Refeeding Syndrome

Refeeding syndrome is a potentially fatal condition that occurs in response to the rapid reintroduction of nutrition (oral, enteral, or parenteral) in a malnourished patient. It is characterized by rapid electrolyte and fluid shifts resulting from the metabolic changes triggered by feeding.

Pathophysiology

The syndrome is driven by the shift from a catabolic (starvation) state to an anabolic (growth/storage) state.

• Starvation State (Reductive Adaptation):

  • When intake is insufficient, the body conserves energy and prolongs life through "reductive adaptation".
  • Insulin levels fall, and glucagon increases.
  • Fat and muscle stores are mobilized for energy.
  • Intracellular stores of electrolytes (phosphate, potassium, magnesium) become depleted, although serum levels may remain normal due to homeostatic mechanisms and reduced renal excretion.
  • The heart becomes smaller and weaker with reduced cardiac output.

• Refeeding State:

  • Insulin Surge: The reintroduction of carbohydrates/nutrition causes a sudden surge in insulin.
  • Intracellular Shift: Insulin stimulates the cellular uptake of glucose, potassium, magnesium, and phosphate for protein synthesis and glycogen storage.
  • Serum Depletion: This rapid uptake leads to profound hypophosphatemia, hypokalemia, and hypomagnesemia in the blood.
  • Fluid Retention: Insulin stimulates the sodium-potassium pump, causing sodium retention. The kidneys, already adapted to conserve sodium, cannot excrete the excess, leading to fluid overload and expansion of the extracellular volume.
  • Thiamine Depletion: Reactivation of carbohydrate metabolism consumes thiamine (Vitamin B1), risking acute deficiency.

Risk Factors

According to NICE guidelines, patients are at high risk if they have one or more of the following:

• Body Mass Index (BMI) < 16 kg/m².
• Unintentional weight loss of >15% in the previous 3–6 months.
• Little or no nutritional intake for >10 days.
• Low levels of potassium, phosphorus, or magnesium before refeeding.

Or two or more of the following:

• BMI < 18.5 kg/m².
• Unintentional weight loss >10% in the previous 3–6 months.
• Little or no nutritional intake for >5 days.
• History of alcohol/drug use, chemotherapy, or diuretic use.

Clinical Manifestations

The clinical features are diverse and primarily result from electrolyte deficiencies and fluid overload (Table 63.1):

• Cardiovascular:
  • Heart failure due to fluid overload and weakened myocardium (from atrophy and hypophosphatemia).
  • Hypotension, arrhythmias, and sudden death.
• Respiratory:
  • Respiratory failure due to impaired diaphragm contractility (severe hypophosphatemia).
  • Dyspnea and pulmonary edema.
• Neurological:
  • Paresthesia, weakness, paralysis (hypokalemia/hypophosphatemia).
  • Confusion, delirium, seizures, and coma.
  • Wernicke’s encephalopathy (due to thiamine deficiency).
• Hematologic:
  • Hemolysis, thrombocytopenia, and leukocyte dysfunction.
• Gastrointestinal:
  • Lactase deficiency is common due to mucosal atrophy.

Management of Refeeding Syndrome

Management involves anticipating the risk, starting feeds cautiously ("start low, go slow"), and aggressively monitoring and correcting electrolytes.

1. Prevention and Initial Feeding Strategy

• Identification: Recognize patients at risk (e.g., anorexia nervosa, severe acute malnutrition).
• Thiamine Supplementation: Administer thiamine and multivitamin supplements before or with the start of feeding to prevent Wernicke's encephalopathy.
• Caloric Restriction:
  • Avoid aggressive refeeding.
  • For Severe Acute Malnutrition (SAM), start with Starter Diet (F-75). This provides 75 kcal/100 mL and only 0.9 g protein/100 mL.
  • The target initial volume is usually 130 mL/kg/day (100 kcal/kg/day), but reduced to 100 mL/kg/day if severe edema is present.
  • Feeds should be small and frequent (every 2 hours) to avoid overwhelming metabolic capacity.
• Avoid Diuretics: Edema should be treated by nutritional rehabilitation, not diuretics, to avoid exacerbating electrolyte imbalances.

2. Electrolyte Replacement and Monitoring

Serum electrolyte levels must be monitored daily. Deficits should be corrected as follows (based on guidance for adolescents/eating disorders):

• Hypophosphatemia:
  • Phosphate 2.5–2.9 mg/dL: Phos-Na-K supplement, 1 packet (250 mg) orally three times daily.
  • Phosphate 2.0–2.4 mg/dL: Phos-Na-K, 2 packets (500 mg) orally three times daily.
  • Phosphate <2.0 mg/dL: Consider IV Na-K-Phos (0.24 mmol/kg, max 15 mmol/dose) and intensive care consultation.
• Hypokalemia:
  • Potassium 3.1–3.4 mmol/L: Extended-release KCl 20 mEq orally (recheck in 8–12 hours).
  • Potassium 2.5–3.0 mmol/L: Extended-release KCl 40 mEq orally (recheck in 8–12 hours).
  • Potassium <2.5 mmol/L: Immediate oral or IV replacement and intensive care consultation.
  • Note: In SAM protocols, extra potassium (3–4 mEq/kg/day) is added routinely to feeds for at least 2 weeks.
• Hypomagnesemia:
  • Magnesium 1.3–1.7 mg/dL: Magnesium oxide 1 tablet (133–200 mg elemental Mg) twice daily.
  • Magnesium 1.0–1.2 mg/dL: Magnesium oxide 2 tablets twice daily.
  • Magnesium <1.0 mg/dL: IV Magnesium sulfate (50 mg/kg, max 2 g) and intensive care consultation.
  • Note: In SAM, magnesium is routinely supplemented (0.4–0.6 mEq/kg daily).

3. Monitoring for Complications

• Fluid Overload: Monitor pulse rate and respiratory rate carefully. An increase in pulse by 25 beats/min or respiratory rate by 5 breaths/min indicates fluid overload/heart failure. If this occurs, stop feeds/infusions and reassess.
• Blood Glucose: Monitor for hyperglycemia (due to insulin resistance) or hypoglycemia (due to liver dysfunction).

4. Transition to Rehabilitation

• Only advance to higher calorie feeds (Catch-up F-100: 100 kcal/100 mL, ~2.9 g protein) when the child has stabilized:
  • Return of appetite (eating well).
  • Resolution or reduction of edema.
  • No medical complications.
• The transition should be gradual (over ~3 days) to prevent precipitating heart failure. Replace F-75 with F-100 gradually, increasing volume by 10 mL per feed until some food is left uneaten.

Nutrition Recovery Syndrome

A distinct but related entity known as "Nutrition Recovery Syndrome" may occur during therapy (typically day 20-40). It is characterized by:

• Hepatomegaly (enlargement of the liver).
• Abdominal distension and ascites.
• Hypertrichosis (excessive hair growth).
• Parotid swelling.
• Gynaecomastia.
• Eosinophilia.
• This is a self-limiting condition attributed to hormonal changes during recovery rather than protein excess, though it requires differentiation from heart failure.