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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

Funcke, Sandra MD*; Pinnschmidt, Hans O. PhD; Wesseler, Stefan*; Brinkmann, Charlotte*; Beyer, Burkhard MD; Jazbutyte, Virginija PhD§; Behem, Christoph R. MD*; Trepte, Constantin MD*; Nitzschke, Rainer MD*

doi: 10.1213/ANE.0000000000004388
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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−1·minute−1·10−3) 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·liter1·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·liter1·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.

From the *Department of Anesthesiology, Center of Anesthesiology and Intensive Care Medicine, University Medical Center Hamburg-Eppendorf, Hamburg, Germany

Institute of Medical Biometry and Epidemiology, University Medical Center Hamburg-Eppendorf, Hamburg, Germany

Martini-Klinik, Prostate Cancer Centre, University Medical Center Hamburg-Eppendorf, Hamburg, Germany

§Institute of Clinical Chemistry and Laboratory Medicine, University Medical Center Hamburg-Eppendorf, Hamburg, Germany.

Accepted for publication July 17, 2019.

Funding: Institutional and/or departmental. The Nociception Level monitoring device was loaned by the company because it was not available in the department.

The authors declare no conflicts of interest.

Supplemental digital content is available for this article. Direct URL citations appear in the printed text and are provided in the HTML and PDF versions of this article on the journal’s website (www.anesthesia-analgesia.org).

Clinical Trial Number and URL: Registration with ClinicalTrials.gov (Ref. NCT03303651): https://clinicaltrials.gov/ct2/show/NCT03303651; for access to the full trial protocol, contact the first author.

Reprints will not be available from the authors.

Address correspondence to Sandra Funcke, MD, Department of Anesthesiology, Center of Anesthesiology and Intensive Care Medicine, University Medical Center Hamburg-Eppendorf, Martinistrasse 52, 20246 Hamburg, Germany. Address e-mail to s.funcke@uke.de.

© 2019 International Anesthesia Research Society
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