Nucleotide polymorphism in ARDS outcome: a whole exome sequencing association study.

BACKGROUND: Genetic locus were identified associated with acute respiratory distress syndrome (ARDS). Our goal was to explore the associations between genetic variants and ARDS outcome, as well as subphenotypes. METHODS: This was a single-center, prospective observational trial enrolling adult ARDS patients. After baseline data were collected, blood samples were drawn to perform whole exome sequencing, single nucleotide polymorphism (SNP)/insertion-deletion to explore the quantitative and functional associations between genetic variants and ICU outcome, clinical subphenotypes. Then the lung injury burden (LIB), which was defined as the ratio of nonsynonymous SNP number per megabase of DNA, was used to evaluate its value in predicting ARDS outcome. RESULTS: A total of 105 ARDS patients were enrolled in the study, including 70 survivors and 35 nonsurvivors. Based on the analysis of a total of 65,542 nonsynonymous SNP, LIB in survivors was significantly higher than nonsurvivors [1,892 (1,848-1,942)/MB versus 1,864 (1,829-1,910)/MB, P=0.018], while GO analysis showed that 60 functions were correlated with ARDS outcome, KEGG enrichment analysis showed that SNP/InDels were enriched in 13 pathways. Several new SNPs were found potentially associated with ARDS outcome. Analysis of LIB was used to determine its outcome predicting ability, the area under the ROC curve of which was only 0.6103, and increase to 0.712 when combined with APACHE II score. CONCLUSIONS: Genetic variants are associated with ARDS outcome and subphenotypes; however, their prognostic value still need to be verified by larger trials. TRIAL REGISTRATION: Clinicaltrials.gov NCT02644798. Registered 20 April 2015.

Venovenous extra-corporeal membrane oxygenation for severe acute respiratory distress syndrome: a matched cohort study.

BACKGROUND: Although the use of extra-corporeal membrane oxygenation (ECMO) has been rapidly increasing, the benefit of ECMO in patients with acute respiratory distress syndrome (ARDS) remains unclear. Our objective was to investigate the effect of venovenous ECMO (VV-ECMO) on adult patients with severe ARDS. METHODS: We conducted a multi-center, retrospective, cohort study in the intensive care units (ICUs) of six teaching hospitals between January 2013 and December 2018. Patients with severe ARDS who received VV-ECMO support were included. The detailed demographic data and physiologic data were used to match ARDS patients without ECMO. The primary endpoint was the 28-day mortality. RESULTS: Ninety-nine patients with severe ARDS supported by VV-ECMO and 72 patients without ECMO were included in this study. The acute physiology and chronic health evaluation II score was 23.1 ±â€Š6.3 in the ECMO group and 24.8 ±â€Š8.5 in the control group (P = 0.1195). The sequential organ failure assessment score was 12.8 ±â€Š3.4 in the ECMO group and 13.7 ±â€Š3.5 in the control group (P = 0.0848). The 28-day mortality of patients with ECMO support was 39.4%, and that of the control group was 55.6%. The survival analysis curve showed that the 28-day mortality in the ECMO group was significantly lower than that in the control group (P = 0.0097). Multivariate Cox regression analysis showed that the independent predictors of the 28-day mortality were the requirement of vasopressors before ECMO (hazard ratio [HR]: 1.006; 95% confidence interval [CI]: 1.001-1.013; P = 0.030) and duration of mechanical ventilation before ECMO (HR: 3.299; 95% CI: 1.264-8.609; P = 0.034). CONCLUSIONS: This study showed that ECMO improved the survival of patients with severe ARDS. The duration of mechanical ventilation and the requirement of vasopressors before ECMO might be associated with an increased risk of death.

Genetic Modification of Mesenchymal Stem Cells Overexpressing Angiotensin II Type 2 Receptor Increases Cell Migration to Injured Lung in LPS-Induced Acute Lung Injury Mice.

