Congenital Heart Disease, Postoperative Pulmonary Complications, Acute Lung Injury
Conditions
Keywords
Lidocaine, Lung injury, Infant cardiac surgery, Cardiopulmonary bypass
Brief summary
Cardiopulmonary bypass-associated pulmonary injury is a common complication after infant cardiac surgery and may contribute to impaired oxygenation, prolonged mechanical ventilation, and longer intensive care stay. Lidocaine has anti-inflammatory and membrane-stabilizing properties and may attenuate perioperative lung injury. This investigator-initiated, randomized, placebo-controlled, double-blind trial will evaluate whether perioperative intravenous lidocaine reduces postoperative pulmonary injury in infants undergoing corrective non-palliative congenital cardiac surgery with cardiopulmonary bypass.
Detailed description
Infants undergoing cardiac surgery with cardiopulmonary bypass are at risk of postoperative pulmonary injury due to systemic inflammatory activation, ischemia-reperfusion injury, and disruption of the alveolar-capillary barrier. Intravenous lidocaine has been reported to exert anti-inflammatory, anti-arrhythmic, and potential organ-protective effects. However, evidence in infants undergoing cardiac surgery remains limited. This randomized, double-blind, placebo-controlled superiority trial will enroll infants aged 0 to 12 months scheduled for corrective, non-palliative congenital cardiac surgery with cardiopulmonary bypass at a tertiary pediatric center. Participants will be randomized in a 1:1 ratio to receive either perioperative intravenous lidocaine or volume-matched normal saline placebo. The trial will assess postoperative pulmonary injury severity over the first 72 hours after surgery, together with respiratory, laboratory, echocardiographic, and safety outcomes until postoperative day 7 or at discharge.
Interventions
Intravenous lidocaine hydrochloride 2%: loading dose 1.0 mg/kg administered over 20 minutes starting at the surgery, followed by continuous infusion at 1.0 mg/kg/hour for 24 hours. Dosing is based on standard body weight or actual body weight according to protocol-defined rules.
DRUGNormal Saline (0.9% NaCl)
Volume-matched 0.9% normal saline placebo administered according to the same schedule as the lidocaine group.
Sponsors
The Children's Hospital of Zhejiang University School of Medicine
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
PREVENTION
Masking
QUADRUPLE (Subject, Caregiver, Investigator, Outcomes Assessor)
Masking description
Participants, parents/guardians, treating clinicians, investigators, and outcome assessors/statisticians will remain blinded to treatment allocation. Study medication will be prepared by designated anesthesia staff not involved in outcome assessment.
Intervention model description
Participants will be randomized in a 1:1 ratio to receive either intravenous lidocaine or volume-matched normal saline placebo.
Eligibility
Sex/Gender
ALL
Age
No minimum to 12 Months
Healthy volunteers
No
Inclusion criteria
1. Infants aged 0 to 12 months. 2. Congenital heart disease requiring corrective, non-palliative cardiac surgery with cardiopulmonary bypass. 3. American Society of Anesthesiologists (ASA) physical status I to III. 4. Written informed consent provided by parent(s) or legal guardian(s).
Exclusion criteria
1. Multiple malformations, chromosomal abnormalities, or immunodeficiency. 2. Known or suspected allergy to lidocaine. 3. Concomitant continuous infusion of another local anesthetic. 4. Conditions associated with increased risk of lidocaine accumulation or toxicity, including severe conduction block or severe bradycardia. 5. ASA physical status IV or higher. 6. Severe malnutrition expected to substantially impair postoperative recovery. 7. Severe hepatic or renal dysfunction. 8. Significant pre-existing pulmonary disease or markedly impaired preoperative pulmonary function. 9. Central nervous system disorders that may increase susceptibility to lidocaine neurotoxicity, including epilepsy or prior central nervous system infection. 10. Use of medications that may interact with lidocaine or constitute an exclusion, including class I or class III antiarrhythmic agents, cimetidine, or antiviral drugs, as determined by the clinical team. 11. Current or recent participation in another interventional clinical trial in its active intervention phase.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Acute Lung Injury Score within 72 hours after surgery | Assessed at 0, 12, 24, 36, 48, 60, and 72 hours after surgery | Composite lung injury severity score ranging from 0 to 4, based on oxygenation index or oxygen saturation index, chest radiograph findings, positive en-expiratory pressure, and pulmonary compliance. Higher scores indicate more severe lung injury. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Arterial partial pressure of oxygen | 0, 12, 24, 36, 48, 60, and 72 hours after surgery | Measured by arterial blood gas analysis, reported in mmHg. |
