Refeeding syndrome: update and clinical advice for prevention, diagnosis and treatment.

PURPOSE OF REVIEW: The aim of this review is to provide a brief overview of the refeeding syndrome, to discuss more recent advice on diagnosis and treatment, and to raise awareness of this still poorly understood metabolic condition. RECENT FINDINGS: To date, evidence regarding the refeeding syndrome has been very limited. A number of reviews and case reports exist, but only a few are randomized trials. Recently, it has been shown that the vast majority of physicians are unaware of this metabolic condition. Precise guidelines for diagnosis and treatment of this syndrome were lacking for a long time. Now, a consensus statement is available, providing guidance from experts in the field on the management of patients at increased risk of refeeding syndrome (RFS) receiving nutritional therapy. SUMMARY: Due to the increased use of nutritional therapy in inpatient settings, physicians should be aware of possible side effects, particularly in connection with the refeeding syndrome. In this context, every patient should undergo a risk assessment for refeeding syndrome and stratification before starting nutritional therapy. For patients at high risk, nutritional support should be administered with adapted energy and fluid support during the replenishment phase. In addition, the occurrence of RFS during nutritional therapy must be continuously evaluated, and appropriate steps taken if necessary.

Refeeding Syndrome in the Critically Ill: a Literature Review and Clinician's Guide.

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. 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 Syndrome.

Refeeding syndrome describes the metabolic disturbances and clinical sequelae that occur in response to nutritional rehabilitation of patients who are moderate to severely malnourished. When risk factors are not identified and nutrition therapy is not managed appropriately, devastating consequences such as electrolyte depletion and imbalances, fluid overload, arrhythmia, seizure, encephalopathy, and death may occur. As this entity is often unrecognized, especially in pediatrics, becoming familiar with the pathophysiology, clinical manifestations, and management strategies will help clinicians caring for children avoid unnecessary morbidity and mortality. [Pediatr Ann. 2019;48(11):e448-e454.].

Second-Trimester Fetal Loss in a Patient With Hyperemesis Gravidarum Complicated by Refeeding Syndrome.

BACKGROUND: Refeeding syndrome is a rare constellation of electrolyte abnormalities after reintroduction of glucose during an adaptive state of starvation and malnutrition, resulting in fluid shifts, end-organ damage, and, potentially, death. We present a case of fetal death in a patient with hyperemesis gravidarum complicated by refeeding syndrome. CASE: A 32-year-old obese, multigravid patient was admitted at 16 weeks of gestation with hyperemesis gravidarum and laboratory abnormalities concerning for refeeding syndrome after consuming a sugar-rich beverage. She was admitted to the hospital for electrolyte and fluid repletion; however, on hospital day 2, fetal death was diagnosed. CONCLUSION: Refeeding syndrome is a potentially fatal complication of hyperemesis gravidarum. Caution should be taken when reintroducing glucose during prolonged states of malnutrition to prevent the development of refeeding syndrome.

Hyperemesis gravidarum followed by refeeding syndrome causes electrolyte abnormalities induced rhabdomyolysis and diabetes insipidus.

