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The Membrane versus Bubble Oxygenator Controversy
The Membrane versus Bubble Oxygenator Controversv J
E. Converse Peirce, 11, M.D. On the basis of a prospective randomized study of membrane and bubble oxygenators that resulted in few differences in 60 consecutive operations in infants and children, Sade and coworkers (this issue, p 502) concluded that the theoretical physiological advantages of membrane oxygenators should not be a factor in deciding which type of device to use. Before accepting this as a valid conclusion, it is necessary to consider if there are very undesirable effects of clinical perfusion, whether these are likely to be moderated by using a membrane device, and if the numbers of patients and the tests chosen by Sade and associates were appropriate and likely to justify their sweeping conclusion. In the clinical setting, postperfusion damage of vital organs such as the kidney, lung, and brain has not been uniformly recognized, but many reports do show that such problems are important [l, 3, 6-8, 12, 13, 151. For example, Yeboah and associates [15] reported a 30% incidence of postoperative renal impairment after open-heart operation, and Javid and colleagues [7] reported that at the time of discharge from the hospital, 15% of patients who had had open-heart operation had neurological abnormalities. Since there is much particle and bubble traffic in the arterial line [3, 4, 10, 121 and since 85% of patients not surviving openheart operation have been found by Hill and colleagues [61 to have gross or microscopic changes indicative of emboli in organs at postmortem examination, the oxygenator is clearly implicated. Further strong evidence is provided by the recent report of Stoney and colleagues [13], who obtained, by means of a survey, postperfusion data not heretofore available. There were 429 recognized instances of arterial air embolism, 472 problems of disseminated intravas-
cular coagulation, and 124 examples of outright oxygenator failure in 374,819 operations carried out in North America from 1972 through 1977. These accounted for approximately 1 death or permanent injury per 1,000 patients. The overwhelming evidence is that membrane devices produce less trauma to formed elements and proteins of blood, induce fewer bubbles and solid particles, and consequently are responsible for less organ damage than nonmembrane ones [3, 6, 9, 11, 141. For example, hemolysis is an order of magnitude greater with bubble oxygenators than with membrane oxygenators, and there is a significantly greater loss of platelets and white blood cells also [9]. Red blood cell ghosts, damaged platelets, and white blood cells are demonstrably pathogenic [2, 6, 141. There is strong presumption that oxygenator-induced protein denaturation plays a part in perfusion pathology [ll].Clinical evidence indicates that the bubble and particle traffic in the arterial perfusion line has pathophysiological import and is greater when a bubble oxygenator is used [3, 61. Furthermore, there is very persuasive evidence that the level of trauma from the membrane oxygenator is clinically tolerable for many days while the safe perfusion period with the bubble oxygenator is measured in hours [lll. On the basis of previously published clinical comparisons between membrane and bubble oxygenators, discussed by Sade and coworkers, it is clear that even sensitive indices of trauma, such as plasma hemoglobin, platelet counts and function, and white blood cell counts, will not be very different unless the cardiotomy suction is greatly moderated or eliminated. This is, of course, difficult in a group of patients with congenital heart disease, particularly when 40% are of the cyanotic type. It is unfortunate that in the study under From the Department of Surgery, The Veterans Adminis- scrutiny, the volume of cardiotomy suction was tration Medical Center, Bronx, and the Mount Sinai School of Medicine, the City University of New York, 100th St and not monitored nor was the degree of trauma in the cardiotomy return blood determined. The 5th Ave, New York, NY 10029. 497
0003-4975/80/060497-03$01.25 @ 1980 by E. Converse Peirce, I1
498 The Annals of Thoracic Surgery Vol 29
No 6 June 1980
