Etiology Of Acute Respiratory Distress Syndrome Research Articles

Open Tracheostomy Gastric Acid Aspiration Murine Model of Acute Lung Injury Results in Maximal Acute Nonlethal Lung Injury.

Acid pneumonitis is a major cause of sterile acute lung injury (ALI) in humans. Acid pneumonitis spans the clinical spectrum from asymptomatic to acute respiratory distress syndrome (ARDS), characterized by neutrophilic alveolitis, and injury to both alveolar epithelium and vascular endothelium. Clinically, ARDS is defined by acute onset of hypoxemia, bilateral patchy pulmonary infiltrates and non-cardiogenic pulmonary edema. Human studies have provided us with valuable information about the physiological and inflammatory changes in the lung caused by ARDS, which has led to various hypotheses about the underling mechanisms. Unfortunately, difficulties determining the etiology of ARDS, as well as a wide range of pathophysiology have resulted in a lack of critical information that could be useful in developing therapeutic strategies. Translational animal models are valuable when their pathogenesis and pathophysiology accurately reproduce a concept proven in both in vitro and clinical settings. Although large animal models (e.g., sheep) share characteristics of the anatomy of human trachea-bronchial tree, murine models provide a host of other advantages including: low cost; short reproductive cycle lending itself to greater data acquisition; a well understood immunologic system; and a well characterized genome leading to the availability of a variety of gene deletion and transgenic strains. A robust model of low pH induced ARDS requires a murine ALI that targets mainly the alveolar epithelium, secondarily the vascular endothelium, as well as the small airways leading to the alveoli. Furthermore, a reproducible injury with wide differences between different injurious and non-injurious insults is important. The murine gastric acid aspiration model presented here using hydrochloric acid employs an open tracheostomy and recreates a pathogenic scenario that reproduces the low pH pneumonitis injury in humans. Additionally, this model can be used to examine interaction of a low pH insult with other pulmonary injurious entities (e.g., food particles, pathogenic bacteria).

Value of procalcitonin on predicting the severity and prognosis in patients with early ARDS: a prospective observation study

To investigate the value of procalcitonin (PCT) on predicting the severity and prognosis in patients with early acute respiratory distress syndrome (ARDS). A prospective observation study was conducted. A total of 113 patients with ARDS undergoing mechanical ventilation admitted to intensive care unit (ICU) of Affiliated People's Hospital of Jiangsu University from October 2012 to April 2016 were enrolled. Based on oxygenation index (PaO2/FiO2), the patients were classified into mild, moderate, and severe groups according to Berlin Definition. Twenty-five healthy volunteers were served as controls. Demographics, acute physiology and chronic health evaluation II (APACHE II) score, and Murray lung injury score were recorded. Within 24 hours after diagnosis of ARDS, the serum levels of PCT and C-reactive protein (CRP) were determined by enzyme-linked fluorescence analysis (ELFA) and immune turbidimetric method, respectively. The patients were also divided into survival and non-survival groups according to clinical outcome within 28-day follow-up, and the clinical data were compared between the two groups. Spearman rank correlation was applied to determine the correlation between variables. The predictive value of the parameters on 28-day mortality was evaluated with receiver operating characteristic curve (ROC). Kaplan-Meier survival curve analysis was used to compare different PCT levels of patients with 28-day cumulative survival rate. After excluding patients who did not meet the inclusion criteria and loss to follow-up, the final 89 patients were enrolled in the analysis. Among 89 ARDS patients analyzed, 27 of them were mild, 34 moderate, and 28 severe ARDS. No significant differences were found in age and gender between ARDS and healthy control groups. Infection and trauma were the most common etiology of ARDS (55.1% and 34.8%, respectively). Compared with healthy control group, both CRP and PCT in serum of ARDS group were higher [CRP (mg/L): 146.32 (111.31, 168.49) vs. 6.08 (4.47, 7.89), PCT (μg/L): 3.46 (1.98, 5.56) vs. 0.02 (0.01, 0.04), both P < 0.01], and the two showed sustained upward trends with the ARDS course of disease. Compared with mild group, severe group had significantly higher APACHE II and Murray scores. Spearman rank correlation analysis showed that both serum PCT and CRP in patients with ARDS was correlated well with APACHE II score (r values were 0.669 and 0.601, respectively, both P < 0.001), while PCT was weakly but positively correlated with Murray score (r = 0.294, P = 0.005), but not the case of CRP (r = 0.203, P = 0.052). APACHE II score and serum PCT in non-survival group (n = 38) were significantly higher than those of the survival group [n = 51; APACHE II score: 26.00 (23.00, 28.50) vs. 21.00 (17.00, 25.00), PCT (μg/L): 6.38 (2.82, 9.49) vs. 3.09 (1.08, 3.57), both P < 0.01], but Murray score and CRP level were similar between survivors and non-survivors. The areas under ROC curve (AUC) of APACHE II score and PCT for predicting 28-day mortality were 0.781 and 0.793, respectively, which were better than those of AUC of Murray score and CRP (0.606 and 0.561, respectively, all P < 0.05). The AUC of APACHE II score combined with PCT was significantly higher than that of PCT (0.859 vs. 0.793, P = 0.048) or APACHE II score alone (0.859 vs. 0.781, P = 0.038). Using a PCT cut-off value of > 4.35 μg/L for predicting 28-day mortality, the sensitivity and specificity was 92.2% and 63.2%, respectively, and the positive and negative likelihood ratios were 2.50 and 0.12 respectively. Kaplan-Meier survival curve analysis indicated that the patients whose PCT more than 4.35 μg/L, had lower 28-day cummulative survival rate as compared with those with PCT ≤ 4.35 μg/L (log-rank test: χ2 = 5.013, P = 0.025). The elevated serum PCT level in patients with ARDS seems to be correlated well with the severity of lung injury, and appears to be a useful prognostic marker of outcome in the early phases of ARDS.

