Accepted Manuscript

Title: Anesthetic and Perioperative Management of Patients with Brugada

Syndrome.

Author: Gregory Dendramis, Claudia Paleologo, Giuseppe Sgarito, Umberto

Giordano, Roberto Verlato, Adrian Baranchuk, Pedro Brugada

PII: S0002-9149(17)31042-1
DOI: http://dx.doi.org/doi: 10.1016/j.amjcard.2017.06.034
Reference: AJC 22709

To appear in: The American Journal of Cardiology

Received date: 19-3-2017

Revised date: 30-5-2017

Please cite this article as: Gregory Dendramis, Claudia Paleologo, Giuseppe Sgarito, Umberto
Giordano, Roberto Verlato, Adrian Baranchuk, Pedro Brugada, Anesthetic and Perioperative
Management of Patients with Brugada Syndrome., The American Journal of Cardiology (2017),
http://dx.doi.org/doi: 10.1016/j.amjcard.2017.06.034.

This is a PDF file of an unedited manuscript that has been accepted for publication. As a service
to our customers we are providing this early version of the manuscript. The manuscript will
undergo copyediting, typesetting, and review of the resulting proof before it is published in its
final form. Please note that during the production process errors may be discovered which could
affect the content, and all legal disclaimers that apply to the journal pertain.
Anesthetic and Perioperative Management of Patients with Brugada Syndrome.

Gregory Dendramis, MDa,e; Claudia Paleologo, MDb; Giuseppe Sgarito, MD, PhDc; Umberto

Giordano, MDc; Roberto Verlato, MDa; Adrian Baranchuk, MDd; Pedro Brugada, MD, PhDe.

Institutions:
a
Cardiovascular Division, Pietro Cosma Hospital, ULSS 6 Euganea, Camposampiero, Padova, Italy.
b
Department of Biopathology, Medical and Forensic Biotechnologies, Section of Anesthesiology,

Analgesia, Intensive Care and Emergency, University Hospital “Paolo Giaccone”, Palermo, Italy.
c
Division of Cardiology, ARNAS Ospedale Civico e Benfratelli, Palermo, Italy.
d
Division of Cardiology, Queen's University, Kingston, Ontario, Canada.
e
Heart Rhythm Management Centre, UZ Brussel-VUB, Brussels, Belgium.

Corresponding author:

Gregory Dendramis, MD
C.da S.Caterina, snc. CAP 90037.
Piana degli Albanesi, Palermo, Italy.
Tel/Fax: 0918574873.
E-mail: gregorydendramis@libero.it

Running head: Anesthetic management of Brugada syndrome patients.

Total word count: 3.657

No conflict of interest.

1
Page 1 of 17
Abstract:

The Brugada syndrome (BrS) is an arrhythmogenic disease reported to be one among the leading

causes of cardiac death in subjects under the age of 40 years. In these patients episodes of lethal

arrhythmias may be induced by several factors or situations and for this reason management during

anesthesia and surgery must provides some precautions and drugs restrictions.

To date it is difficult to formulate guidelines for anesthetic management of BrS patients due to

the absence of prospective studies and there is not a definite recommendation for neither general

nor for regional anesthesia and there are no large studies in merit. For this reason, in the anesthesia

management of BrS patients, the decision of using each drug must be made after careful

consideration and always in controlled conditions, avoiding other factors that are known to have the

potential to induce arrhythmias and with a close cooperation between anesthetists and cardiologists

that is essential before and after surgery.

In conclusion, given the absence of large studies in literature, we want to focus on some general

rules, resulted from cases series and clinical practice, to be followed during the perioperative and

anesthetic management of patients with BrS.

Key words: Brugada syndrome, anesthetic management, regional anesthesia, general anesthesia,

surgery, perioperative management, drugs, general rules.

