Magnesium sulfate is a common medication in the hospital setting with a variety of uses. It currently holds many FDA-approvals but also has numerous off-label uses for a variety of clinical situations.
To fully understand how magnesium sulfate works clinically, a basic understanding of how magnesium works intracellularly is helpful. Magnesium is a positively charged divalent cation that is absorbed in the gastrointestinal tract from our diets. Regulation of magnesium concentration in the serum occurs mostly through renal reabsorption and excretion. Parathyroid hormone causes magnesium reabsorption in the cortical thick ascending limb, but hypercalcemia and hypermagnesemia will cause magnesium excretion to occur. Serum levels of magnesium should remain within a range of 0.7 to 1 mmol/L (1.4 to 2.0 meq/L) concentration, but almost half of the total body magnesium is taken up by the bone.
Physiological Role of Magnesium
One role that magnesium plays is helping ion transport and maintain balance across the cellular membrane. Magnesium also acts as cofactors for enzymatic activation in multiple biochemical pathways such as glycolysis and the Krebs cycle. Intracellular magnesium is vital for neurochemical transmission and muscular contractions by working indirectly at the neuromuscular junction. More specifically, Mg2+ ions compete on voltage-gated calcium channels, thus affecting the distribution of calcium uptake and release. Magnesium also affects calcium metabolism by stimulation or suppression of Parathyroid Hormone (PTH).
Hypermagnesemia is a state of elevated magnesium levels with serum concentrations higher than 2 mmol/L and rarely presents unless renal insufficiency is present or the patient exposed to high levels of exogenous magnesium. Clinical signs of hypermagnesemia result in neuromuscular blockade or vasodilation. High levels of circulating magnesium lead to inhibition of calcium influx through the voltage-gated channels. Without calcium influx into the cell at the neuromuscular junction, there will be no acetylcholine released, thus leading to muscle contraction slowing. Clinical symptoms of hypermagnesemia include, but not limited to, weakness, decreased respiratory drive, hyporeflexia, hypotension, or electrocardiogram (ECG) changes. Most notable ECG changes are P-R interval prolongation, increase in Q-T interval, or an increase in QRS duration leading to heart block.
Usually defined as depletion of magnesium and is seen when serum concentrations are less than 0.7 mmol/L. Typically due to intestinal malabsorption or renal disease leading to failed reabsorption. Low levels of magnesium can result in the loss of competitive inhibition at the neuromuscular junction allowing for increased acetylcholine release, thus resulting in neuromuscular irritability. Without competitive inhibition, the threshold of motor nerve excitation diminished, leading to enhanced myofiber contraction. Clinical symptoms of hypomagnesemia include, but not limited to, muscle spasms, hyperreflexia, or ECG changes. Most notable changes seen on ECG include the widening of the P-R interval, widening of the QRS complex, and peaking of the T waves.
Magnesium sulfate can administration can be oral (PO), intramuscular (IM), intraosseous (IO), or intravenous (IV). For every 1 gram of magnesium sulfate, it contains 98.6 mg or 8.12Eq of elemental magnesium. Magnesium sulfate can be combined with dextrose 5% or water to make intravenous solutions.
Magnesium given orally leads to osmotic shifts of fluid, which can help alleviate constipation. If given parenterally, magnesium sulfate will be broken down into elemental magnesium and used to replete and maintain circulating magnesium stores, thus changing the serum concentration of magnesium. When given to patients, the route of administration will ultimately determine the overall mechanism of action.
When giving magnesium sulfate, there are minimal side effects with standard therapeutic doses, but magnesium sulfate has a broad therapeutic index. Patients most commonly complain of minor facial flushing and warmth with the administration; however, symptoms typically resolve spontaneously. In patients with neuromuscular disease, such as in myasthenia gravis, the neuromuscular function may become worse at lower concentrations of medication. If given rapidly or in high doses, patients may experience transient hypotension due to smooth muscle inhibition causing a vasodilatory effect that will resolve. If the patient is on a continuous magnesium sulfate infusion, serum levels must be accounted for as symptoms related to hypermagnesemia may become clinically evident. At supratherapeutic serum concentrations, absent reflexes, abnormal cardiac conduction, and muscle weakness may occur.
