Incidence and Risk Factors of Refeeding Syndrome in Preterm Infants.

This study aimed to evaluate the incidence and risk factors associated with refeeding syndrome (RFS) in preterm infants (≤32 weeks gestational age) during their first week of life. Infants (gestational age ≤ 32 weeks; birth weight < 1500 g) who were admitted to the neonatal intensive care unit (NICU), level III, and received parenteral nutrition between January 2015 and April 2024 were retrospectively evaluated. Modified log-Poisson regression with generalized linear models and a robust variance estimator was applied to adjust the relative risk of risk factors. Of the 760 infants identified, 289 (38%) developed RFS. In the multivariable regression analysis, male, intraventricular hemorrhage (IVH), and sodium phosphate significantly affected RFS. Male infants had significantly increased RFS risk (aRR1.31; 95% CI 1.08-1.59). The RFS risk was significantly higher in infants with IVH (aRR 1.71; 95% CI 1.27-2.13). However, infants who received higher sodium phosphate in their first week of life had significantly lower RFS risk (aRR 0.67; 95% 0.47-0.98). This study revealed a notable incidence of RFS among preterm infants aged ≤32 gestational weeks, with sex, IVH, and low sodium phosphate as significant risk factors. Refined RFS diagnostic criteria and targeted interventions are needed for optimal management.

Hypophosphatemia after Start of Medical Nutrition Therapy Indicates Early Refeeding Syndrome and Increased Electrolyte Requirements in Critically Ill Patients but Has No Impact on Short-Term Survival.

Refeeding syndrome (RFS) is a potentially life-threatening complication in malnourished (critically ill) patients. The presence of various accepted RFS definitions and the inclusion of heterogeneous patient populations in the literature has led to discrepancies in reported incidence rates in patients requiring treatment at an intensive care unit (ICU). We conducted a prospective observational study from 2010 to 2013 to assess the RFS incidence and clinical characteristics among medical ICU patients at a large tertiary center. RFS was defined as a decrease of more than 0.16 mmol/L serum phosphate to values below 0.65 mmol/L within seven days after the start of medical nutrition therapy or pre-existing serum phosphate levels below 0.65 mmol/L. Overall, 195 medical patients admitted to the ICU were included. RFS was recorded in 92 patients (47.18%). The presence of RFS indicated significantly altered phosphate and potassium levels and was accompanied by significantly more electrolyte substitutions (phosphate, potassium, and magnesium). No differences in fluid balance, energy delivery, and insulin requirements were detected. The presence of RFS had no impact on ICU length of stay and ICU mortality. Screening for RFS using simple diagnostic criteria based on serum phosphate levels identified critically ill patients with an increased demand for electrolyte substitutions. Therefore, stringent monitoring of electrolyte levels is indicated to prevent life-threatening complications.

Refeeding syndrome and psychopharmacological interventions in children and adolescents with Anorexia Nervosa: a focus on olanzapine-related modifications of electrolyte balance.

This study aims to investigate the potential correlation between the use of olanzapine, a psychopharmacological intervention commonly prescribed in Anorexia Nervosa treatment, and the occurrence of Refeeding Syndrome. Despite the acknowledged nutritional and biochemical impacts of olanzapine, the literature lacks information regarding its specific association with Refeeding Syndrome onset in individuals with Anorexia Nervosa. This is a naturalistic, retrospective, observational study, reporting the occurrence of Refeeding Syndrome in children and adolescents with Anorexia Nervosa, treated or untreated with olanzapine. Dosages and serum levels of olanzapine were assessed for potential associations with the occurrence of Refeeding Syndrome and specific variations in Refeeding Syndrome-related electrolytes. Overall, 113 patients were enrolled, including 46 (41%) who developed a Refeeding Syndrome. Mild (87%), moderate (6.5%), and severe (6.5%) Refeeding Syndrome was described, at a current average intake of 1378 ± 289 kcal/day (39 ± 7.7 kcal/kg/die), frequently associated with nasogastric tube (39%) or parenteral (2.2%) nutrition. Individuals receiving olanzapine experienced a more positive phosphorus balance than those who did not (F(1,110) = 4.835, p = 0.030), but no difference in the occurrence of Refeeding Syndrome was documented. The mean prescribed doses and serum concentrations of olanzapine were comparable between Refeeding Syndrome and no-Refeeding Syndrome patients.    Conclusion: The present paper describes the occurrence of Refeeding Syndrome and its association with olanzapine prescriptions in children and adolescents with Anorexia Nervosa. Olanzapine was associated with a more positive phosphorus balance, but not with a different occurrence of Refeeding Syndrome. Further, longitudinal studies are required. What is Known: • Refeeding Syndrome (RS) is a critical complication during refeeding in malnourished patients, marked by electrolyte (phosphorus, magnesium, potassium) imbalances. • Olanzapine, an atypical antipsychotic with nutritional and biochemical impacts, is used in Anorexia Nervosa (AN) treatment, however data concerning its association with RS are lacking. What is New: • The study observed RS in 46/113 (41%) young patients with AN. • Olanzapine-treated individuals showed a higher improvement in serum phosphate levels than untreated ones, although no impact on the occurrence of Refeeding Syndrome was observed.

