Modified Ultrafiltration During Cardiopulmonary Bypass

Conclusions:

Consequently, MUF has been associated with attenuation of morbidity after pediatric cardiac surgery. In this review, we tried to evaluate the current evidence about MUF on the organ performance and its effect on post-CPB morbidity in pediatric patients.

Modified Ultrafiltration Technique

Naik and colleagues applied this technique at the Hospital of Pediatrics in London more than 20 years ago. In this method, the arterial line is connected to the inlet of the ultrafilter and the venous line is connected to the outlet of the ultrafilter in the CPB circuit. The inlet of the filter was clamped throughout the CPB (8). As the patient is separated from the CPB, the clamp is removed from the inlet of the filter, allowing the blood to flow through the arterial line to the filter (10-15 mL/kg/min), and finally from the cardioplegic cannula, as a venous line returns to the right atrium (Figure 1) (13). The filter allows passage of molecules smaller than molecular weight of 65,000 D. When it is needed to maintain the intravascular volume and stabilize the hemodynamics, the blood returns back by the venous reservoir and the venous cannula to the right atrium. This technique was performed until the hematocrit achieved the target of 35% (14).

Cardiovascular Performance and MUF

The use of CPB in cardiac surgery is a nonphysiologic situation, leading to unfavorable alterations such as hemodynamics changes (27). In the CPB circuit, contact of blood with foreign materials of the tubing surface, activates the leukocytes and leads to release of a range of cytotoxic factors. These factors include proteases, lysosomal hydrolases, arachidonic acid, and some agents that increase the vessels permeability (29). Throughout CPB, controlled hypothermic cardiac arrest may influence the transmembrane fluid transfer due to hypothermia and increase the myocardial interstitial fluid. In addition, ischemia predisposes the heart to pathologic fluid accumulation after return of coronary blood flow (30). Numerous products of cardiovascular activity such as endothelin-1 (ET-1) elevate after CPB (31). Numerous investigations have shown significant improvements of hemodynamic variables after MUF (Table 2) (17, 27, 32–35). These studies have shown improvements in hemodynamic parameters after MUF, including heart rate, systolic and diastolic blood pressure, right and left atrial pressures, pulmonary arterial pressure, and cardiac function. Systemic vascular resistance did not change after MUF, and a remarkable decrease was observed in pulmonary vascular resistance. Hematocrit was increased 25% to 30% after MUF and reduction of ejection fraction was obviously fewer throughout MUF (32–35). Hodges et al. demonstrated that MUF made no change in the depth of anesthesia, because plasma levels of fentanyl remained in the therapeutic range (34). Davies and colleagues showed hemodynamic parameters improvements and decrease in myocardial edema (36). The study of Gaynor and colleagues demonstrated improvement in the left ventricular function that led to reduced need for inotropes in the early postoperative period (37).

The Effect of MUF on Pulmonary Function

CPB can lead to various degrees of pulmonary injury in most of pediatric patients with severe pulmonary arterial hypertension. Pulmonary dysfunction was marked by reduced pulmonary compliance, increased pulmonary vascular resistance, and also reduced gas exchange (31). Severe acute pulmonary involvement can occasionally lead to fatality (38, 39). CPB hemodilution decreases serum levels of albumin and colloid osmotic force, and augments the efficiency of capillary filtration force. These changes may lead to increase of plasma fluid in the interstitial space, which will reduce the lung compliance and damage the gas exchange through the respiratory membrane. Following aortic cross-clamp, lungs will be ischemic and give off metabolic products to the interstitial liquid. Once the declamping of aorta and the oxygenated blood flow in the lungs creates oxygen free radicals and toxic agent, ischemic-reperfusion injury of the lungs occur. In addition, contact of blood to the CPB circuit as well as hypothermia and hemodynamic fluctuations, promote the discharge of inflammatory factors, leading to an extensive inflammatory reaction causing additional lung injury (38, 40). Several methods have been used to handle the overloaded tissue fluid. Conventional ultrafiltration in CPB (CUF) has been used, which was effective in reducing the water retention after the surgery. Naik et al. descripted that MUF was superior to CUF principally in its capability to decrease the fluid retention related to CPB in pediatrics (35). Numerous trials have shown that MUF may reduce the pulmonary dysfunction in pediatrics populations (Table 3) (18, 19, 41–44).

On the other hand, results of different studies demonstrated that the use of MUF in the post-CPB period in pediatrics patients can improve the pulmonary compliance and gas exchange, which may successfully reduce the pulmonary dysfunction after the pediatric cardiac surgery. MUF may lead to decreased period of tracheal intubation and mechanical ventilation, ICU stay, and total hospitalization after the surgery (40–44).