Although mesenchymal stem cells (MSCs) transplantation has been shown to promote the lung respiration in acute lung injury (ALI) in vivo, its overall restorative capacity appears to be restricted mainly because of low retention in the injured lung. Angiotensin II (Ang II) are upregulated in the injured lung. Our previous study showed that Ang II increased MSCs migration via Ang II type 2 receptor (AT2R). To determine the effect of AT2R in MSCs on their cell migration after systemic injection in ALI mice, a human AT2R expressing lentiviral vector and a lentivirus vector carrying AT2R shRNA were constructed and introduced into human bone marrow MSCs. A mouse model of lipopolysaccharide-induced ALI was used to investigate the migration of AT2R-regulated MSCs and the therapeutic potential in vivo. Overexpression of AT2R dramatically increased Ang II-enhanced human bone marrow MSC migration in vitro. Moreover, MSC-AT2R accumulated in the damaged lung tissue at significantly higher levels than control MSCs 24 and 72 hours after systematic MSC transplantation in ALI mice. Furthermore, MSC-AT2R-injected ALI mice exhibited a significant reduction of pulmonary vascular permeability and improved the lung histopathology and had additional anti-inflammatory effects. In contrast, there were less lung retention in MSC-ShAT2R-injected ALI mice compared with MSC-Shcontrol after transplantation. Thus, MSC-ShAT2R-injected group exhibited a significant increase of pulmonary vascular permeability and resulted in a deteriorative lung inflammation. Our results demonstrate that overexpression of AT2R enhance the migration of MSCs in ALI mice and may provide a new therapeutic strategy for ALI. Stem Cells Translational Medicine 2018;7:721-730.

Predictive utilities of neutrophil gelatinase-associated lipocalin (NGAL) in severe sepsis.

BACKGROUND: We aim to investigate the predictive value of plasma neutrophil gelatinase-associated lipocalin (pNGAL) in patients with severe sepsis. METHODS: A total of 124 patients were enrolled in this observational study. Blood samples were obtained at admission, on day 2 and day 7. Receiver operating characteristic (ROC) curves were generated to assess the utility of pNGAL in prediction of 28-day mortality and need for CRRT. Cox regression curves were built with and without pNGAL for 28-day mortality prediction to determine NGAL's contributive predictive value. RESULTS: Plasma NGAL was significantly increased in non-survivors group on day 2 and 7 and predicted 28-day mortality with AuROC values of 0.675 (95% CI 0.570-0.780) and 0.752 (95% CI 0.619-0.885). Addition of day 2 NGAL to the clinical model resulted in a net reclassification index (NRI) increment of 0.40 (95% CI 0.06-0.75, P = 0.028) for prediction of 28-day mortality. The AuROC of NGAL at admission and day 2 was greater than creatinine in prediction of the need for CRRT. CONCLUSION: Plasma NGAL discriminated 28-day survivors from non-survivors on day 2 and 7 and was a relatively robust predictor of 28-day mortality prediction. Plasma NGAL possibly outperformed creatinine in the prediction of need for CRRT.

Plasma microRNAs levels are different between pulmonary and extrapulmonary ARDS patients: a clinical observational study.

BACKGROUND: Mesenchymal stem cells (MSC) obviously alleviate the damage of the structure and function of pulmonary vascular endothelial cells (VEC). The therapeutic effects of MSC are significantly different between pulmonary ARDS (ARDSp) and extrapulmonary ARDS (ARDSexp). MicroRNAs (miRNAs), as important media of MSC regulating VEC, are not studied between ARDSp and ARDSexp. We aimed to explore the plasma levels difference of miRNAs that regulate VEC function and are associated with MSC (MSC-VEC-miRNAs) between ARDSp and ARDSexp patients. METHODS: MSC-VEC-miRNAs were obtained through reviewing relevant literatures screened in PubMed database. We enrolled 57 ARDS patients within 24 h of admission to the ICU and then collected blood samples, extracted plasma supernatant. Patients' clinical data were collected. Then, plasma expression of MSC-VEC-miRNAs was measured by real-time fluorescence quantitative PCR. Simultaneously, plasma endothelial injury markers VCAM-1, vWF and inflammatory factors TNF-α, IL-10 were detected by ELISA method. RESULTS: Fourteen miRNAs were picked out after screening. A total of 57 ARDS patients were included in this study, among which 43 cases pertained to ARDSp group and 14 cases pertained to ARDSexp group. Plasma miR-221 and miR-27b levels in ARDSexp group exhibited significantly lower than that in ARDSp group (miR-221, 0.22 [0.12-0.49] vs. 0.57 [0.22-1.57], P = 0.008, miR-27b, 0.34 [0.10-0.46] vs. 0.60 [0.20-1.46], P = 0.025). Plasma vWF concentration in ARDSexp group exhibited significantly lower than that in ARDSp group (0.77 [0.29-1.54] vs. 1.80 [0.95-3.51], P = 0.048). Significant positive correlation was found between miR-221 and vWF in plasma levels (r = 0.688, P = 0.022). Plasma miR-26a and miR-27a levels in non-survival group exhibited significantly lower than that in survival group (miR-26a, 0.17 [0.08-0.20] vs. 0.69 [0.24-2.33] P = 0.018, miR-27a, 0.23 [0.16-0.58] vs. 1.45 [0.38-3.63], P = 0.021) in ARDSp patients. CONCLUSION: Plasma miR-221, miR-27b and vWF levels in ARDSexp group are significantly lower than that in ARDSp group. Plasma miR-26a and miR-27a levels in non-survival group are significantly lower than that in survival group in ARDSp patients.

