Early Phase Of Acute Respiratory Distress Syndrome Research Articles

A closed-loop ventilation mode that targets the lowest work and force of breathing reduces the transpulmonary driving pressure in patients with moderate-to-severe ARDS

IntroductionThe driving pressure (ΔP) has an independent association with outcome in patients with acute respiratory distress syndrome (ARDS). INTELLiVENT-Adaptive Support Ventilation (ASV) is a closed-loop mode of ventilation that targets the lowest work and force of breathing.AimTo compare transpulmonary and respiratory system ΔP between closed-loop ventilation and conventional pressure controlled ventilation in patients with moderate-to-severe ARDS.MethodsSingle-center randomized cross-over clinical trial in patients in the early phase of ARDS. Patients were randomly assigned to start with a 4-h period of closed-loop ventilation or conventional ventilation, after which the alternate ventilation mode was selected. The primary outcome was the transpulmonary ΔP; secondary outcomes included respiratory system ΔP, and other key parameters of ventilation.ResultsThirteen patients were included, and all had fully analyzable data sets. Compared to conventional ventilation, with closed-loop ventilation the median transpulmonary ΔP with was lower (7.0 [5.0–10.0] vs. 10.0 [8.0–11.0] cmH2O, mean difference − 2.5 [95% CI − 2.6 to − 2.1] cmH2O; P = 0.0001). Inspiratory transpulmonary pressure and the respiratory rate were also lower. Tidal volume, however, was higher with closed-loop ventilation, but stayed below generally accepted safety cutoffs in the majority of patients.ConclusionsIn this small physiological study, when compared to conventional pressure controlled ventilation INTELLiVENT-ASV reduced the transpulmonary ΔP in patients in the early phase of moderate-to-severe ARDS. This closed-loop ventilation mode also led to a lower inspiratory transpulmonary pressure and a lower respiratory rate, thereby reducing the intensity of ventilation.Trial registration Clinicaltrials.gov, NCT03211494, July 7, 2017. https://clinicaltrials.gov/ct2/show/NCT03211494?term=airdrop&draw=2&rank=1.

Lumican is elevated in the lung in human and experimental acute respiratory distress syndrome and promotes early fibrotic responses to lung injury

BackgroundFibroproliferative repair starts early in the inflammatory phase of acute respiratory distress syndrome (ARDS) and indicates a poor prognosis. Lumican, a small leucine-rich proteoglycan, is implicated in homeostasis and fibrogenesis, but its role in ARDS is unclear.MethodsBronchoalveolar lavage fluid (BALF) samples were obtained from ARDS patients (n = 55) enrolled within 24 h of diagnosis and mechanically ventilated (n = 20) and spontaneously breathing (n = 29) control subjects. Lipopolysaccharide (LPS)-induced acute lung injury (ALI) mouse models were intratracheally administered an adeno-associated virus (AAV) vector expressing lumican shRNA. Primary human lung fibroblasts (HLF) and small airway epithelial cells (SAECs) were cultured with tumour necrosis factor (TNF)-α or lumican. Luminex/ELISA, histochemistry/immunohistochemistry, immunofluorescence microscopy, quantitative real-time PCR, and western blotting were performed.ResultsLumican levels were significantly higher in the BALF of ARDS patients than in that of ventilated or spontaneously breathing controls (both p < 0.0001); they were correlated with the PaO2/FiO2 ratio and levels of proinflammatory cytokines (interleukin-6, interleukin-8, and TNF-α) and profibrotic factors (fibronectin, alpha-1 type I collagen [COL1A1], and alpha-1 type III collagen [COL3A1]). Lumican expression was enhanced in the alveolar walls and airway epithelium in the ALI mouse model. Murine lumican levels were also linked to proinflammatory and profibrotic cytokine levels in the BALF. In vitro, TNF-α induced the synthesis and secretion of lumican in HLF. In turn, lumican increased the expression of alpha-smooth muscle actin (α-SMA), COL1A1, and COL3A1 in HLF, upregulated α-SMA and COL3A1, downregulated E-cadherin, and caused spindle-shaped morphological changes in SAECs. Moreover, increased ERK phosphorylation and Slug were noted in both HLF and SAECs treated with lumican. In vivo, AAV-mediated knockdown of lumican inhibited the pulmonary production of fibronectin and COL3A1 and alleviated lung fibrotic lesions in LPS-challenged mice.ConclusionsPulmonary lumican levels were increased early in human and experimental ARDS and linked to disease severity and inflammatory fibrotic processes. Lumican triggers the transdifferentiation of lung fibroblasts into myofibroblasts and epithelial-mesenchymal transition in SAECs, possibly via the ERK/Slug pathway. Knockdown of pulmonary lumican attenuated extracellular matrix deposition in ALI mice. Overall, lumican promotes fibrotic responses in the early phase of ARDS, suggesting its potential as a therapeutic target.

