Early Acute Respiratory Distress Syndrome Research Articles

Increased expression of neutrophil-related genes in patients with early sepsis-induced ARDS.

The early sequence of events leading to the development of the acute respiratory distress syndrome (ARDS) in patients with sepsis remains inadequately understood. The purpose of this study was to identify changes in gene expression early in the course of illness, when mechanisms of injury may provide the most relevant treatment and prognostic targets. We collected whole blood RNA in critically ill patients admitted from the Emergency Department to the intensive care unit within 24 h of admission at a tertiary care center. Whole genome expression was compared in patients with sepsis and ARDS to patients with sepsis alone. We selected genes with >1 log2 fold change and false discovery rate <0.25, determined their significance in the literature, and performed pathway analysis. Several genes were upregulated in 29 patients with sepsis with ARDS compared with 28 patients with sepsis alone. The most differentially expressed genes included key mediators of the initial neutrophil response to infection: olfactomedin 4, lipocalin 2, CD24, and bactericidal/permeability-increasing protein. These gene expression differences withstood adjustment for age, sex, study batch, white blood cell count, and presence of pneumonia or aspiration. Pathway analysis demonstrated overrepresentation of genes involved in known respiratory and infection pathways. These data indicate that several neutrophil-related pathways may be involved in the early pathogenesis of sepsis-related ARDS. In addition, identifiable gene expression differences occurring early in the course of sepsis-related ARDS may further elucidate understanding of the neutrophil-related mechanisms in progression to ARDS.

Double-blind, placebo-controlled pilot randomized trial of methylprednisolone infusion in pediatric acute respiratory distress syndrome.

Low-dose methylprednisolone therapy in adults with early acute respiratory distress syndrome reduces systemic inflammation, duration of mechanical ventilation, and ICU length of stay. We report a pilot randomized trial of glucocorticoid treatment in early pediatric acute respiratory distress syndrome. Double-blind, placebo-controlled randomized clinical trial. Le Bonheur Children's Hospital, Memphis, TN. Children (0-18 yr) with acute respiratory distress syndrome undergoing mechanical ventilation. Patients were randomly assigned to steroid or placebo groups within 72 hours of intubation. IV methylprednisolone administered as loading dose (2 mg/kg) and continuous infusions (1 mg/kg/d) on days 1-7 and then tapered over days 8-14. Both groups were ventilated according to the Acute Respiratory Distress Syndrome Network protocol modified for children. Daily surveillance was performed for adverse effects. Thirty-five patients were randomized to the steroid (n = 17, no death) and placebo groups (n = 18, two deaths). No differences occurred in length of mechanical ventilation, ICU stay, hospital stay, or mortality between the two groups. At baseline, higher plateau pressures (p = 0.006) and lower Pediatric Logistic Organ Dysfunction scores (p = 0.04) occurred in the steroid group; other characteristics were similar. Despite higher plateau pressures on days 1 (p = 0.006) and 2 (p = 0.025) due to poorer lung compliance in the steroid group, they had lower PaCO2 values on days 2 (p = 0.009) and 3 (p = 0.014), higher pH values on day 2 (p = 0.018), and higher PaO2/FIO2 ratios on days 8 (p = 0.047) and 9 (p = 0.002) compared with the placebo group. Fewer patients in the steroid group required treatment for postextubation stridor (p = 0.04) or supplemental oxygen at ICU transfer (p = 0.012). Steroid therapy was not associated with detectable adverse effects. This study demonstrates the feasibility of administering low-dose glucocorticoid therapy and measuring clinically relevant outcomes in pediatric acute respiratory distress syndrome. Changes in oxygenation and/or ventilation are consistent with early acute respiratory distress syndrome pathophysiology and results of similar clinical trials in adults. We propose and design a larger randomized trial to define the role of glucocorticoid therapy in pediatric acute respiratory distress syndrome.