Effects of Propofol on Respiratory Drive and Patient-ventilator Synchrony during Pressure Support Ventilation in Postoperative Patients: A Prospective Study.

BACKGROUND: Propofol is increasingly used during partial support mechanical ventilation such as pressure support ventilation (PSV) in postoperative patients. However, breathing pattern, respiratory drive, and patient-ventilator synchrony are affected by the sedative used and the sedation depth. The present study aimed to evaluate the physiologic effects of varying depths of propofol sedation on respiratory drive and patient-ventilator synchrony during PSV in postoperative patients. METHODS: Eight postoperative patients receiving PSV for <24 h were enrolled. Propofol was administered to achieve and maintain a Ramsay score of 4, and the inspiratory pressure support was titrated to obtain a tidal volume (VT) of 6-8 ml/kg. Then, the propofol dose was reduced to achieve and maintain a Ramsay score of 3 and then 2. At each Ramsay level, the patient underwent 30-min trials of PSV. We measured the electrical activity of the diaphragm, flow, airway pressure, neuro-ventilatory efficiency (NVE), and patient-ventilator synchrony. RESULTS: Increasing the depth of sedation reduced the peak and mean electrical activity of the diaphragm, which suggested a decrease in respiratory drive, while VT remained unchanged. The NVE increased with an increase in the depth of sedation. Minute ventilation and inspiratory duty cycle decreased with an increase in the depth of sedation, but this only achieved statistical significance between Ramsay 2 and both Ramsay 4 and 3 (P < 0.05). The ineffective triggering index increased with increasing sedation depth (9.5 ± 4.0%, 6.7 ± 2.0%, and 4.2 ± 2.1% for Ramsay 4, 3, and 2, respectively) and achieved statistical significance between each pair of depth of sedation (P < 0.05). The depth of sedation did not affect gas exchange. CONCLUSIONS: Propofol inhibits respiratory drive and deteriorates patient-ventilator synchrony to the extent that varies with the depth of sedation. Propofol has less effect on breathing pattern and has no effect on VT and gas exchange in postoperative patients with PSV.

Noninvasive Ventilation in Acute Hypoxemic Nonhypercapnic Respiratory Failure: A Systematic Review and Meta-Analysis.

OBJECTIVE: To evaluate the effectiveness of noninvasive ventilation in patients with acute hypoxemic nonhypercapnic respiratory failure unrelated to exacerbation of chronic obstructive pulmonary disease and cardiogenic pulmonary edema. DATA SOURCES: PubMed, EMBASE, Cochrane library, Web of Science, and bibliographies of articles were retrieved inception until June 2016. STUDY SELECTION: Randomized controlled trials comparing application of noninvasive ventilation with standard oxygen therapy in adults with acute hypoxemic nonhypercapnic respiratory failure were included. Chronic obstructive pulmonary disease exacerbation and cardiogenic pulmonary edema patients were excluded. The primary outcome was intubation rate; ICU mortality and hospital mortality were secondary outcomes. DATA EXTRACTION: Demographic variables, noninvasive ventilation application, and outcomes were retrieved. Internal validity was assessed using the risk of bias tool. The strength of evidence was assessed using Grading of Recommendations Assessment, Development, and Evaluation methodology. DATA SYNTHESIS: Eleven studies (1,480 patients) met the inclusion criteria and were analyzed by using a random effects model. Compared with standard oxygen therapy, the pooled effect showed that noninvasive ventilation significantly reduced intubation rate with a summary risk ratio of 0.59 (95% CI, 0.44-0.79; p = 0.0004). Furthermore, hospital mortality was also significantly reduced (risk ratio, 0.46; 95% CI, 0.24-0.87; p = 0.02). Subgroup meta-analysis showed that the application of bilevel positive support ventilation (bilevel positive airway pressure) was associated with a reduction in ICU mortality (p = 0.007). Helmet noninvasive ventilation could reduce hospital mortality (p = 0.0004), whereas face/nasal mask noninvasive ventilation could not. CONCLUSIONS: Noninvasive ventilation decreased endotracheal intubation rates and hospital mortality in acute hypoxemia nonhypercapnic respiratory failure excluding chronic obstructive pulmonary disease exacerbation and cardiogenic pulmonary edema patients. There is no sufficient scientific evidence to recommend bilevel positive airway pressure or helmet due to the limited number of trials available. Large rigorous randomized trials are needed to answer these questions definitely.