Although hyperemesis gravidarum (HG), an extreme form of morning sickness, is a common complication during pregnancy, HG associated simultaneous onset of rhabdomyolysis and diabetes insipidus due to electrolyte abnormalities are rare. A 34-year-old woman with severe HG at 17 weeks of gestation complicated with appetite loss, weight reduction by 17 kg, general fatigue, myalgia, weakness and polyuria was identified to have simultaneous hypophosphatemia (1.6 mg/dL) and hypokalemia (2.0 mEq/L). Appetite recovery and the improvement of the hypophosphatemia (3.2 mg/dL) were observed prior to the first visit to our department. At the admission, she presented polyuria around 7,000~8,000 mL/day with impaired concentrating activity (U-Osm 185 mOsm/L), and abnormal creatine kinase elevation (4,505 U/L). The electrolyte disturbances and physio-metabolic abnormalities in undernourished state due to HG let us diagnose this case as refeeding syndrome (RFS). In this case, abnormal loss by vomiting, insufficient intake and previous inappropriate fluid infusion as well as the development of RFS may accelerate the severity of hypokalemia due to HG. Thus, as her abnormalities were considered as results of rhabdomyolysis and diabetes insipidus due to severe HG associated hypokalemia based on RFS, oral supplementation of potassium chloride was initiated. After 6 days of potassium supplementation, her symptoms and biochemical abnormalities were completely resolved. Severe HG followed by RFS can be causes of electrolyte abnormalities and subsequent complications, including rhabdomyolysis and renal diabetes insipidus. Appropriate diagnosis and prompt interventions including adequate nutrition are necessary to prevent electrolyte imbalance induced cardiac, neuromuscular and/or renal complications.

Refeeding syndrome as treatment complication of anorexia nervosa. / Zespól realimentacyjny jako powiklanie leczenia jadlowstretu psychicznego.

Refeeding syndrome (RS) is one of the serious complications during treatment of anorexia nervosa. It includes hormonal and metabolic changes that occur during the process of refeeding in chronically malnourished patient when nutrition is introduced in an excessive and improper amount. RS manifests in water-electrolyte imbalances, including hypophosphatemia (the mostimportant diagnosticmarker), hypokalemia, hyponatremia, hypomagnesaemia, fluid retention, vitamin deficiency and metabolic acidosis. It applies to either oral and parenteral supplementation. In the treatment of malnourished patients with anorexia nervosa, it is essential to establish an initial caloric amount that will stimulate weight gain from the beginning of treatment, increase its effectiveness while minimizing the risk of RS. Recent research suggests that the current recommendations may be too stringent in this respect and require further updating. Awareness of the risks associated with RS, including significant mortality, appears to be currently insufficient also among physicians. There is a need for far more specialized multidisciplinary centers for patients with anorexia nervosa and also appropriate algorithms and standards of care for that population. The aim of this paper is to systematize the current knowledge about RS and RS prevention, to increase awareness of its occurrence and present the results of the latest research on safe resupplementation of patients suffering from anorexia nervosa.

Refeeding syndrome in the gastroenterology practice: how concerned should we be?

Clinical nutrition is emerging as a major area in gastroenterology practice. Most gastrointestinal disorders interfere with digestive physiology and compromise nutritional status. Refeeding syndrome (RS) may increase morbidity and mortality in gastroenterology patients. Literature search using the keywords "Refeeding Syndrome", "Hypophosphatemia", "Hypomagnesemia" and "Hypokalemia". Data regarding definition, pathophysiology, clinical manifestations, risk factors, management and prevention of RS were collected. Most evidence comes from case reports, narrative reviews and scarse observational trials. RS results from the potentially fatal shifts in fluid and electrolytes that may occur in malnourished patients receiving nutritional therapy. No standard definition is established and epidemiologic data is lacking. RS is characterized by hypophosphatemia, hypomagnesemia, hypokalemia, vitamin deficiency and abnormal glucose metabolism. Oral, enteral and parenteral nutrition may precipitate RS. Awareness and risk stratification using NICE criteria is essential to prevent and manage malnourished patients. Nutritional support should be started using low energy replacement and thiamine supplementation. Correction of electrolytes and fluid imbalances must be started before feeding. Malnourished patients with inflammatory bowel disease, liver cirrhosis, chronic intestinal failure and patients referred for endoscopic gastrostomy due to prolonged dysphagia present high risk of RS, in the gastroenterology practice. RS should be considered before starting nutritional support. Preventive measures are crucial, including fluid and electrolyte replacement therapy, vitamin supplementation and use of hypocaloric regimens. Gastroenterology patients must be viewed as high risk patients but the impact of RS in the outcome is not clearly defined in current literature.

