Efficacy of multiple intraarterial papaverine infusions for improvement in cerebral circulation time in patients with recurrent cerebral vasospasm

James K. Liu Departments of Neurosurgery and Radiology, University of Utah School of Medicine, Salt Lake City, Utah; and New York Medical College, Valhalla and New York, New York

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Michael S. Tenner Departments of Neurosurgery and Radiology, University of Utah School of Medicine, Salt Lake City, Utah; and New York Medical College, Valhalla and New York, New York

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Oren N. Gottfried Departments of Neurosurgery and Radiology, University of Utah School of Medicine, Salt Lake City, Utah; and New York Medical College, Valhalla and New York, New York

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Edwin A. Stevens Departments of Neurosurgery and Radiology, University of Utah School of Medicine, Salt Lake City, Utah; and New York Medical College, Valhalla and New York, New York

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Joshua M. Rosenow Departments of Neurosurgery and Radiology, University of Utah School of Medicine, Salt Lake City, Utah; and New York Medical College, Valhalla and New York, New York

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Neel Madan Departments of Neurosurgery and Radiology, University of Utah School of Medicine, Salt Lake City, Utah; and New York Medical College, Valhalla and New York, New York

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Joel D. Macdonald Departments of Neurosurgery and Radiology, University of Utah School of Medicine, Salt Lake City, Utah; and New York Medical College, Valhalla and New York, New York

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John R. W. Kestle Departments of Neurosurgery and Radiology, University of Utah School of Medicine, Salt Lake City, Utah; and New York Medical College, Valhalla and New York, New York

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William T. Couldwell Departments of Neurosurgery and Radiology, University of Utah School of Medicine, Salt Lake City, Utah; and New York Medical College, Valhalla and New York, New York

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Object. Cerebral vasospasm that is caused by aneurysmal subarachnoid hemorrhage and that is refractory to maximal medical management can be treated with selective intraarterial papaverine infusions. The effects of single papaverine treatments on cerebral circulation time are well known. The purpose of this study was to assess the efficacy of multiple, repeated papaverine infusions on the cerebral circulation time in patients with recurrent vasospasm.

Methods. A retrospective study was conducted in 17 patients who received multiple intraarterial papaverine infusions in 91 carotid artery (CA) territories for the treatment of cerebral vasospasm. Cerebral circulation times were measured from the first angiographic image, in which peak contrast was seen above the supraclinoid internal CA, to the peak filling of cortical veins. Glasgow Outcome Scale (GOS) scores assessed 12 months after discharge were reviewed. Cerebral circulation times in 16 CA territories were measured in a control group of 11 patients.

Seventeen patients received a total of 91 papaverine treatments. Prolonged cerebral circulation times improved after 90 (99%) of 91 papaverine treatments. The prepapaverine mean cerebral circulation time was 6.54 seconds (range 3.35–27 seconds) and the immediate postpapaverine mean cerebral circulation time was 4.19 seconds (range 2.1–12.6 seconds), an overall mean decrease of 2.35 seconds (36%, p < 0.001). Recurrent vasospasm reflected by prolonged cerebral circulation times continued to improve with subsequent papaverine infusions. Repeated infusions were just as successful quantitatively as the primary treatment (mean change 2.06 seconds). The mean cerebral circulation time in the control group was 5.21 seconds (range 4–6.8 seconds). In five patients a dramatic reversal of low-attenuation changes was detected on computerized tomography scans. The mean GOS score at 12 months after discharge was 3.4.

Conclusions. The preliminary results indicate that multiple intraarterial papaverine treatments consistently improve cerebral circulation times, even with repeated infusions in cases of recurrent vasospasm.

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  • 1.

    Awad IA, , Carter LP, & Spetzler RF, et al: Clinical vasospasm after subarachnoid hemorrhage: response to hypervolemic hemodilution and arterial hypertension. Stroke 18:365372, 1987 Awad IA, Carter LP, Spetzler RF, et al: Clinical vasospasm after subarachnoid hemorrhage: response to hypervolemic hemodilution and arterial hypertension. Stroke 18:365–372, 1987

    • PubMed
    • Search Google Scholar
    • Export Citation
  • 2.

