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A Quick Reference on Magnesium
A Q u i c k R e f e ren c e o n Magnesium Shane W. Bateman,
DVM, DVSc
KEYWORDS Magnesium Veterinary Dog Cat Critical care KEY POINTS Magnesium is a predominantly intracellular ion and supports electrolyte gradients as a cofactor for many ATPase pumps. Magnesium deficit is difficult to diagnose because of its intracellular distribution, and supplementation is often based on clinical suspicion. Patients with polyuria, diarrhea, or anorexia and those with concurrent hypokalemia should be suspected of magnesium deficit and supplemented accordingly. Common clinical scenarios where magnesium supplementation should be considered: congestive heart failure patients on furosemide, those with diabetic ketoacidosis, and ventricular arrhythmia patients refractory to potassium supplementation.
INTRODUCTION
Distribution of magnesium In human beings, 1% of the total body magnesium is in the extracellular fluid, whereas the remaining 99% is intracellular.1,2 Approximately two-thirds of body magnesium is stored with calcium and phosphorus in bones, 20% in muscles, and 11% in soft tissues other than muscles. Like calcium, extracellular magnesium is present in 3 forms: Ionized or free form (55%) thought to constitute the biologically active fraction Protein-bound form (20%–30%) Complexed form (15%–25%) Magnesium is only 20% to 30% bound to protein, less affected by changes in albumin concentration than calcium. Magnesium handling The primary site of magnesium absorption seems to be the ileum, but the jejunum and colon also contribute substantially to net absorption. The kidneys control and regulate magnesium balance. The author has nothing to disclose. Department of Clinical Studies, Ontario Veterinary College, University of Guelph, 50 Stone Road, Guelph, Ontario N1G 2W1, Canada E-mail address: [email protected] Vet Clin Small Anim - (2016) -–http://dx.doi.org/10.1016/j.cvsm.2016.09.002 0195-5616/16/ª 2016 Elsevier Inc. All rights reserved.
vetsmall.theclinics.com
2
Bateman
Various segments of the nephron play an important role in magnesium homeostasis. Of the filtered magnesium 10% to 15% of magnesium is reabsorbed within the proximal tubule. 60% to 70% is reabsorbed in the cortical thick ascending limb of the loop of Henle. 10% to 15% is reabsorbed in the distal convoluted tubule. The final concentration of magnesium in the urine is determined at the distal convoluted tubule under hormonal and nonhormonal control. Magnesium role Within the cell, magnesium functions as a cofactor for most ATPase enzymes. Magnesium, therefore, is critical in supporting electrolyte movement and creation and maintenance of electrochemical gradients that drive many cellular activities and functions. ANALYSIS
Currently, there is no consensus regarding the best assay for diagnosis. Serum magnesium concentration does not correlate well with magnesium deficit based on clinical signs or with serum ionized magnesium concentration. Serum reference intervals reported vary but generally are in the range of 0.6 mmol/L to 1.2 mmol/L (1.5–3.0 mg/dL) Reference intervals reported for ionized magnesium concentration vary but generally are in the range of 0.4 mmol/L to 0.8 mmol/L (1–1.9 mg/dL) Ionized serum magnesium and total serum magnesium may be useful when results are low and are consistent with clinical suspicion of a magnesium deficit. The magnesium retention test may be useful but due to requirements for urine collection over 24 hours has not found widespread clinical use. MAGNESIUM DEFICIT Causes
See Box 1. Clinical Signs
Cardiovascular Intracellular and extracellular magnesium concentrations play an important role in cardiac excitability, contraction, and conduction through regulatory effects on calcium movement. Magnesium may act as an antiarrhythmic agent by limiting intracellular calcium overload and by supporting intracellular potassium repletion and correction of hypokalemia. Neuromuscular Magnesium depletion enhances neuronal excitability and neuromuscular transmission. Magnesium may act as an analgesic by blocking N-methyl-D-aspartate receptors within the central nervous system. Electrolyte disturbances Depletion of magnesium has a permissive effect on potassium exit from cells, leading to extracellular accumulation of potassium.
