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Biomarker-based risk model to predict persistent multiple organ dysfunctions after congenital heart surgery â€" A
Alexis L Benscoter1, Jeffrey A Alten1, Mihir R Atreya2
1University of Cincinnati College of Medicine, Cincinnati Children's Hospital Medical Center.
Insights
A new model using IL-8, CCL3, and age predicts persistent multiple organ dysfunction syndrome (MODS) in children after cardiac surgery. This tool aids early identification of high-risk patients for targeted interventions.
Area of Science:
- Pediatric critical care medicine
- Cardiovascular surgery outcomes
- Inflammatory biomarkers in critical illness
Background:
- Pediatric cardiac surgery patients are at risk for multiple organ dysfunction syndrome (MODS) post-cardiopulmonary bypass (CPB).
- Inflammation plays a key role in CPB-related MODS, similar to septic shock pathways.
- The PERSEVERE model identifies sepsis risk, prompting investigation for its application in post-CPB MODS prediction.
Approach:
- A cohort of 306 pediatric patients undergoing CPB for congenital heart disease was studied.
- Persistent MODS was defined as dysfunction in ≥2 organ systems on postoperative day 5.
- Classification and Regression Trees were used to develop a predictive model incorporating PERSEVERE biomarkers and clinical data.
Key Points:
- An optimal risk prediction model included interleukin-8 (IL-8), chemokine ligand 3 (CCL3), and patient age.
- The model demonstrated strong discrimination for persistent MODS with an AUROC of 0.86.
- A high negative predictive value of 99% was achieved, indicating excellent rule-out capability.
Conclusions:
- A novel risk prediction model for persistent MODS after pediatric cardiac surgery requiring CPB has been developed.
- This model utilizes readily available biomarkers and clinical data for early risk stratification.
- Further prospective validation is needed to confirm its utility in guiding interventions to mitigate post-operative organ dysfunction.
Abstract:
Background: 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. Methods: 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. Results: 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. Conclusions: 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. Clinical Trial Registration Number: This study does not meet criteria for a clinical trial per the WHO International Clinical Trials Registry Platform as no intervention was performed.
