Early intervention with nimodipine in subarachnoid haemorrhage

Abstract

Seventy-five consecutive patients with subarachnoid haemorrhage (SAH) were entered into a randomized, double-blind, placebo-controlled trial prior to angiography in order to determine the effect of early intervention with nimodipine on blood pressure (BP), cerebral blood flow (CBF), and clinical outcome. Of these patients, 50 fulfilled the criteria for the final analysis (i.e. SAH due to cerebral aneurysm and receiving 21 days of treatment). There was no difference between the BP recordings of the two treatment groups, but mean CBF decreased slightly in the nimodipine group over the 21-day treatment period. At three months, one patient on nimodipine and six patients receiving placebo had died (P = 0.049, Fisher's exact test), but no significant difference was observed between the two groups, when the 'intent to treat' group of 75 patients was considered. We conclude that nimodipine does not increase CBF or alter BP following SAH, but an improved clinical outcome is evident at three months for patients with SAH due to cerebral aneurysm who had been treated with nimodipine. There were no side-effects due to nimodipine.

Vasospasm on transcranial Doppler is predictive of delayed cerebral ischemia in aneurysmal subarachnoid hemorrhage: a systematic review and meta-analysis

“…20,25 Cerebral vasospasm is noted on angiography in as many as 70% of patients following aSAH and is predicted by high mean flow velocities (MFVs) on transcranial Doppler (TCD) ultrasonography. 19,24,26,35 Vasospasm is strongly associated with delayed cerebral ischemia (DCI) 12 and cerebral infarction, 11,39,49 although poor outcomes can still occur in its absence. Of the current techniques available for diagnosing cerebral vasospasm, catheter angiography and CT angiography are invasive, and require contrast-dye injection and radiation exposure, and therefore do not allow dynamic monitoring of vasospasm.…”

“…Unlike angiography, TCD can predict symptomatic vasospasm and has high sensitivity, specificity, and positive and negative predictive value. 16,19,24,26,35 Although approved and recommended by the American Heart Association/American Stroke Association (rated Class IIA/Level B evidence), American Academy of Neurology, and Neurocritical Care Society (moderate quality evidence/strong recommendation) as a safe and effective modality for noninvasive daily monitoring in aSAH, lack of knowledge of the impact on patient-centered outcomes (disability, quality of life, stroke, mortality, etc.) and weak strength of evidence has prevented it from becoming mandated as a standard of care.…”

Calcium antagonists: stroke therapy coming of age.

“…48 Neil-Dwyer et al reported an 83% reduction in mortality and 50% decrease in poor outcome in SAH patients treated with oral and intraoperative intracisternal nimodipine. 49 In the Petruk et al study, which was limited to poor neurologic grade patients (Hunt and Hess grades III-V), there was an overall 7% reduction of poor outcome in patients treated with nimodipine. 50 Also, there was a significant increase in good recovery (Glasgow Outcome Scale 1), 29.2% in the nimodipine group compared with 9.8% in controls.…”

Effect of Fasudil Hydrochloride, a Protein Kinase Inhibitor, on Cerebral Vasospasm and Delayed Cerebral Ischemic Symptoms After Aneurysmal Subarachnoid Hemorrhage-Results of a Randomized Trial of Fasudil Hydrochloride Versus Nimodipine-

“…The mechanism of action is different from that of calcium channel blockers such as nimodipine, which are widely used clinically for the treatment of cerebral vasospasm. 1,[14][15][16][17][18] Fasudil hydrochloride inhibits protein kinases such as Rho kinase, myosin light chain kinase, and protein kinase C, resulting in the inhibition of myosin light chain phosphorylation. 7,12,25) Animal experiments demonstrated that fasudil hydrochloride antagonizes the cerebral blood vessel contracting effect of endothelin, 5) and dilates spastic cerebral artery in a dog cerebral hemorrhage model, 22,27) resulting in decreased ischemic damage.…”