use of microporous filters in the cardiotomy return line or in the arterial line could have muted differences produced by the oxygenators [4, 10, 121, but the authors do not state whether such filters were used. It is noteworthy that hemolysis was significantly less and that platelet counts were higher at all time intervals, thereby indicating that blood trauma was almost certainly less in the membrane group. This has been the case with most clinical comparisons of oxygenators. Many of the tests employed by Sade and colleagues were predictably too insensitive or primarily dependent for their postperfusion differences on factors other than the type of oxygenator, such as the trauma of the operation or hemodilution. Also too insensitive are blood urea nitrogen (BUN),prothrombin time, partial thromboplastin time, urine volume, and intelligence tests. Variables related to blood replacement are sensitive indices of operation but not of oxygenator differences. The hematocrit, total protein, albumin, glucose, fibrinogen, complement, and IgG show large changes as a result of hemodilution but are nondiscriminating as far as the oxygenator is concerned. Some of the tests would not reasonably be expected to show differences unless preoperative control values were paired with postoperative ones. This is the case with creatinine clearance, shunt fraction (preoperative values would not be useful in the cyanotic group), pulmonary compliance, intelligence tests, and behavioral indices. Even if paired, most of these would not be very useful tests because they are insensitive or not likely to vary with perfusion damage. For example, in a recent study [5] of renal failure after open-heart operation, 9 patients who later experienced renal failure had early creatinine clearance values of 67 k 12 ml per minute while the values for 30 patients without renal dysfunction were 96 k 12 ml per minute. These values are not greatly dissimilar to those of the present study and are not significantly different. In the same study, free-water clearance values were much more useful. They became significantly different during perfusion and remained so throughout an interval of eighteen hours, accu-
rately predicting the later rise in BUN and creatinine in those patients in whom renal failure developed. Although the behavioral tests in the present study showed significantly altered scores postoperatively, it would be necessary to use these tests with other surgical populations before concluding that they are suitable for detecting perfusion-related problems, and they should, of course, be paired. An additional possible point of confusion is the fact that priming of the membrane device used may influence the degree of blood trauma and initial bubble embolization. Experience and careful attention to the details, which include use of vacuum in the gas phase and flushing with carbon dioxide, are important. These things are not mentioned in the study of Sade and coworkers and could easily not have been done optimally in such a small series. Finally, since identifiable postperfusion problems are relatively infrequent and since differences in factors such as age, size, extent of cardiac lesion, and cardiotomy volume are probably large, it is unlikely that 60 patients, no matter how well studied and analyzed using contemporary tests, could provide any firm comparative conclusions. Sade and associates present no evidence indicating that the membrane oxygenator is pathophysiologically inferior to the bubble oxygenator. What little positive information there is in this study, especially the reduced hemolysis, favors the membrane lung as being less traumatic. In addition, it is correctly pointed out that the membrane oxygenator is probably safer, providing increased protection against gas embolization. A shift to the membrane oxygenator, properly employed, could produce a real decrease in morbidity, organ damage, and death, but this would be apparent only after analysis of large numbers of patients. The slowly increasing use of membrane devices, greater attention to moderating cardiotomy suction, appropriate blood filtration, and the development of more sensitive and specific tests for perfusion damage should make truly meaningful comparisons possible eventually. In sum, although difficult to prove at the
499
Editorial: Peirce: Membrane versus Bubble Oxygenator
present time, there are good reasons to regard the membrane oxygenator as superior and worthy of clinical use. Other things, i.e., cost and gross device function, being reasonably equal, the membrane oxygenator should be preferred.
References 1. Ashmore PG, Svitek V, Ambrose P: The inci-
2.
3.
4.
