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Magnesium

Open AccessPublished:November 26, 2012DOI:https://doi.org/10.1016/j.jpainsymman.2012.10.005
      Therapeutic Reviews aim to provide essential independent information for health professionals about drugs used in palliative and hospice care. Additional content is available on www.palliativedrugs.com. Country-specific books (Hospice and Palliative Care Formulary USA, and Palliative Care Formulary, British and Canadian editions) are also available and can be ordered from www.palliativedrugs.com. The series editors welcome feedback on the articles ( [email protected] ).

      Abbreviations/Key

      Off-label use
      ATP
      Adenosine triphosphate
      CNS
      Central nervous system
      CRP
      C-reactive protein
      CSCI
      Continuous subcutaneous infusion
      GI
      Gastrointestinal
      IM
      Intramuscular
      IV
      Intravenous
      IVI
      Intravenous infusion
      OTC
      Over the counter (i.e., obtainable without a prescription)
      PO
      Per os, by mouth
      PPI
      Proton pump inhibitor
      RCT
      Randomized controlled trial
      WFI
      Water for injection
      Indications: Hypomagnesemia, constipation, arrhythmia, eclampsia, †asthma, †myocardial infarction.

      Pharmacology

      Magnesium is the second most abundant intracellular ion after potassium. It is involved in numerous enzymatic reactions and is a co-factor for many biological processes, most of which use ATP. It is important for bone mineralization, muscular relaxation and neurotransmission. About half of the total body magnesium is in soft tissue, the other half in bone, with less than 1% present in blood.
      • Romani A.
      Regulation of magnesium homeostasis and transport in mammalian cells.
      • Martin K.J.
      • González E.A.
      • Slatopolsky E.
      Clinical consequences and management of hypomagnesemia.
      • Elin R.J.
      Assessment of magnesium status for diagnosis and therapy.
      Intracellular magnesium is mostly bound to ribosomes, phospholipids and nucleotides.
      • Romani A.
      Regulation of magnesium homeostasis and transport in mammalian cells.
      The estimated average requirement for magnesium in adults is ∼265mg for females and ∼350mg/24h for males.
      Standing Committee on the Scientific Evaluation of Dietary Reference Intakes
      Food and Nutrition Board, Institute of Medicine. DRI dietary reference intakes for calcium, phosphorous, magnesium, Vitamin D, and fluoride.
      However, magnesium intake is falling as the use of processed and fast-foods increases, and about half of the US population does not meet this requirement.
      • Elin R.J.
      Assessment of magnesium status for diagnosis and therapy.
      • Rosanoff A.
      • Weaver C.M.
      • Rude R.K.
      Suboptimal magnesium status in the United States: are the health consequences underestimated?.
      Thus, the incidence of chronic magnesium deficiency is probably increasing, with possible health implications, but is unrecognized because of the diagnostic limitations of serum magnesium (see below).
      • Elin R.J.
      Assessment of magnesium status for diagnosis and therapy.
      • Rosanoff A.
      • Weaver C.M.
      • Rude R.K.
      Suboptimal magnesium status in the United States: are the health consequences underestimated?.
      Magnesium competes with calcium for absorption in the small intestine, probably by active transport. The normal serum magnesium is 1.5–1.91mEq/L. However, some have argued that for optimal health, the lower limit for serum magnesium should be considered to be 1.7mEq/L.
      • Elin R.J.
      Assessment of magnesium status for diagnosis and therapy.
      This is based on a progressive increase in the frequency of magnesium deficiency seen with serum levels between 1.7mEq/L and 1.5mEq/L (from <10% to 90%), which is associated with an increased risk of morbidity, e.g., impaired glucose tolerance, type 2 diabetes mellitus, and mortality, e.g., sudden cardiac death.
      • Elin R.J.
      Assessment of magnesium status for diagnosis and therapy.
      • Rosanoff A.
      • Weaver C.M.
      • Rude R.K.
      Suboptimal magnesium status in the United States: are the health consequences underestimated?.
      Magnesium is excreted by the kidneys, 6–24mEq/24h. Magnesium and calcium share the same transport system in the renal tubules and there is a reciprocal relationship between the amounts excreted.
      Magnesium deficiency can result from:
      • reduced intake, e.g., an inadequate dietary intake (common)
