Search

Hypophosphatemia (serum phosphate < 2.5 mg/dL) is a major concern when initiating nutritional support. We evaluated which factors contribute to hypophosphatemia development in critically ill patients, as well as the association between hypophosphatemia and mortality. A retrospective cohort study of patients who were ventilated for at least 2 days in a 16-bed mixed ICU. Data collected includes demographics, Acute Physiology & Chronic Health Evaluation 2 (APACHE2) admission score, Sequential Organ Failure Assessment score at 24 h (SOFA24), hourly energy delivery, plasma phosphate levels during the first 2 weeks of admission, ICU length of stay (LOS), length of ventilation (LOV), and mortality (ICU and 90 days). For the hypophosphatemia development model, we considered mortality as a competing risk. For mortality analysis, we used the Cox proportional hazards model considering hypophosphatemia development as a time-varying covariate. 462 patients were used in the analysis. 59.52% of the patients developed hypophosphatemia. Several factors were associated with a decreased risk of hypophosphatemia: age, BMI, pre-admission diabetes diagnosis, APACHE2, SOFA24, first kidney SOFA score, hospital admission time before ICU admission, and admission after liver transplantation. Admission due to trauma was associated with an increased risk of hypophosphatemia. Survival analysis with hypophosphatemia as a time-varying covariate showed a protective effect of hypophosphatemia from mortality (HR 0.447, 95% CI 0.281, 0.712). Age, APACHE2, and SOFA24 score were found to be significantly associated with ICU mortality. Fasting duration in the ICU before nutritional support initiation was not found to be significantly associated with hypophosphatemia. We examined several fasting intervals (12 h, 24 h, 36 h, 48 h, 60 h, 72 h). In each fast interval, we compared the prevalence of hypophosphatemia among patients who fasted the specified length of time, with those who did not fast for the same length of time. In each fasting interval, hypophosphatemia prevalence was lower in the fasting group compared to the non-fasting group. However, this difference was insignificant. BMI, APACHE2, and hospital LOS before ICU admission were inversely associated with hypophosphatemia development. Fasting for up to 72 h in the ICU before starting nutritional support did not affect hypophosphatemia occurrence. Hypophosphatemia was associated with lower mortality., (© 2024. The Author(s).)

Objective: To describe the incidence of hypophosphatemia in patients admitted to the ICU who have required mechanical ventilation. To analyze the presence of risk factors and its relationship with nutritional practice., Design: Prospective observational study., Setting: Polyvalent ICUs of 2 University Hospitals., Patients or Participants: Patients on invasive mechanical ventilation ≥72 h with normal level of phosphorus at admission., Interventions: None., Main Variables of Interest: Electrolyte levels (phosphorus, magnesium, potassium) were determined on admission to the ICU and at 96 h. Risk categories on admission, caloric intake, insulin doses and acid-base status during the first 4 days of admission were recorded. Incidence was calculated as the number of patients who developed hypophosphataemia after admission. Univariate analysis was performed for between-group comparison and multivariate analysis of potential risk factors., Results: 89 patients were included. The incidence of hypophosphataemia was 32.6%. In these patients phosphorus decreased from 3.57 ± 1.02 mmol/l to 1.87 ± 0.65 mmol/l (52.3%). The mean kcal/kg/24 h provided in the first 4 days was 17.4 ± 4.1, with no difference between the group that developed hypophosphataemia and the group that did not. Significant risk factors were insulin doses administered and pH and PaCO 2 values., Conclusions: The incidence of hypophosphataemia at 96 h from admission in mechanically ventilated patients is high and unrelated to the risk category and hypocaloric nutritional practice used. Insulin dosis and acid-base status are the main determinants of its occurrence., (Published by Elsevier España, S.L.U.)

This study aims to investigate the potential correlation between the use of olanzapine, a psychopharmacological intervention commonly prescribed in Anorexia Nervosa treatment, and the occurrence of Refeeding Syndrome. Despite the acknowledged nutritional and biochemical impacts of olanzapine, the literature lacks information regarding its specific association with Refeeding Syndrome onset in individuals with Anorexia Nervosa. This is a naturalistic, retrospective, observational study, reporting the occurrence of Refeeding Syndrome in children and adolescents with Anorexia Nervosa, treated or untreated with olanzapine. Dosages and serum levels of olanzapine were assessed for potential associations with the occurrence of Refeeding Syndrome and specific variations in Refeeding Syndrome-related electrolytes. Overall, 113 patients were enrolled, including 46 (41%) who developed a Refeeding Syndrome. Mild (87%), moderate (6.5%), and severe (6.5%) Refeeding Syndrome was described, at a current average intake of 1378 ± 289 kcal/day (39 ± 7.7 kcal/kg/die), frequently associated with nasogastric tube (39%) or parenteral (2.2%) nutrition. Individuals receiving olanzapine experienced a more positive phosphorus balance than those who did not (F(1,110) = 4.835, p = 0.030), but no difference in the occurrence of Refeeding Syndrome was documented. The mean prescribed doses and serum concentrations of olanzapine were comparable between Refeeding Syndrome and no-Refeeding Syndrome patients.    Conclusion: The present paper describes the occurrence of Refeeding Syndrome and its association with olanzapine prescriptions in children and adolescents with Anorexia Nervosa. Olanzapine was associated with a more positive phosphorus balance, but not with a different occurrence of Refeeding Syndrome. Further, longitudinal studies are required. What is Known: • Refeeding Syndrome (RS) is a critical complication during refeeding in malnourished patients, marked by electrolyte (phosphorus, magnesium, potassium) imbalances. • Olanzapine, an atypical antipsychotic with nutritional and biochemical impacts, is used in Anorexia Nervosa (AN) treatment, however data concerning its association with RS are lacking. What is New: • The study observed RS in 46/113 (41%) young patients with AN. • Olanzapine-treated individuals showed a higher improvement in serum phosphate levels than untreated ones, although no impact on the occurrence of Refeeding Syndrome was observed., (© 2024. The Author(s).)

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

Background: Hypophosphatemia is associated with prolonged mechanical ventilation and may affect growth, bone mineralization, nephrocalcinosis, and mortality in preterm infants. Optimal nutrition practices may decrease risk for hypophosphatemia and improve outcome., Methods: A quality improvement project was established to improve parenteral and enteral phosphorus intake with the goal to decrease prevalence and duration of hypophosphatemia in the first 14 days in infants <32 weeks' gestation., Results: Among 406 preterm infants, the prevalence of moderate hypophosphatemia decreased from 44% to 19% (P < 0.01) over 4 years. The median duration of moderate hypophosphatemia decreased from 72 h (48-128) to 24 (24-53) (P < 0.01). Daily intakes of parenteral calcium and phosphorus on the fourth day of life increased from 1.5 to 2.5 mEq/kg/day (P < 0.01) and 0.6 to 1.3 mmol/kg/day (P < 0.01), respectively. The median postnatal age of first serum phosphorus concentration assessment decreased from 53 h (41-64) to 32 (24-40) (P < 0.01)., Conclusion: During this quality improvement project, reduced prevalence and duration of hypophosphatemia in infants <32 weeks' gestation in the first 14 days of life was achieved through the optimization of parenteral and enteral phosphorus intake and improved response to acute hypophosphatemia., (© 2023 American Society for Parenteral and Enteral Nutrition.)

