2. Materials and methods

#### 2.1. Study design

A prospective, randomized, analytic, and clinical case-control trial was designed at the Department of Pediatric Cardiac and Congenital Heart Surgery of a single center during a 1-year period of time. Inclusion criteria were age ≤ 18 years, and simple congenital heart disease that required elective surgical treatment with CPB use for at least 30 min. Exclusion criteria were preoperative renal failure, preoperative cardiogenic shock requiring the use of inotropics, preoperative sepsis, and preoperative mechanical ventilatory support of ≤48 h, preoperative lactate seric levels of ≥3 mmol/l, and cardiac reoperation. Patients were randomized into two study groups: problem group (with MUF) and control group (without MUF). With the use of an electronic URNA software, a statistical person randomized the patients and told the perfussionist, which was the only surgical team person informed about the results of randomization. All patients included in this study were operated on with informed consent signed by their parents or tutors. The study was also approved by our institutional research and ethics committee.

#### 2.2. Modified ultrafiltration technique

1. Introduction

170 Advances in Extra-corporeal Perfusion Therapies

Cardiopulmonary bypass (CPB) allowed the correction of several congenital heart diseases such as intracardiac malformations, but it is well-known that this is not a harmless procedure because it can lead to a systemic inflammatory response syndrome (SIRS), with activation of complement, cytokines, coagulation, and fibrinolysis pathways. Factors that contribute to the development of SIRS include blood contact with the synthetic surface of cardiopulmonary bypass components, as well as leukocyte and endothelial activation after tissue ischemia and reperfusion [1–5]. If there is a severe inflammatory response, it could also develop a multiorganic dysfunction syndrome that increases morbidity and mortality of the patients at pediatric intensive care units (PICUs). Some of the methods used to quantify the magnitude of SRIS due to the use of CPB include measurement of blood cytokine concentrations (interleukins 1 and 6), complement activation products (C3d and C4d), and also coagulation activated

There are several operative strategies for diminishing SRIS and its clinical repercussion, such as the use of steroids, modified tubular surfaces for CPB, and ultrafiltration. Despite the single or combined use of these strategies [7–12], ultrafiltration is the one that probably removes a larger amount of pro-inflammatory agents, as well as water (volume) [13]. The two ultrafiltration technique modalities widely accepted for pediatric cardiac surgery are conventional ultrafiltration (CUF) and modified ultrafiltration (MUF). CUF is applied in CPB during the

Currently, there is no enough evidence that favor the routine use of MUF [14–19], and we can still find some controversies regarding the benefits of this technique [20–22]. In addition, most reports of the study are focalized in adult cohorts of patients, and there is few information provided for pediatric population that show the real impact of MUF in the re-motion of proinflammatory agents due to CPB use. Therefore, we aimed to study the real utility of MUF for re-motion of pro-inflammatory agents induced by CPB in operated pediatric patients with simple congenital heart disease. We made a special emphasis in hemodynamic variables,

A prospective, randomized, analytic, and clinical case-control trial was designed at the Department of Pediatric Cardiac and Congenital Heart Surgery of a single center during a 1-year period of time. Inclusion criteria were age ≤ 18 years, and simple congenital heart disease that required elective surgical treatment with CPB use for at least 30 min. Exclusion criteria were preoperative renal failure, preoperative cardiogenic shock requiring the use of inotropics, preoperative sepsis, and preoperative mechanical ventilatory support of ≤48 h, preoperative lactate seric levels of ≥3 mmol/l, and cardiac reoperation. Patients were randomized into two

factors (Von Willebrand, fibrinogen and factor VIII) [6].

heart re-warming period and MUF right after ending CPB.

morbidity, and mortality at the operative period.

2. Materials and methods

2.1. Study design

Patients randomized to problem group (with MUF), when informed to the perfussionist, were prepared for CPB with an additional MUF set. Once CPB was ended and hemodynamic stability of the patient was provided, the surgeon was told not to remove the venous canula, and the venous line was clamped just before its connection to the reservoir. Arterial and venous line pathways were released in order to begin MUF with a 10–20-ml/kg/min flow. MUF continuous flow was achieved, pumping the venous residual reservoir volume by means of the arterial line to the patient. A 150–200-mmHg venous vacuum was applied when needed. MUF lasted 10–20 min in order to reach a desired hematocrit level and obtain also a suitable volume and electrolyte balance. MUF was stopped in case of hemodynamic instability. Once ended, MUF volume was restored to the patient from the hemofilter and venous canula, allowing the surgeon for decanulation of the patient.

