Capillary leak syndrome in children with C4A-deficiency undergoing cardiac surgery with cardiopulmonary bypass: a double-blind, randomised controlled study.

Abstract

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.

• Authors: Shihai Zhang, Shouyong Wang, Qing Li, Shanglong Yao, Bangxiong Zeng, Roy C Ziegelstein, Qinghua Hu
• Journal: Lancet (London, England) (Lancet) 2005 Aug 13-19 Vol. 366 Issue 9485 Pg. 556-62 ISSN: 1474-547X [Electronic] England
• PMID: 16099291 (Publication Type: Clinical Trial, Journal Article, Randomized Controlled Trial, Research Support, Non-U.S. Gov't)

Chemical References

• Inflammation Mediators
• Complement C4a

Topics

• Capillary Leak Syndrome (blood, etiology, physiopathology, prevention & control)
• Capillary Permeability
• Cardiac Surgical Procedures
• Cardiopulmonary Bypass (adverse effects)
• Child
• Child, Preschool
• Complement C4a (administration & dosage, deficiency)
• Double-Blind Method
• Female
• Heart Septal Defects (surgery)
• Humans
• Infant
• Infant, Newborn
• Inflammation Mediators (blood)
• Male