Objective To compare the effects of high and low positive end-expiratory pressure( PEEP) levels on mortality and risk of barotrauma in patients with acute respiratory distress syndrome ( ARDS) . Methods Randomized controlled trials ( RCTs) were recruited from PubMed( 1966-2008. 9) ,EMBASE( 1980-2008. 9) , Cochrane Database ( Issue 2, 2008) , Chinese Cochrane Centre Database and CBMdisc ( 1978-2008. 9) . Related published and unpublished data and attached references were hand searched. All RCTs about ventilation with PEEP for patients with ARDS were included, then a systematic review were performed. Results Five eligible trials were enrolled in the systematic review. According to ventilation strategy, all trials were divided into subgroup A( low tidal volumes + high PEEP vs traditional tidal volumes + low PEEP) and subgroup B( low tidal volumes + high PEEP vs low tidal volumes + low PEEP) . In subgroup A, high PEEP was associated with a lower mortality[ RR 0. 59, 95%CI( 0. 43, 0. 82) ] and a lower prevalence of barotraumas [ RR 0. 24, 95% CI( 0. 09, 0. 70) ] in patients with ARDS. In subgroup B, the difference in mortality[ RR 0. 97, 95%CI( 0. 83, 1. 13) ] and barotraumas[ RR 1. 13, 95% CI( 0. 78, 1. 63) ]were not significant. Conclusions As compared with conventional ventilation, low tidal volumes and high PEEP ventilation strategy is associated with improved survival and a lower prevalence of barotraumas in patients with ARDS. It is necessary to further confirm the role of sole high PEEP in the ventilation strategy.
Objective To investigate the serumlevel of endothelin-1 ( ET-1) in patients with acute lung injury/acute respiratory distress syndrome ( ALI/ARDS) and its clinical significance. Methods Thirty-one ALI/ARDS patients received mechanical ventilation in ICUand 25 normal subjects were recruited in the study. The patients who died in two weeks fell in death group, and the patients who did not died in two weeks fell in survival group. The serum level of ET-1 measured by EIA method were compared between thepatients with different severity of lung injury [ evaluated by American-European Consensus Conference on ARDS ( AECC) criteria and lung injury score( LIS) ] , and between the patients with different prognosis ( death or survival ) . The correlation was analyzed between the level of ET-1 and clinical parameters.Results The ET-1 level was higher in the ALI/ARDS patients than that in the control subjects [ ( 6. 18 ±4. 48) ng/L vs. ( 2. 68 ±1. 34) ng/L, P lt;0. 05] . There was no significant difference in the patients with different severity [ ALI vs. ARDS, ( 5. 43 ±4. 39) ng/L vs. ( 7. 01 ±4. 51) ng/L, P gt; 0. 05; LIS≤2. 5 vs.LISgt;2. 5, ( 5. 93 ±5. 21) ng/L vs. ( 6. 68 ±2. 76) ng/L, P gt; 0. 05] . The ET-1 level in the death group continued to increase, and higher than that in the survival group on the 5th day [ ( 7. 96 ±3. 30) ng/L vs.( 4. 36 ±3. 29) ng/L, P lt; 0. 05] . The ET-1 level was positively correlated with SIRS, SAPSⅡ and APACHEⅡ ( r = 0. 359, 0. 369 and 0. 426, respectively, P lt; 0. 05 ) , and negatively correlated with PaO2 /FiO2 and AaDO2 ( r = - 0. 286 and - 0. 300, respectively, P lt;0. 05) . Conclusion The measurementof serum ET-1 can help to evaluate the severity and prognosis of ALI/ARDS patients.
Objective To investigate the effect of microRNA-22-3p (miR-22-3p) on the inflammation of human pulmonary microvascular endothelial cells (HPMEC) induced by lipopolysaccharide (LPS) by regulating the HMGB1/NLRP3 pathway. Methods miRNA microarray was taken from peripheral blood of patients with acute respiratory distress syndrome (ARDS) caused by abdominal infection and healthy controls for analysis, and the target miRNA was selected. miRNA mimics, inhibitor and their negative controls were transfected in HPMECs which were stimulated with LPS. Real time fluorescent quantitative polymerase chain reaction (RT-qPCR) and Western blot were used to detect the mRNA and protein levels of high mobility group box-1 protein (HMGB1) and nucleotide binding oligomerization segment like receptor family 3 (NLRP3). RT-qPCR and enzyme linked immunosorbent assay were used to detect the levels of inflammatory factors in the cells and supernatant. Results miRNA microarray showed that miR-22-3p was down-regulated in the plasma of patients with ARDS. Compared with the negative control group, after miR-22-3p over-expression, the protein and mRNA levels of HMGB1 and NLRP3 decreased significantly. Similarly, the level of cleaved-caspase-1 decreased significantly. At the same time, interleukin (IL)-6, IL-8 and IL-1β mRNA level in cytoplasm and supernatant were down-regulated by miR-22-3p mimics. After transfected with miR-22-3p inhibitor, the expression levels of HMGB1, NLRP3, caspase-1 protein and inflammatory factors were significantly up-regulated. Conclusion miR-22-3p is significantly downregulated in peripheral blood of ARDS patients caused by abdominal infection, which can inhibit the expression of HMGB1 and NLRP3 and its downstream inflammatory response in HPMECs.
