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

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

Effects of procalcitonin testing on antibiotic use and clinical outcomes in patients with upper respiratory tract infections. An individual patient data meta-analysis.

BACKGROUND: Several trials found procalcitonin (PCT) helpful for guiding antibiotic treatment in patients with lower respiratory tract infections and sepsis. We aimed to perform an individual patient data meta-analysis on the effects of PCT guided antibiotic therapy in upper respiratory tract infections (URTI). METHODS: A comprehensive search of the literature was conducted using PubMed (MEDLINE) and Cochrane Library to identify relevant studies published until September 2016. We reanalysed individual data of adult URTI patients with a clinical diagnosis of URTI. Data of two trials were used based on PRISMA-IPD guidelines. Safety outcomes were (1) treatment failure defined as death, hospitalization, ARI-specific complications, recurrent or worsening infection at 28 days follow-up; and (2) restricted activity within a 14-day follow-up. Secondary endpoints were initiation of antibiotic therapy, and total days of antibiotic exposure. RESULTS: In total, 644 patients with a follow up of 28 days had a final diagnosis of URTI and were thus included in this analysis. There was no difference in treatment failure (33.1% vs. 34.0%, OR 1.0, 95% CI 0.7-1.4; p=0.896) and days with restricted activity between groups (8.0 vs. 8.0 days, regression coefficient 0.2 (95% CI -0.4 to 0.9), p=0.465). However, PCT guided antibiotic therapy resulted in lower antibiotic prescription (17.8% vs. 51.0%, OR 0.2, 95% CI 0.1-0.3; p<0.001) and in a 2.4 day (95% CI -2.9 to -1.9; p<0.001) shorter antibiotic exposure compared to control patients. CONCLUSIONS: PCT guided antibiotic therapy in the primary care setting was associated with reduced antibiotic exposure in URTI patients without compromising outcomes.

Effect of hyperglycaemia on inflammatory and stress responses and clinical outcome of pneumonia in non-critical-care inpatients: results from an observational cohort study.

AIMS/HYPOTHESIS: Despite the condition's high prevalence, the influence of hyperglycaemia on clinical outcomes in non-critical-care inpatients with infections remains ill defined. In this study, we analysed associations of glucose levels at admission and during initial inpatient treatment with the inflammatory response and clinical outcome in community-acquired pneumonia (CAP) patients. METHODS: This secondary observational analysis included 880 confirmed CAP patients. We used severity-adjusted multivariate regression models to investigate associations of initial and 96 h mean glucose levels with serially measured biomarker levels over 7 days (C-reactive protein [CRP], procalcitonin, white blood cell count [WBC], pro-adrenomedullin [ProADM]) and adverse clinical course (death and intensive-care unit admission). RESULTS: In the 724 non-diabetic patients (82.3% of the study population), moderate or severe hyperglycaemia (glucose 6-11 mmol/l and >11 mmol/l, respectively) was associated with increased risk for adverse clinical course (adjusted OR [95% CI] 1.4 [0.8, 2.4] and 3.0 [1.1, 8.0], respectively) and with higher CRP, WBC and ProADM levels over 7 days (p < 0.05, ANOVA, all days). In diabetic patients (n = 156), no similar associations were found for initial hyperglycaemia, although mean 96 h glucose levels ≥ 9 mmol/l were associated with adverse clinical course (adjusted OR 5.4 [1.1, 25.8]; p = 0.03). No effect modification by insulin treatment was detected (interaction terms p > 0.2 for all analyses). CONCLUSIONS/INTERPRETATION: Initial hyperglycaemia in non-diabetic CAP patients, and prolonged hyperglycaemia in diabetic or non-diabetic CAP patients, are associated with a more pronounced inflammatory response and CAP-related adverse clinical outcome. Optimal glucose targets for insulin treatment of hyperglycaemia in non-critical-care settings should be defined.

Refeeding Syndrome: A Critical Reality in Patients with Chronic Disease.

