Page 119 - Biomedical Engineering and Design Handbook Volume 2, Applications

98 MEDICAL DEVICE DESIGN

combination of operative trauma, reperfusion injury, and exposure to endotoxin during the procedure
(Asimakopoulos et al., 1999). Hemorrhagic and thrombotic problems during CPB are of grave con-
cern, and traditionally, CPB support has required the use of high doses of anticoagulant to prevent
clotting in the extracorporeal circuit at the expense of a possible increase in bleeding. This bleeding
risk is further magnified by the consumption of coagulation factors and platelets by extracorporeal
surfaces and activation of fibrinolytic pathways. Investigations into minimizing this phenomenon
have led to the development of anticoagulant (heparin) fiber coatings for the oxygenators (Wendel
and Ziemer, 1999). The presence of a heparin coating have led some to reduce the amount of sys-
temic heparin provided during CPB in an effort to limit bleeding (Aldea et a1., 1996; Aldea et al.,
1998). Although there is evidence that bleeding is reduced, the approach is controversial in many cir-
cles as clinical markers of blood clotting remain elevated, resulting in lingering thromboembolism
concerns (Kuitunen et al., 1997; Kumano et al., 1999). In addition, it is not clear how much
benefit can be attributed to the heparinized circuit itself. Retrospective data using identical heparin-
bonded circuits with full versus reduced anticoagulation show a significant benefit of the reduced
anticoagulation in terms of postoperative bleeding and blood loss, along with reduced ventilation
support requirements (Ovrum et al., 2003). Further research is required to elucidate what and how
much protective effect is provided by heparin-coated fibers.
The more chronic support provided by ECMO is plagued by complications and poor outcomes.
Survival rates for ECMO support range from 88 percent for neonates in respiratory failure to 33 percent
for adults in cardiac failure (Bartlett et. al., 2000). Similar to CPB, hemorrhagic and thrombotic
complications occur and have led to intense investigation into the long-term neurologic outcomes of
these patients (Graziani et al., 1997; Nield et al., 2000), although the exact relationship between
ECMO and outcomes remains unclear (Vaucher et al., 1996; Rais-Bahrami et al., 2000). In addition,
longer-term support with hollow fiber membrane oxygenators results in the manifestation of a par-
ticular phenomenon where plasma from the blood side seeps into the pores of the fibers in a process
termed weeping. The effect of this phenomenon is to increase the diffusion distance for oxygen and
carbon dioxide, thereby reducing mass transfer performance. Originally thought to be due to tem-
perature changes and condensation of water in the fiber interior (Mottaghy et al., 1989), evidence
suggests deposition of circulating phospholipid at the fluid-gas interface results in a change in
hydrophobicity on the pore surface that mediates penetration of the plasma (Montoya et al., l992).

3.9.5 Future Trends
Future developments in cardiopulmonary bypass will focus on improving the biocompatibility of the
device through minimization of hematologic alterations. One current approach involves coating the oxy-
genator fibers with a layer of polysiloxane in an effort to limit the postperfusion syndrome (Shimamoto
et al., 2000). ECMO, with its higher longevity requirements, will similarly benefit from new coatings
and materials. General measures to improve the biocompatibility of the fibers include coatings and addi-
tives to limit plasma infiltration into the device (Shimono et al., 1996), limit platelet deposition on the
surface (Gu et al., 1998) and platelet activation (Defraigne et al., 2000), and minimize leukocyte and
complement activation (Watanabe et al., 1999; Saito et a1., 2000). Although not a new concept, novel
methods to improve mass transfer through the thinning or disruption of the boundary layer are currently
being developed. Some approaches include the use of fibers mounted on a rapidly spinning disc
(Borovetz et al., 1997; Reeder et al., 1998), cone (Makarewicz et a1., 1994) or cylinder (Svitek et a1.,
2005), the pulsing and distention of silicone sheets (Fiore et al., 2000), and the pulsation of a balloon
mounted inside circumferentially organized fibers designed for placement in the vena cava (Federspiel
et al., 1997). Some of these devices offer the opportunity to combine the features of a blood pump and
artificial lung, and therefore represent a significant leap over current bypass systems.

ACKNOWLEDGMENTS

The support of the McGowan Institute for Regenerative Medicine at the University of Pittsburgh is
acknowledged. Fellowship support was provided to Kenneth Gage during the writing of the first