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Zafrani L, Canet E, Walter-Petrich A, Joly-Laffargue B, Veyradier A, Faguer S, Bigé N, Calvet L, Mayaux J, Grangé S, Rafat C, Poulain C, Klouche K, Perez P, Pène F, Pichereau C, Duceau B, Mariotte E, Chevret S, Azoulay E. Magnesium sulphate in patients with thrombotic thrombocytopenic purpura (MAGMAT): a randomised, double-blind, superiority trial. Intensive Care Med 2023; 49:1293-1304. [PMID: 37867165 DOI: 10.1007/s00134-023-07178-6] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/29/2023] [Accepted: 07/24/2023] [Indexed: 10/24/2023]
Abstract
PURPOSE Studies have suggested benefits from magnesium sulphate in thrombotic thrombocytopenic purpura (TTP). We aimed to measure the effects of magnesium sulphate supplementation on TTP recovery. METHODS In this multicenter, randomised, double-blind, controlled, superiority study, we enrolled adults with a clinical diagnosis of TTP. Patients were randomly allocated to receive magnesium sulphate (6 g intravenously followed by a continuous infusion of 6 g/24 h for 3 days) or placebo, in addition to the standard treatment. The primary outcome was the median time to platelet normalisation (defined as a platelet count ≥ 150 G/L). Efficacy and safety were assessed by intention-to-treat. RESULTS Overall, we enrolled 74 participants, including one who withdrew his/her consent. Seventy-three patients were further analyzed, 35 (48%) allocated to magnesium sulphate and 38 (52%) to placebo. The median time to platelet normalisation was 4 days (95% confidence interval [CI], 3-4) in the magnesium sulphate group and 4 days (95% CI 3-5) in the placebo group. The cause-specific hazard ratio of response was 0.93 (95% CI 0.58-1.48, p = 0.75). The number of patients with ≥ 1 serious adverse reactions was similar in the two groups. By day 90, four patients in the magnesium sulphate group and two patients in the placebo group had died (p = 0.42). The most frequent adverse event was low blood pressure occurring in 34% in the magnesium sulphate group and 29% in the placebo group (p = 0.80). CONCLUSION Among patients with TTP, the addition of magnesium sulphate to the standard of care did not result in a significant improvement in time to platelet normalisation.
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Affiliation(s)
- Lara Zafrani
- Department of Medical Intensive Care Unit, Saint-Louis Hospital, Assistance Publique-Hôpitaux de Paris, University of Paris Cité, Paris, France.
- INSERM U944, Saint-Louis Research Institute, University of Paris Cité, Paris, France.
| | - Emmanuel Canet
- Department of Medical Intensive Care Unit, Nantes University Hospital, Nantes University, Nantes, France
| | - Anouk Walter-Petrich
- Department of Biostatistics, Saint-Louis Hospital, Assistance Publique-Hôpitaux de Paris, University of Paris Cité, INSERM S 717, Paris, France
| | - Bérangère Joly-Laffargue
- Service d'Hématologie Biologique, Lariboisière Hospital and EA3518, Institut de Recherche Saint-Louis, Saint-Louis Hospital, Assistance Publique-Hôpitaux de Paris, University of Paris Cité, Paris, France
| | - Agnès Veyradier
- Service d'Hématologie Biologique, Lariboisière Hospital and EA3518, Institut de Recherche Saint-Louis, Saint-Louis Hospital, Assistance Publique-Hôpitaux de Paris, University of Paris Cité, Paris, France
| | - Stanislas Faguer
- Department of Nephrology and Organ Transplantation, National Reference Center for Rare Kidney Diseases, University Hospital of Toulouse, INSERM UMR 1297 (I2MC), Toulouse, France
| | - Naïke Bigé
- Department of Medical Intensive Care Unit, Saint-Antoine Hospital, Assistance Publique-Hôpitaux de Paris, Sorbonne University, Paris, France
| | - Laure Calvet
- Department of Medical Intensive Care Unit, Clermont-Ferrand University Hospital, Clermont-Ferrand, France
| | - Julien Mayaux
- Department of Medical Intensive Care Unit, Pitié-Salpêtrière Hospital, Assistance Publique-Hôpitaux de Paris, Sorbonne University, Paris, France
| | - Steven Grangé
- Department of Nephrology, Rouen University Hospital, Rouen, France
| | - Cédric Rafat
- Service de Soins Intensifs Néphrologiques et Rein Aigu (SINRA), French Intensive Renal Network, Tenon Hospital, Assistance Publique-Hôpitaux de Paris, Paris, France
| | - Coralie Poulain
- Department of Nephrology Internal Medicine Dialysis Transplantation, Amiens University Medical Center, F-80054, Amiens, France
| | - Kada Klouche
