Effect of probiotics on the incidence of ventilator-associated pneumonia in critically ill patients: a randomized controlled multicenter trial.

PURPOSE: To evaluate the potential preventive effect of probiotics on ventilator-associated pneumonia (VAP). METHODS: This was an open-label, randomized, controlled multicenter trial involving 235 critically ill adult patients who were expected to receive mechanical ventilation for ≥48 h. The patients were randomized to receive (1) a probiotics capsule containing live Bacillus subtilis and Enterococcus faecalis (Medilac-S) 0.5 g three times daily through a nasogastric feeding tube plus standard preventive strategies or (2) standard preventive strategies alone, for a maximum of 14 days. The development of VAP was evaluated daily, and throat swabs and gastric aspirate were cultured at baseline and once or twice weekly thereafter. RESULTS: The incidence of microbiologically confirmed VAP in the probiotics group was significantly lower than that in the control patients (36.4 vs. 50.4 %, respectively; P = 0.031). The mean time to develop VAP was significantly longer in the probiotics group than in the control group (10.4 vs. 7.5 days, respectively; P = 0.022). The proportion of patients with acquisition of gastric colonization of potentially pathogenic microorganisms (PPMOs) was lower in the probiotics group (24 %) than the control group (44 %) (P = 0.004). However, the proportion of patients with eradication PPMO colonization on both sites of the oropharynx and stomach were not significantly different between the two groups. The administration of probiotics did not result in any improvement in the incidence of clinically suspected VAP, antimicrobial consumption, duration of mechanical ventilation, mortality and length of hospital stay. CONCLUSION: Therapy with the probiotic bacteria B. Subtilis and E. faecalis are an effective and safe means for preventing VAP and the acquisition of PPMO colonization in the stomach.

[Effect of continuous high-volume hemofiltration in patients with severe acute respiratory distress syndrome].

OBJECTIVE: To investigate the effect of continuous high-volume hemofiltration (CHVHF) in patients with severe acute respiratory distress syndrome (ARDS). METHODS: A prospective randomized controlled trial was conducted. Sixty-five patients with severe ARDS admitted to intensive care unit (ICU) from June 2007 to June 2011 were divided into control group (n=28) and treatment group (n=37). Patients in treatment group were treated with CHVHF and other routine treatments. Patients in control group received routine treatments only. The oxygenation index (PaO2/FiO2), extravascular lung water index (EVLWI), arterial partial pressure of carbon dioxide (PaCO2), heart rate (HR), mean arterial pressure (MAP) were compared between control group and treatment group before and 6, 24, 48, 72 hours after treatment. The duration of mechanical ventilation (MV), ICU stay time, percentage of weaning from MV, and 28-day survival rate were also compared. RESULTS: The indexes of pulmonary function were improved after treatment in both groups. With prolonged time of treatment, PaO2/FiO2 was elevated, and EVLWI, PaCO2 were lowered, and the improvements were more marked in treatment group compared with control group (6-hour PaO2/FiO2: 92.6±7.2 mm Hg vs. 83.8±11.4 mm Hg, 24-hour EVLWI: 10.8±3.7 ml/kg vs. 12.6±4.5 ml/kg, 24-hour PaCO2: 47.2±8.5 mm Hg vs. 51.4±4.8 mm Hg, all P<0.05). HR and MAP were improved after the treatment in both groups, and there was no significant difference between groups. Compared with control group, the duration of MV and ICU stay were shortened in treatment group (duration of MV: 12±4 days vs. 19±6 days, ICU stay time: 21±4 days vs. 33±8 days, both P<0.05), and percentage of successful weaning from MV and 28-day survival rate were higher in treatment group (percentage of successful weaning from MV: 81.1% vs. 64.3%, 28-day survival rate: 86.5% vs. 71.4%, both P<0.05). CONCLUSIONS: CHVHF is an effective adjuvant treatment for severe ARDS. It can improve the lung function, shorten the duration of MV, improve the percentage of successful weaning from MV, and the survival rate, and it lowers the mortality, but it imparts no obvious influence to hemodynamics in patients.

Effectiveness of combining plasma exchange with continuous hemodiafiltration on acute Fatty liver of pregnancy complicated by multiple organ dysfunction.

