Refeeding Syndrome

The syndrome is under recognized and can be fatal.

The principle metabolic effects include:

• Hypophosphataemia (hallmark feature)
• Hypokalaemia
• Hypomagnesaemia
• Acute thiamine deficiency.

Patients at risk of refeeding syndrome should be referred to

• Specialist Dietitian
• Gastroenterologist

Pathophysiology

Refeeding syndrome is most likely to occur in the first week of refeeding. It results from rapid shifts in electrolytes as well as rapid thiamine depletion. Physiological effects of acute refeeding in a seriously starved patient include

• Hypophosphataemia
• Insulin release
• Thiamine depletion

Hypophosphataemia

The body enters into fasting (starvation) state and becomes catabolic (breaking down muscle mass). Phosphate is lost from muscle, then lost from the body in the urine. Though serum phosphate levels can be normal, total body stores are depleted. Severe hypophosphataemia can be precipitated by:

• Increased glycolysis (which generates ATP by utilizing phosphate) during refeeding with carbohydrates when carbohydrate replaces body fat as the main source of energy.
• Cellular reuptake via insulin.

The already depleted phosphate stores are further reduced, leading to significant hypophosphataemia.

Insulin release

On refeeding, the patient begins to use glucose as the primary source of energy. This results in greatly increased insulin release. As glucose is taken up into the cells, so too is potassium and magnesium, which can lead to

• Hypokalaemia
• Hypomagnesaemia

Thiamine depletion

Any available thiamine is rapidly utilised as a coenzyme for the increased carbohydrate metabolism. Glycolysis-induced thiamine depletion can lead to Wernicke encephalopathy.

Risk assessment

HIGH RISK: Patients classified as high risk have two or more of the following:

• BMI less than 18.5 kg/m2 
• Frail elderly patients assessed by the dietitian as being at nutritional risk
• Unintentional weight loss greater than 10% within the last 3 – 6 months
• Little or no nutritional intake for more than 5 days
• Morbidly obese patients with rapid weight loss (e.g. after gastric ballooning or banding)
• Oncology therapy (i.e chemo or radiation treatments) especially head/neck/gastrointestinal patients
• Major stressors without food for > 3 days
• Post-operative or fasted for long periods of time

EXTREMELY HIGH RISK: Patients classified as extremely high risk have one or more of the following:

• BMI less than 16 kg/m2
• Anorexia nervosa
• Unintentional weight loss greater than 15% within the last 3 – 6 months (includes obese patients)
• Little or no nutritional intake for more than 10 days
• Low levels of potassium, phosphate or magnesium prior to feeding
  • However normal serum levels do not mean that the patient is not at risk. Their total body stores may be significantly depleted
• Chronic malnutrition:
  • Alcoholism
  • Marasmus
  • Kwashiorkor
  • Hunger strikers
  • Malabsorption states

Clinical features

Clinical features of refeeding syndrome include:

Severe hypophosphataemia which may result in:

• Neuromuscular disturbances:
  • Progressive myopathy to paralysis
  • Confusion and seizures.
• Cardiorespiratory disturbances:
  • Respiratory muscular failure.
  • Heart failure
  • Arrhythmias.
• Haematological disturbances:
  • Haemolysis
  • Impaired leukocyte function
  • Thrombocytopenia
• Rhabdomyolysis

Hypomagnesaemia which may result in:

• Arrhythmias
• Seizures

Hypokalaemia which may result in:

• Arrhythmias 
• Muscle weakness

Acute thiamine deficiency:

• Wernicke’s encephalopathy.

Investigations

• FBC
• U&Es/ glucose
• Magnesium
• Calcium/ Phosphate
• LFTs
• Folate/ B12

Management

Feeding is commenced with concurrent electrolyte and thiamine replacement. Close laboratory monitoring is required. Close guidance by a Dietician is required.

1. Fluid resuscitation (as required)

Care must be taken to avoid fluid overload. In the severely starved individual, cardiac mass may be significantly depleted, leading to the risk of fluid overload and cardiac failure if fluid provision is too rapid.

2. Calories:

Start slowly (e.g. 30% to 50% of estimated caloric requirement) and increase gradually over a week to the patient’s estimated needs.

3. Micronutrients:

Multivitamin and trace element supplementation:

• Zinc/ iron/ selenium
• Folate/ B12/ B6 (pyridoxine)/ Fat soluble vitamins

4. Thiamine:

Thiamine 100 mg b.d at least 30 minutes before each feeding.

5. Potassium:

The amount and route of administration will be determined by the severity of deficiency. Exact dosing regimens should be guided by a Dietician or Gastroenterologist

In general terms:

• Normal level of potassium is 3.5 – 5.0 mmol / L
• Low normal                           3.5 – 4.0 mmol / L
• Mild hypokalaemia                 3.0 – 3.5 mmol / L
• Moderate hypokalaemia        2.5 – 3.0 mmol / L
• Severe hypokalaemia              Less than 2.5 mmol / L.

           

6. Magnesium:

The amount and route of administration will be determined by the severity of deficiency. Exact dosing regimens should be guided by a Dietician or Gastroenterologist

In general terms:

• Normal                                               0.8 to 1.0 mmol/L
• Mild hypomagnesaemia                   0.6 – 0.8 mmol / L
• Moderate hypomagnesaemia           0.4 – 0. 6 mmol / L.
• Severe hypomagnesaemia                < 0.4 mmol / L.

7. Phosphate:

The amount and route of administration will be determined by the severity of deficiency. Exact dosing regimens should be guided by a Dietician or Gastroenterologist

In general terms:

• Normal:          0.8 mmol/L – 1.5 mmol/L.
• Mild hypophosphataemia:               0.7 – 0.8 mmol/L.
• Moderate hypophosphataemia:      0.50 – 0.7 mmol/L.
• Severe hypophosphataemia:            ≤ 0.5 mmol/L.

Disposition

Patients at risk of refeeding syndrome should be referred to:

• Specialist Dietitian
• Gastroenterologist. 
• Severe cases should also be referred to HDU/ICU.

References

FOAMed

• Nickson C. Refeeding Syndrome. CCC

Publications

• han LU, Ahmed J, Khan S, Macfie J. Refeeding syndrome: a literature review. Gastroenterol Res Pract. 2011;2011:410971.
• Mehanna HM, Moledina J, Travis J. Refeeding syndrome: what it is, and how to prevent and treat it. BMJ. 2008 Jun 28;336(7659):1495-8