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Respiratory Depression after Epidural Morphine—An Experimental and Clinical Study

Recived from the Department of Anesthesiology and Intensive Care, Örebro Medical Center Hospital, Örebro, and the Department of Anesthesiology, Linköping University, Sweden. Presented in part at the Meeting of the Swedish Society of Anesthesiologists, Örebro, Sweden, September 1982; and at the XXXI Annual Conference of the Indian Society of Anaesthesiologists, Mangalore, India, December 1982.

Abstract

This study was comprised of an experimental part (20 volunteers) and a clinical part (10 surgical patients). In the experimental part, the effects of either 2-, 4-, or 10-mg doses of epidural morphine on ventilatory responses to a standardized CO₂ challenge were studied in healthy volunteers. In the clinical part, ventilatory responses to CO₂ were evaluated in patients receiving 4 mg of epidural morphine for pain relief after gall bladder surgery. Naloxone infusion was given to five volunteers to determine whether ventilatory changes due to epidural morphine could be prevented. Using a nonrebreathing method, end-tidal Pco₂ (P_ETCO₂) and minute ventilation (tidal volume x frequency) were measured before and 1, 5, 8, 13, and 22 hr after epidural morphine injection. Ventilation was stimulated by 4% CO₂ in 21 % O₂ and 75% N₂. In the experimental study, a dose-related depression of ventilatory drive was seen after epidural morphine. After 2– and 4-mg doses, increases in P_ETCO₂ were present up to 5 hr after injection with a corresponding reduction in minute ventilation. Ten mg of epidural morphine was followed by a significant reduction in minute ventilation and an increase in P_ETco₂ that started 1 hr after injection, peaked at 5 hr, and then remained almost unchanged for the next 17 hr. P_ETco₂ was higher and remained elevated longer in surgical patients than in volunteers given the same amount of epidural morphine (4 mg). Naloxone infusion (5 µg·kg^–1·hr^–1), prevented the reduction of minute volume and decreased the elevation of P_ETco₂ due to epidural morphine. After larger doses (10 µg·kg^–1·hr^–1), minute volume and respiratory frequency were well above control levels, and P_ETco₂ was restored to near control values. Thus infusion of naloxone could prevent the respiratory changes after 4 mg of epidural morphine.

Key Words: ANALGESICS—morphine • ANESTHETIC TECHNIQUES, EPIDURAL

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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