Refeeding Syndrome
NICE Clinical guideline [CG32] Nutrition support for adults: oral nutrition support, enteral tube feeding and parenteral nutrition. Last updated: Aug 2017.
Background Information
Definition
Refeeding syndrome is defined as a potentially life-threatening condition: [Ref]
- That may develop in severely malnourished patients / after prolonged starvation at the initiation of nutritional therapy (e.g. feeding)
- It is characterised by rapid shifts of phosphate, potassium, and magnesium into cells
Pathophysiology
Refeeding syndrome occurs when nutritional therapy is introduced too rapidly in patients who are severely malnourished or have experienced prolonged starvation [Ref]
- Prolonged starvation or severe malnutrition leads to reduced insulin secretion and a catabolic state → depletion of intracellular phosphate, potassium, magnesium, and thiamine
- Initiation of nutritional therapy (esp. with carbohydrate) triggers a surge in insulin secretion
- Insulin promotes cellular uptake of glucose, phosphate, potassium, and magnesium → rapid shift of these electrolytes from the serum into cells → hypophosphatemia, hypokalemia, and hypomagnesemia.
- Increased metabolic activity during refeeding increases thiamine requirements → Wernicke’s encephalopathy (as intracellular thiamine has already been depleted)
The hallmark of refeeding syndrome is hypophosphataemia. [Ref]
While hypokalemia and hypomagnesemia are also common and clinically relevant, hypophosphatemia is the earliest and most prominent laboratory abnormality, often preceding other electrolyte disturbances.
Risk Factors
NICE states that a patient is at high risk of developing refeeding syndrome if they meet either of the following criteria:
| At least 1 of the following: | 2 or more of the following: |
|
NB the first 2 points (BMI and weight loss bit) are also used to define malnutrition, see the malnutrition and risk section |
Diagnosis
Clinical Manifestation
Classic clinical symptoms: [Ref]
- Tachycardia and tachypnoea (from the hypophosphataemia)
- Oedema (peripheral / pulmonary) (driven by insulin-mediated renal sodium reabsorption)
The clinical manifestation of refeeding syndrome is directly related to the specific electrolyte deficits: [Ref1][Ref2]
| Deficit | Clinical manifestation |
|---|---|
| Phosphate | Cardiac and respiratory failure (due to impaired ATP production and muscle weakness) |
| Potassium | Cardiac arrhythmias (esp. ventricular arrhythmias)
Also see the Hypokalaemia article |
| Magnesium | Neuromuscular irritability, tetany, arrhythmias (QTc prolongation)
Also see the Hypomagnesaemia article |
| Thiamine | Wernicke’s encephalopathy (triad of altered mental status + ocular abnormalities + ataxia), or even wet beriberi
Also see the Wernicke Encephalopathy and Korsakoff Syndrome article |
Investigation and Diagnosis
Biochemical findings in refeeding syndrome: [Ref]
- ↓ Serum phosphate – hallmark
- ↓ Serum potassium
- ↓ Serum magnesium
- ↑ Serum glucose (due to reintroduction of nutrition, esp. carbohydrates)
The hallmark of refeeding syndrome is hypophosphataemia. [Ref]
While hypokalemia and hypomagnesemia are also common and clinically relevant, hypophosphatemia is the earliest and most prominent laboratory abnormality, often preceding other electrolyte disturbances.
Management
Refeeding Syndrome Prevention
Feeding in High-Risk Individuals
NICE states that a patient is at high risk of developing refeeding syndrome if they meet either of the following criteria:
| At least 1 of the following: | 2 or more of the following: |
|
NB the first 2 points (BMI and weight loss bit) are also used to define malnutrition, see the malnutrition and risk section |
Key considerations when introducing nutrition in patients at risk of refeeding syndrome:
| Feeding requirements and amount | Most patients: start at a maximum of 10 kcal/kg/day, and increase slowly over 4–7 days to meet full needs
In extreme cases (e.g. BMI <14 kg/m2 or negligible intake for >15 days) → start at 5 kcal/kg/day and perform continuous cardiac monitoring |
| Electrolyte supplementation | Provide the following electrolyte supplements (unless pre-feeding levels are high):
|
| Vitamin supplementation | Provide the following immediately before and during the first 10 days of feeding:
|
It is important to identify and correct any pre-feeding electrolyte imbalances (esp. hypophosphataemia, hypokalaemia, hypomagnesaemia)
Feeding in Medium Risk Individuals
Medium risk individuals are those who have eaten little or nothing for >5 days (but do NOT meet the high-risk criteria)
- These patients should start at ≤50% of their requirements for the first 2 days
- The routine requirements are (see the Nutrition Support and Feeding article for more information)
- Total energy: 25-35 kcal/kg/day
- Protein: 0.8-1.5 g/kg/day
- Fluid: 30-35 mL/kg/day
Enteral / Parenteral Nutrition in Seriously Ill or Injured Individuals
Seriously ill or injured individuals who are receiving enteral / parenteral nutrition should be started at ≤50% of their requirements and built up to meet full needs over the first 24 to 48 hours according to metabolic and GI tolerance.
The routine requirements are (see the Nutrition Support and Feeding article for more information)
- Total energy: 25-35 kcal/kg/day
- Protein: 0.8-1.5 g/kg/day
- Fluid: 30-35 mL/kg/day
Refeeding Syndrome Management
Management for patients who have already developed refeeding syndrome: [Ref]
- Immediately reduce caloric and fluid delivery
- Correct any low serum levels of phosphate, potassium and magnesium
- Treat thiamine deficiency (usually with IV Pabrinex)
- Slowly increase nutrients and fluids to recommended levels over 4 to 7 days
Careful monitoring of serum phosphate, potassium, magnesium, and thiamine is essential.