The Effect of MUF on Total Body Water

CPB in pediatric cardiac surgery exposes children to severe hypothermia, hemodilution and contact of blood to surface bypass circuit, initiating a systemic inflammatory reaction (45). Total body water (TBW) increases as a result of capillary permeability which often leads to tissue edema and is followed by multiple organ dysfunctions, principally in lungs, heart and brain (8). TBW usually expands 11% to 18% in the post-CPB period (8). Causes of TBW increase include hemodilution, hypothermia, young age and long duration of CPB (46, 47). Some methods have been used to reduce tissue edema and hemodilution after CPB, including ultrafiltration through CPB or conventional ultrafiltration, peritoneal dialysis after the surgery, forceful use of diuretics, and MUF (45, 47). The significantly positive result of MUF is reducing TBW after bypass. Reduction in TBW resulted in the elevation of hematocrit to pre-CPB levels and explained better organ function and reduction in postoperative morbidity (48, 49).

The Effect of MUF on Coagulation and Blood Transfusion Requirements

Post-CPB coagulopathy is a well-known complication (50–52). Some studies described that MUF considerably decreased the CPB-related coagulopathy in children undergoing congenital heart surgery (53–55). Ootaki et al. studied seven infants undergoing pediatric cardiac surgery (54). They explained that MUF was associated with considerable rises in platelet count, hematocrit, total albumin and plasma protein. Furthermore, prothrombin, factor VII and fibrinogen levels elevated considerably by MUF (55,56). In addition, increase in hematocrit is a reliable effect of MUF. Bleeding and need for transfusion in the postoperative period have multiple factors including hemodilution, fibrinolysis disorder, and platelet activation (11, 56). Several strategies have modified the hemostatic changes after CPB. MUF improved the hemostasis in the post-CPB period with useful effects on the blood loss, chest tube drainage, and blood transfusion requirements after the surgery. Need for blood products including red blood cells, fresh frozen plasma, cryoprecipitates and platelets were considerably lesser in MUF patients compared with the control group of infants (5, 53, 57).

MUF considerably decreased the necessity for blood transfusion in both deep and moderate hypothermia patients (5, 54, 58). MUF has been demonstrated as a reliable and valuable method for haemoconcentration with positive impacts on reducing the blood loss and transfusion requirements after cardiac surgery (8, 59,60).

Complications of MUF

Complications of MUF were lung air emboli, dysrhythmia, hypothermia, persistent systemic hypotension, and neurological deficits. These were avoided with application of safety strategy for MUF (61, 62). These strategies included continuous arterial line pressure monitoring, use of bypass arterial line filter, application of a bubble trap in the MUF circuit, hemoconcentrator inversion, changing the position of the bubble detector, warming before haemoconcentration, and use of a heat exchanger in the MUF circuit. It was necessary to apply a warm blood for transfusion line in the MUF circuit, regulate the operating room temperature to be adequately warm, consider a positive pressure servo-regulated MUF, apply an ultrasound flow-meter, assign an in-a-row hematocrit sensor, and use a veno-venous ultrafiltration method (63, 64). Additionally, MUF could change the plasma levels of some drugs, including midazolam, fentanyl, alfentanil, aprotinin and heparin (37, 65).

Conclusions

Use of modified ultrafiltration after separation from CPB can improve the pulmonary compliance and alveolar gas exchange, which may successfully reduce the lung dysfunction after pediatric cardiac surgery. MUF led to decrease of TBW accumulation with improvement in heart and lung function in the post-CPB period in neonates, infants and children. MUF was associated with lower red blood cell transfusion and reduced morbidity. MUF was recognized as a safe and reliable method for haemoconcentration. Use of MUF was not associated with detrimental hemodynamic fluctuation.

