ABSTRACT
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
Subject(s)
Humans , Male , Female , Analgesics, Opioid , Nalbuphine , Drug Combinations , Treatment Outcome , Abdomen/surgeryABSTRACT
Background: major spinal fusion surgery causes severe postoperative pain, which persists for at least 3 days. Efficient and safe methods for postoperative analgesia after spinal fusion surgery are, therefore, mandatory. This study aimed to compare the analgesic effect of different epidural analgesia combinations and their effects on blood level of Beta-endorphin. We also studied the impact of these analgesic regimens on defined postoperative mobilization maneuvers and on patient satisfaction
Methods: This study was registered in clinical trials number NCT01838707. Sixty patients scheduled for elective posterior lumbar fusion surgery for correction of Spondylolisthesis were enrolled in this study. Patients were randomly allocated into three equal groups [20 each] according to analgesic drugs combinations administered through epidural catheter inserted intraoperatively. All patients received standard general anesthesia. Al the end of posterior instrumentation, the surgeon inserted the epidural catheter under direct vision in the midline. All patients in this study were nursed in a high dependency intensive care facility and received analgesics according to the following protocol. Continuous drug flow will be maintained with a syringe pump. The syringe pump was connected to the epidural catheter [with the reservoir contain either: 0.125% Bupivacaine HCI at flow rate of 4 5 ml/h [5-6.25mg/h bupivacaine]. 0.125% Bupivacaine HCI fentanyl 100 microg at flow rate of 3 5 ml/h [3.75-6.24 mg/h bupivacaine I 6-10 microg /h fentanyl] 0.125% Bupivacaine HCI morphine sulphate 3 mg at flow rate of 3 5 ml/h [3.75-6.24 mg/h bupivacaine 0.18-0.3 mg/h morphine]. Infusion was continued until the third postoperative day. The rate was increased if pain VAS >3 [visual analogue scale] at rest or VAS >6 with movement. The rate was decreased when patients have intolerable relevant motor block [Bromage score >0] or sensory disturbances [numbness], or hypotension [systolic blood pressure <90 mm Hg]. IV rescue analgesia will be Ketrolactromethamine 30 mg. Epidural catheters were removed on the third postoperative day. Pain was assessed using the VAS ranging from "0" [no pain] to "10" [worst imaginable pain]. Pain was evaluated at rest and during mobilization. Maneuvers of particular clinical importance for postoperative mobilization [alone and with help] were chosen: Turning in bed. Standing in front of the bed and walking, and using the toilet without help. The time needed until the patient can first successfully perform these maneuvers was documented. Three venous samples to measure serum B-endorphin level first one preoperative base line, second at first time VAS more three at rest and third sample when VAS less than three at rest. For assessment of patients satisfaction with postoperative pain management a verbal rating score was used. Motor block was quantified with the Bromage scale. Patients will be asked about sensory deficits. Verbal rating scores was used for sedation. Nausea and vomiting and the incidence of pruritus were recorded
Results: There were no significant differences observed between the studied groups regarding patient characteristics [age, sex, ASA status, anesthesia time, surgery duration and number of segments fused]. There were no significant differences in all hemodynamic variables between the three groups, the results of this study showed less pain scores as recorded by VAS all over the study time for group 3 [bupivacaine+ morphine]. Pain scores were lowest for group Ill [bupivacaine + morphine] all over the study time when testing pain during movement. The mean times to turn in bed with and without assistance were lowest in group Ill [bupivacaine morphine]. B-endorphin level, there was no significant differences between means of B-endorphin samples between the groups or within each group. Patients were more satisfied in group 3 all over the study period. The incidence of nausea, vomiting or itching within the observation period was significantly different between the three groups. It was more common in the bupivacaine morphine group
In Conclusion: Epidural analgesia after spine surgery improve pain control and enhance functional recovery, but potential cost issues related to maintenance of the epidural infusion and ICU slay versus potential cost savings in hospital stay and effect on long term outcome must be considered. Also the cost of use B-endorphin as a biomarker of pain severity needs to be revised against the subjective assessment of pain