Direct current shockand antidysrhythmic drugs

British HeartyJournal, I9703 32, 209.

Direct current shock and antidysrhythmicdrugs

Paul Szekely, N. A. Wynne, D. T. Pearson, G. A. Batson, and D. A. SiderisFrom the Cardiovascular Department, Newcastle General Hospital and the Department ofPharma-

cology, University of Newcastle upon Tyne

A review is given of 457 episodes of atrialfibrillation that occurred in 318 patients and were treatedby DC shock. Antidysrhythmic drugs, such as quinidine, procainamide, and propranolol, givensingly or in combination, were used concomitantly in 389 instances, and DC shock alone was givenin 68 instances. The combined effects of quinidine and DC shock, and of procainamide and DCshock were studied in the experimental animal.

Combined DC shock and drug therapy gave a higher conversion rate than DC shock alone,and a statistically significant difference was found in respect of the group of patients receivingprocainamide and propranolol together (p < o-oi).

Antidysrhythmic drugs failed on the whole to reduce the incidence of DC shock-induced dys-rhythmias. However, the incidence of certain digitalis and DC shock-induced dysrhythmias wassignificantly less when propranolol and procainamide were given as pretreatment than whenprocainamide or quinidine was given alone (p < o-oI).

In animal experiments, quinidine had no protective action against digitalis and DC shock-induced ectopic tachycardias.

Clinical and experimental observations suggest that the cardiotoxicity of these drugs may beenhanced by DC shock. Immediate or delayed post-shock rhythm disorders can be drug relatedand, therefore, great caution should be exercised in the use of antidysrhythmic drugs in conjunctionwith DC shock therapy.

In a previous paper (Szekely et al., I969) wereported on the effects of the concomitantuse of digitalis and direct current (DC) shock,and presented clinical and experimentalevidence, in agreement with others (Lown,Kleiger, and Williams, I965; Kleiger andLown, I966; Oram, I967), that DC shockpotentiates the cardiotoxicity of digitalis.In the present communication, our aim is toevaluate clinical and experimental observa-tions on the concomitant use of various anti-dysrhythmic drugs and DC shock.

Method, clinical groups, andexperimental material(A) Clinical Five hundred and fifty consecu-tive episodes of ectopic tachycardia treated byDC shock have been reviewed. Of these, a totalof 457 episodes of atrial fibrillation occurring in3I8 patients form the basis of the present obser-vations. 24I patients had rheumatic heart disease,30 had coronary heart disease with or withouthypertension, 4 had congenital heart disease, ii hadthyrotoxicosis, I had chronic pulmonary heartdisease, and there were 31 patients with no firmclinical diagnosis, and a number of these wereReceived 14 July I969.

suspected to have cardiomyopathy. In 389instances digitalis, quinidine, procainamide, andpropranolol were used singly or in combinationat the time of DC shock therapy, and in theremaining 68 instances no antidysrhythmic drugswere used at all. The method of DC shock treat-ment was the same as described before (Szekely,Batson, and Stark, I966; Szekely et al., I969).

(B) Experimental A total of 30 experimentswas carried out in cats weighing between I4 and3.5 kg. The animals were anaesthetized withintraperitoneal sodium pentobarbitone, 45-50mg./kg. The trachea was cannulated, and arti-ficial ventilation was given intermittently with arespiratory pump. The arterial blood pressurewas continuously recorded by a mercury man-ometer which was attached to the carotid artery.A standard lead II or occasionally lead III elec-trocardiogram was recorded throughout theexperiment. Quinidine and procainamide weregiven by injection into the femoral vein. DCshocks were delivered at an energy level settingof 40 to 6o joules.

