Persistent Acute Respiratory Distress Syndrome Research Articles

Time to split: biomarker trajectories in pediatric acute respiratory distress syndrome hint at underlying disease.

Pediatric acute respiratory distress syndrome (ARDS) is severe, noncardiac hypoxemic respiratory failure that carries a substantial risk of death. Given the complexity of this clinically defined syndrome and the repeated failure of therapeutic trials, there has been an effort to identify subphenotypes of ARDS that may share targetable mechanisms of disease. In this issue of the JCI, Yehya and colleagues measured 19 plasma biomarkers in 279 children over the first seven days of ARDS. Increases in select tissue injury makers and inflammatory cytokines in peripheral blood were associated with multiple organ dysfunction syndrome and death, but not persistent ARDS. These findings argue that splitting patients by clinical and molecular phenotype may be more informative than lumping them under the umbrella diagnosis of ARDS. However, future studies are needed to determine whether these plasma factors represent targetable pathways in lung injury or are a consequence of systemic organ dysfunction.

Inflammatory and tissue injury marker dynamics in pediatric acute respiratory distress syndrome.

BACKGROUNDThe molecular signature of pediatric acute respiratory distress syndrome (ARDS) is poorly described, and the degree to which hyperinflammation or specific tissue injury contributes to outcomes is unknown. Therefore, we profiled inflammation and tissue injury dynamics over the first 7 days of ARDS, and associated specific biomarkers with mortality, persistent ARDS, and persistent multiple organ dysfunction syndrome (MODS).METHODSIn a single-center prospective cohort of intubated pediatric patients with ARDS, we collected plasma on days 0, 3, and 7. Nineteen biomarkers reflecting inflammation, tissue injury, and damage-associated molecular patterns (DAMPs) were measured. We assessed the relationship between biomarkers and trajectories with mortality, persistent ARDS, or persistent MODS using multivariable mixed effect models.RESULTSIn 279 patients (64 [23%] nonsurvivors), hyperinflammatory cytokines, tissue injury markers, and DAMPs were higher in nonsurvivors. Survivors and nonsurvivors showed different biomarker trajectories. IL-1α, soluble tumor necrosis factor receptor 1, angiopoietin 2 (ANG2), and surfactant protein D increased in nonsurvivors, while DAMPs remained persistently elevated. ANG2 and procollagen type III N-terminal peptide were associated with persistent ARDS, whereas multiple cytokines, tissue injury markers, and DAMPs were associated with persistent MODS. Corticosteroid use did not impact the association of biomarker levels or trajectory with mortality.CONCLUSIONSPediatric ARDS survivors and nonsurvivors had distinct biomarker trajectories, with cytokines, endothelial and alveolar epithelial injury, and DAMPs elevated in nonsurvivors. Mortality markers overlapped with markers associated with persistent MODS, rather than persistent ARDS.FUNDINGNIH (K23HL-136688, R01-HL148054).

The Impact of Steroid Responder Status on Long-Term Outcomes in Critically Ill Patients With Acute Respiratory Distress Syndrome Receiving High-Dose Glucocorticoids.

Background and objective High-dose intravenous pulsed glucocorticosteroids (GCS) are not part of the standard treatment in acute respiratory distress syndrome (ARDS), and the evidencesupporting their use is conflicting. In clinical practice, however, they are used in specialist settings when clinico-patho-radiological features suggest a potentially steroid-responsive pattern, or as a last resort in cases where patients are unable to be weaned off mechanical ventilation. This study aimed to investigate if an early objective response to high-dose GCS treatment in selected critically ill patients is predictive of survival in ARDS. Methods This study involved a case series of 63 patients treated at a tertiary specialist respiratory ICUbetween 2009 and 2017 who received high-dose GCS for ARDS following a multidisciplinary board agreement. Patients were stratified according to the change in their modified lung injury score (mLIS) between days 0 and 10 following GCS initiation. Changes in mLIS (range: 0-4)were grouped as follows - full responders: ≥2, partial responders: ≥1 and <2, and non-responders: <1. Mortality on discharge and at 6, 12, 18, and 24 months post-ICU discharge was assessed for each group. Data were analysed using logistic regression and a receiver operating curve (ROC) to determine a statistically significant association between the change in mLIS and survival. Results Of the 63 patients, there were seven full responders, 12 partial responders, and 44 non-responders to high-dose GCS. Overall mortality at ICU discharge and 6, 12, 18 and 24 months post-discharge was 29/63 (46.0%), 33/63 (52.4%), 34/63 (54.0%), 34/63 (54.0%), and 35/63 (55.6%) respectively. Mortality was significantly lower in the partial and full-response groups than in the non-response group at all time frames. Logistic regression showed a significant association between the change in mLIS and survival (p<0.001), and a ROC demonstrated that categorising the change in mLIS was a good predictive model for survival (c-statistic 0.86). Conclusions Measuring the change in mLIS by day 10 following high-dose GCS administration for ARDS may beclinically useful in prognosticating such patients. Further research using mLIS as a measure of response to GCS, and larger datasets to enable the evaluation of prognostic factors, may assist clinicians in predicting which patients with persistent ARDS are likely to respond to GCS therapy.