2
Page 2 of 17
Introduction

Electrocardiographically characterized by a distinct ST-segment elevation in the right precordial

leads, Brugada syndrome (BrS) is an arrhythmogenic disease reported to be one among the leading

causes of cardiac death in subjects under the age of 40 years (figure 1, 2, table 1). Global prevalence

of BrS varies from 5 to 20 in every 10,000 inhabitants worldwide and it is considered endemic in

Asian and Southeast Asian countries, especially Thailand, Philippines and Japan, where the

prevalence is higher. However, to date, no precise data are available on the epidemiology of this

disease. As far as we know inheritance of BrS occurs via an autosomal dominant mode of

transmission and about eighteen genes have been associated with BrS and thus far genetic

abnormalities are found in 30-50% of genotyped BrS patients. Mutations in the cardiac sodium

channel gene SCN5A, which encodes the alpha-subunit of the human cardiac sodium channel, are

identified in 11–28% of patients with BrS. Since genotype remains lacking for at least half of

probands, a negative genetic test does not rule out BrS [1]. Patients with BrS may present with

syncope due to polymorphic ventricular tachycardia, ventricular fibrillation or aborted cardiac

arrest. Palpitations, presyncope, and syncope are the three most important symptoms requiring

further characterization in patients suspected of having ventricular arrhythmias due to BrS [1,2].

Discussion

Any factor that unbalances the parasympathetic and sympathetic traffic may precipitate a lethal

arrhythmia in BrS patients. Medications and increased vagal activity can augment ST segment

elevation, but a clear causal link between acute worsening of ST segment abnormalities and

subsequent ventricular arrhythmias has not been established, however multiple reports suggest such

a relationship [3-8]. Episodes of arrhythmias can be also induced during anesthesia by episodes of

sinus bradycardia, anesthetics, vagotonic agents, beta-adrenergic blockers, alpha-adrenergic

agonists, thermal variations, hyperkalemia, hypokalemia, and hypercalcemia; but to date it is

difficult to formulate guidelines for anesthetic management of BrS patients due to the absence of
3
Page 3 of 17
prospective studies and the low prevalence of BrS [1]. For this reason, in the anesthesia

management of BrS patients, the decision of using each drug must be made after careful

consideration and in controlled conditions, avoiding other factors that are known to have the

potential to induce arrhythmias (table 2).

In 2011 Kloesel et al. published a retrospective chart review of anesthesia records from patients

diagnosed with BrS at the Mayo Clinic; with the emphasis on administered drugs, ST segment

changes and occurrence of complications, including death, hemodynamic instability and

dysrhythmias. Eight patients were identified who underwent a total of 17 operative procedures from

2000 to 2010 and a total of 20 significant ST segment elevations were recorded in four patients,

several of which occurred in close temporal relation to anesthetic drug administration. These

elevations resolved uneventfully and no dysrhythmias were recorded and recovery from anesthesia

occurred uneventfully.

A review of patients with BrS yielded 52 anesthetic procedures in 43 patients. The only recorded

complications included unmasking of a Brugada ECG pattern, one episode of polymorphic

ventricular tachycardia, which converted spontaneously to sinus rhythm, and one episode of

postoperative ventricular fibrillation in the setting of epidural anesthesia. The authors concluded

that in this series and in the literature, BrS patients tolerated anesthesia without untoward disease

related complications [9].

For patients with BrS to date there is a definite recommendation for neither general nor for

regional anesthesia and there are no large studies in merit. The measures to be implemented are

derived from clinical cases and from daily clinical practice.

Regional anesthesia and neuroaxial blockade may be performed with caution in BrS patients

because local anesthetics are class Ib antiarrhythmics and thus they block voltage-gated sodium

channels. Their time to onset, duration of action, and adverse effects are all drug-specific, though

share similar characteristics. Those with rapid dissociation properties used for local anesthesia as

lidocaine does seem to be safe when combined with adrenaline/epinephrine and the amount
4
Page 4 of 17
administered is low with a local effect only and the utmost care should be taken to avoid systemic

injection. Local anesthetics with slow dissociation properties as bupivacaine, levobupivacaine and

ropivacaine should be avoided as long as several complications have been reported, especially when

performing epidural infusions and rapid absorption into the systemic circulation. For these reasons

the use of large amounts of these anesthetics should be avoided or they should be used cautiously;

doses should be minimized and the patient should be monitored closely, even if several authors

reported uneventful regional or wound infiltration with local anesthetics in these patients. Moreover

recently discovery that lipid emulsion may improve the chance of successful resuscitation after

local anesthetic overdose has lead to recommendations that this lipid emulsion for a security issue

should be available where regional anesthesia is performed.