- Intensive Care Medicine Department, Lapeyronie University Hospital, Montpellier, France
| | - Pierre Perez
- Medical Intensive Care Unit, Brabois Hospital, Vandoeuvre Les Nancy, France
| | - Frédéric Pène
- Medical Intensive Care Unit, Cochin Hospital, Assistance Publique -Hôpitaux de Paris, University of Paris Cité, Cochin Institute, INSERM U1016, CNRS UMR8104, Paris, France
| | - Claire Pichereau
- Department of Intensive Care Unit, Poissy Saint Germain en Laye Hospital, Poissy, France
| | - Baptiste Duceau
- Department of Anesthesiology and Critical Care Medicine, Pitié-Salpêtrière Hospital, Assistance Publique-Hôpitaux de Paris, Sorbonne University, Paris, France
| | - Eric Mariotte
- Department of Medical Intensive Care Unit, Saint-Louis Hospital, Assistance Publique-Hôpitaux de Paris, University of Paris Cité, Paris, France
| | - Sylvie Chevret
- Department of Biostatistics, Saint-Louis Hospital, Assistance Publique-Hôpitaux de Paris, University of Paris Cité, INSERM S 717, Paris, France
| | - Elie Azoulay
- Department of Medical Intensive Care Unit, Saint-Louis Hospital, Assistance Publique-Hôpitaux de Paris, University of Paris Cité, Paris, France
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Pickering ME. Cross-Talks between the Cardiovascular Disease-Sarcopenia-Osteoporosis Triad and Magnesium in Humans. Int J Mol Sci 2021; 22:ijms22169102. [PMID: 34445808 PMCID: PMC8396464 DOI: 10.3390/ijms22169102] [Citation(s) in RCA: 5] [Impact Index Per Article: 1.3] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/28/2021] [Revised: 08/11/2021] [Accepted: 08/13/2021] [Indexed: 02/06/2023] Open
Abstract
Magnesium (Mg) is a pivotal and very complex component of healthy aging in the cardiovascular-muscle-bone triad. Low Mg levels and low Mg intake are common in the general aging population and are associated with poorer outcomes than higher levels, including vascular calcification, endothelial dysfunction, osteoporosis, or muscle dysfunction/sarcopenia. While Mg supplementation appears to reverse these processes and benefit the triad, more randomized clinical trials are needed. These will allow improvement of preventive and curative strategies and propose guidelines regarding the pharmaceutical forms and the dosages and durations of treatment in order to optimize and adapt Mg prescription for healthy aging and for older vulnerable persons with comorbidities.
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Affiliation(s)
- Marie-Eva Pickering
- Rheumatology Department, CHU Gabriel Montpied, 63000 Clermont-Ferrand, France
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Mathew AA, Panonnummal R. 'Magnesium'-the master cation-as a drug-possibilities and evidences. Biometals 2021; 34:955-986. [PMID: 34213669 PMCID: PMC8249833 DOI: 10.1007/s10534-021-00328-7] [Citation(s) in RCA: 45] [Impact Index Per Article: 11.3] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/29/2020] [Accepted: 06/19/2021] [Indexed: 02/06/2023]
Abstract
Magnesium (Mg2+) is the 2nd most abundant intracellular cation, which participates in various enzymatic reactions; there by regulating vital biological functions. Magnesium (Mg2+) can regulate several cations, including sodium, potassium, and calcium; it consequently maintains physiological functions like impulse conduction, blood pressure, heart rhythm, and muscle contraction. But, it doesn't get much attention in account with its functions, making it a "Forgotten cation". Like other cations, maintenance of the normal physiological level of Mg2+ is important. Its deficiency is associated with various diseases, which point out to the importance of Mg2+ as a drug. The roles of Mg2+ such as natural calcium antagonist, glutamate NMDA receptor blocker, vasodilator, antioxidant and anti-inflammatory agent are responsible for its therapeutic benefits. Various salts of Mg2+ are currently in clinical use, but their application is limited. This review collates all the possible mechanisms behind the behavior of magnesium as a drug at different disease conditions with clinical shreds of evidence.
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Affiliation(s)
- Aparna Ann Mathew
- Amrita School of Pharmacy, Amrita Institute of Medical Science & Research Centre, Amrita VishwaVidyapeetham, Kochi, 682041, India
| | - Rajitha Panonnummal
- Amrita School of Pharmacy, Amrita Institute of Medical Science & Research Centre, Amrita VishwaVidyapeetham, Kochi, 682041, India.
