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ObjectiveTo investigate in extremely low birthweight (ELBW; <1000 g) babies the associations between refeeding syndrome (serum phosphate <1.4 mmol·L-1 and serum total calcium>2.8 mmol·L-1) and hypophosphataemia in the first week and death or neurodisability at 2 years’ corrected age (CA).DesignSecondary cohort analysis of the ProVIDe trial participants with serum biochemistry within 7 days of birth. At 2 years’ CA, neurodisability was assessed by Bayley Scales of Infant Development Edition III and neurological examination. Associations between neurodisability and other variables were analysed using t-tests and logistic regression adjusted for sex and smallness-for-gestational age.SettingSix tertiary neonatal intensive care units (NICUs) in New Zealand.Participants352 ELBW babies born between 29 April 2014 and 30 October 2018.Main outcome measureDeath or neurodisability at 2 years’ CA.ResultsFifty-nine babies died, two after discharge from the NICU. Of the 336 babies who survived to 2 years’ CA, 277 had neurodevelopmental assessment and 107 (39%) had a neurodisability. Death or neurodisability was more likely in babies who had refeeding syndrome (aOR 1.96 (95% CI 1.09 to 3.53), p=0.02) and in babies who had hypophosphataemia (aOR 1.74 (95% CI 1.09 to 2.79), p=0.02). Hypophosphataemia was associated with increased risk of death (aOR 2.07 (95% CI 1.09 to 3.95), p=0.03)) and severe hypophosphataemia (<0.9 mmol·L-1) with increased risk of death (aOR 2.67 (95% CI 1.41 to 5.00), p=0.002) and neurodisability (aOR 2.31 (95% CI 1.22 to 4.35), p=0.01).ConclusionsIn ELBW babies, refeeding syndrome and hypophosphataemia in the first week are associated with death or neurodisability. Until optimal phosphate requirements are determined through further research, monitoring for hypophosphataemia and mitigation strategies are indicated.Trial registration numberACTRN12612001084875

Refeeding syndrome (RS) is defined as the spectrum of metabolic and biochemical disorders related to rapid nutritional replenishment after a prolonged period of fasting. It is caused by an abrupt shift in electrolytes and fluid among intra- and extracellular compartments, leading to metabolic disturbances like hypophosphatemia, vitamin deficiency, and fluid overload. RS often remains underdiagnosed due to variability in definition and diagnostic criteria adopted, overlapping clinical features with other complications and low awareness among clinicians. Critically ill individuals, particularly those admitted to intensive care units (ICUs), represent a cohort with peculiar features that may heighten RS risk due to their baseline frailty, frequent undernutrition, and the metabolic stress of acute illness. However, studies specifically conducted in ICU settings have yielded conflicting results regarding incidence rates, prognostic impact, and specific risk factors. Despite these differences, all evidence consistently highlights RS as a frequent and serious complication in critically ill patients. Early detection and prevention are essential, relying on prompt nutritional assessment at ICU admission, careful monitoring of serum electrolytes before and during refeeding, and a conservative caloric approach to nutrient reintroduction, alongside supportive therapy and electrolyte supplementation if RS manifestations occur. Clinicians should be aware of the significant prevalence and potential severity of RS in critically ill patients, along with the ongoing challenges related to its early recognition, prevention, and optimal nutritional management. This review aims to provide a comprehensive overview of the current knowledge on the incidence, prognostic impact, risk factors, clinical manifestations, and nutritional management of RS in critically ill patients while highlighting existing evidence gaps and key areas requiring clinical attention.

