Narrative review of inpatient nutritional management of anorexia nervosa with management recommendations for Australian tertiary health services.

BACKGROUND: Patients with anorexia nervosa (AN) may experience life-threatening malnutrition-related complications requiring inpatient medical stabilisation. Several management guidelines have been developed but discrepancies exist because of limited high-level evidence. AIMS: To review the evidence base for recommendations contained in Victorian health services guidelines for the nutritional management of inpatients with AN. METHODS: MEDLINE and Embase databases were searched for published studies on the nutritional management of inpatients with AN, combined with a manual search through citations. Studies including patients with AN aged 16 years and older were included. Case reports, small case series of <10 patients, studies of nonmedical management and studies with an exclusive paediatric population were excluded. The search results were compared with AN inpatient medical management guidelines sourced from large tertiary health services across Victoria, Australia. RESULTS: The search yielded 584 studies, subsequently reduced to nine studies using the inclusion and exclusion criteria. The results suggest that commencing refeeding at a higher caloric value allows faster weight gain and shorter hospitalisation. Enteral tube feeding is preferential to parenteral nutrition because of infrequent and milder complications. Zinc supplementation showed a doubled rate of body mass index increase compared with placebo. Comparison with Victorian health services guidelines revealed inconsistent recommendations for high-calorie refeeding and micronutrient supplementation. CONCLUSION: The evidence supports high-calorie refeeding of 2000 kcal/day in AN inpatient medical management and zinc supplementation in improving the rate of weight restoration. This is inconsistently reflected in different Victorian health services guidelines. Updated national consensus guidelines could assist in improving consistency of evidence-based health care.

[Refeeding syndrome]. / Syndrome de renutrition inappropriée.

Refeeding syndrome (RS) is a rare but severe condition that is poorly understood, often under-diagnosed and can lead to death. It occurs within 5 days after refeeding in patients after prolonged fasting or in a context of undernutrition. As a consequence of the abrupt transition from catabolism to anabolism, RS is defined as a decrease in plasma levels of phosphorus, potassium and/or magnesium, whether or not associated with organ dysfunction resulting from a decrease in one of the electrolytes or a thiamine deficiency, after refeeding. The clinical symptoms are varied and non-specific and are related to hydro electrolyte disorders, sodium-hydroxide retention or failure of one or more organs. Patient management should be appropriate with regular clinical examination and careful biological monitoring, including hydro electrolyte monitoring. The correction of hydroelectrolytic disorders and systematic thiamine supplementation are essential during refeeding, that must be done carefully and very progressively, whatever its form (oral, enteral or parenteral). The severity of the refeeding syndrome indicates that its prevention and screening are the corners of its management in at-risk patients.

Mortality associated with new risk classification of developing refeeding syndrome in critically ill patients: A cohort study.

BACKGROUND & AIMS: Although refeeding syndrome (RFS) has been recognized as a potentially fatal metabolic complication, the definition of RFS has remained unclear. Recently, European researchers suggested an evidence-based and consensus-supported algorithm that consisted of a new RFS risk classification and treatment strategies for medical inpatients. The classification was based on the National Institute for Health and Clinical Excellence (NICE) criteria for patients at risk of developing RFS. In this study, we aimed to investigate the frequency of each applied new risk group and the association between the new classification and mortality in critically ill patients. METHODS: This cohort study was conducted at a Japanese metropolitan tertiary-care university hospital from December 2016 to December 2018. We included critically ill adult patients who were admitted to the intensive care unit (ICU) via the emergency department and who stayed in the ICU for 24 h or longer. We applied the new risk classification based on the NICE RFS risk factors on ICU admission. The main exposure was risk classification of RFS: no risk, low risk, high risk, or very high risk. The primary outcome was in-hospital mortality censored at day 30 after ICU admission. We performed a multivariable analysis using Cox proportional hazard regression. RESULTS: We analyzed 542 patients who met the eligibility criteria. The prevalence of the four RFS risk classification groups was 25.8% for no risk, 25.7% for low risk, 46.5% for high risk, and 2.0% for very high risk. The 30-day mortality was 5.0%, 7.2%, 16.3%, and 27.3%, respectively (log-rank trend test: p < 0.001). In the multivariable Cox regression, adjusted hazard ratios with no risk group as a reference were 1.28 (95% CI 0.48-3.38) for low risk, 2.81 (95% CI 1.24-6.35) for high risk, and 3.17 (95% CI 0.78-12.91) for very high risk. CONCLUSIONS: Approximately half the critically ill patients were categorized as high or very high risk based on the new risk classification. Furthermore, as the risk categories progressed, the 30-day in-hospital mortality increased. Early recognition of patients at risk of developing RFS may improve patient outcomes through timely and optimal nutritional treatment.

