A 19 Year old Woman Admitted to Hospital Confused and Agitated with Intermittent Twitching of her Upper and Lower Limbs

Transcription

1 Investigation vignette A 19 Year old Woman Admitted to Hospital Confused and Agitated with Intermittent Twitching of her Upper and Lower Limbs CASE REPORT A 19 year old woman was admitted to the accident and emergency department (A & E) confused and agitated with intermittent twitching of her upper and lower limbs. She had a past history of depression and pseudoseizures and had been managed by her local medical practitioner for the previous 4 years with numerous antidepressant agents. The morning of her admission she had a violent argument with her partner and locked herself in the bathroom. Her partner called the police who forcibly opened the bathroom door and found the woman curled up in one corner of the room drowsy, confused and agitated, with an empty amitriptyline packet by her side. She was taken by ambulance to hospital for further assessment. In the A & E department her vital signs revealed a pulse rate of 60 beats per minute, blood pressure 95/45 mmhg and temperature of 36.1 C. She was obtunded but occasionally responded non-purposefully to pain. She was intubated using 150 mg thiopentone and 75 mg suxamethonium intravenously and mechanically ventilated. The plasma biochemistry on admission revealed a sodium of 142 mmol/l, potassium 4.4 mmol/l, chloride of 106 mmol/l and bicarbonate 28 mmol/l. The haemoglobin was 115 g/l and the white cell count was 6.3 x 10 9 /L. A blood gas taken just prior to intubation revealed a PO 2 of 75 mmhg, PCO 2 54 mmhg and ph 7.29 and a plasma lactate 3.1 mmol/l A cerebral computed tomography (CT) was performed which revealed no abnormality. An ECG performed on admission is shown in figure 1. Figure 1. A 12 lead ECG taken on admission to the accident and emergency department 147

2 K. DESHPANDE Critical Care and Resuscitation 2003; 5: Diagnosis: Amitriptyline poisoning with a Brugada syndrome electrocardiographic pattern The Brugada syndrome describes a group of patients with the ECG findings of an apparent RBBB pattern with ST segment elevation in the right precordial leads ( Brugada sign ) who have no definable structural heart disease and who are at risk for the recurrence of sudden death due to ventricular fibrillation. 1,2,3 The ECG findings may normalise transiently in up to 40% of cases or be concealed in up to 50% of cases, with the latter being provoked by flecainide, 4 procainamide, 4 α-adrenergic agonists, 4 β- adrenergic blockers, 4 fever 5,6 or insulin and glucose. 7,8 The ECG changes may also be found with tricyclic, 9,10,11 phenothiazine 12 and antihistamine overdosage, acute myocardial ischaemia or infarction (particularly right ventricular infarction or ischaemia), acute pulmonary embolism, 13 right ventricular dysplasia, pericarditis, 24 hours following cardioversion or defibrillation, dissecting aortic aneurysm, central nervous system abnormalities (e.g. acute subdural haemorrhage), electrolyte abnormalities (e.g. hypercalcaemia, hyperkalaemia), cocaine intoxication, thiamine deficiency, Duchenne muscular dystrophy, Friedreich s ataxia, and acute myocarditis or other infiltrative cardiomyopathies. 2,3,14 These conditions should be excluded before the diagnosis can be made. The disorder is inherited as an autosomal dominant with incomplete penetrance 2 and arises from genetic defects of the α subunit of the cardiac sodium channel causing a reduction in the sodium current (INa). 4 Approximately 20% of Brugada patients have documented SCN5A gene mutations (the gene encoding for the α subunit of the cardiac sodium channel). 15,16 Inactivation of the INa current (Phase 0 of the myocardial action potential) can leave I to (Phase 1 of the myocardial action potential) unopposed, an effect that is observed largely in the right ventricle which has a denser I to current than the left ventricular myocardium thereby causing ST segment elevation in the right precordial leads. Agents that block both INa and I to (e.g. quinidine, disopyramide) restore the electrical homogeneity and suppress antiarrhythmic activity, 17 whereas agents that block INa but not I to (e.g. flecainide, procainamide) exacerbate or unmask the Brugada syndrome. 7 Agents that increase the calcium current including isoproterenol (a β 2 - adrenergic agonist) and cilostazol (a phosphordiesterase III inhibitor) also normalise the ST segment. 2 The prognosis is poor in symptomatic patients with the Brugada syndrome who have spontaneous ECG abnormalities, and who do not receive an implantable cardioverter-defibrillator, 18,19 whereas the risk of ventricular tachyarrhythmias is low in asymptomatic patients who have drug induced ECG changes only. 20 Figure 2. A 12 lead ECG taken on discharge from the intensive care unit 148

