Clevidipine for Vasospasm After Subarachnoid Hemorrhage (SAH)

Cerebral vasospasm after aneurysmal subarachnoid hemorrhage (SAH) is a major cause of morbidity and mortality days after securing the aneurysm due to development of cerebral ischemia and strokes. Vasospasm is detected by measuring the blood flow velocities in the cerebral circulation via daily Transcranial Dopplers (TCD). There is no effective treatment except for a per os calcium channel blocker (nimodipine) and for keeping the patient hypertensive and with euvolemia or hypervolemia. A recently proposed option is to dilate the cerebral vessels by infusing continuously another vasodilatory calcium channel blocker, nicardipine, and supporting the systemic blood pressure (BP) with vasopressors which do not constrict the cerebral vasculature at the same time. Nicardipine has also been used extensively intra-arterially as a bolus or infusion to dilate the vasospastic cerebral vessels as a rescue therapy for severe vasospasm. Clevidipine is a novel, short-acting calcium channel blocker, which in a small series of patients with SAH at Henry Ford Hospital, was able to control the elevated BP very efficiently and within a narrow window, without adverse events. It has never been used before for ameliorating vasospasm, but theoretically offers advantages compared to nicardipine due to its shorter half-life and easier titratability. Except for use of clevidipine for BP control in the investigators previous study, there are no data on clevidipine use after SAH and no data about effect of the drug on vasospasm. In this single-center, open-label, uncontrolled, pilot clinical study, the investigators hypothesize that clevidipine low-rate infusion will decrease sonographically-detected moderate cerebral vasospasm after aneurysmal SAH. The dose of the drug in this exploratory study is 2.5 to 5 times lower than the dose used previously to control BP. The effect of the drug will be evaluated in 20 patients by TCD monitoring during 3 periods: 1-hour pre-infusion, 4-hour infusion and 4-hour post infusion. The cerebral blood flow velocities, which are a surrogate marker of vasospasm, will be compared between the 3 periods. The primary efficacy end-point will be the percentage of measurements with at least a 10% or more decrease of the velocities during the infusion period. Potential long-term effects after discontinuation of the drug will be also evaluated in the post-infusion 4-hour period and beyond, until the last follow up. The major safety issue is hypotension induced by the drug during a period when vasospasm is present. For that reason, two measures will be taken. First, only patients with moderate vasospasm will be evaluated. Second, vasopressors will be used as needed during the infusion period to counteract the systemic circulatory effect of the drug and maintain a stable systemic Mean Arterial Pressure (MAP) within 10% range compared to pre-infusion. Potential effect of cerebral vasodilation on intracranial pressure (ICP) will be also evaluated during the infusion and post-infusion periods and any elevation \> 10 mm Hg will be reported.