Weaning critically ill patients from mechanical ventilation: a protocol from a multicenter retrospective cohort study.

BACKGROUND: Mechanical ventilation (MV) is an important lifesaving method in intensive care unit (ICU). Prolonged MV is associated with ventilator associated pneumonia (VAP) and other complications. However, premature weaning from MV may lead to higher risk of reintubation or mortality. Therefore, timely and safe weaning from MV is important. In addition, identification of the right patient and performing a suitable weaning process is necessary. Although several guidelines about weaning have been reported, compliance with these guidelines is unknown. Therefore, the aim of this study is to explore the variation of weaning in China, associations between initial MV reason and clinical outcomes, and factors associated with weaning strategies using a multicenter cohort. METHODS: This multicenter retrospective cohort study will be conducted at 17 adult ICUs in China, that included patients who were admitted in this 17 ICUs between October 2020 and February 2021. Patients under 18 years of age and patients without the possibility for weaning will be excluded. The questionnaire information will be registered by a specific clinician in each center who has been evaluated and qualified to carry out the study. DISCUSSION: In a previous observational study of weaning in 17 ICUs in China, weaning practices varies nationally. Therefore, a multicenter retrospective cohort study is necessary to be conducted to explore the present weaning methods used in China. TRIAL REGISTRATION: Chinese Clinical Trial Registry (ChiCTR) (No. ChiCTR2100044634).

Cathepsin B aggravates acute pancreatitis by activating the NLRP3 inflammasome and promoting the caspase-1-induced pyroptosis.

OBJECTIVES: Cathepsin B (CTSB), nod-like receptor family pyrin domain-containing 3 (NLRP3), and caspase-1 play an important role in the development of Acute Pancreatitis (AP). Besides, the relationship between the proteins remains poorly understood. In addition, whereas previous studies have found caspase-1 activation in AP, pyroptosis, a caspase-1 induced cell death mode, has never been proposed and proved in AP. METHODS: We induced AP in mice by intraperitoneal injection of cerulein. Mice in the inhibitor group of CTSB were pretreated with injection of CA-074me, while mice in the inhibitor group of caspase-1 were of Ac-YVAD-CHO, 1 h earlier. We evaluated the inflammation of the pancreas and the detected expression of activated CTSB, NLRP3, ASC, caspase-1p20, IL-1ß and IL-18. TUNEL staining was used to detect acinar cell death. RESULTS: The inflammation of the pancreas in the two inhibitor groups was significantly reduced compared with that in the AP group. We observed that CA-074me not only inhibits CTSB, but also suppresses the expression and activity of NLRP3, ASC and caspase-1. We found that CA-074me further inhibits the downstream event of caspase-1, including pro-inflammatory cytokine secretion and pyroptosis. Whereas Ac-YVAD-CHO inhibited caspase-1 and decreased pro-inflammatory cytokine secretion and pyroptosis, it did not down-regulate the expression and activity ofCTSB, NLRP3 and ASC. CONCLUSION: The results indicate that CTSB may aggravate AP by activating the NLRP3 inflammasome and promoting Caspase-1-induced pyroptosis. These provide clues about the pathophysiological mechanisms of AP, shedding light on new ideas and potential targets for the prevention and treatment of AP.

MiRNA-133a aggravates inflammatory responses in sepsis by targeting SIRT1.

