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.
ObjectiveTo explore the value of procalcitonin-to-albumin (PAR) in patients with acute respiratory distress syndrome (ARDS).MethodsA retrospective study was carried on patients diagnosed with ARDS from December 2016 to March 2018. The receiver-operating characteristics (ROC) curve was used to identify the cutoff value of PAR. The association of PAR and 28-day mortality was evaluated using univariate and multivariable Cox regression.ResultsIn the final analysis, there were a total of 255 patients included. Of whom 164 (64.3%) was male, 91 (35.7%) was female and the mean age was 52.1±14.5 years old. The 28-day mortality of all the patients was 32.9% (n=84). ROC curve revealed that the cutoff value of PAR was 0.039 (specificity: 0.714, sensitivity: 0.702) and area under the curve was 0.793 (95%CI: 0.735 - 0.850, P<0.001). The following variables were considered for multivariable adjustment: age, body mass index, pneumonia, aspiration, sepsis, surgery, PaO2/FiO2, red blood cell counts and PAR (P<0.01 in univariate analysis). After multivariable analysis, only age (HR: 1.033, 95%CI: 1.009 - 1.059, P=0.008), PaO2/FiO2 (HR: 0.992, 95%CI: 0.985 - 1.000, P=0.044) and PAR (HR: 4.899, 95%CI: 2.148 - 11.174, P<0.001) remained independently associated with 28-day mortality (P<0.05).ConclusionHigh PAR predicts a poor outcome in ARDS patients, therefore it appears to be a prognostic biomarker of outcomes in patients with ARDS.
Objective To investigate the expression of granulysin ( GNLY) in lung of rats with acute lung injury ( ALI) stimulated with lipopolysaccharide ( LPS) . Methods Thirty-six healthy adult Wistar rats were randomly divided into a normal control group and a LPS group, with 18 rats in each group. LPS ( 4 mg/kg) was given intraperitoneally in the LPS group to induce ALI. The same amount of normal saline was given in the control group. The rats were randomly assigned to three subgroups ( n = 6) to be sacrificed respectively at 6, 18, and 30 hours after intraperitoneal injection. Wet/dry lung weight ratio ( W/D) and pathological changes of the lung were observed. The expression of GNLY in lung tissue was assayed by immunohistochemistry. Results In the LPS group, the W/D ratio was higher than that of the control group at each time point ( P lt;0. 05) and there were a large number of inflammatory cells infiltration and edema in interstitial spaces which suggested ALI. Compared with the control group, the expression of GNLY in the LPS group was significantly increased at all time points ( P lt;0. 05) . Conclusion GNLY may participate in ALI inflammatory process, which might play a role in preventing infection induced ALI.
Objective To investigate the protective mechanism of ulinastatin（UTI） in pulmonary microvascular endothelial cells （PMVECs） attacked by serum from the patients with severe sepsis. Methods PMVECs were cultured in vitro and randomly divided into 4 groups，ie. a normal group （culture medium with 10% fetal bovine serum，group N），a health group （culture medium with 10% healthy human serum，group H），a patient group （culture medium with 10% human septic shock serum，group S），and a ulinastatin group （culture medium with 1000 U/mL UTI and 10% human septic shock serum，group U）. The proliferation activity of PMVECs was measured by MTT expressed by optical density （OD）. The concentration of TNF-α in supernatant of culture medium was examined by ELISA at 0，1，2，4，6 hours. The expression of NF-κB was examined by immunohistochemistry at 1 hour. Results Compared with group N，the cell proliferation activity of group S decreased significantly，and the cell proliferation activity of group U decreased slightly at each time poi nt. Compared with group N，the cell proliferation activity of group S and group U at 1，4，6 hours were significant different （Plt;0.05 ）. Compared with group S，the cell proliferation activity of group U at 1，2，6 hours increased significantly （Plt;0.05）. Obviously positive expression of NF-κB in PMVECs could be seen in group S，a little positive expression in group S，and no expression in group N and group H. Compared with group N，the TNF-α levels of group S and group U increased significantly at each time point with significant differences （Plt;0.01）. Compared with group S，the TNF-α levels were significantly reduced at each time point in group U （Plt;0.01）. Conclusions UTI can reduce the release of TNF-α by inhibiting NF-κB activation，thus reduce PMVECs injury attacked by serum from severe sepsis patients.
