Nociception Level Index–Guided Intraoperative Analgesia for Improved Postoperative Recovery: A Randomized Trial

Abstract

BACKGROUND: Nociception is the physiological response to nociceptive stimuli, normally experienced as pain. During general anesthesia, patients experience and respond to nociceptive stimuli by increasing blood pressure and heart rate if not controlled by preemptive analgesia. The PMD-200 system from Medasense (Ramat Gan, Israel) evaluates the balance between nociceptive stimuli and analgesia during general anesthesia and generates the nociception level (NOL) index from a single finger probe. NOL is a unitless index ranging from 0 to 100, with values exceeding 25 indicating that nociception exceeds analgesia. We aimed to demonstrate that titrating intraoperative opioid administration to keep NOL <25 optimizes intraoperative opioid dosing. Specifically, we tested the hypothesis that pain scores during the initial 60 minutes of recovery are lower in patients managed with NOL-guided fentanyl than in patients given fentanyl per clinical routine. METHODS: We conducted a randomized, single-center trial of patients having major abdominal open and laparoscopic surgeries. Patients were randomly assigned 1:1 to intraoperative NOLguided fentanyl administration or fentanyl given per clinical routine. The primary outcome was pain score (0-10 verbal response scale) at 10-minute intervals during the initial 60 minutes of recovery. Our secondary outcome was a measure of adequate analgesia, defined as a pain score <5, assessed separately at each interval. RESULTS: With a planned maximum sample size of 144, the study was stopped for futility after enrolling 72 patients from November 2020 to October 2021. Thirty-five patients were assigned to NOL-guided analgesic dosing and 37 to routine care. Patients in the NOL group spent significantly less time with a NOL index >25 (median reduction [95% confidence interval {CI}] of 14 [4-25] minutes) were given nearly twice as much intraoperative fentanyl (median [quartiles] 500 [330, 780] vs 300 [200, 330] µg), and required about half as much morphine in the recovery period (3.3 [0, 8] vs 7.7 [0, 13] mg). However, in the primary outcome analysis, NOL did not reduce pain scores in the first 60 minutes after awakening, assessed in a linear mixed effects model with mean (standard error [SE]) of 4.12 (0.59) for NOL and 4.04 (0.58) for routine care, and estimated difference in means of 0.08 (−1.43, 1.58), P = .895. CONCLUSIONS: More intraoperative fentanyl was given in NOL-guided patients, but NOL guidance did not reduce initial postoperative pain scores. (Anesth Analg 2023;136:761-71) KEY POINTS• Question: Does guiding intraoperative opioid administration to nociception level (NOL, PMD-200 system from Medasense) improve initial pain recovery characteristics in the postanesthesia care unit (PACU)? • Findings: In this randomized trial with 72 patients, patients in the NOL group were given nearly twice as much intraoperative fentanyl and required about half as much morphine during the initial 60 minutes of recovery, but pain scores did not differ between groups. • Meaning: Under the circumstanc...

Effect of nociception level index‐guided intra‐operative analgesia on early postoperative pain and opioid consumption: a systematic review and meta‐analysis

“…However, it should be noted that the standard care varied between the included studies. Analgesia in the standard care group was titrated according to changes in blood pressure [26,32,34], heart rate and blood pressure [25,29,35] or clinical signs and judgement [27,28,31,33].…”

Generalizability of nociception level as a measure of intraoperative nociceptive stimulation: A retrospective analysis

“…Previous studies have shown that NOL reliably distinguishes non‐nociceptive and nociceptive events 7,10,20,21 . Sensitivity and specificity are both high with a cutoff of 25 which is what we used in this analysis 22 .…”

“…Previous studies have shown that NOL reliably distinguishes nonnociceptive and nociceptive events. 7,10,20,21 Sensitivity and specificity are both high with a cutoff of 25 which is what we used in this analysis. 22 Our summary results from eight prospective studies are consistent, showing that NOL was nearly always <25 without noxious stimulation or when stimulation was blunted by opioids.…”

Nociception level index-guided antinociception versus routine care during remifentanil-propofol anaesthesia for moderate-to-high risk cardiovascular surgery

“…For example, NOL-guided fentanyl during abdominal surgery decreased opioid administration and was associated with improved postoperative comfort in one centre 2 . However, in another study, fentanyl administration was higher in the NOL-group and no difference in postoperative pain scores occurred 7 . In other words, differences in opioid concentrations and potentially in haemodynamic variables depends critically on the centre's routine care.…”

“…2 However, in another study, fentanyl administration was higher in the NOL-group and no difference in postoperative pain scores occurred. 7 In other words, differences in opioid concentrations and potentially in haemodynamic variables depends critically on the centre's routine care. If our centre had been more permissive about opioid use and more tolerant of hypotension during routine care, differences between the groups may have emerged -although we note that our trial was not powered to detect haemodynamic differences.…”