The incidence and mortality of refeeding syndrome in older hospitalized patients, based on three different diagnostic criteria: A longitudinal study.

BACKGROUND & AIMS: Refeeding syndrome (RFS) lacks both a global definition and diagnostic criteria. Different diagnostic criteria are used; serum phosphate (traditional criterion (TC)), the Friedli consensus recommendations, and the ASPEN. We investigated the incidence of RFS in older hospitalized patients and the mortality rates in patients with or without RFS using these three different diagnostic criteria. METHODS: This is a longitudinal study with data originating from a randomized controlled trial conducted between March 2017 and August 2019. A total of 85 malnourished hospitalized patients at risk of RFS according to the National Institute for Health and Clinical Excellence tool for detecting patients at risk of RFS, were included. All patients were provided with enteral tube feeding, and electrolytes were measured daily during the intervention period. Friedli and ASPEN included phosphate, magnesium, and potassium in their definitions, but used different cut-off values. Incidences were recorded, and Kaplan-Meier estimates were used to determine whether mortality was more prevalent in patients with RFS. Regression analysis was used to test for confounders regarding the association between RFS and death, and Kappa was used to test for agreement between the three diagnostic criteria. RESULTS: The mean (SD) age of the patients was 79.8 (7.4) years, and the mean (SD) BMI was 18.5 (3.4) kg/m2. The mean (SD) kcal/kg/day was 19 (11) on day one and 26 (15) on day seven. The incidences of RFS differed with the criteria used; 12.9% (TC), 31.8% (Friedli), and 65.9% (ASPEN). Mortality was high, with 36.5% (n = 31) and 56.5% (n = 48) of patients dead at three-month and one-year follow-up, respectively. In the TC, 8/11 (72.7%) with RFS vs. 40/74 (54.1%) without RFS died within one-year, in Friedli 15/27 (55.5%) with RFS vs. 33/58 (56.9%) without RFS died, and in ASPEN 32/56 (65.9%) with RFS, vs. 16/29 (55.2%) without RFS died within one-year. There was no statistically significant difference in mortality between patients with or without RFS regardless of which criteria were used. Age was the only variable associated with death at one-year. The Kappa analysis showed very low agreement between the categories. CONCLUSION: Our results show that using different diagnostic criteria significantly impacts incidence rates. However, regardless of criteria used, the mortality was not significantly higher in the group of patients with RFS compared to the patients without RFS. Furthermore, none of the criteria showed a significant association with death at one-year. This supports the need for a global unified diagnostic criterion for RFS. This study was registered in ClinicalTrials.gov (identifier NCT03141489).

Refeeding syndrome occurs among older adults regardless of refeeding rates: A systematic review.

Refeeding syndrome is a life-threatening clinical disorder that can occur when treating malnutrition. The aim was to examine the current knowledge of refeeding syndrome in patients ≥ 65 + years with special focus on the incidence of hypophosphatemia (HP) in relation to refeeding rate (kcal/kg/day), number of days until the lowest level of phosphate occurs (day of nadir), refeeding rates and adverse events, and death. Specifically, we hypothesized that higher energy provision would cause a higher incidence of HP. A search was conducted in the available databases. Two cohort studies, 1 case control, and a total of 12 case series/case reports, which accounted for 19 individual patient cases, were eligible. The incidence of HP (<0.5 mmol/L) was 15% and 25% in the 2 cohort studies and 4% in the case control study. The mean day of nadir was between days 2 and 3 in the cohort studies, day 11 in the case control study, and day 3 in the cases series/case reports. Importantly, a rapid drop in phosphate occurred receiving both 30 kcal/kg/day and 8 to 10 kcal/kg/day. The cohort studies reported high death rates-26% and 23%-using both 10 and 20 kcal/kg/day, respectively. Adverse events were noted in most all case series/case reports. Clinicians should be aware that HP may occur in up to 25% of older hospitalized adults, and importantly, it occurs even when refeeding cautiously. Hence, electrolytes should be closely monitored, especially between days 2 and 4, which is when the day of nadir occurs most frequently.

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.

Refeeding syndrome in hematological cancer patients - current approach.

Introduction: According to estimates based on the GLOBOCAN database of the International Agency for Research on Cancer, in 2018 alone, 18 100 000 cancers were globally diagnosed. Importantly, the majority of cancer patients experience unintended weight loss that leads to many adverse clinical consequences, including malnutrition and cancer cachexia. At the same time, each nutritional intervention must be carried out individually, as it can lead to critical complications, resulting in a threat to the health and life of the cachectic patient. An example of this type of risk is refeeding syndrome.Areas covered: Three factors seem to be crucial in this case: early identification of patients at risk of malnutrition, the introduction of an individualized diet regimen and constant monitoring of nutritional intervention. It seems equally important to spread awareness about the possibility of refeeding syndrome and knowledge about its patomechanisms and consequences among medical staff. This should lead to minimizing the risk of refeeding syndrome.Expertopinion: It should be noted that current guidelines on the pathogenesis, risk factors and methods of prevention and treatment of refeeding syndrome require further modifications, that would harmonize the management regimen in both prevention and therapy of refeeding syndrome.