A Quick Reference on Magnesium
Box 1 Causes of magnesium deficit Gastrointestinal Decreased intake/starvation/malnutrition Chronic diarrhea Gastric suction Malabsorption syndromes Short bowel syndrome Gastric bypass surgery Colonic neoplasia Familial or inherited Renal Diabetes mellitus/diabetic ketoacidosis Diuretics (except potassium-sparing agents) Osmotic agents (including hyperglycemia) Intrinsic renal causes of diuresis Postobstructive Polyuric acute failure Hyperaldosteronism Hyperthyroidism Renal tubular acidosis Concurrent electrolyte disorders Hypokalemia Hypercalcemia/hyperparathyroidism Hypophosphatemia Drugs Gentamicin Carbenicillin Ticarcillin Cyclosporine Cisplatin Postrenal transplantation Familial or inherited Miscellaneous Excessive loss from Sweat Lactation Redistribution Acute myocardial infarction Acute pancreatitis Insulin Catecholamine excess Idiopathic From Bateman SW. Disorders of magnesium: magnesium deficit and excess. In: DiBartola, SP, editor. Fluid, electrolyte and acid-base disorders in small animal practice. 4th edition. St Louis (MO): Elsevier; 2012. p. 220.
3
4
Bateman
When filtered in the kidney, potassium retention is inefficient (because of magnesium deficit), leading to potassium excretion. Frequently, this potassium deficiency is refractory to supplementation until the magnesium deficit also has been corrected. Hypocalcemia also occurs in human beings as a concurrent electrolyte disturbance when a magnesium deficit is present but is infrequently reported in veterinary patients. STEPWISE APPROACH
See Fig. 1. Clinical situations in which magnesium supplementation may be considered Cardiac arrhythmias Torsades de pointes, digitalis toxicity, and ventricular ectopy
Fig. 1. Algorithm of the clinical approach to magnesium deficit/excess.
A Quick Reference on Magnesium
Table 1 Dose range for magnesium salts Rapid replacement MgSO4 MgCl2
mEq mg/g of Salt 8.12 9.25
mEq/kg/d 0.75–1 0.75–1
mEq/kg/h 0.03–0.04 0.03–0.04
mg/kg/h 3.7–4.9 3.2–4.3
MgSO4 MgCl2
mEq mg/g of Salt 8.12 9.25
mEq/kg/d 0.3–0.5 0.3–0.5
mEq/kg/h 0.013–0.02 0.013–0.02
mg/kg/h 1.6–2.5 1.4–2.2
MgSO4
mEq/kg 0.15–0.3
mg/kg 19–37
MgCl2
0.15–0.3
16–32
Duration 5 min–1 h (emerg) 24 h (load) 5 min–1 h (emerg) 24 h (load)
Several
mEq/kg/d 1–2
Slow replacement
Emergency/loading
Oral
Abbreviation: emerg, emergency situation requiring rapid administration. From Bateman SW. Disorders of magnesium: magnesium deficit and excess. In: DiBartola, SP, editor. Fluid, electrolyte and acid-base disorders in small animal practice. 4th edition. St Louis (MO): Elsevier; 2012. p. 223; with permission.
Metabolic Diabetic ketoacidosis, hypokalemia refractory to supplementation, and hypocalcemia refractory to supplementation Use with caution if renal insufficiency is present. See Table 1. MAGNESIUM EXCESS
Naturally occurring clinically relevant excess is rare. Most often associated with renal insufficiency Rarely associated with some medication administration Clinically relevant iatrogenic excess was reported in anesthetized normal dogs after cumulative administration of 1 mEq/kg to 3.9 mEq/kg (0.12 mEq/kg/min). Death occurred with cumulative infusions of 5.9 mEq/kg to 10.9 mEq/kg. Symptoms of iatrogenic excess reported in humans include Loss of deep tendon reflexes, impaired respiration, mild to moderate hypotension, cardiac conduction disturbances, and cutaneous flushing REFERENCES
1. Bateman SW. Disorders of magnesium: magnesium deficit and excess. In: DiBartola SP, editor. Fluid, electrolyte and acid-base disorders in small animal practice. 3rd edition. Philadelphia: Elsevier; 2006. p. 210–26. 2. Cortes YE, Moses L. Magnesium disturbances in critically ill patients. Compend Contin Educ Vet 2007;29(7):420–7.
