Utilisation du flumazénil (Ro 15-1788) après perfusion prolongée de midazolam en anesthésie pour chirurgie intracrânienne

Abstract

Midazolam, with a half-life of about 1.5–3.5 h, is inappropriate for the maintenance of anaesthesia during long procedures, especially when rapid recovery is necessary. The efficacy of flumazenil, a specific benzodiazepine antagonist, in the treatment of patients with benzodiazepine overdose suggests that rapid recovery from anaesthesia induced and maintained with midazolam might be obtained in patients needing immediate assessment. The rate of recovery, the side-effects and the feasibility of an early and accurate neurological assessment were studied in 18 ASA III patients after craniotomy in whom the prolonged effects of midazolam had been antagonized by flumazenil. Surgery lasted 5.5 ± 1.3 h (x̄ ± sd). The induction dose of midazolam was 0.32 ± 0.08 mg · kg −1 and the infusion rate was 0.2 ± 0.08 mg · kg −1 · h −1. Fentanyl was added at a dose and rate of 5.0 ± 3.6 μg · kg −1 and 2.0 ± 0.9 μg · kg −1 · h −1 respectively. At the end of the dressing, 0.5 mg of flumazenil ( t 0) was injected, followed by 0.1 mg every minute up to a total of 1 mg. After 2 min, 14 patients (78 %) opened their eyes (p < 0.05) and 13 (72 %) obeyed orders (p < 0.05). After 10 min, 16 patients (89 %) were extubated and speaking. During the first 10 min, the Glasgow score and the sedation score used for this study showed the same progression, with 13 patients (72 %) having a Glasgow score of 14–15 (p < 0.05). Thereafter, both scores decreased progressively till t 60, then increased again, reaching their t 10 level at t 120. Three patients required another dose of antagonist. No tachycardia was observed ; seven patients developed transient increases (> 20 % of baseline) in blood pressure ; two patients were agitated. In conclusion, flumazenil gave rapid an complete recovery after prolonged administration of midazolam for intracranial surgery, enabling the surgeon to perform and accurate neurological assessment. This early examination was important for the detection of postoperative deficits and assessment of the subsequent postoperative course. The degree of sedation increased after 10 min, a consequence of the large doses of midazolam used and the short half-life of flumazenil. A second injection of the antagonist eliminated this problem.