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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. 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. 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). 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. [ABSTRACT FROM AUTHOR]

The decrease of nutritional status has affected one-third hospitalized patients, while there is no widely used definition of malnutrition. Refeeding syndrome is a severe complication of refeeding in people with malnutrition, it includes a series of electrolyte disorders and clinical symptoms. Further research is warranted to determine whether refeeding syndrome prolongs the length of stay, and to verify the effect of different energy intakes during refeeding on the length of stay in people with malnutrition. Our review aimed to explore the effects of refeeding syndrome and initial calorie intake on the length of stay in patients with malnutrition. This study aids the understanding of clinical nutrition strategies to prevent and treat refeeding syndrome. PubMed, Embase, Cochrane Library, Web of Knowledge, and two Chinese databases were systematically searched until October 2021. Controlled studies of patients' refeeding process with the outcome of length of stay were included. Effect sizes were expressed as 95% confidence intervals (CIs) and calculated using random-effects models. Eighteen studies involving 3868 participants were included in our review. The pooled length of stay of 2965 patients with refeeding syndrome in 11 studies was 25.55 (95% CI , 20.20–30.90) days. The pooled impact of refeeding syndrome on length of stay of 2634 patients in 10 studies was weighted mean difference (WMD) = 2.91 (95% CI , −0.18 – 6.00; P = 0.065) days. The pooled effect of higher calorie intake of 1234 patients in 8 studies was WMD = −3.04 (95% CI , −5.10 to −0.99, P = 0.003) days. The average length of stay in patients with refeeding syndrome was 25.55 days with a very high heterogeneity between studies. Refeeding syndrome affects the length of stay in part of, but not all, patients. In the present review, we concluded that higher initial calorie intake may help shorten the length of stay in patients with malnutrition. More well-designed randomized controlled trials are needed to explore the effect of calorie intake during refeeding. [ABSTRACT FROM AUTHOR]

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. 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. 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). In critically ill enterally-fed patients who developed hypophosphatemia, intravenous thiamine did not cause measurable differences in blood lactate or clinical outcomes. Australian and New Zealand Clinical Trials Registry (ACTRN12619000121167). [ABSTRACT FROM AUTHOR]

Refeeding syndrome occurs with the reintroduction of food after an individual has undergone a substantial period of malnutrition. The development of this condition is not uncommon but is neglected in most cases. To identify the incidence of refeeding syndrome in hospitalized patients undergoing total parenteral nutrition and factors that may be associated with this condition. Observational retrospective and prospective cohort study. Data collection took place at the Hospital de Clínicas de Porto Alegre, from 2015 to 2018. Data was collected consecutively from patient electronic medical records. All hospitalized individuals aged 18 years or more and having a prescription for total parenteral nutrition were included in the study. Exclusion criteria included patients with diabetic ketoacidosis; receiving renal replacement therapy or chronic kidney disease with a glomerular filtration rate <30 mL/min; severe metabolic acidosis or any disease that could affect serum phosphorus levels. WinPepi software, version 11.65, was used to calculate sample size. Data analysis was performed using SPSS version 20.0. A 5% significance level was considered for the established comparisons. The project was approved by the Research Ethics Committee of Hospital de Clínicas de Porto Alegre (number 17–0313). Data from 97 patients was collected. The incidence of refeeding syndrome in our sample was 43.3% (n = 42). Factors positively associated with the syndrome were use of standard parenteral nutrition (p < 0.01), advancing age (mean 62.8 yr versus 55.1 yr; p = 0.013), and amount of total energy administered, which were 25.6 kcal/kg/day versus 23.6 kcal/kg/day for patients with and without refeeding syndrome, respectively (p < 0.01). The incidence of refeeding syndrome in individuals using total parenteral nutrition was high. The supply of a greater quantity of total energy in the first week of nutritional therapy, the absence of electrolytes in the parenteral nutrition solution and advancing age were all factors associated with the emergence of refeeding syndrome. [ABSTRACT FROM AUTHOR]

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. 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. 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. 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. [ABSTRACT FROM AUTHOR]

