A systemic inflammatory response after pediatric cardiac surgery is not uncommon. The cardiopulmonary bypass (CPB) circuit is seen as the main activator of the inflammatory response. For that reason, several coatings have been developed to create a more biocompatible CPB circuit. At this moment, several coatings are commercially available: human albumin coating, Duraflo II and Carmeda coatings (both based on heparin), phosphorylcholine PHISIO coating (which mimics the outer cell membrane), polymethoxyethylacrylate coating, and the biopassive surface Trillium coating.
Do these coatings result in less inflammatory response after pediatric cardiac surgery? In reviewing the literature on coating of pediatric CPB circuits, a lot of controversies are found. In vitro studies show significantly better biocompatibility of coated circuits than of noncoated circuits.1–3 The outcomes of in vivo or clinical studies are less convincing; many times only a few parameters show improvement.4–7 Some of the problems found in reviewing studies on coatings are: different methodologies, lack of proper control groups, differences between the patients concerning age and bodyweight, and different prime volumes in different groups. Furthermore, measured parameters are numerous, and sample moments show large variability (Table 1).
In the adult population, many more studies on coatings have been published. Here, we find more evidence for beneficial effects of coatings, but it is not clear whether the results of these studies can simply be extrapolated to the practice of pediatric cardiac surgery.13
Several factors may cause an inflammatory response. The artificial surface of the CPB circuit is an important activator, but other activators are probably as important: ischemia-reperfusion, surgical trauma (especially that of cardiovascular surgery), endotoxemia, and blood–air contact.14 Patients that have cardiovascular operations without the use of CPB have been reported to show also signs of serious inflammatory response.15–17
Although CPB is not the only causative factor for an inflammatory response, coating of the CPB circuit is expected to result in improved biocompatibility with less activation of the complement system, the contact system, as well as a reduced activation of leucocytes and platelets.
To what should we thus adhere? In vitro studies provide the most reliable information because of their controlled environment and similar outcomes. The most important for clinical studies is a homogeneous patient group, especially in the pediatric population where a wide spread in age, bodyweight, and diagnosis is commonly encountered.
Our group recently performed a prospective, randomized, and blinded clinical study in 28 neonates and small infants to compare complement activation and leucocytes stimulation of phosphorylcholine coated and noncoated CPB circuits. Strict inclusion criteria were used: bodyweight between 3 and 6 kg, no syndromal anomalies such as Down syndrome, no severe cyanosis (oxygen saturation > 75%), no circulation arrest, no reoperations, and no premature patients. All patients received the same protocolized way of anesthesia and CPB management; none of the patients received aprotinin or other drugs that might interfere with the inflammatory response. No ultrafiltration, conventional or modified, was used in the study patients. No differences were observed between the two groups for the changes of complement factor C3b/c, elastase HNE, interleukin-6, and C-reactive protein before, during, and after CPB until 6 hours postoperatively. We concluded that phosphorylcholine coating does not result in a reduction of inflammatory response (unpublished data).
Summarizing the review of the literature and our study, we conclude that an improved biocompatibility by coating is most reliably demonstrated by in vitro studies, whereas clinical studies in the pediatric population do not show equally convincing beneficial effects. More strictly protocolized randomized prospective clinical studies will be needed to gather evidence for positive effects of CPB circuit coating in pediatric cardiac surgery. In the meantime, we should realize that coating alone cannot lead to an adequate reduction of inflammatory response. Other agents should be considered for this purpose, such as ultrafiltration during and/or after CPB, corticosteroids and protease inhibitors, and the use of monoclonal antibodies.18 Efforts to further miniaturize the pediatric CPB-circuit will also be helpful.
1. Wendel HP, Scheule AM, Eckstein FS, Ziemer G: Haemocompatibility of paediatric membrane oxygenators with heparin-coated surfaces. Perfusion
14: 21–28, 1999.
2. Lappegrd KT, Fung M, Bergseth G, et al: Artificial surface-induced cytokine synthesis: Effect of heparin coating and complement inhibition. Ann Thorac Surg
78: 38–45, 2004.
3. Zimmermann AK, Aebert H, Reiz A, et al: Hemocompatibility of PMEA coated oxygenators used for extracorporeal circulation procedures. ASAIO
50: 193–199, 2004.
4. Horton SB, Butt WW, Mullaly RJ, et al: Il-6 and Il-8 levels after cardiopulmonary bypass are not affected by surface coating. Ann Thorac Surg
68: 1751–1755, 1999.
5. Böning A, Scheewe J, Ivers T, et al: Phosphorylcholine or heparin coating for pediatric extracorporeal circulation causes similar biologic effects in neonates and infants. J Thorac Cardiovasc Surg
127: 1458–1465, 2004.
6. Somer F, De, François K, van Oeveren, W, et al: Phosphorylcholine coating of extracorporeal circuits provides natural protection against blood activation by the material surface. Eur J CardioThorac Surg
18: 602–606, 2000.
7. Gunaydin S: Clinical significance of coated extracorporeal circuits: A review of novel technologies. Perfusion
19: S33–S41, 2004.
8. Schreurs HH, Wijers MJ, Gu YJ, et al: Heparin-coated bypass circuits: effects on inflammatory response in pediatric cardiac operations. Ann Thorac Surg
66: 166–71, 1998.
9. Jensen E, Andréasson S, Bengtsson A: Changes in hemostasis during pediatric heart surgery: Impact of a biocompatible heparin-coated perfusion system. Ann Thorac Surg
77: 962–967, 2004.
10. Grossi EA, Kallenbach K, Chau S, et al: Impact of heparin bonding on pediatric cardiopulmonary bypass: A prospective randomized study. Ann Thorac Surg
70: 191–196, 2000.
11. Olsson C, Siegbahn A, Henze A, et al: Heparin-coated cardiopulmonary bypass circuits reduce circulating complement factors and interleukin-6 in paediatric heart surgery. Scand Cardiovasc J
34: 33–40, 2000.
12. Ashraf SS, Tian Y, Zacharrias S, et al: Effects of cardiopulmonary bypass on neonatal and paediatric inflammatory profiles. Eur J Cardiothorac Surg
12: 862–868, 1997.
13. Gu YL, van Oeveren, W, Akkerman C, et al: Heparin-coated circuits reduce the inflammatory response to cardiopulmonary bypass. Ann Thorac Surg
55: 917–922, 1993.
14. Seghaye MC: The clinical implications of the systemic inflammatory reaction related to cardiac operations in children. Cardiol Young
13: 228–239, 2003.
15. Prondzinsky R, Knüpfer A, Loppnow H, et al: Surgical trauma affects the proinflammatory status after cardiac surgery to a higher degree than cardiopulmonary bypass. J Thorac Cardiovasc Surg
129: 760–766, 2005.
16. Tárnok A, Hambsch J, Emmrich F, et al: Complement activation, cytokines, and adhesion molecules in children undergoing cardiac surgery with or without cardiopulmonary bypass. Pediatr Cardiol
20: 113–125, 1999.
17. Biglioli P, Cannata A, Alamanni F, et al: Biological effects of off-pump vs. on-pump coronary artery surgery: Focus on inflammation, hemostasis and oxidative stress. Eur J CardioThorac Surg
24: 260–269, 2003.
18. Uumlndar, A, Eichstaedt HC, Clubb FJ, et al: Novel anti-factor D monoclonal antibody inhibits complement and leukocyte activation in a baboon model of cardiopulmonary bypass. Ann Thorac Surg
74: 35–362, 2002.