Effects of pupillary reflex dilation-guided opioid administration on remifentanil and morphine consumption during laparoscopic surgery: A randomised controlled trial

BACKGROUND Analysis of pupillary reflex dilation (PRD) assesses the balance of nociception--antinociception. Laparoscopic surgery induces haemodynamic variations that are misleading. During laparoscopy, PRD guidance helps differentiate haemodynamic changes because of excess nociception from secondary changes related to the reflex release of endocrine factors. OBJECTIVE The present study evaluated the effect of PRD-guided antinociception on the administration of intra-operative remifentanil and immediate postoperative morphine consumption in patients undergoing elective laparoscopic surgery. DESIGN The study was a single-blind, randomised controlled trial. SETTING The study took place at two sites at the University Hospital of Nancy from March 2014 to November 2017. PATIENTS A total of 100 patients who underwent scheduled laparoscopic surgery were included. INTERVENTIONS Patients were randomly given remifentanil guided by PRD (PRD-guided) or standard anaesthesia care (control). MAIN OUTCOME MEASURES The primary outcome was intra-operative remifentanil consumption. Secondary outcomes included morphine consumption in the immediate postoperative period and the number of intra-operative haemodynamic events. RESULTS Data from 95 patients were analysed. Intraoperative remifentanil consumption was lower in the PRD-guided group than in the control group: median [IQR], 0.09 [0.07 to 0.11] vs. 0.14 [0.12 to 0.16] μg kg min, with a mean difference (95% confidence Interval, CI) of 0.048 (0.035 to 0.060) μg kg min; P < 0.0001. Morphine consumption was 0.13 [0.1 to 0.5] vs. 0.15 [0.11 to 0.4] mg kg (P = 0.52) in the PRD-guided and control groups, respectively. The number of hypertensive and tachycardia events was greater in the PRD-guided group than in the control group: Hypertensive events 60.4 vs. 32.6%, relative risk 1.85 (95% CI, 1.24 to 2.84), P = 0.004; tachycardia events 31.6% vs. 4.3%, relative risk 2.09 (95% CI, 1.45 to 2.84), P < 0.001. CONCLUSIONS When PRD is used to differentiate between haemodynamic events arising from noxious stimuli and those events because of other nonsurgical stimuli, then intra-operative remifentanil administration is reduced intra-operatively during laparoscopic surgery but there was no change in postoperative morphine consumption. TRIAL REGISTRATION Clinicaltrials.gov NCT02116868.