Stratified Causal Inference for Intensive Care Unit Risk Prediction: Informatics-Based Modeling of Anesthetic Drug Combinations

Background: Postoperative intensive care unit (ICU) admission affects 15% to 20% of surgical patients and represents a major source of morbidity and health care costs. Current anesthetic dosing relies on empirical guidelines rather than individualized risk assessment. We developed a counterfactual dose-response model to identify optimal fentanyl-propofol combinations. Objective: This study aimed to develop and evaluate a stratified, causal machine learning framework using electronic health record data to identify optimal fentanyl-propofol dose combinations and predict postoperative ICU admission risk, enabling precision anesthesia and individualized clinical decision support. Methods: We analyzed perioperative electronic health records of 67,134 surgical procedures from UC Irvine Medical Center (2017-2022). A hierarchical learning framework was used to estimate causal effects while controlling for confounding variables. A total of 6 dose-sensitive subgroups were identified through stratified analysis. The primary end point was postoperative ICU admission. Results: High-risk combinations (fentanyl >5 mcg/kg with propofol