Neurotoxicity of intra-arterial papaverine preserved with chlorobutanol used for the treatment of cerebral vasospasm after aneurysmal subarachnoid hemorrhage.
OBJECTIVE
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.
Smith
Wade S
WS
Department of Neurology, University of California, San Francisco, Calif 94134-0114, USA. wssmith@itsa.ucsf.edu
Dowd
Christopher F
CF
Johnston
S Claiborne
SC
Ko
Nerissa U
NU
DeArmond
Stephen J
SJ
Dillon
William P
WP
Setty
Deepa
D
Lawton
Michael T
MT
Young
William L
WL
Higashida
Randall T
RT
Halbach
Van V
VV
D000368:Aged; D001921:Brain / Q000187:drug effects* / Q000473:pathology; D002724:Chlorobutanol / Q000009:adverse effects; D005260:Female; D006801:Humans; D007261:Infusions, Intra-Arterial; D008279:Magnetic Resonance Imaging; D008297:Male; D008875:Middle Aged; D010208:Papaverine / Q000008:administration & dosage / Q000009:adverse effects* / Q000627:therapeutic use; D011310:Preservatives, Pharmaceutical / Q000009:adverse effects; D012189:Retrospective Studies; D013345:Subarachnoid Hemorrhage / Q000150:complications / Q000188:drug therapy*; D014665:Vasodilator Agents / Q000008:administration & dosage / Q000009:adverse effects* / Q000627:therapeutic use; D020301:Vasospasm, Intracranial / Q000188:drug therapy* / Q000209:etiology
D011310:Preservatives, Pharmaceutical; D014665:Vasodilator Agents; D010208:Papaverine; D002724:Chlorobutanol