With the growth of offshore activities, the incidence rates of seawater drowning (SWD) induced acute lung injury (ALI) and acute respiratory distress syndrome (ARDS) increase significantly higher than before. Pulmonary interstitial edema, alveolar septum fracture, red blood cells, and inflammatory cells infiltration can be seen under light microscope in the pathologic changes of lungs. The major clinical manifestations are continual hyoxemia and acidosis, which lead to a severe condition, a high death rate, and a poor treatment effect. Bone marrow mesenchymal stem cells are capable of self-renewal, multilineage differentiation and injured lung-homing, which are induced to differentiate into alveolar epithelial cells and pulmonary vascular endothelial cells for tissues repairing. This may be a new way to treat SWD-ALI and SW-ARDS.
ObjectiveTo investigate effects of high expression of miR-499a-5p on lung injury in rats with acute respiratory distress syndrome (ARDS) by targeting matrix metallopeptidase-16 (MMP-16).MethodsThe experiment set up sham operation group, model group, miR-499a-5p mimic group, MMP-16 group, miR-499a-5p mimic+MMP-16 group, D-ribofuranosylbenzimidazole (DRB, Nrf2 signaling pathway inhibitor) group, miR-499a-5p mimic+DRB group. A rat model of ARDS was constructed by cecal puncture. One hour before surgery, the transfection complex (50 μL) was injected into the trachea with a micro-syringe. DRB (5 mg/kg) was intraperitoneally injected 30 min before surgery. The expression levels of miR-499a-5p and MMP-16 in lung tissue were detected by RT-qPCR; Alveolar type Ⅱ epithelial cells of model group rats were separated and MMP-16 3 'UTR WT and MUT luciferase report plasmid were transfected into alveolar type Ⅱ epithelial cells with miR-499 respectively to verify the targeting relationship between miR-499 and MMP-16; the targeted relationship was verified by the dual luciferase reporter gene; lung injury was observed by hematoxylin-eosin staining; The level of inflammatory factors in bronchoalveolar lavage fluid (BALF) and the level of oxidative stress in lung tissue were detected by enzyme-linked immunosorbent assay; The expression levels of NAD(P)H: quinone oxidoreductase 1 (NQO1), heme oxygenase (HO)-1, and nuclear factor-erythroid 2-related factor 2 (Nrf2) proteins in lung tissues were analyzed by Western blotting.ResultsmiR-499a-5p was down-regulated in the lungs of ARDS model rats (P<0.01), while MMP-16 was highly expressed (P<0.01); miR-499a-5p and MMP-16 3'UTR regions had binding sites, and miR-499a-5p directly targeted negative regulation of MMP-16 expression (P<0.01); overexpression of miR-499a-5p significantly reduced the right lung wet-to-dry weight ratio in the ARDS rats (P<0.05), reduced lung tissue damage (P<0.01), and reduced tumor necrosis factor α, interleukin (IL)-1β and IL-6 levels in BALF (P<0.01), decreased malondialdehyde and myeloperoxidase levels in lung tissue, increased total anti-oxidant capacity (P<0.01), and up-regulated NQO1, HO-1, Nrf2 protein expression in lung tissue (P<0.01). However, this phenomenon was significantly reversed after the addition of MMP-16 and DRB.ConclusionOverexpression of miR-499a-5p attenuates lung injury in rats with ARDS by targeting negative regulation of MMP-16 via activating the Nrf2 signaling pathway.
