Today, I was present during a Brugada provocation test using ajmaline, a class 1a antiarrhythmic drug much like class 1c drug, flecainide, in that it acts as a Na channel blocker. As its action lengthens the action potential phase 0, in non-pacemaker myocytes, it induces bradycardia, and encourages the transient Brugada rhythm to present itself.
Indications for the test are outlined here, and the procedure itself, is a relatively simple one;
- Ajmaline is prepared at a total dose of 1mg/kg-1
- 12 lead ECG is applied to the patient
- V1 and V2 should be positioned on IC3 or IC2
- The ECG should be viewable in real time, as well as be printable
- Intravenous Ajmaline is administered in a 10mg bolus, every 2 minutes
- Fractions should be administered slowly over 1 minute
- ECG should be printed after each dose
Indications for terminating the test are as follows:
- Ajmaline dosage is completely administered
- Typical Brugada criteria present on the ECG
- ST coving present in more than 1 right precordial lead
- J point elevation greater than 2mm
- Incidence of:
- AV Block (2nd° or 3rd°)
- Sinus arrest
During the test, the patient indicated that the initial 10mg was very unpleasant, and caused “a horrible feeling” at the back of her throat. She did say that this initial bolus was the worst, however, and that subsequent injections were bearable, by comparison. Towards the end of the test, i.e., one injection from termination, the patient indicated that her lips had become almost completely numb.
The test, in this case, was negative, and the patient’s ECG showed no changes to suggest Brugada at any point throughout the procedure.
Ajmaline is unlicensed in the UK, but this is not indicative of its level of safety, rather it is because it is manufactured in Germany, and imported to trusts in this country. Curious as to why ajmaline was being used, I asked the nurse practitioner who was on hand to implement the test, who informed me why the trust opted to use ajmaline as oppose to flecainide, when both seemingly do the same thing. She cited the time taken for each pharmaceutical agent to leave the patient after the test; in the event of a negative outcome, ajmaline allows a patient to be discharged safely in around 3 hours, whereas flecainide takes a great deal longer to be removed.
Not knowing the costs associated with each drug, I decided to look for other reasons as to why an imported medication is used in this provocative study, and discovered research by Wolpert et al published in 2005, that tested ajmaline and flecainide against each other in a blind trial.
22 patients for whom a diagnosis of Brugada was already known, underwent IV flecainide and ajmaline testing, and the results were then studied by 3 physicians who were unaware of the drug being used in provocation.
The results for flecainide showed
- Significant ST changes in 15/22 of the patients tested (68%)
- Mean V1 amplitude of 0.19mV
- Mean V2 amplitude of 0.31mV
- Mean V3 amplitude of 0.1mV
The results for ajmaline showed
- Significant ST changes in 22/22 of the patients tested
- Mean V1 amplitude of 0.22mV
- Mean V2 amplitude of 0.39mV
- Mean V3 amplitude of 0.1mV
It is important to note, that whilst these results show a more favourable outcome when using ajmaline over flecainide, in provocative studies, this research is limited in that, despite being a blinded study, it was not a randomised trial and was not repeated. Nevertheless, it does suggest that provocative studies using flecainide may not successfully unmask Brugada syndrome in patients, and its longer life within the patient may favour the use of ajmaline in investigations.