Incidence and prevention of supraventricular tachyarrhythmias after coronary bypass surgery

Inrernatronol Journal of Cardrolog,

13 ( 1986) 12% 134

125

Elsevier

IJC 00454

Incidence and prevention of supraventricular tachyarrhythmias after coronary bypass surgery Romeo J. Vecht i, Evagoras P. Nicolaides i, Jerome K. Ikweuke Christos Liassides ‘, John Cleary *, Warren B. Cooper 3

I,

’ Academic Surgical and Cardtovascular Units, St. Mary’s Hospital MedIcal School, London, ’ Medical Unit, St. Macv’s Hospital, London, ’ Medical Department, Merck Sharp & Dohme (Received

24 February

1986; revision accepted

13 May 1986)

Vecht RJ, Nicolaides EP, Ikweuke JK, Liassides C, Cieary J. Cooper WB. Incidence and prevention of supraventricular tachyarrhythmias after coronary bypass surgery. Int J Cardiol

1986;13:125-134.

Supraventricular tachyarrhythmias are a frequent complication encountered after coronary artery bypass grafting. A retrospective survey of 102 consecutive patients undergoing exclusive bypass grafting at St. Mary’s Hospital supplemented by a review of 16 published reports over a period of 10 years revealed a mean incidence of post-operative tachyarrhythmia of 33.4% in 1344 patients (range 11.4-100%). One hundred and thirty two patients undergoing exclusive bypass surgery, were randomised prospectively in double blind fashion to receive either oral timolol or matched placebo approximately 24 hours after surgery. In the 66 patients receiving timolol, there was a significant reduction of post-operative arrhythmias compared to the 66 patients receiving placebo: from 19.7 to 7.5% (P < 0.05). Of all arrhythmias, two thirds appeared under 48 hours after surgery. In the timolol group, 4 patients developed systemic hypotension. This was readily reversed by withdrawing the drug. No other side effects were noted. The use of oral timolol after coronary artery surgery significantly lowers the incidence of post-operative supraventricular arrhythmias.

(Key words: Coronary artery bypass surgery; Supraventricular Post-operative; Timolol)

Reprint requests to: Dr. R.J. Vecht, London W2 1PG. U.K.

0167-5273/86/$03.50

Academic

Surgical

0 1986 Elsevier Science Publishers

Unit,

St. Mary’s

B.V. (Biomedical

tachyarrhythmias;

Hospital

Division)

Medical

School,

126

Introduction Coronary artery bypass surgery is increasingly performed to alleviate the symptoms of angina and prolong life in carefully selected populations. By 1983 an estimated 191,000 such operations were being carried out annually in the U.S.A. [l] and by 1985, an approximate total of 2,000,OOO had been performed. It is well

TABLE

1

Retrospective study. after surgery).

Incidence

of SVTA in 102 consecutive

No. of patients 99

Early Late

patients

undergoing

CABG

(all digitalised

A. Fib.

A. Tach.

A. Flut.

8 4 (1 DC)

3 (1 DC) 4 (3 DC)

1 3 (1 DC)

Total incidence of SVTA 18.2% Percentage SVTA occurring early (under 48 hours) 66.6% (3 patients died in the perioperative period.) SVTA = supraventricular tachyarrhythmias; fibrillation; A. Tach. = atria1 tachycardia;

TABLE Incidence

CABG = coronary artery bypass graft; A. Flut. = atria1 flutter: DC = direct current

A. Fib. = atrial cardioversion.

2 of arrhythmias

after CABG.

Year

Authors

1974 1975 1976 1979 1979 1979 1979 1980 1980 1981 1981 1981 1981 1982 1983 1984 1984

Angelini [3] Rose [12] Johnson [9] * Boudoulas [17] * Michelson [23] Salazar [ZO] * Tyras [ll] * Stephenson [18] * Oka [Zl] * Csicsko [lo] * Buxton [24] Mohr [22] * St. Mary’s Chee [8] Mills [14] * Ormerod [ 131 * White [25] *

Review of 16 publications

No. of patients

% VT/VF

study.

Mean appearance time SVTA (hr)

75 15 66 50

13.3 40.0 25.7 30.0

13.3 6.6 5.0 _

50 22

28.0 50.0

4.0 _

79 136 52 270 99 48 102 137

11.4 18.0 38.4 15.2 29.0 40.0 18.2 54.0

5.0 _ 1.8 _ _ 6.8 _

30.0 27.0 100.00

8.9 3.0 _

68 (47% < 48 hr)

33.4

6.0

60.3

90 33 20 1344

* Randomised Abbreviations

% SVTA

and retrospective

studies, control groups only considered. as in Table 1. VT = ventricular tachycardia;

VF = ventricular

78% within 48 hr 104 (20% i 48 hr)

_ 62 (55% < 48 hr) 72 (54% < 48 hr) 38.4% within 24 hr 79% within 72 hr 32 (95% < 48 hr) 67.1% within 48 hr _

_

fibrillation:

hr = hours.