Objective To establish a rabbit model of ventilator-induced lung injury. Methods Fourty healthy New Zealand rabbits were randomly divided into 3 groups: ie. a routine 8 mL/kg tidal volume group( VT8 group) , 25 mL/kg large tidal volume group( VT25 group) , and 40 mL/kg large tidal volume group( VT40 group) . VT25 and VT40 group were further divided into 2 hours and 4 hours ventilation subgroups. Arterial blood gas, lung mechanical force and hemodynamic parameters were monitored. Lungtissue was sampled for evaluate lung wet/dry ratio and lung injury by HE stain. Bronchoalveolar lavage fluid ( BALF) was collected for measurement of protein concentration, total and differential cell counts. Results Compared with VT8 group, lung injury score in both VT40 and VT25 groups were elevated significantly, ofwhich 4 hour VT40 subgroup was the highest. Lung pathology examination of VT40 group revealed apparent alveolar deformation, interstitial and alveolar space exudation, inflammatory cells infiltration, pulmonary consolidation and alveolar hemorrhage. Lung pathology examination of VT25 group showed pulmonary intervalthickening, inflammatory cells infiltration, while alveolar intravasation was mild. Blood gas analysis showed that PaO2 /FiO2 was deteriorated with time in VT25 and VT40 groups, and PaO2 /FiO2 at the 3 hours in VT40 group( lt; 300 mm Hg) had met the acute lung injury standard, while which in VVT25 group was above 300 mmHg. Lung wet/dry ratio, BALF protein concentration, total nucleated cell and neutrophilic leukocyte were elevated in both VT25 and VT40 groups, of which 4 hours VT40 group was the highest. Conclusion Using 4 hours ventilation at a tidal volume of 40 mL/kg can successfully establish the rabbit model of ventilator-induced lung injury.
Objective To explore the role of renin-angiotensin system( RAS) in acute lung injury( ALI) /acute respiratory dysfunction syndrome( ARDS) by using amouse cecal ligation and puncture ( CLP)model.Methods The ALI/ARDS animal models were assessed bymeasuring blood gas, wet/dry lung weight ratio( W/D) , and lung tissue histology 18 hours after CLP operation. After the ALI/ARDS models was successfully established, immunohistochemistry, western blotting and radioimmunity were used to investigate the changes of several key enzymes of RAS, such as ACE, ACE2 and Ang Ⅱ. In addition, two groups of animals received a separate intraperitoneal injection of angiotensin-converting enzyme ( ACE) inhibitor captopril or recombinant mouse ACE2 ( rmACE2) after CLP, then the changes of RAS in ALI/ARDS modelswere observed. Results The extensive lung injuries can be observed in the lung tissues from CLP-treated animals 18 hours after operation. The CLP-induced ALI/ARDS led to an increase in the wet/dry weight ratio of the lung tissues, and a decrease in the PaO2 /FiO2 [ ( 194. 3 ±23. 9) mm Hg vs ( 346. 7 ±20. 5) mm Hg,P lt;0. 01] . Immunohistochemistry and western blotting tests of the lung tissues from CLP-treated animals showed a decrease in the ACE2 protein level. However, in both the CLP and sham mice there were no significant differences between the two groups. CLP markedly increased Ang Ⅱ level in lungs and plasma of mice, and RAS drugs significantly impacted the Ang Ⅱ levels of mice. Compared with the CLP group,captopril or rmACE2 led to a decrease of the Ang Ⅱ level in mice [ Lung: ( 1. 58 ±0. 16) fmol /mg,( 1. 65 ±0. 21) fmol /mg vs ( 2. 38 ±0. 41) fmol /mg; Plasma: ( 178. 04 ±17. 87) fmol /mL, ( 153. 74 ±10. 24) fmol /mL vs ( 213. 38 ± 25. 44) fmol /mL] . Conclusions RAS activation is one of the characteristics of CLP-induced ALI/ARDS in mice models. ACE and ACE2 in RAS have a different role in the regulation of AngⅡ synthesis, while ACE has a positive effect in generating AngⅡ, and ACE2 shows a negative effect.
Objective To investigate the effects of antithrombin-Ⅲ ( AT-Ⅲ) on the inflammatory reaction in oleic acid-induced acute lung injury ( ALI) rats. Methods Sixtymale Sprague-Dawley rats were randomly divided into five groups, ie. a normal control group, an ALI group, an AT-Ⅲ treatment group, an AT-Ⅲ +heparin treatment group, and a heparin treatment group ( n =12) . The ALI rats were induced by injecting oleic acid ( 0. 2 mL/kg) intravenously. The lung histology was scored by modified Smithtechnique. The albumin permeability of pulmonary microvascular ( Palb) was measured by single nuclide tracer technique. The extravascular lung water ( EVLW) and wet/dry weight ratio ( W/D) of lung tissues were measured by gravity way. The activity of AT-Ⅲ in plasma was determined by the method of syntheticchromogenic substrate. Tumor necrosis factor α( TNF-α) , interleukin 6 ( IL-6) and von Willebrand factor ( vWF) levels in serum were determined using commercial enzyme-linked immunosorbent assay kits. The expressions of lung tissue extacellular signal-regulated kinases ( ERK) -1 /2, P38 mitogen-activated proteinkinase ( MAPK) and c-jun N-terminal kinases ( JNK) were determined by Western blot. Results The Smith scores, EVLW, Palb , plasma level of vWF, lung tissue levels of phospho-ERK1 /2 and phospho-P38 MAPK expressions in the ALI group were all significantly higher than those in the normal control group ( P lt; 0.05) , while not significant differentwith other three treatment groups. There were not significant differences in the activity of AT-Ⅲ in plasma and phospho-JNK expression among all five groups. The serum levels of TNF-αand IL-6 in the ALI group were significantly higher than those in the normal control group and three treatment groups. Conclusions AT-Ⅲ downregulates the levels of downstreamcytokines TNF-αand IL-6,but can not inhibite the activation of ERK1 /2 and P38 MAPK, and can not relieve endothelial permeability.The study do not demonstrate the lung protective effect of AT-Ⅲ in oleic acid-induced acute lung injury.
