Brugada syndrome

Brugada syndrome

Anesthetic relevance	Moderate
Anesthetic management	Avoid triggers for arrhythmia such as autonomic instability and fever. Do not use propofol drips or medications known to activated Na+ channels. Treat arrhythmic storm with isoproterenol (IV) followed by quinidine (only PO formulation)
Specialty	Cardiology
Signs and symptoms	Syncope, palpitations, sudden cardiac arrest
Diagnosis	"Coved" or "saddleback" ST elevation on right precordial leads on ECG
Treatment	Implantable cardioverter defibrillator, antiarrhythmic medications
Article quality
Editor rating	Unrated
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Brugada syndrome (BrS) is a genetic disorder associated with an increased risk of ventricular arrhythmias and sudden cardiac arrest. It is defined by characteristic ECG changes that occur spontaneously or with a drug challenge. The heart is otherwise structurally normal. Patients are often asymptomatic but may present with sudden cardiac arrest, syncope, atrial fibrillation, and nocturnal agonal respiration. Brugada pattern refers to ECG changes alone without corresponding symptoms or clinical criteria.

There are two (sometimes three) types of characteristic ECG changes seen in the Brugada pattern:

• Type 1 (“coved type”): Elevated ST segment >2mm in >1 right precordial lead with pronounced J point elevation, followed by an inverted, symmetrical T wave

• Type 2 (“saddleback”): ST segment descends towards baseline followed by an upright or biphasic T wave
• Type 3: > 2 mm J point, positive T wave, saddleback ST-T configuration, ST segement (terminal portion) elevated < 1 mm

Treatment for Brugada syndrome includes anti-arrhythmic medications and implantable cardioverter defibrillator (ICD) placement for those at risk of sudden cardiac death. All patients should avoid factors known to induce ventricular arrhythmias, such as fever and certain medications.

Anesthetic implications

Perioperative management of patients with BrS should focus on avoidance of factors known to precipitate ventricular arrhythmias. Few clinical trials have been conducted on this subject, therefore guidance for avoidance of specific drugs comes primarily from case reports.

Overview of key points for the perioperative management of BrS:

• Local anesthetics should be avoided if possible
• Propofol is safe for induction but prolonged drips should not be used
• Avoid increases in vagal tone or variations in temperature, avoid ischemia
• Ensure adequate depth of anesthesia and avoid variation in autonomic tone
• Avoid medications that are known to precipitate ventricular arrhythmias (primarily class 1A and 1C antiarrhythmics)
• Sugammadex should be used for neuromuscular blockade reversal
• Manage arrhythmic storm with defibrillation, isoprotenerol, and quinidine

Preoperative optimization

Check history is patient, such as history of arrhythmias (especially ventricular), and history of sudden cardiac death in family (reports of autosomal dominant inheritance, incomplete penetrance). ICDs should be disabled prior to surgery. Pacemakers should be switched to non-sensing mode. External defibrillator pads should be placed on patient prior to surgery if possible. Electrolytes (especially potassium, calcium, magnesium) should be checked and replenished as needed.

Intraoperative management

There is no definitive recommendation for general anesthesia vs regional, however special considerations must be taken into account for both techniques.

Neuraxial and Regional Anesthesia

Local anesthetics are class 1b antiarrhythmics and block voltage-gated sodium channels, and therefore should be avoided if possible. If their use is necessary, the dose should be limited and the patient carefully monitored. Lidocaine with epinephrine is preferred over other local anesthetics.   

For neuraxial anesthesia, caution should be taken to avoid hypotension and bradycardia.

Bupivacaine has been described to cause ECG changes, but also has been given via epidural without issues (Edge 2002, n = 1, epidural bupi 0.25% 10 mL; Dash 2017 n = 1, epidural bupi 0.125% 10 mL over 20 minutes).

General Anesthesia

Induction

Propofol, etomidate, and thiopental have all been shown to be safe induction agents in patients with BrS. Note that Kloesel (2011) described etomidate to cause ST elevations on ECG (without sequelae). Propofol blocks sodium channels in a dose-dependent fashion and has been known to induce the Brugada pattern when administered as a prolonged infusion. Therefore, propofol infusions and drips should be avoided. With regards to induction, two recent prospective studies have found propofol to be a safe induction agent for BrS patients, and may even attenuate the BrS pattern.

Volatile anesthetics

Sevoflurane, nitrous oxide, desflurane, and isoflurane have all been used without issue in BrS patients.  Sevoflurane may be preferred because it does not affect the QT interval.