Incidence of hypophosphataemia after ICU admission in mechanically ventilated patients and its relationship with risk factors for refeeding syndrome.

OBJECTIVE: To describe the incidence of hypophosphatemia in patients admitted to the ICU who have required mechanical ventilation. To analyze the presence of risk factors and its relationship with nutritional practice. DESIGN: Prospective observational study. SETTING: Polyvalent ICUs of 2 University Hospitals. PATIENTS OR PARTICIPANTS: Patients on invasive mechanical ventilation ≥72 h with normal level of phosphorus at admission. INTERVENTIONS: None. MAIN VARIABLES OF INTEREST: Electrolyte levels (phosphorus, magnesium, potassium) were determined on admission to the ICU and at 96 h. Risk categories on admission, caloric intake, insulin doses and acid-base status during the first 4 days of admission were recorded. Incidence was calculated as the number of patients who developed hypophosphataemia after admission. Univariate analysis was performed for between-group comparison and multivariate analysis of potential risk factors. RESULTS: 89 patients were included. The incidence of hypophosphataemia was 32.6%. In these patients phosphorus decreased from 3.57 ±â€¯1.02 mmol/l to 1.87 ±â€¯0.65 mmol/l (52.3%). The mean kcal/kg/24 h provided in the first 4 days was 17.4 ±â€¯4.1, with no difference between the group that developed hypophosphataemia and the group that did not. Significant risk factors were insulin doses administered and pH and PaCO2 values. CONCLUSIONS: The incidence of hypophosphataemia at 96 h from admission in mechanically ventilated patients is high and unrelated to the risk category and hypocaloric nutritional practice used. Insulin dosis and acid-base status are the main determinants of its occurrence.

Association between energy delivery from parenteral nutrition and refeeding syndrome in hospitalized adults: A retrospective cohort study.

BACKGROUND: Patients receiving parenteral nutrition (PN) may develop refeeding syndrome (RFS). This study determined RFS prevalence in hospitalized adults on PN and evaluated whether higher energy delivered by PN on day 1 of PN initiation was associated with RFS development. METHODS: We reviewed the medical records of adult patients receiving PN at a Thai quaternary hospital from June 2019 to May 2022. RFS was defined based on the Nutrition Management Clinical Practice Recommendation by the Society of Parenteral and Enteral Nutrition of Thailand. The association between PN energy delivery and RFS development was determined using a generalized estimating equation for multiple logistic regression analysis adjusted for NICE guideline risk factors. RESULTS: A total of 547 patients was included (mean age 59.8 ± 17.2 years, mean body mass index 20.7 ± 4.8 ). The prevalence of RFS was 45%. Factors associated with RFS included energy from PN on the first day of PN initiation (adjusted odds ratio [aOR] 1.17; 95% CI 1.04-1.33; for every 5 kcal/kg/day increase), starvation >5 days prior to PN (aOR 1.54; 95% CI 1.04-2.26), concomitant diuretic use (aOR 1.81; 95% CI 1.25-2.64), low baseline potassium level (aOR 1.79; 95% CI 1.19-2.70), and individual compounding PN (aOR 1.61; 95% CI 1.04-2.51). CONCLUSION: RFS was common among hospitalized patients receiving PN. The amount of energy delivered on the first day of PN was independently associated with RFS, raising a concern regarding initiation of PN with higher energy.

