Continuous Blood Purification Group Research Articles

Continuous Blood purification on Influenza-Associated Neurological Disease in children: a retrospective cohort study

BackgroundDue to lack of proven therapies, we evaluated the effect of CBP on Influenza-Associated Neurological Disease in children.MethodsA single-center, retrospective, cohort study was conducted in Luoyang, Henan province, China from January 2018 to January 2020. Children (<18 years) with influenza-associated neurological disease were enrolled in the study. Children with indications for CBP and parental consent received CBP (Continuous Blood purification), while others received maximal intensive care treatment because of the absence of parental consent. The outcomes of the CBP and non-CBP groups were compared. Categorical variables were presented as percentage and compared by Chi-square test. Continuous variables were expressed as median (interquartile ranges) and compared with non-parametric independent sample test. Statistical analyses were carried out by SPSS (version 26.0) and p < 0.05 (2 tailed) was considered to be statistically significant.Results30 children with influenza-associated neurological disease were recruited to the study. 18 received CBP and the other 12 received maximal intensive care. There were no differences between CBP and non-CBP children in age, sex, body weight, type of influenza virus, neurological complications, Glasgow score, PIM-2 score and PCIS at admission (p > 0.05). The inflammatory factors (CRP, PCT and IL-6) of 30 cases were tested at admission and after 3 days of admission. In the CBP group, there was a significant decrease in IL-6 levels at 3 days of admission (p = 0.003) and a decrease in CRP and PCT levels, but no significant difference (p > 0.05). In the non-CBP group, there were no significant difference on levels of CRP, PCT and IL-6 at admission and 3-day of admission (p > 0.05). The 28-day mortality was significantly lower in the CBP group compared with the non-CBP group (11.11% vs. 50%, p = 0.034).ConclusionsCBP definitely reduces IL-6 levels significantly. We did find that the survival rate of patients in the CBP group was improved. But we don’t know if there is a relationship between the reduction of IL-6 levels and the survival rate. Trial registration: http://www.chictr.org.cn/index.aspx(ChiCTR2000031754).

Effect of sub-hypothermia blood purification technique in cardiac shock after valvular disease surgery.

To observe the effect of sub-hypothermia (HT) blood purification technique in the treatment of cardiac shock after heart valve disease.The patients were randomly divided into normothermic (NT) continuous blood purification (CBP) group (NT group) and HT CBP group (HT group). Observe the cardiac index (CI), the oxygen delivery (DO2) and oxygen consumption (VO2) ratio, Acute Physiology and Chronic Health Evaluation III(APACHE III) score, multiple organ dysfunction syndrome (MODS) score, dynamic monitoring of electrocardiograph, blood loss with or without muscle tremors, intensive care unit stay, mechanical ventilation time, CBP time, and the cases of infection and mortality at 0 day, 1 day, 2 day, 3 day; all above indicators were compared between 2 groups.Ninety-five patients were randomly assigned into HT group (48 cases) and NT group (47 cases); there were no significant differences between the 2 groups for age, gender, pre-operative cardiac function, cardiothoracic ratio, and type of valve replacement (P > .05). There were no significant differences among the 1 day, 2 day, 3 day after recruited for CI, DO2/VO2 ratio, APACHE III score, MODS score (P > .05). But in HT group, DO2/VO2 ratio had been significantly improved after treatment for 1 day (2.5 ± 0.7 vs 1.8 ± 0.4, P = .024), and CI (3.0 ± 0.5 vs 1.9 ± 0.7, P = .004), APACHE III score (50.6 ± 6.2 vs 77.5 ± 5.5 P = .022), MODS score (6.0 ± 1.5 vs 9.3 ± 3.4, P = .013) also had been significantly improved after treatment for 3 days. In clinical outcomes, there were no significant differences between 2 groups for blood loss (617.0 ± 60.7 ml vs 550.9 ± 85.2 ml, P = .203), infection ratio (54.17% vs 53.19%, P = .341), the incidence of ventricular arrhythmia (31.25% vs 36.17%, P = .237), and muscle tremors (14.58% vs 8.51%, P = .346), while there were significant differences between 2 groups for intensive care unit stay (6.9 ± 3.4 days vs 12.5 ± 3.5 days, P = .017,), mechanical ventilation time (4.2 ± 1.3 days vs 7.5 ± 2.7 days, P = .034,), CBP time (4.6 ± 1.4 days vs 10.5 ± 4.0 days, P = .019), mortality (12.50% vs 23.40%, P = .024). But the incidence of bradycardia in HT group was much higher than the NT group (29.16% vs 14.89%, P = .029).HT blood purification is a safer and more effective treatment than NT blood purification for patients who suffered from cardiac shock after valve surgery.