Refeeding syndrome is associated with increased mortality in malnourished medical inpatients: Secondary analysis of a randomized trial.

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 ±â€Š6.9 vs 9.0 ±â€Š6.6 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.

Refeeding Syndrome as a Possible Cause of Very Early Mortality in Acute Pancreatitis.

Background/Aims: Refeeding syndrome (RFS) is a fatal clinical complication that can occur as a result of fluid and electrolyte shifts during early nutritional rehabilitation for malnourished patients. This study was conducted to determine the clinical implications of RFS in patients with acute pancreatitis (AP). Methods: Between 2006 and 2016, AP patients with very early mortality were retrospectively enrolled from three university hospitals. Results: Among 3,206 patients with AP, 44 patients died within 3 days after diagnosis. The median age was 52.5 years (range, 27 to 92 years), male-to-female ratio was 3:1, and median duration from admission to death was 33 hours (range, 5 to 72 hours). The etiology of AP was alcohol abuse in 32 patients, gallstones in five patients, and hypertriglyceridemia in two patients. Ranson score, bedside index for severity of AP, and acute physiology and chronic health evaluation-II were valuable for predicting very early mortality (median, [range]; 5 [1 to 8], 3 [0 to 5], and 19 [4 to 45]). RFS was diagnosed in nine patients who died of septic shock (n=5), cardiogenic shock (n=2), or cardiac arrhythmia (n=2). In addition, patients with RFS had significant hypophosphatemia compared to non-RFS patients (2.6 mg/dL [1.3 to 5.1] vs 5.8 mg/dL [0.8 to 15.5]; p=0.001). The early AP-related mortality rate within 3 days was approximately 1.4%, and RFS occurred in 20.5% of these patients following sudden nutritional support. Conclusions: The findings of current study emphasize that clinicians should be aware of the possibility of RFS in malnourished AP patients with electrolyte imbalances.

Impact of caloric intake in critically ill patients with, and without, refeeding syndrome: A retrospective study.

BACKGROUND & AIMS: Refeeding syndrome comprises metabolic disturbances that occur after the reintroduction of feeding after prolonged fasting. Standard care consists of correcting fluid and electrolytes imbalances. Energy intake during refeeding syndrome is heavily debated. This study addresses the effect of caloric intake on outcome during the management of refeeding syndrome. METHODS: A retrospective study among critically ill invasive mechanically ventilated patients admitted for >7 days to a medical-surgical ICU. Refeeding syndrome was diagnosed by the occurrence of new onset hypophosphatemia (<0.65 mmol/l) within 72 h of the start of nutritional support. Primary outcome was 6-month mortality. Secondary outcomes were 3-month mortality, ICU and hospital length of stay and duration of mechanical ventilation. Outcomes of patients with and without refeeding syndrome were compared and subgroup analysis on energy intake within the refeeding population was performed for the duration of survival. RESULTS: Of 337 enrolled patients, 124 (36.8%) developed refeeding syndrome and 213 patients (63.2%) maintained normal serum phosphate levels. Between the two groups, no statistical significant differences in clinical outcomes were observed. Within the refeeding syndrome group, a reduced 6-month mortality risk for low caloric intake (<50% of target) was seen compared with normal intake, adjusted Hazard Ratio 0.39, (95% CI 0.16-0.95, p = 0.037). In this group, low caloric intake was associated with an increased overall survival time at day 180 (153.0 (SE 10.1) vs 119.1 (SE 8.0) days, log-rank p = 0.018). CONCLUSIONS: Refeeding syndrome is common among prolonged mechanically ventilated critically ill patients, however not predictable by baseline characteristics. Among patients that develop refeeding syndrome low caloric intake was associated with a reduction in 6-month mortality risk. This effect was not seen in patients without refeeding syndrome. Findings support caloric restriction in refeeding syndrome during critical illness.

Throw caution to the wind: is refeeding syndrome really a cause of death in acute care?

