A randomized trial of nicardipine in subarachnoid hemorrhage: angiographic and transcranial Doppler ultrasound results

A report of the Cooperative Aneurysm Study

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  • 1 Central Registry, Departments of Neurology and Neurosurgery, University of Virginia Health Sciences Center, Charlottesville, Virginia
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✓ Calcium antagonist drugs were proposed for use in patients with recent aneurysmal subarachnoid hemorrhage (SAH) because of their ability to block the effects of a wide variety of vasoconstrictor substances on cerebral arteries in vitro. It was suggested that these agents might, therefore, be useful in ameliorating cerebral vasospasm and its ischemic consequences which frequently complicate SAH. This hypothesis was tested in an arm of a randomized double-blind placebo-controlled trial of high-dose intravenous nicardipine in patients with recently ruptured aneurysms. Participating investigators were required to send selected copies of all admission and follow-up angiograms obtained between Days 7 and 11 following hemorrhage (the peak period of risk for vasospasm) to the Central Registry of the Cooperative Aneurysm Study for blinded interpretation and review for the presence and severity of angiographic vasospasm. In centers with transcranial Doppler ultrasound (TCD) capabilities, middle cerebral artery (MCA) mean flow velocities were measured and recorded.

Angiograms obtained between Days 7 and 11 were available for 103 (23%) of 449 patients receiving nicardipine and 121 (26%) of 457 receiving placebo. There was a balance of prognostic factors for vasospasm between the groups. Fifty-one percent of placebo-treated patients had moderate or severe vasospasm on “Day 7–11 angiograms” compared to 33% of nicardipine-treated patients. This difference is statistically significant (p < 0.01). Sixty-seven (49%) of 137 placebo-treated patients examined with TCD between Days 7 and 11 had mean MCA flow velocities exceeding 120 cm/sec compared to 26 (23%) of 112 nicardipine-treated patients (significant difference, p < 0.001). These data suggest that high-dose intravenous nicardipine reduces the incidence and severity of delayed cerebral arterial narrowing in patients following aneurysmal SAH.

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Contributor Notes

Address reprint requests to: E. Clarke Haley, Jr., M.D., Department of Neurology, Box 394, University of Virginia Health Sciences Center, Charlottesville, Virginia 22908.
  • 1.

    Aaslid R, , Huber P, & Nornes H: Evaluation of cerebrovascular spasm with transcranial Doppler ultrasound. J Neurosurg 60:3741, 1984 Aaslid R, Huber P, Nornes H: Evaluation of cerebrovascular spasm with transcranial Doppler ultrasound. J Neurosurg 60:37–41, 1984

    • Search Google Scholar
    • Export Citation
  • 2.

    Aaslid R, , Markwalder TM, & Nornes H: Noninvasive transcranial Doppler ultrasound recording of flow velocity in basal cerebral arteries. J Neurosurg 57:769774, 1982 Aaslid R, Markwalder TM, Nornes H: Noninvasive transcranial Doppler ultrasound recording of flow velocity in basal cerebral arteries. J Neurosurg 57:769–774, 1982

    • Search Google Scholar
    • Export Citation
  • 3.

    Adams HP Jr, , Kassell NF, & Torner JC, et al: Predicting cerebral ischemia after aneurysmal subarachnoid hemorrhage: influences of clinical condition, CT results, and antifibrinolytic therapy. A report of the Cooperative Aneurysm Study. Neurology 37:15861591, 1987 Adams HP Jr, Kassell NF, Torner JC, et al: Predicting cerebral ischemia after aneurysmal subarachnoid hemorrhage: influences of clinical condition, CT results, and antifibrinolytic therapy. A report of the Cooperative Aneurysm Study. Neurology 37:1586–1591, 1987

    • Search Google Scholar
    • Export Citation
  • 4.

    Allen GS: Cerebral arterial spasm: a discussion of present and future research. Neurosurgery 1:142148, 1977 Allen GS: Cerebral arterial spasm: a discussion of present and future research. Neurosurgery 1:142–148, 1977

    • Search Google Scholar
    • Export Citation
  • 5.

    Allen GS, , Ahn HS, & Preziosi TJ, et al: Cerebral arterial spasm — a controlled trial of nimodipine in patients with subarachnoid hemorrhage. N Engl J Med 308:619624, 1983 Allen GS, Ahn HS, Preziosi TJ, et al: Cerebral arterial spasm — a controlled trial of nimodipine in patients with subarachnoid hemorrhage. N Engl J Med 308:619–624, 1983

    • Search Google Scholar
    • Export Citation
  • 6.

    American Academy of Neurology, Therapeutics and Technology Assessment Subcommittee: Assessment: transcranial Doppler. Neurology 40:680681, 1990 American Academy of Neurology, Therapeutics and Technology Assessment Subcommittee: Assessment: transcranial Doppler. Neurology 40:680–681, 1990

    • Search Google Scholar
    • Export Citation
  • 7.

    Flamm ES, , Adams HP Jr, & Beck DW, et al: Dose-escalation study of intravenous nicardipine in patients with aneurysmal subarachnoid hemorrhage. J Neurosurg 68:393400, 1988 Flamm ES, Adams HP Jr, Beck DW, et al: Dose-escalation study of intravenous nicardipine in patients with aneurysmal subarachnoid hemorrhage. J Neurosurg 68:393–400, 1988

    • Search Google Scholar
    • Export Citation
  • 8.