#### 2.3. Biochemical and clinical operative analysis

Biochemical and clinical results were compared between the two study groups at the operative period. Biochemical results were the concentration of cytokine (interleukins 6 and 10) and complement activated products (C3d and C4d). These concentrations were measured from blood samples at the following times: T0 (baseline, at the beginning of anesthesia induction), T1 (before CPB), T2 (immediately after CPB), and T3 (immediately after MUF, in the problem group). The same agents were measured in the MUF fluid concentrate of the problem group after the procedure (T4). Clinical operative results were evaluated in terms of hemodynamic instability (>20% post CPB variation with respect to previous CPB values of at least three of the following five hemodynamic variables: heart rate, systolic, diastolic and mean blood pressure, and central venous pressure), operative morbidity and mortality. Operative clinical end points of success were defined as hemodynamic stability, absence of morbidity, and lack of mortality.

#### 2.4. Laboratory analysis of the fluid samples

All patient samples were obtained from central or peripheral blood and collected in tubes without heparin (vacutainer, Beckton Dickinson). A 3-ml blood sample was obtained for each of the study times (T0, T1, T2, and T3). The same volume of T4 samples was obtained from the ultrafiltration fluid concentrate. All of the samples were centrifugated at 3000 rpm for 15 min, 4C, and cryopreserved in aliquots of 15 ml at 75C. Interleukin concentrations (IL-6 and IL-10) were measured by means of an ELISA-Sandwich technique with the use of monoclonal antibodies (Peprotech, NJ, EUA). Complement activation products (C3d and C4d) were measured with the same technique, using commercial kits (Bachem, San Carlos, CA, EUA). Optical density was determined at 450 nm in the ELISA lector. Concentrations of IL-6, IL-10 (pg/ml), as well as C3d and C4d (ng/ml) were calculated by means of a GraphPad Software v. 4.2.

Variable Total series n (%) or

Gender

Anthropometric data

Body surface area (m2

Cardiovascular background

Circulating blood volume (ml)

Pathologic background

Pulmonary artery hypertension

NYHA/Ross pre-operative functional class

Syndromes

Operative risk

support

Preoperative morbidity

Preoperative inotropic

Preoperative laboratory exams

mean SD (range)

Problem group (with MUF) n (%) or mean SD (range)

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

) 0.56 0.27 (0.25–1.32) 0.58 0.31 (0.25–1.32) 0.53 0.18 (0.28–0.78) NS

1032 627 (343–2660) 1164 756 (343–2660) 867 385 (452–1560) NS

4 (13%) 0 (0%) 4 (25%) NS

Age (years) 4.26 4.11 (0.38–17.18) 37 14 (18–76) 31 11 (18–56) NS

Male 12 (39%) 8 (53%) 4 (25%) NS Female 19 (61%) 7 (47%) 12 (75%) NS

Weight (kg) 14.9 10.8 (4–47) 14.1 10.4 (4–38.3) 15.9 11.6 (5.3–47) NS Height (cm) 90 31.1 (12–159) 94.2 31.2 (55–158) 86 31.5 (12–159) NS

Previous surgery 0 (0%) 0 (0%) 0 (0%) NS Previous catheterization 2 (6%) 0 (0%) 2 (6%) NS

Preoperative infection 1 (3%) 0 (0%) 1 (6%) NS

None 26 (84%) 15 (100%) 11 (69%) NS

Down 3 (10%) 0 (0%) 3 (19%) NS None 28 (90%) 15 (100%) 13 (81%) NS

I 8 (26%) 4 (27%) 4 (25%) NS II 21 (68%) 9 (60%) 12 (75%) NS III 2 (6%) 2 (13%) 0 (0%) NS

RACHS-1 score 2.4 0.5 (1–3) 2.4 0.5 (2–3) 2.4 0.6 (1–3) NS Basic aristoteles 7.2 1.5 (3–9) 7 1.2 (6–9) 7.4 1.9 (3–9) NS Complete aristoteles 8.1 1.8 (4–11) 7.8 1.5 (6–10) 8.4 2.1 (4–11) NS

Mechanic ventilation 0 (0%) 0 (0%) 0 (0%) NS

Preoperative infection 1 (3%) 0 (0%) 1(6%) NS None 30 (97%) 15 (100%) 15 (94%) NS

Lactate 1.2 0.3 (0.6–1.7) 1.2 0.3 (0.7–1.7) 1.1 0.3 (0.6–1.5) NS

0 (0%) 0 (0%) 0 (0%) NS

Control group (without MUF) n (%) or mean SD (range)

173

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

#### 2.5. Statistical analysis

Information was registered in evaluation sheets, stored in an electronic Excel page and analyzed by means of a Prisma Graphics v3.1 statistical software. Continuous variables are presented as a mean, standard deviation, and variability ranges (minimum and maximum). Categorical data are presented by means of frequency and percentages in relation to the population at risk. Comparison between the two study groups was made by means of a Student's t-test for continuous variables. A chi-squared (X2 ) test was used for comparing categorical variables with a 95% confidence interval (CI). A p-value <0.05 was considered as statistically significant.
