What is Refeeding Syndrome
Refeeding syndrome is a potentially life-threatening metabolic condition characterized by severe electrolyte disturbances—particularly hypophosphatemia, hypokalemia, and hypomagnesemia—that occurs when nutrition is reintroduced too aggressively in malnourished patients. 1
Pathophysiology
The syndrome develops when prolonged starvation causes the body to shift from carbohydrate to fat and protein metabolism. 2 When feeding resumes, the sudden influx of glucose triggers insulin release, which drives phosphate, potassium, and magnesium intracellularly, causing dangerous plasma depletion of these electrolytes. 3 Simultaneously, anabolic metabolism resumes, leading to sodium and water retention. 1
Clinical Presentation
Symptoms typically develop within the first 72 hours after nutrition therapy is commenced, making this the critical monitoring period. 1
Cardiovascular Manifestations
- Cardiac arrhythmias, congestive heart failure, and hypotension are the most lethal complications 1
- Sudden cardiac death occurs in up to 20% of severe cases 1
- Heart failure from fluid overload and electrolyte-induced myocardial dysfunction 1
Neurological Manifestations
- Delirium, confusion, and encephalopathy from rapid phosphate drops 1
- Wernicke's encephalopathy or Korsakoff's syndrome from thiamine deficiency, presenting with diplopia, confabulation, and potentially progressing to coma 1
- Seizures in severe cases 1
Respiratory Manifestations
- Respiratory failure requiring increased ventilatory support 1
- Difficulty weaning from mechanical ventilation 1
Other Manifestations
- Peripheral edema progressing to generalized fluid retention 1
- Muscle weakness and rhabdomyolysis 1
- Hepatic dysfunction with excessive fat and glycogen storage 1
- Lethargy progressing to coma 1
Laboratory Findings
Hypophosphatemia is the most frequent and clinically significant electrolyte disturbance and serves as the primary diagnostic marker. 1
Additional laboratory abnormalities include:
- Hypokalemia contributing to cardiac and neuromuscular complications 1
- Hypomagnesemia often accompanying other electrolyte abnormalities 1
- Hypocalcemia 1
- Hyperlactatemia suggesting thiamine deficiency 1
- Disturbed glucose homeostasis with potential hypoglycemia if feeding is stopped abruptly 1
High-Risk Patient Identification
Patients meeting any of the following criteria require aggressive preventive protocols:
NICE High-Risk Criteria
- BMI <16 kg/m² 1
- Unintentional weight loss >15% in 3-6 months 1
- Little or no nutritional intake for >10 days 1
- Low baseline levels of potassium, phosphate, or magnesium before feeding 1
Additional Risk Factors
- History of chronic alcoholism 1
- Anorexia nervosa or eating disorders 1
- Oncologic patients with severe malnutrition 1
- Chronic vomiting or diarrhea 1
- Older hospitalized patients have significant overlap between malnutrition risk and refeeding syndrome risk 1
- History of chronic drug use (insulin, antacids, diuretics) 1
Prevention Protocol
Prevention is the cornerstone of management, as refeeding syndrome is preventable but potentially fatal. 4
Pre-Feeding Requirements (Mandatory Before Starting Nutrition)
- Administer thiamine 200-300 mg IV daily before initiating any feeding 1
- Provide full B-complex vitamins IV 1
- Supplement with multivitamins from day 1 1
- Check baseline electrolytes, especially phosphate, potassium, magnesium, and calcium 1
Caloric Starting Points (Risk-Stratified)
- Very high-risk patients: Start at 5-10 kcal/kg/day 1
- Standard high-risk patients: Start at 10-20 kcal/kg/day 1
- Gradually increase over 4-7 days until full requirements are reached 1
- Patients with severe acute pancreatitis at risk: Limit to 15-20 non-protein kcal/kg/day 1
Macronutrient Distribution
- 40-60% carbohydrate 1
- 30-40% fat 1
- 15-20% protein 1
- Maintain protein intake of at least 1 g/kg actual body weight/day if BMI <30 1
Aggressive Electrolyte Replacement During Refeeding
- Potassium: approximately 2-4 mmol/kg/day 1
- Phosphate: approximately 0.3-0.6 mmol/kg/day IV 1
- Magnesium: approximately 0.2 mmol/kg/day IV or 0.4 mmol/kg/day orally 1
- Calcium supplementation as needed 1
Monitoring Protocol
- Daily electrolyte monitoring for the first 3 days is mandatory 1
- Monitor fluid status, glucose, and clinical signs (edema, arrhythmias, confusion, respiratory failure) 1
- Continue regular monitoring after 3 days according to clinical evolution 1
Critical Warnings
Never initiate feeding without prior thiamine administration, as thiamine deficiency can precipitate Wernicke's encephalopathy, Korsakoff's syndrome, acute heart failure, and death. 1
Avoid isolated electrolyte correction pre-feeding without concurrent nutrition, as this provides false security without correcting massive intracellular deficits. 1
If feeding must be discontinued, taper gradually to prevent rebound hypoglycemia from persistent hyperinsulinemia. 1
Route of Nutrition
Enteral feeding is preferred over parenteral when intestinal function is preserved, as it maintains gut barrier function, reduces infectious complications, and lowers costs. 1 However, refeeding syndrome can occur with any form of nutritional reintroduction (oral, enteral, or parenteral). 1
For enteral feeding, position patients at 30° or more during and for 30 minutes after feeding to minimize aspiration risk. 5
Special Population Considerations
Older Patients
- Require particular attention due to high overlap between malnutrition and refeeding syndrome risk 1
- Avoid pharmacological sedation or physical restraints to facilitate feeding, as these lead to muscle mass loss and cognitive deterioration 1
- Start early but increase slowly 1