What is refeeding syndrome?

What is Refeeding Syndrome

Refeeding syndrome is a potentially life-threatening metabolic condition characterized by severe electrolyte disturbances, fluid retention, and organ dysfunction that occurs when nutrition is reintroduced too aggressively in severely malnourished patients. 1

Pathophysiology and Core Features

The syndrome develops when the starved body's metabolism shifts abruptly in response to nutritional repletion, causing dangerous electrolyte shifts from the extracellular to intracellular compartments. 2, 3 The key metabolic disturbances include:

• Hypophosphatemia - the most frequent and clinically significant electrolyte abnormality, serving as the primary diagnostic marker 1, 4
• Hypokalemia - contributing to cardiac arrhythmias and neuromuscular complications 1
• Hypomagnesemia - frequently accompanying other electrolyte derangements 1
• Thiamine deficiency - manifesting as hyperlactatemia and potentially precipitating Wernicke's encephalopathy 1
• Fluid retention - leading to peripheral edema and potentially congestive heart failure 1

Clinical Manifestations

Symptoms typically emerge within the first 72 hours after initiating nutritional support, with the first four days representing the critical monitoring period. 1 The syndrome can occur with any form of nutrition delivery—oral, enteral, or parenteral. 1

Organ System Complications:

• Cardiovascular: Cardiac arrhythmias, congestive heart failure, hypotension, and sudden cardiac death (occurring in up to 20% of cases) 1, 2
• Neurological: Delirium, confusion, seizures, encephalopathy, Wernicke's encephalopathy, and progression to coma in severe cases 1
• Respiratory: Respiratory failure and difficulty weaning from mechanical ventilation 1
• Neuromuscular: Profound weakness and lethargy 1
• Hepatic: Liver dysfunction with excessive fat and glycogen storage 1

High-Risk Patient Identification

You must screen all patients before initiating nutritional support. 5 The following criteria identify patients at highest risk:

• BMI <16 kg/m² 1, 5
• Unintentional weight loss >15% in 3-6 months 1, 5
• Little or no nutritional intake for >10 days 1, 5
• Low baseline electrolytes (potassium, phosphate, or magnesium) before feeding 1
• Chronic alcoholism 1
• Anorexia nervosa or eating disorders 1
• Oncologic patients 6
• Chronic vomiting or diarrhea 6
• Older age with high Nutritional Risk Screening scores (NRS-2002 ≥3) 6, 1
• History of chronic drug use (insulin, antacids, diuretics) 1

Note that starvation itself is the most reliable predictor, though traditional screening criteria have limited sensitivity (67%) and specificity (80%). 6

Prevention Protocol

The cornerstone of management is prevention through cautious refeeding. 5, 2

Step 1: Pre-Feeding Preparation

• Administer prophylactic thiamine 200-300 mg daily BEFORE initiating any feeding 1 - this is non-negotiable as starting nutrition without thiamine can precipitate Wernicke's encephalopathy, Korsakoff syndrome, acute heart failure, and death 1
• Provide complete B-complex vitamin supplementation intravenously for at least the first 3 days 1
• Check baseline electrolytes (phosphate, potassium, magnesium, calcium) 1
• Aggressively correct electrolyte abnormalities before feeding 1

Step 2: Initiate Low-Calorie Feeding

For very high-risk patients: Start at 5-10 kcal/kg/day 6, 1, 5

For standard high-risk patients: Start at 10-20 kcal/kg/day 1

For patients with severe acute pancreatitis at risk: Limit to 15-20 non-protein kcal/kg/day 1

Macronutrient distribution should be:

• 40-60% carbohydrate
• 30-40% fat
• 15-20% protein 6, 1

Step 3: Aggressive Electrolyte Replacement

Provide daily supplementation:

• Potassium: 2-4 mmol/kg/day 1
• Phosphate: 0.3-0.6 mmol/kg/day 1
• Magnesium: 0.2 mmol/kg/day IV or 0.4 mmol/kg/day orally 1
• Calcium: As needed based on monitoring 1

Step 4: Gradual Advancement

Increase caloric intake slowly over 5-10 days, according to individual risk category and clinical tolerance. 6 This gradual approach represents the best available evidence despite limited randomized trials. 6

Monitoring Requirements

• Daily electrolyte monitoring for the first 3 days, then regularly until stable 5
• Strict glucose monitoring to prevent hyperglycemia 1
• Clinical surveillance for edema, arrhythmias, confusion, respiratory failure 1
• Continuous cardiac monitoring during the first 72 hours in high-risk patients 1

Critical Pitfalls to Avoid

• Never initiate feeding without prior thiamine supplementation - this single error can be fatal 1
• Avoid isolated electrolyte correction pre-feeding - this provides false security without addressing massive intracellular deficits 1
• Do not use hypocaloric diets routinely in hospitalized patients - they increase malnutrition risk even in obese patients 6
• If feeding must be discontinued, taper gradually to prevent rebound hypoglycemia 1
• Avoid overfeeding - this is particularly detrimental to cardiopulmonary and hepatic function 1
• Do not position patients flat during feeding - maintain 30° elevation during and for 30 minutes after feeding to minimize aspiration risk 1

Special Population Considerations

Older patients require particular vigilance as they have significant overlap between malnutrition risk and refeeding syndrome risk. 1, 5 Avoid pharmacological sedation or physical restraints to facilitate feeding, as these lead to muscle mass loss and cognitive deterioration. 1

Pediatric patients show an estimated incidence of up to 7.4% in intensive care settings receiving nutritional support. 7