    Barker FG II, & Ogilvy CS: Efficacy of prophylactic nimodipine for delayed ischemic deficit after subarachnoid hemorrhage: a metaanalysis. J Neurosurg 84:405414, 1996 Barker FG II, Ogilvy CS: Efficacy of prophylactic nimodipine for delayed ischemic deficit after subarachnoid hemorrhage: a metaanalysis. J Neurosurg 84:405–414, 1996

    • PubMed
    • Search Google Scholar
    • Export Citation
  • 3.

    Barr JD, , Mathis JM, & Horton JA: Transient severe brain stem depression during intraarterial papaverine infusion for cerebral vasospasm. AJNR 15:719723, 1994 Barr JD, Mathis JM, Horton JA: Transient severe brain stem depression during intraarterial papaverine infusion for cerebral vasospasm. AJNR 15:719–723, 1994

    • PubMed
    • Search Google Scholar
    • Export Citation
  • 4.

    Clouston JE, , Numaguchi Y, & Zoarski GH, et al: Intra-arterial papaverine infusion for cerebral vasospasm after subarachnoid hemorrhage. AJNR 16:2738, 1995 Clouston JE, Numaguchi Y, Zoarski GH, et al: Intra-arterial papaverine infusion for cerebral vasospasm after subarachnoid hemorrhage. AJNR 16:27–38, 1995

    • PubMed
    • Search Google Scholar
    • Export Citation
  • 5.

    Clyde BL, , Firlik AD, & Kaufmann AM, et al: Paradoxical aggravation of vasospasm with papaverine infusion following aneurysmal subarachnoid hemorrhage. Case report. J Neurosurg 84:690695, 1996 Clyde BL, Firlik AD, Kaufmann AM, et al: Paradoxical aggravation of vasospasm with papaverine infusion following aneurysmal subarachnoid hemorrhage. Case report. J Neurosurg 84:690–695, 1996

    • PubMed
    • Search Google Scholar
    • Export Citation
  • 6.

    Cook P, & James I: Drug therapy: cerebral vasodilators (first of two parts). N Engl J Med 305:15081513, 1981 Cook P, James I: Drug therapy: cerebral vasodilators (first of two parts). N Engl J Med 305:1508–1513, 1981

    • PubMed
    • Search Google Scholar
    • Export Citation
  • 7.

    Cross DT III, , Moran CJ, & Angtuaco EE, et al: Intracranial pressure monitoring during intraarterial papaverine infusion for cerebral vasospasm. AJNR 19:13191323, 1998 Cross DT III, Moran CJ, Angtuaco EE, et al: Intracranial pressure monitoring during intraarterial papaverine infusion for cerebral vasospasm. AJNR 19:1319–1323, 1998

    • PubMed
    • Search Google Scholar
    • Export Citation
  • 8.

    Eskridge JM, , Newell DW, & Winn HR: Endovascular treatment of vasospasm. Neurosurg Clin N Am 5:437447, 1994 Eskridge JM, Newell DW, Winn HR: Endovascular treatment of vasospasm. Neurosurg Clin N Am 5:437–447, 1994

    • PubMed
    • Search Google Scholar
    • Export Citation
  • 9.

    Fandino J, , Kaku Y, & Schuknecht B, et al: Improvement of cerebral oxygenation patterns and metabolic validation of superselective intraarterial infusion of papaverine for the treatment of cerebral vasospasm. J Neurosurg 89:93100, 1998 Fandino J, Kaku Y, Schuknecht B, et al: Improvement of cerebral oxygenation patterns and metabolic validation of superselective intraarterial infusion of papaverine for the treatment of cerebral vasospasm. J Neurosurg 89:93–100, 1998

    • PubMed
    • Search Google Scholar
    • Export Citation
  • 10.