127

known that supraventricular tachyarrhythmias occur commonly after these procedures. The arrhythmias (atria1 tachycardia, flutter and fibrillation) are usually encountered in the first post-operative days. Since present-day practice still consists on the whole of maintaining patients on beta-blocking agents until the day of operation, we were interested to establish whether the re-introduction of such a drug after surgery (without using digoxin) would lower the overall incidence of rhythm problems. A retrospective study was undertaken relating to 102 consecutive patients undergoing exclusive coronary artery surgery at St. Mary’s Hospital, London. over a period of 6 months. Anaesthetic agents and cardioplegic solutions were identical to those used presently. None of these patients received beta-blockers and all were routinely digitalised after surgery. In this group the overall incidence of arrhythmias was 18.2% (Table 1). On the basis of this retrospective analysis and a review of the pertinent literature (Tables 1, 2) it became evident that setting up a prospective controlled trial was necessary.

Materials and Methods One hundred and thirty two patients undergoing exclusive bypass grafting were randomised in a double-blind placebo controlled clinical trial. Oral timolol (Blocadren - Merck Sharp & Dohme), 5 mg 12 hourly for 24 hours then 10 mg twice daily or matched placebo was administered on the first post-operative day. Suitable patients entered in the trial were of either sex and any age. Pre-operative medication details were obtained prior to surgery and administration of various beta-blockers was continued to and including the day of surgery. Post-operative randomisation into the trial took place as soon as oral therapy was instituted. Exclusion criteria included cardiogenic shock, hypotension (systolic blood pressure below 90 mm Hg), bradycardia (heart rate under 48 beats/minute), atrioventricular dissociation and supraventricular arrhythmias occurring before randomisation had taken place. Standard contra-indications for receiving betablockers were observed and the use of post-operative digoxin was not permitted. No other anti-arrhythmics were administered prophylactically. Patient monitoring was by means of continuous electrocardiographic oscilloscope for a period of 24 hours. under constant supervision by nursing staff specially instructed about the aims of the trial. After transfer to a High Dependency Unit, further oscilloscope monitoring was maintained by equally informed nursing staff for a further 48 hours. Subsequently and to the time of discharge (usually the 10th post-operative day) daily electrocardiograms and additional four hourly clinical observations were obtained. Supraventricular rhythm disturbances were defined as sustained if they persisted for half an hour or more. Heart rate and blood pressure were recorded on the day before surgery and at 12 hourly intervals until discharge from hospital. A number of patients developed early post-operative arrhythmias, i.e. before it was possible to be randomised into the trial. Though not entered, they were

128

carefully monitored and subjected to accurate patients gave informed consent and the study hospital’s Ethics Committee.

progress protocol

reports (Table was approved

4). All by the

Data Analysis The chi-squared test was used to evaluate the difference in incidence of rhythm problems between study groups. Student’s c-test paired and unpaired as appropriate was used to compare continuous variables related to baseline characteristics, operative parameters, blood pressure and heart rate results.

Results A total of 209 patients underwent exclusive coronary arterial surgery during the period of the trial. Seventy seven patients though not included were closely documented (Table 3). Fourteen out of 77 developed supraventricular rhythm problems (18.2%): 10 early (under 24 hours) and 4 later in the post-operative period before randomisation was possible. In this group a total of 71.4% of the rhythm problems were encountered under 48 hours. One hundred and thirty two patients were equally randomised to receive either timolol or placebo. The baseline characteristics of these 2 groups are outlined in Table 5. There was no significant difference with regard to patient age, sex, preoperative blood pressure or heart rate, cardiothoracic ratios or operative details. The mean time of administration of trial medication was not significantly different between the two groups. The frequency of preoperative use of beta blockers was similar in both groups. Thirteen patients in the placebo group developed abnormally fast supraventricular rhythms (19.7%) compared to only 5 patients in the timolol group (7.5%). This was statistically significant (P < 0.05) (Table 4).

TABLE

3

Reasons

for non-inclusion:

77 patients. No.

Early post-operative hypotension Post-operative arrhythmia occurring Respiratory complications Hypertension Coronary artery and carotid surgery Peri-operative myocardial infarction Peri-operative death Refused consent Digoxin given inadvertently Consent not requested Lost to follow-up: foreign patients

before randomisation

17 14 4 3 2 1 1 3 8 8 16

129 TABLE

4

SVTA in placebo

Placebo Timolol Patients

(H = 66): timolol (n = 66) and patients

not in trial

not included

in trial

(n = 77).