Diets with high carbohydrate contents were associated with refeeding hypophosphatemia: A retrospective study in Japanese inpatients with anorexia nervosa.

OBJECTIVE: Refeeding hypophosphatemia (RH) is a potentially fatal complication in patients with anorexia nervosa (AN), and its dietary preventive strategy is not well established. We aimed to examine the association between carbohydrate content in the diet and the occurrence of RH in inpatients with AN via retrospective medical chart review. METHOD: We performed a chart review to collect data of patients with AN hospitalized at the Department of Psychosomatic Medicine of the University of Tokyo Hospital between April 1, 2012, and February 29, 2020. Receiver operating characteristic (ROC) analysis was performed to determine the cutoff point of the percentage of carbohydrate content in the diet for the occurrence of RH. Multivariate logistic regression analysis was performed with occurrence of RH as the dependent variable and the carbohydrate content of more than the identified cutoff point as the independent variable adjusting for the risk factors for RH. RESULTS: The percentage of carbohydrate content that is higher than the cutoff point obtained from the ROC analysis (58.4%) was significantly associated with the occurrence of RH, even after adjusting for variables associated with RH in univariate logistic regression analysis (age and body mass index) as well as the average daily calorie intake (odds ratio, 5.37; 95% confidence interval, 1.60-18.1; p = .0066). DISCUSSION: We identified that diets with higher carbohydrate contents were associated with RH in inpatients with AN, even after adjusting for known risk factors. Our findings may promote the development of dietary preventive strategies against RH in inpatients with AN.

Refeeding syndrome in small ruminants receiving parenteral nutrition.

BACKGROUND: Small ruminants presented to tertiary care facilities commonly suffer from severe protein-calorie malnutrition. Some of these patients require parenteral nutrition (PN; amino acids and dextrose with or without lipids) during hospitalization. Refeeding syndrome, a potentially fatal shift of electrolytes seen in malnourished patients during refeeding, may occur. OBJECTIVE: (a) To report the prevalence of refeeding syndrome in small ruminants receiving PN and (b) to determine risk factors for the development of refeeding syndrome. ANIMALS: Hospitalized small ruminants (n = 20) that received PN from 2010 to 2018 and that had serial (≥2) monitoring of serum electrolyte concentrations after initiation of PN. METHODS: Retrospective case series. Refeeding syndrome was defined as the presence of at least 2 of the following electrolyte abnormalities after initiation of PN: hypophosphatemia, hypokalemia, hypomagnesemia, or some combination of these. Data was analyzed using Fisher's exact test, followed by univariate logistic regression. RESULTS: Eleven of 20 (55%) animals met the definition of refeeding syndrome. Mean minimum serum phosphorus concentration in animals with refeeding syndrome was 1.96 ± 0.69 mg/dL (reference range, 4.2-7.6 mg/dL). Eleven of 20 animals survived to discharge. Survival rate did not differ significantly between refeeding cases (4/11, 36.3%) and nonrefeeding cases (7/9, 77.8%; P = .09). Mean serum phosphorus concentration was significantly lower in nonsurvivors than in survivors (1.88 ± 0.10 mg/dL vs 4.32 ± 0.70 mg/dL, P = .006). CONCLUSIONS AND CLINICAL IMPORTANCE: We report the prevalence of refeeding syndrome in small ruminants receiving PN. Clinicians should anticipate refeeding syndrome after initiation of PN and consider pre-emptive supplementation with phosphorus, potassium, magnesium, or some combination of these.

ASPEN Consensus Recommendations for Refeeding Syndrome.

INTRODUCTION: In the spring of 2017, the American Society for Parenteral and Enteral Nutrition (ASPEN) Parenteral Nutrition Safety Committee and the Clinical Practice Committee convened an interprofessional task force to develop consensus recommendations for identifying patients with or at risk for refeeding syndrome (RS) and for avoiding and managing the condition. This report provides narrative review and consensus recommendations in hospitalized adult and pediatric populations. METHODS: Because of the variation in definitions and methods reported in the literature, a consensus process was developed. Subgroups of authors investigated specific issues through literature review. Summaries were presented to the entire group for discussion via email and teleconferences. Each section was then compiled into a master document, several revisions of which were reviewed by the committee. FINDINGS/RECOMMENDATIONS: This group proposes a new clinical definition, and criteria for stratifying risk with treatment and screening strategies. The authors propose that RS diagnostic criteria be stratified as follows: a decrease in any 1, 2, or 3 of serum phosphorus, potassium, and/or magnesium levels by 10%-20% (mild), 20%-30% (moderate), or >30% and/or organ dysfunction resulting from a decrease in any of these and/or due to thiamin deficiency (severe), occurring within 5 days of reintroduction of calories. CONCLUSIONS: These consensus recommendations are intended to provide guidance regarding recognizing risk and identifying, stratifying, avoiding and managing RS. This consensus definition is additionally intended to be used as a basis for further research into the incidence, consequences, pathophysiology, avoidance, and treatment of RS.

