What is refeeding syndrome?

What is Refeeding Syndrome?

Refeeding syndrome is a life-threatening metabolic condition characterized by severe electrolyte disturbances—particularly hypophosphatemia, hypokalemia, and hypomagnesemia—along with fluid retention and organ dysfunction that occurs when nutrition is reintroduced too aggressively in malnourished or starved patients. 1

Core Pathophysiology

The syndrome results from feeding-induced hormonal and metabolic derangements triggered by the refeeding process itself. 1 When carbohydrates are reintroduced after starvation:

• Insulin secretion surges, driving glucose, phosphate, potassium, and magnesium intracellularly to support anabolic metabolism 1
• Massive intracellular electrolyte deficits exist from prior starvation that cannot be detected by baseline serum levels alone 1
• Acute water and sodium retention occurs from the sudden insulin increase, leading to volume overload 1
• Thiamine (vitamin B1) becomes critically depleted as it is consumed during carbohydrate metabolism 1

Clinical Presentation

Timing and Onset

• Symptoms typically develop within the first 4 days after nutrition therapy begins, with the first 72 hours being the most critical monitoring period 1

Cardiovascular Manifestations

• Cardiac arrhythmias from electrolyte imbalances (hypophosphatemia, hypokalemia, hypomagnesemia) 1
• Congestive heart failure from fluid retention and cardiac muscle dysfunction 1
• Hypotension and sudden cardiac death occurring in up to 20% of severe cases 1
• QTc prolongation particularly in patients with pre-existing malnutrition 2

Neurological Complications

• Wernicke's encephalopathy from thiamine deficiency, presenting with confusion, diplopia, and potentially progressing to Korsakoff's syndrome 1
• Delirium, confusion, and seizures provoked by rapid drops in plasma phosphate 1
• Encephalopathy that can progress to coma in severe cases 1

Respiratory and Musculoskeletal

• Respiratory failure requiring increased ventilatory support or difficulty weaning from mechanical ventilation 1
• Muscle weakness and rhabdomyolysis from severe hypophosphatemia 1
• Lethargy progressing to more severe neurological impairment 1

Other Organ Systems

• Hepatic dysfunction with excessive fat and glycogen storage 1
• Peripheral edema from sodium and water retention 1
• Anemia as a complication in malnourished patients 1

Laboratory Hallmarks

Primary Electrolyte Disturbances

• Hypophosphatemia is the most frequent and clinically significant abnormality, with severity classified as mild (<0.81 mmol/L), moderate (<0.61 mmol/L), or severe (<0.32 mmol/L) 1
• Hypokalemia contributing to cardiac and neuromuscular complications 1
• Hypomagnesemia often accompanying other electrolyte abnormalities 1
• Hypocalcemia may occur alongside other disturbances 1

Metabolic Markers

• Disturbed glucose homeostasis with potential hypoglycemia if feeding is stopped abruptly 1
• Hyperlactatemia suggesting thiamine (vitamin B1) deficiency 1

High-Risk Patient Populations

Nutritional Risk Factors

• BMI <16 kg/m² 1, 2
• Unintentional weight loss >15% in 3-6 months 1
• Little or no nutritional intake for >10 days (or even >5 days in some contexts) 1
• Patients with minimal food intake for ≥5 days should receive no more than half of calculated energy requirements during the first 2 days 1

Medical Conditions

• Chronic alcoholism with 30-80% having thiamine deficiency 1
• Anorexia nervosa or eating disorders, particularly those <70% ideal body weight 2
• Oncologic patients with severe malnutrition 1
• Chronic vomiting or diarrhea 1
• Acute illness in depleted patients 1

Laboratory Risk Factors

• Low baseline levels of potassium, phosphate, or magnesium before feeding begins 1
• These baseline levels provide false security, as they do not reflect massive intracellular deficits 1

Other Risk Factors

• Older age with high Nutritional Risk Screening scores (≥3) 1
• History of chronic drug use (insulin, antacids, diuretics) 1
• Fasting >72 hours in adults requiring parenteral nutrition 1

Critical Prevention Principles

Pre-Feeding Protocol (Mandatory)

• Thiamine 200-300 mg IV daily MUST be administered BEFORE any feeding begins and continued for minimum 3 days 1
• Full B-complex vitamins IV simultaneously with thiamine throughout refeeding 1
• Never initiate feeding without prior thiamine—carbohydrate loading in thiamine-deficient patients precipitates acute Wernicke's encephalopathy, cardiac failure, and sudden death 1

Nutritional Reintroduction Strategy

• Very high-risk patients: Start at 5-10 kcal/kg/day 1, 3
• Standard high-risk patients: Start at 10-20 kcal/kg/day 1
• Severe acute pancreatitis with refeeding risk: Limit to 15-20 non-protein kcal/kg/day 1
• Gradually increase over 4-7 days until full requirements (25-30 kcal/kg/day) are reached 1
• Macronutrient distribution: 40-60% carbohydrate, 30-40% fat, 15-20% protein 1

Aggressive Electrolyte Replacement (Concurrent with Feeding)

• Phosphate: 0.3-0.6 mmol/kg/day IV 1, 3
• Potassium: 2-4 mmol/kg/day 1, 3
• Magnesium: 0.2 mmol/kg/day IV or 0.4 mmol/kg/day orally 1, 3
• Calcium supplementation as needed 1

Critical pitfall: Correcting electrolytes alone before feeding provides false security without addressing massive intracellular deficits—electrolytes must be supplemented simultaneously with feeding initiation. 1

Monitoring Protocol

• Daily electrolyte monitoring (phosphate, potassium, magnesium, calcium) for the first 3 days, extending beyond if abnormalities persist 1, 3
• When hypophosphatemia is detected: Measure electrolytes 2-3 times daily 1
• Strict glucose monitoring to avoid hyperglycemia 1
• Monitor volume status, fluid balance, heart rate and rhythm closely 1, 3
• Watch for clinical signs: edema, arrhythmias, confusion, respiratory failure 1

Route of Nutrition

• Enteral feeding (oral or nasogastric) is preferred when intestinal function is preserved—it maintains gut barrier integrity, has fewer infectious complications, and is more cost-effective 1, 3
• Parenteral nutrition should only be used when: enteral feeding cannot meet energy needs, intestinal failure is present, severe upper-GI obstruction exists, or severe acute pancreatitis is not tolerated enterally 1

Management of Established Refeeding Syndrome

If Symptoms Develop

• Temporarily reduce caloric intake to 5-10 kcal/kg/day rather than stopping completely to avoid rebound hypoglycemia 1
• Increase electrolyte supplementation and monitoring frequency 1
• Never stop feeding abruptly—taper gradually if necessary 1

Special Population Considerations

• Older patients: Start early but increase slowly, avoid sedation or physical restraints 1, 3
• Anorexia nervosa patients: Extremely high risk during first week, require close cardiac monitoring and very slow progression 2, 3
• Cancer patients with severe malnutrition: Increase nutrition slowly over several days 3

Common Pitfalls to Avoid

• Never initiate feeding without thiamine—this is the single most critical error that precipitates catastrophic complications 1
• Do not rely on baseline electrolytes alone—they do not reflect intracellular deficits 1
• Avoid aggressive refeeding in severely malnourished patients—rapid refeeding can be fatal 2
• Do not stop thiamine prematurely—continue for full minimum 3-day period even if symptoms improve 1
• Never stop feeding abruptly—this causes rebound hypoglycemia 1