Clinical analysis of continuous blood purification in the treatment of severe sepsis in infants

Objective To investigate the clinical efficacy and safety of continuous blood purification (CBP) in the treatment of severe sepsis in infants. Methods A retrospective analysis of 40 infants with severe sepsis treated with CBP was performed at PICU of Hunan Children′s Hospital from January 2014 to July 2017, and 50 infants with severe sepsis who were not treated with CBP at the same period were enrolled as control group.The indicators included blood gas analysis, lactic acid (Lac), blood glucose, electrolytes, blood routine, C-reaction protein (CRP) and procalcitonin (PCT), alanine aminotransferase (ALT) and aspartate aminotransferase (AST), total bilirubin(TB), urea nitrogen (BUN), serum creatinine (Scr) and creatine kinase isoenzyme MB (CK-MB), pediatric critical illness score (PCIS). Results (1) After 3 days of treatment, the recovery of body temperature, heart rate, respiratory rate and blood pressure in CBP group were better than those in the control group, and the differences between two groups were statistically significant(P 0.05). (5) Two cases of thrombocytopenia, 2 cases of femoral vein thrombosis, 2 cases of hypovolemic shock, and 1 case of blood coagulation in filter happened in CBP gruop, all cases had no puncture site infection. Conclusion CBP can improve the vital signs, internal environment, inflammatory reaction and organ function of infants with severe sepsis, and the effect is better than that of traditional methods.The complications of CBP in infants with severe sepsis are relatively large, so we should strictly master the indications of CBP in the treatment of severe sepsis in children. Key words: Continuous blood purification; Severe sepsis; Infants; Clinical efficacy; Safety

Effect of continuous blood purification on peripheral blood monocyte membrane binding CD14 expression and inflammatory response in patients with traumatic sepsis

Objective To investigate the effect of continuous blood purification (CBP) on peripheral blood monocyte membrane CD14 (mCD14) expression and inflammatory response in patients with traumatic sepsis Methods A retrospective case control study was conducted on the clinical data of 50 patients with severe sepsis after trauma treated between January 2015 and December 2016. There were 34 males and 16 females, with an average age of 45.37 years (range, 16-73 years). Patients were divided into CBP group (25 cases) and non-CBP group (25 cases) according to whether they agreed to receive CBP treatment. The peripheral blood samples were collected at 0, 12, 24, 48, and 72 hours after treatment, and the mCD14 and leukocyte elastase (HLE) expressions were detected by flow cytometry and by ELISA, respectively. The peripheral blood mononuclear cells were isolated from the two groups 24 h after treatment and cultured in vitro. The variations of mCD14 expression in mononuclear cells were measured at 4, 8, 12, 24, 48, and 72 h after stimulation with lipopolysaccharide (LPS). The expression levels of tumor necrosis factor (TNF)-α, interleukin (IL)-6, and IL-10 in mononuclear cells were detected by ELISA. Results At 12, 24, 48, and 72 hours after treatment, the leukocyte elastase levels in the two groups were lower than those before treatment (P 0.05). Conclusions CBP treatment can increase monocyte mCD14 expressions through eliminating inflammatory factors and pro-inflammatory mediators and reducing HLE directly or indirectly in patients with traumatic sepsis. When the body is stimulated again, its anti-inflammatory response ability is markedly stronger than that of patients who have not received CBP treatment. Key words: Sepsis; Wounds and injuries; Hemofiltration; Membrane CD14

