Refeeding syndrome

Definition

• Potentially fatal fluid and electrolyte shifts that occur in malnourished patients who receive artificial refeeding
• Most notable shift causes hypophosphatemia

Pathophysiology

• During starvation, electrolytes shift from intracellular to intravascular to maintain intravascular levels
• An increase in serum glucose (from refeeding) causes release of insulin, which stimulates fat, glycogen, and protein synthesis and shifts phosphate, potassium, and magnesium intracellularly
  • The increase in cellular activity requires phosphate, which is pulled in from the serum and is already decreased from malnutrition
  • Hypophosphatemia causes a number of problems
  • Hypokalemia causes arrhythmias
  • Hypomagnesemia causes arrhythmias and muscle dysfunction
• Due to thiamine deficiency, refeeding risks Wernicke's encepalopathy or Korsakoff syndrome

Risk factors

• Chronic alcoholism
• Oncology patients
• Elderly patients with multiple comorbidities
• Uncontrolled diabetes mellitus
• Chronic malnutrition
• High stress patients unfed for 7 or more days
• Malabsorptive syndrome
  • Inflammatory bowel disease
  • Short gut syndrome
  • Cystic fibrosis
  • Chronic pancreatitis

Clinical Manifestations

• History of severely restricted intake
• Physical exam
  • Loss of subcutaneous fat, indicated by a loss of fullness or loose skin in the following areas:
    • Triceps
    • Costal margin at the midaxillary line
    • Interosseous and palmar areas
    • Deltoid
  • Muscle wasting, indicated by:
    • Quadriceps losing bulk or tone
    • Deltoids, with a more squared-off appearance of the shoulders
  • Edema from extravasation of fluid, indicated by:
    • Ankle edema
    • Sacral edema
    • Ascites

Investigations

• Electrolytes and extended electrolytes
  • Hypophosphatemia
  • Hypokalemia
  • Hypocalcemia
  • hypomagnesemia

Complications

• Hypophosphatemia
  • Neurologic: fits, weakness, paresthesia, altered mental status, acute encepalopathy
  • Muscular: weakness, myalgia, rhabdomyolysis
  • Cardiac: decreased contractility, cardiomyopathy
  • Hematologic: platelet and leukocyte dysfunction, thrombocytopenia, hemolysis
  • Respiratory: respiratory muscle dysfunction
  • Bone: osteomalacia
  • Renal: acute tubular necrosis
• Hypomagnesemia
  • Neurologic: tetany, paresthesias, seizures, ataxia, tremor, weakness
  • Cardiac: arrhythmias including torsades de pointes, hypertension
  • Gastrointestinal: anorexia, abdominal pain
  • Electrolytes: hypokalemia, hypocalcemia
• Hypokalemia
  • Neurologic: paralysis, paresthesias
  • Muscular: rhabdomyolysis, respiratory depression, weakness
  • Cardiac: arrhythmias, hypotension, cardiac arrest
  • Gastrointestinal: constipation, paralytic ileus
• Hypoglycemia
• Metabolic alkalosis

Management

• Patients starting parenteral nutrition
  • Include phosphate supplementation
• Patients at risk of refeeding syndrome
  • Identify patients at risk
  • Check extended electrolytes (calcium, magnesium, potassium, phosphate)
  • Before feeding
    • Thiamine 200-300mg po once daily or 250mg IV once daily or 100mg once daily for three days
    • Multivitamin po once daily
  • Careful rehydration with electrolyte supplementation
  • Start feeds at no more than 50% of total daily energy requirements (50% of ~30 Kcal/kg/day) with full protein requirement (~1-1.2g/kg/day)
  • Monitor electrolytes for first two weeks, supplementing as necessary

Further Reading

• Refeeding syndrome: what it is, and how to prevent and treat it. BMJ. 2008;336:1495.