The Effect of Early Goal-Directed Therapy on Outcome in Adult Severe Sepsis and Septic Shock Patients: A Meta-Analysis of Randomized Clinical Trials.

BACKGROUND: Whether early goal-directed therapy (EGDT) improves outcome in severe sepsis and septic shock remains unclear. We performed a meta-analysis of existing clinical trials to examine whether EGDT improved outcome in the resuscitation of adult sepsis patients compared with control care. METHODS: We searched for eligible studies using MEDLINE, Elsevier, Cochrane Central Register of Controlled Trials, and Web of Science databases. Studies were eligible if they compared the effects of EGDT versus control care on mortality in adult patients with severe sepsis and septic shock. Two reviewers extracted data independently. Data including mortality, sample size of the patients with severe sepsis and septic shock, and resuscitation end points were extracted. Data were analyzed using methods recommended by the Cochrane Collaboration Review Manager 4.2 software. Random errors were evaluated by trial sequential analysis (TSA). RESULTS: Nine studies compared EGDT with control care, and 5202 severe sepsis and septic shock patients were included. A nonsignificant trend toward reduction in the longest all-cause mortality was observed in the EGDT group compared with control care (relative risk, 0.89; 99% confidence interval, 0.74-1.07; P = 0.10). However, EGDT significantly reduced intensive care unit mortality in severe sepsis and septic shock patients (relative risk, 0.72; 99% confidence interval, 0.57-0.90; P = 0.0002). TSA indicated lack of firm evidence for a beneficial effect. CONCLUSIONS: In this meta-analysis, a nonsignificant trend toward reduction in the longest all-cause mortality in patients resuscitated with EGDT was noted. However, EGDT significantly reduced intensive care unit mortality in severe sepsis and septic shock patients. TSA indicated a lack of firm evidence for the results. More powered, randomized controlled trials are needed to determine the effects.

Comparison of the effects of albumin and crystalloid on mortality in adult patients with severe sepsis and septic shock: a meta-analysis of randomized clinical trials.

INTRODUCTION: The aim of this study was to examine whether albumin reduced mortality when employed for the resuscitation of adult patients with severe sepsis and septic shock compared with crystalloid by meta-analysis. METHODS: We searched for and gathered data from MEDLINE, Elsevier, Cochrane Central Register of Controlled Trials and Web of Science databases. Studies were eligible if they compared the effects of albumin versus crystalloid therapy on mortality in adult patients with severe sepsis and septic shock. Two reviewers extracted data independently. Disagreements were resolved by discussion with other two reviewers until a consensus was achieved. Data including mortality, sample size of the patients with severe sepsis, sample size of the patients with septic shock and resuscitation endpoints were extracted. Data were analyzed by the methods recommended by the Cochrane Collaboration Review Manager 4.2 software. RESULTS: A total of 5,534 records were identified through the initial search. Five studies compared albumin with crystalloid. In total, 3,658 severe sepsis and 2,180 septic shock patients were included in the meta-analysis. The heterogeneity was determined to be non-significant (P = 0.86, I(2) = 0%). Compared with crystalloid, a trend toward reduced 90-day mortality was observed in severe sepsis patients resuscitated with albumin (odds ratio (OR) 0.88; 95% CI, 0.76 to 1.01; P = 0.08). However, the use of albumin for resuscitation significantly decreased 90-day mortality in septic shock patients (OR 0.81; 95% CI, 0.67 to 0.97; P = 0.03). Compared with saline, the use of albumin for resuscitation slightly improved outcome in severe sepsis patients (OR 0.81; 95% CI, 0.64 to 1.08; P = 0.09). CONCLUSIONS: In this meta-analysis, a trend toward reduced 90-day mortality was observed in severe sepsis patients resuscitated with albumin compared with crystalloid and saline. Moreover, the 90-day mortality of patients with septic shock decreased significantly.

