Pro: the superiority of the membrane oxygenator

PRO AND CON J. E a r l Wynands, M D , E d i t o r

BUBBLE OXYGENATORS ARE OUTDATED AND NO LONGER APPROPRIATE FOR CARDIOPULMONARY BYPASS

Pro: The Superiority of the Membrane Oxygenator Roy G. M a s t e r s , M D

ARDIOPULMONARY bypass (CPB) is an established procedure during cardiac surgery, and low mortality rates attest to its safety. Nevertheless, end-organ dysfunction, hemorrhage, infection, and transcapillary fluid loss are manifestations of a functional impairment that results from the interaction of blood components with the extracorporeal circuit. Important in this is the method of oxygenating blood, using either a bubble oxygenator (BO) or a membrane oxygenator (MO) (Table 1). During CPB, complement activation has been demonstrated. This results in the release of anaphylotoxins C3a and C5a, which stimulate release of mast cell histamine, contraction of smooth muscle, and an increase in vascular permeability. In addition, C5a possesses the ability to interact directly with neutrophils, initiating chemotaxis, lysosomal enzyme release, superoxide generation, autoaggregation, and increased adherence. While plasma levels of C3a increase during CPB with both types of oxygenators, the levels reached are statistically lower with the MO. 13 Pulmonary sequestration of C5a-activated neutrophils has also been demonstrated during CPB, related both to the duration of bypass and the type of oxygenator.3 After 120 minutes of bypass, C5a levels increase slightly with the MO, while a statistically significant increase is seen with the BO. 3Through its myriad of effects, complement has been incriminated in the pathophysiology of CPB. The anaphylotoxins can induce a systemic inflammatory-like reaction manifested by increased capillary permeability and interstitial edema. Activated complement with pulmonary leukostasis has also been

C

implicated in the development of pulmonary dysfunction following cardiac surgery. 4,s Complement activation, however, appears less with use of the MO. During CPB, an immediate drop in corrected and uncorrected total WBC count occurs. In those patients on the MO, it reaches a nadir at 30 minutes and is followed thereafter by a leukocytosis with levels reaching approximately 200% of preoperative values at the end of bypass. 68 In those patients on the BO, the leukopenia continues for 90 minutes, and the subsequent leukocytosis only reaches approximately 160% of preoperative values. 7'8 Statistically, there is a greater decrease in WBC count during bypass with the BO. 7 During bypass with the BO, WBC function is also more impaired, as measured by chemoluminescence and the bacterial killing of Staphylococcus aureus. Chemoluminescence, measuring the ability of neutrophils and monocytes to produce reactive oxygen species that are essential to the bactericidal process, is decreased during bypass of two hours' duration with the BO, while it is maintained or increased with the MO, a difference that is statistically significant] Both groups, however, show increased chemoluminescence at 24 hours following CPB. 7 The ability of neutrophils to kill S aureus after two

From the Division o f Cardiac Surgery, University o f Ottawa Heart Institute, Ottawa Canada. Address reprint requests to Roy G. Masters, MD, Division o f Cardiac Surgery, University o f Ottawa Heart Institute, Ottawa Canada K1 Y 4E9. © 1989 by W.B. Saunders Company. 0888-6296/89/0302-002053.00/0

Journal of Cardiothoracic Anesthesia, Vol 3, No 2 (April), 1989: pp 235-237

235

236

ROY G. MASTERS

Table 1. Comparison of the Two Designs of Oxygenator

Oxygenator Membrane

Complement C3a C5a WBC Number Function Chemoluminescence Bacterial killing

Pulmonary sequestration Opsonization Infection rate

Platelet Number Function ADP-Aggregation Bleeding RBC Destruction--Plasma HGB Survival--Cr 51

Bubble

Reference

T T

~T1`* TI'T*

1,2,3 3

~

~*

6, 7, 8

~ ~~ * ~* 1'1'1`* ~ ~~* 1'1`i" *

7 7 3, 4, 5 7, 8 7

,~

~*

6, 9, 10

~ --*

H~* 1`1'1'*

6, 9 10

T ~

1'1'1'* ~

6, 9 18

*-~ *-* 1' ~ *-~

* Statistically significant.