Refeeding syndrome: relevance for the critically ill patient.

PURPOSE OF REVIEW: To provide an overview of recent findings concerning refeeding syndrome (RFS) among critically ill patients and recommendations for daily practice. RECENT FINDINGS: Recent literature shows that RFS is common among critically ill ventilated patients. Usual risk factors for non-ICU patients addressed on ICU admission do not identify patients developing RFS. A marked drop of phosphate levels (>0.16 mmol/l) from normal levels within 72 h of commencement of feeding, selects patients that benefit from hypocaloric or restricted caloric intake for at least 48 h resulting in lower long-term mortality. SUMMARY: RFS is a potentially life-threatening condition induced by initiation of feeding after a period of starvation. Although a uniform definition is lacking, most definitions comprise a complex constellation of laboratory markers (i.e. hypophosphatemia, hypokalemia, hypomagnesemia) or clinical symptoms, including cardiac and pulmonary failure. Recent studies show that low caloric intake results in lower mortality rates in critically ill RFS patients compared with RFS patients on full nutritional support. Therefore, standard monitoring of RFS-markers (especially serum phosphate) and caloric restriction when RFS is diagnosed should be considered. Furthermore, standard therapy with thiamin and electrolyte supplementation is essential.

[Hypophosphatemia in preterm infants: a bimodal disorder]. / Hipofosfemia en recién nacidos prematuros: un trastorno bimodal.

New nutritional approaches to treat extreme premature babies have demonstrated relevant eviden ce of metabolic disturbances with early hypophosphatemia, especially in patients with intrauterine growth restriction (IUGR). They have shown late hypophosphatemia, as well, which is characteristic in the metabolic bone disease. A sytematic search of literature describing metabolic disturbances of phosphorus in preterm newborns is presented, related to the use of early parenteral nutrition and also in the context of metabolic bone disease. The articles were gathered from electronic data bases, such as PubMed and Rima. We include articles in english and spanish which were selected by titles and abstracts. Several strategies for early nutrition have been proposed in order to ensure an adequate amount of nutrients to accomplish the development and growth of preterm babies. Patients with parenteral nutrition support with different doses of phosphate, or inadequate calcium phosphate relation, or an increased amino acid content, may present hypophosphatemia, hypercalcemia, hy pomagnesemia, hypokalemia and hyperglycemia, all of these are additionally noteworthy in the pre sence of intrauterine growth restriction. Furthermore, said alterations are associated with prolonged mechanical ventilation, as well as bronchopulmonary dysplasia and increase in late onset sepsis. The late hypophosphatemia, described several years ago, arises as normocalcemia and as an increment of alkaline phosphatases in the metabolic bone disease in preterm babies, and also with an inadequate mineralization in different grades, secondary to an inadequate supply due to high nutritional requi rements in these patients. When early or late hypophosphatemia appears in preterm babies, it shall require timely control of phosphemia and will need to adjust the nutritional intake in order to correct it. In case of preterm babies with early parenteral nutrition it will also need a control of calcemia in the first week of birth, especially if those belonging to the IUGR group. Adjustment must be made along with metabolic follow up, as well. In late hypophosphatemia, a weekly or every two weeks fo llow up will be a must for all preterm babies in risk and they should be given supplements to get an optimum mineral supply.

[Refeeding syndrome : Pathophysiology, risk factors, prevention, and treatment]. / Refeeding-Syndrom : Pathophysiologie, Risikofaktoren, Prophylaxe und Therapie.

Refeeding syndrome is a life-threatening complication that may occur after initiation of nutritional therapy in malnourished patients, as well as after periods of fasting and hunger. Refeeding syndrome can be effectively prevented and treated if its risk factors and pathophysiology are known. The initial measurement of thiamine level and serum electrolytes, including phosphate and magnesium, their supplementation if necessary, and a slow increase in nutritional intake along with close monitoring of serum electrolytes play an important role. Since refeeding syndrome is not well known and the symptoms can be extremely heterogeneous, this complication is poorly recognized, especially against the background of severe disease and multimorbidity. This overview aims to summarize the current knowledge and increase awareness about refeeding syndrome.

