"Impact of Nociception Level (NOL) index intraoperative guidance of fentanyl administration on opioid consumption, postoperative pain scores and recovery in patients undergoing gynecological laparoscopic surgery. A randomized controlled trial"

J Clin Anesth. 2021 Dec;75:110497. doi: 10.1016/j.jclinane.2021.110497. Epub 2021 Sep 28.


Study objective: The Nociception Level (NOL) index uses a multiparametric approach to measure the balance between sympathetic and parasympathetic systems activity. Recently, a strong correlation between the NOL index response to nociceptive stimuli and the level of opioid analgesia during surgery was reported. Others observed that intraoperative doses of remifentanil and sufentanil were reduced when the NOL index was used. So far, no study has evaluated the impact of NOL-guided fentanyl antinociception in laparoscopic gynecological surgery. The primary hypothesis of this present study was to evaluate whether intraoperative NOL-guided fentanyl administration would reduce intra-operative opioid consumption. Secondary hypotheses were to assess whether this would lead to lower postoperative opioid consumption and pain scores, as well as improved postoperative outcomes.

Setting: University hospital, operating room.

Patients: 70 adult patients, ASA 1-3, scheduled for total laparoscopic hysterectomy.

Interventions: Patients were randomized into 2 groups: SOC (standardization of care) and NOL (using the NOL index to guide the administration of fentanyl). The depth of anesthesia was monitored with BIS™. Intraoperative fentanyl boluses were administered based on heart rate and mean arterial pressure variations in the SOC group, and NOL index for the NOL group.

Measurements: Fentanyl total intraoperative dose administered was collected and also averaged per hour. Pain scores and hydromorphone consumption were assessed in the post-anesthesia care unit and up to 24 h.

Main results: Sixty-six patients completed the study, 33 in each group. Total intraoperative fentanyl administration was not different between the two groups (217 (70) in the NOL group vs 280 (210) in the SOC group (P = 0.11)). Nevertheless, intraoperative fentanyl administration per hour was reduced by 25% in the NOL-guided group compared to the SOC group: 81 (24) vs 108 (66) μg.h-1, respectively (P = 0.03). Hydromorphone consumption and pain scores in the post-anesthesia care unit and at 24 h were not significantly different between the two groups.

Conclusion: NOL-guided analgesia allowed for a 22% reduction of the total amount of intraoperative fentanyl which was not significant. Nevertheless, results reported a significant reduction by 25% in the doses of fentanyl averaged per hour of surgery and administered in the NOL-guided group compared with the standardized practice in laparoscopic gynecological surgery. The pain measured postoperatively was similar in the two groups while the average postoperative consumption of opioids to achieve the same level of pain scores in post-anesthesia care unit and at 24 h was not significantly reduced. Further larger multicenter studies centered towards postoperative outcomes are needed.

Keywords: Fentanyl; Intraoperative; NOL index; Opioid consumption; Pain.

Publication types

  • Randomized Controlled Trial

MeSH terms

  • Adult
  • Analgesics, Opioid*
  • Female
  • Fentanyl
  • Humans
  • Hysterectomy / adverse effects
  • Laparoscopy*
  • Nociception
  • Pain, Postoperative / drug therapy
  • Pain, Postoperative / prevention & control


  • Analgesics, Opioid
  • Fentanyl