Refeeding Syndrome: Proven Prevention Methods

How to Prevent Refeeding Syndrome in Eating Disorder Patients

What is Refeeding Syndrome?

Refeeding syndrome was first described during World War II when prisoners of war were experiencing death, for unclear reasons, during nutritional rehabilitation. Today we understand that when individuals with malnutrition are provided aggressive nutritional rehabilitation, they run the risk of developing refeeding syndrome, defined as the various clinical complications that develop due to the potentially fatal shift in fluids and electrolytes that occurs in significantly malnourished patients receiving artificial refeeding, whether orally (ingested through the mouth), enterally (through a feeding tube into the stomach or intestines) or parenterally (though an intravenous [IV] or surgically placed central line).  Patients with severe eating disorders are at very high risk for this complication, given their state of malnutrition.

However, the rate of refeeding syndrome is largely unknown due to differences in definitions across studies, with more consistent studies looking at specific conditions parallel with refeeding syndrome, like hypophosphatemia (low levels of phosphate in the blood).

Why Refeeding Syndrome Occurs: Pathophysiology and Risk Factors

How does refeeding syndrome develop?

Malnourished individuals are in a state of catabolism (a breaking down of the tissues and organs in the body) due to the lack of nutritional substrates and hormonal changes that accompany starvation. The deficient nutritional substrates include depleted energy reserves such as fatty acids, glycogen (glucose polymers largely stored in the liver and muscles) and proteins as well as vitamins and intracellular electrolytes. The most important intracellular electrolyte, as it pertains to refeeding syndrome, is phosphorous. Phosphorous is the most important component of adenosine triphosphate (ATP), which is needed by all the cells of the body to perform all their basic functions.

When the body suddenly starts to take in nutrition, it changes from a catabolic state to one of anabolism (building up of the tissues and organs). Carbohydrates make up a large majority of the consumed macronutrients, and when starved individuals begin to consume carbohydrates, insulin is released. Insulin has anabolic properties and acts to push phosphorous, potassium and glucose into the cells of the body. This can further deplete available phosphorous that is needed by the more active cells and tissues of the body. The brain, muscles (including the heart and diaphragm, a muscle used to help with breathing) and the cells in our blood, such as red blood cells, are highly dependent on phosphorous for various reason and so these tissues can quickly start to fail, leading to:

• Brain dysfunction
• Rupture of blood cells
• Abnormal heart rhythms
• Reduced heart contractility (heart failure)
• Other organ dysfunction
• In severe cases, death

Full blown refeeding syndrome is characterized by:

• Hypophosphatemia (low phosphorous)
• Hypokalemia (low potassium)
• Respiratory insufficiency
• Heart failure with swelling
• Rhabdomyolysis (muscle break down)
• Hemolysis (rupture of blood cells as they travel in the blood stream)
• Seizures

And refeeding syndrome can be defined as:

• A decrease in any 1, 2 or 3 of serum phosphorous, potassium and/or magnesium levels by 10-20% (mild refeeding syndrome), 20-30% (moderate refeeding syndrome) or >30% and/or organ dysfunction resulting from a decrease in any of these and/or due to thiamin deficiency (severe refeeding syndrome)
• The above occurs within 5 days of reinitiating or substantially increasing energy provision

Who is at the Greatest Risk for Refeeding Syndrome?

The ASPEN 2020 guidelines identify various criteria for identifying increased risk to develop refeeding syndrome²:

Patient has one or more of the following:

• BMI <16 kg/m²
• 7.5% weight loss in 3 months or >10% in 6 months
• Little or no nutritional intake for >7 days
• Low levels of potassium, phosphorus, or magnesium before refeeding
• Clinical exam consistent with severe loss of subcutaneous fat or muscle mass
• Severely advanced disease that predisposes toward malnutrition (see below)

Or patient has two or more of the following:

• BMI 16-18.5 kg/m²
• Unintentional weight loss of >5% during the last month
• Little or no nutritional intake for >5 days
• Minimally low levels of potassium, phosphorous, or magnesium before refeeding
• Clinical exam consistent with moderate loss of subcutaneous fat or muscle mass
• Moderately advanced disease that predisposes toward malnutrition (see below)

