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Ann Thorac Surg 1996;61:1083-1085
© 1996 The Society of Thoracic Surgeons

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Original Article: General Thoracic

Verapamil as Prophylactic Treatment for Atrial Fibrillation After Lung Operations

Department of Pulmonary Medicine, Universitair Ziekenhuis Gasthuisberg, Leuven, Belgium

Accepted for publication December 11, 1995.

	Abstract

Top Footnotes Abstract Introduction Material and Methods Results Comment References

 
Background. Atrial fibrillation is a frequently occurring arrhythmia after thoracic operations. Preventive strategies for this complication have been extensively evaluated after cardiac operations.

Methods. We performed a prospective, open randomized study, comparing intravenous verapamil and placebo in 199 patients after pneumonectomy or lobectomy at the University Hospital of Leuven. Verapamil was administered as a bolus of 10 mg over 2 minutes followed by a 30-minute infusion of 0.375 mg/min and then 0.125 mg/min for 3 days. The patients were continuously monitored in the postoperative intensive care unit.

Results. Atrial fibrillation occurred in 15% of the patients receiving placebo and in 8% of the patients receiving verapamil (difference not significant). The verapamil infusion was interrupted in 9% of the patients because of bradycardia and in 14% because of hypotension.

Conclusions. If tolerated, continuous intravenous verapamil infusion showed only a modest prophylactic efficacy for the occurrence of atrial fibrillation after lung operations. In the dose employed the verapamil infusion was accompanied with a high incidence of side effects necessitating interruption of the therapy.

	Introduction

Top Footnotes Abstract Introduction Material and Methods Results Comment References

 
See also page 1086.

Atrial fibrillation is a frequently occurring arrhythmia after thoracic operations. Over a period of 4 years we observed atrial fibrillation in 17% of 310 patients undergoing lobectomy procedures and in 21% of 242 having pneumonectomies. In most patients antiarrhythmic treatment was considered necessary because of a fast heart rate or hemodynamic consequences. After pneumonectomy it has been reported that atrial fibrillation has severe prognostic implications, with a postoperative mortality of 25% [1]. We therefore decided to evaluate prospectively a prophylactic antiarrhythmic therapy comparing amiodarone, verapamil, and placebo. Either drug has been reported safe and effective in the prevention of postoperative atrial dysrhythmias after cardiac operations [2, 3]. Our study was interrupted after 10 months because of an unacceptable high incidence of adult respiratory distress syndrome after pneumonectomy in patients treated with amiodarone [4], but resumed afterward comparing verapamil and placebo.

	Material and Methods

Top Footnotes Abstract Introduction Material and Methods Results Comment References

 
A prospective, open, randomized study was planned to compare verapamil and placebo as prophylactic treatment for atrial fibrillation after pneumonectomy and lobectomy. All patients in whom a pulmonary resection was performed at the University of Leuven were considered for the study, within 1 hour of return from the operating room to the intensive care unit. Exclusion criteria were a heart rate of less than 50 beats/min, a systolic blood pressure less than 100 mm Hg, atrial dysrhythmias, heart failure, or thyroid dysfunction. Digitalis, ß-blockers, calcium antagonists, and other antiarrhythmic agents were not allowed for at least 1 week before operation. Verapamil was administered as a bolus of 10 mg intravenously over 2 minutes followed by a 30-minute infusion of 0.375 mg/min and then 0.125 mg/min for 3 days [5]. All patients remained in the intensive care unit under continuous electrocardiographic monitoring during the 3-day study period. The treatment routinely used after lung operations was given as usual, ie, prophylactic antibiotics, subcutaneous low molecular weight heparin, ß₂ agonists in aerosol, and an H₂ antagonist intravenously. Other forms of treatment were given as required. The prophylactic antiarrhythmic treatment was interrupted when side effects occurred that were thought to be related to the antiarrhythmic drug (such as rhythm or conduction disturbances and hypotension) or when other antiarrhythmic therapy seemed needed.

A full explanation of the study protocol was given to each patient preoperatively, and informed consent was obtained before inclusion.