BACKGROUND: Sepsis is a systemic inflammatory response syndrome. MicroRNA (miRNA) plays an important role in immune cell activation, inflammatory cytokine release and immune response. However, the mechanism of miR-133a in sepsis remains largely unknown. METHODS: Sepsis mice models were established by applying the cecal ligation and puncture (CLP) method. Quantitative real-time polymerase chain reaction (qRT-PCR) assay was performed to detect the relative expression of miR-133a and inflammatory cytokines. Hematoxylin and eosin (H&E) staining and enzyme-linked immunosorbent assay (Elisa) were used to evaluate organ injury and inflammatory response. Besides, lipopolysaccharide (LPS)-induced RAW264.7 macrophages were used to construct sepsis cell models. Further, dual-luciferase reporter assay and RNA immunoprecipitation (RIP) assay were carried out to confirm the relationship between miR-133a and sirtuin-1 (SIRT1). In addition, western blot (WB) assay was performed to measure the relative SIRT1 protein level. RESULTS: MiR-133a was highly expressed in sepsis patients and CLP mice models. Knockdown of miR-133a inhibited sepsis-induced lung, liver and kidney injuries and inflammatory response in CLP mice models. Besides, miR-133a inhibitor also alleviated the inflammatory response of RAW264.7 macrophages induced by LPS. SIRT1 was a target of miR-133a, and silenced SIRT1 could reverse the anti-inflammatory effect of miR-133a inhibitor on LPS-induced sepsis cell models. CONCLUSION: MiR-133a promoted the inflammatory response of sepsis by inhibiting the expression of SIRT1, which might provide a new therapeutic strategy for sepsis.

Early Immunoparalysis Was Associated with Poor Prognosis in Elderly Patients with Sepsis: Secondary Analysis of the ETASS Study.

PURPOSE: Although immune dysfunction has been investigated in adult septic patients, early immune status remains unclear. In this study, our primary aim was to assess early immune status in adult patients with sepsis stratified by age and its relevance to hospital mortality. PATIENTS AND METHODS: A post hoc analysis of a multicenter, randomized controlled trial was conducted; 273 patients whose immune status was evaluated within 48 hours after onset of sepsis were enrolled. Early immune status was evaluated by the percentage of monocyte human leukocyte antigen-DR (mHLA-DR) in total monocytes within 48 hours after onset of sepsis and it was classified as immunoparalysis (mHLA-DR ≤30%) or non-immunoparalysis (>30%). Three logistic regression models were conducted to explore the associations between early immunoparalysis and hospital mortality. We also developed two sensitivity analyses to find out whether the definition of early immune status (24 hours vs 48 hours after onset of sepsis) and immunotherapy affect the primary outcome. RESULTS: Of the 181 elderly (≥60yrs) and 92 non-elderly (<60yrs) septic patients, 71 (39.2%) and 25 (27.2%) died in hospital, respectively. The percentage of early immunoparalysis in the elderly was twice of that in the non-elderly patients (32% vs 16%, p=0.006). For the elderly, hospital mortality was higher in the immunoparalysis ones than the non-immunoparalysis ones (53.4% vs 32.5%, p=0.009). But there was no significant difference in hospital mortality between immunoparalysis non-elderly patients and non-immunoparalysis non-elderly ones (33.5% vs 26.0%, p=0.541). By means of logistic regression models, we found that early immunoparalysis was independently associated with increased hospital mortality in elderly, but not in non-elderly patients. Sensitivity analysis further confirmed the definition of early immune status and immunotherapy did not affect the outcomes. CONCLUSION: The elderly were more susceptible to early immunoparalysis after onset of sepsis. Early immunoparalysis was independently associated with poor prognosis in elderly, but not in non-elderly patients.

Desmopressin acetate decreases blood loss in patients with massive hemorrhage undergoing gastrointestinal surgery.

BACKGROUND/AIMS: Intraoperative blood loss more than 400 mL during gastrointestinal surgery is an independent predictor of mortality. Desmopressin acetate (DDAVP) could reduce perioperative blood loss. Few studies have prompted concerning the effects of DDAVP on gastrointestinal surgery. This study was to investigate whether DDAVP can decrease blood loss in patients with massive hemorrhage undergoing gastrointestinal surgery. MATERIALS AND METHODS: A multiple-centers, double-blind clinical trial was conducted, patients who underwent gastrointestinal surgery were recruited from 3 hospitals, randomly assigned to two different groups. Patients in the treatment group received desmopressin 0.3 ug/kg,30 min once a day after surgery, patients in the control group received 50 ml saline for 30 min. The primary outcome was the changes of hemoglobin at 24 hours after the surgery. And the secondary outcomes included coagulation function, urine volume, serum creatinine, and safety. RESULTS: There were 59 patients enrolled between 1 June 2015 and 1 June 2017. At 24hr.after surgery, a decrease in hemoglobin in the DDAVP group was significantly lower than that in the NS group (-5.0±6.9 g/L vs. -10.2±9.3g/L, p=0.03). Sonoclot® showed that the platelet function in the DDAVP group was higher than that in NS group at 24 hr. (2.56 ±0.59 vs. 1.91 ±0.72, p<0.05). There was no difference in urine volume and serum creatinine at 24 hr. between two group. CONCLUSION: DDAVP could reduce post-operation blood loss in patients with massive hemorrhage undergoing surgery by improving the platelet function. We observed no difference in urine volume and serum creatinine in two groups.

