Radial Artery Spasm Prevention (RASP Study): A Retrospective Analysis of Oral Pharmacologic Prophylaxis for Prevention of Radial Artery Spasm During Transradial Access for Cardiac Catheterization

This article received a double-blind peer review from members of the Cath Lab Digest editorial board.
Disclosures: The authors report no conflicts of interest regarding the content herein. Contact Dr. Thomas Waggoner at twaggoner.med@gmail.com. 
*Peter V. Wassmer, BS, is not currently employed at Northside Hospital.

Abstract   

  Objectives. The aim of this study was to evaulate the occurrence of radial artery spasm during transradial access cardiac catheterizations in patients previously prescibed and taking oral long-acting nitrates or calcium-channel blockers, or the combination of both drugs.

  Background. Radial artery spasm is the one of the most frequent complications of transradial access cardiac catheterization and/or percuntaneous coronary interventions, and it is important to prevent due to increased access site utilization, increased risk of vascular damage, procedural failure, patient comfort, and possibly radial artery occlusion.

  Methods. We did a retrospective analysis of 308 patients at our institution’s cardiac catheterization laboratories, in whom a successful right radial artery cannulation was achieved. We determined if the presence of radial artery spasm was reduced in patients previously prescibed and taking oral long-acting nitrates or calcium-channel blockers, or the combination of both drugs, versus patients not already taking oral vasodilator agents. This was done utilizing post-treatment vasodilatory administration as a surrogate for radial artery spasm. 

Results. A total of 308 patients were evaluated for radial artery spasm. Of the total number of patients studied, 46 patients needed repeat vasodilatory treatment at the end of the procedure. Forty-one patients who had not been pre-treated with oral vasodilators prior to the procedure needed a repeat treatment. Three patients who had been taking calcium-channel blockers only required a post-vasodilator treatment. Two patients required a repeat vasodilator treatment if they had pretreatment with oral nitrates only. Zero patients required repeat treatment if they had been pretreated with a combination of oral nitrates and calcium-channel blockers.

  Conclusion. Pharmacologic prophylaxis with oral long-acting nitrates or calcium-channel blockers for prevention of notorious radial artery spasm is clinically important, because of the increasingly routine use of transradial access for diagnostic cardiac catheterization and/or percuntaneous coronary interventions. In this study, patients previously prescibed oral long-acting nitrates or calcium-channel blockers had fewer associated episodes of possible radial artery spasm.

Introduction

Transradial access (TRA) for diagnostic or interventional coronary and vascular procedures has become more utilized in recent years. Kiemeneij et al described transradial access for coronary angioplasty and intervention in 1993, fourteen years after Campeau reported the first 100 cases of percutaneous transradial coronary angiograms.^1-3 Radial access for cardiac catheterization is being adopted by a growing number of invasive and interventional cardiologists.^4,5 In comparison with femoral access, the radial route is safer and reduces major adverse cardiac events, bleeding and patient discomfort^5,6, especially in certain subgroups (older, obese patients, those undergoing an intervention for a myocardial infarction^5,6, as noted in the RIVAL and RIFLE-STEACS studies^7,8. The cost-benefit analysis of TRA compared to transfemoral access, in both low and high risk percutaneous coronary interventions, was recently reported as greater than $800 USD per procedure.⁹ With its clinical and financial benefits, TRA has become the preferred access site for many cardiac catheterization laboratories. 

Radial artery spasm (RAS) is the most frequent complication of transradial cardiac catheterization.^7,10-14 It causes patient discomfort and reduces the procedure success rate.^7,10-14 The occurrence of radial artery spasm offsets the advantages of this arterial access route, increasing the degree of patient discomfort and reducing the chances of a successful catheterization. Fukuda et al in 2004 reported severe radial spasms in more than 50% of patients after the transradial approach for coronary angiography and angioplasty strongly correlated with arterial diameter size.¹⁵ At high-volume centers with extensive radial experience, radial spasm is reported to occur in 15% to 30% of procedures.^16,17  