Objective To evaluate the efficiency and associated factors of noninvasive positive pressure ventilation( NPPV) in the treatment of acute lung injury( ALI) and acute respiratory distress syndrome( ARDS) .Methods Twenty-eight patients who fulfilled the criteria for ALI/ARDS were enrolled in the study. The patients were randomized to receive either noninvasive positive pressure ventilation( NPPV group) or oxygen therapy through a Venturi mask( control group) . All patients were closely observed and evaluated during observation period in order to determine if the patients meet the preset intubation criteria and the associated risk factors. Results The success rate in avoiding intubation in the NPPV group was 66. 7%( 10/15) , which was significantly lower than that in the control group ( 33. 3% vs. 86. 4% , P = 0. 009) . However, there was no significant difference in the mortality between two groups( 7. 7% vs.27. 3% , P =0. 300) . The incidence rates of pulmonary bacteria infection and multiple organ damage were significantly lower in the NPPV success subgroup as compared with the NPPV failure group( 2 /10 vs. 4/5, P =0. 01;1 /10 vs. 3/5, P = 0. 03) . Correlation analysis showed that failure of NPPV was significantly associated with pulmonary bacterial infection and multiple organ damage( r=0. 58, P lt;0. 05; r =0. 53, P lt;0. 05) . Logistic stepwise regression analysis showed that pulmonary bacterial infection was an independent risk factor associated with failure of NPPV( r2 =0. 33, P =0. 024) . In the success subgroup, respiratory rate significantly decreased( 29 ±4 breaths /min vs. 33 ±5 breaths /min, P lt; 0. 05) and PaO2 /FiO2 significantly increased ( 191 ±63 mmHg vs. 147 ±55 mmHg, P lt;0. 05) at the time of 24 hours after NPPV treatment as compared with baseline. There were no significant change after NPPV treatment in heart rate, APACHEⅡ score, pH and PaCO2 ( all P gt;0. 05) . On the other hand in the failure subgroup, after 24 hours NPPV treatment, respiratory rate significantly increased( 40 ±3 breaths /min vs. 33 ±3 breaths /min, P lt;0. 05) and PaO2 /FiO2 showed a tendency to decline( 98 ±16 mmHg vs. 123 ±34 mmHg, P gt; 0. 05) . Conclusions In selected patients, NPPV is an effective and safe intervention for ALI/ARDS with improvement of pulmonary oxygenation and decrease of intubation rate. The results of current study support the use of NPPV in ALI/ARDS as the firstline choice of early intervention with mechanical ventilation.
Objective To explore the value of pulmonary ultrasound in the evaluation of pulmonary edema and the guidance of pulmonary therapy in patients with acute respiratory distress syndrome (ARDS). Methods Sixty patients with ARDS admitted to the Department of Critical Medicine of Shanghai Seventh People’s Hospital were randomly divided into a lung ultrasound group and a control group, with 30 patients in each group. The gender, age and etiology of patients were collected, and the relevant data were recorded at the time of admission and on the 7th day, including Acute Physiology and Chronic Health Evaluation Ⅱ (APACHEⅡ) score, Sequential Organ Failure Assessment score (SOFA), white blood cell count (WBC), C-reactive protein (CRP), procalcitonin (PCT), extravascular pulmonary water index, oxygenation index, and mechanical ventilation treatment time. Pulmonary ultrasound score was collected in the pulmonary ultrasound group. The 7-day improvement rate, intensive care unit (ICU) hospitalization time and 28 day mortality rate of the two groups were also collected. The value of pulmonary ultrasound in evaluating the severity, treatment process and prognosis of patients, and the correlation between pulmonary ultrasound score and extravascular pulmonary water index were studied. Results There was no significant difference in APACHEⅡ score, SOFA score, oxygenation index, extravascular pulmonary water index, WBC, CRP or PCT between the two groups before and after treatment (all P>0.05). After 7 days of treatment, the two groups improved, and the pulmonary ultrasound group improved more significantly with more shorter mechanical ventilation time, higher 7-day improvement rate, shorter ICU hospitalization time, and lower 28-day mortality rate (all P<0.05). The extravascular pulmonary water index was positively correlated with APACHEⅡ score and SOFA score, and negatively correlated with oxygenation index. The pulmonary ultrasound score was positively correlated with APACHEⅡ, and SOFA score and extravascular pulmonary water index, and negatively correlated with oxygenation index. Conclusions Pulmonary ultrasound can effectively evaluate the severity of ARDS patients, guide the individualized treatment, and predict the prognosis. It can be used as a routine monitoring method for patients with ARDS.
