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November - 2018

   

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Energy-Dense versus Routine Enteral Nutrition in the Critically Ill

The TARGET Investigators, for the the ANZICS Clinical Trials Group New Eng J Med, 2018, Online first

Comment

Should we continue to aim for caloric targets in critically ill patients based on the recommendation that energy intake match energy expenditure in order to prevent cumulative energy deficits? Particularly with the knowledge that we don’t achieve this, ie due to feeding intolerance, fasting, etc, we deliver less than 60% of this target. 

The TARGET trial answers this. This multicenter, double-blind, RCT randomised 3957 adult patients receiving mechanical ventilation in 46 Australian and New Zealand intensive care units (ICUs), to;

  • Energy-dense (1.5 kcal/ml) vs routine (1.0 kcal/ml) enteral nutrition at a dose of 1 ml/kg IBW/hr, commenced within 12 hours of initiation of nutrition support, and continuing for up to 28 days while the patient was in the ICU. The difference in calories in the enteral feeds was made up by increases in fat and carbohydrate, with similar protein density.
  • Baseline: groups were well matched, about 70% were medical.
  • Their was clear treatment separating. Volume of EN was similar, but energy-dense received more calories than routine  1863±478 kcal/day vs 1262±313 kcal/day (mean diff, 601 kcal per day; 95% CI, 576 to 626). 
  • Overall calorie delivery (from trial and non-trial sources) was 30 Kcal/kg/day energy-rich vs 22 kcal/kg/day routine, with similar protein delivery 1 g/kg/day.
  • Estimations of daily calorie requirements were available for 65% of the patients in the trial; enteral nutrition delivered 103±27% of estimated requirements in energy dense vs 69±18% in the 1.0-kcal group (mean diff, 34%)
  • Primary outcome was day 90-mortality and was not different - 26.8% energy-dense vs 25.7% routine (RR 1.05; 95% CI, 0.94 to 1.16; P=0.41). These were similar in seven predefined subgroups. 
  • Higher calorie delivery did not affect survival time, receipt of organ support, number of days alive and out of the ICU and hospital or free of organ support, or the incidence of infective complications or adverse events.
  • Routine feed was associated with a smaller median largest gastric residual volume (180 ml vs 250 ml), less regurgitation or vomiting (15.7% vs 18.9%), less promotility use (39,.6% vs 47.4%), less insulin use (0.0 vs 3.0 u/d, and 49% vs 56%), and lower median daily blood glucose levels. 

Overall this large RCT tells us that in patients undergoing mechanical ventilation, administering 1 ml/kg/hr of energy dense calories did not result in improved outcomes compared to routine enteral nutrition. In practical terms, delivery of 70% estimate energy requirements, 22 kcal/kg/day, by prescribing routine EN as 1 ml/kg/hr, results in the same outcomes as delivery of 100% estimate energy requirements, 30 Kcal/kg/day, using energy dense EN. In addition, routine nutrition is perhaps simpler, with lower GRVs, pro kinetic and insulin use, although there is no clinical benefit. We don’t know if delivering 70% energy target with energy-dense EN at low  rate vs routine EN at 1ml/kg/hr makes a difference, and we dont know if altering the protein would have made a difference.

 

Abstract

BACKGROUND

The effect of delivering nutrition at different calorie levels during critical illness is uncertain, and patients typically receive less than the recommended amount.

METHODS

We conducted a multicenter, double-blind, randomized trial, involving adults un- dergoing mechanical ventilation in 46 Australian and New Zealand intensive care units (ICUs), to evaluate energy-dense (1.5 kcal per milliliter) as compared with routine (1.0 kcal per milliliter) enteral nutrition at a dose of 1 ml per kilogram of ideal body weight per hour, commencing at or within 12 hours of the initiation of nutrition support and continuing for up to 28 days while the patient was in the ICU. The primary outcome was all-cause mortality within 90 days.

RESULTS

There were 3957 patients included in the modified intention-to-treat analysis (1971 in the 1.5-kcal group and 1986 in the 1.0-kcal group). The volume of enteral nutri- tion delivered during the trial was similar in the two groups; however, patients in the 1.5-kcal group received a mean (±SD) of 1863±478 kcal per day as compared with 1262±313 kcal per day in the 1.0-kcal group (mean difference, 601 kcal per day; 95% confidence interval [CI], 576 to 626). By day 90, a total of 523 of 1948 pa- tients (26.8%) in the 1.5-kcal group and 505 of 1966 patients (25.7%) in the 1.0-kcal group had died (relative risk, 1.05; 95% CI, 0.94 to 1.16; P=0.41). The results were similar in seven predefined subgroups. Higher calorie delivery did not affect survival time, receipt of organ support, number of days alive and out of the ICU and hospital or free of organ support, or the incidence of infective complications or adverse events.

CONCLUSIONS

In patients undergoing mechanical ventilation, the rate of survival at 90 days as- sociated with the use of an energy-dense formulation for enteral delivery of nutri- tion was not higher than that with routine enteral nutrition.

November


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