Nociception level-guided opioid administration in radical retropubic prostatectomy: a randomised controlled trial.

BACKGROUND: This RCT investigated the effect of opioid titration by three different nociception monitoring devices or clinical signs during general anaesthesia. METHODS: Ninety-six patients undergoing radical retropubic prostatectomy with propofol/remifentanil anaesthesia were randomised into one of four groups to receive remifentanil guided by one of three nociception monitoring devices (surgical pleth index [SPI], pupillary pain index [PPI], or nociception level [NOL]) or by clinical judgement (control). Intraoperative remifentanil requirement was the primary endpoint, whereas recovery parameters and stress hormone levels were secondary endpoints. RESULTS: The mean [95% confidence interval {CI}] remifentanil administration rate differed between the groups: control 0.34 (0.32-0.37), SPI 0.46 (0.38-0.55), PPI 0.07 (0.06-0.08), and NOL 0.16 (0.12-0.21) µg kg-1 min-1(P<0.001). Intraoperative cessation of remifentanil administration occurred in different numbers (%) of patients: control 0 (0%), SPI 1 (4.3%), PPI 18 (75.0%), and NOL 11 (47.8%); P=0.002. The area under the curve analyses indicated differences in cumulative cortisol levels (mg L-1 min-1) amongst the groups: control 37.9 (33.3-43.1), SPI 38.6 (33.8-44.2), PPI 72.1 (63.1-82.3), and NOL 54.4 (47.6-62.1) (mean [95% CI]). Pairwise group comparison results were as follows: control vs SPI, P=0.830; control vs PPI, P<0.001; control vs NOL, P=0.001; SPI vs PPI, P<0.001; SPI vs NOL, P=0.002; and PPI vs NOL, P=0.009. CONCLUSIONS: The nociception monitoring devices and clinical signs reflect the extent of nociception differently, leading to dissimilar doses of remifentanil. Very low remifentanil doses were associated with an increase and higher remifentanil doses were accompanied by a decrease in serum cortisol concentrations. Use of nociception monitoring devices for guiding intra-operative opioid dosing needs further validation. CLINICAL TRIAL REGISTRATION: NCT03380949.

Guiding Opioid Administration by 3 Different Analgesia Nociception Monitoring Indices During General Anesthesia Alters Intraoperative Sufentanil Consumption and Stress Hormone Release: A Randomized Controlled Pilot Study.

BACKGROUND: This pilot study investigated the effect of sufentanil titration by 3 different analgesia monitoring devices or clinical signs during general anesthesia. METHODS: Forty-eight patients undergoing radical retropubic prostatectomy with sevoflurane/sufentanil anesthesia were randomly assigned into 4 groups and received sufentanil guided either by 1 of 3 analgesia monitoring devices (Surgical Pleth Index [SPI], Pupillary Pain Index [PPI], Nociception Level [NoL]) or by clinical judgment (control). The primary end point was intraoperative sufentanil consumption. Adrenocorticotropic hormone (ACTH) and cortisol were measured at 4 time points during the day of surgery. Data were analyzed by Kruskal-Wallis and Mann-Whitney U tests and by mixed model and area under the curve (AUC) analyses for group comparisons and time effects of stress hormones. RESULTS: The total amount of sufentanil administration (µg·kg·minute·10) differed between the groups (median [quartiles]: control = 5.6 [4.4-6.4], SPI = 7.2 [4.8-8.4], PPI = 2.0 [1.8-2.9], NoL = 3.8 [3.3-5.1]; PPI versus SPI, -5.1 [-6.6 to -1.3], P < .001; NoL versus SPI, -3.0 [-5.2 to 0.2], P = .024; control versus SPI, -1.6 [-3.7 to 1.7], P = .128; NoL versus PPI, 1.7 [0.6-3.4], P < .001; control versus PPI, 3.4 [2.0-4.6], P < .001; control versus NoL, 1.6 [-0.2 to 3.3], P = .017) (Hodges-Lehmann estimator [99% confidence interval {CI}], P values). The AUC analysis indicated differences among groups in cumulative ACTH levels (ng·liter·minute, natural logarithm (ln)-transformed data) of NoL versus PPI (-1.079 [-1.950 to -0.208], P = .001) and PPI versus SPI (1.192 [0.317-2.068], P= .001), as well as differences in cortisol levels (µg·liter·minute) for PPI versus SPI (46,710 [21,145-72,274], P < .001), NoL versus SPI (27,645 [3163-52,126], P = .003), and control versus SPI (31,824 [6974-56,675], P = .001) (differences in means [99% CI], P value). Secondary end points (postoperative recovery, pain level, and analgesia medication) showed no differences. CONCLUSIONS: The type of analgesia nociception monitoring affected the total amount of sufentanil administered. Lower sufentanil doses in the PPI group were associated with an increased endocrine stress response. Titration by SPI caused no opioid reduction compared to the control but was associated with a reduced endocrine stress response.