Digitalis-induced cardiac arrhythmias

Annotations

The use of quinidine

with

Because of the frequent occurrence of arrhythmias in patients with artificial cardiac pacemakers, antiarrhythmic drugs such as quinidine may be indicated. However Kothfeld and associates’ recently cautioned against the use of quinidine in patients with competition between fixed-rate pacemakers and either normal or ectopic spontaneous rhythms because of their observation of ventricular tachyarrhythmias in 14 of 20 dogs with similar pacemaker competition. These repetitive rhythms were initiated by pacemaker stimuli occurring in the vulnerable period after the administration of quinidine, but not during control periods. In order to confirm these observations, we studied 17 mongrel dogs, using essentially the same protocol except for the anesthesia as described in the report of the Rothfeld group. Fifteen dogs were anesthetized with a mixture of chloralose and urethane and two with sodium pentobarbital. Temporary fixed-rate pacing was initiated after a bipolar catheter was passed via the external jugular vein into the right ventricle. A stable state with competition 50 per cent of the time was attained by adjusting the pacemaker rate. After a 15 minute control period quinidine was administered intravenously *This

investigation 04 from The Public Health

was supported National Institutes Service.

in part

by Grant HE of Health, United

Digitalis-induced

09416States

cardiac

Digitalis is an indispensable drug in the treatment of congestive heart failure and most supraventricular tachyarrhythmias, but it may cause or aggravate the congestive heart failure or various cardiac arrhythmias if the patient develops digitalis intoxication.1 Although such gastrointestinal symptoms as anorexia, nausea, and vomiting have been said to be the most common early symptoms, arrhyth-

fixed-rate

pacemakers*

in a dose of 5 mg. per kilogram. Twelve dogs received three doses over a 30 minute period while 5 dogs received a single injection. Continuous electrocardiographic monitoring for 30 minutes failed to reveal any episode of ventricular tachycardia or fibrillation and there were no fatalities. The disparity between these results and those of Rothfeld and co-workers could not be explained but it should be noted that in the latter study pentobarbital was used as an anesthetic whereas in this study chloralose-urethane was employed in all but 2 dogs. On the basis of these findings, there does not seem to be any contraindication to the use of quinidine in patients with fixed-rate pacemakers and competitive rhythms. Michael Nevins, M.D. Leonard Mattes, M.D. Ephraim Donoso, M.D. Charles K. Friedbern. M.D. Division of Ca%iology Department of Medicine Mount Sinai School of Medicine New York, N. Y. REFERENCE 1. Rothfeld, E. L., Zucker, R., Lotti, V., and Bernstein, A.: The effect experimental competitive cardiac ology 18:122, 1967.

L., Parsonnet, of quinidine on pacing, Angi-

arrhythmias

mias may often indicate digitalis toxicity withousuch signs.’ The occurrence of arrhythmias is part titularly common and is frequently the only sign of digitalis intoxication when using purified preparations.’ It is a well-known fact that digitalis may produce every known type of cardiac arrhythmia via an alteration of impulse formation, conduction, or both.1 It is commonly observed that patients with 84.5

846

Annotations

Rhythm

Sinus bradycardia Sinus arrhythmia Sinus tachycardia S-A block Sinus arrest Atria1 tachycardia Atria1 fibrillation Atria1 flutter A.P.C. W.A.P. A-V nodal tachycardia A-V N.E.R. A-V dissociation N.P.C. 1’ A-V block 2” A-V block 3” A-V block V.P.C. Bigeminy Multifocal Ventricular tachycardia Ventricular fibrillation Idioventricular rhythm

Herrmann Flaxman” 1944 1948 (44) (SO) 2

Crwch4 1966

Shrage? 1957

(80)

(40)

ran Capeller” 1959

(141)

4

4 16 3 -

9

18 12

11 6

-

-

1

(69)

4

-

13 3

Abbreviations: A.P.C., Atria1 premature contraction; nodal premature contraction: V.P.C., ventricular *Total patients in each study indicated in parentheses.

