Intraoperative Nebulization of Lidocaine and Postoperative Pulmonary Complications

Introduction Globally, over 313 million surgical procedures are performed annually, with postoperative pulmonary complications (PPCs) occurring in 5-33% of cases. PPCs, the second most common postoperative complication after surgical site infections, encompass conditions such as respiratory infections, respiratory failure, pleural effusion, atelectasis, pneumothorax, bronchospasm, and aspiration pneumonia. These complications significantly prolong hospital stays, increase healthcare costs, and elevate 30-day and 1-year mortality rates.

Pathophysiology of PPCs PPCs are closely linked to perioperative pulmonary inflammatory responses. Mechanical ventilation during general anesthesia alters pulmonary ventilation distribution, leading to atelectasis in over 90% of patients. Atelectasis increases mechanical stress and hypoxia in collapsed lung regions while causing hyperinflation and hyperoxia in adjacent areas. These conditions promote the release of pro-inflammatory cytokines, reactive oxygen species, and leukocyte infiltration. Additionally, atelectasis-induced hypoxia and mechanical stress contribute to endothelial damage, increasing vascular permeability and protein leakage. Major abdominal and thoracic surgeries further exacerbate systemic inflammation and airway hyperreactivity, impairing alveolar epithelial barrier function and mucociliary clearance.

Lidocaine's Anti-Inflammatory and Lung-Protective Mechanisms Lidocaine has emerged as a potential therapeutic agent due to its anti-inflammatory properties. Studies indicate that it inhibits neutrophil infiltration and reduces pro-inflammatory cytokines (e.g., IL-6, TNF-α) by blocking Toll-like receptor 4/NF-κB signaling. Inhaled lidocaine has shown efficacy in murine asthma models by suppressing GATA-3 expression, eosinophilic inflammation, mucus overproduction, and airway hyperreactivity. It has also been explored as an adjunct therapy for severe COVID-19 respiratory symptoms, mitigating cytokine storms and improving outcomes. In pediatric patients, lidocaine reduces postoperative cough incidence.

Current Challenges and the Promise of Nebulization Despite its potential, lidocaine's clinical application for lung protection remains inconsistent. Intravenous administration poses risks due to narrow therapeutic windows, with fluctuating plasma concentrations potentially causing neurotoxicity or cardiotoxicity. nebulized lidocaine achieve direct anti-inflammatory effects within the pulmonary compartment.

Research Objective and Hypothesis The role of nebulization lidocaine in reducing PPCs remains underexplored. This study aims to evaluate its impact on PPC incidence within seven days post-surgery. The hypothesis is that intraoperative nebulized lidocaine administration will decrease PPC rates, offering a safer and more effective approach to perioperative lung protection.

Inclusion criteria

• Patients who have signed the informed consent form and are willing to complete the study according to the protocol
• Age ≥18 years old and ≤90 years old
• ASA classification grades I-III
• Elective major non-cardiac surgery
• General anesthesia under tracheal intubation
• Monitor invasive arterial blood pressure
• The expected operation time ≥2 hours

Exclusion criteria

• Untreated ischemic heart disease Severe cardiovascular and cerebrovascular diseases
• Severe asthma, pulmonary bullae, pneumothorax, bronchopleural fistula, etc
• Severe underlying liver and kidney diseases
• Age under 18 years old or over 90 years old
• The expected operation time is ≥2 hours