Refeeding Syndrome - Causes, Prevalence, Complications, and Treatment

What Is Refeeding Syndrome?

Refeeding syndrome is a clinical complication when a patient is given nutrition after prolonged starvation. It is a medical complication associated with nutrition replenishment seen in malnourished persons, those having eating disorders like anorexia nervosa (a condition characterized by low body weight), and on hemodialysis (as seen in renal failure patients). As soon as the patients start eating, fluids and electrolytes balance shift, metabolic activities get disturbed, and cardiopulmonary, neurological, and renal dysfunctions occur.

The characteristics of refeeding syndrome are hypophosphatemia (when the serum phosphate level is less than 2.5 mg/dL), hypokalemia (serum potassium level less than 3.5mEq/L), hypomagnesemia (serum magnesium level less than 1.8 mg/dL) abnormal blood glucose levels, and thiamine deficiency, making this syndrome a highly morbid and mortal condition requiring immediate medical treatment. Evidence proves that more prolonged periods of starvation lead to death following nutritional and vitamin replenishment.

What Is the Etiology of the Refeeding Syndrome?

The genesis of refeeding syndrome is considered to be multifactorial. Usually, the malnourished patients, when suddenly fed after a long period of starvation, are the primary sufferers of the syndrome. The leading causes of refeeding syndrome include:

• Chronic alcoholism.

• Poorly controlled diabetes.

• Chronic malnutrition.

• Inflammatory bowel disease.

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• Oncological conditions.

• Post-operative state.

What Is the Prevalence of the Syndrome?

As per the National Institute for Healthcare and Excellence guidelines, the following risk factors are accountable for refeeding syndrome - low body mass index (BMI), unintentional weight loss, low initial electrolyte concentrations, alcohol abuse history, and starvation. Hypophosphatemia is a clinical sign of refeeding syndrome. The prevalence of refeeding syndrome is still undefined as there is no uniform study methodology. In a study conducted on ICU patients, it has been seen that 34% of the patients show nutritional replenishment following feeding after days of starvation. In critical care units, the patients suffering from refeeding syndrome show hyperglycemia and increased insulin levels associated with TPN (total parenteral nutrition), thus leading to electrolyte imbalance.

How Does It Occur?

When a patient is starving for a more extended period, gluconeogenesis and proteolysis increase. Also, there is a depletion of vitamins and intracellular electrolytes. As the sequence continues, there is an increase in glucose levels in the bloodstream, due to which a rise in insulin levels occurs.

Hypokalemia: There is an intracellular movement of phosphorus and potassium, resulting in a decrease in extracellular levels of potassium. An increase in insulin and intracellular migration of electrolytes causes an electrolyte imbalance. Hypokalemia is responsible for causing severe diseases like cardiac arrhythmias, generalized weakness, respiratory distress, fatigue, paralysis, hypoventilation, etc.

Hypophosphatemia: It follows the exact pathophysiology of hypokalemia. If the starvation continues, the phosphorus reserves start depleting as phosphorus is a critical component required for forming ATP (adenosine triphosphate) and plays a significant role in the heart's conduction. Decreased levels of phosphorus, called hypophosphatemia, cause fatal conditions like cardiac arrhythmias and contractility. Also, these decreased levels are accountable for a decrease in 2, 3 diphosphoglycerate (2,3 DPG), leading to a high affinity of hemoglobin for oxygen. Thus, the release of oxygen to tissues is diminished. This causes secondary organ failure due to a poor prognosis. Hypophosphatemia also causes acute respiratory failure.

Hypomagnesemia: It is associated with refeeding syndrome; however, it worsens hypokalemia. Enzymes involved in the process of formation of ATP are seen to be dependent on the levels of manganese, too, therefore, decreased levels of manganese are associated with many neuromuscular disorders like ataxia convulsions, vomiting, vertigo, paresthesia, etc. in the patients suffering from refeeding syndrome.

What Is the Relation Between Refeeding Syndrome And Thiamine?

Refeeding syndrome is usually seen to be associated with thiamine. For the metabolism of glucose, thiamine is required. Thiamine levels increase in patients suffering from starvation as there is a replenishment of nutrients, but lactate levels are stored up. Due to insufficient amounts of thiamine, cardiac dysfunction occurs. Karsakoff’s encephalopathy and Wernick’s diseases occur due to deficiency of thiamine; the classical triad of this disease is ophthalmoplegia, gait disturbances, and mental status changes like hallucinations and confabulations. A shortage of thiamine also causes alcohol abuse.

What Are the Complications?

Refeeding syndrome affects different organ systems in humans. Following are the complications associated with this syndrome:

• Cardiac arrest.

• Fluid retention.

• Paralysis.

• Seizures.

• Confusion.

• Respiratory distress.

• Bowel changes.

• Cardiac arrhythmia - Irregular heartbeat, either tachycardia (fast heartbeat) or bradycardia (slow heartbeat).

How Does It Get Treated?

• To the patients who are in hospital for a prolonged duration or are being metabolically starved, enteral feeding is given initially.

• The focus is to be given to carefully depleting nutrients and conserving calories. Patients suffering from critical burns are also given enteral feeding rather than parenteral, depending upon the parent’s tolerance level.

• Gut flora preservation, immunity development, and systemic bacteria reduction are crucial factors for treating the refeeding syndrome.

• L-arginine and glutamine supplements are required for maintaining these factors.

• Potassium, phosphorus, and manganese levels should be monitored before nutritional replenishment. The nutritional replenishment should be delayed in case any of these minerals are decreased.

• Electrolyte monitoring should also be done after 12 hours for the first three days in high-risk patients.

What Do the Studies Suggest for Management?

As per the ASPEN’S guidelines, before the initiation of dextrose supplement intake in the patients, 100 mg thiamine is to be administered. Thiamine levels are to be checked regularly. There must be protein restriction, no use of fluids, sodium intake, and vitals should be monitored every four hours in high-risk patients.

According to the National Institute for Health and Clinical Excellence (NICE), high-risk patients need to undergo- weight fluctuations check, screening for previous alcohol use, and nutritional assessment. There must be an evaluation of all potassium, phosphorus, and magnesium levels as the nutritional replenishment is associated with specific electrolytes such as potassium- 2 to 4 mmol/kg/day, phosphate - 0.3 to 0.6 mmol/kg/day, magnesium- 0.2 mmol/kg/day to be given. 100 mg thiamine should be issued 30 minutes before the nutritional replenishment, which is to be continued for seven to ten days to prevent neurological complications.

What Is the Differential Diagnosis of the Syndrome?

In the case of refeeding syndrome, the differential diagnosis is difficult as other medical conditions need to be ruled out as well. There can be fluid overload resulting in the depletion of many electrolytes like sodium, potassium, magnesium, and phosphorus. Due to this electrolyte imbalance, high-risk patients suffering from cardiac arrhythmias show long QT segments.

How Does the Prognosis Go?

In mild electrolyte imbalance, the patients may not show apparent symptoms, and the refeeding syndrome remains unpredicted. The prognosis is based on biochemical and electrolyte changes. The patients show comorbidities in cases where symptoms do not subside but are exaggerated by alcohol abuse; thus, the prognosis worsens.

Conclusion:

Refeeding syndrome is a metabolic condition that mainly affects individuals undergoing prolonged starvation or those hospitalized for a longer duration. As soon as the nutritional replenishment begins, three primary disorders- hypokalemia, hypophosphatemia, and hypomagnesemia thus decrease the levels of nutrition. The management requires the proper monitoring and care of the patient as he starts getting fed. Many studies provide guidelines regarding the control of the syndrome.