The role of eosinophils in sepsis and acute respiratory distress syndrome: a scoping review.

PurposeSeptic shock and acute respiratory distress syndrome (ARDS) are characterized by a dysregulated immune host response that may respond to steroid therapy. Eosinophils contribute to type 2 inflammation that often responds to steroid therapy; their role in immune dysregulation and outcomes in sepsis and ARDS is unclear.SourceA systematic search of Cochrane Library, MEDLINE, and EMBASE was performed from inception to 9 September 2020. The search comprised the following terms: eosinophils, sepsis, septic shock, and ARDS. Two reviewers independently screened abstracts and texts and extracted data on disease severity and clinical outcomes.Principal findingsThirty-nine studies were identified: 30 evaluated serum eosinophil count in sepsis, one evaluated eosinophil activity in sepsis, three assessed bronchoalveolar lavage (BAL) eosinophil count in ARDS, four assessed eosinophil activity in ARDS, and one assessed peripheral eosinophil count in ARDS. Eleven studies showed an association between eosinopenia and sepsis, and eight studies found persistent eosinopenia at > 48 hr of intensive care unit admission to predict mortality and readmission in septic patients. Three studies found BAL eosinophil count to be low in ARDS, although one found that levels rose in late-phase ARDS. Three studies found eosinophil activity markers in BAL to be high in ARDS and correlate with ARDS severity.ConclusionPersistent peripheral eosinopenia is a marker of bacterial sepsis and is independently associated with poor outcomes. Bronchoalveolar lavage eosinophil counts are low in early-phase ARDS, but increase in late-phase ARDS, while elevated markers of eosinophil activity correlate with ARDS severity. Further studies understanding the mechanisms leading to eosinopenia in sepsis and increased eosinophil activity in ARDS are needed.Supplementary InformationThe online version of this article (10.1007/s12630-021-01920-8) contains supplementary material, which is available to authorized users.

Secretory Phospholipase A2-IIA Protein and mRNA Pools in Extracellular Vesicles of Bronchoalveolar Lavage Fluid from Patients with Early Acute Respiratory Distress Syndrome: A New Perception in the Dissemination of Inflammation?

Secretory phospholipase-IIA A2 (sPLA2-IIA) is expressed in a variety of cell types under inflammatory conditions. Its presence in the bronchoalveolar lavage (BAL) fluid of patients with acute respiratory distress syndrome (ARDS) is associated with the severity of the injury. Exosomal type extracellular vesicles, (EVs), are recognized to perform intercellular communication. They may alter the immune status of recipient target cells through cargo shuttling. In this work, we characterized the exosomal type EVs isolated from BAL fluid of patients with early and late ARDS as compared to control/non-ARDS patients, through morphological (confocal and electron microscopy) and biochemical (dynamic light scattering, qRT-PCR, immunoblotting) approaches. We provide evidence for the presence of an sPLA2-IIA-carrying EV pool that coprecipitates with exosomes in the BAL fluid of patients with ARDS. PLA2G2A mRNA was present in all the samples, although more prominently expressed in early ARDS. However, the protein was found only in EVs from early phase ARDS. Under both forms, sPLA2-IIA might be involved in inflammatory responses of recipient lung cells during ARDS. The perception of the association of sPLA2-IIA to the early diagnosis of ARDS or even with a mechanism of development and propagation of lung inflammation can help in the adoption of appropriate and innovative therapeutic strategies.

Acetazolamide, Nifedipine and Phosphodiesterase Inhibitors: Rationale for Their Utilization as Adjunctive Countermeasures in the Treatment of Coronavirus Disease 2019 (COVID-19).

