Colorectal Cancer Surgical Treatments (11)
Enhanced Recovery After Surgery (10)
Colorectal Cancer Screening and Detection (9)
Genetic factors in colorectal cancer (7)
Nausea and vomiting management (7)
Paterson H, Vadiveloo T, Innes K, Balfour A, Atter M , et al.
Health technology assessment (Winchester, England) •
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. 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. Multicentre, pragmatic, placebo-controlled, randomised trial with cost-effectiveness analysis. 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. 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. 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. 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. 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. 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. There remains a need for an effective, acceptable, safe and affordable intervention to improve recovery of gut function after minimally invasive colonic surgery. 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.
Paterson H, Vadiveloo T, Innes K, Balfour A, Atter M , et al.
JAMA •
Despite the recovery advantages of minimally invasive surgical techniques, delayed return of gut function after colectomy is a common barrier to timely discharge from hospital. To evaluate the effect of 2% perioperative intravenous lidocaine infusion on return of gut function after elective minimally invasive colon resection. The ALLEGRO trial was a randomized, placebo-controlled, double-blind trial conducted in 27 UK hospitals. A total of 590 adults scheduled for elective minimally invasive colon resection for benign or malignant disease were randomized 1:1 to 2% intravenous lidocaine or saline placebo. Enrollment occurred from August 13, 2018, to April 11, 2023, with a pause in recruitment from March 20, 2020, through July 6, 2020; final follow-up was on August 10, 2023. The intervention patients received 2% intravenous lidocaine administered as 1.5-mg/kg bolus at induction of anesthesia followed by 1.5 mg/kg/h for 6 or 12 hours. Control patients received 0.9% saline placebo for 6 or 12 hours. The primary outcome was the proportion of patients with return of gut function at 72 hours after surgery, defined by the GI-3 composite end point of tolerating diet (ingestion of food and drink without significant nausea or vomiting for 3 consecutive meals) and passage of flatus or stool. There were 11 secondary outcomes, including time to GI-3 recovery, time to GI-2 recovery (tolerance of oral diet and passage of stool), prolonged postoperative ileus, postoperative nausea and vomiting score, Overall Benefit of Analgesia Score, postoperative opioid consumption, Quality of Recovery-15, quality of life (EuroQol 5-Dimension 5-Level), enhanced recovery protocol adherence, time to meeting medically defined criteria for discharge, and time to patient self-assessed readiness for discharge. The trial enrolled 590 patients (295 intervention, 295 control); after 33 postrandomization exclusions, 557 patients were included (279 intervention, 278 control; 249 female patients [44.7%]; mean [SD] age, 66 [10.9] years); 532 (96%) received the randomized treatment. Return of gut function as defined by the GI-3 composite outcome was achieved at 72 hours by 160 patients (57.3%) in the intravenous lidocaine group vs 164 patients (59.0%) in the placebo group (adjusted absolute difference, -1.9% [95% CI, -8.0% to 4.2%]; relative risk, 0.97 [95% CI, 0.88 to 1.07]). There was no significant difference between the intervention and control groups in any of the 11 secondary end points. Among patients undergoing elective minimally invasive colon resection, perioperative administration of 2% intravenous lidocaine did not improve return of gut function at 72 hours. isrctn.org Identifier: ISRCTN52352431.
Atter M, Stoddart A, Cotton S, Vadiveloo T, Innes K , et al.
BMJ open •
To compare costs, health outcomes and cost-effectiveness of using intravenous lidocaine (bolus given at induction of anaesthesia, followed by infusion for 6-12 hours) during colorectal surgery to improve the return of gastrointestinal function. Within-trial planned analysis of data from a randomised controlled trial using an intention-to-treat approach. 27 hospitals from across the UK. 557 patients aged 25-91 having minimally invasive elective colorectal resection. A 1:1 randomisation between intravenous lidocaine and placebo, minimised for age (<50 years, 50-74 years, ≥75 years), gender, and trial centre. Mean differences between trial arms in 30-day and 90-day quality-adjusted life-years (QALYs) and 30-day total National Health Service costs, as well as the 30-day incremental cost-effectiveness ratio. Compliance and data quality were high. Intravenous lidocaine is associated with differences of £38 (95% CI: -£463, £589) in total 30-day costs, -0.0005 (95% CI: -0.0027, 0.0015) in 30-day QALYs and -0.0008 (95% CI: -0.0066, 0.0048) in 90-day QALYs. No large, statistically significant or meaningful differences in primary or secondary outcome measures between trial arms were detected, other than for the intervention costs. Intravenous lidocaine is not found to impact costs or health outcomes for patients undergoing colorectal surgery. In the absence of a clinical effect, disinvestment from perioperative lidocaine could save costs associated with infusion monitoring. International Standard Randomised Controlled Trial Number 52352431.