Research in context
Evidence before this study
We searched PubMed without date or language restrictions for studies assessing enteral and parenteral nutritional support in critically ill patients. We also screened the reference lists in published guidelines, meta-analyses, and reviews. At the time our trial was designed, published studies including meta-analyses indicated reduced infectious complications and improved prognosis with enteral feeding compared to parenteral feeding. Observational studies suggested that factors associated with greater benefits from enteral nutrition might have worse critical illness severity and earlier compared with delayed enteral feeding. Recently, during the course of the NUTRIREA-2 study, the multicentre randomised CALORIES trial in an unselected population of critically ill patients was published. The results showed no differences in outcome or infectious complications between early enteral and early parenteral nutrition. A meta-analysis including the CALORIES trial and previous published studies found no difference in mortality; although early enteral nutrition was associated with shorter intensive-care unit (ICU) stay lengths and fewer infectious complications compared with early parenteral nutrition, subgroup analyses suggested that these effects might be limited to trials in which the energy intake was lower with enteral than with parenteral nutrition. The most recently published guidelines recommend early enteral feeding, at the early stage of critical illness. Thus, whether the route of early feeding influences outcomes of patients with severe critically illnesses remains controversial.
Added value of this study
The NUTRIREA-2 study is the second, large, randomised, controlled trial assessing the effect of the route of nutritional support in critically ill adults without contraindications to enteral or parenteral nutrition. By contrast with the CALORIES trial, NUTRIREA-2 focused on patients treated with invasive mechanical ventilation and vasopressor support for shock, because previous studies suggested that mechanically ventilated patients in ICU with haemodynamic instability might have better survival when early nutrition is given enterally rather than parenterally. In the NUTRIREA-2 trial, nutrition delivery was adapted according to a predetermined definition of the acute phase of critical illness. Furthermore, nutritional intakes were far closer to targets than in the CALORIES trial. The groups given early normocaloric enteral versus parenteral nutrition showed no significant differences in day 28 mortality; frequency of infectious complications; organ failure severity or duration; life support duration; ICU and hospital stay lengths; and ICU, hospital, or day 90 mortality. Compared with the parenteral route, the enteral route was associated with slightly lower calorie and protein intakes and with higher frequencies of hypoglycaemia. Proportions of patients with bowel ischaemia and colonic pseudo-obstruction were higher in the enteral group than in the parenteral group.
Implications of all the available evidence
The findings of NUTRIREA-2 are to some extent consistent with those of the CALORIES trial but not with those of meta-analyses suggesting benefits from the enteral route compared with the parenteral route. However, whereas the CALORIES trial also showed no outcome differences between feeding routes, NUTRIREA-2 raises concern about a rare but major complication of enteral feeding in patients with severe critical illness. Our data do not support a preference for early enteral compared with parenteral nutrition during the acute phase of critical illness in patients who have no contraindications to enteral or parenteral nutrition and who are receiving mechanical ventilation and vasopressor support for shock. Furthermore, our data suggest potential harmful effects on the gut of enteral nutrition with a normocaloric target.