Neurocritically ill patients are more likely to be comatose and suffer from dysphagia, conditions that inevitably require nutritional support. Inappropriate nutritional support may lead to refeeding syndrome (RFS). This study aimed to explore the incidence and outcome of RFS in neurocritically ill patients. We conducted a retrospective study among neurocritically ill patients who received total enteral nutrition for >72 h in a university-affiliated hospital. RFS was defined as the occurrence of new-onset hypophosphatemia (<0.65 mmol/L) within 72 h of the commencement of nutritional support. The primary outcome was 6-month mortality. The secondary outcomes included 30-day mortality, neurocritical care unit (NCU) stay, and hospital length of stay. A total of 328 patients were enrolled, and 56 (17.1%) of them developed RFS within 72 h of nutrition support. Significantly, we found that patients with high malnutrition universal screening tool (MUST) and sequential organ failure assessment (SOFA) scores were more likely to develop RFS. The occurrence of RFS was associated with a longer NCU stay, higher 30-day mortality and 6-month mortality, and poorer 6-month functional outcome. Moreover, RFS was identified as an independent risk factor for 6-month mortality. RFS is not rare in neurocritically ill patients and is more likely to occur in patients with nutritional risk and more severe conditions. RFS is an independent risk factor for 6-month mortality in neurocritically ill patients. [ABSTRACT FROM AUTHOR]

Despite the presumed importance of preventing and treating micronutrient and mineral deficiencies, it is still not clear how to optimize measurement and administration in critically ill patients. In order to design future comparative trials aimed at optimizing micronutrient and mineral management, an important first step is to gain insight in the current practice of micronutrient, phosphate and magnesium monitoring and administration. Within the metabolism-endocrinology-nutrition (MEN) section of the European Society of Intensive Care Medicine (ESICM), the micronutrient working group designed a survey addressing current practice in parenteral micronutrient and mineral administration and monitoring. Invitations were sent by the ESICM research department to all ESICM members and past members. Three hundred thirty-four respondents completed the survey, predominantly consisting of physicians (321 [96.1%]) and participants working in Europe (262 [78.4%]). Eighty-one (24.3%) respondents reported to monitor micronutrient deficiencies through clinical signs and/or laboratory abnormalities, and 148 (44.3%) reportedly measure blood micronutrient concentrations on a routine basis. Two hundred ninety-two (87.4%) participants provided specific data on parenteral micronutrient supplementation, of whom 150 (51.4%) reported early administration of combined multivitamin and trace element preparations at least in selected patients. Among specific parenteral micronutrient preparations, thiamine (146 [50.0%]) was reported to be the most frequently administered micronutrient, followed by vitamin B complex (104 [35.6%]) and folic acid (86 [29.5%]). One hundred twenty (35.9%) and 113 (33.8%) participants reported to perform daily measurements of phosphate and magnesium, respectively, whereas 173 (59.2%) and 185 (63.4%) reported to routinely supplement these minerals parenterally. The survey revealed a wide variation in current practices of micronutrient, phosphate and magnesium measurement and parenteral administration, suggesting a risk of insufficient prevention, diagnosis and treatment of deficiencies. These results provide the context for future comparative studies, and identify areas for knowledge translation and recommendations. [ABSTRACT FROM AUTHOR]

