3. Results

A total of 31 patients were enrolled and randomized to this trial: 15 to the problem group (with MUF) and 16 to the control group (without MUF).

#### 3.1. Preoperative characteristics

Table 1 shows the type of congenital diseases that were operated by means of CPB in both groups of study. There are no differences in the total number of congenital heart disease in the studied groups, but control group (without MUF) showed more patients with AV channel than the problem group (with MUF).


Table 1. Congenital heart disease type in the studied groups.

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.

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

categorical variables with a 95% confidence interval (CI). A p-value <0.05 was considered as

A total of 31 patients were enrolled and randomized to this trial: 15 to the problem group (with

Table 1 shows the type of congenital diseases that were operated by means of CPB in both groups of study. There are no differences in the total number of congenital heart disease in the studied groups, but control group (without MUF) showed more patients with AV channel

Ventricular septal defect 13 (42%) 8 (52%) 5 (31%) NS Balanced AV channel 8 (26%) 1 (7%) 7 (44%) 0.04 Congenital mitral valve disease 4 (13%) 3 (20%) 1 (6%) NS Subaortic membrane 3 (10%) 1 (7%) 2 (13%) NS Right ventricular outflow tract obstruction 1 (3%) 1 (7%) 0 (0%) NS Double chamber right ventricle 1 (3%) 1 (7%) 0 (0%) NS Atrial septal defect 1 (3%) 0 (0%) 1 (6%) NS Total 31 (100%) 15 (100%) 16 (100%) NS

Problem group (with MUF) (n = 15) n (%)

(n = 31) n (%)

) test was used for comparing

Control group (without MUF) (n = 16) n (%)

p

Student's t-test for continuous variables. A chi-squared (X2

MUF) and 16 to the control group (without MUF).

3.1. Preoperative characteristics

than the problem group (with MUF).

Congenital heart disease type Total series

Table 1. Congenital heart disease type in the studied groups.

2.5. Statistical analysis

172 Advances in Extra-corporeal Perfusion Therapies

statistically significant.

3. Results



MUF), without differences in both groups for the rest of pro-inflammatory agents (IL-10, C3d,

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

On the other hand, Table 4 shows a lack of statistically significant difference in the concentrations of pro-inflammatory agents at the control group before surgical correction (T0) and after CPB (T2). Finally, Table 5 shows the comparison between the concentration of pro-inflammatory agents in the problem group before surgical correction (T0) and after MUF (T4). There is a statistically significant removal of IL-6, but no difference in the concentrations of the rest of pro-

Table 6 summarizes the comparison of clinical end point variables in both groups of study (with and without MUF). There is a statistically significant decrease of hemoglobin (Hb) in the problem group after MUF compared with the baseline level, which is not observed in the

Both groups show an increase in lactate levels and heart rate after surgery when comparing these values with the baseline ones before CPB. Control group (without MUF) showed a statistically significant increase in the central venous pressure after CPB compared with the ones before CPB. There were no differences before and after CPB in the other hemodynamic variables (systolic, diastolic, and mean blood pressures), nor in operative morbidity and mortality. Successful clinical operative endpoints were achieved in both groups of study.

C3d (ng/ml) 413.248 316.804 264.33 198.12 NS C4d (ng/ml) 213.89 116.72 210.65 141.13 NS IL-6 (pg/ml) 246.874 365.69 289.499 301.913 NS IL-10 (pg/ml) 299.618 370.148 387.26 306.07 NS

Table 4. Comparison between concentrations of pro-inflammatory agents at T0 (baseline) and T2 (after CPB) for the

C3d (ng/ml) 368.66 331.87 379.99 264.64 NS C4d (ng/ml) 199.57 201.56 172.89 139.64 NS IL-6 (pg/ml) 672.249 433.186 366.31 280.25 0.0293 IL-10 (pg/ml) 239.698 381.517 230.453 352.27 NS

Table 5. Comparison between concentrations of pro-inflammatory agents at baseline (T0) and after MUF (T4) for the

T2 Control group (without MUF) n = 16 Media DE

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175

T4 Problem group (with MUF) n = 15 Media DE p

p

inflammatory agents analyzed (IL-10, C3d, and C4d).

Pro-inflammatory agent T0 Group control (sin UFM)

Pro-inflammatory agent T0 Grupo problema (con

n = 16 Media SD

UFM) n = 15 Media SD

The words and numbers in "bold" highlight the variables that have a statistical significance (p<0.005).

3.3. Clinical operative results

control group.

control group (without MUF).

problem group (with MUF).

and C4d).

Table 2. Preoperative characteristics of the studied groups.

Table 2 shows the rest of preoperative characteristics in both studied groups. Note that there are no statistical differences in all variables analyzed between the two groups.

Although more random patients with AV channel in the control group, the rest of the preoperative data showed that both groups are absolutely comparable.