A.Fib.

A.Flut.

A.Tach.

Total

7 5 10

0 0 3

6 0 1

13 (19.7%) (P i 0.05) 5 (7.5%) 14 (18.2%)

In those patients who developed abnormal rhythms, the mean administration time of trial medication after surgery was 21.7 hours in the placebo group and 23.4 hours in the timolol group (P NS) (Table 5). The mean appearance time of the arrhythmias was virtually identical: 77.7 hours in the placebo and 77.6 in the timolol group (Table 5). Fifty-five patients in the placebo group and 57 receiving timolol were on beta-blocking agents before surgery (Table 5). Of the 18 patients who developed rhythm problems: 17 (12 in the placebo, 5 in the timolol group) were on beta-blocking agents prior to surgery and only 1 (placebo group) was not (Table 5). This suggested that patients on beta-blockers before surgery were more liable to post-operative arrhythmias although statistical significance was not attained.

TABLE

5

Comparison

of placebo

and timolol groups:

Mean age (years) Range Sex male female Mean BP pre-op. post-op. (4th day) CTR Mean pump time (min) Mean cross clamp time (min) Mean administration time P or T post-op. (hours) Mean administration time P or T post-op. (hours) in 18 pts with SVTA Mean appearance time of SVTA post-op. (hours) Beta-blockers pre-op. BP = blood pressure; placebo; T = timolol;

baseline

characteristics

n-= 66)

Placebo (n = 66)

Timolol

54.0 34-71

54.2 38-70

61 5

60 6

129/79 110/69 P < 0.005 0.46 89 50

127/80 103/66 P < 0.005 0.46 87 47

NS NS

23.7

25.5

NS

21.7

23.4

NS

(13 pts) 77.1 (range 24-168) Y = 55 (12 SVTA) N=ll (1 SVTA)

(5 pts) 71.6 (range 24-120) Y = 57 (5 SVTA) N = 9 (0 SVTA)

CTR = cardiothoracic ration: Y = Yes: pts = patients.

min = minutes;

(

N = no; NS = not

NS

NS

significant; p =

130

Systolic mm Hg

B.P

60-

I

I

2

3

4

5

6

1

Days pwt-op

Fig. 1. The mean post-operative systolic blood pressure for the two groups (placebo and timolol) shows slightly lower levels for the patients on timolol (P NS). BP = blood pressure; mm Hg = millimetres of mercury; post-op = post-operative: 1 SD = 1 standard deviation.

MEL” L 1SD. llO-

Pulse rate beats/mm so

I 70

I 1 pc6.05

0.01

0.01

0.01

0.01

4

5

6

7

50

I Pre-op

3

2

Days post-op

Fig. 2. The mean post-operative heart rates for the two groups show a significantly third post-operative day in the timolol group. beats/min = beats per minute; deviation; pre-op = pre-operative; post-op = post-operative.

TABLE

6

Comparison

of long- and short-acting

beta-blockers

No. of patients

Atenolol Propranolol beats/mm

lower rate from the 1 SD = 1 standard

Placebo

Timolol

14 23

16 22

= beats per minute.

administered

before

surgery

Mean heart rate (1st post-op. before randomisation) 87 + 14 beats/min 92 * 12 beats/mm

NS

day

131

The mean post-operative systolic blood pressure was reduced in both groups. This difference was not statistically significant on a day-to-day analysis (Fig. 1). Post-operative heart rates were significantly lower in the patients on timolol, from the third post-operative day i.e. on the day after timolol was given (Fig. 2). There was no significant difference in heart rate on the first post-operative day (before randomisation) between patients receiving long-acting (atenolol) versus shorter-acting (propranolol) beta-blocking agents prior to surgery (Table 6). From the literature it was observed that 62% of rhythm problems arose on average under 48 hours after surgery (Table 2). In the retrospective study, two-thirds occurred under 48 hours after surgery and in the 77 patients not in the trial 71.4% under 48 hours.