Early infectious acute respiratory distress syndrome is characterized by activation and proliferation of alveolar T-cells.

Acute respiratory distress syndrome (ARDS) in humans is characterized by the infiltration of polymorphonuclears in the alveolar spaces. However, the role of T-cells in ARDS is unknown. Our aim was to characterize the T-cell phenotype in bronchoalveolar lavage (BAL) during the early phase of acute lung infection(ALI)/ARDS-infected patients in comparison to a control group (CG). BAL lymphocyte phenotypes of two ALI, 16 ARDS, and eight CG were examined by flow cytometry. ALI/ARDS showed a significant increase in CD4 and CD8 T-cell activation as compared to CG. Moreover, a significant level of proliferation was observed using the Ki67 marker in ARDS patients as compared to controls (median): 37 versus 6 % for CD4 T-cells (p = 0.022) and 34 versus 2 % for CD8 T-cells (p = 0.009). In contrast, the percentage of T-regulatory cells and apoptotic T-cells were similar in both groups. Among costimulatory molecules, we observed an overexpression of CTLA-4/CD152 on CD4 T-cells in ALI/ARDS as compared to CG: 30 versus 7 %, respectively (p = 0.063). In further characterizing T-cell subsets expressing high levels of CD152, we found the presence of IL-17 secreting CD4 T-cells in ALI/ARDS. In humans, ALI/ARDS due to infection is associated with a high level of T-cell activation and proliferation, along with the presence of Th17 cells, which are known to attract polymorphonuclears.

The effects of dexamethasone and oxygen in ventilated adult sheep with early phase acute respiratory distress syndrome.

Acute respiratory distress syndrome (ARDS) is a life-threating condition with high morbidity and mortality. Inflammation is the main factor in the pathogenesis of ARDS. Therefore systemic corticosteroids are a rational therapeutic approach, but the effect of corticosteroids is still unclear. In this study, we looked at the effects of corticosteroids in ventilated sheep with ARDS, induced by lung lavage. We performed a prospective, randomised study in 64 ventilated sheep with ARDS, to evaluate the effect of corticosteroids and oxygen concentration on gas exchange and lung injury. Oxygenation index (OI) and ventilation efficacy index (VEI) were calculated to evaluate gas exchange. Lung injury was assessed by inflammatory response in broncho-alveolar lavage fluid (BALF) and plasma and histology of the lung. OI, VEI, lung inflammation, surfactant production, or lung histology was not influenced by corticosteroids. In the 100 % oxygen groups, OI was higher and total number of cells and disaturated phospholipids were lower in BALF. Our study showed that corticosteroids did not influence inflammation in early phase ARDS and that hyperoxia aggravated lung injury which could not be modulated by dexamethasone in early phase ARDS.

Predictors of Response to Corticosteroid Treatment in Patients with Early Acute Respiratory Distress Syndrome: Results of a Pilot Study

Prospective observational cohort study was performed to evaluate predictors for responsiveness to corticosteroid treatment in patients with acute respiratory distress syndrome (ARDS). Over the study period, a total of 20 patients (male 70%, median age 69) with ARDS were treated with corticosteroid within 72 h after intubation. The median lung injury score (LIS) and partial pressure of arterial oxygen (PaO2)/fraction of inspired oxygen (FiO2) ratios (PF ratios) were 3.0 (interquartile range, 2.7-3.0) and 146.6 (119.9-179.4), respectively. The median levels of triggering receptor expressed on myeloid cells (TREM-1) and procollagen peptide type III in bronchoalveolar lavage (BAL) fluid were 349.3 (225.6-634.9) pg/mL and 19.6 (11.7-39.7) pg/mL, respectively. After 7 days of corticosteroid treatment, 10 (50%) patients showed response to the treatment (successful extubation in 7 and 1-point or more reduction in LIS in 3). Compared to non-responders, responders had higher initial PF ratios (170.5 vs. 127.2, p=0.023), lower level of TREM-1 in BAL fluid (313.6 pg/mL vs. 520.5 pg/mL, p=0.029), and greater reduction in LIS at 3 days (-1 vs. 0, p<0.001). In conclusion, PF ratios and TREM-1 level in BAL fluid at baseline, and reduction in LIS at day 3 after the treatment were associated with the response to prolonged corticosteroid treatment (ClinicalTrials.gov Identifier: NCT01093287).