Clinical observationsThe 457 episodes of atrial fibrillation treatedby DC shock were divided into several

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TABLE i Direct current shock and concomitant drug therapy in atrial fibrillation: underlyingpathology and results

Underlying Concomitant drug therapypathology

Quindine Quinidine Procain- Procain- Propranolol No drug Totaland amide amide and therapy

propranolol propranolol

AF SR re- AF SR re- AF SR re- AF SR re- AF SR re- AF SR re- AF SR re-No. stored No. stored No. stored No. stored No. stored No. stored No. stored

(%) (%) (%) (%) (%) (%) (%)Rheumatic heart A 26 88 5 100 74 84 23 96 3 100 2I 85 152 87

disease B 50 go 8 ioo 76 84 48 96 4 IOO 25 85 21I 89Total 76 89 I3 IOO I50 84 7I 96 7 100 46 85 363 88

Coronary heart 0 0 0 0 I5 80 4 IOO I IOO II 73 3I 8idisease

Thyrotoxicosis 0 0 0 0 8 Ioo 3 66 I Ioo 0 0 I2 92Cor pulmonale 0 0 0 0 0 0 0 0 0 0 I 0 I 0Congenital heart 4 100 0 0 4 50 I IOO 0 0 I 100 IO 8o

diseaseLone atrial fibrillation 3 33 0 0 15 60 I2 75 I 0 9 55 40 60

Total 83 88 I3 IOO I92 82 9I 92 IO 90 68 78 457 85

A pre-surgical; B post-surgical; AF atrial fibrillation; SR sinus rhythm.

groups according to the concomitant drug time intervals after cardiac surgery (Grouptherapy. The nature of the underlying patho- B).logy in the various drug groups and the im-mediate results are shown in Table i. In the Quinidine 83 episodes of atrial fibrillationrheumatic group, I52 episodes of atrial occurring in 66 patients were studied in thisfibrillation were treated partly in patients group. On 23 occasions the patients receivedwho underwent cardiovascular surgery sub- quinidine sulphate, i g. daily, and on 6osequently and partly in patients who have occasions a long-acting quinidine preparationnot had surgical treatnent to date (Group A), (Kinidin durules) was used, 800 to I200 mg.and 2I1 episodes were treated at varying daily, 3 to 5 days before electroconversion.

TABLE 2 Direct current shock and concomitant drug therapy in atrialfibrillation: immediateresults and post-shock dysrhythmias

Nature and incidence of post-shock dysrhythmiasDrugs used No. of Sinus

episodes rhythm Atrial Atrial Nodal Ventricular Ventricular AVtreated restored extra- tachy- rhythm extra- tachy- block

systoles cardia systoles cardia

No. % No. % No. % No. % No. % No. % No. %

[With digitalis 22 20 90 3 I3.5 4 i8 5 23 9 4I 3 I3.5 0 0Quinidine. No digitalis 6i 53 87 7 11.5 2 3-5 2 3-5 9 15 2 3-5 I i-6

lTotal 83 73 88 IO 12 6 7 7 8.5 i8 22 5 6 I I'2Quinidine and propranolol, I3 13 100 2 15 0 0 I 7-5 I 7-5 0 0 0 0no digitalis

rWith digitalis II5 96 84 13 II 15 I3 IO 8-5 35 30 8 7 2 I7Procainamide No digitalis 77 6i 8o 8 IO 3 4 3 4 9 II-5 3 4 I I3

LTotal 192 I57 82 21 II i8 9.5 I3 7 44 23 II 6 3 I-5Procainamide rWith digitalis 60 57 95 6 IO 4 7 4 7 10 17 5 8.5 I i-6and . No digitalis 31 27 87 3 10 I 3 I 3 3 IO I 3 0 0propranolol LTotal 9I 84 92 9 IO 5 5.5 5 5.5 13 I4 6 6-5 I I-I

Propranolol, no digitalis IO 9 90 I 10 0 0 I IO I 10 0 0 0 0No drug therapy 68 53 78 7 IO 2 3 I I 5 3 4-5 0 0 0 0

Total 457 389 85 50 11 3I 7 28 6 801 7.5 22 5 5 I*I



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Direct current shock and antidysrhythmnic drugs 211

