Cardiopulmonary bypass (CPB) is a cornerstone of modern cardiac surgery, enabling complex coronary artery bypass grafting and valvular interventions. However, CPB is also a potent trigger of systemic inflammatory response syndrome (SIRS), contributing to postoperative complications such as vasoplegia, acute kidney injury, respiratory dysfunction, delirium, myocardial injury, and prolonged intensive care unit (ICU) stays. The article titled “Evaluation of the Effect of Intravenous Lidocaine on the Systemic Inflammatory Response Associated With Cardiopulmonary Bypass in Valvular and/or Coronary Cardiac Surgery: Protocol for a Double-Blind Randomized Clinical Trial” outlines the LEONARD Trial, a rigorously designed study investigating whether intravenous lidocaine can attenuate CPB-induced inflammation and improve clinical outcomes.
The inflammatory cascade associated with CPB results from blood contact with artificial surfaces, ischemia-reperfusion injury, endotoxemia, complement activation, and endothelial glycocalyx degradation. Key proinflammatory cytokines such as interleukin-6 (IL-6), tumor necrosis factor-alpha (TNF-α), and C-reactive protein (CRP) rise sharply following surgery. These biomarkers correlate with organ dysfunction and adverse outcomes. Although multiple pharmacologic strategies have been explored to mitigate inflammation during cardiac surgery, no standard anti-inflammatory therapy has been universally adopted.
Intravenous lidocaine, widely used for analgesia and arrhythmia management, has demonstrated membrane-stabilizing and anti-inflammatory properties. Evidence from noncardiac surgery suggests that lidocaine reduces inflammatory cytokine release, postoperative pain, and opioid consumption. However, data specific to cardiac surgery involving CPB remain limited. The LEONARD Trial addresses this knowledge gap with a prospective, double-blind, placebo-controlled randomized clinical trial conducted at San Pedro University Hospital in Spain.
The study plans to enroll 90 adult patients undergoing elective valvular and/or coronary cardiac surgery requiring CPB. Participants will be randomized in a 1:1 ratio to receive either intravenous lidocaine or placebo. The lidocaine group will receive a 1.5 mg/kg bolus during anesthetic induction, followed by a continuous infusion of 1.5 mg/kg/h until sternal closure. Obese patients will have dosing adjusted according to ideal body weight. The placebo group will receive equivalent volumes of normal saline. Strict double-blinding is maintained through pharmacy-prepared indistinguishable infusions.
The primary endpoint is plasma IL-6 concentration measured six hours after surgery, capturing the expected cytokine peak. Secondary endpoints include temporal trajectories of IL-6, TNF-α, CRP, and high-sensitivity troponin T at five time points: baseline, start of CPB, end of surgery, 6 hours postoperatively, and 24 hours postoperatively. Clinical outcomes assessed include acute kidney injury (KDIGO criteria), vasoplegia requiring vasopressors, multiorgan dysfunction (SOFA score), respiratory dysfunction, neurologic complications, transfusion requirements, postoperative atrial fibrillation, ICU length of stay, opioid consumption, and 30-day mortality.
The study employs robust statistical methodology, including linear mixed-effects models to analyze biomarker trajectories and area-under-the-curve calculations. Intention-to-treat analysis will be used, and adjustments will be made for confounding factors such as CPB duration and cross-clamp time. The sample size of 90 patients was calculated to detect a clinically significant difference of 12 pg/mL in IL-6 levels with 80% power.
Importantly, the LEONARD Trial is framed as a proof-of-concept study. While adequately powered for its primary biochemical endpoint, it may be underpowered for definitive conclusions regarding secondary clinical outcomes. Nevertheless, the trial is designed to establish a methodologic foundation for future multicenter investigations.
From a clinical perspective, if intravenous lidocaine demonstrates meaningful reductions in inflammatory markers and complication rates, it could represent a low-cost, safe, and easily implementable strategy to improve outcomes in cardiac surgery. Lidocaine’s well-established safety profile and familiarity in anesthetic practice enhance its translational potential.
The protocol emphasizes strict control of confounding factors, including standardized anesthetic management, transfusion thresholds, temperature regulation, and prohibition of corticosteroids and other immunomodulatory drugs during the perioperative period. Such rigor enhances internal validity.
In summary, the LEONARD Trial is a carefully designed randomized controlled trial evaluating intravenous lidocaine as a potential anti-inflammatory therapy during cardiopulmonary bypass. By targeting the inflammatory cascade that contributes to organ dysfunction after cardiac surgery, this study may pave the way for innovative perioperative strategies aimed at reducing morbidity, ICU length of stay, and mortality in patients undergoing valvular or coronary procedures.
