Time of dissociation between microcirculation, macrocirculation, and lactate levels in a rabbit model of early endotoxemic shock.

BACKGROUND: The relationship between macrocirculation and microcirculation remains controversial. The loss of coherence between microcirculation and macrocirculation has already been found in late-stage sepsis shock. The objective of this study was to determine the earliest possible time of detecting the loss of coherence between microcirculation and macrocirculation in early-stage endotoxemic shock. METHODS: We randomized 24 female New Zealand white rabbits into two groups: endotoxemic shock group (n = 14) and control group (n = 10). Rabbits in the endotoxemic shock group were equipped with arterial and venous catheters and received an intravenous infusion of Escherichia coli lipopolysaccharide (LPS, 2 mg/kg over 10 min). Rabbits in the control group received the same dose of saline infusion. Microcirculatory perfusion parameters were assessed in the sublingual mucosa using sidestream dark-field video microscopy. Systemic hemodynamics and blood lactate levels were measured at baseline and over a 120-min period. RESULTS: Ninety minutes after completing LPS infusion, all animals in the endotoxemic shock group developed a hypodynamic septic condition, characterized by low cardiac output and increased systemic vascular resistance; 120 min after completing LPS infusion, the mean arterial pressure decreased by 25% (P = 0.01), confirming ongoing endotoxemic shock. However, significant decreases in sublingual microcirculatory parameters of small vessels (microvascular flow index, perfused vessel density, and proportion of small perfused vessels) were observed 30 min after completing LPS infusion (P = 0.01, for all), and threshold decreases of 30% were found 60 min after completing LPS infusion (P = 0.001, for all) in the endotoxemic shock group. Lactate levels significantly increased to more than 2 mm/L at 90 min and more than 4 mm/L at 120 min in the endotoxemic shock group (P = 0.02 and P = 0.01, respectively). CONCLUSIONS: Changes in microcirculatory perfusion precede changes in macrocirculation and lactate levels in a rabbit model of endotoxemia shock. Microcirculation, macrocirculation, and oxygen metabolism are distinct in early-stage endotoxic shock.

Sources of multidrug-resistant Acinetobacter baumannii and its role in respiratory tract colonization and nosocomial pneumonia in intensive care unit patients.

BACKGROUND: Multidrug-resistant Acinetobacter baumannii (MDRAB) is an important and emerging hospital-acquired pathogen worldwide. This study was conducted to identify the sources of MDRAB and its role in respiratory tract colonization and nosocomial pneumonia in intensive care unit (ICU) patients. METHODS: We conducted a prospective active surveillance study of MDRAB in three ICUs at a Chinese Hospital from April to August 2011, to identify the sources of MDRAB and its role in respiratory tract colonization and nosocomial pneumonia. RESULTS: One hundred and fourteen (13.0%) MDRAB isolates were detected from 876 specimens, with a sensitivity of 11.6% (55/474) in screening of the pharyngeal and tracheal swabs, and 14.7% (59/402) of the sputum/endotracheal aspirates. MDRAB colonization/infection was found in 34 (26.8%) of 127 patients, including 16 (12.6%) cases of pure colonization and 18 (14.2%) cases of pneumonia (two pre-ICU-acquired cases of pneumonia and 16 ICU-acquired cases of pneumonia). Previous respiratory tract MDRAB colonization was found in 22 (17.3%) patients: eight (6.3%) were pre-ICU-acquired colonization and 14 (11.0%) ICU-acquired colonization. Of eight pre-ICU-colonized patients, five were transferred from other wards or hospitals with hospitalization > 72 hours, and three came from the community with no previous hospitalization. Overall, 6/22 colonized patients presented with secondary pneumonia; only two (9.1%) colonized MDRAB strains were associated with secondary infections. Respiratory tract MDRAB colonization had no significant relationship with nosocomial pneumonia (P = 0.725). In addition, acute respiratory failure, mechanical ventilation, renal failure, and prior carbapenem use were risk factors for MDRAB colonization/infection. CONCLUSIONS: A high proportion of cases of MDRAB colonization/infection in ICU patients were detected through screening cultures. About one-third were acquired from general wards and the community before ICU admission. The low incidence of MDRAB colonization-related pneumonia questions the appropriateness of targeted antibiotic therapy.