Effect of early-stage keep warm intervention on improving low temperature risk in children underwent blood purification treatment

Objective To evaluate the clinical effectiveness of early-stage keep warm intervention on improving low temperature risk children treated with blood purification (BP). Methods Ninety children were randomized into observation group (46 cases) and control group of (44 cases) from July 2013 to September 2015. Control group were nursed with conventional BP standard operation process, while the observation group were nursed additionally with heat insulation blanket before 30 min of booting machine, and recorded the central body temperature of 0 min,30 min,60 min,90 min,120 min for each 60 min 1 time in the future. Until the end of the blood purification 60 min. Low temperature complications were recorded and judged between the two groups. Results In the observation group, 107 cases of low body temperature occurred during the course of 7 cases of blood purification, occurrence rate of 6.5% (7/107). The control group was 15.8% (16/101). The difference between the 2 groups was statistically significant (χ2=4.569, P<0.05); In the continuous blood purification group, observation group 10.6% (5/47), The incidence rate of control group was 29.3% (12/41), he difference between the 2 groups was statistically significant (χ2=4.876, P <0.05). Conclusions Application of heat insulation blanket at the early-stage may effectively reduce the risk of hypothermia complications in the children treated with blood purification. The continuous blood purification effect is more significant. Key words: Child; Blood purification; Hypothermia

Effects and risks of hypothermia during blood purification in the treatment of postoperative cardiogenic shock in valvular heart diseases

To implement hypothermia during blood purification to investigate its effect and risk in the treatment of postoperative cardiogenic shock in valvular heart disease. A non-blinded prospective randomized controlled trial (RCT) was conducted. Patients with valvular heart disease suffering from postoperative cardiogenic shock admitted to intensive care unit (ICU) of Wuhan Asian Heart Hospital from January 2011 to December 2014 were enrolled, and they were randomly divided into normothermic continuous blood purification (CBP) group (NT group) and hypothermia CBP group (HT group) according to random number table and envelope enclosed method. The patients in both groups were given continuous renal replacement therapy (CVVH), the blood temperature in NT group was remained at 36.5-37.3 °C , and it was controlled at 34.0-35.0 °C in HT group. The data were collected before and 1, 2, 3 days after treatment, including cardiac index (CI), the oxygen supply/oxygen consumption ratio (DO₂/VO₂), acute physiology and chronic health evaluation III (APACHE III) score, multiple organ dysfunction (MODS) score. The length of ICU stay, duration of mechanical ventilation, duration of CBP, ICU mortality and the incidence of complication were recorded. A total of 95 patients were enrolled, with 47 patients in NT group, and 48 in HT group. There was no significant difference in gender, age, preoperative cardiac function, cardiothoracic ratio and type of valve replacement between two groups. Compared with those before treatment, no significant difference was found in CI, DO₂/VO₂ ratio, APACHE III score, MODS score on 1, 2, 3 days after treatment in NT group (all P > 0.05). But in HT group, DO₂/VO₂ ratio was significantly improved on 1 day after treatment (2.5 ± 0.7 vs. 1.8 ± 0.4, P < 0.05), CI (mL · s⁻¹ · m⁻²: 50.01 ± 8.34 vs. 31.67 ± 11.67), APACHE III score ( 50.6 ± 6.2 vs. 77.5 ± 5.5), and MODS score (6.0 ± 1.5 vs. 9.3 ± 3.4) were significantly improved 3 days after treatment (all P < 0.05). Compared with those in NT group, DO₂NO2 ratio in HT group was significantly increased from 1 day after treatment (2.5 ± 0.7 vs. 1.8 ± 0.4, P < 0.05), and CI (mL · s⁻¹ · m⁻²: 38.34 ± 10.00 vs. 35.01 ± 6.67), APACHE III score (68.9 ± 7.1 vs. 81.2 ± 7.3), and MODS score (8.9 ± 2.7 vs. 10.6 ± 2.4) were significantly improved from 2 days after treatment (all P < 0.05). In respect of clinical outcomes, compared with NT group, the length of ICU stay (days: 6.9 ± 3.4 vs. 12.5 ± 3.5, t = 2.024, P = 0.017) and duration of mechanical ventilation (days: 4.2 ± 1.3 vs. 7.5 ± 2.7, t = 1.895, P = 0.034) in HT group was significantly shortened, duration of CBP was also significantly shortened (days: 4.6 ± 1.4 vs. 10.5 ± 4.0, t = 2.256, P = 0.019), and ICU mortality was significantly lowered (12.50% vs. 23.40, χ² = 1.987, P = 0.024), but there was no significant difference in incidence of infection (54.17% vs. 53.19%, χ² = 0.689, P = 0.341), ventricular arrhythmia (31.25% vs. 36.17%, χ² = 0.772, P = 0.237), and muscle fibrillation (14.58% vs. 8.51%, χ² = 0.714, P = 0.346), and blood loss (mL: 617.0 ± 60.7 vs. 550.9 ± 85.2, t = 1.290, P = 0.203) between HT group and NT group. The incidence of bradycardia in HT group was significantly higher than that of the NT group (29.17% vs. 14.89%, χ² = 2.368 P = 0.029). Blood purification under hypothermia is a safe and effective therapeutic procedure for postoperative cardiogenic shock in patients with valvular heart disease, and it may improve the prognosis of postoperative patients.

