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.

Changing paradigms in metabolic support and nutrition therapy during critical illness.

PURPOSE OF REVIEW: To summarize the most recent advances in acute metabolic care and critical care nutrition. RECENT FINDINGS: Recent research has demonstrated unknown consequences of high protein and amino acid administration in the early phase of ICU stay associated with dysregulated glucagon release leading to hepatic amino acid breakdown and suggested adverse effects on autophagy and long-term outcome. Progress has been made to measure body composition in the ICU. Refeeding hypophosphatemia and refeeding syndrome are common during critical illness, phosphate monitoring is essential after the start of nutrition therapy, and caloric restriction is recommendable in these patients.In recent studies, enteral nutrition is no longer superior to parenteral nutrition and signals of harm using the enteral route in shock have been suggested. However, during extracorporeal life support, enteral nutrition seems well tolerated. Intermittent or bolus enteral feeding seems an exciting concept concerning its potential anabolic effects. Studies on vitamin C, thiamine, and corticosteroid combinations suggest potential to improve outcome. SUMMARY: These new findings will probably change the practice of metabolic and nutrition therapy in critical illness and challenge paradigms advocated for long.

Hipofosforemia precoz en recién nacidos de riesgo. Frecuencia y magnitud / Early hypophosphataemia in at risk newborns. Frequency and magnitude

OBJETIVO: Conocer la frecuencia y la magnitud de la hipofosforemia neonatal (< 4 mg/dl) en una UCIN y definir los grupos de riesgo. PACIENTES Y MÉTODOS: Estudio retrospectivo en neonatos hospitalizados, en periodo de 44 meses (fase 1). Estudio retrospectivo en < 1.500 g/< 32 semanas de gestación en período posterior de 6 meses (fase 2). Estudio prospectivo en < 1.500 g o CIR con peso 1.500-2.000 g. Determinaciones en días 1, 3, 7 y 14 de vida (fase 3). RESULTADOS: Fase 1: 34 de 1.394 pacientes (2,4%) fueron diagnosticados de hipofosforemia, 76% de ellos ≤ 32 semanas de gestación y < 1.500 g, y 24% > 32 semanas con peso < P10. Fase 2: 12 de 73 pacientes (16,4%) fueron diagnosticados de hipofosforemia, 5 (6,8%) con hipofosofremia< 2mg/dl. De ellos 8 fueron CIR y 4 < 1.000 g. Cinco pacientes asociaron hipopotasemia y 3 hipercalcemia. Fase 3: 9 de 20 pacientes (45%) presentaron hipofosforemia, todos < 1.000 g o con peso al nacer < 1.200 g y percentil < 10. El 33% de las muestras de los días 1, 3 y 7 mostraron hipofosforemia, < 2 mg/dl en 4 muestras. Asociaron hipopotasemia leve 5 casos (55%) e hipercalcemia leve 2 (22%). La hipofosforemia se asoció a menor nutrición enteral y más aporte parenteral de aminoácidos en los primeros días. CONCLUSIONES: La hipofosforemia es frecuente y puede ser crítica en la primera semana en prematuros < 1.000 g y en los nacidos con desnutrición fetal y peso < 1.200 g que reciben aminoácidos en la nutrición parenteral precoz