Effect of serum from patients with severe acute pancreatitis on vascular endothelial permeability.

OBJECTIVE: This study aimed to investigate the effect of serum taken from patients with severe acute pancreatitis (SAP) on vascular endothelial permeability. METHODS: The monolayer permeability of endothelial cells (ECs) was assessed. Morphological changes in ECs, induced by serum from patients with SAP were assessed. Expressions of RhoA, myosin light chain (MLC) phosphorylation, and VE-cadherin protein were detected by Western blot. RESULTS: Compared with the control group, 20% SAP serum significantly increased endothelial monolayer permeability (P < 0.01), markedly induced transcellular F-actin redistribution with stress fiber formation and VE-cadherin derangement with fragmentations located at the cell borders, and increased gaps between ECs. Furthermore, Western blotting showed that SAP serum induced rapid activation of Rho protein, and markedly increased the level of phosphorylated MLC. However, pretreatment with Y-27632 (an inhibitor for Rho kinase) significantly inhibited endothelial hyperpermeability and the morphological changes of F-actin rearrangement and VE-cadherin redistribution. This was associated with a down-regulation of Rho protein expression and a reduction in the level of MLC phosphorylation. CONCLUSIONS: The SAP serum induces the loss of vascular endothelial monolayer integrity, with endothelial F-actin stress fiber formation and VE-cadherin redistribution. One of the mechanisms for this process involves the activation of the Rho/Rho kinase signaling pathway.

Study of Astragalus mongholicus polysaccharides on endothelial cells permeability induced by HMGB1.

Astragalus mongholicus polysaccharide (APS) shows various biological activities. Here, we explored the effect of APS on high mobility group protein 1 (HMGB1) -induced endothelial cell permeability. The results indicated APS pretreatment effectively inhibited HMGB1-induced increased permeability in endothelial cells (ECs). Signal transduction studies showed APS inhibited not only the activation of small guanylate Rho and its downstream effector Rho kinase (ROCK), but also the subsequent phosphorylation of myosin light chain (MLC) in ECs. In conclusion, our investigations suggested that APS inhibited HMGB1-induced increased permeability in ECs, regulated by Rho/ROCK signal pathways.

Management of severe sepsis in patients admitted to Asian intensive care units: prospective cohort study.

OBJECTIVES: To assess the compliance of Asian intensive care units and hospitals to the Surviving Sepsis Campaign's resuscitation and management bundles. Secondary objectives were to evaluate the impact of compliance on mortality and the organisational characteristics of hospitals that were associated with higher compliance. DESIGN: Prospective cohort study. SETTING: 150 intensive care units in 16 Asian countries. PARTICIPANTS: 1285 adult patients with severe sepsis admitted to these intensive care units in July 2009. The organisational characteristics of participating centres, the patients' baseline characteristics, the achievement of targets within the resuscitation and management bundles, and outcome data were recorded. MAIN OUTCOME MEASURE: Compliance with the Surviving Sepsis Campaign's resuscitation (six hours) and management (24 hours) bundles. RESULTS: Hospital mortality was 44.5% (572/1285). Compliance rates for the resuscitation and management bundles were 7.6% (98/1285) and 3.5% (45/1285), respectively. On logistic regression analysis, compliance with the following bundle targets independently predicted decreased mortality: blood cultures (achieved in 803/1285; 62.5%, 95% confidence interval 59.8% to 65.1%), broad spectrum antibiotics (achieved in 821/1285; 63.9%, 61.3% to 66.5%), and central venous pressure (achieved in 345/870; 39.7%, 36.4% to 42.9%). High income countries, university hospitals, intensive care units with an accredited fellowship programme, and surgical intensive care units were more likely to be compliant with the resuscitation bundle. CONCLUSIONS: While mortality from severe sepsis is high, compliance with resuscitation and management bundles is generally poor in much of Asia. As the centres included in this study might not be fully representative, achievement rates reported might overestimate the true degree of compliance with recommended care and should be interpreted with caution. Achievement of targets for blood cultures, antibiotics, and central venous pressure was independently associated with improved survival.

