Title: Refeeding hypophosphataemia

 

Key words: refeeding syndrome, electrolytes, oral, parenteral, enteral feeding, starvation, anorexia, cancer, ICU, total parenteral nutrition, TPN, weight loss, malnutrition, acid-base balance, glucose, potassium, magnesium, phosphorus, insulin, nutritional deprivation, phospholipids, phosphorylation, red cells, haemoglobin, hypoxia, hypophosphataemia, homeostasis, calcium, cell membrane potentials, muscular, muscle weakness, spasm, neurological disturbances, paralysis, myopathy, cardiomyopathy, rhabdomyolysis, seizures, paraesthesiae, thiamine, cognitive defects, nerve conduction, haematological, thrombocytopaenia, renal function, tubular necrosis, Vannatta regimen, plasma phosphate, hyperphosphataemia

 

Date: Oct 2006

 

Category:

 

Nutrimed Module:

 

Type: Article

 

Author: Morgan, G

 

Refeeding hypophosphataemia

 

The “refeeding syndrome” refers to a state of electrolyte, metabolic and physiologic imbalance induced in patients recommencing feeding, either orally, enterally or parentally, after a period of starvation or weight loss. It has been observed following starvation, in anorexics, in cancer patients, in ICU cases, and in those undergoing total parenteral nutrition. In general it occurs within the first week of refeeding though, in some ICU cases undergoing TPN, it has been recorded within the first 48 hours (Marik 1996). There is a strong association with weight loss and malnutrition (Mezoff 1989, Crook 2001), the incidence amongst anorexics, for example, being 27% in one series (Ornstein 2003), the severity of the syndrome being directly linked to weight loss (McClain 1993, Ornstein 2003).

 

In a series of cancer patients there was an incidence of 25%, which was higher in those receiving TPN (Gonzalez 1996). Starvation and malnutrition are associated with cell membrane disturbances, changes in acid-base balance, and changes in glucose and other metabolic pathways. Intracellular losses of potassium, magnesium and phosphorus occur and there is a down-regulation of insulin-mediated glucose metabolism. A too rapid restoration of glucose intake following nutritional deprivation can lead to major fluxes of these electrolytes back into cells from the extracellular compartment. Drops in plasma phosphate levels, in particular, can lead to severe clinical repercussions (Paula 1998). A low metabolic pool of phosphorus has profound implications to many intracellular systems. Phosphorus is a key structural component of nuclear proteins, phospholipids and enzymes, plays a central role in glycolysis and oxidative phosphorylation, and, through 2,3- diphosphoglycerate, plays an important role in red cell stability and the dissociation of oxygen from haemoglobin. Hypophosphataemia leads to poor oxygen transport, relative tissue hypoxia and acidosis, reduced oxidative phosphorylation and ATP production, and a major dysregulation of important metabolic pathways (Crook 2001). The close association of phosphorus with calcium homeostasis, coupled with dysregulation of magnesium and ATP function, leads to major disturbances in cell membrane potentials. Both muscular and neurological disturbances may ensue. Neuromuscular dysfunction may lead to muscle weakness, spasm, and even paralysis. Respiratory failure secondary to diaphragmatic paralysis has been reported (Newman 1977). Myopathy, cardiomyopathy, and rhabdomyolysis have also been described (Crook 2001). Neurologically, seizures, paraesthesiae, cognitive and other neurological disturbances, indicative of nerve conduction defects, have been reported (Silva 1980). Thiamine deficiency, not an uncommon accompaniment to the refeeding syndrome, may compound these neurological disorders (Solomon 1990).

 

Several haematological functions are affected by hypophosphataemia. White cell activity is impaired, a relative thrombocytopaenia with poor clotting may occur, and red cell membrane stability is affected – this coupled with reduced 2,3-diphosphoglycerate levels predisposes red blood cells to haemolysis (Crook 2001).

 

Hypophosphataemia also leads to reduced renal function. Acute tubular necrosis has in addition been reported secondary to rhabdomyolysis (Crook 2001) These and other disturbances play an important role in the acid-base, fluid and physiologic changes seen in the refeeding syndrome. Fluid, electrolyte, conduction disorders and cardiomyopathy play a critical role in the high morbidity associated with the syndrome. Given the important part played by hypophosphataemia in this disorder, it is therefore of vital importance to monitor and correct any changes occurring in phosphorus homeostasis during the refeeding period. This implies daily monitoring of serum phosphorus during this period, along with the other critical electrolytes: sodium, potassium, magnesium and calcium. Fluid status and renal function should also be monitored. Urinary electrolyte estimations are helpful, particularly to detect sodium losses. Electrolyte imbalances should be corrected prior to refeeding and refeeding commenced at around 20 Kcal/Kg per day, increasing over the course of the week. Prophylactic thiamine should also be given. Following such protocols, hypophosphataemia is a rare development. In one series of patients fasted for 43 days, following a 9-day refeeding programme, no cases of hypophosphataemia were reported amongst the 8 hunger strikers (Faintuch 2001). In those with cancer or anorexia nervosa, weight loss and more severe nutritional deficiencies increase the likelihood of hypophosphataemia considerably. The use of Vannatta regime, giving 9 mmol of phosphate intravenously over 12 hours was recommended for many years (Vannatta 1981). It is now thought that giving 50 mmol of phosphate over 24 hours in severe cases (plasma phosphate <0.30 mmol/L) is safe.

In one series of 30 cases given this intensive regime, only 3 cases of transient hyperphosphataemia were reported, none serious (Terlevich 2003). With careful monitoring this regime appears to be safe and is now the recommended protocol. 

 

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