A combination of mild-moderate hypoxemia and low compliance is highly prevalent in persistent ARDS: a retrospective study

BackgroundThe Acute Respiratory Distress Syndrome (ARDS) is characterized by lung inflammation and edema, impairing both oxygenation and lung compliance. Recent studies reported a dissociation between oxygenation and compliance (severe hypoxemia with preserved compliance) in early ARDS and COVID-19-related-ARDS (CARDS). During the pandemic, in patients requiring prolonged mechanical ventilation, we observed the opposite combination (mild-moderate hypoxemia but significantly impaired compliance). The purpose of our study was to investigate the prevalence of this combination of mild-moderate hypoxemia and impaired compliance in persistent ARDS and CARDS.MethodsFor this retrospective study, we used individual patient-level data from two independent cohorts of ARDS patients. The ARDSNet cohort included patients from four ARDS Network randomized controlled trials. The CARDS cohort included patients with ARDS due to COVID-19 hospitalized in two intensive care units in Greece. We used a threshold of 150 for PaO2/FiO2 and 30 ml/cmH2O for compliance, estimated the prevalence of each of the four combinations of oxygenation and compliance at baseline, and examined the change in its prevalence from baseline to day 21 in the ARDSNet and CARDS cohorts.ResultsThe ARDSNet cohort included 2909 patients and the CARDS cohort included 349 patients. The prevalence of the combination of mild-moderate hypoxemia and low compliance increased from baseline to day 21 both in the ARDSNet cohort (from 22.2 to 42.7%) and in the CARDS cohort (from 3.1 to 33.3%). Among surviving patients with low compliance, oxygenation improved over time. The 60-day mortality rate was higher for patients who had mild-moderate hypoxemia and low compliance on day 21 (28% and 56% in ARDSNet and CARDS), compared to those who had mild-moderate hypoxemia and high compliance (20% and 50%, respectively).ConclusionsAmong patients with ARDS who require prolonged controlled mechanical ventilation, regardless of ARDS etiology, a dissociation between oxygenation and compliance characterized by mild-moderate hypoxemia but low compliance becomes increasingly prevalent. The findings of this study highlight the importance of monitoring mechanics in patients with persistent ARDS.

Effects of early versus delayed application of prone position on ventilation–perfusion mismatch in patients with acute respiratory distress syndrome: a prospective observational study

BackgroundProne position has been shown to improve oxygenation and survival in patients with early acute respiratory distress syndrome (ARDS). These beneficial effects are partly mediated by improved ventilation/perfusion (V/Q) distribution. Few studies have investigated the impact of early versus delayed proning on V/Q distribution in patients with ARDS. The aim of this study was to assess the regional ventilation and perfusion distribution in early versus persistent ARDS after prone position.MethodsThis is a prospective, observational study from June 30, 2021, to October 1, 2022 at the medical ICU in Zhongda Hospital, Southeast University. Fifty-seven consecutive adult patients with moderate-to-severe ARDS ventilated in supine and prone position. Electrical impedance tomography was used to study V/Q distribution in the supine position and 12 h after a prone session.ResultsOf the 57 patients, 33 were early ARDS (≤ 7 days) and 24 were persistent ARDS (> 7 days). Oxygenation significantly improved after proning in early ARDS (157 [121, 191] vs. 190 [164, 245] mm Hg, p < 0.001), whereas no significant change was found in persistent ARDS patients (168 [136, 232] vs.177 [155, 232] mm Hg, p = 0.10). Compared to supine position, prone reduced V/Q mismatch in early ARDS (28.7 [24.6, 35.4] vs. 22.8 [20.0, 26.8] %, p < 0.001), but increased V/Q mismatch in persistent ARDS (23.8 [19.8, 28.6] vs. 30.3 [24.5, 33.3] %, p = 0.006). In early ARDS, proning significantly reduced shunt in the dorsal region and dead space in the ventral region. In persistent ARDS, proning increased global shunt. A significant correlation was found between duration of ARDS onset to proning and the change in V/Q distribution (r = 0.54, p < 0.001).ConclusionsProne position significantly reduced V/Q mismatch in patients with early ARDS, while it increased V/Q mismatch in persistent ARDS patients.Trial registration ClinicalTrials.gov (NCT05207267, principal investigator Ling Liu, date of registration 2021.08.20).

