Patients receiving invasive mechanical ventilation (IMV) and vasoactive drugs in the intensive care unit (ICU) had fewer complications and faster recovery with early calorie and protein restriction compared with patients who had standard calorie and protein intake, according to study findings published in The Lancet Respiratory Medicine.
Historically, greater calorie and protein deficits among patients in the ICU have been associated with higher risks of prolonged mechanical ventilation, long ICU stays, and mortality. Recently, however, standard targets for ICU calorie and protein intake have been challenged. Researchers therefore sought to compare the effects of low-calorie, low-protein feeding with standard-calorie, standard-protein feeding during the acute phase of critical illness in the NUTRIREA-3 trial (ClinicalTrials.gov Identifier: NCT03573739)
Primary outcomes were time to ICU discharge and 90-day all-cause mortality. Secondary outcomes included secondary infections, liver dysfunction, and gastrointestinal events.
The parallel-group, open-label, controlled, randomized study was conducted in 61 ICUs in France from July 2018 through early December 2020. The trial involved 3036 adults receiving invasive mechanical ventilation and vasopressor support for shock (adrenaline, dobutamine, or noradrenaline) who were randomly assigned to receive early nutrition (within 24 hours of intubation) during their first 7 days in ICU with either low or standard calorie and protein targets (low group: 6 kcal/kg per day and 0.2-0.4 g/kg per day protein; standard group: 25 kcal/kg per day and 1.0-1.3 g/kg per day protein).
The low calorie/protein group included 1521 patients (33.6% women; mean age, 66 years); the standard calorie/protein group included 1515 patients (32.3% women; mean age, 66 years). Almost 70% of patients in each group had no fatal underlying disease and more than 25% were expected to die within 5 years, with the balance expected to survive less than 1 year according to patients’ McCabe scores. More than 70% had a pre-existing illness at ICU admission including more than 9% with malnutrition. Other baseline characteristics were similar between groups.
Protocol adherence was high, with daily calorie and protein intakes near target levels in both groups, and nearly 60% of patients in each group receiving enteral feeding only. There was no between-group difference in cumulative incidence of hypoglycemia, blood concentrations of potassium and magnesium, or in serum C-reactive protein.
The researchers found no statistically significant between-group difference in mortality. Notably, 41.3% of patients in the low group and 42.8% of patients in the standard group died by day 90 (absolute difference, -1.5%; 95% CI, -5.0 to 2.0; P =.41).
There was a significant between-group difference in time to discharge. Median time to readiness for ICU discharge in the low group was 8.0 days (interquartile range [IQR], 5.0-14.0) and 9.0 days in the standard group (IQR, 5.0-17.0) (hazard ratio [HR], 1.12; 95% CI, 1.02-1.22; P =.015).
No statistically significant between-group difference was found in the proportions of patients with secondary infections (HR, 0.85; 95% CI, 0.71-1.01; P =.06). The low group had statistically significant lower proportions of patients with liver dysfunction (HR, 0.92; 95% CI, 0.86-0.99; P =.032), bowel ischemia (HR, 0.50; 95% CI, 0.26-0.95; P =.030), diarrhea (HR, 0.83; 95% CI, 0.73-0.94; P =.004), and vomiting (HR, 0.77; 95% CI, 0.67-0.89; P <.001).
Study limitations include the lack of accounting for variation in the duration of the acute phase of critical illness and the lack of adjustment for multiple outcomes in final analysis.
“Day 90 all-cause mortality did not differ between low versus standard calorie and protein intakes during the acute phase of critical illness requiring invasive mechanical ventilation and vasoactive support,” researchers concluded. “Compared with patients receiving standard calorie and protein intakes, those receiving low intakes had a shorter time to readiness for ICU discharge analyzed with death as a competing event.”
Reignier J, Plantefeve G, Mira JP, et al. Low versus standard calorie and protein feeding in ventilated adults with shock: a randomized, controlled, multicenter, open-label, parallel-group trial (NUTRIREA-3). Lancet Respir Med. Published online March 20, 2023. doi:10.1016/S2213-2600(23)00092-9