Abstract
The purpose of this study was to evaluate the effects of flumazenil (1 mg iv) on the ventilatory response of premedicated patients receiving a continuous infusion of midazolam for sedation. After assessing baseline ventilatory function using a modified Read rebreathing method for determining hypercapnic ventilatory drive, 16 healthy outpatients were administered fentanyl, 50 μg iv, and midazolam 2 mg iv followed by a variable-rate midazolam infusion, 0.3–0.5 mg · min−1. Upon termination of the midazolam infusion, serum midazolam concentrations were measured and ventilatory function was reassessed. Then, 10 ml of either saline or flumazenil (1 mg) were administered according to a randomized, double-blind protocol. Ventilatory function was subsequently measured at 5 min, 30 min and 60 min intervals after study drug. Compared with the baseline value, midazolam infusion reduced tidal volume and increased respiratory rate and alveolar dead space. However, midazolam did not decrease the slope of the CO2-response curve. Flumazenil reduced the degree of midazolam-induced sedation and the decrease in tidal volume (P < 0.05), but not the change in resting respiratory rate. In some patients, the ventilatory response to hypercarbia actually decreased after flumazenil administration compared with the immediate prereversal (sedated) values. It is concluded that midazolam infusion, 0.43 mg · min−1, did not impair CO2-responsiveness. Flumazenil’s effect on central ventilatory drive was more variable than its reversal of midazolam-induced sedation.
Résumé
Cette étude vise à évaluer les effets du flumazénil (1 mg iv) sur la réponse ventilatoire de patients prémédiqués qui reçoivent, pour fin de sédation, une perfusion continue de midazolam. Après avoir établi la ventilation initiale avec une méthode de réinspiration de Read modifiée, dans le but de déterminer l’effort ventilatoire hypercapnique, 16 patients ambulatoires bien portants reçoivent fentanyl 50 μg iv et midazolam 2 mg iv suivis d’une perfusion de midazolam à débit variable à la vitesse de 0,3–0,5 mg · min−1. Une fois la perfusion terminée, les concentrations sériques de midazolam sont mesurées et la ventilation réévaluée. Par la suite, une solution de 10 ml contenant soit du soluté physiologique soit du flumazénil (1 mg) est administrée aléatoirement et à double aveugle. La ventilation est par la suite mesurée à des intervalles de 5 min, 30 min et 60 min. Comparativement aux valeurs de base, la perfusion de midazolam diminue le volume minute et augmente la fréquence respiratoire et l’espace mort alvéolaire. Cependant, le midazolam ne modifie pas la pente de la courbe de réponse au CO2. Le flumazénil diminue le niveau de sédation induit par le midazolam et la baisse du volume courant (P < 0,05), mais non le changement de la fréquence respiratoire. Chez certains patients, la réponse ventilatoire à l’nypercarbie diminue après l’administration de flumazénil comparativement aux valeurs qui précèdent immédiatement l’antagonisme. En conclusion, une perfusion de midazolam 0,43 mg · min−1 n’altère pas la réactivité au CO2. L’effet du flumazénil sur l’effort respiratoire central est plus variable que sa capacité de renverser la sédation induite par le midazolam.
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This study was supported in part fey a research grant from the Ambulatory Anesthesia Research Foundation, Dallas, TX.
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Mora, C.T., Torjman, M. & White, P.F. Sedative and ventilatory effects of midazolam infusion: effect of flumazenil reversal. Can J Anaesth 42, 677–684 (1995). https://doi.org/10.1007/BF03012664
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DOI: https://doi.org/10.1007/BF03012664