Effects of intravenous patient-controlled analgesia with buprenorphine and morphine alone and in combination during the first 12 postoperative hours: A randomized, double-blind, four-arm trial in adults undergoing abdominal surgery

Background: Intense pain in the first 12 hours after major abdominal surgery requires the use of large amounts of analgesics, mainly opioids, which may produce undesirable effects. Buprenorphine (BUP) is not typically used intravenously in this setting, particularly in combination with morphine (MO), due to concerns that BUP might inhibit the analgesic effect of MO. Objective: This study compared the analgesic effect of BUP and MO separately and in combination for postoperative pain control in patients undergoing abdominal surgery. Methods: In this double-blind study, adult patients were randomized to receive 1 of 4 regimens for 12 hours: a basal BUP infusion (BUP-i) of 0.4 μg/kg/h + BUP boluses (BUP-b) of 0.15 μg/kg each; a basal MO infusion (MO-i) of 10 μg/kg/h + MO boluses (MO-b) of 5 μg/kg each; a basal BUP-i of 0.4 μg/kg/h + MO-b of 5 μg/kg each; or a basal MO-i of 10 μg/kg/h + BUP-b of 0.15 μg/kg each. Bolus doses were delivered by intravenous patient-controlled anesthesia, with a bolus lockout time of 7 minutes. Diclofenac 75 mg IM q6h was available as rescue pain medication. Every 15 minutes during the first 2 postoperative hours and hourly thereafter, patients used visual analog scales to rate their pain (from 0 = totally free of pain to 10 = unbearable pain), level of sedation (from 1 = totally awake to 10 = heavily sedated), and satisfaction with treatment (from 1 = totally unsatisfied to 10 = fully satisfied). Blood pressure, heart rate, respiration rate, and arterial blood oxygen saturation (SpO₂) were monitored, and adverse effects reported by patients or noted by clinicians were recorded at the same times. Study end points included total opioid consumption (infusion + boluses), demand:delivery ratio, and use of rescue medication. Results: One hundred twenty patients (63 men, 57 women; age range, 21-80 years; weight range, 40-120 kg) were included in the study. Seventy-four percent had other mild, treated diseases (American Society of Anesthesiologists physical class 2). Pain visual analog scale ratings were comparably high in all groups during the first 2 postoperative hours. Pain intensity ratings at 3 to 12 hours were significantly lower in those who received BUP-i + BUP-b compared with the other treatment groups (P = 0.018). The drug requirement during the postoperative period decreased significantly in all groups (P = 0.01); however, there was a significant difference between groups in the demand:delivery ratio at 3 to 12 hours (group * psydrug interaction, P = 0.026). The numerically lowest demand:delivery ratio was seen with BUP-i + BUP-b. BUP-i was associated with a significantly lower heart rate compared with the other groups (P = 0.027); there were no drug-related differences in respiration rate, SpO₂, or sedation. Patients' level of satisfaction with treatment was significantly higher in the group that received BUP-i + BUP-b compared with the other 3 groups (P < 0.001). Postoperative nausea and vomiting were mild and occurred at a similar incidence in all groups, as did rescue diclofenac use. Conclusions: In these patients undergoing abdominal surgery, the BUP-i + BUP-b regimen controlled postoperative pain as well as did MO-i + MO-b or the combinations of BUP and MO. BUP neither inhibited the analgesia provided by MO nor induced undesired sedation or hemodynamic or respiratory effects.