4. Discussion

Problem group (with MUF)

> Operative clinical end point

> Control group Problem group p

Before CPB n/total n (%) or n/total n (%) or

Mean

Laboratory examinations

Hematocrit

Hemoglobin

CPB hematocrit Lactate (mmol/l)

Hemodynamic

Heart rate (beats per minute)

Systolic blood pressure (mmHg)

Diastolic blood pressure

(mmHg)

Mean blood pressure (mmHg)

Central venous pressure

(mmHg)

Operative morbidity and mortality

Morbidity

Mortality \*CPB measured values (due to

Shades: The words and numbers in "bold"

Table 6.

Comparison

 between operative clinical end point variables in both groups of study (with and without MUF).

hemodilution).

highlight the variables that have a statistical significance

 (p<0.005).

 64 10

 8

 12

 NS

8 1

10

 3

 0.0203

3 (20%)

0 (0%)

 0 (0%)

 1 (6%)

NS

NS

12

 7

10

 3

NS

 7

 61

 NS

 64

 64

 NS

 61

 12

64

 17

NS

 17

 13

 12

 18

 97

 85 53

 15

 52

 NS

 49

 49

 NS

 52

 12

49

 12

NS

 12

 7

 12

 89

 NS

 83

 90

 NS

 89

 12

90

 20

NS

 20

 10

 12

 16

 113

 18

 0.012

 97

 112

 15

 0.0116

113

 18

 112

 15

 NS

 16

 15

 variables

 1.2

 0.3 3.5

 1.4

 0.0001

 1.1

 0.3 3.3

 1.2

 0.0001

 (%)

 (g/dl)

 (%)

38

14

 5

 11

 0.0344

12

 2

 11

 NS

26

3.5

 1.4 3.3

 1.2

 NS

 5\* 24

 4\*

NS

 11

 2

11

 2

NS

 2

 2

 7

 34

 NS

 37

 34

 NS

 34

 6

34

 7

NS

 7

 5

 6

 SD

 Mean

 SD

Mean

 SD

 Mean

 SD

Mean

 SD

 Mean

 SD

176 Advances in Extra-corporeal Perfusion Therapies

 After MUF

 Control group Problem group p

Before CPB n/total n (%) or n/total n (%) or

 After MUF

variable

Control group (without MUF)

Problem versus control groups (with vs.

without MUF)

 Problem group

After MUF n/total n (%) or n/total n (%) or

 After CPB

 Control group

 p

> Cardiopulmonary bypass (CPB) is able to trigger a systemic inflammatory response syndrome (SRIS) due to several factors that include (1) cell activation secondary to contact with CPB synthetic surfaces, (2) mechanic stress, (3) tissue ischemia and reperfusion, (4) hypotension, (5) non-pulsatile flow, (6) hemodilution relative anemia, (7) blood and blood products transfusion, (8) heparin and protamine administration, and (9) hypothermic effects. CPB activates the vessels endothelium and releases pro-inflammatory agents such as tumoral necrosis factor α (TNF-α), interleukins, and endotoxins. These agents activate the intracellular transcription factor as well, which increases endothelial pro-inflammatory cytokines and the molecular expression of leukocyte adhesion.

> It is a well-known fact that younger age increases the inflammatory effects of CPB even more. Some reasons include an increased metabolic demand in these patients, hyperactivity of their pulmonary vessels, immaturity of their organs/systems, and altered homeostasis. Risk is particularly high in neonates and young infants due to a mismatch between CPB and patient's size, with CPB circuit volume usually 200–300% higher than that of the patient. In addition, an increased metabolic demand requires elevated pump flow up to 200 ml/kg/min in neonates. Combining a relative major size of CPB with an increased perfusion rate leads to a greater blood exposure to synthetic surfaces of the circuit components [23]. In our series, there was no age difference between the studied groups, and it is important to highlight that none of the groups included neonate patients for the reasons already discussed.

> One of the most involved cytokines in SRIS development is, indeed, IL-6. Increased concentrations of IL-6 have been reported in patients with postoperative complications and a correlation with the posterior left ventricular wall dyskinesia detected by means of transesophageal echocardiography has been established. IL-6 is also an endogenous pyrogen agent that activates acute phase reactant proteins. Concentration of IL-6 increases independently of the oxygenator type, degree of hypothermia, or heparin use in the CPB circuit surfaces [24, 25]. Although in our study IL-6 concentrations were significantly higher before surgery in the problem group than in the control group, this agent is also the one that is significantly more removed by MUF. This is probably the most relevant fact of our study because it shows that the benefit of MUF in congenital heart disease surgery is the removal of IL-6, an important proinflammatory agent, particularly in patients that SRIS is enhanced because of the immaturity of their immune system. Another effect that is important to discuss is the fact that if MUF benefits patients with simple congenital heart disease surgery as were the ones included in our study, it would indeed improve operative outcomes in those operated on for complex congenital heart disease [26]. This single fact justifies the routine use of MUF in all patients with congenital heart disease that are operated on with CPB.

