Iatrogenic magnesium overdose: 2 case reports

Objective: To describe the clinical manifestations and treatment of hypermagnesemia and the potential drug errors that can lead to iatrogenic electrolyte toxicities. Summary: We report 2 cases of iatrogenic intravenous (IV) magnesium (Mg) overdose. Both cases developed extreme cardiovascular and neurologic symptoms consisting of vomiting, hypotension, bradycardia, flaccid paralysis, and severe mental depression. Diagnosis was made based upon serum ionized Mg levels (3.47 mmol/L; reference range: 0.43–0.58 mmol/L for Case #1; and 4.64 mmol/L; reference range: 0.42–0.55 mmol/L for Case #2). Each animal was treated with 0.9% NaCl for diuresis and IV calcium gluconate. Within 24 hours, the cardiovascular and neurologic status of both animals, as well as the serum Mg concentration, had normalized. Each animal was discharged with no complications. Both animals had been hospitalized for critical illness and had developed hypomagnesemia that was being treated with Mg sulfate infusions. The cause for the hypermagnesemia was due to miscalculations in treatment orders that led to erroneously administered Mg‐containing solutions. Confusing drug labels and varying units of measurement can lead to erroneous miscalculations, especially in critically ill patients that receive multiple IV infusions. New information provided: This is the first case report of iatrogenic Mg overdose in veterinary medicine. These 2 cases had a good clinical outcome with prompt recognition and supportive care.     

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

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.     

High-magnesium exposure to bullfrog heart causes ST segment elevation

Hypermagnesemia occurs in elderly people or patients with renal insufficiency after excessive ingestion of magnesium-containing laxatives. In addition to typical electrocardiogram (ECG) findings caused by conduction defects, changes in the ST segments and T waves are also observed in patients with severe hypermagnesemia. This suggested the involvement of similar pathophysiology to acute myocardial infarction, as we previously demonstrated using burn-induced subepicardial injury model in frog hearts. In the present study, by exposing the bullfrog heart to high-magnesium solution, we reproduced prominent ST segment changes in ECG as actually observed in patients with severe hypermagnesemia. In addition to the great increase in the T waves, the ECG showed a marked elevation of the ST segments and the cardiac action potential demonstrated a marked shift of the resting membrane potential to the depolarized side. High-magnesium exposure did not affect the abundance of Na⁺/K⁺-ATPase proteins. However, the pharmacological stimulation of Na⁺/K⁺-ATPase activity by insulin quickly retrieved the elevated ST segments in ECG. From these results, the functional blockade of Na⁺/K⁺-ATPase activity by magnesium ions was thought to be responsible for generating the potassium concentration gradient and the subsequent ST segment changes.     

Magnesium in the 1990's: Implications for Veterinary Critical Care

Magnesium is the second most abundant intracelular cation, exceeded only by potassium. The majority of magnesium is found in bone and muscle. This cation is required for many metabolic functions, most notably as a coenzyme for the sodium-potassium ATPase pump. Magnesium functions to maintain the electrolyte gradient across all membranes. Interference with this gradient may result in changes in the resting membrane potential and disturbances in repolarization, resulting in cardiovascular and neuromuscular abnormalities.
Hypomagnesemia may be the most underdiagnosed electrolyte disorder. Incidence rates greater than 50 percent have been reported in critically ill human patients. Currently there is little or no information available regarding the incidence and significance of hypomagnesemia in hospitalized animals. Causes of magnesium deficiency can be divided into four general categories: gastrointestinal, renal, endocrine and miscellaneous. The diagnosis of magnesium depletion can be difficult since less than one percent of total body magnesium is located in serum. Alternative methods of evaluating magnesium status include determining ultrafilterable magnesium levels, mononuclear blood cell magnesium levels or by quantifying magnesium retention of an administered loading dose.