Silencing of long non-coding RNA MALAT1 suppresses inflammation in septic mice: role of microRNA-23a in the down-regulation of MCEMP1 expression.

OBJECTIVE: Sepsis is a life-threatening disease without ideal biomarkers. Some long non-coding RNAs (lncRNAs) are found to be implicated in sepsis. Thus, we investigated the effects of lncRNA metastasis-associated lung adenocarcinoma transcript 1 (MALAT1) on inflammation in septic mice and the potential mechanisms of the MALAT1/microRNA-23a (miR-23a)/MCEMP1 axis. METHODS: The sepsis mice model was generated by cecal ligation and puncture (CLP). Then the expressions of lncRNA MALAT1, mast cell-expressed membrane protein 1 (MCEMP1), and miR-23a in septic mice were determined. The interaction between lncRNA MALAT1, miR-23a and MCEMP1 was confirmed. Loss- and gain-of-function approaches were used to verify the roles of the lncRNA MALAT1, miR-23a, and MCEMP1 in inflammation, cell proliferation and apoptosis in septic mice. RESULTS AND CONCLUSION: The myeloperoxidase (MPO) activity and the expression of interleukin 6 (IL-6), IL-1ß, IL-10, and tumor necrosis factor-α (TNF-α) were detected. High expression of the lncRNA MALAT1 and MCEMP1, as well as low expression of miR-23a, was observed in septic mice. LncRNA MALAT1 competitively bound to miR-23a, and miR-23a targeted MCEMP1. Moreover, the down-regulation of lncRNA MALAT1 repressed the expression of MPO, IL-6, IL-10, TNF-α, and IL-1ß. Silencing of lncRNA MALAT1 or overexpression of miR-23a reduced inflammation, inhibited cell proliferation, and promoted cell apoptosis in septic mice. Taken together, MALAT1 promotes the inflammation in septic mice by binding to miR-23a to up-regulate MCEMP1. Therefore, silencing of lncRNA MALAT1 might provide a novel therapeutic target for sepsis.

Impact of hypophosphatemia on outcome of patients in intensive care unit: a retrospective cohort study.

BACKGROUND: Hypophosphatemia generally occurs in Intensive Care Units (ICUs), but its impact is often ignored. The aim of this study was to investigate whether hypophosphatemia can be a risk factor for ICU 28-day mortality. METHODS: A single-center retrospective cohort study was conducted by collecting data from 1073 patients admitted to general ICU and then presented to the Sixth Affiliated Hospital, Sun Yat-sen University (Guangzhou City, Guangdong Province, China) from 1 January 2016 to 31 December 2017. The patients were divided into a normal control group (serum phosphate levels 0.80-1.60 mmol/L) and a hypophosphatemia group (serum phosphate levels < 0.80 mmol/L), based on the concentration of phosphorus at the time of ICU admission. The association between phosphate levels and ICU 28-day mortality was evaluated by binary logistic regression analysis. Multivariate logistic regression was employed to predict the ICU 28-day mortality. RESULTS: The cohort included 946 patients with a median phosphate concentration of 0.77 mmol/L (interquartile range 0.55-1.03 mmol/L). Patients with hypophosphatemia had a higher ICU 28-day mortality than the normal control group (33.3% vs 24.0%, P < 0.05). Patients with hypophosphatemia had a longer ICU and hospital stays, and prolonged duration of mechanical ventilation (all P < 0.05). Hypophosphatemia was an independent risk factor for ICU 28-day mortality (adjusted OR = 1.5, 95% CI = 1.1-2.1, P = 0.01) in the multivariate logistic regression analysis. CONCLUSIONS: Hypophosphatemia at admission is an independent risk factor for 28-day mortality in general ICU patients. TRIAL REGISTRATION: The medical study was approved by the Institutional Ethics Committee of the Six Affiliated Hospital, Sun Yat-sen University (Approval number: 2017ZSLYEC-110). No consent was given as the data were analyzed anonymously.

