Author + information
- Received December 14, 2009
- Revision received February 18, 2010
- Accepted March 4, 2010
- Published online May 1, 2010.
- Sudhir Rathore, MD⁎ (, )
- Rodney H. Stables, MD,
- Maheshwar Pauriah, MD,
- Abdul Hakeem, MBBS,
- Joseph D. Mills, MD,
- Nick D. Palmer, MD,
- Raphael A. Perry, MD and
- John L. Morris, MD
- ↵⁎Reprint requests and correspondence:
Dr. Sudhir Rathore, Liverpool Heart and Chest Hospital, Department of Cardiology, Thomas Drive, Liverpool L14 3PE, United Kingdom
Objectives The aim of this study was to assess the impact of length and hydrophilic coating of the introducer sheath on radial artery spasm, radial artery occlusion, and local vascular complications in patients undergoing transradial coronary procedures.
Background Radial artery spasm is common during transradial procedures and the most common cause for procedural failure.
Methods We randomly assigned, in a factorial design, 790 patients scheduled for a transradial coronary procedure to long (23-cm) or short (13-cm) and hydrophilic-coated or uncoated introducer sheaths. The primary outcome measure was clinical evidence of radial artery spasm, and secondary outcome measures were patient discomfort and local vascular complications.
Results Procedural success was achieved in 96% of the cases, and radial artery spasm accounted for 17 of 33 failed cases. There was significantly less radial artery spasm (19.0% vs. 39.9%, odds ratio [OR]: 2.87; 95% confidence interval [CI]: 2.07 to 3.97, p < 0.001) and patient reported discomfort (15.1% vs. 28.5%, OR: 2.27; 95% CI: 1.59 to 3.23, p < 0.001) in patients receiving a hydrophilic-coated sheath. No difference was observed between long and short sheaths. Radial artery occlusion was observed in 9.5% of the patients and was not influenced by sheath length or coating. A local large hematoma or arterial dissection was seen in 2.6% of the patients with no difference in groups allocated at randomization. Younger age, female sex, diabetes, and lower body mass index were identified as independent predictors of radial artery spasm.
Conclusions Hydrophilic sheath coating, but not sheath length, reduces the incidence of radial artery spasm during transradial coronary procedures.
- transradial coronary procedures
- radial artery spasm
- randomized study
- radial artery occlusion
- introducer sheaths
Transradial coronary artery access has been employed for diagnostic and interventional procedures since it was first described by Campeau in 1989 (1) and its improvement described by Kiemeneij and Laarman in 1993 (2). Improvement in the technique and the equipment has led to the use of the radial approach for diagnostic and interventional procedures in varied coronary syndromes (3–8). The radial approach has become increasingly popular due to lower vascular complications rates, reduced procedural costs, high procedural success, early patient mobilization, and reduced hospitalization when compared with the femoral approach (9,10). Transradial intervention has been found to be safe and feasible in a large spectrum of clinical practice (11–14). Radial artery spasm (RAS) is one of the most common complications of the technique, causing significant discomfort to the patient and reducing the procedural success rate (15–21). A number of small studies have shown that sheaths and catheters with hydrophilic coating can reduce spasm and cause less discomfort to the patient (22–25). Long introducer sheaths are used by some operators to reduce spasm and difficulty in catheter manipulation. However, there are no studies assessing the impact of introducer sheath length on the incidence of RAS during transradial angiography and intervention.
The objectives of this study are to assess the impact of length and hydrophilic coating of the introducer sheath on the incidence of RAS, radial artery occlusion (RAO) rates, and local vascular complications in patients undergoing coronary angiography or intervention via the radial artery.
Patients considered for coronary catheterization and intervention by the transradial approach were screened for participation. Exclusion criteria were kept to a minimum but were as follows: hemodynamically unstable patients; patients with forearm arteriovenous fistulae or with chronic renal failure, previous ipsilateral transradial procedure; and patients unwilling to participate. All patients had an Allen test performed, but were not excluded on the basis of an unfavorable result.