Malnutrition is one of the most frequent metabolic challenges in the population of chronically ill patients. This results in increased administration of nutritional therapy in inpatient settings, which poses the risk of side effects, in particular, the development of refeeding syndrome. If not managed accordingly, it leads to a significant rise in morbidity and mortality. However, despite its importance, evidence-based recommendations on the management of refeeding syndrome are largely lacking, and only a few randomized controlled trials have been conducted. In light of this, the aim of this review is to raise awareness of refeeding syndrome in chronically ill patients by critically reviewing recent literature and providing a short overview as well as diagnosis and treatment algorithms of this underreported metabolic condition. In summary, recent findings suggest undergoing risk assessment and stratification for every patient receiving nutritional therapy. According to this, adaptation of energy and fluid support during the replenishment phase should be implemented in the nutritional therapy for patients at high risk. Additionally, continuous monitoring should take place, and appropriate actions should be initiated when necessary.

Refeeding syndrome is associated with increased mortality in malnourished medical inpatients: Secondary analysis of a randomized trial.

BACKGROUND: Whether the occurrence of refeeding syndrome (RFS), a metabolic condition characterized by electrolyte shifts after initiation of nutritional therapy, has a negative impact on clinical outcomes remains ill-defined. We prospectively investigated a subgroup of patients included in a multicentre, nutritional trial (EFFORT) for the occurrence of RFS. METHODS: In this secondary analysis of a randomized-controlled trial investigating the effects of nutritional support in malnourished medical inpatients, we prospectively screened patients for RFS and classified them as "RFS confirmed" and "RFS not confirmed" based on predefined criteria (i.e. electrolyte shifts, clinical symptoms, clinical context, and patient history). We assessed associations of RFS and mortality within 180 days (primary endpoint) and other secondary endpoints using multivariable regression analysis. RESULTS: Among 967 included patients, RFS was confirmed in 141 (14.6%) patients. Compared to patients with no evidence for RFS, patients with confirmed RFS had significantly increased 180-days mortality rates (42/141 (29.8%) vs 181/826 (21.9%), adjusted odds ratio (OR) 1.53 (95% CI 1.02 to 2.29), P < .05). Patients with RFS also had an increased risk for ICU admission (6/141 (4.3%) vs 13/826 (1.6%), adjusted OR 2.71 (95% CI 1.01 to 7.27), P < .05) and longer mean length of hospital stays (10.5 ±â€Š6.9 vs 9.0 ±â€Š6.6 days, adjusted difference 1.57 days (95% CI 0.38-2.75), P = .01). CONCLUSION: A relevant proportion of medical inpatients with malnutrition develop features of RFS upon hospital admission, which is associated with long-term mortality and other adverse clinical outcomes. Further studies are needed to develop preventive strategies for RFS in this patient population.

Management of Refeeding Syndrome in Medical Inpatients.

Refeeding syndrome (RFS) is the metabolic response to the switch from starvation to a fed state in the initial phase of nutritional therapy in patients who are severely malnourished or metabolically stressed due to severe illness. It is characterized by increased serum glucose, electrolyte disturbances (particularly hypophosphatemia, hypokalemia, and hypomagnesemia), vitamin depletion (especially vitamin B1 thiamine), fluid imbalance, and salt retention, with resulting impaired organ function and cardiac arrhythmias. The awareness of the medical and nursing staff is often too low in clinical practice, leading to under-diagnosis of this complication, which often has an unspecific clinical presentation. This review provides important insights into the RFS, practical recommendations for the management of RFS in the medical inpatient population (excluding eating disorders) based on consensus opinion and on current evidence from clinical studies, including risk stratification, prevention, diagnosis, and management and monitoring of nutritional and fluid therapy.

Refeeding syndrome in the frail elderly population: prevention, diagnosis and management.