Ultrasensitive ELISA for the detection of hCG based on assembled gold nanoparticles induced by functional polyamidoamine dendrimers.

Amplifying the signal of ELISA is important in the early disease diagnosis. Herein we report an ultrasensitive ELISA applying for the detection of hCG based on the assemble of AuNPs induced by functional PAMAM. The AuNP-PAMAM probe shows a competitive advantage sensitivity of 0.03 IU L-1 compared to traditional ELISA and mAb1-AuNP-HRP probe. The line range is ranged from 0.1 to 6.4 IU L-1. Moreover, the precision and reproducibility and specificity of AuNP-PAMAM probe are also eligible for the detection of hCG. The assembled AuNPs was firstly used in the signal enhancement in immunoassay.

Terlipressin versus norepinephrine as infusion in patients with septic shock: a multicentre, randomised, double-blinded trial.

PURPOSE: Recent clinical data suggest that terlipressin, a vasopressin analogue, may be more beneficial in septic shock patients than catecholamines. However, terlipressin's effect on mortality is unknown. We set out to ascertain the efficacy and safety of continuous terlipressin infusion compared with norepinephrine (NE) in patients with septic shock. METHODS: In this multicentre, randomised, double-blinded trial, patients with septic shock recruited from 21 intensive care units in 11 provinces of China were randomised (1:1) to receive either terlipressin (20-160 µg/h with maximum infusion rate of 4 mg/day) or NE (4-30 µg/min) before open-label vasopressors. The primary endpoint was mortality 28 days after the start of infusion. Primary efficacy endpoint analysis and safety analysis were performed on the data from a modified intention-to-treat population. RESULTS: Between 1 January 2013 and 28 February 2016, 617 patients were randomised (312 to the terlipressin group, 305 to the NE group). The modified intention-to-treat population comprised 526 (85.3%) patients (260 in the terlipressin group and 266 in the NE group). There was no significant difference in 28-day mortality rate between the terlipressin group (40%) and the NE group (38%) (odds ratio 0.93 [95% CI 0.55-1.56]; p = 0.80). Change in SOFA score on day 7 was similar between the two groups: - 7 (IQR - 11 to 3) in the terlipressin group and - 6 (IQR - 10 to 5) in the NE group. There was no difference between the groups in the number of days alive and free of vasopressors. Overall, serious adverse events were more common in the terlipressin group than in the NE group (30% vs 12%; p < 0.001). CONCLUSIONS: In this multicentre, randomised, double-blinded trial, we observed no difference in mortality between terlipressin and NE infusion in patients with septic shock. Patients in the terlipressin group had a higher number of serious adverse events. TRIAL REGISTRATION: This trial is registered at ClinicalTrials.gov: ID NCT01697410.

The role of ERK and Smad2 signal pathways in the alternatively activated macrophages induced by TGF-ß1 and high-ambient glucose.

Macrophages can be alternatively activated by TGF-ß1 and high-ambient glucose, in which the role of Smad2 and the crosstalk between ERK and Smad2 pathways are not fully understood. The activation of ERK and Smad2 pathways and the expression of arginase-1 were detected by Western blot. The role of Smad2 and the relationship between ERK and Smad2 pathways were investigated by using biochemical inhibitors. The protein of arginase-1 was significantly overexpressed in RAW264.7 cells stimulated by TGF-ß1 and high-ambient glucose, which can be partially blocked by not only U0126 (ERK inhibitor) but also SB431542 (Smad2 inhibitor). Furthermore, simply inhibiting one pathway had no effect on the other pathway. In conclusion, both ERK and Smad2 signal pathways are involved in the activation of macrophages induced by TGF-ß1 and high-ambient glucose, while there is no crosstalk shown in the process.