On 22 occasions the patients received digi-talis in full or reduced maintenance doses.On 6I occasions digitalis was discontinued3 to 5 days before DC shock treatment. Theimmediate results together with the incidenceand nature of post-shock dysrhythmias inthe two groups are shown in Table 2. Sinusrhythm was restored in go per cent and 87per cent ofthe cases, respectively. The averageserum quinidine level was 3X2 mg./l. at thetime of attempted conversion, as estimatedaccording to the method described by Brodieand Udenfriend (I943). The average energywhich achieved conversion was I40 joules.The over-all incidence of atrial extrasystoleswas I2 per cent, and of short runs of atrialtachycardia or persisting atrial tachycardia7 per cent. Nodal rhythm was observed in8-5 per cent, ventricular extrasystoles in22 per cent, and ventricular tachycardia or

aberrant conduction simulating ventriculartachycardia in 6 per cent of the cases. Therewas i episode (I12%) of partial heart blockpersisting for 2 hours. However, the inci-dence of most of these dysrhythmias was lesswhen digitalis was not used, as seen inTable 2. The serum potassium which was

determined in the great majority of thepatients, ranged from 3-6 to 4.5 mEq/l. theaverage being 4-0 mEq/l. in both digitalis andnon-digitalis groups.

The immediate post-shock dysrhythmiaswere of short duration and disappeared as a

rule spontaneously. In 2 instances of atrialtachycardia and one instance of ventriculartachycardia a further DC shock was appliedsuccessfully. In 2 instances of bradycardia,one sinus in origin and one from nodal rhythm,intravenous atropine resulted in an increasein the heart rate. These two episodes ofbradycardia were associated with significantarterial hypotension, 8o/6o and 75/50 mm. Hg,respectively.

There were 2 serious late complications:a 54-year-old woman with rheumatic heartdisease developed a fatal syncope due toventricular fibrillation 6 days after atrialdefibrillation while on quinidine sulphatei g. daily and digoxin 0-25 mg. daily. An-other patient, a 42-year-old woman withrheumatic heart disease who had a successfulmitral valvotomy 9 years earlier and de-veloped atrial fibrillation only 2 weeks before,had a syncope due to ventricular fibrillation24 hours after atrial defibrillation. At this stageshe had been on quinidine sulphate (Kinidindurules), 800 mg. daily, for 5 days. The serumquinidine level was 6-i mg./L on the daythe syncope occurred. A post-conversionelectrocardiogram taken 22 hours after atrial

defibrillation and 2 houts before the onset ofventricular fibrillation showed deeply invertedT waves and slight prolongation of the QTinterval suggesting myocardial injury andquinidine effect (Fig. i). The serum trans-aminase level was raised to 85 units/ml.Quinidine was discontinued and propranololsubstituted. The patient made a good recoveryand she is still in sinus rhythm I2 monthsafter the episode.

Quinidine and propranolol In I3 in-stances in 9 patients quinidine sulphate800 mg. daily and propranolol 30 to 6o mg.daily were used '3 to 5 days before electiveelectroconversion (Table 2). Sinus rhythmwas restored in all 13 cases. The averageserum quinidine level was 3.5 mg./I. Theaverage energy necessary for conversionwas I50 joules. Atrial extrasystoles wereobserved immediately after conversion inI5 per cent, nodal rhythm in 7.5 per cent,and ventricular extrasystoles in 7-5 per centof the cases. In this group, serum potassiumlevels ranged from 3-8 to 4-8 mEq/l., averag-ing 4-2 mEq/l.On 2 occasions, the heart rate immediately

after DC shock was unduly slow for a fewseconds, suggesting sino-atrial node depres-sion.

Procainamide Included in this group areI92 episodes of atrial fibrillation occurringin I71 patients. The patients received pro-cainamide, 3 g. daily, 3 to 5 days beforeelectroconversion. On II5 occasions thepatients continued on a maintenance dose ofdigitalis and on 77 occasions digitalis wasdiscontinued 3 to 5 days before electrocon-version, or not used at all (Table 2). Sinusrhythm was restored in the two groups in84 and 80 per cent of the cases, respectively.The average energy necessary to restoresinus rhythm was I25 joules. The over-allincidence of atrial extrasystoles was ii percent, of atrial tachycardia 9.5 per cent, ofnodal rhythm 7 per cent, of ventricular extra-systoles 23 per cent, and of ventricular tachy-cardia 6 per cent. There were 3 episodes ofpartialAV block (I *5 %), lasting a few seconds,30 minutes, and 3 hours, respectively. Hereagain, the incidence of post-shock dys-rhythmias was higher when digitalis wasgiven as well, as seen in Table 2. Serumpotassium levels ranged from 3-8 to 4.4mEq/l., averaging 3.9 mEq/l. in the digitalisgroup, and 4-0 mEq/l. in the non-digitalisgroup.



