Refeeding syndrome (RFS)

Refeeding syndrome

• is a potentially fatal condition that occurs when patients whose food intake has been severely restricted are given nutrition via oral, enteral or parenteral routes (1)
• was first described in Far East prisoners of war after the second world war (2)
  • starting to eat again after a period of prolonged starvation seemed to precipitate cardiac failure
    • while refeeding syndrome is an important threat to patients with anorexia nervosa and other restrictive eating disorders, there have been more reported deaths in anorexia nervosa from underfeeding, which sometimes occurs because staff fear inducing refeeding syndrome (1)
• sudden reversal of prolonged starvation by the reintroduction of food leads to rapid shifts of electrolytes back into cells from which they had, during starvation, been leached out
  • in starvation the secretion of insulin is decreased in response to a reduced intake of carbohydrates (2)
    • instead fat and protein stores are catabolised to produce energy
      • results in an intracellular loss of electrolytes, in particular phosphate
      • malnourished patients' intracellular phosphate stores can be depleted despite normal serum phosphate concentrations
      • when they start to feed a sudden shift from fat to carbohydrate metabolism occurs and secretion of insulin increases
        • stimulates cellular uptake of phosphate, which can lead to profound hypophosphataemia
        • phosphate, potassium and magnesium levels can fall very rapidly within the first week of refeeding, with neurological and cardiovascular consequences: this is known as the refeeding syndrome (1)
          • resulting effects, most notably cardiac compromise, can be fatal. Respiratory failure, liver dysfunction, central nervous system abnormalities, myopathy and rhabdomyolysis are also recognised complications and patients are at risk of vitamin deficiencies
• refeeding syndrome usually occurs within 72 hours of beginning refeeding, with a range of 1-5 days
  • however, it can occur late (in one study, up to 18 days) in the most malnourished (1)
    • hence patients discharged before 20 days should be followed up to check electrolytes and detect late appearing refeeding syndrome
• refeeding syndrome can occur with parenteral as well as enteral feeding (2)

Indicators of higher risk for refeeding syndrome

• predictors for the development of refeeding hypophosphataemia include low white blood cell count and higher haemoglobin level (1)
• patients at the highest risk of refeeding syndrome are those with very low weight, minimal or no nutritional intake for more than 3-4 days, weight loss of over 15% in the past 3 months, and with abnormal electrolytes and medical comorbidities such as pneumonia or other serious infections, cardiac dysfunction or disease and liver damage (e.g. due to alcohol dependence) before refeeding (1)

Management

• seek expert advice
• macronutrients
  • various studies and guidelines have shown a beneficial effect of starting energy intake at a lower rate than generally used, in order to prevent refeeding syndrome in patients at high risk (3)
    • based on a patient’s individual risk for refeeding syndrome, energy supply should be initiated at lower levels, starting with an initial amount of 5-15 kcal/kg/day, and increased stepwise depending on the laboratory parameters and clinical situation of the patient
    • full energy requirements should be met within 5 to 10 days, depending on the prior risk stratification, using a common nutritional macronutrients composition of 40-60% carbohydrates, 30-40% fats, and 15-20% proteins
    • nutritional rehabilitation of patients with risk to develop a refeeding syndrome should be typically started with oral intake of regular food
    • parenteral nutrition is indicated when oral and/or enteral nutrition are insufficient or in the case of failure of the gut function
• micronutrients
  • after the initiation of nutritional therapy, the intracellular flux of vitamins and electrolytes increases, causing serum levels to drop
    • is therefore essential to correct electrolyte levels before initiation of the replenishment phase, with the supplementation of phosphate and thiamine being particularly important

Notes:

• phosphate is necessary for the generation of adenosine triphosphate from adenosine diphosphate and adenosine monophosphate and other crucial phosphorylation reactions
  • serum phosphate concentrations of less than 0.50 mmol/l (normal range 0.85-1.40 mmol/l) can produce the clinical features of refeeding syndrome, which include rhabdomyolysis, leucocyte dysfunction, respiratory failure, cardiac failure, hypotension, arrhythmias, seizures, coma, and sudden death (2)
  • early clinical features of refeeding syndrome are non-specific and may go unrecognised

Reference:

• UK Royal College of Psychiatrists. Medical Emergencies in Eating Disorders: Guidance on Recognition and Management 2022- College Report CR233
• Hearing SD. Refeeding syndrome. BMJ. 2004;328(7445):908-909. doi:10.1136/bmj.328.7445.908
• Reber E, Friedli N, Vasiloglou MF, Schuetz P, Stanga Z. Management of Refeeding Syndrome in Medical Inpatients. Journal of Clinical Medicine. 2019 Dec;8(12):E2202. DOI: 10.3390/jcm8122202. PMID: 31847205; PMCID: PMC6947262.