Rapidly improving acute respiratory distress syndrome in COVID-19: a multi-centre observational study

BackgroundBefore the pandemic of coronavirus disease (COVID-19), rapidly improving acute respiratory distress syndrome (ARDS), mostly defined by early extubation, had been recognized as an increasingly prevalent subphenotype (making up 15–24% of all ARDS cases), associated with good prognosis (10% mortality in ARDSNet trials). We attempted to determine the prevalence and prognosis of rapidly improving ARDS and of persistent severe ARDS related to COVID-19.MethodsWe included consecutive patients with COVID-19 receiving invasive mechanical ventilation in three intensive care units (ICU) during the second pandemic wave in Greece. We defined rapidly improving ARDS as extubation or a partial pressure of arterial oxygen to fraction of inspired oxygen ratio (PaO2:FiO2) greater than 300 on the first day following intubation. We defined persistent severe ARDS as PaO2:FiO2 of equal to or less than 100 on the second day following intubation.ResultsA total of 280 intubated patients met criteria of ARDS with a median PaO2:FiO2 of 125.0 (interquartile range 93.0–161.0) on day of intubation, and overall ICU-mortality of 52.5% (ranging from 24.3 to 66.9% across the three participating sites). Prevalence of rapidly improving ARDS was 3.9% (11 of 280 patients); no extubation occurred on the first day following intubation. ICU-mortality of patients with rapidly improving ARDS was 54.5%. This low prevalence and high mortality rate of rapidly improving ARDS were consistent across participating sites. Prevalence of persistent severe ARDS was 12.1% and corresponding mortality was 82.4%.ConclusionsRapidly improving ARDS was not prevalent and was not associated with good prognosis among patients with COVID-19. This is starkly different from what has been previously reported for patients with ARDS not related to COVID-19. Our results on both rapidly improving ARDS and persistent severe ARDS may contribute to our understanding of trajectory of ARDS and its association with prognosis in patients with COVID-19.

