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Magnesium Sulphate during Transradial Cardiac Catheterization: A New Use for an Old Drug?
ABSTRACT: Objective. To assess the effect of intra-arterial magnesium on the radial artery during transradial cardiac catheterization. Background. Transradial coronary angiography has become popular in the last decade and offers several advantages over transfemoral angiography. Radial artery spasm is a major limitation of this approach, and a vasodilatory cocktail is usually given. The aim of this study was to examine the effect of magnesium sulphate on the radial artery during cardiac catheterization. Methods. This was a prospective, double-blind, randomized trial of 86 patients undergoing radial catheterization. Patients were randomized to receive magnesium sulphate (150 mg) or verapamil (1 mg) into the radial sheath. Radial dimensions were assessed using Doppler ultrasound. The primary endpoint of the study was a change in radial artery diameter following administration. Secondary endpoints included operator-defined radial artery spasm and patient pain. Results. Following administration of the study drug, there was an increase in radial artery diameter in both groups (p < 0.01), although the increase seen was greater in the group receiving magnesium (magnesium 0.36 ± 0.03 mm; verapamil 0.27 ± 0.03 mm; p < 0.05). Administration of verapamil resulted in a fall in mean arterial pressure (MAP) (change in MAP -6.6 ± 1.4 mmHg; p < 0.01), whereas magnesium did not have a hemodynamic effect. Severe arm pain (pain score > 5) was observed in 14 (30%) patients receiving verapamil and 9 (27%) receiving magnesium (p = NS). Conclusion. This study demonstrates that magnesium is a more effective vasodilator when compared to verapamil, with a reduced hemodynamic effect, and is equally effective at preventing radial artery spasm. As such, the use of this agent offers distinct advantages over verapamil during radial catheterization.
J INVASIVE CARDIOL 2008;20:539–542
Transradial coronary angiography has become increasingly popular over the past decade. It offers distinct advantages to patients with more rapid mobilization and a lower access-site complication rate when compared to femoral angiography.1 One of the major limitations of this approach is the development of radial artery spasm, which can lead to significant pain and an inability to complete the procedure.2 Development of radial spasm is due, in part, to the small size of the vessel and its marked vasoreactivity.3 Prevention of radial artery spasm is therefore of great importance when using the transradial approach, and in most cases, a vasodilatory cocktail is given at the start of the procedure. In most institutions a calcium channel antagonist, predominantly verapamil, is used alone or in combination with a nitrate. This is effective in reducing rates of radial spasm from the 20–25% seen with placebo to ~10% in previous randomized studies.4,5 Magnesium sulphate is a physiological calcium antagonist that has been used for many years in obstetric practice for the treatment of eclampsia and pre-eclampsia. Previous studies have also shown magnesium to be effective in the treatment and prevention of coronary artery vasospasm in variant angina6–8 In addition to vasodilation, magnesium also has potent analgesic affects, mediated via calcium channels and N-methyl daspartate (NMDA) receptors.9,10 The purpose of this study was to assess the effect of intra-arterial magnesium on the radial artery during cardiac catheterization.
Methods
The study was approved by our local institutional review board. All patients gave written informed consent before any study-related procedure was performed. Our center performs > 3,000 procedures per year, of which 90% are undertaken transradially. All procedures were performed by experienced operators. Between May and September 2007, 86 patients were included in the study; all patients had a favorable Allen’s test and were considered suitable candidates for transradial angiography. The indication for performing coronary angiography were stable angina, unstable angina and preoperative assessment for valvular surgery.
Exclusion criteria. The exclusion criteria were documented aortic stenosis, oral calcium channel antagonists or nitrates in the previous 24 hours, intravenous nitrates in the previous 8 hours and acute myocardial infarction.
Primary endpoint. The primary endpoint of the study was a change in radial artery diameter following drug administration. Secondary endpoints included operator-defined radial artery spasm, defined as severe limitation of catheter movement, with or without angiographic confirmation, and patient pain score. Pain scores were assessed using a numerical reference scale (NRS) at the end of the procedure.11 A threshold of > 5 was used to define severe pain.
Study protocol. Prior to coronary angiography, bilateral radial artery dimensions in the mid-forearm were measured using Doppler ultrasound (SonoSite, Bothell, Washington) by a single operator with a 10 MHz hockey stick vascular probe (Figure 1). Three measurements were taken and then averaged. The site used for radial artery measurement in the mid-forearm was marked to ensure that subsequent measurements were taken in the same position.
Local anesthesia was administered with a subcutaneous injection of lidocaine (1 ml). Routine sedation was not given. Puncture was performed using a 20 gauge needle following which a 5 Fr or 6 Fr sheath was inserted over a hydrophilic guidewire. Heparin (70–100 IU/kg) was then administered intravenously in the contralateral arm. Following sheath insertion, patients were randomized to receive either verapamil (1 mg) or magnesium sulphate (150 mg) given as an intra-arterial bolus over 1 minute. Both the operator and the patient were blinded to the treatment received. The same Doppler ultrasound probe was used to assess radial artery diameter immediately pre- and post drug administration (three measurements were recorded and then averaged). The length of procedure, contrast volume, sedation used and number of catheter exchanges during the procedure were recorded. At the end of the procedure, the radial artery diameter was measured again prior to sheath removal.
Statistical analysis. Continuous variables are expressed as mean ± SEM and were analyzed using unpaired Student’s t-test. Repeated measures were analyzed using paired t-tests and ANOVA of repeated measures. Categorical data were analyzed using Pearson’s chi-square and Fisher’s exact test. A p-value < 0.05 was considered significant. Statistical analysis was performed using JMP 7 (SAS Institute, Cary, Illinois).
