- Email: [email protected]
Magnesium and phosphorus
CORRESPONDENCE
between plasma (or serum) magnesium and intracellular concentrations, for example, in erythrocytes or muscle cells (irrespective of measuring ionised or total magnesium). Serum total magnesium can be normal in the presence of intracellular depletion. 4 Thus, among patients at risk for magnesium deficiency, oral supplementation of magnesium may be warranted, even if serum (total) magnesium concentration is within the normal range.5 Renal impairment is a common relative contraindication. P Schuck, G Gammelin, *K L Resch Saxon Balneology and Rehabilitation Medicine Research Institute, Lindenstr 5, D-08645 Bad Elster, Germany (e-mail: [email protected]) 1
2
3
4
5
Weisinger JR, Bellorín-Font E. Magnesium and phosphorus. Lancet 1998; 352: 392–96. Whang R, Hampton EM, Whang DD. Magnesium homeostasis and clinical disorders of magnesium deficiency. Ann Pharmacother 1994; 28: 220–26. Herbert P, Mehta N, Wang J, Hindmarsh T, Jones G, Cardinal P. Functional magnesium deficiency in critically ill patients identified using a magnesium-loading test. Crit Care Med 1997; 25: 749–55. Al-Ghamdi SMG, Cameron EC, Sutton RAL. Magnesium deficiency: pathophysiologic and clinical overview. Am J Kidney Dis 1994; 24: 737–52. Durlach J, Bac P, Durlach V, Bara M, Guiet-Bara A. Neurotic, neuromuscular and autonomous nervous form of magnesium imbalance. Magnes Res 1997; 10: 169–95.
Sir—José R Weisinger and Ezequiel Bellorín-Font 1 do not give a full account of hypophosphataemia. Phosphate retention occurs in acute and chronic renal failure, and although phosphate is mainly an intracellular anion, this results in hyperphosphataemia. Whereas most patients with chronic renal failure have an increased total body phosphate, those who develop acute renal failure, may not, especially patients with a history of alcohol abuse, chronic diarrhoeal illnesses, antacid prescription, and proximal renal tubular disorders. Phosphate is poorly removed during standard intermittent low-flux haemodialysis, because phosphate is removed only from plasma water. After the dialysis session, there is then a rebound in serum phosphate, because of the re-equilibration from the intracellular stores. Many patients with acute renal failure admitted to the intensive-care unit are treated by continuous renal-replacment therapy (CRRT), which can lead to notable phosphate losses. The amount of
THE LANCET • Vol 352 • October 31, 1998
phosphate removed depends upon the design of the CRRT circuit. For continuous dialysis circuits, phosphate losses are increased with increasing dialysate flow, countercurrent rather than concurrent dialysate flow pathway, and to a lesser extent higher blood flows.2 Similarly, phosphate losses are greatest during continuous haemofiltration with increasing ultrafiltration volumes and postdilutional rather than predilutional fluid replacement. For solutes of low molecular weight, clearance is greater with continuous forms of dialysis than haemofiltration.3 Serum phosphate may also fall because of redistribution of phosphate to the intracellular space, from nutrition and elective hyperventilation in the intensive-care unit. The changes in acid-base balance may again be exacerbated by CRRT. If a dialysate or haemofiltration replacement solution with a high lactate concentration is used, it can lead to a hypochloraemic metabolic alkalosis,4 so driving phosphate into the intracellular compartment. Thus, hypophosphataemia in patients with acute renal failure treated by CRRT after several days is common. Some groups of patients, such as those with liver failure, are more prone to hypophosphataemia,5 and in extreme cases this has led to death. Parenteral phosphates can be readily given to support the serum phosphate because patients treated by CRRT do not develop hypocalcaemia, because the serum ionised-calcium concentration is supported by the calcium content of the dialysate/haemofiltration fluid. Andrew Davenport The Royal Free Hampstead NHS Trust, Lawn Road Division, Royal Free Hospital, London, NW3 2QG, UK 1
2
3
4
5
Weisinger JR, Bellorín-Font E. Magnesium and phosphorus. Lancet 1998; 352: 391–96. Davenport A, Will EJ, Davison AM. Effect of the direction of dialysate flow in the efficiency of continuous ateriovenous haemodialysis. Blood Purif 1990; 8: 329–36. Joy MS, Matzke R, Fryre RF, Palevsky PM. Determinants of vancomycin clearance by continuous veno-venous haemofiltration and continuous venovenous haemodialysis. Am J Kidney Dis 1998; 38: 1019–27. Davenport A, Worth DP, Will EJ. Hypochloraemic alkalosis after high flux continuous haemofiltration and continuous arteriovenous haemofiltration with dialysis. Lancet 1988; i: 658. Davenport A, Kirby SA. Intensive care management of patients with acute hepatic and renal failure. Contrib Nephrol 1995; 116: 22–27.