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212 Szekely, Wynne, Pearson, Batson, and Sideris

Procainamide and propranolol Therewere 77 patients who received on 9I occasions2 g. procainanide and 30 to 8o mg. propra-nolol daily for 3 to 5 days before electrocon-version. On 6o occasions the patients con-tinued with a maintenance dose of digoxin,and on 3I occasions digitalis was discontinued3 tO 5 days before electroconversion. Theresults are shown in Table 2. Sinus rhythmwas restored in 95 and 87 per cent of thecases, respectively. The average energynecessary for conversion was i i5 joules.Of the various post-shock dysrhythmias,atrial extrasystoles occurred in IO per centof the cases, atrial tachycardia in 5.5 percent, nodal rhythm in 5-5 per cent, ventri-cular extrasystoles in 14 per cent, and ven-tricular tachycardia in 6-5 per cent of the

cases. There was i transient episode ofpartial AV block, and 2 episodes which wereconsidered to represent sino-atrial block.When the patients were divided into 2 groups,namely those who had digitalis as well, andthose in whom digitalis was discontinuedor not used at all before electroconversion,the incidence of post-shock dysrhythmiaswas higher in the former group. Serumpotassium levels were between 3.5 and 4.4mEq/l., with an average of 4-0 mEq/l. in bothdigitalis and non-digitalis groups.

Propranolol Ten patients received pro-pranolol, 6o to 80 mg. daily, for 5 days beforeelectroconversion (Table 2). Sinus rhythmwas restored in go per cent of the patients.The average energy level necessary for con-

FIG. I (A) Lead II, atrial fibrillation. DC shock, 8o joules. Slow nodal rhythm immediatelyafter shock. Normal sinus rhythm 8 seconds later. (B) Leads I, II, III, Vi, V2, V4, V7. In-verted T waves and slight prolongation of QT interval 22 hours after DC shock. (C) Lead II,2 hours after (B). Transient ventricular fibrillation causing syncope followed by runs of ventri-cular ectopic beats interrupted by sinus complexes. (D) Same leads as in (B), 3 weeks later. In-version of T waves disappeared.

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Direct current shock and antidysrhythmic drugs 213

version was I90 joules. Of post-shock dys-rhythmias, atrial extrasystoles occurred inio per cent, nodal rhythm in I0 per cent,and ventricular extrasystoles in I0 per centof the patients. Serum potassium levels werebetween 3-6 and 4-2 mEq/l., with an averageof 4-0 mEq/l.

In 2 patients who received 80 mg. pro-pranolol daily, post-shock sinus bradycardiaoccurred, which was abolished by i mg.atropine in one, and in the other patient theheart rate increased spontaneously.

Direct current shock without concomi-tant drug therapy On 68 occasions in 63patients DC shock was used without con-comitant drug therapy (Table 2). Sinusrhythm was restored in 78 per cent of thecases by an average energy of 130 joules. Theincidence of post-shock atrial extrasystoles

was io per cent, of atrial tachycardia 3 percent, of nodal rhythm I5 per cent, and ofventricular extrasystoles 4-5 per cent. Serumpotassium levels ranged from 3-8 to 4-4mEq/l., with an average value of 4-I mEq/1.

Experimental observationsFirst a synchronized DC shock of 40 to 6ojoules was delivered in all 30 animals beforethe administration of drugs. The results ofthe combined use of DC shock and drugswere evaluated in all animals, includingthose in whom the initial DC shock producedelectrocardiographic changes.

Quinildine Twenty-six experiments formthe basis of these observations. After theinitial shock of between 40 to 60 joules,quinidine was injected into the femoralvein as quinidine hydrochloride in doses

FIG. 2 Cat, weight 2-4 kg. Lead II. (x) Initial tracing. (2) After 4 mg./kg. of quinidine, notewider QRS complex. (3) and (4) Continuous tracing. DC shock, 60 joules. (5) One minute later,slower heart rate, further widening of QRS complex, transient lengthening of PR interval, withoccasional AV block.

