Nutritional Adequacy Is Associated with Improved Survival Within Specific Physiological Windows in Critically Ill Patients.

BACKGROUND: The survival benefit of achieving nutritional adequacy in critically ill patients remains uncertain and may vary across physiological conditions. This study aimed to identify specific physiological windows in which adequate nutritional intervention is associated with improved survival and to provide supportive evidence for these findings using an independent cohort. METHODS: We conducted a retrospective cohort study using longitudinal data from the MIMIC-IV database. Adult ICU patients with a length of stay ≥7 days who received nutritional support were included. Marginal structural Cox models were applied to evaluate the time-varying associations between daily energy and protein adequacy and 28-day mortality while accounting for time-dependent confounding. Stratified analyses based on key physiological indicators were performed to identify potential physiological windows of benefit. These windows were subsequently evaluated in an independent cohort from the NEED study using stratified Cox regression analyses. RESULTS: A total of 5370 patients from MIMIC-IV were included. In the overall cohort, higher energy adequacy (HR 0.61, 95% CI 0.50-0.74; P < 0.001) and protein adequacy (HR 0.51, 95% CI 0.42-0.63; P < 0.001) were associated with lower 28-day mortality. However, these associations were restricted to specific physiological conditions. For energy adequacy, the association with lower mortality was observed when the norepinephrine equivalent dose was <0.3 μg/kg/min and lactate was <2 mmol/L. For protein adequacy, similar associations were observed when norepinephrine was <0.3 μg/kg/min, lactate was <2 mmol/L, and creatinine was <5 mg/dL. These associations were attenuated or no longer significant outside these windows. In the NEED cohort (n = 1322), higher energy and protein adequacy were likewise associated with lower 28-day mortality only within the corresponding physiological strata. CONCLUSION: The association between nutritional adequacy and survival in critically ill patients appears to depend on physiological status rather than being uniform across all patients. Relatively stable hemodynamics and lower lactate levels may help identify patients most likely to benefit from more adequate nutritional support. These indicators may help inform individualized nutritional strategies in critical care.