Perioperative Lidocaine for Lung Protection in Infants Undergoing Cardiac Surgery (PLICS)

Evaluation of the Effect of Perioperative Lidocaine Administration on Reducing Pulmonary Injury in Infants Following Cardiac Surgery: A Randomized, Placebo-Controlled, Double-Blind, Multi-center Superiority Trial.

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.

Study Overview

• Status: Not yet recruiting
• Conditions: Acute Lung Injury; Congenital Heart Disease; Postoperative Pulmonary Complications
• Intervention / Treatment: Drug: Lidocaine %2 ampoule; Drug: Normal Saline (0.9% NaCl)

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.

• Study Type: Interventional
• Enrollment (Estimated): 320
• Phase: Phase 4

Contacts and Locations

• Study Contact: Name: Xiangming Fan, MD, PhD; Phone Number: +86 13616532813; Email: fanxiangming@zju.edu.cn

Study Locations

• China
  • Zhejiang
    • Hangzhou, Zhejiang, China, 310052
      • Children's Hospital, Zhejiang University School of Medicine
      • Contact: Qian Chen, MD, PhD; Phone Number: +86 13883350798; Email: qian.chen@zju.edu.cn

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Child
• Accepts Healthy Volunteers: No

Description

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.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Prevention
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Quadruple

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Lidocaine Group; Participants receive intravenous lidocaine beginning at the surgery, with a loading infusion over 20 minutes followed by continuous infusion for 24 hours.	Drug: Lidocaine %2 ampoule; 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.
Placebo Comparator: Placebo Group; Participants receive volume-matched intravenous normal saline placebo beginning at the surgery, with the same administration schedule as the active intervention.	Drug: Normal Saline (0.9% NaCl); Volume-matched 0.9% normal saline placebo administered according to the same schedule as the lidocaine group.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Acute Lung Injury Score within 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.	Assessed at 0, 12, 24, 36, 48, 60, and 72 hours after surgery

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Arterial partial pressure of oxygen	Measured by arterial blood gas analysis, reported in mmHg.	0, 12, 24, 36, 48, 60, and 72 hours after surgery
Arterial partial pressure of carbon dioxide	Measured by arterial blood gas analysis, reported in mmHg.	0, 12, 24, 36, 48, 60, and 72 hours after surgery
Arterial oxygen saturation	Measured by arterial blood gas analysis, reported as percentage (%).	0, 12, 24, 36, 48, 60, and 72 hours after surgery
Arterial lactate concentration	Measured by arterial blood gas analysis, reported in mmol/L.	0, 12, 24, 36, 48, 60, and 72 hours after surgery
Duration of mechanical ventilation	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.	From postoperative ICU admission until successful discontinuation of invasive mechanical ventilation, assessed up to 72 hours after surgery.
PICU length of stay	Duration of stay in the pediatric intensive care unit, measured in days.	From postoperative admission to the pediatric intensive care unit until discharge from the pediatric intensive care unit, assessed up to 7 days after surgery.
Left ventricular ejection fraction (LVEF)	Left ventricular fractional shortening assessed by transthoracic echocardiography, reported as percentage (%).	Baseline, 24, 48, and 72 hours after surgery
Plasma lidocaine concentration	Plasma lidocaine concentration measured using the assay specified in the study laboratory manual, reported in ug/mL	6, 12, 18, 24 hours after surgery
Incidence of postoperative pulmonary complications	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.	Assessed within 72 hours after surgery
Prothrombin time (PT)	Measured in venous blood by routine clinical laboratory testing, reported in seconds.	Baseline, 24, 48, and 72 hours after surgery
Activated partial thromboplastin time (aPTT)	Measured in venous blood by routine clinical laboratory testing, reported in seconds.	Baseline, 24, 48, and 72 hours after surgery
Alanine aminotransferase (ALT)	Measured by routine clinical laboratory testing, reported in U/L.	Baseline, 24, 48, and 72 hours after surgery
Aspartate aminotransferase (AST)	Measured by routine clinical laboratory testing, reported in U/L.	Baseline, 24, 48, and 72 hours after surgery
Serum creatinine	Measured by routine clinical laboratory testing, reported in umol/L.	Baseline, 24, 48, and 72 hours after surgery
Blood urea nitrogen	Measured by routine clinical laboratory testing, reported in mmol/L.	Baseline, 24, 48, and 72 hours after surgery
Plasma soluble intercellular adhesion molecule-1 (sICAM-1) concentration	Measured using ELISA assay kit, reported in umol/L	Baseline, 24, 48, and 72 hours after surgery
Plasma surfactant protein D (SP-D) concentration	Measured using ELISA assay kit, reported in umol/L	Baseline, 24, 48, and 72 hours after surgery
Plasma soluble receptor for advanced glycation end products (sRAGE) concentration	Measured using ELISA assay kit, reported in umol/L	Baseline, 24, 48, and 72 hours after surgery
Plasma interleukin-1 beta (IL-1β) concentration	Measured using ELISA assay kit, reported in umol/L	Baseline, 24, 48, and 72 hours after surgery
Plasma angiopoietin-2 concentration	Measured using ELISA assay kit, reported in umol/L	Baseline, 24, 48, and 72 hours after surgery
Plasma double-stranded DNA (dsDNA) concentration	Measured using ELISA assay kit, reported in umol/L	Baseline, 24, 48, and 72 hours after surgery
Plasma high-mobility group box 1 (HMGB1) concentration	Measured using ELISA assay kit, reported in umol/L	Baseline, 24, 48, and 72 hours after surgery
Plasma neurofilament light chain (NFL) concentration	Measured using ELISA assay kit, reported in umol/L	Baseline, 24, 48, and 72 hours after surgery
Plasma S100B concentration	Measured using ELISA assay kit, reported in umol/L	Baseline, 24, 48, and 72 hours after surgery

