High-Dose Intra-arterial Verapamil for the Treatment of Cerebral Vasospasm After Subarachnoid Hemorrhage: Prolonged Effects on Hemodynamic Parameters and Brain Metabolism

Abstract

Studies attempting to establish the safety and efficacy of standard and high-dose intra-arterial infusions of calcium channel blockers for treatment of cerebral vasospasm have focused on hemodynamic changes during the angiographic procedure. To evaluate longer-term drug effects over the hours following infusion and the effects on brain tissue oxygen tension or cerebral metabolism. We studied 11 patients with poor-grade aneurysmal subarachnoid hemorrhages who underwent multimodality brain monitoring and angiography with infusion of high-dose intra-arterial verapamil (≥15 mg total dose). Hourly intracerebral microdialysis measurements and continuously recorded mean arterial pressure (MAP), intracranial pressure (ICP), cerebral perfusion pressure (CPP), and Pbto₂ were analyzed for 6 hours before and 12 hours following treatment. A median dose of 23 mg (range, 15-55 mg) of intra-arterial verapamil was given. Compared with baseline values, reductions in CPP and MAP were maximal at 3 hours postangiography (from 105 ± 13 mm Hg to 95 ± 15 mm Hg and from 116 ± 12 mm Hg to 106 ± 16 mm Hg, P < .01) and persisted for up to 6 hours (P < .04); increases in vasopressor therapy were required in 8 procedures (53%). ICP significantly increased during the first 3 hours post angiography (P < .03). Brain glucose increased by 33% by hour 9 (P < .001). There were no significant changes in Pbto₂ or the lactate/pyruvate ratio. High-dose intra-arterial verapamil causes increases in ICP and reductions in CPP, followed by an increase in brain glucose levels, without altering brain oxygen tension or oxidative metabolism. Patients undergoing high-dose intra-arterial verapamil therapy warrant close hemodynamic and ICP monitoring for at least 12 hours following treatment.