Effective treatments for Coronavirus Disease 2019 (COVID-19) outbreak are urgently needed. While anti-viral approaches and vaccines are being considered immediate countermeasures are unavailable. The aim of this article is to outline a perspective on the pathophysiology of COVID-19 in the context of the currently available clinical data published in the literature. This article appreciates clinical data published on COVID-19 in the context of another respiratory illness - high altitude pulmonary edema (HAPE). Both conditions have significant similarities that portend pathophysiologic trajectories. Following this potential treatment options emerge.Both COVID-19 and HAPE exhibit a decreased ratio of arterial oxygen partial pressure to fractional inspired oxygen with concomitant hypoxia and tachypnea. There also appears to be a tendency for low carbon dioxide levels in both as well. Radiologic findings of ground glass opacities are present in up to 86% of patients with COVID-19 in addition to patchy infiltrates. Patients with HAPE also exhibit patchy infiltrates throughout the pulmonary fields, often in an asymmetric pattern and CT findings reveal increased lung markings and ground glass-like changes as well. Widespread ground-glass opacities are most commonly a manifestation of hydrostatic pulmonary edema. Similarly, elevated fibrinogen levels in both conditions are likely an epiphenomenon of edema formation rather than coagulation activation. Autopsy results of a COVID-19 fatality revealed bilateral diffuse alveolar damage associated with pulmonary edema, pro-inflammatory concentrates, and indications of early-phase acute respiratory distress syndrome (ARDS). HAPE itself is initially caused by an increase in pulmonary capillary pressure and induces altered alveolar-capillary permeability via high pulmonary artery hydrostatic pressures that lead to a protein-rich and mildly hemorrhagic edema. It appears that COVID-19 and HAPE both discretely converge on ARDS. In light of this, a countermeasure that has been shown to be effective in the analogous condition of HAPE is Acetazolamide. Acetazolamide has a myriad of effects on different organ systems, potently reduces hypoxic pulmonary vasoconstriction, improves minute ventilation and expired vital capacity. Other therapeutics to consider that are also directed towards decreased pulmonary pressure include Nifedipine and Phosphodiesterase inhibitors.This review describes COVID-19 in parallel to HAPE. Deranged respiratory parameters that are present in both conditions are highlighted. The utilization of medications found to be effective in HAPE, for the treatment of COVID-19, is proposed. Given the medical emergency of a growing contagion and the thousands of lives at stake, expedient attempts to improve survival are needed. Acetazolamide, Nifedipine and Phosphodiesterase inhibitors may be potential countermeasures.

Effect of different dosages of dexamethasone therapy on lung function and inflammation in an early phase of acute respiratory distress syndrome model.

Inflammation associated with acute respiratory distress syndrome (ARDS) can damage the alveolar epithelium and surfactant and worsen the respiratory failure. Glucocorticoids (GC) appear to be a rational therapeutic approach, but the effect is still unclear, especially for early administration and low-dose. In this study we compared two low doses of dexamethasone in early phase of surfactant-depleted model of acute respiratory distress syndrome (ARDS). In the study, lung-lavaged New Zealand rabbits with respiratory failure (PaO(2)<26.7 kPa in FiO(2) 1.0) were treated with intravenous dexamethasone (DEX): 0.5 mg/kg (DEX-0.5) and 1.0 mg/kg (DEX-1.0), or were untreated (ARDS). Animals without ARDS served as controls. Respiratory parameters, lung edema, leukocyte shifts, markers of inflammation and oxidative damage in the plasma and lung were evaluated. Both doses of DEX improved the lung function vs. untreated animals. DEX-1.0 had faster onset with significant improvement in gas exchange and ventilation efficiency vs. DEX-0.5. DEX-1.0 showed a trend to reduce lung neutrophils, local oxidative damage, and levels of TNFalpha, IL-6, IL-8 more effectively than DEX-0.5 vs. ARDS group. Both dosages of dexamethasone significantly improved the lung function and suppressed inflammation in early phase ARDS, while some additional enhancement was observed for higher dose (1 mg/kg) of DEX.

Recruitment maneuvers in acute respiratory distress syndrome.