      • reduced absorption, e.g., small bowel resection, cholestasis, pancreatic insufficiency, diarrhea, stoma, fistula, PPI (rare and generally with prolonged use, i.e., >1 year)
        Medicines and Healthcare Products Regulatory Agency
        Proton pump inhibitors in long term use: reports of hypomagnesaemia.
        • Ito T.
        • Jensen R.T.
        Association of long-term proton pump inhibitor therapy with bone fractures and effects on absorption of calcium, vitamin B12, iron, and magnesium.
      • increased excretion, e.g., alcoholism, diabetes mellitus, interstitial nephritis, diuretic phase of acute tubular necrosis, hyperthyroidism, hyperparathyroidism, hyperaldosteronism, drug-induced (aminoglycosides, amphotericin, anti-epidermal growth factor receptor monoclonal antibodies, cisplatin, cyclosporine, loop diuretics).
      The risk of hypomagnesemia with cisplatin is dose-dependent and increases with cumulative doses (40% cycle 1 → 100% cycle 6).
      • Hodgkinson E.
      • Neville-Webbe H.L.
      • Coleman R.E.
      Magnesium depletion in patients receiving cisplatin-based chemotherapy.
      It can persist for 4–5 months, and sometimes years, after completing treatment.
      • Schilsky R.L.
      • Barlock A.
      • Ozols R.F.
      Persistent hypomagnesemia following cisplatin chemotherapy for testicular cancer.
      • Buckley J.E.
      • Clark V.L.
      • Meyer T.J.
      • Pearlman N.W.
      Hypomagnesemia after cisplatin combination chemotherapy.
      Although generally mild and asymptomatic, it can be severe and symptomatic.
      Hypomagnesemia is an emerging toxicity of anti-epidermal growth factor receptor monoclonal antibodies, e.g., cetuximab, panitumumab.
      • Costa A.
      • Tejpar S.
      • Prenen H.
      • Van Cutsem E.
      Hypomagnesaemia and targeted anti-epidermal growth factor receptor (EGFR) agents.
      • Cao Y.
      • Liao C.
      • Tan A.
      • Liu L.
      • Gao F.
      Meta-analysis of incidence and risk of hypomagnesemia with cetuximab for advanced cancer.
      The risk increases in the elderly, in those with a higher baseline serum magnesium, and with duration of treatment (e.g., 5% <3 months → 50% >6 months of cetuximab).
      • Costa A.
      • Tejpar S.
      • Prenen H.
      • Van Cutsem E.
      Hypomagnesaemia and targeted anti-epidermal growth factor receptor (EGFR) agents.
      It is reversible, with magnesium levels returning to normal 4–6 weeks after discontinuation of treatment.
      • Costa A.
      • Tejpar S.
      • Prenen H.
      • Van Cutsem E.
      Hypomagnesaemia and targeted anti-epidermal growth factor receptor (EGFR) agents.
      When magnesium deficiency develops acutely, the symptoms may be obvious and severe, particularly muscle cramps, which aids diagnosis (Box A). In chronic deficiency, symptoms may be insidious in onset, less severe and non-specific.
      Symptoms and signs of magnesium deficiency and excess
      Tabled 1
      Magnesium deficiency
      • Muscle
        • weakness
        • tremor
        • twitching
        • cramps
        • tetany (positive Chvostek's sign)
      • Paresthesia
      • Apathy
      • Depression
      • Delirium
      • Choreiform movements
      • Nystagmus
      • Seizures
      • Prolonged QT interval
      • Cardiac arrhythmia, including torsade
        • de pointes
      • Increased pain (?)
      • Hypomagnesemia (not always)
      • Hypokalemia
      • Hypocalcemia
      • Hypophosphatemia
      Magnesium excess
      • Muscle
        • weakness
        • hypotonia
        • loss of reflexes
      • Sensation of warmth (IV)
      • Flushing (IV)
      • Drowsiness
      • Slurred speech
      • Double vision
      • Delirium
      • Hypotension
      • Cardiac arrhythmia
      • Respiratory depression
      • Nausea and vomiting
      • Thirst
      • Hypermagnesemia
      In animal studies, magnesium deficiency results in an increased release of substance P and other mediators from nerve endings. These activate immune cells to release histamine and cytokines, producing a pro-inflammatory state and increased levels of oxygen-derived free radicals and nitric oxide. Manifestations include:
      • Mazur A.
      • Maier J.A.
      • Rock E.
      • et al.
      Magnesium and the inflammatory response: Potential physiopathological implications.
      • Tejero-Taldo M.I.
      • Kramer J.H.
      • Mak IuT
      • Komarov A.M.
      • Weglicki W.B.
      The nerve-heart connection in the pro-oxidant response to Mg-deficiency.
      • Maier J.A.
      Endothelial cells and magnesium: implications in atherosclerosis.
      • cutaneous vasodilation → erythema and edema
      • leukocytosis