BACKGROUND/OBJECTIVES: Refeeding syndrome (RFS), a life-threatening medical condition, is commonly associated with acute or chronic starvation. While the prevalence of patients at risk of RFS in hospital reportedly ranges from 0 to 80%, the prevalence and types of patients who die as a result of RFS is unknown. We aimed to measure the prevalence rate and examine the case histories of patients who passed away with RFS listed as a cause of death. SUBJECTS/METHODS: Patients were eligible for inclusion provided their death occurred within a Queensland hospital. Medical charts were reviewed, for medical, clinical and nutrition histories with results presented using descriptive statistics. RESULTS: Across 18 years (1997-2015) and ~260000 hospital deaths, five individuals (4F, 74 (37-87)yrs) were identified. No patient had a past or present diagnosis, such as anorexia nervosa, that would classify them as at high risk for RFS. RFS was not listed as the primary cause of death for any patient. No individual consumed >3400 kJ per day. Limited consensus was observed in the signs and symptoms used to diagnose RFS, although all patients experienced low levels of potassium, phosphate and/or magnesium. Eighty percent of electrolytes improved before death. CONCLUSIONS: RFS was a rare underlying cause of death, despite reported high prevalence rates of risk. Patient groups usually considered to be at high risk were not identified, suggesting a level of imprecision with the interpretation of criteria used to identify RFS risk. More detailed research is warranted to assist in the identification of those distinctly at risk of RFS.

Risk factors for death in children during inpatient treatment of severe acute malnutrition: a prospective cohort study.

BACKGROUND: Children who receive in-hospital treatment of severe acute malnutrition often have high mortality rates, and the reasons are not well understood. OBJECTIVE: We assessed risk factors for death in children who were treated for malnutrition in a hospital. DESIGN: In a prospective observational study of 120 children who were receiving in-hospital treatment of severe acute malnutrition in Uganda with therapeutic formulas F-75 and F-100, we collected data on symptoms, clinical findings, plasma markers of refeeding syndrome (electrolytes and phosphate), and acute phase reactants, and recorded the nutritional therapy given in hospital. RESULTS: Seventeen children (14%) died. Clinical risk factors for death were the presence of oral thrush (HR: 5.0; 95% CI: 1.6, 15.2), a caretaker-reported severity of illness on a visual analog scale (HR: 1.7; 95% CI: 1.1, 2.6), impaired consciousness (HR: 16.7; 95% CI: 3.1, 90.4), and a capillary refill time >2 s (HR: 3.9; 95% CI: 1.4, 11.3). HIV infection was not associated with mortality (HR: 3.0; 95% CI: 0.7, 12.4), which was most likely due to low power. Biochemical risk factors were a plasma C-reactive protein concentration >15 mg/L on admission and low plasma phosphate that was measured on day 2 (HR: 8.7; 95% CI: 2.5, 30.1), particularly in edematous children. The replacement of F-75 with unfortified rice porridge to ameliorate diarrhea was associated with a higher risk of death, particularly if given during the first 2 d (HR: 5.0; 95% CI: 1.9, 13.3), which was an association that remained after adjustment for potential confounders (HR: 69.5; 95% CI: 7.0, 694.6). CONCLUSIONS: Refeeding syndrome may occur in children who are treated for malnutrition, even with moderately low plasma phosphate, and, in particular, in children with edematous malnutrition. The replacement of F-75 with unfortified rice porridge is associated with increased risk of death, which is possibly mediated by lowering plasma phosphate. The identified clinical risk factors may potentially improve the triage of children with malnutrition. This trial was registered at www.isrctn.com as ISRCTN55092738.

Leptin and insulin growth factor 1: diagnostic markers of the refeeding syndrome and mortality.

Refeeding syndrome is difficult to diagnose since the guidelines for identifying those at risk are largely based on subjective clinical parameters and there are no predictive biochemical markers. We examined the suitability of insulin-like growth factor 1 (IGF1) and leptin as markers to identify patients at risk of the refeeding syndrome before initiation of parenteral nutrition (PN). A total of thirty-five consecutive patients referred for commencement of PN were included. Serum leptin and IGF1 were measured before starting PN. Electrolytes, liver and renal function tests were conducted before and daily for 1 week after initiating PN. The primary outcome was a decrease in phosphate 12-36 h after initiating PN. 'Refeeding index' (RI) was defined as leptin × IGF1 divided by 2800 to produce a ratio of 1·0 in patients who are well nourished. RI had better sensitivity (78 %; 95 % CI 40, 97 %) and specificity (78 %; 95 % CI 40, 97 %) with a likelihood ratio of 3·4, at a cut-off value of 0·19 for predicting a ≥ 30 % decrease in phosphate concentration within 12-36 h after starting PN, compared with IGF1 or leptin alone. However, IGF1 was a better predictor of mortality than either leptin or the RI. The present study is the first to derive and test the 'RI', and find that it is a sensitive and specific predictor of the refeeding syndrome in hospitalised patients before starting PN.

