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Sedative Doses of Midazolam Depress Hypoxic Ventilatory Responses in Humans

Received from the Departments of Anesthesia, University of Pennsylvania, and Philadelphia Veterans Administration Medical Center, Philadelphia, Pennsylvania.

Abstract

The effect of midazolam on the hypoxic ventilatory response of eight healthy volunteers was examined during isocapnic rebreathing. The magnitude of the slope of the ventilatory response to hypoxia (E vs SaO₂) decreased from 1.48 ± 0.24 to 0.70 ± 0.13 L·min^–1 ± %SaO₂^–1 ( ± SE, P < 0.005) after midazolam 0.1 mg/kg IV. The calculated ventilation at an arterial saturation of 90% also decreased from 28.6 ± 4.4 to 19.9 ± 2.7 L/min (P < 0.05). Before midazolam, hypoxia to an SaO₂ of 75 ± 2% was associated with a 23 ± 3 beatslmin increase in heart rate; after midazolam, the increase in heart rate with hypoxia was only 4 ± 2 beatslmin (P < 0.003). Additionally, a double-blind crossover study evaluated the effect of phy-sostigmine on awareness and hypoxic ventilatory response after midazolam. The change in hypoxic response slope after physostigmine 2.0 mg IV (an increase of 0.28 ± 0.34 L-min^–1 ± %SaO₂^–1) did not differ significantly from that after placebo (an increase of 0.03 ± 0.22 L-min^–1 ± %SaO₂^–1), although physostigmine significantly increased awareness. It is concluded that a sedative dose of midazolam depresses hypoxic ventilatory response and attenuates the hyperpnea andtachycardia associated with hypoxemia. Furthermore, physostigmine-glycopyrrolate reversal of midazolam-induced sedation was associated with nausea (five subjects), vomiting (three subjects), and tachycardia without reversal of the depressed hypoxic ventilatory response.

Key Words: ANTAGONISTS, MISCELLANEOUS—physostigmine • ANTAGONISTS, CHOLINERGIC—glycopyrrolate • HYPNOTICS, BENZODIAZEPINES—midazolam • VENTILATION—hypoxic response

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Anesthesia & Analgesia® is published for the International Anesthesia Research Society® by Lippincott Williams & Wilkins with the assistance of Stanford University Libraries' HighWire Press®. Copyright 2006 by the International Anesthesia Research Society. Online ISSN: 1526-7598   Print ISSN: 0003-2999