Reduced postoperative pain using Nociception Level-guided fentanyl dosing during sevoflurane anaesthesia: a randomised controlled trial

Fleur Meijer, Maarten Honing, Tessa Roor, Samantha Toet, Paul Calis, Erik Olofsen, Chris Martini, Monique van Velzen, Leon Aarts, Marieke Niesters, Martijn Boon, Albert Dahan, Fleur Meijer, Maarten Honing, Tessa Roor, Samantha Toet, Paul Calis, Erik Olofsen, Chris Martini, Monique van Velzen, Leon Aarts, Marieke Niesters, Martijn Boon, Albert Dahan

Abstract

Background: The majority of postoperative patients report moderate to severe pain, possibly related to opioid underdosing or overdosing during surgery. Objective guidance of opioid dosing using the Nociception Level (NOL) index, a multiparameter artificial intelligence-driven index designed to monitor nociception during surgery, may lead to a more appropriate analgesic regimen, with effects beyond surgery. We tested whether NOL-guided opioid dosing during general anaesthesia results in less postoperative pain.

Methods: In this two-centre RCT, 50 patients undergoing abdominal surgery under fentanyl/sevoflurane anaesthesia were randomised to NOL-guided fentanyl dosing or standard care in which fentanyl dosing was based on haemodynamics. The primary endpoint of the study was postoperative pain assessed in the PACU.

Results: Median postoperative pain scores were 3.2 (inter-quartile range 1.3-4.3) and 4.8 (3.0-5.3) in NOL-guided and standard care groups, respectively (P=0.006). Postoperative morphine consumption (standard deviation) was 0.06 (0.07) mg kg-1 (NOL-guided group) and 0.09 (0.09) mg kg-1 (control group; P=0.204). During surgery, fentanyl dosing was not different between groups (NOL-guided group: 6.4 [4.2] μg kg-1vs standard care: 6.0 [2.2] μg kg-1, P=0.749), although the variation between patients was greater in the NOL-guided group (% coefficient of variation 66% in the NOL-guided group vs 37% in the standard care group).

Conclusions: Despite absence of differences in fentanyl and morphine consumption during and after surgery, a 1.6-point improvement in postoperative pain scores was observed in the NOL-guided group. We attribute this to NOL-driven rather than BP- and HR-driven fentanyl dosing during anaesthesia.

Clinical trial registration: www.trialregister.nl under identifier NL7845.

Keywords: nociception; nociception level-guided anaesthesia; opioid; postoperative pain; stress hormones.

Copyright © 2020 The Author(s). Published by Elsevier Ltd.. All rights reserved.

Figures

Fig. 1
Fig. 1
(a) Box plot of the pain scores at each of the measurement points in the PACU. Red boxes: standard clinical care; blue boxes Nociception Level (NOL)-guided analgesia. (b) Box plots of the median pain scores observed per subject in the PACU. Each symbol reflects the individual median pain scores during the subject stay in the PACU.
Fig. 2
Fig. 2
Fire plots of the Nociception Level (NOL) index values during anaesthesia in NOL-guided analgesia (a) and during standard care (b) patients. To guide the eye, one horizontal line is added to the graph representing a NOL index value of 25. The colours reflect the percentage of subjects at any 5-s time point and range from 0% (dark blue) to 30% (dark red).
Fig. 3
Fig. 3
Cumulative fentanyl dosing in Nociception Level (NOL)-guided patients (red symbols) and patients receiving standard clinical care (blue symbols). Data are 1-min averages (95% confidence intervals).
Fig. 4
Fig. 4
Adrenocorticotropic hormone (ACTH) (a) and cortisol (b) concentrations from induction on until discharge from the PACU in subjects receiving standard clinical care (red symbols) and subjects receiving fentanyl dosing based on the Nociception Level index (blue symbols). Measurements were (1) 10–30 min before induction, (2) 1–2 min after intubation, (3) 1–2 min after incision, (4) at skin closure, (5) 15 min into the PACU, and (6) at discharge from the PACU. Data are mean values relative to baseline (1) (95% confidence interval).
Figs1
Figs1

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