Refeeding hypophosphataemia is more common in enteral than parenteral feeding in adult in patients.

BACKGROUND & AIMS: Refeeding hypophosphataemia (RH) can result in sudden death. This study aimed to compare the incidence of RH between patients fed enterally and those fed parenterally. METHODS: The risk of RH in adult patients fed parenterally (PN) or nasogastrically (NG) was assessed by comparison of patient records with the UK NICE guidelines for refeeding syndrome, between December 2007 and December 2008. A fall in serum phosphate to less than 0.6 mmol/L was indicative of RH. RESULTS: Of 321 patients,92 were at risk of RH. Of these, 23 (25%) patients developed RH (p = 0.003). 18 (33%) of NG fed, 'at-risk' patients developed RH vs 5 (13%) fed parenterally (p = 0.03). Death within 7 days and RH were not associated. The sensitivity and specificity of the NICE criteria for defining patient's risk of RH was calculated: 0.76 and 0.50 respectively for NG feeding; 0.73 and 0.38 respectively for parenteral feeding. CONCLUSION: Patients fed by NG tube and deemed at risk of RH are more likely to develop RH than patients fed by PN. The higher risk with NG feeding may be due to the incretin effect from absorption of glucose. The UK guidelines lack specificity.

Refeeding syndrome influences outcome of anorexia nervosa patients in intensive care unit: an observational study.

INTRODUCTION: Data on the epidemiology and management of anorexia nervosa (AN) in the intensive care unit (ICU) are scarce. The aim of this study was to evaluate the prevalence and associated morbidity and mortality of AN in French ICUs. METHODS: We randomly selected 30 ICUs throughout France. Thereafter, we retrospectively analyzed all patients with AN admitted to any of these 30 ICUs between May 2006 and May 2008. We considered demographic data, diagnosis at admission and complications occurring during the stay, focusing on refeeding syndrome and management of refeeding. RESULTS: Eleven of the 30 ICUs participated in the retrospective study, featuring 68 patients, including 62 women. Average body mass index at the admission was 12 ± 3 kg/m2. Twenty one were mechanically ventilated, mainly for neurological reasons. The reported average calorie intake was 22.3 ± 13 kcal/kg/24 h. Major diagnoses at admission were metabolic problems, refeeding survey and voluntary drug intoxication and infection. The most common complications were metabolic, hematological, hepatic, and infectious events, of which 10% occurred during refeeding. Seven patients developed refeeding syndrome. At day one, the average calorie intake was higher for patients who developed refeeding syndrome (23.2 ± 5 Kcal/kg/j; n = 7) versus patients without refeeding syndrome (14.1 ± 3 Kcal/kg/j; n = 61) P = 0.02. Seven patients died, two from acute respiratory distress syndrome and five from multiorgan-failure associated with major hydroelectrolytic problems. CONCLUSIONS: The frequency of AN in ICU patients is very low and the crude mortality in this group is about 10%. Prevention and early-detection of refeeding syndrome is the key point.

Mortality after nasogastric tube feeding initiation in long-term care elderly with oropharyngeal dysphagia--the contribution of refeeding syndrome.

BACKGROUND: The refeeding syndrome (RS) is an underappreciated but clinically important entity characterized by acute electrolyte abnormalities, mainly hypophosphatemia, fluid retention and dysfunction of various organs and systems, which can result in significant morbidity and occasionally death. OBJECTIVE: To examine the incidence of death cases and death causes following nasogastric tube (NGT) feeding initiation in frail elderly with particular reference to RS. METHODS: Forty patients with feeding problems for at least 72 h before restarting of alimentation by NGT were included. Excluded were those in any critical clinical situation. Clinical parameters and nutritional assessment were recorded before and after refeeding. Blood samples were taken before, daily for the first 3 days and 1 week after refeeding initiation. RESULTS: During the 1st week of refeeding, 9 patients (22.5%) died and within 1 month 10 more, summing to 47.5%. Most deaths were due to infectious causes [15 out of 19, (79%)]; some were due to no obvious reason [4 out of 19, (21%)]. Significant electrolyte changes were observed in the 2-3 days following refeeding. Significant were the decreases in phosphorus and elevations in potassium and lymphocytes (day 7). We found no correlations between the severity of decreases in levels of phosphorus and mortality. CONCLUSIONS: Mortality after NGT feeding initiation was high, mainly due to infectious complications. However, in a considerable number of patients hypophosphatemia was noted, suggesting that RS could be a contributory factor of mortality. Since this is a treatable condition, more attention should be paid to detecting and coping with this problem.