Fat-Modified Enteral Formula Improves Feeding Tolerance in Critically Ill Patients: A Multicenter, Single-Blind, Randomized Controlled Trial.

BACKGROUND: Improvement of fat digestion and absorption was supposed to relieve feeding intolerance. This trial aimed to evaluate the effect of a fat-modified enteral formula on feeding tolerance in critically ill patients. MATERIALS AND METHODS: This trial was conducted in 7 hospitals in China. In total, 144 intensive care unit (ICU) patients with estimated need of enteral nutrition (EN) for at least 5 days were randomly given fat-modified enteral formula containing medium-chain triglycerides (MCT), carnitine, and taurine (interventional feed group, n = 71) or standard enteral formula (control feed group, n = 73). EN intake, feeding intolerance (diarrhea, vomiting, gastric retention, and abdominal distension) and outcomes (mechanical ventilator-free days of 28 days, length of ICU stay, length of hospital stay, and in-hospital mortality) were collected. RESULTS: Daily calories and protein intake were increased in the interventional feed group compared with the control feed group ( P < .01). Total incidence of feeding intolerance was 42.3% in the interventional feed group and 65.7% in the control feed group ( P < .001). Daily incidence of feeding intolerance was 11.3%, 18.3%, 14.1%, 25.4%, and 26.1% in the interventional feed group and 31.5%, 32.9%, 34.2%, 34.2%, and 30.4% in the control feed group from study days 1-5 ( P = .0083). Incidence of feeding intolerance without abdominal distention was 32.9% in the interventional feed group and 49.3% in the control feed group ( P = .047), while the incidence of abdominal distension was 26.8% in the interventional feed group and 43.8% in the control feed group ( P = .03). No significant differences existed in outcomes between the 2 groups. CONCLUSIONS: The fat-modified enteral formula containing MCT, carnitine, and taurine may improve feeding tolerance in critically ill patients.

Association of Megsin gene polymorphism with IgA nephropathy risk.

This meta-analysis was conducted to assess the association of Megsin 2093C/T, 2180C/T, C25663G gene polymorphism with the risk of IgA nephropathy (IgAN). The association literatures were identified from PubMed, Embase, Cochrane Library and CBM-disc (China Biological Medicine Database) on 1 January 2014, and eligible reports were recruited and synthesized. Seven eligible reports were recruited into this meta-analysis for the association of Megsin 2093C/T, 2180C/T, C25663G gene polymorphism with IgAN risk. In this meta-analysis, the association of Megsin 2093C/T TT genotype with IgAN risk in Asians was found. Interestingly, Megsin C25663G G allele and GG genotype were associated with the risk of IgAN in Asian population. However, Megsin 2180C/T gene polymorphism was not associated with IgAN risk in Asians. In conclusion, Megsin 2093C/T TT genotype, and C25663G G allele and GG genotype were associated with the risk of IgAN in Asian population. However, more studies should be performed in the future to confirm this association.

The efficacy of thymosin alpha 1 for severe sepsis (ETASS): a multicenter, single-blind, randomized and controlled trial.