The study conformed to the standards set by the Declaration of Helsinki, and ethical approval was obtained from the Liverpool Local Research Ethics Committee. All patients gave written informed consent.
Study protocol and randomization
This is a prospective randomized study and patients were assigned in a factorial design to 1 of 4 different introducer sheaths: long (23-cm) hydrophilic-coated, long uncoated, short (13-cm) hydrophilic-coated, and short uncoated (Cook Medical, Inc., Bloomington, Indiana). Randomization was performed by computer-generated random numbers from a proprietary database. The randomization was performed in the blocks of 8 to keep an equal number of patients in different groups throughout the study period. The randomization list was generated and patients were assigned to the randomized intervention on an intention-to-treat basis. The person responsible for patient registration and randomization (S.R.) was not in any way concerned or involved in the treatment of the patient. The treating doctor was informed by the investigator of the randomization code prior to the procedure.
Radial artery cannulation
The radial artery was approached with the arm extended and supported, with the wrist in mild hyperextension. Local anesthetic (2% lignocaine) was given after skin preparation at the puncture site. The radial artery was punctured with a 21-gauge arterial needle through which a 0.018-inch platinum-tipped nitinol guidewire was introduced. Following this, the needle was withdrawn and a small skin incision was made. A 6-F introducer sheath with a dilator taper length of 2.5 cm was inserted over the guidewire. The sheath length was determined by the randomization. All introducer sheath kits used were from the same manufacturer (Cook Medical Inc.). A weight-adjusted dose of heparin was administered into the central circulation following the introduction of the first catheter. Routine use of a vasodilator cocktail was avoided (to abolish the impact of vasodilator agent on primary end point, and this is also a standard practice at our institution), and intra-arterial vasodilators (nitroglycerin and verapamil) were only used in the event of RAS. The rest of the procedure was performed according to the operator's preference.
All introducer sheaths were removed immediately after the procedure and hemostasis was achieved in the catheterization laboratory by either TR Band (Terumo Medical Corp., Somerset, New Jersey) or Radistop (RADI Medical Systems, St. Paul, Minnesota).
Patients were followed up clinically according to usual post-procedural care with most patients reviewed as outpatients after 4 to 6 months. At the time of follow-up, complications related to radial artery patency and late access site were reassessed.
The primary outcome measure was the incidence of operator-defined RAS. Secondary end points were the discomfort experienced by the patient during sheath manipulation, procedural success rates, rates of RAO, local vascular complications, and local inflammatory reactions.
Clinical RAS was defined as pain perceived by the patient and or difficulty perceived by the operator during insertion, manipulation, and/or withdrawal of the introducer sheath or catheter. This was assessed by questionnaires completed by operators and patients separately.
Operators reported the presence of spasm on the following scores:
1. Patient reported presence of continuous forearm pain.
2. Patient reported forearm pain only during catheter manipulation.
3. Patient reported forearm pain during sheath insertion or retrieval.
4. Firm grip of the catheters during manipulation.
5. Augmented resistance to sheath retrieval.
This excludes cases of difficult catheter manipulation because of severely tortuous radial or subclavian artery. Radial artery spasm was defined as the occurrence of at least 2 features or only 1 feature and a need for intra-arterial vasodilators.
Patients reported the pain perceived during removal of the introducer sheath on the following score:
1. Nothing felt.
2. Noticeable sensation but no pain.
3. Mild pain.
4. Significant (moderate) pain.
5. Unbearable (severe) pain.
Radial artery spasm was considered present when patient reported moderate or severe pain on sheath withdrawal.
