カテゴリー 栄養 の記事一覧


更新日時: 2013/01/09  カテゴリ: ポケットガイド, 栄養

Refeeding syndrome: what it is, and how to prevent and treat it
Hisham M Mehanna, Jamil Moledina and Jane Travis
BMJ 2008;336;1495-1498



The hallmark biochemical feature of refeeding syndrome is hypophosphataemia.However, the syndrome is complex and may also feature abnormal sodium and fluid balance; changes in glucose, protein, and fat metabolism; thiamine deficiency;hypokalaemia; and hypomagnesaemia.


Studies report a 100% incidence of hypophosphataemia in patients receiving total parenteral nutrition solutions that do not contain phosphorus. When solutions containing phosphate are used, the incidence can decrease to 18%.



The net result of metabolic and hormonal changes in early starvation is that the body switches fromusing carbohydrate to using fat and protein as the main source of energy, and the basal metabolic rate decreases by as much as 20-25%.
During prolonged fasting, hormonal and metabolic changes are aimed at preventing protein and muscle breakdown. Muscle and other tissues decrease their use of ketone bodies and use fatty acids as the main energy source. This results in an increase in blood levels of ketone bodies, stimulating the brain to switch from glucose to ketone bodies as its main energy source. The liver decreases its rate of gluconeogenesis, thus preserving muscle protein. During the period of prolonged starvation, several intracellular minerals become severely depleted. However, serum concentrations of these minerals (including phosphate) may remain normal. This is because these minerals are mainly in the intracellular compartment, which contracts during starvation. In addition, there is a reduction in renal excretion.


During refeeding, glycaemia leads to increased insulin and decreased secretion of glucagon. Insulin stimulates glycogen, fat, and protein synthesis. This processrequires minerals such as phosphate and magnesium and cofactors such as thiamine. Insulin stimulates the absorption of potassium into the cells through thesodium-potassium ATPase symporter, which also transports glucose into the cells. Magnesium and phosphate are also taken up into the cells. Water followsby osmosis. These processes result in a decrease in the serum levels of phosphate, potassium, and magnesium, all of which are already depleted. The clinical features of the refeeding syndrome occur as a result of the functional deficits of these electrolytes and the rapid change in basal metabolic rate.


Phosphorus is predominantly an intracellular mineral. It is essential for all intracellular processes and for the structural integrity of cell membranes. In addition, manyenzymes and second messengers are activated by phosphate binding. Importantly it is also required for energy storage in the form of adenosine triphosphate (ATP). It regulates the affinity of haemoglobin for oxygen and thus regulates oxygen delivery to tissues. It is also important in the renal acid-base buffer system. In refeeding syndrome, chronic whole body depletion of phosphorus occurs. Also, the insulin surge causes a greatly increased uptake and use of phosphate in the cells. These changes lead to a deficit in intracellular as well as extracellular phosphorus. In this environment, even small decreases in serumphosphorus may lead to widespread dysfunction of cellular processes affecting almost every physiological system (see box A on bmj.com).


Potassium, the major intracellular cation, is also depleted in undernutrition. Again, serum concentrationmayremain normal. With the change to anabolism on refeeding, potassium is taken up into cells as they increase in volume and number and as a direct result of insulin secretion. This results in severe hypokalaemia. This causes derangements in the electrochemical membrane potential, resulting in, for example,arrhythmias and cardiac arrest.


Magnesium, another predominantly intracellular cation, is an important cofactor in most enzyme systems, including oxidative phosphorylation and ATP production. It is also necessary for the structural integrity of DNA, RNA, and ribosomes. In addition,it affects membrane potential, and deficiency can lead to cardiac dysfunction and neuromuscular complications.


Glucose intake after a period of starvation suppresses gluconeogenesis through the release of insulin. Excessive administration may therefore lead to hyperglycaemiaand its sequelae of osmotic diuresis, dehydration, metabolic acidosis, and ketoacidosis. Excess glucose also leads to lipogenesis (again as a result of insulin stimulation), which may cause fatty liver, increased carbon dioxide production, hypercapnoea, and respiratory failure.


Although all vitamin deficienciesmay occur at variable rates with inadequate intake, thiamine is of most importance in complications of refeeding. Thiamine is an essential coenzyme in carbohydrate metabolism. Its deficiency result in Wernicke’s encephalopathy (ocular abnormalities, ataxia, confusional state, hypothermia, coma) or Korsakoff’s syndrome (retrograde and anterograde amnesia, confabulation).


Changes in carbohydrate metabolism have a profound effect on sodium and water balance. The introduction of carbohydrate to a diet leads to a rapid decrease inrenal excretion of sodium and water.20 If fluid repletion is then instituted to maintain a normal urine output, patients may rapidly develop fluid overload. This canlead to congestive cardiac failure, pulmonary oedema, and cardiac arrhythmia.



Plasma electrolytes (especially phosphate, sodium, potassium, and magnesium) and glucose should be measured at baseline before feeding and any deficiencies corrected during feeding with close monitoring.


The NICE guidelines recommend that refeeding is started at no more than 50% of energy requirements in “patients who have eaten little or nothing for more than 5 days.” The rate can then be increased if no refeeding problems are detected on clinical and biochemical monitoring (level D recommendation.see box 3).

ハイリスク患者では、最大でも 10kcal/kg/24時間の栄養投与から始め、モニタリングしながら徐々に増量する。4~7日かければ予定の全投与量が達成できる。

For patients at high risk of developing refeeding syndrome, nutritional repletion of energy should be started slowly (maximum 0.042 MJ/kg/24 hours) and should be tailored to each patient.

非常に栄養状態が不良な患者(BMI<14あるいは2週間以上の飢餓状態)の場合、最大でも 5kcal/kg/24時間の栄養投与で開始し、循環モニタリングも密に行う。

In patients who are very malnourished (body mass index .14 or a negligible intake for two weeks or more), the NICE guidelines recommend that refeeding should start at a maximum of 0.021 MJ/kg/ 24 hours, with cardiac monitoring owing to the risk of cardiac arrhythmias.


The NICE guidelines also state that correcting electrolyte and fluid imbalances before feeding is not necessary and that this should be done along with feeding.


Good quality studies on the exact levels of supplementation are lacking.


A prospective comparative cohort study of 27 patients with severe hypophosphataemia showed the safety of administering 15-30 mmol phosphate over three hours via a central venous catheter in an intensive care unit.


Terlevich et al reported efficacy of 50 mmol phosphate infused into a peripheral vein over 24 hours in 30 patients with no pre-existing renal dysfunction on general wards.