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Ann Thorac Surg 1997;64:1387-1388
© 1997 The Society of Thoracic Surgeons


Discussion

Discussion

See also page 1381.

DR WILLIAM A. BAUMGARTNER (Baltimore, MD): I congratulate you on a terrific study and for getting the leukocyte filters to work. We have had an interest in this for many years. In a clinical adult setting, we have never been able to reduce leukocytes to the level that I think you need to demonstrate a reduction in oxygen free radical release.

I have a couple questions. We saw that there was a correlation with a rise in white blood cell counts during filtration once rewarming took place. I wonder if you saw that in your clinical study?

Second, how long were your patients on bypass, and what were your mean bypass runs? Do you think that the reduction in white blood cells in your model was a result of the size of the patients, as opposed to some other mechanism?

My last question is, did you look at any other evidence that led to a decrease in the overall inflammatory state usually initiated by cardiopulmonary bypass, such as cytokine production or lung function, which at least experimentally has enjoyed a really beneficial effect of reducing the number of white blood cells? I enjoyed your paper very much.

DR ALLEN: Thank you for your comments. We are well aware of your previous work, and it helped stimulate our interest in this subject. The question of how to obtain low white blood cell counts in patients is an excellent one, and it is extensively addressed in the manuscript. We all recognize that leukocytes are deleterious, but because most filters are unable to effectively reduce the white blood cell count, they have only been sporadically used. However, we did several things in this study that allowed us to obtain low white blood cell counts. Because we used blood to prime the bypass circuit, we prefiltered the blood using a Pall RC-400 filter in all patients. This resulted in white blood cell counts in the cardiopulmonary bypass circuit of almost zero. Because we believe the reoxygenation injury occurs early, initiating cardiopulmonary bypass with very low white blood cell counts is very important. Next, instead of using one of the standard arterial white blood cell filters, we used one designed for the cardioplegia circuit (Pall-BC-1) but placed it in the arterial line. The company says these filters can be used at flows of up to 500 mL/min, but we used them at flows of up to 700 mL/min. However, this meant they could only be used in patients weighing less than 4 kg. The advantage of this filter is that it is very effective and removes almost all white blood cells during one pass. The problem is that it gets filled up over time. In contrast, the Pall LG-6 leukocyte filter is specifically designed to be used in the arterial line of the bypass circuit and it can accommodate flows of up to 6 L/min. However, it is not very effective at higher flow rates, removing white blood cells very slowly over time. This probably explains why most investigators have not been able to significantly reduce white blood cell counts in adult patients. We measured the pressure across the BC-1 filter during cardiopulmonary bypass, and it did not increase during the 30 to 60 minutes it was in place. We then removed it from the bypass circuit by redirecting the flow through a standard arterial filter for fear of increased resistance. However, we never had any problems in this study, or in our laboratory, where the filter was left in place for up to 90 minutes. I should mention that although the BC-1 filter cannot be used at higher flow rates, we still leukodeplete the bypass prime in all children, as this has been shown to be beneficial, even when used without an arterial line filter. We have considered using a Pall LG-6 leukocyte-depleting filter in smaller children, say those weighing between 5 and 15 kg, because the removal of white blood cells by this filter is flow dependent. Therefore, at low flow rates, this filter may be more effective than it is in adults.

As you have stated, the white blood cell counts do rise over time, and we found that they were back to normal by the time the patients arrive in the intensive care unit (see Figures 1A and 1B in the article).

We did not assay the myocardial tissue for other evidence of inflammation, because most of our patients were infants or neonates and the amount of tissue that could be sampled was limited. This is especially true in our patients because we took biopsy specimens both before and after bypass to make comparisons. However, as you have mentioned, there is abundant evidence that many inflammatory substances are reduced if the white blood cells are effectively filtered out.

DR JOHN E. MAYER, JR (Boston, MA): This makes me wonder a little bit about what the effects of chronic hypoxia or cyanosis are on neutrophil function and on neutrophils in general. Is there any information about that that you know of?

DR ALLEN: I am not currently aware of the effects of chronic hypoxia on neutrophil function. Several studies have shown that neutrophils can be deleterious after ischemia, and this study shows that neutrophils may also be detrimental after chronic hypoxia. Chronic hypoxia does, however, affect the immune system as well as increase neutrophil adherence to endothelial cells. This would imply that hypoxia increases the ability of the neutrophil to cause injury.

DR MAYER: The effect of chronic cyanosis on endothelial cells would be another interesting question.

DR ALLEN: Experimental studies have shown that endothelial function may be preserved, but I am unaware of any clinical studies that have specifically examined endothelial cell function after chronic hypoxia. However, the vascular endothelial cell does increase neutrophil adherence during hypoxia, thereby increasing the chance for injury.

DR MAYER: And one last question. Did you have any clinical impressions or do you have any data on what the impact was on myocardial or other organ system function?

DR ALLEN: I do not have any firm data, but I do have several clinical impressions, both my own and those of our pediatric intensivists. This group of infants had a wide variety of diagnoses, and most were very sick with severe congenital abnormalities. For instance, 6 patients had hypoplastic left heart syndrome. This would be very difficult to compare with, say, tetralogy of Fallot. It was therefore impossible for us to compare the hemodynamics or other organ system function in such a small, diverse group of patients. However, our intensivists always seemed to be able to tell us which patients had undergone white blood cell filtration. They would say "This must be a white blood cell–filtered patient, because the oxygenation and pulmonary compliance are excellent." We also seemed to have fewer problems with postoperative pulmonary hypertension and lower requirements for inotropic support. So, anecdotally we noticed a significant difference, but I have no hard data to support these observations.

DR DUKE E. CAMERON (Baltimore, MD): I think this subject of the modification of perfusion for the cyanosed infant is fascinating. And many of the things we have been doing for years may not be right, the most obvious being hyperoxic reperfusion after a period of aortic cross-clamping. We have known for years that oxygen on reperfusion is detrimental, yet we still have the arterial blood PO2 up to 300 or 400 mm Hg when the cross-clamp comes off.

I would like to take a quick survey, if I could, among those who do operations on cyanosed infants, on whether you modify your perfusion in terms of the oxygen concentration or PO2 level on bypass or use leukocyte filtration. Let me ask first if you could raise your hand to show if you do pediatric heart operations? (Audience responds)

DR CAMERON: And how many do not modify perfusion for cyanosed infants? (Audience responds)

DR CAMERON: And those who do? (Audience responds)

DR CAMERON: I think there is a slight majority of those who, at least up to today, have not modified their perfusion practice. Thank you very much, Dr Allen.


Related Article

Detrimental Effects of Cardiopulmonary Bypass in Cyanotic Infants: Preventing the Reoxygenation Injury
Bradley S. Allen, Shaikh Rahman, Michel N. Ilbawi, Michael Kronon, Kirk S. Bolling, Ari O. Halldorsson, and Harold Feinberg
Ann. Thorac. Surg. 1997 64: 1381-1388. [Abstract] [Full Text]




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