    Firlik KS, , Kaufmann AM, & Firlik AD, et al: Intra-arterial papaverine for the treatment of cerebral vasospasm following aneurysmal subarachnoid hemorrhage. Surg Neurol 51:6674, 1999 Firlik KS, Kaufmann AM, Firlik AD, et al: Intra-arterial papaverine for the treatment of cerebral vasospasm following aneurysmal subarachnoid hemorrhage. Surg Neurol 51:66–74, 1999

    • PubMed
    • Search Google Scholar
    • Export Citation
  • 11.

    Gado M, , Eichling J, & Grubb R, et al: Appraisal of the angiographic circulation time as an index of cerebral blood flow. Radiology 115:107112, 1975 Gado M, Eichling J, Grubb R, et al: Appraisal of the angiographic circulation time as an index of cerebral blood flow. Radiology 115:107–112, 1975

    • PubMed
    • Search Google Scholar
    • Export Citation
  • 12.

    Greitz T: Evaluation of circulation time in angiography of the vertebral artery. Acta Radiol Diagn 9:300309, 1969 Greitz T: Evaluation of circulation time in angiography of the vertebral artery. Acta Radiol Diagn 9:300–309, 1969

    • PubMed
    • Search Google Scholar
    • Export Citation
  • 13.

    Greitz T: Normal cerebral circulation time as determined by carotid angiography with sodium and methylglucamine diatrizoate (Urografin). Acta Radiol Diagn 7:331336, 1968 Greitz T: Normal cerebral circulation time as determined by carotid angiography with sodium and methylglucamine diatrizoate (Urografin). Acta Radiol Diagn 7:331–336, 1968

    • PubMed
    • Search Google Scholar
    • Export Citation
  • 14.

    Greitz T: A radiologic study of the brain circulation by rapid serial angiography of the carotid artery. Acta Radiol 46 (Suppl 140):1123, 1956 Greitz T: A radiologic study of the brain circulation by rapid serial angiography of the carotid artery. Acta Radiol 46 (Suppl 140):1–123, 1956

    • PubMed
    • Search Google Scholar
    • Export Citation
  • 15.

    Handa Y, , Weir BKA, & Nosko M, et al: The effect of timing of clot removal on chronic vasospasm in a primate model. J Neurosurg 67:558564, 1987 Handa Y, Weir BKA, Nosko M, et al: The effect of timing of clot removal on chronic vasospasm in a primate model. J Neurosurg 67:558–564, 1987

    • PubMed
    • Search Google Scholar
    • Export Citation
  • 16.

    Hendrix LE, , Dion JE, & Jenson ME, et al: Papverine-induced mydriasis. AJNR 15:716718, 1994 Hendrix LE, Dion JE, Jenson ME, et al: Papverine-induced mydriasis. AJNR 15:716–718, 1994

    • PubMed
    • Search Google Scholar
    • Export Citation
  • 17.

    Heros RC, , Zervas NT, & Varsos V: Cerebral vasospasm after subarachnoid hemorrhage: an update. Ann Neurol 14:599608, 1983 Heros RC, Zervas NT, Varsos V: Cerebral vasospasm after subarachnoid hemorrhage: an update. Ann Neurol 14:599–608, 1983

    • PubMed
    • Search Google Scholar
    • Export Citation
  • 18.

    Iseda T, , Nakano S, & Yoneyama T, et al: Angiographic cerebral circulation time before and after endovascular therapy for symptomatic vasospasm. Clin Radiol 55:679683, 2000 Iseda T, Nakano S, Yoneyama T, et al: Angiographic cerebral circulation time before and after endovascular therapy for symptomatic vasospasm. Clin Radiol 55:679–683, 2000

    • PubMed
    • Search Google Scholar
    • Export Citation
  • 19.

    Jennett B, & Bond M: Assessment of outcome after severe brain damage. A practical scale. Lancet 1:480484, 1975 Jennett B, Bond M: Assessment of outcome after severe brain damage. A practical scale. Lancet 1:480–484, 1975

    • PubMed
    • Search Google Scholar
    • Export Citation
  • 20.