5.
dence and effects of particulate aggregation and microembolism in pump-oxygenator systems. J Thorac Cardiovasc Surg 55:691, 1968 Bernstein EF, Castaneda AR, Varco RL: Some biologic limitations to prolonged blood pumping. Trans Am SOCArtif Intern Organs 11:118, 1965 Carlson RG, Lande AJ, Landis B, et al: The Lande-Edwards membrane oxygenator during heart surgery: oxygen transfer, microemboli counts, and Bender-Gestalt visual motor test scores. J Thorac Cardiovasc Surg 66:894, 1973 Connell RS, Page US, Bartley TD, et al: The effect on pulmonary ultrastructure of Dacron-wool filtration during cardiopulmonary bypass. Ann Thorac Surg 15:217, 1973 Heimann T, Brau S, Sakurai H, et al: Urinary osmolal changes in renal dysfunction following open-heart operations. Ann Thorac Surg 22:44, 1976
6. Hill JD, Aguilar MJ, Baranco A, et al: Neuropathological manifestations of cardiac surgery. Ann Thorac Surg 7:409, 1969 7. Javid H, Tufo H, Najafi H, et al: Neurological abnormalities following open heart surgery. J Thorac Cardiovasc Surg 58:502, 1969 8. Lee WH Jr, Miller W Jr, Rowe J, et al: Effects of extracorporeal circulation on personality and cerebration. Ann Thorac Surg 7:562, 1969 9. Mortensen JD: Evaluation of tests for blood damage produced by oxygenators. Trans Am SOC Artif Intern Organs 23:747, 1977 10. Page US, Bigelow JC, Carter CR, et al: Emboli (debris) produced by bubble oxygenators: removal by filtration. Ann Thorac Surg 18:164, 1974 11. Peirce EC 11: Is the blood-gas interface of clinical importance? (editorial.) Ann Thorac Surg 17:526, 1974 12. Solis RT, Noon GP, Beall AC Jr, et al: Particulate microembolism during cardiac operation. Ann Thorac Surg 17:332, 1974 13. Stoney WS, Alford WC Jr, Burrus GR, et al: Air embolism and other accidents using pump oxygenators. Ann Thorac Surg 29:336, 1980 14. Ward BD, Berry GL: Comparative platelet function during prolonged extracorporeal bubble and membrane oxygenation. Am SECT Proceedings 3:6, 1975 15. Yeboah ED, Petrie A, Pead JL:Acute renal failure and open heart surgery. Br Med J 1:415, 1972
E. Converse Peirce, 11, M.D. On the basis of a prospective randomized study of membrane and bubble oxygenators that resulted in few differences in 60 consecutive operations in infants and children, Sade and coworkers (this issue, p 502) concluded that the theoretical physiological advantages of membrane oxygenators should not be a factor in deciding which type of device to use. Before accepting this as a valid conclusion, it is necessary to consider if there are very undesirable effects of clinical perfusion, whether these are likely to be moderated by using a membrane device, and if the numbers of patients and the tests chosen by Sade and associates were appropriate and likely to justify their sweeping conclusion. In the clinical setting, postperfusion damage of vital organs such as the kidney, lung, and brain has not been uniformly recognized, but many reports do show that such problems are important [l, 3, 6-8, 12, 13, 151. For example, Yeboah and associates [15] reported a 30% incidence of postoperative renal impairment after open-heart operation, and Javid and colleagues [7] reported that at the time of discharge from the hospital, 15% of patients who had had open-heart operation had neurological abnormalities. Since there is much particle and bubble traffic in the arterial line [3, 4, 10, 121 and since 85% of patients not surviving openheart operation have been found by Hill and colleagues [61 to have gross or microscopic changes indicative of emboli in organs at postmortem examination, the oxygenator is clearly implicated. Further strong evidence is provided by the recent report of Stoney and colleagues [13], who obtained, by means of a survey, postperfusion data not heretofore available. There were 429 recognized instances of arterial air embolism, 472 problems of disseminated intravas-