The rationale for the use of recruitment maneuvers (RMs) in acute respiratory distress syndrome (ARDS) is to promote alveolar recruitment, leading to an increased end-expiratory lung volume and thus decreased ventilator-induced lung injury (VILI). RMs consists of a transient increase in transpulmonary pressure that can re-open previously collapsed alveoli. RMs represents a physiological response to lung aggression in different conditions by re-opening the collapsed part of the lung and decreasing lung oedema. This process can be accomplished through a variety of methods. The RM that has probably been used most commonly is sustained inflation, but recruitment can be achieved by a prolonged sigh, leading to a lesser increase in transpulmonary pressure for a longer period of time. This extended sigh seems to be more efficient, with less haemodynamic compromise. Knowledge of physiological determinants is crucial to selecting good levels of pressure and time required to perform an efficient and well-tolerated RM. Identifying ARDS patients who may benefit from RMs is a major issue, depending essentially on the amount of recruitable lung involved. In any case, however, RMs should be done at the early phase of ARDS.

Early application of low-dose glucocorticoid improves acute respiratory distress syndrome: A meta-analysis of randomized controlled trials.

Previous clinical trials have investigated the effect of glucocorticoid therapy in acute respiratory distress syndrome (ARDS), with controversial results, particularly with regard to the early administration of low dose glucocorticoid. The present meta-analysis aimed to assess whether the application of glucocorticoid was able to reduce mortality in patients with ARDS. A literature search was performed using online databases, including MEDLINE, Embase, Cochrane and CNKI regardless of whether the studies were published in English or Chinese. Following assessment via inclusion and exclusion criteria, two reviewers screened controlled randomized trials which investigated glucocorticoid therapy in ARDS patients and independently extracted data. The quality of all of the included trials was evaluated based on blinding, randomization and other methods. A total of 14 studies with 1,441 patients met the inclusion criteria. The results of the meta-analysis demonstrated that glucocorticoid significantly reduced the overall mortality of patients with ARDS [relative ratio (RR), 0.68; 95% confidence interval (CI), 0.50–0.91; P<0.05], particularly with a low-dose of glucocorticoid (RR, 0.57; 95% CI, 0.39–0.84; P<0.05) at the early phase of ARDS (RR, 0.37; 95% CI, 0.16–0.86; P<0.05), and a longer duration of steroids (RR, 0.44; 95% CI, 0.30–0.64; P<0.05). Administration of steroids also significantly increased the number of days that patients remained alive and were off mechanical ventilation (RR, 3.08; 95% CI, 1.49–4.68; P<0.05) without significantly increasing the novel infection rate (RR, 1.00; 95% CI, 0.44–2.25; P<0.05). Due to inconsistencies and other limitations, the quality of the studies used for the meta-analysis of the effect of glucocorticoid on mortality was low. In conclusion, early use of low dose glucocorticoid may effectively reduce mortality in patients with ARDS. However, this conclusion may be affected by the limited quality of the studies included in the present meta-analysis.

Effects of pressure control and pressure support ventilation on ventilator induced lung injury in experimental acute respiratory distress syndrome with intra-abdominal hypertension

In acute respiratory distress syndrome (ARDS), intra-abdominal hypertension (IAH) increases intra-thoracic pressures, leading atelectasis and deterioration of respiratory mechanics and gas-exchange. The optimal setting of mechanical ventilation (MV) and its impact on respiratory function and ventilator-induced lung injury (VILI) in ARDS associated with IAH needs to be better clarified. Lung-protective MV with low tidal volume (VT) and positive end-expiratory pressure (PEEP) has been recommended; however, assisted MV may be a favorable alternative to controlled MV at the early phase of ARDS, since it requires less sedation, no paralysis and is associated with better lung protection, reducing the risk of VILI. We hypothesized that pressure-support ventilation (PSV) improve pulmonary morphofunction and minimize lung injury in ARDS with IAH.

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.

Proteomic Profiles in Acute Respiratory Distress Syndrome Differentiates Survivors from Non-Survivors

