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

BACKGROUND: Remifentanil, 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. METHODS: In 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(−1)min(−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. RESULTS: VAS 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). CONCLUSIONS: Intraoperative 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 REGISTRATION: This 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.