Leeds Teaching Hospitals Guidelines on the use of Ajmaline in Children for Diagnosis of Brugada Syndrome Only to be used under the direction of a Consultant Cardiologist Fully informed consent MUST be taken for the ajmaline challenge using a standard hospital consent form. Attention should be given to the unlicensed indication for use and small risk of arrhythmic complications and a patient information leaflet should be given. Indication Confirmation of Brugada Syndrome in patients with a normal or equivocal ECG. Please Note: the latest professional opinion is that it is not particularly useful pre- puberty as there is a high risk of a false negative result, therefore providing false reassurance. Any child with a strong suspicion will therefore need a further post- pubertal test. Brugada Syndrome Brugada syndrome is a recently recognized disorder of the cardiac sodium channel. It is genetically determined, and inherited in an autosomal dominant pattern. It is an important cause of malignant arrhythmia and cardiac arrest. The underlying abnormality seems to be a defect in the cardiac SCN5A sodium channel causing disruption of the ion-mediated phase 1 of the cardiac action potential. There is no proven pharmacological intervention, and affected individuals may require implantation of automated cardioverter defibrillator (AICD). The condition is characterised by the presence of a specific ECG pattern. This is a “coved”-type Right Bundle Branch Block (RBBB) pattern, with a terminal r wave, and a J-point elevation of at least 0.2mV with a slowly descending ST segment in continuation of a flat or negative T wave in the precordial leads V1 to V3. These electrocardiographic manifestations may be intermittent, and may be unmasked by Class IA and II antiarrhythmic drugs (flecainide, propafenone, ajmaline, disopyramide, procainamide). Ajmaline, which is only available in intravenous form due to poor oral bioavailability, seems to be the best drug to unmask Brugada Syndrome. Cautions and Contraindications Cardiac failure Caution should be taken in children with conduction abnormalities, since it can lead to higher degree block (sinus node disease, Mobitz Type II, Complete Heart Block, Bifuscicular Block) Diagnostic criteria of Brugada Syndrome on resting 12 Lead ECG M:\Medicines Information Permanent Documents\24. paed medicine\originals\Ajmaline in paeds for diagnosis of brugada syndrome.doc Mode of action Ajmaline is a Rauwolfia alkaloid which when administered intravenously acts as a rapidly acting class Ia antiarrhythmic agent. Like other class I agents its primary site of action is the fast sodium channel of the cardiac myocyte acting to slow the dV/dtmax of phase 1 of the cardiac action potential. No randomized comparison of different class I agents for the diagnosis of Brugada syndrome has been performed. It is likely that all agents used are roughly equivalent in terms of diagnostic accuracy, although some have suggested that procainamide is less reliable. The advantages of ajmaline are those of safety and utility due to its short duration of action Environment Patients should be fasted prior to the procedure Other antiarrhythmic medication should be stopped prior to admission An experienced physician with skills in acute resuscitation should be present Electrolyte abnormalities should be corrected Full resuscitation facilities MUST be available including an external defibrillator, intubation equipment and resuscitation drugs. The procedure should be performed at the High Dependency Unit or in the cardiac catheter laboratory. Dosing Regimen, Administration and Monitoring Each intravenous preparation contains 50mg in 10mL Draw up a total of 1mg/Kg in a clearly labelled syringe. It can be diluted, for easier administration in Glucose 5% Get secure venous access Perform a baseline 12 Lead ECG and Blood Pressure For patients over 40Kg administer 10mg intravenously every 2 minutes under continuous ECG monitoring to a MAXIMUM dose of 1mg/Kg (Do not exceed 50mg). For patients less than or equal to 40Kg administer 0.25mg/Kg intravenously every 2 minutes under continuous ECG monitoring to a MAXIMUM dose of 1mg/Kg Perform a 12 Lead ECG after each dose and if the ECG is abnormal see termination criteria Perform a 12 Lead ECG, and measure blood pressure 30 minutes and 1 hour after last dose Discharge patient after 2 hours if baseline observations and 12 Lead ECG has returned to baseline If ECG is abnormal during the test, keep patient in hospital and inform consultant in charge. Termination Criteria Target dose of 1mg/kg or maximum dose is reached QRS prolongation of greater than 30% compared to baseline Occurrence of frequent premature ventricular ectopics, ventricular tachycardia, sinus arrest or 2nd/ 3rd degree AV block Diagnostic ECG pattern of Brugada Syndrome in at least one right precordial lead M:\Medicines Information Permanent Documents\24. paed medicine\originals\Ajmaline in paeds for diagnosis of brugada syndrome.doc Pharmacokinetics Ajmaline has a distribution half life of 6 minutes and an elimination half life of 95 minutes. 75% protein bound Side effects Similar to all class I antiarrhythmics. Include AV block and widening of the QRS complex. Dysrhythmias on overdosage or on too rapid injection, the commonest being ventricular tachycardia. In extreme overdose respiratory depression, hypotension, shock, anuria, coma, cardiac arrest, intrahepatic cholestasis, eosinophilia, thrombocytopaenia, agranulocytosis. The latter effects are those of more long term administration and are extremely unlikely after administration of a single dose. References Pepper C. Ajmaline monograph. Drug and Therapeutics Committee. Leeds Teaching Hospitals NHS Trust. 5th July 2006 Wilde et al. Proposed diagnostic criteria for Brugada Syndrome. A Consensus Report. Circulation 2002;106:2514-2519 Rolf et al. The ajmaline challenge in Brugada Syndrome: Diagnostic Impact, safety and recommended protocol. European Heart Journal 2003; 24(12): 1104-1112 Dart C D et al. Medical Toxicology. Third Edition. Lippincott Williams & Wilkins 2004 Written by: Teresa Brooks (Pharmacist) and Demetris Taliotis (Specialist Registrar) Reviewed by: Teresa Brooks, ACP for Paediatric Cardiology Checked and approved by: Dr Dom Hares Date; 28th November 2018 Review date: September 2021 M:\Medicines Information Permanent Documents\24. paed medicine\originals\Ajmaline in paeds for diagnosis of brugada syndrome.doc .