Respiratory Depression after Epidural Morphine???An Experimental and Clinical Study

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 (PETCO2) and minute ventilation (tidal volume × 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 PETCO2 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 PETco2 that started 1 hr after injection, peaked at 5 hr, and then remained almost unchanged for the next 17 hr. PETco2 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 PETco2 due to epidural morphine. After larger doses (10 μg·kg−1·hr−1), minute volume and respiratory frequency were well above control levels, and PETco2 was restored to near control values. Thus infusion of naloxone could prevent the respiratory changes after 4 mg of epidural morphine.