By Carrio, M L Fortia, C; Javierre, C; Rodriguez, D; Farrero, E; Ricart, A; Castells, E; Ventura, J L
Aim. It was believed that amiodarone-related adverse respiratory effects were found only when receiving amiodarone on a long-term basis, but several reports seem to contradict this hypothesis. The aim of this study was to evaluate, in an intensive care unit (ICU), the possibility of acute respiratory toxicity induced by short-term amiodarone administration following cardiac surgery. Methods. We conducted a prospective clinical trial of 111 consecutive patients admitted to our ICU after cardiac surgery (basically, coronary artery bypass graft and/or valve surgery) and who received short- term prophylactic amiodarone treatment if they were considered at high risk of developing atrial fibrillation. We administered 900 mg/ day intravenously for the first 2 days and 600 mg/day on the following days of the ICU stay. The oxygenation index (Pa02/Fi02 ratio) was evaluated at admission, and then 24 and 48 h postsurgery. Results. One-hundred and two patients were included in the study (9 were excluded for bradycardia), and 25 received amiodarone treatment The Parsonnet and APACHE II scores differed slightly between the treated and nontreated groups. There were no significant differences between the treated and nontreated groups with respect to left atrial pressure, the number of packed red cells transfused or the oxygenation index at admission and 24 and 48 h postsurgery.
Conclusion. The short-term administration of amiodarone under the conditions of the present study does not seem to affect respiratory function.
Keywords: Amiodarone – Lung diseases, toxicity – Cardiac surgical procedures.
Amiodarone is a highly effective class III antiarrhythmic drug that is frequently used following cardiac surgery.1 It has numerous adverse effects,2 especially pulmonary toxicity,3’4 which has been documented even with low doses given for an average of 2 years.5
Traditionally it was believed that amiodarone-related adverse effects were only found in patients receiving amiodarone on a long- term basis, but several reports seem to contradict this hypothesis:
1. A study of 67 patients undergoing an automatic defibrillator implantation or subendocardial resection in which some of them developed adult respiratory distress syndrome (ARDS) after as few as 7-14 days of amiodarone administration; however, most of them had already been receiving amiodarone on a long-term basis.6
2. Another study of 32 patients undergoing pneumectomy and receiving a 150 mg e.v. bolus of amiodarone
3. In a retrospective review of 10 patients who died in the intensive care unit (ICU) from ARDS and who were examined postmortem, 3 had received amiodarone for > 48 h and there was histologic evidence of lipoid pneumonia, presumably from amiodarone.8 It has thus been postulated that amiodarone can play a potentially important role in inducing respiratory failure in some ICU patients such as those undergoing cardiac surgery, probably because in this case the lungs have also been exposed to physical insults.9
The American-European Consensus Conference Committee 10 considered the oxygenation index (PaO^sub 2^/FiO^sub 2^ ratio), in the absence of left atrial pressure > 18 mm Hg, to be the best clinical marker of lung injury.
The aim of the present study was to investigate, by means of the oxygenation index, the possibility that acute respiratory toxicity could be induced by shortterm amiodarone administration following cardiac surgery; the study was conducted in the ICU, a clinical scenario where amiodarone is often used.
Materials and methods
We studied a series of 111 consecutive patients admitted to our ICU after cardiac surgery, basically coronary artery bypass graft (CABG) and/or valve surgery, and who received prophylactic amiodarone treatment if they were considered at high risk of developing atrial fibrillation (AF), in accordance with previous findings.11 The inclusion criteria were: had not taken amiodarone during the previous week; being in sinus rhythm > 65 bpm; and without either atrioventricular block or systolic blood pressure
The protocol was approved by the Ethics Committee of our hospital.
The variables evaluated in the previous study to identify those patients at high risk of AF were: sex, age, previous AF at any time, left ventricular ejection fraction, left ventricular hypertrophia (both in the echocardiography), treatment in the previous week with a beta-blocker or with amiodarone, mitral valve procedure, aortic valve procedure, coronary bypass, cardiopulmonary bypass, aortic clamp more than 60 min, cardiopulmonary bypass > 100 min, complete coronary revascularization (no significant coronary stenosis without being revascularized) and perioperative myocardial infarction (new pathologic Q waves in two or more contiguous ECG leads and plasmatic troponine I concentration at 24 h of admission >15 [mu]g/L).