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The Effect of Early Treatment with Intravenous Magnesium Sulfate on the Incidence of Cardiac Comorbidities in Hospitalized Stroke Patients. Cardiovasc Ther 2020; 2020:1494506. [PMID: 33072188 PMCID: PMC7533752 DOI: 10.1155/2020/1494506] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.4] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 03/19/2020] [Accepted: 07/07/2020] [Indexed: 12/12/2022] Open
Abstract
Background Cardiac adverse events are common among patients presenting with acute stroke and contribute to overall morbidity and mortality. Prophylactic measures for the reduction of cardiac adverse events in hospitalized stroke patients have not been well understood. We sought to investigate the effect of early initiation of high-dose intravenous magnesium sulfate on cardiac adverse events in stroke patients. Methods This is a secondary analysis of the prehospital Field Administration of Stroke Therapy-Magnesium (FAST-MAG) randomized phase-3 clinical trial, conducted from 2005-2013. Consecutive patients with suspected acute stroke and a serum magnesium level within 72 hours of enrollment were selected. Twenty grams of magnesium sulfate or placebo was administered in the ambulance starting with a 15-minute loading dose intravenous infusion followed by a 24-hour maintenance infusion in the hospital. Results Among 1126 patients included in the analysis of this study, 809 (71.8%) patients had ischemic stroke, 277 (24.6%) had hemorrhagic stroke, and 39 (3.5%) with stroke mimics. The mean age was 69.5 (SD13.4) and 42% were female. 565 (50.2%) received magnesium treatment, and 561 (49.8%) received placebo. 254 (22.6%) patients achieved the target, and 872 (77.4%) did not achieve the target, regardless of their treatment group. Among 1126 patients, 159 (14.1%) had at least one CAE. Treatment with magnesium was not associated with fewer cardiac adverse events. A multivariate binary logistic regression for predictors of CAEs showed a positive association of older age and frequency of CAEs (R = 1.04, 95% CI 1.03-1.06, p < 0.0001). Measures of early and 90-day outcomes did not differ significantly between the magnesium and placebo groups among patients who had CAEs. Conclusion Treatment of acute stroke patients with magnesium did not result in a reduction in the number or severity of cardiac serious adverse events.
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Prevention of Cardiovascular Disease: Screening for Magnesium Deficiency. Cardiol Res Pract 2019; 2019:4874921. [PMID: 31192005 PMCID: PMC6525869 DOI: 10.1155/2019/4874921] [Citation(s) in RCA: 34] [Impact Index Per Article: 5.7] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 01/26/2019] [Accepted: 03/17/2019] [Indexed: 12/15/2022] Open
Abstract
Magnesium is an essential mineral naturally present in the human body, where it acts as cofactor in several enzymatic reactions. Magnesium is a key cardiovascular regulator, which maintains electrical, metabolic, and vascular homeostasis. Moreover, magnesium participates in inflammation and oxidative processes. In fact, magnesium deficiency is involved in the pathophysiology of arterial hypertension, diabetes mellitus, dyslipidemia, metabolic syndrome, endothelial dysfunction, coronary artery disease, cardiac arrhythmias, and sudden cardiac death. In consideration of the great public-health impact of cardiovascular disease, the recognition of the negative effects of magnesium deficiency suggests the possible role of hypomagnesaemia as cardiovascular risk factor and the use of serum magnesium level for the screening and prevention of cardiovascular risk factors and cardiovascular diseases. Moreover, it might help with the identification of new therapeutical strategies for the management of cardiovascular disease through magnesium supplementation.
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Serum magnesium and risk of new onset heart failure in men: the Kuopio Ischemic Heart Disease Study. Eur J Epidemiol 2016; 31:1035-1043. [DOI: 10.1007/s10654-016-0164-4] [Citation(s) in RCA: 17] [Impact Index Per Article: 1.9] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/08/2015] [Accepted: 05/17/2016] [Indexed: 10/21/2022]
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Ghodraty MR, Homaee MM, Farazmehr K, Nikzad-Jamnani AR, Soleymani-Dodaran M, Pournajafian AR, Nader ND. Comparative induction of controlled circulation by magnesium and remifentanil in spine surgery. World J Orthop 2014; 5:51-56. [PMID: 24649414 PMCID: PMC3952694 DOI: 10.5312/wjo.v5.i1.51] [Citation(s) in RCA: 17] [Impact Index Per Article: 1.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 09/05/2013] [Revised: 12/10/2013] [Accepted: 12/19/2013] [Indexed: 02/06/2023] Open
Abstract
AIM: To evaluate the efficacy of magnesium sulfate (MGS) in comparison with remifentanil for induction of relative hypotension in posterior fusion of spine (PSF).