Comparison of the effects of treatment was performed using Student's t test and the Fisher exact test. Verapamil plasma levels were determined in 10 randomly chosen patients after lobectomy or pneumonectomy during the 3-day infusion.

	Results

Top Footnotes Abstract Introduction Material and Methods Results Comment References

 
The results are summarized in Tables 1 and 2. After pneumonectomy, 35 patients were assigned to verapamil therapy and 34 to placebo. After lobectomy 65 patients were included in each group. None of the patients had a history of cardiac arrhythmias or had been treated with digitalis, ß-blockers, or other antiarrhythmic agents for the last 6 months.

None of the patients had a predisposition for these hemodynamic side effects. The complications of hypotension and bradycardia always occurred within the first 6 hours of the infusion and subsided rapidly after discontinuation of verapamil. They had no impact on the further clinical evolution of the patients. Atrial fibrillation occurred in 15% of the patients receiving placebo and in 8% of the patients assigned to verapamil therapy (difference not significant). When we considered only the patients who received a full course of verapamil, the incidence of atrial fibrillation was 6.4% (difference not significant).

The mean heart rate of the patients 5 minutes after the onset of atrial fibrillation was 147 ± 20 (standard deviation) beats/min for patients receiving placebo and 132 ± 22 beats/min (standard deviation) for those receiving verapamil (difference not significant). Atrial fibrillation apart, other arrhythmias were rare. One patient after lobectomy had an episode of atrial flutter during verapamil therapy, and during placebo infusion 1 patient after lobectomy had an episode of atrioventricular nodal reentry tachycardia. One patient after pneumonectomy had, in addition to atrial fibrillation, an episode of atrial flutter after stopping of the verapamil infusion.

The verapamil plasma levels in 10 randomly chosen patients throughout the 72-hour infusion are summarized in Figure 1. Atrial fibrillation occurred in 1 of these patients. Only 2 of the episodes of atrial fibrillation were seen on the first postoperative day, in contrast with 9 episodes on day 2 and 12 episodes on day 3. The 30-day mortality in the pneumonectomy group was 4 patients, each after the development of adult respiratory distress syndrome; each of the patients had an episode of atrial fibrillation. Three patients died after lobectomy, and only 1 of them had an episode of atrial fibrillation.

View larger version (30K): [in this window] [in a new window]   Fig 1. . Verapamil plasma levels in 10 randomly chosen patients during the 72-hour verapamil infusion (see text). (I.V. = intravenous.)

	Comment

Top Footnotes Abstract Introduction Material and Methods Results Comment References

After cardiac operations prophylactic strategies with antiarrhythmic drugs for the prevention of atrial fibrillation have been successful only with ß-blocking agents [7], with the exception of one study with oral verapamil [3] and one with amiodarone [2]. Efficacy of verapamil for the prevention of atrial tachyarrhythmias has been suggested after a small, randomized study in patients after elective thoracotomy [8].

In our study of 199 patients, verapamil was not useful for the prevention of atrial fibrillation after lung operation, despite plasma verapamil concentrations higher than those obtained by Lindgren and associates [8]. Contrary to their report we found a high incidence of side effects such as bradycardia and hypotension, especially after pneumonectomy. These side effects subsided rapidly after interruption of the verapamil infusion and did not influence the further clinical evolution, but had significant hemodynamic repercussions. A high incidence of hypotension has been reported previously when oral verapamil was used for prophylaxis of supraventricular tachycardia after coronary bypass operations [9]. The bradycardia is due to a direct effect of verapamil on the formation of the sinus node action potential. The large incidence of arterial hypotension is due to the vasodilator effect of the drug accentuated by our policy of relative fluid restriction, especially after pneumonectomy, hoping to decrease the incidence of postoperative adult respiratory distress syndrome. The verapamil dose used in the study protocol may seem rather large but was reported by other authors as safe and effective [5].