Aging is linked to physiological and pathophysiological changes. In this context, elderly patients often are frail, which strongly correlates with negative health outcomes and disability. Elderly patients are often malnourished, which again is an independent risk factor for both frailty and adverse clinical outcomes. Malnutrition and resulting frailty can be prevented by adequate nutritional interventions. Yet, use of nutritional therapy can also have negative consequences, including a potentially life-threatening metabolic alteration called refeeding syndrome (RFS) in high-risk patients. RFS is characterized by severe electrolyte shifts (mainly hypophosphatemia, hypomagnesemia and hypokalemia), vitamin deficiency (mainly thiamine), fluid overload and salt retention leading to organ dysfunction and cardiac arrhythmias. Although the awareness of malnutrition among elderly people is well established, the risk of RFS is often neglected, especially in the frail elderly population. This partly relates to the unspecific clinical presentation and laboratory changes in the geriatric population. The aim of this review is to summarize recently published recommendations for the management of RFS based on current evidence from clinical studies adapted with a focus on elderly patients.

Management and prevention of refeeding syndrome in medical inpatients: An evidence-based and consensus-supported algorithm.

OBJECTIVES: Refeeding syndrome (RFS) can be a life-threatening metabolic condition after nutritional replenishment if not recognized early and treated adequately. There is a lack of evidence-based treatment and monitoring algorithm for daily clinical practice. The aim of the study was to propose an expert consensus guideline for RFS for the medical inpatient (not including anorexic patients) regarding risk factors, diagnostic criteria, and preventive and therapeutic measures based on a previous systematic literature search. METHODS: Based on a recent qualitative systematic review on the topic, we developed clinically relevant recommendations as well as a treatment and monitoring algorithm for the clinical management of inpatients regarding RFS. With international experts, these recommendations were discussed and agreement with the recommendation was rated. RESULTS: Upon hospital admission, we recommend the use of specific screening criteria (i.e., low body mass index, large unintentional weight loss, little or no nutritional intake, history of alcohol or drug abuse) for risk assessment regarding the occurrence of RFS. According to the patient's individual risk for RFS, a careful start of nutritional therapy with a stepwise increase in energy and fluids goals and supplementation of electrolyte and vitamins, as well as close clinical monitoring, is recommended. We also propose criteria for the diagnosis of imminent and manifest RFS with practical treatment recommendations with adoption of the nutritional therapy. CONCLUSION: Based on the available evidence, we developed a practical algorithm for risk assessment, treatment, and monitoring of RFS in medical inpatients. In daily routine clinical care, this may help to optimize and standardize the management of this vulnerable patient population. We encourage future quality studies to further refine these recommendations.

Revisiting the refeeding syndrome: Results of a systematic review.

OBJECTIVE: Although described >70 y ago, the refeeding syndrome (RFS) remains understudied with lack of standardized definition and treatment recommendations. The aim of this systematic review was to gather evidence regarding standardized definition, incidence rate and time course of occurrence, association with adverse clinical outcomes, risk factors, and therapeutic strategies to prevent or treat this condition. METHODS: We searched MEDLINE and EMBASE for interventional and observational clinical trials focusing on RFS, excluding case reports and reviews. We extracted data based on a predefined case report form and assessed bias. RESULTS: Of 2207 potential abstracts, 45 records with a total of 6608 patients were included (3 interventional trials, 16 studies focusing on anorexic patients). Definitions for RFS were highly heterogenous with most studies relying on blood electrolyte disturbances only and others also including clinical symptoms. Incidence rates varied between 0% and 80%, depending on the definition and patient population studied. Occurrence was mostly within the first 72 h of start of nutritional therapy. Most of the risk factors were in accordance with National Institute for Health and Care Excellence guidelines, with older age and enteral feeding being additional factors. There was no strong evidence regarding association of RFS and adverse outcomes, as well as regarding preventive measures and treatment algorithms. CONCLUSION: This systematic review focusing on RFS found consensus regarding risk factors and timing of occurrence, but wide variations regarding definition, reported incidence rates, preventive measures and treatment recommendations. Further research to fill this gap is urgently needed.