Neuromuscular blockade

The nondepolarizing muscle relaxants rocuronium (Sahinkaya n = 1, dose 50 mg), vecuronium (Edge n = 1, dose 2 mg increments; Dash n = 1; Staikou), and cisatracurium (Staikou) have been used in case studies without issues.

For succinylcholine there have been case studies of its use without issue (Edge n = 1, dose 100 mg; Staikou), additionally has been described to also be associated with ST changes without sequelae (Kloesel 2011).

For reversal, cholinergic agents such as neostigmine and pyridostigmine may increase parasympathetic tone, even when used in conjunction with glycopyrrolate or atropine. Thus, sugammadex is the preferred reversal agent in patients with BrS.

Other anesthetic drug considerations

• No adverse effects have been seen with benzodiazepines, opioids (caution with tramadol), ketorolac, or antiemetics such as dexamethasone and ondansetron
• Benzodiazepines
  • Midazolam and diazepam have been described in case studies without issues (Staikou)
• Opioids
  • Note that tramadol is on list of medications to use with caution from www.brugadadrugs.org, although there have been case reports of its use without issues (Dash n = 1, dose 50 mg; Biricik n = 1, dose 2 mg/kg)
  • The following have been used without issues in case reports: hydromorphone (Kloesel n = 1), fentanyl (Edge n = 1; Staikou), remifentanil (Sahinkaya n = 1, dose 0.5 mcg/kg/min), sufentanil (bolus per-induction, dose 0.1 – 0.3 mcg/kg; Flamee, n = 80)
• Antibiotics
  • The following have been used without issues in case reports: cefuroxime (Edge n = 1, dose 1.5 g), metronidazole (Edge n = 1, dose 500 mg), gentamicin (Edge n = 1, dose 320 mg)
• Alpha-agonists and beta-antagonists may worsen the Brugada ECG pattern, while alpha-antagonists and beta-agonists may improve it
  • Case reports of use of phenylephrine without issue; case report of patient receiving oxymetazoline and association with ST changes (Kloesel 2011)
  • Case reports of using labetalol and esmolol without issue (Kloesel 2011)

Management of intraoperative arrhythmias

Ventricular tachycardia or ventricular fibrillation should be managed with immediate defibrillation. The following are pharmacologic options for acute management of recurrent ventricular arrhythmias:

• Isoprotenerol (1^st line): 2-10 micrograms/minute IV titrated to clinical response
• Quinidine: enteral administration only
  • Quinidine sulfate (immediate release): 200mg PO every 6 hours
  • Quinidine gluconate (extended release): 324mg PO every 8 hours

Watanabe (2006) describes for VT storm (>2 episodes of VF or VT in 24 hours) IV isoproterenol bolus 1-2 micrograms followed by infusion of 0.15-0.30 micrograms/min for 1-3 days. Jongman (2007), describes (for n =1) that an isoproterenol infusion at 1 microgram/min was able to suppress the VF (continued up to 1 day, until quinidine was on board).

Check electrolytes intraop and correct if abnormal. Return temperature to normal.

Postoperative management

Continuous ECG monitoring for the first 24-36hrs after surgery is recommended

Related surgical procedures

Radiofrequency catheter ablation for ventricular arrhythmias

Pathophysiology

BrS is an autosomal dominant defect in the sodium channels of cardiac myocytes (mutation in SCN5A identified in about 20-30% of patient with Brugada syndrome (Staikou)). This affects the action potentials of cells in the right-ventricular outflow tract, leading to altered repolarization and subsequent ST elevation in the precordial leads. Not all cells are equally affected, creating a discrepancy in refractory periods and subsequent premature ventricular beats. This is called phase 2 reentry and can lead to sustained ventricular arrhythmias.

Signs and symptoms

Patients are often asymptomatic, but may present with palpitations, syncope, chest discomfort, nocturnal agonal respirations, ventricular arrhythmias or sudden cardiac arrest. Not all patients will have the Brugada pattern ECG at baseline. A family history of Brugada syndrome or sudden cardiac death raises suspicion for diagnosis.

Diagnosis

The following are diagnostic criteria from the Heart Rhythm Society (HRS), European Heart Rhythm Association (EHRA), and the Asian Pacific Heart Rhythm Society (APHRS) 2013 expert consensus:

1.     ECG type 1 morphology in at least 1 right precordial lead occurring either spontaneously or after provocative drug test with Class I antiarrhythmic drugs

2.     ECG type 2 morphology in at least 1 right precordial lead when a provocative drug test induces a type I ECG morphology

Workup should include evaluation for underlying structural heart disease, which would suggest an alternative diagnosis. Genetic testing may be appropriate if a specific mutation has been identified within a family.

