Assessment of creatinine production rate as a predictive biomarker to individualize nutrition in the ICU: a secondary analysis of the EPaNIC-RCT

The creatinine-production-rate (CPR) was suggested as integrative indicator of muscle-status, which may identify patients upon intensive-care-unit (ICU) admission benefiting from certain treatments. Initiating supplemental parenteral nutrition early to reach caloric targets (early-PN) harmed ICU-patients as compared with omitting PN for one week (late-PN). We investigated whether CPR can identify patient subgroups who could benefit from early-PN. In this EPaNIC-RCT ( n = 4640) secondary analysis, we studied the impact of early-PN vs. late-PN on CPR and body-size-corrected CPR-index profiles from ICU-day 2–14, excluding patients on renal-replacement-therapy. We investigated whether day-2 CPR or CPR-index statistically interacted with the randomized intervention for impact on duration of mechanical-ventilation as surrogate for muscle-weakness, adjusting for baseline risk factors. Finally, impact of early-PN vs. late-PN was assessed in patients with high (> mean) or low (≤ mean) day-2 CPR or CPR-index. Significance was set at P < 0.05, except for interaction- P < 0.1. Day-2 CPR was available for 1322 early-PN and 1382 late-PN patients. Early-PN patients had a higher CPR and CPR-index than late-PN patients from day 4–11. Day-2 CPR ( P = 0.067) and CPR-index ( P = 0.058) interacted with randomization for impact on mechanical-ventilation. A lower likelihood of earlier live ventilator-weaning was observed with early-PN vs. late-PN in patients with high CPR (adjusted-hazard-ratio 0.871 (0.778–0.981), P = 0.022) or CPR-index (0.858 (0.764–0.963), P = 0.0095), unlike in patients with low CPR ( P = 0.60) or CPR-index ( P = 0.73). Early-PN affected CPR and CPR-index profiles in the former group only. The day-2 CPR and CPR-index did not identify ICU-patients who could benefit from intensive nutritional therapy with early-PN. ClinicalTrials.gov NCT00512122, registered July 31, 2007.