METHODS: In this randomized clinical trial, 40 patients with the American Society of Anesthesiologists I and II physical status undergoing lumbar PSF were randomized to receive remifentanil (REM) 0.15 μg/kg or MGS 50 mg/kg for controlled hypotension. The administering anesthesiologist was blinded to the medication. Continuous infusion was maintained at a fixed volume rate to deliver precalculated doses of either study drugs. All other aspects of anesthesia and surgery were similar in the two groups. The target mean arterial pressure (MAP) range used in this study was 60-70 mmHg. In the course of surgery, the hemodynamic variables, volume of blood loss, urine output, fluid intake and surgeon’s satisfaction were recorded. Data was analyzed with SPSS version 13.0 and P values less than 0.05 were considered significant.
RESULTS: Twenty patients in the MGS group and 19 patients in the REM group were studied. There was no difference between the two groups in the hemodynamic variables, blood loss, urine output, fluid requirement and surgeon’s satisfaction for exposure. The target MAP was achieved in 75% of Mg and 58% of remifentanil groups. Although a higher number of patients in the REM group required nitroglycerin (42.1%) to reach the target MAP than those in the MGS group (25%), this difference was not statistically significant (P = 0.32).
CONCLUSION: Our findings showed that in patients undergoing lumbar PSF surgery, remifentanil and MGS have a similar hypotensive effect and comparable amount of blood loss without any significant adverse effects.
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Dumont LA, Gangloff G, Grolleau-Raoux JL, Chavoin JP, Garrido-Stowhas I. [Evidence-based medicine and prevention of thrombosis in microsurgery. Critical review]. ANN CHIR PLAST ESTH 2010; 56:219-31. [PMID: 20646817 DOI: 10.1016/j.anplas.2010.01.002] [Citation(s) in RCA: 4] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/15/2009] [Accepted: 01/09/2010] [Indexed: 11/28/2022]
Abstract
Prevention of thrombosis in microsurgery was the point of numerous publications without any referenced protocol. The question of this article was to know if it existed, for a patient who needed a microsurgical procedure, any medical treatment used, proved to lower the thrombotic risk. Using principles of evidence-based medicine, we observed that none of the medical treatments proved efficiency on preventing vascular thrombosis, arterial or venous. The low molecular weight heparins (LMWH) could be used on postoperatives to prevent the deep venous thrombosis of lower limbs but not to lower specially the microvascular thrombosis rate. Aspirin did not improve the positive rates and its adjunction to LMWH increased the bleeding. The evidence-based medicine, as we used it here, permits to conclude that the microsurgeon should not wait any miracle of the medical treatments. Until scientific studies prove efficacity of a treatment, the surgeon has to make a personal choice: keeping habits or following evidence-based medicine. The experience of the surgeon, of the anesthetist and of the paramedical team seem to be the main point to decrease the thrombotic risk during the multidisciplinary healing care of the patient.
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Affiliation(s)
- L-A Dumont
- Service de chirurgie plastique, reconstructrice et esthétique, hôpital Rangueil, Toulouse, France.