> There are several additional methods, despite ultrafiltration, that had been developed in order to diminish SRIS secondary to CPB at surgical correction of congenital heart disease in pediatric population. Some of them are steroids (e.g., dexamethasone 10–30 mg/kg, 6–12 h before CPB), and modified tubular synthetic surfaces in the CPB circuit. However, none of these methods are as useful for this purpose as MUF, which is established right after ending the CPB and before

decanulation of the patient [27]. Since 1973, different types of hemofilters have been developed in order to remove priming volume (water) following the principle of pressure gradient, particularly those made of polycarbonate. These filters have been replaced by the ones made out of poliariletersulfonate in 1986, and later by the current generation of polyamide hemofilters. These are the most practical ones because of its greater biocompatibility, reduced surface, and more ultrafiltration effectiveness due to a less than physiological pressure.

Conflict of interest

Author details

Pedro José Curi-Curi<sup>1</sup>

Mexico City, Mexico

References

Jorge Luis Cervantes-Salazar<sup>1</sup>

or publication of this manuscript.

The authors declare no potential conflicts of interest with respect to the research, authorship,

Utility of Modified Ultrafiltration in Congenital Heart Disease Patients Operated with Cardiopulmonary Bypass

1 Department of Congenital Heart Disease and Pediatric Cardiac Surgery, "Ignacio Chávez"

[1] Brix-Christensen V. The systemic inflammatory response after cardiac surgery with cardiopulmonary bypass in children. Acta Anaesthesiologica Scandinavica. 2001;45:671-679

[2] Seghaye MC. The clinical implications of the systemic inflammatory reaction related to

[3] Kozik D, Tweddell J. Characterizing the inflammatory response to cardiopulmonary

[4] Kirklin JK, Westaby S, Blackstone EH, Kirklin JW, Chenowelh DE, Pacifico AD. Complement and the damaging effects of cardiopulmonary bypass. The Journal of Thoracic and

[5] Seghaye M, Duchateau J, Grabitz RG, Nitsch G, Marcus C, Messmer BJ, von Bernuth G. Complement, leukocytes and leukocyte elastase in full-term neonates undergoing cardiac

[6] Seghaye M, Grabitz RG, Duchateau J, Bussea S, Däbritz S, Koch D, et al. Inflammatory reaction and capillary leak syndrome related to cardiopulmonary bypass in neonates undergoing cardiac operations. The Journal of Thoracic and Cardiovascular Surgery.

[7] Ashraf SS, Tian Y, Zacharrias S, Cowan D, Martin P, Watterson K. Effects of cardiopulmonary bypass on neonatal and paediatric inflammatory profiles. European Journal of

cardiac operations in children. Cardiology in the Young. 2003;13:228-239

bypass in children. The Annals of Thoracic Surgery. 2006;81:S2347-S2354

operation. Journal of Thoracic and Cardiovascular Surgery. 1994;108:29-36

2 Department of Pediatric Cardiology, "Ignacio Chávez" National Cardiology Institute,

, Samuel Ramírez-Marroquín<sup>1</sup> and

http://dx.doi.org/10.5772/intechopen.77122

179

\*, Juan Calderón-Colmenero<sup>2</sup>

\*Address all correspondence to: pcuricuri001@gmail.com

National Cardiology Institute, Mexico City, Mexico

Cardiovascular Surgery. 1983;86:845-847

Cardio-Thoracic Surgery. 1997;12:862-868

1996;112:687-697

The effectiveness of ultrafiltration for removing pro-inflammatory agents depends also on the type of hemofilter and on the modality of ultrafiltration procedure used. Berdat et al. studied the effectiveness of poliariletersulfonate filters versus polyamide ones in the two ultrafiltration modalities for the removal of pro-inflammatory agents such as IL-6, IL-10, and TNFα [10]. They prove that IL-6 was better removed by conventional ultrafiltration (CUF) with poliariletersulfonate filter, while TNFα was better removed by modified ultrafiltration (MUF) and poliariletersulfonate filter. The rest of the pro-inflammatory agents were not modified neither for the ultrafiltration modality nor for the hemofilter type. Therefore, it seems that MUF with poliariletersulfonate hemofilter is the better strategy for removing pro-inflammatory agents in pediatric patients with congenital heart surgery. Our results are based on the ultrafiltration modality rather than the type of filter, since the material of hemofilters that we used was variable.

It has been reported that MUF is not only useful for removing extracellular fluid excess but also cytokines and other inflammatory agents triggered by CPB and surgical trauma. There is some controversy in the study regarding the efficacy of filters in the removal of cytokines, as well as in the differences between the two ultrafiltration modalities [28]. In addition, the comparative results between both ultrafiltration modalities are difficult to interpret due to variations in the ultrafiltration technique, equipment, definitions and objectives, and measurements of cytokines. Finally, it is still not known if the clinical benefits of MUF are due to the removal of cytokines and other inflammatory agents, or to the isolated reduction of tissue edema [29–33].
