Using Labs to Detect and Treat Refeeding Syndrome | ACUTE

How to Use Labs to Detect and Treat Refeeding Syndrome

Patients experiencing severe eating disorders or malnutrition are at an increased risk of developing refeeding syndrome during their nutritional rehabilitation. Refeeding syndrome develops shortly after the refeeding process begins and, as a result, is very preventable with the utilization of lab work. Running daily, and eventually transitioning to every few days, labs allow clinicians to monitor the key electrolyte serum levels and other substances that can indicate refeeding syndrome.

The Importance of Using Labs to Detect Refeeding Syndrome

Continuous medical monitoring during the nutritional rehabilitation process is vital to preventing refeeding syndrome and helps clinicians to address it early when it does occur by giving key insight into what electrolytes and substances are abnormal and how deficiencies need to be addressed.

What is refeeding syndrome?

In 2020, a consensus definition for refeeding syndrome was put forth by ASPEN. They conceptually defined refeeding syndrome as “a measurable reduction in levels of one or any combination of phosphorous, potassium, and/or magnesium, or the manifestation of thiamin deficiency, developing shortly (hours to days) after initiation of calorie provision to an individual who has been exposed to a substantial period of undernourishment.” More specifically in the paper, it is outlined 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 thiamine deficiency (severe refeeding syndrome); this occurs within 5 days of reinitiating or substantially increasing energy provision.”

Physiologically, when a malnourished individual is provided nutrition, specifically carbohydrates, insulin is released. Insulin helps the body to build up some of these very unhealthy tissues (anabolism) as it pushes phosphorous along with the other mentioned electrolytes into the various cells of the body. However, the body is already deplete of phosphorous, creating further depletion in the production of ATP, which is basically considered the energy currency of cells, in those metabolically active cells. Without adequate ATP production, the various organs can start to fail.

Therefore, close monitoring of these electrolytes are warranted to prevent additional organ dysfunction and/or the development of mortality.  

Phosphorous

Phosphorous plays a vital role in intracellular processes, the structural integrity of cells, enzyme and second messenger activation, and oxygen delivery to tissue.

Hypophosphatemia (low phosphorous levels) is the hallmark of refeeding syndrome and a significant cause for development of refeeding syndrome. It develops during the refeeding process when the glucose load of the ingested food increases insulin release, increasing uptake and use of phosphate in the cells. This leads to a deficit of intracellular and extracellular phosphate.

Hypophosphatemia can cause diaphragmatic muscle fatigue, respiratory failure, bursting of red blood cells as they circulate through the bloodstream (hemolysis), rhabdomyolysis (skeletal muscle injury), edema, and seizures.

Potassium

Potassium is essential to nerve and muscle function as well as maintaining normal fluid levels within the cells of the body .³ Like phosphorous, potassium is taken up into cells as they increase in volume and number and as a direct result of insulin secretion, resulting in hypokalemia (low potassium levels).Hypokalemia can cause a wide variety of complications across multiple organ systems:

• Cardiac complications: cardiac arrhythmias, hypotension and cardiac arrest
• Gastrointestinal complications: ileus and constipation
• Renal complications: inability to concentrate urine and abnormalities in other important electrolytes
• Neuromuscular dysfunctions: weakness, paralysis, paresthesia, confusion, rhabdomyolysis and respiratory depression

Magnesium

Magnesium is a vital cofactor in most enzyme systems, necessary for the structural integrity of DNA, RNA and ribosomes and affects membrane potential. Refeeding syndrome is associated with hypomagnesemia (low magnesium levels). Unlike with potassium and phosphorous, the mechanism through which hypomagnesemia is caused by refeeding syndrome is unclear, possibly from intracellular movement of magnesium ions into cells during the refeeding process.

Severe hypomagnesemia can result in cardiac arrhythmias, abdominal discomfort, neuromuscular dysfunctions (tremor, paresthesia, tetany, seizures, weakness and ataxia), irritability and confusion.

Other Substances Associated with Refeeding Syndrome

While serum levels of electrolytes like phosphorous, potassium and magnesium are critical in identifying refeeding syndrome, monitoring glucose, vitamins and body fluid distribution can also be valuable.

Glucose

Glucose ingestion after a period of chronic malnutrition can suppress gluconeogenesis (production of new glucose from non-carbohydrates) through the release of insulin. This surge in insulin can cause hypoglycemia and possibly osmotic diuresis, dehydration, metabolic acidosis and ketoacidosis.^3,4 Excess glucose can also cause lipogenesis, which may cause fatty liver, increased carbon dioxide production, hypercapnia or respiratory failure.

