Multi-Organ Intervention State Space (MOISS): A Collision Geometry Framework for Quantifying Therapeutic Windows Across 10 Organ Systems in 301,470 ICU Patients

Background: Severity scoring systems such as SOFA, NEWS2, and qSOFA effectively identify deteriorating ICU patients by aggregating physiological parameters into composite indices that trigger clinical alerts. However, these systems evaluate patient state at discrete time points and do not model the temporal dynamics of organ deterioration or the pharmacokinetic constraints that govern whether a given intervention can achieve therapeutic effect before an organ trajectory crosses an irreversible threshold. This limitation is consequential because interventions across critical care span pharmacokinetic onset times from seconds (vasopressors) to hours (metabolic corrections, blood products, enzymatic cofactors), yet no existing framework quantifies timing adequacy as a function of these intervention-specific pharmacokinetic properties. Methods: We developed the Multi-Organ Intervention State Space (MOISS), a collision geometry framework that classifies intervention timing adequacy by computing the temporal relationship between the predicted time for a biomarker trajectory to reach a critical threshold and the time required for the administered intervention to achieve peak therapeutic effect. Biomarker trajectories were estimated using the Kunche Adaptive Estimator (KAE), a reliability-adaptive Kalman filter that provides continuous position and velocity estimates from intermittent laboratory measurements. MOISS assigns each intervention event to one of six ordinal categories: PROPHYLACTIC, ON_TIME, PARTIAL, MARGINAL, FUTILE, or TOO_LATE. We applied this framework to 301,470 ICU patients across three databases (eICU-CRD, MIMIC-IV, MIMIC-III), evaluating 65 distinct intervention-organ pairs spanning 10 organ systems: Cardiovascular, Metabolic, Respiratory, Renal, Hematologic, Hepatic, Gastrointestinal, Infection, Endocrine, and Neurological. Results: Timing-mortality associations were identified across all 10 organ systems, with 87 intervention-database combinations achieving statistical significance (p