Efficacy and safety of early nitric oxide inhalation therapy after congenital heart surgery

doi:10.3877/cma.j.issn.2095-6568.2023.04.004

Abstract

Abstract:

Objective

To investigate the stability, safety and efficacy of a new domestic portable nitric oxide (NO) generator in children with pulmonary hypertension after surgery for congenital heart disease.

Methods

Children with refractory pulmonary hypertension after congenital heart disease from October 2022 to September 2023 were continuously enrolled in Heart Center of Shanghai Children's Medical Center. Basic information, diagnosis, ventilator parameters, concentration and duration of NO treatment, hemodynamic indexes and biochemical indexes were collected. The stability of the gas concentration of the portable NO generator in the early 24 hours after surgery were evaluated. The concentrations of related gases including nitrogen dioxide and methemoglobin were tested to evaluate the safety. Pulmonary artery pressure, oxygenation index, central venous pressure (CVP), N-terminal pro-B-type natriuretic(NT-proBNP), urine output, serum creatinine before and after NO inhalation therapy were compared to evaluate the effectiveness.

Results

Among the 18 children, 8 were males,and 10 were females, with a median,weight of 11.0 (3.4,22.3) kg, a median age of 422.5 (44.0,2 327.3) d, a preoperative percutaneous arterial oxygen saturation (SPO₂) of (84.3±11.7)%, 12 cases with biventricular correction, and 6 cases with single ventricular correction. The inhalation treatment time of NO was (95±11.2) h, the concentration of inhaled NO ranged from 3-80 (19±3.5)ppm. The tidal volume on the ventilator was 25-290 ml. The mortality rate was 16.7% in 3 children, and the causes of death were sepsis, right heart failure and multiorgan insufficiency. After inhalation, the mean pulmonary artery pressure decreased significantly [(50.2±20.6) mmHg vs. (28.6±10.5) mmHg, P=0.01), CVP decreased significantly [(15.3±2.1) mmHg vs. (13.8±1.3) mmHg, P<0.01], NT-proBNP decreased significantly [(10 583.9±7 938.4) pg/ml vs. 9 (866.0±7 802.5) pg/ml, P=0.02], and oxygenation index was significantly increased. [(91.4±35.9)% vs. (103.4±39.9)%, P<0.01] The concentration of nitrogen dioxide was (0.1±0.02) ppm, the content of methemoglobin was 0.9±0.6%, and the maximum content was 2.8%. All within the safe range.

Conclusion

The NO concentration produced by this domestic portable NO generator is stable, which can significantly reduce the pulmonary artery pressure and central venous pressure in children with pulmonary hypertension refractory to congenital heart disease surgery, significantly improve the oxygenation index with the related products including nitrogen dioxide and methemoglobin within the safe range, which is safe and effective.

Key words: Nitric oxide, Congenital heart disease, Pulmonary hypertension, Portable, Inhalation

Mingjie Zhang, Liping Liu, Chunxiang Li, Yujie Liu, Zhuoming Xu. Efficacy and safety of early nitric oxide inhalation therapy after congenital heart surgery[J]. Chinese Journal of Heart and Heart Rhythm(Electronic Edition), 2023, 11(04): 210-215.

/ / Recommend

Add to citation manager EndNote|Ris|BibTeX

URL: https://zhxzyxldzzz.cma-cmc.com.cn/EN/10.3877/cma.j.issn.2095-6568.2023.04.004

https://zhxzyxldzzz.cma-cmc.com.cn/EN/Y2023/V11/I04/210

Figures/Tables 4

项目	总体
男［例（%）］	8（44.4）
体重（kg， $x ¯ ± s$ ）	11（3.4，22.3）
身高（cm， $x ¯ ± s$ ）	87.5（53.7，107.3）
年龄（d， $x ¯ ± s$ ）	422.5（44.0，2 327.3）
术前SPO₂（%， $x ¯ ± s$ ）	84.3±11.7
双心室［例（%）］	12（66.7）
单心室［例（%）］	6（33.3）
延迟关胸［例（%）］	4（22.2）
CPB时间（min， $x ¯ ± s$ ）	101.0±56.9
AC时间（min， $x ¯ ± s$ ）	92.5±58.2

项目	总体
男［例（%）］	8（44.4）
体重（kg， $x ¯ ± s$ ）	11（3.4，22.3）
身高（cm， $x ¯ ± s$ ）	87.5（53.7，107.3）
年龄（d， $x ¯ ± s$ ）	422.5（44.0，2 327.3）
术前SPO₂（%， $x ¯ ± s$ ）	84.3±11.7
双心室［例（%）］	12（66.7）
单心室［例（%）］	6（33.3）
延迟关胸［例（%）］	4（22.2）
CPB时间（min， $x ¯ ± s$ ）	101.0±56.9
AC时间（min， $x ¯ ± s$ ）	92.5±58.2

临床数据	吸入前	吸入后	P值
平均肺动脉压力（mmHg， $x ¯ ± s$ ）	50.2±20.6	28.6±10.5	0.01
CVP（mmHg， $x ¯ ± s$ ）	15.3±2.1	13.8±1.3	<0.001
IS（分， $x ¯ ± s$ ）	73.6±19.5	72.5±18.6	0.71
氧合指数（%， $x ¯ ± s$ ）	91.4±35.9	103.4±39.9	<0.001
尿量［ml/（kg·hr） $x ¯ ± s$ ］	2.5±0.7	2.6±0.8	0.68
肌酐（mmol/L， $x ¯ ± s$ ）	43.1±12.5	42.1±11.7	0.67
NT-proBNP（pg/ml， $x ¯ ± s$ ）	10 583.9±7 938.4	9 866.0±7 802.5	0.02

