Clinical PotpourriTotal and ionized magnesium testing in the surgical intensive care unit – Opportunities for improved laboratory and pharmacy utilization☆,☆☆
Introduction
Magnesium (Mg) is the second most prevalent intracellular cation and is considered an important cofactor in many enzymatic reactions, including protein synthesis, DNA replication, mRNA transcription, mitochondrial function, and energy production through adenosine triphophatase [1]. Derangements in measured magnesium levels in the critically ill are more common than for any other electrolyte [2] and much attention is paid towards maintaining normal Mg homeostasis in these patients, as hypomagnesemia has been associated with neuromuscular symptoms (weakness, delirium, convulsions, etc.) cardiac arrhythmias (premature contractions, atrial fibrillation, torsades de pointes, etc.), metabolic derangements (refractory hypokalemia, hypocalcemia), and increased mortality [1], [3]. Most intensive care units (ICUs) routinely measure total plasma Mg and have developed protocols for Mg administration.
Nearly 99% of the total body magnesium is confined to the intracellular compartment [1], [4]. Extracellular plasma magnesium exists in three states: bound to protein (particularly albumin, 25% of total plasma magnesium), complexed with anions such as phosphate bicarbonate, and citrate (8%), and in ionized form (65%) [5]. Measurement of intracellular magnesium is not possible in routine clinical practice and total plasma magnesium is poorly reflective of intracellular levels [6]. Within the extracellular compartment, the ionized magnesium (iMg) fraction is acknowledged to be the physiologically active form of Mg [7]. Thus, it follows that clinical decisions should be based on the ionized fraction rather than the total Mg level. However, because the total Mg and iMg concentrations are independent of albumin concentration within the normal range, it is not possible to accurately correct for hypoalbuminemia or calculate an iMg; it must be measured directly [8], [9], [10], [11]. Additionally, the correlation between total magnesium and ionized magnesium has been shown to be poor in critically ill patients [12]. While the measurement of iMg has been commercially available since 1994 [13], routine iMg measurement has not become widespread, in part because the iMg assay is only offered by one device manufacturer in the United States. For this reason, most ICUs continue to measure total Mg levels and provide Mg supplementation based on the total plasma Mg.
The primary purpose of this study was to assess the feasibility of implementing iMg into clinical practice and to estimate the potential impact on utilization and laboratory charges. We hypothesized that a large proportion of “low” total magnesium levels would actually be normal on ionized magnesium testing and that substitution of iMg for Mg would lead to significant decreases in repetitive testing and unnecessary magnesium replacement therapy. A secondary objective of this study was to explore potential reasons for why patients received additional magnesium monitoring and replacement outside the bounds of standard protocol.
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Material and methods
This prospective study was approved by our Institutional Review Board. We enrolled patients admitted to the surgical ICU of an academic hospital. The surgical ICU admits post-traumatic and post-surgical patients from the following specialties: general surgery, surgical oncology, hepatobiliary, vascular, thoracic, orthopedic, obstetrics and gynecology, and neurosurgery. Medical patients are occasionally admitted secondary to medical ICU bed shortages. There are two 18-bed surgical ICUs in our
Agreement between Mg and iMg
There were 470 pairs of Mg and iMg measurements from 173 patients in the pilot ICU. The Pearson Correlation Coefficient between Mg and iMg was 0.70 (p < 0.0001), showing a moderate correlation (Fig. 1).
Among 470 pairs, 34 (7%) were classified as low, 364 (78%) were normal (1.8–2.4 mg/dL), and 72 (15%) were high (> 2.4 mg/dL) based on the normal range for Mg, while 19 (4%) were classified as low (< 1.8 mg/dL), 325 (69%) were normal (0.45–0.60 mmol/L), and 126 (27%) were high (> 0.60 mmol/L) based on the
Discussion
Our study has several interesting and important findings. First, the majority (> 80%) of plasma Mg tests which are reported as “low” are, in fact, associated with normal levels of ionized Mg, the biologically active fraction. These erroneously low Mg measurements can result in unnecessary medication administration and repeat testing. Second, hypermagnesemia is more prevalent than hypomagnesemia in our surgical ICUs. Finally, we unexpectedly discovered that despite normal Mg measurements,
Conclusion
In the surgical ICU, > 80% of “low” total plasma magnesium values are erroneous and may result in unnecessary additional measurements and unnecessary magnesium supplementation. Hypermagnesemia is common and excessive repeated testing and supplementation represents an opportunity for improvement.
Conflict of interest statement
On behalf of all authors, the corresponding author states that there is no conflict of interest.
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Cited by (16)
Measuring magnesium – Physiological, clinical and analytical perspectives
2022, Clinical BiochemistryCitation Excerpt :Most of the methods described below involve the measurement of total serum magnesium, which itself has several limitations, and is typically performed in a central laboratory. The total serum magnesium measurements are not largely influenced by sex or age in the adult population and can be useful in monitoring acute changes, although analytical requirements can be improved for some methods [1,3,9,15,39–41]. Given that total serum magnesium levels are primarily controlled by magnesium excretion in the urine, analysis of magnesium in the urine provides an alternative to total serum magnesium measurements [3].
Pharmacokinetics of Magnesium in Cardiac Surgery: Implications for Prophylaxis Against Atrial Fibrillation
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2022, Laboratory Screening and Diagnostic Evaluation: An Evidence-Based Approach
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Funding: This work was supported by Nova Diagnostics (Waltham, MA, USA). The sponsor provided reagents and testing equipment but did not have any role in the design, execution, data collection, data analysis, or manuscript preparation.
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Conflicts of interest: none.