We know as up to half of patients receiving spinal anesthesia may develop transient hypotension

and bradycardia as a consequence to the sympathetic block. This condition usually responds to

prompt fluid replacement with crystalloids but occasionally hypotension can be severe and may

require vasopressors along with fluids. Therefore, in patient with BrS this complication should be

prevented and avoided. For all these reasons, in these patients ultrasound-guided peripheral nerve

blocks, which implies lowers doses of anesthetic and consequently lower systemic absorption,

should be preferred over neuroaxial/central blockade [10-12].

General anesthesia can be performed safely in patients with BrS, both as inhalational and as

balanced with opiates and induction agents as propofol, thiopental and etomidate [1].

Propofol is a sedative-hypnotic medication commonly used as an induction agent for preoperative

sedation, prior to endotracheal intubation and other procedures as well as for sedation in the

intensive care unit. Propofol infusion syndrome (PRIS), characterized by development of metabolic

acidosis and cardiac dysfunction along with at least one of: rhabdomyolysis, hypertriglyceridemia

or renal failure is a rare complication which affects patients undergoing long-term treatment with

high doses of intravenous propofol. Cardiovascular manifestations of PRIS include widening of

QRS complex, Brugada type 1 ECG pattern, ventricular tachyarrhythmias, cardiogenic shock, and
5
Page 5 of 17
asystole. In several cases propofol bolus or infusion was noted to have significant ST segment

elevations in Brugada patients (figure 3) [1,11,13].

Propofol exerts a dose-dependent blockade of whole cell sodium current and induces a

hyperpolarizing shift in the voltage-dependence of the inactivation of sodium currents and has also

been found to inhibit cardiac L-type calcium channels, attenuate beta-adrenergic signal transduction

and augment acetylcholine receptor activity [14-17].

The development of coved ST elevation in the right precordial leads, similar to that seen in BrS,

may be the first sign of cardiac instability that is commonly associated with PRIS; but also the

metabolic acidosis which follows PRIS by itself, may unmask an arrhythmogenic environment such

as that the one present in BrS patients [18,19].

To date, clinical experience does not support the recommendation of avoiding bolus dosing for

induction in BrS patients and propofol infusion for maintenance of general anesthesia is probably

safe if duration and dose are limited. However extreme caution is recommended when BrS patients

are sedated with propofol for longer periods, especially when given as a continuous infusion. The

electrocardiographic changes in a patient receiving propofol infusion may warn the clinician. It is

recommended that for long-term sedation, propofol dose should not exceed 4 mg/kg/hour and

arterial blood gases, serum lactate, and creatine kinase should be monitored frequently, especially if

propofol sedation is required for more than 48 h [15,20].

Regarding other induction agents, thiopental use has been described in multiple case reports

without problems, whereas no studies reported the use of etomidate [21].

Regarding halogenated anesthetics, we know as they may interfere with or alter the QT interval but

in BrS patients general anesthesia has been successfully maintained with nitrous oxide, desflurane,

sevoflurane and isoflurane. It has been suggested that sevoflurane might be best since it has no

effect on QT length [1,22]. Niyazi et al. found an increase in QTc interval during induction with

isoflurane and no changes were found with sevoflurane but a modest reduction using halothane was

observed. High dose ketamine instead should be used with caution [1,23].
6
Page 6 of 17
 Benzodiazepines, narcotics, opioids and ketorolac have not been associated with any adverse

events but is recommended to avoid phenothiazine antipsychotics (trifluoperazine, thioridazine,

perphenazine) because overdoses have resulted in Brugada ECG patterns with a mechanism related

to a reversible blockade of the Nav1.5 sodium current and the Kv4.3 transient outward potassium

current (Ito) in rat RVOT cardiomyocytes; moreover also lithium and many antiepileptic drugs act

through ion channel blockade resulting in cardiac ion channel blockade with BrS manifestation

[1,11, 24-28].

Vasoactive agents as α-receptor agonists (norepinephrine, methoxamine, phenylephrine) and β-

receptor antagonists can worsen ECG patterns by increasing the ST segment elevation or

unmasking a Brugada ECG pattern; whereas α-receptor antagonists and β-receptor agonists improve

ECG patterns or decreasing the ST segment elevations. Vasopressors with dual alpha and beta

agonist action as dopamine have unpredictable effects [7].

β1 and β2 receptor agonistic activity of isoproterenol and dobutamine increases calcium current and

has been used to reduce ST segment elevation and suppress arrhythmic events in patients with BrS

to treat electrical storm; ephedrine was used also without complication to treat intraoperative

hypotension [29-30].

