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(Stroke. 2004;35:2518.)
© 2004 American Heart Association, Inc.

Original Contributions

Neurotoxicity of Intra-arterial Papaverine Preserved with Chlorobutanol Used for the Treatment of Cerebral Vasospasm After Aneurysmal Subarachnoid Hemorrhage

Wade S. Smith, MD PhD; Christopher F. Dowd, MD; S. Claiborne Johnston, MD PhD; Nerissa U. Ko, MD; Stephen J. DeArmond, MD PhD; William P. Dillon, MD; Deepa Setty, PharmD; Michael T. Lawton, MD; William L. Young, MD; Randall T. Higashida, MD Van V. Halbach, MD

From the Departments of Neurology (W.S.S., S.C.J., N.U.K.), Radiology (C.F.D., W.P.D., R.T.H., V.V.H.), Pathology (S.J.D.), Clinical Pharmacy (D.S.), Neurosurgery (M.T.L.), and Anesthesia (W.L.Y.), University of California, San Francisco, Calif.

Correspondence to Dr Wade S. Smith, Associate Professor of Neurology, Department of Neurology, 505 Parnassus Avenue, San Francisco, CA 94134-0114. E-mail wssmith{at}itsa.ucsf.edu

Background and Purpose— Papaverine is used to vasodilate cerebral arteries undergoing vasospasm from subarachnoid hemorrhage. However, papaverine inhibits cellular respiration in vitro and could cause neurotoxicity in humans.

Methods— We studied 5 consecutive patients with cerebral vasospasm who were treated with intra-arterial papaverine preserved with chlorobutanol and imaged with MRI fluid-attenuated inversion recovery and diffusion-weighted imaging after treatment. One patient had histological analysis of the brain at autopsy.

Results— All 5 patients exhibited marked neurological decline immediately after treatment, and this was sustained through hospital discharge. In all cases, MRI images showed selective gray matter–only signal changes within the vascular territory treated with papaverine. Histological analysis of 1 case brought to autopsy showed selective injury to islands of neurons with relative sparing of white matter.

Conclusions— Intra-arterial delivery of papaverine preserved with chlorobutanol into vasospastic anterior cerebral arteries may result in marked neurological deterioration with selective gray matter changes on MRI imaging. This effect is consistent with a permanent toxic effect to human brain. It is unclear whether this toxicity is caused by papaverine or chlorobutanol, and its use in the treatment of cerebral vasospasm should be reserved for cases without alternatives.

Key Words: endovascular therapy • papaverine • subarachnoid hemorrhage • vasospasm

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