Other Outcome Measures

Outcome Measure	Measure Description	Time Frame
Postoperative sedative and analgesic use	Total cumulative dose and frequency of administration of postoperative sedative and analgesic medications administered during the first 72 hours after surgery, as recorded in the medication administration record.	0 to 72 hours after surgery

Collaborators and Investigators

• Sponsor: The Children's Hospital of Zhejiang University School of Medicine

Publications and helpful links

General Publications

• Weibel S, Jelting Y, Pace NL, Helf A, Eberhart LH, Hahnenkamp K, Hollmann MW, Poepping DM, Schnabel A, Kranke P. Continuous intravenous perioperative lidocaine infusion for postoperative pain and recovery in adults. Cochrane Database Syst Rev. 2018 Jun 4;6(6):CD009642. doi: 10.1002/14651858.CD009642.pub3.
• Fischer MO, Brotons F, Briant AR, Suehiro K, Gozdzik W, Sponholz C, Kirkeby-Garstad I, Joosten A, Nigro Neto C, Kunstyr J, Parienti JJ, Abou-Arab O, Ouattara A; VENICE study group. Postoperative Pulmonary Complications After Cardiac Surgery: The VENICE International Cohort Study. J Cardiothorac Vasc Anesth. 2022 Aug;36(8 Pt A):2344-2351. doi: 10.1053/j.jvca.2021.12.024. Epub 2021 Dec 25.
• Zhang C, Foo I. Is intravenous lidocaine protective against myocardial ischaemia and reperfusion injury after cardiac surgery? Ann Med Surg (Lond). 2020 Sep 11;59:72-75. doi: 10.1016/j.amsu.2020.09.008. eCollection 2020 Nov.
• Gregory AJ, Arora RC, Chatterjee S, Crisafi C, Morton-Bailey V, Rea A, Salenger R, Engelman DT, Grant MC; ERAS Cardiac Working Group. Enhanced Recovery After Surgery (ERAS) cardiac turnkey order set for perioperative pain management in cardiac surgery: Proceedings from the American Association for Thoracic Surgery (AATS) ERAS Conclave 2023. JTCVS Open. 2024 Sep 6;22:14-24. doi: 10.1016/j.xjon.2024.08.018. eCollection 2024 Dec.
• Wang L, Wang M, Li S, Wu H, Shen Q, Zhang S, Fang L, Liu R. Nebulized lidocaine ameliorates allergic airway inflammation via downregulation of TLR2. Mol Immunol. 2018 May;97:94-100. doi: 10.1016/j.molimm.2018.03.010. Epub 2018 Mar 30.
• Lee JM, Suh JK, Jeong JS, Cho SY, Kim DW. Antioxidant effect of lidocaine and procaine on reactive oxygen species-induced endothelial dysfunction in the rabbit abdominal aorta. Korean J Anesthesiol. 2010 Aug;59(2):104-10. doi: 10.4097/kjae.2010.59.2.104. Epub 2010 Aug 20.
• Kavcic H, Jug U, Mavri J, Umek N. Antioxidant activity of lidocaine, bupivacaine, and ropivacaine in aqueous and lipophilic environments: an experimental and computational study. Front Chem. 2023 Jun 20;11:1208843. doi: 10.3389/fchem.2023.1208843. eCollection 2023.
• Simonato M, Padalino M, Vedovelli L, Carollo C, Sartori A, Vida V, Gregori D, Carnielli V, Cogo P. Effect of preoperative pulmonary hemodynamic and cardiopulmonary bypass on lung function in children with congenital heart disease. Eur J Pediatr. 2023 Jun;182(6):2549-2557. doi: 10.1007/s00431-023-04926-0. Epub 2023 Mar 18.
