Brugada Syndrome: A Review of Perioperative Management

Daniela Smith, MD

Staff Anesthesiologist
Laurel Regional Hospital
Laurel, Maryland

Douglas G. Martz, MD

Associate Professor
Department of Anesthesiology
University of Maryland School of Medicine
Baltimore, Maryland

Brugada syndrome (BrS) is a rare cardiac channelopathy that describes patients with a structurally normal heart at risk for ventricular arrhythmias and sudden death.¹

First identified in 1992, BrS accounts for 4% of all sudden deaths, and up to 20% of sudden deaths in patients without structural cardiac defects.² Since patients with known and unknown BrS can present for surgery at any time, it is important for anesthesiologists to be familiar with this syndrome in order to be able to safely manage these patients perioperatively.

Syncope and sudden death can occur without warning, and are caused by fast polymorphic ventricular tachycardia or fibrillation.³ The characteristic ECG findings can be transient with “pseudonormalization” of the ECG.⁴ Three ECG patterns have been identified, with type 1 being the only one diagnostic of BrS (Figure 1).⁵ In this pattern, a coved-type ST-segment elevation greater than 2 mm is followed by a negative or flat T wave.⁴

 

Recognition of BrS is crucial as the 2-year mortality rate approaches 30%.³ A right bundle branch block may be present but is not required for diagnosis.²Between 20% and 30% of patients have concomitant supraventricular tachycardia, most frequently atrial fibrillation, which may be the first manifestation of the disease.⁴ The BrS ECG pattern is more pronounced with sleep, rest, or after eating, when vagal activity dominates. It also occurs in sudden unexpected nocturnal death syndrome and may be linked to sudden infant death syndrome.² The clinical presentation of BrS varies from patients being asymptomatic to having a history of syncope, seizures, palpitations, nocturnal agonal respiration, and aborted sudden death.⁴

The prevalence of BrS differs according to population and is more common in Southeast Asia (12 per 10,000) than Europe (1-5 per 10,000).² The average age of diagnosis is 40 to 45 years, and 80% of patients are men.² Brugada syndrome has an autosomal dominant inheritance with variable penetrance, and the majority of patients have a family history of sudden death or malignant arrhythmias.^2,3

Table. Anesthetic Drug Recommendations17 Safe to administer All depolarizing and nondepolarizing paralytics Benzodiazepines, narcotics, ketorolac Dexamethasone, ondansetron, droperidol Ephedrine, phenylephrine, dopamine Isoproterenol Muscle relaxant reversals Nitrous oxide, all volatile anesthetics Propofol and barbiturates Regional and neuraxial anesthesia with a variety of local anesthetics Contraindicated (class I) Flecainide, procainamide Avoid if possible (classes IIa and IIb) α-agonists β-blockers Amiodarone Carbamazepine Cocaine Dimenhydrinate Diphenhydramine Edrophonium Ergonovine Ketamine Metoclopramide Phenytoin Propofol infusion Tramadol Verapamil No clear evidence of adverse effects (class III) Diltiazem Nifedipine? Nitroglycerin BrS, Brugada Syndrome Class I: Strong evidence and general agreement that the drug is potentially arrhythmic in BrS patients. Class IIa: Conflicting evidence, but weight/opinion is in favor of a potentially arrhythmic effect in BrS patients. Class IIb: Conflicting evidence, and the potential arrhythmic effect is less well established in BrS patients. Class III: Little to no evidence of a potential arrhythmic effect in BrS patients.

Mutations in 10 genes have been linked to BrS, the most common being a SCN5A mutation that affects cardiac sodium channel conduction.² The prevalence of SCN5A mutations is approximately 18% to 30%, and causes reduced cardiac sodium current.^4,5 Other mutations lead to a decrease in L-type calcium current and decreased transient outward potassium current.⁶ These electrolyte abnormalities lead to right ventricular conduction disturbances and the associated BrS ECG pattern.⁶ At this time, it is unclear whether the exact mechanism is due to an abnormal depolarization or repolarization pattern, or possibly both.²

An implantable cardioverter defibrillator is the only effective treatment. It is recommended for patients who are symptomatic or have a spontaneous type 1 BrS ECG pattern inducible with electrophysiologic studies.² A review of the literature revealed a series of case reports detailing a variety of methods for administering a successful anesthetic to patients with BrS, including general, sedation, and regional anesthesia.⁷Nevertheless, there are certain guidelines to follow intraoperatively in order to minimize the risk for adverse cardiac events.

We report a case in which a patient with known BrS received a successful general anesthetic on 2 consecutive days. A review of the literature is also presented along with a summary of perioperative care recommendations.

