Dynamic phenotyping and organ cross-talk in sepsis-associated organ injury: from physiological trajectories to precision critical care

Sepsis-associated organ injury remains a major cause of mortality in critically ill patients. Conventional assessment relies largely on physiological indicators, including lactate, mean arterial pressure (MAP), PaO2/FiO2 ratio, creatinine, urine output, and organ dysfunction scores. However, these isolated values or single-variable trends may incompletely capture the temporal instability and biological heterogeneity that characterize sepsis. Increasing evidence indicates that dynamic trajectories, variability patterns, and evolving subphenotypes may better characterize disease progression, organ recovery, and treatment responsiveness. In parallel, critical care medicine is moving from syndrome-level classification toward treatable traits, individualized treatment effects, and precision critical care. Dynamic phenotyping focuses on physiological trajectories, including lactate clearance, oxygenation evolution, hemodynamic variability, glycemic variability, and renal recovery, but its major value may lie in interpreting relationships among trajectories across organ systems. Interpretation of dynamic phenotypes therefore requires attention to cross-system temporal relationships, including coordinated recovery, coupled deterioration, and discordant recovery. From this trajectory-based perspective, sepsis-associated organ injury can be viewed as an interconnected multiorgan network involving lung-kidney, gut-lung, gut-liver, gut-kidney, and endothelial-organ cross-talk. Organ cross-talk may help explain dynamic coupling among organ systems, whereas microcirculatory-mitochondrial dysfunction may contribute to trajectory mismatch through impaired tissue perfusion, oxygen delivery-utilization uncoupling, bioenergetic failure, maladaptive metabolic reprogramming, and defective mitochondrial quality control. This trajectory-based perspective may inform future precision critical care, while most trajectory-guided strategies remain investigational and require prospective validation before routine clinical adoption.