Benscoter Alexis L, Alten Jeffrey A, Atreya Mihir R, Cooper David S, Byrnes Jonathan W, Nelson David P, Ollberding Nicholas J, Wong Hector R
University of Cincinnati College of Medicine, Cincinnati Children's Hospital Medical Center.
University of Cincinnati, Cincinnati Children's Hospital Medical Center.
Res Sq. 2023 Jan 27:rs.3.rs-2488327. doi: 10.21203/rs.3.rs-2488327/v1.
Multiple organ dysfunction syndrome (MODS) is an important cause of post-operative morbidity and mortality for children undergoing cardiac surgery requiring cardiopulmonary bypass (CPB). Dysregulated inflammation is widely regarded as a key contributor to bypass-related MODS pathobiology, with considerable overlap of pathways associated with septic shock. The pediatric sepsis biomarker risk model (PERSEVERE) is comprised of seven protein biomarkers of inflammation, and reliably predicts baseline risk of mortality and organ dysfunction among critically ill children with septic shock. We aimed to determine if PERSEVERE biomarkers and clinical data could be combined to derive a new model to assess the risk of persistent CPB-related MODS in the early post-operative period. This study included 306 patients <18 years old admitted to a pediatric cardiac ICU after surgery requiring cardiopulmonary bypass (CPB) for congenital heart disease. Persistent MODS, defined as dysfunction of two or more organ systems on postoperative day 5, was the primary outcome. PERSEVERE biomarkers were collected 4 and 12 hours after CPB. Classification and Regression Tree methodology was used to derive a model to assess the risk of persistent MODS. The optimal model containing interleukin-8 (IL-8), chemokine ligand 3 (CCL3), and age as predictor variables, had an area under the receiver operating characteristic curve (AUROC) of 0.86 (0.81-0.91) for differentiating those with or without persistent MODS, and a negative predictive value of 99% (95-100). Ten-fold cross-validation of the model yielded a corrected AUROC of 0.75. We present a novel risk prediction model to assess the risk for development of multiple organ dysfunction after pediatric cardiac surgery requiring CPB. Pending prospective validation, our model may facilitate identification of a high-risk cohort to direct interventions and studies aimed at improving outcomes via mitigation of post-operative organ dysfunction. This study does not meet criteria for a clinical trial per the WHO International Clinical Trials Registry Platform as no intervention was performed.
多器官功能障碍综合征(MODS)是接受需要体外循环(CPB)的心脏手术的儿童术后发病和死亡的重要原因。炎症调节失控被广泛认为是与体外循环相关的MODS病理生物学的关键因素,与脓毒性休克相关的途径有相当多的重叠。儿童脓毒症生物标志物风险模型(PERSEVERE)由七种炎症蛋白生物标志物组成,可可靠地预测脓毒性休克重症患儿的基线死亡风险和器官功能障碍。我们旨在确定是否可以将PERSEVERE生物标志物和临床数据结合起来,得出一个新模型,以评估术后早期持续性CPB相关MODS的风险。本研究纳入了306例18岁以下因先天性心脏病接受需要体外循环(CPB)手术的患儿,术后入住儿科心脏重症监护病房。持续性MODS定义为术后第5天两个或更多器官系统功能障碍,是主要结局。在CPB后4小时和12小时收集PERSEVERE生物标志物。采用分类与回归树方法得出一个评估持续性MODS风险的模型。包含白细胞介素-8(IL-8)、趋化因子配体3(CCL3)和年龄作为预测变量的最佳模型,用于区分有无持续性MODS的受试者工作特征曲线下面积(AUROC)为0.86(0.81 - 0.91),阴性预测值为99%(95 - 100)。该模型的十折交叉验证得出校正后的AUROC为0.75。我们提出了一种新的风险预测模型,以评估接受需要CPB的小儿心脏手术后发生多器官功能障碍的风险。在进行前瞻性验证之前,我们的模型可能有助于识别高危队列,以指导旨在通过减轻术后器官功能障碍来改善结局的干预措施和研究。根据世界卫生组织国际临床试验注册平台的标准,本研究不符合临床试验的标准,因为未进行干预。