The effect of prone positioning on mortality in patients with acute respiratory distress syndrome: a meta-analysis of randomized controlled trials.

INTRODUCTION: Prone positioning (PP) has been reported to improve the survival of patients with severe acute respiratory distress syndrome (ARDS). However, it is uncertain whether the beneficial effects of PP are associated with positive end-expiratory pressure (PEEP) levels and long durations of PP. In this meta-analysis, we aimed to evaluate whether the effects of PP on mortality could be affected by PEEP level and PP duration and to identify which patients might benefit the most from PP. METHODS: Publications describing randomized controlled trials (RCTs) in which investigators have compared prone and supine ventilation were retrieved by searching the following electronic databases: PubMed/MEDLINE, the Cochrane Library, the Web of Science and Elsevier Science (inception to May 2013). Two investigators independently selected RCTs and assessed their quality. The data extracted from the RCTs were combined in a cumulative meta-analysis and analyzed using methods recommended by the Cochrane Collaboration. RESULTS: A total of nine RCTs with an aggregate of 2,242 patients were included. All of the studies received scores of up to three points using the methods recommended by Jadad et al. One trial did not conceal allocation. This meta-analysis revealed that, compared with supine positioning, PP decreased the 28- to 30-day mortality of ARDS patients with a ratio of partial pressure of arterial oxygen/fraction of inspired oxygen ≤ 100 mmHg (n = 508, risk ratio (RR) = 0.71, 95 confidence interval (CI) = 0.57 to 0.89; P = 0.003). PP was shown to reduce both 60-day mortality (n = 518, RR = 0.82, 95% CI = 0.68 to 0.99; P = 0.04) and 90-day mortality (n = 516, RR = 0.57, 95% CI = 0.43 to 0.75; P < 0.0001) in ARDS patients ventilated with PEEP ≥ 10 cmH2O. Moreover, PP reduced 28- to 30-day mortality when the PP duration was >12 h/day (n = 1,067, RR = 0.73, 95% CI = 0.54 to 0.99; P = 0.04). CONCLUSIONS: PP reduced mortality among patients with severe ARDS and patients receiving relatively high PEEP levels. Moreover, long-term PP improved the survival of ARDS patients.

Positive end expiratory pressure titrated by transpulmonary pressure improved oxygenation and respiratory mechanics in acute respiratory distress syndrome patients with intra-abdominal hypertension.

BACKGROUND: Intra-abdominal hypertension (IAH) is common in acute respiratory distress syndrome (ARDS) patients and when resulting in decrease of chest wall compliance will weaken the effect of positive end expiratory pressure (PEEP). We investigated the effect of PEEP titrated by transpulmonary pressure (Ptp) on oxygenation and respiratory mechanics in ARDS patients with IAH compared with PEEP titrated by ARDSnet protocol. METHODS: ARDS patients admitted to the intensive care unit (ICU) of the Zhongda Hospital were enrolled. Patients were ventilated with volume control mode with tidal volume of 6 ml/kg under two different PEEP levels titrated by Ptp method and ARDSnet protocol. Respiratory mechanics, gas exchange and haemodynamics were measured after 30 minutes of ventilation in each round. IAH was defined as intra-abdominal pressure of 12 mmHg or more. RESULTS: Seven ARDS patients with IAH and 8 ARDS patients without IAH were enrolled. PEEP titrated by Ptp were significant higher than PEEP titrated by ARDSnet protocol in both ARDS patients with IAH ((17.3 ± 2.6) cmH2O vs. (6.3 ± 1.6) cmH2O and without IAH ((9.5 ± 2.1) cmH2O vs. (7.8 ± 1.9) cmH2O). Arterial pressure of O2/fraction of inspired oxygen (PaO2/FiO2) was much higher under PEEP titrated by Ptp when compared with PEEP titrated by ARDSnet protocol in ARDS patients with IAH ((27.2 ± 4.0) cmHg vs. (20.9 ± 5.0) cmHg. But no significant difference of PaO2/FiO2 between the two methods was found in ARDS patients without IAH. In ARDS patients with IAH, static compliance of lung and respiratory system were higher under PEEP titrated by Ptp than by ARDSnet protocol. In ARDS patients with IAH, central venous pressure (CVP) was higher during PEEP titrated by Ptp than by ARDSnet protocol. CONCLUSION: Positive end expiratory pressure titrated by transpulmonary pressure was higher than PEEP titrated by ARDSnet protocol and improved oxygenation and respiratory mechanics in ARDS patients with IAH.

