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Ann Thorac Surg 1997;63:1381-1382
© 1997 The Society of Thoracic Surgeons
Dr Thomas R. J. Todd (Toronto, Ont, Canada): I congratulate Dr Amar for a great study and a great presentation, and thank him for sending me the manuscript ahead of time.
This is a trial comparing one drug with another. And whenever you are looking at a trial, you not only have to look at the results that they got, you also have to look at how valid the trial was in its construction. And when you do that, there are a number of questions that you have to ask, and the answer to each of the questions should be a resounding "Yes."
Is the trial randomized? Yes, it was.
Was there a sample size calculation and a power calculation to enable you to determine how powerful this trial was? Unfortunately, the answer to that is no.
Was it controlled? Yes, it was. The control patients were not part of the randomization sequence, but it was controlled for the reasons that Dr Amar pointed out to you.
Is the population representative of the standard practice? Here I have to put a question mark. Half the patients throughout the trial had either an extrapleural pneumonectomy or an intrapericardial pneumonectomy. By my standards that is a high incidence of both of those, and I think it reflects the kind of difficult patient who frequently gets referred to Memorial.
To put this in perspective, I went back and looked at the same number of patients consecutively operated on in the last year in my own institution and looked at the incidence of supraventricular tachycardia, and indeed, it was 6.7%. Now, why is it so low? It may be because it was a random group of patients and it is anecdotal, and that is certainly possible. But I think it is also possible that it is great preoperative selection and it may be a lot of fluid restriction postoperatively, because our incidence used to be about 25% to 26%.
Were patients properly monitored? Absolutely. They were monitored extremely well, as Dr Amar pointed out to you. The only thing I would have liked to have seen were magnesium levels because we know that magnesium deficiency is very common after pneumonectomy and that magnesium sulfate is extremely efficacious in treating and preventing supraventricular tachycardia.
Now, there is a sixth question in here. Was it statistically significant? And unfortunately, as he told you, no, it was not for the whole group. In addition, the number of deaths, for some reason, in the digoxin group was much higher than in the diltiazem group. And in my own experience I have to tell you that in every patient who has a pneumonectomy that goes sour supraventricular tachycardia does develop. So if I take the deaths out and recalculate the data, the incidences of supraventricular tachycardia in the two groups become even closer together.
Now, having said all this in critique, I have to tell you I agree with Dr Amar and associates 100%. I think that diltiazem is superior prophylaxis to digoxin in preventing supraventricular arrhythmias after pulmonary resections. Indeed, there are at least a half a dozen trials in the literature comparing diltiazem with a variety of other antiarrhythmic agents in postoperative coronary bypass grafting. So I think it is valid; I think it is true. Unfortunately, it did not reach statistical significance.
But based on what I have said, I would like to ask Dr Amar three questions:
First, do you believe that your data are generalizable? In other words, do you believe that your data in this group of patients should tell us all to use diltiazem as routine prophylaxis after pneumonectomy?
Second, did you measure magnesium levels? And if you did, were you able to correlate magnesium deficiency to supraventricular tachycardia?
And third, am I right that supraventricular tachycardia developed in all the patients who died?
Dr Jack J. Curtis (Columbia, MO): I appreciate having a chance to comment on this paper, which I enjoyed. I have always been confused by the preponderance of literature in cardiac surgery that does not support or suggest that prophylaxis with digoxin prevents supraventricular dysrhythmias, whereas the preponderance of literature does support the use of digoxin to prevent supraventricular dysrhythmias in pneumonectomy.
At the University of Missouri we have reviewed prospectively 120 consecutive patients with pulmonary resections, including 36 patients with pneumonectomy, and found exactly the same incidence of supraventricular dysrhythmias, that is, about 28%, in those having pneumonectomy. This is twice as much as those having lesser resections.
So I want to ask Dr Amar, you have looked at a lot of potential predictors for development of dysrhythmias: Would you now speculate what the cause for supraventricular dysrhythmias is postoperatively and how you might explain why it would be different for pneumonectomy as opposed to other types of resection?
My last comment would be that it looks like that you monitored for 3 days. We found a significant incidence of supraventricular dysrhythmias in pulmonary resections occurring on the fourth postoperative day as well.
DR AMAR: I thank Dr Todd for his kind remarks and would like to respond to his questions. With respect to the incidence of SVD after pneumonectomy, I think that the most recent paper by Dr Harpole from Dr Sugarbaker's group shows a similar incidence of postoperative SVD to the one that we have found. Their study was a retrospective review of prospectively collected data. Similarly, Dr Pairolero's group from the Mayo Clinic [1] showed the exact same incidence of dysrhythmias after pneumonectomy as we did. So I believe that our data are consistent with those reports and are not institution specific.
With respect to magnesium levels, we did not consistently measure the levels in our patients, but anecdotally, most patients in whom SVD developed had magnesium levels drawn, which were found not to be low. We published an abstract on a separate group of patients undergoing mostly lobectomy and pneumonectomy documenting that magnesium levels were unchanged from preoperative values. I believe that this patient population is different from the cardiac surgery population and that magnesium may not be as useful.
With respect to the data on patients who had 30-day mortality, I am not sure how the data would be without those patients, but we did our analysis with intent-to-treat. I do not believe that all patients who had mortality sustained dysrhythmias, but perhaps due to the higher incidence of adult respiratory distress syndrome found in those patients they were more prone to the development of SVD.
With respect to Dr Curtis's question, I think that the most common predictor of supraventricular dysrhythmias after lung resection is older age. We are not sure at this point if it is age 75 years or greater, or 70, or 65, but I believe that in the general population not undergoing operation, age greater than 60 years has been demonstrated to be the age cutoff for risk of the development of atrial fibrillation.
In addition, the adrenergic response to operation is sustained for 3 or 4 days. And it is intriguing that dysrhythmias after operation, like myocardial ischemia and infarction, have been demonstrated to peak after 2 or 3 days after operation and not so much intraoperatively.
We believe the reason that pneumonectomy patients have an incidence of about 20% to 25% of dysrhythmias compared with the 15% seen after lobectomy is that, in addition to those previous risk factors and predictors, there is a greater resection of sympathovagal nerve fibers to the heart, thus increasing the risk of arrhythmia generation.
Reference
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