Radial Artery Spasm During Transradial Coronary Procedures

Abstract: Although transradial access (TRA) for coronary procedures has many advantages over the transfemoral approach, it’s still not the dominant route used in coronary interventions. Radial artery spasm (RAS) is an important limitation of TRA. We performed a search of published literature to estimate the prevalence and possible risk factors of RAS in patients undergoing transradial coronary procedure. Nineteen published papers including 7197 patients were identified as relevant; reported incidence of RAS was 14.7% altogether. It varies depending upon the criteria used, on applied premedications, and on sheath or catheter selection. Use of hydrophilic coated sheaths and catheters can reduce the incidence of RAS to 1%, while intra-arterial application of verapamil (1.25-5 mg) and nitroglycerin (100-200 µg) can reduce the incidence of RAS up to 3.8%. We concluded that RAS is still problematic in transradial access, and that besides hydrophilic materials, the use of intra-arterial vasodilators remains mandatory in RAS prevention. However, the optimal spasmolytic cocktail is yet to be confirmed by valid spasm criteria.

J INVASIVE CARDIOL 2011;23(12):527-531

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Transradial access (TRA) is a well established approach since Campeau introduced this technique in 1989 and Kiemeneij and Laarman adapted it for therapeutic procedures.^1,2 Two large meta-analyses documented the advantages of TRA over transfemoral approach (TFA) in both diagnostic and therapeutic procedures, in terms of fewer local complications, major bleedings, ischemic events, and major adverse events with similar rates of procedural success.^3,4 Patients prefer TRA over TFA because of less discomfort and earlier ambulation. Nevertheless, the acceptance of TRA varies considerably around the world; it dominates in France and Canada, while in the United States it is still present in a negligible percentage.^5-7

However, we found some limitations of TRA, with a prolonged learning curve likely resulting in prolonged radiation exposure and radial artery spasm (RAS). The radial artery is a so-called type III artery, reflecting a higher sensitivity for spasm compared to other somatic vessels.⁸ Tonic contraction of the smooth muscle layers is regulated by circulating humoral factors stimulating specific receptors and direct mechanical stimulation of the artery wall. RAS sometimes diminishes the advantages of the TRA, and may result in a very unpleasant experience for both patient and operator and result in procedural failure. RAS may provoke radial artery injury and radial artery occlusion (RAO), mostly during follow-up. RAO occurs in 1.4% of patients and it is rarely symptomatic due to collateral ulnar artery supply and may be successfully prevented by heparin therapy.⁹ RAS as a specific complication of TRA can occur at any phase of the procedure. Occurrence at the beginning of the procedure can result in failure of artery cannulation or difficulty in sheath or catheter introduction. During the procedure, the catheter can be trapped and seriously limit or cause pain. At the end of procedure, it may result in difficult and painful sheath withdrawal. Development of RAS is associated with small radial artery diameters and its marked vasoreactivity.¹⁰ Prevention of RAS is therefore of great interest and different spasmolytic drugs and a variety of sheaths, catheters, and guidewires were studied in RAS prevention. These studies were inconsistent in methods and results, especially regarding the incidence and severity of RAS.

The aim of this review was to estimate the reported prevalence of RAS and possible factors that could influence RAS. Medline, Scopus, Cochrane Database of Systematic Reviews, and Cochrane Central Register of Controlled Trials (1970 to January 2011) were searched, and a total of 998 hits including the terms radial, artery, and spasm were identified. After reviewing titles and abstracts, 19 papers evaluating the occurrence of RAS were found to be relevant.