Assessment of Radial Artery Patency
Radial artery patency was assessed before patient's discharge and at follow-up. Patients were assessed at the time of routine follow-up scheduled for 4 to 6 months. RAO was defined as the absence of palpable radial artery pulsation confirmed by an abnormal reverse Allen test (26), plethysmography and oximetery test or absent flow signal on handheld Doppler. In brief, reverse Allen test is performed by compressing both radial and ulnar arteries and having the patient make a fist several times. In contrast to Allen test in which pressure on the ulnar artery is released, for the reverse Allen test, occlusion of the ulnar artery is maintained while pressure on the radial artery is released. If there is return of blush to the palm within 10 s, the test is considered positive and indicates patency of radial artery. Similarly, plethysmography and oximetry test was performed as described, and the test was recorded with the occlusion of the ulnar artery to assess radial artery patency.
Access Site Hemostasis and Local Complications
Vascular complications were assessed after the removal of compression device and were defined as oozing (leakage of blood from puncture site requiring digital pressure), ecchymosis (bleeding into subcutaneous tissue planes causing bluish-purple discoloration >4 cm in diameter); local hematomas were classified as small (<2 cm in all diameter) and large (>2 cm in diameter). Radial, brachial, and subclavian artery dissections were reported if proven angiographically.
Assessment of Ulno-Palmar Circulation
All patients were assessed for ulno-palmar arch circulation with the use of modified Allen test and the use of plethysmography and oximetry test as described by Barbeau et al. (27). The time taken for Allen test was recorded in seconds and plethysmography and oximetry test was graded in 4 categories. Plethysmography readings were divided into 4 types: A = no damping of pulse tracing immediately after radial artery compression; B = damping of pulse tracing; C = loss of pulse tracing followed by recovery of pulse tracing within 2 min; D = loss of pulse tracing without recovery within 2 min. Oximetry results were either positive or negative during radial artery compression.
Procedural success was defined as successful completion of the intended coronary procedure via the radial route.
Clinical RAS is reported to occur in 20% to 30% of cases in studies in the literature, using several qualitative and quantitative definitions. We assumed that a 50% reduction in the incidence of RAS would be clinically significant. A factorial design was used to compare hydrophilic-coated and uncoated sheaths and short and long sheaths. We calculated that we needed 375 patients in each of the 2 arms of different introducer sheath types to detect this difference with significance level of 0.02 (alpha error) and power of 95% (beta error 0.05). We decided to recruit 400 patients in each arm to compensate for missing cases.
Continuous variables are described as mean ± SD and compared using Student t test. Categorical variables are expressed as frequencies and compared using chi-square tests and, where appropriate, Fisher exact test. The comparison between long introducer sheaths and short introducer sheaths and between coated and uncoated introducer sheaths uses a factorial design. Analysis of variance was applied to detect any interaction between coating and length of the introducer sheaths. Multivariate analysis was performed using logistic regression model to assess predictors of clinical RAS. Variables included in the model were age, sex, height, body weight, body mass index (BMI), diabetes, procedure time, and number of catheters used during the study. Variables were entered through forward stepwise analysis. All analyses were performed using SPSS version 15 (SPSS Inc., Chicago, Illinois).
Between November 2006 and January 2008, 794 patients were included in the study. During the initial 5 months, 570 patients were screened and 505 patients were included in the study. The most common reason for exclusion was previous ipsilateral transradial procedure (n = 60) and 5 patients refused to consent. The recruitment occurred in 2 distant time periods with a gap imposed by external factors. The remaining patients were recruited between July 2008 and January 2008; during this period, 344 patients were screened and 289 patients were included in the study: 40 patients were excluded because they had had previous ipsilateral transradial procedure, 10 patients refused to participate in the study, and another 5 patients were not included because of physician's preference. Out of these 794 patients, 4 patients underwent primary femoral approach (physician preference, protocol violation), and the results from 790 patients are included in this analysis.
Patients were compared in 2 different analyses considering length and coating of the introducer sheath. Baseline characteristics as stratified by length and coating of the sheath are shown in Table 1.
The mean age was 62.88 years, and 74.2% of the patients were men. Patient age, height, weight, wrist circumference, BMI, male sex, hypertension, diabetes, hypercholesterolemia, and smoking incidence were similar in both groups. About two-thirds of patients presented with stable angina, and the proportion of patients with unstable presentations was similar in all groups. The procedure time and compression device usage were also similar in all groups.
