Influence of naloxone infusion an analgesia and respiratory depression following epidural morphine

The influence of two different concentrations of iv naloxone infusion on the analgesia and adverse effects of epidural morphine were compared in a double-blind, placebo-controlled study. Forty-five patients undergoing gallbladder surgery were provided postoperative analgesia by 4 mg epidural morphine; they then received an iv infusion over a 12-h period consisting of either 5 micrograms X kg-1 X h-1 naloxone, 10 micrograms X kg-1 X h-1 naloxone, or saline. Pain relief was assessed by hourly visual analog scoring (VAS) and by direct questioning of the patient. Requirement of additional analgesia was noted. Respiratory frequency was monitored every 15 min and arterial blood gases were analyzed every 2 h for 24 h. Peak expiratory flow (PEF) was recorded 6 and 24 h postoperatively. Steady-state kinetics of naloxone were determined by a modified radioimmunoassay (RIA) method. All patients had good to excellent postoperative pain relief. Naloxone, 5 micrograms X kg-1 X h-1, did not appear to have any effect on epidural morphine analgesia. However, naloxone infusion at the rate of 10 micrograms X kg-1 X h-1 reduced the duration of analgesia by about 25%, and more frequent injections of epidural morphine were required to give effective analgesia. Complete reversal of analgesia was not seen in any patient. A dose-related stimulatory effect on respiratory frequency was noted in the groups receiving naloxone. PaCO2 values also were better in these groups as compared to values in the placebo group.