Risk Factors and Disease Predisposition

While patients with severe eating disorders are at risk for developing refeeding syndrome, there are various conditions and populations that are also at risk:

• Anorexia nervosa and other eating disorders
• Patients with chronic alcoholism
• Cancer patients
• Postoperative patients
• Bariatric surgery patients
• Elderly patients
• Acquired immunodeficiency syndrome (AIDS)
• Patients with chronic malnutrition:
  • Prolonged fasting or low energy diet
  • Morbid obesity with profound weight loss
  • Major stressors without nutrition for prolonged periods
  • Malabsorptive syndrome (such as inflammatory bowel disease, chronic pancreatitis, cystic fibrosis, short bowel syndrome)
• Long term users of antacids
• Long term users of diuretics

How to Prevent Refeeding Syndrome

Check Blood Chemistry Values Frequently

Since a variety of fluid and electrolyte abnormalities can accompany the refeeding process, it is important to monitor electrolytes, blood counts and glucose values very closely. Thiamin (vitamin B1) should be supplemented before initiating nutrition. As patients become more medically stable, the frequency of monitoring can be reduced but this is best determined by a professional. Monitoring phosphorous levels is particularly important since hypophosphatemia is a leading factor in the development of refeeding syndrome.

Other minerals/electrolytes and vitals to monitor include:

• Potassium
• Magnesium
• Glucose
• Hemoglobin
• Heart rate
• Oxygenation

Determine Caloric Needs

Use the Harris-Benedict equation to determine the basal energy expenditure (BEE) of the patient. BEE is the amount of energy required to maintain the body's normal metabolic activity and reflects the energy used when the body is at rest. You must also determine the total energy expenditure (TEE), the amount of energy used during the day. TEE typically exceeds the BEE by 10-60%, depending on the patient’s activity level. TEE should be used as a goal or target to achieve weeks into the refeeding process, although development of refeeding syndrome can slow progression to achieving this caloric goal.

Proceed With Caution

While it is important that patients gain a significant amount of weight to facilitate recovery, there is no agreed upon optimal dietary intervention due to the lack of rigorous research covering nutritional interventions for those suffering from severe malnutrition or eating disorders. The ASPEN guidelines recommend very conservative caloric increases but this needs to be balanced with the medical complications that have developed due to the malnutrition, as weight restoration resolves these complications.

If food intake is too little, using liquid supplements during the early stages of refeeding can be effective, as can use of enteral nutrition (via a feeding tube). Patients may also not gain weight for the first few weeks of nutritional rehabilitation given the anabolic processes that develop early in refeeding. It can be tempting to increase calories to promote weight gain, but instead you should investigate if there is covert purging, other medical complications or modify nutritional rehabilitation based on changes in BEE.

How Refeeding Syndrome is Treated

Prevention is the best treatment! However, if refeeding syndrome is suspected, a patient should be hospitalized and aggressive correction of electrolytes needs to occur, either orally or through the intravenous route, depending on the serum values. Patients also require very close cardiorespiratory monitoring given the increased risk of heart failure and arrhythmias, close monitoring of lab values, vitamin supplementation and close monitoring of nutritional intake and daily weights. Treatment and stabilization need to be addressed immediately.

References

• Mehanna, H. M., Moledina, J., & Travis, J. (2008, June 26). Refeeding syndrome: what it is, and how to prevent and treat it. BMJ, 336(7659), 1495–1498. https://doi.org/10.1136/bmj.a301
• Da Silva JS, et al. ASPEN Consensus Recommendations for Refeeding Syndrome. Nutrition in Clinical Practice 2020;35(20):178-95.

• Mehler, P. S., Winkelman, A. B., Andersen, D. M., & Gaudiani, J. L. (2010). Nutritional Rehabilitation: Practical Guidelines for Refeeding the Anorectic Patient. Journal of Nutrition and Metabolism, 2010, 1–7. https://doi.org/10.1155/2010/625782

• Brown, C. A., Sabel, A. L., Gaudiani, J. L., & Mehler, P. S. (2015, April 2). Predictors of hypophosphatemia during refeeding of patients with severe anorexia nervosa. International Journal of Eating Disorders, 48(7), 898–904. https://doi.org/10.1002/eat.22406