OBJECTIVE: To determine the frequency and magnitude of neonatal hypophosphataemia (< 4 mg/dL) in a neonatal Intensive Care Unit and to describe risk groups. PATIENTS AND METHODS: Retrospective study of hospitalised newborns over a 44 month period (phase 1). Retrospective study of < 1,500g /< 32 weeks of gestation newborns over a 6 month period (phase 2). Prospective study of < 1,500 g or 1,550-2,000 g, and intrauterine growth restriction (IUGR) newborns. Measurements were made on the 1st, 3rd, 7th, and 14th days of life (phase 3). RESULTS: Phase 1: 34 (2.4%) of 1,394 patients had a diagnosis of hypophosphataemia, 76% of them ≤ 32 weeks of gestation and < 1500 grams, and 24% > 32 weeks with weight < P10. Phase 2: 12 (16.4%) of 73 patients had a diagnosis of hypophosphataemia, with < 2 mg/dL in 5 (6.8%). Eight (75%) of those with hypophosphataemia had IUGR, and 4 (25%) weighed < 1,000 g. Five cases had associated hypokalaemia, and three hypercalcaemia. Phase 3: 9 (45%) of 20 patients had hypophosphataemia, all of them < 1,000 g or < 1,200 g and weight percentile < 10. Thirty-three percent of samples on days 1, 3, and 7 showed hypophosphataemia, four of them < 2mg/dL. There was mild hypokalaemia in 5 (55%), and mild hypercalcaemia in 2 (22%) cases. Hypophosphataemia was associated with lower enteral nutrition and higher parenteral amino acid intake in the early days of life. CONCLUSIONS: Hypophosphataemia is common, and can be severe, in the first week of life in premature infants < 1,000 grams, and newborns < 1,200 g with foetal malnutrition and receiving amino acids in early parenteral nutrition

Incidencia de hipofosfatemia en pacientes ingresados no críticos con nutrición enteral / Incidence of hypophosphatemia in not critically ill patients with enteral feeding

Introducción: se ha descrito una incidencia de hipofosfatemia en pacientes con soporte nutricional especializado (SNE) de hasta el 30-40%. La hipofosfatemia leve y la moderada son generalmente asintomáticas, mientras que la severa es el hecho fundamental del síndrome de realimentación. Objetivo: evaluar la incidencia y gravedad de la hipofosfatemia en pacientes hospitalizados no críticos con nutrición enteral (NE). Material y métodos: se diseñó un estudio observacional y prospectivo en condiciones de práctica clínica habitual. Se recogieron datos clínicos, antropométricos y analíticos de 181 pacientes a los que se les inició nutrición enteral. El seguimiento fue de siete días. Resultados: el 51,9% de los pacientes estaban en riesgo de desarrollar síndrome de realimentación según las guías del United Kingdom National Institute for Health and Clinical Excellence (NICE). La incidencia de hipofosfatemia fue del 31,5% y la de la hipofosfatemia severa, del 1,1%. De todos los parámetros clínicos, antropométricos y analíticos analizados, solo la edad y unas proteínas séricas más bajas se correlacionaron de forma estadísticamente significativa con el aumento en la incidencia de hipofosfatemia. Conclusión: la incidencia de hipofosfatemia grave en nuestra serie es muy baja, lo que hace imposible extraer conclusiones específicas para este grupo de pacientes (AU)

Background: Up to 30-40% of the patients starting artificial nutritional support develop hypophosphatemia. In general, patients with mild and moderate hypophosphatemia do not have symptoms, but severe hypophosphatemia is the hallmark of refeeding syndrome. Aim: To determine the incidence of hypophosphatemia in not critically ill patients receiving enteral feeding. Material and methods: Prospective study. We assessed during seven days 181 not critically ill patients started on enteral artificial nutrition support during seven days. Results: 51.9% of the patients were considered to be at risk of developing refeeding syndrome (United Kingdom National Institute for Health and Clinical Excellence criteria). The incidence of hypophosphatemia was 31.5%, but only 1.1% of the patients developed severe hypophosphatemia. Older age and lower plasma proteins were significantly associated with hypophosphatemia. Conclusion: The incidence of severe hypophosphatemia in our study is low, so we can’t offer robust conclusions about the risk of hypophosphatemia in the type of patients receiving enteral nutrition (AU)

Using phosphate supplementation to reverse hypophosphatemia and phosphate depletion in neurological disease and disturbance.