References

1. Chew MS, Brandslund I, Brix-Christensen V, Ravn HB, Hjortdal VE, Pedersen J, et al. Tissue injury and the inflammatory response to pediatric cardiac surgery with cardiopulmonary bypass: a descriptive study. Anesthesiology. 2001;94(5):745–53. [PubMed]

2. Radaelli A, Loardi C, Cazzaniga M, Balestri G, DeCarlini C, Cerrito MG, et al. Inflammatory activation during coronary artery surgery and its dose-dependent modulation by statin/ACE-inhibitor combination.Arterioscler Thromb Vasc Biol. 2007;27(12):2750–5. doi: 10.1161/ATVBAHA.107.149039. [PubMed][Cross Ref]

3. Paparella D, Yau TM, Young E. Cardiopulmonary bypass induced inflammation: pathophysiology and treatment. An update. Eur J Cardiothorac Surg. 2002;21(2):232–44. [PubMed]

4. Kotani N, Hashimoto H, Sessler DI, Muraoka M, Wang JS, O’Connor MF, et al. Cardiopulmonary bypass produces greater pulmonary than systemic proinflammatory cytokines. Anesth Analg.2000;90(5):1039–45. [PubMed]

5. Bando K, Vijay P, Turrentine MW, Sharp TG, Means LJ, Ensing GJ, et al. Dilutional and modified ultrafiltration reduces pulmonary hypertension after operations for congenital heart disease: a prospective randomized study. J Thorac Cardiovasc Surg. 1998;115(3):517–25. [PubMed]

6. Allen M, Sundararajan S, Pathan N, Burmester M, Macrae D. Anti-inflammatory modalities: their current use in pediatric cardiac surgery in the United Kingdom and Ireland. Pediatr Crit Care Med.2009;10(3):341–5. doi: 10.1097/PCC.0b013e3181a3105d. [PubMed] [Cross Ref]

7. McEvoy MD, Sabbagh MJ, Taylor AG, Zavadzkas JA, Koval CN, Stroud RE, et al. Aprotinin modifies left ventricular contractility and cytokine release after ischemia-reperfusion in a dose-dependent manner in a murine model. Anesth Analg. 2009;108(2):399–406. doi: 10.1213/ane.0b013e31818cdb13.[PMC free article] [PubMed] [Cross Ref]

8. Naik SK, Knight A, Elliott MJ. A successful modification of ultrafiltration for cardiopulmonary bypass in children. Perfusion. 1991;6(1):41–50. [PubMed]

9. Brancaccio G, Villa E, Girolami E, Michielon G, Feltri C, Mazzera E, et al. Inflammatory cytokines in pediatric cardiac surgery and variable effect of the hemofiltration process. Perfusion. 2005;20(5):263–8.[PubMed]

10. Castro RPd, Croti UA, Machado MdN, Murillo HG, Rincon OYP, Policarpo SR, et al. Ultrafiltração convencional com modificação técnica no tratamento cirúrgico dos defeitos cardíacos congênitos. Rev Bras Cir Cardiovasc. 2006;21(1):42–9. doi: 10.1590/S0102-76382006000100009. [Cross Ref]

11. Luciani GB, Menon T, Vecchi B, Auriemma S, Mazzucco A. Modified ultrafiltration reduces morbidity after adult cardiac operations: a prospective, randomized clinical trial. Circulation. 2001;104(12 Suppl 1):I253–9. [PubMed]

12. Atkins BZ, Danielson DS, Fitzpatrick CM, Dixon P, Petersen RP, Carpenter AJ. Modified ultrafiltration attenuates pulmonary-derived inflammatory mediators in response to cardiopulmonary bypass. Interact Cardiovasc Thorac Surg. 2010;11(5):599–603. doi: 10.1510/icvts.2010.234344. [PubMed][Cross Ref]

13. Gaynor JW. The effect of modified ultrafiltration on the postoperative course in patients with congenital heart disease. Semin Thorac Cardiovasc Surg Pediatr Card Surg Annu. 2003;6:128–39. doi: 10.1053/pcsu.2003.50006. [PubMed] [Cross Ref]

14. Thompson LD, McElhinney DB, Findlay P, Miller-Hance W, Chen MJ, Minami M, et al. A prospective randomized study comparing volume-standardized modified and conventional ultrafiltration in pediatric cardiac surgery. J Thorac Cardiovasc Surg. 2001;122(2):220–8. doi: 10.1067/mtc.2001.114937.[PubMed] [Cross Ref]

15. Kawamura T, Wakusawa R, Okada K, Inada S. Elevation of cytokines during open heart surgery with cardiopulmonary bypass: participation of interleukin 8 and 6 in reperfusion injury. Can J Anaesth.1993;40(11):1016–21. [PubMed]

16. Wan S, Yim AP, Ng CS, Arifi AA. Systematic organ protection in coronary artery surgery with or without cardiopulmonary bypass. J Card Surg. 2002;17(6):529–35. [PubMed]

17. Chaturvedi RR, Shore DF, White PA, Scallan MH, Gothard JW, Redington AN, et al. Modified ultrafiltration improves global left ventricular systolic function after open-heart surgery in infants and children. Eur J Cardiothorac Surg. 1999;15(6):742–6. [PubMed]