      • inflammatory lesions in cardiac muscle
      • atherogenesis
      • increased levels of oxidative stress
      • hyperalgesia.
      In humans, the incidence of magnesium deficiency increases with aging (due to poor diet, reduced intestinal absorption, increased urinary loss, etc.) and obesity. Magnesium deficiency, aging and obesity are all associated with low-grade inflammation and increased oxidative stress. This has led some to postulate that magnesium deficiency is a contributing factor to age- and obesity-related diseases such as diabetes mellitus, cardiac failure, some cancers (e.g., breast, colon), and hypertension.
      • Tejero-Taldo M.I.
      • Kramer J.H.
      • Mak IuT
      • Komarov A.M.
      • Weglicki W.B.
      The nerve-heart connection in the pro-oxidant response to Mg-deficiency.
      • Barbagallo M.
      • Belvedere M.
      • Dominguez L.J.
      Magnesium homeostasis and aging.
      • Nielsen F.H.
      Magnesium, inflammation, and obesity in chronic disease.
      • King D.E.
      Inflammation and elevation of C-reactive protein: does magnesium play a key role?.
      • Song Y.
      • Ridker P.M.
      • Manson J.E.
      • et al.
      Magnesium intake, C-reactive protein, and the prevalence of metabolic syndrome in middle-aged and older U.S. women.
      In support of this, an inverse relationship between serum magnesium and CRP has been demonstrated in patients with cardiac failure, with magnesium supplementation attenuating the elevated CRP.
      • Almoznino-Sarafian D.
      • Berman S.
      • Mor A.
      • et al.
      Magnesium and C-reactive protein in heart failure: an anti-inflammatory effect of magnesium administration?.
      The underlying mechanisms remain to be clarified, but in part may relate to magnesium acting as a natural “calcium antagonist.”
      • Rosanoff A.
      • Weaver C.M.
      • Rude R.K.
      Suboptimal magnesium status in the United States: are the health consequences underestimated?.
      Thus, in magnesium deficiency, intracellular calcium levels increase, activating processes which contribute to inflammation.
      • King D.E.
      Inflammation and elevation of C-reactive protein: does magnesium play a key role?.
      Serum magnesium is associated with muscle performance, e.g., in the elderly
      • Dominguez L.J.
      • Barbagallo M.
      • Lauretani F.
      • et al.
      Magnesium and muscle performance in older persons: the InCHIANTI study.
      and in patients with coronary artery disease.
      • Pokan R.
      • Hofmann P.
      • von Duvillard S.P.
      • et al.
      Oral magnesium therapy, exercise heart rate, exercise tolerance, and myocardial function in coronary artery disease patients.
      In the latter, the use of magnesium supplements improved exercise capacity. However, evidence that the use of magnesium supplements or the correction of mild magnesium deficiency, e.g., in patients with diabetes, is of consistent benefit is lacking.
      • Martin K.J.
      • González E.A.
      • Slatopolsky E.
      Clinical consequences and management of hypomagnesemia.
      Hypomagnesemia (and hypokalemia) are risk factors for drug-induced torsade de pointes arrhythmia. Thus, when using a drug known to prolong the QT interval, e.g., methadone, monitoring of serum electrolytes is generally recommended in patients with cardiac disease or other risk factors for prolonged QT, and in those at risk of electrolyte imbalance, e.g., because of vomiting, diarrhea or diuretics.
      • Al-Khatib S.M.
      • LaPointe N.M.
      • Kramer J.M.
      • Califf R.M.
      What clinicians should know about the QT interval.
      • Twycross R.
      • Wilcock A.
      Prolongation of the QT interval in palliative care.
      Hypermagnesemia is rare and is seen most often in patients with renal impairment who take OTC medicines containing magnesium. Serum concentrations >8mEq/L produce drowsiness, vasodilation, slowing of atrioventricular conduction and hypotension. Over 12mEq/L, there is profound CNS depression and muscle weakness (Box A). Calcium gluconate IV is used to help reverse the effects of hypermagnesemia.
      When drugs such as cisplatin cause severe renal wasting of magnesium, hypomagnesemia is generally present and aids diagnosis. If necessary, this can be confirmed by the high urinary excretion of magnesium. In deficiency states which develop more insidiously, the serum magnesium is an insensitive guide to total body stores and hypomagnesemia is not always present.
      • Dyckner T.
      • Wester P.
      Magnesium deficiency - guidelines for diagnosis and substitution therapy.
      • Ismail Y.
      • Ismail A.A.
