Optimizing the dynamic administration regimen of prophylactic enoxaparin in critically ill patients using reinforcement learning

This study aims to optimize the dynamic administration regimen of prophylactic enoxaparin in critically ill patients to reduce the risk of VTE, major bleeding, and 30-day all-cause mortality. We developed and internally and externally validated an artificial intelligence (AI) policy utilizing Double dueling deep Q network, using data from the Medical Information Mart for Intensive Care IV (MIMIC-IV) database (training and internal test set) and the eICU Collaborative Research Database (eICU-CRD, external test set). We compared the performance among the AI policy, the clinician's policy, the weight-tiered policy, and the fixed 40- mg-once-daily (QD) policy. The rationality and explainability of AI policy were investigated. In the internal test set, the AI policy achieved the highest policy value of 13.17 and the lowest estimated incidence of all outcomes of 5.53%, compared with the clinician's policy (9.81; 23.60%), the weight-tired policy (12.14; 10.72%), and the 40-mg-QD policy (12.31; 9.05%). Compared with the clinician's policy, the AI policy was associated with a decreased risk of VTE with statistical significance (OR: 0.44, 95%CI: 0.28-0.69, P<0.001). The superiority of AI policy was confirmed in the external test set. The SHAP analysis showed that sex, primary diagnosis, time to major surgery, and weight followed by vasopressor administration were the most important features contributing to AI policy. The AI policy could provide effective and clinically reasonable recommendations for the optimal dynamic frequency and dose of prophylactic enoxaparin and could potentially be applied in clinical practice after prospective evaluation.