Thiamin (Vitamin B1)

Thiamine is an essential coenzyme in carbohydrate metabolism. It’s believed that carbohydrates introduced during the refeeding process cause an increase in cellular thiamine utilization, leading to Vitamin B1 deficiency.³ Thiamine deficiency can cause Wernicke’s encephalopathy, or Korsakoff’s syndrome in severe long-standing cases.

Body Fluid Distribution

The reintroduction of carbohydrates during the refeeding process rapidly decreases the renal excretion of sodium and water. If fluid repletion is then instituted to maintain a normal urine output, patients may rapidly develop fluid overload. Refeeding with protein or lipids can result in weight loss and urinary sodium excretion, leading to negative sodium balance.

Laboratory Abnormalities Indicating Refeeding Syndrome

Low serum levels of specific electrolytes, including phosphate, magnesium, and potassium are the leading indicators of refeeding syndrome. Other lab tests, like thiamine deficiency (vitamin B1), elevated creatine phosphokinase (CPK) and acute worsening of anemia can suggest developing of refeeding syndrome.

Low Serum Phosphate

Serum levels of phosphorous should be monitored daily for at least the first week of refeeding. Phosphorous should be administered either via the oral route or intravenously (IV), depending on the severity of the deficit. A normal serum phosphorous is considered greater than 2.8 mg/dL.

Low Serum Magnesium

Serum levels of magnesium should be monitored regularly during the refeeding process. Magnesium can also be administered either via the oral or intravenous route, depending on the severity of the deficit. A normal serum magnesium level is considered greater than 1.6 mg/dL.

Low Serum Potassium

Serum levels of potassium should be monitored daily for at least the first week of the refeeding process. Normal concentrations of Potassium (K+) are 3.6-5.2 mmol/L.

Anemia

Hemolysis can develop due to refeeding syndrome. Without adequate ATP, it can be difficult for the red blood cells to maintain appropriate levels of potassium within the cells while exuding sodium outside the cells. This can cause increased water to move into the cells (osmosis), increasing the pressure within the cell and increasing the risk that the red blood cells will lyse as they circulate throughout the bloodstream. Labs suggestive of hemolysis can include increased lactate dehydrogenase (LDH), low haptoglobin, increased unconjugated bilirubin, and increased reticulocytes.

High Creatinine Phosphokinase (CPK)

CPK is an enzyme found in a few different organs but largely in the muscles of the body. An increase in serum CPK levels can be indicative of rhabdomyolysis (muscle breakdown), although the serum values may be difficult to interpret in an individual with malnutrition given the significant muscle loss (atrophy) that results from catabolic state of malnutrition.

Low thiamine

Low serum thiamine (vitamin B1) is an important enzyme involved in the metabolism of carbohydrates. Although low thiamine is not indicative of refeeding syndrome, it is a significant risk factor for the development of refeeding syndrome.

Effective Refeeding Syndrome Treatment Protocols

Effective refeeding is a delicate process. Each patient requires individual care dependent on their weight, rate of weight gain, electrolyte abnormalities, medical complications and clinical presentation.

Correct electrolyte abnormalities before refeeding

Close monitoring of electrolytes, glucose, liver function tests and blood cell counts are very important at baseline and during the refeeding process. Electrolyte deficiencies prior to refeeding significantly increase the risk for development of the refeeding syndrome upon beginning nutritional repletion.

Slowly increase caloric intake

Nutritional rehabilitation for an eating disorder patient should be individualized and increasing caloric intake should be based on the expert opinion of a registered dietician and other clinical team members who have excellent knowledge of eating disorders. Weight gain early in the refeeding process can also be very slow as the body switches from a catabolic state to an anabolic state. It is important not to drastically increase dietary calories during this time.

Clinically monitor patient

During the refeeding process, you should not only monitor lab results but also look out for the physical manifestations and complications that result from refeeding syndrome. This can include:

• Worsening fatigue
• Increasing weakness
• Confusion
• Difficulty breathing
• Seizures
• Irregular heartbeat and other arrhythmias
• Edema
• Heart failure
• Coma

References

• Mehler, P. S., & Andersen, A. E. (2017, November 29). Eating Disorders: A Guide to Medical Care and Complications (third edition). Johns Hopkins University Press.
• 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
• Crook, M., Hally, V., & Panteli, J. (2001, July). The importance of the refeeding syndrome. Nutrition, 17(7–8), 632–637. https://doi.org/10.1016/s0899-9007(01)00542-1
• 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, 1–7. https://doi.org/10.1155/2010/625782
• da Silva, J.S.V., Seres, D.S., Sabino, K., et al. (2020). ASPEN consensus recommendations for refeeding syndrome. Nutrition in Clinical Practice, 35(2): 178-95.