Refeeding Syndrome in Pediatric Age, An Unknown Disease: A Narrative Review.

Refeeding syndrome (RS) is characterized by electrolyte imbalances that can occur in malnourished and abruptly refed patients. Typical features of RS are hypophosphatemia, hypokalemia, hypomagnesemia, and thiamine deficiency. It is a potentially life-threatening condition that can affect both adults and children, although there is scarce evidence in the pediatric literature. The sudden increase in food intake causes a shift in the body's metabolism and electrolyte balance, leading to symptoms such as weakness, seizures, and even heart failure. A proper management with progressive increase in nutrients is essential to prevent the onset of this condition and ensure the best possible outcomes. Moreover, an estimated incidence of up to 7.4% has been observed in pediatric intensive care unit patients receiving nutritional support, alone or as an adjunct. To prevent RS, it is important to carefully monitor feeding resumption, particularly in severely malnourished individuals. A proper strategy should start with small amounts of low-calorie fluids and gradually increasing the calorie content and amount of food over several days. Close monitoring of electrolyte levels is critical and prophylactic use of dietary supplements such as thiamine may be required to correct any imbalances that may occur. In this narrative review, we aim to provide a comprehensive understanding of RS in pediatric clinical practice and provide a possible management algorithm.

Assessment of refeeding syndrome definitions and 30-day mortality in critically ill adults: A comparison study.

BACKGROUND: Patients in the intensive care unit (ICU) are at high risk for refeeding syndrome (RFS), yet there is uncertainty regarding how RFS should be operationalized in the ICU. We evaluated different definitions for RFS and tested how they associated with patient-centered outcomes in the ICU. METHODS: This was a retrospective comparison study. Patients age ≥18 years were eligible if they were newly initiated on enteral feeding while hospitalized in the ICU. Eight definitions for RFS were operationalized, including that from the American Society for Parenteral and Enteral Nutrition (ASPEN), all based on electrolyte levels from immediately before until up to 5 days after the initiation of enteral nutrition. Patients were followed for death or for ICU-free days, a measure of healthcare utilization. RESULTS: In all, 2123 patients were identified, including 406 (19.1%) who died within 30 days of ICU admission and 1717 (80.9%) who did not. Prevalence of RFS varied from 1.5% to 88% (ASPEN definition) depending on the RFS definition used. The excess risk for death associated with RFS varied from 33% to 92% across definitions. The development of RFS based on the ASPEN definition was associated with a greater decrease in ICU-free days compared with other definitions, but the relationship was not statistically significant. CONCLUSION: Eight definitions for RFS were evaluated, none of which showed strong associations with death or ICU-free days. It may be challenging to achieve a standardized definition for RFS that is based on electrolyte values and predicts mortality or ICU-free days.

Hyoro-zeme in the Battle for Tottori Castle: The first description of refeeding syndrome in Japan.

Eating after a period of starvation can cause refeeding syndrome, a fatal condition caused by a shift in fluids and electrolytes that can result in sudden death. The Battle for Tottori Castle (1581) during the Warring States Period of Japan, which witnessed the use of hyoro-zeme, the tactic of intentionally starving a besieged enemy, was followed by a dramatic episode of mass death among starving soldiers not from fighting but from eating; accounts from the period relate that many of the besieged soldiers survived the hyoro-zeme only to die soon afterwards when they were fed immediately after surrendering. We herein reviewed the Japanese historical records of the Battle for Tottori Castle and hypothesized that the hyoro-zeme episode they recount is possibly the oldest description of refeeding syndrome to be documented in Japan. Our investigation revealed sufficient evidence that refeeding syndrome was the cause of the mass deaths reported after the famous battle.

Unpredictable refeeding syndrome with severe hypophosphatemia in borderline personality disorder comorbidity: A case report.

