Mittel Aaron, Drubin Casey, Hua May, Nitta Suzuka, Wagener Gebhard, Vidal Melo Marcos F
From the Department of Anesthesiology, Columbia University Irving Medical Center, New York, New York.
Anesth Analg. 2025 Apr 1;140(4):947-956. doi: 10.1213/ANE.0000000000007122. Epub 2024 Aug 8.
Postoperative pulmonary complications (PPCs) occur frequently after cardiac surgery. Absolute postoperative values of biomarkers of inflammation (interleukin [IL]-6, IL-8, and tumor necrosis factor-alpha [TNF-α]) and alveolar epithelial injury (soluble receptor for advanced glycation end-products [sRAGE]) have been associated with hypoxia and prolonged ventilation. However, relationships between these biomarkers and PPCs, contextualized to preoperative inflammation and perioperative lung injury risk factors, are uncertain. We aimed to determine associations between perioperative increases in biomarkers of inflammation and alveolar epithelial injury with a patient-centric PPC definition in adult cardiac surgical patients, accounting for the influence of intraoperative risk factors for lung injury.
Adults undergoing elective cardiac surgery were eligible for this observational cohort study. Blood concentrations of IL-6, IL-8, TNF-α, and sRAGE were collected after anesthesia induction (baseline) and on postoperative day 1 (POD 1). The primary outcome was the occurrence of moderate or severe PPCs, graded using a validated scale, in POD 0 to 7. We estimated the association between POD 1 IL-6, IL-8, TNF-α, and sRAGE concentrations and moderate/severe PPC presence using separate logistic regression models for each biomarker, adjusted for baseline biomarker values and risk factors for postoperative lung injury (age, baseline PaO 2 /F i O 2 , left ventricle ejection fraction [LVEF], procedural type, cardiopulmonary bypass duration, and transfusions). Covariables were chosen based on relevance to lung injury and unadjusted between-group differences among patients with versus without PPCs. The secondary outcome was postoperative ventilation duration, which was log-transformed and analyzed using linear regression, adjusted using the same variables as the primary outcome.
We enrolled 204 patients from 2016 to 2018. Biomarkers were analyzed in 2023 among 175 patients with complete data. In adjusted analyses, POD 1 IL-8 and IL-6 were significantly associated with moderate/severe PPCs. The odds ratio (OR) for developing a PPC for every 50 pg/mL increase in POD 1 IL-8 was 7.19 (95% confidence interval [CI], 2.13-28.53, P = .003) and 1.42 (95% CI, 1.13-1.93, P = .01) for every 50 pg/mL increase in POD 1 IL-6. In adjusted analyses, postoperative ventilation duration was significantly associated with POD 1 sRAGE; each 50 pg/mL increase in sRAGE was associated with a 25% (95% CI, 2%-52%, P = .03) multiplicative increase in hours of ventilation. TNF-α was not significantly associated with PPCs or ventilation duration.
Acute systemic inflammation is significantly associated with PPCs after elective cardiac surgery in adults when taking into consideration preoperative inflammatory burden and perioperative factors that may influence postoperative lung injury.
心脏手术后肺部并发症(PPCs)很常见。炎症生物标志物(白细胞介素[IL]-6、IL-8和肿瘤坏死因子-α[TNF-α])和肺泡上皮损伤(晚期糖基化终产物可溶性受体[sRAGE])的术后绝对值与缺氧和通气时间延长有关。然而,这些生物标志物与PPCs之间的关系,结合术前炎症和围手术期肺损伤风险因素来看,尚不确定。我们旨在确定成年心脏手术患者中,以患者为中心的PPC定义下,围手术期炎症生物标志物和肺泡上皮损伤增加之间的关联,并考虑术中肺损伤风险因素的影响。
接受择期心脏手术的成年人符合本观察性队列研究的条件。在麻醉诱导后(基线)和术后第1天(POD 1)采集IL-6、IL-8、TNF-α和sRAGE的血药浓度。主要结局是在POD 0至7天内发生中度或重度PPCs,使用经过验证的量表进行分级。我们使用针对每个生物标志物的单独逻辑回归模型,估计POD 1时IL-6、IL-8、TNF-α和sRAGE浓度与中度/重度PPCs存在之间的关联,并对基线生物标志物值和术后肺损伤风险因素(年龄、基线PaO₂/F i O₂、左心室射血分数[LVEF]、手术类型、体外循环持续时间和输血)进行调整。根据与肺损伤的相关性以及有或无PPCs患者之间未调整的组间差异选择协变量。次要结局是术后通气时间,对其进行对数转换并使用线性回归分析,使用与主要结局相同的变量进行调整。
我们在2016年至2018年招募了204名患者。在175名有完整数据的患者中对2023份生物标志物进行了分析。在调整分析中,POD 1时的IL-8和IL-6与中度/重度PPCs显著相关。POD 1时IL-8每增加50 pg/mL发生PPC的比值比(OR)为7.1(95%置信区间[CI],2.13 - 28.53,P = 0.003),POD 1时IL-6每增加50 pg/mL为1.42(95%CI,1.13 - 1.93,P = 0.01)。在调整分析中,术后通气时间与POD 1时的sRAGE显著相关;sRAGE每增加50 pg/mL,通气小时数增加25%(95%CI,2% - 52%,P = 0.03)。TNF-α与PPCs或通气时间无显著关联。
在考虑术前炎症负担和可能影响术后肺损伤的围手术期因素时,急性全身炎症与成年择期心脏手术后的PPCs显著相关。