    Jin Y, , Sagher O, & Thai QA, et al: The effects of papaverine on phorbol dibutyrate-induced vasoconstriction in brain slice microvessels. J Neurosurg 81:574578, 1994 Jin Y, Sagher O, Thai QA, et al: The effects of papaverine on phorbol dibutyrate-induced vasoconstriction in brain slice microvessels. J Neurosurg 81:574–578, 1994

    • PubMed
    • Search Google Scholar
    • Export Citation
  • 21.

    Kaku Y, , Yonekawa Y, & Tsukahara T, et al: Superselective intraarterial infusion of papaverine for the treatment of cerebral vasospasm after subarachnoid hemorrhage. J Neurosurg 77:842847, 1992 Kaku Y, Yonekawa Y, Tsukahara T, et al: Superselective intraarterial infusion of papaverine for the treatment of cerebral vasospasm after subarachnoid hemorrhage. J Neurosurg 77:842–847, 1992

    • PubMed
    • Search Google Scholar
    • Export Citation
  • 22.

    Kassell NF, , Helm G, & Simmons N, et al: Treatment of cerebral vasospasm with intra-arterial papaverine. J Neurosurg 77:848852, 1992 Kassell NF, Helm G, Simmons N, et al: Treatment of cerebral vasospasm with intra-arterial papaverine. J Neurosurg 77:848–852, 1992

    • PubMed
    • Search Google Scholar
    • Export Citation
  • 23.

    Kassell NF, , Sasaki T, & Colohan ART, et al: Cerebral vasospasm following aneurysmal subarachnoid hemorrhage. Stroke 16:562572, 1985 Kassell NF, Sasaki T, Colohan ART, et al: Cerebral vasospasm following aneurysmal subarachnoid hemorrhage. Stroke 16:562–572, 1985

    • PubMed
    • Search Google Scholar
    • Export Citation
  • 24.

    Liu JK, , Tenner MS, & Oestreich HM, et al: Reversal of radiographically impending stroke with multiple intraarterial papaverine infusions in severe diffuse cerebral vasospasm induced by subarachnoid hemorrhage. Acta Neurochir 143:12491256, 2001 Liu JK, Tenner MS, Oestreich HM, et al: Reversal of radiographically impending stroke with multiple intraarterial papaverine infusions in severe diffuse cerebral vasospasm induced by subarachnoid hemorrhage. Acta Neurochir 143:1249–1256, 2001

    • PubMed
    • Search Google Scholar
    • Export Citation
  • 25.

    Livingston K, , Guterman LR, & Hopkins LN: Intraarterial papaverine as an adjunct to transluminal angioplasty for vasospasm induced by subarachnoid hemorrhage. AJNR 14:346347, 1993 Livingston K, Guterman LR, Hopkins LN: Intraarterial papaverine as an adjunct to transluminal angioplasty for vasospasm induced by subarachnoid hemorrhage. AJNR 14:346–347, 1993

    • PubMed
    • Search Google Scholar
    • Export Citation
  • 26.

    Lugnier C, & Stoclet JC: Inhibition by papaverine of cGMP and cAMP phosphodiesterases from the rat heart. Biochem Pharmacol 23:30713074, 1974 Lugnier C, Stoclet JC: Inhibition by papaverine of cGMP and cAMP phosphodiesterases from the rat heart. Biochem Pharmacol 23:3071–3074, 1974

    • PubMed
    • Search Google Scholar
    • Export Citation
  • 27.

    Marks MP, , Steinberg GK, & Lane B: Intraarterial papaverine for the treatment of vasospasm. AJNR 14:822826, 1993 Marks MP, Steinberg GK, Lane B: Intraarterial papaverine for the treatment of vasospasm. AJNR 14:822–826, 1993

    • PubMed
    • Search Google Scholar
    • Export Citation
  • 28.