临床数据	吸入前	吸入后	P值
平均肺动脉压力（mmHg， $x ¯ ± s$ ）	50.2±20.6	28.6±10.5	0.01
CVP（mmHg， $x ¯ ± s$ ）	15.3±2.1	13.8±1.3	<0.001
IS（分， $x ¯ ± s$ ）	73.6±19.5	72.5±18.6	0.71
氧合指数（%， $x ¯ ± s$ ）	91.4±35.9	103.4±39.9	<0.001
尿量［ml/（kg·hr） $x ¯ ± s$ ］	2.5±0.7	2.6±0.8	0.68
肌酐（mmol/L， $x ¯ ± s$ ）	43.1±12.5	42.1±11.7	0.67
NT-proBNP（pg/ml， $x ¯ ± s$ ）	10 583.9±7 938.4	9 866.0±7 802.5	0.02

References 20

[1]	Clark RH, Kueser TJ, Walker MW, et al. Low-dose nitric oxide therapy for persistent pulmonary hypertension of the newborn. Clinical Inhaled Nitric Oxide Research Group[J]. N Engl J Med, 2000, 342(7):469-474.
[2]	Liu Y, Zhu Y, Jiang C, et al. An electrochemical nitric oxide generator for in-home inhalation therapy in pulmonary artery hypertension[J]. BMC Med, 2022, 20(1):481.
[3]	Kirbas A, Yalcin Y, Tanrikulu N, et al. Comparison of inhaled nitric oxide and aerosolized iloprost in pulmonary hypertension in children with congenital heart surgery[J]. Cardiol J, 2012, 19(4):387-394.
[4]	Liu K, Wang H, Yu SJ, et al. Inhaled pulmonary vasodilators: a narrative review[J]. Ann Transl Med, 2021, 9(7):597.
[5]	Legrand M, Mebazaa A, Ronco C, et al. When cardiac failure, kidney dysfunction, and kidney injury intersect in acute conditions: the case of cardiorenal syndrome[J]. Crit Care Med, 2014, 42(9):2109-2017.
[6]	Coutrot M, Dépret F, Legrand M. Is Nitric oxide nephro- or cardioprotective?[J]. Am J Respir Crit Care Med, 2019, 199(11):1441-1442.
[7]	中华医学会小儿外科分会心脏学组, 国家儿童医学中心心血管专科联盟. 儿童先天性心脏病相关性肺高压诊断与治疗指南[J]. 中华小儿外科杂志, 2022, 43(11):966-980.
[8]	Hopkins RA, Bull C, Haworth SG, et al. Pulmonary hypertensive crises following surgery for congenital heart defects in young children[J]. Eur J Cardiothorac Surg, 1991, 5(12):628-634.
[9]	Hoskote A, Carter C, Rees P, et al. Acute right ventricular failure after pediatric cardiac transplant: predictors and long-term outcome in current era of transplantation medicine[J]. J Thorac Cardiovasc Surg, 2010, 139(1):146-153.
[10]	Carmona MJ, Auler JO. Effects of inhaled nitric oxide on respiratory system mechanics, hemodynamics, and gas exchange after cardiac surgery[J]. J Cardiothorac Vasc Anesth, 1998, 12(2):157-161.
[11]	Fullerton DA, Jones SD, Jaggers J, et al. Effective control of pulmonary vascular resistance with inhaled nitric oxide after cardiac operation[J]. J Thorac Cardiovasc Surg, 1996, 111(4):753-763.
[12]	Gianetti J, Del Sarto P, Bevilacqua S, et al. Supplemental nitric oxide and its effect on myocardial injury and function in patients undergoing cardiac surgery with extracorporeal circulation[J]. J Thorac Cardiovasc Surg, 2004, 127(1):44-50.
[13]	Rich GF, Murphy GD, Roos CM, et al. Inhaled nitric oxide. selective pulmonary vasodilation in cardiac surgical patients[J]. Anesthesiology, 1993, 78(6):1028-1035.
[14]	Morris K, Beghetti M, Petros A, et al. Comparison of hyperventilation and inhaled nitric oxide for pulmonary hypertension after repair of congenital heart disease[J]. Crit Care Med, 2000, 28(8):2974-2978.
[15]	Wessel DL, Adatia I, Giglia TM, et al. Use of inhaled nitric oxide and acetylcholine in the evaluation of pulmonary hypertension and endothelial function after cardiopulmonary bypass[J]. Circulation, 1993, 88(5 Pt 1):2128-2138.
[16]	Turanlahti MI, Laitinen PO, Pesonen EJ. Preoperative and postoperative response to inhaled nitric oxide[J]. Scand Cardiovasc J, 2000, 34(1):46-52.
[17]	Miller OI, Tang SF, Keech A, et al. Inhaled nitric oxide and prevention of pulmonary hypertension after congenital heart surgery: a randomised double-blind study[J]. Lancet, 2000, 356(9240):1464-1469.
[18]	Yoshimura N, Yamaguchi M, Oka S, et al. Inhaled nitric oxide therapy after Fontan-type operations[J]. Surg Today, 2005, 35(1):31-35.
[19]	Ma M, Gauvreau K, Allan CK, et al. Causes of death after congenital heart surgery[J]. Ann Thorac Surg, 2007, 83(4):1438-1445.
[20]	Curran RD, Mavroudis C, Backer CL, et al. Inhaled nitric oxide for children with congenital heart disease and pulmonary hypertension[J]. Ann Thorac Surg, 1995, 60(6):1765-1771.

Please choose a citation manager

Content to export