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Effect of flumazenil on ventilatory drive during sedation with midazolam and alfentanil.

Abstract：

BACKGROUND:Patients who receive a combination of a benzodiazepine and an opioid for conscious sedation are at risk for developing respiratory depression. While flumazenil effectively antagonizes the respiratory depression associated with a benzodiazepine alone, its efficacy in the presence of both a benzodiazepine and an opioid has not been established. This study was designed to determine whether flumazenil can reverse benzodiazepine-induced depression of ventilatory drive in the presence of an opioid. METHODS:Twelve healthy volunteers completed this randomized, double-blind, crossover study. Ventilatory responses to carbon dioxide and to isocapnic hypoxia were determined during four treatment phases: (1) baseline, (2) alfentanil infusion; (3) combined midazolam and alfentanil infusions, and (4) combined alfentanil, midazolam, and "study drug" (consisting of either flumazenil or flumazenil vehicle) infusions. Subjects returned 2-6 weeks later to receive the alternate study drug. RESULTS:Alfentanil decreased the slope of the carbon dioxide response curve from 2.14 +/- 0.40 to 1.43 +/- 0.19 l.min-1.mmHg-1 (x +/- SE, P < 0.05), and decreased the minute ventilation at P(ET)CO2 = 50 mmHg (VE50) from 19.7 +/- 1.2 to 14.8 +/- 0.9l.min-1 (P < 0.05). Midazolam further reduced these variables to 0.87 +/- 0.17 l.min-1.mmHg-1 (P < 0.05) and 11.7 +/- 0.8 l.min-1 (P < 0.05), respectively. With addition of flumazenil, slope and VE50 increased to 1.47 +/- 0.37 l.min-1.mmHg-1 (P < 0.05) and 16.4 +/- 2.0l.min-1 (P < 0.05); after placebo, the respective values of 1.02 +/- 0.19 l.min-1.mmHg-1 and 12.5 +/- 1.2 l.min-1 did not differe significantly from their values during combined alfentanil and midazolam administration. The effect of flumazenil differed significantly from that of placebo (P < 0.05). Both the slope and the displacement of the hypoxic ventilatory response, measured at P(ET)CO2 = 46 +/- 1 mmHG, were affected similarly, with flumazenil showing a significant improvement compared to placebo. CONCLUSIONS:Flumazenil effectively reverses the benzodiazepine component of ventilatory depression during combined administration of a benzodiazepine and an opioid.

journal_name

Anesthesiology

journal_title

Anesthesiology

authors

Gross JB,Blouin RT,Zandsberg S,Conard PF,Häussler J

doi

10.1097/00000542-199610000-00005

subject

Has Abstract

pub_date

1996-10-01 00:00:00

pages

713-20

issue

eissn

0003-3022

issn

1528-1175

journal_volume

pub_type

临床试验,杂志文章,随机对照试验

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Effect of flumazenil on ventilatory drive during sedation with midazolam and alfentanil.