[Change in number of circulating endothelial progenitor cells and its significance in septic rats].

OBJECTIVE: To observe the change in number of circulating endothelial progenitor cells (cEPCs) and analyze its significance in septic rat. METHODS: Septic model of male Sprague-Dawley (SD) rats was reproduced by cecum ligation and puncture (n=80), and the normal control group (n=16) and sham operation group (n=80) were established. Nine rats in each group were used, and the cEPCs numbers in peripheral blood mononuclear cells (PBMCs, by flow cytometry), tumor necrosis factor-α (TNF-α), interleukin-10 (IL-10), D-dimer (by enzyme linked immunosorbent assay, ELISA), antithrombase-III ( AT-III , by immunonephelometry), wet/dry (W/D) ratio of liver, kidney and lung were determined at 0, 6, 12, 18 hours and 1, 2, 3, 7 days after reproduction of model. Eight rats in each group were used, and the pathologic changes in liver, kidney and lung at 1 day were observed, and the injury scores were evaluated. RESULTS: The cEPCs number was markedly increased, reaching the peak [(7 161.9±689.8)/10(6) PBMCs]at 18 hours. Circulating TNF-α, IL-10, D-dimer, AT-III were found to be increased, and the levels reached the peak at 12 hours, 12 hours, 3 days, 18 hours, respectively[(51.3±6.8) ng/L, (77.9±8.6) ng/L, (93.5±11.5) mg/L, (193.8±43.0) mg/L]. W/D ratio was elevated and signs of injury to the liver,kidney, lung became more obvious (18-hour W/D of liver: 3.79±0.09, kidney: 4.25±0.08, lung: 4.91±0.09; 1-day tissue evaluation of liver:1.86±0.26, kidney: 5.14±0.34, lung: 6.57±0.37). The levels of all parameters in model group were significantly higher than those in sham operation group[18-hour cEPCs numbers: (2 235.5±472.7)/10(6) PBMCs, 12-hour TNF-α: (14.3±5.8) ng/L, 12-hour IL-10: (35.0±5.8) ng/L, 3-day D-dimer: (14.2±4.4) mg/L, 18-hour AT-III: (100.1±12.8) mg/L; 18-hour liver W/D ratio: 3.50±0.07, kidney: 3.96±0.04, lung: 4.54±0.14; 1-day tissue evaluation of liver:0.29±0.18,kidney: 0.57±0.20, lung: 1.14±0.51, P<0.05 or P<0.01]. There was positive correlation between cEPCs numbers and TNF-α (r=0.587), IL-10 (r=0.497), D-dimer (r=0.294), AT-III (r=0.690), and W/D ratio of liver, kidney, lung (r(1)=0.532, r(2)=0.532, r(3)=0.679, all P<0.01). CONCLUSION: The cEPCs number markedly increases in septic rats, and it shows positive correlation with the degree of inflammatory reaction, blood clotting activation, capillary leakage and tissue damage. The increase of number of cEPCs is the result of reaction to sepsis, and its change in number might be valuable in evaluating the pathogenesis of sepsis.

Rapid hemodilution is associated with increased sepsis and mortality among patients with severe acute pancreatitis.

