What is the pathophysiology and management of refeeding syndrome?

From the Guidelines

Refeeding syndrome is a potentially fatal condition that occurs when nutritional support is reintroduced too rapidly in malnourished patients, and management requires identifying high-risk patients and implementing a careful refeeding protocol, starting with 5-10 kcal/kg/day and increasing by 200-300 kcal every 1-2 days while monitoring for complications and aggressively replacing electrolytes. The pathophysiology of refeeding syndrome involves sudden shifts in electrolytes and fluids when carbohydrate metabolism resumes after starvation, causing dangerous serum deficiencies of phosphate, potassium, and magnesium 1. During starvation, the body depletes intracellular electrolytes while maintaining normal serum levels, and when feeding resumes, insulin secretion increases, driving glucose, phosphate, potassium, and magnesium into cells, causing hypophosphatemia, hypokalemia, and hypomagnesemia 1.

Key Principles of Management

• Identify high-risk patients, including those with BMI <16, weight loss >15%, little or no nutrition for >10 days, or low baseline electrolytes 1
• Start with 5-10 kcal/kg/day (approximately 500-800 kcal/day) for severely malnourished patients, increasing by 200-300 kcal every 1-2 days while monitoring for complications 1
• Prophylactic electrolyte replacement should include phosphate (0.5-0.8 mmol/kg/day), potassium (1-3 mmol/kg/day), magnesium (0.3-0.4 mmol/kg/day), and thiamine (200-300mg daily for 3-5 days, then 100mg daily) before and during refeeding 1
• Daily monitoring of serum electrolytes, fluid balance, and cardiovascular status is essential for the first week, and multivitamin supplementation should also be provided 1

Monitoring and Prevention

• Monitor plasma electrolyte and phosphorus levels strictly, especially in patients with kidney disease 1
• Start enteral nutrition at low rates and increase slowly (over days) until requirements are met, and consider supplementation of one or more nutrients by the parenteral route if necessary 1
• Be aware of the risk of refeeding syndrome in patients with chronic insufficient dietary intake and/or uncontrollable malabsorption, and consider home enteral nutrition or parenteral nutrition in suitable patients 1

From the Research

Pathophysiology of Refeeding Syndrome

• Refeeding syndrome (RS) is characterized by electrolyte imbalances, including hypophosphatemia, hypokalemia, hypomagnesemia, and thiamine deficiency, which can occur in malnourished patients who are abruptly refed 2, 3, 4.
• The sudden increase in food intake causes a shift in the body's metabolism and electrolyte balance, leading to symptoms such as weakness, seizures, and even heart failure 2.
• The syndrome reflects the change from catabolic to anabolic metabolism, and it can affect both adults and children, although there is scarce evidence in the pediatric literature 2, 3.

Management of Refeeding Syndrome

• A proper management with progressive increase in nutrients is essential to prevent the onset of RS and ensure the best possible outcomes 2.
• Close monitoring of electrolyte levels is critical, and prophylactic use of dietary supplements such as thiamine may be required to correct any imbalances that may occur 2, 5.
• A recommended strategy for preventing RS includes careful monitoring of feeding resumption, particularly in severely malnourished individuals, and starting with small amounts of low-calorie fluids and gradually increasing the calorie content and amount of food over several days 2, 5.
• Recognizing patients at risk, providing adequate electrolyte, vitamin, and micronutrient supplementation, careful fluid resuscitation, cautious and gradual energy restoration, and monitoring of critical laboratory indices are also crucial in preventing or treating RS 5.
• Despite nutritional assessment, treatment, and follow-up in accordance with national recommendations, a significant proportion of patients commencing total parenteral nutrition (TPN) may still develop biochemical features of RS, highlighting the need for additional research to optimize the initial nutritional approach to prevent RS in high-risk patients 6.