    Haley EC Jr, , Kassell NF, & Torner JC, et al: A randomized controlled trial of high-dose intravenous nicardipine in aneurysmal subarachnoid hemorrhage: A report of the Cooperative Aneurysm Study. J Neurosurg 78:537547, 1993 Haley EC Jr, Kassell NF, Torner JC, et al: A randomized controlled trial of high-dose intravenous nicardipine in aneurysmal subarachnoid hemorrhage: A report of the Cooperative Aneurysm Study. J Neurosurg 78:537–547, 1993

    • Search Google Scholar
    • Export Citation
  • 9.

    Hutchison K, & Weir B: Transcranial Doppler studies in aneurysm patients. Can J Neurol Sci 16:411416, 1989 Hutchison K, Weir B: Transcranial Doppler studies in aneurysm patients. Can J Neurol Sci 16:411–416, 1989

    • Search Google Scholar
    • Export Citation
  • 10.

    Lindegaard KF, , Nornes H, & Bakke SJ, et al: Cerebral vasospasm after subarachnoid haemorrhage investigated by means of transcranial Doppler ultrasound. Acta Neurochir Suppl 42:8184, 1988 Lindegaard KF, Nornes H, Bakke SJ, et al: Cerebral vasospasm after subarachnoid haemorrhage investigated by means of transcranial Doppler ultrasound. Acta Neurochir Suppl 42:81–84, 1988

    • Search Google Scholar
    • Export Citation
  • 11.

    Neil-Dwyer G, , Mee E, & Dorrance D, et al: Early intervention with nimodipine in subarachnoid haemorrhage. Eur Heart J 8 (Suppl K):4147, 1987 Neil-Dwyer G, Mee E, Dorrance D, et al: Early intervention with nimodipine in subarachnoid haemorrhage. Eur Heart J 8(Suppl K):41–47, 1987

    • Search Google Scholar
    • Export Citation
  • 12.

    Petruk KC, , West M, & Mohr G, et al: Nimodipine treatment in poor-grade aneurysm patients. Results of a multicenter double-blind placebo-controlled trial. J Neurosurg 68:505517, 1988 Petruk KC, West M, Mohr G, et al: Nimodipine treatment in poor-grade aneurysm patients. Results of a multicenter double-blind placebo-controlled trial. J Neurosurg 68:505–517, 1988

    • Search Google Scholar
    • Export Citation
  • 13.

    Philippon J, , Grob R, & Dagreou F, et al: Prevention of vasospasm in subarachnoid haemorrhage. A controlled study with nimodipine. Acta Neurochir 82:110114, 1986 Philippon J, Grob R, Dagreou F, et al: Prevention of vasospasm in subarachnoid haemorrhage. A controlled study with nimodipine. Acta Neurochir 82:110–114, 1986

    • Search Google Scholar
    • Export Citation
  • 14.

    Pickard JD, , Murray GD, & Illingworth R, et al: Effect of oral nimodipine on cerebral infarction and outcome after subarachnoid haemorrhage: British Aneurysm Nimodipine Trial. Br Med J 298:636642, 1989 Pickard JD, Murray GD, Illingworth R, et al: Effect of oral nimodipine on cerebral infarction and outcome after subarachnoid haemorrhage: British Aneurysm Nimodipine Trial. Br Med J 298:636–642, 1989

    • Search Google Scholar
    • Export Citation
  • 15.

    Robinson MJ, & Teasdale GM: Calcium antagonists in the management of subarachnoid hemorrhage. Cerebrovasc Brain Metab Rev 2:205226, 1990 Robinson MJ, Teasdale GM: Calcium antagonists in the management of subarachnoid hemorrhage. Cerebrovasc Brain Metab Rev 2:205–226, 1990

    • Search Google Scholar
    • Export Citation
  • 16.

    Shibuya M, , Suzuki Y, & Sugita K, et al: Effect of AT877 on cerebral vasospasm after aneurysmal subarachnoid hemorrhage. Results of a prospective placebo-controlled double-blind trial. J Neurosurg 76:571577, 1992 Shibuya M, Suzuki Y, Sugita K, et al: Effect of AT877 on cerebral vasospasm after aneurysmal subarachnoid hemorrhage. Results of a prospective placebo-controlled double-blind trial. J Neurosurg 76:571–577, 1992

    • Search Google Scholar
    • Export Citation
  • 17.

    Shuster JJ: CRC Handbook of Sample Size Guidelines for Clinical Trials. Boca Raton: CRC Press, 1990, pp 1819 Shuster JJ: CRC Handbook of Sample Size Guidelines for Clinical Trials. Boca Raton: CRC Press, 1990, pp 18–19

    • Search Google Scholar
    • Export Citation
  • 18.

    Sloan MA, , Haley EC Jr, & Kassell NF, et al: Sensitivity and specificity of transcranial Doppler ultrasonography in the diagnosis of vasospasm following subarachnoid hemorrhage. Neurology 39:15141518, 1989 Sloan MA, Haley EC Jr, Kassell NF, et al: Sensitivity and specificity of transcranial Doppler ultrasonography in the diagnosis of vasospasm following subarachnoid hemorrhage. Neurology 39:1514–1518, 1989

    • Search Google Scholar
    • Export Citation
  • 19.

    Snedecor GW, & Cochran WG: Statistical Methods, ed 7. Ames, Iowa: Iowa State University Press, 1980, pp 5657, 208–210 Snedecor GW, Cochran WG: Statistical Methods, ed 7. Ames, Iowa: Iowa State University Press, 1980, pp 56–57, 208–210

    • Search Google Scholar
    • Export Citation
  • 20.

    Weir B: Calcium antagonists, cerebral ischemia and vasospasm. Can J Neurol Sci 11:239246, 1984 Weir B: Calcium antagonists, cerebral ischemia and vasospasm. Can J Neurol Sci 11:239–246, 1984

    • Search Google Scholar
    • Export Citation

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