Gradual withdrawal of remifentanil delays initial post-operative analgesic demand after thyroid surgery; double-blinded, randomized controlled trial

Abstract

Background: Mismanagement of remifentanil leads to severe side effects such as opioid-induced tolerance and hyperalgesia. Recently studies revealed an alternative withdrawal method to limit these side effects. A gradual withdrawal of remifentanil seems to be associated with less pain. The hypothesis of this double-blinded, randomized controlled trial was that a gradual withdrawal of remifentanil would be associated with less immediate post-operative pain compared to after an abrupt discontinuation of remifentanil in patients who underwent thyroid surgery.

Methods: This double-blinded, randomized controlled trial was conducted in a tertiary level hospital in Brussels (Belgium) from April until August 2017. 34 patients undergoing thyroid surgery were randomized and 29 patients completed the study. After randomization, patients undergoing thyroid surgery were allocated to two groups: one with an abrupt discontinuation of remifentanil after surgery and one with a gradual withdrawal of remifentanil after surgery. The primary outcome was the initial post-operative demand of analgesic medication.

Results: Gradual withdrawal of remifentanil was associated with a delayed initial post-operative demand of analgesic medication (P = 0.006). The first morphine bolus was given after 76.3 +/- 89.0 min in the group with a gradual withdrawal of remifentanil versus after 9.0 +/- 13.5 min in the group with an abrupt discontinuation of remifentanil. However, overall morphine consumption, numeric rating scale scores, Ramsay Sedation Scale scores, and quality of recovery scores (QoR-40) were similar in both groups (P > 0.05).

Conclusion: Though overall morphine consumption, numeric rating scale scores, Ramsay Sedation Scale scores, and quality of recovery scores (QoR-40) are not altered, a gradual withdrawal of remifentanil after thyroid surgery is safe and associated with a delayed initial post-operative demand of analgesic drugs. The withdrawal process does, however, require vigilance and training.

Trial registration: Clinicaltrials.gov NCT03110653 (PI: Luc Barvais; date of registration: 03/31/2017).

Conflict of interest statement

Ethics approval and consent to participate

This study was approved by the internal review board (03/30/2017; P2017/074; Comité Ethique, Erasme hospital, Brussels; Chairman: Jean-Marie Boeymans). The trial was registered on clinicaltrials.gov (NCT03110653; PI: Luc Barvais; date of registration: 03/31/2017).

Written informed consent was obtained from each patient participating in the study.

Consent for publication

Written informed consent was obtained from each patient participating in the study.

Competing interests

The authors declare that they have no competing interests.

As of October 2017, SS is a recipient of a research fellowship of the Belgian American Education Foundation.

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Figures

Fig. 1

Flow diagram

Fig. 2

a Illustrates the Numeric Rating Scale (NRS) values in both groups during their stay in the PACU while at rest. Pain evaluation was done upon arrival to the PACU and every 15 min during the first 2 h post-operatively, as well as after 4 h. Patients evaluating their pain as > 3/10 on the NRS received a morphine bolus (2 mg every 5 min as needed). Values are Means ± SD. 2 way-ANOVA for repeated measures. P value for difference between both groups: 0.358; P value for difference between times: < 0.001; P value for interaction: < 0.001. b Illustrates the Numeric Rating Scale (NRS) values in both groups during their stay in the PACU during a light head flexion. Upon arrival and every 15 min during the first 2 h post-operatively, as well as after 4 h, patients were asked to do a light head flexion. During this moment, NRS values were recorded. Values are Means ± SD. 2 way-ANOVA for repeated measures. P value for difference between both groups: 0.418; P value for difference between times: < 0.001; P value for interaction: < 0.001