Incidence of RAS

The 19 extracted relevant studies included  7197 patients reporting RAS incidence of 14.7% (1064 patients with spasm) (Table 1). Incidences varied depending on premedication, sheath or catheter types, but also on which criteria were used in certain studies. One of the first published large series of patients reported RAS incidence of 12%, but presented no RAS definition.¹¹ In the next 7 trials, subjective RAS definitions were used (pain perceived from patient and/or difficulties in catheter manipulation or sheath removal perceived from operator). In those studies, RAS incidence varied from 6.8% to 30%.^12-18 In some, spasm was defined unclearly as extreme pain and inability to freely manipulate the catheter,¹⁹ while in others RAS was defined by questionnaires using an analog scale with a score of 5 out of 10 arbitrarily presented as a sign of spasm.²⁰

In the next 6 trials, subjective criteria were combined with objective confirmation (angiography or ultrasound-visualized stenosis), but an exact angiographic definition of confirmation was missing.^16,21 Reported RAS incidences in those trials were between 4.0% and 20.2%.^19-24 Kiemeneij et al proposed that a maximum pullback force (MPF) during sheath removal by automatic pullback device higher than 1.0 kg in patients who also experienced pain was an objective definition of severe RAS. When RAS was so defined, it was reported in 2-22% of patients in 3 conducted trials.^25-27 Initially, they correlated pain assessed by questionnaire with MPF during sheath removal by APD and found that all patients with severe pain had MPF >1.0 kg, and proposed it as reliable criteria for spasm.²⁵ In a second trial, they found an RAS reduction with a vasodilating cocktail (nitroglycerin and verapamil) from 22% to 8%.²⁶ In a third trial, they confirmed the benefit of hydrophilic-coated sheaths over non-hydrophilic sheaths in reduction of patient discomfort, but it is unusual that RAS incidence was only 2% in both groups, while in the previous trial, comparing cocktail and placebo, it was 8% and 22%.²⁷ However, this measurement technique required a unique constructed device and it is not available for broader evaluation. On the other hand, it measures artery reaction only during the sheath removal period at the end of the procedure, even though spasm can occur during any phase of the procedure. In those studies, long sheaths were used (23 or 25 cm), and MPF measures reaction of the artery segment in contact with the sheath, not in the proximal segment, which is in our opinion responsible for clinically relevant RAS.

Finally, two trials with a small number of patients used only angiographic definition and reported extremely high RAS incidence, from 51.3% to almost 100%.^28,29 Those authors tried to be more objective, but they defined spasm tentatively: in mild, moderate, or severe, on the basis of the stenosis percent (<30%, 30-70%, >70%). They didn’t explain why 30% was considered moderate or the clinical importance of spasm under 30%, and they were missing any clinical correlation.²⁹

The major limitation of the above-mentioned studies is the absence of an objective method to evaluate radial spasm. We found the mean incidence of RAS to be 14.7%, but the lowest reported RAS rate was only 1%, using a 5 Fr hydrophilic coated catheter, in patients premedicated with verapamil 5 mg intraradially, when RAS was defined only subjectively by operator or patient,¹⁵ while on the other side, studies that assessed RAS only by angiography resulted in some degree of spasm in almost all patients, and in such a way moderate or severe RAS was reported in up to 73% of patients.²⁸ Therefore, a direct comparison of the RAS rates between trials is somewhat difficult in view of the variable RAS definition, and different materials used in trials comparing drugs or different premedication used in trials comparing materials. A further problem in the objective evaluation of RAS is the different reaction of the proximal and distal parts of the radial artery.^30,31 Salmeron evaluated angiographically only the 30-40 mm mid-portion of the radial artery, Hwan-Kim measured only a 20 mm-long segment, whereas Chen CW expressed spasm as diffuse narrowing while Deffereos described it as “severe constriction.”^19,23,24,29 Only Fukuda evaluated differences between proximal and distal sites of the radial artery, but didn’t clearly present this data.²⁸ These findings all suggest that there is no precise definition of RAS. It certainly should be based on a combination of clinical and objective criteria.