Purpose of Review To provide an overview of current methods of diagnosis and management of refeeding syndrome in the critically ill patient population. Recent Findings Despite recent publications indicating refeeding syndrome (RFS) is an ongoing problem in critically ill patients, there is no standard for the diagnosis and management of this life-threatening condition. There is not a “gold standard” nutrition assessment tool for the critically ill. Currently, the National Institute for Health and Clinical Excellence criteria represent the best clinical assessment tool for RFS . Diagnosis and management with the help of a multidisciplinary metabolic team can decrease morbidity and mortality. Summary Although a universal definition of RFS has yet to be defined, the diagnosis is made in patients with moderate to severe malnutrition who develop electrolyte imbalance after beginning nutritional support. The imbalances potentially can lead to cardiac, pulmonary, and gastrointestinal complications and failure. Standardizing a multidisciplinary nutrition care plan and formulating a protocol for critically ill patients who develop RFS can potentially decrease complication rates and overall mortality.

Refeeding in anorexia nervosa is a collaborative enterprise involving multidisciplinary care plans, but clinicians currently lack guidance, as treatment guidelines are based largely on clinical confidence rather than more robust evidence. It seems crucial to identify reproducible approaches to refeeding that simultaneously maximize weight recovery and minimize the associated risks, in addition to improving long-term weight and cognitive and behavioral recovery and reducing relapse rates. We discuss here various approaches to refeeding, including, among others, where, by which route, how rapidly patients are best refed, and ways of choosing between them, taking into account the precautions or the potential effects of medication or of psychological care, to define better care plans for use in clinical practice.Conclusion: The importance of early weight gain for long-term recovery has been demonstrated by several studies in both outpatient and inpatient setting. Recent studies have also provided evidence to support a switch in current care practices for refeeding from a conservative approach to higher calorie refeeding. Finally, the risks of undernutrition/“underfeeding syndrome” and a maintenance of weight suppression are now better identified. Greater caution should still be applied for more severely malnourished < 70% average body weight and/or chronically ill, adult patients.What is Known:• Refeeding is a central part of the treatment in AN and should be a multidisciplinary and collaborative enterprise, together with nutritional rehabilitation and psychological support, but there are no clear guidelines on the management of refeeding in clinical practice.• The risk of a refeeding syndrome is well known and well managed in severely malnourished patients (“conservative approaches”).What is New:• There is evidence that early weight restoration has an impact on outcome, justifying an aggressive approach to refeeding in the early stages of the illness.• The risks of “underfeeding syndrome” and of a maintenance of weight suppression are now better identified and there is sufficient evidence to support a switch in current care practices for refeeding from a conservative approach to higher calorie refeeding.

Refeeding syndrome (RFS) broadly encompasses a severe electrolyte disturbance (principally low serum concentrations of intracellular ions such as phosphate, magnesium, and potassium) and metabolic abnormalities in undernourished patients undergoing refeeding whether orally, enterally, or parenterally. RFS reflects the change from catabolic to anabolic metabolism. RFS sometimes is undiagnosed and unfortunately some clinicians remain oblivious to its presence. This is particularly concerning as RFS is a life-threatening condition, although it need not be so and early recognition reduces morbidity and mortality. Careful patient monitoring and multidiscipline nutrition team management may help to achieve this goal. The diagnosis of RFS is not facilitated by the fact that there is no universal agreement as to its definition. The presence of hypophosphatemia alone does not necessarily mean that RFS is present as there are many other causes for this, as discussed later in this article. RFS is increasingly being recognized in neonates and children. An optimal refeeding regimen for RFS is not universally agreed on due to the paucity of randomized controlled trials in the field.