Sir—We are concerned by José R Weisinger and Ezequiel BellorínFont’s statement 1 that “the safest mode of therapy is oral. 1000 mg phosphorus per day will usually correct phosphate depletion”. This recommendation is incorrect because the absorption of enteral supplemental phosphate is unreliable, more so in the case of diarrhoea, which is frequently provoked by phosphate salts.2 The only safe subsitution for serious hypophosphataemia or a hypophosphataemia in the cachectic is a meticulously monitored intravenous one. W Terryn, D Van Caesbroeck Department of Nephrology, AZ st Jozef, Turnhout, Belgium. 1
2
Weisinger JR, Bellorín-Font E. Magnesium and phosphorus. Lancet 1998; 352: 391–96. Maier-Dobersberger L. Enteral supplementation of phosphate does not prevent hypophosphataemia during refeeding of cachectic patients. J Parent Enteral Nutr, 1994; 18: 182–84.
Authors’ reply Sir—Peter Schuck and colleagues are correct in their comment about the concentration of magnesium in figure 1. It refers to total serum magnesium and not to ionised magnesium, as it would appear with the notation [Mg2+]. Andrew Davenport’s comment about hypophosphataemia from CRRT could be included as an additional cause of hypophosphataemia, as he suggests. The main mechanism seems to be phosphate loss in the dialysate effluent. However, a shift of phosphate to the intracellular compartment could be an additional mechanism of hypophosphataemia from respiratory alkalosis. With regard to the comments by W Terryn and D Van Caesbroeck, we would like to insist that oral replacement is the safest mode of therapy for patient with mild or moderate hypophosphataemia. However, in cases with severe symptomatic hypophosphataemia due to phosphate depletion, there is no doubt that the parenteral route is the most effective and reliable. In addition, in cases of hypophosphataemia secondary to severe diarrhoea, the parenteral administration of phosphorus could assure prompt correction of phosphate deficit without the risk of aggravating diarrhoea. *J R Weisinger, E Bellorín-Font
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between plasma (or serum) magnesium and intracellular concentrations, for example, in erythrocytes or muscle cells (irrespective of measuring ionised or total magnesium). Serum total magnesium can be normal in the presence of intracellular depletion. 4 Thus, among patients at risk for magnesium deficiency, oral supplementation of magnesium may be warranted, even if serum (total) magnesium concentration is within the normal range.5 Renal impairment is a common relative contraindication. P Schuck, G Gammelin, *K L Resch Saxon Balneology and Rehabilitation Medicine Research Institute, Lindenstr 5, D-08645 Bad Elster, Germany (e-mail: [email protected]) 1
2
3
4
5
Weisinger JR, Bellorín-Font E. Magnesium and phosphorus. Lancet 1998; 352: 392–96. Whang R, Hampton EM, Whang DD. Magnesium homeostasis and clinical disorders of magnesium deficiency. Ann Pharmacother 1994; 28: 220–26. Herbert P, Mehta N, Wang J, Hindmarsh T, Jones G, Cardinal P. Functional magnesium deficiency in critically ill patients identified using a magnesium-loading test. Crit Care Med 1997; 25: 749–55. Al-Ghamdi SMG, Cameron EC, Sutton RAL. Magnesium deficiency: pathophysiologic and clinical overview. Am J Kidney Dis 1994; 24: 737–52. Durlach J, Bac P, Durlach V, Bara M, Guiet-Bara A. Neurotic, neuromuscular and autonomous nervous form of magnesium imbalance. Magnes Res 1997; 10: 169–95.