Given that increased vagal tone may increase arrhythmia susceptibility, the anticholinergic

action of atropine, glycopyrrolate and scopolamine drugs could exert a beneficial effect on typical

ST segment changes in BrS patients [7].

Regarding neuromuscular blockade antagonisation, avoid cholinergic agents seems to be prudent,

even though likelihood of complications may be reduced by simultaneous administration of atropine

or glycopirrolate. Neuromuscular blockade antagonisation with neostigmine and pyridostigmine

may increase parasympathetic drive inducing bradycardia, even if some authors have used

neostigmine without complications, but in some others cases report accidents at awakening and

recommend a spontaneous restoring from the neuromuscular blockade antagonisation. For these

7
Page 7 of 17
reasons, to date, when using steroidal nondepolarizing agents to achieve neuromuscular blockade,

antagonisation, sugammadex would be the reversal agent of choice.

Antiemetics as ondansetron, granisetron, and dexamethasone, have not been associated with any

reported adverse effects in BrS patients [1].

Regarding general rules about management during surgery of patients with BrS we can affirm

that general and regional anesthesia in these patients requires special vigilance and external

defibrillation pads have to be applied before starting anesthesia (table 3).

A continuous ECG recording and monitoring of some parameters such as the bispectral index (BIS),

temperature, the degree of neuromuscular block and arterial blood pressure are very important;

particularly BIS monitoring of anesthetic depth is useful in preventing very deep anesthesia which

increase vagal tone by suppression of sympathetic system.

In general, anesthetists should be careful during intraoperative position changes to avoid

unintentional parasympathetic stimulation and reflexes because ventricular arrhythmias in these

patients usually occur during periods of bradycardia and increased vagal tone. So it is very

important to provide adequate analgesia in order to prevent potential arrhythmias that may be

triggered by changes of the autonomic tone. Thermal variations can also induce tachyarrhythmias,

so the core temperature should be monitored with attention, especially in surgery of long duration.

If asymptomatic and clinically stable patient must undergo for elective surgery, any further

particular cardiological/arrhytmologic assessment in not necessary and the patient can be subjected

to the intervention only with proper precautions; furthermore if patient needs an urgency/emergency

surgery, if there are no additional reasons, surgery should not be delayed for the only reason that

patient is affected from BrS. In any case we should not forget that the safest place for these patients

is the operating room, just because the patient is under close clinical and instrumental monitoring.

If patient already has an ICD, the pre/intraoperative management of the device should be performed

under the supervision of a cardiologist/electrophysiologist and the ICD should be turned off before

surgery to prevent inappropriate shocks due to monopolar surgical diathermy. Furthermore, if

8
Page 8 of 17
patients are pacemaker dependent, the pacemaker/ICD should be switched to a non-sensing mode

(VOO or DOO) so that does not occur noise and oversensing on catheters with a subsequent

inhibition of the stimulation. Also of particular importance is the time spent in non-sensing mode

that should be limited the more possible to prevent a potential R on T phenomenon. Anyway, in

case of arrhythmic storm, isoproterenol as first choice and quinidine may be used in patients with

ICD and multiple shocks [1].

After the end of the surgical procedure, the pacemaker/ICD should be reprogrammed and the

antitachycardia therapies should soon be turned on. If no programmer is available, another easy way

to deactivate therapies in an ICD is to place a magnet on top of the ICD pocket. This will inactivate

the ICD therapies without affecting its pacing capabilities. Parameters return to previously

programmed ones upon removing the magnet.

As for any other procedure, the degree of postoperative assistance and monitoring depends on the

specific surgical procedure, intraoperative complications and preoperative conditions of the patient

but certainly the follow-up of these patients should continue in the immediate postoperative period

with continuous ECG monitoring during the first 24 hours after surgery [1,9,30].

In conclusion to date, due to the absence of large studies, for patients with BrS there are not

definite recommendations neither for general anesthesia nor for regional anesthesia. The anesthetic

management during surgery of these patients requires special vigilance, avoiding factors and

situations that are known to have the potential to induce arrhythmias and nowadays the suggestions

to be implemented are only derived from daily clinical practice and are summarized in this paper.