Preoperative statin administration does not protect against early postoperative acute respiratory distress syndrome: a retrospective cohort study.

Statins have been shown to possess antiinflammatory and immunomodulatory effects. In this study, we sought to determine if preoperative statin therapy is associated with a reduced frequency of postoperative acute respiratory distress syndrome (ARDS) in surgical populations at increased risk of developing ARDS. We performed a retrospective cohort evaluation of the association between preoperative statin therapy and early postoperative ARDS in patients undergoing elective high-risk thoracic and aortic vascular surgery. The association between preoperative statin therapy and postoperative ARDS was assessed using propensity-adjusted analyses to control for indication bias and confounding factors. Of 1845 patients, 722 were receiving preoperative statin therapy. One hundred twenty patients developed postoperative ARDS. Frequencies of ARDS among those receiving statin therapy versus those who were not was 7.2% and 6.1%, respectively (OR = 1.20; 95% CI, 0.83-1.75; P = 0.330). Neither the stratified propensity score analysis (pooled OR 0.93; 95% CI, 0.60-1.43) nor matched analysis (OR = 0.78; 95% CI, 0.48-1.27) identified a statistically significant association between preoperative statin administration and postoperative ARDS. When compared to matched controls, patients who developed postoperative ARDS did not differ in mortality (7.7% vs 8.8%, P = 0.51), hospital length of stay (21 days vs 15 days, P = 0.21), or ventilator-free days (24 days vs 25 days, P = 0.62). In patients undergoing high-risk surgery, preoperative statin therapy was not associated with a statistically significant reduction in postoperative ARDS. These results do not support the use of statins as prophylaxis against ARDS in patients undergoing high-risk surgery.

Fluids in ARDS: from onset through recovery.

Early acute respiratory distress syndrome (ARDS) is characterized by protein-rich inflammatory lung edema often associated with a hydrostatic component. Mechanical ventilation with positive intrathoracic pressure further induces salt and water retention, while impairing the pathways designed for edema clearance. In this framework, we will review the recent findings on fluid strategy and edema clearance in ARDS. Consistently, conservative strategies lead to better oxygenation and reduce the length of mechanical ventilation. A possible drawback associated with conservative strategy is the impaired cognitive function. Echography may be used for safer use of furosemide or hemofiltration therapy during edema clearance. Albumin and furosemide techniques may accelerate edema clearance, particularly when pulmonary capillary permeability is restored. Beta-2 agonist therapy does not accelerate edema clearance and is potentially dangerous. Lung edema is likely the single pathogenic factor more relevant for ARDS severity and outcome. Fluid overload must be avoided. Several monitoring techniques are available to reach this target. No specific studies are available to recommend a given fluid composition in ARDS. In our opinion, the general recommendations for fluid composition suggested for severe sepsis and septic shock should be applied to ARDS that may be considered an organ-confined sepsis.

Administration of intrapulmonary sodium polyacrylate to induce lung injury for the development of a porcine model of early acute respiratory distress syndrome.