RATIONALE: Refeeding syndrome (RS) is a fatal condition caused by rapid calorie intake during starvation. Self-neglected fasting in psychiatric disorders is associated with RS. However, overeating resulting from circumventing the clinician's instructions does not have a reportedly high risk of RS. PATIENT CONCERNS: A 47-year-old undernourished woman with borderline personality disorder was hospitalized for nausea, vomiting, and diarrhea. CLINICAL FINDINGS: She had not eaten much for 10 days and had lost weight (56.5-51.1 kg) over 3 weeks. No abnormalities were indicated on physical examination and imaging examinations. DIAGNOSES, INTERVENTIONS, AND OUTCOMES: Infectious diseases and malignancies were excluded from the differential diagnosis. On the third day of admission, the patient's serum phosphorus level significantly decreased to 0.7 mg/dL, and additional sodium phosphate was administered intravenously. On the fourth day, despite our instructions, the patient was found to be eating nonhospital food from the first day of admission. In conjunction with her history, a final diagnosis of RS was made. After appropriate treatments, the patient was discharged on the 15th day of hospitalization. The patient's nausea, vomiting, and diarrhea were improved. LESSONS: When undernourished patients have psychiatric disorders, including borderline personality disorder or schizophrenia, the occurrence of RS should be considered based on the patients' poor adherence to physicians' instructions.

Recognizing neonatal refeeding syndrome and thiamin supplementation: A case report.

Refeeding syndrome (RS) is a condition characterized by electrolyte derangements, thiamin deficiency, and organ dysfunction after the provision of nutrition to an individual who had been deprived of nutrients. Published guidelines outlining the recognition and definition of RS exist for adult and children, but there are limited newborn-specific guidelines because of a paucity of available literature and variation in reporting. We describe a small-for-gestational-age, full-term newborn with neonatal encephalopathy who underwent therapeutic hypothermia. Electrolyte derangements and lactic acidosis developed and persisted after the introduction of intravenous nutrition. After the exclusion of other etiologies, neonatal RS was suspected, and the newborn was treated with thiamin. We provide a brief review of the current literature on neonatal RS, present a case report consistent with neonatal RS, and provide suggestions for the utility of thiamin replacement in newborns with suspected neonatal RS.

The Performances of SNAQ, GLIM, mNICE, and ASPEN for Identification of Neurocritically Ill Patients at High Risk of Developing Refeeding Syndrome.

We previously found that neurocritically ill patients are prone to refeeding syndrome (RFS), a potentially life-threatening complication. However, there is no unified or validated consensus on the screening tool for RFS so far. We aimed to validate and compare the performance of four screening tools for RFS in neurocritically ill patients. We conducted a single-center, observational, retrospective cohort study among neurocritically ill adult patients who were admitted to the neurocritical care unit (NCU), and who received enteral nutrition for 72 h or longer. They were scored on the Short Nutritional Assessment Questionnaire (SNAQ), the Global Leadership Initiative on Malnutrition (GLIM), the modified criteria of the Britain's National Institute for Health and Care Excellence (mNICE), and ASPEN Consensus Recommendations for Refeeding Syndrome (ASPEN) scales to predict RFS risk via admission data. The performance of each scale in predicting RFS was evaluated. Logistic regression analysis was used to identify the independent risk factors for RFS, and they were added to the above scales to strengthen the identification of RFS. Of the 478 patients included, 84 (17.57%) developed RFS. The sensitivity of the SNAQ and GLIM was only 20.2% (12.6-30.7%), although they had excellent specificities of 84.8% (80.8-88.1%) and 86.0% (82.1-89.2%), respectively; mNICE predicted RFS with a sensitivity of 48.8% (37.8-59.9%) and a specificity of 65.0% (60.0-69.9%); ASPEN had the highest Youden index, with a sensitivity and specificity of 53.6% (42.4-64.4%) and 64.7% (59.8-69.4%), respectively. The Area Under the receiver operating characteristic Curves (AUC) of SNAQ, GLIM, mNICE, and ASPEN to predict RFS were 0.516 (0.470-0.561), 0.533 (0.487-0.579), 0.568 (0.522-0.613), and 0.597 (0.551-0.641), respectively. We identified age, Acute Physiology and Chronic Health Evaluation II (APACHE II), Sequential Organ Failure Assessment (SOFA), and Glasgow Coma Scale (GCS) score as independent risk factors of RFS, and the combination of GCS and age can improve the AUC of ASPEN to 0.664 (0.620-0.706) for predicting RFS. SNAQ, GLIM, mNICE, and ASPEN do not perform well in identifying neurocritically ill patients at high risk of RFS, although ASPEN appears to have relatively a good validity among them. Combining GCS and age with ASPEN slightly improves RFS recognition, but it still leaves a lot of room for improvement.

