Capillary leak syndrome in children with C4A-deficiency undergoing cardiac surgery with cardiopulmonary bypass: a
Shihai Zhang1, Shouyong Wang, Qing Li
1Department of Anaesthesiology, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, People's Republic of China.
Insights
Priming with C4A-rich plasma significantly reduced capillary leak syndrome in children with C4A deficiency undergoing cardiopulmonary bypass. This intervention also attenuated the systemic inflammatory response post-procedure.
Area of Science:
- Cardiovascular Surgery
- Immunology
- Pediatric Critical Care
Background:
- Capillary leak syndrome (CLS) is a severe complication post-cardiopulmonary bypass (CPB), affecting 4-37% of pediatric patients.
- C4A deficiency is a known risk factor for CLS, necessitating targeted preventive strategies.
Purpose of the Study:
- To investigate the efficacy of C4A-rich plasma priming in preventing CLS in pediatric patients with C4A deficiency.
- To evaluate the impact of C4A-rich plasma on systemic inflammatory markers and oxygenation post-CPB.
Main Methods:
- A randomized controlled trial involving 116 children with C4A deficiency undergoing CPB.
- Patients received either C4A-free or C4A-rich plasma priming (20 mL/kg).
- Primary outcome: incidence of CLS. Secondary outcomes: inflammatory mediators, plasma protein, and PaO2/FiO2 ratios pre- and post-CPB.
Main Results:
- CLS incidence was significantly lower in the C4A-rich plasma group (5%) compared to the C4A-free group (97%) (p<0.0001).
- C4A-rich plasma attenuated increases in activated C4, IL-6, IL-8, and TNF-alpha, and maintained higher PaO2/FiO2 ratios and plasma protein levels post-CPB.
- Activated C4 levels correlated with inflammatory markers and CLS severity.
Conclusions:
- C4A-rich plasma priming is effective in reducing CPB-related CLS in pediatric patients with C4A deficiency.
- This strategy mitigates the systemic inflammatory response and improves outcomes following CPB.
Background:
Capillary leak syndrome is a life-threatening complication after cardiopulmonary bypass (CPB), with an incidence of about 4-37% in children worldwide. On the basis of previous results, we undertook a randomised controlled study to investigate the priming with plasma rich in the C4A isotype of complement component 4 on the incidence of capillary leak syndrome in children with C4A deficiency.
Methods:
In a hospital in Wuhan, China, we randomly assigned 116 neonates, infants, and children lacking complement component C4A to receive C4A-free or C4A-rich plasma priming (n=58 each, 20 mL/kg). The primary outcome was capillary leak syndrome, identified as an increased transvascular escape rate of Evans blue dye from plasma. Concentrations of activated complement components C4 and C3, inflammatory mediators interleukin 6, interleukin 8, tumour necrosis factor (TNF) alpha, plasma protein, and PaO2/F(I)O2 ratios (ratio of the partial arterial pressure of oxygen to the fractional concentration of oxygen in inspired air) were measured before and 4 h after CPB. Analysis was by intention to treat.
Findings:
Three (5%) patients given C4A-rich plasma priming had capillary leak syndrome compared with 56 (97%) given C4A-free plasma (p<0.0001). At 4 h after CPB, activated C4, interleukin 6, interleukin 8, and TNFalpha concentrations were higher, whereas PaO2/F(I)O2 ratios and plasma protein concentrations were significantly lower in the C4A-free group than changes in the C4A-rich group. Activated C3 rose equally in both groups. Activated C4 significantly correlated with interleukin 6, interleukin 8, and TNFalpha concentrations; PaO2/F(I)O2 ratios; and the escape rate of Evans blue dye at 4 h after CPB. Two patients in the C4A-free group died of respiratory and renal failure on day 3 after CPB.
Interpretation:
In paediatric patients with C4A deficiency, C4A-rich plasma priming reduces the incidence of CPB-related capillary leak syndrome by blocking the activated C4 increase and attenuating the systemic inflammatory response after CPB.