DELAYED DIAGNOSIS OF COCCIDIODES IMMITIS INFECTION WITH PULMONARY ABSCESS AND ARDS DIAGNOSED IN CHICAGO

TOPIC: Chest Infections TYPE: Fellow Case Reports INTRODUCTION: Coccidiodes immitis is a highly pathogenic fungus that is found in western and southern California's desert's regions. It frequently presents as a pneumonia that does not get better after anti-biotic therapy. With less than 5% of immunocompetent patient's progressing to have disseminated or severe infections (1). A disseminated Coccididiodes infection can be treated with liposomal amphotericin B, fluconazole, and steroids when there is Acute Respiratory Distress Syndrome (ARDS) (1,2). CASE PRESENTATION: In this case, a relatively healthy 80-year-old male with a past medical history of gastroesophageal reflux disease, hypertension, and hyperlipidemia who comes in shortness of breath, cough, and congestion. He had completed a course of azithromycin without resolution of symptoms. His initial chest x-ray showed a right upper lobe consolidation (Figure 1a). Bronchoscopy with transbronchial biopsies was performed which showed an acute organizing pneumonia (Figure 2). Despite antibiotic therapy and steroids, the patient did not have significant clinical improvement. So liposomal amphotericin B was started. An open lung biopsy was performed on day 14 as his chest X-ray was significantly worse with significant hypoxia (Figure 1b). Open lung biopsy showed a large abscess. A chest tube was placed. The abscess was irrigated with saline containing antibiotics. Pathology reported numerous coccidiodes spores (Figure 3). Antibiotics were discontinued. The patient's hospital course was complicated by a persistent air leak post lung biopsy and ARDS. Adjunctive steroids were added with improvement of his hypoxia. The patient was transitioned to a lower dose of steroids and to high dose fluconazole for long term treatment of his Coccidiodes infection. He was stable for placement of a tracheostomy and discharged to a long term acute care hospital (LTACH) for further care. His chest x-ray showed significant fibrosis (Figure 1c). DISCUSSION: When we re-examined the patient's history, he had a short trip to the southwestern United states for a total of 10 days with his family. This is the source of the patient's exposure. A thorough history may have helped, but urine Coccidiodes antigen testing was negative even after the open lung biopsy was performed. Despite clinical improvement, the patient passed 6 weeks after discharge to long term acute care hospital. CONCLUSIONS: Severe Coccoidiodes pulmonary infections can progress to ARDS. While, it is responsive to liposomal amphotericin B and steroids, it is still associated with a high morbidity and mortality (2). A high index of suspicion for a fungal infection should be maintained in patient's who have pneumonia refractory to antibiotic therapy. Speaking directly with the pathologist will also aide in the diagnosis of fungal infections non-endemic to the area especially like in this case (3). REFERENCE #1: Kirkland TN, Fierer J. Coccidioides immitis and posadasii; A review of their biology, genomics, pathogenesis, and host immunity. Virulence. 2018;9(1):1426-1435. doi:10.1080/21505594.2018.1509667 REFERENCE #2: Shibli M, Ghassibi J, Hajal R, O'Sullivan M. Adjunctive corticosteroids therapy in acute respiratory distress syndrome owing to disseminated coccidioidomycosis. Crit Care Med. 2002 Aug;30(8):1896-8. doi: 10.1097/00003246-200208000-00037. PMID: 12163812. REFERENCE #3: Pitcher JH, Zuckerman JB. Coccidioides Immitis Infection with Involvement of the Airway. Conn Med. 2016 Oct;80(9):539-541. PMID: 29772139 DISCLOSURES: No relevant relationships by Justin Ching, source=Web Response

Efficacy and Safety of Corticosteroids for Persistent Acute Respiratory Distress Syndrome

Objective: The aim of this study is to determine the efficacy and safety of corticosteroids for persistent acute respiratory distress syndrome. Study Design: Randomized Control Trial Place and Duration: The study was conducted at the emergency department of Lady Reading hospital Peshawar for the duration of six months during the period July to December 2020. Methods: Total 150 patients suffering from acute respiratory distress syndrome were presented in this study. Patients were aged between 40-75 years. Patients’ detailed demographics age, sex and body mass index were recorded after taking informed written consent. Patients were equally divided into-2 groups. Group I received corticosteroids and group II received placebo for 7-days of duration. At 28th day efficacy among both groups were assessed and compared in terms of low mortality, free from ventilator and reduction in complications. Complete data was analyzed by SPSS 24.0 version. Results: There were 120 males (60 in each group) and 30 (15 in each group) were females. Mean age of the patients in group I was 59.14±6.45 years with mean BMI 25.88±3.42 kg/m2 and in group II mean age was 58.38±7.46 years with mean BMI 26.41±3.54 kg/m2.Smoking was the most common cause of ARDS, in group I among 40 (53.3%) patients and 42 (56%), followed by chronic lung disease 20 (26.7%) in group I and 19 (25.3%) in group II. After regular follow up, mortality rate among patients of group II was greater 18 (24%) as compared to steroids group 13 (17.3%) and frequency of ventilator free patients were higher among steroids group 39 (52%) as compared to placebo 31 (41.3%). We found that complications reduction in steroids group was greater with minimum recurrence rate. Conclusion: We concluded in this study that the use of corticosteroids for persistent acute respiratory distress syndrome was effective and reliable in terms of low mortality and shorten the time of ventilation. Except this reduction in complications with minimum recurrence rate was found among patients those received steroids. Keywords: Acute respiratory distress syndrome, Placebo, Corticosteroids, Efficacy, Ventilator

Persistent lymphopenia after diagnosis of COVID-19 predicts acute respiratory distress syndrome: A retrospective cohort study