We acknowledge that we need further investigations and strong evidences about this topic but to

date we hope to have provided an adequate starting framework with useful suggestions for daily

clinical practice.

9
Page 9 of 17
References:

1. Dendramis G, Antzelevitch C, Brugada P, Paleologo C, Baccillieri MS, De Asmundis C.

Brugada Syndrome: Diagnosis, Clinical Manifestations, Risk Stratification and Treatment,

first ed., Nova Science Publishers, New York 2015:1-90.

2. Antzelevitch C, Brugada P, Borggrefe M, Brugada J, Brugada R, Corrado D, Gussak I,

LeMarec H, Nademanee K, Perez Riera AR, Shimizu W, Schulze-Bahr E, Tan H, Wilde A.

Brugada syndrome: report of the second consensus conference: Endorsed by the Heart

Rhythm Society and the European Heart Rhythm Association. Circulation

2005;111(5):659-670.

3. Mizumaki K, Fujiki A, Tsuneda T, Sakabe M, Nishida K, Sugao M, Inoue H. Vagal activity

modulates spontaneous augmentation of ST elevation in the daily life of patients with

Brugada syndrome. J Cardiovasc Electrophysiol 2004;15:667-673.

4. Kasanuki H, Ohnishi S, Ohtuka M, Matsuda N, Nirei T, Isogai R, Shoda M, Toyoshima Y,

Hosoda S. Idiopathic ventricular fibrillation induced with vagal activity in patients without

obvious heart disease. Circulation 1997;95:2277-2285.

5. Noda T, Shimizu W, Taguchi A, Satomi K, Suyama K, Kurita T, Aihara N, Kamakura S.

ST-segment elevation and ventricular fibrillation without coronary spasm by intracoronary

injection of acetylcholine and/or ergonovine maleate in patients with Brugada syndrome. J

Am Coll Cardiol 2002;40:1841-1847.

6. Matsuo K, Shimizu W, Kurita T, Inagaki M, Aihara N, Kamakura S. Dynamic changes of

12-lead electrocardiograms in a patient with Brugada syndrome. J Cardiovasc

Electrophysiol 1998;9:508-512.

7. Miyazaki T, Mitamura H, Miyoshi S, Soejima K, Aizawa Y, Ogawa S. Autonomic and

antiarrhythmic drug modulation of ST segment elevation in patients with Brugada

syndrome. J Am Coll Cardiol 1996;27:1061-1070.

10
Page 10 of 17
8. Postema PG, Wolpert C, Amin AS, Probst V, Borggrefe M, Roden DM, Priori SG, Tan HL,

Hiraoka M, Brugada J, Wilde AA. Drugs and Brugada syndrome patients: review of the

literature, recommendations, and an up-to-date website (www.brugadadrugs.org). Heart

Rhythm 2009;6:1335-1341.

9. 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;58(9):824-836.

10. Fujiwara Y, Shibata Y, Kurokawa S, Satou Y, Komatsu T. Ventricular tachycardia in a

patient with Brugada syndrome during general anesthesia combined with thoracic

paravertebral block. Anesth Analg 2006;102:1590-1591.

11. Inamura M, Okamoto H, Kuroiwa M, Hoka S. General anestesia for patients with Brugada

syndrome. A report of six cases. Can J Anesth 2005;52:409-412.

12. Theodotou N, Cillo JE Jr. Brugada syndrome (sudden unexpected death syndrome):

perioperative and anesthetic management in oral and maxillofacial surgery. J Oral

Maxillofac Surg 2009;67:2021-2025.

13. Santambrogio LG, Mencherini S, Fuardo M, Caramella F, Braschi A. The surgical patient

with Brugada syndrome: a four-case clinical experience. Anesth Analg 2005;100:1263-6.

14. Saint DA. The effects of propofol on macroscopic and single channel sodium currents in rat

ventricular myocytes. Br J Pharmacol 1998;124:655-662.

15. Zhou W, Fontenot HJ, Liu S, Kennedy RH. Modulation of cardiac calcium channels by

propofol. Anesthesiology 1997;86:670-675.

16. Kurokawa H, Murray PA, Damron DS. Propofol attenuates betaadrenoreceptor-mediated

signal transduction via a protein kinase C-dependent pathway in cardiomyocytes.

Anesthesiology 2002;96:688-698.