Increased risk of refeeding syndrome-like hypophosphatemia with high initial amino acid intake in small-for-gestational-age, extremely-low-birthweight infants.

BACKGROUND: Recent nutrition guidelines for extremely-low-birth-weight infants (ELBWIs) recommend implementation of high initial amino acid (AA) supplementation in parenteral nutrition. OBJECTIVE: We sought to evaluate the influence of AA intake on refeeding syndrome-like electrolyte disturbances including hypophosphatemia in ELBWIs. STUDY DESIGN: Medical records of 142 ELBWIs were reviewed. Demographic, nutritional, outcome, and electrolyte data were compared between ELBWIs with initial low (1.5 g/kg/day) and high (3 g/kg/day) AA intake. Multivariate analysis was conducted to determine the odds ratio of hypophosphatemia with high AA intake and small-for-gestational-age (SGA) ELBWIs. RESULTS: The incidence of hypophosphatemia and severe hypophosphatemia increased from 51% and 8% in period I to 59% and 20% in period II, respectively (p = 0.36 and < 0.01). Specifically, SGA ELBWIs showed higher incidence of hypophosphatemia than appropriate-for-gestational age (AGA) ELBWIs in period II, whereas there was no difference in period I. For severe hypophosphatemia, SGA ELBWIs presented a 27% incidence versus a 2% incidence in AGA ELBWIs, even with low initial AA intake. Despite no difference in phosphate intake between infants with and without hypophosphatemia, serum phosphate level reached a nadir at the sixth postnatal day and gradually recovered over the second week in infants with hypophosphatemia. In multivariate analyses, the odds ratios for severe hypophosphatemia were 3.6 and 6.6 with high AA intake and SGA status, respectively, with the highest being 18.0 with combined high AA intake and SGA status. CONCLUSIONS: In summary, high initial AA intake significantly increased the risk of refeeding syndrome-like electrolyte dysregulations including severe hypophosphatemia in ELBWIs. In SGA ELBWIs, the risk of electrolyte disturbance was significantly higher, even with low initial AA intake. Therefore, new tailored parenteral nutrition protocols starting with lower energy intake and a gradual increase over the first week may be warranted for application in high-risk SGA ELBWIs.

Hypophosphatemia before endoscopic gastrostomy predicts higher mortality during the first week and first month post-gastrostomy: a risk marker of refeeding syndrome in gastrostomy-fed patients.

INTRODUCTION: Introduction: starvation is usual in patients referred for endoscopic gastrostomy (PEG). A high risk of refeeding syndrome (RS) may contribute to poor prognosis. Objectives: this study aims to: a) evaluate serum phosphorus and magnesium when patients underwent PEG; b) determine the mortality rate during the first week and first month of enteral nutrition; and c) assess if hypophosphatemia or hypomagnesemia are associated with early mortality. Material and methods: retrospective study with patients followed in the Artificial Nutrition Clinic and died under PEG feeding. General nutritional assessment included NRS 2002, anthropometry and serum proteins. Serum phosphorus and magnesium were measured immediately before gastrostomy. Survival was recorded and compared to electrolyte and nutritional status. Results: one hundred and ninety-seven patients (137 men/60 women) aged 26-100 years. Most underwent PEG due to neurologic disorders (60.9%) and were malnourished according to body mass index (BMI) and serum proteins. Low phosphorus and magnesium were found in 6.6% and 4.6%, respectively. Hypophosphatemia was associated with malnutrition (p < 0.05). Mean survival was 13.7 ± 15.4 months. Mortality was 4.6% in the first week and 13.2% in the first month post-gastrostomy. Overall survival was shorter in malnourished patients but malnutrition did not directly influence early mortality (p > 0.05). Hypophosphatemia was associated with mortality during the first week (p = 0.02) and the first month of PEG feeding (p = 0.02). Conclusions: hypophosphatemia was uncommon but predicted early mortality after PEG. Although RS may be less frequent than expected, hypophosphatemia may be used as a RS marker and RS is the probable cause of increase early mortality in hypophosphatemic PEG-fed patients.