There are many conditions that may mimic the Brugada pattern on ECG, including pericarditis, myocardial infarction, electrolyte abnormalities, as well as ECG abnormalities such as atypical right bundle branch block and left ventricular hypertrophy.

Reports of provocative testing being done if diagnosis unclear (with class 1 antiarrhythmic agent) (Levy 2018).

Treatment

Treatment for BrS involves antiarrhythmic drugs and/or an ICD. Patients with history of sudden cardiac arrest or ventricular arrhythmias should receive an ICD. Patients who are not candidates for an ICD can receive quinidine or amiodarone. Catheter ablation may be considered for patients with recurring arrhythmias resulting in ICD shocks. The following factors may provoke arrhythmias and should be avoided in all patients:  

• Fever
• Class 1A and 1C anti-arrhythmic medications such as flecainide, procainamide, and ajmaline
• Bupivicaine and procaine
• Tricyclic antidepressants
• Lithium
• Acetylcholine

For a complete list of medications to avoid visit www.brugadadrugs.org

Medication

Patients who are not candidates for ICD implantation or have frequent shocks with their ICD can receive antiarrhythmic therapy. The two medications used are quinidine and amiodarone. Quinidine is preferred due to long-term side effects of amiodarone.

Surgery

Patients who continue to have shocks with an ICD may undergo radiofrequency catheter ablation

Prognosis

Patients with a history of ventricular arrhythmias or sudden cardiac arrest are at greatest risk for future events. Asymptomatic patients are at a lower risk for sudden cardiac death. Other factors that may increase risk for future cardiac events include family history of sudden cardiac arrest, atrial fibrillation, and male gender.

Epidemiology

The overall prevalence of the Brugada ECG pattern ranges between 0.1 and 1 percent. There is a higher prevalence in the Philippines, Thailand and Japan. The mean age of sudden cardiac death is 41. The youngest patient was diagnosed 2 days of age, the oldest at 84 years; 20% of Brugada syndrome patients may develop supraventricular arrythmias (Antzelevitch). Brugada syndrome has an incidence of 1/5000 to 1/2000, Brugada pattern on ECG 0.12 – 0.8% (Ranucci).

References

C. J. Edge, D. J. Blackman, K. Gupta, M. Sainsbury, General anaesthesia in a patient with Brugada syndrome, BJA: British Journal of Anaesthesia, Volume 89, Issue 5, November 2002, Pages 788–791, https://doi.org/10.1093/bja/89.5.788

Dash S, Pragathee S. Anaesthetic Management in Brugada Syndrome - A Case Report. J Clin Diagn Res. 2017 Feb;11(2):UD03-UD04. doi: 10.7860/JCDR/2017/24898.9457. Epub 2017 Feb 1. PMID: 28384965; PMCID: PMC5376781.

Jongman JK, Jepkes-Bruin N, Ramdat Misier AR, Beukema WP, Delnoy PP, Oude Lutttikhuis H, Dambrink JH, Hoorntje JC, Elvan A. Electrical storms in Brugada syndrome successfully treated with isoproterenol infusion and quinidine orally. Neth Heart J. 2007;15(4):151-5. doi: 10.1007/BF03085972. PMID: 17612676; PMCID: PMC1847769.

Kloesel B, Ackerman MJ, Sprung J, Narr BJ, Weingarten TN. Anesthetic management of patients with Brugada syndrome: a case series and literature review. Can J Anaesth. 2011 Sep;58(9):824-36. doi: 10.1007/s12630-011-9546-y. Epub 2011 Jun 23. PMID: 21698509.

Şahinkaya HH, Yaşar E, Tekgül ZT, Horsanalı BÖ, Özeroğlu E. Anaesthetic Management of a Patient with Brugada Syndrome. Turk J Anaesthesiol Reanim. 2016 Apr;44(2):96-8. doi: 10.5152/TJAR.2016.22230. Epub 2016 Apr 1. PMID: 27366566; PMCID: PMC4894205.

Staikou C, Chondrogiannis K, Mani A. Perioperative management of hereditary arrhythmogenic syndromes. Br J Anaesth. 2012 May;108(5):730-44. doi: 10.1093/bja/aes105. PMID: 22499746.

Watanabe A, Fukushima Kusano K, Morita H, Miura D, Sumida W, Hiramatsu S, Banba K, Nishii N, Nagase S, Nakamura K, Sakuragi S, Ohe T. Low-dose isoproterenol for repetitive ventricular arrhythmia in patients with Brugada syndrome. Eur Heart J. 2006 Jul;27(13):1579-83. doi: 10.1093/eurheartj/ehl060. Epub 2006 Jun 7. PMID: 16760208.