Effect of Perioperative Intravenous Lidocaine on Postoperative Opioid-Related Side Effects Following Open Hepatectomy: A Multicentre Prospective Randomized Controlled Trial

The primary objective is to compare the effects of perioperative intravenous lidocaine infusion versus placebo on postoperative opioid-related side effects following open hepatectomy. This evaluation aims to assess the clinical utility of lidocaine in mitigating adverse outcomes associated with opioid administration in this surgical population.

Secondary objectives include determining the occurrence of opioid-related adverse events, such as nausea and vomiting, hypoxemia, ileus, or the absence of flatus and stools, within 48 hours post-extubation. Additional outcomes evaluated are the impact on postoperative analgesia, total opioid consumption, and the time required to achieve an Aldrete score of 9 or greater. The study further examines clinical recovery through the QoR40 score, the rate of unscheduled intensive care unit admissions, and the total hospital length of stay. Safety assessments focus on monitoring lidocaine-related adverse effects and the incidence of complications including pneumonia, acute kidney injury, surgical reinterventions, and atrial fibrillation. An ancillary study will also evaluate drug exposure.

The sponsor did not provide information regarding the total number of participants. The study population consists of patients undergoing a scheduled open hepatectomy. Eligible individuals include both males and females within specific age cohorts. Required inclusion criteria involve being at least 18 years of age and utilizing effective contraception. Participants must be affiliated with a social security scheme. The investigation focuses on postanesthetic complications following the surgical procedure.

This multicentre, prospective, randomized, double-blind, controlled study evaluates the effects of perioperative intravenous lidocaine infusion compared to a sodium chloride placebo on postoperative opioid-related side effects following open hepatectomy. The study aims to assess a composite primary endpoint consisting of postoperative nausea and vomiting, postoperative hypoxemia, or postoperative ileus occurring within 48 hours after extubation. Secondary endpoints include opioid consumption, postoperative pain, hospital length of stay, and the incidence of complications such as pneumonia, acute kidney insufficiency, or postoperative atrial fibrillation. The research methodology involves the administration of either lidocaine hydrochloride or a placebo via intravenous infusion. Participant involvement extends from the initial screening to the final assessments, with data collection continuing through hospital discharge or a maximum of 28 days post-extubation. An ancillary pharmacological study will measure plasma lidocaine concentration in a subset of 20 patients.

The experimental treatment consists of lidocaine hydrochloride administered via intravenous infusion. The dosage is set at 1.50 mg/kg/h.

The control group receives a placebo consisting of sodium chloride. This substance is administered through intravenous bolus injection or infusion at a dosage of 1.50 mg/kg/h.

The primary efficacy assessment is a composite endpoint consisting of postoperative opioid-related adverse events occurring within the first 48 hours following extubation. These events include postoperative nausea and vomiting, postoperative hypoxemia (defined as SpO₂ < 95% requiring oxygen supplementation), and postoperative ileus, such as intolerance to an oral diet. These parameters are evaluated through blinded assessment relative to the randomization group.

Secondary endpoints include the following:

• Occurrence of postoperative opioid-related nausea and vomiting and the requirement for anti-emetic medication within 48 hours after extubation.
• Occurrence of postoperative opioid-related hypoxemia and the duration of oxygen treatment within 48 hours after extubation.
• Occurrence of postoperative opioid-related ileus and the absence of flatus or stools within 48 hours after extubation.
• Postoperative pain levels measured via a numeric rating scale at rest and during movement, with assessments conducted every 10 minutes in the post-anesthesia care unit and every 6 hours until 48 hours post-surgery.
• Total opioid consumption in milligrams during the 48 hours following extubation.
• Time elapsed between extubation and achieving an Aldrete score ≥ 9.
• The rate of unscheduled admission to the intensive care unit.
• Hospital length of stay, measured as the number of days from extubation to discharge, up to a maximum of 28 days.
• Incidence of pneumonia based on modified CDC criteria within 7 days after surgery or until discharge.
• Incidence of acute kidney insufficiency defined by KDIGO ≥ 2 within 7 days after surgery or until discharge.
• Requirement for reintervention due to surgical complications within 7 days after surgery or until discharge.
• New onset of postoperative atrial fibrillation within 7 days after surgery or until discharge.
• Quality of recovery assessed using the QoR40 score between 24 and 48 hours after extubation.
• Adverse effects related to the intravenous experimental treatment.
• Plasma lidocaine concentration as part of an ancillary pharmacological study.