Kolcz Jacek, Karnas Elzbieta, Madeja Zbigniew, Zuba-Surma Ewa K
Department of Pediatric Cardiac Surgery, Jagiellonian University Medical College, Wielicka 265 Street, 30-663, Krakow, Poland.
Department of Cell Biology, Faculty of Biochemistry, Biophysics and Biotechnology, Jagiellonian University, Krakow, Poland.
J Intensive Care. 2022 Oct 13;10(1):48. doi: 10.1186/s40560-022-00639-y.
Fontan surgery with cardiopulmonary bypass (CPB) causes tremendous systemic stress and inflammatory responses, affecting postoperative organ function, morbidity, and mortality. Although this reaction triggers partially protective anti-inflammatory responses, it is harmful in patients with single ventricle congenital heart defects. Despite decades of research, an effective anti-inflammatory and stress defense strategy is lacking. This study investigated the influence of inhaled nitric oxide (NO) during CPB on early clinical results, including the duration of postoperative respiratory support as a primary outcome and a panel of laboratory analytes.
In this study, 115 patients were randomized to the Fontan-NO group (n = 48) and the Fontan group (n = 49). Eighteen patients were excluded from the study. The Fontan-NO group received NO inhaled directly into the oxygenator during CPB. Clinical data were collected, and blood samples were drawn for analysis at repeated intervals. Multiplex assays were used to analyze a proteome profile of molecules involved in stress response, inflammation, metabolic reactions, as well as heart and lung protection.
Fontan-NO patients had significantly shorter respiratory support time with a median of 9.3 h (7.0; 13,2) vs 13.9 h (3.7; 18.5) by the absolute difference of 4.6 h [95% confidence interval, - 30.9 to 12.3; (p = 0.03)]. In addition, they have a shorter time in intensive care (p = 0.04) and lower pulmonary artery pressure after CPB discontinuation (p = 0.04), 4 h (p = 0.03) and 8 h (p = 0.03) after surgery. Fontan-NO patients also had a lower concentration of lactates (p = 0.04) and glucose after separation from CPB (p = 0.02) and lower catecholamine index (p = 0.042). Plasma factors analysis has shown a significantly higher concentration of interleukin-10, and a lower concentration of interleukin-6, interleukin-8, interleukin-1β, pentraxin, matrix metalloproteinase-8, troponin-I, creatine kinase myocardial band (CK-MB), and insulin in Fontan-NO group.
NO inhaled into the oxygenator during CPB can improve short-term clinical outcomes. It shortens intubation time and intensive care time. It reduces inflammatory response, improves myocardial and lung protection, and diminishes metabolic stress in patients with a single ventricle undergoing Fontan surgery.
The trial was preregistered, supervised, and supported by The Polish National Science Center ( NCN/01/B/NZ5/04246 ).
体外循环（CPB）下的Fontan手术会引发巨大的全身应激和炎症反应，影响术后器官功能、发病率和死亡率。尽管这种反应会触发部分保护性抗炎反应，但对单心室先天性心脏缺陷患者却是有害的。尽管经过了数十年的研究，但仍缺乏有效的抗炎和应激防御策略。本研究调查了CPB期间吸入一氧化氮（NO）对早期临床结果的影响，包括术后呼吸支持时间作为主要结局以及一组实验室分析指标。
在本研究中，115例患者被随机分为Fontan-NO组（n = 48）和Fontan组（n = 49）。18例患者被排除在研究之外。Fontan-NO组在CPB期间将NO直接吸入氧合器。收集临床数据，并在不同时间间隔采集血样进行分析。采用多重分析方法分析参与应激反应、炎症、代谢反应以及心肺保护的分子蛋白质组图谱。
Fontan-NO组患者的呼吸支持时间明显缩短，中位数为9.3小时（7.0；13.2），而Fontan组为13.9小时（3.7；18.5），绝对差值为4.6小时[95%置信区间，-30.9至12.3；（p = 0.03）]。此外，他们在重症监护室的时间更短（p = 0.04），CPB停止后4小时（p = 0.03）和8小时（p = 0.03）的肺动脉压力更低（p = 0.04）。Fontan-NO组患者在脱离CPB后的乳酸浓度（p = 0.04）和葡萄糖浓度（p = 0.02）也更低，儿茶酚胺指数更低（p = 0.042）。血浆因子分析显示，Fontan-NO组白细胞介素-10浓度显著更高，白细胞介素-6、白细胞介素-8、白细胞介素-1β、五聚素、基质金属蛋白酶-8、肌钙蛋白-I、肌酸激酶心肌型（CK-MB）和胰岛素浓度更低。
CPB期间将NO吸入氧合器可改善短期临床结局。它缩短了插管时间和重症监护时间。它减轻了炎症反应，改善了心肌和肺保护，并减轻了接受Fontan手术的单心室患者的代谢应激。
该试验已由波兰国家科学中心预先注册、监督和支持（NCN/01/B/NZ5/04246）。