Refeeding syndrome in adults with celiac crisis: a case report.

BACKGROUND: Refeeding syndrome is a rare and life-threatening pathology with polyvisceral manifestations occurring in severely malnourished patients. It is rarely described in adults with celiac disease. CASE PRESENTATION: We report the case of a 28-year-old Tunisian woman followed up for celiac disease, who did not adhere to the gluten-free diet. She presented to our hospital with celiac crisis manifested by severe diarrhea, and metabolic and electrolyte disturbances. The treatment of electrolyte abnormalities, hydration, and nutritional support was marked by the occurrence on the fifth day of refeeding syndrome with psychomotor agitation followed by respiratory distress and a state of cardiogenic shock. CONCLUSIONS: Refeeding syndrome is still under-recognized. It should be systematically prevented for high-risk patients. Nutritional support in patients with celiac crisis should be monitored carefully since the risk of refeeding syndrome is very high with a poor prognosis.

Hipofosfemia en recién nacidos prematuros: un trastorno bimodal / Hypophosphatemia in preterm infants: a bimodal disorder

Las estrategias nutricionales para prematuros extremos con alto aporte de proteínas, han mostrado alteraciones metabólicas con hipofosfemia precoz, especialmente en el grupo de pacientes con restricción de crecimiento intrauterino (Rein). También se presenta hipofosfemia tardía, característica de la enfermedad metabólica ósea. En este artículo se revisan y actualizan conceptos en relación a la fisiopatología del metabolismo del fósforo en recién nacidos prematuros y uso de parenterales precoces en el contexto de enfermedad metabólica ósea. Los artículos fueron identificados en base de datos electrónicas como Pubmed y Rima. Fueron incluidos artículos en inglés y español. Fueron filtrados por título y resumen. La literatura actual propone diversas estrategias de nutrición precoz que permitan asegurar una adecuada cantidad de nutrientes para continuar con el crecimiento y desarrollo extrauterino. En pacientes con nutrición parenteral pero con diferentes aportes de fósforo, o relación calcio: fósforo inadecuada, a mayor contenido de aminoácidos, se presenta hipofosfemia, hipercalcemia, hipomagnesemia, hipokalemia e hiperglicemia, especialmente en casos de Rein. Estas alteraciones se asocian a prolongación de ventilación mecánica, mayor riesgo de displasia broncopulmonar y aumento de sepsis tardía. La hipofosfemia tardía, descrita ya hace muchos años, se presenta con normocalcemia y aumento de fosfatasas alcalinas, en la enfermedad metabólica ósea del prematuro, con alteración de la mineralización en distintos grados, secundaria a un inadecuado aporte de este mineral para los altos requerimientos de estos pacientes. Esta presentación de hipofosfemia precoz y tardía en el prematuro alerta sobre el control oportuno de fosfemia para ajustar el aporte nutricional. En el prematuro con nutrición parenteral precoz, el control en conjunto con la calcemia en la primera semana de vida, especialmente en Rein, permite tratar la hipofosfemia y prevenir sus complicaciones. En hipofosfemia tardía, el seguimiento semanal o quincenal desde las 4 semanas a los prematuros con riesgo, permite lograr un aporte óptimo de minerales.