Acute fatty liver of pregnancy (AFLP) is a rare disease of progressive hepatic insufficiency and secondary systemic complications that induce significant maternal risk. The application of combining plasma exchange (PE) and continuous hemodiafiltration (CHDF) is a novel concept for patients with AFLP. Since 2002, we have utilized the combination of PE with CHDF as adjunctive medical therapy for 11 AFLP patients with multiple organ dysfunction. Before PE and CHDF initiation, four patients had signs and symptoms of encephalopathy, four required ventilatory support, and all 11 were developing liver failure, significant renal compromise, and coagulopathy. PE combined with CHDF for patients was initiated a mean of 2 days postpartum (range, days 0-3). Daily or every other day PE combined with CHDF was undertaken on two to eight occasions for each of the 11 patients. Ten patients responded with composite clinical and laboratory improvement and were discharged to the ward, then cured and discharged from hospital; one patient died of septic shock. Average duration of hospitalization was 17 days (range, days 9-38) from time of admission to discharge; the average duration of intensive care unit was 10 days (range, days 4-23). No significant PE- and CHDF-related complications occurred. These results indicate that combing PE and CHDF in a series-parallel circuit is an effective and safe treatment for patients with severe AFLP. This finding may have important implications for the development of an effective treatment for patients with AFLP suffering multiple organ dysfunction.

[The effects of joint administration of 6% hydroxyethyl starch 130/0.4 and high-volume hemofiltration on patients with acute lung injury and acute kidney injury].

OBJECTIVE: To evaluate the effects of administration of 6% hydroxyethyl starch (6% HES 130/0.4, voluven) in combination with high volume hemofiltration (HVHF) in patients with ALI and AKI. METHODS: One hundred and eight patients with acute lung injury (ALI) and acute kidney injury (AKI) were enrolled from Department of Intensive Care Unit (ICU) of the provincial Hospital Affiliated to Shandong University between August 2006 and May 2011. The patients were randomly divided into two groups A (n = 68) and B (n = 40) to receive voluven (i.v., for volume resuscitation) and voluven+HVHF for 72 hours. The arterial blood lactate concentration (Lac), high sensitivity C-reactive protein (hs-CRP) serum concentration, pulmonary function index alveolar-arterial oxygen pressure difference [P(A-a)DO2] and oxygenation index (OI), as well as kidney function index serum cystatin C (Cyst C) and serum creatinine clearance rate (CCr) were measured at the time of admission and 72 hours after the treatment for statistical analysis. RESULTS: In comparison with group A, group B had significantly (all P < 0.01) lower mean value in the level of arterial Lac (mmol/L: 1.7 ± 0.7 vs. 2.7 ± 1.5), serum hs-CRP (mg/L: 35.8 ± 18.8 vs. 99.5 ± 20.4), P(A-a)DO2 (mm Hg, 1 mm Hg=0.133 kPa: 115.5 ± 23.1 vs. 155.4 ± 27.4), Cyst C (mg/L: 2.06 ± 1.12 vs. 3.95 ± 2.06) and significantly higher (both P < 0.01) mean value of OI (mm Hg: 295.2 ± 38.8 vs. 239.5 ± 32.7) and CCr (ml/min: 108.71 ± 31.33 vs. 90.21 ± 30.35) 72 hours after treatment. The mortality rate of group B was significantly lower than group A [10.00%(4/40) vs. 29.41%(20/68), P < 0.05] 7 days after the admission. CONCLUSION: 6% HES 130/0.4 in combination with HVHF could improve the lung and kidney function of the patients with ALI and AKI, prevent the development of multiple organ dysfunction syndrome (MODS), therefore improve the survival rate of these patients.

Effects of high-volume hemofiltration on alveolar-arterial oxygen exchange in patients with refractory septic shock.

BACKGROUND: High-volume hemofiltration (HVHF) is technically possible in severe acute pancreatitis (SAP) patients complicated with multiple organ dysfunction syndrome (MODS). Continuous HVHF is expected to become a beneficial adjunct therapy for SAP complicated with MODS. In this study, we aimed to explore the effects of fluid resuscitation and HVHF on alveolar-arterial oxygen exchange, the Acute Physiology and Chronic Health Evaluation II (APACHE II) score in patients with refractory septic shock. METHODS: A total of 89 refractory septic shock patients, who were admitted to ICU, the Provincial Hospital affiliated to Shandong University from August 2006 to December 2009, were enrolled in this retrospective study. The patients were randomly divided into two groups: fluid resuscitation (group A, n=41), and fluid resuscitation plus high-volume hemofiltration (group B, n=48). The levels of O2 content of central venous blood (CcvO2), arterial oxygen content (CaO2), alveolar-arterial oxygen pressure difference P(A-a)DO2, ratio of arterial oxygen pressure/alveolar oxygen pressure (PaO2/PaO2), respiratory index (RI) and oxygenation index (OI) were determined. The oxygen exchange levels of the two groups were examined based on the arterial blood gas analysis at different times (0, 24, 72 hours and 7 days of treatment) in the two groups. The APACHE II score was calculated before and after 7-day treatment in the two groups. RESULTS: The levels of CcvO2, CaO2 on day 7 in group A were significantly lower than those in group B (CcvO2: 0.60±0.24 vs. 0.72±0.28, P<0.05; CaO2: 0.84±0.43 vs. 0.94±0.46, P<0.05). The level of oxygen extraction rate (O2ER) in group A on the 7th day was significantly higher than that in group B (28.7±2.4 vs. 21.7±3.4, P<0.01). The levels of P(A-a)DO2 and RI in group B on the 7th day were significantly lower than those in group A. The levels of PaO2/PaO2 and OI in group B on 7th day were significantly higher than those in group A (P<0.05 or P<0.01). The APACHE II score in the two groups reduced gradually after 7-day treatment, and the APACHE II score on the 7th day in group B was significantly lower than that in group A (8.2±3.8 vs. 17.2±6.8, P<0.01). CONCLUSION: HVHF combined with fluid resuscitation can improve alveolar-arterial-oxygen exchange, decrease the APACHE II score in patients with refractory septic shock, and thus it increases the survival rate of patients.