BackgroundThe loss of alveolar epithelial and endothelial integrity is a central component in acute respiratory distress syndrome (ARDS); however, experimental models investigating the mechanisms of epithelial injury are lacking. The purpose of the present study was to design and develop an experimental porcine model of ARDS by inducing lung injury with intrapulmonary administration of sodium polyacrylate (SPA).MethodsThe present study was performed at the Centre for Comparative Medicine, University of British Columbia, Vancouver, British Columbia. Human alveolar epithelial cells were cultured with several different concentrations of SPA; a bioluminescence technique was used to assess cell death associated with each concentration. In the anesthetized pig model (female Yorkshire X pigs (n = 14)), lung injury was caused in 11 animals (SPA group) by injecting sequential aliquots (5 mL) of 1% SPA gel in aqueous solution into the distal airway via a rubber catheter through an endotracheal tube. The SPA was dispersed throughout the lungs by manual bag ventilation. Three control animals (CON group) underwent all experimental procedures and measurements with the exception of SPA administration.ResultsThe mean (± SD) ATP concentration after incubation of human alveolar epithelial cells with 0.1% SPA (0.92 ± 0.27 μM/well) was approximately 15% of the value found for the background control (6.30 ± 0.37 μM/well; p < 0.001). Elastance of the respiratory system (ERS) and the lung (EL) increased in SPA-treated animals after injury (p = 0.003 and p < 0.001, respectively). Chest wall elastance (ECW) did not change in SPA-treated animals. There were no differences in ERS,EL, or ECW in the CON group when pre- and post-injury values were compared. Analysis of bronchoalveolar lavage fluid showed a significant shift toward neutrophil predominance from before to after injury in SPA-treated animals (p < 0.001) but not in the CON group (p = 0.38). Necropsy revealed marked consolidation and congestion of the dorsal lung lobes in SPA-treated animals, with light-microscopy evidence of bronchiolar and alveolar spaces filled with neutrophilic infiltrate, proteinaceous debris, and fibrin deposition. These findings were absent in animals in the CON group. Electron microscopy of lung tissue from SPA-treated animals revealed injury to the alveolar epithelium and basement membranes, including intra-alveolar neutrophils and fibrin on the alveolar surface and intravascular fibrin (microthrombosis).ConclusionsIn this particular porcine model, the nonimmunogenic polymer SPA caused a rapid exudative lung injury. This model may be useful to study ARDS caused by epithelial injury and inflammation.

High-frequency oscillatory ventilation for early acute respiratory distress syndrome in adults

High-frequency oscillatory ventilation (HFOV) has been considered a potentially ideal mode of lung-protective ventilation. A recent meta-analysis suggested improved oxygenation and reduced mortality in adults and children with acute respiratory distress syndrome (ARDS), but the use of outdated control strategies and small numbers of patients in many of the studies rendered these findings hypothesis-generating only. During 2013, two large randomized controlled trials comparing HFOV with a conventional lung-protective ventilation were published - the Oscillation for Acute Respiratory Distress Syndrome Treated Early (OSCILLATE) and the Oscillation in ARDS (OSCAR) trials. These trials suggested no benefit or even harm with HFOV in adults with early moderate-to-severe ARDS. In this article, the major characteristics of these two studies and the possible reasons for failure to achieve the expected theoretical benefits are reviewed. Moreover, future directions with potential new technical advances and the use of new bedside monitoring techniques are addressed. The OSCILLATE and OSCAR trials showed that the early application of HFOV in moderate-to-severe adult ARDS does not reduce mortality compared with conventional ventilation strategies. Future studies on HFOV will need to identify those patients who might benefit most from HFOV and to determine the best oscillator settings. Both goals require an improved capability of monitoring recruitment and overdistension, and oscillatory volumes.

What is the future of acute respiratory distress syndrome after the Berlin definition?

