Intravenous lidocaine for gastrointestinal recovery after colorectal surgery: the ALLEGRO placebo-controlled randomised trial and cost-effectiveness analysis.

Background: Delayed return of gut function after colonic resection is a common impediment to early postoperative recovery. Small clinical studies, combined into meta-analyses, have suggested that intravenous lidocaine can improve return of gut function after colorectal surgery. Objective(s): To determine the clinical effectiveness and cost-effectiveness of perioperative intravenous lidocaine infusion compared with placebo in return of gut function after elective minimally invasive colonic resection. Design and methods: Multicentre, pragmatic, placebo-controlled, randomised trial with cost-effectiveness analysis. Setting and participants: Twenty-seven hospital sites across the United Kingdom. Adult patients scheduled for elective minimally invasive colon resection were randomised in 1 : 1 ratio to treatment or control groups using a web-based portal, stratified by age, sex and trial site. Interventions: A sterile solution of 2% lidocaine (made isotonic with sodium chloride) and matching placebo (a sterile solution of 0.9% sodium chloride). Participants received an intravenous bolus of study drug/placebo at induction of anaesthesia (1.5 mg/kg ideal body weight) given over 20 minutes, followed by intravenous infusion of 1.5 mg/hour/kg ideal body weight with a maximum rate of 120 mg/hour (6 ml/hour) for a minimum of 6 hours up to a maximum of 12 hours. The planned duration of infusion was determined by the participating unit's availability of postoperative continuous cardiac monitoring. Main outcome measures: Primary outcome: return of gut function at 72 hours postoperatively measured by 'GI-3 recovery' (defined as tolerating diet and passage of flatus or stool). Other outcomes were GI-2 recovery, prolonged postoperative ileus, patient-reported measures of quality of life, recovery and pain, 30- and 90-day mortality, unplanned re-admissions, adverse events, serious adverse events and cost per quality-adjusted life-year at 30 days. Participants, care givers and those assessing the outcomes were blinded to group assignment. Results: The trial enrolled 590 patients (295 interventions, 295 control); after 33 post-randomisation exclusions, 557 patients were included (279 interventions, 278 control). There was no statistically significant or clinically meaningful difference in GI-3 recovery at 72 hours after surgery [160/279 patients (57.3%) for intravenous lidocaine versus 164/278 patients (59%) for placebo (absolute difference 1.9% (-8.0 to 4.2), odds ratio 0.97 (0.88 to 1.07), Limitations: For pragmatic reasons, relatively short durations of infusion were delivered in the ALLEGRO trial - we cannot discount the possibility that longer durations might be effective. Conclusions: We found no evidence for benefit from perioperative intravenous lidocaine on return of gut function, nor any other objective patient-reported outcome measure, nor cost-efficiency. Future work: There remains a need for an effective, acceptable, safe and affordable intervention to improve recovery of gut function after minimally invasive colonic surgery. Funding: This synopsis presents independent research funded by the National Institute for Health and Care Research (NIHR) Health Technology Assessment programme as award number 15/130/95.