Combination of opioid agonist and agonist-antagonist admixtures for postoperative pain relieve after upper abdominal surgery

Nalbuphine, a mixed agonist-antagonist opioid, has a potential to attenuate the mu-opoid effects and to enhance the kappa-opioid effects. However, when morphine and nalbuphine are mixed together, the clinical interactions in different combining ratios on analgesic effect and adverse events are unknown. This study was designed to evaluate the interaction of combining different ratios of morphine and nalbuphine in i. v boluses for postoperative pain relieve in upper abdominal surgery and their effects on pulmonary function. This study enrolled 75 patients aged between 18 and 65 yr with an ASA physical status I and II underwent upper abdominal surgery under general anesthesia Patients were allocated randomly into one of five groups: In group I, 10 mg morphine were added into normal saline to a total of 10 ml [concentration of [morphine] [nalbuphine] =1/0 mg/ ml; pure morphine]. In group II, 7.5 mg morphine and 2.5 mg nalbuphine morphine: nalbuphine=3:1]. In group III, 5 mg morphine and 5 mg nalbuphine ratio of morphine: nalbuphine=1: 1]. In group IV, 2.5 mg morphine and 7.5 mg nalbuphine were added morphine: nalbuphine=1:3,]. In group V 10 mg nalbuphine were added into normal saline to a total of 10 ml morphine: nalhuphine=0: 1 mg /ml; pure nalbuphine]. Patients received standard general anesthetic technique without premedication, Postoperative analgesia was commenced with a loading dose of 3 ml solution i. v. immediately after patient recovery. The boluses of the drug were given on the patient request 1 ml/bolus. Pain intensity was evaluated with a 0-10 VAS at rest [1 hour after loading dose then at 2, 4, 12 and 24 hours] and upon movement [during coughing or changing body position from supine to lateral on bed]. FVC, FEV1 and /FEVI /FVC were measured by spirometry [SPIRO 601] preoperatively, immediately postoperatively [1h after loading dose] and 24 h postoperatively [on discharge]. Arterial pH, PaCO2 and PaO2 were measured preoperatively, immediately postoperatively and 24 hours postoperatively [on discharge]. Nausea, vomiting and pruritus were recorded by incidence. Sedation was reported using the Ramsay sedation score. Treatment failures were considered to be: Insufficient analgesia was de fined as VAS >4 at rest during 4-24 h after operation. Adjunctive analgesic with i.v. meperidine 50 mg or ketorolac 30 mg was given for insufficient analgesia. Intolerable nausea and vomiting were defined as persistent nausea or vomiting episodes that required more than three administrations of antiemetic [metoelopromide]. Intolerable Pruritus was defined as persistent Pruritus that required more than three administrations of antipruritics [diphenhydramine] Twenty-four hour analgesic requirements were similar among the five studied groups. Verbal analogue scores far pain were statistically similar among the five groups. The incidences of pruritus, nausea, and vomiting were higher in Group I than in other groups. There were no significant differences between the five groups as regards the incidences and severity of sedation. Pulmonary function tests [FVC and FEVI] were decreased significantly from the preoperative base line value to the immediately postoperative value and values after 24 hours in the five groups, while FEVI/FVC ratios increased significantly in the two postoperative times intervals compared to the baseline value. There were no significant differences in between the five groups. The effects of adding morphine and nalbuphine in admixture on analgesia far upper abdominal surgery is additive. Combinations of morphine and nalbuphine decreased the incidence of pruritus, nausea and vomiting. This may provide a novel combination strategy of opioid agonist and agonist-antagonist for postoperative pain management