Patient Characteristics
During the study period, 59 children under two years old were referred to our surgical unit for congenital heart disease with a left-to-right shunt; 27 patients were female (45.76%), and 32 patients were male (54.24%). Echocardiography assessed patients before cardiac surgery; 34 patients (57.63%) had PAH, and 25 patients (42.37%) did not have PAH. Preoperative PASP was 59.94 mmHg ± 17.56 mmHg in the PAH group. All patients underwent successful closure of the cardiac shunt. Demographic data and associated congenital heart lesions are presented in Table 1. There were no significant differences in the demographic characteristics of the patients between those with PAH and those without PAH. No significant difference in the preoperative serum levels of inflammatory cytokines, including IL-8, IL-6, IL-10, IL-1β, and TNF-α, was found between these two groups. (Table 2)
Table 1. Demographic data of patients with and without PAH
Variable
|
No PAH group(n=25)
|
PAH group(n=34)
|
P Value
|
Agea (months)
|
7.90 ± 0.75
|
6.62 ± 1.06
|
0.3597
|
Gender
|
|
0.8173
|
Male (n)
|
14
|
18
|
Female (n)
|
12
|
15
|
Weight a(Kg)
|
7.49 ± 0.36
|
6.60 ± 0.39
|
0.1162
|
mPAP(mmHg)
|
<20mmHg
|
56.73±20.58
|
<0.0001
|
Type of CHD
|
0.1693
|
VSD (n)
|
10
|
17
|
PAPVC (n)
|
8
|
3
|
PDA/VSD (n)
|
1
|
1
|
VSD/ASD (n)
|
4
|
7
|
VSD/MR (n)
|
2
|
1
|
DORV/VSD (n)
|
0
|
2
|
COA/VSD (n)
|
0
|
3
|
Abbreviations: PAH, pulmonary atrial hypertension; CHD, congenital heart disease; VSD, ventricular septal defect; PAPVC, Partial anomalous pulmonary venous connection; PDA, Patent ductus arteriosus; CAVC, Complete atrioventricular septal defect,; COA, Coarctation of aorta.
Table 2. Preoperative proinflammatory factors of patients with and without PAH
Variable
|
No PAH group(n=25)
|
PAH group(n=34)
|
P Value
|
Il-6 (pg/ml)
|
6.45 ± 2.79
|
5.52 ± 1.52
|
0.7616
|
Il-8 (pg/ml)
|
20.58 ± 5.54
|
44.10 ± 16.62
|
0.2267
|
Il-10 (pg/ml)
|
12.31 ± 6.79
|
7.98 ± 1.43
|
0.4936
|
IL-1β(pg/ml)
|
6.70 ± 0.80
|
7.18 ± 0.90
|
0.6940
|
TNF-α(pg/ml)
|
16.47 ± 1.438
|
19.51 ± 1.976
|
0.2458
|
a Descriptive data presented as median and interquartile range.
Clinical early postoperative outcomes
There was no mortality in either group. As shown in Figure 2, the PAH group had a significant impact on early postoperative surgical outcomes; the duration of mechanical ventilation time was significantly longer in the PAH group (22.76 hours ± 2.49 hours) compared with the No PAH group (13.72 hours ± 2.51 hours) (p=0.0485). Importantly, the lengths of ICU and ward stay after surgery were also longer in the PAH group than in the No PAH group (p=0.0432 and 0.0039, respectively).
Change of inflammatory cytokines after CPB
After surgery, CPB can produce and release numerous pro-inflammatory cytokines. We analyzed the changes in postoperative inflammatory cytokines. As shown in Figure 3, the levels of inflammatory cytokines, including IL-6, IL-8, and IL-10, increased significantly after CPB in both PAH and non-PAH patients (p < 0.05). However, the levels of IL-1β and TNF-α did not show significant changes. Interestingly, these inflammatory cytokines increased more in the PAH group compared to the non-PAH group (P=0.0380, 0.0359, and 0.0078, respectively). Then we compared the duration of CPB time and aortic cross-clamping (ACC) time of these two groups. The CPB time for patients with PAH and without PAH was (66.64 ± 7.53) hours and (75.63 ± 3.65) hours, respectively. The ACC time was (48.19 ± 6.23) hours for PAH patients and (53.22 ± 3.32) hours for patients without PAH. No significant difference was found in the CPB and ACC durations between PAH and non-PAH patients (p=0.2438 and 0.4510).
To investigate whether preoperative PAH is associated with higher levels of inflammatory cytokines, Spearman correlation coefficients were calculated between preoperative PASP and postoperative levels of inflammatory cytokines in the PAH-CHD group. As shown in Table 3, preoperative PASP was found to be correlated with postoperative levels of IL-6 (rs=0.5156, p=0.0083) and IL-10 (rs=0.5027, p=0.0397), but not with the level of IL-8.
Table 3. Spearman’s correlation coefficient analysis between PASP and postoperative inflammatory cytokines
Spearman’s correlation coefficient
|
|
Post-IL 6
|
Post-IL 8
|
Post-IL 10
|
rs
|
p value
|
rs
|
p value
|
rs
|
p value
|
Pre- PASP
|
0.5156
|
0.0083
|
0.1099
|
0.6263
|
0.5027
|
0.0397
|
Preoperative PASP is associated with prolonged postoperative mechanical ventilation
CPB causes a series of inflammatory events that have adverse effects on postoperative outcomes, and the release of cytokines plays a key role in the pathophysiology of this process. Given that preoperative high PASP is associated with higher levels of IL-6 and IL-10 after CPB, we hypothesize that preoperative high PASP, linked to more robust inflammatory responses by CPB, leads to subsequent poor postoperative outcomes in pediatric patients with PAH-CHD. To verify this hypothesis, the study assessed the reliability of preoperative PASP in predicting early postoperative outcomes. The results summarized in Figure 4 show the sensitivity, specificity, AUC, and p-value of preoperative PASP for predicting ventilation time > 21 hours, ICU length of stay > 4.5 days, and ward length of stay > 11 days. Preoperative PASP > 52 mmHg is associated with ventilation time > 21 hours, but not with ICU length of stay > 4.5 days and ward length of stay > 11 days.