Background: Normocaloric vs. calorie-restricted feeding in Intensive Care Unit (ICU) patients with refeeding hypophosphatemia (RH) is associated with increased mortality rates. Until now, only total energy provision has been studied. Data on individual macronutrients (proteins, lipids, and carbohydrates) and clinical outcomes are lacking. This study evaluates associations between macronutrient intake among RH patients during the first week of ICU admission and clinical outcomes., Methods: A single-centre retrospective observational cohort study was conducted among prolonged mechanically ventilated RH ICU patients. The primary outcome was the association of separate macronutrient intakes during the first week of ICU admission with 6-month mortality, adjusted for relevant variables. Other parameters included ICU-, hospital- and 3-month mortality, mechanical ventilation duration and length of ICU and hospital stay. Macronutrient intakes were subsequently analyzed during day 1-3 and day 4-7 of ICU admission., Results: In total, 178 RH patients were included. Six-month all-cause mortality was 29.8%. Higher protein intake during days 1-3 of ICU admission (>0.71 g/kg∗day; HR 2.224, 95%CI 1.261-3.923, p = 0.006), higher age (HR 1.040, 95%CI 1.015-1.066, p = 0.002) and higher APACHE II scores on ICU admission (HR 1.086, 95%CI 1.034-1.140, p = 0.001) were associated with increased 6-month mortality. No differences in other outcomes were observed., Conclusion: High protein - not carbohydrate or lipid - intake during the first three days of ICU admission in patients with RH is associated with increased 6-month mortality, but not short-term outcomes. We hypothesize a time-dependent and dose-response relationship between protein intake and mortality in refeeding hypophosphatemia ICU patients, although additional (randomized controlled) studies are needed to confirm this hypothesis., Competing Interests: Declaration of competing interest Prof. Dr A.R.H. van Zanten reported receiving honoraria for advisory board meetings, lectures, research, and travel expenses from Abbott, AOP Pharma, Baxter, Cardinal Health, Danone-Nutricia, Dim-3, Fresenius Kabi, Mermaid, Lyric, and Nestle-Novartis. The other authors have nothing to declare., (Copyright © 2023 The Author(s). Published by Elsevier Ltd.. All rights reserved.)

Background: Early nutritional therapy may aggravate hypophosphatemia in critically ill patients., Aim: To investigate the influence of the type nutritional therapy on the survival of critically-ill malnourished patients at refeeding hypophosphatemia risk., Methods: Retrospective cohort study including malnourished, critically-ill adults, admitted from June 2014-December 2017 in an intensive care unit (ICU) at a tertiary hospital. Refeeding hypophosphatemia risk was defined as low serum phosphorus levels (<2.5 mg/dL) seen at two timepoints: before the initiation and at day 4 of the nutritional therapy. Patients receiving enteral nutrition (EN) were compared with those receiving supplemental parenteral nutrition (SPN-EN plus parenteral nutrition). Primary outcome was 60 d survival. Secondary endpoint was the incidence of refeeding hypophosphatemia risk., Results: We included 468-321 patients (68.6%) received EN and 147 (31.4%) received SPN. The mortality rate was 36.3% (n = 170). Refeeding hypophosphatemia risk was found in 116 (24.8%) patients before and in 177 (37.8%) at day 4 of nutritional therapy. The 60 d mean survival probability was greater for patients receiving SPN both before (42.4 vs. 22.4%, p = 0.005) and at day 4 (37.4 vs. 25.8%, p = 0.014) vs. patients receiving EN at the same timepoints. Cox regression showed a hazard ratio of 3.3 and 2.4 for patients at refeeding hypophosphatemia risk before and at day 4 of EN, respectively, compared to the SPN group at the same timepoints., Conclusion: Refeeding hypophosphatemia risk was frequent in malnourished ICU patients and the survival for patients receiving SPN seemed associated with better survival than EN only., Competing Interests: Conflict of Interests All authors have no conflict of interests to declare., (Copyright © 2023. Published by Elsevier Inc.)

Background & Aims: Hypophosphatemia during critical illness has been associated with adverse outcome. The reintroduction of enteral or parenteral nutrition, leading to refeeding hypophosphatemia (RFH), has been presented as potential risk factor. We investigated the occurrence of early RFH, its association with clinical outcome, and the impact of early parenteral nutrition (PN) on the development of early RFH in pediatric critical illness., Methods: This is a secondary analysis of the PEPaNIC randomized controlled trial (N = 1440), which showed that withholding supplemental parenteral nutrition (PN) for 1 week (late-PN) in the pediatric intensive care unit (PICU) accelerated recovery and reduced new infections compared to early-PN (<24 h). Patients with renal replacement therapy or unavailable phosphate concentrations were excluded from this analysis. Early RFH was defined as serum/plasma phosphate <0.65 mmol/L and a drop of >0.16 mmol/L within 3 days of admission to the PICU. The association between baseline characteristics and early RFH, and the association of early RFH with clinical outcome were investigated using logistic and linear regression models, both uncorrected and corrected for possible confounders. To examine the impact of nutritional intake on phosphate concentrations, structural nested mean models with propensity score and censoring models were used., Results: A total of 1247 patients were eligible (618 early-PN, 629 late-PN). Early RFH occurred in 40 patients (3%) in total, significantly more in the early-PN group (n = 31, within-group occurrence 5%) than in the late-PN-group (n = 9, within-group occurrence 1%, p < 0.001). Patients who were older (OR 1.14 (95% CI 1.08; 1.21) per year added, p < 0.001) and who had a higher Pediatric Risk of Mortality (PIM3) score had a higher risk of developing early RFH (OR 1.36 (95% CI 1.15; 1.59) per unit added, p < 0.001), whereas patients in the late-PN group had a lower risk of early RFH (OR 0.24 (95% CI 0.10; 0.49), p < 0.001). Early RFH was significantly associated with a 56% longer PICU stay (p = 0.003) and 42% longer hospital stay (p = 0.007), but not with new infections (OR 2.01 (95% CI 0.90; 4.30), p = 0.08) or length of mechanical ventilatory support (OR 1.05 (95% CI -3.92; 6.03), p = 0.68), when adjusted for possible confounders. Increase of parenteral nutrition intake (in % kcal of predicted resting energy expenditure) decreased phosphate concentrations (c = -0.002 (95% CI -0.002; -0.001)., Conclusions: Early RFH occurred in 3% of critically ill children. Patients randomized to late-PN had a lower chance of developing early RFH, which may be explained by the more gradual build-up of nutrition. As early RFH might impact recovery, it is important to closely monitor phosphate concentrations in patients, especially of those at risk for early RFH., Competing Interests: Conflict of interest The authors declare no competing interests., (Copyright © 2022 The Authors. Published by Elsevier Ltd.. All rights reserved.)

Background: Refeeding hypophosphatemia (RH) in individuals with anorexia nervosa (AN) is a potentially fatal complication of nutrition restoration; yet, little is known about risk. This retrospective cohort study examined factors found in hospitalized youth with AN that may contribute to RH., Methods: We reviewed medical records of 300 individuals diagnosed with AN admitted between the years of 2010 and 2016. Logistic regression examined factors associated with RH. Multivariate regression examined factors associated with phosphorus nadir., Results: For 300 participants, the mean (SD) age was 15.5 (2.5) years, 88.3% were White, and 88.3% were female. Participants lost an average of 11.3 (9.7) kg of body weight and were 82% (12.1) of median body mass index (BMI). Age (P = .022), nasogastric (NG) tube feeding (P = .054), weight gain (P = .003), potassium level (P = .001), and magnesium level (P = .024) were contributors to RH. Odds of RH were 13.7 times higher for each unit reduction in magnesium, 9.2 times higher for each unit reduction in potassium, three times higher in those who received NG feeding, 1.5 times higher for each kg of weight gain, and 1.2 times higher for each year of age. Regarding phosphorus nadir, serum magnesium level (P < .001) and admission BMI (P = .002) contributed significantly., Conclusion: The results indicate that age, NG feeding, weight gain, electrolyte abnormalities, and BMI on admission are potential indicators of the development of RH in youth. This study identifies clinical risk factors associated with RH and may guide further investigation., (© 2021 American Society for Parenteral and Enteral Nutrition.)

