Interactive Cardiovascular and Thoracic Surgery 3:656-662(2004)
© 2004 European Association of Cardio-Thoracic Surgery
Best evidence topic - Thoracic general |
Is there a role for prophylaxis against atrial fibrillation for patients undergoing lung surgery?
Vivek Shrivastava,
Brian Nyawo,
Joel Dunning* and
Graham Morritt
Department of Cardiothoracic Surgery, James Cook University Hospital, Marton Road, Middlesbrough, UK
* Corresponding author. Address: Department of Cardiothoracic Surgery, Freeman Hospital, Freeman Road, Newcastle upon Tyne NE7 7AZ, UK. Tel.: +44-780-1548-122. (E-mail: joeldunning{at}doctors.org.uk).
Received July 30, 2004;
accepted August 3, 2004
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Abstract
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A best evidence topic in thoracic surgery was written according to a structured protocol. The question addressed whether prophylactic anti-arrhythmic drugs may prevent atrial fibrillation (AF) following lung resection. Altogether 457 papers were found using the reported search, of which 14 presented the best evidence to answer the clinical question. The author, journal, date and country of publication, patient group studied, study type, relevant outcomes, results and study weaknesses of these papers are tabulated. We identified single randomized trials that have demonstrated a benefit for Diltiazem, Bupivacaine epidural and magnesium for prophylaxis against AF in patients undergoing non-cardiac thoracic surgery, with a number needed to treat of between 4 and 8 with these regimes.
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1. Introduction
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A best evidence topic was constructed according to a structured protocol. The protocol is fully described in the ICTVS [1].
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2. Clinical scenario
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You are the thoracic registrar assessing a patient scheduled for lobectomy or possibly pneumonectomy the following day. Whilst explaining the risks of the operation you mention the risk of developing post-operative atrial fibrillation (AF), which increases with the extent of lung resected. You tell him that the reported incidence of AF post-lung resection varies, with the lowest after a wedge resection (2–4%) increasing to 10–15% after lobectomy and 20–30% post-pneumonectomy. The patient asks whether you will be giving him any drugs to stop him getting AF. Your consultant never uses prophylaxis against AF for thoracic procedures, but you wonder whether you should be giving something, as all your cardiac patients get Beta-blockers.
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3. Three part question
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In [patients undergoing lung resection] is there a role for [prophylactic anti-arrhythmics] to reduce the incidence of [post-operative atrial fibrillation]?
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4. Search strategy
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Medline 1966–Jul 2004 and EMBASE 1980–Jul 2004 using the OVID interface
[Pneumonectomy.mp OR exp pneumonectomy/ OR lobectomy.mp OR lung surgery.mp OR Thoracic surgery.mp OR lung resection.mp OR pulmonary surgery.mp ] AND [atrial fibrillation.mp OR exp Atrial Fibrillation/OR Atrial flutter.mp OR AF.mp OR exp Atrial flutter/ OR exp Tachycardia, Supraventricular/ OR SVT.mp OR arrhythmia$.mp ]
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5. Search outcome
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289 papers were found in MEDLINE and 168 papers were found in EMBASE of which 14 papers were deemed to be relevant [2–15]. These are presented in Table 1.
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6. Comments
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Randomized controlled trials were identified that studied the prophylactic effects of diltiazem, B-blockers, digoxin, verapamil, flecainide, amiodarone, magnesium and epidural anaesthesia. However, both the quality and sizes of these studies varied greatly, ranging from 330 patients to only 30 patients.
The strongest paper was by Amar et al. [2] that evaluated prophylactic diltiazem. They demonstrated a significant reduction in post-operative AF in lung resection patients with the incidence of 26% in control patients reduced to 14% in diltiazem patients. Furthermore, using a loading dose of 0.25mg/kg of diltiazem administered over 30min followed by a continuous infusion (0.1mg/kg/h) for 18–24h there were no significant increased adverse reactions to drug treatment in this study. This well-conducted study gives a number needed to treat of eight to prevent one episode of AF.
This group also published a paper in 1997 comparing diltiazem with digoxin [3] in 70 patients. The incidence of AF reduced from 31% to 14%, but due to the small sample size this was not a significant finding (P=0.09).