Refeeding syndrome (RFS) represents a group of clinical findings that occur in severely malnourished individuals undergoing nutritional support. Cardiac arrhythmias, multisystem organ dysfunction, and death are the most severe symptoms observed. As the cachectic body attempts to reverse its adaptation to the starved state in response to the nutritional load, symptoms result from fluid and electrolyte imbalances, with hypophosphatemia playing a central role. Because guidelines for feeding the malnourished patient at risk for refeeding syndrome is scarce, we have provided management recommendations based on the knowledge derived from a collection of reported English literature cases of the RFS. A MEDLINE search using keywords including “refeeding syndrome,” “RFS,” and “refeeding hypophosphatemia” was performed. References from initial cases were utilized for more literature on the subject. We have emphasized the continued importance of managing patients at risk for RFS, compared how management of the severely malnourished patients have evolved over time, and provided comprehensive clinical guidelines based on the sum of experience documented in the case reports for the purpose of supplementing the guidelines available. Based on our review, the most effective means of preventing or treating RFS were the following: recognizing the patients at risk; providing adequate electrolyte, vitamin, and micronutrient supplementation; careful fluid resuscitation; cautious and gradual energy restoration; and monitoring of critical laboratory indices.

Background/Objectives: Refeeding syndrome (RFS) is challenging to prevent and manage in hospitalized patients receiving enteral nutrition (EN). Nebraska Medicine implemented an Electronic Medical Record (EMR) Refeeding Risk Order Set (RROS) to standardize prevention measures, including structured electrolyte monitoring, thiamine supplementation, and conservative EN initiation. This study evaluated whether RROS implementation reduced RFS occurrence or severity and assessed its operational impact. Methods: In this retrospective cohort study, adults receiving EN before and after RROS implementation were compared. Primary outcomes were RFS occurrence and severity; secondary outcomes included EN initiation and advancement rates, electrolyte trends, lab frequency, and electrolyte repletion. Results: RFS occurrence did not differ significantly between groups (92.3% vs. 91.3%, p = 0.694), nor did severity (p = 0.535). The post-RROS group received more electrolyte boluses on EN Day 0 (p = 0.027) and had a lower EN starting rate (15.7 vs. 18.3 mL/h, p = 0.045). Conclusions: Although the RROS did not reduce RFS occurrence or severity, integrating American Society for Parenteral and Enteral Nutrition (ASPEN)-based guidance into the EMR was highly feasible and adopted immediately. Automating electrolyte monitoring, micronutrient supplementation, and conservative feeding initiation reduces the risk of errors and promotes consistent care. These benefits improve workflow efficiency and support providers during high census periods, limited staffing, or when experience varies. Future research should explore combining EMR tools with predictive analytics to optimize early risk identification and individualized management.

Key Summary Points Aim Does a more assertive compared to a cautious initial refeeding protocol improve patient handgrip strength? Findings In this randomized clinical trial of 85 older adults whom received two different refeeding protocols, with tight control of electrolytes, no significant difference in in by handgrip strength was found ( p  = 0.78). Message A more assertive refeeding protocol providing 20 kcal/kg/day did not improve hand grip strength nutritional status at 3 months compared with a cautious refeeding protocol (10 kcal/kg/day), neither did it show a higher incidence of mortality. Purpose Optimal refeeding protocols in older malnourished hospital patients remain unclear. We aimed to compare the effect of two different refeeding protocols; an assertive and a cautious protocol, on HGS, mortality and refeeding syndrome (RFS), in patients ≥ 65 years Methods Patients admitted under medical or surgical category and at risk of RFS, were randomized to either an enteral nutrition (EN) refeeding protocol of 20 kcal/kg/day, reaching energy goals within 3 days (intervention group), or a protocol of 10 kcal/kg/day, reaching goals within 7 days (control group). Primary outcome was the difference in hand grip strength (HGS) at 3 months follow-up, in an intention to treat analysis. RFS (phosphate < 0.65 mmol/L) during the hospital stay and mortality rates at 3 months were secondary outcomes. Results A total of 85 patients were enrolled, with mean (SD) age of 79.8(7.4) and 54.1% female, 41 in the intervention group and 44 in the control group. HGS was similar at 3 months with mean change of 0.78 kg (95% CI − 2.52 to 3.36, p  = 0.42). Serum phosphate < 0.65 mmol/L was seen in 17.1% in the intervention group and 9.3% in the control group, p  = 0.29. There was no difference in mortality rates (39% vs 34.1%, p  = 0.64). An indication of more respiratory distress was found in the intervention group, 53.6% vs 30.2%, p  = 0.029. Conclusion A more assertive refeeding protocol providing 20 kcal/kg/day did not result in improved HGS measured 3 months after discharge compared with a cautious refeeding (10 kcal/kg/day) protocol. No difference in incidence of mortality or RFS was found. Trial registration ClinicalTrials.gov Protocol Record 2017/FO148295, Registered: 21st of February, 2017.