Medical stabilization, nutrition rehabilitation, and weight restoration, while minimizing risk for the potentially fatal complication of refeeding syndrome, are the primary goals for the treatment of hospitalized individuals with anorexia nervosa and other restrictive-type eating disorders. The purpose of this review was to examine the literature exploring the prophylactic supplementation of phosphate, magnesium, and potassium, in addition to routine thiamin and multivitamin supplementation, for the prevention of refeeding syndrome in adolescents and adults with anorexia nervosa. Through evaluation of outcomes (including serum electrolyte levels and clinical signs and symptoms such as respiratory failure, cardiac failure, peripheral edema, rhabdomyolysis, and encephalopathy), three studies found that prophylactic supplementation of potassium, magnesium, and/or phosphate were effective in preventing refeeding syndrome or refeeding hypophosphatemia (a characteristic of refeeding syndrome). Although all studies found that prophylactic supplementation was effective in preventing refeeding syndrome, refeeding approaches (including the method, amount, and duration of nutrient delivery) as well as the populations studied varied considerably, making it difficult to arrive at specific recommendations for practice. Randomized controlled trials are needed to further examine the safety and effectiveness of prophylactic supplementation of phosphate, magnesium, and potassium on the prevention of refeeding syndrome, utilizing similar feeding and supplementation protocols., (© 2021 American Society for Parenteral and Enteral Nutrition.)

Objective: Refeeding syndrome is a feared complication of refeeding patients with anorexia nervosa. There are now a number of controlled studies showing that refeeding with an initial high calorie count is more beneficial than cautious refeeding and is safe under continuous monitoring. However, there have yet not been studies in severe anorexia nervosa., Method: We present an observational study in two different samples. The first sample consists of those 1075 out of a total of 3230 patients with anorexia nervosa treated in our hospital within 4 years for whom a complete admission laboratory was available and who had an age of at least 18 years at admission. A risk score was calculated from the number of pathological laboratory values out of 12 parameters indicating either refeeding syndrome or health hazards related to malnutrition. The second sample was obtained from a special ward for patients with eating disorders medically at-risk. During the period in question, 410 patients with anorexia nervosa were treated there. 142 patients had a BMI of 13 or less and at the same time a complete data set with the mentioned 12 laboratory parameters at admission and weekly in the following 4 weeks after admission., Results: The risk represented by the laboratory parameters is significantly and negatively correlated to BMI and much higher for the group of patients with a BMI below 13 than for those with a higher BMI (χ 2 sig < 0.000). The 142 patients in the special care unit gain an average of more than 4.1 kg within 4 weeks on the high-calorie diet. With this rapid weight gain, the risk score decreases highly significantly. Neither hypophosphatemia nor rhabdomyolysis is found under phosphate substitution. Hyperhydration occurred often, which manifests itself in the drop in haematocrit by the second week., Discussion: Under thorough medical surveillance, supplementation of phosphate and thiamine, and substitution of electrolytes whenever necessary rapid renutrition appeared to be save even in extremely malnourished inpatients with anorexia nervosa. As measured by the laboratory values, the health status of the severely malnourished patients improves significantly on a high-calorie diet. Except for hyperhydration, there was no evidence of a refeeding syndrome., (© 2021 The Authors. European Eating Disorders Review published by Eating Disorders Association and John Wiley & Sons Ltd.)

Objective: To assess the perceived and actual role of critical care nurses in nutritional care, and their knowledge regarding the identification and management of hypophosphataemia and refeeding syndrome., Design and Methods: Data were collected in one intensive care unit in Israel, from a self-administered questionnaire completed by 42 critical care nurses. The questionnaire was designed to assess their perceived and actual roles in the administration of nutritional care, and knowledge regarding electrolyte monitoring, hypophosphataemia and refeeding syndrome, including risk factors, consequences, and treatment., Results: The majority participants that dieticians are solely responsible for nutrition care and follow-up. Most agreed that the measurement of phosphate levels was not important and that patients should receive full nutrition upon admission, while important risk factors for the development of refeeding syndrome were not recognised or considered. This informed their actual practice. A correlation was found between nurses' knowledge and their actual practice so that the greater the nurses' knowledge, the more they adhered to current nutrition guidelines (p < 0.05)., Conclusions: This study revealed critical care nurses' lack of clarity of their role and lack of knowledge regarding nutrition care. We suggest that this complex task is best managed by a multidisciplinary team, including nurses and dieticians, with clear role definitions., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2021 The Author(s). Published by Elsevier Ltd.. All rights reserved.)

Background & Aims: Refeeding syndrome (RFS) is a disease that occurs when feeding is restarted and metabolism changes from catabolic to anabolic status. RFS can manifest variously, ranging from asymptomatic to fatal, therefore it may easily be overlooked. RFS prediction using explainable machine learning can improve diagnosis and treatment. Our study aimed to propose a machine learning model for RFS prediction, specifically refeeding hypophosphatemia, to evaluate its performance compared with conventional regression models, and to explain the machine learning classification through Shapley additive explanations (SHAP) values., Methods: A retrospective study was conducted including 806 patients, with 2 or more days of nothing-by-mouth prescription, and with phosphate (P) level measurements within 5 days of refeeding were selected. We divided the patients into hypophosphatemia (n = 367) and non-hypophosphatemia groups (n = 439) at a P level of 0.8 mmol/L. Among the features examined within 48 h after admission, we reviewed laboratory test results and electronic medical records. Logistic, Lasso, and ridge regressions were used as conventional models, and performances were compared with our extreme gradient boosting (XGBoost) machine learning model using the area under the receiver operating characteristic curve. Our model was explained using the SHAP value., Results: The areas under the curve were 0.950 (95% confidence interval: 0.924-0.975) for our XGBoost machine learning model and surpassed the performance of conventional regression models; 0.760 (0.707-0.813) for logistic regression, 0.751 (0.694-0.807) for Lasso regression, and 0.758 (0.701-0.809) for ridge regression. According to the SHAP values in the order of importance, low initial P, recent weight loss, high creatinine, diabetes mellitus with insulin use, low haemoglobin A1c, furosemide use, intensive care unit admission, blood urea nitrogen level of 19-65, parenteral nutrition, magnesium below or above the normal range, low potassium, and older age were features to predict refeeding hypophosphatemia., Conclusions: The machine learning model for predicting RFS has a substantially higher effectiveness than conventional regression methods. Creating an accurate risk assessment tool based on machine learning for early identification of patients at risk for RFS can enable careful nutrition management planning and monitoring in the intensive care unit, towards reducing the incidence of RFS-related morbidity and mortality., Competing Interests: Declaration of competing interest All authors declare no competing interests., (Copyright © 2021 European Society for Clinical Nutrition and Metabolism. Published by Elsevier Ltd. All rights reserved.)

Background: Hypophosphatemia may be a useful biomarker to identify thiamine deficiency in critically ill enterally-fed patients. The objective was to determine whether intravenous thiamine affects blood lactate, biochemical and clinical outcomes in this group., Method: This randomized clinical trial was conducted across 5 Intensive Care Units. Ninety critically ill adult patients with a serum phosphate ≤0.65 mmol/L within 72 h of commencing enteral nutrition were randomized to intravenous thiamine (200 mg every 12 h for up to 14 doses) or usual care (control). The primary outcome was blood lactate over time and data are median [IQR] unless specified., Results: Baseline variables were well balanced (thiamine: lactate 1.2 [1.0, 1.6] mmol/L, phosphate 0.56 [0.44, 0.64] mmol/L vs. control: lactate 1.0 [0.8, 1.3], phosphate 0.54 [0.44, 0.61]). Patients randomized to the intervention received a median of 11 [7.5, 13.5] doses for a total of 2200 [1500, 2700] mg of thiamine. Blood lactate over the entire 7 days of treatment was similar between groups (mean difference = -0.1 (95 % CI -0.2 to 0.1) mmol/L; P = 0.55). The percentage change from lactate pre-randomization to T = 24 h was not statistically different (thiamine: -32 (-39, -26) vs. control: -24 (-31, -16) percent, P = 0.09). Clinical outcomes were not statistically different (days of vasopressor administration: thiamine 2 [1, 4] vs. control 2 [0, 5.5] days; P = 0.37, and deaths 9 (21 %) vs. 5 (11 %); P = 0.25)., Conclusions: In critically ill enterally-fed patients who developed hypophosphatemia, intravenous thiamine did not cause measurable differences in blood lactate or clinical outcomes., Trial Registration: Australian and New Zealand Clinical Trials Registry (ACTRN12619000121167)., (Copyright © 2021 Elsevier Ltd and European Society for Clinical Nutrition and Metabolism. All rights reserved.)