Acute Respiratory Distress Syndrome (ARDS) continues to have a high mortality. Currently, there are no biomarkers that provide reliable prognostic information to guide clinical management or stratify risk among clinical trial participants. The objective of this study was to probe the bronchoalveolar lavage fluid (BALF) proteome to identify proteins that differentiate survivors from non-survivors of ARDS. Patients were divided into early-phase (1 to 7 days) and late-phase (8 to 35 days) groups based on time after initiation of mechanical ventilation for ARDS (Day 1). Isobaric tags for absolute and relative quantitation (iTRAQ) with LC MS/MS was performed on pooled BALF enriched for medium and low abundance proteins from early-phase survivors (n = 7), early-phase non-survivors (n = 8), and late-phase survivors (n = 7). Of the 724 proteins identified at a global false discovery rate of 1%, quantitative information was available for 499. In early-phase ARDS, proteins more abundant in survivors mapped to ontologies indicating a coordinated compensatory response to injury and stress. These included coagulation and fibrinolysis; immune system activation; and cation and iron homeostasis. Proteins more abundant in early-phase non-survivors participate in carbohydrate catabolism and collagen synthesis, with no activation of compensatory responses. The compensatory immune activation and ion homeostatic response seen in early-phase survivors transitioned to cell migration and actin filament based processes in late-phase survivors, revealing dynamic changes in the BALF proteome as the lung heals. Early phase proteins differentiating survivors from non-survivors are candidate biomarkers for predicting survival in ARDS.

Early-phase changes of extravascular lung water index as a prognostic indicator in acute respiratory distress syndrome patients.

BackgroundThe features of early-phase acute respiratory distress syndrome (ARDS) are leakage of fluid into the extravascular space and impairment of its reabsorption, resulting in extravascular lung water (EVLW) accumulation. The current study aimed to identify how the initial EVLW values and their change were associated with mortality.MethodsThis was a post hoc analysis of the PiCCO Pulmonary Edema Study, a multicenter prospective cohort study that included 23 institutions. Single-indicator transpulmonary thermodilution-derived EVLW index (EVLWi) and conventional prognostic factors were prospectively collected over 48 h after enrollment. Associations between 28-day mortality and each variable including initial (on day 0), mean, maximum, and Δ (subtracting day 2 from day 0) EVLWi were evaluated.ResultsWe evaluated 192 ARDS patients (median age, 69 years (quartile, 24 years); Sequential Organ Failure Assessment (SOFA) score on admission, 10 (5); all-cause 28-day mortality, 31%). Although no significant differences were found in initial, mean, or maximum EVLWi, Δ-EVLWi was significantly higher (i.e., more reduction in EVLWi) in survivors than in non-survivors (3.0 vs. −0.3 mL/kg, p = 0.006). Age, maximum, and Δ-SOFA scores and Δ-EVLW were the independent predictors for survival according to the Cox proportional hazard model. Patients with Δ-EVLWi > 2.8 had a significantly higher incidence of survival than those with Δ-EVLWi ≤ 2.8 (log-rank test, χ2 = 7.08, p = 0.008).ConclusionsDecrease in EVLWi during the first 48 h of ARDS may be associated with 28-day survival. Serial EVLWi measurements may be useful for understanding the pathophysiologic conditions in ARDS patients. A large multination confirmative trial is required.

Alveolar neopterin, procalcitonin, and IL-6 in relation to serum levels and severity of lung injury in ARDS

To the Editor,Tsantes et al. evaluated plasma and bronchoalveolar lavage fluid (BALF) procalcitonin (PCT) and interleukin-6 (IL-6) in discriminating septic from non-septic causes of acute respiratory distress syndrome (ARDS) [1]. They concluded that early plasma, but not BALF-PCT concen-trations, can help distinguish between septic and non-septic ARDS causes and are associated with the severity of multiple organ dysfunction syndrome in septic ARDS patients. In addition to PCT and IL-6 we want to point out the role of alveolar and serum neopterin and PCT in the early phase of ARDS and acute lung injury (ALI) as a valu -able marker of increased activity of the cellular immune system [2]. Elevated levels of neopterin in serum and BALF in various lung diseases, e.g., sarcoidosis and interstitial lung disease, have been reported [3]. Pneumonia was associated with significantly elevated neopterin levels in BALF compared to controls [4]. Serum PCT determination in early ARDS was used to discriminate between septic and non-septic underlying disease [5]. PCT was detectable in BALF of patients with severe lung contusion, however, it failed to be a reliable parameter in the assessment of lung contusion severity [6]. IL-6 concentrations are high in the BALF of patients at risk for ARDS and remain elevated throughout the course of ARDS [7].We would like to contribute the so far unpublished results of a previous study concerning alveolar and serum neopterin, PCT and IL-6 in the early phase of ARDS and ALI. In our study, we measured neopterin, PCT, granulo-cyte colony-stimulating factor (G-CSF), TNF-α, IL-6, IL-8, epithelial neutrophil-activating peptide (ENA)-78, soluble TNF-α receptor type I (sTNF-RI), soluble TNF-α receptor type II (sTNF-RII), IL-1 receptor antagonist (IL-1RA), and IL-10 in BALF and serum within 12 and 24 h after onset of ARDS/ALI. Alveolar G-CSF, IL-8, and ENA-78 in relation to serum levels, pulmonary neutrophilia, and severity of lung injury in ARDS, and the association of endogenous G-CSF with anti-inflammatory mediators in patients with ARDS have been published previously [8, 9]. Addition-ally, we determined the concentration of neopterin, PCT, IL-6 in lung epithelial lining fluid (ELF) by using the urea dilution method for estimating the volume of ELF in the lavaged lung segment [10].We evaluated levels of neopterin, PCT, and IL-6 in BALF, ELF and serum for comparison of the concentra-tions of these compounds between the blood circulating compartment and the alveolar space. Furthermore, we evaluated whether there is a difference between ARDS and ALI, septic and non-septic ARDS/ALI, survivors and non-survivors or a correlation to lung injury expressed as PaO