Purpose Patients with oral squamous cell carcinoma (OSCC) often have difficulties in obtaining sufficient nutrition and may develop refeeding syndrome (RFS) during hospitalization. RFS may be fatal if not treated properly. This study clarified changes in perioperative phosphate levels and occurrence of RFS symptoms in OSCC patients to identify clinically notable predisposing factors for RFS in this specific patient population. Methods A retrospective analysis included primary OSCC patients with microvascular free flap reconstruction. Patients with treatment for additional malignancy, hypoparathyroidism, and missing values of preoperative and/or postoperative plasma phosphate (P-Pi) concentration were excluded. The outcome variable was severe postoperative hypophosphataemia (mmol/l) during the postoperative period (P-Pi < 0.50 mmol/l). Predictor variables were age, sex, smoking, heavy alcohol use, diabetes, body mass index (BMI), weight, height, tumour site, tumour size, tracheostomy, nutritional route, and preoperative P-Pi concentration. Results Of the 189 patients with primary OSCC, 21 (11%) developed severe hypophosphataemia. Of these patients, 17 (81%) developed RFS symptoms. Higher age ( p  = 0.01), lower patient height ( p  = 0.05), and no current smoking ( p  = 0.04) were significantly associated with postoperative hypophosphataemia. In multivariable regression analyses, higher age (OR 1.06 per year) and age over 70 years (OR 3.77) were independently associated with development of severe hypophosphataemia. Conclusion Restoration of nutritional balance and close follow-up of electrolyte balance in the perioperative phase are necessary to prevent RFS, especially in patients with oral cancer requiring extensive reconstructions. Special attention should be focused on elderly patients since they are prone to this unnoticeable but potentially life-threatening electrolyte disturbance.

Although described >70 y ago, the refeeding syndrome (RFS) remains understudied with lack of standardized definition and treatment recommendations. The aim of this systematic review was to gather evidence regarding standardized definition, incidence rate and time course of occurrence, association with adverse clinical outcomes, risk factors, and therapeutic strategies to prevent or treat this condition. We searched MEDLINE and EMBASE for interventional and observational clinical trials focusing on RFS, excluding case reports and reviews. We extracted data based on a predefined case report form and assessed bias. Of 2207 potential abstracts, 45 records with a total of 6608 patients were included (3 interventional trials, 16 studies focusing on anorexic patients). Definitions for RFS were highly heterogenous with most studies relying on blood electrolyte disturbances only and others also including clinical symptoms. Incidence rates varied between 0% and 80%, depending on the definition and patient population studied. Occurrence was mostly within the first 72 h of start of nutritional therapy. Most of the risk factors were in accordance with National Institute for Health and Care Excellence guidelines, with older age and enteral feeding being additional factors. There was no strong evidence regarding association of RFS and adverse outcomes, as well as regarding preventive measures and treatment algorithms. This systematic review focusing on RFS found consensus regarding risk factors and timing of occurrence, but wide variations regarding definition, reported incidence rates, preventive measures and treatment recommendations. Further research to fill this gap is urgently needed. •This is the first systematic review focusing on refeeding syndrome (RFS).•Definitions for RFS rely on electrolyte disturbances with or without clinical symptoms.•Incidence rates for RFS highly depend on the definition used.•Most of risk factors for RFS are in accordance with the National Institute for Health and Care Excellence guidelines.•No strong evidence for adverse outcomes and preventive measures in patients with RFS was found.