Thread by @DogICUma

Results of the #TARGETtrial, the largest critical care nutrition trial ever undertaken, are now online @NEJM
nejm.org/doi/full/10.10…
What we did, what we found, and what it means follows…
Please RT to help translate this new knowledge.

Thanks to funding from @HRCNewZealand & @NHMRC we randomised 4000 participants from 46 Australian and New Zealand ICUs in less than a year and a half!

Adults mechanically ventilated & expected to require enteral nutrition in ICU beyond the calendar day after randomisation were assigned to energy dense enteral nutrition (1.5kcal/mL) or standard care enteral nutrition (1.0kcal/mL) at a dose of 1mL/kg/hr based on ideal body weight

The primary end point was day 90 mortality; secondaries included survival time, receipt of organ support, number of days alive and out of the ICU, number of days alive and free of organ support, & the incidence of infections.

Patients assigned to 1.5 kcal/ml received ≈1900kcal per day on average while those assigned to 1.0kcal/ml received ≈1300kcal per day on average.

TARGET is the first large multicentre trial to deliver guideline-recommended goal calories using the enteral route.

26.8% of the energy-dense group and 25.7% of the standard care group died by day 90 (relative risk, 1.05 [95% confidence interval 0.94-1.16]; P=0.41). Secondary end points showed no difference.

There were no differences between groups by treatment allocation in a range of prespecified subgroups: trauma, sepsis, medical vs. surgical, & brain injury.

Use of energy-dense nutrition was associated with larger residual volumes, more vomiting, and marginally lower serum potassium and phosphate levels compared with standard care.

Given the overall evidence base, here is what we now know:

No. 1: Guidelines that were written prior to the # TARGETtrial recommend an energy intake of 25-30kcal/kg/day (1875-2250kcal/day for a 75 kg patient)

No. 2: The #TARGETtrial is the first large multicentre trial to deliver recommended goal calories (≈1900kcal) using the enteral route. There is no suggestion that doing this improves patient outcomes.

No. 3: Early trophic feeding (≈400kcal/day) appears to result in similar outcomes to standard care feeding (≈1300kcal/day)
jamanetwork.com/journals/jama/…

No. 4. Permissive underfeeding underfeeding (≈800kcal/day) appears to result in similar outcomes to standard care feeding (≈1300kcal/day)
nejm.org/doi/full/10.10…

No. 5. Early supplementation of caloric intake with parenteral nutrition does not appear to improve outcomes
nejm.org/doi/10.1056/NE…

Here is what I think it all means & what I think we should do:

No. 1: Given that patient outcomes are similar across a broad range of calorie delivery, minor adjustments of targets up or down by a few mL make no sense to me.

No. 2: A reasonable response if one encounters difficulty achieving recommended calorie goals by the enteral route is to reduce the calorie target.

No. 3: Before you prescribe prokinetics or place small bowel feeding tubes, you should ask yourself ‘why am I doing this?’ and consider the alternate approach of doing less.

Here are some major uncertainties:

No. 1: The findings from existing trials may not apply in developing countries where malnutrition is more common

No. 2: While protein delivery was, by design, almost identical between groups in the #TARGETtrial, protein & calories are usually coupled so that if you reduce delivery of one you reduce the delivery of the other. The optimal dose of protein for ICU patients is uncertain.

Some people will argue that in the #TARGETtrial we should have ‘individualised’ but, in fact, feeding rates were individualised based on lean body weight & adjusted if feed intolerance occurred.

Evidence for further ‘individualisation’ of nutrition therapy is lacking. I challenge people who espouse such views to respond with evidence rather than rhetoric because…

To quote Richard Feynman, "It doesn't matter how beautiful your theory is, it doesn't matter how smart you are. If it doesn't agree with experiment, it's wrong."

Feel free to reply and tell me what you think.

If you want to keep up to date with the next project, then you should follow @ProteinTarget