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equivalent to 2 mg./kg. of quinidine sul-phate at 5-minute intervals. When a quinidineeffect appeared in the electrocardiogram,mostly a widening of the QRS complex,further DC shocks of the same energy weredelivered, and also further injections ofquinidine were given about 5 minutes beforeeach shock.

In I4 out of 20 experiments the combineduse of quinidine and DC shock resulted inprogressive widening of the QRS complexand/or partial or complete heart block. In 6of these 14 experiments, DC shock did notincrease or alter in any way the quinidine-induced intraventricular or atrioventricularconduction disorder. In 8 experiments, how-ever, the immediate post-shock electrocardio-grams frequently showed further transient

or persisting widening of the QRS complexor increase in the AV block, as comparedwith the immediate pre-shock electrocardio-grams. Illustrative tracings are shown inFig. 2 and 3. In the other 6 experiments theadministration of quinidine and DC shockresulted in ectopic impulse production:ventricular tachycardia on 4 occasions,ventricular fibrillation on i occasion, andventricular extrasystoles on i occasion. In3 of these 6 experiments the initial DC shockbefore the first quinidine injection resultedin conspicuous ST segment depression, Twave inversion, and ST segment elevation,respectively. An illustrative tracing is shown inFig. 4. Of the 14 experiments in which thecombined use of quinidine and DC shocksresulted in signs of cardiac depression,

FIG. 3 Cat, weight I.s kg. Lead II. (i) Initial tracing. (2) and (3) DC shock, 40 joules; nochange. (4) After 4 mg./kg. of quinidine. Deep S waves and widening of the QRS complex.(5) After further 2 mg./kg. of quinidine, 2: I AV block. (6) and (7) Continuous tracing. DC shock,40 joules. Asystole followed by further increase in AV block.

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significant ST segment or T wave changesinduced by the initial DC shock were ob-served only on 2 occasions.

In 6 further experiments the administra-tion of a single dose of digoxin 0o25 mg.,either early and simultaneously with aquinidine injection or later at the stage ofquinidine-induced depression of intraven-tricular conduction, followed by a DC shock,resulted in transient or persistent ectopictachycardia on 4 occasions, ventricularfibrillation on i occasion, and no change inthe quinidine-induced electrocardiographicpattern on I occasion. In 2 of this specialgroup of 6 experiments, further DC shockswere given during the stage of ectopictachycardia, but the ectopic rhythm was notabolished (Fig. 5).

Procainamide Four experiments were car-ried out in this group. Amounts of IO tO20 mg./kg. procainamide per dose wereinjected intravenously and each injection wasfollowed by a DC shock. The procedure wasexactly the same as for quinidine. The com-bined use of procainamide and DC shockresulted in progressive intraventricular andAV conduction defect in all 4 experiments(Fig. 6). In 3 experiments, several immediatepost-shock electrocardiograms showed poten-tiation of the procainamide-induced depres-sion of atrioventricular and intraventricularconduction, and in i experiment DC shocksdid not increase the procainamide-inducedchanges.

DiscussionAntidysrhythmic drugs have been used inconjunction with DC shock in an attemptto increase the conversion rate and to pre-vent early recurrence of the ectopic rhythm.Rossi and Lown (I967) advocated the use ofquinidine before electroconversion, being ofthe opinion that patients receiving quinidinerequired fewer shocks and lower energylevels to restore sinus rhythm. They alsostated that pretreatment with quinidinereduced the incidence of post-shock dys-rhythmias and prevented prompt relapse ofatrial fibrillation. Hall and Wood (I968) alsofound that premedication with quinidinereduced the frequency of post-conversiondysrhythmias.

