On-label, off-label and over-the-counter: Magnesium is one of the simplest medications imaginable, but its mechanisms are still not fully understood.
On-label, off-label and over-the-counter: Magnesium is one of the simplest medications imaginable, but its mechanisms are still not fully understood
In General
Magnesium sulfate is given PO, IV, and IM for problems as broad as eclampsia, Torsades de Pointes, migraines, pre-term labor, and constipation. How does it work for all of these disorders? The evidence is varied and its mechanisms not fully understood.
Major Indications
Over the counter it is used orally as a laxative, topically as Epsom salts for soaking minor cuts and bruises, and as a dietary supplement. On-label uses include eclampsia/pre-eclampsia, hypomagnesemia, and cardiac dysrhythmias caused by hypomagnesemia. Off-label uses include polymorphic VT (without known hypomagnesemia), and moderate to severe asthma exacerbations.
In The News
IV magnesium sulfate improves pulmonary function in adults and children with severe asthma exacerbations. It reduces hospital admissions in moderate to severe adult asthmatics with an impressive number needed to treat of 3 [1]. A meta-analysis of magnesium use for migraine headaches, however, found more side effects and no therapeutic benefit in patients receiving magnesium [2].
How it Works
Magnesium is an inorganic, divalent cation, one of the simplest medications imaginable. In hypmognesemia, administration repletes body stores of magnesium. In cases of concurrent hypokalemia, magnesium repletion is required to prevent renal excretion of potassium by inhibiting ROMK channels in the distal tubules [3]. For eclampsia, the mechanism of action is unclear but may be due to systemic or cerebral vasodilation [4]. As a tocolytic it is thought to act through calcium antagonism [5]. For dysrhythmias, magnesium is required for functioning of the Na/K ATPase enzyme, and hypomagnesemia can lead to prolonged QT and PR. However, its precise role in the treatment of dysrhythmias and cardiac events in normomagnesemic patients is not fully understood. In the treatment of severe asthma exacerbations, magnesium has long been known to cause bronchodilation, though the mechanism by which it produces this is not well established [6].
Notable History
Magnesium has long been used for medical purposes, with articles in the British Medical Journal discussing its use in dysentery dating to the 1890s [7].
Dosing
For moderate to severe asthma exacerbations and for polymorphic ventricular tachycardia, dosing is typically 1-2g IV. For eclampsia-associated seizures, the dose is 4-6g IV followed by 1-2g IV/hr (max 40g in 24hrs). For repletion in hypomagnesemia, dosing ranges from 1-8mg IV depending on severity. Mild hypomagnesemia can also be treated with PO magnesium oxide (250-500mg). Reduce dose by 50% in patients with renal dysfunction, as the magnesium will be excreted more slowly, and could build up to toxic levels.
Cautions
Use is contraindicated in patients with heart block because at high doses it can cause heart block and bradycardia. Use with caution in patients with myasthenia gravis and other neuromuscular disorders. It is considered pregnancy class D, but is used in pregnant women to prevent pre-term delivery and in eclampsia/pre-eclampsia. It is safe for lactating mothers [8].
Adverse Events
Rapid administration through an IV can result in vasodilation, flushing, and hypotension in a dose- and rate-dependent manner. In patients receiving repeat or high doses (such as for tocolysis and pre-eclampsia), monitor for signs of magnesium toxicity such as pulmonary edema, respiratory depression, hyporeflexia, and bradycardia.
Cost
Magnesium is generally cheap. Cost varies depending on formulation: 4g in 100mL costs $7.67; 5g in 10mL costs $1.60.
Christina Shenvi, MD, PhD is an assistant professor in the department of emergency medicine at the University of North Carolina
REFERENCES
1. Rowe BH, Bretzlaff JA, Bourdon C, Bota GW, Camargo CA,Jr. Magnesium sulfate for treating exacerbations of acute asthma in the emergency department. Cochrane Database Syst Rev. 2000;(2)(2):CD001490.
2. Choi H, Parmar N. The use of intravenous magnesium sulphate for acute migraine: Meta-analysis of randomized controlled trials. Eur J Emerg Med. 2014;21(1):2-9. 3. Huang CL, Kuo E. Mechanism of hypokalemia in magnesium deficiency. J Am Soc Nephrol. 2007;18(10):2649-2652.
4. Euser AG, Cipolla MJ. Magnesium sulfate for the treatment of eclampsia: A brief review. Stroke. 2009;40(4):1169-1175.
5. Abramovici A, Cantu J, Jenkins SM. Tocolytic therapy for acute preterm labor. Obstet Gynecol Clin North Am. 2012;39(1):77-87.
6. Kelly HW. Magnesium sulfate for severe acute asthma in children. J Pediatr Pharmacol Ther. 2003;8(1):40-45.
7. Rouget FA. Magnesium sulphate in tropical dysentery. Br Med J. 1899;2(2029):1413-1414.
8. Hale TW. Medications and mothers’ milk: A manual of lactational pharmacology. 12th ed. Amarillo, TX: Hale Publishing L.P.; 2012:1331.
