Prevention of atrial fibrillation with moderate doses of amiodarone in the postoperative period of cardiac surgery is safe and effective in patients with high risk for developing this arrhythmia

Abstracts

OBJETIVO: Avaliar se a profilaxia com amiodarona em moderada dosagem, no pós-operatório de cirurgia cardíaca (revascularização miocárdica e/ou cirurgia valvar), reduz a incidência de fibrilação atrial em pacientes de alto risco para desenvolver essa arritmia. MÉTODOS: Estudo clínico, randomizado e prospectivo, realizado em 68 pacientes submetidos a cirurgia cardíaca eletiva. A média de idade foi de 64 anos e 59% dos participantes eram do sexo masculino. Os pacientes com três ou mais fatores de risco para fibrilação atrial, de acordo com a literatura, foram randomizados em dois grupos, para receber ou não profilaxia com amiodarona no primeiro dia de pós-operatório. A dose administrada foi de 600 mg/dia a 900 mg/dia, por via intravenosa, no primeiro dia de pós-operatório, seguida de 400 mg/dia por via oral até a alta hospitalar ou até completar sete dias. Os demais pacientes, com dois ou menos fatores de risco, foram seguidos até a alta hospitalar. Todos os pacientes foram observados por monitorização cardíaca e/ou eletrocardiografia. RESULTADOS: No grupo que recebeu amiodarona, 7% dos pacientes apresentaram fibrilação atrial, enquanto no grupo controle 70% desenvolveram a arritmia. Nos indivíduos não-randomizados (com dois ou menos fatores de risco), apenas 24% apresentaram fibrilação atrial. CONCLUSÃO: O uso profilático de amiodarona foi eficaz na prevenção de fibrilação atrial nos pacientes com três ou mais fatores de risco para essa arritmia. Esse tratamento pode ser benéfico na redução da permanência na Unidade de Terapia Intensiva e, conseqüentemente, nas complicações advindas do maior tempo de internação hospitalar.

Fibrilação atrial; amiodarona; cirurgia torácica; cuidados pós operatórios

ORIGINAL ARTICLE

Prevention of atrial fibrillation with moderate doses of amiodarone in the postoperative period of cardiac surgery is safe and effective in patients with high risk for developing this arrhythmia

Renato Jorge Alves; Glaucylara Reis Geovanini; Gisele de Brito; Gabriel A. S. Miguel; Valéria A. Glauser; Kenji Nakiri

Real e Benemérita Associação Portuguesa de Beneficência de São Paulo - Hospital Santa Cruz - São Paulo, SP - Brazil

^{Mailing address}

SUMMARY

OBJECTIVE: To assess if prophylaxis with moderate doses of amiodarone in the postoperative period of cardiac surgery (coronary artery bypass grafting and/or valve surgery), reduces the incidence of atrial fibrillation in patients with high risk for developing this arrhythmia.

METHODS: A randomized and prospective clinical study involving 68 patients who underwent elective cardiac surgery. Mean age was 64 years and 59% of participants were males. Patients with three or more risk factors for atrial fibrillation, according to the literature, were randomized into two groups to receive or not prophylaxis with amiodarone in the first postoperative day. The dose administered ranged from 600 mg/day to 900 mg/day, intravenously, on the first postoperative day, followed by 400 mg/day orally until hospital discharge or until completing seven days. The other patients, who presented two or fewer risk factors, were followed up until hospital discharge. All patients were evaluated by means of cardiac and/or electrocardiographic monitoring.

RESULTS: In the group treated with amiodarone, 7% of patients presented atrial fibrillation, whereas in the control group 70% of patients developed arrhythmia. Among the non-randomized individuals (with two or fewer risk factors), only 24% presented atrial fibrillation.

CONCLUSION: The prophylactic use of amiodarone was effective in the prevention of atrial fibrillation in patients with three or more risk factors for this arrhythmia. This treatment can be useful to reduce stay at the Intensive Care Unit and, consequently, the complications originating from longer hospitalization.

Key words: Atrial fibrillation/therapy; amiodarone; thoracic surgery; postoperative care.

Introduction

Atrial fibrillation is the most common arrhythmia in the postoperative period of cardiac surgery. It can occur due to multiple mechanisms¹.

The prevalence of this arrhythmia is approximately of 11% to 40% after coronary artery bypass grafting, but it can reach 50% of cases after valve surgery^2-4. It generally occurs between the first and fifth postoperative days, and it is more prevalent in patients over 65 years^5-8 of age.

