Effect of Intraoperative High-Dose Remifentanil on Postoperative Pain: A Prospective, Double Blind, Randomized Clinical Trial

Abstract

BackgroundRemifentanil, an ultra-short-acting opioid, is widely used for pain control during surgery. However, regular dose (RD) remifentanil exacerbates postoperative pain in a dose-dependent manner. Recent studies suggest that high-dose (HD) remifentanil offers sustained analgesia in experimental studies. We thus hypothesized that intraoperative administration of high-dose remifentanil may attenuate postoperative pain.MethodsIn this prospective, randomized, double blind, controlled clinical study, sixty patients undergoing thyroidectomy (18–60 years-of-age) received an intraoperative infusion of 0.2 (RD group) or 1.2 μg kg−1min−1 (HD group) remifentanil during thyroidectomy. A visual analogue scale (VAS) was used to measure pain intensity. Mechanical pain threshold on the forearm was assessed using von Frey filaments before surgery (baseline), 2 h postoperatively and 18–24 h postoperatively. The primary outcome was to compare the difference of VAS score at different time points after operation and morphine consumption 24 h postoperatively between RD and HD groups. The second outcome was to compare the difference of mechanical pain thresholds in the forearm postoperatively between RD and the HD groups.ResultsVAS scores were lower 30 min postoperatively in the HD group (1.29±1.67, 95% CI 0.64–1.94) compared with the RD group (2.21±1.67, 95% CI 1.57–2.84) (t = 3.427, p = 0.0043, RD group vs. HD group). Postoperative morphine consumption was much lower in the HD group compared with the RD group (1.27±1.88 mg vs. 0.35±1.25 mg, p = 0.033). In both groups, mechanical pain threshold was decreased 18–24 h postoperatively (2.93±0.209 Ln(g) vs. 3.454±2.072 Ln(g), p = 0.032 in RD group; 2.910±0.196 Ln(g) vs. 3.621±0.198 Ln(g), p = 0.006 in HD group, 18–24 h postoperatively vs baseline).ConclusionsIntraoperative administration of high-dose remifentanil decreased VAS scores and morphine consumption postoperatively. Thus, modulation of intraoperative opiates may be a simple and effective method of postoperative pain management.Trial RegistrationThis trial is registered in ClinicalTrials.gov, with the Name: Effect of Higher Doses of Remifentanil on Postoperative Pain in Patients Undergoing Thyroidectomy, and ID number: NCT01761149.

Impact of intraoperative remifentanil on postoperative pain and opioid use in thyroid surgery

“…It has been demonstrated that intraoperative RI use may lead to acute opioid tolerance and a hyperalgesic state with increased postoperative pain and analgesic requirements. 6,8,9 We did observe that thyroidectomy patients who received RI intraoperatively also Abbreviations: CI, confidence interval; MMEs, morphine milligram equivalents. Intraoperative narcotics and maximum postoperative pain mean differences were adjusted for age, gender, BMI, ASA, surgical approach, amount of intraoperative acetaminophen, amount of anesthesiologist administered lidocaine, and OR (odds ratio) time.…”

Low‐ versus high‐dose intraoperative opioids: A systematic review with meta‐analyses and trial sequential analyses

“…35 All trials administered opioids before surgical incision. The administered dose ratio between lowand high-dose groups were respectively 1:15 in one trial, 27 between 1:8 and 1:6 in five trials, 29,34,37,41,52 between 1:5 and 1:2 in 18 trials 26,28,[31][32][33]35,36,[38][39][40]42,43,[46][47][48][49][50][51] and at a ratio of 1:1.5 in three trials. 30,44,45 Of note, one trial administered dose that are beyond what is commonly used in the clinical practice.…”

“…Over 60% (18 of 27) of the included trials used a volatile-based anaesthesia maintenance, [26][27][28][29][33][34][35][37][38][39][40][41][42]44,46,48,50 while the remaining trials administered propofol. [30][31][32]36,43,45,47,49,51,52 Regarding the types of surgery, authors included patients scheduled for gynaecological surgery in seven trials, [27][28][29][30]35,42,44 for abdominal surgery in nine trials, 33,34,[37][38][39]41,43,49,50 for cardiac surgery in four trials, 31,32,45,51 and finally, we combined the remaining seven trials together into an "other surgeries" group. 26,…”

“…[30][31][32]36,43,45,47,49,51,52 Regarding the types of surgery, authors included patients scheduled for gynaecological surgery in seven trials, [27][28][29][30]35,42,44 for abdominal surgery in nine trials, 33,34,[37][38][39]41,43,49,50 for cardiac surgery in four trials, 31,32,45,51 and finally, we combined the remaining seven trials together into an "other surgeries" group. 26,36,40,[46][47][48]52 Five trials included nonsteroidal anti-inflammatory drugs in the post-operative analgesic regimen, 36,[40][41][42]44 and two trials included acetaminophen. 45,48 Pain scores at rest at 24 post-operative hours were significantly Figure 3).…”

“…presents the trial characteristics. Twenty-two trials investigated remifentanil as an intraoperative opioid regimen,26,[28][29][30][32][33][34][36][37][38][39][40][41][42][43][45][46][47][48][49][50]52 two explored fentanyl, 27,51 two sufentanil…”