Refeeding Syndrome: Anticipation is Key

Refeeding syndrome has received much attention among medical professionals of late, particularly the surgeons. Being a rare syndrome, it is seen in 0.8% of hospitalized adults. However, its importance lies in the fact that mortality in hospitalized patients who develop severe hypophosphatemia (serum phosphate <1 mg/dL) is 30%. The syndrome was first described after the Second World War in Japanese prisoners of war taken by the United States in the Philippines.

It is commonly construed as a cause of serum abnormalities, and is typically characterized by hypophosphatemia. Phosphate is interestingly the most abundant intracellular anion, majority of which is found in bones. Hence, measured serum phosphate does not correlate with the total-body content of phosphate. The importance of phosphate lies in its biological importance – it is an important component of cell membrane as phospholipids, enzyme systems, and bone matrix. Cellular energy in the form of ATP has phosphate as a component.

Pathophysiology of Refeeding Syndrome

Refeeding syndrome typically occurs when enteral or parenteral nutrition is initiated in a patient with one of the high-risk factors such as prolonged malnutrition, gastrointestinal losses (as in vomiting, diarrhea, and nasogastric aspiration), chronic alcohol abuse, abdominal surgery, and metastatic cancer. Patients of anorexia nervosa are especially prone to developing this syndrome when started on an inappropriate diet.

Introduction of carbohydrate suddenly stimulates a release of insulin, which results in an intracellular shift of phosphate, potassium, and magnesium. This transcellular shift frequently occurs in the presence of reduced body stores of these key electrolytes. Refeeding syndrome should be anticipated if there is disturbance in any of the electrolytes cited above.

Clinical Presentation

A common manifestation in at risk population is respiratory failure secondary to diaphragm and intercostal muscle weakness as a result of ATP depletion. Acute respiratory failure in a spontaneously breathing patient or inability to wean a patient from mechanical ventilation should incite us to think of refeeding syndrome.

2,3-DPG deficiency results in impaired oxygen off-loading at the cellular level causing dyspnea and fatigue, further compromising respiration.

Generalized skeletal muscle weakness due to depleted ATP stores, ventricular dysrhythmias, left ventricular dysfunction, confusion, lethargy, and gait disturbances.

Refeeding syndrome usually starts 4 to 6 days following restarting of feeds.

Treatment Strategy in Refeeding Syndrome

Anticipating development in patients at risk holds the key to treatment of refeeding syndrome. In at-risk groups, refeeding should be introduced gradually. A rule of thumb to follow would be to begin with a one-half nutrition goal of 5,040 kilocalories and increasing by 840 kilocalories every 24 to 48 hours, with careful attention to serum electrolytes.

Moderate hypophosphatemia with serum levels of 1 to 2.5 mg/dL may be managed with oral or enteral replacement.

Severe or symptomatic hypophosphatemia mandates intravenous replacement. Sodium phosphate 0.16 to 0.32 mmol/kg administered over 4 to 6 hours is a practical way of correcting the deficiency. However, caution must be practiced in hypercalcemia and serum electrolytes monitored meticulously. Ionized calcium levels should be monitored as overzealous dosing of phosphate may result in hypocalcemia.