The Role of Neuromuscular Blockers in Early ARDS

The use of neuromuscular blocking agents (NMBAs) in patients with acute respiratory distress syndrome (ARDS) and acute lung injury (ALI) remains controversial. However, NMBAs are used in 25% to 45% of ALI/ARDS patients for a mean period of 1±2 days, especially in severe ARDS. Hypoxemia and facilitation of mechanical ventilation are the main indications of NMBAs. Three randomized, controlled trials showed that the systematic early use of NMBAs is associated with a sustained improvement in oxygenation in ARDS patients. The most recent trial reported a decrease in 90-day in-hospital mortality rate when severe ARDS patients received a short course of muscle relaxants. The use of NMBAs in the early phase of ARDS could reinforce the beneficial effects of a lung-protective ventilation strategy. However, the role of prolonged NMBA administration in intensive care unit–acquired paresis in ARDS patients remains largely questioned. This review analyzes the recent findings in the literature concerning the effects of NMBAs on gas exchange and patient outcomes, and their potential adverse effects in ARDS.

Early and marked up-regulation of TNF-α in acute respiratory distress syndrome after cardiopulmonary bypass

Despite the technique of cardiopulmonary bypass (CPB) improved the development of modern cardiac surgery, many factors during CPB have been reported to induce acute respiratory distress syndrome (ARDS). The present study was to investigate which pro-inflammatory factors involved in the early phase of ARDS. Ten patients underwent valve replacement surgery with or without ARDS were enrolled for analysis of pulmonary function and inflammatory factors release including white blood cell (WBC), neutrophils, CD11b, CD18, interleukin (IL)-8 and tumor necrosis factor-α (TNF-α). The results demonstrated that the ratio of arterial oxygen tension/fraction of inspire oxygen (PaO(2)/FiO(2)) was greatly reduced in ARDS patients, but only the release of TNF-α was significantly increased, which was reversely correlated to the values of PaO(2)/FiO(2). Also, the count of neutrophils adhesive to pulmonary endothelial cells was significantly increased in ARDS patients. Therefore, we concluded that TNF-α was quickly up-regulated and involved in the pathogenesis of CPB-induced ARDS via guiding primed neutrophils to pulmonary interstitium.

Plasma Neutrophil Elastase and Elafin Imbalance Is Associated with Acute Respiratory Distress Syndrome (ARDS) Development