I

digitalis intoxication demonstrate various combinations of arrhythmias. Arrhythmias may change from one to another in the same electrocardiographic tracing. In general, cardiac arrhythmias occur in 80 to 90 per cent of patients presenting with digitalis intoxication.’ The purpose of this paper is to review the previous literature concerning digitalis intoxication, with particular emphasis placed on the importance of early recognition of digitalis-induced arrhythmias especially A-V nodal arrhythmias in the presence of atria1 fibrillation. One hundred and eighty cases of digitalis intoxication are included for discussion. The incidences of various digitalis-induced arrhythmias studied at nine different institutionse-g are shown in Table I. A precise comparison between this author’s study and that of others is unfortunately impossible since most authors failed to describe various arrhythmias. Among 180 cases of the present study, 102 were men and 78 patients were women. The ages ranged between 20 and 95 years. One hundred and twentyseven patients had two or more different arrhythmias. The total incidence of digitalis-induced arrhythmias was 346 episodes in 180 patients. As can be expected, every known type of cardiac

4 1

16 2

17 17 -

17 8

-3 43

31

35 15

4 3

17

30

W.A.P.. premature

56 30 17

74

25 .~

4 36 19 9 108 49 85

10 7 14 65 34

8

23

3 5

8

-

wandering contraction.

atria1

pacemaker;

N.E.R.,

nodal

1 (180)

10 5 7 4 2 19 3 3 25 3 44 39 75 5 22 36 6 85 28 30

-

9

7

(161)

-

9 15 27 3 7 6 8 s

7 19

4 5

Dubno@ Chung 1965 ! 1968

12

2 lo

(88)

DreifusX 1968

5

16

20 10 -

Rode&y7 1961

1

escape

rhythm;

Total [%I j

(726)

25 5 37 4 13 102 72

[3.4]

15.11 [I.81 [14.1]

[lO.O] 13 [1.8]

55 19 134 69 127 9 102 122 81 391 184 132

[7.6] [2.6] [18.5] [9.5] [17.5] L14.11 [16.8] [11.2] t53.91 [25.4] [lg. 0]

86 [Il.91 10 il.41 1

N.P.C.,

arrhythmia was encountered. The basic rhythm was atria1 fibrillation in 87 patients and almost all of these patients (83 patients: 46 per cent) showed either nonparoxysmal A-V nodal tachycardia (Fig. 1) or A-V nodal escape rhythm induced by digitalis (Table I). This information is extremely important since A-V nodal arrhythmias in the presence of atria1 fibrillation are frequently misinterpreted as uncomplicated atria1 fibrillation.*-6 Continued administration of digitalis would lead to irreversible congestive heart failure or even death under these circumstances. In this study, atria1 fibrillation and flutter were each found in only 3 patients. It is quite interesting to note that atria1 fibrillation or flutter, which were both very rare digitalis-induced arrhythmias, have been reported by different investigators as relatively common arrhythmias in digitalis toxicity*-fl (Table I). This is usually due to misinterpreting A-V nodal arrhythmias in the presence of atria1 fibrillation. Nineteen patients (10.6 per cent) had atria1 tachycardia, but in the majority (12 patients) of these patients, it was associated with A-V block. One interesting observation in this study was a relatively high incidence (11 patients) of blocked (nonconducted) atria1 premature contractions (Fig. 2). This author

Volume Number

Annotations

79 6

847

Fig. 1. Leads Vr+ V,+ and Vi-, are continuous. The rhythm is atria1 fibrillation and there is intermittent A-V nodal tachycardia (ventricular rate: 120 per minute) with intermittent aberrant ventricular conduction producing incomplete A-V dissociation. Arrows indicate the QRS complexes in A-V nodal tachycardia. FB designates fusion beats.

Fig. 2. Leads 0.23 second). by occasional show aberrant

VI-. and VI+ are continuous. The basic rhythm is sinus with first degree A-V block (P-R interval: There are frequent nonconducted atria1 premature contractions (indicated by arrows) followed A-V nodal escape beats (marked X). It is interesting to note that all of the A-V nodal escape beats ventricular conduction.

believes that the frequent occurrence of nonconducted atria1 premature contractions is au almost pathognomonic sign of digitalis toxicity during digitalis therapy. Disturbances of sinus impulse formation and conduction were found only in 28 subjects (15.6 per cent). A-V conduction disturbances in various degrees were encountered in 64 patients (35.6 per cent). Second degree A-V

block was the most common (36 patients) form noted. Only 6 patients had complete A-V block in the presence of sinus mechanism in the atria, whereas 35 patients showed complete or advanced A-V block in the presence of atrial fibrillation. First degree A-V block was seen in 22 subjects (12.2 per cent). The over-all incidence of ventricular arrhythmias was highest (104 patients: 57.8 per cent)

