Nitroglycerin, Nitroprusside, or Both, in Preventing Radial Artery Spasm during Transradial Artery Catheterization

With aggressive anticoagulation and antiplatelet therapy being used in interventional cardiology, transradial interventions are becoming more popular due to lower bleeding complication rates.^1,2 A common situation encountered in transradial catheterization is radial artery spasm, which can lead to patient discomfort, and in some cases, prevent completion of the procedure.^1,3 Various vasodilator solutions have been employed to prevent this complication. Most of them contain a calcium channel blocker, nitroglycerin, or a combination of both.^4–6 The role of a direct nitric oxide (NO) donor added to both nitroglycerin and a calcium channel blocker on radial artery spasm is unknown. Our objective was to evaluate the effect of three different antispastic solutions on radial artery spasm in a large cohort of patients, as well as the eventual predictors of arterial spasm. Materials and Methods A total of 379 patients undergoing elective transradial coronary angiography or angioplasty were enrolled in the study after obtaining their informed consent. Patients had standard indications for coronary angiography. All patients had a positive Allen’s test and were considered eligible for the transradial approach. Exclusion criteria were: previous transradial or transbrachial intervention, continuous infusion of diltiazem, nitroglycerin or nitroprusside, allergy to one of the study drugs, or cardiogenic shock. Patients were enrolled consecutively. All patients who consented to the study were randomized to receive one of the three antispastic solutions listed in Table 1. The dosing of lidocaine, diltiazem and nitroglycerin was based on prior experience in similar studies.^3–6 The investigators agreed that based on the pharmacokinetics of the drugs, 100 µg of nitroglycerin, 100 µg nitroprusside, or a combination of both, would elicit an arterial vasodilator response without a significant drop in blood pressure. The interventional cardiologist who performed all the procedures was blinded to the content of each solution mixture. After randomization, and before any instrumentation of the radial artery, the patients underwent a preliminary ultrasound study to measure the diameter of the radial artery. The interventional cardiologist was blinded to the ultrasound results as well. The right radial artery was utilized in all cases, and the corresponding area was prepared conventionally for the examination. Local anesthesia included 1 ml of lidocaine, with 2% administered 1 cm below the styloid process of the radius. The right radial artery was punctured with a 21 gauge needle, and a 0.018 inch guidewire was introduced, followed by a either 5 Fr or 6 Fr sheath (Cook Inc., Bloomington, Indiana). After the sheath insertion into the artery, one of the three study solutions was injected intra-arterially. During catheterization, a 0.035 inch guidewire, 260 cm long, was positioned in the ascending aorta to exchange the catheters. Our first choice was the Judkins 4 curve for the right coronary artery, the Judkins 3.5 curve for the left coronary artery, and a pigtail catheter. Clinical history, demographics, and the patient’s height and weight were recorded. The duration of the procedure from the introduction of the sheath until its removal, the size of catheters used, and the complications that occurred during the catheterization were recorded. A single operator, experienced in over 6,000 transradial cases, subjectively determined the presence of spasm. The spasm was defined as an inability to freely manipulate the catheter, difficulty in removing the catheter at the end of the procedure, or presence of arm pain experienced by the patient. Once the procedure ended, the sheath was removed slowly, and a compressive dressing was applied. The Ethics and Research Committee of the hospital approved the protocol. Statistical analysis. Data were expressed as mean ± standard deviation. Quantitative variables were compared using the paired t-test. Qualitative variables were compared using the Chi-square test. Multigroup ANOVA was used to compare the three different groups. Finally, a backward multivariate analysis was performed to establish the predictors of radial artery spasm. Statistical significance was considered for p Results Characteristics of clinical variables and characteristics of procedural variables were similar in all three groups, including the procedure time (Table 2). Radial artery spasm occurred in 44 patients (11.6%). The addition of nitroprusside to a calcium channel blocker was no better than the addition of nitroglycerin, and the combination of both did not decrease the incidence of spasm (Table 2). By univariate analysis, the duration of the procedure, age of the patient, and diameter of the radial artery were predictors of spasm (Table 3). Procedure duration may not have been an independent variable, since spasm increases procedure time. In