18. Keenan HT, Thiagarajan R, Stephens KE, Williams G, Ramamoorthy C, Lupinetti FM. Pulmonary function after modified venovenous ultrafiltration in infants: a prospective, randomized trial. J Thorac Cardiovasc Surg. 2000;119(3):501–5. [PubMed]

19. Huang H, Yao T, Wang W, Zhu D, Zhang W, Chen H, et al. Continuous ultrafiltration attenuates the pulmonary injury that follows open heart surgery with cardiopulmonary bypass. Ann Thorac Surg.2003;76(1):136–40. [PubMed]

20. Hiramatsu T, Imai Y, Kurosawa H, Takanashi Y, Aoki M, Shinoka T, et al. Effects of dilutional and modified ultrafiltration in plasma endothelin-1 and pulmonary vascular resistance after the Fontan procedure. Ann Thorac Surg. 2002;73(3):861–5. [PubMed]

21. Wang W, Huang HM, Zhu DM, Chen H, Su ZK, Ding WX. Modified ultrafiltration in paediatric cardiopulmonary bypass. Perfusion. 1998;13(5):304–10. [PubMed]

22. Pearl JM, Manning PB, McNamara JL, Saucier MM, Thomas DW. Effect of modified ultrafiltration on plasma thromboxane B2, leukotriene B4, and endothelin-1 in infants undergoing cardiopulmonary bypass.Ann Thorac Surg. 1999;68(4):1369–75. [PubMed]

23. Portela F, Espanol R, Quintans J, Pensado A, Vazquez A, Sanchez A, et al. [Combined perioperative ultrafiltration in pediatric cardiac surgery. The preliminary results]. Rev Esp Cardiol. 1999;52(12):1075–82. [PubMed]

24. Yndgaard S, Andersen LW, Andersen C, Petterson G, Baek L. The effect of modified ultrafiltration on the amount of circulating endotoxins in children undergoing cardiopulmonary bypass. J Cardiothorac Vasc Anesth. 2000;14(4):399–401. doi: 10.1053/jcan.2000.7944. [PubMed] [Cross Ref]

25. Chew MS, Brix-Christensen V, Ravn HB, Brandslund I, Ditlevsen E, Pedersen J, et al. Effect of modified ultrafiltration on the inflammatory response in paediatric open-heart surgery: a prospective, randomized study. Perfusion. 2002;17(5):327–33. [PubMed]

26. Harig F, Meier C, Hakami L, Strasser R, Bretzger J, Munch F, et al. Does the additional use of heparin-coated extracorporeal circuits (ECC) optimize the effect of modified ultrafiltration (MUF) in pediatric perfusion? Thorac Cardiovasc Surg. 2006;54(3):168–72. doi: 10.1055/s-2005-872863. [PubMed][Cross Ref]

27. Yokoyama K, Takabayashi S, Komada T, Onoda K, Mitani Y, Iwata H, et al. Removal of prostaglandin E2 and increased intraoperative blood pressure during modified ultrafiltration in pediatric cardiac surgery.J Thorac Cardiovasc Surg. 2009;137(3):730–5. doi: 10.1016/j.jtcvs.2008.09.017. [PubMed] [Cross Ref]

28. Papadopoulos N, Bakhtiary F, Grun V, Weber CF, Strasser C, Moritz A. The effect of normovolemic modified ultrafiltration on inflammatory mediators, endotoxins, terminal complement complexes and clinical outcome in high-risk cardiac surgery patients. Perfusion. 2013;28(4):306–14. doi: 10.1177/0267659113478450. [PubMed] [Cross Ref]

29. Journois D, Pouard P, Greeley WJ, Mauriat P, Vouhe P, Safran D. Hemofiltration during cardiopulmonary bypass in pediatric cardiac surgery. Effects on hemostasis, cytokines, and complement components. Anesthesiology. 1994;81(5):1181–9. [PubMed]

30. Patel B, Jeroudi MO, Bolli R. Pathogenesis of ischemic myocardial injury and methods of myocardial protection. In: Garson AJ, Bricker JT, McNamara DG, editors. The Science and Practice of Pediatric Cardiology. Philadelphia, PA: Lea & Febiger; 1990. pp. 266–79.

