What is Refeeding Syndrome
Refeeding syndrome is a 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 after a period of starvation. 1
Pathophysiology
The syndrome develops when the body shifts from a prolonged catabolic (starvation) state to an anabolic (fed) state. 1, 2 During this transition:
- Insulin secretion surges in response to carbohydrate intake, driving glucose, phosphate, potassium, and magnesium intracellularly, causing profound serum depletion 1
- Sodium and water retention occurs as anabolic metabolism resumes, leading to dangerous volume overload 1
- Thiamine (vitamin B1) stores become critically depleted as they are rapidly consumed during glucose metabolism 1
Clinical Presentation
Symptoms typically develop within the first 72 hours after nutrition therapy is commenced, though delayed presentations can occur up to 4 days later. 1, 3
Cardiovascular Manifestations
- Cardiac arrhythmias from electrolyte imbalances 1
- Congestive heart failure from fluid overload and myocardial dysfunction 1, 3
- Hypotension and sudden cardiac death occurring in up to 20% of severe cases 1
Neurological Manifestations
- Delirium, confusion, and encephalopathy from rapid phosphate drops 1
- Wernicke's encephalopathy from thiamine deficiency, presenting with diplopia, confabulation, and potentially progressing to coma 1
- Seizures from severe electrolyte disturbances 1
Respiratory Manifestations
- Respiratory failure requiring increased ventilatory support 1
- Difficulty weaning from mechanical ventilation 1
Musculoskeletal Manifestations
- Muscle weakness and pain, particularly in the torso and legs, from impaired ATP production 1, 4
- Rhabdomyolysis in severe cases 1
Other Manifestations
- Peripheral edema from sodium and water retention 1
- Hepatic dysfunction with excessive fat and glycogen storage 1
- Lethargy progressing to coma 1
Laboratory Findings
Electrolyte Abnormalities
- Hypophosphatemia—the most frequent and clinically significant disturbance 1
- Hypokalemia—contributing to cardiac and neuromuscular complications 1
- Hypomagnesemia—often accompanying other abnormalities 1
- Hypocalcemia—may occur alongside other disturbances 1
Other Laboratory Changes
- Hyperlactatemia suggesting thiamine deficiency 1
- Disturbed glucose homeostasis with potential hypoglycemia if feeding is stopped abruptly 1
High-Risk Patient Characteristics
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 age with high Nutritional Risk Screening scores (≥3) 1
- History of chronic drug use (insulin, antacids, diuretics) 1
Prevention Protocol
Pre-Feeding Requirements (Mandatory Before Starting Nutrition)
- Thiamine 200-300 mg daily IV must be administered before initiating any feeding 1
- Full B-complex vitamin supplementation IV alongside thiamine 1
- Check baseline electrolytes (phosphate, potassium, magnesium, calcium) 1
- Correct severe electrolyte deficiencies before starting nutrition 1
Caloric Starting Points Based on Risk Stratification
- Very high-risk patients: 5-10 kcal/kg/day 1, 4
- Standard high-risk patients: 10-20 kcal/kg/day 1
- Gradual increase over 4-7 days until full requirements are reached 1
Macronutrient Distribution
- 40-60% carbohydrate 1
- 30-40% fat 1
- 15-20% protein 1
- Protein intake: at least 1 g/kg actual body weight/day if BMI <30 1
Aggressive Electrolyte Replacement During Refeeding
- Potassium: 2-4 mmol/kg/day 1, 4
- Phosphate: 0.3-0.6 mmol/kg/day IV 1, 4
- Magnesium: 0.2 mmol/kg/day IV or 0.4 mmol/kg/day orally 1, 4
- Calcium supplementation as needed 1
Monitoring Protocol
- Daily electrolyte monitoring for the first 3 days (phosphate, potassium, magnesium, calcium) 1
- Strict glucose monitoring to avoid hyperglycemia 1
- Clinical assessment for edema, arrhythmias, confusion, respiratory failure 1
- Continue regular monitoring after 3 days according to clinical evolution 1
Critical Pitfalls to Avoid
- Never initiate feeding without prior thiamine supplementation—this can precipitate Wernicke's encephalopathy, Korsakoff's syndrome, acute heart failure, and death 1
- Never correct electrolytes in isolation pre-feeding—this provides false security without correcting massive intracellular deficits 1
- Never advance feeding while symptoms persist—ongoing electrolyte depletion can progress to cardiac arrest or respiratory failure 4
- Never stop feeding abruptly—discontinue gradually to prevent rebound hypoglycemia 1, 4
- Never focus solely on phosphate—all three electrolytes (phosphate, potassium, magnesium) must be replaced simultaneously 4
Special Population Considerations
Older Patients
- Significant overlap between malnutrition risk 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
- Require particularly cautious caloric advancement 1
Pediatric Patients
- Estimated incidence up to 7.4% in pediatric intensive care units receiving nutritional support 5
- Weight-based dosing adjustments required 1
- Careful monitoring essential 5
Route of Nutrition
Enteral feeding is preferred over parenteral if intestinal function is preserved, as it maintains gut barrier function, has fewer infectious complications, and lower costs. 1 However, refeeding syndrome can occur with any form of nutritional reintroduction (oral, enteral, or parenteral). 1
Clinical Outcomes
The syndrome significantly impacts patient outcomes: