Pharmacokinetics of Magnesium Bolus Therapy in Cardiothoracic Surgery

Biesenbach, Peter; Mårtensson, Johan; Lucchetta, Luca; Bangia, Ravi; Fairley, Jessica; Jansen, Irmelin; Matalanis, George; Bellomo, Rinaldo

doi:10.1053/j.jvca.2017.08.049

Cited by 13 publications

(13 citation statements)

References 17 publications

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“…The authors are not aware of any pharmacokinetic studies using a single intravenous bolus of MgSO 4 in healthy horses. This study provides the first look at the effect of a single intravenous administration of MgSO 4 in horses and reports a volume of distribution of 0.94 L/kg, which is higher than the 0.31 L/kg reported in a human study (Biesenbach et al., 2018). However, that study evaluated a 20 mmol intravenous infusion of MgSO 4 administered over one hour and subjects were followed for 12 hr.…”

Section: Discussionmentioning

confidence: 53%

“…The rapid time to T max (mean 6.6 min; 4.8–10.2 min) and the C 0 (mean 1.33 mmol/L; 1.00–1.88 mmol/L) was more than a threefold increase, which are values not previously reported in the horse. The terminal half‐life for Mg 2+ of 5.5 hr was longer than that reported for humans (3.01 hr) (Biesenbach et al., 2018), clearly reflecting species differences. It was not clearly discernible from this study when plasma Mg 2+ concentration returned to baseline values, but occurred between 12 and 24 hr.…”

Section: Discussionmentioning

confidence: 71%

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Pharmacokinetics of magnesium and its effects on clinical variables following experimentally induced hypermagnesemia

Schumacher

Toribio

Scansen

et al. 2020

Vet Pharm & Therapeutics

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The objectives of this study were to describe pharmacokinetic and pharmacodynamic changes as a result of a single intravenous administration of magnesium sulfate (MgSO4) to healthy horses. MgSO4 is a magnesium salt that has been used to calm horses in equestrian competition and is difficult to regulate because magnesium is an essential constituent of all mammals. Six healthy adult female horses were administered a single intravenous dose of MgSO4 at 60 mg/kg of body weight over 5 min. Blood, urine, and cerebrospinal fluid (CSF) samples were collected, and cardiovascular parameters were monitored and echocardiograms performed at predetermined times. Noncompartmental pharmacokinetic analysis was applied to plasma concentrations of ionized magnesium (Mg2+). Objective data were analyzed using the Wilcoxon rank‐sum test with p < .05 used as a determination for significance. Plasma concentrations of Mg2+ increased nearly fivefold, ionized calcium (Ca2+) decreased by nearly 10%, and the Ca2+ to Mg2+ ratio declined more than 3.5‐fold and remained different than baseline until 24 hr (p < .05). Significant changes were seen with urinary fractional excretion of electrolytes, cardiovascular parameters, and echocardiographic measurements. No changes were detected in CSF electrolyte concentrations. The decrease in Ca2+ result of hypermagnesemia supports the interaction between these cations. Alterations detected in plasma electrolyte concentrations and urinary fractional excretion of electrolytes may serve as biomarkers for regulatory control for the nefarious administration of MgSO4.

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Section: Discussionmentioning

confidence: 53%

Section: Discussionmentioning

confidence: 71%

Pharmacokinetics of magnesium and its effects on clinical variables following experimentally induced hypermagnesemia

Schumacher

Toribio

Scansen

et al. 2020

Vet Pharm & Therapeutics

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“…The terminal half-life of the terminal phase (HL_Lambda z; t 1/2 ) reported in this study was the geometric mean of 3.7 h with a minimum of 2.4 and maximum of 5.8 h, and previously reported values with the same administration strategy, but different collection time points, was 5.5 ± 0.65 SD hours. In humans the terminal half-life for intravenous Mg 2+ has been reported to be around 3 h (47, 48). As t 1/2 is dependent upon the clearance of the drug and the volume of distribution, the increased Cl observed for this study can account for part of the decrease in t 1/2 ; as clearance increases, there is less “drug” in the plasma at each of the successive time points.…”

Section: Discussionmentioning

confidence: 99%

Radio-Telemetric Assessment of Cardiac Variables and Locomotion With Experimentally Induced Hypermagnesemia in Horses Using Chronically Implanted Catheters

et al. 2019

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The objective of this study was to characterize the pharmacokinetics and pharmacodynamics of intravenous administration of magnesium sulfate to horses using a novel radio-telemetry system for physiologic signal capture. Five Horses were surgically implanted with a radio-telemetric carotid catheter. Implants were paired with a non-invasive telemetric unit which acquired a six lead ECG and 3-axis acceleration to assess activity acquired wirelessly in real-time for future analysis. Horses were exposed to a new stall environment before (baseline) and after 60 mg/kg (30 mL) of magnesium sulfate (MgSO4), or the same volume of 0.9% saline, administered intravenously in a blinded, random crossover design. Blood for pharmacokinetics, telemetric data, and body temperature were recorded serially for 24 h. Data were analyzed across time and between treatments. Significance was set at P < 0.05. Ionized magnesium concentration (Mg2+) increased and the Ca2+ to Mg2+ ratio decreased and persisted for 5 h after MgSO4 administration. Heart rate (HR) increased and mean arterial blood pressure (MAP) decreased for at least 6 h. Electrocardiogram (ECG) intervals (RR) decreased and (PR and QTc) increased in duration compared to controls indicating an increase in heart rate, and slower myocardial conduction in the MgSO4 group. Acceleration in all planes was less in the MgSO4 group compared to controls indicating decreased locomotion. This novel method permitted collection of physiologic signals without interference by handlers or animal restraint. An intravenous bolus of MgSO4 produced cardiac variable changes associated with the reduction of locomotion in these horses, and in a direction that may be causal. Locomotion was decreased when horses were first introduced into a new environment which reflects the calming effect desired in sport horses. Telemetric monitoring can be used as a model to elucidate the behavior and physiologic effects of other drugs. The administration of MgSO4 may be detected for regulatory purposes with the monitoring of Mg2+ and Ca2+ concentrations and their ratio.

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“…Mg has been used to treat different types of arrhythmias for decades, such as AF [ 43 , 44 , 45 , 198 , 199 ], TdP [ 41 , 42 , 200 ], and VA [ 46 , 47 , 199 ] (for reviews [ 6 , 201 , 202 , 203 , 204 ]). Mg is also frequently used in patients undergoing cardiac and pulmonary surgery when lethal arrhythmias often occur [ 44 , 199 , 204 , 205 , 206 ]. For example, a meta-analysis of randomized controlled trials on 2069 patients demonstrates that prophylactic Mg administration (IV MgSO 4 or MgCl 2 ) reduces the risk of supraventricular tachycardia and VA after cardiac surgery [ 205 ].…”

Section: Mg Supplementation As a Therapeutic Treatment For Cardiommentioning

confidence: 99%

Magnesium, Oxidative Stress, Inflammation, and Cardiovascular Disease

Liu

Dudley

2020

Antioxidants

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Hypomagnesemia is commonly observed in heart failure, diabetes mellitus, hypertension, and cardiovascular diseases. Low serum magnesium (Mg) is a predictor for cardiovascular and all-cause mortality and treating Mg deficiency may help prevent cardiovascular disease. In this review, we discuss the possible mechanisms by which Mg deficiency plays detrimental roles in cardiovascular diseases and review the results of clinical trials of Mg supplementation for heart failure, arrhythmias and other cardiovascular diseases.

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Pharmacokinetics of Magnesium Bolus Therapy in Cardiothoracic Surgery

Cited by 13 publications

References 17 publications

Pharmacokinetics of magnesium and its effects on clinical variables following experimentally induced hypermagnesemia

Pharmacokinetics of magnesium and its effects on clinical variables following experimentally induced hypermagnesemia

Radio-Telemetric Assessment of Cardiac Variables and Locomotion With Experimentally Induced Hypermagnesemia in Horses Using Chronically Implanted Catheters

Magnesium, Oxidative Stress, Inflammation, and Cardiovascular Disease

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