      • Ismail A.A.A.
      The underestimated problem of using serum magnesium measurements to exclude magnesium deficiency in adults; a health warning is needed for "normal" results.
      In this situation, the finding of a low urinary excretion of magnesium may help the diagnosis. Currently, the best method for detecting magnesium deficiency is the magnesium loading test (Box B).
      • Dyckner T.
      • Wester P.
      Magnesium deficiency - guidelines for diagnosis and substitution therapy.
      • Ryzen E.
      • Elbaum N.
      • Singer F.R.
      • Rude R.K.
      Parenteral magnesium testing in the evaluation of magnesium deficiency.
      • Crosby V.
      • Wilcock A.
      • Lawson N.
      • Corcoran R.
      The importance of low magnesium in palliative care.
      The magnesium loading test
      • Ryzen E.
      • Elbaum N.
      • Singer F.R.
      • Rude R.K.
      Parenteral magnesium testing in the evaluation of magnesium deficiency.
      Collect pre-infusion urine sample for urinary magnesium (Mg)/creatinine (Cr) ratio. Measure Mg and Cr in mg/L; divide the Mg value by the Cr value to calculate the Mg/Cr ratio.
      By IVI over 4h, give 0.2mEq/kg (2.4mg/kg) of elemental magnesium, using magnesium sulphate 500mg/mL (4mEq or 48.6mg elemental magnesium/mL) diluted to 50mL with 5% dextrose (glucose).
      Simultaneously, start a 24h urine collection for magnesium and creatinine. Measure the total amounts of magnesium and creatinine excreted in mg (not the concentrations in mgl/L).
      Calculate % magnesium retention:
      >50% retention implies definite deficiency.
      If it is not possible to perform a magnesium loading test, hypokalemia (±hypocalcemia) not responding to potassium supplementation should raise the possibility of magnesium deficiency, and a trial of magnesium replacement therapy should be considered.
      • Martin K.J.
      • González E.A.
      • Slatopolsky E.
      Clinical consequences and management of hypomagnesemia.
      Magnesium blocks calcium channels including the NMDA-receptor channel and this probably accounts for its analgesic effect (Box C).
      • Mauskop A.
      • Altura B.T.
      • Cracco R.Q.
      • Altura B.M.
      Intravenous magnesium sulphate relieves migraine attacks in patients with low serum ionised magnesium levels: a pilot study.
      • Tramer M.R.
      • Schneider J.
      • Marti R.A.
      • Rifat K.
      Role of magnesium sulfate in postoperative analgesia.
      • Crosby V.
      • Wilcock A.
      • Corcoran R.
      The safety and efficacy of a single dose (500mg or 1g) of intravenous magnesium sulfate in neuropathic pain poorly responsive to strong opioid analgesics in patients with cancer.
      • Bondok R.S.
      • Abd El-Hady A.M.
      Intra-articular magnesium is effective for postoperative analgesia in arthroscopic knee surgery.
      However, despite the overall positive outcome from numerous RCTs, the role of magnesium as an analgesic in palliative care is yet to be determined and ideally such use should be in the setting of a clinical trial.
      Magnesium as an analgesic
      A number of studies have explored the effects of magnesium, mainly as an adjuvant analgesic for postoperative pain, with mixed results.
      A systematic review of 14 studies concluded that there is no convincing evidence of reduced postoperative pain intensity or decreased analgesic requirements when magnesium was used as an adjuvant.
      • Lysakowski C.
      • Dumont L.
      • Czarnetzki C.
      • Tramèr M.R.
      Magnesium as an adjuvant to postoperative analgesia: a systematic review of randomized trials.
      However, of numerous RCTs undertaken since this systematic review, all but two have reported reduced postoperative pain and decreased analgesic requirements.
      • Tauzin-Fin P.
      • Sesay M.
      • Delort-Laval S.
      • Krol-Houdek M.C.
      • Maurette P.
      Intravenous magnesium sulphate decreases postoperative tramadol requirement after radical prostatectomy.
      • Ozcan P.E.
      • Tugrul S.
      • Senturk N.M.
      • et al.
      Role of magnesium sulfate in postoperative pain management for patients undergoing thoracotomy.
      • Mentes O.
      • Harlak A.
      • Yigit T.
      • et al.
      Effect of intraoperative magnesium sulphate infusion on pain relief after laparoscopic cholecystectomy.
      • Ryu J.H.
      • Kang M.H.
      • Park K.S.
      • Do S.H.
      Effects of magnesium sulphate on intraoperative anaesthetic requirements and postoperative analgesia in gynaecology patients receiving total intravenous anaesthesia.
      • Dabbagh A.
      • Elyasi H.