To analyze recently published articles in the medical literature that studied distinct aspects of adult patients with acute respiratory distress syndrome (ARDS) after the new Berlin definition introduced in 2012. The degree of ARDS severity according to this new classification correlated well with extravascular lung water index, pulmonary vascular permeability index and the finding of diffuse alveolar damage on autopsy. The new possibility of bedside echocardiographic evaluation of biventricular cardiac function is indicating the necessity of including a subgroup of severity of patients with right ventricular dysfunction. High-resolution CT evaluation showed that signs of pulmonary fibroproliferation in early ARDS predict increased ventilator dependency, multiple organ failure and mortality. The median development of ARDS 1 or 2 days after hospital admission emphasizes the need for ARDS intrahospital prevention, especially protective ventilation in non-ARDS patients. The better outcome with the use of prone position in patients with PaO2/FIO2 below 150 recently observed questioned the Berlin definition thresholds to decide the future best treatment strategies according to the proposed degree of severity of the syndrome. The impact of the Berlin definition of ARDS on the incidence, better treatment stratification and mortality ratio of ARDS is still to be determined.

SpO2/FiO2 Ratio on Hospital Admission Is an Indicator of Early Acute Respiratory Distress Syndrome Development Among Patients at Risk

Oxygen saturation to fraction of inspired oxygen ratio (SpO(2)/FiO(2)) has been validated as a surrogate marker for partial pressure of oxygen to fraction of inspired oxygen ratio among mechanically ventilated patients with acute respiratory distress syndrome (ARDS). The validity of SpO(2)/FiO(2) measurements in predicting ARDS has not been studied. Recently, a Lung Injury Prediction Score (LIPS) has been developed to help identify patients at risk of developing ARDS. This was a secondary analysis of the LIPS-1 cohort. A multivariate logistic regression included all established variables for LIPS, Acute Physiology and Chronic Health Evaluation 2, age, and comorbid conditions that could affect SpO(2)/FiO(2). The primary outcome was development of ARDS in the hospital. The secondary outcomes included hospital mortality, hospital day of ARDS development, and hospital day of death. Of the 5584 patients, we evaluated all 4646 with recorded SpO(2)/FiO(2) values. Median SpO(2)/FiO(2) in those who did and did not develop ARDS was 254 (100, 438) and 452 (329, 467), respectively. There was a significant association between SpO(2)/FiO(2) and ARDS (P ≤ .001). The SpO(2)/FiO(2) was found to be an independent predictor of ARDS in a "dose-dependent" manner; for SpO(2)/FiO(2) < 100--odds ratios (OR) 2.49 (1.69-3.64, P < .001), for SpO(2)/FiO(2) 100 < 200--OR 1.75 (1.16-2.58, P = .007), and for SpO(2)/FiO(2) 200 < 300--OR 1.62 (1.06-2.42, P = .025). The discriminatory characteristics of the multivariable model and SpO2/FiO2 as a single variable demonstrated area under the curve (AUC) of 0.81 and AUC of 0.74, respectively. The SpO2/FiO2, measured within the first 6 hours after hospital admission, is an independent indicator of ARDS development among patients at risk.

High-Frequency Oscillation in Early Acute Respiratory Distress Syndrome

Ferguson, Niall D.*†‡; Cook, Deborah J.§∥¶; Guyatt, Gordon H.∥¶; Mehta, Sangeeta*#**; Hand, Lori¶; Austin, Peggy¶; Zhou, Qi¶; Matte, Andrea††; Walter, Stephen D.∥¶; Lamontagne, Francois‡‡; Granton, John T.*‡#; Arabi, Yaseen M.§§; Arroliga, Alejandro C.∥∥; Stewart, Thomas E.*#**; Slutsky, Arthur S.*¶¶##; Meade, Maureen O.§∥¶ for the Oscillate Trial Investigators and the Canadian Critical Care Trials Group Author Information

High-Resolution Computed Tomography Findings of Acute Respiratory Distress Syndrome, Acute Interstitial Pneumonia, and Acute Exacerbation of Idiopathic Pulmonary Fibrosis

Diffuse alveolar damage (DAD) is the pathologic feature of rapidly progressive lung diseases, including acute respiratory distress syndrome, acute interstitial pneumonia, and acute exacerbation of idiopathic pulmonary fibrosis. The clinical significance and limitation of high-resolution computed tomography (HRCT) findings in these diseases were reviewed. The HRCT findings correlate well with pathologic phases (exudative, proliferative, and fibrotic) of DAD, although it cannot detect early exudative phase. Traction bronchiolectasis or bronchiectasis within areas of increased attenuation on HRCT scan is a sign of progression from the exudative to the proliferative and fibrotic phase of DAD. Extensive abnormalities seen on HRCT scans, which are indicative of fibroproliferative changes, were independently predictive of poor prognosis in patients with clinically early acute respiratory distress syndrome, acute interstitial pneumonia, and acute exacerbation of idiopathic pulmonary fibrosis.

