Comparison of IV and Oral Magnesium in Patients With CVD

In This Article

Abstract and Introduction

Abstract

Purpose The results of an investigation of serum magnesium concentrations (SMCs) after i.v. versus oral delivery of magnesium in cardiovascular critical care are presented.
Methods A retrospective case review was conducted to compare the net gain of magnesium after i.v. (n = 188) or oral (n = 164) magnesium therapy for the prevention of ventricular fibrillation and arrhythmias in patients hospitalized for serious cardiovascular disorders, as determined by assessing SMCs. The primary study outcome was the change from baseline SMC values 6–24 hours after the completion of magnesium courses; secondary outcomes included the impact of renal impairment, concomitant medication use, and other clinical variables on SMC changes.
Results Although consistent elevations in SMC were produced by oral magnesium delivery, i.v. administration resulted in greater and more rapid elevations relative to baseline SMC. The degree of change in SMC was significantly influenced by the timing of SMC measurement after a magnesium course, by renal function, and by concomitant use of i.v. loop diuretics.
Conclusion A comparison of 24-hour courses of magnesium replacement therapy showed that magnesium sulfate 2 g i.v. was associated with larger changes in SMC than magnesium oxide 800, 1200, or 1600 mg orally when the baseline SMC was 1.4–1.8 mg/dL. At baseline SMCs of 1.4–1.8 mg/dL, oral magnesium oxide provided a consistent median increase in SMC of 0.1 mg/dL. The change in the number of bowel movements did not differ significantly between courses of i.v. magnesium sulfate and oral magnesium oxide.

Introduction

Magnesium plays a critical role as a cofactor in several hundred intracellular reactions. However, less than 50% of Americans obtain adequate amounts of the element in their diet, and magnesium deficiency has been associated with several disease states and conditions, including ischemic heart disease, heart failure, and diabetes mellitus.^[1] For these reasons, magnesium replacement is often recommended as an approach to maintaining normal physiological concentrations. In patients with ischemic heart disease, achieving a serum magnesium concentration (SMC) of ≥2.0 mg/dL (near the high end of the normal physiological range) is recommended in order to reduce the risk of ventricular fibrillation.^[2] Additionally, magnesium administration has been shown to reduce the frequency of ventricular arrhythmias in patients with heart failure.^[3,4]

Magnesium is predominantly an intracellular cation, so the SMC may not accurately reflect total magnesium stores. However, direct measurement of intracellular magnesium concentrations is impractical in the clinical setting, so SMC values are often used to guide therapeutic decision making. At our institution, the normal range of SMC values is considered to be 1.6–2.2 mg/dL. In order to achieve recommended SMCs (≥2.0 mg/dL) in patients with cardiovascular disease, magnesium is replaced often and, in some patients, daily. The two preferred agents for repletion at our institution are i.v. magnesium sulfate and oral magnesium oxide. To our knowledge, no published investigations have compared these two routes of administration for the purpose of routine magnesium replacement, and little information is available to guide clinicians as to which route is most appropriate for that indication.

A dose of 2 g of i.v. magnesium sulfate provides 16.2 meq of magnesium. However, the net gain of magnesium depends largely on baseline intracellular and extracellular concentrations, as well as strict renal regulation, which may waste up to 50% of an administered dose.^[5] Oral magnesium oxide 400 mg provides 19.8 meq of magnesium, but net absorption is limited by several factors (e.g., dependence on an acidic gastric pH, saturable absorption processes, wide interpatient variability) that can contribute to poor overall bioavailability. Diarrhea is the primary dose-limiting effect of oral magnesium; for that reason, many clinicians are reluctant to prescribe an oral formulation, although the average dose of elemental magnesium thought to produce a laxative effect is 40–80 meq (800–1600 mg of magnesium oxide) in a single dose.^[6]

The primary objective of the investigation described here was to compare the effects of i.v. and oral magnesium replacement on the change from baseline SMC values in patients with cardiovascular disease. Our study was also designed to evaluate factors that might affect the net gain of magnesium when the element is administered by the i.v. and oral routes. Finally, the effect of oral magnesium replacement on patients' bowel movements was assessed.

Table 1. Characteristics of Courses of Magnesium Replacement Therapy ^a
Characteristic	I.V. Magnesium Sulfate (n = 188)	Oral Magnesium Oxide (n = 164)
No. (%) courses with male pt	93 (49.5)	93 (57.3)
Mean ± S.D. pt age (yr)	58 ± 15	56 ± 14
Mean ± S.D. pt weight (kg)	83.9 ± 32.6	85.9 ± 24.1
Mean ± S.D. creatinine clearance of pt (mL/min)^b	94.2 ± 28.2	86.7 ± 27.6^c
Mean ± S.D. total magnesium dose (meq)	16.2 ± 0.0	46.4 ± 10.8^c
Mean ± S.D. baseline SMC (mg/dL)	1.65 ± 0.13	1.78 ± 0.13
Median time (interquartile range) between course completion and blood sampling for SMC (hr)	18.00 (15.75–20.00)	8.25 (7.00–17.81)^c
No. (%) courses with pt receiving ≥1 medication affecting magnesium absorption^d	136 (72.4)	104 (63.4)
No. (%) courses with pt receiving ≥1 medication affecting magnesium excretion^e	67 (36.0)	63 (38.4)

^a SMC = serum magnesium concentration.
^bEstimated with the method of Cockcroft and Gault.⁷
^c p < 0.05 for comparison with i.v. magnesium sulfate.
^dIncludes proton pump inhibitors, histamine H₂-receptor antagonists, vitamin D, and calcium supplements.
^eIncludes diuretics, calcineurin inhibitors, aminoglycosides, and amphotericin B.

Table 2. Change in Serum Magnesium Concentration (SMC) After Courses of I.V. Magnesium Sulfate or Oral Magnesium Oxide
Baseline SMC (mg/dL)	I.V. Magnesium Sulfate			Oral Magnesium Oxide			p
Baseline SMC (mg/dL)	n	Mean ± S.D. Change (mg/dL)	Median Change (mg/dL)	n	Mean ± S.D. Change (mg/dL)	Median Change (mg/dL)	p
1.2	2	0.50 ± 0.00	0.5	1	0.00 ± 0.00	0.0	0.0
1.3	2	0.40 ± 0.10	0.4	1	0.40 ± 0.00	0.4	0.5
1.4	15	0.39 ± 0.19	0.4	12	0.14 ± 0.22	0.1	0.003
1.5	20	0.27 ± 0.18	0.3	15	0.07 ± 0.11	0.1	<0.001
1.6	39	0.27 ± 0.19	0.2	23	0.11 ± 0.16	0.1	<0.001
1.7	52	0.21 ± 0.19	0.2	44	0.10 ± 0.15	0.1	<0.001
1.8	58	0.19 ± 0.19	0.2	68	0.09 ± 0.16	0.1	0.001

Table 3. Association Between Total Magnesium Dose and Change in Serum Magnesium Concentration (mg/dL)
Magnesium Dose	No. Courses	Mean ± S.D. Change	Median Change
I.V. Magnesium Sulfate
2 g	188	0.24 ± 0.2	0.2
Oral Magnesium Oxide
800 mg	127	0.10 ± 0.16^a	0.1
1200 mg	18	0.11 ± 0.15^b	0.1
1600 mg	19	0.05 ± 0.14^a	0.1

^a p < 0.001 for comparison with i.v. magnesium sulfate.
^b p = 0.003 for comparison with i.v. magnesium sulfate.

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