Goldstein Stephanie A, Beshish Asaad G, Bush Lauren B, Lowery Ray E, Wong Joshua H, Schumacher Kurt R, Halligan Nadine L N, Cornell Timothy T, Rocchini Albert P
University of Michigan Congenital Heart Center, 1540 E. Hospital Dr, Ann Arbor, MI, 48109, USA.
Lucile Packard Children's Hospital, Palo Alto, CA, USA.
Pediatr Cardiol. 2019 Apr;40(4):744-752. doi: 10.1007/s00246-019-02059-6. Epub 2019 Feb 1.
Prolonged pleural drainage is a common complication in patients after Fontan palliation and is associated with short- and long- term morbidities. Among many potential etiologies, prolonged drainage has an inflammatory component, but there are no descriptions of cytokines in Fontan pleural drainage to date. This study aimed to examine the inflammatory make-up of Fontan pleural drainage. This prospective age-range-matched cohort study recruited 25 patients undergoing Fontan procedure and 15 bi-ventricular patients undergoing cardiopulmonary bypass (CPB). Chest tube samples were taken on postoperative day (POD) 1-4, 7, and 10. Cytokines were measured using Bio-Plex Assays. Univariate comparisons were made in patient characteristics and cytokine levels. Median age was 3.7 y (IQR 2.8-3.9) for controls and 2.5 y (IQR 2.1-2.9) in Fontan patients (p = 0.02). Median drainage duration and daily volume was higher in Fontan patients (both p < 0.001). Inflammatory cytokines (IL-17A, IFN-y, MIP-1β, and TNF-α) were higher in Fontan patients than controls (all p < 0.02). There was an increase in pro-inflammatory cytokines (IL-8, MIP-1β, and TNF-α) from POD1 to the last chest tube day (LCD) in Fontan patients (all p < 0.0001) and a decrease in the anti-inflammatory cytokine IL-10 (p = 0.001). There was no difference in cytokine concentration from POD1 to LCD among controls. There was a significant association with the cytokine concentration of TNF-α on POD1 and duration of chest tube drainage (p < 0.05). Inflammatory cytokine levels in the pleural fluid of Fontan patients are higher compared to bi-ventricular controls and rise over time where controls do not. This suggests ongoing localized inflammation that is not a result of CPB alone and may be an important contributor to pleural drainage in patients after the Fontan procedure.
长期胸腔引流是Fontan姑息治疗后患者常见的并发症，与短期和长期发病率相关。在众多潜在病因中，长期引流有炎症成分，但迄今为止尚无关于Fontan胸腔引流中细胞因子的描述。本研究旨在检测Fontan胸腔引流的炎症构成。这项前瞻性年龄范围匹配的队列研究招募了25例接受Fontan手术的患者和15例接受体外循环（CPB）的双心室患者。在术后第1 - 4天、第7天和第10天采集胸管样本。使用生物芯片分析测定细胞因子。对患者特征和细胞因子水平进行单因素比较。对照组的中位年龄为3.7岁（四分位间距2.8 - 3.9），Fontan患者为2.5岁（四分位间距2.1 - 2.9）（p = 0.02）。Fontan患者的中位引流持续时间和每日引流量更高（均p < 0.001）。Fontan患者的炎症细胞因子（IL - 17A、IFN - γ、MIP - 1β和TNF - α）高于对照组（均p < 0.02）。Fontan患者从术后第1天到最后一次胸管置管日（LCD）促炎细胞因子（IL - 8、MIP - 1β和TNF - α）增加（均p < 0.0001），抗炎细胞因子IL - 10减少（p = 0.001）。对照组从术后第1天到LCD细胞因子浓度无差异。术后第1天TNF - α的细胞因子浓度与胸管引流持续时间有显著相关性（p < 0.05）。与双心室对照组相比，Fontan患者胸腔积液中的炎症细胞因子水平更高，且随时间升高，而对照组则不然。这表明存在持续的局部炎症，并非仅由CPB导致，可能是Fontan手术后患者胸腔引流的重要原因。