New nutritional approaches to treat extreme premature babies have demonstrated relevant eviden ce of metabolic disturbances with early hypophosphatemia, especially in patients with intrauterine growth restriction (IUGR). They have shown late hypophosphatemia, as well, which is characteristic in the metabolic bone disease. A sytematic search of literature describing metabolic disturbances of phosphorus in preterm newborns is presented, related to the use of early parenteral nutrition and also in the context of metabolic bone disease. The articles were gathered from electronic data bases, such as PubMed and Rima. We include articles in english and spanish which were selected by titles and abstracts. Several strategies for early nutrition have been proposed in order to ensure an adequate amount of nutrients to accomplish the development and growth of preterm babies. Patients with parenteral nutrition support with different doses of phosphate, or inadequate calcium phosphate relation, or an increased amino acid content, may present hypophosphatemia, hypercalcemia, hy pomagnesemia, hypokalemia and hyperglycemia, all of these are additionally noteworthy in the pre sence of intrauterine growth restriction. Furthermore, said alterations are associated with prolonged mechanical ventilation, as well as bronchopulmonary dysplasia and increase in late onset sepsis. The late hypophosphatemia, described several years ago, arises as normocalcemia and as an increment of alkaline phosphatases in the metabolic bone disease in preterm babies, and also with an inadequate mineralization in different grades, secondary to an inadequate supply due to high nutritional requi rements in these patients. When early or late hypophosphatemia appears in preterm babies, it shall require timely control of phosphemia and will need to adjust the nutritional intake in order to correct it. In case of preterm babies with early parenteral nutrition it will also need a control of calcemia in the first week of birth, especially if those belonging to the IUGR group. Adjustment must be made along with metabolic follow up, as well. In late hypophosphatemia, a weekly or every two weeks fo llow up will be a must for all preterm babies in risk and they should be given supplements to get an optimum mineral supply.

Nutrition in the ICU: new trends versus old-fashioned standard enteral feeding?

PURPOSE OF REVIEW: The narrative review aims to summarize the relevant studies from the last 2 years and provide contextual information to understand findings. RECENT FINDINGS: Recent ICU studies have provided insight in the pathophysiology and time course of catabolism, anabolic resistance, and metabolic and endocrine derangements interacting with the provision of calories and proteins.Early provision of high protein intake and caloric overfeeding may confer harm. Refeeding syndrome warrants caloric restriction and to identify patients at risk phosphate monitoring is mandatory.Infectious complications of parenteral nutrition are associated with overfeeding. In recent studies enteral nutrition is no longer superior over parenteral nutrition.Previously reported benefits of glutamine, selenium, and fish oil seem to have vanished in recent studies; however, studies on vitamin C, thiamine, and corticosteroid combinations show promising results. SUMMARY: Studies from the last 2 years will have marked impact on future nutritional support strategies and practice guidelines for critical care nutrition as they challenge several old-fashioned concepts.

Is refeeding syndrome relevant for critically ill patients?

PURPOSE OF REVIEW: To summarize recent relevant studies regarding refeeding syndrome (RFS) in critically ill patients and provide recommendations for clinical practice. RECENT FINDINGS: Recent knowledge regarding epidemiology of refeeding syndrome among critically ill patients, how to identify ICU patients at risk, and strategies to reduce the potential negative impact on outcome are discussed. SUMMARY: RFS is a potentially fatal acute metabolic derangement that ultimately can result in marked morbidity and even mortality. These metabolic derangements in ICU patients differ from otherwise healthy patients with RFS, as there is lack of anabolism. This is because of external stressors inducing a hypercatabolic response among other reasons also reflected by persistent high glucagon despite initiation of feeding. Lack of a proper uniform definition complicates diagnosis and research of RFS. However, refeeding hypophosphatemia is commonly encountered during critical illness. The correlations between risk factors proposed by international guidelines and the occurrence of RFS in ICU patients remains unclear. Therefore, regular phosphate monitoring is recommended. Based on recent trials among critically ill patients, only treatment with supplementation of electrolytes and vitamins seems not sufficient. In addition, caloric restriction for several days and gradual increase of caloric intake over days is recommendable.

[Refeeding syndrome in geriatric patients : A frequently overlooked complication]. / Refeeding-Syndrom bei geriatrischen Patienten : Eine oft übersehene Komplikation.

