Timing of PROTein INtake and clinical outcomes of adult critically ill patients on prolonged mechanical VENTilation: The PROTINVENT retrospective study

Abstract

Optimal protein intake during critical illness is unknown. Conflicting results on nutritional support during the first week of ICU stay have been published. We addressed timing of protein intake and outcomes in ICU patients requiring prolonged mechanical ventilation. We retrospectively collected nutritional and clinical data on the first 7 days of ICU admission of adult critically ill patients, who were mechanically ventilated in our ICU for at least 7 days and admitted between January 1st 2011 and December 31st 2015. Based on recent literature, patients were divided into 3 protein intake categories, <0.8g/kg/day, 0.8-1.2g/kg/day and >1.2g/kg/day. Our primary aim was to identify the optimum protein dose and timing related to the lowest 6 month mortality. Secondary endpoints were ventilation duration, need for renal replacement therapy (RRT), ICU length of stay (LOS) and mortality and hospital LOS and mortality. In total 455 patients met the inclusion criteria. We found a time-dependent association of protein intake and mortality; low protein intake (<0.8g/kg/day) before day 3 and high protein intake (>0.8g/kg/day) after day 3 was associated with lower 6-month mortality, adjusted HR 0.609; 95% CI 0.480-0.772, p<0.001) compared to patients with overall high protein intake. Lowest 6-month mortality was found when increasing protein intake from <0.8g/kg/day on day 1-2 to 0.8-1.2g/kg/day on day 3-5 and >1.2g/kg/day after day 5. Moreover, overall low protein intake was associated with the highest ICU, in-hospital and 6-month mortality. No differences in ICU LOS, need for RRT or ventilation duration were found. Our data suggest that although overall low protein intake is associated with the highest mortality risk, high protein intake during the first 3-5 days of ICU stay is also associated with increased long-term mortality. Therefore, timing of high protein intake may be relevant for optimizing ICU, in-hospital and long-term mortality outcomes.