#### 3.2. Biochemical operative results

Table 3 compares the concentration of pro-inflammatory agents between groups before surgical correction (T0). Note a baseline elevated concentration of IL-6 in the problem group (with


Table 3. Comparison between concentrations of pro-inflammatory agents in both groups of study (with and without MUF) at baseline (T0).

MUF), without differences in both groups for the rest of pro-inflammatory agents (IL-10, C3d, and C4d).

On the other hand, Table 4 shows a lack of statistically significant difference in the concentrations of pro-inflammatory agents at the control group before surgical correction (T0) and after CPB (T2).

Finally, Table 5 shows the comparison between the concentration of pro-inflammatory agents in the problem group before surgical correction (T0) and after MUF (T4). There is a statistically significant removal of IL-6, but no difference in the concentrations of the rest of proinflammatory agents analyzed (IL-10, C3d, and C4d).

### 3.3. Clinical operative results

Table 2 shows the rest of preoperative characteristics in both studied groups. Note that there

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

Creatinine 0.4 0.1 (0.2–0.7) 0.4 0.1 (0.2–0.7) 0.4 0.1 (0.3–0.5) NS

Baby Rx 14 (52%) 7 (47%) 7 (58%) NS Terumo SX10 6 (22%) 4 (27%) 2 (17%) NS Terumo SX18 1 (4%) 1 (7%) 0 (0%) NS Mini max 5 (19%) 2 (13%) 3 (25%) NS Safe Mini 1 (4%) 1 (7%) 0 (0%) NS Arterial filter use 18 (67%) 12 (80%) 6 (50%) NS

CPB time (min) 81.9 26.9 (40–131) 76.5 23.7 (40–122) 87 29.4 (41–131) NS

Temperature (C) 27 1.6 (24–30) 27 1.5 (24–29) 27.3 1.8 (24–30) NS

Blood cardioplegia 29 (94%) 14 (93%) 15 (94%) NS

53.7 23.6 (12–96) 49.5 21.8 (18–90) 57.6 25.2 (12–96) NS

29 (94%) 14 (93%) 15 (94%) NS

T0 Control group (without MUF)

p

n = 16 Mean DE

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

Although more random patients with AV channel in the control group, the rest of the preop-

Table 3 compares the concentration of pro-inflammatory agents between groups before surgical correction (T0). Note a baseline elevated concentration of IL-6 in the problem group (with

C3d (ng/ml) 368.66 331.87 413.248 316.804 NS C4d (ng/ml) 199.57 201.56 213.89 116.72 NS IL-6 (pg/ml) 672.249 433.186 246.874 365.69 0.0061 IL-10 (pg/ml) 239.698 381.517 299.618 370.148 NS

Table 3. Comparison between concentrations of pro-inflammatory agents in both groups of study (with and without

The words and numbers in "bold" highlight the variables that have a statistical significance (p<0.005).

are no statistical differences in all variables analyzed between the two groups.

erative data showed that both groups are absolutely comparable.

T0 Problem group (with MUF)

n = 15 Mean DE

3.2. Biochemical operative results

Table 2. Preoperative characteristics of the studied groups.

Variable Total series n (%) or

174 Advances in Extra-corporeal Perfusion Therapies

Perfusion variables Oxigenator type

Surgical variables

Anterograde cardioplegia

Pro-inflammatory

MUF) at baseline (T0).

agent

(min)

Aortic cross clamp time

mean SD (range)

Table 6 summarizes the comparison of clinical end point variables in both groups of study (with and without MUF). There is a statistically significant decrease of hemoglobin (Hb) in the problem group after MUF compared with the baseline level, which is not observed in the control group.

Both groups show an increase in lactate levels and heart rate after surgery when comparing these values with the baseline ones before CPB. Control group (without MUF) showed a statistically significant increase in the central venous pressure after CPB compared with the ones before CPB. There were no differences before and after CPB in the other hemodynamic variables (systolic, diastolic, and mean blood pressures), nor in operative morbidity and mortality. Successful clinical operative endpoints were achieved in both groups of study.


Table 4. Comparison between concentrations of pro-inflammatory agents at T0 (baseline) and T2 (after CPB) for the control group (without MUF).


Table 5. Comparison between concentrations of pro-inflammatory agents at baseline (T0) and after MUF (T4) for the problem group (with MUF).


Table 6. Comparison between operative clinical end point variables in both groups of study (with and without MUF). 4. Discussion

expression of leukocyte adhesion.

size, with CPB circuit volume usually 200

(TNF-

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

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

α), interleukins, and endotoxins. These agents activate the intracellular transcription factor as well, which increases endothelial pro-inflammatory cytokines and the molecular

–300% higher than that of the patient. In addition, an

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

–30 mg/kg, 6

–12 h before CPB),

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

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

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

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

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

groups included neonate patients for the reasons already discussed.

congenital heart disease that are operated on with CPB.

population. Some of them are steroids (e.g., dexamethasone 10

α

177
