Refeeding Syndrome (RS)

What is RS?

Refeeding syndrome can be defined as the potentially fatal shifts in fluids and electrolytes that may occur in malnourished patients receiving artificial refeeding
(whether enterally or parenterally).

Hypophosphataemia is the biochemical hallmark of RS, though hypomagnesaemia and hypokalaemia are commonly present as well.

What are the clinical consequences of RS?

In RS, whole body depletion of phosphate occurs. Insulin surge cause by refeeding causes a greatly increased uptake and use of phosphate in the cells. These changes lead to a deficit in intracellular as well as extracellular phosphate. In this environment, even small decreases in serum phosphate can lead to widespread dysfunction of cellular processes affecting almost every physiological system.
Phosphate depletion leads to reduced levels adenosine triphosphate (ATP), causing failure of cell functions dependent upon energy rich phosphate compounds. Low phosphate also lead to reduced levels of red cell 2,3- DPG (diphosphoglycerate), thereby increasing the affinity of hemoglobin for oxygen and reducing oxygen release at the tissue level.
These processes cause impaired tissue functioning leading to;

  • Cardiac failure and cardiac arrhythmias (thiamine deficiency can compound failure)
  • Convulsions and coma
  • Respiratory failure
  • Muscle weakness and pain

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. Low potassium and magnesium also affects membrane potential and can lead to cardiac arrhythmias and neuromuscular complications

What is the pathogenesis of RS?

  • During undernutrition, the body down regulates membrane pumping to conserve energy. This causes leakage of intracellular potassium (K), magnesium (Mg), calcium (Ca) and phosphate (PO4), with subsequent whole body depletion.
  • In starvation the secretion of insulin is decreased in response to a reduced intake of carbohydrates.   This results in further intracellular loss of electrolytes, in particular phosphate.
  • Refeeding leads to reversal of the above processes and leads to movements of electrolytes into cells. This can lead to precipitous falls in circulating levels of K, Mg, Ca and PO4. This phenomenon usually occurs within four days of starting to feed again.

How to identify patients at high risk of developing refeeding problems?
The National Institute for Health and Clinical Excellence (NICE) in England and Wales identifies the following groups at high risk of RS: 7

A.  Patient has one or more of the following:

  • BMI less than 16 kg/m2
  • unintentional weight loss greater than 15% within the last 3–6 months
  • little or no nutritional intake for more than 10 days
  • low levels of potassium, phosphate or magnesium prior to feeding

B.  Or patient has two or more of the following:

  • BMI less than 18.5 kg/m2
  • unintentional weight loss greater than 10% within the last 3–6 months
  • little or no nutritional intake for more than 5 days
  • a history of alcohol abuse or drugs including insulin, chemotherapy, antacids(binds phosphate) or diuretics (loss of electrolytes)

How to prevent development of RS?

  • Identification of high risk patients is crucial. Any patient who is malnourished or had negligible food intake for more than 5-10 days is at risk of developing refeeding problems.
  • Check baseline potassium, calcium, phosphate and magnesium. However, correction of electrolyte deficiencies before feeding is not necessary. It should be done alongside feeding. Electrolyte replacement prior to refeeding may provide a false sense of security as improvement in plasma levels could occur with no significant change in overall electrolyte status. A severely malnourished individual would be unable to correct intracellular electrolyte deficits unless simultaneous feeding is given to encourage transmembrane transfer.   It therefore seems logical to provide generous supplements of oral, enteral or intravenous supplements of potassium (likely requirement 2–4 mmol/kg/day), phosphate (likely requirement 0.3–0.6 mmol/kg/day) and magnesium (likely requirement 0.2 mmol/kg/day intravenous, 0.4 mmol/kg/day oral) with feeding unless pre-feeding plasma levels are high.
  • The electrolytes should be monitored daily for 7 days and at least three times in the following week.
  • Specific micronutrient deficiencies can compound the problems of RS. Although all vitamin deficiencies may occur at variable rates with inadequate intake, thiamine is of most importance in complications of refeeding. Thiamine is an essential coenzyme in carbohydrate metabolism. NICE recommends vitamin and mineral supplementation immediately before and during the first 10 days of feeding: oral thiamine 200–300 mg daily, vitamin B co strong 1 or 2 tablets, three times a day (or full dose daily intravenous vitamin B preparation, if necessary) and a balanced multivitamin/trace element supplement once daily.
  • Refeeding should be started at a maximum of10 kcal/kg/day (no more than 50% of energy requirements). The rate can be increased slowly to meet full needs by 4–7 days, if no refeeding problems are detected on clinical or biochemical monitoring.
  • Refeeding should be started using only 5 kcal/kg/day in extreme cases (for example, BMI less than 14 kg/m2 or negligible intake for more than 15 days) and monitoring cardiac rhythm continually in these people and any others who already have or develop any cardiac arrhythmias

How can refeeding syndrome be detected and treated?

Refeeding syndrome is detected by considering the possibility of its existence and by measuring serum electrolytes described above. If the syndrome is detected, the rate of feeding should be slowed down and essential electrolytes should be replenished.

Discuss phosphate replacement treatment?
The best method for electrolyte repletion has not yet been determined. Hypophosphatemia is ideally treated with intravenous supplementation in hospitalized patients, but this is not without risks.  Intravenous phosphate can precipitate with calcium and produce a variety of adverse effects including hypocalcaemia, renal failure, and potentially fatal arrhythmias.
We use intravenous phosphate at phosphate levels less than 0.5 mmol/l. The maximum intravenous dose used is 18mmol in 24 hours.


  1. NICE guidance: Nutrition support in adults
  2. British Society of Gastroenterology Guidelines for enteral feeding in adult hospital patients
  3. Mehanna HM et al. Refeeding syndrome: what it is, and how to prevent and treat it.  BMJ. 2008 Jun 28; 336(7659):1495-8.

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