The TARGET: Energy density of enteral nutrition not associated with mortality

1. Patients undergoing mechanical ventilation randomized to receive energy-dense enteral nutrition experienced similar rates of mortality at 90-days compared to patients treated with routine energy density enteral nutrition.

2. Patients receiving energy-dense nutrition experienced similar rates of complications or adverse events patients receiving routine enteral nutrition.

Evidence Rating Level: 1 (Excellent)      

Study Rundown: Critically ill patients often do not receive adequate caloric intake to match their energy expenditure. Previous studies differ in their assessment of whether “permissively underfeeding” patients is clinically harmful, and studies evaluating feeding patients with greater than standard caloric intake have often not been ideally designed. The randomized Augmented versus Routine Approach to Giving Energy Trial (TARGET) assessed how 90-day all-cause mortality rates differed in critically ill patients receiving either standard or energy-dense enteral nutrition. No difference in all-cause mortality was detected between the two treatment groups, and pre-specified secondary outcomes such as rates of adverse events, receipt of organ support, and number of days alive and out of the intensive care unit (ICU) did not differ between treatment groups.

This study provided a robust means of evaluating how nutritional support which differs by significant caloric values can affect mortality in critically ill patients. Strengths of the study include its randomized design, large number of patients included, and extensive subgroup analysis. Limitations include lack of measurement of patient energy expenditure and constrained inclusion of surgical or trauma patients.

Click to read the study, published today in NEJM

Relevant Reading: Parenteral vs. enteral nutrition in the critically ill patient: a meta-analysis of trials using the intention to treat principle

In-Depth [randomized controlled trial]: This multicenter, double-blind, randomized controlled trial was conducted between 2016 and 2017. Eligible adult patients were undergoing mechanical ventilation and had not yet begun enteral nutrition or had done so in the previous 12 hours. Patients were excluded if death was soon anticipated. Patients were randomized to receive either energy-dense (1.5 kcal/mL, n=1971) or routine (1.0 kcal/mL, n=1986) enteral nutrition and all patients received nutrition at a rate of 1 mL/hr. Enteral nutrition was continued up to 28 days, until the patient died, or until they were discharged from the ICU (whichever occurred first). The primary outcome was all-cause mortality at 90-days. Patients in the energy-dense group received on average 1863 kcal/day, while the routine group received on average 1262 kcal/day. At 90-days 26.5% of patients in the energy-dense group had died compared to 25.7%  of patients in the routine group (relative risk [RR], 1.05; 95% confidence interval [CI], 0.94 to 1.16). For secondary outcomes, no difference was detected between treatment groups for death by 28-days, percentage of patients with positive blood cultures, frequency of adverse events, or receipt of vasopressor or renal support. Prespecified subgroup analysis showed no difference between treatment groups for 90-day overall mortality when evaluating by patients with or without trauma, with or without sepsis, receiving medical or surgical treatment, or by body mass index (BMI) groupings.

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