Comparison of the Therapeutic Effectiveness of Sustained Low-Efficiency Dialysis (SLED) with Continuous Blood Purification (CBP) in Critically Ill Patients

The differences in therapeutic effectiveness between sustained low-efficiency dialysis (SLED) and continuous blood purification (CBP) were investigated. In order to assess the different treatment methods, 56 critically ill patients were divided into two groups, the CBP group and the SLED group. A comparison was made between all the biochemical indicators, in-hospital duration, hemodynamic parameters, acute physiology and chronic health evaluation (APACHE-II), the survival, and the mortality rates. After treatment, the levels of serum creatine kinase isozyme MB (CK-MB), creatine kinase, creatinine, glutamate-oxalacetate transaminase (AST), glutamate-pyruvate transaminase (ALT), APACHE II score on the 1st, 2nd, and 7th day in both the treatment groups were lower than that before the treatment (P < 0.05). There are no statistical differences in in-hospital duration, biochemical indicators, APACHE II score, hemodynamic parameters, the survival rate and the mortality rate between the two groups (P > 0.05). It was concluded that SLED has similar hemodynamic stability with CBP and the two methods have similar treatment effects in critically ill patients. However, we noticed that SLED can be relatively economical and convenient for critically ill patients in clinical practice.

Treatment of lactic acidosis with early continuous blood purification

To observe the therapeutic effect of early continuous blood purification (CBP) on lactic acidosis patients. Using prospective randomized study method, 41 patients with lactic acidosis in intensive care unit (ICU) from January 2010 to April 2012 were randomly divided into CBP group (n=21) and control group (n=20). Among them, blood gas analysis, lactic acid, blood biochemistry were prospectively monitored at the time before treatment, 12, 24 and 72 hours after treatment. They were also evaluated with acute physiology and chronic health evaluation II (APACHEII) score, and length of stay in ICU and mortality in 28 days were recorded. Lactic acid level and APACHEII score were gradually decreased after treatment in both groups. Compared with control group, lactic acid at 12, 24 and 72 hours in CBP group was obviously lowered (12 hours: 8.23±3.94 mmol/L vs. 12.47±4.62 mmol/L, 24 hours: 4.46±1.57 mmol/L vs. 10.54±3.48 mmol/L, 72 hours: 2.69±1.03 mmol/L vs. 5.74±1.56 mmol/L, all P<0.01), while the APACHEII score at 12, 24 and 72 hours in CBP group was also significantly lowered (12 hours: 18.23±5.85 vs. 21.64±5.38, 24 hours: 16.49±4.62 vs. 20.61±5.71, 72 hours: 11.54±3.67 vs. 16.02±4.34, all P<0.05). Compared with control group, length of stay in ICU was also significantly shorter in CBP group (6.58±3.45 days vs. 11.65±4.94 days, P<0.05), and 28-day mortality was significantly lower in CBP group (23.8% vs. 45.0%, P<0.05). Early correction of lactic acidosis with CBP could reduce the mortality of lactic acidosis.

