澳大利亚墨尔本皇家儿童医院Warwick Butt团队研究了体外循环一氧化氮对婴幼儿先天性心脏病手术无呼吸机天数的影响。相关论文发表在2022年6月27日出版的《美国医学会杂志》上。

在接受心脏手术的儿童中，向体外循环氧合器的气流中注入一氧化氮可减少术后低心排血量综合征，从而改善恢复，缩短呼吸支持时间。目前尚不清楚，在体外循环氧合器中注入一氧化氮是否能改善无呼吸机天数（存活且无机械通气天数）。

为了确定一氧化氮应用于体外循环氧合器与标准护理对接受先天性心脏病手术的儿童无呼吸机天数的影响，研究组在澳大利亚、新西兰和荷兰的6个儿童心脏外科中心进行了一项双盲、多中心、随机临床试验。2017年7月至2021年4月，共招募1371名2岁以下接受先天性心脏手术的儿童，最后一名参与者的28天随访于2021年5月24日完成。

患儿被随机分配接受浓度为20 ppm的一氧化氮注入体外循环氧合器（679例）或无一氧化氮的标准护理体外循环（685例）。主要终点是从开始旁路手术到第28天的无呼吸机天数。有4个次要终点，包括低心排血量综合征、体外生命支持或死亡；在重症监护病房的住院时间；住院时间；以及术后肌钙蛋白水平。

1371名随机分组的患儿平均年龄为21.2周；587名为女孩（42.8%），1364名（99.5%）完成了试验。一氧化氮组和标准治疗组的中位无呼吸机天数分别为26.6天和26.4天，无显著差异。一氧化氮组中有22.5%的患儿在48小时内出现低心排血量综合征，48小时内需要体外支持，或在28天内死亡；标准护理组中有20.9%，校正后的优势比为1.12。两组之间的其他次要结局没有显著差异。

研究结果表明，在2岁以下因先天性心脏病手术接受体外循环的幼儿中，通过体外循环使用一氧化氮对无呼吸机天数没有显著影响。该发现不支持在心脏手术期间使用一氧化氮输送至体外循环氧合器。

附：英文原文

Title: Effect of Nitric Oxide via Cardiopulmonary Bypass on Ventilator-Free Days in Young Children Undergoing Congenital Heart Disease Surgery: The NITRIC Randomized Clinical Trial

Author: Luregn J. Schlapbach, Kristen S. Gibbons, Stephen B. Horton, Kerry Johnson, Debbie A. Long, David H. F. Buckley, Simon Erickson, Marino Festa, Yves d’Udekem, Nelson Alphonso, David S. Winlaw, Carmel Delzoppo, Kim van Loon, Mark Jones, Paul J. Young, Warwick Butt, Andreas Schibler, NITRIC Study Group, the Australian and New Zealand Intensive Care Society Clinical Trials Group (ANZICS CTG), and the ANZICS Paediatric Study Group (PSG), Johnny Millar, Kate Masterson, John Beca, Taryn Evans, Shelley Coetzer, Claire Sherring, Jennifer Darvas, Killian OShaughnessy, Chong Tien Goh, Gail Harper, Sam Barr, Rae Kelly, Hannah Thomson, Kelly Holmes, Nigel Slade, David Andrews, Carla Zazulak, Benjamin Anderson, Antje Blumenthal, Jonas Fooken, Endrias Ergetu, Brenda Gannon, Renate Le Marsney, Trang Pham, Annelies Hennink, Erik Koomen, Nicole J.C.W. van Belle-van Haaren, Bram van Wijk

Issue&Volume: 2022-06-27

Abstract:

Importance  In children undergoing heart surgery, nitric oxide administered into the gas flow of the cardiopulmonary bypass oxygenator may reduce postoperative low cardiac output syndrome, leading to improved recovery and shorter duration of respiratory support. It remains uncertain whether nitric oxide administered into the cardiopulmonary bypass oxygenator improves ventilator-free days (days alive and free from mechanical ventilation).

Objective  To determine the effect of nitric oxide applied into the cardiopulmonary bypass oxygenator vs standard care on ventilator-free days in children undergoing surgery for congenital heart disease.

Design, Setting, and Participants  Double-blind, multicenter, randomized clinical trial in 6 pediatric cardiac surgical centers in Australia, New Zealand, and the Netherlands. A total of 1371 children younger than 2 years undergoing congenital heart surgery were randomized between July 2017 and April 2021, with 28-day follow-up of the last participant completed on May 24, 2021.

Interventions  Patients were assigned to receive nitric oxide at 20 ppm delivered into the cardiopulmonary bypass oxygenator (n=679) or standard care cardiopulmonary bypass without nitric oxide (n=685).

Main Outcomes and Measures  The primary end point was the number of ventilator-free days from commencement of bypass until day 28. There were 4 secondary end points including a composite of low cardiac output syndrome, extracorporeal life support, or death; length of stay in the intensive care unit; length of stay in the hospital; and postoperative troponin levels.

Results  Among 1371 patients who were randomized (mean [SD] age, 21.2 [23.5] weeks; 587 girls [42.8%]), 1364 (99.5%) completed the trial. The number of ventilator-free days did not differ significantly between the nitric oxide and standard care groups, with a median of 26.6 days (IQR, 24.4 to 27.4) vs 26.4 days (IQR, 24.0 to 27.2), respectively, for an absolute difference of 0.01 days (95% CI, 0.25 to 0.22; P=.92). A total of 22.5% of the nitric oxide group and 20.9% of the standard care group developed low cardiac output syndrome within 48 hours, needed extracorporeal support within 48 hours, or died by day 28, for an adjusted odds ratio of 1.12 (95% CI, 0.85 to 1.47). Other secondary outcomes were not significantly different between the groups.

Conclusions and Relevance  In children younger than 2 years undergoing cardiopulmonary bypass surgery for congenital heart disease, the use of nitric oxide via cardiopulmonary bypass did not significantly affect the number of ventilator-free days. These findings do not support the use of nitric oxide delivered into the cardiopulmonary bypass oxygenator during heart surgery.

DOI: 10.1001/jama.2022.9376

Source: https://jamanetwork.com/journals/jama/fullarticle/2793781