BACKGROUND: Hemoconcentration may be an important factor that determines the progression of severe acute pancreatitis (SAP). In addition, it has been proposed that biomarkers may be useful in predicting subsequent necrosis in SAP. However, it is still uncertain whether hemodilution in a short term can improve outcome. We aimed to investigate the effect of rapid hemodilution on the outcome of patients with SAP. METHODS: One hundred and fifteen patients were admitted prospectively according to the criteria within 24 hours of SAP onset. Patients were randomly assigned to either rapid hemodilution (hematocrit (HCT) < 35%, n = 56) or slow hemodilution (HCT > or = 35%, n = 59) within 48 hours of onset. Balthazar CT scores were calculated on admission, day 7, and day 14, after onset of the disease. Time interval for sepsis presented, incidence of sepsis within 28 days and in-hospital survival rate were determined. RESULTS: The amount of fluid used in rapid hemodilution was significantly more than that used in slow hemodilution (P < 0.05) on the admission day, the first day, and the second day. There were significant differences between the rapid and slow hemodilution group in terms of hematocrit, oxygenation index, pH values, APACHE II scores and organ dysfunction at different time during the first week. There were significant differences in the time interval to sepsis in rapid hemodilution ((7.4 +/- 1.9) days) compared with the slow hemodilution group ((10.2 +/- 2.3) days), and the incidence of sepsis (78.6%) was higher in the rapid group compared to the slow (57.6%) in the first 28 days. The survival rate of the slow hemodilution group (84.7%) was better than the rapid hemodilution (66.1%. P < 0.05). CONCLUSIONS: Rapid hemodilution can increase the incidence of sepsis within 28 days and in-hospital mortality. Hematocrit should be maintained between 30%-40% in the acute response stage.

[Investigation of distribution of bacteria and fungi in severe acute pancreatitis].

OBJECTIVE: To investigate the spectrum of bacteria and fungi in different sites in severe acute pancreatitis (SAP). METHODS: The prospective study was performed in 205 patients with SAP treated from January 2000 to December 2008. The Infection rate of bacteria and fungi was observed prospectively in pancreatic necrosis and(or) pus form abdomen, body fluids and deep vein catheter in SAP. Body fluids and pancreatic necrosis were cultured twice a week. Central venous catheter was cultured when it had been placed for two weeks. Blood was cultured for bacteria and fungi when body temperature was more than 39 degrees C. Constituent ratio of bacteria and fungi was observed in different sites and in all sites within 28 days after onset of SAP. RESULTS: There were 937 pathogens, among which infection rates of gram-negative bacteria was higher than gram-positive bacteria and fungi (P < 0.05), the infection rates of gam-positive bacteria and fungi were similar. Infection rates of gram-negative bacteria in pancreatic necrosis (55.2%), bile (55.4%), blood (68.1%) and central venous catheter (44.4%) were increased significantly (P < 0.05) compared with gram-positive bacteria and (30.2%, 33.9%, 23.4%, 38.9%) and fungi (14.6%, 10.7%, 8.5%, 16.7%); however, infection rate of fungi (59.6%) was increased significantly (P < 0.05) compared with gram-negative bacteria (24.0%) and gram-positive bacteria (16.3%) in urine; infection rate of gram-negative bacteria (53.2%) was significantly higher (P < 0.05) than that of fungi (27.1%) and gram-positive bacteria (19.7%) in sputum. Infection rate of non-zymogenic bacteria (Pseudomonas aeruginosa, Acinetobacter baumannii and Stenotrophomonas maltophilia) in gram-negative bacteria in pancreatic necrosis, bile, blood, central venous catheter and sputum was significantly higher than that of zymogenic bacteria (Klebsiella pneumoniae, Escherichia coli and Enterobacter cloacae) (P < 0.01); infection rate of zymogenic bacteria (Klebsiella pneumoniae, Escherichia coli) was higher significantly (P < 0.01) than that of non-zymogenic bacteria (Pseudomonas aeruginosa, Acinetobacter baumannii). Infection rate of staphylococcus aureus, Staphylococcus epidermidis and Staphylococcus haemolyticus was significantly higher (P < 0.05) than that of Enterococcus faecalis and Enterococcus faecium in pancreatic necrosis and sputum;but infection rate of Enterococcus faecium in bile and urine was significantly higher than other gram-positive bacteria (P < 0.05). There was not difference among gram-positive bacteria;however, infection rate of Staphylococcus epidermidis in central venous catheter was increased significantly (P < 0.05). Infection rate of candida mycoderma in pancreatic necrosis, bile, urine and sputum was significantly higher than that of tricho bacteria (P < 0.05). The peak of infection rate of microbes in body fluid was within 2 to 3 weeks. CONCLUSIONS: Constituent ratio in gram-negative, gram-positive bacteria and fungi as well as their species in different sites is diverse. The peak of infection rate of microbes is 2 to 3 weeks after onset of the disease.