ObjectiveTo evaluate the effect of positive end-expiratory pressure (PEEP) on respiratory function and hemodynamics in acute lung injury (ALI) with intra-abdominal hypertension (IAH). MethodsSix pigs were anesthetized and received mechanical ventilation (MV). Volume controlled ventilation was set with tidal volumn(VT) of 8 mL/kg,respiratory rate(RR) of 16 bpm,inspired oxygen concentration (FiO2) of 0.40,and PEEP of 5 cm H2O. ALI was induced by repeated lung lavage with diluted hydrochloric acid (pH<2.5) until PaO2/FiO2 declined to 150 mm Hg or less to established ALI model. Intra-abdominal hypertension was induced by an nitrogen inflator to reach intra-abdominal pressure of 20 mm Hg. Respiratory parameters and hemodynamics were continuously recorded at different PEEP levels(5,10,15,and 20 cm H2O). Every level was maintained for one hour. ResultsPaO2/FiO2 in PEEP5,10,15 and 20 were 90±11,102±10,172±23 and 200±34 mm Hg respectively. PaO2/FiO2 in PEEP15 and 20 were significantly higher than those in PEEP5 and 10 (P<0.05). Chest wall compliance (Ccw) in PEEP5,15 and 20 were 26±3,76±15 and 85±14 mL/cm H2O respectively. Ccw in PEEP15 and 20 were significantly higher than those in PEEP5 (P<0.05). There was no significant difference in lung compliance (CL) in different PEEP levels (P>0.05). Plateau pressure(Pplat) in PEEP5,10,15 and 20 were 30±3,31±2,36±2 and 38±4 cm H2O respectively. Pplat in PEEP15 and 20 were significantly higher than those in PEEP5 and 10 (P<0.05). There was no significant difference in Pplat between PEEP15 and 20 (P>0.05). Heart rate (HR) in PEEP5,15 and 20 were 113±17,147±30,and 160±30 beat/min respectively. HR in PEEP15 and 20 were significantly higher than those in PEEP5 (P<0.05). There was no significant difference in HR between PEEP15 and 20 (P>0.05).Cardiac index (CI) in PEEP5 and 20 were 4.5±0.6 and 3.5±0.6 L·min-1·m-2 respectively. CI in PEEP20 was significantly lower than that in PEEP5 (P<0.05). There was no significant difference in CI in PEEP5,10 or 15(P>0.05). Central venous pressure(CVP) in PEEP5,15 and 20 were 12±2,17±2,and 18±3 mm Hg respectively. CVP in PEEP15 and 20 were significantly higher than those in PEEP5 (P<0.05). There was no significant difference in CVP between PEEP15 and 20 (P>0.05). There were no significant differences in MAP,SVRI,ITBVI,GEDI,PVPI,or EVLWI between different PEEP levels. ConclusionConcomitant ALI and IAH can induce great impairments in respiratory physiology. When PEEP is gradually increased,oxygenation and the respiratory function are improved without significant secondary hemodynamic disturbances.
Objective To investigate whether pulse pressure variation( ΔPP) reflect the effects of PEEP and fluid resuscitation ( FR) on hemodynamic effects. Methods Twenty critical patients with acute lung injury was ventilated with volume control ( VT =8 mL/kg, Ti/Te = 1∶2) , and PaCO2 was kept at 35 to 45 mm Hg. PEEP was setted as 5 cm H2O and 15 cmH2O in randomized order. Hemodynamic parameters including cardiac index, pulse pressure, central venous pressure, etc. were monitered by PiCCO system.Measurements were performed after the application of 5 cmH2O PEEP ( PEEP5 group) and 15 cm H2OPEEP ( PEEP15 group) respectively. When the PEEP-induced decrease in cardiac index ( CI) was gt; 10% ,measurements were also performed after fluid resuscitation. Results Compared with PEEP5 group, CI was decreased significantly in PEEP15 group( P lt;0. 05) , and ΔPP was increased significantly( P lt; 0. 05) . In 14 patients whose PEEP-induced decrease in CI was gt; 10% , fluid resuscitation increased CI from ( 3. 01 ±0. 57) L·min - 1·m- 2 to ( 3. 62 ±0. 68) L·min- 1 ·m- 2 ( P lt;0. 01) , and decreased ΔPP from ( 17 ±3) % to ( 10 ±2) % ( P lt;0. 01) . PEEP15 -induced decrease in CI was correlated negatively with ΔPP on PEEP5 ( r= - 0.91, P lt;0. 01) and with the PEEP15 -induced increase in ΔPP ( r = - 0. 79, P lt;0. 01) . FR-induced changes in CI correlated with ΔPP before FR ( r =0. 96, P lt; 0. 01) and with the FR-induced decrease in ΔPP ( r= - 0. 95, P lt; 0. 01) . Conclusions In ventilated patients with ALI, ΔPP may be a simple anduseful parameter in predicting and assessing the hemodynamic effects of PEEP and FR.
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.