Impact of Different Sheaths and Catheters on Occurrence of RAS

Among the 19 extracted relevant trials, 5 of them investigated the impact of sheath length and coating, or impact of catheter coating on RAS occurrence.^{14,15,17,18,27} The incidence of RAS varied from 1% when the procedure was performed with a hydrophilic-coated catheter and patients were premedicated with the vasodilator verapamil to 39.9% when the procedure was performed with an uncoated sheath and a catheter without vasodilators.^15,18 Hydrophilic coating of sheaths decreased spasm occurrence and lessened pain experience.^15,17,27 Sheath length, in spite of coating, didn’t have any significant effect on RAS reduction.¹⁸ Only one trial investigated the impact of catheter coating, and found a lower RAS incidence using hydrophilic-coated catheters.¹⁵ In those trials, investigators were inconsistent in vasodilator application and only 2 of 5 trials reported some intraradial vasodilators (verapamil and/or nitroglycerin), while in one trial even use of unfractionated heparin (UFH) wasn’t reported.^14,15,17,18 However, the impact of those different premedications wasn’t the endpoint in any of these trials (Table 2).

Anyway, it seems that choice of sheath length and hydrophilic coating are important issues in avoiding RAS. In trials where less spasm was reported using coated sheats,^14,17,27 16-25 cm-long sheaths were used with possible protection of a vessel segment from catheter advancement and manipulation, influencing painfulness for the patient. On the other hand, Rathore found significant effect of sheath coating in RAS reduction but no effect of sheath length.¹⁸ It therefore remains unclear whether we should use long sheaths or short, 10-15 cm or even shorter, because head to head comparisons of the same sheath type are missing. Influence of catheters on RA segment proximal to the sheaths was investigated by Koga, who found that hydrophilic coating of catheters was useful in the reduction of RAS.¹⁵

Many studies addressed that small-diameter radial arteries are at high risk for RAS, and it seems important to take care of the ratio between sheath outer diameter and artery diameter to minimize conflict between sheath and artery wall. Consequently, the majority of operators use 5 or 6 Fr sheaths.³² However, Varenne found that arterial sheath size (5 or 6 Fr) and the number of catheters used during procedure were not associated with RAS occurrence.²¹ Although Goldberg found a comparable radial approach success rate in inexperienced and experienced operators,¹³ in a larger sample Hildick-Smith found that success rate is integrally related to operator volume.¹¹ However, there are no studies correlating RAS and operator experience. It seems obvious that a gradual learning curve for radial access should be rewarded in RAS reduction.^13,33

Impact of Different Vasodilating Cocktails on Occurrence of RAS

Seven trials were considered to be relevant in evaluating intraradial vasodilators on RAS occurrence. A cocktail composed of nitroglycerin 200 µg and verapamil 5 mg reduced RAS occurrence to 8%, compared to 22% in placebo group when RAS was defined as MPF >1.0 kg using APD, also reducing pain score from 34% to 14%.²⁶ Verapamil 2.5 mg compared to phentolamine 2.5 mg was more efficacious in RAS prevention, reducing it from 23.2% to 13.2%, when it was defined as a combination of angiographic criteria and operator-reported difficulties, although there were no differences in mean change of RA diameter.¹⁹ Nitroglycerin 100 µg decreased occurrence of RAS from 20.4% to 4.4%, but adding verapamil 1.25 mg did not have significant additional benefit (RAS 3.8%) when RAS was defined by operator and patient subjective perception and confirmed by angiography.²³ In another study, addition of nitroglycerin 100 µg, nitroprusside 100 µg, or both to a basic cocktail (unfractionated heparin 2500 U, lidocaine 20 mg, diltiazem 5 mg) did not show any benefit in RAS prevention, with a mean incidence of RAS of 11.6% when it was defined by the operator or by the pain perceived by patient.¹⁶ In the two largest trials (SPASM 1 and SPASM 2; n = 1219) RAS was defined by operator, not necessarily with angiographic confirmation, and by patient using an analogical pain scale. Incidence of RAS in the placebo group was 22.2%, but combination of verapamil 2.5 mg and molsidonine 1 mg reduced it to 4.9% and was more effective than either of them alone. It is interesting in this study that verapamil 5 mg did not offer any additional effect over a dose of 2.5 mg.²¹ Nicorandil 4 mg was not inferior in RAS prevention to a cocktail composed of a small dose of verapamil 100 µg and nitroglycerin 200 µg, although nicorandil itself was a more potent vasodilator. In this study, RAS was assessed only by angiography, precisely but tentatively dividing RAS in three categories (<30, 30-69, >70% stenosis) and incidence of RAS was extremely high in both groups (50.7% vs 52%).²⁹ The latest published trial compared magnesium sulphate 150 mg to verapamil 1 mg and didn’t find any difference in RAS incidence (12.2% vs 13.6%), when RAS was defined as serious limitations of catheter movement and pain reported by patient (Table 3).¹²

