Milrinone for the Treatment of Cerebral Vasospasm After Aneurysmal Subarachnoid Hemorrhage

Abstract

Attempts to reverse cerebral vasospasm (CVS) after aneurysmal subarachnoid hemorrhage (aSAH) rely on a limited number of treatments. Calcium channel blockers have proven a benefit but their vasodilating effect on spastic cerebral arteries is relatively modest. Milrinone, a phosphodiesterase inhibitor, combines vasodilating and inotropic properties, but limited data exist to support its use for the treatment of CVS. We assessed the efficacy and tolerance of milrinone in patients with CVS secondary to aSAH. Twenty-two consecutive patients with angiographically-proven CVS (arterial diameter reduction >40%) have been studied. Intraarterial milrinone was infused in the cerebral territory(ies) involved and followed by continuous intravenous infusion until Day 14 after initial bleeding. We evaluated angiographic reversal of CVS, hemodynamic tolerance, and neurological outcome 1 year after aSAH. Thirty-four selective intraarterial infusions of milrinone were required to treat 72 vasospastic territories. Intraarterial milrinone resulted in 53+/-37% increase in arterial diameter (P<.0001). Milrinone infusion resulted in moderately increased heart rate, but systemic arterial pressure remained unchanged. Five patients (23%) had angiographically-proven vasospasm recurrence within 48 hours after the procedure. Two of them were successfully reversed after another intraarterial infusion of milrinone. The remaining 3 underwent mechanical angioplasty. Two patients (9%) died in ICU, and 2 were lost to follow-up. All other patients had very good neurological outcome (modified Rankin scale: 0.8+/-1.0; Barthel index: 100 [95-100]). This study suggests that milrinone is effective and safe for reversal of CVS after aSAH and should be tested in a large randomized trial.