Refeeding syndrome

• Refeeding syndrome is an adverse clinical and biochemical response to feeding in severely malnourished patients.
• Any patient regardless of weight, who has had little or no nutritional intake for > 5 days is at risk of RFS
• Biochemical response to starvation:

  • Leads to fall in glucose levels with a subsequent fall in insulin
  • Intracellular potassium, phosphate and magnesium are depleted - move into blood to maintain normal serum levels
  • Cell metabolism reduces the conserve energy - loss of intracellular electrolytes
  • Fatty acids become the main source of energy
  • This stage is characterised by - loss of glycogen stores, low insulin, ketogenesis, relatively normal serum electrolyte levels, severe intracellular depletion, fatty liver (reduced LDL transport)
• Biochemical response to refeeding:

  • glucose leads to rise in insulin - drives the synthesis of glycogen, protein and fat - requires phosphate, magnesium and vitamins
  • Insulin stimulates activation of sodium/potassium ATPase to drive intracellular movement of potassium and sodium out of the cells - transport of glucose, magnesium and phosphate
  • fall in potassium, magnesium and thiamine
  • This stage characterised by: hypophosphatemia, hypokalaemia, hypomagnesaemia, low thiamine, fluid overload (water following sodium into extracellular space), cardiac arrhythmias
• Consider RFS if one or more of the following:

  • BMI < 16 kg/m2
  • Unintentional weight loss >15% within last 3-6 months
  • Little or no nutritional intake for > 10 days
  • Low potassium, magnesium or phosphate prior to feeding
• Consider RFS if two or more of the following:

  • BMI < 18.5 kg/m2
  • Unintentional weight loss >10% within last 3-6 months
  • Little or no nutritional intake for > 5 days
  • History of alcohol excess or drugs including insulin, chemotherapy, antacids or diuretics
• RFS is characterised by hypophosphataemia, hypomagnesaemia and hypokalaemia.
• Hypophosphataemia may be asymptomatic, but when moderate-severe features of low phosphate include:

  • Lethargy
  • Weakness
  • Bone pain
  • Altered mental status
  • Neurological sequelae (e.g. paraesthesia, seizures)
  • Ileus (smooth muscle)
  • Rhabdomyolysis (skeletal muscle)
  • Arrhythmias
• Features of low magnesium include:

  • Neuromuscular: tremor, tetany, seizures, weakness, confusion
  • Cardiovascular: palpitations, chest pain, arrhythmias
• Features of hypocalcaemia may occur because hypomagnesaemia impairs the action of parathyroid hormone (PTH) leading to resistance and in severe cases reduced secretion. Features of hypocalcaemia include paraesthesia (tingling) and tetany (muscle spasm).
• Features of low potassium include:

  • Fatigue
  • Generalised weakness
  • Muscle cramps & pain
  • Palpitations
  • Constipation
  • Arrhythmias
  • Muscle paralysis & rhabdomyolysis (if severe)
• Clinical syndromes associated with thiamine deficiency include:

  • Wernicke’s encephalopathy: characterised by a triad of confusion, ataxia and nystagmus.
  • Korsakoff’s syndrome: the end-stage result of untreated Wernicke’s. An irreversible amnesic syndrome characterised by short-term memory loss, long-term memory is preserved.
  • Wet beriberi disease: refers to thiamine deficiency with cardiovascular involvement. Causes high-output cardiac failure.
  • Dry beriberi disease: refers to thiamine deficiency with peripheral nerve involvement. Causes weakness and paralysis.
• In patients with poor baseline cardiac function due to severe malnutrition, the sudden sodium and fluid load can lead to oedema, left ventricular failure and cardiac arrhythmias.

  Features of cardiac dysfunction include:

  • Relative tachycardia (if low BMI, should expect to find bradycardia)
  • Tachypnoea +/- dyspnoea
  • Oedema
  • Bilateral crackles on auscultation
  • Hypotension
• Other clinical abnormalities

  • Hypoglycaemia: due to depleted glycogen, decreased gluconeogenesis and increased peripheral utilisation.
  • Hyperglycaemia: may occur due to blunted basal insulin secretion.
  • Infection: patients with severe malnutrition often do not mount the same systemic inflammatory response.
  • Liver dysfunction: fatty liver is common in starvation due to altered lipid metabolism and transport. May see mild transaminitis (rise in ALT/AST) before and during refeeding. Insulin promotes lipogenesis and deposition of fat in the liver.
• The hallmark of RFS is the development of hypophosphataemia following refeeding in a patient who is deemed at high risk or malnourished. The severity of RFS is variable and usually more severe the more malnourished the patient is.
• Baseline investigations

  • Body mass index
  • Observations
  • ECG
  • Full blood count
  • Urea & electrolytes
  • Bone profile
  • Magnesium
  • Liver function tests
• Before initiation of feeding, electrolyte derangements should be corrected (see management) and patients started on thiamine or Pabrinex (intravenous vitamin B substances with ascorbic acid). An ECG is important to identify any arrhythmias and the baseline QTc interval.
• ‘Refeeding’ bloods

  • Urea & electrolytes (gives a potassium)
  • Bone profile (gives a phosphate)
  • Magnesium
  • Blood glucose monitoring
• Management will be according to the local protocol under specialist supervision:

  • Slowly reintroducing food with limited calories
  • Magnesium, potassium, phosphate and glucose monitoring
  • Fluid balance monitoring
  • ECG monitoring in severe cases
  • Supplementation with electrolytes and vitamins, particularly B vitamins and thiamine
• Electrolyte derangement should be corrected and started on thiamine before initiation of feeding
• Feeding:

  • No more than 50% of energy requirements if >5 days with minimal intake
  • Alternatively aim for 10-20 kcal/kg/day in high risk patients and increase over 5-7 days as possible with electrolyte correction