Impact of early low-calorie low-protein versus standard-calorie standard-protein feeding on outcomes of ventilated adults with shock: design and conduct of a randomised, controlled, multicentre, open-label, parallel-group trial (NUTRIREA-3)

Abstract

IntroductionInternational guidelines include early nutritional support (≤48 hour after admission), 20–25 kcal/kg/day, and 1.2–2 g/kg/day protein at the acute phase of critical illness. Recent data challenge the appropriateness of providing standard amounts of calories and protein during acute critical illness. Restricting calorie and protein intakes seemed beneficial, suggesting a role for metabolic pathways such as autophagy, a potential key mechanism in safeguarding cellular integrity, notably in the muscle, during critical illness. However, the optimal calorie and protein supply at the acute phase of severe critical illness remains unknown. NUTRIREA-3 will be the first trial to compare standard calorie and protein feeding complying with guidelines to low-calorie low-protein feeding. We hypothesised that nutritional support with calorie and protein restriction during acute critical illness decreased day 90 mortality and/or dependency on intensive care unit (ICU) management in mechanically ventilated patients receiving vasoactive amine therapy for shock, compared with standard calorie and protein targets.Methods and analysisNUTRIREA-3 is a randomised, controlled, multicentre, open-label trial comparing two parallel groups of patients receiving invasive mechanical ventilation and vasoactive amine therapy for shock and given early nutritional support according to one of two strategies: early calorie-protein restriction (6 kcal/kg/day-0.2–0.4 g/kg/day) or standard calorie-protein targets (25 kcal/kg/day, 1.0–1.3 g/kg/day) at the acute phase defined as the first 7 days in the ICU. We will include 3044 patients in 61 French ICUs. Two primary end-points will be evaluated: day 90 mortality and time to ICU discharge readiness. The trial will be considered positive if significant between-group differences are found for one or both alternative primary endpoints. Secondary outcomes include hospital-acquired infections and nutritional, clinical and functional outcomes.Ethics and disseminationThe NUTRIREA-3 study has been approved by the appropriate ethics committee. Patients are included after informed consent. Results will be submitted for publication in peer-reviewed journals.Trial registration numberNCT03573739.

Association between early nutrition support and 28-day mortality in critically ill patients: the FRANS prospective nutrition cohort study

“…Compared to other macronutrients such as glucose and lipids, early administration of amino acids was associated with poor outcomes in a preplanned post hoc analysis of the PEPaNIC study [ 55 ]. The soon-to-be-published NUTRIREA-3 trial evaluating early low-energy, low-protein versus standard feeding in severe ICU-ventilated shock patients will add further light on these results [ 56 ].…”

Sepsis-like Energy Deficit Is Not Sufficient to Induce Early Muscle Fiber Atrophy and Mitochondrial Dysfunction in a Murine Sepsis Model

“…Finally, the nutrition of ICU patients in the early phase of sepsis is a major issue. Whether artificial hypo- or normocaloric nutrition is the best treatment has been debated by clinicians for many years, and the discussion is ongoing [ 84 , 85 , 86 ]. The use of artificial hypocaloric nutrition in the early phase of sepsis increases the energy deficit in humans compared with normocaloric nutrition—which is currently recommended in humans [ 22 ].…”

Gastrointestinal failure, big data and intensive care

“…Therefore, reaching target within 48 h may be deleterious for the tolerance of enteral feeding in addition to the risks of overfeeding. The NUTRIREA 3 study [21 ▪▪ ] confirmed that enteral feeding administered early and with a low target of 6 kcal/kg/day was associated with a significant lower proportions of patients with vomiting (hazard ratio 0·77, 0.67–0.89; P < 0.001), diarrhea (0.83, 0.73–0.94; P = 0·004), bowel ischemia (0.50, 0.26–0.95; P = 0.030), and liver dysfunction (0.92, 0.86–0.99; P = 0.032) when compared with early and large energy target (25 kcal/kg/day). A recent meta-analysis compared gastric to postpyloric tube feeding and found that postpyloric feeding was associated with shorter ICU length of stay, length of ventilation and improved feeding adequacy [22].…”