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EI-Sherif N, Khan A, Savarese J, Turitto G. Sudden Cardiac Death and Coronary Artery Disease —Pathophysiology and Risk Stratification. J Arrhythm 2009. [DOI: 10.1016/s1880-4276(09)80010-0] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/01/2022] Open
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Abstract
BACKGROUND Mortality and morbidity from acute myocardial infarction (AMI) remain high. Intravenous magnesium started early after the onset of AMI is thought to be a promising adjuvant treatment. Conflicting results from earlier trials and meta-analyses warrant a systematic review of available evidence. OBJECTIVES To examine the effect of intravenous magnesium versus placebo on early mortality and morbidity. SEARCH STRATEGY We searched CENTRAL (The Cochrane Library Issue 3, 2006), MEDLINE (January 1966 to June 2006) and EMBASE (January 1980 to June 2006), and the Chinese Biomedical Disk (CBM disk) (January 1978 to June 2006). Some core Chinese medical journals relevant to the cardiovascular field were hand searched from their starting date to the first-half year of 2006. SELECTION CRITERIA All randomized controlled trials that compared intravenous magnesium with placebo in the presence or absence of fibrinolytic therapy in addition to routine treatment were eligible if they reported mortality and morbidity within 35 days of AMI onset. DATA COLLECTION AND ANALYSIS Two reviewers independently assessed the trial quality and extracted data using a standard form. Odds ratio (OR) were used to pool the effect if appropriate. Where heterogeneity of effects was found, clinical and methodological sources of this were explored. MAIN RESULTS For early mortality where there was evidence of heterogeneity, a fixed-effect meta-analysis showed no difference between magnesium and placebo groups (OR 0.99, 95%CI 0.94 to 1.04), while a random-effects meta-analysis showed a significant reduction comparing magnesium with placebo (OR 0.66, 95% CI 0.53 to 0.82). Stratification by timing of treatment (< 6 hrs, 6+ hrs) reduced heterogeneity, and in both fixed-effect and random-effects models no significant effect of magnesium was found. In stratified analyses, early mortality was reduced for patients not treated with thrombolysis (OR=0.73, 95% CI 0.56 to 0.94 by random-effects model) and for those treated with less than 75 mmol of magnesium (OR=0.59, 95% CI 0.49 to 0.70) in the magnesium compared with placebo groups.Meta-analysis for the secondary outcomes where there was no evidence of heterogeneity showed reductions in the odds of ventricular fibrillation (OR=0.88, 95% CI 0.81 to 0.96), but increases in the odds of profound hypotension (OR=1.13, 95% CI 1.09 to 1.19) and bradycardia (OR=1.49, 95% CI 1.26 to 1.77) comparing magnesium with placebo. No difference was observed for heart block (OR=1.05, 95% CI 0.97-1.14). For those outcomes where there was evidence of heterogeneity, meta-analysis with both fixed-effect and random-effects models showed that magnesium could decrease ventricular tachycardia (OR=0.45, 95% CI 0.31 to 0.66 by fixed-effect model; OR=0.40, 95% CI 0.19 to 0.84 by random-effects model) and severe arrhythmia needing treatment or Lown 2-5 (OR=0.72, 95% CI 0.60 to 0.85 by fixed-effect model; OR=0.51, 95% CI 0.33 to 0.79 by random-effects model) compared with placebo. There was no difference on the effect of cardiogenic shock between the two groups. AUTHORS' CONCLUSIONS Owing to the likelihood of publication bias and marked heterogeneity of treatment effects, it is essential that the findings are interpreted cautiously. From the evidence reviewed here, we consider that: (1) it is unlikely that magnesium is beneficial in reducing mortality both in patients treated early and in patients treated late, and in patients already receiving thrombolytic therapy; (2) it is unlikely that magnesium will reduce mortality when used at high dose (>=75 mmol); (3) magnesium treatment may reduce the incidence of ventricular fibrillation, ventricular tachycardia, severe arrhythmia needing treatment or Lown 2-5, but it may increase the incidence of profound hypotension, bradycardia and flushing; and (4) the areas of uncertainty regarding the effect of magnesium on mortality remain the effect of low dose treatment (< 75 mmol) and in patients not treated with thrombolysis.
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Affiliation(s)
- J Li
- West China Hospital,Sichuan University, Chinese Cochrane Centre, Chengdu, Sichuan, China, 610041.
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Karagülle O, Kleczka T, Vidal C, Candir F, Gundermann G, Külpmann WR, Gehrke A, Gutenbrunner C. Magnesium absorption from mineral waters of different magnesium content in healthy subjects. Complement Med Res 2006; 13:9-14. [PMID: 16582545 DOI: 10.1159/000090016] [Citation(s) in RCA: 15] [Impact Index Per Article: 0.8] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/19/2022]
Abstract
OBJECTIVE To assess the absorption of magnesium (Mg) from mineral waters of different Mg content in comparison to low mineralized water and a Mg capsule. MATERIALS AND METHODS DESIGN Randomized, controlled, double- blind trial in a crossover design with an additional control with a Mg capsule. SETTING Institute of Balneology and Medical Climatology, Medical School of Hanover, Germany. SUBJECTS 22 healthy male volunteers aged between 23-46 years. INTERVENTION After a standardized breakfast, each participant received, in Latin square order, 500 ml of either of two Mg-rich mineral waters (281 or 120 mg/l). As a control condition, a mineral water of low Mg content (8 mg/l) was used. A Mg capsule (Magnesium-Diasporal 150, Protina, Ismaning, Germany) was used for further comparisons. RESULTS Changes in serum Mg levels in the first 4 hours after intake differed significantly between the groups (p = 0.030; ANOVA). Mean values differed between the Mg-rich mineral water conditions and the control conditions though did not reach statistical significance (p = 0.055), however, mean values did not differ between the test waters and the capsule (p = 0.338). CONCLUSION Magnesium from mineral waters can easily be absorbed and its absorption rate is similar to that from a pharmaceutical Mg preparation.