    Mathis JM, , DeNardo A, & Jensen ME, et al: Transient neurologic events associated with intraarterial papaverine infusion for subarachnoid hemorrhage-induced vasospasm. AJNR 15:16711674, 1994 Mathis JM, DeNardo A, Jensen ME, et al: Transient neurologic events associated with intraarterial papaverine infusion for subarachnoid hemorrhage-induced vasospasm. AJNR 15:1671–1674, 1994

    • PubMed
    • Search Google Scholar
    • Export Citation
  • 29.

    Mathis JM, , DeNardo AJ, & Thibault L, et al: In vitro evaluation of papaverine hydrochloride incompatibilities: a simulation of intra-arterial infusion for cerebral vasospasm. AJNR 15:16651670, 1994 Mathis JM, DeNardo AJ, Thibault L, et al: In vitro evaluation of papaverine hydrochloride incompatibilities: a simulation of intra-arterial infusion for cerebral vasospasm. AJNR 15:1665–1670, 1994

    • PubMed
    • Search Google Scholar
    • Export Citation
  • 30.

    McAuliffe W, , Townsend M, & Eskridge JM, et al: Intracranial pressure changes induced during papaverine infusion for treatment of vasospasm. J Neurosurg 83:430434, 1995 McAuliffe W, Townsend M, Eskridge JM, et al: Intracranial pressure changes induced during papaverine infusion for treatment of vasospasm. J Neurosurg 83:430–434, 1995

    • PubMed
    • Search Google Scholar
    • Export Citation
  • 31.

    Milburn JM, , Moran CJ, & Cross DT III, et al: Effect of intraarterial papaverine on cerebral circulation time. AJNR 18:10811085, 1997 Milburn JM, Moran CJ, Cross DT III, et al: Effect of intraarterial papaverine on cerebral circulation time. AJNR 18:1081–1085, 1997

    • PubMed
    • Search Google Scholar
    • Export Citation
  • 32.

    Milburn JM, , Moran CJ, & Cross DT III, et al: Increase in diameters of vasospastic intracranial arteries by intraarterial papaverine administration. J Neurosurg 88:3842, 1998 Milburn JM, Moran CJ, Cross DT III, et al: Increase in diameters of vasospastic intracranial arteries by intraarterial papaverine administration. J Neurosurg 88:38–42, 1998

    • PubMed
    • Search Google Scholar
    • Export Citation
  • 33.

    Miller JA, , Cross DT, & Moran CJ, et al: Severe thrombocytopenia following intraarterial papaverine administration for treatment of vasospasm. J Neurosurg 83:435437, 1995 Miller JA, Cross DT, Moran CJ, et al: Severe thrombocytopenia following intraarterial papaverine administration for treatment of vasospasm. J Neurosurg 83:435–437, 1995

    • PubMed
    • Search Google Scholar
    • Export Citation
  • 34.

    Minami H, , Kuwamura K, & Tamaki N: Intraarterial infusion of papaverine and change of cerebral hemodynamics in symptomatic cerebral vasospasm. Kobe J Med Sci 47:169179, 2001 Minami H, Kuwamura K, Tamaki N: Intraarterial infusion of papaverine and change of cerebral hemodynamics in symptomatic cerebral vasospasm. Kobe J Med Sci 47:169–179, 2001

    • PubMed
    • Search Google Scholar
    • Export Citation
  • 35.

    Newell DW, , Elliott JP, & Eskridge JM, et al: Endovascular therapy for aneurysmal vasospasm. Crit Care Clin 15:685699, 1999 Newell DW, Elliott JP, Eskridge JM, et al: Endovascular therapy for aneurysmal vasospasm. Crit Care Clin 15:685–699, 1999

    • PubMed
    • Search Google Scholar
    • Export Citation
  • 36.

    Numaguchi Y, , Zoarski GH, & Clouston JE, et al: Repeat intra-arterial papaverine for recurrent cerebral vasospasm after subarachnoid haemorrhage. Neuroradiology 39:751759, 1997 Numaguchi Y, Zoarski GH, Clouston JE, et al: Repeat intra-arterial papaverine for recurrent cerebral vasospasm after subarachnoid haemorrhage. Neuroradiology 39:751–759, 1997

    • PubMed
    • Search Google Scholar
    • Export Citation
  • 37.

