Postgrad Med J: first published as 10.1136/pgmj.56.654.229 on 1 April 1980. Downloaded from Postgradiuate Medical Journal (April 1980) 56, 229-233 Some cardiovascular problems with disopyramide S. J. WARRINGTON JOHN HAMER M.A., M.R.C.P. M.D., Ph.D., F.R.C.P. Department of Clinical Pharmnacology, St Bartholomew's Hospital, London, E.C.I Summary review assessed the mortality of simple quinidine Five patients with apparent adverse cardiovascular conversion of atrial fibrillation as 3% (Thomson, effects of disopyramide are reviewed. Attention is 1956). drawn to the following problems. Four aspects of the cardiac effects of diso- (1) A vagolytic effect may produce a sinus tachy- pyramide noted by the authors recently seem worthy cardia with wide QRS complexes due to aberrant ofcomment: (1) adversecardiovasculareffects related conduction or intraventricular block superficially to the additional vagolytic effect of disopyramide, resembling a ventricular tachycardia, or may allow similar to those seen with quinidine; (2) adverse increased transmission of an atrial tachycardia or effects in sinus node disease; (3) a capacity to provoke atrial flutter to the ventricles by improving atrio- dangerous ventriculararrhythmias as is also seen with ventricular conduction. quinidine (Krikler and Curry, 1976); in addition, (2) Although the vagolytic effect is helpful in (4) the authors wish to stress the need for caution increasing sinus rate in patients with sinus node with intravenous injection to avoid side effects which disease, disopyramide may lead to bradycardia and may be related to immediate transient high plasma copyright. asystolic cardiac arrest, and should not be used concentrations before distribution of the drug can without a demand pacemaker. occur. (3) Dangerous ventricular arrhythmias may be provoked in susceptible subjects, as with quinidine. Vagolytic effects (4) Rapid intravenous injection may produce Case I transient toxic effects before the drug is distributed. Sinus tachycardia with bundle branch block in a The rate of injection as a loading dose for prophylaxis female patient with hypertension, maturity-onset should be slower (2 mg/kg in 15 min) than for the diabetes mellitus, and a recent anterior myocardial http://pmj.bmj.com/ urgent conversion of a resistant tachycardia (2 mg/kg infarction. in 5 min). This 72-year-old housewife, with acute anterior Although disopyramide seems less toxic than quini- myocardial infarction, had a history of inferior dine, caution is advised, as over-enthusiastic applica- infarction 5 years previously, and there was long- tion of disopyramide, particularly with rapid intra- standing hypertension and maturity-onset diabetes venous injection, might tend to bring a useful new mellitus. Her initial progress was stormy, with agent into disrepute. bradycardia requiring atropine therapy, and ventri- cular extrasystoles and ventricular tachycardia on September 26, 2021 by guest. Protected Introduction which were treated with lignocaine. On the day after Although disopyramide has been used in France admission, lignocaine no longer controlled the for many years (Desruelles et al., 1967; Granier, ventricular dysrhythmias, although doses sufficient 1968), the recent more widespread use of the drug to cause mild confusion were used. Disopyramide has brought to prominence some apparent unwanted 2-5 mg/kg (= 180mg) was therefore given by effects, and since it has been suggested that diso- intravenous injection over 5 min. As the injection pyramide is safe enough for use as a routine pro- was nearing completion, the sinus rate increased phylactic in cardiac infarction (Kidner, 1977; from 80 to 120/min, with remarkable widening of Zainal et al., 1977) it seems appropriate to assess the QRS complex. Maximum QRS duration was the significance of some apparent adverse reactions. 0.16 sec. The combination of increased heart rate It is important that a promising new drug should and QRS widening simulated a ventricular tachy- not fall into the same position as quinidine where the cardia, but a long ECG recording confirmed the use of cumulative dose schedules (Sokolow and gradual development of the bizarre appearance. The Edgar, 1970) led to widespread disenchantment with ECG returned to normal within 30 min of the end the drug because of severe toxic effects. A sober of the injection. 