Effect of intraoperative high-dose remifentanil on postoperative pain: a prospective, double blind, randomized clinical trial

Abstract

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.

Conflict of interest statement

Competing Interests: The authors have declared that no competing interests exist.

Figures

Figure 1. Trial profile.

Figure 2. VAS scored at different times postoperatively.

Note the VAS score at 30(ppost hoc test). **, p<0.01, RD group vs HD group.

Figure 3. Time course of mechanical pain threshold in the forearm after surgery.

Note the significantly decreased mechanical pain threshold at 2–24 h postoperatively compared to baseline in RD group (ppost hoc test). In HD group, the mechanical pain threshold is also significantly decreased at 18–24 h postoperatively when compared with baseline (p<0.01, Two-way ANOVA analysis followed by Bonferroni’s post hoc test). *p<0.05, post-2 h or 18–24 h postoperatively vs baseline.