What is refeeding syndrome?

Refeeding Syndrome: Definition, Pathophysiology, and Management

Refeeding syndrome is a potentially fatal condition characterized by severe fluid and electrolyte shifts that occurs when nutrition is reintroduced too rapidly in malnourished patients after a period of starvation or inadequate intake. 1

Pathophysiology

Refeeding syndrome develops through the following mechanism:

• During starvation, the body adapts by down-regulating membrane pumping to conserve energy
• This causes intracellular electrolyte depletion (potassium, magnesium, calcium, phosphate)
• When nutrition is suddenly reintroduced, especially carbohydrates:
  • Insulin secretion increases dramatically
  • Rapid cellular uptake of electrolytes occurs
  • Precipitous drops in serum phosphate, potassium, and magnesium follow
  • Fluid shifts and sodium retention worsen the situation

The classic biochemical hallmark is hypophosphatemia, typically accompanied by hypokalemia, hypomagnesemia, and thiamine deficiency 1.

Clinical Manifestations

Refeeding syndrome typically occurs within the first 4 days of nutritional repletion 1 and can cause:

• Fluid retention and peripheral edema
• Cardiac complications (arrhythmias, heart failure)
• Respiratory failure
• Neurological manifestations (delirium, seizures, encephalopathy)
• Hematologic abnormalities
• Organ dysfunction
• Death (in severe cases)

High-Risk Patients

Patients at highest risk include those with:

• BMI <16 kg/m² or BMI <18.5 kg/m² with additional risk factors
• Unintentional weight loss >15% in 3-6 months
• Little or no nutritional intake for >10 days
• Low baseline levels of potassium, phosphate, or magnesium
• History of:
  • Chronic alcoholism
  • Anorexia nervosa
  • Severe chronic undernutrition
  • Prolonged fasting
  • Bariatric surgery
  • Cancer with cachexia
  • Chronic medication use (insulin, antacids, diuretics) 1

Prevention and Management

Screening and Identification

• All patients admitted to healthcare facilities should be screened for malnutrition risk within 24-48 hours
• Those identified as malnourished should be assessed for refeeding risk 1

Prevention Strategy

For patients at risk of refeeding syndrome, nutrition should be reintroduced slowly and cautiously with careful monitoring of electrolytes and clinical status. 1

1. Initial feeding recommendations:

   • Start at 5-10 kcal/kg/day for severely malnourished patients
   • Gradually increase over 4-7 days until full requirements are met
   • Avoid exceeding 50% of calculated requirements in the first 2 days 1

2. Electrolyte supplementation:

   • Before and during refeeding, provide:
     • Thiamine: 200-300 mg daily
     • Potassium: 2-4 mmol/kg/day (monitor and supplement as needed)
     • Phosphate: 0.3-0.6 mmol/kg/day (monitor and supplement as needed)
     • Magnesium: 0.2 mmol/kg/day IV or 0.4 mmol/kg/day orally 1
   • Supplement even in cases of mild deficiency 1

3. Monitoring:

   • Closely monitor electrolytes (phosphate, potassium, magnesium)
   • Check fluid balance, heart rate and rhythm
   • Monitor clinical status for signs of cardiac or respiratory distress
   • Pay particular attention during the first 72 hours of nutritional support 1

Common Pitfalls and Caveats

1. Failure to identify at-risk patients

   • Refeeding syndrome is often overlooked despite its potentially fatal consequences
   • Recent studies show incidence as high as 18.7% in general medical wards 2

2. Overly aggressive initial feeding

   • Resist the temptation to rapidly correct nutritional deficits
   • The sickest, most malnourished patients need the slowest refeeding approach

3. Inadequate electrolyte monitoring

   • Regular monitoring of phosphate, potassium, and magnesium is essential
   • Electrolyte abnormalities can develop rapidly even with cautious feeding

4. Overlooking thiamine supplementation

   • Thiamine deficiency can lead to Wernicke's encephalopathy or cardiac failure
   • Always provide thiamine before starting carbohydrate feeding

5. Assuming normal electrolyte levels eliminate risk

   • Even with normal baseline levels, rapid shifts can occur during refeeding
   • Intracellular deficits may exist despite normal serum levels 1

Refeeding syndrome significantly impacts clinical outcomes, with affected patients experiencing longer hospital stays and higher mortality rates 2. Early identification of at-risk patients and appropriate preventive measures are essential to avoid this potentially life-threatening complication.