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

Abstract

Antifibrinolytic drags reduce the risk of rebleeding during the first 2 weeks after aneurysmal subarachnoid 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. T he use of antifibrinolytic drugs in the management of aneurysmal subarachnoid hemorrhage (SAH) is controversial. 1 " 3 Recently two large multicenter trials showed that the risk of rebleeding was substantially reduced in patients receiving antifibrinolytic drugs compared with a comparable group of patients not receiving antifibrinolytic drugs. 45 However, the overall mortality rate at 3 months between the groups was similar. The reduction of mortality due to rebleeding was negated by increased mortality due to cerebral ischemia among the patients given antifibrinolytic drugs.4 " 6 Antifibrinolytic drugs could become a useful preoperative therapy in patients with recent SAH if the risks of vasospasm and cerebral ischemia could be reduced.We recently performed a prospective dosage escala- Received June 3, 1987; accepted July 14, 1987. tion study of nicardipine, a dihydropyridine calcium ion entry blocking agent that preferentially binds to cerebrovascular smooth muscle, in 67 patients with recent SAH. Forty-two patients had delayed operations planned for the treatment of the aneurysm and were given aminocaproic acid before surgery. These 42 patients were studied for any effect on the incidence and severity of symptomatic vasospasm by the concomitant administration of nicardipine and aminocaproic acid. Subjects and MethodsPatients between the ages of 18 and 75 admitted to University of Iowa Hospitals or to New York University Medical Center within 7 calendar days of SAH from a documented cerebral aneurysm were included in the study. The details of this study are described elsewhere. 7 In all cases, blood in the subarachnoid space was evident on either computed tomography (CT) or nontraumatic lumbar puncture. Cerebral angiography to demonstrate the presence of a saccular aneurysm and the absence of vasospasm was performed before patients were entered into the study. Patients were excluded if they were deeply comatose, if they had a large intracerebral hemorrhage, or if arterial narrowing was found on the initial arteriogram. Patients were also excluded if they were taking a calcium ion blocking

Role of platelet function in symptomatic cerebral vasospasm following aneurysmal subarachnoid hemorrhage.

“…The patients' clinical grades according to the World Federation of Neurological Surgeons scale 21 were II or III (Table 1). No patient was given antiplatelet drugs, and none received calcium antagonists just prior to SAH.…”

Clipping surgery for aneurysmal subarachnoid hemorrhage in patients aged 75 years or older

“…8 We dichotomized clinical condition into good (WFNS I-III) and poor (WFNS IV and V). Based on CT scans, the bleeding severity was classified according to the Fisher classification.…”

Antifibrinolytic Therapy To Prevent Early Rebleeding After Subarachnoid Hemorrhage

“…A number of studies using both antifibrinolytics and either nicardipine or nimodipine reported decreased rebleeding, no increase in ischemic deficits, and improved outcomes [15,26,28,41,42]. Rebleeding rates ranged from 7% to 13% and mortality ranged from 11% to 12%.…”

“…Different doses as well as routes of administration had been used in earlier trials, and effective blood and CSF drug levels might not have been achieved [22][23][24][25]. In addition, studies have shown that calcium channel blocking agents can decrease the incidence of vasospasm and cerebral ischemia among patients treated with antifibrinolytics [26][27][28]. Although long-term use of antifibrinolytic agents in aSAH is no longer an accepted practice, there still might be a role for short-term administration to reduce early rebleeding.…”