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),  = 0.54)]. There was no effect of intravenous lidocaine found in predetermined subgroup analyses (6- vs. 12-hour duration of infusion, right vs. non-right colectomy, sex, age band and enhanced recovery after surgery compliance). There was no evidence of a difference in other measures of gut function return, pain, quality of recovery, quality of life, perioperative complications, length of stay or total healthcare costs. There was no clinical difference between the groups in the usage of anti-emetic drug and postoperative analgesia. The intervention was not cost-effective under National Institute for Health and Care Excellence reference case criteria. Adverse events were few and evenly distributed between arms.

[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.