Background Lymphopenia is a marker of immunosuppression after severe coronavirus disease-2019 (COVID-19) which is characterized by acute respiratory distress syndrome (ARDS). This study aimed to evaluate the relationships between persistent lymphopenia and ARDS. Methods A retrospective cohort study of 125 patients with COVID-19 admitted to government-designated treatment center between 14 January 2020, and 20 March 2020 was conducted. We recorded all complete blood cell counts during the day 0th, 3rd, and 7th following the diagnosis of COVID-19. Patients were grouped based on the depression of the lymphocyte cell count, their return, or their failure to normal. The primary outcome was the occurrence of ARDS, and secondary outcomes included developing vital organ dysfunction and hospital lengths of stay. Results 17.6% (22/125) patients developed ARDS. The lymphocyte counts with ARDS and non-ARDS were 0.94 × 109/L, 1.20 × 109/L at admission, respectively ( p = 0.02). On the 3rd and 7th day, the median of lymphocyte count in ARDS was significantly lower than that of non-ARDS. Multivariable logistic regression, which was adjusting for potentially confounding factors (including age, comorbidities, and APACHE II score), showed that persistent lymphopenia within the 7th day was independently associated with ARDS (OR, 3.94 [95% CI, 1.26–12.33, p = 0.018). Further, patients with persistent lymphopenia had longer hospital lengths of stay ( p &lt; 0.001). Conclusion The results showed persistent lymphopenia predicted ARDS after COVID-19. Further studies are needed to investigate whether immunostimulation of lymphocytes within 1 week can reduce ARDS occurrence in patients with COVID-19.

Gas exchange, specific lung elastance and mechanical power in the early and persistent ARDS

PurposeAim of this study was to evaluate the effect of acute respiratory distress syndrome (ARDS) duration on gas-exchange, respiratory mechanics, specific lung elastance and mechanical power. Materials and methodsIn a single center prospective study 28 ARDS patients (66.4 ± 10.0 years, BMI 23.6[21.3–28.8] kg/m2, PaO2/FiO2 148.9[99.6–173.5]) who still presented ARDS criteria after 7-days of mechanical ventilation were studied in early and persistent phase of the disease (day-1 and after 7-days). Each patient underwent PEEP trial at 5–15 cmH2O in both phases. ResultsAt both PEEP levels the PaO2 was similar in both phases (early: 70.7[65.1–84.4] vs 102.0[85.5–131.8] mmHg; persistent 70.7[63.0–76.2] vs 97.4[86.5–117.1] mmHg, 5–15 cmH2O respectively), the PaCO2 was significantly higher in the persistent phase at both PEEP levels (early 50.6 ± 10.2 vs 52.1 ± 10.5 mmHg; persistent 57.7 ± 13.4 vs 56.9 ± 12.8 mmHg). Specific lung elastance was not different in the early compared to the persistent phase 12.5 ± 3.1 vs 12.2 ± 3.8 cmH2O. The mechanical power normalized for the functional residual capacity increased with PEEP and was similar in both phases (early 23.4[12.8–32.8] vs 34.3[25.3–47.9], persistent 16.3[10.9–24.1] vs 26.7[19.9–46.0] J/min/L, 5–15 cmH2O respectively). ConclusionsThe persistent phase of ARDS for 7-days did not affect the respiratory mechanics while significantly impaired the PaCO2 exchange.

Steroids to Soften the Blow in Persistent Acute Respiratory Distress Syndrome.

Steroids to Soften the Blow in Persistent Acute Respiratory Distress Syndrome.

Evaluating the efficacy of dexamethasone in the treatment of patients with persistent acute respiratory distress syndrome: study protocol for a randomized controlled trial.

BackgroundAlthough much has evolved in our understanding of the pathogenesis and factors affecting outcome of patients with acute respiratory distress syndrome (ARDS), still there is no specific pharmacologic treatment for ARDS. Several clinical trials have evaluated the utility of corticoids but none of them has demonstrated a definitive benefit due to small sample sizes, selection bias, patient heterogeneity, and time of initiation of treatment or duration of therapy. We postulated that adjunctive treatment of persistent ARDS with intravenous dexamethasone might change the pulmonary and systemic inflammatory response and thereby reduce morbidity, leading to a decrease in duration of mechanical ventilation and a decrease in mortality.Methods/designThis is a prospective, multicenter, randomized, controlled trial in 314 patients with persistent moderate/severe ARDS. Persistent ARDS is defined as maintaining a PaO2/FiO2 ≤ 200 mmHg on PEEP ≥ 10 cmH2O and FiO2 ≥ 0.5 after 24 hours of routine intensive care. Eligible patients will be randomly allocated to two arms: (i) conventional treatment without dexamethasone, (ii) conventional treatment plus dexamethasone. Patients in the dexamethasone group will be treated with a daily dose of 20 mg iv from day 1 to day 5, and 10 mg iv from day 6 to day 10. Primary outcome is the number of ventilator-free days, defined as days alive and free from mechanical ventilation at day 28 after intubation. Secondary outcome is all-cause mortality at day 60 after enrollment.DiscussionThis study will be the largest randomized controlled clinical trial to assess the role of dexamethasone in patients with persistent ARDS.Trial registrationRegistered on 21 November 2012 as DEXA-ARDS at ClinicalTrials.gov website (NCT01731795).Electronic supplementary materialThe online version of this article (doi:10.1186/s13063-016-1456-4) contains supplementary material, which is available to authorized users.

