Impact of Refeeding Syndrome on Short- and Medium-Term All-Cause Mortality: A Systematic Review and Meta-Analysis

Background: The refeeding syndrome has been described as a potentially life-threatening complication of renutrition. However, moving from single reports to larger population studies, the real impact of refeeding syndrome on all-cause mortality is still unknown. Methods: PubMed/Medline, EMBASE, Cochrane library, and CINAHL databases were systematically searched until September 2020 for studies reporting mortality rates in patients who developed the syndrome at renutrition compared with those who did not develop it. Effect sizes were pooled through a random-effect model. Results: Thirteen studies were finally considered in the meta-analysis, for a total of 3846 patients (mean age 64.5 years; 58% males). Pooled data showed a nonsignificant trend toward an increased short-term (≤1 month) mortality in patients developing the refeeding syndrome (odds ratio = 1.27, 95% confidence interval 0.93-1.72), mostly driven by studies in which renutrition was not prescribed and supervised by a nutritional support team (P =.01 at subgroup analysis) and by studies published in previous years (P =.04 at meta-regression). When examining medium-term (≤6 month) mortality, an overall statistical significance toward higher risk was observed (odds ratio = 1.54, 95% confidence interval 1.04-2.28). Conclusion: This was the first meta-analysis that specifically assessed the impact of refeeding syndrome on mortality. Our results suggested a nonsignificant trend toward increased mortality in the short term but a significantly increased mortality in the medium term. The supervision/management of the refeeding process by a nutrition specialist might be a key factor for the limitation of this mortality excess.