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

BACKGROUND & AIMS: 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. METHODS: 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, <0.8 g/kg/day, 0.8-1.2 g/kg/day and >1.2 g/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. RESULTS: In total 455 patients met the inclusion criteria. We found a time-dependent association of protein intake and mortality; low protein intake (<0.8 g/kg/day) before day 3 and high protein intake (>0.8 g/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 <0.8 g/kg/day on day 1-2 to 0.8-1.2 g/kg/day on day 3-5 and >1.2 g/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. CONCLUSIONS: 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.

Impact of caloric intake in critically ill patients with, and without, refeeding syndrome: A retrospective study.

BACKGROUND & AIMS: Refeeding syndrome comprises metabolic disturbances that occur after the reintroduction of feeding after prolonged fasting. Standard care consists of correcting fluid and electrolytes imbalances. Energy intake during refeeding syndrome is heavily debated. This study addresses the effect of caloric intake on outcome during the management of refeeding syndrome. METHODS: A retrospective study among critically ill invasive mechanically ventilated patients admitted for >7 days to a medical-surgical ICU. Refeeding syndrome was diagnosed by the occurrence of new onset hypophosphatemia (<0.65 mmol/l) within 72 h of the start of nutritional support. Primary outcome was 6-month mortality. Secondary outcomes were 3-month mortality, ICU and hospital length of stay and duration of mechanical ventilation. Outcomes of patients with and without refeeding syndrome were compared and subgroup analysis on energy intake within the refeeding population was performed for the duration of survival. RESULTS: Of 337 enrolled patients, 124 (36.8%) developed refeeding syndrome and 213 patients (63.2%) maintained normal serum phosphate levels. Between the two groups, no statistical significant differences in clinical outcomes were observed. Within the refeeding syndrome group, a reduced 6-month mortality risk for low caloric intake (<50% of target) was seen compared with normal intake, adjusted Hazard Ratio 0.39, (95% CI 0.16-0.95, p = 0.037). In this group, low caloric intake was associated with an increased overall survival time at day 180 (153.0 (SE 10.1) vs 119.1 (SE 8.0) days, log-rank p = 0.018). CONCLUSIONS: Refeeding syndrome is common among prolonged mechanically ventilated critically ill patients, however not predictable by baseline characteristics. Among patients that develop refeeding syndrome low caloric intake was associated with a reduction in 6-month mortality risk. This effect was not seen in patients without refeeding syndrome. Findings support caloric restriction in refeeding syndrome during critical illness.

Antioxidant Vitamins and Trace Elements in Critical Illness.

This comprehensive narrative review summarizes relevant antioxidant mechanisms, the antioxidant status, and effects of supplementation in critically ill patients for the most studied antioxidant vitamins A, C, and E and the enzyme cofactor trace elements selenium and zinc. Over the past 15 years, oxidative stress-mediated cell damage has been recognized to be fundamental to the pathophysiology of various critical illnesses such as acute respiratory distress syndrome, ischemia-reperfusion injury, and multiorgan dysfunction in sepsis. Related to these conditions, low plasma levels of antioxidant enzymes, vitamins, and trace elements have been frequently reported, and thus supplementation seems logical. However, low antioxidant plasma levels per se may not indicate low total body stores as critical illness may induce redistribution of antioxidants. Furthermore, low antioxidant levels may even be beneficial as pro-oxidants are essential in bacterial killing. The reviewed studies in critically ill patients show conflicting results. This may be due to different patient populations, study designs, timing, dosing regimens, and duration of the intervention and outcome measures evaluated. Therefore, at present, it remains unclear whether supplementation of antioxidant micronutrients has any clinical benefit in critically ill patients as some studies show clear benefits, whereas others demonstrate neutral outcomes and even harm. Combination therapy of antioxidants seems logical as they work in synergy and function as elements of the human antioxidant network. Further research should focus on defining the normal antioxidant status for critically ill patients and to study optimal supplement combinations either by nutrition enrichment or by enteral or parenteral pharmacological interventions.