Intravenous colistin sulfate: a rarely used form of polymyxin E for the treatment of severe multidrug-resistant Gram-negative bacterial infections.

In recent reports polymyxins have been considered an effective and safe treatment option for the management of multidrug-resistant (MDR) Gram-negative bacterial infections. Here we report our clinical experience with the use of intravenous colistin sulfate in critically ill patients hospitalized from January 2006 to October 2008, as a last treatment resort in China, and assess its effectiveness and adverse effects. Fifteen patients who suffered from severe infections caused by MDR or pandrug-resistant (PDR) Gram-negative bacteria (13 isolates of Acinetobacter baumannii, 4 isolates of Pseudomonas aeruginosa and 2 isolates of Klebsiella pneumoniae), unresponsive to the initial empirical regimens, were treated with colistin sulfate (daily dose of 1.28 +/- 0.25 million IU and duration of 22.3 +/- 6.2 days), based on sensitivity results. The treatment resulted in a good clinical response in 73.3%, microbiological clearance in 60% and mortality in 20%. Possible nephrotoxicity occurred in 1 patient and no patients developed neurotoxicity. In conclusion, intravenous colistin sulfate is a safe and viable alternative for the treatment of severe infections due to sensitive MDR Gram-negative bacteria.

[Characteristics of hemoglobin changes and its significance in critically ill patients].

OBJECTIVES: To investigate characteristics of hemoglobin changes in surgical critically ill patients. METHODS: One hundred and ten consecutive critically ill patients admitted to the surgical ICU of Shanghai Ruijin Hospital were prospectively included in the clinical trial from January 2004 to December 2006. And changes of hemoglobin and prognosis were retrospectively analyzed. The inclusion criteria were surgical critical illness, APACHE II > or = 8 points, and admission to ICU within 48 hours after onset of critical illness, except for patients with bleeding. According to hemoglobin level before transfusion, 110 patients divide into the low level hemoglobin group (< or = 100 g/L) and the high level hemoglobin group (> 100 g/L). Time interval for valley value of hemoglobin within 28 days and incidence of hypo-hemoglobin (< or = 100 g/L) were investigated; the mean hemoglobin level, mean APACHE II scores, amount of concentrated red blood cells and rate of mechanical ventilation as well as duration of ventilation within 28 days were calculated. ICU survival rate was observed. RESULTS: Level of hemoglobin in low level group was decreased significantly compared to high level group [(86.3 +/- 23.8) g/L vs. (112.9 +/- 20.4) g/L, P < 0.01]; and time of its valley values was shorter than that of high level group [(3 +/- 1) d vs. (5 +/- 2) d, P < 0.01]; the responding level of hemoglobin was (89.3 +/- 11.3) g/L and (110.0 +/- 12.5) g/L (P = 0.001), respectively. Incidence of hypo-hemoglobin was 92.9% in low level group and 0 in high level group within 28 days (P < 0.01). Hemoglobin level of high level group was significantly higher than that of low level group within 28 days [(120.2 +/- 12.5) g/L vs. (89.3 +/- 11.3) g/L, P < 0.05], and the total amount of blood transfusion in high level group was less significantly than that of low level group [(12.4 +/- 10.1) U vs. (24.0 +/- 15.6) U, P = 0.042]; mean APACHE II score in high level group was significantly lower than that of low level group [(8.7 +/- 2.4) vs. (13.2 +/- 4.3), P < 0.001]; rate of mechanical ventilation was no difference (56.4% vs. 52.7%, P = 0.765); but duration of mechanical ventilation was shorter than that of low level group [(12 +/- 5) d vs. (25 +/- 7) d, P < 0.001]. Survival rate in high level group in ICU was significantly higher than that of low level group (80.0% vs. 61.8%, P = 0.036). CONCLUSION: Prolonged hypo-hemoglobin level (< or = 100 g/L) and valley value in advance suggest bad prognosis.

