Development and Validation of a Policy Tree Approach for Optimizing Intravenous Fluids in Critically Ill Patients with Sepsis and Acute Kidney Injury.

Purpose: Intravenous fluids are mainstay of management of acute kidney injury (AKI) after sepsis but can cause fluid overload. Recent literature shows that restrictive fluid strategy may be beneficial in some patients with AKI, however, identifying these patients is challenging. We aimed to develop and validate a machine learning algorithm to identify patients who would benefit from a restrictive fluid strategy.
Methods: We included patients with sepsis who developed AKI within 48 hours of ICU admission and defined restrictive fluid strategy as receiving <500mL fluids within 24 hours after AKI. Our primary outcome was early AKI reversal within 48 hours of AKI onset, and secondary outcomes included sustained AKI reversal and major adverse kidney events (MAKE) at discharge. We used a causal forest, a machine learning algorithm to estimate individual treatment effects and policy tree algorithm to identify patients who would benefit by restrictive fluid strategy. We developed the algorithm in MIMIC-IV and validated it in eICU database.
Results: Among 2,091 patients in the external validation cohort, policy tree recommended restrictive fluids for 88.2%. Among these, patients who received restrictive fluids demonstrated significantly higher rate of early AKI reversal (48.2% vs 39.6%, p<0.001), sustained AKI reversal (36.7% vs 27.4%, p<0.001) and lower rates of MAKE by discharge (29.3% vs 35.1%, p=0.019). These results were consistent in adjusted analysis.
Conclusion: Policy tree based on causal machine learning can identify septic patients with AKI who benefit from a restrictive fluid strategy. This approach needs to be validated in prospective trials.
Competing Interests: Competing Interests GNN is a founder of Renalytix, Pensieve, Verici and provides consultancy services to AstraZeneca, Reata, Renalytix, Siemens Healthineer and Variant Bio, serves a scientific advisory board member for Renalytix and Pensieve. He also has equity in Renalytix, Pensieve and Verici. LC is a consultant for Vifor Pharma INC and has received honorarium from Fresenius Medical Care. JAK reports receiving consulting fees from Astute Medical/bioMerieux, Astellas, Alexion, Chugai Pharma, Novartis, Mitsubishi Tenabe and GE Healthcare and is a Full-time employee of Spectral Medical. All remaining authors have declared no conflicts of interest.