Low-dose buprenorphine infusion to prevent postoperative hyperalgesia in patients undergoing major lung surgery and remifentanil infusion: a double-blind, randomized, active-controlled trial

摘要

Background. Postoperative secondary hyperalgesia arises from central sensitization due to pain pathways facilitation and/udor acute opioid exposure. The latter is also known as opioid-induced hyperalgesia (OIH). Remifentanil, a potent l-opioid agonist,udreportedly induces postoperative hyperalgesia and increases postoperative pain scores and opioid consumption. Theudpathophysiology underlying secondary hyperalgesia involves N-methyl-D-aspartate (NMDA)-mediated pain pathways. Inudthis study, we investigated whether perioperatively infusing low-dose buprenorphine, an opioid with anti-NMDA activity, inudpatients receiving remifentanil infusion prevents postoperative secondary hyperalgesia.udMethods. Sixty-four patients, undergoing remifentanil infusion during general anaesthesia andmajor lung surgery, were randomlyudassigned to receive either buprenorphine i.v. infusion (25lg h1 for 24h) ormorphine (equianalgesic dose) perioperatively. Theudpresence and extent of punctuate hyperalgesia were assessed one day postoperatively. Secondary outcome variables included postoperativeudpain scores, opioid consumption and postoperative neuropathic pain assessed one and threemonths postoperatively.udResults. A distinct area of hyperalgesia or allodynia around the surgical incision was found in more patients in the controludgroup than in the treated group. Mean time from extubation to first morphine rescue dose was twice as long in theudbuprenorphine-treated group than in the morphine-treated group: 18 vs 9min (P¼0.002). At 30min postoperatively, patientsudreceiving morphine had a higher hazard ratio for the first analgesic rescue dose than those treated with buprenorphineud(P¼0.009). At three months, no differences between groups were noted.udConclusions. Low-dose buprenorphine infusion prevents the development of secondary hyperalgesia around the surgicaludincision but shows no long-term efficacy at three months follow-up.