Refeeding syndrome is a life-threatening clinical disorder that can occur when treating malnutrition. The aim was to examine the current knowledge of refeeding syndrome in patients ≥ 65 + years with special focus on the incidence of hypophosphatemia (HP) in relation to refeeding rate (kcal/kg/day), number of days until the lowest level of phosphate occurs (day of nadir), refeeding rates and adverse events, and death. Specifically, we hypothesized that higher energy provision would cause a higher incidence of HP. A search was conducted in the available databases. Two cohort studies, 1 case control, and a total of 12 case series/case reports, which accounted for 19 individual patient cases, were eligible. The incidence of HP (<0.5 mmol/L) was 15% and 25% in the 2 cohort studies and 4% in the case control study. The mean day of nadir was between days 2 and 3 in the cohort studies, day 11 in the case control study, and day 3 in the cases series/case reports. Importantly, a rapid drop in phosphate occurred receiving both 30 kcal/kg/day and 8 to 10 kcal/kg/day. The cohort studies reported high death rates-26% and 23%-using both 10 and 20 kcal/kg/day, respectively. Adverse events were noted in most all case series/case reports. Clinicians should be aware that HP may occur in up to 25% of older hospitalized adults, and importantly, it occurs even when refeeding cautiously. Hence, electrolytes should be closely monitored, especially between days 2 and 4, which is when the day of nadir occurs most frequently., (Copyright © 2021. Published by Elsevier Inc.)

Background: Patients receiving parenteral nutrition (PN) support may develop refeeding hypophosphatemia (RH), and its prevalence is highly variable in the literature. Identifying at-risk patients is crucial to minimize clinical complications. The National Institute for Health and Clinical Excellence (NICE) guidelines are used widely to assess the risk of RH, but they lack validation. We aim to (1) identify the prevalence of RH by multiple diagnostic criteria; (2) assess the predictive ability of the NICE guidelines for RH; and (3) identify important risk factors for RH and evaluate their predictive abilities for RH in a new model., Methods: This is a single-center retrospective study on adult patients with PN ≥48 hours. Prevalence of RH was determined by 4 established diagnostic criteria. Prognostic accuracy of the NICE guidelines were assessed by the area under the receiver operating characteristic (ROC) curve. Multivariable logistic regressions were performed to develop a new risk-assessment model., Results: Of 149 enrolled patients, 23%-48% (35 to 72 of 149 patients) developed RH (depending on the diagnostic criteria used). The NICE guidelines demonstrated poor discrimination across all diagnostic criteria (ROC, 0.43-0.53). Critical illness, the use of diuretics, and hypomagnesemia prior to PN were independently associated with RH. These risk factors formed the new model for predicting RH and had good discrimination (ROC 0.74; 95% confidence interval, 0.66-0.82)., Conclusion: Prevalence of RH varied according to established diagnostic criteria. The current NICE guidelines poorly predict the occurrence of RH, and modification is likely beneficial. A new risk-assessment model was developed; nevertheless, further validation is required., (© 2020 American Society for Parenteral and Enteral Nutrition.)

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., (Copyright © 2020. Published by Elsevier Masson SAS.)

Background & Aims: Phosphate is the main intracellular anion essential for numerous biological processes. Symptoms of hypophosphatemia are non-specific, yet potentially life-threatening. This systematic review process was initiated to gain a global insight into hypophosphatemia, associated morbidity and treatments., Methods: A systematic review was conducted (PROSPERO CRD42020163191). Nine clinically relevant questions were generated, seven for adult and two for pediatric critically ill patients, and prevalence of hypophosphatemia was assessed in both groups. We identified trials through systematic searches of Medline, EMBASE, Scopus, Cochrane Central Register of Controlled Trials, CINAHL, and Web of Science. Quality assessment was performed using the Cochrane risk of bias tool for randomized controlled trials and the Newcastle-Ottawa Scale for observational studies., Results: For all research questions, we identified 2727 titles in total, assessed 399 full texts, and retained 82 full texts for evidence synthesis, with 20 of them identified for several research questions. Only 3 randomized controlled trials were identified with two of them published only in abstract form, as well as 28 prospective and 31 retrospective studies, and 20 case reports. Relevant risk of bias regarding selection and comparability was identified for most of the studies. No meta-analysis could be performed. The prevalence of hypophosphatemia varied substantially in critically ill adults and children, but no study assessed consecutive admissions to intensive care. In both critically ill adults and children, several studies report that hypophosphatemia is associated with worse outcome (prolonged length of stay and the need for respiratory support, and higher mortality). However, there was insufficient evidence regarding the optimal threshold upon which hypophosphatemia becomes critical and requires treatment. We found no studies regarding the optimal frequency of phosphate measurements, and regarding the time window to correct hypophosphatemia. In adults, nutrient restriction on top of phosphate repletion in patients with refeeding syndrome may improve survival, although evidence is weak., Conclusions: Evidence on the definition, outcome and treatment of clinically relevant hypophosphatemia in critically ill adults and children is scarce and does not allow answering clinically relevant questions. High quality clinical research is crucial for the development of respective guidelines., Competing Interests: Conflict of Interest None of the co-authors has any competing interest to declare regarding the present systematic review., (Copyright © 2020 Elsevier Ltd and European Society for Clinical Nutrition and Metabolism. All rights reserved.)

Refeeding syndrome can occur in malnourished patients with acute pancreatitis who have electrolyte imbalances. Refeeding syndrome is characterized by severe electrolyte imbalances (mainly hypophosphatemia, hypomagnesemia, and hypokalemia), vitamin deficiency (mainly thiamine deficiency), fluid overload, and salt retention resulting in organ dysfunction and cardiac arrhythmias. We herein report a case involving a patient with severe pancreatitis and gallbladder stones who developed refeeding syndrome with shock and loss of consciousness. The patient was treated by opportune vitamin and electrolyte supplementation therapy and showed substantial improvement after 2 weeks of hospitalization, gaining the ability to eat small bites of solid food orally. Early diagnosis and treatment of refeeding syndrome may reduce morbidity and mortality in patients with acute pancreatitis. Patients should be fasted only if alimentation is contraindicated, and electrolyte values must be closely monitored.

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., (© 2020 Wiley Periodicals LLC.)

Objective: To investigate the prevalence of hypophosphatemia as a marker of refeeding syndrome (RFS) before and after the start of nutritional therapy (NT) in critically ill patients., Methods: Retrospective cohort study including 917 adult patients admitted at the intensive care unit (ICU) of a tertiary hospital in Cuiabá-MT/Brasil. We assessed the frequency of hypophosphatemia (phosphorus <2.5mg/dl) as a risk marker for RFS. Serum phosphorus levels were measured and compared at admission (P1) and after the start of NT (P2)., Results: We observed a significant increase (36.3%) of hypophosphatemia and, consequently, a greater risk of RFS from P1 to P2 (25.6 vs 34.9%; p<0.001). After the start of NT, malnourished patients had a greater fall of serum phosphorus. Patients receiving NT had an approximately 1.5 times greater risk of developing RFS (OR= 1.44 95%CI 1.10-1,89; p= 0.01) when compared to those who received an oral diet. Parenteral nutrition was more associated with hypophosphatemia than either enteral nutrition (p=0,001) or parenteral nutrition supplemented with enteral nutrition (p=0,002)., Conclusion: The frequency of critically ill patients with hypophosphatemia and at risk for RFS on admission is high and this risk increases after the start of NT, especially in malnourished patients and those receiving parenteral nutrition.

