1 Nuffield Department of Anaesthetics and 2 Department of Cardiology, Oxford Radcliffe Hospitals Trust, Oxford, OX3 9DU, UK*Corresponding author
Accepted for publication: July 5, 2002
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Abstract |
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Br J Anaesth 2002; 89: 78891
Keywords: complications, Brugada syndrome
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Introduction |
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Case report |
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On investigation, the patient had a 12-lead ECG showing a partial right bundle branch block with a coved pattern of ST elevation in leads V1 to V3 (Fig. 1). Cardiac enzymes were not elevated. Subsequent cardiac catheterization showed normal left ventricular function and coronary arteries. The patient underwent a flecainide challenge with an i.v. bolus of 150 mg. This produced accentuation of the ST elevation, consistent with Brugada syndrome. In view of the documented VF arrest, characteristic ECG features, and the absence of underlying structural heart disease, a diagnosis of Brugada syndrome was made. A single-chamber implantable cardioverterdefibrillator (ICD) was inserted under local anaesthesia and sedation. The patient was discharged home on aspirin, ranitidine, nadolol (subsequently changed to bisoprolol) and amiloride.
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Discussion |
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Establishing the diagnosis of Brugada syndrome can be difficult. The electrocardiographic signature is concealed in up to 30% of affected individuals3 and can only be seen after administration of potent sodium channel blockers, such as flecainide, propafenone and procainamide.4 However, recent follow-up data indicate that the risk of ventricular tachyarrhythmias is low in the absence of a resting ECG abnormality.5 In patients with an abnormal resting ECG, electrophysiological study incorporating programmed electrical stimulation is recommended to further define the risk of malignant tachyarrhythmia. In the presence of inducible VT/VF, the risk of sudden death is 510% per year and ICD implantation is recommended, as it is in any Brugada patient with a history of documented VT/VF or resuscitated cardiac arrest.
The molecular basis for the ventricular arrhythmias remains uncertain. Mutations have been identified in patients with Brugada syndrome in the SCN5A gene, which codes for the tetrodotoxin-insensitive human cardiac sodium channel (hH1).6 The functional abnormalities of the expressed mutant channels are opposite to those found in sodium channel mutants associated with long-QT syndrome. In Brugada syndrome, as in some of the other idiopathic ventricular fibrillation syndromes, the sodium channels show loss-of-function features, such as enhanced inactivation.7 However, it is difficult to see how these features give rise to ventricular arrhythmias. A clue may come from the finding that calmodulin, a ubiquitous calcium-sensing protein, binds to the carboxy-terminal IQ domain of the hH1 channel in a calcium-dependent manner.8 A naturally occurring mutation (A1924T) in the IQ domain alters hH1 function in a manner characteristic of the Brugada syndrome, but at the same time inhibits slow inactivation induced by calciumcalmodulin, yielding a clinically benign (arrhythmia-free) phenotype. Further studies will be required to elucidate the precise mechanism(s) by which the other mutations in hH1 give rise to Brugada syndrome.
So far as we can ascertain, this is only the third report of a general anaesthetic having been administered to a patient with Brugada syndrome. The first case report9 describes a 47-yr-old Japanese male undergoing hemilaminectomy. Anaesthesia was induced with fentanyl 50 µg, droperidol 2.5 mg and propofol 120 mg, and the neuromuscular blocking drug used was vecuronium 8 mg. Maintenance of anaesthesia continued with the use of sevoflurane and further fentanyl 150 µg. Antagonism of the neuromuscular block was accomplished using neostigmine 2.5 mg and atropine 1.0 mg; during antagonism the authors noted an elevation of the ST segments on the ECG.
A second case report10 describes a 49-yr-old man with Brugada syndrome who had surgery for a polyp on the vocal cords. Despite episodes of vertigo and an ECG showing a right bundle branch block with elevation of the ST segments in leads V1 and V2, the cardiologist did not consider that there was an indication for an ICD. The patient was given diazepam 10 mg orally as a premedication and monitored using ECG, a non-invasive blood pressure cuff, pulse oximetry and capnography. Induction of anaesthesia was carried out using fentanyl 0.2 mg, propofol 200 mg, mivacurium 18 mg and glycopyrrolate 0.3 mg. A portable defibrillator was placed in theatre in case ventricular dysrhythmias developed. Anaesthesia was maintained using 1% isoflurane with a nitrous oxideoxygen gas mixture. After surgery, the patient was transferred to the recovery room and monitored for 2 h. No problems were reported with this anaesthetic.
Both sets of authors in these case reports note that the administration of drugs that block sodium channels, such as procainamide and flecainide, are contraindicated in patients with Brugada syndrome.
