Calcium Antagonists Improve Outcomes After Subarachnoid Hemorrhage

Abstract & Commentary

Synopsis: This meta-analysis of 10 studies in 2756 patients found that calcium antagonists reduce the risk for death and dependence, for secondary ischemia-related deficits, and for cerebral vasospasm in acute subarachnoid hemorrhage.

Source: Feigin VL, et al. Neurology 1998;50:876-883.

Feigin and colleagues at the university of Utrecht performed a systematic review of randomized controlled trials comparing treatment with a calcium antagonist drug to control therapy in patients with acute subarachnoid hemorrhage (SAH). They used the Cochrane Stroke Review Group’s trial register as well as an electronic database from 1966-1995 and several other sources, and used only those studies that met rigorous inclusion and exclusion criteria. In addition to information on study design and patient characteristics, Feigin et al examined death, poor neurologic outcome, secondary ischemia, cerebral vasospasm, recurrent hemorrhage, and adverse effects of therapy in each study, as well as in the aggregate.

Ten studies involving 2756 patients were included in Feigin et al’s meta-analysis. In all 10 studies, the administration of calcium antagonists within 10 days of the initial SAH reduced the risk for secondary ischemia-related neurologic deficit or for cerebral infarction as shown by computed tomography. Trends toward reduced mortality (9 studies) and fewer incidents of rebleeding (6 studies) with the use of calcium antagonists were found. A poor overall neurologic outcome (death or dependence) was significantly less likely if patients with acute SAH were given calcium antagonists. Although a variety of agents were used in the studies included in this meta-analysis, Feigin et al recommend oral nimodipine and intravenous nicardipine as the calcium antagonists of choice, depending upon the patient’s severity of acute illness.

COMMENT BY DAVID J. PIERSON, MD, FACP, FCCP

Acute SAH is a common and serious problem in the ICU. In the acute management of patients with SAH, whether calcium antagonists such as nimodipine and nicardipine should be administered to reduce the likelihood of cerebral vasospasm or delayed ischemia remains controversial. Cerebral vasodilation is desirable, but the controversy relates to the risk of concomitant hypotension with the use of these agents. In patients with acute brain injury and derangement of normal cerebral autoregulation, systemic hypotension with a drop in cerebral perfusion pressure can lead to severe worsening of neurologic status, even when it is transient. This carefully performed systematic review of previously reported studies provides strong support for the use of calcium antagonists in SAH. Clearly, however, every effort should be made to prevent even brief episodes of hypotension when these agents are used in this setting.