If any known hypersensitivity reaction to magnesium sulfate has occurred in the past, it should not be administered. If a patient is in a known heart block, magnesium sulfate should not be given as it can exacerbate the already slowed cardiac conduction. Many manufacturing labels recommend withholding magnesium sulfate infusions in patients with preeclampsia/eclampsia two hours before fetal delivery due to possible interaction with neuromuscular blocking agents given intraoperatively; however, the medication should not be stopped due to the possibility of precipitating seizure activity.
Magnesium levels must be monitored frequently by checking serum levels every 6 to 8 hours or clinically by following patellar reflexes or urinary output. If serum concentration levels are low, a proper dose of magnesium sulfate can be given parenterally to replete low serum concentrations with recommended follow up laboratory testing.
If patients exhibit signs and symptoms of hypermagnesemia, the recommendation is to discontinue magnesium sulfate products immediately. If the patient consumed magnesium sulfate orally, then the use of magnesium-free enemas or cathartics can be useful in removing excess magnesium from the GI tract. Patients should receive parenteral doses of calcium gluconate to help alleviate symptoms, but continued doses may be necessary as the calcium provides temporary improvement. IV hydration should also occur if clinically appropriate. In patients with severe renal disease, then hemodialysis should be considered.
Magnesium sulfate is a very commonly used medication in the hospital setting with multiple therapeutic uses. Physicians, physician assistants, nurse practitioners, and pharmacists who prescribed this medication should be aware of the on and off label uses and current magnesium levels to ensure appropriate dosing occurs. The pharmacist should help monitor for potential drug-drug interactions, and nursing staff needs to be fully aware of the proper administration of the medications. All individuals taking care of the patient should be mindful of potential side effects from magnesium sulfate administration and how to manage complications.
|||Lu JF,Nightingale CH, Magnesium sulfate in eclampsia and pre-eclampsia: pharmacokinetic principles. Clinical pharmacokinetics. 2000 Apr; [PubMed PMID: 10803454]|
|||Hypertension in pregnancy. Report of the American College of Obstetricians and Gynecologists’ Task Force on Hypertension in Pregnancy. Obstetrics and gynecology. 2013 Nov; [PubMed PMID: 24150027]|
|||Urbano FL, Review of the NAEPP 2007 Expert Panel Report (EPR-3) on Asthma Diagnosis and Treatment Guidelines. Journal of managed care pharmacy : JMCP. 2008 Jan-Feb; [PubMed PMID: 18240881]|
|||Link MS,Berkow LC,Kudenchuk PJ,Halperin HR,Hess EP,Moitra VK,Neumar RW,O'Neil BJ,Paxton JH,Silvers SM,White RD,Yannopoulos D,Donnino MW, Part 7: Adult Advanced Cardiovascular Life Support: 2015 American Heart Association Guidelines Update for Cardiopulmonary Resuscitation and Emergency Cardiovascular Care. Circulation. 2015 Nov 3; [PubMed PMID: 26472995]|
|||Schwalfenberg GK,Genuis SJ, The Importance of Magnesium in Clinical Healthcare. Scientifica. 2017; [PubMed PMID: 29093983]|
|||Dubé L,Granry JC, The therapeutic use of magnesium in anesthesiology, intensive care and emergency medicine: a review. Canadian journal of anaesthesia = Journal canadien d'anesthesie. 2003 Aug-Sep; [PubMed PMID: 12944451]|
|||Committee Opinion No. 455: Magnesium sulfate before anticipated preterm birth for neuroprotection. Obstetrics and gynecology. 2010 Mar; [PubMed PMID: 20177305]|