Ulno-palmar circulation was assessed in all patients but was not an exclusion criterion. Ninety-four percent of the patients had a favorable Allen test and plethysmography and oximetry test, and 6% to 7% of patients had apparently unfavorable ulno-palmar circulation, which was similar in both groups.
Procedural success was high in both groups at 758 of 790 (96%) patients. RAS prevented the completion of the procedure in 17 (2.2%) cases. In 15 patients, we were unable to enter the radial artery or advance the catheter into the aorta because of unfavorable vascular anatomy, and 1 case was abandoned because of poor backup from the guide catheter.
Radial artery spasm
Operator-defined RAS was observed in 230 (29.4%) of the patients and 172 (21.8%) patients reported discomfort of moderate or severe intensity. There was significantly less clinical RAS (relative reduction 50%) observed in patients randomized to a hydrophilic sheath (Table 2). There was significantly less RAS (19.0% vs. 39.9%, odds ratio [OR]: 2.87; 95% confidence interval [CI]: 2.07 to 3.97, p < 0.001) and patient-reported discomfort (15.1% vs. 28.5%, OR: 2.27; 95% CI: 1.59 to 3.23, p < 0.001) observed in patients receiving a hydrophilic sheath. No significant difference was observed between the groups receiving long and short sheaths.
An interaction test was applied to investigate the interaction between length and coating of the introducer sheath. There was no significant interaction observed between length and coating for operator-defined RAS (p = 0.108) and patient-assessed RAS (p = 0.631).
Local vascular complications
RAO at the time of discharge was observed in 9% of the patients, which was similar in both groups as shown in Table 2 (9.6% vs. 8.9%, p = 0.892, in Radistop and TR Band groups). None of these patients exhibited any clinical evidence of compromised perfusion of the hand.
A large local hematoma or arterial dissection was seen in 17 patients (2.2%) as shown in Table 2. The rates were similar in all groups and all access-related complications were managed conservatively. There was a slightly higher incidence of a large local hematoma in patients randomized to an uncoated sheath. Minor complications such as small hematoma, ecchymosis, and oozing were observed in about 20% of the patients in each group.
Predictors of clinical RAS
As shown in Table 3, several factors were associated with occurrence of operator-defined RAS during transradial procedures. Patients with spasm were younger and were more frequently female. There was a significantly higher incidence of spasm when an uncoated sheath was used. Patients with spasm were more frequently diabetic, had smaller wrist circumferences, and had lower body weight. Other baseline characteristics, ulno-palmar circulation, clinical presentation, introducer sheath length, procedure time, and number of catheters used were not found to be associated with RAS.
In logistic regression analysis, the use of uncoated sheath, young age, female sex, diabetes, and lower BMI were shown to be independent predictors of RAS in patients undergoing transradial coronary procedures (Table 4).
Long-term follow-up for late complications
Follow-up was completed in 625 patients (79.1%) and persistent RAO was observed in 43 patients (6.9%) (8.0% vs. 5.6%, p = 0.273, in Radistop and TR Band groups). There was no difference seen in RAO rates between the groups receiving hydrophilic and uncoated sheaths; however, there was a higher incidence of RAO at follow-up in patients receiving longer sheaths (8.3% vs. 5.3%, p = 0.042). In all affected patients, the RAO was asymptomatic.
Local infection or abscess at the radial artery puncture site was reported by 21 patients (3.4%) with no difference between the long and short sheath groups. There was a significantly higher incidence of late local access site swelling and discomfort in patients randomized to hydrophilic sheaths (5.1% vs. 0.3%, p = 0.001). These symptoms were usually noticed after 2 to 4 weeks, often with a remitting and relapsing course, and a majority were treated conservatively with antibiotics. One patient underwent local surgical drainage with no long-term adverse effects.
