Prevention of epidural morphine-induced respiratory depression with intravenous nalbuphine infusion in post-thoracotomy patients

Abstract

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

A Comparision of Nalbuphine with Morphine for Analgesic Effects and Safety : Meta-Analysis of Randomized Controlled Trials

“…If the study by Etches et al 20 was included into evaluation of analgesic effects, the incidence of pain relief in pooled analyses was still no significant difference (RRs,1.00; 95% [CI], 0.89 to 1.12; P = 0.95; I 2 = 51%). The study by Baxter et al 25 compared the analgesic efficacy and side-effects of epidural nalbuphine with epidural morphine in a randomised double-blind study in post-thoracotomy patients, revealing the pain scores were lowest in the morphine group ( P < 0.01), which indicated an advantage in analgesic efficacy for morphine. Figure 1 shows the outcome of analgesic effects comparing nalbuphine with morphine, then we can find that the study by Minai et al 9 presented a positive result, which was one of factors causing heterogeneity.…”

Treatment of intrathecal morphine-induced pruritus following Caesarean section

“…Reversal of epidural morphine analgesia by nalbuphine has not been described in either obstetric or non-obstetric patients treated with epidural morphine and our findings are consistent with this. 6 ' 14 ' 15 There is a case report describing improved analgesia and reversal of side effects by nalbuphine in a patient who had received epidural morphine after cesarean section. 16 Although opioids may liberate histamine from mast cells, this does not appear to be the mechanism underlying pruritus after intrathecal opioids.…”

A dose-response study of nalbuphine for post-thoracotomy epidural analgesia

“…The incidence of PaCO2 elevation with morphine was similar to that observed previously in post-thoracotomy patients. 18 Despite administration of naloxone, the mean PaCO2 in the morphine group was higher for the first two four-hour periods than in the nalbuphine-treated patients, even though the latter received more supplemenlary fentanyl. The lower PaCO2 in the nalbuphine patients may have been the result of poorer analgesia, or of nalbuphine reversal of respiralory depression caused by the additional iv fentany128 administered in the nalbuphine groups.…”