Sir—José R Weisinger and Ezequiel Bellorín-Font 1 do not give a full account of hypophosphataemia. Phosphate retention occurs in acute and chronic renal failure, and although phosphate is mainly an intracellular anion, this results in hyperphosphataemia. Whereas most patients with chronic renal failure have an increased total body phosphate, those who develop acute renal failure, may not, especially patients with a history of alcohol abuse, chronic diarrhoeal illnesses, antacid prescription, and proximal renal tubular disorders. Phosphate is poorly removed during standard intermittent low-flux haemodialysis, because phosphate is removed only from plasma water. After the dialysis session, there is then a rebound in serum phosphate, because of the re-equilibration from the intracellular stores. Many patients with acute renal failure admitted to the intensive-care unit are treated by continuous renal-replacment therapy (CRRT), which can lead to notable phosphate losses. The amount of
THE LANCET • Vol 352 • October 31, 1998
phosphate removed depends upon the design of the CRRT circuit. For continuous dialysis circuits, phosphate losses are increased with increasing dialysate flow, countercurrent rather than concurrent dialysate flow pathway, and to a lesser extent higher blood flows.2 Similarly, phosphate losses are greatest during continuous haemofiltration with increasing ultrafiltration volumes and postdilutional rather than predilutional fluid replacement. For solutes of low molecular weight, clearance is greater with continuous forms of dialysis than haemofiltration.3 Serum phosphate may also fall because of redistribution of phosphate to the intracellular space, from nutrition and elective hyperventilation in the intensive-care unit. The changes in acid-base balance may again be exacerbated by CRRT. If a dialysate or haemofiltration replacement solution with a high lactate concentration is used, it can lead to a hypochloraemic metabolic alkalosis,4 so driving phosphate into the intracellular compartment. Thus, hypophosphataemia in patients with acute renal failure treated by CRRT after several days is common. Some groups of patients, such as those with liver failure, are more prone to hypophosphataemia,5 and in extreme cases this has led to death. Parenteral phosphates can be readily given to support the serum phosphate because patients treated by CRRT do not develop hypocalcaemia, because the serum ionised-calcium concentration is supported by the calcium content of the dialysate/haemofiltration fluid. Andrew Davenport The Royal Free Hampstead NHS Trust, Lawn Road Division, Royal Free Hospital, London, NW3 2QG, UK 1
2
3
4
5
Weisinger JR, Bellorín-Font E. Magnesium and phosphorus. Lancet 1998; 352: 391–96. Davenport A, Will EJ, Davison AM. Effect of the direction of dialysate flow in the efficiency of continuous ateriovenous haemodialysis. Blood Purif 1990; 8: 329–36. Joy MS, Matzke R, Fryre RF, Palevsky PM. Determinants of vancomycin clearance by continuous veno-venous haemofiltration and continuous venovenous haemodialysis. Am J Kidney Dis 1998; 38: 1019–27. Davenport A, Worth DP, Will EJ. Hypochloraemic alkalosis after high flux continuous haemofiltration and continuous arteriovenous haemofiltration with dialysis. Lancet 1988; i: 658. Davenport A, Kirby SA. Intensive care management of patients with acute hepatic and renal failure. Contrib Nephrol 1995; 116: 22–27.
Sir—We are concerned by José R Weisinger and Ezequiel BellorínFont’s statement 1 that “the safest mode of therapy is oral. 1000 mg phosphorus per day will usually correct phosphate depletion”. This recommendation is incorrect because the absorption of enteral supplemental phosphate is unreliable, more so in the case of diarrhoea, which is frequently provoked by phosphate salts.2 The only safe subsitution for serious hypophosphataemia or a hypophosphataemia in the cachectic is a meticulously monitored intravenous one. W Terryn, D Van Caesbroeck Department of Nephrology, AZ st Jozef, Turnhout, Belgium. 1
2
Weisinger JR, Bellorín-Font E. Magnesium and phosphorus. Lancet 1998; 352: 391–96. Maier-Dobersberger L. Enteral supplementation of phosphate does not prevent hypophosphataemia during refeeding of cachectic patients. J Parent Enteral Nutr, 1994; 18: 182–84.
Authors’ reply Sir—Peter Schuck and colleagues are correct in their comment about the concentration of magnesium in figure 1. It refers to total serum magnesium and not to ionised magnesium, as it would appear with the notation [Mg2+]. Andrew Davenport’s comment about hypophosphataemia from CRRT could be included as an additional cause of hypophosphataemia, as he suggests. The main mechanism seems to be phosphate loss in the dialysate effluent. However, a shift of phosphate to the intracellular compartment could be an additional mechanism of hypophosphataemia from respiratory alkalosis. With regard to the comments by W Terryn and D Van Caesbroeck, we would like to insist that oral replacement is the safest mode of therapy for patient with mild or moderate hypophosphataemia. However, in cases with severe symptomatic hypophosphataemia due to phosphate depletion, there is no doubt that the parenteral route is the most effective and reliable. In addition, in cases of hypophosphataemia secondary to severe diarrhoea, the parenteral administration of phosphorus could assure prompt correction of phosphate deficit without the risk of aggravating diarrhoea. *J R Weisinger, E Bellorín-Font
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