Refeeding syndrome

Definition. A potentially fatal shift of fluid and electrolytes that occurs when nutrition is reintroduced to a malnourished or starved patient, characterised by hypophosphataemia (the hallmark), hypokalaemia, hypomagnesaemia, thiamine deficiency and sodium and water retention.

Pathophysiology. Prolonged starvation shifts metabolism to fat and protein catabolism and depletes intracellular phosphate, potassium and magnesium despite normal serum levels. Reintroduction of carbohydrate triggers insulin release, which drives glucose, phosphate, potassium and magnesium intracellularly, consumes phosphate for ATP and 2,3-DPG synthesis, and depletes thiamine as a cofactor in carbohydrate metabolism; insulin also causes renal sodium and water retention.

Patients at risk (NICE criteria). Any one of — BMI <16 kg/m², unintentional weight loss >15% in 3–6 months, little or no intake for >10 days, or low potassium, phosphate or magnesium before feeding. Or any two of — BMI <18.5, weight loss >10%, negligible intake >5 days, alcohol misuse, or drugs such as insulin, chemotherapy, antacids or diuretics. Relevant geriatric groups: anorexia of ageing, post-stroke dysphagia, cancer cachexia, prolonged hospitalisation, post-operative starvation and alcohol misuse.

Clinical features. Mostly attributable to hypophosphataemia — muscle weakness, rhabdomyolysis, respiratory failure and failure to wean from ventilation, cardiac failure and arrhythmias, delirium, seizures, haemolysis and thrombocytopenia; thiamine deficiency causes Wernicke's encephalopathy and wet beriberi; fluid retention causes oedema and pulmonary congestion. Onset is typically within 72 hours of restarting feeding.

Prevention. Identify risk before feeding begins. Give thiamine 200–300 mg daily orally (or intravenous Pabrinex) together with a vitamin B complex and multivitamins, starting 30 minutes before feeding and continuing for the first 10 days. Start feeding at 10 kcal/kg/day — or 5 kcal/kg/day in extreme risk (BMI <14 or negligible intake for >15 days) — and increase slowly to full requirements over 4–7 days. Restrict sodium and fluid, and avoid rapid volume expansion.

Monitoring and treatment. Check potassium, phosphate, magnesium, calcium and glucose before feeding, then daily for the first 3 days and on alternate days for the first week. Correct electrolytes concurrently but do not delay feeding to do so — replace phosphate (intravenously if <0.6 mmol/L), potassium approximately 2–4 mmol/kg/day and magnesium 0.2–0.4 mmol/kg/day. Monitor fluid balance, daily weight and ECG; reduce or temporarily hold the feed if severe biochemical disturbance or cardiac failure develops.

ASPEN consensus recommendations for refeeding syndrome (Nutr Clin Pract/JPEN 2020) — provided the first standardised definition and severity grading: refeeding syndrome is a fall in serum phosphate, potassium and/or magnesium of 10–20% (mild), 20–30% (moderate), or >30% with organ dysfunction (severe), occurring within 5 days of restarting or substantially increasing nutrition. It recommends starting with 100–150 g of dextrose or 10–20 kcal/kg in the first 24 hours, advancing by about 33% of the goal every 1–2 days, with thiamine given before feeding and continued for 5–7 days or longer in high-risk patients.