INTRODUCCIÓN: Introducción: la inanición es habitual en pacientes referenciados para gastrostomía endoscópica (PEG). Un riesgo alto de síndrome de realimentación (SR) puede contribuir a un mal pronóstico. Objetivos: este estudio pretende: a) estudiar el fósforo y el magnesio séricos cuando los pacientes son sometidos a PEG; b) determinar la tasa de mortalidad durante la primera semana y el primer mes de nutrición entérica; y c) evaluar si la hipofosfatemia y la hipomagnesemia se asocian con una mortalidad temprana. Material y métodos: estudio retrospectivo con pacientes seguidos en la consulta de nutrición artificial y que fallecieron utilizando alimentación por PEG. La evaluación nutricional genérica ha incluido el NRS 2002, la antropometría y la determinación de las proteínas séricas. El fósforo y el magnesio séricos se han determinado inmediatamente antes de la gastrostomía. La sobrevida fue registrada y comparada con el perfil iónico y el estado nutricional de los pacientes. Resultados: el estudio se realizó en 197 pacientes (137 hombres/60 mujeres) de 26-100 años. La mayoría se sometieron a PEG por trastornos neurológicos (60,9%) y estaban desnutridos de acuerdo con el índice de masa corporal (IMC) y las proteínas séricas. El fósforo y el magnesio séricos estaban bajos, con un 6,6% y un 4,6%, respectivamente. La hipofosfatemia se asoció con la desnutrición (p < 0,05). La sobrevida media fue de 13,7 ± 15,4 meses. Se ha registrado una mortalidad del 4,6% en la primera semana y del 13,2% en el primer mes después de la gastrostomía. La sobrevida general fue más corta en los pacientes desnutridos, pero la desnutrición no ha afectado directamente a la mortalidad temprana (p > 0,05). La hipofosfatemia se asoció con la mortalidad durante la primera semana (p = 0,02) y el primer mes de alimentación con PEG (p = 0,02). Conclusiones: la hipofosfatemia fue infrecuente, pero predijo una mortalidad temprana después del PEG. Aunque el SR es aparentemente menos frecuente de lo esperado, la hipofosfatemia puede ser utilizada como un marcador del SR y el SR es probablemente la causa de una mortalidad temprana en pacientes hipofosfatémicos alimentados con PEG.

The refeeding syndrome. Importance of phosphorus. / El síndrome de realimentación. Importancia del fósforo.

Refeeding syndrome (RS) is a complex disease that occurs when nutritional support is initiated after a period of starvation. The hallmark feature is the hypophosphataemia, however other biochemical abnormalities like hypokalaemia, hypomagnesaemia, thiamine deficiency and disorder of sodium and fluid balance are common. The incidence of RS is unknown as no universally accepted definition exists, but it is frequently underdiagnosed. RS is a potentially fatal, but preventable, disorder. The identification of patients at risk is crucial to improve their management. If RS is diagnosed, there is one guideline (NICE 2006) in place to help its treatment (but it is based on low quality of evidence). The aims of this review are: highlight the importance of this problem in malnourished patients, discuss the pathophysiology and clinical characteristics, with a final series of recommendations to reduce the risk of the syndrome and facilitate the treatment.

Risk Factors for the Development of Refeeding Syndrome-Like Hypophosphatemia in Very Low Birth Weight Infants.

BACKGROUND: Refeeding syndrome is characterized by metabolic disturbance including hypophosphatemia and hypokalemia upon reinstitution of nutrition in severely malnourished patients. OBJECTIVE: The present study sought to identify the risk factors for the development of refeeding syndrome-like metabolic disturbance in very low birth weight infants. METHODS: The correlations of severe hypophosphatemia with the serum levels of potassium and ionized calcium, daily calorie and phosphate intake, and umbilical cord blood flow on ultrasonography were analyzed in 49 very low birth weight infants. RESULTS: Fifteen infants (36%) presented with hypophosphatemia during the first postnatal week. Hypophosphatemia was significantly associated with birth weight z score (odds ratio, 1.60; 95% confidence interval, 1.04-2.47; p = 0.034) and umbilical artery resistance index (odds ratio, 7.72E-04; 95% confidence interval, 1.14E-06-0.523; p = 0.031). Multiple regression analysis revealed that umbilical artery resistance index was independently associated with hypophosphatemia. CONCLUSIONS: Umbilical artery resistance index may serve as a useful marker for future development of refeeding syndrome-like hypophosphatemia in very low birth weight infants. Close monitoring of serum phosphorus and potassium levels and early intervention are important for the management of very low birth weight infants with intrauterine growth restriction due to placental dysfunction.