As mentioned, many agents were evaluated for RAS prevention, but comparison among them suffers from the same weakness that definition of RAS varies from one study to another. On the other hand, dosing of specific agents varies considerably, so verapamil was administrated from 100 µg to 5 mg and nitroglycerin from 100 to 200 µg. From the first evaluations, most frequently were used isosorbide dinitrite, nitroglycerin, and verapamil, which is reflected in current practice. Finally, because of sensitivity of the radial artery to circulating humoral factors, it seems that adequate analgesia and sedation to avoid systemic reaction to pain could be helpful in RAS relief. However, we found that only 2 relevant trials administered anxyolitics before procedure, but without any correlation to outcomes.^13,17 Larger trials evaluating impact of anxyolitics are necessary.

Predictors of RAS

Some of the trials reported predictors of RAS, i.e., baseline RA diameter, outer sheath diameter/RA diameter ratio, RA flow-mediated dilatation, number of exchanged catheters, unsuccessful first attempt of cannulation, volume of contrast used, diabetes, female sex, RA anomalies, painful catheterization, younger age, lower body mass index, and shorter wrist circumference. Only four studies strongly detached factors and confirmed them by logistic regression or multivariate analyses (Table 4).^18,20,22,24

Jia found small RA diameter, diabetes, female gender, and unsuccessful cannulation to be good predictors of RAS.²⁰ Ruiz-Salmeron found radial artery anomalies, >3 catheters used, painful cannulation, and postvasodilatation RA diameter to be good predictors.²² Deftereos found flow-mediated dilatation of the RA to be a good predictor of RAS.^23,24 Identification of RAS predictors, despite proposed vasodilators and different available sheaths and catheters, is an important issue in patient selection and avoidance of complications, including RAS.

Conclusion

RAS is still an important problem in transradial access, and operators dedicated to this method are trying to find the best way to avoid this complication. Incidence of RAS seems to be 14.7% on the basis of current literature, but it varies depending on criteria used, premedication applied, and on sheath or catheter selection. Despite analgesia and adequate sedation, intra-arterial vasodilators remain mandatory in RAS prevention. The combination of verapamil (1.25-5 mg) and nitroglycerin (100-200 µg) can reduce RAS incidence up to 3.8%, while use of hydrophilic-coated sheaths and catheters can further reduce RAS incidence to 1%. However, the optimal spasmolytic cocktail is yet to be confirmed in further larger trials by valid spasm criteria. Small radial artery diameter, its anomalies, and low FMD seem to be the strongest predictors of RAS.

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From the Division of Cardiology, Department of Internal Medicine, University Hospital Split, Split, Croatia.
Disclosure: The authors have completed and returned the ICMJE Form for Disclosure of Potential Conflicts of Interest. The authors report no conflicts of interest regarding the content herein.
Manuscript submitted June 30, 2011, provisional acceptance given July 27, 2011, final version accepted September 28, 2011.
Address for correspondence: Ivica Kristic´ , MD, University Hospital Split, Division of Cardiology, Department of Internal Medicine, Split, Croatia. Email: kristicivica@gmail.com