Refeeding Syndrome Is Associated With Increased Mortality in Malnourished Medical Inpatients: Secondary Analysis of a Randomized Trial

Medicine (Baltimore). 2020 Jan; 99(1):e18506. doi: 10.1097/MD.0000000000018506.
Friedli, N., Baumann, J., Hummel, R., Kloter, M., Odermatt, J., Fehr, R., Felder, S., Baechli, V., Geiser, M., Deiss, M., Tribolet, P., Gomes, F., Mueller, B., Stanga, Z., & Schuetz, P.


Background: Whether the occurrence of refeeding syndrome (RFS), a metabolic condition characterized by electrolyte shifts after initiation of nutritional therapy, has a negative impact on clinical outcomes remains ill-defined. We prospectively investigated a subgroup of patients included in a multicentre, nutritional trial (EFFORT) for the occurrence of RFS.

Methods: In this secondary analysis of a randomized-controlled trial investigating the effects of nutritional support in malnourished medical inpatients, we prospectively screened patients for RFS and classified them as "RFS confirmed" and "RFS not confirmed" based on predefined criteria (i.e. electrolyte shifts, clinical symptoms, clinical context, and patient history). We assessed associations of RFS and mortality within 180 days (primary endpoint) and other secondary endpoints using multivariable regression analysis.

Results: Among 967 included patients, RFS was confirmed in 141 (14.6%) patients. Compared to patients with no evidence for RFS, patients with confirmed RFS had significantly increased 180-days mortality rates (42/141 (29.8%) vs 181/826 (21.9%), adjusted odds ratio (OR) 1.53 (95% CI 1.02 to 2.29), P < .05). Patients with RFS also had an increased risk for ICU admission (6/141 (4.3%) vs 13/826 (1.6%), adjusted OR 2.71 (95% CI 1.01 to 7.27), P < .05) and longer mean length of hospital stays (10.5 ± 6.9 vs 9.0 ± 6.6 days, adjusted difference 1.57 days (95% CI 0.38-2.75), P = .01).

Conclusion: A relevant proportion of medical inpatients with malnutrition develop features of RFS upon hospital admission, which is associated with long-term mortality and other adverse clinical outcomes. Further studies are needed to develop preventive strategies for RFS in this patient population.

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List of abbreviations

DGEM German Society for Nutritional Medicine (German Deutsche Gesellschaft für Ernährungsmedizin)
GESKES  Swiss Society for Clinical Nutrition (German Gesellschaft für klinische Ernährung der Schweiz) 
ESPEN European Society of Clinicl Nutrition and Metabolism