Site-specific, sustained-release drug delivery for subarachnoid hemorrhage

Abstract

Drugs approved for use to combat angiographic vasospasm or to improve the sequelae of subarachnoid hemorrhage include nimodipine in North America, Europe, and other countries and fasudil and OKY-046 in Japan. There may be others. Other drugs may be effective, but their efficacy has been difficult to show in clinical trials. The reasons for this are unclear: either they are not effective or they have off-target and systemic side effects when delivered orally or intravenously, the studies are underpowered, the outcomes are insensitive to important clinical benefits, and/or rescue therapies in the placebo groups are effective enough to balance the effect of the drug in the treated patients. This chapter addresses the first issue, which is to deliver drugs that are likely to be effective, yet cannot be delivered enterally or systemically in adequate doses because of dose-limiting side effects, by direct, intracranial methods.