Radial artery spasm is important to prevent due to increased risk of vascular damage and procedural failure, and patient comfort. The literature suggests an association between radial artery spasm and radial artery occlusion affecting long-term patency.¹⁵ Radial artery occlusion is one of the few and probably most feared complications of transradial arterial access, despite being subclinical in many cases. Radial artery occlusion compromises vascular circulation, prevents future TRA procedures, limits radial harvesting for coronary bypass grafts, and affects future arterio-venous shunt maturation for hemodialysis access.^11,13-14

The gold standard for evaluation of RAS is radial artery angiography.^11-19 In the absence of angiography, the diagnosis of RAS is overwhelmingly operator-dependent. Kiemeneij et al described the use of an automatic pullback device for removal of transradial introducer sheaths to establish a parameter to quantify RAS.¹⁰ The pullback device measured mean maximal pullback force (MPF). A mean MPF of >1.0 kg correlated with clinical radial artery spasm and severe pain during sheath removal. The device has not been well adopted by invasive cardiologists likely due to lack of availability, unfamiliarity, additional costs, and increased procedural time. Ruiz-Salmerón et al in 2005¹⁵ assessed radial artery spasm utilizing a scoring system based on clinical peri-procedural factors, including resistence of introducer sheath withdrawal. Other inherently subjective scoring systems have been reported, but not frequently adopted clinically, including a questionnaire system by Rathmore et al in 2010 where five points were assessed by the operator: 1) continuous forearm pain; 2) pain with catheter manipulation; 3) pain during sheath insertion or removal; 4) a firm grip by the operator to remove the sheath, and; 5) augmented resistence to sheath retrieval.¹¹ In that study, RAS was defined if at least two features, or one feature plus the need for intra-arterial vasodilator use, was present.¹¹ Overall, clinical standards for determining RAS remain overwhelmingly operator-dependent and subjective, particularly regarding “resistance felt during sheath removal” and/or when the patient reports “moderate to severe pain” with introducer sheath manipulations and retrieval.¹⁰

The advent of hydrophilic-coated sheaths, not sheath lengths, has been reported to reduce RAS during TRA.^11,12 However, patients with clinical risk factors may still have clinically significant RAS. With the goal of avoiding periprocedural radial spasm with catheterization, there is still limited long-term data regarding the prophylactic prevention of RAS.

Pharmacologic prophylaxis for prevention of notorious radial artery spasm is germane because of the increasingly routine use of TRA. A calcium channel antagonist in combination with nitroglycerin is more potent than a calcium channel antagonist alone or nitroglycerin alone in prevention of human radial artery vasospasm after coronary bypass¹⁸; however, intra-arterial diltiazem plus nitroglycerin showed no significant advantage compared to nitroglycerin alone, as a vasodilator to prevent RAS in patients undergoing coronary angiography or angioplasty procedures.¹⁹

The purpose of this study was to evaulate the peri-procedural occurrence of radial artery spasm during transradial access during diagnostic and/or interventional cardiac catheterizations in patients previously prescibed and taking oral long-acting nitrates, calcium-channel blockers, or the combination.

Patients and method  

Patient population. Transradial access for cardiac catheterization was attempted in 938 patients between January 1, 2009 and July 7, 2012 at our institution. A total of 419 were transradial percutaneous interventions. A successful right radial artery cannulation was achieved in 637 patients. After screening for complete medical charting data and excluding multiple transradial access attempts, transradial peripheral access, and crossover to transfemoral approach, 308 patients were consecutively retrospectively analyzed in the study.  

Baseline characteristics. Individual patient clinical characteristics are shown in Table 1.

Study protocol. This was a retrospective chart review that examined three groups in a factorial design: patients already prescibed and taking oral long-acting nitrates, calcium-channel blockers, or the combination versus patients not taking long-acting nitrates and/or calcium-channel blockers.  