Open Lung Approach for the Acute Respiratory Distress Syndrome: A Pilot, Randomized Controlled Trial.

The open lung approach is a mechanical ventilation strategy involving lung recruitment and a decremental positive end-expiratory pressure trial. We compared the Acute Respiratory Distress Syndrome network protocol using low levels of positive end-expiratory pressure with open lung approach resulting in moderate to high levels of positive end-expiratory pressure for the management of established moderate/severe acute respiratory distress syndrome. A prospective, multicenter, pilot, randomized controlled trial. A network of 20 multidisciplinary ICUs. Patients meeting the American-European Consensus Conference definition for acute respiratory distress syndrome were considered for the study. At 12-36 hours after acute respiratory distress syndrome onset, patients were assessed under standardized ventilator settings (FIO2≥0.5, positive end-expiratory pressure ≥10 cm H2O). If Pao2/FIO2 ratio remained less than or equal to 200 mm Hg, patients were randomized to open lung approach or Acute Respiratory Distress Syndrome network protocol. All patients were ventilated with a tidal volume of 4 to 8 ml/kg predicted body weight. From 1,874 screened patients with acute respiratory distress syndrome, 200 were randomized: 99 to open lung approach and 101 to Acute Respiratory Distress Syndrome network protocol. Main outcome measures were 60-day and ICU mortalities, and ventilator-free days. Mortality at day-60 (29% open lung approach vs. 33% Acute Respiratory Distress Syndrome Network protocol, p = 0.18, log rank test), ICU mortality (25% open lung approach vs. 30% Acute Respiratory Distress Syndrome network protocol, p = 0.53 Fisher's exact test), and ventilator-free days (8 [0-20] open lung approach vs. 7 [0-20] d Acute Respiratory Distress Syndrome network protocol, p = 0.53 Wilcoxon rank test) were not significantly different. Airway driving pressure (plateau pressure - positive end-expiratory pressure) and PaO2/FIO2 improved significantly at 24, 48 and 72 hours in patients in open lung approach compared with patients in Acute Respiratory Distress Syndrome network protocol. Barotrauma rate was similar in both groups. In patients with established acute respiratory distress syndrome, open lung approach improved oxygenation and driving pressure, without detrimental effects on mortality, ventilator-free days, or barotrauma. This pilot study supports the need for a large, multicenter trial using recruitment maneuvers and a decremental positive end-expiratory pressure trial in persistent acute respiratory distress syndrome.

Pharmacological interventions in acute respiratory distress syndrome

Pharmacological interventions are commonly considered in acute respiratory distress syndrome (ARDS) patients. Inhaled nitric oxide (iNO) and neuromuscular blockers (NMBs) are used in patients with severe hypoxemia. No outcome benefit has been observed with the systematic use of iNO. However, a sometimes important improvement in oxygenation can occur shortly after starting administration. Therefore, its ease of use and its good tolerance justify iNO optionally combined with almitirne as a rescue therapy on a trial basis. Recent data from the literature support the use of a 48-h infusion of NMBs in patients with a PaO2 to FiO2 ratio <120 mmHg. No strong evidence exists on the increase of ICU-acquired paresis after a short course of NMBs. Fluid management with the goal to obtain zero fluid balance in ARDS patients without shock or renal failure significantly increases the number of days without mechanical ventilation. On the other hand, patients with hemodynamic failure must receive early and adapted fluid resuscitation. Liberal and conservative fluid strategies therefore are complementary and should ideally follow each other in time in the same patient whose hemodynamic state progressively stabilizes. At present, albumin treatment does not appear to be justified for limitation of pulmonary edema and respiratory morbidity. Aerosolized β2-agonists do not improve outcome in patients with ARDS and one study strongly suggests that intravenous salbutamol may worsen outcome in those patients. The early use of high doses of corticosteroids for the prevention of ARDS in septic shock patients or in patients with confirmed ARDS significantly reduced the duration of mechanical ventilation but had no effect or even increased mortality. In patients with persistent ARDS after 7 to 28 days, a randomized trial showed no reduction in mortality with moderate doses of corticosteroids but an increased PaO2 to FiO2 ratio and thoracopulmonary compliance were found, as well as shorter durations of mechanical ventilation and of ICU stay. Conflicting data exist on the interest of low doses of corticosteroids (200 mg/day of hydrocortisone) in ARDS patients. In the context of a persistent ARDS with histological proof of fibroproliferation, a corticosteroid treatment with a progressive decrease of doses can be proposed.