Objective: Refeeding hypophosphatemia (RH) is a life-threatening complication in underweight patients with eating disorders (EDs). Although a lower body mass index (BMI) has been reported as a risk factor for RH, the exact BMI cut-off point is not known. Herein, we aimed to identify the optimal BMI cut-off point for RH in adults with EDs., Method: The medical charts of Japanese inpatients with EDs at our hospital between April 1, 2012 and March 31, 2017 were retrospectively reviewed. The optimal BMI cut-off point for RH was determined via receiver operating characteristic analysis. Logistic regression analysis was subsequently performed to assess the association between RH and the BMI cut-off point after adjusting for the propensity score, which was based on known risk factors for RH., Results: The optimal BMI cut-off point was identified as 12.6 kg/m 2 . A BMI lower than the cut-off point significantly correlated with the occurrence of RH after adjusting for the propensity score., Discussion: The optimal BMI cut-off point for the occurrence of RH was 12.6 kg/m 2 in adults with EDs. The findings of the present study may facilitate clinical decision making and early identification of patients who require prophylactic treatment for RH., (© 2019 Wiley Periodicals, Inc.)

Phosphate in both inorganic and organic form is essential for several functions in the body. Plasma phosphate level is maintained by a complex interaction between intestinal absorption, renal tubular reabsorption, and the transcellular movement of phosphate between intracellular fluid and bone storage pools. This homeostasis is regulated by several hormones, principally the parathyroid hormone, 1,25-dihydroxyvitamin D and fibroblast growth factor 23. Abnormalities in phosphate regulation can lead to serious and fatal complications. In this review phosphate homeostasis and the aetiology, pathophysiology, clinical features, investigation and management of hypophosphataemia and hyperphosphataemia will be discussed., Competing Interests: Competing interests: None declared., (© Author(s) (or their employer(s)) 2019. No commercial re-use. See rights and permissions. Published by BMJ.)

Background: Early hypophosphatemia is common in premature infants ≤1250 g. The aim of this study was to assess the frequency and severity of hypophosphatemia after sodium glycerophosphate supplementation from first day of life in parenteral nutrition and to address the safety of this practice., Methods: Prospective cohort study of infants ≤1250 g birth weight born in a tertiary-care level neonatal intensive care unit and supplied with sodium glycerophosphate from the first day of life. Primary outcome was the presence of hypophosphatemia (<4 mg/dL) on the first week. Data were compared with our 2014 prospective subcohort of infants ≤1250 g receiving phosphate after 48 hours of life and morbidity with that of our 2016 retrospective cohort of ≤1250 g., Results: Fifty-four neonates were included. The frequency of hypophosphatemia was 29.6%. Only 1 patient presented hypophosphatemia <2 mg/dL. Mild hypokalemia was found in 8 patients (50%). No cases of hypernatremia were observed. Patients with hypophosphatemia had significantly lower gestational age (27.4 vs 28.8 weeks, P = .032) and lower z-score birth weight (-1.68 vs -0.47; P = .001). When compared with the 2014 subcohort, we found a lower frequency of hypophosphatemia (29.6% vs 69.2%; P = .008) and a lower rate of samples with hypophosphatemia (20.4% vs 51.4%; P = .0002) and critical hypophosphatemia (0.68% vs 11.4%, P = .0005). No differences were found in morbidity or mortality., Conclusions: Sodium glycerophosphate supplementation in parenteral nutrition from the first day of life significantly decreased the frequency of hypophosphatemia. No adverse events were reported., (© 2018 American Society for Parenteral and Enteral Nutrition.)

Refeeding syndrome (RFS) is characterized by the metabolic and clinical changes that occur following aggressive nutritional supplementation in malnourished patients. Hypophosphatemia is the hallmark of RFS and is key to its prevention and treatment in clinical practice. However, the mechanism of hypophosphatemia during RFS is unclear because of the lack of an animal model. In this study, we developed a rat RFS model as a first step to clarifying the molecular mechanism. After establishing the parenteral route, rats were fasted for 5 days and refeeding was started using total parenteral nutrition. The animals were infused with a high calorie solution with or without insulin administration. Results showed that plasma phosphate levels did not decrease in rats infused with the high calorie solution alone;in contrast, a 20% reduction compared to baseline was observed in rats administered insulin. In addition, rats infused with the high calorie solution containing added phosphate did not present with hypophosphatemia. Thus, we developed a rat RFS model with hypophosphatemia by tube feeding and insulin administration, and demonstrated the importance of phosphate in preventing refeeding hypophosphatemia. J. Med. Invest. 65:50-55, February, 2018.

Background and Objectives: Refeeding hypophosphataemia (RH) is characterized by an acute electrolyte derangement following nutrition therapy. Complications associated include heart failure, respiratory failure, paraesthesia, seizure and death. We aim to assess its incidence, risk factors, and outcome in our local intensive care unit (ICU)., Methods and Study Design: A prospective observational cohort study was conducted at the mixed medical- surgical of a tertiary ICU in Kuantan, Malaysia. The study was registered under the National Medical Research Register (NMRR-14-803-19813) and has received ethical approval. Inclusion criteria include adult admission longer than 48 hours who were started on enteral feeding. Chronic renal failure patients and those receiving dialysis were excluded. RH was defined as plasma phosphate less than 0.65 mmol/L and a drop of more than 0.16 mmol/L following feeding., Results: A total of 109 patients were recruited, of which 44 (42.6%) had RH. Patients with RH had higher SOFA score compared to those without (p=0.04). There were no differences in the APACHE II and NUTRIC scores. Serum albumin was lower in those with RH (p=0.04). After refeeding, patients with RH had lower serum phosphate, magnesium and albumin, and higher supplementation of phosphate, potassium and calcium. There were no differences in mortality, length of hospital or ICU stay., Conclusions: Refeeding hypophosphataemia occurs in almost half of ICU admission. Risk factors for refeeding include high organ failure score and low albumin. Refeeding was associated with imbalances in phosphate, magnesium, potassium and calcium. Future larger study may further investigate these risk factors and long-term outcomes.

Introduction: Hypophosphatemia has been associated with refeeding malnourished patients, but its clinical significance is unclear. We investigated the incidence of refeeding hypophosphatemia (RH) in the surgical intensive care unit (SICU) and its association with early enteral nutrition (EN) administration and clinical outcomes., Methods: We performed a retrospective review of a 2-year database of patients receiving EN in the SICU. RH was defined as a post-EN phosphorus (PHOS) level decrement of >0.5 mg/dL to a nadir <2.0 mg/dL within 8 days from EN initiation. We investigated the risk factors for RH and examined its association with clinical outcomes using multivariable regression analyses., Results: In total, 213 patients comprised our analytic cohort. Eighty-three of 213 (39%) individuals experienced RH and 43 of 130 (33%) of the remaining patients experienced non-RH hypophosphatemia (nadir PHOS level <2.0 mg/dL). Overall, there was a total 59% incidence of hypophosphatemia of any cause (N = 126). Nutrition parameters did not differ between groups; most patients were initiated on EN within 48 hours of SICU admission, and timing of EN initiation was not a significant predictor for the development of RH. The median hospital length of stay (LOS) was 21 and 24 days for those with and without RH, respectively ( P = .79); RH remained a nonsignificant predictor for hospital LOS in the multivariable analysis., Conclusions: RH is common in the SICU but is not related to timing or amount of EN. Hypophosphatemia is also common in the critically ill, but regardless of etiology, it was not found to be a predictor of worse clinical outcomes.