      • Razavi S.S.
      • Fathi M.
      • Rajaei S.
      Intravenous magnesium sulfate for post-operative pain in patients undergoing lower limb orthopedic surgery.
      • Kogler J.
      The analgesic effect of magnesium sulfate in patients undergoing thoracotomy.
      • Kaya S.
      • Kararmaz A.
      • Gedik R.
      • Turhanoğlu S.
      Magnesium sulfate reduces postoperative morphine requirement after remifentanil-based anesthesia.
      • Hwang J.Y.
      • Na H.S.
      • Jeon Y.T.
      • et al.
      I.V. infusion of magnesium sulphate during spinal anaesthesia improves postoperative analgesia.
      • Saadawy I.M.
      • Kaki A.M.
      • Abd E.I.
      • Latif A.A.
      • Abd-Elmaksoud A.M.
      • Tolba O.M.
      Lidocaine vs. magnesium: effect on analgesia after a laparoscopic cholecystectomy.
      • Paech M.J.
      • Magann E.F.
      • Doherty D.A.
      • Verity L.J.
      • Newnham J.P.
      Does magnesium sulfate reduce the short- and long-term requirements for pain relief after caesarean delivery? A double-blind placebo-controlled trial.
      • Tramer M.R.
      • Glynn C.J.
      An evaluation of a single dose of magnesium to supplement analgesia after ambulatory surgery: randomized controlled trial.
      • Kiran S.
      • Gupta R.
      • Verma D.
      Evaluation of a single-dose of intravenous magnesium sulphate for prevention of postoperative pain after inguinal surgery.
      • Gupta S.D.
      • Mitra K.
      • Mukherjee M.
      • et al.
      Effect of magnesium infusion on thoracic epidural analgesia.
      • Olgun B.
      • Oğuz G.
      • Kaya M.
      • et al.
      The effects of magnesium sulphate on desflurane requirement, early recovery and postoperative analgesia in laparascopic cholecystectomy.
      Further, eight RCTs of spinal magnesium have all reported lower pain scores and decreased analgesic requirements.
      • Bilir A.
      • Gulec S.
      • Erkan A.
      • Ozcelik A.
      Epidural magnesium reduces postoperative analgesic requirement.
      • Arcioni R.
      • Palmisani S.
      • Tigano S.
      • et al.
      Combined intrathecal and epidural magnesium sulfate supplementation of spinal anesthesia to reduce post-operative analgesic requirements: a prospective, randomized, double-blind, controlled trial in patients undergoing major orthopedic surgery.
      • Farouk S.
      Pre-incisional epidural magnesium provides pre-emptive and preventive analgesia in patients undergoing abdominal hysterectomy.
      • Ghatak T.
      • Chandra G.
      • Malik A.
      • Singh D.
      • Bhatia V.K.
      Evaluation of the effect of magnesium sulphate vs. clonidine as adjunct to epidural bupivacaine.
      • Yousef A.A.
      • Amr Y.M.
      The effect of adding magnesium sulphate to epidural bupivacaine and fentanyl in elective caesarean section using combined spinal-epidural anaesthesia: a prospective double blind randomised study.
      • Ouerghi S.
      • Fnaeich F.
      • Frikha N.
      • et al.
      The effect of adding intrathecal magnesium sulphate to morphine-fentanyl spinal analgesia after thoracic surgery. A prospective, double-blind, placebo-controlled research study.
      • Khalili G.
      • Janghorbani M.
      • Sajedi P.
      • Ahmadi G.
      Effects of adjunct intrathecal magnesium sulfate to bupivacaine for spinal anesthesia: a randomized, double-blind trial in patients undergoing lower extremity surgery.
      • Khezri M.B.
      • Yaghobi S.
      • Hajikhani M.
      • Asefzadeh S.
      Comparison of postoperative analgesic effect of intrathecal magnesium and fentanyl added to bupivacaine in patients undergoing lower limb orthopedic surgery.
      In a RCT of PO magnesium in patients with neuropathic pain, although the frequency of pain paroxysms and the emotional component of behavior improved, there was no overall difference in pain intensity or quality of life
      • Pickering G.
      • Morel V.
      • Simen E.
      • et al.
      Oral magnesium treatment in patients with neuropathic pain: a randomized clinical trial.
      Cancer cells preferentially accumulate magnesium, which is used to activate or inhibit various metabolic and genetic pathways in order to promote cell survival and proliferation.
      • Castiglioni S.
      • Maier J.A.
      Magnesium and cancer: a dangerous liaison.
      Animal studies suggest that magnesium deficiency inhibits the growth of the primary cancer but exacerbates metastatic disease, possibly by enhancing inflammation.
      • Castiglioni S.
      • Maier J.A.
      Magnesium and cancer: a dangerous liaison.
      The relevance of these findings for patients is unknown.