Results
Patient demographics are shown in Table 1. The patients were well matched in terms of baseline characteristics, although those in the magnesium group tended to be older (p = 0.5) and had a slightly lower body mass. Radial artery dimensions were similar in both groups, with smaller diameters observed in the contralateral (primarily nondominant) arm. Procedural details are shown in Table 2. Few differences were noted between the two study groups. The procedure was performed via the right radial approach in 78 (91%) patients. A 6 Fr sheath was used for the majority of transradial procedures (98% in the magnesium group, 94% in the verapamil group), with 5 Fr for the remainder. A non-hydrophilic Arrow sheath (Arrow International, Reading, Pennsylvania) was used for the majority of cases (77%) with the hydrophilic Cook sheath (Cook Medical, Bloomington, Indiana) used for the remainder (25% in the verapmil group; 22% in the magnesium group; p = NS). The length of the procedure was longer in the magnesium group, an effect that was probably due to the higher proportion of percutaneous coronary interventional procedures performed in this group (49% versus 27% in the verapamil group p < 0.05). Procedural failure due to the development of occlusive radial artery spasm occurred in 1 case in the magnesium study arm.
Following administration of the study drug there was an increase in radial artery diameter in both groups (Figure 1; p < 0.01), although the increase seen was greater in the group receiving magnesium (magnesium 0.36 ± 0.03 mm compared to verapamil 0.27 ± 0.03 mm p < 0.05; Figure 2). Radial artery diameter at the end of the procedure was no different from initial baseline measurements.
The hemodynamic response is shown in Figure 3. Administration of verapamil resulted in a fall in mean arterial pressure (change in MAP -6.6 ± 1.4 mmHg; p < 0.01), whereas magnesium did not have a significant hemodynamic effect (change in MAP -0.25 ± 1.4 mmHg; p = NS). No change in heart rate was seen following administration of either drug (change in HR following study drug; magnesium +0.4 ± 1.5 bpm versus verapamil -0.8 ± 0.9 bpm; p = NS). Three patients in the verapamil group and 1 in the magnesium group suffered vagal reactions requiring treatment with intravenous atropine. Mean pain scores were similar between both groups (Figure 4). Severe arm pain (pain score > 5) was observed in 14 (30%) patients receiving verapamil and 9 (27%) receiving magnesium (p = NS). A similar number of patients in both groups required additional vasodilators for radial artery spasm. Operator-defined spasm was similar in both groups.
Discussion
This is the first study, to our knowledge, to evaluate the efficacy of intra-arterial magnesium sulphate during transradial coronary angiography. Magnesium serves to physiologically control and regulate calcium entry into smooth muscle cells13,14 and can be considered a potent, natural calcium antagonist.15 Although the precise mechanism of action is not fully elucidated, it may, in part, mediate its effects via endothelium-dependent vasorelaxation and NMDA receptors.10,12,16 It also acts as a noncompetitive inhibitor of the inositol 1,4,5-triphosphate (IP3)-gated calcium channel to inhibit IP3 binding. Intra-arterial magnesium sulphate has been previously used to determine forearm vasodilation in vivo.17
This study chose to compare our standard radial vasodilator with magnesium. The dose of verapamil used reflects current practice in our laboratory and the data presented clearly show that it has important vasodilatory and systemic hemodynamic effects at this dose. Few previous studies have used intra-arterial magnesium, particularly in the peripheral vasculature. Fujiita et al infused a total of 1 and 2 mmol of magnesium intra-arterially over a 20-minute period in healthy men to induce vasodilation.17 Since vasodilators are usually given as a bolus during transradial angiography, we elected to give a total dose of 1.2 mmol (150 mg) over 1 minute to determine response. Higher doses than this have not been used as a bolus injection. Indeed, our study demonstrated important local, but not systemic, effects at this dose. The study was not placebo-controlled, but several previous trials have shown the clear benefit of using a vasodilator cocktail when compared to placebo. In a study of 100 consecutive patients undergoing transradial angiography, Kiemeneij et al showed a three-fold increase in radial artery spasm in the placebo group compared to those treated with vasodilators.4 In the SPASM study, Varenne and colleagues demonstrated almost identical findings in the placebo group.5
In light of these data, we did not consider a placebo-controlled limb ethically appropriate. This study demonstrates that magnesium is a more effective vasodilator when compared to verapamil at the doses used in this study, with a reduced hemodynamic effect. Rather surprisingly, neither agent had any effect on heart rate following administration. Pain severity scoring and operator-defined spasm were no different between the two groups, and equivalent numbers received additional vasodilatory and sedation therapy for wrist pain. The number of patients who suffered a profound vagal reaction requiring intravenous fluid or atropine, was small in both groups (2 patients in the verapamil group, 1 in the magnesium group). A direct comparison of the rates of radial artery spasm between this and previous studies is somewhat difficult, in view of the variable definition of severe radial artery spasm used. Severe pain in this study was defined as a NRS pain score of > 5, and occurred in a similar proportion of patients in both groups, and although these figures are higher than those reported in previous studies, this remains a relatively subjective means of assessing radial artery discomfort.
Conclusion
The use of calcium antagonists during radial angiography is widespread, but not universal. They are undoubtedly effective vasodilators and useful in preventing radial artery spasm, however their perceived effect on hemodynamics is viewed as a major limitation. This study demonstrates that magnesium is a more effective vasodilator when compared to verapamil at the doses used in this study, and has no effect on MAP. This lack of any hemodynamic effect offers a distinct advantage over verapamil, particularly when there is already concern in patients with preexisting hypotension. Furthermore, the use of this natural calcium antagonist may offer therapeutic benefit in other clinical situations where effective vasodilation is required with a limited effect on blood pressure, such as no-reflow during coronary intervention.