Radial artery cannulation. The standard radial access procedural approach at our institution was as follows: 

The right wrist was prepared and draped using standard sterile technique. A modified Allen’s test was used as the standard radial ischemic test to verify a patent superficial ulnar arterial system. Local anesthetic with 2% lidocaine was utilized. The radial artery was cannulated using a modified Seldinger technique with a 21-gauge arterial needle and a 0.018-inch guidewire was advanced. The needle was removed, a small skin incision was made at the point of entry, and then a 6 French introducer hydrophilic sheath with a tapered dilator was advanced over the guidewire into position. Hydophilic sheaths were either 11 cm short (Cook Medical) or 23 cm long (Terumo Medical Corporation).

An initial intra-arterial vasodilator cocktail of nitroglycerin (100-200mcg and/or verapamil 1.0-2.5mg, depending on systemic blood pressure) was administered, along with 3,000-5,000 units of intraarterial heparin or 50U/kg intravenously, depending on the operator. All introducer sheaths, guide catheters, and wires were removed immediately following the procedure, and hemostasis was directly obtained with a radial hemoband (TR Band, Terumo).

Outcome measures. The primary outcome measure was the occurrence of radial artery spasm during transradial access cardiac catheterizations in patients previously prescibed oral long-acting nitrates, calcium-channel blockers, or the combination of CCB/nitrate, measured as a surrogate of repeat peri-procedural vasodilator administration. Secondary measures were elucidating clinical risk characteristics promoting radial artery spasm during transradial access cardiac catheterizations.

Definitions. Radial artery spasm (RAS) was retrospectively accessed if a repeat dose of intra-arterial vasodilator cocktail of nitroglycerin (100-200mcg and/or verapamil 1.0-2.5mg, depending on systemic blood pressure) was administered a second time at the completion of the procedure by the operator. A second dose of intra-arterial vasodilator is not routinely utilized based on the clinical practice characteristics of the invasive cardiologist or interventionalist at this institution, aside from one that was excluded from this study. Catheterization technologist procedural and primary operator reports were resptrospectively analyzed to determine the reason for repeat vasodilator administration. Repeat vasodilator administration was considered in this study if documentation at the completion of the procedure was given for continuous forearm pain, pain with catheter manipulation, pain during sheath removal, or a firm grip used by the operator during sheath removal or resistance felt by the operator during sheath removal.

Statistical analysis. The statistical analysis was performed with the GraphPad software. We used a Chi-squared analysis with the variables associated with the development of spasm during the procedure and to evaluate the impact of spasm during follow-up. Continuous variables were expressed and categorical data were listed as percentages. After dividing the study population into two groups according to whether or not they had experienced radial spasm, we used a P-value of <0.05 to assess statistical significance for each continuous variable. 

Results

A total of 308 patients were evaluated for RAS. Of the total number of patients studied, 46 patients needed repeat vasodilatory treatment at the end of the procedure. Forty-one patients who had not been pre-treated with oral vasodilators prior to the procedure needed a repeat treatment. Three patients who had been taking calcium-channel blockers only required a post-vasodilator treatment. Two patients required a repeat vasodilator treatment if they had pretreatment with oral nitrates only. Zero patients required repeat treatment if they had been pretreated with a combination of oral nitrates and calcium-channel blockers.

The average age was 63.5 years old. There were 105 females (34.1%) and 203 males (65.9%), of which 88 (28.6%) were diabetic (including all types), 95 (30.8%) had tobacco use within the last 1 year, 48 (15.5%) were already taking oral calcium-channel blocker, 35 (11.4%) were already taking long-acting oral nitrates, and 9 (2.9%) were taking the combination. Female gender alone was a risk factor for possible spasm, with the  highest repeat vasodilator administration.

The clinical groups, arranged by whether or not a repeat vasodilator dose was administered and the type of vasodilator, can be seen in Table 2 and Figures 1-2. 