[The role of p38 mitogen-activated protein kinase in interleukin-6 induction by lipopolysaccharide in vascular smooth muscle cells].

OBJECTIVE: To investigate the regulation mechanism of p38 mitogen-activated protein kinase (p38MAPK) in interleukin-6 (IL-6) expression of vascular smooth muscle cell (VSMC) induced by lipopolysaccharide (LPS). METHODS: Rat VSMCs were divided into LPS group, SB203580+LPS group, SB203580 group and control group. LPS group was treated with 100 microg/L LPS for 0, 3, 6, 12, 24 hours, SB203580+LPS group was first treated with 10 micromol/L SB203580 for 2 hours and then exposed to 100 microg/L LPS for 0, 3, 6, 12, 24 hours, SB203580 group was pretreated with 10 micromol/L SB203580 for 2 hours. The level of IL-6 mRNA was determined by real-time polymerase chain reaction (PCR) and IL-6 secretion in the culture medium was measured by enzyme linked immunosorbent assay (ELISA) at different time points. RESULTS: The expression of IL-6 mRNA and the release of IL-6 were increased significantly in VSMC as early as 3 hours after being treated with LPS [mRNA: (21.3+/-3.2)x10(4), protein: (296.2+/-19.6) ng/L], peaked in 12 hours [mRNA: (131.4+/-11.2)x10(4), protein: (897.7+/-34.0) ng/L], and the elevation persisted up to 24 hours after treatment [mRNA: (15.3+/-4.7)x10(4), protein: (194.3+/-24.0) ng/L] compared with control group [mRNA: (9.4+/-1.9)x10(4), protein: (29.4+/-4.4) ng/L, all P<0.05]. On the other hand, the expression of IL-6 was significantly suppressed by p38MAPK inhibitor SB203580 at 3, 6, 12 hours [mRNA: (15.4+/-3.6)x10(4), (43.2+/-6.6)x10(4), (56.2+/-5.5)x10(4), protein: (180.3+/-23.6), (432.2+/-56.8), (546.2+/-57.9) ng/L, all P<0.05]. CONCLUSION: The release of IL-6 and the expression of IL-6 mRNA was increased significantly in LPS-challenged VSMC; however, the induction of IL-6 was significantly suppressed by p38MAPK inhibitor. p38MAPK may play an important role in the release of IL-6 induced by LPS.

Incidence and risk factors of gastrointestinal bleeding in mechanically ventilated patients.

BACKGROUND: The widespread use of gastrointestinal bleeding prophylaxis in critically ill patients was one of the most controversial issues. Since few studies reported the incidence of gastrointestinal bleeding in mechanically ventilated patients, this study aimed to identify the incidence and risk factors related to gastrointestinal bleeding in patients undergoing mechanical ventilation for more than 48 hours. METHODS: A total of 283 ICU patients who had received mechanical ventilation for longer than 48 hours at a provincial hospital affiliated to Shandong University from January 1, 2007 to December 31, 2009 were analyzed retrospectively. Those were excluded from the study if they had a history of gastrointestinal bleeding or ulceration, recent gastrointestinal surgery, brain death and active bleeding from the nose or throat. Demographic data of the patients included patient age, diagnosis on admission, duration of ICU stay, duration of ventilation, patterns and parameters of ventilation, ICU mortality, APACHE II score, multiple organ dysfunction, and indexes of biochemistry, kidney function, liver function and coagulation function. Risk factors of gastrointestinal bleeding were analyzed by univariate analysis and multiple logistic regression analysis. RESULTS: In the 242 patients who were given mechanical ventilation longer than 48 hours, the incidence of gastrointestinal bleeding was 46.7%. The bleeding in 3.3% of the patients was clinically significant. Significant risk factors were peak inspiratory pressure ≥30cmH2O, renal failure, liver failure, PLT count<50×10(9)/L and prolonged APTT. Enteral nutrition had a beneficial effect on gastrointestinal bleeding. However, the multiple logistic regression analysis revealed that the independent risk factors of gastrointestinal bleeding were as follows: high pressure ventilator setting ≥ 30cmH2O(RR=3.478, 95%CI=2.208-10.733), renal failure(RR=1.687, 95%CI = 1.098-3.482), PLT count<50×1 0(9)/L (RR=3.762, 95%CI=2.346-14.685), and prolonged APTT(RR=5.368, 95%CI=2.487-11.266). Enteral nutrition(RR=0.436, 95%CI= 0.346-0.764) was the independent protective factor. CONCLUSIONS: The incidence of gastrointestinal bleeding was high in the patients who received mechanical ventilation, and bleeding usually occurred within the first 48 hours. High pressure ventilator setting, renal failure, decreased PLT count and prolonged APTT were the significant risk factors of gastrointestinal bleeding. However, enteral nutrition was the independent protective factor.