• Jenke A, Yazdanyar M, Miyahara S, Chekhoeva A, Immohr MB, Kistner J, Boeken U, Lichtenberg A, Akhyari P. AdipoRon Attenuates Inflammation and Impairment of Cardiac Function Associated With Cardiopulmonary Bypass-Induced Systemic Inflammatory Response Syndrome. J Am Heart Assoc. 2021 Mar 16;10(6):e018097. doi: 10.1161/JAHA.120.018097. Epub 2021 Mar 5.
• Sperotto F, Cogo P, Amigoni A, Pettenazzo A, Thiagarajan RR, Polito A. Extracorporeal Membrane Oxygenation Support for Failure to Wean From Cardiopulmonary Bypass After Pediatric Cardiac Surgery: Analysis of Extracorporeal Life Support Organization Registry Data. Crit Care Explor. 2020 Sep 15;2(9):e0183. doi: 10.1097/CCE.0000000000000183. eCollection 2020 Sep.
• Cholette JM, Muszynski JA, Ibla JC, Emani S, Steiner ME, Vogel AM, Parker RI, Nellis ME, Bembea MM; Pediatric Critical Care Transfusion and Anemia EXpertise Initiative-Control/Avoidance of Bleeding (TAXI-CAB), in collaboration with the Pediatric Critical Care Blood Research Network (BloodNet), and the Pediatric Acute Lung Injury and Sepsis Investigators (PALISI) Network. Plasma and Platelet Transfusions Strategies in Neonates and Children Undergoing Cardiac Surgery With Cardiopulmonary Bypass or Neonates and Children Supported by Extracorporeal Membrane Oxygenation: From the Transfusion and Anemia EXpertise Initiative-Control/Avoidance of Bleeding. Pediatr Crit Care Med. 2022 Jan 1;23(13 Supple 1 1S):e25-e36. doi: 10.1097/PCC.0000000000002856.

Study record dates

Study Major Dates

• Study Start (Estimated): April 1, 2026
• Primary Completion (Estimated): December 1, 2027
• Study Completion (Estimated): December 31, 2027

Study Registration Dates

• First Submitted: March 12, 2026
• First Submitted That Met QC Criteria: March 23, 2026
• First Posted (Actual): March 30, 2026

Study Record Updates

• Last Update Posted (Actual): March 30, 2026
• Last Update Submitted That Met QC Criteria: March 23, 2026
• Last Verified: March 1, 2026

More Information

Terms related to this study

• Keywords: Lidocaine; Cardiopulmonary bypass; Lung injury; Infant cardiac surgery
• Additional Relevant MeSH Terms: Cardiovascular Diseases; Wounds and Injuries; Heart Diseases; Respiratory Tract Diseases; Lung Diseases; Congenital Abnormalities; Cardiovascular Abnormalities; Thoracic Injuries; Congenital, Hereditary, and Neonatal Diseases and Abnormalities; Heart Defects, Congenital; Lung Injury; Acute Lung Injury; Pharmaceutical Preparations; Crystalloid Solutions; Isotonic Solutions; Solutions; Saline Solution
• Other Study ID Numbers: 2026-IRB-0031-P-01

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: UNDECIDED

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No