31. Hashimoto K, Miyamoto H, Suzuki K, Horikoshi S, Matsui M, Arai T, et al. Evidence of organ damage after cardiopulmonary bypass. The role of elastase and vasoactive mediators. J Thorac Cardiovasc Surg.1992;104(3):666–73. [PubMed]

32. Zhou G, Feng Z, Xiong H, Duan W, Jin Z. A combined ultrafiltration strategy during pediatric cardiac surgery: a prospective, randomized, controlled study with clinical outcomes. J Cardiothorac Vasc Anesth.2013;27(5):897–902. doi: 10.1053/j.jvca.2013.01.006. [PubMed] [Cross Ref]

33. Ricci Z, Polito A, Netto R, De Razza F, Favia I, Carotti A, et al. Assessment of modified ultrafiltration hemodynamic impact by pressure recording analytical method during pediatric cardiac surgery. Pediatr Crit Care Med. 2013;14(4):390–5. doi: 10.1097/PCC.0b013e31828a7113. [PubMed] [Cross Ref]

34. Hodges UM, Berg S, Naik SK, Bower S, Lloyd-Thomas A, Elliot M. Filtration of fentanyl is not the cause of the elevation of arterial blood pressure associated with post-bypass ultrafiltration in children. J Cardiothorac Vasc Anesth. 1994;8(6):653–7. [PubMed]

35. Naik SK, Balaji S, Elliott MJ. Modified ultrafiltration improves hemodynamics after cardiopulmonary bypass in children. J Am Coll Cardiol. 1992;19:37A.

36. Davies MJ, Nguyen K, Gaynor JW, Elliott MJ. Modified ultrafiltration improves left ventricular systolic function in infants after cardiopulmonary bypass. J Thorac Cardiovasc Surg. 1998;115(2):361–9.[PubMed]

37. William Gaynor J, Tulloh RMR, Owen CH, Sullivan ID, Elliott MJ. 953-31 Modified Ultrafiltration Reduces Myocardial Edema and Reverses Hemodilution Following Cardiopulmonary Bypass in Children.J Am Coll Cardiol. 1995;25(2, Supplement 1):200A. doi: 10.1016/0735-1097(95)92288-G. [Cross Ref]

38. Butler J, Rocker GM, Westaby S. Inflammatory response to cardiopulmonary bypass. Ann Thorac Surg. 1993;55(2):552–9. [PubMed]

39. Asimakopoulos G, Smith PL, Ratnatunga CP, Taylor KM. Lung injury and acute respiratory distress syndrome after cardiopulmonary bypass. Ann Thorac Surg. 1999;68(3):1107–15. [PubMed]

40. Miller BE, Levy JH. The inflammatory response to cardiopulmonary bypass. J Cardiothorac Vasc Anesth. 1997;11(3):355–66. [PubMed]

41. Liu JP, Long C, Feng ZY, Ji BY, Li CH. [Comparative study of pulmonary function after conventional ultrafiltration or modified ultrafiltration during cardiac surgery of infants]. Zhongguo Yi Xue Ke Xue Yuan Xue Bao. 2002;24(4):364–6. [PubMed]

42. Onoe M, Oku H, Kitayama H, Matsumoto T, Kaneda T. Modified ultrafiltration may improve postoperative pulmonary function in children with a ventricular septal defect. Surg Today.2001;31(7):586–90. [PubMed]

43. Torina AG, Petrucci O, Oliveira PP, Severino ES, Vilarinho KA, Lavagnoli CF, et al. The effects of modified ultrafiltration on pulmonary function and transfusion requirements in patients underwent coronary artery bypass graft surgery. Rev Bras Cir Cardiovasc. 2010;25(1):59–65. [PubMed]

44. Mahmoud AB, Burhani MS, Hannef AA, Jamjoom AA, Al-Githmi IS, Baslaim GM. Effect of modified ultrafiltration on pulmonary function after cardiopulmonary bypass. Chest. 2005;128(5):3447–53. doi: 10.1378/chest.128.5.3447. [PubMed] [Cross Ref]

45. Kirklin JK, Blackstone EH, Kirklin JW. Cardiopulmonary bypass: studies on its damaging effects.Blood Purif. 1987;5(2-3):168–78. [PubMed]

46. Maehara T, Novak I, Wyse RK, Elliot MJ. Perioperative monitoring of total body water by bio-electrical impedance in children undergoing open heart surgery. Eur J Cardiothorac Surg. 1991;5(5):258–64. [PubMed]

