Summary
A cerebral Ca2+ overload blocker-flunarizine hydrochloride — was used with excellent results for prophylaxis of delayed ischaemic neurological deficit (DIND) in severe subarachnoid haemorrhage.
The drug was administered orally at a dose of 10 mg, four times daily for four days, followed by three times daily for three days and twice daily for 14 more days.
Of 72 patients treated with flunarizine, only one developed permanent DIND. 37 consecutive patients who were in Fisher's group III and were treated with flunarizine from immediately after early surgery were compared retrospectively with the 37 consecutive Control Group patients, who also belong to Fisher's group III. Among the Control Group patients, eight died from DIND and ten developed infarction from DIND, while flunarizine strongly prevented (p<0.001) DIND. Furthermore, the only one DIND was attributable to failure of administration of flunarizine.
There were no side-effects from flunarizine.
The association of severe angiographic vasospasm was less frequent in the Flunarizine Group (18% vs 57%, p<0.02).
From this evidence, it might be concluded that flunarizine significantly inhibits the occurrence of severe neurological deficit due to delayed vasospasm. This highly beneficial effect on severe delayed vasospasm might be attributable to its intense inhibitory action on intracellular Ca2+ overloads especially in severe pathological situations.
Similar content being viewed by others
References
Allen GS, Ahn HS, Preziosi TJet al (1983) Cerebral arterial spasm. A controlled trial of nimodipine in patients with subarachnoid hemorrhage. New Engl J Med 308: 619–624
Auer LM, Brandt L, Ebeling Uet al (1986) Nimodipine and early operation in good conditions SAH patients. Acta Neurochir (Wien) 82: 7–13
Borgers M, Clerck FD, Van Reempts Jet al (1984) Selective blockade of cellular Ca2+-overload by flunarizine. Inter Angio 3: 25–31
Farber JL (1981) The role of calcium in cell death. Life Sci 29: 1289–1295
Fisher CM, Kistler JP, Davis JM (1980) Relation of cerebral vasospasm to subarachnoid hemorrhage visualized by computerized tomographic scanning. Neurosurgery 6: 1–9
Flamm ES, Adams HP, Beck DW (1988) Dose-escalation study of intravenous nicardipine in patients with aneurysmal subarachnoid hemorrhage. J Neurosurg 68: 393–400
Fujita S (1985) Computed tomographic grading with Houndsfield number related to delayed vasospasm in cases of ruptured cerebral aneurysm. Neurosurgery 17: 609–612
Godfraind T (1986) Calcium entry blockade and excitation contraction coupling in the cardiovascular system (with an attempt of pharmacological classification). Acta Pharmacol Toxicol [Suppl II] 58: 5–30
Hladovec J, De Clerck F (1981) Protection by flunarizine against endothelial cell injury in vivo. Angiology 32: 447–462
Hunt WE, Hess RM (1968) Surgical risk as related to time of intervention in the repair of intracranial aneurysms. J Neurosurg 28: 14–21
Jennett B, Bond M (1975) Assessment of outcome after severe brain damage. A practical Scale. Lancet March 1: 480–484
Kassell NF, Peerless SJ, Durward QJet al (1982) Treatment of ischemic deficits from vasospasm with intravascular volume expansion and induced arterial hypertension. Neurosurgery 11: 337–343
Kassell NF, Sasaki T, Colohan ARTet al (1985) Cerebral vasospasm following aneurysmal subarachnoid hemorrhage. Stroke 16: 562–572
Kubo K, Yoshitake I, Kumadaet al (1984) Radical scavenging action of flunarizine in rat brain in vitro. Arch Int Pharmacodyn 272: 283–295
Ljunggren B, Brandt L, Säveland Het al (1984) Outcome in 60 consecutive patients treated with early aneurysm operation and intravenous nimodipine. J Neurosurg 61: 864–873
Mee E, Dorrance D, Lowe Det al (1988) Controlled study of nimodipine in aneurysm patients treated early after subarachnoid hemorrhage. Neurosurgery 22: 484–491
Michiels M, Hendriks R, Knaeps Fet al (1983) Absorption and tissue distribution of flunarizine in rats, pigs and dogs. Arzneim-Forsch/Drug Res 33: (II), 8: 1135–1142
Mizukami M, Kawase T, Usami Tet al (1982) Prevention of vasospasm by early operation with removal of subarachnoid blood. Neurosurgery 10: 301–307
Öhman J, Heiskanen O (1988) Effect of nimodipine on the outcome of patients after aneurysmal subarachnoid hemorrhage and surgery. J Neurosurg 69: 683–686
Petruk KC, West M, Mohr Get al (1988) Nimodipine treatment in poor-grade aneurysm patients. Results of a multicenter double-blind placebo-controlled trial. J Neurosurg 68: 505–517
Philippon J, Grob R, Dagreou Fet al (1986) Prevention of vasospasm in subarachnoid haemorrhage. A controlled study with nimodipine. Acta Neurochir (Wien) 82: 110–114
Scott CK, Persico F, Carpenter K (1980) The effects of flunarizine, a new calcium antagonist, on human red blood cells in vitro. Angiology 31: 320–330
Taneda M (1982) Effect of early operation for ruptured aneurysms on prevention of delayed ischemic symptoms. J Neurosurg 57: 622–628
Van Nueten JM, Vanhoutte PM (1981) Selectivity of calcium-antagonism with respect to venous and arterial tissues. Angiology 32: 476–484
Van Zwieten PA (1985) Calcium antagonists-terminology, classification and comparison. Arzneimittelforschung 35: 298–301
Wauquier A, Ashton D, Clincke Get al (1985) “Calcium entry blockers” as cerebral protecting agents: Comparative activity in tests of hypoxia and hyperexcitability. Japan J Pharmacol 38: 1–7
Wauquier A (1984) Effect of calcium entry blockers in model of brain hypoxia. In: Godfraind T, Herman AG, Wellens D (eds) Calcium entry blockers in cardiovascular and cerebral dysfunctions. Martinus Nijhoff Publishers, Boston, pp 241–253
Author information
Authors and Affiliations
Rights and permissions
About this article
Cite this article
Fujita, S., Kawaguchi, T., Shose, Y. et al. Flunarizine treatment in poor-grade aneurysm patients. Acta neurochir 103, 11–17 (1990). https://doi.org/10.1007/BF01420186
Issue Date:
DOI: https://doi.org/10.1007/BF01420186