cular coagulation, and 124 examples of outright oxygenator failure in 374,819 operations carried out in North America from 1972 through 1977. These accounted for approximately 1 death or permanent injury per 1,000 patients. The overwhelming evidence is that membrane devices produce less trauma to formed elements and proteins of blood, induce fewer bubbles and solid particles, and consequently are responsible for less organ damage than nonmembrane ones [3, 6, 9, 11, 141. For example, hemolysis is an order of magnitude greater with bubble oxygenators than with membrane oxygenators, and there is a significantly greater loss of platelets and white blood cells also [9]. Red blood cell ghosts, damaged platelets, and white blood cells are demonstrably pathogenic [2, 6, 141. There is strong presumption that oxygenator-induced protein denaturation plays a part in perfusion pathology [ll].Clinical evidence indicates that the bubble and particle traffic in the arterial perfusion line has pathophysiological import and is greater when a bubble oxygenator is used [3, 61. Furthermore, there is very persuasive evidence that the level of trauma from the membrane oxygenator is clinically tolerable for many days while the safe perfusion period with the bubble oxygenator is measured in hours [lll. On the basis of previously published clinical comparisons between membrane and bubble oxygenators, discussed by Sade and coworkers, it is clear that even sensitive indices of trauma, such as plasma hemoglobin, platelet counts and function, and white blood cell counts, will not be very different unless the cardiotomy suction is greatly moderated or eliminated. This is, of course, difficult in a group of patients with congenital heart disease, particularly when 40% are of the cyanotic type. It is unfortunate that in the study under From the Department of Surgery, The Veterans Adminis- scrutiny, the volume of cardiotomy suction was tration Medical Center, Bronx, and the Mount Sinai School of Medicine, the City University of New York, 100th St and not monitored nor was the degree of trauma in the cardiotomy return blood determined. The 5th Ave, New York, NY 10029. 497
0003-4975/80/060497-03$01.25 @ 1980 by E. Converse Peirce, I1
498 The Annals of Thoracic Surgery Vol 29
No 6 June 1980
use of microporous filters in the cardiotomy return line or in the arterial line could have muted differences produced by the oxygenators [4, 10, 121, but the authors do not state whether such filters were used. It is noteworthy that hemolysis was significantly less and that platelet counts were higher at all time intervals, thereby indicating that blood trauma was almost certainly less in the membrane group. This has been the case with most clinical comparisons of oxygenators. Many of the tests employed by Sade and colleagues were predictably too insensitive or primarily dependent for their postperfusion differences on factors other than the type of oxygenator, such as the trauma of the operation or hemodilution. Also too insensitive are blood urea nitrogen (BUN),prothrombin time, partial thromboplastin time, urine volume, and intelligence tests. Variables related to blood replacement are sensitive indices of operation but not of oxygenator differences. The hematocrit, total protein, albumin, glucose, fibrinogen, complement, and IgG show large changes as a result of hemodilution but are nondiscriminating as far as the oxygenator is concerned. Some of the tests would not reasonably be expected to show differences unless preoperative control values were paired with postoperative ones. This is the case with creatinine clearance, shunt fraction (preoperative values would not be useful in the cyanotic group), pulmonary compliance, intelligence tests, and behavioral indices. Even if paired, most of these would not be very useful tests because they are insensitive or not likely to vary with perfusion damage. For example, in a recent study [5] of renal failure after open-heart operation, 9 patients who later experienced renal failure had early creatinine clearance values of 67 k 12 ml per minute while the values for 30 patients without renal dysfunction were 96 k 12 ml per minute. These values are not greatly dissimilar to those of the present study and are not significantly different. In the same study, free-water clearance values were much more useful. They became significantly different during perfusion and remained so throughout an interval of eighteen hours, accu-