In addition to the above variables we recorded: the Parsonnet score for cardiac surgery,12 the APACHE II severity score,13 the oxygenation index (PaO^sub 2^/FiO^sub 2^ ratio) at admission and at 24 and 48 h postsurgery, the left atrial pressure and the number of packed red cells transfused. We did not take into consideration the chest radiography as it cannot be applied consistently by experienced clinicians.14,15
Table I.-Results for the amiodarone and non-amiodarone treatment groups.
Statistical analysis
The chi^sup 2^ method was used for qualitative variables and analysis of variance for quantitative variables. Summary data are expressed as mean +- (SD) or percentages of patients. A value of P
Results
One hundred and two patients were included in the study: 78 men and 24 women; 25 received the amiodarone treatment and 77 did not. The Parsonnet and APACHE II scores differed slightly (but not significantly) between the treated and nontreated groups (Parsonnet 10.0+-5.7 in the amiodarone group and 6.9+-6.6 in the non amiodarone group; APACHE II 11.4+-4.9 in the amiodarone group and 10.9+-4.7 in the non amiodarone group).
There were no significant differences between the treated and nontreated groups with respect to the respiratory variables: the oxygenation index at admission and at 24 and 48 h postsurgery. Neither were there significant differences between the treated and nontreated groups in terms of left atrial pressure at admission and 24 h postsurgery, or in the number of packed red cells transfused (Table I).
Differences in the incidence of risk factors prior to the intervention were observed between the amiodarone and non amiodarone treatment groups, since they were used to decide whether to apply amiodarone prophylaxis. The amiodarone group contained a significantly higher number of patients age older than 60 years (84% vs 58.4%, P=0.029), a greater incidence of patients with left ventricular hypertrophy (44% vs 16.9%, P=0.013), and more aortic valve surgery (64.0% vs 16.9%, P=0.000). In contrast, the treatment group included fewer coronary revascularization patients (36% vs 84.4%, P=0.000). A cardiopulmonary bypass time over 100 min was more common in the amiodarone treatment group, although the difference was at the limit of significance (52.0% vs 28.6%, P=0.051).
Although the amiodarone group had worse baseline clinical conditions, we found no significant difference with respect to the evolution of the oxygenation index between the treatment and nontreatment groups. At admission to the ICU, the amiodarone group presented a lower oxygenation index (not significant), but the evolution at 24 and 48 h was favorable (Figure 1).
Discussion
The patients differed in terms of the variables conferring a different risk for AF, this being the subject of the previous study,11 and there were some differences between the amiodarone and non amiodarone groups in terms of the Parsonnet score and, to a minimal extent, in the APACHE II score. The Parsonnet score was worse in the amiodarone group, indicating an expectation of poorer clinical outcome, although not specifically for respiratory function.
The oxygenation index has become a widely accepted measure 16 due to its sensitivity, objectivity and ease to recording. The lack of differences in the oxygenation index at different times of evolution seems to indicate that selective prophylaxis of AF with amiodarone n does not produce any noticeable deterioration in respiratory function. The respiratory insufficiency that is sometimes observed in the short term with amiodarone may thus be related to previous administration, longer administration times 6-8 or more time breathing high inspired oxygen (FiO^sub 2^), as reported in several studies.17-19
Figure 1.-Evolution of the oxygenation index in the amiodarone treatment group and non-amiodarone group. Whatever the case, the lack of noticeable negative respiratory effects, under the conditions of the present study, seems to indicate that amiodarone can be administered immediately after cardiac surgery without running the risk of additional and significant respiratory problems. The present results support the general impression in the ICU setting as regards the safety of amiodarone, mostly in the absence of high FiO^sub 2^.17
Conclusions
In sum, when administering the standard dose of amiodarone on a short-time basis following cardiac surgery, we detected no deterioration in respiratory function.
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M. L CARRIO 1, C. FORTIA 1, C. JAVIERRE 2, D. RODRIGUEZ 1, E. FARRERO 1, A. RICART1
E. CASTELLS 3, J. L. VENTURA1
1 Critical Care Service
University Hospital of Bellvitge, Barcelona, Spain
department of Physiological Sciences II
University of Barcelona, Barcelona, Spain
3Cardiac Surgery Service
Hospital Universitari de Bellvitge
Barcelona, Spain
Received on September 15, 2006.
Accepted for publication on June 7, 2007.
Address reprint requests to: M. L. Carrio, Critical Care Service, Hospital Universitari de Bellvitge, C/ Feixa Llarga s/n, 08907 L’Hospitalet de Llobregat, Barcelona, Spain. E-mail: [email protected]
Copyright Edizioni Minerva Medica Aug 2007
(c) 2007 Journal of Cardiovascular Surgery. Provided by ProQuest Information and Learning. All rights Reserved.
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