11
Page 11 of 17
17. Yamamoto S, Kawana S, Miyamoto A, Ohshika H, Namiki A. Propofol-induced depression

of cultured rat ventricular myocytes is related to the M2-acetylcholine receptor-NO-cGMP

signaling pathway. Anesthesiology 1999;91:1712-1719.

18. Vernooy K, Delhaas T, Cremer OL, Di Diego JM, Oliva A, Timmermans C, Volders PG,

Prinzen FW, Crijns HJ, Antzelevitch C, Kalkman CJ, Rodriguez LM, Brugada R.

Electrocardiographic changes predicting sudden death in propofol-related infusion

syndrome. Heart Rhythm 2006;3:131-137.

19. Roberts RJ, Barletta JF, Fong JJ, Schumaker G, Kuper PJ, Papadopoulos S, Yogaratnam D,

Kendall E, Xamplas R, Gerlach AT, Szumita PM, Anger KE, Arpino PA, Voils SA,

Grgurich P, Ruthazer R, Devlin JW. Incidence of propofol related infusion syndrome in

critically ill adults: a prospective, multicenter study. Crit Care 2009;13:R169.

20. Flamée P, De Asmundis C, Bhutia JT, Conte G, Beckers S, Umbrain V, Verborgh C,

Chierchia GB, Van Malderen S, Casado-Arroyo R, Sarkozy A, Brugada P, Poelaert J. Safe

single-dose administration of propofol in patients with established Brugada syndrome: a

retrospective database analysis. Pacing Clin Electrophysiol 2013;36(12):1516-1521.

21. Jindai R, Tanaki N, Ohmura S, Yamamoto K, Kobayashi T. Anesthetic management of a

patient with Brugada syndrome for implantable cardioverter defibrillator implantation.

(Japanese). Hokuriku J Anesthesiol 2000;34:21-24.

22. Carey SM, Hocking G. Brugada syndrome--a review of the implications for the anaesthetist.

Anaesth Intensive Care 2011;39:571-577.

23. Niyazi G, Ismail K, Cengiz BD, Mehmet B, Beyhan E, Cevat T. The effects of volatile

anesthetics on The Q-Tc interval. J Cardio Vasc Anesth 2001;15:188-191.

24. Edge CJ, Blackman DJ, Gupta K, Sainsbury M. General anaesthesia in a patient with

Brugada syndrome. Br J Anaesth 2002;89:788-791.

12
Page 12 of 17
25. Ohmori A, Sugimoto K, Fujii K. General anesthesia by use of tramadol in a Brugada

syndrome patient with an implantable cardioverter defibrillator (Japanese). Anesthesia

Resusc 2006;42:7-9.

26. Copetti R, Proclemer A, Pillinini PP. Brugada-like ECG abnormalities during thioridazine

overdose. Br J Clin Pharmacol 2005;59:608.

27. Rouleau F, Asfar P, Boulet S, Dube L, Dupuis JM, Alquier P, Victor J. Transient ST

segment elevation in right precordial leads induced by psychotropic drugs: relationship to

the Brugada syndrome. J Cardiovasc Electrophysiol 2001;12:61-65.

28. Bébarová M, Matejovic P, Pásek M, Jansová D, Simurdová M, Nováková M, Simurda J.

Effect of antipsychotic drug perphenazine on fast sodium current and transient outward

potassium current in rat ventricular myocytes. Naunyn Schmiedebergs Arch Pharmacol

2009;380:125-133.

29. Watanabe A, Fukushima Kusano K, Morita H, et al. Low-dose isoproterenol for repetitive

ventricular arrhythmia in patients with Brugada syndrome. Eur Heart J 2006;27:1579-1583.

30. Ohgo T, Okamura H, Noda T, Satomi K, Suyama K, Kurita T, Aihara N, Kamakura S, Ohe

T, Shimizu W. Acute and chronic management in patients with Brugada syndrome

associated with electrical storm of ventricular fibrillation. Heart Rhythm 2007;4:695-700.

13
Page 13 of 17
Figure 1: The two ECG patterns of BrS proposed in the Consensus Report of 2012. Only two ECG

patterns have to be considered, the new type 2 pattern combines patterns 2 and 3 of previous

consensus. From A. Bayés de Luna et al. J Electrocardiol. 2012;45(5):433-442.