To our knowledge, this is the first prospective, large, randomized study comparing the clinical efficacy of several introducer sheaths in the prevention of RAS during unselected coronary procedures. The primary aim of our study is to assess the impact of length and coating of introducer sheath on the incidence of clinically relevant spasm during transradial coronary procedures. In the current study, there was a 50% reduction in RAS with a hydrophilic sheath, with 40.5% of patients assigned to an uncoated sheath experiencing RAS compared with only 19.1% in the hydrophilic sheath group. There were higher occurrences of forearm pain and the augmented resistance during sheath retrieval with the use of uncoated sheath as compared to hydrophilic sheath (42.4% vs. 20.9%, p < 0.001; and 37.4% vs. 11.5%, p < 0.001, respectively). These results are similar to those in previous small studies (23,24,28). These reductions in spasm were also reflected in the level of discomfort experienced by the patient during withdrawal of the introducer sheath. In the uncoated group, 29.1% of patients experienced moderate to severe discomfort compared with only 15.3% experiencing this discomfort in the hydrophilic sheath group. Dery et al. (23) demonstrated significant reduction in peak traction force (265 ± 167g vs. 865 ± 318g) and mean maximal pain score (0.6 ± 1.2 vs. 4.8 ± 2.9) during withdrawal of hydrophilic-coated sheath. However, there is a potential for bias in this study as they used introducer sheaths of different lengths. Similarly, Kiemeneij et al. (22) demonstrated a significant reduction in maximal pull-back force (0.24 ± 0.31 kg vs. 0.44 ± 0.33 kg, p = 0.003) and patient discomfort (7% vs. 27%, p = 0.02) with the use of a hydrophilic-coated sheath in a randomized study of 90 patients. Saito et al. (24) have also shown that a hydrophilic coating on the introducer sheath reduced friction resistance by 70% with reduced trends in the incidence of spasm.
We have not demonstrated any significant difference in the overall incidence of spasm between long and short sheaths. In this study, 30.9% of patients assigned to short sheath group experienced spasm compared with 28.9% of the patients in the long sheath group. These results were similar when compared to the level of discomfort noticed by the patient during pull-back of the sheath. We have not come across any study comparing the performance of different length sheaths in the literature.
Overall in our study, we have observed that one-quarter of the patients experienced some degree of RAS, similar to that noticed in other studies (15–21). Although, the procedure was successfully completed via the radial route in 96% of the cases, RAS was the most common cause of procedural failure, accounting for about one-half of failed cases, with tortuous vascular anatomy accounting for another one-third of failures. The radial artery could not be punctured in only 3 cases, and in 1 patient, the procedure could not be completed because of poor guide catheter backup. In the majority of these patients, the procedure was successfully completed via the other radial artery and femoral access was needed in a few patients. These results are consistent with other large studies reported in the literature. The ACCESS study (9) has shown procedural success rates of 93% with radial approach with the major causes of procedural failure being an inability to puncture the radial artery or RAS.
We have also identified factors associated with occurrence of spasm in patients undergoing transradial coronary procedures. Young age and female sex were identified as independent predictors for spasm, which is consistent with previous studies (29,30). Small wrist circumference, lower height, and lower weight were also found to be associated with high incidence of spasm. It could be postulated that all these factors may reflect a small radial artery size in these patients that can predispose to clinically evident spasm. We did not measure the size of radial artery, but 1 previous study (28) has shown that a ratio of radial diameter to sheath size of <1:1 predisposes to spasm. High levels of anxiety and increased circulating levels of catecholamines in the young patients could also predispose to spasm, and females have been reported to have smaller radial artery diameter (28).
Previous studies have reported RAO rates ranging from 3% to 10% (9,31,32). RAO following a transradial coronary procedure was observed before discharge in 9% of our patients. Leferve et al. (33) has reported high (30%) RAO rates with 1,000 U of heparin. In our study, all patients undergoing coronary intervention received weight-adjusted heparin (70 U/kg). The administration of heparin in diagnostic cases was left at the operator's discretion, and 11.8% of patients did not receive any heparin. RAO rate was 7.2% in patients undergoing coronary angioplasty and receiving weight-adjusted heparin, similar to that reported in literature.