Reabsorption atelectasis in a porcine model of ARDS: regional and temporal effects of airway closure, oxygen, and distending pressure

Little is known about the small airways dysfunction in acute respiratory distress syndrome (ARDS). By computed tomography (CT) imaging in a porcine experimental model of early ARDS, we aimed at studying the location and magnitude of peripheral airway closure and alveolar collapse under high and low distending pressures and high and low inspiratory oxygen fraction (FIO2). Six piglets were mechanically ventilated under anesthesia and muscle relaxation. Four animals underwent saline-washout lung injury, and two served as healthy controls. Beyond the site of assumed airway closure, gas was expected to be trapped in the injured lungs, promoting alveolar collapse. This was tested by ventilation with an FIO2 of 0.25 and 1 in sequence during low and high distending pressures. In the most dependent regions, the gas/tissue ratio of end-expiratory CT, after previous ventilation with FIO2 0.25 low-driving pressure, was significantly higher than after ventilation with FIO2 1; with high-driving pressure, this difference disappeared. Also, significant reduction in poorly aerated tissue and a correlated increase in nonaerated tissue in end-expiratory CT with FIO2 1 low-driving pressure were seen. When high-driving pressure was applied or after previous ventilation with FIO2 0.25 and low-driving pressure, this pattern disappeared. The findings suggest that low distending pressures produce widespread dependent airway closure and with high FIO2, subsequent absorption atelectasis. Low FIO2 prevented alveolar collapse during the study period because of slow absorption of gas behind closed airways.

Prevalence and prognostic value of acute cor pulmonale and patent foramen ovale in ventilated patients with early acute respiratory distress syndrome: a multicenter study

We sought to determine the prevalence of and factors associated with acute cor pulmonale (ACP) and patent foramen ovale (PFO) at the early phase of acute respiratory distress syndrome (ARDS), and to assess their relation with mortality. In this prospective multicenter study, 200 patients submitted to protective ventilation for early moderate to severe ARDS [PaO₂/F(I)O₂: 115 ± 39 with F(I)O₂: 1; positive end-expiratory pressure (PEEP): 10.6 ± 3.1 cmH2O] underwent transthoracic (TTE) and transesophageal echocardiography (TEE) <48 h after admission. Echocardiograms were independently interpreted by two experts. Factors associated with ACP, PFO, and 28-day mortality were identified using multivariate regression analysis. TEE depicted ACP in 45/200 patients [22.5%; 95% confidence interval (CI) 16.9-28.9%], PFO in 31 patients (15.5%; 95% CI 10.8-21.3%), and both ACP and PFO in 9 patients (4.5%; 95% CI 2.1-8.4%). PFO shunting was small and intermittent in 27 patients, moderate and consistent in 4 patients, and large or extensive in no instances. PaCO₂ >60 mmHg was strongly associated with ACP [odds ratio (OR) 3.70; 95% CI 1.32-10.38; p = 0.01]. No factor was independently associated with PFO, with only a trend for age (OR 2.07; 95% CI 0.91-4.72; p = 0.08). Twenty-eight-day mortality was 23%. Plateau pressure (OR 1.15; 95% CI 1.05-1.26; p < 0.01) and air leaks (OR 5.48; 95% CI 1.30-22.99; p = 0.02), but neither ACP nor PFO, were independently associated with outcome. TEE screening allowed identification of ACP in one-fourth of patients submitted to protective ventilation for early moderate to severe ARDS. PFO shunting was less frequent and never large or extensive. ACP and PFO were not related to outcome.