Effect of continuous blood purification on concentrations of plasma vasoactive substances and cardiac function in endotoxic shock

To evaluate the effect of continuous blood purification on cardiac function and plasma vasoactive substances in endotoxic shock in piglets. This was a randomized controlled trial in an animal laboratory in a tertiary care pediatric center. Twenty-three healthy Shanghai white piglets weighing 8-14 kg were randomly assigned to one of the four groups: control group (n = 5), continuous blood purification without lipopolysaccharide infusion group (continuous blood purification, n = 6), lipopolysaccharide-induced endotoxin shock without continuous blood purification group (lipopolysaccharide, n = 6), and lipopolysaccharide-induced endotoxin shock with continuous blood purification group (continuous blood purification/lipopolysaccharide, n = 6). The lipopolysaccharide and continuous blood purification/lipopolysaccharide groups were injected intravenously with Escherichia coli endotoxin to induce septic shock. The continuous blood purification and continuous blood purification/lipopolysaccharide groups received continuous venovenous hemodiafiltration right after model establishment. At baseline state (T0), following the injection of lipopolysaccharide (T), 1 hr later (T1), 3 hrs later (T3), and 5 hrs later (T5) after model establishment, clinical systemic inflammatory response syndrome parameters, hemodynamic indexes, and plasma concentration of vasoactive substances were obtained. Plasma concentration of dopamine was measured by enzyme-linked immunosorbent assay (DSL Company) and endothelin-1 by enzyme-linked immunosorbent assay (R&D Company). Nitric oxide synthase activity was measured by chromatometry (Nanjing Jiancheng Bioengineering Institute, China). In continuous blood purification/lipopolysaccharide group, after treatment with CPB, heart rate decreased significantly (p < .05) and pulse contour cardiac index, systematic vascular resistance index, and stroke volume index increased significantly (p < .05) when compared with lipopolysaccharide and continuous blood purification groups. After treatment with continuous blood purification, dopamine and endothelin-1 level increased and nitric oxide synthase activities decreased in continuous blood purification/lipopolysaccharide group when compared with the lipopolysaccharide group. In the continuous blood purification/lipopolysaccharide group, improvement in hemodynamic indexes was strongly correlated with increases in plasma dopamine and endothelin-1 level and decreases in nitric oxide synthase activity (r > .9, p < .05). The adverse cardiovascular effects of lipopolysaccharide-induced endotoxin shock can be improved by continuous blood purification. Improvement is correlated with increases in the concentration of plasma vasoactive substances (endothelin and dopamine) and decreases in nitric oxide synthase activity.

Application of high volume continuous blood purification in the treatment of multiple organ dysfunction syndrome

Objective To compare the effect of high volume continuous blood purification (CBP) with routine CBP on multiple organ dysfunction syndrome(MODS).Methods 38 patients with MODS were randomly divided into high volume CBP group( treatment group,18 cases) and routine CBP group (control group,20 cases).And they were respectively detected on mean arterial pressure(MAP),dosage of Dopamine,PaO2/FiO2,APACHE [ score,lactic acid,length of stay and mortality in ICU post-treatment 24h and 48h.Results Compared with control group,MAP and PaO2/FiO2 on treatment group were more higher( P ＜ 0.05 ),while dosage of Dopamine,APACHE Ⅱ score,lactic acid were significantly shorter than these of treatment group( P ＜ 0.05 ),and length of stay and mortality in ICU were significantly lower than those of treatmen group [ ( 8.54 ± 4.15 ) d vs ( 11.82 ± 5.76) d,P ＜ 0.05:22.2％ vs 35.0％,P ＜0.05 ].Conclusion High volume CBP could reduce the mortality in ICU compared with control group routine CBP. Key words: Hemodiafiltration; Multiple organ failure

