Perioperative use of physostigmine to reduce opioid consumption and peri-incisional hyperalgesia: a randomised controlled trial.

Christoph Klivinyi, Gudrun Rumpold-Seitlinger, Christian Dorn, Larissa Sampl, Nikki Sivro, Kordula Lang-Illievich, Sabine Fleck, Sylvia Farzi, Helmar Bornemann-Cimenti

British journal of anaesthesia 2021 Mar

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Several studies have shown that cholinergic mechanisms play a pivotal role in the anti-nociceptive system by acting synergistically with morphine and reducing postoperative opioid consumption. In addition, the anti-cholinesterase drug physostigmine that increases synaptic acetylcholine concentrations has anti-inflammatory effects. In this randomised placebo-controlled trial including 110 patients undergoing nephrectomy, we evaluated the effects of intraoperative physostigmine 0.5 mg h-1 i.v. for 24 h on opioid consumption, hyperalgesia, pain scores, and satisfaction with pain control. Physostigmine infusion did not affect opioid consumption compared with placebo. However, the mechanical pain threshold was significantly higher (2.3 [sd 0.3]) vs 2.2 [0.4]; P=0.0491), and the distance from the suture line of hyperalgesia (5.9 [3.3] vs 8.5 [4.6]; P=0.006), wind-up ratios (2.2 [1.5] vs 3.1 [1.5]; P=0.0389), and minimum and maximum postoperative pain scores at 24 h (minimum 1.8 [1.0] vs 2.4 [1.2]; P=0.0451; and maximum 3.2 [1.4] vs 4.2 [1.4]; P=0.0081) and 48 h (minimum 0.9 [1.0] vs 1.6 [1.1]; P=0.0101; and maximum 2.0 [1.5] vs 3.2 [1.6]; P=0.0029) were lower in the study group. Pain Disability Index was lower and satisfaction with pain control was higher after 3 months in the physostigmine group. In contrast to previous trials, physostigmine did not reduce opioid consumption. As pain thresholds were higher and hyperalgesia and wind-up lower in the physostigmine group, we conclude that physostigmine has anti-hyperalgesic effects and attenuates sensitisation processes. Intraoperative physostigmine may be a useful and safe addition to conventional postoperative pain control. EudraCT number 2012-000130-19. Copyright © 2020 British Journal of Anaesthesia. Published by Elsevier Ltd. All rights reserved.

Citation

Christoph Klivinyi, Gudrun Rumpold-Seitlinger, Christian Dorn, Larissa Sampl, Nikki Sivro, Kordula Lang-Illievich, Sabine Fleck, Sylvia Farzi, Helmar Bornemann-Cimenti. Perioperative use of physostigmine to reduce opioid consumption and peri-incisional hyperalgesia: a randomised controlled trial. British journal of anaesthesia. 2021 Mar;126(3):700-705