What causes refeeding syndrome?

Causes of Refeeding Syndrome

Refeeding syndrome is primarily caused by a sudden shift from a catabolic to anabolic state when nutrition is reintroduced after prolonged starvation, resulting in dangerous electrolyte shifts, particularly hypophosphatemia, along with fluid and vitamin imbalances. 1

Pathophysiological Mechanism

Refeeding syndrome develops through the following sequence:

1. Initial Starvation State:

   • During prolonged starvation, the body depletes glycogen stores
   • Metabolism shifts to using fat and protein as primary energy sources
   • Insulin secretion decreases while glucagon increases
   • Intracellular electrolytes (phosphate, potassium, magnesium) become depleted but serum levels remain normal due to reduced cell mass 1, 2

2. Metabolic Shift During Refeeding:

   • Reintroduction of carbohydrates triggers:
     • Rapid increase in insulin secretion
     • Shift from fat to carbohydrate metabolism
     • Sudden cellular uptake of phosphate, potassium, and magnesium
     • Increased thiamine utilization for carbohydrate metabolism 1, 3

3. Resulting Electrolyte Abnormalities:

   • Hypophosphatemia (most significant and diagnostic marker)
   • Hypokalemia
   • Hypomagnesemia
   • Fluid retention and sodium imbalance 1, 4

Risk Factors

Patients at highest risk for developing refeeding syndrome include those with:

• 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 electrolyte levels (potassium, phosphate, magnesium) 1
• History of:
  • Chronic alcoholism
  • Anorexia nervosa
  • Severe malnutrition with acute illness 1, 5

Additional risk factors include:

• BMI <18.5 kg/m²
• Weight loss >10% in 3-6 months
• No nutritional intake for >5 days
• History of alcohol misuse or chronic drug use (insulin, antacids, diuretics) 1

Clinical Manifestations

Refeeding syndrome typically manifests within the first 72 hours of nutritional reintroduction with:

• Cardiovascular: Heart failure, arrhythmias, hypotension
• Neurological: Confusion, seizures, weakness, paresthesias
• Respiratory: Respiratory failure, diaphragm weakness
• Hematologic: Hemolytic anemia, thrombocytopenia
• Musculoskeletal: Rhabdomyolysis, weakness, fatigue 3, 2

Prevention Strategies

To prevent refeeding syndrome:

1. Identify at-risk patients using the risk factors listed above 1

2. Start nutrition cautiously:

   • Begin with 5-10 kcal/kg/day for first 24 hours
   • Gradually increase over 5-10 days
   • Aim to reach full nutritional requirements by days 7-10 1

3. Provide prophylactic supplementation before initiating nutrition:

   • Thiamine: 300 mg IV before starting nutrition, then 200-300 mg IV daily for at least 3 more days
   • Potassium: 2-4 mmol/kg/day
   • Phosphate: 0.3-0.6 mmol/kg/day
   • Magnesium: 0.2 mmol/kg/day IV or 0.4 mmol/kg/day orally 1

4. Monitor closely:

   • Check electrolytes (phosphate, potassium, magnesium) frequently during first 72 hours
   • Monitor for clinical signs of fluid overload and cardiac dysfunction
   • Perform daily weight measurements to detect fluid retention 1

Common Pitfalls

1. Failure to recognize risk: Many healthcare providers underestimate the risk of refeeding syndrome, particularly in patients who don't appear severely malnourished 2

2. Overly aggressive nutrition: Starting with too many calories or advancing too quickly can precipitate refeeding syndrome 1, 3

3. Inadequate monitoring: Failing to check electrolytes frequently during the first 72 hours of refeeding 1

4. Overlooking thiamine supplementation: Thiamine must be administered before initiating nutrition to prevent Wernicke's encephalopathy 1

5. Ignoring fluid status: Excessive fluid administration can worsen the syndrome 1, 2

Remember that refeeding syndrome can occur with any form of nutritional repletion, including oral, enteral, or parenteral nutrition, and requires vigilant monitoring in at-risk patients.