Effects of extravascular lung water on severity of illness and survival of patients with acute respiratory distress syndrome

Objective To evaluate the relationship between the extravascular lung water (EVLW) and other markers of lung injury and determine whether or not EVLW predicts survival in patients with acute respiratory distress syndrome (ARDS) and examine if indexing EVLW with predicted body weight (EVLWp) strengthens its discriminative power. Methods EVLW and other markers of lung injury [including: PaO2/FiO2 (P/F), oxygenation index (OI) = mean pressure (Pm) ×FiO2×100/PaO2, static compliance (Cst) and lung injury score (LIS)] were measured prospectively for 3 days in 27 patients with early ARDS between January 2011 and December 2011 at intensive care units (ICU) of Subei People's Hospital. The relationship between indexing EVLW with actual body weight (EVLWa), EVLWp and other markers of lung injury, the 28-day mortality were evaluated. Results Acute physiology and chronic health evaluation Ⅱ (APACHE Ⅱ), fluid balance in first 3 days, days of mechanical ventilation and ICU stay were significantly higher on admission in nonsurvivors compared with survivors (P 0.05). ROC curve analysis indicated that EVLWp (0.759, P 0.05) discriminated between survivors and nonsurvivors. Three-day average EVLWp ≥12.5 ml/kg predicted the 28-day mortality with 62.5% specificity and 80% sensitivity. Conclusion Increased extravascular lung water is a feature of early ARDS and predicts survival. EVLWp, instead of EVLWa, improves the predictive value of extravascular lung water for survival and it is correlated with markers of disease severity. Key words: Pulmonary edema; Respiratory distress syndrome, adult; Prognosis

Effect of recruitment maneuver on acute respiratory distress syndrome

Objective To investigate the effect of recruitment maneuver (RM) on acute respiratory distress syndrome (ARDS).Methods A total of 7 patients with early ARDS were involved in this investigate with pressure-control ventilation of FiO2 =1.Hemodynamics and extravascular lung water index (EVLWI) were monitored.After airway preparation,the ventilation parameters were adjusted to inspiration pressure (Pi) =24 cm H2O,positive end-expiratory pressure (PEEP) =10 cm H2O,frequency (f) =50,inspiration/expiration (I/E) =5/1.Up regulated PEEP to 24 cm H2O and Pi to 45 cm H2O for 3 respiration cycles.Then down regulated Pi to 30 cm H2O and had the artery blood gas analysis immediately.If PaO2 ＜ 450 mm Hg,Pi was increased 5 cm H2O above the last one,until PaO2 ＞ 450 mm Hg,which was considered RM success.Then PEEP was decreased 2 cm H2O and repeated the cycle as formers until PaO2 ＜350 mm Hg.The optimal PEEP was 2cm H2O above that.Maintained this airway pressure at least for 4 hours.Artery blood gas and hemodynamics of pre-and post-RM were monitored.The RM would be stopped by any unstable hemodynamic.Results In 6 of 7 patients,PaO2 and PEEP were higher than the baseline (P ＜ 0.01) after 4 hours of RM ; EVLWI decreased (P ＜ 0.01).RM was stopped in 1 patient,because of the unstable hemodynamic.None of the 7 patients got RM complications ; meanwhile,6 patients were cured.Conclusions Applying RM on ARDS is safe and effective. Key words: Recruitment maneuver; Acute respiratory distress syndrome; Hemoduynamics; Extravascular lung water index; Inspiration pressure; Positive end expiratory pressure; Blood gas analysis; Mechanical ventilation

Biomarkers for early stage of acute respiratory distress syndrome in septic patients: surfactant protein D and Clara cell protein

The injury of alveolar epithelium and endothelium is the basis of pathogenesis for the early stage of acute respiratory distress syndrome (ARDS). A prompt detection of this injury will provide us with a possibility for early ARDS diagnosis and treatment. Currently no biomarkers of alveolar epithelial injury are clinically available. The purpose of our study was to investigate the role of surfactant protein D (SPD) and Clara cell protein (CCP) as biomarkers of early ARDS.

