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Ann Thorac Surg 1997;63:1256
© 1997 The Society of Thoracic Surgeons
DR JOSEPH B. ZWISCHENBERGER (Galveston, TX): On review of this well-written manuscript, I am pleased to see a clinically relevant study of the heralded molecule nitric oxide as a selective pulmonary vasodilator in postoperative cardiac surgical patients. I also congratulate the Program Committee for selecting a timely, yet negative study for presentation.
This clinical study does not use matched controls or prospective randomization, but it does compare clinically pertinent groups with carefully controlled secondary variables such as anesthesia technique, ventilator management, and preload. Likewise, all the raw data are included for critical review. Notably, nitric oxide produced a significant reduction in pulmonary artery pressure in patients after coronary artery bypass grafting with no change in cardiac output, left atrial pressure, or mean systemic arterial pressure. These findings suggest, as you said, direct pulmonary vasodilation. However, nitric oxide failed to produce pulmonary vasodilation in patients with valvular heart disease.
I have only two questions. First, why did you choose 40 ppm of nitric oxide? I realize the potential for toxicity over time at higher doses, but brief exposure to 80 or 120 ppm may still produce a positive risk to benefit ratio. In the recently published prospective, randomized multicenter trial using nitric oxide for adult respiratory distress syndrome, 5 ppm showed the most promise as a useful dose.
Second, did the altitude in Denver perhaps affect the outcome of this study?
DR FULLERTON: Thank you, Dr Zwischenberger. We chose 40 ppm on the basis of some work we reported previously. We published a dose--response curve to inhaled nitric oxide in patients undergoing aortocoronary bypass grafting. In that study, we found that at greater than 20 ppm, there was no additional reduction in pulmonary vascular resistance. Therefore we chose 40 ppm because we had prior experience with this dose of nitric oxide and because in patients undergoing coronary artery bypass grafting, we had exceeded the ability to maximally vasodilate the pulmonary circulation with nitric oxide.
You correctly point out that it is possible, as with any negative study, to have a type II error. Perhaps had we increased the dose of nitric oxide, we might have seen some reduction in pulmonary vascular resistance in the patients undergoing valve replacement. The data are not published, but I can tell you anecdotally that we did try that in several patients and found no response to 80 ppm.
You also point out that there is some risk in terms of generating methemoglobin and nitrogen dioxide with the higher doses of nitric oxide. We thought that for the purposes of this type of study, it was important to avoid those sorts of toxicities. It may be that in a situation in the intensive care unit in which pulmonary vascular resistance is truly refractory, the risk to benefit ratio may shift in favor of using a higher dose.
As for the difference in altitude, that is a very interesting question, and I do not know the answer. My anecdotal observation since moving to Chicago is that pulmonary artery pressures and pulmonary vascular resistances are both lower after routine coronary artery bypass grafting procedures at sea level than they are at 5,000 feet in Denver. In Denver, these patients are still mechanically ventilated, and their inspired oxygen fractions are the same, but I suspect that patients who have lived at that altitude for some time may have some sort of a chronic elevation of pulmonary vascular resistance or change in their pulmonary vascular smooth muscle that alters the response to the injuries of cardiopulmonary bypass or conversely, alters the response to nitric oxide. We hope to generate some experience at sea level, and it will be interesting to compare the data.
Related Article
Ann. Thorac. Surg. 1997 63: 1251-1256.
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