Potential Effects of Corticosteroids on Physiological Dead-Space Fraction in Acute Respiratory Distress Syndrome

Increased dead-space fraction is common in patients with persistent acute respiratory distress syndrome (ARDS). We evaluated the changes in the oxygenation and dead-space fraction in patients with persistent ARDS after corticosteroid therapy. This was a non-randomized non-placebo, controlled observational study including 19 patients with persistent ARDS treated with corticosteroids. We measured P(aO(2))/F(IO(2)) and dead-space fraction at days 0, 4, and 7 after corticosteroids treatment (methylprednisolone) initiation. Patients were classified in intermediate group when corticosteroids were initiated between days 8-14 after ARDS onset, and in late group when initiated after 14 days. Mean time from the diagnosis of the ARDS to methylprednisolone treatment was 11 ± 2 days in the intermediate group (10 patients) and 21 ± 8 days in the late group (9 patients). When comparing days 0, 4, and 7 after methylprednisolone treatment, we found an increase in the P(aO(2))/F(IO(2)) (145 ± 64 mm Hg, 190 ± 68 mm Hg, and 226 ± 84 mm Hg, respectively, P < .001) and a decrease in the physiological dead-space fraction (0.66 ± 0.10, 0.58 ± 0.12, and 0.53 ± 0.11, respectively, P < .001). No differences were found between the intermediate and late groups. In patients with persistent ARDS, the increase in oxygenation was accompanied by a decrease in the dead-space fraction after a few days of corticosteroid treatment. To confirm potential benefit of corticosteroids on physiological parameters and mortality will require a powered randomized placebo controlled trial.

Sepsis-induced acute respiratory distress syndrome with fatal outcome is associated to increased serum transforming growth factor beta-1 levels

BackgroundTGF-β1 is a promoter of pulmonary fibrosis in many chronic inflammatory diseases. TGF-β1 circulating levels in patients with sepsis-induced Acute Respiratory Distress Syndrome (ARDS) have not been established. MethodsIn this prospective pilot cohort study, serum bioactive TGF-β1 concentration, determined by sandwich ELISA, was analyzed in 52 patients who fulfilled criteria for septic shock at admission and on days 3 and 7. ResultsOf the 52 patients enrolled in the study, 46.1% fulfilled the criteria for ARDS on admission. At ICU admission, there were not statistical differences in TGF-β1 concentrations between septic shock patients with or without ARDS. After 7days of follow-up in ICU, circulating TGF-β1 levels were significantly higher in patients with sepsis and ARDS than in those without ARDS [55.47 (35.04–79.48pg/ml) versus 31.65 (22.89–45.63pg/ml), respectively] (p=0.002). Furthermore, in septic shock associated ARDS patients, TGF-β1 levels were significantly higher in nonsurvivors than in survivors [85.23 (78.19–96.30pg/ml) versus 36.41 (30.21–55.47pg/ml), respectively] (p=0.006) on day 7 of ICU follow-up. ConclusionsIn patients with septic shock, persistent ARDS is accompanied with increased circulating TGF-β1 levels. Furthermore, ARDS patients with fatal outcome show higher TGF-β1 concentrations than survivors. These results suggest the relevance of TGF-β1 levels found in the pathogenesis of persistent sepsis-induced ARDS.