Miyazaki and colleagues11 describe four patients who underwent investigation for Brugada syndrome. They noted that selective -adrenoceptor stimulation by i.v. norepinephrine in the presence of propranolol or by i.v. methoxamine consistently augmented ST segment elevation whereas
-adrenoceptor block reduced it in three of the patients. Additionally, i.v. neostigmine and class IA antiarrhythmic drugs augmented ST elevation without inducing coronary spasm, but class IB antiarrhythmic drugs had no effect on ST elevation. However, the number of patients was very small and it is difficult to draw firm conclusions from this study, especially in the light of the heterogeneous nature of the mutations leading to Brugada syndrome.
In the case described by Lafuente Martin and colleagues10 and in our case, isoflurane was administered as an anaesthetic agent. It is perhaps surprising (and illustrates the lack of detailed understanding of the physiology and pharmacology behind Brugada syndrome) that no cardiac arrhythmias were detected during anaesthesia in these cases, in the light of recent evidence suggesting that isoflurane should be avoided in patients with prolonged QTc syndrome.12
Administration of i.v. neostigmine with glycopyrrolate in our patient did not give rise to any detectable cardiac arrhythmia. Likewise, bupivacaine given via the epidural route did not cause problems. However, in view of the fact that drugs that block the sodium channels may cause problems in patients with Brugada syndrome, it may be wise in future to avoid systemic administration of local anaesthetics by routes that cause a rapid increase in serum concentrations of local anaesthetic.
Reported experience of general anaesthesia in Brugada syndrome is limited at present. However, it is an increasingly recognized disorder, and one which many anaesthetists are likely to encounter in their clinical practice in the future. Caution should be exercised when using -agonists or neostigmine, while class I antiarrhythmic drugs must be avoided. In any patient with an ICD, the device must be disabled immediately before surgery. Close cooperation of the anaesthetist with a cardiologist is essential both before and after surgery. In patients with Brugada syndrome in whom no ICD has been fitted, recovery should take place in either a coronary care unit or a high-dependency unit. This will permit detection and treatment of cardiac arrhythmias, which are most likely to occur in the postoperative period,13 in a timely manner.
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References |
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2 Priori SG, Napolitano C, Giordano U, Collisani G, Memmi M. Brugada syndrome and sudden cardiac death in children. Lancet 2000; 355: 8089[ISI][Medline]
3 Brugada R, Brugada J, Antzelevitch C, et al. Sodium channel blockers identify risk for sudden death in patients with ST-segment elevation and right bundle branch block but structurally normal hearts. Circulation 2000; 101: 5105
4 Priori SG, Napolitano C, Gasparini M, et al. Clinical and genetic heterogeneity of right bundle branch block and ST-segment elevation syndrome: a prospective evaluation of 52 families. Circulation 2000; 102: 250915
5 Brugada J, Brugada R, Antzelevitch C, Towbin J, Nademanee K, Brugada P. Long-term follow-up of individuals with the electrocardiographic pattern of right bundle-branch block and ST-segment elevation in precordial leads V1 to V3. Circulation 2002; 105: 738
6 Rook MB, Bezzina Alshinawi C, Groenewegen WA, et al. Human SCN5A gene mutations alter cardiac sodium channel kinetics and are associated with the Brugada syndrome. Cardiovasc Res 1999; 44: 50717[ISI][Medline]
7 Balser JR. Sodium channelopathies and sudden death: must you be so sensitive? Circ Res 1999; 85: 8724
8 Tan HL, Kupershmidt S, Zhang R, et al. A calcium sensor in the sodium channel modulates cardiac excitability. Nature 2002; 415: 4427[ISI][Medline]
9 Sugi Y, Mori M, Ono M, Kurihara Y. Anesthetic management of a patient with Brugada syndrome. Masui Jpn J Anesthesiol 2000; 49: 8846
10 Lafuente Martin FJ, Pascual Bellosta A, Abengochea Beisty JM, Fraca Cardiel C, Sanchez Tirado JA, Urieta Solanas JA. Brugada syndrome and anesthesia: a case report. Rev Esp Anestesiol Reanim 1998; 45: 3012[Medline]
11 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: 106170[ISI][Medline]
12 Guler N, Kati I, Demirel CB, Bilge M, Eryonucu B, Topal C. The effects of volatile anesthetics on the QTc interval. J Cardiothorac Vasc Anesth 2001; 15: 18891[ISI][Medline]
13 OKelly B, Browner WS, Massie B, Tubau J, Ngo L, Mangano DT. Ventricular arrhythmias in patients undergoing noncardiac surgery. The Study of Perioperative Ischemia Research Group. JAMA 1992; 268: 21721[Abstract]