Remifentanil used as adjuvant in general anesthesia for spinal fusion does not exhibit acute opioid tolerance

Abstract

BackgroundAlthough acute tolerance to opioids, especially to remifentanil, has been demonstrated consistently in animal studies, the results of clinical trials in humans are controversial. The aim of this study was to determine whether intraoperative infusions of remifentanil used as an adjuvant in general anesthesia result in acute tolerance, an event manifested by increased postoperative pain and a higher opioid requirement than usual.MethodsSixty patients who underwent surgery under general anesthesia for spinal fusion were randomly assigned to receive sevoflurane-nitrous oxide-oxygen (group SO, n = 20), sevoflurane-remifentanil-nitrous oxide-oxygen (group SR, n = 20), or propofol-remifentanil-oxygen (group PR, n = 20) in a double-blinded manner. All patients within 1 hour after induction received PCA (fentanyl 0.4 µg/kg/ml and ondansetron 16 mg) administered intravenously at a basal infusion rate of 1 ml/h, after being intravenously injected with a loading dose of fentanyl (1 µg/kg). Data for fentanyl requirement, verbal Numerical Rating Scale (NRS) pain score at rest, and presence of nausea or vomiting were collected at 1, 24, and 48 hours after surgery.ResultsWe did not find any significant difference in postoperative PCA fentanyl requirements, NRS or side effects among the groups.ConclusionsRemifentanil as an adjuvant to sevoflurane or propofol in general anesthesia for adults having surgery for spinal fusion does not appear to cause acute opioid tolerance or hyperalgesia in patients. However, further studies are needed to elucidate whether sevoflurane and propofol exert a clinically significant effect on opioid-induced tolerance or hyperalgesia and whether this effect is related to the age of the patient, the dose and duration of remifentanil given and the intensity of pain experienced postoperatively.

Intraoperative use of remifentanil and opioid induced hyperalgesia/acute opioid tolerance: systematic review

“…A prospective, randomized, double-blind study, showed that 3 h infusion of remifentanil of 0.3 μg/kg/min did not increase postoperative pain or opioid consumption in cardiac surgery patients who underwent sufentanil/propofol-based general anesthesia ( Lahtinen et al, 2008 ). Yeom et al (2012) suggested that remifentanil did not appear to cause AOT and OIH in patients undergoing spinal fusion even though there was significant differences in the mean intraoperative infusion rate of remifentanil (0.16 μg/kg/min vs. 0.03 μg/kg/min) for a short period of time (averaging 225 and 216 min, respectively). Schraag et al (1999) found that Remifentanil infusion using specially designed patient-maintained TCI systems, which was controlled according to the patients demand for postoperative pain control by up-and-down method (intervals 0.2 ng/ml) did not show any evidence of rapid development of acute tolerance in patients maintained hypnotic dose of remifentanil in the first six postoperative hours from end of total intravenous anesthesia with remifentanil and propofol.…”

“…There is controversial results on AOT and OIH induced by remifentanil at the perioperative period, even though many authors suggested that remifentanil could induce them ( Schraag et al, 1999 ; Cortinez et al, 2001 ; Hansen et al, 2005 ; Lahtinen et al, 2008 ; Angst et al, 2009 ; Yeom et al, 2012 ). Angst et al (2009) documented that 3 h infusion of remifentanil of up to 4.0 ng/ml was not associated with the development of significant tolerance to analgesic in placebo-controlled, double-blind study.…”

Analgesic impact of intra‐operative opioids vs. opioid‐free anaesthesia: a systematic review and meta‐analysis

“…All included trials administered volatile anaesthetics to maintain anaesthesia except five that administered propofol [27,30,31,36,39]. Regarding the types of surgery, authors included patients scheduled for gynaecological surgery in eight trials [25-27, 31, 33, 37, 44, 45]; patients undergoing abdominal surgery in six trials [28,35,36,38,41,42]; and finally, we combined the remaining nine trials together into an 'other surgery' group [29,30,32,34,39,40,43,46,47].…”

Intraoperative Use of Remifentanil for TIVA: Postoperative Pain, Acute Tolerance, and Opioid-Induced Hyperalgesia

“…[16][17][18][19]21,22,24 Differences in the cumulative intraoperative opioid dose could at least partially explain the divergent findings. Focusing on studies administering remifentanil indicates that aggravated postoperative pain and/or increased opioid consumption was consistently reported if patients received a cumulative dose greater than 50 µg/kg but could not reliably be detected if patients received a smaller cumulative dose (Fig 2).…”