Although spontaneous recovery of sinus rhythm may occur after 6 to 8 weeks⁹, this arrhythmia increases the time spent at the Intensive Care Unit (ICU), thus increasing the risk of nosocomial infections and hemodynamic instability¹⁰.

Among the main risk factors contributing to the onset of this arrhythmia are: old age, male gender, valve disease, increased atrial size, previous arrhythmias, chronic obstructive pulmonary disease, previous cardiac surgery, discontinuation of betablockers, use of digoxin, ventricular dysfunction and anemia¹¹.

It is known that the more risk factors, the greater the likelihood of atrial fibrillation in the postoperative period of cardiac surgery^12,13.

Prophylaxis of atrial fibrillation can be effectively performed using betablockers or amiodarone. On the other hand, the use of verapamil, digoxin and/or procainamide has not brought any benefits^12,14-17.

The efficacy of amiodarone is generally equivalent or greater than that of other drugs with the same indications, and there is no consensus regarding an optimum dose. It must be administered at the lowest possible dosage for the best intended effect, in order to avoid side effects that are generally dose-dependent. These are the reasons that made the authors of this study choose amiodarone, a class-III- antiarrhythmic drug. This drug is able to relax the smooth muscles and decrease both coronary and peripheral vascular resistance. Its effect prolongs the action potential and refractoriness of all cardiac fibers, without affecting the resting potential. It also reduces the sinus and atrioventricular (AV) rates and prolongs the AV conduction time. Additionally, it may trigger widening of QT interval and appearance of the U-wave. It can be indicated to treat ventricular arrhythmias, supraventricular paroxysmal tachycardia, fibrillation and atrial flutter. Moreover, it has also shown to be safe and effectivve in the prevention of atrial fibrillation in cardiac surgery postoperative period¹⁸.

Contrary to previous studies carried out with prophylactic treatment as early as in the preoperative period, there are no scientific studies demonstrating the benefits for high risk patients - who are therefore more susceptible to this arrhythmia - of pharmacological intervention started only in the postoperative period.

Methods

A prospective clinical study carried out between August 2004 and February 2005 in 68 patients, with 59% males and a mean age of 64 years. The patients underwent elective cardiac surgery (coronary artery bypass graft and/or valve surgery) with cardiopulmonary bypass.

The inclusion criteria were defined for patients presenting three or more risk factors for atrial fibrillation according to the literature (Table 1). This criterion was adopted from a statistical method (a multivariate analysis known as CART – Classification and Regression Tree) used in a previous study performed but not yet published, which stated that the presence of three or more risk factors among those listed in the literature would increase the incidence of this arrhythmia in the postoperative period of cardiac surgery.

After inclusion, patients were selected for a second randomization and were divided into two groups: Amiodarone (Group 1) and Control (Group 2). The exclusion criteria and the stratification model used to select patients are described in Tables 2 and 3, respectively.

On the first postoperative day, Group 1 patients received intravenous amiodarone at a dose between 600 mg and 900 mg, in 24 hours, followed by 400 mg/day, orally, until completion of seven-day treatment or hospital discharge. Group 2 patients followed the conventional treatment. Those with two or fewer risk factors and who would not be randomized for prophylaxis with the study medication were followed up until hospital discharge.

All patients were evaluated by means of electrocardiography and/or cardiac monitoring.

Statistical analysis - To evaluate the association between the occurrence of atrial fibrillation and risk factors we used the Fisher's exact test. Student's t test was used to compare the mean age of patients. The evaluation of amiodarone efficacy in the prevention of atrial fibrillation was carried out using Fisher's exact test. To compare the mean age between the groups (groups with up to two, groups with three or more risk factors, and groups with and without amiodarone), we used the variance analysis (ANOVA). The significance level in this study was 5% (p < 0.05).

Results

Of the 68 patients analyzed, 33 (49%) presented two or fewer risk factors and were followed up until hospital discharge. The remaining 35 (51%) patients who had three or more risk factors were randomized to receive or not amiodarone (Figure 1). In the group treated with amiodarone (n = 15), only one patient (7%) developed atrial fibrillation, whereas in the control group (n = 20), without prophylaxis, 14 patients (70%) developed arrhythmia (Table 4). Hence, it was observed that the group treated with amiodarone presented lower incidence of atrial fibrillation (significance level of 5%).