The key to preventing refeeding syndrome (RS) is identifying and appropriately managing patients at risk. We evaluated our clinical management of RS risk in patients starting total parenteral nutrition (TPN). Patients commencing TPN at University College London Hospital between January and July 2015 were prospectively followed-up for 7-days. Eighty patients were risk assessed for RS and categorized into risk groups. High and low risk RS groups were compared focussing on the onset of biochemical features of RS (hypophosphatemia, hypokalaemia and hypomagnesemia) and initial clinical assessment. Statistical analysis was conducted using t -tests and Mann–Whitney U tests. Sixty patients (75%) were identified as high-risk for RS and received lower initial calories (12.8 kcal/kg/day, p < 0.05). All high-risk patients received a high potency vitamin preparation compared to 35% in the low risk group (p < 0.05). Daily phosphate, magnesium and potassium plasma levels were monitored for seven days in 25%, 30% and 53.8% of patients, respectively. Hypophosphatemia developed in 30% and hypomagnesaemia and hypokalaemia in 27.5% of all patients. Approximately 84% of patients had one or more electrolyte abnormalities, which occurred more frequently in high-risk RS patients (p < 0.05). Low risk patients developed mild hypophosphatemia at a much lower percentage than high-risk RS (20% vs 33.3%, respectively). A significant proportion of patients commencing TPN developed biochemical features of RS (but no more serious complications) despite nutritional assessment, treatment, and follow up in accordance with national recommendations. High vs low risk RS patients were more likely to have electrolyte abnormalities after receiving TPN regardless of preventative measures. Additional research is required to further optimise the initial nutritional approach to prevent RS in high-risk patients. • The key to preventing refeeding syndrome is identifying and appropriately managing patients at risk. • 75% were identified as high-risk for refeeding syndrome before starting total parenteral nutrition. • Phosphate, magnesium and potassium levels were monitored for seven days in 25%, 30% and 53.8% of patients, respectively. • Hypophosphatemia developed in 30% and hypomagnesaemia and hypokalaemia in 27.5% of all patients. • High vs low risk refeeding syndrome patients were more likely to have electrolyte abnormalities regardless of prevention. [ABSTRACT FROM AUTHOR]

Summary Background & aims Refeeding syndrome comprises metabolic disturbances that occur after the reintroduction of feeding after prolonged fasting. Standard care consists of correcting fluid and electrolytes imbalances. Energy intake during refeeding syndrome is heavily debated. This study addresses the effect of caloric intake on outcome during the management of refeeding syndrome. Methods A retrospective study among critically ill invasive mechanically ventilated patients admitted for >7 days to a medical-surgical ICU. Refeeding syndrome was diagnosed by the occurrence of new onset hypophosphatemia (<0.65 mmol/l) within 72 h of the start of nutritional support. Primary outcome was 6-month mortality. Secondary outcomes were 3-month mortality, ICU and hospital length of stay and duration of mechanical ventilation. Outcomes of patients with and without refeeding syndrome were compared and subgroup analysis on energy intake within the refeeding population was performed for the duration of survival. Results Of 337 enrolled patients, 124 (36.8%) developed refeeding syndrome and 213 patients (63.2%) maintained normal serum phosphate levels. Between the two groups, no statistical significant differences in clinical outcomes were observed. Within the refeeding syndrome group, a reduced 6-month mortality risk for low caloric intake (<50% of target) was seen compared with normal intake, adjusted Hazard Ratio 0.39, (95% CI 0.16–0.95, p = 0.037). In this group, low caloric intake was associated with an increased overall survival time at day 180 (153.0 (SE 10.1) vs 119.1 (SE 8.0) days, log-rank p = 0.018). Conclusions Refeeding syndrome is common among prolonged mechanically ventilated critically ill patients, however not predictable by baseline characteristics. Among patients that develop refeeding syndrome low caloric intake was associated with a reduction in 6-month mortality risk. This effect was not seen in patients without refeeding syndrome. Findings support caloric restriction in refeeding syndrome during critical illness. [ABSTRACT FROM AUTHOR]

Summary Background & aims Identification of Refeeding Syndrome (RFS) is vital for prevention and treatment of metabolic disturbances, yet no information exists that describes identification rates by dietitians in acute care. We aimed to describe rates and demographics of inpatients identified by dietitians as at-risk of RFS and factors associated with electrolyte levels post-dietetic assessment. Methods Eligible participants were adult (≥18 yrs) acute care inpatients reviewed by dietitians between March 2012–February 2013 and not admitted to intensive care prior to first dietetic assessment. Patient information was sourced from medical charts. Chi-squared, t -tests and linear regression analyses were conducted. Results Of 1661 eligible inpatients (55%F, 65 ± 18yrs), 9% ( n = 151) were documented as at-risk of RFS in the first dietetic medical chart entry. On average, patients identified with RFS-risk had four days greater hospital stay, were 13 kg lighter, more likely classified SGA C (36% vs. 7%), and on a modified diet (52% vs. 35%) than non-RFS patients ( p < 0.05). Very low and low electrolyte values occurred within seven days post-dietetic assessment in 7% and 52%, respectively, of inpatients with RFS-risk. Regression analysis showed that electrolyte supplementation was positively associated ( β = 0.145–0.594), and number of RFS-related risk factors negatively associated ( β = −0.044–0.122), with potassium, magnesium and phosphate levels within seven days post-dietetic assessment ( p < 0.05). Conclusion Nine percent of adult inpatients were documented as at-risk of RFS by dietitians. Identification of at-risk patients was in accordance with RFS guidelines. Electrolyte supplementation was positively associated with electrolyte levels post-assessment. Consistency of RFS-risk identification between dietitians requires determination. [ABSTRACT FROM AUTHOR]