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Affiliation(s)
- Oguz Karagülle
- Institute of Balneology and Medical Climatology, Medical School of Hanover, Germany.
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Abstract
Magnesium (Mg) deficiency commonly occurs in critical illness and correlates with a higher mortality and worse clinical outcome in the intensive care unit (ICU). Magnesium has been directly implicated in hypokalemia, hypocalcemia, tetany, and dysrhythmia. Moreover, Mg may play a role in acute coronary syndromes, acute cerebral ischemia, and asthma. Magnesium regulates hundreds of enzyme systems. By regulating enzymes controlling intracellular calcium, Mg affects smooth muscle vasoconstriction, important to the underlying pathophysiology of several critical illnesses. The principle causes of Mg deficiency are gastrointestinal and renal losses; however, the diagnosis is difficult to make because of the limitations of serum Mg levels, the most common assessment of Mg status. Magnesium tolerance testing and ionized Mg2+ are alternative laboratory assessments; however, each has its own difficulties in the ICU setting. The use of Mg therapy is supported by clinical trials in the treatment of symptomatic hypomagnesemia and preeclampsia and is recommended for torsade de pointes. Magnesium therapy is not supported in the treatment of acute myocardial infarction and is presently undergoing evaluation for the treatment of severe asthma exacerbation, for the prevention of post-coronary bypass grafting dysrhythmias, and as a neuroprotective agent in acute cerebral ischemia.
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Affiliation(s)
- Garrison M Tong
- University of Southern California, School of Medicine, Los Angeles, CA 90089-9317, USA
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Abstract
Risk Stratification and Management of SCD. Management of SCD is undergoing radical change in direction. It is becoming increasingly appreciated that besides depressed left ventricular systolic function and the conventional risk stratification tools, new markers for plaque vulnerability, enhanced thrombogenesis, specific genetic alterations of the autonomic nervous system, cardiac sarcolemmal and contractile proteins, and familial clustering may better segregate patients with atherosclerotic coronary artery disease who are at high risk for SCD from those who may suffer from nonfatal ischemic events. Better understanding of pathophysiologic processes, such as postmyocardial infarction remodeling, the transition from compensated hypertrophy to heart failure, and the increased cardiovascular risk of coronary artery disease in the presence of diabetes or even a prediabetic state will help to improve both risk stratification and management. The rapidly developing fields of microchips technology and proteomics may allow rapid and cost-effective mass screening of multiple risk factors for SCD. The ultimate goal is to identify novel methods for risk stratification, risk modification, and prevention of SCD that could be applied to the general public at large.
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Affiliation(s)
- Nabil El-Sherif
- Cardiology Division, Department of Medicine, State University of New York, Downstate Medical Center, and New York Harbor Health Care Center, Brooklyn, New York, USA.
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Abstract
Nutritional and herbal supplements may have harmful or beneficial effects on arrhythmias. Potential supplements that may have antiarrhythmic activity include omega-3 polyunsaturated fatty acids (N-3 PUFA), coenzyme Q10, and carnitine. Clinical studies show that N-3 PUFA or fish oil supplementation appears to reduce mortality and sudden death. Coenzyme Q10, used in treatment of heart failure, and carnitine and its derivatives may have beneficial effects on arrhythmias, although clinical studies have been limited. Antioxidant supplements may be beneficial, but large studies with vitamin E have been disappointing in that it does not reduce mortality. Correction of electrolyte disturbances has been long advised and magnesium supplementation has been beneficial in the treatment of torsades de pointes and in some studies after cardiac surgery. However, routine electrolyte supplementation with empiric potassium or magnesium in non-deficient patients has not been convincingly beneficial. Several herbal supplements have also been promoted to have antiarrhythmic activity. However, clinical studies are lacking to support routine use of these herbal medications. In addition, some herbal supplements may cause serious proarrhythmia, and many supplements significantly interact with warfarin and digoxin.
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Affiliation(s)
- Mina K Chung
- Department of Cardiovascular Medicine, The Cleveland Clinic Foundation, Cleveland, OH 44195, USA.
