Early Predictor Of Lung Injury And Copy Number Polymorphisms Within Defension Gene Cluster In Infant And Young Children After Cardiopulmonary By Pass

Part I Perioperative Risk Factors for Prolonged Mechanical Ventilation Following Cardiac Surgery in Neonates and Young InfantsBackground and Objective:Prolonged mechanical ventilation (PMV) after cardiac surgery in children isassociated with a high postoperative morbidity and mortality, as well as increased ICU and hospital resource utilization. Little has been done to identify the predictors of PMV in neonates and young infants. This study was performed to evaluate the perioperative risk factors for PMV and to provide the theoretical for early warning of lung injury in neonates and young infants undergoing cardiac surgery.Methods:This prospective study reviewed the clinical records of consecutive children aged<3months. Patients with mechanical ventilation (MV)>72h following operation were PMV group and all others were the non-PMV group. After univariate analysis, a stepwise logistic regression analysis was used to evaluate the independent risk factors for PMV following cardiac surgery. The predictive ability of risk factors for PMV was assessed using an area under the receiver operating characteristic curve (ROC). The statistical analysis was performed with SPSS16.0for Windows. P<0.05was considered statistically different.Results:From2001to2007, a total of216patients'clinical records were reviewed, which included42neonates. After excluded the patients with incomplete clinical data, prematurity, or death within the first24h after surgery, we enrolled172consecutive children. Sixty-one patients required PMV after cardiac surgery and the incidence of PMV was35.4%. The median duration of MV was150h (rang72to600) in PMV patients, while it was28h (rang4to70) in non-PMV patients. The independent risk factors for PMV were risk adjustment for surgery for congenital heart disease (RACHS-1)(OR6.60,95%CI1.08-40.29P=0.041), nosocomial pneumonia (OR54.78,95%CI5.72-524.36P=0.001), low cardiac output syndrome (LCOS)(OR37.06,95%CI3.99-344.31P=0.001), postoperative cumulative positive fluid balance (OR10.06,95%CI1.19-95.15P=0.032), and extubation failure (EF)(OR15.61,95%CI1.37-178.53P=0.027). The value for the ROC curve was0.940.Conclusion:We found that neonates and young infants undergoing cardiac surgery had a high incidence of PMV. RACHS-1, nosocomial pneumonia, LCOS, fluid retention postoperatively, and EF are risk factors for PMV and this was valuable for early warning PMV and lung injury in neonates and young infants undergoing reparative surgery for congenital heart disease. Part II Early Prediction of Acute Lung Injury following Cardiac Surgery necessitating Cardiopulmonary Bypass in Infants and Young children:a pilot studyBackground and Objective:Acute lung injury (ALI) after cardiac surgery is associated with a high postoperative morbidity and mortality. There are little predictors for the occurrence of the complication. The primary objective was to evaluate whether elevated plasma levels of soluble receptor for advanced glycation end products (sRAGE) and S100A12reflect impaired lung function and to explore the early warning biomarkers for ALI in infants and young children after cardiac surgery necessitating cardiopulmonary bypass (CPB).Methods:This was a prospective and case-control study. The study protocols were approved by the hospital ethical committee (Medical Ethical Committee of the Children's Hospital of Zhejiang University). The subjects included all children aged<3years old who underwent cardiac surgery with CPB during the period from May1st to June31st2011. The enrolled children were assigned into ALI group and non-ALI group according to the American-European Consensus Criteria. After approved by supervisors, plasma concentrations of sRAGE and S100A12were measured using ELISA at baseline, before and immediately after CPB, as well as1h,12h and24h after operation. Differences concentrations between two groups were analyzed with t test and Mann-Whitney U test. A stepwise logistic regression analysis was used to indentify the independent risk factor for ALI. The predictive ability of risk factors for ALI was assessed using an area under the receiver operating characteristic (ROC) curve. A P value<0.05was considered statistically significant.Results:During the study period, fifty-eight patients were enrolled and16(27.6%) developed postoperative ALI. Plasma sRAGE and S100A12levels increased immediately after CPB and their levels kept significantly higher in the ALI group even24h after operation (P<0.01). In multivariate logistic regression analysis, plasma sRAGE level immediately after CPB remained as a predictor for postoperative ALI (OR1.088,95%CI1.011-1.171, P=0.025). Increased sRAGE and S100A12levels immediately after CPB significantly correlated with lower PaO2/FiO2ratio (sRAGE: r=-0.404, P=0.002; S100A12:r=-0.56, P<0.001) and higher radiographic lung injury sore (P<0.05), as well as longer mechanical ventilation time (sRAGEN:r=0.405, P=0.002; S100A12N:r=0.322, P=0.014), longer surgical Intensive Care Unit stay (sRAGEN:r=0.421, P=0.001; S100A12N:r=0.365, P=0.005) and hospital stay (sRAGEN: r=0.329, P=0.012; S100A12N:r=0.471, P=0.001).Conclusion:Our study indicted that plasma concentrations of sRAGE and S100A12were increased significantly immediately after CPB. Elevated sRAGE and S100A12levels correlate with impaired lung function, and sRAGE is a useful early warning biomarker of ALI in infants and young children undergoing reparative surgery for congenital heart disease. Part II Association Study between CNPs within Defensin Gene Cluster and Lung Injury following Cardiac Surgery necessitating Cardiopulmonary Bypass in Infants and Young childrenBackground and Objective:There are copy number polymorphisms within defensin gene cluster. To investigate whether these variation in chromosome8p22-23are associated with the incidence acute lung injury (ALI) after cardiopulmonary bypass by case-control association analysis, and to elucidate the mechanism of defensin in the pathophysiology of severe sepsis.Methods:The study protocols were approved by the hospital ethical committee (Medical Ethical Committee of the Children's Hospital of Zhejiang University). According to the ALI criteria of (NAECC), children with ALI after cardiopulmonary bypass were enrolled. Quantitative real-time PCR was performed to study the copy number variation of DEFA1/DEFA3gene and DEFB4gene within the defensin gene cluster. Plasma a-defensin and β-defensin levels were measured by ELISA. The association of copy number polymorphisms within the defensin gene cluster with the incidence of ALI was analyzed by χ2test or Fisher's exact test. Student's t was sued to determine the difference of plasma defensin levels in the two groups. The statistical analysis was performed with SPSS16.0for Windows. P<0.05was considered statistically different.Results:Eighty-three patients with ALI were enrolled, which included49(59%) boys and186patients without ALI were in the control group. In the controls, copy number of DEFA1/DEFA3had a range of2-15per genome, with a median number of7copies. The median copy number of DEFA1/DEFA3in the patients with ALI was5copies per genome (range4-12copies). There were no significant differences between the copy numbers of DEFA1/DEFA3in the two groups (P>0.05). In addition, there were also no significant difference between the copy number of DEFB4in the control (a range of2-13, with a median number of5copies) and ALI (a range of2-12, with a median number of5copies, P>0.05). Plasma levels of a-defensin after cardiopulmonary bypass were significantly associated with the occurrence of ALI (P<0.05).Conclusion:Present study first reported the association between copy number polymorphisms within defensin gene cluster and the occurrence of ALI after cardiopulmonary bypass, and demonstrated that the CNP of DEFA1/DEFA3gene and DEFB4gene were not associated with ALI after cardiopulmonary bypass. Plasma a-defensin levels after cardiopulmonary bypass were associated with the occurrence of ALI after cardiopulmonary bypass in infants and young children.