A Multicenter Prospective Clinical Study Of Continuous Blood Purification In Treating Child Severe Sepsis

A multicenter prospective clinical study of continuous blood purification in treating child severe sepsisBackgroundSevere sepsis morbidity increases year by year and there is currently no effective treating method for it, which seriously threats children’s health. The study of its pathogenesis in recent years, it is considered that the severe sepsis was caused by the destruction of body’s pro-inflammatory reaction and anti-inflammatory balance. Therefore, regulating immune balance and reducing the inflammatory response is thought to be one of the feasible ways. Continuous blood purification (CBP) has attracted much attention because of its abilities to maintain a stable internal environment, eliminate inflammation medium, and hence to adjust the immunity, reduce organ damage. But it is still a big controversy whether CBP could improve organ function, decrease plasma level of inflammatory mediators and improve prognosis, etc. Pediatric CBP starts late. It has been gradually applied as the treatment for child sepsis in the recent ten years globally, which applied and promoted in China for about five years. There lacks a multicenter, large sample clinical research about the effect of CBP at present, and there is no basis of evidence-based medicine for CBP treatment for child sepsis.ObjectivesWe evaluate the treating efficacy of CBP in PICU of five children’s hospitals in Shanghai and Zhejiang, through observing the changes of organ function, inflammatory mediators and prognosis when the CBP is applied for treating child sepsis.Me hods1.Multicenter:Children’s Hospital of Fudan University. Children’s Hospital of Shanghai, Children’s Medical Center of Shanghai, Children’s Hospital of Zhejiang Province, Yuying Children’s Hospital of Wenzhou Medical College2.Prospective:October 1,2011-September 30,2012(one year)3.Inclusion criteria:29 days-16 years old children who hospitalize in PICU for severe sepsis (infected or may be infected+SIRS+＜1 organ dysfunction)4. Grouping principles:Logged group, cases meeting the requirements of inclusion criteria; unlogged group, meeting the requirements of inclusion criteria, who do not accept the treatment of CBP, but still require the standardization of conventional treatment due to parents’ economic, intention-to-treat considerations or other reasons.5.Observational indexes:l) Observe the changes of cardiovascular function(HR、MAP、 Lac), respiratory function(PaO2/FiO2、SaO2), kidney function (BUN、Cr), inflammatory indexes[total white blood cell count (TWCC), C-reactive protein (CRP) concentration, IL-6, IL-10, TNF-alpha concentration, PRISM score Ⅲ and PCIS between the logged group and unlogged group children at different time points (0d,1d, 2d,3d,5d); 2) Compare the differences between the two groups at different time points (0d,1d,2d,3d,5d); 3) compare the 28-day survival rate differences between the two groups.Results1.There are not differences in age, gender, underlying disease and primary infection disease between two groups(P>0.05).2. Organ function:Cardiovascular, respiratory, renal function1) Cardiovascular function indexes (HR, MAP,Lac)-Heart rate(HR):Logged group declines gradually over time, which 3d is lower than Od time point(P<0.05), unlogged group does not have significant downward trend; logged group is lower than unlogged group at 3d and 5d (P<0.05). Mean arterial pressure (MAP) logged group gradually increases, unlogged group does not have significant upward trend; logged group is higher than unlogged group at 3d and 5d (P<0.05). The arterial blood lactate concentration (Lac),there are not differences within and between the two groups at each time point (P> 0.05).2)Respiratory function indexes (PaO2/FiO2、SaO2):Oxygenation index (PaO2/FiO2) logged group gradually increases,2d is higher than Od (P<0.05),3d,5d is higher than each previous time point (P<0.05), unlogged group dose not significant increase; there are not differences between two groups at each time point (P> 0.05). Arterial oxygen saturation (SaO2), logged group gradually increases, 1d,2d,3d,5d is higher than each of the previous time point(P<0.05),unlogged group does not significant increase; there are not differences between two group (P>0.05).3.Inflammatory mediators indexes(TWCC、CRP、IL-6、IL-10、TNF-α)1) Non-specific indexes (TWCC, CRP):The differences of white blood cell (TWCC) count within and between the two groups at each time point are not statistically significant (P> 0.05). C-reactive protein (CRP), logged group is lower at each time point (1d,2d,3d,5d) (P<0.05) than the previous point time, unlogged group does not significant decrease;there are not differences between two groups at each time point(P> 0.05).2)Specific indexes (IL-6, IL-10, TNF-a):Interleukin-6(IL-6) of logon group at each time point is not significant different(P> 0.05), unlogged group decreases,2d is lower than 0d(P<0.05),3d is lower than 2d (P<0.05); because of quite difference at 0d(P <0.05), two group are not comparable. The differences of Interleukin-10 (IL-10) within and between the two groups are not significant at each time point (P> 0.05). Tumor necrosis factor-alpha (TNF-alpha), there are not differences within two groups at each time point (P> 0.05), logged group is lower than unlogged group at 2d(P <0.05).4.Prognosis (PRISM Ⅲ score, PCIS,28-day survival rate)1)PRISM Ⅲ score:Logged group is downward trend, but not different at each time point (P> 0.05), unlogged group is no significant downward trend; it is not different between two group at each time point(P> 0.05).2) PCIS:The logged group gradually increased,2d is higher than Od(P<0.05), unlogged group does not significantly increase;it is not different between two groups at each time point(P> 0.05).3)28-day survival rate:Logged group survival rate is 70.0%, unlogged group is 52.9%, it is not different between two group (P> 0.05).ConclusionsContinuous blood purification can improve circulation and oxygenation function and obviously improve renal function indexes of children with severe sepsis. This study did not find continuous blood purification can obviously decrease the level of plasma inflammation medium, improve critical score and 28 days survival rate of children with severe sepsis.