Abstract

Multicenter early diuretic response (DR) analysis of single furosemide dosing following neonatal cardiac surgery is lacking to inform whether early DR predicts adverse clinical outcomes. We performed a retrospective cohort study utilizing data from the NEPHRON registry. Random forest machine learning generated receiver operating characteristic-area under the curve (ROC-AUC) and odds ratios for mechanical ventilation (MV) and respiratory support (RS). Prolonged MV and RS were defined using ≥ 90th percentile of observed/expected ratios. Secondary outcomes were prolonged CICU and hospital length of stay (LOS) and kidney failure (stage III acute kidney injury (AKI), peritoneal dialysis, and/or continuous kidney replacement therapy on postoperative day three) assessed using covariate-adjusted ROC-AUC curves. A total of 782 children were included. Cumulative urine output (UOP) metrics were lower in prolonged MV and RS patients, but DR poorly predicted prolonged MV (highest AUC 0.611, OR 0.98, sensitivity 0.67, specificity 0.53, p = 0.006, 95% OR CI 0.96-0.99 for cumulative 6-h UOP) and RS (highest AUC 0.674, OR 0.94, sensitivity 0.75, specificity 0.54, p < 0.001, 95% CI 0.91-0.97 UOP between 3 and 6h). Secondary outcome results were similar. DR had fair discrimination for kidney failure (AUC 0.703, OR 0.94, sensitivity 0.63, specificity 0.71, 95% OR CI 0.91-0.98, p < 0.001, cumulative 6-h UOP). Early DR poorly discriminated patients with prolonged MV, RS, and LOS in this cohort, though it may identify severe postoperative AKI phenotype. Future work is warranted to determine if early DR or late postoperative DR later, in combination with other AKI metrics, may identify a higher-risk phenotype.

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