hours of bypass is also impaired with the BO, but not with the MO. 7 Further, the opsonizing capacity of serum throughout two hours of CPB and also on the first postoperative day is lower with the use of the BO than MO. 7'8 Animal studies have clearly demonstrated an increased risk of wound contamination, infection, and bacteremia with the use of the B O . 7 Aerosolized S a u r e u s was shown to contaminate the cardiotomy reservoir in 55% of dogs on the BO, but only 11% on the MO. Bacteremia developed in no animals on the MO but in 53% on the BO. Further, S a u r e u s was isolated from 50% of wounds in the BO group but only once in the MO group. 7 Thus, the potential for infection appears greater using the BO. Numerous studies have assessed the effect of CPB on platelet number and function. Platelet numbers corrected for hemodilution decrease during bypass with both designs of oxygenat o r . 6'9'1° However, platelet counts are statistically higher with the MO after perfusion times of 90 minutes or longer. At three hours of perfusion, patients in whom the MO was used have approximately 150 x 10 9 platelets/L, while patients in whom the BO was used have approximately 80 x 109 platelets/L. Platelet function is also impaired during CPB. As measured by adenosine diphosphate (ADP)-induced platelet aggregation,

platelet function is more severely impaired with the B O . 6'9 This difference becomes statistically significant with two hours or more of perfusion time.9 Platelet activation and damage, as measured by levels of beta-thromboglobulin, are also statistically greater with the BO. 8 While the use of cardiotomy suction and the duration of CPB contribute to platelet damage, when these are controlled, the superiority of the MO is still apparent. 9'11At least one prospective randomized trial has demonstrated that blood loss and transfusion requirements are greater with the BO and are associated with the greater decrease in platelet number and function after two hours of CPB. 1° Thus, the BO is more damaging to platelets. Platelets activated during CPB are deposited on foreign surfaces and in the microcirculation of a variety of organs including the liver and the heart. The MO, because of reduced blood-gas interface, results in decreased platelet activation as compared to the BO. Platelet depletion is also lessened with the use of the MO, because it causes less complement activation and leukocyte stimulation. Studies of platelet emboli have shown that with the BO there are greater numbers of circulating platelet microaggregates than with the M O . lz Use of the MO resulted in a tenfold reduction in the occurrence of platelet microemboli >50 tzm in size. While the importance of ptatelet microemboli in producing endorgan damage has not been proven, the CNS and the kidneys appear most susceptible to embolization. In animal studies, Patterson et al and Brennan et al have demonstrated improved neurologic function in those animals perfused with filters of 25-~zm diameter.13'14 The platelet release reaction stimulated by blood coming into contact with the synthetic surfaces of the extracorporeal circuit is associated with cyclic endoperoxide and thromboxane synthesis.15One function of thromboxanes is as a mediator of platelet secretion of alphagranules. With the onset of CPB, thromboxane levels immediately rise with both types of oxygenator until bypass is terminated. 16 However, thromboxane is not the only mediator of the platelet release reaction. With the MO, the addition of acetylsalicylic acid (ASA), which prevents thomboxane synthesis, reduces platelet secretion by approximately 50%. 16'17 This, however, does not occur with the BO, suggesting a

PRO: SUPERIORITY OF MEMBRANE OXYGENATOR

237

different m e d i a t o r of p l a t e l e t secretion in the presence of a large blood-gas interface. P l a s m a h e m o g l o b i n has been used as a m e a s u r e o f red cell d e s t r u c t i o n d u r i n g CPB. P l a s m a h e m o g l o b i n rises with the onset of bypass a n d r e t u r n s to n o r m a l by postoperative d a y 1.6'9 W i t h the M O , the rise in p l a s m a h e m o g l o b i n is less t h a n with the BO, t h o u g h it is not statistically significant. However, the difference between o x y g e n a t o r s does b e c o m e a p p a r e n t with bypass times > 2 hours. 9 A t t h r e e hours of CPB, the p l a s m a h e m o g l o b i n level in patients with the

BO reaches a p p r o x i m a t e l y twice t h a t seen with the M O . 9 Studies of red cell survival using C r 51t a g g e d red cells d e m o n s t r a t e red cell injury with CPB. However, t h e y have not shown differences between the two o x y g e n a t o r d e s i g n s ) 8 In s u m m a r y , e x t r a c o r p o r e a l oxygenation is unphysiologic a n d is associated with a complex a r r a y of clinical sequelae postoperatively. To the extent t h a t these sequelae a r e the result of the interaction of blood with the e x t r a c o r p o r e a l circuit, use of the m e m b r a n e o x y g e n a t o r is the safer choice.