0032-5473/80/0400-0229 $02.00 © 1980 The Fellowship of Postgraduate Medicine Postgrad Med J: first published as 10.1136/pgmj.56.654.229 on 1 April 1980. Downloaded from 230 S. J. Warrington and John Hamer The patient noticed no ill effects from the diso- progressed to asystole requiring resuscitation. pyramide injection, and she later tolerated oral Temporary cardiac pacing was eventually needed; disopyramide. the patient later died from left ventricular failure and pulmonary embolism. Case 2 Restoration of 1 :1 conduction of atrial tachy- Ventricular arrhythmia cardia in acute inferior myocardial infarction. Case 4 This 56-year-old man with an acute inferior Ventricular fibrillation in a patient with cardio- myocardial infarction had ventricular fibrillation myopathy. This 39-year-old woman commenced and was resuscitated in the Accident and Emergency disopyramide 100 mg thrice daily because of mul- Department. On arrival in the Coronary Care Unit, tiple, multifocal ventricular extrasystoles which he had atrial tachycardia at a rate of 150/min and a were thought to be due to a cardiomyopathy of the ventricular rate of 75/min due to 2 : 1 atrio-ventri- congestive type. She was also receiving treatment cular block. Repeated episodes of ventricular tachy- with frusemide 80 mg daily and potassium supple- cardia interrupted the atrial tachycardia and did not ments. Five months later she was admitted for respond to 100 mg i.v. of either lignocaine or investigation. Cardiac catheterization confirmed phenytoin. Disopyramide 100 mg was given by i.v. the diagnosis of congestive cardiomyopathy; 24-hr injection over 5 min, and immediately after this the ECG tape monitoring still showed multiple ventri- ventricular rate increased to 150/min owing to cular extrasystoles and the dose of disopyramide was restoration of 1 :1 conduction of the atrial tachy- increased to 200 mg thrice daily. This produced no cardia. Sinus rhythm was ultimately achieved after obvious benefit, but after 3 days the patient sustained intravenous propranolol. cardiac arrest due to ventricular fibrillation. During the subsequent 12 hr, at least 30 electroversions (DC Sinus node disease shocks) were performed to correct ventricular tachy- Case 3 cardia or fibrillation. Drug therapy with intravenous arrest in a Asystolic cardiac patient with sick disopyramide, propranolol and lignocaine wascopyright. sinus syndrome and hypertension complicated by ineffective. Phenytoin 700 mg suppressed the dys- acute renal failure. rhythmia, but a slow ventricular rhythm took its This 60-year-old man, a known hypertensive with place and temporary cardiac pacing was required. a history of recurrent supraventricular tachycardia, All anti-dysrhythmic drugs except propranolol was admitted to hospital with persistent atrial tachy- were stopped, and the patient made a steady recovery. cardia which did not respond to intravenous Ultimately propranolol was also discontinued be- propranolol 8 mg and disopyramide 100 mg. A cause it was not preventing extrasystoles. At out- single DC shock of 30 J restored sinus rhythm. The patient follow-up 6 weeks later the patient felt well http://pmj.bmj.com/ next day he became anuric, with consequent but the extrasystoles persisted. hyperkalaemia, hyponatraemia and hypocalcaemia; this was probably due to prolonged hypotension in Rapid intravenous injection the presence of renovascular disease. Twenty-four Case 5 hour ECG tape monitoring showed periods of Transient right bundle branch block after i.v. sinus arrest and bradycardia consistent with 'sick disopyramide for atrial ectopic beats and atrial sinus syndrome'. fibrillation in a man aged 55 years with transient Although the renal failure improved, atrial impairment of renal function after coronary arterial on September 26, 2021 by guest. Protected tachycardia recurred 3 days after admission, and vein grafting. responded to i.v. disopyramide 100 mg. Diso- This patient had a triple coronary artery vein pyramide 100 mg 6 hourly orally was prescribed, graft. His chest was reopened for control of a bleed- but the tachycardia recurred in spite of this treat- ing aortic puncture wound; recovery was very ment and, during the subsequent 3 days, i.v. diso- stormy, and a total of 70 units of blood was trans- pyramide 100 mg was given on at least 3 occasions; fused. On the 4th day after operation the chest was propranolol 40 mg thrice daily orally was also opened again to remove packing material, and atrial given. fibrillation developed. This was treated successfully Eight days after admission, sinus bradycardia with electroversion but recurred on the 5th day after 48/min and ventricular ectopics required treatment operation. Disopyramide 100 mg 8 hourly i.v. was with i.v. atropine. Tachycardia recurred several prescribed. This treatment prevented the atrial hours later, and did not respond to 50mg i.v. fibrillation, but atrial ectopic beats persisted. During disopyramide. Eight hr after this dose, a further 100 this stage of recovery the patient was jaundiced mg dose of disopyramide was given. Thirty min after owing to multiple transfusions, and had some the injection, sinus bradycardia developed and impairment