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Dubé L, Granry JC. The therapeutic use of magnesium in anesthesiology, intensive care and emergency medicine: a review. Can J Anaesth 2003; 50:732-46. [PMID: 12944451 DOI: 10.1007/bf03018719] [Citation(s) in RCA: 132] [Impact Index Per Article: 6.0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 02/03/2023] Open
Abstract
PURPOSE To review current knowledge concerning the use of magnesium in anesthesiology, intensive care and emergency medicine. METHODS References were obtained from Medline(R) (1995 to 2002). All categories of articles (clinical trials, reviews, or meta-analyses) on this topic were selected. The key words used were magnesium, anesthesia, analgesia, emergency medicine, intensive care, surgery, physiology, pharmacology, eclampsia, pheochromocytoma, asthma, and acute myocardial infarction. PRINCIPLE FINDINGS Hypomagnesemia is frequent postoperatively and in the intensive care and needs to be detected and corrected to prevent increased morbidity and mortality. Magnesium reduces catecholamine release and thus allows better control of adrenergic response during intubation or pheochromocytoma surgery. It also decreases the frequency of postoperative rhythm disorders in cardiac surgery as well as convulsive seizures in preeclampsia and their recurrence in eclampsia. The use of adjuvant magnesium during perioperative analgesia may be beneficial for its antagonist effects on N-methyl-D-aspartate receptors. The precise role of magnesium in the treatment of asthmatic attacks and myocardial infarction in emergency conditions needs to be determined. CONCLUSIONS Magnesium has many known indications in anesthesiology and intensive care, and others have been suggested by recent publications. Because of its interactions with drugs used in anesthesia, anesthesiologists and intensive care specialists need to have a clear understanding of the role of this important cation.
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Affiliation(s)
- Laurent Dubé
- Department of Anesthesiology, University Hospital, Angers, France.
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Booth JV, Phillips-Bute B, McCants CB, Podgoreanu MV, Smith PK, Mathew JP, Newman MF. Low serum magnesium level predicts major adverse cardiac events after coronary artery bypass graft surgery. Am Heart J 2003; 145:1108-13. [PMID: 12796771 DOI: 10.1016/s0002-8703(03)00077-2] [Citation(s) in RCA: 36] [Impact Index Per Article: 1.6] [Reference Citation Analysis] [Abstract] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 10/27/2022]
Abstract
BACKGROUND Despite improved myocardial protection strategies and enhanced surgical techniques, mortality after coronary artery bypass graft surgery (CABG) remains essentially unchanged. This may be because of the increasing age of patients who undergo primary CABG. Magnesium is an important regulator of vascular tone, reperfusion injury, and thrombosis. Therefore, we decided to investigate the relationship between serum magnesium levels and major adverse cardiac events (MACE) after CABG. METHODS A total of 957 patients undergoing primary CABG were prospectively recruited into the Duke Cardiovascular database and had daily serum magnesium levels measured. Low magnesium was defined as <1.8 mmol/L(-1) at any point during the first 8 days after surgery. Adverse events were defined as Q-wave infarction or death measured 1 year after surgery. A Kaplan-Meier survival analysis was performed, followed by a Cox proportional hazards model, to account for other known predictors of adverse events. RESULTS In the low magnesium group, 12.3% of patients had adverse events, compared with 9.2% of patients in the normal magnesium group. A serum magnesium level <1.8 mmol/L(-1) decreased the event-free survival rate (2-fold increased risk of death or myocardial infarction at 1 year; hazard ratio 2.0, 95% CI 1.19-3.37). CONCLUSIONS We demonstrated a robust relationship between low serum magnesium levels after CABG and a 2-fold increased incidence of Q-wave infarction and all-cause mortality rate as long as 1 year after surgery. This relationship is independent of known preoperative and intraoperative predictors of adverse outcomes. This study provides a rationale for a randomized controlled trial of magnesium therapy during CABG.
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Affiliation(s)
- John V Booth
- Department of Anesthesiology, Duke University Medical Center, Durham, NC 27710, USA.