REFERENCES

1. Cavarocchi NC, Pluth JR, Schaff HV, et al: Complement activation during cardiopulmonary bypass. J Thorac Cardiovasc Surg 91:252-258, 1986 2. Chenoweth DE, Cooper SW, Hugli TE, et al: Complement activation during cardiopulmonary bypass. N Engl J Med 304:497-503, 1981 3. Tamuja T, Yamasaki M, Maeo Y, et al: Complement activation during cardiopulmonary bypass with special reference to anaphylotoxin production in membrane and bubble oxygenators. Ann Thorac Surg 46:47-57, 1988 4. Craddock PR, Fehr J, Bringham KL, et al: Complement and leukocyte-mediated pulmonary dysfunction in hemodialysis. N Engl J Med 296:769-774, 1977 5. Jacob HS: Complement-mediated leukoembolization. A mechanism of tissue damage during extracorporeal perfusion, myocardial infarction and in shock. Q J Med 52:289-296, 1983 6. Boors M, Van den Dungen J JAM, Karliczek GF: Two membrane oxygenators and a bubbler: A clinical comparison. Ann Thorac Surg 35:455-462, 1982 7. Van Oevern W, Dankert J, Wildervuur RH: Bubble oxygenation and cardiotomy suction impair host defense during cardiopulmonary bypass: A study in dogs. Ann Thorac Surg 44:523-528, 1987 8. Van Oeveren W, Kazatchkine MD, DeschampsLatscha B, et al: Deleterious effects of cardiopulmonary bypass. J Thorac Cardiovasc Surg 89:889-899, 1985 9. Boonstra PW, Vermeulen FEE, Leusink JA, et al: Hematological advantage of a membrane oxygenator over a bubble oxygenator in long perfusions. Ann Thorac Surg 41:297-300, 1986 10. Teoh KH, Christakis GT, Weisel RD, et al: Blood

conservation with membrane oxygenators and dipyridamole. Ann Thorac Surg 44:40-47, 1987 11. Edmunds LH, Ellison N, Colman RW, et al: Platelet function during cardiac operation. J Thorac Cardiovasc Surg 83:805-812, 1982 12. Dutton RC, Edmunds LH, Hutchinson JC, et al: Platelet aggregate emboli produced in patients during cardiopulmonary bypass with membrane and bubble oxygenators and blood filters. J Thorac Cardiovasc Surg 67:258-265, 1974 13. Patterson RH Jr, Kessler J, Bergland RM: A filter to prevent cerebral damage during experimental cardiopulmonary bypass. Surg Gynecol Obstet 132:71-76, 1971 14. Brennan RW, Patterson RH Jr, Kessler J: Cerebral blood flow and metabolism during cardiopulmonary bypass: Evidence of microembolic encephalopathy. Neurol 21:665-668, 1971 15. Addonizio VP, Smith JB, Guiod LR, et al: The relationship between thromboxane synthesis and platelet release during simulated extracorporeal circulation. Blood 54:371-376, 1979 16. Addonizio VP, Smith JB, Straus JF, et al: Thromboxane synthesis and platelet secretion during cardiopulmonary bypass with bubble oxygenator. J Thorac Cardiovasc Surg 79:91-96, 1980 17. Greeley WJ, Bushman GA, Kong DL, et al: Effects of cardiopulmonary bypass on eicosanoid metabolism during pediatric cardiovascular surgery. J Thorac Cardiovasc Surg 95:842-849, 1988 18. Tabak C, Eugene J, Stemmer EA: Erythrocyte survival following extracorporeal circulation. J Thorac Cardiovasc Surg 81:30-33, 1981