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

Background: 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 anticholinesterase drug physostigmine that increases synaptic acetylcholine concentrations has anti-inflammatory effects. Methods: 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. Results: 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. Conclusions: 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 antihyperalgesic effects and attenuates sensitisation processes. Intraoperative physostigmine may be a useful and safe addition to conventional postoperative pain control.

Automated summary

The study found that intraoperative physostigmine did not affect opioid consumption but increased mechanical pain thresholds, reduced hyperalgesia distance and wind-up ratios, and lowered postoperative pain scores. Patients in the physostigmine group also reported lower Pain Disability Index and higher satisfaction with pain control after 3 months, suggesting that physostigmine has antihyperalgesic effects and can attenuate sensitisation processes.