INTRODUCTION: Severe sepsis is associated with a high mortality rate despite implementation of guideline recommendations. Adjunctive treatment may be efficient and require further investigation. In light of the crucial role of immunologic derangement in severe sepsis, thymosin alpha 1 (Tα1) is considered as a promising beneficial immunomodulatory drug. The trial is to evaluate whether Tα1 improves 28-day all-cause mortality rates and immunofunction in patients with severe sepsis. METHODS: We performed a multicenter randomized controlled trial in six tertiary, teaching hospitals in China between May 12, 2008 and Dec 22, 2010. Eligible patients admitted in ICU with severe sepsis were randomly allocated by a central randomization center to the control group or Tα1 group (1:1 ratio). The primary outcome was death from any cause and was assessed 28 days after enrollment. Secondary outcomes included dynamic changes of Sequential Organ Failure Assessment (SOFA) and monocyte human leukocyte antigen-DR (mHLA-DR) on day 0, 3, 7 in both groups. All analyses were done on an intention-to-treat basis. RESULTS: A total of 361 patients were allocated to either the control group (n = 180) or Tα1 (n = 181) group. The mortalities from any cause within 28 days in the Tα1 group and control group were 26.0% and 35.0% respectively with a marginal P value (nonstratified analysis, P = 0.062; log rank, P = 0.049); the relative risk of death in the Tα1 group as compared to the control group was 0.74 (95% CI 0.54 to 1.02). Greater improvement of mHLA-DR was observed in the Tα1 group on day 3 (mean difference in mHLA-DR changes between the two groups was 3.9%, 95% CI 0.2 to 7.6%, P = 0.037) and day 7 (mean difference in mHLA-DR changes between the two groups was 5.8%, 95% CI 1.0 to 10.5%, P = 0.017) than in the control group. No serious drug-related adverse event was recorded. CONCLUSIONS: The use of Tα1 therapy in combination with conventional medical therapies may be effective in improving clinical outcomes in a targeted population of severe sepsis. TRIAL REGISTRATION: ClinicalTrials.gov NCT00711620.

[The study of the mechanism of the effect of heparin on tissue perfusion of sepsis patients].

OBJECTIVE: To assess the role of heparin administration in the early stage of sepsis and its mechanism of action. METHODS: This was a prospective study. One hundred and nineteen patients were enrolled in the study and were randomly divided into control group (64 cases) and therapy group (55 cases). Except the basic therapy of sepsis given to patients in both groups, the patients in the control group received normal saline, while the patients in the therapy group received heparin 2 mg.kg(-1).d(-1) with the aid of intravenous pump continuously after the onset of sepsis. The platelet count (PLT), D-dimer, and lactic acid in the blood were analyzed before therapy and on the 1st, 3rd, 5th and 10th day. The bleeding tendency was also observed. In every patient an acute physiology and chronic heath evaluation II (APACHE II) score was made. RESULTS: Patients in both groups had a similar APACHE II score. The pathogenetic and therapeutic condition were similar in both groups. The rate of the active bleeding in the therapy group was lower significantly than that of the control group (12.5% vs. 5.4%, P < 0.05). The PLT of the therapy group decreased on the 1st day, but began to rise on the 3rd day gradually, and up to the same level of the admission day on the 10th day. The PLT of the control group decreased progressively every day (P < 0.05 or P < 0.01). D-dimer in the therapy group raised significantly on the 1st day, but lowered to normal level after 3 days. D-dimer in the control group went up progressively every day (all P < 0.01). Lactic acid in the therapy group went up significantly on the 1st day (P < 0.01), but it no longer rose after 3 days (all P > 0.05). The lactic acid level in the control group rose progressively every day (all P < 0.01). There were no significant differences for the PLT, D-dimer, and lactic acid between the two groups before therapy and on the 1st day (all P > 0.05). However, on the 3rd, 5th and 10th day, the PLT in the therapy group was significant higher than that of the control group, the D-dimer and the lactic acid level in the therapy group were significantly lower than that of the control group (P < 0.05 or P < 0.01). CONCLUSION: The use of heparin at the earlier period of sepsis can inhibit the lowering of PLT and increase of D-dimer and lactic acid significantly, prevent microvascular thrombosis, improve the tissue perfusion, and decrease active bleeding.

[Protective effect of ethyl pyruvate on barrier function of intestinal mucosa in dogs with septic shock].

OBJECTIVE: To investigate the effect of ethyl pyruvate on barrier function of intestinal mucosa in dogs with septic shock. METHODS: Twenty dogs with septic shock induced by lipopolysaccharides(LPS) were randomly divided into two groups. Dogs randomly received placebo (Ringer's solution, control group, n=8) or ethyl pyruvate in lactated Ringer's solution (0.05 g/kg loading dose over 10 mins, thereafter 0.05 g.kg(-1).h(-1) for 12 hours, EP treatment group, n=12). The diamine oxidase(DAO) activity and D-lactate content were detected at the 0, 8 th, 12 th and 24 th hour of septic shock. Animals were sacrificed at the 24 th hour after septic shock and the jejunal tissue was taken for histopathological examination. RESULTS: The levels of plasma DAO and D-lactate were significantly elevated in both groups after septic shock than those before septic shock. The changes in intestinal parameters of hemoperfusion and permeability in EP treatment group were significantly lowered than those in control group. Inflammation of small intestinal mucosa was more severe in control group than that in EP group, and the pathologic score was significantly lower in EP group(2.33+/-0.25) than that in control group(3.39+/-0.38)(P<0.05). CONCLUSION: Ethyl pyruvate can lessen intestinal permeability and protect intestinal barrier function in dogs with septic shock.

