Time course of changes in breathing pattern in morphine‐ and oxycodone‐induced respiratory depression

Abstract

SummaryThe time course of changes in breathing pattern in opioid-induced respiratory depression was characterised for two opioids. Intravenous morphine (0.039 mg.kg À1 bolus 0.215 mg.kg À1 .h À1 infusion) and oxycodone (0.05 mg.kg À1 bolus 0.275 mg.kg À1 .h À1 infusion) were administered to six healthy male volunteers for 2 h in a random, double-blind and cross-over fashion. Monitoring included pulse oximetry and noninvasive respiratory-inductive plethysmography for the measurement of breathing pattern. The total amounts of drugs given were 35.1 (0.0) mg [mean (SD)] morphine and 41.3 (8.0) mg oxycodone. Four of the six oxycodone infusions had to be stopped at 99 (14) min because of respiratory depression as judged by pulse oximetry. No morphine infusions were stopped. The ®rst changes in breathing pattern were a decrease in respiratory rate and an increase in the contribution of the rib cage to tidal volume, while the compensatory increase in tidal volume became evident later. A decrease in minute ventilation and inspiratory duty cycle were also found. Opioids are known to decrease both hypoxic and hypercapnic respiratory drive [1]. However, little is known about opioid-induced changes in breathing pattern. The aim of this study was to describe the time, dose and concentration dependence of changes in breathing pattern for two m-agonist opioids, morphine and oxycodone and, if possible, to ®nd an ideal parameter for detecting early respiratory depression. MethodsSix healthy male volunteers, aged 21±30 years and weighing 68±80 kg, participated in this double-blind, randomized cross-over study. The subjects were non-smokers and had no medication or history of drug or alcohol abuse. The study protocol was approved by the Institutional Ethics Committee of Turku University Hospital and written informed consent was obtained from all participants. The subjects participated in two study sessions at least 10 days apart. After fasting for at least 12 h (only a glass of juice was allowed), the volunteers were admitted to the laboratory. The radial artery and an antecubital vein were cannulated. In the second session, the radial artery of the contralateral hand was used. After attaching the sensor bands of the respiratory-inductive plethysmograph, breathing and haemodynamics were allowed to settle over 20 min in the supine position before baseline measurements were taken.The drugs were diluted with saline to 50 ml by an independent anaesthetist. An intravenous bolus dose of oxycodone (Oxanest 10 mg.ml À1 , Leiras, Finland) 0.05 mg.kg À1 or morphine (Morphin 20 mg.ml À1 , Leiras, Finland) 0.039 mg.kg À1 was given in 1 min followed by an infusion of 0.275 mg.kg À1 .h À1 or 0.215 mg.kg À1 .h À1 , respectively lasting 115 min. If arterial oxygenation was seriously impaired, determined by an oxygen saturation under 90% over 30 s, the infusion was stopped. After stopping the infusion, the measurements were continued for 60 min, after which naloxone 0.8 mg was given.

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