In our whole series of 457 episodes of atrialfibrillation, sinus rhythm was restored byDC shock in 85 per cent of the cases. Theconversion rate was 78 per cent in the groupof patients not receiving any drugs at all. Itwas higher in those receiving concomitantlyvarious antidysrhythmic drugs, with a sig-

nificant increase (92%) in the combinedprocainamide and propranolol group(p <o.oi). This latter group and the groupof patients not treated concomitantly withdrugs were comparable regarding the under-lying pathology, especially lone atrial fibrilla-tion which accounted for I3 per cent of allepisodes treated in both groups. This isrelevant, for, in agreement with the observa-tions of Oram and Davies (I964) and ofResnekov and McDonald (I968), the con-

FIG. 4 Cat, weight I.5 kg. Lead II.(I) Initial tracing. (2) DC shock, 6o jQules.Inverted T waves. (3) After a total of6 mg./kg. of quinidine. S waves with widerQRS complex. (4) and (5) Continuous tracing.DC shock, 6o joules. Further widening of theQRS complex with transition into ectopictachycardia, probably ventricular. (6) and(7) Continuous tracing. DC shock, 6o joules.No immediate change. Tachycardia stopsabout 8 seconds later. (8) I minute later,slow ventricular rate with wide QRS com-plexes. No atrial activity seen.

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version rate was in our experience signifi-cantly lower in lone atrial fibrillation thanwhen atrial fibrillation had a detectableunderlying cause, 60 per cent and 87-5 percent, respectively (p <oooi). Addition ofpropranolol to quinidine also resulted in avery much higher than average conversionrate, but the numbers in this group were toosmall to establish a statistically significantadvantage. However, this small group con-tained no patients with lone atrial fibrilla-tion, and this undoubtedly contributed tothe high success rate. When quinidine alonewas used as pretreatment, the conversionrate was higher than when procainamnidealone was given, 88 per cent and 82 per cent,respectively, but this difference is statisticallynot significant.

Antidysrhythmic drugs did not reduce theenergy requirements necessary for the restora-tion of sinus rhythm.

In the rheumatic group, which is far thelargest, representing 75 per cent of allpatients and 78 per cent of all episodes in-cluded, the conversion rate was 87 per centin the combined pre-surgical and non-surgical group, and 89 per cent in the post-surgical group, a difference that is statis-tically not significant.We reported previously that the duration

of atrial fibrillation was an important factorin influencing the conversion rate, being98 per cent in those with less than i yearduration and 82 per cent in those with morethan i year duration (Szekely et al., I966).This trend has remained unchanged. In thepresent series, the patients in the variousgroups were comparable with regard to theduration of atrial fibrillation.

In our experience, the concomitant use ofantidysrhythmic drugs did not result on thewhole in a reduction of post-shock dysrhyth-mias. Having regard to the importance ofdigitalis in causing post-shock dysrhythmias(Szekely et al., I969), we compared theincidence of post-shock dysrhythmias inpatients who received quinidine or procain-amide and/or propranolol but no digitaliswith that in patients who received no drugsat all, and found that post-shock dysrhyth-mias were even more frequent in the drug-treated groups of patients. However, whendigitalis was continued, the combined use ofprocainamide and propranolol resulted in asignificant decrease in the incidence of post-shock atrial tachycardia and ventricularextrasystoles, as compared with the use ofprocainamide or quinidine alone (p <ooi).This was especially the case when largerdoses of propranolol, 8o mg. daily, were used.

This is of interest in the light of the recentobservations of Wittenberg and Lown (I969)who found in animal experiments that pro-

FIG. 5 Cat, weight 2 kg. Lead II. (I)Initial tracing. (2) and (3) Continuous tracing.DC shock, 40 joules. No significant change.(4) After 4 mg./kg. of quinidine and 025 mg.of digoxin. Change in ventricular complex.(5) to (7) Continuous tracing. DC shock, 40joules. Ectopic beats followed by ectopictachycardia, probably ventricular. (8) Fur-ther DC shock, 40 joules. Ectopic tachycardiapersists.

