Epidural morphine has become accepted as an efficient means of postoperative pain management. However, the problem of delayed respiratory depression has restricted its use, and in most centres patients are monitored for 24 hours following the last dose of epidural morphine, in an intensive care setting. Naloxone has been found to reverse this respiratory depression ~ but there are reported problems with reversal of analgesia. 2 Many investigators now believe naloxone to have significant effects on cardiovascular function with or without prior narcotic analgesia administration. 3-s Nalbuphine has been shown to reverse intravenous opioid-indnced respiratory depression. 6'7 It might have a lesser tendency for reversal of analgesia since it is a partial agonist at the ma opioid receptor and an agonist at the Kappa opioid receptor. ~2There have been no previous published studies of nalbuphine's effect on the respiratory depression and analgesia produced by epidural morphine. The purpose of our study was therefore to determine if intravenously administered nalbuphine could reverse epidural morphineinduced respiratory depression, pruritus and to assess its effects on analgesia. MethodsAfter approval by our Human Research Ethics Committee, informed consent was obtained from 20 ASA physical status I patients scheduled for elective total abdominal hysterectomy. The study was prospective, randomized, double-blind and placebo controlled. Randomization was achieved using a random numbers table.Premedication was with diazepam 5 mg PO 1.5 hours preoperatively. Ventilatory ~esponse to CO2 was assessed using the rebreathing method described by Read) A Portex epidural catheter was introduced 3-4 cm into the epiduml space at spinal level L2-a or L3-4 via a 17 gauge Touhy needle, the bevel of which faced cephalad. A test dose of 3 ml carbonated lidocaine with 1:200,000 epinephrine was then administered. While awaiting the development of some sensory block to confirm successful CAN J ANAESTH 1988 / 35:6 / pp599-604
This double-blind randomised study compared the analgesic efficacy, respiratory effects, side effects, and pharmacokinetic disposition of 24 hr lumbar epidural and intravenous infusions of the same dosage regimen of fentanyl (1.5 #g" kg -t bolus then 1 l~g" kg -I" hr -~ infusion) in 50 patients
The efficacy of nalbuphine, an agonistlantagonist opioid, in preventing respiratory depression from epidural morphine analgesia after thoracotomy, was assessed in a randomized double-blind placebo controlled trial. After a standardized general anaesthetic and 0.15 rag. kg -t of epidural morphine, patients received a bolus and then a 24 h infusion of nalbuphine (2001zg.kg -j + 501.~g.kg-l.hr -l. lO01.Lg.kg -I + 25 I~g.kg -t . hr -j, or 50 t~g'kg -1 + 12.5 txg.kg-l'hr -I) Epidural opioids provide excellent postoperative analgesia 1 and facilitate the recovery of pulmonary function. 2 Side effects such as pruritus, nausea, vomiting and urinary retention, are common, 1 but the most serious problem is respiratory depression. While mild respiratory depression is common with any method of opioid administration, the occasional occurrence of delayed and unpredictable severe respiratory depression with the use of epidural opioids has been a major concern and has limited their use in many centres to areas where the patient can be closely monitored. 3,a While the incidence of severe respiratory depression is low, s CO2 retention and an abnormal respiratory pattern 6 are seen much more frequently. This is a problem especially in patients needing larger doses of opioid, or repeated administration of smaller doses, to produce good analgesia, e.g., after thoracotomy 6 or upper abdominal surgery. 7 Nalbuphine hydroehloride, an opioid agonist/antagonist, has a plateau effect on respiratory depression when given on its own. s It has been shown to reverse the respiratory depression from both intravenous 9 and epidural opioids.I~ This study was undertaken to determine whether a continuous intravenous infusion of nalbuphine would reduce the incidence and severity of respiratory depression in post-thoracotomy patients receiving epidural morphine analgesia. We were also interested to see if this combination could reduce the incidence of other sideeffects, and to assess its impact on analgesia. Finally, we attempted to determine the dosage and serum levels required for optimal outcome. MethodThis was a double-blind placebo-controlled trial of three doses of nalbuphine, given as a loading bolus followed by a 24-hour infusion. Patients between the ages of 21 and 70 CAN J ANAESTH 1989 / 36; 5 / pp503-509
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