[The value of nitrogen washout/washin method in assessing alveolar recruitment volume in acute lung injury patients].

OBJECTIVE: To evaluate the precision and feasibility of nitrogen washout/washin method in assessing lung recruitment of acute lung injury (ALI) patients. METHODS: Fifteen ALI patients underwent mechanical ventilation were involved. Two positive end-expiratory pressure (PEEP) levels (high and low) were adjusted according to ARDSnet recommendations or measurement of transpulmonary pressure, each for 30 minutes. Tidal volume (Vt), plateau of airway pressure (Pplat), other respiratory mechanics, gas-exchange and hemodynamics were measured. End expiration lung volume (EELV) was measured at different PEEP levels through nitrogen washout/washin method, and formula (EELVhighPEEP-EELVlowPEEP)-VtlowPEEP/(PplatlowPEEP-PEEPlowPEEP)×(PEEPhigh-PEEPlow) was used as recruitment (Rec-N2). Alveolar recruitment was measured using pressure-volume (P-V) curves (Rec-mes). Correlation and consistency of Rec-N2 and Rec-mes were compared by correlation analysis and Bland-Altman technique. RESULTS: PEEP titrated by ARDSnet recommendations or transpulmonary pressure were (7 ± 2) cm H2O (1 cm H2O = 0.098 kPa) vs (14 ± 5) cm H2O (P = 0.008); and there were significant differences in peak pressure (23 ± 5) cm H2O vs (28 ± 6) cm H2O, plateau of airway pressure (17 ± 4)cm H2O vs (22 ± 6) cm H2O, esophageal pressure, transpulmonary pressure and other respiratory mechanics between the two PEEP levels (P < 0.05). The P-V curve technique gave Rec-mes a value of 100 (-25 ∼ 185)ml. The nitrogen washout/washin technique gave Rec-N2 a value of 180 (-19 ∼ 255) ml, which showed a good correlation with a bias of 46 (8 ∼ 80) ml (R(2) = 0.755, P < 0.0001). CONCLUSION: Nitrogen washout/washin technique can be used to determine lung recruitment volume of ALI patients.

Computer-driven automated weaning reduces weaning duration in difficult-to-wean patients.

BACKGROUND: Weaning difficulties occur in 31% of total intubated patients, and result in prolonged weaning duration. A computer-driven automated weaning system can perform a spontaneous breathing trial (SBT) automatically and display a message when the trial is successfully passed. Such a system might have a beneficial effect on difficult-to-wean patients. The aim of this study was to examine whether the computer-driven automated weaning system can accelerate discontinuation of mechanical ventilation and improve outcomes in difficult-to-wean patients. METHODS: This randomized controlled study included 39 difficult-to-wean patients who failed their first spontaneous breathing trial. Before initiating weaning, eligible patients were randomly allocated to wean by computer-driven automated weaning system (CDW group, n = 19) or a physician-controlled local protocol (PW group, n = 20). Weaning duration, defined as the time from inclusion until first extubation, was the primary endpoint. Secondary endpoints were total duration of mechanical ventilation, the length of intensive care unit (ICU) stay, the number of reintubations, the mortality rate in the ICU, the number of noninvasive ventilations, the number of complications in the ICU, and the number of ventilator-associated pneumonia cases. RESULTS: The weaning duration was reduced with the computer-driven weaning as compared with the usual protocol (median 29.0 hours vs. 45.5 hours, P = 0.044). Total duration of mechanical ventilation and duration of the ICU stay did not differ between the CDW and PW groups. There was no difference in the number of reintubations between the CDW and PW groups (3 and 4 patients, P = 0.732). The study groups showed comparable numbers of tracheostomy, self-extubations, ventilator-associated pneumonia, and non-invasive ventilation. Mortality in the ICU was similar in the CDW and the PW groups (21.1% vs. 20.0%, P = 0.935). CONCLUSION: The computer-driven automated weaning system can reduce weaning duration in difficult-to-wean patients as compared with a physician-controlled weaning protocol.

[The effect of stress dose glucocorticoid on patients with acute respiratory distress syndrome combined with critical illness-related corticosteroid insufficiency].