BackgroundWe conducted an exploratory study of genome-wide gene expression in whole blood and found that the expression of neutrophil elastase inhibitor (PI3, elafin) was down-regulated during the early phase of ARDS. Further analyses of plasma PI3 levels revealed a rapid decrease during early ARDS development. PI3 and secretory leukocyte proteinase inhibitor (SLPI) are important low-molecular-weight proteinase inhibitors produced locally at neutrophil infiltration site in the lung. In this study, we tested the hypothesis that an imbalance between neutrophil elastase (HNE) and its inhibitors in blood is related to the development of ARDS.Methodology/Principal FindingsPI3, SLPI, and HNE were measured in plasma samples collected from 148 ARDS patients and 63 critical ill patients at risk for ARDS (controls). Compared with the controls, the ARDS patients had higher HNE, but lower PI3, at the onset of ARDS, resulting in increased HNE/PI3 ratio (mean = 14.5; 95% CI, 10.9–19.4, P<0.0001), whereas plasma SLPI was not associated with the risk of ARDS development. Although the controls had elevated plasma PI3 and HNE, their HNE/PI3 ratio (mean = 6.5; 95% CI, 4.9–8.8) was not significantly different from the healthy individuals (mean = 3.9; 95% CI, 2.7–5.9). Before the onset (7-days period prior to ARDS diagnosis), we only observed significantly elevated HNE, but the HNE-PI3 balance remained normal. With the progress from prior to the onset of ARDS, the plasma level of PI3 declined, whereas HNE was maintained at a higher level, tilting the balance toward more HNE in the circulation as characterized by an increased HNE/PI3 ratio. In contrast, three days after ICU admission, there was a significant drop of HNE/PI3 ratio in the at-risk controls.Conclusions/SignificancePlasma profiles of PI3, HNE, and HNE/PI3 may be useful clinical biomarkers in monitoring the development of ARDS.

Paralytics in critical care: not always the bad guy

The use of neuromuscular blocking agents (NMBAs) in patients with acute respiratory distress syndrome (ARDS) and acute lung injury remains controversial, although frequent. This review analyzes the effects of NMBAs on thoracopulmonary mechanics, gas exchange, patient outcome and their potential adverse effects. NMBAs are used in 25-45% of acute lung injury/ARDS patients for a mean period of 12 days, especially in severe ARDS. Hypoxemia and facilitation of mechanical ventilation are the main indications of NMBAs. Two randomized controlled trials showed that the systematic early use of NMBAs is associated with a sustained improvement in oxygenation in ARDS patients. The most recent suggests a beneficial effect on proinflammatory response associated with ARDS and mechanical ventilation. The use of NMBAs in acute lung injury/ARDS patients is not marginal. Recent studies suggest a beneficial effect of early use of NMBAs on oxygenation and inflammation. The role of NMBAs in the occurrence of ICU-acquired neuromyopathies and lung atelectasis in ARDS patients remains largely questioned. The use of NMBAs in the early phase of ARDS could reinforce the beneficial effects of a lung-protective ventilation. In this context, the effect of NMBAs on the outcome of ARDS patients must be evaluated.

Application of continuous veno-venous hemofiltration in patients with acute respiratory distress syndrome

To investigate the changes of interleukin (IL)-6 serum level in patients with acute respiratory distress syndrome (ARDS) and the effects of continuous renal replacement therapy (CRRT) on IL-6 level and its clinical significance. Forty ARDS patients were randomly divided into 2 equal groups: Group A undergoing conventional treatment and Group B receiving conventional treatment plus CRRT at onset of ARDS. Serum IL-6 level was measured by enzyme linked immunosorbent assay (ELISA) at the onset (0 h) and 12, 24, 48, and 72 hours later. Dynamic APACHEII score was also evaluated at the time points of 0, 24, 48, and 72 h. The incidence of ventilator-associated pneumonia (VAP), intensive care unit (ICU) mortality rate, duration of total mechanical ventilation, and ICU stay were assessed. Twenty-five healthy examinees were used as controls. The serum IL-6 level of the whole ARDS patients was significantly higher then that of the normal controls (P < 0.01), and the serum IL-6 level of the ARDS patients who died was significantly higher than that of the ARDS patients who survived (P < 0.01). The IL-6 serum level was correlated well with the APACHEIIscore either in the survival subgroup or the non-survival subgroup (for the former: r = 0.560 P = 0.008, and for the latter: r = 0.518 P = 0.023). Group B, contrary to Group A, had persistently decreased serum IL-6 levels and APACHEII scores at the onset and during the progression of ARDS (all P < 0.05). The incidence of VAP in Group B was 45%, significantly lower than that in Group A (80%, P = 0.022) while the ICU mortality rate didn't differ between the two groups (40% vs 55%, P = 0.342). The duration of total mechanical ventilation and ICU stay of the Group B patients who underwent early CRRT were (12 +/- 5) days and (16 +/- 5) days respectively, both significantly shorter than those of Group A patients [(16 +/- 5) days, P = 0.027 and (19 +/- 5) days, P = 0.030]. The elevated serum IL-6 level in ARDS patients seems to be correlated well with the severity of lung injury, and appears to be a good marker to judge the prognosis of the disease combined with APACHEII score. In the early phase of ARDS, CRRT can decrease the high serum level of IL-6, shorten the duration of total mechanical ventilation and ICU stay, and decrease the incidence of VAP. Removal of the circulating proinflammatory cytokines by CRRT may be one of the most vital mechanisms to treat ARDS.

