Trials and guidelines for endocrinology, metabolism and nutrition

This compilation of guidelines reviews and randomised trials on vaguely endocrine nutritional and metabolic topics are mainly derived from such colossi of the industry as Critical Care Reviews, LITFL and The Bottom Line. The reader with more than ten minutes to spare is invited to refer to these sources directly, but for the rest of us, what follows are quick-fire one liners on the most important studies of this area. Wherever possible, the original paper is linked from the name of the study, and the Bottom Line review is linked from the year of publication. Before the reader wastes their time reading the nutrition trials, they are warned about the notable absence of positive treatment effects among them.

Nutrition guidelines

ASPEN guidelines 

ESPEN guidelines

Candian Critical Care Society guidelines

A comparison of them all, from 2019 (thanks, Kopp Luigi et al)

Nutrition trials

ANZICS - 2008 - lol, all these guidelines, how much difference does it make if we follow them? n=1118, Australia and NZ. No difference in anything, even though nutrition goals were reached earlier if the guidelines were followed.

TICACOS - 2011 - Indirect calorimetry instead of giving everyone 25kcal/day? n=112, in Israel. Mortality improved (32.3% vs 47.7%) but LOS increased (17.2 vs 11.7 days). 

EPaNIC - 2011 - early (d2) vs late (d8) TPN. n=4640, in Europe. No difference in mortality; but late TPN had less TPN-related complications (obvs). However: complete mess (39% of patients had an ICU LOS of less than 3 days, so, seriously...)

EDEN - 2012 - what if trophic feeding, but in ARDS? n=1000, in the US. No difference of any sort (mortality and ventilator free days were the same). 

ENTERIC - 2012 - but what if nasojejunal feeding? n=181, Australia and NZ. No difference in basically any of the outcomes, including nutrient delivery. 

EPN - 2013 - what if TPN right away, and then stop it when EN is established? n=1372, Australia and NZ. No difference in mortality, trivial difference in duration of ventilation (7.7 vs 7.2 days, literally 12 hours)

SPN - 2013 - what if both PN and EN to achieve goals? n=305 in Switzerland. Fewer infections (27% vs 38%) in the group that reached goals earlier.

CALORIES - 2014 - PN vs EN - mortality difference? n=2400, in UK. No, there was no mortality difference, or any other difference for that matter.

PermiT - 2015  - maybe only 40-50% of goal is enough? n=894, in Saudi and Canada. No difference in any outcomes. Notably: protein dose was 100%.

EAT-ICU - 2017 - what if goals achieved on Day 1 with PN+EN? n=203, doesn't matter where, no difference of any sort.

TARGET - 2018 - moar calories? 1.5cal vs 1.0cal? n=3914; Australia and NZ. No difference in any primary or secondary outcomes. 

EFFORT Protein - 2023 - moar protein? 1.2 vs 2.2g/kg, n=1329 all over the world. No benefit and perhaps evidence of harm in AKI and more severe illness.

Glycaemic control

Van Den Berghe - 2001 - the trial that NICE-SUGAR debunked (strict vs. conventional BSL control); n=1548, mortality reduced from 8.0% to 4.6% with strict sugar control


NICE-SUGAR - 2009 - n = 3054 in Australia and NZ; lower mortality (27.5% vs 24.9%) in the conventional control group, keeping BSL under 10mmol/L. 

Endocrinology guidelines

Diabetes and ketoacidosis:

Thyroid things

Adrenal things


Heart, The National. "Initial trophic vs full enteral feeding in patients with acute lung injury: the EDEN randomized trial." JAMA: the journal of the American Medical Association 307.8 (2012): 795.

Doig, Gordon S., et al. "Early parenteral nutrition in critically ill patients with short-term relative contraindications to early enteral nutrition: a randomized controlled trial." Jama 309.20 (2013): 2130-2138.

Singer, Pierre, et al. "The tight calorie control study (TICACOS): a prospective, randomized, controlled pilot study of nutritional support in critically ill patients." Intensive care medicine 37 (2011): 601-609.

Casaer, Michael P., et al. "Early versus late parenteral nutrition in critically ill adults." New England Journal of Medicine 365.6 (2011): 506-517.

Heidegger, Claudia Paula, et al. "Optimisation of energy provision with supplemental parenteral nutrition in critically ill patients: a randomised controlled clinical trial." The Lancet 381.9864 (2013): 385-393.

Davies, Andrew R., et al. "A multicenter, randomized controlled trial comparing early nasojejunal with nasogastric nutrition in critical illness." Critical care medicine 40.8 (2012): 2342-2348.

Kopp Lugli, Andrea, et al. "Medical nutrition therapy in critically ill patients treated on intensive and intermediate care units: a literature review." Journal of clinical medicine 8.9 (2019): 1395.

Chapman, Marianne, et al. "Energy-dense versus routine enteral nutrition in the critically ill." (2018): 1823-1834.

Van Den Berghe, Greet, et al. "Intensive insulin therapy in critically ill patients." New England journal of medicine 345.19 (2001): 1359-1367.

Nice-Sugar Study Investigators. "Intensive versus conventional glucose control in critically ill patients." New England Journal of Medicine 360.13 (2009): 1283-1297.

Allingstrup, Matilde Jo, et al. "Early goal-directed nutrition versus standard of care in adult intensive care patients: the single-centre, randomised, outcome assessor-blinded EAT-ICU trial." Intensive care medicine 43 (2017): 1637-1647.

Arabi, Yaseen M., et al. "Permissive underfeeding or standard enteral feeding in critically ill adults." New England Journal of Medicine 372.25 (2015): 2398-2408.

Harvey, Sheila E., et al. "Trial of the route of early nutritional support in critically ill adults." New England Journal of Medicine 371.18 (2014): 1673-1684.

Holt, Richard IG, et al. "The management of type 1 diabetes in adults. A consensus report by the American Diabetes Association (ADA) and the European Association for the Study of Diabetes (EASD)." Diabetes Care 44.11 (2021): 2589-2625.

Mustafa, Omar G., et al. "Management of Hyperosmolar Hyperglycaemic State (HHS) in Adults: An updated guideline from the Joint British Diabetes Societies (JBDS) for Inpatient Care Group." Diabetic Medicine (2022): e15005.

Jonklaas, Jacqueline, et al. "Guidelines for the treatment of hypothyroidism: prepared by the american thyroid association task force on thyroid hormone replacement." thyroid 24.12 (2014): 1670-1751.

Ross, D. S., et al. "ATA hyperthyroidism management guidelines." Thyroid 26.10 (2016): 1343-421.

Lenders, Jacques WM, et al. "Pheochromocytoma and paraganglioma: an endocrine society clinical practice guideline." The Journal of Clinical Endocrinology & Metabolism 99.6 (2014): 1915-1942.

Heyland, Daren K., et al. "The effect of higher protein dosing in critically ill patients with high nutritional risk (EFFORT Protein): an international, multicentre, pragmatic, registry-based randomised trial." The Lancet 401.10376 (2023): 568-576.

Dhatariya, Ketan K., and Joint British Diabetes Societies for Inpatient Care. "The management of diabetic ketoacidosis in adults—An updated guideline from the Joint British Diabetes Society for Inpatient Care." Diabetic Medicine 39.6 (2022): e14788.