Background: Children with severe acute malnutrition (SAM) have increased requirements for phosphorus and magnesium during recovery. If requirements are not met, the children may develop refeeding hypophosphatemia and hypomagnesemia. However, little is known about the effect of current therapeutic diets (F-75 and F-100) on serum phosphate (S-phosphate) and magnesium (S-magnesium) in children with SAM., Methods: Prospective observational study, with measurements of S-phosphate and S-magnesium at admission, prior to rehabilitation phase and at discharge in children aged 6-59 months admitted with SAM to Jimma Hospital, Ethiopia. Due to shortage of F-75, 25 (35 %) children were stabilized with diluted F-100 (75 kcal/100 ml)., Results: Of 72 children enrolled, the mean age was 32 ± 14 months, and edema was present in 50 (69 %). At admission, mean S-phosphate was 0.92 ± 0.34 mmol/L, which was low compared to normal values, but increased to 1.38 ± 0.28 mmol/L at discharge, after on average 16 days. Mean S-magnesium, at admission, was 0.95 ± 0.23 mmol/L, and increased to 1.13 ± 0.17 mmol/L at discharge. At discharge, 18 (51 %) children had S-phosphate below the normal range, and 3 (9 %) had S-phosphate above. Most children (83 %) had S-magnesium above normal range for children. Both S-phosphate and S-magnesium at admission were positively associated with serum albumin (S-albumin), but not with anthropometric characteristics or co-diagnoses. Using diluted F-100 for stabilization was not associated with lower S-phosphate or S-magnesium., Conclusion: Hypophosphatemia was common among children with SAM at admission, and still subnormal in about half of the children at discharge. This could be problematic for further recovery as phosphorus is needed for catch-up growth and local diets are likely to be low in bioavailable phosphorus. The high S-magnesium levels at discharge does not support that magnesium should be a limiting nutrient for growth in the F-100 diet. Although diluted F-100 (75 kcal/100 mL) is not designed for stabilizing children with SAM, it did not seem to cause lower S-phosphate than in children fed F-75.

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.

Purpose: The medical stabilization of adolescent patients with restrictive eating disorders can be associated with refeeding syndrome, a potentially fatal complication preceded by refeeding hypophosphatemia (RH). Whether RH can be prevented by routine prophylactic phosphate supplementation has not been previously examined. This study sought to determine the safety and efficacy of a refeeding strategy that incorporates prophylactic phosphate supplementation to prevent RH., Methods: Retrospective chart data were collected for patients aged younger than 18 years with restrictive eating disorders admitted to a tertiary pediatric inpatient ward between January 2011 and December 2014. All patients were refed with a standardized protocol that included prophylactic oral phosphate supplementation (1.0 ± .2 mmol/kg/day)., Results: During the 4-year study period, 75 admissions (70 patients) were included for analysis. The mean age and percent median body mass index of included patients were 15.3 years and 83.5%, respectively. Seven out of 75 (9%) had percent median body mass index of <70% and 26 out of 75 (35%) had percent body weight loss >20%. All patients were normophosphatemic at the time of admission (mean serum phosphate 1.24 ± .2 mmol/L). Serial laboratory evaluation revealed that all supplemented patients maintained serum phosphate levels >1.0 mmol/L during the initial 7 days of refeeding. Eleven patients became mildly hyperphosphatemic (range 1.81-2.17 mmol/L) with no associated clinical consequences. Additional analysis of 11 patients presenting with hypophosphatemia before refeeding revealed that with supplementation, phosphate values normalized by Day 1, and this group experienced no further RH episodes during initial refeeding., Conclusions: Prophylactic oral phosphate supplementation appears safe, and no episodes of RH occurred in patients with restrictive eating disorders undergoing inpatient refeeding., (Copyright © 2015 The Society for Adolescent Health and Medicine. Published by Elsevier Inc. All rights reserved.)

Background: Anorexia Nervosa is a Psychiatric eating disorder of adolescence age with a high morbidity and mortality., Case Presentation: We describe a common case of anorexia nervosa (AN) in a female adolescent complicated by less known conditions related to refeeding syndrome. At admission, the girl showed a mild hypercholesterolemia with progressive normalization of the values. The initial low hypertransaminasemia worsened after refeeding until very high levels and hypophosphoremia was also described. Only a controlled caloric intake and a specific electrolyte supplementation led to the improvement of hematologic values and the clinical condition of the patient., Conclusions: Refeeding complications must be always suspected because of life-threatening risk. More attention should be paid not only to the acute state of the disease but also to the prevention and the management of refeeding-related manifestations.

Background: Hypophosphatemia, hypomagnesemia, and hypokalemia occur in patients receiving parenteral nutrition (PN), mainly when the body's stores are depleted due to fasting or inflammation. Although these disorders are potentially fatal, few studies have reported the incidence in the pediatric population., Methods: This study evaluated, in a historical cohort of pediatric patients, the prevalence of hypophosphatemia, hypokalemia, and hypomagnesaemia until 48 hours before initiation of PN infusion (P1) and from days 1-4 (P2) and days 5-7 (P3) of PN infusion and investigated if malnutrition, calories, and protein infusion were correlated to these disorders., Results: Malnutrition was present in 32.8% (n = 119) of the subjects; 66.4% of the patients were in the pediatric intensive care unit. Survival rate was 86.6%. P1 had the highest prevalence of mineral disorders, with 54 events (58.1%; P2, n = 35, 37.6%; P3, n = 4, 4.3%). Hypokalemia events were related to malnutrition (odds ratio, 2.79; 95% confidence interval, 1.09-7.14; P = .045). In the first 7 days, infused calories were below the amount recommended by current guidelines in up to 84.9% of patients, and protein infused was adequate in up to 75.7%. Protein infused above the recommendation in the first 4 days was related to hypomagnesaemia (odds ratio, 5.66; 95% confidence interval, 1.24-25.79; P = .033)., Conclusion: Hypophosphatemia, hypokalemia, and hypomagnesemia were frequent in hospitalized pediatric patients before and during the first 4 days of PN infusion. Patients with malnutrition had more chances of having hypokalemia, and those who received high protein infusion had an increased chance of developing hypomagnesemia., (© 2016 American Society for Parenteral and Enteral Nutrition.)

Background: Children treated for severe acute malnutrition (SAM) are at risk of refeeding hypophosphatemia. Therapeutic diets have only recently become fortified with phosphorus to meet United Nations (UN) specifications, but to our knowledge no studies have investigated the effect., Objective: The aim was to assess concentrations and correlates of plasma phosphate (P-phosphate) at admission and during treatment and to identify correlates of changes in P-phosphate., Design: This was a prospective observational study in 6- to 59-mo-old children admitted for treatment of SAM to Mulago Hospital, Uganda. P-phosphate was measured at admission, on the second day of treatment with a therapeutic formula containing 75 kcal/100 mL and 560 mg phosphorus/L (F-75, Nutriset), at the start of the transition to a therapeutic formula containing 100 kcal/100 mL and 579 mg phosphorus/L (F-100; Nutriset), at day 2 of transition, and at discharge., Results: Among 120 children, mean ± SD P-phosphate at admission was 1.04 ± 0.31 mmol/L and increased by 0.43 (95% CI: 0.35, 0.52) mmol/L during the first 2 d and more slowly toward discharge. Most (79%) children experienced their lowest P-phosphate concentration at admission, and none developed severe hypophosphatemia. P-phosphate was lowest in children with edema and with elevated C-reactive protein, and a lower increase was seen with increasing caretaker-reported severity of illness. Partially or fully replacing F-75 with rice porridge (i.e., a local practice to reduce diarrhea) during the first 2 d of stabilization was associated with a 0.34-mmol/L (95% CI: 0.18, 0.50 mmol/L) lower increase in P-phosphate during the same first 2 d., Conclusions: F-75, which complies with UN specifications and provides 73 mg phosphorus · kg(-1) · d(-1) (130 mL · kg(-1) · d(-1)), seems to prevent refeeding hypophosphatemia in children with SAM. Replacing this formula with rice porridge during the first days of treatment to manage diarrhea may have an adverse effect on P-phosphate concentrations. This study was registered at http://www.isrctn.com as ISRCTN55092738., (© 2016 American Society for Nutrition.)

