Combination of aminocaproic acid and nicardipine in treatment of aneurysmal subarachnoid hemorrhage

Antifibrinolytic drags reduce the risk of rebleeding during the first 2 weeks after aneurysmal sub-arachnoid hemorrhage. However, they do not lower overall mortality, largely because of an increased incidence of cerebral ischemia. The usefulness of antifibrinolytic drugs might be increased if a method to prevent or control vasospasm in patients were to be developed. We recently completed late Phase I and Phase II studies of the calcium ion blocking drug nicardipine in 67 patients treated within 1 week of subarachnoid hemorrhage. Of these 67 patients, 42 had delayed operations and were treated concomitantly with the antifibrinolytic drug aminocaproic add (1.5 g/hr) for an average of 6 days before surgery. The outcome of these 42 patients is the subject of this report. Fifteen of 42 patients were treated with the lower dosage levels of nicardipine (0.4-4.5 mg/m²/hr), and 27 patients were treated at the highest dosage level (6.0 mg/m2/hr). Using the World Federation of Neurological Surgeons scale for subarachnoid hemorrhage, at admission 18 patients were Grade 1,15 were Grade II, 6 were Grade HI, and 3 were Grade IV. Five patients (12%) developed clinical signs of deterioration suggestive of cerebral ischemia with concomitant evidence of vasospasm on arteriography. These patients were all treated with hypervolemic hypertensive therapy. Only one patient (2%) developed an Infarction from vasospasm. Two patients developed symptomatic hydrocephalus requiring ventriculo-peritoneal shunting, and a third patient required a temporary ventriculostomy. The 3-month postoperative outcomes were excellent. Three patients (7%) rebled. Three patients died, two from rebleeding of the aneurysm and one who never regained consciousness from the initial hemorrhage. Thirty-two patients (76%) were Grade 1 at 3 months after the subarachnoid hemorrhage. These data suggest that the incidence of vasospasm and cerebral ischemia among patients with antifibrinolytic drugs can be lowered by the concomitant use of a calcium ion blocker. Further investigation of this combination of drugs in patients with recent subarachnoid hemorrhage is warranted.