Does the β-receptor antagonist esmolol have analgesic effects?: A randomised placebo-controlled cross-over study on healthy volunteers undergoing the cold pressor test.

Abstract

Esmolol may attenuate the sympathetic response to pain and reduce postoperative opioid consumption. It is not clear whether esmolol has an analgesic effect per se. The aim of this study was to evaluate the analgesic effect of esmolol in the absence of anaesthetics and opioids. We tested the hypothesis that esmolol would reduce the maximum pain intensity perceived during the cold pressor test (CPT) by 2 points on a 0 to 10 numeric pain rating scale (NRS) compared to placebo. Randomised, placebo-controlled cross-over study. Postoperative recovery area, Örebro University Hospital. Study period, November 2013 to February 2014. Fourteen healthy volunteers. Exclusion criteria included ongoing medication, pregnancy and breastfeeding and participation in other medical trials. At separate study sessions, participants received interventions: esmolol (0.7 mg kg bolus over 1 min followed by infusion at 10 μg kg min); 0.9% normal saline bolus then remifentanil infusion at 0.2 μg kg min and 0.9% normal saline bolus and infusion according to a random sequence. All infusions were administered over 30 min. Perceived maximum pain intensity score, pain tolerance and haemodynamic changes during CPT, and occurrence of side-effects to interventions compared to placebo, respectively. Esmolol did not reduce perceived pain intensity or pain tolerance during the CPT. The NRS-max score was similar for esmolol, 8.5 (±1.4) and placebo, 8.4 (±1.3). The mean difference was 0.1 [95% confidence interval (-1.2 to 1.4)], P value equal to 0.83. Remifentanil significantly reduced NRS-max scores, 5.4 (±2.1) compared to placebo, [mean difference -3.1 (95% confidence interval (-4.4 to -1.8)), P < 0.001]. Side-effects were seen with remifentanil but not with esmolol. No direct analgesic effect of esmolol could be demonstrated in the present study. The postoperative opioid-sparing effect demonstrated in previous studies, could therefore be secondary to other factors such as avoidance of opioid-induced hyperalgesia, synergy with coadministered opioids or altered pharmacokinetics of those drugs. European clinical trials database, https://eudract.ema.europa.eu/, EudraCT no. 2011-005780-24.