IGF1 and IGFBP3 in acute respiratory distress syndrome

IGF1 and its most abundant binding protein, IGF-binding protein 3 (IGFBP3), have been implicated in fibrotic lung diseases and persistent acute respiratory distress syndrome (ARDS) due to profibrogenic and antiapoptotic activity. Whether circulating levels of IGF1 and IGFBP3 are altered in ARDS and whether they predict progression of and survival from ARDS remains unknown. This study aims to characterize the circulating levels of IGF1 and IGFBP3 in patients at risk for ARDS in relation to i) development of ARDS and ii) mortality among ARDS cases. In this case-cohort study, consecutive patients with risk factors for ARDS admitted to the intensive care unit were enrolled and followed prospectively for the development of ARDS. Cases were followed for all-cause mortality through day 60. Of the 2397 patients enrolled in the parent study, plasma samples were available in 531 (22%) patients (356 controls and 175 cases) from early in presentation. Total plasma IGF1 and IGFBP3 levels were measured. After adjusting for relevant clinical covariates including severity of illness, IGF1 and IGFBP3 levels were significantly lower in ARDS cases than in controls (odds ratio (OR), 0.58; P=0.006; OR, 0.57; P=0.0015 respectively). Among the ARDS cases, IGF1 and IGFBP3 levels were significantly lower in the 78 (45%) non-survivors (hazard ratio (HR), 0.70; P=0.024; HR, 0.69; P=0.021 respectively). Lower circulating levels of IGF1 and IGFBP3 were independently associated with ARDS case status. Furthermore, lower levels were associated with mortality among the ARDS cases. These data support the role of the IGF pathway in ARDS.

New images, new insights for VILI

prioritization of high-volume vs. low-volume mechanisms of ventilator-induced lung injury (VILI) is an issue that is often discussed and debated in clinical ventilator management. Abundant laboratory studies ([7][1]), as well as several prominent clinical studies ([1][2], [3][3], [14][4], [19][5]),

A Preliminary Study on the Effect of "Low-dose" Glucocorticoid Therapy for Patients with Persistent Acute Respiratory Distress Syndrome

Background: The role of glucocorticoids for treating persistent acute respiratory distress syndrome (ARDS) is matter of debate. In the previous studies, the side effects of moderate doses of glucocorticoids might have negated positive effects of glucocorticoids. This study aimed at determining the feasibility of administering “low-dose” glucocorticoid to treat the patients who suffer with persistent ARDS. Methods: We retrospectively reviewed the medical records of twelve patients with ARDS of at least seven days’ duration and who were treated with “low-dose” glucocorticoid (starting dose of 1 mg/kg) between June 2007 to December 2008. The patients were divided by whether or not they were successfully weaned from the ventilator after glucocorticoid therapy. The baseline characteristics and physiologic parameters were recorded for up to 7 days after starting glucocorticoid therapy. Results: Five patients (42%) were included in the weaned group. There was no significant difference in the clinical characteristics and the physiologic parameters between the two groups on the day of ARDS. Yet the weaned group had a significantly lower Sequential Organ Failure Assess ment (SOFA) score, as compared to that of the failed group [3 (3−6) vs 8 (5− 12), p = 0.009)] at start of glucocorticoid treatment. After 3 days of glucocorticoid therapy, there was significant improvement in the PEEP, the PaO2/FIO2 ratio, the PCO2 , the SOFA score and the Murray Lung Injury Score of the weaned group, as compared to th at of the failed group. There were no major neuromuscular side effects from the therapy. Conclusions: This study suggests that the “low-dose” glucocorticoid therapy is feasible and that the SOFA score and the physiologic parameters may assist in determining whether or not to initiate and to continue glucocorticoid therapy for the patients who are suffering with persistent ARDS.

Smoke Inhalation Injury of Indoor Fire

In Brief Smoke inhalation injury can be considered as a systemic disease. Early mortality and systemic involvement are due to the severity of thermal injury of the upper airway and to CO poisoning associated with other combustion materials. Prompt administration of 100% oxygen therapy is crucial. Laryngoscopy is useful because it may show pharyngeal or laryngeal mucosal injury despite the absence of respiratory symptoms and consequently the need for endotracheal intubation. Bronchoscopy is useful in identifying severity of airway injury and performing bronchial toilet and BAL culture, thus allowing early diagnosis of pulmonary infections and the adjustment of antibiotic treatment. Corticosteroid therapy should be considered when persistent acute respiratory distress syndrome, interstitial pneumonia, or obliterans bronchiolitis is suspected without evidence of active infection. Obstruction airway disease can persist several months after the smoke inhalation. Smoke inhalation is a major cause of fire-related morbidity and mortality accounting for several thousand deaths annually in different countries. This review describes the respiratory and systemic involvement and some pathophysiology aspects over which treatment strategies should be planned.