Figure 2: Definitions of BrS proposed in the Second Consensus Conference Report. BrS is

diagnosed if a Type 1 ECG pattern is associated with at last one of the other criteria.

Figure 3: Twelve-lead ECG tracings of an asymptomatic man with BrS. Panel A: baseline ECG;

Panel B: ECG after long-term administration of high doses of intravenous propofol. Courtesy of Dr.

G. Dendramis.

14
Page 14 of 17
 Table 1: Diagnostic Criteria for the ECG patterns of Brugada Syndrome in V1-V2 (from
the Consensus Report of 2012)
The typical type 1 coved pattern present in
V1-V2 the following:
a. At the end of QRS, an ascending and quick slope
with a high take-off ≥2mm followed by concave or
rectilinear downsloping ST. There are few cases of coved
pattern with a high take-off between 1 and 2 mm.
b. There is no clear r' wave.
c. The high take-off often does not correspond with the
J point.
d. At 40 ms of high take-off, the decrease in amplitude
of ST is ≤ 4mm. In RBBB and athletes, it is much higher.
e. ST at high take-off > ST at 40 ms > ST at 80 ms.
f. ST is followed by negative and symmetric T wave.
g. The duration of QRS is longer than in RBBB, and
there is a mismatch between V1 and V6.
The typical type 2 saddle-back pattern present in
V1-V2 the following:
a. High take-off of r' (that often does not coincide with
J point) ≥2 mm.
b. Descending arm of r' coincides with beginning of
ST (often is not well seen).
c. Minimum ST ascent ≥0.5 mm.
d. ST is followed by positive T wave in V2 (T peak >
ST minimum >0) and of variable morphology in V1.
e. The characteristics of triangle formed by r' allow to
define different criteria useful for diagnosis.
• β angle (the angles between both arms of r´are
wider).
• Duration of the base of the triangle of r' at 5 mm from
the high take-off greater than 3.5mm.
f. The duration of QRS is longer in type 2 than in other
cases with r' in V1, and there is a mismatch between V1
and V6.
15
Page 15 of 17
Table 2: Drugs in regional and general anesthesia for patients with Brugada Syndrome

SHOULD BE AVOIDED MAY BE USED WITH CAUTION

Lidocaine and others local anesthetics

Bupivacaine , Levobupivacaine, Ropivacaine
(doses should be minimized)
α-receptor agonists
Propofol
(Norepinephrine, Methoxamine,
(not exceed 4 mg/kg/hour)
Phenylephrine

β-receptor antagonists Thiopental, Etomidate, Ketamine

Vasopressors with dual α and β agonist action Nitrous oxide, Desflurane, Sevoflurane,
as Dopamine have unpredictable effects Isoflurane

Cholinergic agents Benzodiazepines, Narcotics, Opioids,

(Neostigmine, Pyridostigmine, Acetylcholine) Ketorolac
Class I C antiarrhytmics
(Ajmaline, Flecainide, Pilsicainide, α-receptor antagonists
Procainamide, Propafenone, Ethacizin)
Phenothiazine antipsychotics β-receptor agonists
(Trifluoperazine, Thioridazine, Perphenazine) (Isoproterenol , Dobutamine)

Anticholinergics
Lithium
(Atropine, Glycopyrrolate, Scopolamine)

Antiepileptic drugs Sugammadex

Tricyclic antidepressants Antiemetics

(Amitriptyline, Nortriptyline, Clomipramine, (Ondansetron, Granisetron,
Desipramine) Dexamethasone)

16
Page 16 of 17
Table 3: Precautions and general rules during surgery of patients with Brugada syndrome

a. External defibrillation pads have to be applied before starting anesthesia;

b. Continuous ECG recording during surgery, until anesthetics have been eliminated and during
the first 24 hours after surgery;
c. Continuous monitoring of temperature, arterial blood pressure, bispectral index, degree of
neuromuscular block;
d. Avoid unintentional parasympathetic stimulation, thermal variations and periods of
bradycardia;
e. Provide adequate analgesia in order to prevent potential arrhythmias that may be triggered
by changes of the autonomic tone;
f. Pre/intraoperative management of pacemakers and ICD should be performed under the
supervision of a cardiologist/electrophysiologist;

g. Isoproterenol and quinidine ready for use in case of arrhythmic storm.

17
Page 17 of 17