Discussion The incidence of supraventricular tachyarrhythmias, following coronary artery surgery has not altered over 10 years (Table 2) although anaesthetic and surgical techniques have changed and presumably improved. From our data and on analysing relevant publications it appears that this complication occurs mainly in the first two post-operative days (Table 2). We have calculated that the mean incidence of post-operative arrhythmias was 42% when monitoring was by means of 24-hour ambulatory method [13,23,25] and 44% when using telemetry [8,14]. Under oscilloscope supervision, the mean calculated post-operative incidence was 25% (5,9-12,17,20,22]. In White’s series [25], ambulatory monitoring was continued over 7 post-operative days and an incidence of 100% was found. This indicates that the more continuous the method of detection, the higher the yield. We were not concerned in examining the incidence of post-operative ventricular arrhythmias. These have a recognised mortality [2-51. On reviewing 9 reports we found an overall incidence of only 6% (Table 2). By contrast, there were no reported fatalities resulting from post-operative supraventricular arrhythmias. These, however, are disabling to the patient and disturbing to the attending staff. They complicate hospital stay and management, can prove difficult to correct and not infrequently require electrical conversion (Table 1). Furthermore, little is known about the haemodynamic consequences resulting from episodes of systemic hypotension and shortened diastolic filling periods. It is plausible that these may have a negative bearing on ultimate recovery, graft patency and perhaps even long-term survival. The role of digitalis as a therapeutic anti-arrhythmic agent has yet to be ascertained. Digitalisation for surgery has been in vogue since the early days of thoracotomy and valve surgery [6,7]. Digitalis used before [8,9] or after [lo] surgery has been advocated by some and considered harmful by others [ll]. There is evidence that digoxin generates post-operative arrhythmias possibly by increasing myocardial sensitivity [12,13]. Recently the use of propranolol and digoxin has proven a successful combination [14]. We found a similar incidence of abnormal supraventricular rhythm on comparing our retrospective group of 102 patients (all

132

routinely digitalised after surgery) to 66 trial patients receiving placebo without digitalis. By the late 1970’s, it was evident that the use of beta-blockers to the time of surgery was safe. Until then, these drugs were interrupted some 48 hours before surgery for fear of reducing left ventricular function. Several reports have demonstrated that beta-blocking agents attenuate sympathetic stimulation without embarrassing left ventricular performance [15,16] and that patients given beta-blockers during or after coronary artery surgery have a reduced incidence of post-operative supraventricular arrhythmia [17-19,261. A recent publication has shown that oral verapamil failed to prevent such arrhythmias following coronary artery surgery [27]. In our study, patients receiving timolol had a lower heart rate from the third post-operative day. This suggested an initial absorption defect and the possibility that intravenous administration of timolol could have achieved a better result. In addition we found no significant difference in mean heart rate on the first post-operative day, comparing 30 patients given long-acting beta-blocker (atenolol) pre-operatively to 45 given propranolol (Table 6). This implied that both drugs were equally “washed out” during cardio-pulmonary bypass. We did not measure the ventricular response of patients who developed post-operative rhythm problems: others have demonstrated a significant decrease in ventricular rate in patients given timolol [25]. We did not attempt to analyse the causations of the post-operative arrhythmias. Numerous factors have been implicated in the past. They include left ventricular dysfunction with left atria1 hypertension and distension, pulmonary complications, trauma to the atria, anaesthetic agents, biochemical alterations, beta-blocker withdrawal [20], percarditis and p wave duration [24]. Prolongation of myocardial ischaemic time has also been held responsible for the appearance of these arrhythmias

1131. And so there is, to date, no agreed policy on post-surgery drug management. Should arrhythmias be treated as they arise or should they be prevented? It seems

Universal “=

1344

Mary’s rst

Not in trial

Placebo

102

77

66

Fig. 3. The mean incidences shown in the groups discussed study: Not in trial = those n = number of patients under

Timolol 66

of supraventricular tachyarrhythmias in this paper. Universal = published patients fully monitored but not scrutiny in each group.

after coronary bypass surgery are reports; Mary’s 81= the retrospective accepted for inclusion in the trial;

133

rational to adopt a policy of continuing beta-blockade after surgery, thereby obviating the need to resort to therapeutic manoeuvres administered in acute situations with uncertain and possible deleterious consequences. Finally, on comparing the mean incidence of post-operative supraventricular tachyarrhythmias in different populations, it is evident that patients given timolol had a significant reduction of this complication (Fig. 3). This has been confirmed in this double-blind trial and we recommend the immediate post-operative re-introduction of a beta-blocking agent. We would postulate from our observations that earlier intravenous administration of timolol may have achieved even better suppression.

Acknowledgements We wish to acknowledge with gratitude the cooperation of the physicians and surgeons whose patients ‘were included in this trial, in particular Dr. E.M.M. Besterman, Dr. P.H. Kidner, Mr. S. Lennox, Prof. A. Nicolaides, Mr. R. Sapsford and Mr. R. Stanbridge. This work was supported by a grant made available by Merck, Sharp & Dohme and by the Leventis Foundation. Our thanks are also extended to Miss M. Petrie and Miss A. Taft for secretarial assistance, to Mrs. S. Jones and the Photographic Department, St. Mary’s Hospital.

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