      Cautions

      Generally, parenteral magnesium should not be given to patients with heart block or severe renal impairment. Risk of hypermagnesemia in patients with renal impairment.

      Undesirable Effects

      Flushing, sweating and sensation of warmth IV; diarrhea PO. Also see features of magnesium excess in Box A.

      Dose and Use

      Severe (serum magnesium <1mEq/L) and symptomatic hypomagnesemia generally necessitates replacement with >2mEq/kg of magnesium; the route of choice is IV, given in divided doses over 3–5 days.
      • Martin K.J.
      • González E.A.
      • Slatopolsky E.
      Clinical consequences and management of hypomagnesemia.
      • Miller S.
      Drug-induced hypomagnesaemia.
      Mild or asymptomatic hypomagnesemia may be treated PO. If the cause of the magnesium deficiency persists, PO maintenance therapy will be needed.
      In mild–moderate renal impairment, reduce IV replacement doses by 50% and monitor plasma magnesium daily. In severe renal impairment, avoid IV replacement if possible.

      Prevention of Deficiency

      • magnesium-rich foods, e.g., meat, seafood, green leafy vegetables, cereals and nuts
      • potassium-sparing diuretics also preserve magnesium, e.g., amiloride.

      IV Correction of Chronic Deficiency

      Because the degree of deficiency is difficult to determine from the plasma magnesium, replacement is empirical, guided by symptoms, plasma magnesium and renal function. Guidelines vary; the following are examples.
      Serum magnesium <1mEq/L with symptoms (life-threatening), e.g., arrhythmia, seizure
      • give 16mEq IV over 1 min
      • give as 4mL of magnesium sulfate 500mg (4mEq)/mL diluted to 10mL with 0.9% saline
      • follow with IVI replacement as below.
      Serum magnesium <1mEq/L with symptoms (not life-threatening)
      • on the first day give about 1mEq/kg, then 0.5mEq/kg daily for 2–5 days until the deficiency is corrected
      • give as an appropriate dose of magnesium sulfate 500mg (4mEq)/mL added to 250mL 0.9% saline or 5% dextrose
      • infuse over a convenient time interval, e.g., 1.5h; ensure the infusion rate is restricted to ≤1.2mEq/min to avoid exceeding the maximum renal tubular resorption capacity for magnesium
      • if undesirable effects occur, e.g., hypotension, increase the infusion time, e.g., up to 4h.
      IV is the parenteral route of choice. If PO and IV routes are not feasible, options include (in order of preference):
      • IM magnesium sulfate: in severe deficiency, give 0.5–1mEq/kg/24h as above in divided doses, e.g., multiple injections q4–6h of magnesium sulfate 500mg (4mEq)/mL; can be painful
      • CSCI magnesium sulfate: data are limited, but use of an isotonic solution is recommended, i.e., 50mEq of magnesium sulfate in 100mL WFI.
        • UK Medicines Information
        Medicines Q&A 350.2. How is acute hypomagnesaemia treated in adults?.
        • UK Medicines Information
        Medicines Q&A 14.3. Can magnesium sulphate be given subcutaneously? UK Medicines Information.
      Serum magnesium >1mEq/L and <1.5mEq/L without symptoms
      Begin with a trial of PO replacement. The main limiting factor is diarrhea, as magnesium salts are generally poorly absorbed PO and have a laxative effect. It is uncommon with doses <80mEq/24h, and the risk is reduced by a gradual introduction and by taking magnesium with or after food. None of the PO products is licensed for magnesium deficiency and products include those used normally as antacids or laxatives, e.g.:
      • magnesium oxide tablets:
        • start with 400mg b.i.d. with food
        • increase weekly by 400mg/day
        • usual maximum 400mg q.i.d. (80mEq/24h)
      • Milk of Magnesia® 5mL q.i.d. with food (56mEq/24h).
      Generally, 6–12months of treatment is required to fully correct a deficiency. If poorly tolerated or ineffective, use IV replacement as above.