| Arterial partial pressure of carbon dioxide | 0, 12, 24, 36, 48, 60, and 72 hours after surgery | Measured by arterial blood gas analysis, reported in mmHg. |
| Arterial oxygen saturation | 0, 12, 24, 36, 48, 60, and 72 hours after surgery | Measured by arterial blood gas analysis, reported as percentage (%). |
| Arterial lactate concentration | 0, 12, 24, 36, 48, 60, and 72 hours after surgery | Measured by arterial blood gas analysis, reported in mmol/L. |
| Duration of mechanical ventilation | From postoperative ICU admission until successful discontinuation of invasive mechanical ventilation, assessed up to 72 hours after surgery. | Total duration of invasive mechanical ventilation, measured in hours, from postoperative admission to the intensive care unit until first successful extubation without the need for reintubation. |
| PICU length of stay | From postoperative admission to the pediatric intensive care unit until discharge from the pediatric intensive care unit, assessed up to 7 days after surgery. | Duration of stay in the pediatric intensive care unit, measured in days. |
| Left ventricular ejection fraction (LVEF) | Baseline, 24, 48, and 72 hours after surgery | Left ventricular fractional shortening assessed by transthoracic echocardiography, reported as percentage (%). |
| Plasma lidocaine concentration | 6, 12, 18, 24 hours after surgery | Plasma lidocaine concentration measured using the assay specified in the study laboratory manual, reported in ug/mL |
| Incidence of postoperative pulmonary complications | Assessed within 72 hours after surgery | Incidence of at least one postoperative pulmonary complication within 72 hours after surgery, defined as the occurrence of any of the following: atelectasis, pulmonary edema, pleural effusion, pneumothorax, or infectious pneumonia. Reported as the percentage of participants with at least one postoperative pulmonary complication. |
| Prothrombin time (PT) | Baseline, 24, 48, and 72 hours after surgery | Measured in venous blood by routine clinical laboratory testing, reported in seconds. |
| Activated partial thromboplastin time (aPTT) | Baseline, 24, 48, and 72 hours after surgery | Measured in venous blood by routine clinical laboratory testing, reported in seconds. |
| Alanine aminotransferase (ALT) | Baseline, 24, 48, and 72 hours after surgery | Measured by routine clinical laboratory testing, reported in U/L. |
| Aspartate aminotransferase (AST) | Baseline, 24, 48, and 72 hours after surgery | Measured by routine clinical laboratory testing, reported in U/L. |
| Serum creatinine | Baseline, 24, 48, and 72 hours after surgery | Measured by routine clinical laboratory testing, reported in umol/L. |
| Blood urea nitrogen | Baseline, 24, 48, and 72 hours after surgery | Measured by routine clinical laboratory testing, reported in mmol/L. |
| Plasma soluble intercellular adhesion molecule-1 (sICAM-1) concentration | Baseline, 24, 48, and 72 hours after surgery | Measured using ELISA assay kit, reported in umol/L |
| Plasma surfactant protein D (SP-D) concentration | Baseline, 24, 48, and 72 hours after surgery | Measured using ELISA assay kit, reported in umol/L |
| Plasma soluble receptor for advanced glycation end products (sRAGE) concentration | Baseline, 24, 48, and 72 hours after surgery | Measured using ELISA assay kit, reported in umol/L |
| Plasma interleukin-1 beta (IL-1β) concentration | Baseline, 24, 48, and 72 hours after surgery | Measured using ELISA assay kit, reported in umol/L |
| Plasma angiopoietin-2 concentration | Baseline, 24, 48, and 72 hours after surgery | Measured using ELISA assay kit, reported in umol/L |
| Plasma double-stranded DNA (dsDNA) concentration | Baseline, 24, 48, and 72 hours after surgery | Measured using ELISA assay kit, reported in umol/L |
| Plasma high-mobility group box 1 (HMGB1) concentration | Baseline, 24, 48, and 72 hours after surgery | Measured using ELISA assay kit, reported in umol/L |
| Plasma neurofilament light chain (NFL) concentration | Baseline, 24, 48, and 72 hours after surgery | Measured using ELISA assay kit, reported in umol/L |
| Plasma S100B concentration | Baseline, 24, 48, and 72 hours after surgery | Measured using ELISA assay kit, reported in umol/L |
Countries
China
Contacts
CONTACTXiangming Fan, MD, PhD
Outcome results
None listed