Objective To evaluate the efficacy of lung-protective strategies of ventilation (LPSV) in acute respiratory distress syndrome (ARDS) patients after thoracic operation. Methods-Thirtyseven ARDS patients without preoperative complications who had underwent thoracic surgery successfully were divided into the conventional mechanical ventilation group (CMV group, n=20) and lungprotective strategies of ventilation group (LPSV group，n=17). Results of arterial blood gas, index of oxygenation (PaO2/FiO2), airway plateau pressure (Pplat), inspiration peak pressure (PIP), PEEP, after ventilation treatment 24 h and mechanical ventilation time， pulmonary barotrauma and so on were observed. Results The mechanical ventilation time， pulmonary barotrauma and mortality of the LPSV group were 7.3d, 5.9％ and 29.4％ respectively, which were significantly better than those in the CMV group(17.6d，15.0％ and 60.0％, Plt;0.05). peak inflation pressure (PIP)，Pplat(plat pressure) in the LPSV group were significantly lower than those in the CMV group (Plt;0.05). However, there were no significant differences including arterial oxygen saturation (SaO2),pH, partial pressure of carbon dioxide in artery (PaCO2) and PaO2/FiO2 in two groups. Conclusion LPSV is more effective for the patients in the ARDS patients after thoracic operation compared to CMV, which can markedly reduce the ventilatorinduced lung injuryand (VILI) and mortality.
Objective To explore clinical significance of interleukin-8 (IL-8), clarada protein 16 (CC16), and intercellular adhesion molecule-1 (ICAM-1) in exhaled breath condensate (EBC) and serum samples collected from patients with acute respiratory distress syndrome (ARDS). Methods A total of 45 ARDS patients were assigned into a mild ARDS group (n=20), a moderate ARDS group (n=15) and a severe ARDS group (n=10) based on the Berlin definition. During the same study period, 45 healthy subjects were recruited as control. Serum and EBC levels of IL-8, CC16 and ICAM-1 were detected on the first and fifth day of admission. Results Compared with the control group, serum and EBC IL-8, CC16 and ICAM-1 were significantly higher in the ARDS groups (P<0.05). Serum and EBC IL-8 levels increased with the severity of ARDS, whereas no significant difference was detected between the three groups (P>0.05). Compared with the mild group and the moderate group, serum and EBC CC16 levels were significantly higher in the severe ARDS group. At the first day after admission, serum ICAM-1 was higher in the severe and moderate ARDS groups than that in the mild ARDS group (P<0.05). Meanwhile, EBC ICAM-1 was significantly different between the three groups (P<0.05). At the fifth day after admission, different EBC ICAM-1 was identified between the severe ARDS group and the other two groups (P<0.05). Regardless of ARDS severity, there were no significant differences in serum and EBC IL-8 and CC16 levels at the first and fifth days after admission (P>0.05). However, serum and EBC ICAM-1 at the first and fifth days showed significant difference (except in the mild ARDS group) (P<0.05). The levels of ICAM-1 in serum and EBC of death group were significantly higher than those of survival group (P<0.05). Conclusion Serum and EBC IL-8, CC16 and ICAM-1 are of significance in diagnosis and prognosis evaluation of ARDS.
Objective To evaluate the effects of neuromuscular blocking agents( NMBAs) in acute respiratory distress syndrome( ARDS) . Methods Randomized controlled trials( RCTs) and non-RCTs were recruited fromPubMed( 1966. 1-2012. 3) , EMBASE( all the years) , Cochrane Library( all the years) and CNKI Database( 1979-2012) . Related published studies and attached references were hand searched. All the RCTs and non-RCTs ( including prospective and retrospective studies) about NMBAs for the patients with ARDS were included. Then a meta-analysis and statistic descriptions for RCTs( using RevMan5. 0 software) and non-RCTs were performed. Jadad and NEWCASTLE-OTTAWA QUALITY ASSESSMENT SCALE were used to assess the methodological quality of the included RCTs and non-RCTs. Results Three eligible RCTs and four non-RCTs were enrolled. The quality of the included trials was high. Pooled analysis for three RCTs showed that NMBAs significantly reduced 28-day mortality [ OR 0. 58, 95% CI( 0. 39, 0. 86) , P = 0. 007] and increased ventilator-free days within 28 days [ WMD 1. 91 d, 95% CI( 0. 28,3. 55) , P =0. 02] in ARDS compared with the control group. Conclusion The present meta-analysis indicates that NMBAs reduce the 28-day mortality and increase ventilator-free days within 28 days in ARDS.