in this study and among these arrh>?hmias, \ ?‘I,tricular premature beats predominated (8.5 patients: 47.3 per cent). The incidence of ventricular bigeminy (28 patients) and multifocal ventricular premature beats (30 patients) was almost equal. Ventricular tachycardia was found in 16 patients (8.9 per cent) and 2 of them had bidirectional ventricular tachycardia. Two patients had ventricular fibrillation and both died. A total of 38 oatients died of intractable heart failure and/or irrei,ersible cardiac arrhythmias. In treating mild cases of digitalis intoxication, discontinuation of the drug alone was satisfactorily effective. However, if intoxication was manifested by frequent premature beats or tachyarrhythmias, potassium or Dilantin (diphenylhydantoin) was administered, in addition to omitting digitalis. Potassium was highly effective even in the presence of a normal serum potassium value. In urgent situations, an intravenous infusion of potassium or Dilantin was carried out. Potassium and Dilantin were equally effective in treating digitalis-induced supraventricular tachyarrhythmias whereas the latter was more effective in treating ventricular arrhythmias. Xylocaine was admitlistered to 6 patients for the treatment of ventricular arrhythmias with various success. A temporary artificial pacemaker was used with good results in 2 patients for complete A-V block. A recognition of digitalis-induced cardiac arrhythmias, particularly A-V nodal arrhythmias in the presence of atrial fibrillation, is extremely important because cardiac arrhythmias may often indicate digitalis intoxication without any other signs. Sudden appearance of rapid or slow heart action during digitalization should make one suspect of digitalis toxicity rather than the need for increased digitalis. There is an appreciable mortality rate in patients with digitalis-induced arrhythmias, particularly if they go unrecognized. Immediate recognition of

digitalis essential rate.

of digitalis are high mortalit!-

Edward

IIPst

K. Chmg, M.L)., F..-I, C.C.* Division of Cardiology Department of Internal A%!tedicine Virginia University, School of Medicine Morgantown, TV. Va.

*Associate Professor Electrocardiographic

of

Medicine Laboratory.

and

Physician-in-Charge,

REFERENCES 1. Chung, E. K.: Heart failure frorn digitalis intoxication, in Meyler, L., and Peck, H. M.: Drug-induced diseases, ed. 3, Amsterdam, The Netherlands. 1968. Excerota Medica. DD. 53-93. 2. Herrmann, ‘G. R., Decheral, G. ‘M., and McKinley, W. F.: Digitalis poisoning, J. A. M. A. 226:760, 1944. 3. Flaxman, N. : Digitalis poisoning-report of 30 cases, Amer. J. Med. Sci. 216:179, 1948. 4. Crouch, R. B., Herrmann, G. R., and Hejtmanik, M. R.: Digitalis intoxication, Texas J. Med. 52:714, 1956. 5. Shrager, M. IV.: Digitalis intoxication, Arch. Intern. Med. 100:881, 1957. 6. Von Capeller, D., Copeland, G. D., and Stern, T. N.: Digitalis intoxication: A clinical report of 148 cases, Ann. Intern. Med. 50:869, 19.59. Rodensky, P. L., and Wasserman, F.: Observations on digitalis intoxication, Arch. Intern. Med. 108:61, 1961. Dreifus, L. S., McKnight, E. H., Katz, M., and Likoff, W.: Digitalis intolerance, Geriatrics 18:494, 1963. Dubnow, M. H., and Burchell, H. B.: A comparison of digitalis intoxication in two separate periods, Ann. Intern. Med. 62:956, 1965.

Of the United States Government, the physical examination

It is well known that it is impossible to place satisfactorily monetary values on professional medical services. Nevertheless, it is attempted even by the United States Government. Unfortunately, remunerations for services often dictate the quality and type of services rendered patients. Through its Medicare and Medicaid programs, the United States Government does have an opportunity to influence the quality and type of medical practice through its remuneration for services. The fact apparently has not been fully appreciated. Senator

toxicit\. and withdrawal to minimize the relativeI>,

history

taking,

and

Warren Magnuson is aware of this and in a statement before the Subcommittee on Executive Reorganization of the Committee on Government Operations has expressed himself clearly. To quote: “Basic to a consideration of medical care costs is the professional fee structure of medicine. I suggest that the fee structure is unsound and in itself contributes to excessive costs. Fee structures are heavily weighted toward encouraging procedures rather than time and skill. Surgically oriented third party fee structures are the