To identify the patients who are at risk of refeeding syndrome
To understand the etiology of refeeding syndrome
To now methods of prevention and treatment of refeeding syndrome
Refeeding syndrome is known as a dangerous consequence of rapid and excessive food intake in severely malnourished subjects. This condition occurred in wartime when prisoners of war were quickly re-nourished after their liberation and they died suddenly. Formerly, various gastrointestinal problems were supposed to be responsible for these problems, but autopsy did not demonstrate any substantial GI changes. However, even at the present time the refeeding syndrome is a not unusual complication of artificial nutrition, with an incidence of 5 to 25% (cancer patients). It occurs commonly with parenteral or enteral realimentation of previously malnourished patients who have lost more than 10% of their body weight over the previous two months. The following groups of patients are especially prone to develop refeeding syndrome:
chronic malnutrition (e.g. cancer, IBD, SBS, bowel fistulas and elderly patients)
prolonged fasting (hunger strikers)
Refeeding syndrome is principally associated with:
Hypophosphataemia – is a prominent feature of the refeeding syndrome. During fasting or in catabolic situations there is loss of phosphate from the intracellular compartment. Subsequent high caloric intake (mainly of carbohydrates), leads to insulin release and to a rapid shift of glucose and phosphate into the cells. Subsequent hypophosphataemia (often below 0.30 mmoll−1) can cause impaired neuromuscular function with paraesthesiae, seizures, cramps or impaired musculo-skeletal function including weakness and impaired muscular contractility. Involvement of ventilatory muscle function can cause hypoventilation and eventually respiratory failure. Rhabdomyolysis has also been described as result of severe hypophosphataemia. Phosphate deficiency can also cause thrombocytopaenia, impaired blood clotting and deficiency of leukocyte function. Psychological changes comprise perturbed mental state, confusion and eventually coma.
Hypomagnesaemia and hypokalaemia – are also connected with refeeding in severely malnourished patients. The aetiology is similar to that of hypophosphataemia. A low concentration of magnesium and potassium in plasma leads to cardiac arrhythmias, and cardiac arrest. Both hypomagnesaemia and hypokalaemia lead to neuromuscular and other dysfunctions such as weakness, paralysis, paresthesia, confusion, rhabdomyolysis, and respiratory depression.
Vitamin deficiency – Thiamine deficiency is the principal vitamin deficiency in refeeding syndrome owing to its rapid consumption in glycolysis. Deficiency impairs glucose metabolism (pyruvate dehydrogenase reaction) with subsequent lactic acidosis. Short-term loss of memory and confabulation (Korsakov's syndrome) can develop as a result of thiamine deficiency.
Fluid retention – Carbohydrate refeeding can reduce water and sodium excretion, which results in expansion of the extracellular fluid compartment and subsequent weight gain. This occurs particularly if sodium intake is increased. Fluid intolerance results in oedema formation; cardiac failure can, therefore, occur in patients with compromised heart function or myocardial atrophy from prolonged and severe starvation.
3. Clinical picture
The sodium retention and extracellular fluid expansion together with thiamine deficiency can lead to congestive cardiac failure. This is more pronounced in patients with reduced cardiac muscle mass due to malnutrition.
Deficiencies of K, P, and Mg are associated with life-threatening cardiac arrhythmias. Neurological problems such as delirium, neuropathy, or seizures can develop in some patients. Poor ventilatory function due to respiratory muscles weakness can result in respiratory failure.
Rhabdomyolysis due to hypophosphataemia not only causes muscle weakness and myalgia but can also be complicated by renal failure due to myoglobinuria.
Infrequently, thrombocytopaenia and impaired blood clotting can also be a consequence of phosphate deficiency.
4. Prevention and treatment
The first step in the prevention of refeeding syndrome development is to anticipate it. Its occurrence can be expected especially in severely malnourished and starved patients (se above). In these persons the following parameters should be monitored during refeeding:
plasma and urinary electrolytes (Na, K, P, Mg, Ca)
heart rate monitoring
Before the onset of either parenteral or enteral nutrition support, electrolyte deficiencies should be corrected and the circulatory volume carefully restored (see chapter 4.5.). Also 50 to 250 mg of thiamine should be given especially when glucose is infused. More thiamine may be necessary until the patient is stabilized.
The energy intake should start at a maximum of 50% of planned energy intake (500–1000 kcalday−1). The patients' needs for fluid, sodium, potassium, magnesium and phosphate should be infused separately. Energy intake, beginning at 20 kcalh−1on the first day, is gradually increased over a week until daily nutritional requirements are met and the patient is metabolically stable. Additional potassium and phosphate should be given to prevent deficiency.
If despite supplementation, hypophosphataemia develops patients should receive intravenous phosphate 40–80 mmolday−1 together with magnesium (8–16 mmolday−1) and potassium (80–120 mmolday−1) according to serum levels. The treatment of hypomagnesaemia and hypophosphataemia can facilitate the treatment of refractory hypokalaemia. It is advisable to begin with a low volume low sodium feed and to monitor fluid balance by daily weighing, adjusting intake according to this and serum sodium levels Any water and sodium retention connected with refeeding should be managed by reducing intake of these. Heart failure is a sign of mismanagement and although diuretics may be needed if it develops, these can make hypokalaemia worse.
The refeeding syndrome is a complication of nutritional support in severely malnourished patients (anorexia nervosa, cancer, IBD, SBS, elderly alcoholism, etc). Its features are salt and water retention and depletion of potassium, magnesium and phosphate with a decrease in their serum levels during enteral or parenteral realimentation. In can be associated with high morbidity and mortality, especially when it is not diagnosed. Knowledge of this complication is, therefore essential for its prevention, recognition, and treatment.
Conflict of interest
There is no conflict of interest.
Published online: August 25, 2009
© 2009 European Society for Clinical Nutrition and Metabolism. Published by Elsevier Inc. All rights reserved.