    Ohkuma H, , Manabe H, & Tanaka M, et al: Impact of cerebral microcirculatory changes on cerebral blood flow during cerebral vasospasm after aneurysmal subarachnoid hemorrhage. Stroke 31:16211627, 2000 Ohkuma H, Manabe H, Tanaka M, et al: Impact of cerebral microcirculatory changes on cerebral blood flow during cerebral vasospasm after aneurysmal subarachnoid hemorrhage. Stroke 31:1621–1627, 2000

    • PubMed
    • Search Google Scholar
    • Export Citation
  • 38.

    Ohkuma H, , Ogane K, & Tanaka M, et al: Assessment of cerebral microcirculatory changes during cerebral vasospasm by analyzing cerebral circulation time on DSA images. Acta Neurochir Suppl 77:127130, 2001 Ohkuma H, Ogane K, Tanaka M, et al: Assessment of cerebral microcirculatory changes during cerebral vasospasm by analyzing cerebral circulation time on DSA images. Acta Neurochir Suppl 77:127–130, 2001

    • PubMed
    • Search Google Scholar
    • Export Citation
  • 39.

    Polin RS, , Hansen CA, & German P, et al: Intra-arterially administered papaverine for the treatment of symptomatic cerebral vasospasm. Neurosurgery 42:12561267, 1998 Polin RS, Hansen CA, German P, et al: Intra-arterially administered papaverine for the treatment of symptomatic cerebral vasospasm. Neurosurgery 42:1256–1267, 1998

    • PubMed
    • Search Google Scholar
    • Export Citation
  • 40.

    Sawada M, , Hashimoto N, & Tsukahara T, et al: Effectiveness of intra-arterially infused papaverine solutions of various concentrations for the treatment of cerebral vasospasm. Acta Neurochir 139:706711, 1997 Sawada M, Hashimoto N, Tsukahara T, et al: Effectiveness of intra-arterially infused papaverine solutions of various concentrations for the treatment of cerebral vasospasm. Acta Neurochir 139:706–711, 1997

    • PubMed
    • Search Google Scholar
    • Export Citation
  • 41.

    Terent A, , Ronquist G, & Bergstrom K, et al: Ischemic edema in stroke. A parallel study with computed tomography and cerebrospinal fluid markers of disturbed brain cell metabolism. Stroke 12:3340, 1981 Terent A, Ronquist G, Bergstrom K, et al: Ischemic edema in stroke. A parallel study with computed tomography and cerebrospinal fluid markers of disturbed brain cell metabolism. Stroke 12:33–40, 1981

    • PubMed
    • Search Google Scholar
    • Export Citation
  • 42.

    Todd NV, , Picozzi P, & Crockard HA, et al: Reperfusion after cerebral ischemia: influence of duration of ischemia. Stroke 17:460466, 1986 Todd NV, Picozzi P, Crockard HA, et al: Reperfusion after cerebral ischemia: influence of duration of ischemia. Stroke 17:460–466, 1986

    • PubMed
    • Search Google Scholar
    • Export Citation
  • 43.

    Varsos VG, , Liszczak TM, & Han DH, et al: Delayed cerebral vasospasm is not reversible by aminophylline, nifedipine, or papaverine in a “two-hemorrhage” canine model. J Neurosurg 58:1117, 1983 Varsos VG, Liszczak TM, Han DH, et al: Delayed cerebral vasospasm is not reversible by aminophylline, nifedipine, or papaverine in a “two-hemorrhage” canine model. J Neurosurg 58:11–17, 1983

    • PubMed
    • Search Google Scholar
    • Export Citation
  • 44.

    Yonas H: Cerebral blood measurements in vasospasm. Neurosurg Clin N Am 1:307318, 1990 Yonas H: Cerebral blood measurements in vasospasm. Neurosurg Clin N Am 1:307–318, 1990

    • PubMed
    • Search Google Scholar
    • Export Citation

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