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Ventilatory Depression Related to Plasma Fentanyl Concentrations during and after Anesthesia in Humans

Sir Humphry Davy Department of Anaesthesia, University of Bristol, United Kingdom.

Abstract

Twenty-four patients were allocated randomly into four groups for the study of the pharmacokinetics of, and effects on postoperative ventilation of, two doses of fentanyl (10 µg/kg or 25 µg/kg) administered at the start of general anesthesia in which ventilation was controlled at a fixed volume, but arterial PCO₂ was adjusted to a range of either 38–42 torr, or 20–25 torr. During the first 2 hr after anesthesia, ventilatory depression (CO₂ responsiveness decreased to <50% of awake values, PACO₂ > 48 torr) occurred only in patients who had received 25 µg/kg fentanyl, and was more marked in patients who were hyperventilated to a low PACO₂ during anesthesia. Plasma fentanyl concentrations associated with 50% depression of CO₂ responsiveness were in the range 1.5–3.0 ng/ml, the lower values found in patients hyperventilated to a low PACO₂. Whole-body clearance of fentanyl was significantly decreased by hypocapnic hyperventilation.

Key Words: ANALGESICS: fentanyl • PHARMACOKINETICS: fentanyl

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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