Hypophosphatemia (HP) with or without intracellular depletion of inorganic phosphate (Pi) and adenosine triphosphate has been associated with central and peripheral nervous system complications and can be observed in various diseases and conditions related to respiratory alkalosis, alcoholism (alcohol withdrawal), diabetic ketoacidosis, malnutrition, obesity, and parenteral and enteral nutrition. In addition, HP may explain serious muscular, neurological, and haematological disorders and may cause peripheral neuropathy with paresthesias and metabolic encephalopathy, resulting in confusion and seizures. The neuropathy may be improved quickly after proper phosphate replacement. Phosphate depletion has been corrected using potassium-phosphate infusion, a treatment that can restore consciousness. In severe ataxia and tetra paresis, complete recovery can occur after adequate replacement of phosphate. Patients with multiple risk factors, often with a chronic disease and severe HP that contribute to phosphate depletion, are at risk for neurologic alterations. To predict both risk and optimal phosphate replenishment requires assessing the nutritional status and risk for re-feeding hypophosphatemia. The strategy for correcting HP depends on the severity of the underlying disease and the goal for re-establishing a phosphate balance to limit the consequences of phosphate depletion.

Avoiding medical complications during the refeeding of patients with anorexia nervosa.

Nutritional rehabilitation and weight restoration are key underpinnings of the treatment protocol for patients with anorexia nervosa. While their inherent state of malnutrition and weight loss is certainly not a healthy one, ironically, the very essence of the refeeding process, if done injudiciously, can also be unsafe for patients with anorexia nervosa. In this article we will provide a review of the major complications that may arise during refeeding, how best to avoid them, and how to treat them.

Refeeding hypophosphatemia in adolescents with anorexia nervosa: a systematic review.

The rate of adolescents presenting with anorexia nervosa (AN) is increasing. Medically unstable adolescents are admitted to the hospital for nutrition restoration. A lack of global consensus on appropriate refeeding practices of malnourished patients has resulted in inconsistent refeeding practices. Refeeding hypophosphatemia (RH) is the most common complication associated with refeeding the malnourished patient. This review sought to identify the range of refeeding rates adopted globally and the implication that total energy intake and malnutrition may have on RH while refeeding adolescents with anorexia nervosa. Studies were identified by a systematic electronic search of medical databases from 1980 to September 2012. Seventeen publications were identified, including 6 chart reviews, 1 observational study, and 10 case reports, with a total of 1039 subjects. The average refeeding energy intake was 1186 kcal/d, ranging from 125-1900 kcal/d, with a mean percentage median body mass index (% mBMI) of 78%. The average incidence rate of RH was 14%. A significant correlation between malnutrition (% mBMI) and post-refeeding phosphate was identified (R (2) = 0.6, P = .01). This review highlights the disparity in refeeding rates adopted internationally in treating malnourished adolescents with anorexia nervosa. Based on this review, the severity of malnutrition seems to be a marker for the development of RH more so than total energy intake.

Enhanced feeding in very-low-birth-weight infants may cause electrolyte disturbances and septicemia--a randomized, controlled trial.

BACKGROUND & AIMS: High supply of protein and energy has been introduced to very-low-birth-weight infants to improve growth and cognitive development. The aim of this study was to compare two different feeding strategies on postnatal growth and clinical outcome during neonatal hospitalization. METHODS: Fifty very-low-birth-weight infants were randomized to either an enhanced or a standard feeding protocol within 24 h after birth. Chi-square and T-tests were applied. RESULTS: First week protein, fat and energy supply was significantly higher in the intervention group compared to the control group (all P < 0.001). After inclusion of 50 patients we observed a higher occurrence of septicemia in the intervention group, 63% vs. 29% (P = 0.02), and no more patients were included. The infants in the intervention group demonstrated improved postnatal growth, but they also disclosed significant electrolyte deviations during the first week of life with hypophosphatemia, hypokalemia and hypercalcemia. First week phosphate nadir was lower in the infants experiencing septicemia (1.23 (0.50) mmol/L) as compared to the infants without (1.61 (0.61) mmol/L) (P = 0.03). CONCLUSION: Our study implies that enhanced feeding may induce electrolyte imbalances in VLBW infants, and that deleterious side effects similar to those seen in refeeding syndrome may occur. ClinicalTrials.gov, number NCT01103219 and the EudraCT number is 2010-020464-38.

