The Association of Tranexamic Acid and Nimodipine in the Pre-operative Treatment of Ruptured Intracranial Aneurysms

Abstract

In the scope of a late intervention policy on ruptured intracranial aneurysms, on D.+12 on an average, we first used tranexamic acid, at moderate doses: 3 g orally or 1.5 g intravenously per day. We, subsequently, added nimodipine, usually 240 mg orally per day or 2 mg intravenously per hour. The medical treatment consisted of amply sufficient hydration, and in systematic and regular administration of analgesics and sedatives. Hypotension was absolutely avoided; if necessary, an antihypertensive treatment was prescribed very cautiously. Phenytoin was regularly given. In the present study, we try to answer the following questions: (1) Can we confirm that the preventive action of tranexamic acid remains as effective, when doses, markedly lower than usually recommended, are used? (2) Does nimodipine prevent the increase of pre-operative ischaemic complications, which should be expected when tranexamic acid is administered? Amongst 101 patients with SAH of proven aneurysmal origin, 84 were treated with tranexamic acid and nimodipine. In 25 patients, an aneurysm was not visualised; 21 received this treatment. For several reasons, only a retrospective study was possible, to evaluate the results of our antifibrinolytic and calcium-blocking therapies, on rebleeding and pre-operative delayed ischaemia. We compared, therefore, similar cases from the literature, with our own cases, taking into consideration the clinical grades, the days of admission and of intervention, the moment of rebleeding and of delayed pre-operative ischaemia, etc. The following impressions emerge: (1) same effectiveness of moderate doses of tranexamic acid; (2) no increase of pre-operative delayed ischaemic complications, in comparison with patients not receiving antifibrinolytics but nimodipine; (3) important role of a devastating initial bleed and of operative complications; (4) difficulty of avoiding rebleeding at D.0, whatever the therapeutic measures, medical and/or surgical.

Immediate administration of tranexamic acid and reduced incidence of early rebleeding after aneurysmal subarachnoid hemorrhage: a prospective randomized study

“…5,17,27,43,46,50,53,58 Nevertheless, although rebleeding occurs in 15 to 30% of patients during the first 2 weeks of conservative treatment, the influence of early intervention on overall outcome is still a matter of debate. 37,52,58 Our data clearly show that close collaboration with local referring hospitals permits effective application of a protocol for immediate diagnosis and transfer of patients with SAH to neurosurgical centers on a large scale. Furthermore, data show that given such an organization, expedited treatment of aneurysms in patients in all clinical grades can virtually eliminate in-hospital rebleeding after the 1st day of SAH.…”

“…28,30,57 Nevertheless, some clinicians still adhere to this treatment policy. 37,48,52 The object of this randomized prospective study was to assess the efficacy of short-term antifibrinolytic treatment with tranexamic acid in preventing rebleeding. 32 …”

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%.…”

“…No differences have been found between EACA and TXA with respect to preventing early recurrence of aSAH, overall pre-operative mortality rates, and side effects [28,53]. An increased incidence of hydrocephalus in patients on long-term antifibrinolytics has been reported [14,21,[54][55][56][57][58].…”

“…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.…”