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

Summary: Background & aims: To report the prognosis in 41 anorexia nervosa (AN) patients suffering from very severe malnutrition (mean BMI: 10.1 ± 0.57 kg/m2). Patients and methods: Compared with 443 less malnourished AN patients, the 41 patients were older (27.8 ± 5.4 vs 22.4 ± 2.1 yrs), their AN was longer (9.6 ± 3.4 vs 5.0 ± 1.5 yrs) and more often of the restrictive subtype (P < 0.05). Results: In 27% of the patients, all nutritional marker levels were in normal range. All patients received a prudent tube-refeeding: energy was increased from 12 to 40 kcal/kg/day, protein from 1.0 to 1.5 g/kg/day within 10 days. During stay, 1 patient died, 2 others suffered from myocardial infarction, 2 others from acute pancreatitis, and 5 from mental confusion. Compared with the other 443 AN patients, the 40 remaining patients had worse 6-yr prognosis: 2 died (7% vs 1.2%), 29% had severe outcome (vs 10%), and only 41% recovered (vs 62%). Conclusion: In AN patients with BMI < 11 kg/m2, a prudent tube-refeeding could avoid short-term mortality, but long-term prognosis was bad. [Copyright &y& Elsevier]

Summary: Background & aims: Refeedinghypophosphataemia (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. [Copyright &y& Elsevier]

Summary: Background & aims: Refeeding severely malnourished patients with Anorexia nervosa requires specialized in-patient treatment to reduce medical risks, to avoid refeeding syndrome and other life-threatening situations. Methods: The authors present a retrospective cohort nutritional rehabilitation study of 33 very severe Anorexia nervosa in-patients, aged 22.8 ± 7.6 years (±SD) and with an initial body mass index ≤ 12 kg/m2, treated in a specialized Eating Disorders Unit. Results: Thirty-three female patients were included and treated. Mean BMI increased from 11.3 ± 0.7 Kg/m2, to 13.5 ± 1 Kg/m2, and mean body weight from 29.1 ± 3.2 Kg to 34.5 ± 3.3 Kg, after 60 days of intensive in-patient treatments (p < 0.0001). Feeding was carefully instituted; caloric intake levels were established after measuring REE by indirect calorimetry. Nutritional support was initiated with temporary nasogastric feeding in 30 patients, and with oral supplementation in 3 patients. Vitamins, potassium and phosphate supplements were administered during refeeding. All patients achieved a significant increase in body weight, none developed refeeding syndrome as far as laboratory and clinical investigations were concerned. Conclusions: Our findings show that, even in cases of extreme undernutrition, if feeding is performed cautiously and in a specialized unit, it is possible to avoid the refeeding syndrome. [Copyright &y& Elsevier]

Many theories have been advanced concerning the cause of Charlotte Brontë's death, none of which fully explain all the symptoms she experienced in the course of her final illness. Her death certificate records the cause of death as phthisis (tuberculosis), but there is no evidence, other than circumstantial, to support this diagnosis. A diagnosis of Addison's disease, caused by tuberculosis of the adrenals, has been proposed, but this is unlikely, since it does not fit well with two and a half months of severe anorexia, nausea and vomiting, followed by remission of these symptoms and eventual death. We agree, as suggested by some authors, that the most likely diagnosis was hyperemesis gravidarum, but suggest that this was complicated by the refeeding syndrome consequent on recovery of her appetite after resolution of hyperemesis gravidarum and that this was the cause of her death. These two diagnoses are compatible with the remission in her symptoms of anorexia, nausea and vomiting in the third week of March 1855, followed by further decline and death. [ABSTRACT FROM AUTHOR]