Hypophosphatemia-mediated hypotension in transgenic mice overexpressing human FGF-23.

Fibroblast growth factor-23 (FGF-23) is a potent circulating phosphaturic factor associated with renal phosphate wasting. The effects of FGF-23 on skeletal and phosphate homeostasis have been investigated widely; however, the effect of FGF-23 on the cardiovascular system (CVS) is unknown. To assess whether FGF-23 influences the function and structure of the CVS and whether the effect of FGF-23 on the CVS is mediated by FGF receptors directly or indirectly by hypophosphatemia, FGF-23 transgenic mice and their wild-type littermates were fed a normal diet or a high-phosphate diet comprising a normal diet plus 1.25% phosphate in drinking water from weaning for 5 wk, and the phenotypes of the CVS were compared between FGF-23 transgenic mice and their wild-type littermates on the same diet. At the end of this time period, transgenic animals on the normal diet developed hypotension. The left ventricle was appropriately hypertrophic, and plasma catecholamine and renin-angiotensin system components were upregulated, indicating compensatory mechanisms in response to the hypotension. Transgenic mice also exhibited an impaired vascular reactivity and a downregulation of vasoconstrictor receptor gene expression, possibly as pathogenetic factors contributing to the hypotension. The high-phosphate diet improved the hypophosphatemia, resulting in a rescue of the cardiovascular phenotype. This study demonstrates that FGF-23 overexpression can result in abnormalities in the CVS and that the effect of FGF-23 overexpression on the CVS is mediated by the secondary severe hypophosphatemia.

Síndrome de realimentación / Refeeding syndrome

El síndrome de realimentación (SR) es un cuadro clínico complejo que ocurre como consecuencia de la reintroducción de la nutrición (oral, enteral o parenteral) en pacientes malnutridos. Los pacientes presentan trastornos en el balance de fl uidos, anomalías electrolíticas —como hipofosfatemia, hipopotasemia e hipomagnesemia— alteraciones en el metabolismo hidrocarbonado y déficits vitamínicos. Esto se traduce en la aparición de complicaciones neurológicas, respiratorias, cardíacas, neuromusculares y hematológicas. En este artículo se han revisado la patogenia y las características clínicas del SR, haciendo alguna sugerencia para su prevención y tratamiento. Lo más importante en la prevención del SR es identificar a los pacientes en riesgo, instaurar el soporte nutricional de forma prudente y realizar una corrección adecuada de los déficits de electrolitos y vitaminas (AU)

Refeeding syndrome is a complex syndrome that occurs as a result of reintroducing nutrition (oral, enteral or parenteral) to patients who are starved or malnourished. Patients can develop fluid-balance abnormalities, electrolyte disorders (hypophosphataemia, hypokalaemia and hypomagnesaemia), abnormal glucose metabolism and certain vitamin defi ciencies. Refeeding syndrome encompasses abnormalities affecting multiple organ systems, including neurological, pulmonary, cardiac, neuromuscular and haematological functions. Pathogenic mechanisms involved in the refeeding syndrome and clinical manifestations have been reviewed. We provide suggestions for the prevention and treatment of refeeding syndrome. The most important steps are to identify patients at risk, reintroduce nutrition cautiously and correct electrolyte and vitamin defi ciencies properly (AU)