Safe Management by a Pop-Up Eating Disorder Team.

Background Anorexia nervosa has a high mortality complicated by risks of under-nourishment, over-nourishment and care can be compromised by behavioural issues. Methods This is a retrospective study of ten patients with eating disorders admitted to Sligo University Hospital, treated by a "pop-up"/on demand multidisciplinary eating disorder team. Results All were female, mean BMI on admission was 14.35kg/m2, on discharge was 16.59kg/m2, (p=0.001) and was significantly lower than the initial measurement and may represent water-loading or bowel retention. Admission biochemistry was normal in nine subjects. Six subjects experienced refeeding syndrome, one was hypoglycaemic (3.1mmol/L) in the setting of an aspiration pneumonia, and five exhibited treatment avoiding behaviour including food caching, micro exercising. The mean length of stay was 38 days and was positively correlated with weight gain during admission (p=0.02). 6-month follow up BMI was higher than admission in eight subjects and the other two voluntarily withdrew from follow-up. Conclusion There was a high incidence of treatment avoiding behaviour, initial weights were misleadingly high, admission biochemistry misleadingly normal, hypoglycaemia associated with infection, and incidence of refeeding syndrome is high. Notwithstanding this these patients can be managed safely and effectively in a general hospital with a coordinated, well-structured approach by a multidisciplinary team.

Refeeding Hypophosphatemia in Hospitalized Adolescents With Anorexia Nervosa.

Refeeding hypophosphatemia in hospitalized adolescents with anorexia nervosa is correlated with degree of malnutrition, with a high index of suspicion for severely malnourished patients (<70% median body mass index). Weight history (greater magnitude or rate of weight loss prior to admission) regardless of presentation weight has also been associated with lower serum phosphate. Higher energy meal-based refeeding starting at 2,000 kcal has not been shown to be associated with higher rates of refeeding hypophosphatemia than the traditional standard of care, lower energy refeeding. Further research is needed to identify risk factors for refeeding hypophosphatemia and develop optimal delivery methods (oral vs. enteral), macronutrient content, and electrolyte replacement strategies to optimize weight gain without increasing the risk for refeeding hypophosphatemia.

Impact of calorie intake and refeeding syndrome on the length of hospital stay of patients with malnutrition: a systematic review and meta-analysis.

BACKGROUND & AIMS: The decrease of nutritional status has affected one-third hospitalized patients, while there is no widely used definition of malnutrition. Refeeding syndrome is a severe complication of refeeding in people with malnutrition, it includes a series of electrolyte disorders and clinical symptoms. Further research is warranted to determine whether refeeding syndrome prolongs the length of stay, and to verify the effect of different energy intakes during refeeding on the length of stay in people with malnutrition. Our review aimed to explore the effects of refeeding syndrome and initial calorie intake on the length of stay in patients with malnutrition. This study aids the understanding of clinical nutrition strategies to prevent and treat refeeding syndrome. METHODS: PubMed, Embase, Cochrane Library, Web of Knowledge, and two Chinese databases were systematically searched until October 2021. Controlled studies of patients' refeeding process with the outcome of length of stay were included. Effect sizes were expressed as 95% confidence intervals (CIs) and calculated using random-effects models. RESULTS: Eighteen studies involving 3868 participants were included in our review. The pooled length of stay of 2965 patients with refeeding syndrome in 11 studies was 25.55 (95% CI, 20.20-30.90) days. The pooled impact of refeeding syndrome on length of stay of 2634 patients in 10 studies was weighted mean difference (WMD) = 2.91 (95% CI, -0.18 - 6.00; P = 0.065) days. The pooled effect of higher calorie intake of 1234 patients in 8 studies was WMD = -3.04 (95% CI, -5.10 to -0.99, P = 0.003) days. CONCLUSIONS: The average length of stay in patients with refeeding syndrome was 25.55 days with a very high heterogeneity between studies. Refeeding syndrome affects the length of stay in part of, but not all, patients. In the present review, we concluded that higher initial calorie intake may help shorten the length of stay in patients with malnutrition. More well-designed randomized controlled trials are needed to explore the effect of calorie intake during refeeding.

