Abstract
Background: Refeeding syndrome (RFS) is a group of metabolic disorders associated with refeeding after starvation. However, the diagnostic criteria of RFS are highly heterogeneous. This study aimed to identify the best diagnostic criteria of RFS in critically ill patients.Methods: A multicenter, parallel, prospective trial enrolled patients (≥18 years) with mechanical ventilation for more than 3 days. RFS, defined as new-onset hypophosphatemia (<0.87mmol/L) within 72h after feeding and a decreased concentration of serum phosphate of more than 30%, from four hospital ICU of Zhejiang provinces in China. The primary endpoint was the 28-day mortality. Results: Between May 1, 2019 and April 30, 2020, 312 patients were enrolled. Of these, 302 patients were included and completed the trial. Except for APACHE II, there were no significant differences in age, gender, admission type, diagnosis, furosemide application, and hormone application. In the RFS2 and RFS3 groups, the APACHE II score was significantly higher than the non-RFS group (p=0.009 and p=0.01, respectively). In the nutritional baseline data, there were no significant differences between the groups in the PNI index, time to start of nutrition treatment, percentage of start nutrition within 48 hours, parenteral nutrition, feeding intolerance, and caloric intake and protein intake within first week. The NRS2002 score in group 2 and 3 was higher than the non-RFS group (p<0.001 and p=0.001, respectively). Moreover, the BMI index in group 3 was lower than the non-RFS group(p=0.001). Furthermore, the 28-day mortality increased in group 2 compared with the non-RFS group. The length of hospital stay in group 3 was significantly longer than that in the non-RFS group (p=0.008). More importantly, according to the preliminary RFS2 screening criteria, patients were further divided into patients with modified RFS and modified non-RFS. The nosocomial infection rate and 28- or 90-day mortality in the modified RFS group were higher than those of the modified non-RFS group (p=0.006 and p=0.02, respectively).Conclusions: The optimal criterion of RFS was a decrease in serum phosphate level of 0.65mmol/L and below, and a reduction of greater than 0.16 mmol/L within 72 h after starting nutritional support. Trial registration: ClinicalTrials.gov database, NCT04005300. Registered 1 July 2019, https://clinicaltrials.gov/ct2/show/ NCT04005300