Among those patients not randomized to receive amiodarone for presenting two or fewer risk factors, only 8 patients (24%) presented atrial fibrillation, while 25 (76%) did not develop this condition. The age factor, already established in the literature as a relevant risk factor for the occurrence of atrial fibrillation in the postoperative period of cardiac surgery, was high in this case series, but there was no statistically significant difference between the groups (Tables 5 and 6). This finding probably occurred due to the advanced age of this population. Coronary artery bypass grafting was the most prevalent type of surgery, occurring in 79.7% of the cases analyzed (Table 7).

Discussion

Atrial fibrillation remains the most frequent complication in the postoperative period of cardiac surgery. According to the literature, its incidence ranges from 20% to 50% of cases, depending on the type of surgery (more frequent in valve surgeries)^1-4. This comorbidity prolongs hospital stay, which can lead to several clinical complications.

Patients with advanced age and the association of risk factors contribute to higher rate of atrial fibrillation in the postoperative period^15,19. In this study, the number of risk factors (three) was the determining factor in the selection of individuals for the prophylaxis - or not - with amiodarone.

Several clinical trials have evaluated the effectiveness of pharmacological interventions in reducing the incidence of this arrhythmia^18-22. However, these trials are generally not much statistically significant when the effects of these treatments on shorter hospital stay or on the occurrence of stroke are estimated to estimate. The main indication in the prophylaxis of atrial fibrillation in the postoperative period of cardiac surgery is still a reduced hospital stay and less complications, such as strokes^16,17.

Some randomized studies assessed the prophylaxis of this arrhythmia with drugs such as amiodarone, betablocker, sotalol and a biatrial pacemaker. The effectiveness of these drugs in the reduction of atrial fibrillation in the postoperative period of cardiac surgery was confirmed. However, a decreased incidence of strokes is still inconclusive¹⁵.

A study with intravenous administration of amiodarone up to 1 g/day compared with placebo has already shown safety and effectiveness of this drug in reducing atrial fibrillation in the postoperative period of cardiac surgery¹⁹. The efficacy of oral administration has also been analyzed in a placebo-controlled study at a dose of 2 g/day, from one to four days before surgery, and 400 mg/day up to seven days after surgery²⁰.

This study did not require previous admission of patients to show the effectiveness of amiodarone in the prevention of atrial fibrillation. The drug was initiated only on the first postoperative day in selected patients (high risk). Additionally, what differentiates this study from other previous studies is the fact that the dose of amiodarone used, both the loading dose (600 mg/24 hours to 900 mg/24 hours, intravenously) and the maintenance dose (400 mg/day orally until hospital discharge or completion of seven days), was lower; therefore, with fewer risks of adverse events to the patients.

The comparison between antiarrhythmic drugs, such as betablockers, sotalol and amiodarone, either as combination therapy or not, has also shown significant reduction in atrial fibrillation in the cardiac surgery postoperative period. In studies where the antiarhythmic agent used was amiodarone, there was a reduction in hospital stay^21,22.

In this study we also observed a shorter hospital stay in the group receiving prophylaxis with amiodarone, as compared to the control group (two and five days, respectively).

The intravenous administration of amiodarone to prevent atrial fibrillation in patients selected according to risk factors (such as advanced age, valve surgery, patients with chronic obstructive pulmonary disease and other risk factors analyzed) showed a good cost-effectiveness ratio favoring prophylaxis^23,24.

The efficacy of prophylactic amiodarone against atrial fibrillation in the postoperative period of cardiac surgery was confirmed in this study. The drug regimen used protected 93% of patients with three or more risk factors, whereas in the control group, 70% of individuals presented atrial fibrillation.

In addition to confirming the need of a more strict selection including patients at a higher risk (with three or more of the above-mentioned risk factors), this study showed the benefit of this drug treatment at a moderate dose, initiated only in the postoperative period.

Conclusion

It was demonstrated that amiodarone is safe and effective in prevention of atrial fibrillation in the postoperative period of cardiac surgery in patients with three or more risk factors for arrhythmia. This prophylaxis proved to be safe and it may reduce hospitalization periods as well as the clinical complications resulting from prolonged stay at ICU.

Potential Conflict of Interest

No potential conflict of interest relevant to this article was reported.

Sources of Funding

This study was funded with the investigator´s own resources.

Study Association with Graduate Work

This study is not associated with any graduation program.

References

Manuscript received November 23, 2006; revised received January 23, 2007; accepted March 13, 2007.

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Publication Dates

• Publication in this collection
  28 Aug 2007
• Date of issue
  July 2007

History

• Received
  23 Nov 2006
• Accepted
  13 Mar 2007