47. Naik SK, Elliott MJ. Ultrafiltration and paediatric cardiopulmonary bypass. Perfusion. 1993;8(1):101–12. [PubMed]

48. Gurbuz AT, Novick WM, Pierce CA, Watson DC. Impact of ultrafiltration on blood use for atrial septal defect closure in infants and children. Ann Thorac Surg. 1998;65(4):1105–8. [PubMed]

49. Gaynor JW. Use of modified ultrafiltration after repair of congenital heart defects. Semin Thorac Cardiovasc Surg Pediatr Card Surg Annu. 1998;1:81–90. [PubMed]

50. Steffens TG, Kohmoto T, Edwards N, Wolman RL, Holt DW. Effects of modified ultrafiltration on coagulation as measured by the thromboelastograph. J Extra Corpor Technol. 2008;40(4):229–33.[PubMed]

51. Andrew M, Paes B, Milner R, Johnston M, Mitchell L, Tollefsen DM, et al. Development of the human coagulation system in the healthy premature infant. Blood. 1988;72(5):1651–7. [PubMed]

52. Tempe DK, Virmani S. Coagulation abnormalities in patients with cyanotic congenital heart disease. J Cardiothorac Vasc Anesth. 2002;16(6):752–65. doi: 10.1053/jcan.2002.128436. [PubMed] [Cross Ref]

53. Friesen RH, Campbell DN, Clarke DR, Tornabene MA. Modified ultrafiltration attenuates dilutional coagulopathy in pediatric open heart operations. Ann Thorac Surg. 1997;64(6):1787–9. [PubMed]

54. Ootaki Y, Yamaguchi M, Oshima Y, Yoshimura N, Oka S. Effects of modified ultrafiltration on coagulation factors in pediatric cardiac surgery. Surg Today. 2002;32(3):203–6. [PubMed]

55. Buchholz BJ, Bert AA, Price DR, Hopkins RA, Stearns GT. Veno-arterial modified ultrafiltration in children after cardiopulmonary bypass. J Extra Corpor Technol. 1999;31(1):47–9. [PubMed]

56. Society of Thoracic Surgeons Blood Conservation Guideline Task F, Ferraris VA, Ferraris SP, Saha SP, Hessel E2, Haan CK, et al. Perioperative blood transfusion and blood conservation in cardiac surgery: the Society of Thoracic Surgeons and The Society of Cardiovascular Anesthesiologists clinical practice guideline. Ann Thorac Surg. 2007;83(5 Suppl):S27–86. doi: 10.1016/j.athoracsur.2007.02.099. [PubMed][Cross Ref]

57. Kamada M, Niibori K, Akimoto H, Yokoyama H, Tofukuji M, Iguchi A, et al. [Efficacy of modified ultrafiltration in reoperation for valvular disease]. Kyobu Geka. 2001;54(2):119–24. [PubMed]

58. Gelb AB, Roth RI, Levin J, London MJ, Noall RA, Hauck WW, et al. Changes in blood coagulation during and following cardiopulmonary bypass: lack of correlation with clinical bleeding. Am J Clin Pathol.1996;106(1):87–99. [PubMed]

59. Spiess BD. The contribution of fibrinolysis to postbypass bleeding. J Cardiothorac Vasc Anesth.1991;5(6):13–7. doi: 10.1016/1053-0770(91)90081-4. [PubMed] [Cross Ref]

60. Elliott MJ. Ultrafiltration and modified ultrafiltration in pediatric open heart operations. Ann Thorac Surg. 1993;56(6):1518–22. [PubMed]

61. Raja SG. Modified ultrafiltration for paediatric cardiac surgical patients: additional benefits and concerns. Chin Med J (Engl). 2004;117(2):318–9. [PubMed]

62. Darling E, Nanry K, Shearer I, Kaemmer D, Lawson S. Techniques of paediatric modified ultrafiltration: 1996 survey results. Perfusion. 1998;13(2):93–103. [PubMed]

63. Ramamoorthy C, Lynn AM. Con: the use of modified ultrafiltration during pediatric cardiovascular surgery is not a benefit. J Cardiothorac Vasc Anesth. 1998;12(4):483–5. [PubMed]

64. Williams GD, Ramamoorthy C, Totzek FR, Oakes RL. Comparison of the effects of red cell separation and ultrafiltration on heparin concentration during pediatric cardiac surgery. J Cardiothorac Vasc Anesth.1997;11(7):840–4. [PubMed]

65. Pouard P, Journois J, Greeley WJ. Hemofi ltration and pediatric cardiac surgery. In: Greeley WJ, editor. Perioperative management of the patient with congenital heart disease. Baltimore: William & Wilkins; 1996. p. 121–32.