rately predicting the later rise in BUN and creatinine in those patients in whom renal failure developed. Although the behavioral tests in the present study showed significantly altered scores postoperatively, it would be necessary to use these tests with other surgical populations before concluding that they are suitable for detecting perfusion-related problems, and they should, of course, be paired. An additional possible point of confusion is the fact that priming of the membrane device used may influence the degree of blood trauma and initial bubble embolization. Experience and careful attention to the details, which include use of vacuum in the gas phase and flushing with carbon dioxide, are important. These things are not mentioned in the study of Sade and coworkers and could easily not have been done optimally in such a small series. Finally, since identifiable postperfusion problems are relatively infrequent and since differences in factors such as age, size, extent of cardiac lesion, and cardiotomy volume are probably large, it is unlikely that 60 patients, no matter how well studied and analyzed using contemporary tests, could provide any firm comparative conclusions. Sade and associates present no evidence indicating that the membrane oxygenator is pathophysiologically inferior to the bubble oxygenator. What little positive information there is in this study, especially the reduced hemolysis, favors the membrane lung as being less traumatic. In addition, it is correctly pointed out that the membrane oxygenator is probably safer, providing increased protection against gas embolization. A shift to the membrane oxygenator, properly employed, could produce a real decrease in morbidity, organ damage, and death, but this would be apparent only after analysis of large numbers of patients. The slowly increasing use of membrane devices, greater attention to moderating cardiotomy suction, appropriate blood filtration, and the development of more sensitive and specific tests for perfusion damage should make truly meaningful comparisons possible eventually. In sum, although difficult to prove at the
499
Editorial: Peirce: Membrane versus Bubble Oxygenator
present time, there are good reasons to regard the membrane oxygenator as superior and worthy of clinical use. Other things, i.e., cost and gross device function, being reasonably equal, the membrane oxygenator should be preferred.
References 1. Ashmore PG, Svitek V, Ambrose P: The inci-
2.
3.
4.
5.
dence and effects of particulate aggregation and microembolism in pump-oxygenator systems. J Thorac Cardiovasc Surg 55:691, 1968 Bernstein EF, Castaneda AR, Varco RL: Some biologic limitations to prolonged blood pumping. Trans Am SOCArtif Intern Organs 11:118, 1965 Carlson RG, Lande AJ, Landis B, et al: The Lande-Edwards membrane oxygenator during heart surgery: oxygen transfer, microemboli counts, and Bender-Gestalt visual motor test scores. J Thorac Cardiovasc Surg 66:894, 1973 Connell RS, Page US, Bartley TD, et al: The effect on pulmonary ultrastructure of Dacron-wool filtration during cardiopulmonary bypass. Ann Thorac Surg 15:217, 1973 Heimann T, Brau S, Sakurai H, et al: Urinary osmolal changes in renal dysfunction following open-heart operations. Ann Thorac Surg 22:44, 1976
6. Hill JD, Aguilar MJ, Baranco A, et al: Neuropathological manifestations of cardiac surgery. Ann Thorac Surg 7:409, 1969 7. Javid H, Tufo H, Najafi H, et al: Neurological abnormalities following open heart surgery. J Thorac Cardiovasc Surg 58:502, 1969 8. Lee WH Jr, Miller W Jr, Rowe J, et al: Effects of extracorporeal circulation on personality and cerebration. Ann Thorac Surg 7:562, 1969 9. Mortensen JD: Evaluation of tests for blood damage produced by oxygenators. Trans Am SOC Artif Intern Organs 23:747, 1977 10. Page US, Bigelow JC, Carter CR, et al: Emboli (debris) produced by bubble oxygenators: removal by filtration. Ann Thorac Surg 18:164, 1974 11. Peirce EC 11: Is the blood-gas interface of clinical importance? (editorial.) Ann Thorac Surg 17:526, 1974 12. Solis RT, Noon GP, Beall AC Jr, et al: Particulate microembolism during cardiac operation. Ann Thorac Surg 17:332, 1974 13. Stoney WS, Alford WC Jr, Burrus GR, et al: Air embolism and other accidents using pump oxygenators. Ann Thorac Surg 29:336, 1980 14. Ward BD, Berry GL: Comparative platelet function during prolonged extracorporeal bubble and membrane oxygenation. Am SECT Proceedings 3:6, 1975 15. Yeboah ED, Petrie A, Pead JL:Acute renal failure and open heart surgery. Br Med J 1:415, 1972