Safe refeeding management of anorexia nervosa inpatients: an evidence-based protocol.

OBJECTIVE: Anorexia nervosa is associated with several serious medical complications related to malnutrition, severe weight loss, and low levels of micronutrients. The refeeding phase of these high-risk patients bears a further threat to health and potentially fatal complications. The objective of this study was to examine complications due to refeeding of patients with anorexia nervosa, as well as their mortality rate after the implementation of guidelines from the European Society of Clinical Nutrition and Metabolism. METHODS: We analyzed retrospective, observational data of a consecutive, unselected anorexia nervosa cohort during a 5-y period. The sample consisted of 65 inpatients, 14 were admitted more than once within the study period, resulting in 86 analyzed cases. RESULTS: Minor complications associated with refeeding during the first 10 d (replenishing phase) were recorded in nine cases (10.5%), four with transient pretibial edemas and three with organ dysfunction. In two cases, a severe hypokalemia occurred. During the observational phase of 30 d, 16 minor complications occurred in 14 cases (16.3%). Six infectious and 10 non-infectious complications occurred. None of the patients with anorexia nervosa died within a follow-up period of 3 mo. CONCLUSIONS: Our data demonstrate that the seriousness and rate of complications during the replenishment phase in this high-risk population can be kept to a minimum. The findings indicate that evidence-based refeeding regimens, such as our guidelines are able to reduce complications and prevent mortality. Despite anorexia nervosa, our sample were affected by serious comorbidities, no case met the full diagnostic criteria for refeeding syndrome.

Refeeding syndrome: screening, incidence, and treatment during parenteral nutrition.

The possible deleterious effects of feeding after a period of prolonged starvation have been known for over 60 years. The resultant biochemical disturbance, symptoms, and signs have been termed the refeeding syndrome (RS). The key to the pathophysiology is the stimulation of insulin release resulting in anabolic activity. Depleted electrolyte and micronutrient stores are overwhelmed and cellular function disrupted. A concise definition of RS is not agreed and hampers interpretation of clinical data. Hypophosphatemia and appearance of tissue edema/pathological fluid shifts are the most often agreed diagnostic criteria. The characteristics of particular patient groups at risk have been recognized for some time, and there are guidelines from the National Institute for Clinical Excellence in the UK to aid recognition of individuals at high risk along with protocols for initiating nutrition. Using loose diagnostic criteria, RS appears to occur in 4% of cases of parenteral nutrition (PN) when case records were reviewed by experts in a large study into PN care in the UK. Disappointingly, prescribers recognized only 50% of at risk cases. Early data from a similar study in New Zealand appear to show a similar pattern. Prospective series looking at patients receiving nutrition support in institutions with Nutrition Support Teams have found an incidence of 1-5%. RS is still underrecognized. Patients receiving PN should be counted as being in a high-risk category and feeding protocols to avoid RS applied. Low rates of RS then occur and death from this cause be avoided.

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

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

Changes in serum magnesium and phosphate in older hospitalised patients--correlation with muscle strength and risk factors for refeeding syndrome.

OBJECTIVES: To evaluate changes in serum magnesium and phosphate over time in hospitalised older patients, examine whether such changes were associated with changes in muscle strength, and assess whether risk factors for refeeding syndrome were associated with falls in serum magnesium and phosphate. DESIGN AND SETTING: Community dwelling patients aged 70 and over, admitted to a specialist Medicine for the Elderly assessment unit were included in a prospective study. MEASUREMENTS: Weight, height, triceps skinfold thickness and mid arm circumference were recorded at baseline. Serum magnesium and phosphate was measured on admission, and at days 1, 2, 3, 5, 7, 10, 14, 21, 28 after admission, along with handgrip and quadriceps strength measured in the non-dominant limbs using a portable dynamometer. RESULTS: 43 patients were recruited with a mean age of 83.8 years (SD 7.5). 58% were female. Mean baseline serum magnesium and phosphate levels were 0.89 mmol/L and 1.07 mmol/L respectively. 10/43 patients had a fall in serum magnesium of at least 0.2 mmol/l from baseline and 20/43 had a similar fall in phosphate. No correlation was shown between these changes in electrolytes and muscle strength. Regression analyses did not show that risk factors for refeeding syndrome were associated with falls in electrolyte levels. CONCLUSION: Changes in serum magnesium and phosphate levels do not correlate with changes in muscle strength in older hospitalised patients. Risk factors for refeeding syndrome did not predict falls in serum phosphate or magnesium.