Pacientes con riesgo de desnutrición: valoración de 11 casos gravemente desnutridos con nutrición parenteral total individualizada / No disponible

nutricional individualizado durante la primera semana con nutriciónparenteral total en pacientes con desnutrición moderada-gravesusceptibles de desarrollar un síndrome de renutrición.Método: Estudio retrospectivo observacional desde enero2003 a junio 2006 incluyendo todos los pacientes adultos condesnutrición moderada-grave que recibieron >= 5 días de nutriciónparenteral total. Se describió el soporte nutricional y se evaluó laaparición de alteraciones hidroelectrolíticas y metabólicas gravesdurante la primera semana de nutrición.Resultados: Se incluyeron 11 pacientes con índice de masacorporal medio de 15,4 kg/m2 que recibieron una media de 23kcal/kg/día. No aparecieron alteraciones hidroelectrolíticas ometabólicas graves. Tres pacientes presentaron hipofosfatemia, 5hipopotasemia y 4 hipomagnesemia, todas leves-moderadas ycorregidas, excepto en dos casos, a la semana de nutrición.Conclusiones: El soporte nutricional individualizado en pacientescon desnutrición moderada-grave no produjo ningún síndromede renutrición. La indivualización de la nutrición es una estrategiaesencial para evitar las complicaciones de una sobrealimentación

Objective: To describe and assess the efficacy and safety ofindividualised nutritional support during the first week of total parenteralnutrition in moderately to severely malnutritioned patientswho are susceptible to the refeeding syndrome.Method: Retrospective observational study carried outbetween January 2003 and June 2006, including adult patientswith moderate to severe malnutrition who received >= 5 days totalparenteral nutrition. The nutritional support was described andthe appearance of severe hydroelectrolytic and metabolic disturbanceswere assessed during the first week of nutrition.Results: The study included 11 patients with a mean bodymass index of 15.4 kg/m2. These patients received an average of23 Kcal/kg/day. They did not show any signs of severe hydroelectrolyticor metabolic disturbances. Three patients presentedwith hypophosphataemia, five with hypokalaemia and four withhypomagnesaemia, all of which were mild to moderate and withthe exception of two cases, all were corrected within one week offeeding.Conclusions: Individualised nutritional support in moderatelyto severely malnourished patients does not produce refeeding syndrome.Individualised nutrition is an essential strategy for avoidingcomplications associated with overfeeding

Calcium deficiency-induced secondary hyperparathyroidism and osteopenia are rapidly reversible with calcium supplementation in growing rabbit pups.

The reversibility of osteopenia secondary to isolated Ca deficiency (CaDef) is still not clear. We studied the effect of severe CaDef on Ca homeostasis and bone accrual in a 'hypercalcaemic' animal, the rabbit, during the post-weaning period and its reversibility on Ca supplementation. Male Belgian 5-week-old rabbit pups were fed CaDef diet (0.026 % Ca) for 10 weeks. As compared with those fed with a normal chow diet (0.45 % Ca), CaDef pups developed significant hypocalcaemia (P < 0.05), hypocalciuria (urinary Ca 76 (SEM 12) v. 17 (SEM 1) mg/l; P < 0.005), hypophosphataemia (serum inorganic P 100 (SEM 6) v. 65 (SEM 4) mg/l; P < 0.005), secondary hyperparathyroidism (SHPT) (serum intact parathyroid hormone human equivalent 18.2 (SEM 1.4) v. 125.0 (SEM 4.5) pg/ml; P < 0.001) and elevated serum calcitriol levels (34.0 (SEM 3.9) v. 91.0 (SEM 1.0) pg/ml; P < 0.005). Elevated urinary C-terminal telopeptide of class I collagen (P < 0.005) and total serum alkaline phosphatase (P < 0.005) suggested increased bone turnover. There was a significantly lower gain in bone mineral density (BMD) and bone mineral content (BMC) in the whole body and lumbar spine in vivo, and various sub-regions of the femur and tibia in vitro. Supplementation of adequate Ca (0.45 % Ca) after 15 weeks on the normal diet resulted in rapid catch-up growth, and resolution of SHPT. Rapid gain in various BMD and BMC parameters continued at 30 weeks of age, and both were comparable with those in rabbits on a normal diet. We conclude that Ca deficiency-induced SHPT and poor bone accrual in growing rabbit pups are rapidly reversible with Ca supplementation. The present study indicates that early intervention may be a more appropriate window period for human nutritional corrective measures.