Perioperative Lidocaine for Lung Protection in Infants Undergoing Cardiac Surgery

Официальное название

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.

Обзор

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.

Подробное описание

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.

Вмешательства

• Препарат 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.
• Препарат Normal Saline (0.9% NaCl)
  Volume-matched 0.9% normal saline placebo administered according to the same schedule as the lidocaine group.

Первичные конечные точки

• Acute Lung Injury Score within 72 hours after surgery [Срок оценки: Assessed at 0, 12, 24, 36, 48, 60, and 72 hours after surgery]

Вторичные конечные точки (12)

• Arterial partial pressure of oxygen [Срок оценки: 0, 12, 24, 36, 48, 60, and 72 hours after surgery]
• Arterial partial pressure of carbon dioxide [Срок оценки: 0, 12, 24, 36, 48, 60, and 72 hours after surgery]
• Arterial oxygen saturation [Срок оценки: 0, 12, 24, 36, 48, 60, and 72 hours after surgery]
• Arterial lactate concentration [Срок оценки: 0, 12, 24, 36, 48, 60, and 72 hours after surgery]
• Duration of mechanical ventilation [Срок оценки: From postoperative ICU admission until successful discontinuation of invasive mechanical ventilation, assessed up to 72 hours after surgery.]
• PICU length of stay [Срок оценки: 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) [Срок оценки: Baseline, 24, 48, and 72 hours after surgery]
• Plasma lidocaine concentration [Срок оценки: 6, 12, 18, 24 hours after surgery]
• Incidence of postoperative pulmonary complications [Срок оценки: Assessed within 72 hours after surgery]
• Prothrombin time (PT) [Срок оценки: Baseline, 24, 48, and 72 hours after surgery]
• Activated partial thromboplastin time (aPTT) [Срок оценки: Baseline, 24, 48, and 72 hours after surgery]
• Alanine aminotransferase (ALT) [Срок оценки: Baseline, 24, 48, and 72 hours after surgery]

Критерии участия

Критерии включения

• Infants aged 0 to 12 months.
• Congenital heart disease requiring corrective, non-palliative cardiac surgery with cardiopulmonary bypass.
• American Society of Anesthesiologists (ASA) physical status I to III.
• Written informed consent provided by parent(s) or legal guardian(s).

Критерии исключения

• Multiple malformations, chromosomal abnormalities, or immunodeficiency.
• Known or suspected allergy to lidocaine.
• Concomitant continuous infusion of another local anesthetic.
• Conditions associated with increased risk of lidocaine accumulation or toxicity, including severe conduction block or severe bradycardia.
• ASA physical status IV or higher.
• Severe malnutrition expected to substantially impair postoperative recovery.
• Severe hepatic or renal dysfunction.
• Significant pre-existing pulmonary disease or markedly impaired preoperative pulmonary function.
• Central nervous system disorders that may increase susceptibility to lidocaine neurotoxicity, including epilepsy or prior central nervous system infection.
• 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.
• Current or recent participation in another interventional clinical trial in its active intervention phase.

Критерии приведены из реестра в оригинале (на английском). Окончательную оценку соответствия проводит исследовательский центр.

Здоровые добровольцы: Нет

Дизайн исследования

Распределение

Рандомизированное

Модель

Параллельные группы

Маскирование

Четверное слепое

Основная цель

Профилактика

Центры проведения

Китай · 1 центр

• Children's Hospital, Zhejiang University School of Medicine — Ханчжоу

Публикации

• 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. PMID 32994986
• 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 PMID 39780778
• 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. PMID 29609129
• 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. PMID 20740215
• 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. PMID 37408557
• 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. PMID 29864216
• 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. PMID 36933017
• 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. PMID 35094928

Идентификаторы

NCT: NCT07499154 · 2026-IRB-0031-P-01

Первоисточники (государственные реестры)

• ClinicalTrials.gov (NIH, США)

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