Recommended Perioperative Management

All patients with a type 1 ECG pattern, regardless of whether they have a known diagnosis of BrS, should be treated as having BrS in the perioperative setting.⁸

Nonpharmacologic Approaches

All patients with BrS should have external defibrillator pads placed.^8-14Implantable cardioverter defibrillators should be turned off preoperatively as applicable and reactivated postoperatively.^8,9,11,12,15 Electrolyte abnormalities should be corrected preoperatively, as hyper- and hypokalemia and hypercalcemia can worsen BrS ST-segment elevation.⁸ As autonomic changes can precipitate arrhythmias, adequate depth of anesthesia should be ensured and postural changes should be minimized.¹⁰ Increased vagal tone has been implicated in the development of BrS ECG changes.⁸ The patient should be kept normothermic because hyperthermia in particular can unmask BrS due to premature inactivation of the sodium channel.^5,8 Some investigators recommend the routine use of arterial lines in all cases in order to accurately monitor hemodynamic changes and the placement of central lines for major cases.^8-11Patients should be observed via telemetry up to 36 hours after surgery since arrhythmias are more likely to occur postoperatively.¹⁰

Pharmacologic Approaches

Benzodiazepines, narcotics, and ketorolac have not been associated with any adverse events.^7,9-12,15,16 Regional and neuraxial anesthesia have been successfully performed with a variety of local anesthetics, including lidocaine, mepivacaine, bupivacaine, and ropivacaine (Naropin, Fresenius Kabi USA).^7,9,10,16Propofol and various barbiturates have been successfully used for induction of general anesthesia.^7-13,15 Etomidate has been associated with one report of self-limited ST-segment elevation.¹⁶ High-dose ketamine should be used with caution.⁸ Although propofol drips have been successfully used in some reports, they are best avoided due to a potential development of propofol infusion syndrome and alteration in ion channel function^16,17.

Although general anesthesia has been successfully maintained with nitrous oxide, desflurane (Suprane, Baxter Healthcare), sevoflurane, and isoflurane, it has been suggested that sevoflurane might be best because it has no effect on QT length.^7-12,15,16 Depolarizing and nondepolarizing paralytics are safe to use, as are reversal agents.^7,9,12,13,16 It is recommended to give reversal agents slowly, as anticholinergics can cause tachycardia, and neostigmine can cause ST elevation.⁸ Atropine (AtroPen, Meridian Medical Technologies), glycopyrrolate, and dopamine have been used to treat bradycardia.^8,14,15 Hypotension has been treated with ephedrine and phenylephrine.¹⁶ β-blockers and α-agonists should be used with caution, as they can increase ST-segment elevation and unmask a BrS ECG pattern.^8,16 Isoproterenol (Isuprel, Hospira) has been used to reduce ST-segment elevation and suppress arrhythmias.^8,16 Commonly used antiemetics such as dexamethasone, droperidol (Inapsine, Taylor), and ondansetron have been used without incident.^7,16

Conclusion

The current understanding of BrS is that it is caused by various rare channelopathies, resulting in aberrant cardiac conduction and a characteristic ECG in patients with a structurally normal heart. Inheritance is autosomal dominant, and patients are at increased risk for sudden death, particularly due to ventricular fibrillation or tachycardia. As these patients may present for surgery with no warning, such as the patient in this case report, it is important for anesthesiologists to be familiar with this syndrome in order to provide a safe anesthetic and perioperative experience.

Case Report A 53-year-old woman presented for emergency embolization of her left facial artery and bilateral internal maxillary arteries due to severe epistaxis on 2 consecutive days. The 63-kg patient had a history of BrS that had been diagnosed at 50 years of age; her brother and father also had BrS. The patient was asymptomatic with a good functional status and was otherwise healthy. Her preoperative ECG showed a sinus rhythm with a heart rate of 86 beats per minute, right bundle branch block, and coved-type ST-segment elevation greater than 2 mm in V1 and V2 followed by a negative T wave (Figure 2). This ECG pattern is consistent with type 1 BrS ECG. For both embolizations, defibrillator pads were placed preoperatively, as the patient did not have an implantable cardioverter defibrillator. Two peripheral IVs and an arterial line were also placed. The patient was premedicated with midazolam for both procedures. The patient was normotensive for both procedures, and a normal sinus rhythm between 60 and 100 beats per minute was maintained. Normothermia was maintained during both procedures with a forced-air underbody warming blanket. For the first embolization, a rapid sequence induction was performed with fentanyl, propofol, and succinylcholine, as the patient had severe epistaxis and had been swallowing a lot of blood. General anesthesia was maintained with sevoflurane and the patient was given rocuronium. The patient received dexamethasone and ondansetron for antiemesis, and paralysis was uneventfully reversed with glycopyrrolate and neostigmine. A second embolization had to be performed the next day due to renewed bleeding. General anesthesia was induced with lidocaine, fentanyl, propofol, and rocuronium, and maintained with isoflurane. She was given 20 mg of esmolol to maintain a heart rate less than 100 beats per minute. The patient received metoclopramide and ondansetron for antiemesis, and paralysis was again reversed with glycopyrrolate and neostigmine. There were no complications during or after either procedure, including further ST-segment changes or hemodynamic changes. The patient remained in a telemetry unit throughout her hospital stay and was discharged 2 days after her second embolization.

References

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