Digoxin has also been studied in comparison to placebo. Ritchie et al. performed a study in 1990 [4] in 140 patients undergoing pneumonectomy, lobectomy, or oesophagectomy, using an unblinded design. The incidence of AF was 36% in the control group and 45% in the digoxin group. They further published two papers, but these are likely to be subset analyses of this first paper [5,6]. Thus, it seems that digoxin has no role in the prophylaxis of AF in lung surgery.
A second large study was performed by Van Mieghem in 1996 [7] in 199 patients in an unblinded PRCT. They evaluated prophylactic verapamil and found that the incidence of AF reduced from 15% to 8%. Unfortunately, this was a non-significant finding and more significantly 23% of patients experienced bradycardia or hypotension as a result of verapamil and had to be withdrawn from the study.
Interestingly Van Mieghem's study was originally a three-arm trial of verapamil, amiodarone and controls. However, it was stopped early after three patients in the amiodarone group developed Adult Respiratory Distress Syndrome (ARDS), with two patients dying of this complication. They then performed a retrospective review of 552 lobectomies and pneumonectomies [8]. Fifty-five of these patients received amiodarone and six got ARDS (11%), but of 497 patients who did not receive amiodarone only 9 (1.8%) got ARDS.
In contrast to this alarming finding with amiodarone, Lanza et al. in 2003 performed a retrospective cohort study of their database, as one of their surgeons always gave 200mg tds orally of amiodarone to his patients while in hospital. They found that the control group had an incidence of 33% but only 10% of the amiodarone group got AF. They reported no complications in this study, but it was retrospective, and small. In addition the dose of amiodarone that caused ARDS was much larger in the Van Meighem study, with 1200mg/24h being given i.v. for 3 days [8]. Therefore, while there is a possibility that amiodarone may reduce AF if given prophylactically, there is a real risk that it will also cause ARDS and thus cannot be recommended at the present time.
Flecainide was examined in two studies by Borgeat [9,10], with 30 patients in each study. Both studies showed reductions from 40 to under 10% in AF, but as there were only 15 patients in each treatment group these findings were on the margins of significance.
Beta-blockers have also been studied. Jakobsen [11] performed a study with 15 patients randomized to metoprolol and 15 controls. They showed a significant reduction from 40 down to 7%. Bayliff et al. [12] randomized 49 patients to propranolol and 50 to controls. They unfortunately only showed some trends towards significance and the propranolol group suffered a 50% rate of hypotension.
One study looked at morphine versus bupivacaine given by epidural in 50 patients [13]. The incidence of AF reduced from 28% in the morphine group to 4.3% in the bupivacaine group and there were no excess of side effects in this group.
Finally, Terzi et al. [14] performed an unblinded PRCT in 194 patients, allocating 93 patients to prophylactic magnesium. They demonstrated a reduction from 23% to an incidence of 10% of AF in the magnesium group, without side effects.
Thus in summary digoxin and verapamil do not reduce the incidence of AF. Amiodarone may cause ARDS, and thus cannot be recommended, and flecainide and beta-blockers have been inadequately studied to make safe recommendations. Single randomized controlled trials have demonstrated evidence for bupivacaine epidural, magnesium and diltiazem for the prophylaxis of AF in patients undergoing non-cardiac thoracic surgery.
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7. Clinical bottom line
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Single randomized trials have demonstrated a benefit for diltiazem, bupivacaine epidural and magnesium for prophylaxis against AF in patients undergoing non-cardiac thoracic surgery, with a number needed to treat of between 4 and 8 with these regimes.
doi:10.1016/j.icvts.2004.08.002
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References
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- Terzi A, Furlan G, Chiavacci P, Dal Corso B, Luzzani A, Dalla Volta S. Prevention of atrial tachyarrhythmias after non-cardiac thoracic surgery by infusion of magnesium sulfate Thorac CardioVasc Surg 1996;44:300-303.[Medline]
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- Lanza LA, Visbal AI, DeValeria PA, Zinsmeister AR, Diehl NN, Trastek VF. Low-dose oral amiodarone prophylaxis reduces atrial fibrillation after pulmonary resection Ann Thorac Surg 2003;75:223-230.[Abstract/Free Full Text]
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Abstract
1. Introduction