Objective: Hypophosphatemia of refeeding is one of the most dangerous complications seen during the treatment of patients with anorexia nervosa. Although easily detectable and treatable, hypophosphatemia is under-recognized as a complication of refeeding. Specific risk factors for the development of hypophosphatemia are likely to exist among patients with severe anorexia nervosa. The purpose of this study was to identify clinically useful markers that may predict the development of or protection from hypophosphatemia during refeeding., Methods: We conducted a retrospective case-control study of 123 patients with severe anorexia nervosa admitted for medical stabilization at the ACUTE Center for Eating Disorders between October 1, 2008 and December 31, 2013. Risk factors for refeeding hypophosphatemia were determined by multivariate logistic regression from clinical parameters and laboratory values measured at the time of admission., Results: The prevalence of hypophosphatemia was 33.3% (41 of 123 patients). Higher hemoglobin was the only risk factor associated with a higher odds of developing hypophosphatemia (adjusted odds ratio [aOR], 1.56 [95% confidence interval [CI], 1.12-2.18]). Statistically significant protective factors against the development of hypophosphatemia were observed with higher body mass index (aOR, 0.54 [95% CI, 0.39-0.75]), higher serum potassium (aOR, 0.29 [95% CI, 0.14-0.62]), and higher serum prealbumin (aOR, 0.91 [95% CI, 0.84-0.99])., Discussion: Four independent factors associated with refeeding hypophosphatemia were identified. Identification of findings which correlate with hypophosphatemia, or the lack thereof, has the potential to facilitate appropriate triage of patients with anorexia nervosa for closer monitoring during refeeding., (© 2015 Wiley Periodicals, Inc.)

Aim: Electrolyte balances have not been sufficiently evaluated in extremely preterm infants after early parenteral nutrition. We investigated the risk of early hypophosphatemia and hypokalemia in extremely preterm infants born small for gestational age (SGA) who received nutrition as currently recommended., Methods: This prospective, observational cohort study included all consecutive extremely preterm infants born at 24-27 weeks who received high amino acids and lipid perfusion from birth. We evaluated the electrolyte levels of SGA infants and infants born appropriate for gestational age (AGA) during the first five days of life., Results: The 12 SGA infants had lower plasma potassium levels from Day One compared to the 36 AGA infants and were more likely to have hypokalemia (58% vs 17%, p = 0.001) and hypophosphatemia (40% vs 9%, p < 0.01) during the five-day observation period. After adjusting for perinatal factors, SGA remained significantly associated with hypophosphatemia (odds ratio 1.39, confidence intervals 1.07-1.81, p = 0.01)., Conclusion: Extremely preterm infants born SGA who were managed with currently recommended early parenteral nutrition had a high risk of early hypokalemia and hypophosphatemia. Potassium and phosphorus intakes should be set at sufficient levels from birth onwards, especially in SGA infants., (©2015 Foundation Acta Paediatrica. Published by John Wiley & Sons Ltd.)

Background: Refeeding syndrome (RS) is a potentially fatal condition that can occur following the re-introduction of nutrition after a period of starvation. Hypophosphataemia following the reintroduction of nutrition is often the only reliable biochemical marker of RS. Refeeding index (RI) generated from baseline insulin-like growth factor-1 (IGF-1) and leptin has been proposed as a useful biochemical marker for the identification of patients at risk of developing refeeding hypophosphataemia (RH)., Methods: A prospective study included 52 patients referred for parenteral nutrition (PN). The sensitivity and specificity of IGF-1 measured using a sensitive assay was compared to the RI in predicting the development of RH (a ≥ 30% drop in PO4 during the first 36-h of PN administration). Leptin and IGF-1 were analysed on baseline samples using a quantitative enzyme-linked immunoassay. Daily blood samples were collected from all patients for routine biochemistry for the full duration of PN administration., Results: High sensitivity IGF-1 measurement alone was comparable with the RI, using receiver-operating characteristic (ROC) curve analysis, with areas under the curve being 0.79 and 0.80, respectively, and superior to leptin alone (0.72) for predicting ≥ 30% drop in PO4. The cut-off value for IGF-1 that gave best sensitivity (91% [95% CI 75-98%]) and specificity (65% [95% CI 41-85%]) was 63.7 µg/L, with a likelihood ratio of 2.59., Conclusion: Baseline IGF-1 is an objective, sensitive and specific biochemical marker in identifying patients who are at high risk of developing RH prior to PN administration and therefore may have a role in clinical practice., (© The Author(s) 2014 Reprints and permissions: sagepub.co.uk/journalsPermissions.nav.)

Aim: To describe the characteristics of hypophosphatemia in severely disabled individuals with neurological disorders and to identify its causative factors., Method: We retrospectively reviewed clinical data from 82 individuals with motor skills classified as sitting, rollover or bedridden. Age, gender and body mass index were compared in individuals with (n=19) and without (n=63) a history of hypophosphatemia (serum phosphate levels <2.0 mg/dl). The clinical course of each patient with hypophosphatemia was reviewed and the cause identified. Laboratory data during hypophosphatemia was compared with that after recovery., Results: The age, gender and body mass index did not differ significantly between the individuals with and without hypophosphatemia. Nineteen patients experienced 25 episodes of hypophosphatemia. The causes included febrile illnesses (n=17), refeeding syndrome (n=4) and Fanconi syndrome (n=3), but was unidentifiable in one episode. Significant elevations in C-reactive protein levels and reductions in sodium levels were observed during hypophosphatemia episodes., Interpretation: Hypophosphatemia is a common complication in severely disabled individuals with frequent bacterial infections, refeeding following malnutrition and valproate administration for epilepsy treatment. Because severe hypophosphatemia is life threatening, serum phosphate levels should be closely monitored in this population., (Copyright © 2013 The Japanese Society of Child Neurology. Published by Elsevier B.V. All rights reserved.)

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.

Purpose: Concerns about refeeding syndrome have led to relatively conservative nutritional rehabilitation in malnourished inpatients with anorexia nervosa (AN), which delays weight gain. Compared to other programs, we aggressively refed hospitalized adolescents. We sought to determine the incidence of hypophosphatemia (HP) in 12-18-year-old inpatients in order to inform nutritional guidelines in this group., Methods: A 1-year retrospective chart review was undertaken of 46 admissions (29 adolescents) with AN admitted to the adolescent ward of a tertiary children's hospital. Data collected over the initial 2 weeks included number of past admissions, nutritional intake, weight, height, body mass index, and weight change at 2 weeks. Serum phosphorus levels and oral phosphate supplementation was recorded., Results: The mean (SD) age was 15.7 years (1.4). The mean (SD) ideal body weight was 72.9% (9.1). Sixty-one percent of admissions were commenced on 1,900 kcal (8,000 kJ), and 28% on 2,200 kcal (9,300 kJ). Four patients were deemed at high risk of refeeding syndrome; of these patients, three were commenced on rehydration therapy and one on 1,400 kcal (6,000 kJ). All patients were graded up to 2,700 kcal (11,400 kJ) with further increments of 300 kcal (1,260 kJ) as required. Thirty-seven percent developed mild HP; no patient developed moderate or severe HP. Percent ideal body weight at admission was significantly associated with the subsequent development of HP (p = .007)., Conclusions: These data support more aggressive approaches to nutritional rehabilitation for hospitalized adolescents with AN compared to current recommendations and practice., (Crown Copyright 2010. Published by Elsevier Inc. All rights reserved.)