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Early administration of intravenous magnesium to high-risk patients with acute myocardial infarction in the Magnesium in Coronaries (MAGIC) Trial: a randomised controlled trial. Lancet 2002; 360:1189-96. [PMID: 12401244 DOI: 10.1016/s0140-6736(02)11278-5] [Citation(s) in RCA: 127] [Impact Index Per Article: 5.5] [Reference Citation Analysis] [Abstract] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 11/17/2022]
Abstract
BACKGROUND The benefits of supplemental administration of intravenous magnesium in patients with ST-elevation myocardial infarction (STEMI) are controversial. Despite promising results from work in animals and the ready availability of this simple, inexpensive treatment, conflicting results have been reported in clinical trials. Our aim was to compare short-term mortality in patients with STEMI who received either intravenous magnesium sulphate or placebo. METHODS We did a randomised, double-blind trial in 6213 patients with acute STEMI who were assigned a 2 g intravenous bolus of magnesium sulphate administered over 15 min, followed by a 17 g infusion of magnesium sulphate over 24 h (n=3113), or matching placebo (n=3100). Our primary endpoint was 30-day all-cause mortality. At randomisation, patients were stratified by their eligibility for reperfusion therapy. The first stratum included patients who were aged 65 years or older and eligible for reperfusion therapy, and the second stratum included patients of any age who were not eligible for reperfusion therapy. Analysis was by intention-to-treat. FINDINGS At 30 days, 475 (15.3%) patients in the magnesium group and 472 (15.2%) in the placebo group had died (odds ratio 1.0, 95% CI 0.9-1.2, p=0.96). No benefit or harm of magnesium was observed in eight prespecified subgroup analyses of patients and in 15 additional exploratory subgroup analyses. After adjustment for factors shown to effect mortality risk in a multivariate regression model, no benefit of magnesium was observed (1.0, 0.8-1.1, p=0.53). INTERPRETATION Early administration of magnesium in high-risk patients with STEMI has no effect on 30-day mortality. In view of the totality of the available evidence, in current coronary care practice there is no indication for the routine administration of intravenous magnesium in patients with STEMI.
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Abstract
Magnesium has been advocated for the treatment of a variety of conditions seen in emergency medicine. The authors present a systematic review and advice on appropriate indications for its use. Evidence supports its use in severe asthma, eclampsia, and torsade de pointes. There is insufficient evidence to justify its routine use in other emergencies.
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Affiliation(s)
- P Kaye
- Emergency Department, Bristol Royal Infirmary, Bristol, UK.
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Sharikabad MN, Ostbye KM, Brørs O. Increased [Mg2+]o reduces Ca2+ influx and disruption of mitochondrial membrane potential during reoxygenation. Am J Physiol Heart Circ Physiol 2001; 281:H2113-23. [PMID: 11668073 DOI: 10.1152/ajpheart.2001.281.5.h2113] [Citation(s) in RCA: 32] [Impact Index Per Article: 1.3] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 11/22/2022]
Abstract
Increase in extracellular Mg2+ concentration ([Mg2+]o) reduces Ca2+ accumulation during reoxygenation of hypoxic cardiomyocytes and exerts protective effects. The aims of the present study were to investigate the effect of increased [Mg(2+)](o) on Ca2+ influx and efflux, free cytosolic Ca2+ ([Ca2+]i) and Mg2+ concentrations ([Mg2+]i), Ca2+ accumulation in the presence of inhibitors of mitochondrial or sarcoplasmatic reticulum Ca2+ transport, and finally mitochondrial membrane potential (Delta(psi)m). Isolated adult rat cardiomyocytes were exposed to 1 h of hypoxia and subsequent reoxygenation. Cell Ca2+ was determined by 45Ca2+ uptake, and the levels of [Mg2+]i and [Ca2+]i were determined by flow cytometry as the fluorescence of magnesium green and fluo 3, respectively. Ca2+ influx rate was significantly reduced by approximately 40%, whereas Ca2+ efflux was not affected by increased [Mg2+]o (5 mM) during reoxygenation. [Ca2+]i and [Mg2+]i were increased at the end of hypoxia, fell after reoxygenation, and were unaffected by increased [Mg2+]o. Clonazepam, a selective mitochondrial Na+/Ca2+ exchange inhibitor (100 microM), significantly reduced Ca2+ accumulation by 70% and in combination with increased [Mg2+]o by 90%. Increased [Mg2+]o, clonazepam, and the combination of both attenuated the hypoxia-reoxygenation-induced reduction in Delta(psi)m, determined with the cationic dye JC-1 by flow cytometry. A significant inverse correlation was observed between Delta(psi)m and cell Ca2+ in reoxygenated cells treated with increased [Mg2+]o and clonazepam. In conclusion, increased [Mg2+]o (5 mM) inhibits Ca2+ accumulation by reducing Ca2+ influx and preserves Delta(psi)m without affecting [Ca2+]i and [Mg2+]i during reoxygenation. Preservation of mitochondria may be an important effect whereby increased [Mg2+]o protects the postischemic heart.
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Affiliation(s)
- M N Sharikabad
- Division of Clinical Pharmacology and Toxicology, Clinical Chemistry Department, Ullevaal University Hospital, N-0407 Oslo, Norway.
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