the modified Rankin scale or (extended) Glasgow outcome scale.…”

To Improve Translational Research in Subarachnoid Hemorrhage

“…The authors thus concluded that there was no evidence from animal studies that treatment with an endothelin receptor antagonist improved clinically relevant outcomes after SAH, while the reduction in cerebral vasospasm observed in animal studies was consistent with that observed in clinical trials, an effect that was not associated with better functional outcome in patients [30]. The different outcomes between experimental and clinical studies may also occur due to misinterpretation of data and confused terminology and definitions [31]. Anyway, we can say that the failed clinical trials could have been predicted and avoided if the review and the meta-analysis had been performed before planning the clinical trials.…”