Background: Refeeding syndrome (RFS) and starvation-associated injuries are significant complications in malnourished patients. Severe weight loss after obesity surgery is frequently associated with malnutrition, consequently increasing the likelihood of RFS and starvation-related injuries as postoperative complications. RFS and starvation-induced injury in a single patient has rarely been reported. In this paper, we present, for the first time, a case of hepatic injury attributed to both refeeding syndrome and starvation-induced hepatic injury in a malnourished woman following bariatric surgery. Case Report: A 27-year-old female patient was admitted to the hospital for severe malnutrition after sleeve gastrectomy. Her body mass index (BMI) dropped from 37.2 kg/m² to 12.4 kg/m² 1 year after surgery. After nutritional supplementation, her liver enzymes levels increased significantly, with severe hypophosphatemia suggesting the development of RFS. During the calorie restriction treatment for RFS, the patient unexpectedly exhibited the recurrent increase of liver enzyme levels and severe reduction in body weight, albumin, and hemoglobin, which is considered to be caused by starvation-induced injury during the treatment of RFS. Following precise nutritional re-supplementation, her liver enzyme levels were dramatically decreased, with significant elevated hemoglobin and albumin levels at discharge and during the follow-up visit. Conclusions: Chronic malnutrition and extreme weight loss can occur following bariatric surgery. Our report highlights the potential for RFS and starvation-related liver injuries as postoperative complications for high-risk patients after bariatric surgery. Liver injury can occur in both RFS and starvation-induced hepatitis. Nutrition initiation and supplementation should be carefully balanced in high-risk patients during nutritional treatments. [ABSTRACT FROM AUTHOR]

Abstract Hypophosphatemia (serum phosphate

Refeeding Syndrome (RS) is poorly understood and remains under-diagnosed, -despite its clinical consequences and the risk of death. It is defined by the clinical and biological manifestations that occur during the refeeding of patients after prolonged fasting or in the context of undernutrition. It results from the abrupt shift from catabolism to anabolism. The intracellular displacement of electrolytes (phosphorus, magnesium, potassium) in response to insulin secretion after -refeeding, and thiamine (vitamin B1) deficiency, play a major role in the pathophysiology of RS. Clinical symptoms are associated with hydroelectrolyte disorders, -hydrosaline retention, and/or organ failure. Patient management should be immediate with regular clinical examinations and close biological monitoring, including electrolytes monitoring. Correction of hydroelectrolyte disorders and systematic thiamine supplementation are essential during refeeding. Whether oral, enteral, or parenteral, refeeding should be cautious and very progressively. Identifying patients at risk of RS and preventive measures are crucial. [ABSTRACT FROM AUTHOR]

Background: Refeeding syndrome is the gravest possible medical complication in malnourished patients undergoing refeeding in the hospital. We previously reported that males with malnutrition secondary to eating disorders required more calories and had longer hospital stays than females; however, sex differences in electrolyte abnormalities indicating refeeding syndrome risk remain unknown. The objective of this study was to assess differences in electrolyte abnormalities indicating refeeding syndrome risk among male and female adolescents and young adults with eating disorders hospitalized for medical instability. Methods: We retrospectively reviewed the electronic medical records of 558 patients aged 9–25 years admitted to the University of California, San Francisco Eating Disorders Program for medical instability between May 2012 and August 2020. Serum was drawn per standard of care between 5 and 7 am each morning and electrolyte abnormalities indicating refeeding syndrome risk were defined as: hypophosphatemia (< 3.0 mg/dL), hypokalemia (< 3.5 mEq/L), and hypomagnesemia (< 1.8 mg/dL). Logistic regression was used to assess factors associated with electrolyte abnormalities indicating refeeding syndrome risk. Results: Participants included 86 (15.4%) males and 472 (84.6%) females, mean (SD) age 15.5 (2.8) years. Rates of refeeding hypophosphatemia (3.5%), hypokalemia (8.1%), and hypomagnesemia (11.6%) in males hospitalized with eating disorders were low, with no statistically significant differences from females. Older age was associated with higher odds of refeeding hypophosphatemia and hypomagnesemia. Lower percent median body mass index and greater weight suppression at admission were associated with higher odds of refeeding hypophosphatemia. Conclusions: Rates of electrolyte abnormalities indicating refeeding syndrome risk were low in males hospitalized for eating disorders and rates did not significantly differ from females. Together with our finding that males have higher caloric requirements and longer hospital length of stay, the finding that electrolyte abnormalities indicating refeeding syndrome risk were not greater in males than females supports future research to evaluate the safety and efficacy of higher calorie and/or faster advancing refeeding protocols for males. [ABSTRACT FROM AUTHOR]

Background: Hypophosphatemia due to excessive carbohydrate administration is considered the primary pathogenesis of refeeding syndrome. However, its association with liver injury and hypoglycemia, often seen in severe malnutrition before re-nutrition, remains unclear. Autophagy reportedly occurs in the liver of patients with severe malnutrition. This study aimed to clarify the pathophysiology of liver injury and hypoglycemia by focusing on liver volume. Methods: Forty-eight patients with anorexia nervosa with a body mass index (BMI) of < 13 kg/m2 were included (median BMI: 10.51 kg/m2 on admission). Liver volume was measured in 36 patients who underwent abdominal computed tomography (CT), and the "estimated liver weight/ideal body weight" was used as the liver volume index. Seventeen blood test items were analyzed during the first 60 days. Results: Liver volume significantly decreased when abdominal CTs were conducted shortly before or after hypoglycemia compared to when the scans were performed during periods without hypoglycemia. Five patients with severe hypoglycemia on days 13–18 after admission had a very low nutritional intake; of them, four showed a marked decrease in liver volume. Severe hypoglycemia was accompanied by low serum triglycerides and liver dysfunction. Patients experiencing hypoglycemia of blood glucose levels < 55 mg/dL (< 3.05 mmol/L) (32 patients; median lowest BMI: 9.45 kg/m2) exhibited significantly poorer blood findings for most of the 17 items, except serum phosphorus and potassium, than did those not experiencing hypoglycemia (16 patients; median lowest BMI: 11.2 kg/m2). All patients with a poor prognosis belonged to the hypoglycemia group. Empirically, initiating re-nutrition at 500 kcal/day (20–25 kcal/kg/day), increasing to 700–800 kcal/day after a week, and then gradually escalating can reduce serious complications following severe hypoglycemia. Conclusions: Liver volume reduction accompanied by hypoglycemia, low serum triglyceride levels, and liver dysfunction occurs when the body's stored energy sources are depleted and external nutritional intake is inadequate, suggesting that the liver was consumed as a last resort to obtain energy essential for daily survival. This pathophysiology, distinct from refeeding syndrome, indicates the terminal stage of malnutrition and is a risk factor for complications and poor prognosis. In treatment, extremely low nutrient levels should be avoided. Plain English summary: This study aimed to clarify the pathophysiology of severe malnutrition in patients with anorexia nervosa by focusing on liver volume. The small size of the liver was almost always accompanied by hypoglycemia within a week. In several cases, extremely low nutritional intake, continued for approximately 2 weeks after admission, resulted in severe hypoglycemia and a marked decrease in liver volume. The 32 patients with hypoglycemia presented worse blood test items related to liver function, nutrition, and blood cell count compared to the 16 patients without such a condition. All cases with poor prognosis were in the hypoglycemia group. These findings suggest that severe hypoglycemia with decreased liver volume indicates the end stage of malnutrition. Liver volume reduction is considered a reflection of the liver's consumption of itself as a last resort for energy procurement for daily survival when the body's stored energy sources are depleted, and external nutritional intake is insufficient. When managing such patients, extremely low nutritional administration should be avoided. [ABSTRACT FROM AUTHOR]