5
DVM, DVSc
KEYWORDS Magnesium Veterinary Dog Cat Critical care KEY POINTS Magnesium is a predominantly intracellular ion and supports electrolyte gradients as a cofactor for many ATPase pumps. Magnesium deficit is difficult to diagnose because of its intracellular distribution, and supplementation is often based on clinical suspicion. Patients with polyuria, diarrhea, or anorexia and those with concurrent hypokalemia should be suspected of magnesium deficit and supplemented accordingly. Common clinical scenarios where magnesium supplementation should be considered: congestive heart failure patients on furosemide, those with diabetic ketoacidosis, and ventricular arrhythmia patients refractory to potassium supplementation.
INTRODUCTION
Distribution of magnesium In human beings, 1% of the total body magnesium is in the extracellular fluid, whereas the remaining 99% is intracellular.1,2 Approximately two-thirds of body magnesium is stored with calcium and phosphorus in bones, 20% in muscles, and 11% in soft tissues other than muscles. Like calcium, extracellular magnesium is present in 3 forms: Ionized or free form (55%) thought to constitute the biologically active fraction Protein-bound form (20%–30%) Complexed form (15%–25%) Magnesium is only 20% to 30% bound to protein, less affected by changes in albumin concentration than calcium. Magnesium handling The primary site of magnesium absorption seems to be the ileum, but the jejunum and colon also contribute substantially to net absorption. The kidneys control and regulate magnesium balance. The author has nothing to disclose. Department of Clinical Studies, Ontario Veterinary College, University of Guelph, 50 Stone Road, Guelph, Ontario N1G 2W1, Canada E-mail address: [email protected] Vet Clin Small Anim - (2016) -–http://dx.doi.org/10.1016/j.cvsm.2016.09.002 0195-5616/16/ª 2016 Elsevier Inc. All rights reserved.
vetsmall.theclinics.com
2
Bateman
Various segments of the nephron play an important role in magnesium homeostasis. Of the filtered magnesium 10% to 15% of magnesium is reabsorbed within the proximal tubule. 60% to 70% is reabsorbed in the cortical thick ascending limb of the loop of Henle. 10% to 15% is reabsorbed in the distal convoluted tubule. The final concentration of magnesium in the urine is determined at the distal convoluted tubule under hormonal and nonhormonal control. Magnesium role Within the cell, magnesium functions as a cofactor for most ATPase enzymes. Magnesium, therefore, is critical in supporting electrolyte movement and creation and maintenance of electrochemical gradients that drive many cellular activities and functions. ANALYSIS
Currently, there is no consensus regarding the best assay for diagnosis. Serum magnesium concentration does not correlate well with magnesium deficit based on clinical signs or with serum ionized magnesium concentration. Serum reference intervals reported vary but generally are in the range of 0.6 mmol/L to 1.2 mmol/L (1.5–3.0 mg/dL) Reference intervals reported for ionized magnesium concentration vary but generally are in the range of 0.4 mmol/L to 0.8 mmol/L (1–1.9 mg/dL) Ionized serum magnesium and total serum magnesium may be useful when results are low and are consistent with clinical suspicion of a magnesium deficit. The magnesium retention test may be useful but due to requirements for urine collection over 24 hours has not found widespread clinical use. MAGNESIUM DEFICIT Causes
See Box 1. Clinical Signs
Cardiovascular Intracellular and extracellular magnesium concentrations play an important role in cardiac excitability, contraction, and conduction through regulatory effects on calcium movement. Magnesium may act as an antiarrhythmic agent by limiting intracellular calcium overload and by supporting intracellular potassium repletion and correction of hypokalemia. Neuromuscular Magnesium depletion enhances neuronal excitability and neuromuscular transmission. Magnesium may act as an analgesic by blocking N-methyl-D-aspartate receptors within the central nervous system. Electrolyte disturbances Depletion of magnesium has a permissive effect on potassium exit from cells, leading to extracellular accumulation of potassium.