OBJECTIVE: To investigate the effect of stress dose glucocorticoid on patients with acute respiratory distress syndrome (ARDS) combined with critical illness-related corticosteroid insufficiency (CIRCI). METHODS: All early ARDS patients combined with CIRCI were screened by an adrenal corticotrophic hormone (ACTH) test and randomly divided into treatment group (hydrocortisone 100 mg intravenous, 3 times/day, consecutively for 7 days, n = 12) and control group (equivalent normal saline, n = 14). General clinical data, changes of arterial blood gas, hemodynamics and respiratory mechanics were observed and recorded at admission and at 7 days after treatment. Ventilator-free and shock-free days, ICU stay within 28 days after admission were recorded and 28-day mortality was used as judge prognosis index. RESULTS: CIRCI rate in 45 early ARDS patients was 57.8% (26 patients), and the shock rate was markedly higher in ARDS patients with CIRCI than patients without CIRCI (46.2% vs 5/19). There were no significant differences in baseline parameters, oxygenation and illness severity between the treatment and control groups, except for markedly lower lactic level in the treatment group [2.7(1.2, 3.9) mmol/L vs 4.6(2.5, 6.3) mmol/L, P < 0.05]. After 7 days of treatment, PaO2/FiO2 markedly increased, while heart rate obviously decreased in the both groups. Compared with the control group, survival time of patients was significantly longer and shock rate of the patients was markedly lower in treatment group within 28 days (5/12 vs 10/14, P < 0.05). The 28-day mortality, which were adjusted by baseline arterial lactic, was lower in the treatment group (2.6/12) than in the control group (5.8/14) while with no significant difference (P > 0.05). There was no significant difference in complication incidence between the two groups. CONCLUSION: Stress dose glucocorticoid could reduce shock incidence and prolong survival time, and has a tendency of lower 28-day mortality in early ARDS patients combined with CIRCI.

[Effect of Xuebijing injection treatment on acute respiratory distress syndrome: a multicenter prospective randomized control clinical trial].

OBJECTIVE: To assess the therapeutic effect of Xuebijing injection on adult patients with acute respiratory distress syndrome (ARDS). METHODS: A multicenter prospective randomized control study was conducted at 10 intensive care units in Jiangsu province. A total of 172 early ARDS patients were randomly divided into Xuebijing treatment and control groups. All patients received routine therapy of ARDS while additional Xuebijing injection 100 ml was administered in the treatment group intravenously for 7 days. Lung injury score, acute physiology and chronic health evaluation II (APACHE II) score, multiple organ dysfunction score (MODS) and PaO2/FiO2 of the patients was recorded before and after treatment. Mortality at 28 days and the duration of mechanical ventilation were compared between two groups. RESULTS: Ninety-one patients were assigned to receive Xuebijing injection and 81 patients as control; Mortality at Days 28 and 90, the duration of mechanical ventilation and ventilation free days showed no difference between two groups (P > 0.05). PaO2/FiO2 improved after randomization versus pre-treatment in all patients. There was no significant difference between two groups. Murray scores were not significantly different between two groups. In a subgroup analysis of patients with pulmonary infection, pulmonary contusion and extra-pulmonary cause, two groups had no difference in mortality at Day 28, mortality at Day 90, the duration of mechanical ventilation, ventilation free days and days of ICU stay (P > 0.05). CONCLUSION: The treatment of Xuebijing injection early in course of ARDS does not improve the mortality of ARDS patients. But it may improve lung function and oxygenation. Further studies are warranted.

[Use of extracorporeal membrane oxygenation in adults with acute respiratory distress syndrome: a meta-analysis].

OBJECTIVE: To evaluate the effects of extracorporeal membrane oxygenation (ECMO) on mortality in adult patients with acute respiratory distress syndrome (ARDS). METHODS: Literature concerning randomized controlled trials (RCTs), case-control studies and prospective cohort studies from January 1966 to July 2011 on ECMO for the treatment of ARDS patients was retrieved by electronic and manual search. Meta-analysis of the use of ECMO in the treatment of ARDS patients was conducted using the methods recommended by the Cochrane Collaboration's software RevMan 5.0. RESULTS: Three papers reporting RCTs and 6 papers concerning observational cohort studies of using ECMO in patients with severe ARDS were enrolled for analysis. Meta-analysis of the 3 RCTs (310 patients, 159 of them treated with ECMO) revealed ECMO did not decrease the mortality of ARDS patients [odds ratio (OR)=0.75, 95% confidence interval (95%CI) 0.45-1.24, P = 0.27]. Meta-analysis of the all 9 studies (1058 patients, 386 of them treated with ECMO) revealed ECMO increased the mortality of ARDS patients (OR=1.58, 95%CI 0.94-2.67, P = 0.08). CONCLUSION: There is no evidence to prove that ECMO is beneficial in adult patients with ARDS, therefore further investigation with a large sample of high quality RCT is warranted.

