Refeeding syndrome

Syndrome

Any individual who has had negligible nutrient intake for many consecutive days and/or is metabolically stressed from a critical illness or major surgery is at risk of refeeding syndrome. Refeeding syndrome usually occurs within four days of starting to re-feed. Patients can develop fluid and electrolyte disorders, especially hypophosphatemia, along with neurologic, pulmonary, cardiac, neuromuscular, and hematologic complications.

During fasting the body switches its main fuel source from carbohydrates to fatty acids or amino acids as the main energy source. The spleen decreases its rate of red blood cell breakdown thus conserving red blood cells. Many intracellular minerals become severely depleted during this period, although serum levels remain normal. Importantly, insulin secretion is suppressed in this fasted state and glucagon secretion is increased.

During refeeding, insulin secretion resumes in response to increased blood sugar, resulting in increased glycogen, fat and protein synthesis. This process requires phosphates, magnesium and potassium which are already depleted and the stores rapidly become used up. Formation of phosphorylated carbohydrate compounds in the liver and skeletal muscle depletes intracellular ATP and 2,3-diphosphoglycerate in red blood cells, leading to cellular dysfunction and inadequate oxygen delivery to the body's organs. Refeeding increases the basal metabolic rate. Intracellular movement of electrolytes occurs along with a fall in the serum electrolytes, including phosphorus and magnesium. Levels of serum glucose may rise and the B₁ vitamin thiamine may fall. Cardiac arrhythmias are the most common cause of death from refeeding syndrome, with other significant risks including confusion, coma and convulsions and cardiac failure.

This syndrome can occur at the beginning of treatment for anorexia nervosa when patients have an increase in calorie intake and can be lethal. It can also occur after the onset of a severe illness or major surgery. The shifting of electrolytes and fluid balance increases cardiac workload and heart rate. This can lead to acute heart failure. Oxygen consumption is also increased which strains the respiratory system and can make weaning from ventilation more difficult.

History

A common error repeated in multiple papers claims that "The syndrome was first described after World War II in Americans who, held by the Japanese as prisoners of war, had become malnourished during captivity and who were then released to the care of United States personnel in the Philippines." However, closer inspection of the 1951 paper by Schnitker reveals the prisoners under study were not American POWs but Japanese soldiers who, already malnourished, surrendered in the Philippines during 1945, after the war was over. It is actually quite difficult to ascertain when the syndrome was first discovered and named, but it is likely the associated electrolyte disturbances were identified well before 1951, perhaps in Holland during the closing months of World War II, before Victory Day in Europe.

Treatment

Refeeding syndrome can be fatal if not recognized and treated properly. An awareness of the condition and a high index of suspicion are required in order to make the diagnosis. The electrolyte disturbances of the refeeding syndrome can occur within the first few days of refeeding. Close monitoring of blood biochemistry is therefore necessary in the early refeeding period. In critically ill patients admitted to an Intensive Care Unit, if phosphate drops to below 0.65 mmol from a previously normal level within three days of starting enteral or parenteral nutrition, caloric intake should be reduced to 480 kcals per day for at least two days whilst electrolytes are replaced. Prescribing thiamine, vitamin B complex (strong) and a multivitamin and mineral preparation is recommended. Biochemistry should be monitored regularly until it is stable. Although clinical trials are lacking in patients other than those admitted to an intensive care, it is commonly recommended that energy intake should remain lower than of normally required for the first 3–5 days of treatment of refeeding syndrome. Patients who have been starved for some time often experience gastrointestinal disturbance during refeeding, in particular colicky abdominal pain, reflux symptoms, nausea and early satiety.