Discussion

Radial artery spasm is the most frequent complication of transradial cardiac catheterization.^10-14 The vasospastic potential of the radial artery has been reported in the literature as intermediate between that of the splanchnic arteries and somatic arteries, such as the internal mammary artery.  Splanchnic arteries such as the hypogastric and gastroepiploic arteries tend to have a greater predisposition toward spasm.^4,5 The marked muscle mass in the radial artery wall, greater than that of most arteries, and its high density in alpha-adrenergic receptors, help explain its proclivity to spasm.^4,5 

The media of the RA is significantly thicker than the media of other arterial conduits¹⁶, meaning RA spasm is more intense and difficult to reverse. The radial artery is a thick-walled vessel composed mainly of smooth muscle cells arranged in concentric layers. This marked muscular component of the artery, together with the high density of alpha-1 receptors, makes this vessel especially susceptible to spasms. Factors shown to increase RAS include: younger age, female, lower body mass index, wrist circumference, tobacco abuse, diabetes mellitus, ad hoc coronary interventions, >3 catheters during a procedure, >6 French catheters, smaller intra-luminal radial artery diameter (average 2.46 mm in most studies), and radial artery anatomic anomalies.^11,17 

Although the incidence of radial spasm during catheterization depends on the experience of the operator⁸, this complication traditionally was reported as ranging from 15 to 30% of performed procedures.³ More recent studies from high-volume TRA centers suggest RAS is substantially less frequent (6-10%), with most reporting a very low occurrence.^16,20-21 

The development of radial artery vasospasm offsets the advantages of radial artery access, since the trapping of the catheter by the artery generates pain and makes its manipulation difficult or even impossible. Moreover, radial spasm can produce other serious complications, such as the perforation or rupture of the vessel, and there have been reports of traumatic transsection when an attempt was made to withdraw the introducer.¹⁰

Radial artery spasm is important to prevent due to the increased risk of vascular damage and procedural failure, and patient comfort. An association is also suggested in the literature between radial artery spasm and radial artery occlusion affecting long-term patency.¹⁵ Radial artery occlusion is one of most feared complications of transradial arterial access. Despite being subclinical in many cases, it prevents future TRA access.^13,14

In our study, both oral long-acting nitrates and calcium-channel blockers were statistically significant for preventing repeat vasodilator dosing (P = 0.0003 and P = 0.0032, respectively). The combination of a both a calcium-channel blocker and long-acting nitrate was limited since there was no sample size in this subset. Of the patients that recieved repeat peri-procedural vasodilatory agents, there was a statistical association with female gender alone. Tobacco, diabetes mellitus, multiple catheter exchanges, percutanous coronary interventions, younger age, male gender and/or having greater than three classical clinical risk factors for radial artery spasm was not associated with repeat vasodilatory administration. 

Our data analysis found a 14.9% incidence of probable RAS at our institution, higher than most recent studies showing 6 to 10%^16,20-21, and can be explained by the fact that our institution is a lower volume TRA center. However, this study puts forth a potential additive solution to clinically relevant RAS that in the right clinical setting, could be utilized as a useful tool to prevent radial artery spasm during attempted TRA. If a patient is seen in either an inpatient or outpatient clinical setting in anticipation of TRA cardiac catheterization, starting an oral calcium-channel blocker or long-acting nitrate could help thwart the most common complication of transradial access, radial artery spasm, particularly if there is another indication for these medications, e.g., hypertension or angina, respectively. This study is at least hypothesis-generating and warrants further elucidation with a larger, prospective trial for clinical validation. 

Limitations  

The major limitation to this study was the evaluation of radial artery spasm by correlation with repeat vasodilatory administration as a surrogate measure for clinically significant RAS, rather than angiographic evidence or mean maximal pullback force (MPF). Forearm discomfort and pain with introducer sheath manipulation is subjective and may not necessarily be due to RAS. However, currently there is no conventional evidenced-based standard for defining radial artery spasm without direct angiographic visualization. Differentiating the initial vasodilator cocktail of nitroglycerin and/or verapamil from the repeat dosing would be valuable in determing if either nitroglycerin or verapamil alone yielded less peri-procedural spasm. Small sample size was another limitation. Duration of the catheterization procedure, which has been reported in literature to promote RAS, was not included in this study. In addition, the study was a retrospective study, which has inherent selection bias and information bias as a result of the retrospective analysis.

References

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