      PO maintenance

      To prevent recurrence of the deficit, prescribe magnesium ∼48mEq/24h in divided doses with food. PO is used unless poorly tolerated or ineffective, e.g., malabsorption.

      Supply

      This is not an exhaustive list.
      Magnesium sulfate
      Injection 50% (500mg/mL), elemental magnesium 4mEq/mL, 2mL, 10mL, 20mL and 50mL vials = $1, $1.50, $2 and $4 respectively.
      Magnesium oxide
      Tablets 400mg (elemental magnesium 20mEq), available OTC.
      Magnesium hydroxide
      Oral suspension 400mg (elemental magnesium 14mEq)/5mL, available OTC as Milk of Magnesia®; do not store in a cold place.

      References

        • Romani A.
        Regulation of magnesium homeostasis and transport in mammalian cells.
        Arch Biochem Biophys. 2007; 458: 90-102
        • Martin K.J.
        • González E.A.
        • Slatopolsky E.
        Clinical consequences and management of hypomagnesemia.
        J Am Soc Nephrol. 2009; 20: 2291-2295
        • Elin R.J.
        Assessment of magnesium status for diagnosis and therapy.
        Magnes Res. 2010; 23: S194-S198
        • Standing Committee on the Scientific Evaluation of Dietary Reference Intakes
        Food and Nutrition Board, Institute of Medicine. DRI dietary reference intakes for calcium, phosphorous, magnesium, Vitamin D, and fluoride.
        National Academy Press, Washington DC1997
        • Rosanoff A.
        • Weaver C.M.
        • Rude R.K.
        Suboptimal magnesium status in the United States: are the health consequences underestimated?.
        Nutr Rev. 2012; 70: 153-164
        • Medicines and Healthcare Products Regulatory Agency
        Proton pump inhibitors in long term use: reports of hypomagnesaemia.
        Drug Saf Update. 2012; 5: A1
        • Ito T.
        • Jensen R.T.
        Association of long-term proton pump inhibitor therapy with bone fractures and effects on absorption of calcium, vitamin B12, iron, and magnesium.
        Curr Gastroenterol Rep. 2010; 12: 448-457
        • Hodgkinson E.
        • Neville-Webbe H.L.
        • Coleman R.E.
        Magnesium depletion in patients receiving cisplatin-based chemotherapy.
        Clin Oncol (R Coll Radiol). 2006; 18: 710-718
        • Schilsky R.L.
        • Barlock A.
        • Ozols R.F.
        Persistent hypomagnesemia following cisplatin chemotherapy for testicular cancer.
        Cancer Treat Rep. 1982; 66: 1767-1769
        • Buckley J.E.
        • Clark V.L.
        • Meyer T.J.
        • Pearlman N.W.
        Hypomagnesemia after cisplatin combination chemotherapy.
        Arch Intern Med. 1984; 144: 2347-2348
        • Costa A.
        • Tejpar S.
        • Prenen H.
        • Van Cutsem E.
        Hypomagnesaemia and targeted anti-epidermal growth factor receptor (EGFR) agents.
        Target Oncol. 2011; 6: 227-233
        • Cao Y.
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