an attempt to account for the influence of body size and sheath size, the following indices were tested: the ratio of the radial artery diameter to the patient’s height (RAH) index; radial artery to the patient’s body surface area (RAS) index; and the ratio of the outer diameter of the sheath to the radial artery diameter (ODRA) index. By univariate analysis, the duration of the procedure, age of the patient, diameter of the radial artery, as well as the three indices (RAH, RAS and ODRA) were found to be statistically significant (Table 3). After multivariate analysis, the only independent predictors of radial artery spasm were: RAH index (1.33 vs. 1.43; p = 0.005), RAS index (0.12 vs. 0.13; p = 0.012), and ODRA index (1.09 vs. 1.04; p = 0.024) (Table 4). Discussion and Conclusion Transradial access to perform diagnostic procedures, introduced by Campeau⁷ and adapted for therapeutic procedures by Kiemeneij and Laarman,1 has increased in popularity due to technological advances in sheath and catheter design, and to improved physician experience with this approach. Due to rapid ambulation postprocedure, radial interventions became particularly attractive for patients with back pain, chronic obstructive lung disease and prostatic hypertrophy.^3,8–10 More importantly, in this cost control era, the savings in closure devices and early discharge have made this a cost-saving approach.^1,11–14 Most of these advantages are offset by a relatively long learning curve, as well as the frequent occurrence of arterial spasm.^3,11–17 Radial artery spasm was reported to occur in approximately 10–12% of patients, and only about 2% of these patients require a change to the femoral access approach.^{1–6,11–20} Vasodilatory drugs injected through the sheath to avoid spasm vary considerably according to the personal experience of each team. Lidocaine use, although abandoned in some centers, is still being used in others. Different organic nitrates have been tested in various combinations and dosages. Isosorbide mononitrate (20 mg), isosorbide dinitrate (2–3 mg), or nitroglycerin (250 µg) separate, or in combination with verapamil (250–500 µg), are the most commonly used drugs.^3–6 Nevertheless, no study evaluated the effect of a direct NO donor or its effect on preventing radial artery spasm when combined with other drugs. This prospective, randomized study in a large cohort of patients establishes the following three conclusions. First, the addition of a direct NO donor to nitroglycerin does not reduce the risk of radial artery spasm. Secondly, the use of nitroglycerin is as effective as the use of nitroprusside. Third, morphometric factors play a significant role in predicting the occurrence of radial artery spasm. In the present study, despite infusing an increasing number of local vasodilators, there was no significant improvement in the incidence of radial artery spasm, which occurred in 11.4% of the patients. Severe spasm was encountered in 3% of the patients, requiring additional use of vasodilators. This is in concordance to other studies that used different vasodilators.^{1–6,11–14} The current literature suggests that independent of which cocktail is being used, radial artery spasm will occur once in every 9 or 10 cases. This supports the concept that certain triggers of arterial spasm cannot be counteracted by the mere use of vasodilators. Also, the age or sex of the patient, the presence of diabetes, BSA and smoking played no role in the prediction of radial spasm, as also suggested by other studies.^{1,2,4–6,11,12} On the other hand, we found a set of three morphometric indices that seem to predict the occurrence of radial spasm. Although they were significant from a statistical point of view, their clinical utility is limited by the narrow differences between the patients who experienced spasm versus those who did not. Nevertheless, these findings suggest that the relationship between the size of the radial artery, body size and sheath size is more important in predicting arterial spasm than each component separately. Study limitations. In our study, the occurrence of radial artery spasm was evaluated subjectively and not objectively, which would have been ideal. The occurrence of spasm in each group ranges between 9.5% and 12.2%, which is very similar to the occurrence of spasm reported in the literature.^1,4–6 This might suggest proper randomization and blinding of the operator who subjectively evaluated the incidences of spasm. In our review of literature, there is only one device that has been reported for the objective measurement of radial artery spasm.²¹ This pullback device is not popular for clinical use, and the radial operator is the one who subjectively decides if the patient has experienced spasm. We performed a preprocedure radial sonogram. A postprocedure sonogram could have provided subjective evaluation of spasm, but it would still not be able to evaluate spasm around the sheath.

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