Sédation du patient présentant un syndrome de détresse respiratoire aiguë

To assess the role of sedation and myorelaxant agents in acute respiratory distress syndrome (ARDS) and to propose an updated management according to recent literature. EXTRACTION OF DATA: From Medline and Cochrane database of English and French language articles. Keywords were: acute respiratory distress syndrome, acute lung injury, general anaesthetics, inhalation, intravenous anaesthetics and intensive care. Selection of original articles, reviews and expert reports. Case reports have been included. ARDS is a clinical picture in which respiratory constraints are major because of hypoxemia. To insure correct haematosis, mechanical ventilation has to be considered. It constitutes, then, the most frequent indication of sedation in the intensive care unit. The objectives are to help the ventilation of lungs and to improve gas exchange, by controlling agitation, fight against ventilation and to reduce mechanical ventilation associated injuries. In this situation, use of myorelaxant agents is aimed at facilitating synchronization of the patient with his/her ventilator and serves to improve oxygenation during the early inflammatory phase of ARDS. Several mechanisms may enflame this improvement of oxygenation. One of the most probable effect on optimization is the possibility of optimize protective ventilation at the cares phase of ARDS and to reduce mechanical ventilation-associated injuries. With regard to benefits and inconvenient, sedation is considered as a treatment of ARDS. Its goals are the well being of patient and his/her adaptation to ventilator, but also the prevention on mechanical ventilation associated injuries. Hence, most authors suggest using a deep sedation at the early phase of ARDS. In this contact, use of myorelaxant agent is an intersecting adjuvant if sedation is not enough. The benefit is terms of survival and outcome remains to show.

Role of corticosteroids in the management of acute respiratory distress syndrome

Background: Evidence exploring the use of corticosteroids for acute respiratory distress syndrome (ARDS) has targeted various stages of disease progression, from preventing ARDS in high-risk patients to halting disease evolution once ARDS has developed. Objective: The aim of this review was to evaluate randomized, controlled trials describing the role of corticosteroids in preventing and treating ARDS. Methods: English-language randomized, controlled trials were identified using MEDLINE via PubMed and EMBASE searches (key terms: acute respiratory distress syndrome, acute lung injury, and corticosteroids; years: 1968-January 2008). Results: A total of 10 trials were found and included in this analysis. Trials describing the role of high-dose corticosteroids compared with controls in preventing ARDS found no benefit, with the range of occurrence of ARDS in at-risk populations from 14% to 64% and absolute increases in mortality from 4% to 31%. Conflicting evidence was found for treating late-phase ARDS with corticosteroids, with 13% hospital mortality among patients receiving corticosteroids versus 63% with controls ( P = 0.03) in one small study, but no significant difference was found when evaluating 60-day mortality (corticosteroid group, 29.2% vs control, 28.6%) in another investigation. The use of highdose corticosteroids for the treatment of early phase ARDS was not associated with significant differences in 45-day mortality (methylprednisolone, 60% vs control, 63%).However,onetrialfoundthatmethylprednisolone taper for early ARDS was associated with significant improvement in lung function or extubation (69.8% vs 35.7%; P = 0.002), fewer days on mechanical ventilation (median, 5.0 vs 9.5; P = 0.002), higher intensive care unit survival (79.4% vs 57.4%; P = 0.03), but similar rates of hospital survival (methylprednisolone, 76.2% vs control, 57.1%; P = NS). Conclusions: Data from clinical trials did not support the use of short-course, high-dose corticosteroids for preventing ARDS or for the treatment of early ARDS. Longer-course corticosteroids have not conclusively been associated with improved survival in the treatment of late-phase ARDS but have provided some benefits in other markers of disease severity in this setting and in early phase ARDS. Published trials support the administration of low- to moderate-dose corticosteroids in the treatment of early (<7 days) and late-phase (days 7\\2-14) ARDS, but this evidence is controversial.