[Refeeding Syndrome: Where Do We Stand in 2022?] / Refeeding-Syndrom: Wo stehen wir 2022?

Refeeding Syndrome: Where Do We Stand in 2022? Abstract. The refeeding syndrome is a potentially life-threatening condition that can occur when refeeding malnourished patients. In recent years, two consensus manuscripts were published by the major clinical nutrition societies ESPEN and ASPEN. Pathophysiological aspects, clinical manifestations, prevention measures and criteria for diagnosis and management have been described in detail. The aim of this mini-review is to provide an evidence-based overview on the refeeding syndrome. For this purpose, the systematic literature search by Friedli et al. 2015 was updated. Evidence that the refeeding syndrome is associated with a negative clinical outcome exists. Many questions about management aspects remain unanswered. A robust randomized controlled trial is urgently needed to answer all these questions in an evidence-based manner and to elicit reliable evidence about independent predictors and an estimate of metabolic risk.

Incidence and Impact of Refeeding Syndrome in an Internal Medicine and Gastroenterology Ward of an Italian Tertiary Referral Center: A Prospective Cohort Study.

Background: Refeeding syndrome (RS) is a neglected, potentially fatal syndrome that occurs in malnourished patients undergoing rapid nutritional replenishment after a period of fasting. The American Society for Parenteral and Enteral Nutrition (ASPEN) recently released new criteria for RS risk and diagnosis. Real-life data on its incidence are still limited. Methods: We consecutively enrolled patients admitted to the Internal Medicine and Gastroenterology Unit of our center. The RS risk prevalence and incidence of RS were evaluated according to ASPEN. The length of stay (LOS), mortality, and re-admission rate within 30 days were assessed. Results: Among 203 admitted patients, 98 (48.3%) were at risk of RS; RS occurred in 38 patients (18.7% of the entire cohort). Patients diagnosed with RS had a higher mean LOS (12.5 days ± 7.9) than those who were not diagnosed with RS (7.1 ± 4.2) (p < 0.0001). Nine patients (4.4%) died. Body mass index (OR 0.82; 95% CI 0.69−0.97), RS diagnosis (OR 10.1; 95% CI 2.4−42.6), and medical nutritional support within 48 h (OR 0.12; 95% CI 0.02−0.56) were associated with mortality. Conclusions: RS incidence is high among clinical wards, influencing clinical outcomes. Awareness among clinicians is necessary to identify patients at risk and to support those developing this syndrome.

Evaluation of the ASPEN guidelines for refeeding syndrome among hospitalized patients receiving enteral nutrition: A retrospective cohort study.

BACKGROUND: Until recently, refeeding syndrome (RFS) has lacked standardized diagnostic criteria. This study sought to (1) determine whether RFS, as operationalized in the 2020 American Society for Parenteral and Enteral Nutrition (ASPEN) guideline definition, is associated with adverse clinical outcomes and (2) identify key risk factors for RFS. METHODS: In this retrospective cohort study, adults hospitalized from 2015 to 2019 were included if they were ordered for enteral feeding during hospitalization. Data were collected for up to 30 days, and RFS was operationalized as per the ASPEN 2020 guidelines as a ≥10% (corresponding to mild RFS), ≥25% (moderate), and ≥50% (severe) decline in prefeeding serum phosphorus, magnesium, or potassium. The mortality associated with RFS was assessed, and risk factors for RFS were identified using multivariable logistic regression modeling. RESULTS: Of 3854 participants, 3480 (90%) developed mild RFS. Thirty-day mortality was higher in those without mild RFS (24%) than in those with mild RFS (18%) (P < 0.01). When RFS was reoperationalized as a 50% decline in electrolytes, 25% of patients developed RFS with a 20% 30-day mortality. Risk factors for development of RFS included renal failure, elevated creatinine, and low platelets; additionally, prefeeding serum phosphorus level was strongly associated with development of RFS (adjusted odds ratio, 6.09; 95% confidence interval, 4.95-7.49 for those in the highest tertile of prefeeding phosphorus compared with the lowest). CONCLUSION: The ASPEN operationalization of RFS as a decline in baseline electrolyte values was not associated with death. Prefeeding serum phosphorus level strongly predicted severe RFS.