Elsevier

Surgical Neurology

Volume 51, Issue 1, January 1999, Pages 66-74
Surgical Neurology

Original Articles
Intra-arterial papaverine for the treatment of cerebral vasospasm following aneurysmal subarachnoid hemorrhage

https://doi.org/10.1016/S0090-3019(97)00370-4Get rights and content

Abstract

BACKGROUND

Intra-arterial papaverine (IAP) has been described as a treatment for cerebral vasospasm refractory to standard therapy.

METHODS

We report a series of 15 consecutive patients with aneurysmal subarachnoid hemorrhage in which IAP was employed for the treatment of symptomatic vasospasm. All patients exhibited delayed ischemic neurologic deficits, focal cerebral hypoperfusion on stable xenon-enhanced computerized tomography cerebral blood flow studies, and angiographically defined arterial narrowing. Papaverine was infused into 32 arteries on 23 occasions. Six patients required multiple treatments between 1 and 8 days apart. In five instances, IAP was combined with angioplasty.

RESULTS

Angiographically defined vasospasm was at least partially reversed immediately following treatment on 18 of 23 occasions. The associated clinical improvement was major on 6 occasions, and either minor or none on 17. Post-treatment cerebral blood flow was assessed on 13 occasions and showed improvement in previously ischemic areas on six occasions and no improvement on seven. Complications were encountered on four occasions. Systemic hypotension and transient brain-stem depression were seen with vertebral artery infusions; a generalized seizure and paradoxical aggravation of vasospasm resulting in hemispheric infarction occurred with internal carotid artery infusions.

CONCLUSIONS

Intra-arterial papaverine resulted in reversal of arterial narrowing in the majority of cases (78%). However, this angiographic improvement was associated with cerebral blood flow augmentation in only 46% of cases analyzed, and major clinical improvement in 26%.

Section snippets

Patient population and initial management

Between June 1992 and February 1995, 214 patients underwent surgery for cerebral aneurysms by cerebrovascular neurosurgeons (HY, AMK) at the University of Pittsburgh Medical Center. All received standard management, including monitoring in the neurosurgical intensive care unit, daily nimodipine, avoidance of hypovolemia and hypotension, and treatment of hydrocephalus and intracranial hypertension. Some patients received Tirilizad. The clinical status of patients was assessed by retrospective

Delayed neurologic deficits

The onset of delayed neurologic deficit attributed to symptomatic vasospasm occurred between 2 and 14 days following the presenting SAH. These deficits consisted of diminished level of consciousness alone (12 occasions), isolated hemiparesis and/or aphasia (5 occasions), or both focal and general deficits (6 occasions) (Table 1). In the 11 patients with either focal or combined focal and general deficits, decreased CBF was demonstrated in the appropriate hemisphere.

Angiographic vasospasm

Cerebral artery narrowing was

Literature review

Papaverine is an opium alkaloid that relaxes smooth muscle, causing arterial dilation by an incompletely understood mechanism. The first reported use of papaverine for the treatment of the cerebral circulation was in 1948; it was administered orally to prevent recurrent cerebral ischemic events of various etiologies [21]. Since then, in vitro 1, 6 and in vivo 12, 20, 23 models have documented the potential role of papaverine in treating cerebral vasospasm. In human subjects, intravenous 17, 18

References (26)

  • G.S Allen et al.

    Part 7In vitro effects of alpha adrenergic agents on canine arteries from six anatomical sites and six blocking agents on serotonin-induced contractions of the canine basilar artery

    Surg Neurol

    (1976)
  • J.D Barr et al.

    Transient severe brain stem depressions during intra-arterial papaverine infusion for cerebral vasospasm

    AJNR

    (1994)
  • J.E Clouston et al.

    Intra-arterial papaverine infusion for cerebral vasospasm after subarachnoid hemorrhage

    AJNR

    (1995)
  • B Clyde et al.

    Paradoxical aggravation of vasospasm with papaverine infusion following aneurysmal subarachnoid hemorrhage. Case Report

    J Neurosurg

    (1996)
  • M.B Fukui et al.

    Xe/CT cerebral blood flow evaluation of delayed symptomatic cerebral ischemia after subarachnoid hemorrhage

    AJNR

    (1992)
  • D.S Heffez et al.

    Sustained release of papaverine for the treatment of cerebral vasospasmin vitro evaluation of release kinetics and biological activity

    J Neurosurg

    (1992)
  • Y Jin et al.

    The effects of papaverine on phorbol dibutyrate-induced vasoconstriction in brain slice microvessels

    J Neurosurg

    (1994)
  • Y Kaku et al.

    Superselective intra-arterial infusion of papaverine for the treatment of cerebral vasospasm after subarachnoid hemorrhage

  • Y Kaku et al.

    Superselective intra-arterial infusion of papaverine for the treatment of cerebral vasospasm after subarachnoid hemorrhage

    J Neurosurg

    (1992)
  • N.F Kassell et al.

    Treatment of cerebral vasospasm with intra-arterial papaverine

    J Neurosurg

    (1992)
  • N.F Kassell et al.

    Cerebral vasospasm following aneurysmal subarachnoid hemorrhage

    Stroke

    (1985)
  • A Kuwayama et al.

    Papaverine hydrochloride and experimental hemorrhagic cerebral arterial spasm

    Stroke

    (1972)
  • K Livingston et al.

    Intra-arterial papaverine as an adjunct to transluminal angioplasty for vasospasm induced by subarachnoid hemorrhage

    AJNR

    (1993)

    • Cited by (0)

    View full text
    Copyright © 1999 Elsevier Science Inc. All rights reserved.