Persistent RAO was observed in only 43 (6.9%) patients at follow-up, and no patient reported any symptoms of compromised perfusion. We observed a high incidence of RAO in patients with documented spasm during their procedure (14.5% vs. 7.4%, p = 0.003). We have not excluded any patient on the basis of Allen test, and there is an ongoing debate about denying radial access to patients with abnormal Allen test (34,35). There is no evidence so far that a normal Allen test is required for the safe undertaking of transradial procedure (36). However, prospective studies involving a large number of patients looking at the incidence and consequences of RAO based on Allen test are needed to answer this question.
In this study, the incidence of large local hematoma or arterial dissection was low. A large hematoma occurred in 17 (2.2%) patients and radial/brachial or subclavian dissection was observed in 3 (0.3%) cases. However, none of these patients needed blood transfusion or surgical intervention. However, about 20% patients had oozing needing manual pressure after compression device removal, ecchymosis, or small hematoma.
There have been reports of allergic or inflammatory reaction at the radial artery puncture site following the use of hydrophilic-coated sheaths (37,38). In this study, we have found a high incidence of local inflammatory reaction in the patients randomized to a hydrophilic-coated sheath. These reactions usually occurred 2 to 4 weeks after the procedure with relapsing and remitting course and usually presented as a small purple colored painful nodule. A majority of patients with this reaction were treated conservatively with antibiotics and analgesics. This phenomenon is seen with hydrophilic-coated sheaths and can cause considerable discomfort to the patient, though has no known long-term sequelae. It has been postulated that the hydrophilic polymer is left behind at the puncture site following the removal of the sheath, causing a local allergic reaction and inflammatory abscess.
The transradial approach for coronary procedures has become more popular over the years and has been used in all clinical situations. The British Cardiovascular Intervention Society audit returns (39) reported that 28.1% of the coronary interventions performed in the United Kingdom in 2007 were done via the transradial route. RAS is the most commonly encountered complication and can result in significant discomfort to the patient and can result in procedural failure in some cases. A hydrophilic coating on the sheath theoretically induces less friction and trauma to the endothelial lining of the radial artery and therefore causes less spasm and consequent discomfort to the patient. RAS results in difficulty in removing the introducer sheath and causes more damage to the endothelium of the radial artery. Theoretically the physical trauma caused by the spasm and the introducer sheath can result in damage to the endothelium and thereby predispose to thrombus formation. This could be one of the reasons for observing a higher incidence of RAO in patients with documented RAS. This is the first study observing this association and can be hypothesis-generating for future large studies.
The ramifications of RAO and injury are important not only in patients undergoing repeat coronary procedures, but also in the patients in whom the radial artery may be used as a conduit for coronary artery bypass surgery or in patients needing an arteriovenous fistula for hemodialysis.
First, our study was single-blinded, and this could result in some bias, but we have included both operator- and patient-defined RAS as end points. We have found a statistically significant association between operator-defined RAS and discomfort experienced by the patient (p < 0.0001). Second, a qualitative definition of RAS was used in the study, increasing the potential effect of bias. However, a close association has been shown between quantitative measurement of spasm and a qualitative definition (18). Third, avoidance of vasodilator use at the time of introducer sheath insertion might influence the incidence of RAS. However, our study was assessing the impact of different introducer sheaths on the incidence of clinical RAS and the role of vasodilator is previously known.
We have shown in this randomized study that there is a significant reduction in the incidence of RAS and patient discomfort with the use of a hydrophilic coating on the introducer sheath during transradial coronary procedures. We have not found any significant effect of sheath length on the incidence of spasm. We have also identified young age, female sex, diabetes, and low BMI to be independent predictors of RAS.
- Abbreviations and Acronyms
- body mass index
- confidence interval
- odds ratio
- radial artery occlusion
- radial artery spasm
- Received December 14, 2009.
- Revision received February 18, 2010.
- Accepted March 4, 2010.
- American College of Cardiology Foundation
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