[Effect of ethyl pyruvate on indices of tissue oxygenation and perfusion in dogs with septic shock].

OBJECTIVE: To investigate the effect of ethyl pyruvate (EP) on indices of tissue oxygenation and perfusion in dogs with septic shock. METHODS: Twenty dogs with septic shock induced by lipopolysaccharides (LPS) were randomly divided into two groups. Dog randomly received placebo (Ringer's solution; control group, n =8) or EP in lactated Ringer's solution (0.05 g/kg loading dose over 10 minutes, thereafter 0.05 g.kg(-1).h(-1) for 12 hours; EP treatment group, n =12). Indices of tissue oxygenation and perfusion were monitored every 2 hours after basic measurements (pre-LPS), including oxygen delivery (DO2), oxygen consumption (VO2), serum levels of lactate (Lac), mixed venous oxygen saturation (SvO2), urine output, intramucosal pH (pHi), gastric-to-arteria partial pressure of carbon dioxide gap (Pg-a CO2). RESULTS: DO2, VO2, SvO2 and urine output dropped significantly after septic shock (all P<0.05), but serum levels of Lac and P g-a CO2 elevated markedly (both P<0.05). DO2 increased gradually in EP group and there were significantly differences compared with control group after 8 hours (P<0.05). VO2 showed such a tendency, but there was no statistically significant intergroup difference (P>0.05). SvO2 elevated gradually in EP group, even higher than those of pre-LPS after 10 hours and there were significantly differences compared with control group (P<0.05). Serum levels of Lac decreased gradually and there was significant difference compared with control group after 8 hours (P<0.05). Urine output increased in EP group after 8 hours, and such phenomenon did not happen in control group after 10 hours (P<0.05). pHi elevated to a higher level after 6 hours, and Pg-a CO2 elevated in the treatment group, and there were significantly differences compared with control group (both P<0.05). CONCLUSION: EP infusion resulted in improved tissue oxygenation and perfusion in dogs with septic shock.

[Effect of continuous veno-venous hemofiltration on the plasma level of cytokines in patients with multiple organ dysfunction syndrome].

OBJECTIVE: To investigate the effect of CVVH on the plasma levels of TNF-alpha, IL-1, IL-6, IL-8 in patients with multiple organ dysfunction syndrome (MODS). METHODS: Twenty-two patients with MODS were treated with continuous veno-venous hemofiltration (CVVH), venous and arterial blood samples were taken at 0, 1, 4, 8 hour following CVVH and ultrafiltration fluid samples were taken at 8 hour following CVVH. Arterial blood samples were used for blood gas analysis, venous blood samples and ultrafiltration fluid were used to measure the levels of cytokines by ELISA. RESULTS: The plasma levels of TNF-alpha and IL-1 were significantly decreased following CVVH (P < 0.05). The IL-1, IL-6, IL-8 were detected in the ultrafiltration fluid and TNF-alpha was not. Heart rate decreased and mean arterial pressure (MAP) increased significantly 4 hrs after CVVH (P < 0.05). PaO(2)/FiO(2) increased significantly (P < 0.05). The APACHE II scores reduced after CVVH (P < 0.05). The reduction of APACHE II score and the elimination of cytokines were positively correlated with ultrafiltration flow rates CONCLUSIONS: CVVH can remove some cytokines in plasma, reduce APACHEII score and improve hemodynamics and oxygenation in MODS. Moreover, higher volume hemofiltration has better effect on the elimination of cytokines and can further improve the prognosis of MODS.