A Quick Reference on Magnesium
Box 1 Causes of magnesium deficit Gastrointestinal Decreased intake/starvation/malnutrition Chronic diarrhea Gastric suction Malabsorption syndromes Short bowel syndrome Gastric bypass surgery Colonic neoplasia Familial or inherited Renal Diabetes mellitus/diabetic ketoacidosis Diuretics (except potassium-sparing agents) Osmotic agents (including hyperglycemia) Intrinsic renal causes of diuresis Postobstructive Polyuric acute failure Hyperaldosteronism Hyperthyroidism Renal tubular acidosis Concurrent electrolyte disorders Hypokalemia Hypercalcemia/hyperparathyroidism Hypophosphatemia Drugs Gentamicin Carbenicillin Ticarcillin Cyclosporine Cisplatin Postrenal transplantation Familial or inherited Miscellaneous Excessive loss from Sweat Lactation Redistribution Acute myocardial infarction Acute pancreatitis Insulin Catecholamine excess Idiopathic From Bateman SW. Disorders of magnesium: magnesium deficit and excess. In: DiBartola, SP, editor. Fluid, electrolyte and acid-base disorders in small animal practice. 4th edition. St Louis (MO): Elsevier; 2012. p. 220.
3
4
Bateman
When filtered in the kidney, potassium retention is inefficient (because of magnesium deficit), leading to potassium excretion. Frequently, this potassium deficiency is refractory to supplementation until the magnesium deficit also has been corrected. Hypocalcemia also occurs in human beings as a concurrent electrolyte disturbance when a magnesium deficit is present but is infrequently reported in veterinary patients. STEPWISE APPROACH
See Fig. 1. Clinical situations in which magnesium supplementation may be considered Cardiac arrhythmias Torsades de pointes, digitalis toxicity, and ventricular ectopy
Fig. 1. Algorithm of the clinical approach to magnesium deficit/excess.
A Quick Reference on Magnesium
Table 1 Dose range for magnesium salts Rapid replacement MgSO4 MgCl2
mEq mg/g of Salt 8.12 9.25
mEq/kg/d 0.75–1 0.75–1
mEq/kg/h 0.03–0.04 0.03–0.04
mg/kg/h 3.7–4.9 3.2–4.3
MgSO4 MgCl2
mEq mg/g of Salt 8.12 9.25
mEq/kg/d 0.3–0.5 0.3–0.5
mEq/kg/h 0.013–0.02 0.013–0.02
mg/kg/h 1.6–2.5 1.4–2.2
MgSO4
mEq/kg 0.15–0.3
mg/kg 19–37
MgCl2
0.15–0.3
16–32
Duration 5 min–1 h (emerg) 24 h (load) 5 min–1 h (emerg) 24 h (load)
Several
mEq/kg/d 1–2
Slow replacement
Emergency/loading
Oral
Abbreviation: emerg, emergency situation requiring rapid administration. From Bateman SW. Disorders of magnesium: magnesium deficit and excess. In: DiBartola, SP, editor. Fluid, electrolyte and acid-base disorders in small animal practice. 4th edition. St Louis (MO): Elsevier; 2012. p. 223; with permission.
Metabolic Diabetic ketoacidosis, hypokalemia refractory to supplementation, and hypocalcemia refractory to supplementation Use with caution if renal insufficiency is present. See Table 1. MAGNESIUM EXCESS
Naturally occurring clinically relevant excess is rare. Most often associated with renal insufficiency Rarely associated with some medication administration Clinically relevant iatrogenic excess was reported in anesthetized normal dogs after cumulative administration of 1 mEq/kg to 3.9 mEq/kg (0.12 mEq/kg/min). Death occurred with cumulative infusions of 5.9 mEq/kg to 10.9 mEq/kg. Symptoms of iatrogenic excess reported in humans include Loss of deep tendon reflexes, impaired respiration, mild to moderate hypotension, cardiac conduction disturbances, and cutaneous flushing REFERENCES
1. Bateman SW. Disorders of magnesium: magnesium deficit and excess. In: DiBartola SP, editor. Fluid, electrolyte and acid-base disorders in small animal practice. 3rd edition. Philadelphia: Elsevier; 2006. p. 210–26. 2. Cortes YE, Moses L. Magnesium disturbances in critically ill patients. Compend Contin Educ Vet 2007;29(7):420–7.
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