[Study the effects of high-volume hemofiltration and fluid resuscitation on removing blood lactic acid and pro-inflammatory cytokines in patients with refractory septic shock].

OBJECTIVE: To evaluate the effects of high-volume hemofiltration (HVHF) and fluid resuscitation on the levels of arterial lactate and inflammatory cytokines, the acute physiology and chronic health evaluation II (APACHE II) score, and sepsis-related organ failure assessment (SOFA) score in patients with refractory septic shock and multiple organ dysfunction syndrome (MODS). METHODS: Eighty-nine patients with refractory septic shock and MODS undergoing HVHF, fluid resuscitation were included in the trial, and they were randomly divided into fluid resuscitation group (group A, 41 cases) and HVHF and fluid resuscitation group (group B, 48 cases). The changes in arterial lactate, lactate clearance rate, interleukin-6 (IL-6), procalcitonin (PCT), high sensitivity C-reactive protein (hs-CRP), APACHE II score and SOFA score in patients with refractory septic shock and MODS were determined before and after the treatment. RESULTS: (1) The arterial lactate clearance rate after treatment in both groups was elevated gradually. The level of lactate clearance rate in group B at 6, 12, 24 hours [(18.8+/-10.3)%, (31.6+/-11.4)%, (39.2+/-16.4)%] were higher than that of group A, respectively [(10.7+/-7.5)%, (14.7+/-10.3)%, (16.5+/-10.2)%, P < 0.05 or P < 0.01]. (2) The levels of pro-inflammatory cytokine IL-6, PCT and hs-CRP were reduced gradually after treatment in both groups. After treatment, the serum concentration of IL-6, PCT and hs-CRP levels in group B were reduced significantly more than that in group A at 1 day and 3 days (P < 0.05 or P < 0.01). (3) The APACHE II and SOFA scores in both groups were reduced gradually on 3 days and 7 days after treatment, but the APACHE II and SOFA scores on 7 days in group B were lower compared with group A (P < 0.05 and P < 0.01). CONCLUSION: HVHF and fluid resuscitation could reduce arterial lactate and cytokines contents, at the same time lower the APACHE II score and SOFA score in patients with refractory septic shock and MODS, thus it could improve the survival rate of MODS patients.

Growth inhibition and gene induction in human hepatocellular carcinoma cell exposed to sodium 4-phenylbutanoate.

BACKGROUND: Sodium 4-phenylbutanoate (NaPB) can induce cellular differentiation and cell cycle arrest. However, its potential anticancer properties in hepatocellular carcinoma and influence on normal liver cell are still unclear. We observed the effects of NaPB on growth inhibition, including differentiation and phase growth arrest in normal liver cell line L-02 and hepatocellular carcinoma cell line Bel-7402. Furthermore, we investigated its mechanism in Bel-7402. METHODS; Hepatocellular carcinoma cells Bel-7402 and normal liver cell line L-02 were treated with NaPB at different concentrations. Light microscopy was used to find morphological change in cells. Cell cycle was detected by flow cytometry. Expression of acetylating histone H4 and of histones deacetylase 4 (HDAC4) were determined by Western blot. The expression of P21WAF1/CIP1 and E-cadherin were observed through immunocytochemistry. RESULTS: NaPB treatment led to time dependent growth inhibition in hepatocellular carcinoma cells Bel-7402. NaPB treatment caused a significant decline in the fraction of S phase cells and a significant increase in G0/G1 cells. NaPB increased the expression of P21(WAF1/CIP1) and E-cadherin in Bel-7402 and significantly decreased the level of HDAC4 in Bel-7402. NaPB significantly improved the level of acetylating histone H4. The normal liver cell line L-02 showed no distinct changes under treatment with NaPB. CONCLUSIONS: NaPB inhibited the growth of hepatocellular carcinoma cells Bel-7402 and induced partial differentiation through enhancing the acetylating histones. In Bel-7402, the expressions of P21(WAF1/CIP1) and E-cadherin may be related to level of acetylating histones and inhibition of cellular growth. NaPB showed no significant effect on normal liver cells.