Document Detail


Neurotoxicity of intra-arterial papaverine preserved with chlorobutanol used for the treatment of cerebral vasospasm after aneurysmal subarachnoid hemorrhage.
MedLine Citation:
PMID:  15472097     Owner:  NLM     Status:  MEDLINE    
Abstract/OtherAbstract:
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.
Authors:
Wade S Smith; Christopher F Dowd; S Claiborne Johnston; Nerissa U Ko; Stephen J DeArmond; William P Dillon; Deepa Setty; Michael T Lawton; William L Young; Randall T Higashida; Van V Halbach
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Publication Detail:
Type:  Journal Article     Date:  2004-10-07
Journal Detail:
Title:  Stroke; a journal of cerebral circulation     Volume:  35     ISSN:  1524-4628     ISO Abbreviation:  Stroke     Publication Date:  2004 Nov 
Date Detail:
Created Date:  2004-10-29     Completed Date:  2005-05-11     Revised Date:  2011-05-24    
Medline Journal Info:
Nlm Unique ID:  0235266     Medline TA:  Stroke     Country:  United States    
Other Details:
Languages:  eng     Pagination:  2518-22     Citation Subset:  IM    
Affiliation:
Department of Neurology, University of California, San Francisco, Calif 94134-0114, USA. wssmith@itsa.ucsf.edu
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MeSH Terms
Descriptor/Qualifier:
Aged
Brain / drug effects*,  pathology
Chlorobutanol / adverse effects
Female
Humans
Infusions, Intra-Arterial
Magnetic Resonance Imaging
Male
Middle Aged
Papaverine / administration & dosage,  adverse effects*,  therapeutic use
Preservatives, Pharmaceutical / adverse effects
Retrospective Studies
Subarachnoid Hemorrhage / complications,  drug therapy*
Vasodilator Agents / administration & dosage,  adverse effects*,  therapeutic use
Vasospasm, Intracranial / drug therapy*,  etiology
Grant Support
ID/Acronym/Agency:
K23 NS044014-05/NS/NINDS NIH HHS
Chemical
Reg. No./Substance:
0/Preservatives, Pharmaceutical; 0/Vasodilator Agents; 57-15-8/Chlorobutanol; 58-74-2/Papaverine

From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine


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