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FIG. 6 Cat, weight 27 kg. Lead II. (I) Initial tracing. DC shock 6o joules. Slight ST segmentand T wave changes. (2) After procainamide, 20 mg./kg. Wide QRS complex. (3) and (4) Con-tinuous tracing. DC shock, 6o joules. Further widening of the QRS complex and slowing ofventricular rate.

pranolol, when given in larger than beta-blocking doses, abolished both digitalis-induced dysrhythmias and digitalis-inducedsensitization to electrical shock.Our experimental findings also suggest

that quinidine has no protective action againstdigitalis and DC shock-induced ectopictachycardia; in fact, quinidine even tendedto reduce digitalis tolerance. This observa-tion is in agreement with that previously re-

ported by Rodensky, Kathe, and Wasser-man (I960).At the time of DC shock treatment, no

patient had significant hypopotassaemia.Hypopotassaemia is an important factor inthe development of post-shock dysrhythmias,as pointed out before by Lown and Witten-berg (I968) and Thind, Blakemore, andZinsser (I969), but in our experience digitaliscaused post-shock dysrhythmias even whenthe serum potassium levels were normal.DC shock per se can cause myocardialpotassium loss, as has been shown recentlyin animal experiments (Regan et al., I969).

It seems from our clinical and experimentalobservations that DC shock can increase thecardiotoxicity not only of digitalis, as pre-viously shown (Szekely et al., I969), but alsoof quinidine. It is possible that such a poten-tiation is more likely to occur when acutepost-shock myocardial injury ensues. Castel-lanos et al. (I965) pointed out earlier thatDC shock enhanced the toxic effect of quini-dine in those instances in which there wasquinidine cardiosensitivity. Published work

contains a number of well-documentedcases of ventricular fibrillation or ventricularstandstill in patients treated with quinidinealone or with the combination of quinidineand DC shock (Selzer and Wray, I964;Oram and Davies, I964; Davies, Leak,and Oram, I965; Bjerkelund and Orming,I968).The cardiotoxicity of procainamide is per-

haps less severe than that of quinidine. Inour experience, it caused no serious side-effects. However, Castellanos and Salhanick(I967) observed conspicuous sino-atrial nodedepression following the combined use ofprocainamide and DC shock.

Propranolol, when given in larger doses(6o to 80 mg. daily), alone or added to quini-dine or procainamide, resulted in post-shockdepression of the sino-atrial node in a fewcases. Lown (I968) previously reportedsino-atrial standstill and cardiac arrest afterthe combined use of propranolol and DCshock.Though currently used antidysrhythmic

drugs, given singly or in combination inconjunction with DC shock, can increase theconversion rate of atrial fibrillation, theyshould be used with great caution, if at all,as their cardiotoxicity may be enhanced byDC shock. Lown (I967) has also statedrecently that the major hazard of DC shocktreatment is related to the use of digitalisbeing partly responsible for the immediatepost-shock dysrhythmias, and of quinidinecausing delayed disorders of the cardiac

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rhythm. Furthermore, large doses of anti-dysrhythmic drugs can depress pacemakeractivity, an effect which becomes unmaskedafter abolition of the ectopic tachycardia byDC shock as pointed out before by Wagnerand McIntosh (I969). The long-term use ofantidysrhythmic drugs in maintaining sinusrhythm after atrial defibrillation is now beingevaluated and will be the subject of a separatecommunication.

Our thanks are due to Drs. G. A. Swan, F.Jackson, and C. B. Henderson, for allowing us toinclude many of their patients in this study. Weshould also like to thank Dr. A. Cassells-Smith,Department of Biochemistry, Newcastle GeneralHospital, for the serum quinidine estimations,the Pharmaceuticals Division, Imperial ChemicalIndustries Ltd., for supplies of propranolol,and Astra-Hewlett Ltd., for supplies of Kinidindurules.

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Castellanos, A., Lemberg, L., Gilmore, H., andJohnson, D. (I965). Countershock exposedquinidine syncope. American Journal of the MedicalSciences, 250, 254.

-, and Salhanick, L. (I967). Electrocardiographicpatterns of procaine amide cardiotoxicity. Ameri-can Journal of the Medical Sciences, 253, 52.

Davies, P., Leak, D., and Oram, S. (I965). Quinidine-induced syncope. British Medical Journal, 2, 5I7.

Hall, J. I., and Wood, D. R. (I968). Factors affectingcardioversion of atrial arrhythmias with specialreference to quinidine. British Heart Journal, 30,84.

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Direct current shockand antidysrhythmic drugs