Can nociception monitors be used to titrate remifentanil with a stable low noxious stimulation response index (NSRI)?

Keywords:

Nociception monitors, NOL index, NSRI, drug interactions, pharmacokinetics, pharmacodynamics


Published online: Mar 21 2023

https://doi.org/10.56126/

N.Van Heck1,2, R. Carette1, J. F.A. Hendrickx1,2,3, A. De Wolf4

1 Department of Anesthesiology, OLV Hospital, Aalst, Belgium
2 Department of Anesthesia, Ghent University Hospital, Gent, Belgium
3 Department of Basic and Applied Medical Sciences, Ghent University, Ghent, Belgium, Department of Anesthesiology, UZLeuven, Leuven, Belgium & Department of Cardiovascular Sciences, KU Leuven, Leuven, Belgium
4 Department of Anesthesiology, Feinberg School of Medicine, Northwestern University, Chicago, Illinois, USA

Abstract

Purpose: Opioids blunt autonomic nervous system (ANS) responses to noxious stimuli. Nociception monitors analyze the same ANS responses and thus might prove useful to guide opioid dosing. However, concomitantly administered hypnotics also blunt ANS responses and may thus jeopardize the usefulness of nociception monitors to guide intra-operative opioid dosing. We therefore studied the PK (prediction probability) of 3 nociception monitors (NOL index, qNOX and SPI) for the prevailing opioid concentration while maintaining the NSRI (noxious stimulus response index) at a low constant value with a range of opioids and inhaled agent combinations.

Methods: In 24 consenting ASA I-II patients undergoing robotic assisted radical prostatectomy, anesthesia was maintained with desflurane in O2/air and remifentanil (target controlled infusion). During the dissection phase, the remifentanil effect site concentration (Ce) in each patient was maintained at 1, 3, or 5 ng/mL for 20 min while the end-expired desflurane concentration (FET) was adjusted to keep the noxious stimulus response index (NSRI) at 5; the sequence in which each patient received each of the three remifentanil Ce was randomized. After stabilization, during each 20 min study period, the following data were collected: NSRI, NOL Index, SPI, qNOX, and FETdes. For each parameter, the prediction probability (PK) for Ce remifentanil was calculated.

Results: All patients remained hemodynamically stable. Surgery was finished before the last data collection period in 5 patients with a remifentanil Ce = 5 ng/mL, and in 1 patient with a remifentanil Ce = 1 ng/mL. All other data have been included in the data analysis. The prediction probability (PK) calculated for NOL Index, qNOX and SPI for Ce remifentanil was 0.519, 0.470, and 0.477, respectively.

Conclusion: Nociception monitoring becomes useless to titrate opioids when the concomitantly administered hypnotic is adjusted to maintain a low NSRI, presumably because suppression of movement to laryngoscopy also ensures suppression of the sympathetic nervous system response to the noxious stimulus present during intra-abdominal resection of the prostate. Both the hypnotic/opioid ratio and stimulus intensity of the stimulus/response pair need to be considered when attempting to use nociception to guide opioid administration.