[Assessment of central venous-to-arterial CO(2) difference during early goal-directed therapy in patients with septic shock].

OBJECTIVE: To detect the changes of central venous-to-arterial carbon dioxide difference (P(cv-a)CO(2)) during early goal-directed therapy (EGDT) in patients with septic shock and evaluate its' value in predicting adequate resuscitation and prognosis. METHODS: From April 2009 to October 2010, 26 septic shock patients were enrolled in the study. EGDT was performed in all the patients immediately after enrollment. According to the whether they achieved early goal with in the 6 hour or not, patients were separated to EGDT achievement and un-achievement groups. At the onset and after the 6 hours EGDT, mean arterial pressure (MAP), cardiac index (CI), central venous oxygen saturation (ScvO(2)), oxygen delivery (DO(2)), oxygen consumption (VO(2)), oxygen extraction ratio (O(2) ext), lactate, P(cv-a)CO(2) were recorded. The Acute Physiology and Chronic Health Evaluation II (APACHE II) score and 28 day mortality were compared between 2 groups. RESULTS: There were no significant difference of age and sex between the 15 patients who achieved early goals and 11 patients who did not. EGDT un-achievement patients had higher APACHE II score (21 ± 5) and 28 day mortality (9/11) when compared with EGDT achievement patients (t = 2.985, χ(2) = 4.547, P < 0.05). In EGDT un-achievement group, MAP, CI, DO(2), VO(2), O(2)ext, ScvO(2), Lac, P(cv-a)CO(2) were comparable between the onset and 6 hours after EGDT. However, in EGDT achievement group, MAP ((90 ± 9) mmHg (1 mmHg = 0.133 kPa)), CI ((4.0 ± 1.8) L×min(-1)×m(-2)), DO(2) ((596 ± 274) ml×min(-1)×m(-2)), ScvO(2) (76.9% ± 4.1%) increased, and P(cv-a)CO(2) ((4.2 ± 2.7) mmHg) decreased significantly after 6 hours of EGDT (t values were -3.393, -2.985, -2.103 and -3.195 respectively, all P < 0.05). The changes of P(cv-a)CO(2) between the onset and 6 hours after EGDT, demonstrated high value for predictability of outcome, according to the area under the ROC curve (AUC) was 0.839 (P = 0.004). As a predictor for death, increasing of P(cv-a)CO(2) after 6 hours of EGDT has a sensibility of 100% and specificity of 60%. CONCLUSIONS: Increasing of P(cv-a)CO(2) after EGDT purports inadequate tissue perfusion in patients with septic shock. Changes of P(cv-a)CO(2) during EGDT demonstrated a useful tool to evaluate adequate resuscitation and prognosis.

[The clinical application of pulmonary vascular permeability index on differential diagnosis of acute pulmonary edema].

OBJECTIVE: To assess the value of pulmonary vascular permeability index in differentiating acute lung injury (ALI) from cardiac pulmonary edema. METHODS: Critically ill patients with acute pulmonary edema were included from May, 2004 to September, 2008. Patients were divided into two groups, the ALI group and the cardiac pulmonary edema group (C group). Pulmonary vascular permeability index (PVPI), intrathoracic blood volume (ITBVI) were determined by pulse indicator continuous cardiac output (PiCCO) system. RESULTS: (1) Thirty-four patients were enrolled, 22 cases in ALI group and 12 cases in C group. (2) The PVPI in patients of ALI group (2.7 ± 1.4) was higher than that of C group (1.9 ± 0.6; P < 0.05). EVLWI and ITBVI did not have the significant difference between the two groups (P > 0.05). (3) PVPI was positively correlated with EVLWI (r = 0.762), negatively correlated with PaO2/FiO2 (r = -0.478). (4) ARDS was diagnosed in 13 cases, including 8 pulmonary cause (ARDSp) and 5 extra-pulmonary cause (ARDSexp). PVPI, EVLW/ITBV and EVLWI of patients with ARDSexp were obviously higher than those with ARDSp. CONCLUSIONS: PVPI may be useful for differentiating the types of pulmonary edema in the critically ill.