Effect of continuous blood purification on endothelial cell function in patients with severe sepsis

To investigate the effect of continuous blood purification (CBP) in patients with severe sepsis, and to evaluate the change in endothelial cell function in patients with severe sepsis during CBP therapy. According to random principle, 45 patients were divided into control group (n=22) and CBP group (n=23). All patients of both groups received routine treatment according to international guidelines 2008 for management of severe sepsis, but the patients in the CBP group also received continuous veno-venous hemofiltration (CVVH) for 72 hours, the ultrafiltrate volume was 40 ml×kg(-1)×h(-1). Blood gas analysis was done before and 24 hours and 72 hours after CVVH therapy. The activated protein C (APC), soluble intercellular adhesion molecule-1 (sICAM-1) and von Willebrand factor (vWF) were measured. Also the length of stay in intensive care unit (ICU), time of mechanical ventilation, and death rate of patients in 28 days were observed. Compared with control group, the length of stay in ICU (days) and length of use of ventilator (days) in CBP group were shorter (9.12±3.07 vs. 11.64±4.82, 5.52±3.48 vs. 8.02±5.25, both P<0.05), and the death rate in 28 days was lower [13.0% (3/23) vs. 40.9% (9/22), P<0.05]. After therapy, patients in CBP group showed more reduction in the APACHEII score compared with control group (3.96±4.07 vs. 1.68±2.43, P<0.05). Patients in control group showed less change in APC, sICAM-1 and vWF. APC in CBP group increased at 72 hours, and sICAM-1 and vWF of CBP group respectively decreased at 24 hours or 72 hours, while the APC (μg/L) and vWF (mg/L) at 72 hours showed significant change compared with that of the control group (15.12±7.57 vs. 10.01±5.83, 1.58±0.73 vs. 2.64±1.34, P<0.05 and P<0.01). In patients who died in 28 days (12 patients) there were little changes in APC, sICAM-1 and vWF, while patients who lived for 28 days (33 patients), showed significantly more reduction in sICAM-1 (μg/L) and vWF (mg/L, 61.03±45.58 vs. 104.64±71.08, 1.88±1.21 vs. 2.70±0.95,both P<0.05). The APC value (μg/L) was increased after treatment in patients who survived for 28 days (13.55±7.11 vs. 10.37±7.60, P<0.01). CBP therapy can protect endothelial cell function and ameliorate dysfunction, and it reduces the severity of the severe sepsis as well as improves the outcome of patients with severe sepsis.

The immune function influence of the CD4 + T helper cell after the treatment of continuous blood purification in a porcine model with multiple organ dysfunction syndrome

Objective To investigate the levels of Th1 and Th2 cell in the peripheral and the cytokines (IFN-γ,TNF-α,IL-12,IL-10,IL-4) in the culture medium at different time in the porcine model with multiple organ dysfunction syndrome(MODS) after continuous blood purification(CBP). Methods Twenty-four young porcines were given intravenous infusion of endotoxin to induce MODS, then were randomly divided into 2 groups:CBP group(n = 12) and MODS group without CBP(n = 12). Continuous venovenous hemodiafiltration (CVVHDF) was the main mode for CBP. At baseline, onset of MODS, and 2 h,4 h,6 h after treatment of CVVHDF,we picked the blood respectively to separate the T helper cell using the beads,detected the Th1 and Th2 cell by FACS and detected the cytokines (IFN-γ,TNF-α,IL-12,IL-10,IL-4) in the culture medium by ELISA. Results The MODS group showed a obvious rise in TNF-α,the drop tendency in IL-12,IFN-γ,IL-10,Th1/Th2 ratio, and no significant change in IL-4. After the treatment, the CBP group showed the drop in TNF-α and IL-4;and increase in IL-12,IFN-γ,IL-10 and Th1/Th2 ratio. Conclusion CBP helps to dear immune function,and restore the balance of Th1/Th2 in porcine MODS model. Key words: MODS; Th1/Th2; Continuous blood purification; Porcine model