3 Critical Care and Resuscitation 2003; 5: Tricyclic antidepressants are a group of compounds that may cause adverse cardiovascular effects particularly when taken as an overdose. They have a mixture of anticholinergic, antiadrenergic and quinidine-like effects; thus their resultant effect on the heart is complex. The ECG effects include widened QRS, prolonged QT c and RAD, and the arrhythmias associated with tricyclic poisoning include ventricular tachycardia, torsade de pointes and ventricular fibrillation. 21 An ECG pattern similar to that observed with the Brugada syndrome has been reported with tricyclic overdosage, 9,10,11 with one report finding an incidence of 15.3% in 98 cases. In this report, one patient with the Brugada ECG pattern and one patient without it died from refractory ventricular fibrillation with the mortality rate being 6.7% among patients with the Brugada ECG pattern and 2.4% among patients without it (p = 0.39). 9 In the case I report, the patient was hyperventilated and treated with intravenous sodium bicarbonate (100 ml 8% in 24 hr). She was extubated within 18 hours slightly drowsy but otherwise oriented in time and place. The patient was discharged from the intensive care unit 24 hours later without developing any ventricular arrhythmias during her admission and with the ECG returning to within normal limits (Figure 2). K. DESHPANDE Department of Critical Care Medicine, Flinders Medical Centre, Bedford Park, SOUTH AUSTRALIA REFERENCES 1. Brugada P, Brugada J. Right bundle branch block, persistent ST segment elevation and sudden cardiac death: a distinct clinical and electrocardiographic syndrome. A multicenter report. J Am Coll Cardiol 1992;20: Antzelevitch C, Brugada P, Brugada J, et al. Brugada syndrome: a decade of progress. Circ Res 2002;91: Wilde AA, Antzelevitch C, Borggrefe M, et al. Proposed diagnostic criteria for the Brugada syndrome: consensus report. Study Group on the Molecular Basis of Arrhythmias of the European Society of Cardiology. Circulation 2002 Nov 5;106: Naccarelli GV, Antzelevitch C, Wolbrette DL, Luck JC. The Brugada syndrome. Curr Opin Cardiol 2002;17: Mok NS, Priori SG, Napolitano C, Chan NY, Chahine M, Baroudi G. A newly characterized SCN5A mutation underlying Brugada syndrome unmasked by K. DESHPANDE hyperthermia. J Cardiovasc Electrophysiol 2003;14: Saura D, Garcia-Alberola A, Carrillo P, Pascual D, Martinez-Sanchez J, Valdes M. Brugada-like electrocardiographic pattern induced by fever. Pacing Clin Electrophysiol 2002;25: Nogami A, Nakao M, Kubota S, et al. Enhancement of J-ST-segment elevation by the glucose and insulin test in Brugada syndrome. Pacing Clin Electrophysiol 2003;26: Nishizaki M, Sakurada H, Ashikaga T, et al. Effects of glucose-induced insulin secretion on ST segment elevation in the Brugada syndrome. J Cardiovasc Electrophysiol 2003;14: Goldgran-Toledano D, Sideris G, Kevorkian JP. Overdose of cyclic antidepressants and the Brugada syndrome. N Engl J Med 2002;346: Tada H, Sticherling C, Oral H, Morady F. Brugada syndrome mimicked by tricyclic antidepressant overdose. Cardiovasc Electrophysiol 2001;12: Babaliaros VC, Hurst JW. Tricyclic antidepressants and the Brugada syndrome: an example of Brugada waves appearing after the administration of desipramine. Clin Cardiol 2002;25: Rouleau F, Asfar P, Boulet S, et al. Transient ST segment elevation in right precordial leads induced by psychotropic drugs: relationship to the Brugada syndrome. J Cardiovasc Electrophysiol 2001;12: Vavricka SR, Himmelmann A, Schaffner A. Uses of error. Brugada syndrome. Lancet 2002;360: Scheinman MM. Is the Brugada syndrome a distinct clinical entity? J Cardiovasc Electrophysiol 1997;8: Wang Q, Shen J, Splawski I, et al. SCN5A mutations associated with an inherited cardiac arrhythmia, long QT syndrome. Cell 1995;80: Viswanathan PC, Benson W, Balser JR. A common SCN5A polymorphism modulates the biophysical effects of an SCN5A mutation. J Clin Invest 2003;111: Yan GX, Antzelevitch C. Cellular basis for the Brugada syndrome and other mechanisms of arrhythmogenesis associated with ST-segment elevation. Circulation 1999;100: Brugada J, Brugada R, Brugada P. Brugada syndrome. Arch Mal Coeur Vaiss 1999;92: Naccarelli GV, Antzelevitch C. The Brugada syndrome: clinical, genetic, cellular, and molecular abnormalities. Am J Med 2001;110: 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: Niemann JT, Bessen HA, Rothstein RJ, Laks MM. Electrocardiographic criteria for tricyclic antidepressant cardiotoxicity. Am J Cardiol 1986;57:

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