Endocrine Abstracts

Purpose: Current international guidelines have not reached consensus on the optimal timing, dose and composition of artificial nutrition in critically ill patients, but several studies have showed harm with early enhanced feeding. Our group demonstrated earlier in the EPaNIC randomized controlled trial (RCT) that as compared to withholding parenteral nutrition (PN) until one week after intensive care unit (ICU) admission, supplementing insufficient enteral nutrition with PN prolonged ICU dependency.¹ Interestingly, the Refeeding RCT showed lower mortality by nutrient restriction in ICU patients developing hypophosphatemia upon the initiation of artificial nutrition.² We hypothesized that early phosphate changes in ICU may identify patients who are harmed by early feeding.

Methods : In this secondary analysis of the EPaNIC RCT, absolute hypophosphatemia (AHP) was defined as a phosphate <0.65 mmol/l on the second ICU-day, relative hypophosphatemia (RHP) as a decrease of >0.16 mmol/l between the first and second ICU- day, and combined hypophosphatemia (CHP) as the combination of AHP and RHP. We studied whether development of AHP/RHP/CHP interacted with the nutritional management (Early PN vs Late PN) for its impact on outcome through multivariable regression analysis.

Results: Of 3520 patients with available phosphate measurements, CHP developed in 5.3% ( n = 187), AHP in 9.1% ( n = 321) and RHP in 23.7% ( n = 834) of patients. There was an interaction between the development of RHP and the randomized nutritional intervention for its impact on outcome. Early PN associated with a lower likelihood of an earlier discharge alive from ICU in patients developing RHP (adjusted hazard ratio 0.76 (0.66-0.88)) as compared to Late PN, which was not observed in patients without RHP. Development of CHP or AHP did not associate with a differential impact of the randomized intervention.

Conclusion: RHP occurred in a significant proportion of critically ill patients and among these patients a higher caloric intake associated with a higher ICU dependency. The development of RHP may identify patients who are harmed by Early PN.

References: 1. Casaer, M. P. et al. Early vs late parenteral nutrition in critically ill adults. N Engl J Med 365, 506-517 (2011). https://doi.org:10.1056/NEJMoa1102662.

2. Doig, G. S. et al. Restricted vs continued standard caloric intake during the management of refeeding syndrome in critically ill adults: a randomised, parallel-group, multicentre, single-blind controlled trial. Lancet Respir Med 3, 943-952 (2015). https://doi.org:10.1016/S2213-2600(15)00418-X