Study the effects of CBP treatment on serum resistin in patients with SIRS

Objective To study the effects of CBP treatment on serum resistin in patients with SIRS. Methods 120 patients with SIRS were randomly divided into conventional treatment group(60 cases)and CBP group(60 cases). CBP group were treated with continuous blood purification for 72 hours besides conventional treatment. Serum levels of resistin was determined with ELISA dynamically before treatment and 24,48,72and 96 hours after the treatment. The APACHE Ⅱ score was evaluated at the same time. Results The level of ser-um resistin in patients in two SIRS groups was significantly higher than control group( P 0. 05 ), after 96 hours of treatment, Patients in each group were significantly lower serum resistin. To lower serum resistin levels slow in the conventional treatment group ( P < 0. 05 ), and the gradual lowering of serum resistin levels in the CBP group ,48 hours after treatment was significantly lower than before treatment ( P < 0. 05 ), 72 hours after treatment to reduce even more pronounced( P < 0. 01 ). There was positive correlation between resis- tin and APACHE Ⅱ scores( r = 0. 68, P < 0. 01 ). Condusion CBP treatment could reduce the role of resistin which is a inflammatory factor in the blood, improve the function of endothelial ceils in patients, and treatment provides a now monitoring indicators for observation of CBP. Key words: Continuous blood purification (CBP); Systemic inflammatory reactive syndrome(SIRS) ; Resistin

Immune and inflammation confusion in severe sepsis and effects of bi-immunomodulation therapy: a prospective, randomized, controlled clinical trial

To investigate the immune and inflammation confusion state in severe sepsis and the effects of two way immunomodulation therapy with continuous blood purification (CBP), thymosin alpha1, and combined therapy of CBP and thymosin alpha(1). 91 Patients with severe sepsis aged > 18, with Marshall score>5. were randomly divided into 4 groups: CBP Group (n = 22) undergoing continuous renal replacement therapy (CRRT) or molecular adsorbents recirculating system (MARS) therapy once a day for 3 days in addition to classical Surviving Sepsis Campaign (SSC) therapy, Thymosin alpha(1) Group (n = 23) undergoing subcutaneous injection of thymosin alpha(1) 1.6 mg once a day for 7 days in addition to SSC therapy, Combined Therapy Group (n = 22) undergoing CBP combined with thymosin alpha(1) treatment in addition to SSC therapy, and SSC Group (treatment control group, n = 24) undergoing SSC therapy only. Peripheral blood samples were collected before treatment, and 3 and 7 days after the beginning of treatment (days 4 and 8) to detect the serum interleukin (IL)-6, IL-10, and tumor necrosis factor (TNF)-alpha. The levels of CD(14)(+) monocyte human leucocyte antigen (HLA)-DR and T lymphocytes were monitored. The mechanical ventilation time, ICU stay length, and mortality within 28 d and mortality within 90 d were observed. Ten healthy persons were used as healthy control group. Thirty-four of the 91 patients died within 28 d with a mortality of 77.4% (Death Group) and other 57 patients were put in Survival Group. The levels of serum IL-6, IL-10, and TNFalpha, and IL-6/IL-10 at different time points of both Death and Survival Groups were all significantly higher, and the HLA-DR level, and CD(3)(+), CD(4)(+), and CD(8)(+) T lymphocyte numbers at different time points of both Death and Survival Groups were all significantly lower than those of the healthy controls (P < 0.05 or < 0.01). The levels of serum IL-6, IL-6/IL-10, TNFalpha, HLA-DR, and CD(3)(+), CD(4)(+), and CD(8)(+) T lymphocyte at different time points of Death Group were all significantly higher than those of Survival Group (P < 0.05 or < 0.01). The CD(3)(+) T lymphocyte number on day 8 of Thymosin Group was significantly higher than that of SSC Group (all P < 0.05). The serum IL-6 and TNFalpha and IL-6/IL-10 were decreased, and HLA-DR, and CD(3)(+), CD(4)(+), and CD(8)(+) were increased significantly on day 8 in CBP and Combined Therapy Groups. The level of TNFalpha decreased, and the numbers of CD(3)(+) and CD(4)(+) T lymphocytes increased significantly on day 4 in Combined Therapy Group (P < 0.05 or P < 0.01). Compared with Thymosin Group, almost all the indexes of CBP and Combined Therapy Groups were improved, only the CD(3)(+) T lymphocyte level on day 4 increased and the IL-6/IL-10 ratio on day 8 was decreased significantly in Combined Therapy Group (both P < 0.05). Compared with those of SSC Group, the mechanical ventilation time, length of ICU stay within 28 days, and 28 days mortality and 90 days mortality of the 3 treatment groups were all decreased, and there were statistical differences in the length of ICU stay of CBP Group and in the mechanical ventilation time and length of ICU stay within 28 days of Combined Therapy Group (both P < 0.05). Systemic inflammatory response and immunodepression exist simultaneously in severe sepsis. Thymosin alpha(1) increases the cellular immunity, and CBP bi-modulates the immune turbulence, reduces the inflammatory mediators, and ameliorates the immune homeostasis. These 2 therapies also improve the clinical prognosis and the combination of both would be more effective.

