Refeeding syndrome is a constellation of electrolyte abnormalities caused by the sudden feeding of a well starved individual. The potentially deadly combination of profound hypophosphataemia with hypokalaemia and hypomagnesaemia probably needs some kind of clinical manifestation to actually be refeeding syndrome.
At risk patients
Patients deep in the starvation response become at risk as the body stores of various electrolytes slowly make their way into the toilet without being replaced.
NICE says that these are the risk factors:
- Low body mass index (BMI).
- Unintentional weight loss.
- Starvation.
- History of alcohol abuse.
- Low initial electrolyte concentrations.
So really anybody that is chronically malnourished.
Mechanisms
Insulin’s effect
The physiological response to feeding causes insulin secretion which shifts potassium intracellularly. This occurs on reactivation of the sodium/potassium pump.
Phosphate is also shuttled into the cells, which is a necessary evil because insulin puts glucose in the cell and hexokinase needs to phosphorylate this glucose and stop it from going outside again. The ultimate outcome of this is the inability to sustain ATP production though oxidative phosphorylation which arrests most of the body’s metabolic pathways. Depletion of phosphate also leads to decreased synthesis of 2,3-bisphosphogylcerate which shifts the oxygen-haemoglobin dissociation curve left and leaves haemoglobin clinging to oxygen, further complicating the metabolic failure.
Electrolyte exchange
Magnesium falls as well on refeeding, for reasons the author will investigate later. It is probably to do with the combination of rapidly synthesis of ATP resulting in depletion of magnesium and insulins inhibitory effect on cellular magnesium efflux (see cellular mechanisms of magnesium homeostasis). One could reasonably assume then that the former mechanism depletes intercellular magnesium stores and results in import of extracellular magnesium the latter prevents an increase in extracellular concentrations to support the increasing cellular requirement. As a result, the serum concentrations fall.
Clinical manifestations
The complications of refeeding syndrome are extensive and can cause failure of various organ systems. They are divided below the causative electrolyte abnormality.
Hypophosphataemia
- Heart failure
- Arrhythmia
- Cardiogenic shock
- Acute tubular necrosis
- Metabolic acidosis
- Rhabdomyolysis
- Diaphragmatic (and other muscle) weakness
- Tetany
- Delerium and coma
- Seizure
- Hyperglycaemia and insulin resistance
- Haemolysis
- Platelet dysfunction and/or thrombocytopaenia
- Leukocyte dysfunction
- Decreased 2,3-BPG synthesis
Hypokalaemia
- Arrhythmia
- Hypoventilation
- Weakness and/or muscle twitching
- Gastrointestinal dysfunction, including ileus
- Metabolic alkalosis
- Seizure
- Rhabdomyolysis
- Liver failure
Hypomagnesaemia
- Arrhythmias
- Seizures
- Tetany
- Confusion and ataxia
- Tremor
- Paraesthesia and weakness
- Poor response to potassium replacement (if also hypokalemic)
- Hypocalcaemia (as magnesium is required for optimal action of parathyroid hormone)
(Preexisting) thiamine deficiency
- Wernicke/Korsakoff
- Heart failure
- Lactic acidosis
- Beriberi
Sodium…
Can go up or down.
Management
Prevention is ideal: identify at risk patients, monitor them, and refeed them slowly. Replace electrolytes proactively if reasonable. If the syndrome develops, management entails correction of the electrolyte (and fluid) abnormalities.
Feeding should be commenced slowly, usually with guidance of the dietician. Initial caloric load should be about 30% of total requirement.
- Staring at 10kcal/kg/day (NICE).
- Increase in increments of 10% of total calorie requirement. NICE recommends increasing to fulfil requirements over 4 to 7 days.
- Patients should also be supplemented with: thiamine (at least 200mg daily), a vitamin B complex, and a balanced multivitamin.
Monitoring
Patients identified as high risk should have serum electrolytes monitored at least daily for the first 3 to 5 days. Then every two days until day 7, and weekly thereafter if abnormalities persist.
- Regular clinical monitoring.
- Blood pressure and pulse.
- If required, catheterisation to monitor urine output.
- In severe cases, ICU might be a good idea.
Electrolyte replacement
If the patient is sick, you probably need central access for aggressive replacement.
Further reading
- De Silva A, Nightingale JMD. Refeeding syndrome : physiological background and practical management. Frontline Gastroenterol. 2020 Sep;11(5):404–9.
- Khan LUR, Ahmed J, Khan S, MacFie J. Refeeding Syndrome: A Literature Review. Gastroenterology Research and Practice. 2011;2011:1–6.