The refeeding syndrome is a life-threatening complication that can occur after initiation of a nutrition therapy in malnourished patients. If the risk factors and pathophysiology are known, the refeeding syndrome can effectively be prevented and treated, if recognized early. A slow increase of food intake and the close monitoring of serum electrolyte levels play an important role. Because the refeeding syndrome is not well known and the symptoms may vary extremely, this complication is poorly recognized, especially against the background of geriatric multimorbidity. This overview is intended to increase the awareness of the refeeding syndrome in the risk group of geriatric patients.

Hyperglycemia and subsequent torsades de pointes with marked QT prolongation during refeeding.

OBJECTIVE: A fatal cardiac complication can occasionally present in malnourished patients during refeeding; this is known as refeeding syndrome. However, to our knowledge, hyperglycemia preceding torsades de pointes with QT prolongation during refeeding has not been reported. In the present study, we present a case in which hyperglycemia preceded torsades de pointes with QT prolongation during refeeding. The aim of this study was to determine the possible mechanism underlying QT prolongation during refeeding and indicate how to prevent it. METHODS: A 32-y-old severely malnourished woman (body mass index 14.57 kg/m2) was admitted to the intensive care unit of our institution after resuscitation from cardiopulmonary arrest due to ventricular fibrillation. She was diagnosed with anorexia nervosa. Although no obvious electrolyte abnormalities were observed, her blood glucose level was 11 mg/dL. A 12-lead electrocardiogram at admission showed sinus rhythm with normal QT interval (QTc 0.448). RESULTS: Forty mL of 50% glucose (containing 20 g of glucose) was intravenously injected, followed by a drip infusion of glucose to maintain blood glucose level within normal range. After 9 h, the patient's blood glucose level increased to 569 mg/dL. However, after 38 h, an episode of marked QT prolongation (QTc 0.931) followed by torsades de pointes developed. CONCLUSIONS: Hyperglycemia during refeeding can present with QT prolongation; consequently, monitoring blood glucose levels may be useful in avoiding hyperglycemia, which can result in QT prolongation. Furthermore, additional monitoring of QT intervals using a 12-lead electrocardiogram should allow the early detection of QT prolongation when glucose solution is administered to a malnourished patient with (severe) hypoglycemia.

NMR-Based Metabonomic Analysis of Physiological Responses to Starvation and Refeeding in the Rat.

Starvation is a postabsorptive condition derived from a limitation on food resources by external factors. Energy homeostasis is maintained under this condition by using sources other than glucose via adaptive mechanisms. After refeeding, when food is available, other adaptive processes are linked to energy balance. However, less has been reported about the physiological mechanisms present as a result of these conditions, considering the rat as a supraorganism. Metabolic profiling using (1)H nuclear magnetic resonance spectroscopy was used to characterize the physiological metabolic differences in urine specimens collected under starved, refed, and recovered conditions. In addition, because starvation induced lack of faecal production and not all animals produced faeces during refeeding, 24 h pooled faecal water samples were also analyzed. Urinary metabolites upregulated by starvation included 2-butanamidoacetate, 3-hydroxyisovalerate, ketoleucine, methylmalonate, p-cresyl glucuronide, p-cresyl sulfate, phenylacetylglycine, pseudouridine, creatinine, taurine, and N-acetyl glycoprotein, which were related to renal and skeletal muscle function, ß-oxidation, turnover of proteins and RNA, and host-microbial interactions. Food-derived metabolites, including gut microbial cometabolites, and tricarboxylic acid cycle intermediates were upregulated under refed and recovered conditions, which characterized anabolic urinary metabotypes. The upregulation of creatine and pantothenate indicated an absorptive state after refeeding. Fecal short chain fatty acids, 3-(3-hydroxyphenyl)propionate, lactate, and acetoin provided additional information about the combinatorial metabolism between the host and gut microbiota. This investigation contributes to allow a deeper understanding of physiological responses associated with starvation and refeeding.