High-Frequency Oscillation in Early Acute Respiratory Distress Syndrome

BackgroundPrevious trials suggesting that high-frequency oscillatory ventilation (HFOV) reduced mortality among adults with the acute respiratory distress syndrome (ARDS) were limited by the use of outdated comparator ventilation strategies and small sample sizes.MethodsIn a multicenter, randomized, controlled trial conducted at 39 intensive care units in five countries, we randomly assigned adults with new-onset, moderate-to-severe ARDS to HFOV targeting lung recruitment or to a control ventilation strategy targeting lung recruitment with the use of low tidal volumes and high positive end-expiratory pressure. The primary outcome was the rate of in-hospital death from any cause.ResultsOn the recommendation of the data monitoring committee, we stopped the trial after 548 of a planned 1200 patients had undergone randomization. The two study groups were well matched at baseline. The HFOV group underwent HFOV for a median of 3 days (interquartile range, 2 to 8); in addition, 34 of 273 patients (12%) in the control group received HFOV for refractory hypoxemia. In-hospital mortality was 47% in the HFOV group, as compared with 35% in the control group (relative risk of death with HFOV, 1.33; 95% confidence interval, 1.09 to 1.64; P=0.005). This finding was independent of baseline abnormalities in oxygenation or respiratory compliance. Patients in the HFOV group received higher doses of midazolam than did patients in the control group (199 mg per day [interquartile range, 100 to 382] vs. 141 mg per day [interquartile range, 68 to 240], P<0.001), and more patients in the HFOV group than in the control group received neuromuscular blockers (83% vs. 68%, P<0.001). In addition, more patients in the HFOV group received vasoactive drugs (91% vs. 84%, P=0.01) and received them for a longer period than did patients in the control group (5 days vs. 3 days, P=0.01).ConclusionsIn adults with moderate-to-severe ARDS, early application of HFOV, as compared with a ventilation strategy of low tidal volume and high positive end-expiratory pressure, does not reduce, and may increase, in-hospital mortality. (Funded by the Canadian Institutes of Health Research; Current Controlled Trials numbers, ISRCTN42992782 and ISRCTN87124254, and ClinicalTrials.gov numbers, NCT00474656 and NCT01506401.)

Is Prolonged Low-Dose Glucocorticoid Treatment Beneficial in Community-Acquired Pneumonia?

Community-acquired pneumonia (CAP) has a significant impact on public health in terms of short-term and long-term morbidity and mortality. Irrespective of microbiological etiology, the host's inability to fully downregulate systemic inflammation is the dominant pathogenetic process contributing to acute and long-term morbidity and mortality in CAP. Glucocorticoids are the natural regulators of inflammation, and their production increases during infection. There is consistent evidence that downregulation of systemic inflammation with prolonged low-dose glucocorticoid treatment in patients with severe sepsis and acute respiratory distress syndrome improves cardiovascular and pulmonary organ physiology. A recent meta-analysis of pooled controlled small trials (n = 970) of patients admitted with CAP found improved short-term mortality in the subgroup with severe CAP and/or receiving >5 days of glucocorticoid treatment. We have expanded on this meta-analysis by including patients with CAP recruited in trials investigating prolonged low-dose glucocorticoid treatment in septic shock and/or early acute respiratory distress syndrome (n = 1,206). Our findings confirm a survival advantage for severe CAP (RR 0.66, 95% confidence interval 0.51-0.84; p = .001). A large randomized trial is in progress to confirm the aggregate findings of these small trials and to evaluate the long-term effect of this low-cost treatment.