A pilot multicentre randomised controlled trial of lidocaine infusion in women undergoing breast cancer surgery.

Abstract

Chronic postoperative pain is common after breast cancer surgery. Peri-operative lidocaine infusion may prevent the development of chronic postoperative pain, but a large-scale trial is required to test this hypothesis. It is unclear whether a pragmatic, multicentre trial design that is consistent with expert guidance, addresses the limitations of previous studies, and overcomes existing translational barriers is safe, effective and feasible. We conducted a double-blind, randomised controlled pilot study in 150 patients undergoing breast cancer surgery across three hospitals in Western Australia. Patients received lidocaine, or equivalent volumes of saline, as an intravenous bolus (1.5mg.kg-1 ) and infusion (2mg.kg-1 .h-1 ) intra-operatively, and a subcutaneous infusion (1.33mg.kg-1 .h-1 ) postoperatively for up to 12h on a standard surgical ward, with novel safety monitoring tools in place. The co-primary outcomes were: in-hospital safety events; serum levels of lidocaine during intravenous and subcutaneous infusion; and annualised enrolment rates per site with long-term data capture. In-hospital safety events were rare, and similar in the placebo and lidocaine arms (3% vs. 1%). Median (IQR [range]) serum lidocaine levels during intravenous (2.16 (1.74-2.83 [1.12-6.06])µg.ml-1 , n=41) and subcutaneous (1.52 (1.28-1.83 [0.64-2.85])µg.ml-1 , n=48) infusion were comparable with previous trials reporting improved pain outcomes. Annualised enrolment approximated 50 patients per site per year, with high levels of protocol adherence and ≥99% capture of outcomes at 3 and 6months. The adjusted odds ratio (95%CI) for postoperative pain at 6months in the lidocaine arm was 0.790 (0.370-1.684). We conclude that this trial, as designed, is safe, effective and feasible in patients undergoing breast cancer surgery, and a larger-scale trial is planned.