Refeeding syndrome

Refeeding syndrome occurs when previously malnourished patients are fed with high carbohydrate loads, the result is a rapid fall in phosphate, magnesium and potassium, along with an increasing ECF volume, leading to a variety of complications.

Patients who are malnourished develop a total body depletion of phosphorous; serum phosphorous levels are maintained by redistribution from the intracellular space. The body uses endogenous fuel stores as it’s main source of energy. Fat and protein (from muscle) are metabolized. - In general, a catabolic state.  In response to chronic undernutrition, there may be compensatory reductions in cardiac output, hemoglobin level, muscle mass, hepatic glycogen content, and renal concentrating ability.

Refeeding syndrome occurs when energy substrates, particularly carbohydrate, are initiated in a catabolic patient. The delivery  of glucose, either enterally or parenterally, as part of a feeding strategy, can cause a huge increase in the circulating insulin level.  The resulting hyperinsulinemia stimulates intracellular uptake of glucose, potassium, phosphorus, and magnesium to support the proliferating body cell mass and hepatic glycogen synthesis.  The serum concentration of these agents falls dramatically.

Water overload, which can result from salt and water retention following the increased insulin concentrations, also is associated with excessive carbohydrate administration.

The dramatic reduction in serum electrolytes and fluid retention leads to a number of systemic pathologies. There is an increase in cardiac workload, with increased stroke work, heart rate and oxygen consumption. This sudden increase in demand for nutrients and oxygen may outstrip supply. Moreover, in patients with cardiovascular disease, the sudden increase in cardiac work and circulating fluid can precipitate acute heart failure, especially if the left ventricle has been thinned by malnutrition. Although excessive fluid administration can result in congestive heart failure in a malnourished patient, fluids alone do not cause the refeeding syndrome. 

The sudden administration of carbohydrates exerts a considerable strain on the respiratory system, whose musculature may well be atrophied due to starvation - and can result in respiratory failure. There is an increase in CO2 production and O2 consumption, and a resultant increase in the respiratory quotient (RQ).  If the amount of carbon dioxide produced during metabolism of the carbohydrate exceeds the ventilatory capacity, the Pco2 will increase, especially in patients who have underlying pulmonary disease.The consequence of this is an increase in minute ventilation, which may cause dyspnea and tachypnea, and make weaning difficult.

The gut atrophies with starvation and the production of digestive enzymes diminishes. With return of enteral nutrition, the gut may be initically intolerant, requiring time to adapt, and many patients complain of nausea and diarrhea.

The serum phosphorous level falls precipitously with refeeding, due to a shift of phosphate from the extracellular to the intracellular compartment, due to the huge demands for this ion for synthesis of phosphorylated compounds. The result of this sudden massive reduction in phosphorous levels is a multitude of life threatening complications involving multiple organs: respiratory failure, cardiac failure, cardiac arrhythmias, rhabdomyolysis, seizures, coma, red cell and leucocyte dysfunction.

The most effective way to treat refeeding is to be aware of it. One should start feeds slowly and aggressively supplement magnesium, phosphate and potassium.  Careful attention to fluid and calorie administration will help to prevent the refeeding syndrome. Using an alternate source of calories (fat), the metabolism of which produces less carbon dioxide, and supplementation with magnesium, potassium, and phosphorus also will decrease the likelihood of refeeding syndrome developing.

On an equimolar basis, lipid metabolism produces less carbon dioxide than does carbohydrate and is, therefore, less likely to cause the respiratory failure associated with the refeeding syndrome. Although acidosis and hypocalcemia can develop in patients receiving parenteral nutrition, they are not associated with the development of respiratory failure in the absence of tetany. Excessive protein intake does not have any effect on respiratory function.

References:
Nichols BL, Alvarado J, Rodriguez J, Hazlewood CF, Viteri F.
Therapeutic implications of electrolyte, water, and nitrogen losses
during recovery from protein-calorie malnutrition. J Pediatr.
1974;84:759-768
Solomon SM, Kirby DF. The refeeding syndrome: a review. J Parenter
Enteral Nutr. 1990;14:90-97