Verapamil has been used to slow the ventricular rate rapidly in patients with atrial fibrillation [10, 11]. Reports on its efficacy for this purpose after cardiac operations have been conflicting, with some reports claiming a significantly slower ventricular rate when atrial fibrillation occurred in patients already receiving verapamil [9] whereas others did not find a significant difference in the heart rate in patients receiving verapamil compared with placebo [12, 13]. We did not find a significant difference in heart rate of atrial fibrillation occurring in our patients given constant verapamil infusion compared with the placebo-treated patients. This is probably explained by high circulatory catecholamine levels after thoracic operations and by our policy of routine administration of ß₂ agonists in aerosol postoperatively.

Postoperative episodes of atrial fibrillation remain a common problem after pulmonary operations. They may cause hemodynamic repercussions but are mostly transient. Contrary to previously reported results in a small number of patients [8], intravenous verapamil in the dose employed showed only a modest prophylactic effect for the occurrence of atrial fibrillation after lobectomy or pneumonectomy, if tolerated. Furthermore, the intravenous administration of verapamil was accompanied by a high incidence of side effects necessitating interruption of the infusion. If atrial fibrillation occurred in patients already on verapamil therapy, the heart rate was not significantly slower compared with that in patients given placebo.

	Footnotes

Top Footnotes Abstract Introduction Material and Methods Results Comment References

 
Address reprint requests to Dr Van Mieghem, Limburgs Hartcentrum, St. Jansziekenhuis, Schiepse Bos, B-3600 Genk, Belgium.

	References

Top Footnotes Abstract Introduction Material and Methods Results Comment References

 

1. Krowka MJ, Pairolero PC, Trastek VF, Payne WS, Bernatz PE. Cardiac dysrhythmia following pneumonectomy: clinical correlates and prognostic significance. Chest 1987;91:490–5.[Abstract/Free Full Text]
2. Hohnloser SH, Meinertz T, Dammbacher T, et al. Electrocardiographic and antiarrhythmic effects of intravenous amiodarone: results of a prospective, placebo-controlled study. Am Heart J 1991;121:89–95.[Medline]
3. Ferraris VA, Ferraris SP, Gilliam H, Berry W. Verapamil prophylaxis for postoperative atrial dysrhythmias: a prospective, randomized, double-blind study using drug level monitoring. Ann Thorac Surg 1987;43:530–3.[Abstract]
4. Van Mieghem W, Coolen L, Malysse I, Lacquet LM, Deneffe G, Demedts M. Amiodarone and the development of ARDS after lung surgery. Chest 1994;105:1642–5.[Abstract/Free Full Text]
5. Reiter MJ, Shand DG, Aanonsen LM, Wagoner R, MacCarthy E, Pritchett ELC. Pharmacokinetics of verapamil: experience with a sustained intravenous infusion regimen. Am J Cardiol 1982;50:716–21.[Medline]
6. Bailey CC, Betts RH. Cardiac arrhythmias following pneumonectomy. N Engl J Med 1943;229:356–9.
7. Andrews TC, Reimold SC, Berlin JA, Antmann EM. Prevention of supraventricular arrhythmias after coronary artery bypass surgery. Circulation 1991;84(Suppl 3):236–44.
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9. Davidson R, Hartz R, Kaplan K, Parker M, Feiereisel P, Michaelis L. Prophylaxis of supraventricular tachyarrhythmia after coronary bypass surgery with oral verapamil: a randomized, double-blind trial. Ann Thorac Surg 1985;39:336–9.[Abstract]
10. Hwang MH, Danoviz J, Pacold I, Rad N, Loeb HS, Gunnar RM. Double-blind cross-over randomized trial of intravenously administered verapamil: its use for atrial fibrillation and flutter following open heart surgery. Arch Intern Med 1984;144:491–4.[Abstract/Free Full Text]
11. Waxmann HL, Myerburg RJ, Appel R, Sung RJ. Verapamil for control of ventricular rate in paroxysmal supraventricular tachycardia and atrial fibrillation or flutter: a double-blind randomized cross-over study. Ann Intern Med 1981;94:1–6.[Abstract/Free Full Text]
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