Effect of biliary tract external drainage on cytokine expression and histomorphology of intestine, liver, and lung in rats with hemorrhagic shock.

OBJECTIVE: To investigate the protective effect of biliary tract external drainage on cytokine expression and pathomorphism of intestine, liver, and lung in rats with hemorrhagic shock. DESIGN: Randomized, control animal study. SETTING: This study was conducted at The Institution Digestive Surgery Research Laboratory of Shanghai Jiao Tong University. SUBJECTS: Sprague-Dawley rats. INTERVENTIONS: Biliary tract external drainage was performed by inserting a cannula into the bile duct. Hemorrhagic shock was induced by drawing blood from the carotid artery. MEASUREMENTS AND MAIN RESULTS: Twenty-four Sprague-Dawley rats were randomized to three equal groups of eight: sham shock; hemorrhagic shock; and hemorrhagic shock plus bile duct drainage. The messenger RNA expression of tumor necrosis factor-alpha, interleukin-6 in the intestine, liver, and lung tissue from the three groups were analyzed by reverse transcription-polymerase chain reaction. Tumor necrosis factor-alpha was analyzed in the bile of the rats by enzyme-linked immunosorbent assay. Histology of intestine, liver, and lung was performed in all groups by hematoxylin and eosin staining. The messenger RNA expression of tumor necrosis factor-alpha was significantly increased in the hemorrhagic shock group compared with the sham shock group (intestine 0.54 +/- 0.07 vs. 0.37 +/- 0.05, liver 1.01 +/- 0.06 vs. 0.56 +/- 0.07, lung 0.94 +/- 0.07 vs. 0.62 +/- 0.06). The messenger RNA expression of interleukin-6 was also significantly increased in the hemorrhagic shock group compared with the sham shock group (intestine 0.89 +/- 0.12 vs. 0.50 +/- 0.09, liver 1.07 +/- 0.10 vs. 0.57 +/- 0.12, lung 1.09 +/- 0.09 vs. 0.67 +/- 0.06). Biliary tract external drainage reduced significantly the messenger RNA expression of tumor necrosis factor-alpha (intestine 0.43 +/- 0.06 vs. 0.54 +/- 0.07, liver 0.74 +/- 0.18 vs. 1.01 +/- 0.06, lung 0.87 +/- 0.15 vs. 0.94 +/- 0.07) and interleukin-6 (intestine 0.60 +/- 0.11 vs. 0.89 +/- 0.12, liver 0.71 +/- 0.16 vs. 1.07 +/- 0.10, lung 0.88 +/- 0.25 vs. 1.09 +/- 0.09). The concentration of tumor necrosis factor-alpha in bile was significantly higher in the hemorrhagic shock group compared with the sham shock group (31.22 +/- 6.44 ng/mL vs. 15.49 +/- 3.64 ng/mL, p < .01). The histologic observation of the intestine, liver, and lung showed that the biliary tract external drainage significantly attenuate the putrescence and exfoliation of intestinal villi, denaturation and putrescence of hepatocytes, edema, and inflammatory cells infiltration of lung. CONCLUSIONS: Biliary tract external drainage decreases the messenger RNA expression of tumor necrosis factor-alpha, interleukin-6 and attenuate the tissue injury of the intestine, liver, and lung in rats model of hemorrhagic shock. The gut-liver axis was implicated to play a crucial role in hemorrhagic shock-induced multiple organ dysfunction syndrome.