Comparision of Various Vasodilators Regimen During Radial Corornary Angiogram : A Prospective Randomised Trial

Methods and Result: This is a single centre, prospective randomized trial between Verapamil, Nitroglycerine (GTN) and cocktail (Verapamil with GTN). All the patient undergoing coronary angiogram via radial approach, without the contraindication were randomized by a computer generated randomization protocol. Patient undergoing coronary procedures via the radial artery were divided into three groups. Patients in group A received intra-arterial cocktail (2.5 mg of Verapamil plus 100 mcg Nitroglycerine in 10 ml of normal saline), patients in group B received Verapamil (5mg) and patient in group C received Nitroglycerine (200mcg). Heparin of 3000U was given intravenously in all three groips. Altogether 207 patients underwent transradial coronary angiogram, 203 were randomized after exclusion. Over all Radial artery spasm was reported in 28 patients (13.79%). There was no statistically significant difference in spasm between the three regimens however when grading, there was significant higher grade of spasm in Verapamil group (13.23%, P value < 0.05). When comparing Verapamil and GTN separately there was significant higher spasm (21% vs 7%, P value < 0.05) with higher grades of spasm in verapamil group.


INTRODUCTION
First reports of radial coronary angiography was by Lucian Campeau in 1989 and radial percutaneous coronary intervention (PCI) by Ferdinand Kiemeneij in 1992 after which there was an increase in the use of transradial access (TRA) around the world. 1,2,3Previous studies have shown that transradial artery approach for coronary artery catheterization and intervention to be safe, easy and effective, as well as cost effective. 4Patients also prefer transradial route in comparison to the femoral access because of lower incidence of back and access site pain and earlier ambulation. 5,6The advantages we get from the radial route has some demerits also and it

*Corresponding author
Bishal KC, National Academy of Medical Sciences, Bir Hospital, Kathmandu, Nepal Email: bishalk@gmail.com is not devoid of complications.The problem which are faced are unsuccessful radial access, coronary catheterization failure, pulse deficit, radial artery occlusion, dissection, and spasm. 1,3,7,8,9The most common of these is the radial spasm 8,9 causing patient discomfort and even procedure failure.There is high propensity of spasm in the radial artery because of its anatomic property.Its wall is thick and consists of smooth muscle in concentric layer and the cells have high density of alpha-1 receptors.This both properties makes radial artery highly susceptible to spasm. 10The reported incidence of radial artery spasm rages from 15-30% even in the centers highlt experienced with the procedure. 11Prevention of the spasm is possible by various premedications. 11Worldwide there has been a lot of studies of spasmolytics which has shown the benefit. 4,5,6,9,11,12,13,14Among these studies it has been recommended by Kiemeneij et al. 11 that the spasm is significantly reduced by 34-14% by the use of cocktail with intra-arterial nitroglycerin and verapamil.Radial access for coronary intervention has been in practice in Nepal for last several years there has been no study regarding the different vasodilator regimen for the prevention of radial artery spasm during the procedure.We report a prospectively randomized study to compare the spasmolytic effects on the radial artery with different premedications, with nitroglycerin alone, verapamil alone and nitroglycerin plus verapamil in radial coronary angiogram.

Definitions
Spasm was graded according to the operative perceived resistance, Maneuverability of the catheters and degree of pain perception by the patients.
Pain score was defined as the patient's assessment of pain during radial artery sheath removal, where I denote nothing felt; II, noticeable sensation but no pain; III, mild pain; IV, significant pain; and V, unbearable pain. 11

Statistical Analysis
Variables were presented as mean ± standard deviation.ANOVA was used for analysis of the difference in the rate of radial spasms between the three groups.An SPSS software program was used for performing the analysis.A p value <0.05 was considered statistically significant.

RESULTS
Altogether 214 coronary angiograms were performed.Seven underwent angiogram via femoral route.Two hundred seven underwent angiogram via radial route and four were rejected due to abnormal anatomy and radial loop.Two hundred and three patients were randomized into three vasodilator regimens.Sixty five were included in group A, 68 in group B and 70 in group C.

DISCUSSION
Due to the presence of dual blood supply to the hand, radial route for coronary catheterization and intervention is relatively safe. 3,5,13,15,16Prevention is better than cure and when it comes to radial artery spasm it holds true.The prevention of spasm is easy than to control when it occurs. 8 and yang classification classifies the radial artery into type III artery graft with high propensity for spasm and also as stated above due to abundance of the alpha receptors slight cathecholamine release during pain or anxiety can induce radial spasm. 17Many studies done in the past have used different spasmolytic regimens. 5,8,9,16In one of the similar studies publish by Kiemeneij et al. 14 which was a prospective study proved that intra-arterial administration of 5 mg of verapamil and 200 mcg of nitroglycerin reduced the occurrence and severity of radial artery spasm.The data showed the evidence of benefit of verapamil in the prevention of spasm but concern still remains regarding the negative inotropic and chronotropic effects of verapamil.The VITRIOL study 18 states that The preventive use of verapamil may be unnecessary for transradial procedures.
The omission of prophylactic verapamil may not only reduce the rate of potential complications related to the drug but also allow the safe extension of the transradial method to those with contraindications to verapamil.So there has been a lot of reluctance in the use of verapamil as spasmolytics.Study done by Chen et al showed that nitroglycerine alone is also effective as compared to placebo in prevention of radial artery spasm. 19echanism by which the nitroglycerine causes vasodilation is by by activating guanylyl cyclase and increasing cGMP. 20itroglycerine has also been compared with the diltiazem and was found to be more effective. 21Our data showed that the nitroglycerine is more effective than verapamil and the cocktail of both in preventing spasm.In this study more spasm was found among the female which may be due to the hormonal effect or due to the low pain threshold but the exact cause is still not known.Further larger study requires confirming this.

Study Limitations
There are few limitations of this study: 1.Not placebo controlled 2. Operators not blinded 3. Due to the different threshold of pain there might be difference in spasm and grading of spasm 4.This is a single center study 5.The follow up of the patient was not done In conclusion, we recommend that the nitroglycerine be used a preferred spasmolytics during radial coronary angiogram.However larger study using large population in multicenter setting is required to confirm the findings of this study.
was conducted for three months from 2015 June 16 to September 17.Altogether 207 patients undergoing elective coronary angiogram from the radial route were randomized into three different vasodilator regimen.All patients above the age of 18 undergoing radial coronary angiogram with hemodynamic stability were included.The baseline characteristics, including patients' age, gender, body weight, body height, serum cholesterol and triglyceride level, the rate of diabetes and smoking, blood pressure, were compared in three groups.Ethical approval was obtained and all patients gave informed consent to this procedure.

Table 1
shows the baseline characteristics, including patients' age, gender, serum cholesterol and triglyceride level, the rate of diabetes and smoking, blood pressure and rate of right and left handed approach.No significant difference in baseline parameters was found between these three groups.Overall radial artery spasm was noted in 14% of the patients.Nine