Effect of continuous blood purification and thymosin alpha1 on the cellular immunity in patients with severe sepsis: a prospective, randomized, controlled clinical trial

To discuss the effect of continuous blood purification (CBP), thymosin alpha1 and combined therapy on cellular immunity in patients with severe sepsis. Ninety-one patients, age over 18 years, suffering from severe sepsis with Marshall score over 5, admitted to the intensive care unit (ICU) from June, 2004 to October, 2007, were randomly divided into four groups. The patients in control group (24 cases) were treated with classical Surviving Sepsis Campaign (SSC) therapy, those in CBP group (22 cases) were treated with continuous renal replacement therapy (CRRT) or molecular adsorbent recirculating system (MARS) in the first 3 days. The group of thymosin alpha1 (23 cases) were treated with thymosin alpha1, in a dose of 1.6 mg subcutaneous injection per day for 7 days. The patients in the group of combined therapy (22 cases) were treated with CBP and thymosin alpha1. All three treatment groups were treated with classical SSC therapy at the same time. Acute physiology and chronic health evaluation II (APACHE II) score and Marshall score were evaluated. CD14(+) monocyte human leucocyte antigen DR (HLA-DR) levels and the count of T lymphocyte were measured before treatment and 3 days and 7 days after the treatment. All 91 patients were included in the study. Compared with the control group, the 28-day mechanical ventilation (MV) time, length of ICU stay, 28-day mortality of three treatment groups were decreased. There was statistically significant difference in the length of ICU stay of the CBP group, and also the 28-day MV time, length of ICU stay of the group of combined therapy group (all P<0.05). Compared with the variables before treatment, Marshall scores were decreased significantly and levels of HLA-DR, CD3(+), CD4(+), CD8(+)T lymphocytes were increased significantly after 7-day treatment with thymosin alpha1 group (all P<0.05) . The above indexes and APACHE II scores were changed significantly as early as 3 days after treatment in CBP group and combined therapy group (P<0.05 or P<0.01). Compared with the variables at the same period in the control group, only CD3(+) T lymphocytes were increased significantly after 7-day treatment in thymosin alpha1 group (P<0.05), APACHE II scores and Marshall scores were decreased significantly , levels of HLA-DR and CD3(+), CD4(+), CD8(+) T lymphocytes were increased significantly after 7-day treatment in CBP group (all P<0.05). The above indexes were already changed significantly after 3-day treatment in the combined therapy group (P<0.05 or P<0.01). Compared with thymosin alpha1 group, all the indexes were improved but only level of CD3(+) T lymphocytes after 3-day treatment in the combined therapy group increased significantly (P<0.05). CBP and thymosin alpha1 could increase cellular immunity in patients with severe sepsis, promote recovery of organ function and improve prognosis. The effect of CBP appears earlier and more pronounced. Combined treatment can be more effective.