ARDS: what experimental models have taught us.

Acute respiratory distress syndrome (ARDS) is characterized by severe pulmonary inflammation, increased blood–gas barrier permeability, and hypoxemia, resulting in high mortality rates. Despite extensive research, there is still no specific therapy for ARDS and management remains supportive, mostly in the form of protective mechanical ventilation. These limited therapeutic options result from the complexity of ARDS pathophysiology, which involves multiple, overlapping signaling pathways depending on etiology. ARDS models are important to elucidate the mechanisms underlying pathogenesis, progression, and resolution of this syndrome, as well as to develop therapeutic approaches [1]. This brief review will address the main features of human ARDS that may be modeled experimentally, major current models of ARDS, and what these models have taught us concerning pathophysiology and new therapeutic strategies. An ideal model for ARDS research should reproduce the parameters found in human ARDS. However, since models that perfectly mimic human ARDS are lacking, a committee was organized to determine which features characterize ARDS in animals and identify the optimal methods to assess these features [2]. ARDS triggers are numerous, as are the animal models used to study this syndrome. The many etiologies of ARDS can be broadly classified into two categories: direct insults to the lung epithelium (pulmonary ARDS) and indirect insults to vascular endothelium (extrapulmonary ARDS), determined by an acute systemic inflammatory response [3]. Pulmonary ARDS can be induced experimentally by administration of bacteria or bacterial products such as lipopolysaccharide (LPS), hydrochloric acid or gastric particulates, high inspired fractions of oxygen, depletion of surfactant by repeated saline lavage, induction of ischemia/reperfusion by hilar clamping, or mechanical stretch secondary to injurious mechanical ventilation. Extrapulmonary ARDS can be induced using standard models of sepsis (cecal ligation and puncture [CLP], intravenous administration of bacteria or LPS, mesenteric ischemia/reperfusion), paraquat, and oleic acid. More recently, two-hit models were developed using saline lavage or LPS followed by mechanical ventilation, CLP followed by hemorrhage, or peritoneal sepsis combined with gut ischemia/reperfusion [4] (Table 1). Selection of ARDS models depends on local availability, cost, number of animals (if survival is the study endpoint, rodents are ideal), blood sampling requirements (if multiple samples are needed, large animals should be used), and measurement of inflammatory mediators, receptors, or other proteins (large animals lack specific reagents to measure these parameters).

多発外傷に併発した呼吸不全に対してvenovenous extracorporeal membrane oxygenationを使用した5例の検討(Use of venovenous extracorporeal membrane oxygenation for multiple trauma patients with respiratory insufficiency: a five–case study)

要旨多発外傷に伴う急性呼吸不全に対するvenovenous extracorporeal membrane oxygenation（VV–ECMO）の使用は出血の増加などのリスクを伴うため確立された指針がない。我々は2011～2014年に当院に搬送された多発外傷症例のうちVV–ECMO使用例を診療録から抽出し，有用性と安全性について検討した。対象は5例でいずれも人工呼吸で管理困難な低酸素血症を有した。呼吸不全の原因は肺挫傷3例，ARDS 2例であった。転帰は3例がECMO離脱に成功し生存，2例は離脱できず死亡した。ECMO導入後は全例でP/F ratioの上昇，PaCO2の低下を認めた。全症例でヘパリン全身投与を行ったが，出血性合併症は3例に生じた。うち1例は胸壁からの出血が制御困難となり大量輸血と開胸下止血術を要した。1例はventilator–induced lung injuryによると思われる肺胞損傷部からの出血が制御困難となり死亡した。また，2例で膜型人工肺に血栓を認め，交換を要した。VV–ECMOは多発外傷症例でもガス交換能の改善と換気条件の緩和に有用と考えられ，とくに肺挫傷例では良好な転帰を得た。受傷早期の導入は出血のリスクが高いため抗凝固薬の投与量を最小限にすべきであるが，実際の用量については今後の検討課題である。

Initial synchronized intermittent mandatory ventilation versus assist/control ventilation in treatment of moderate acute respiratory distress syndrome: a prospective randomized controlled trial.

Assist/control (A/C) ventilation may induce delirium in patients with acute respiratory distress syndrome (ARDS). We conducted a trial to determine whether initial synchronized intermittent mandatory ventilation with pressure support (SIMV + PS) could improve clinical outcomes in these patients. Intubated patients with moderate ARDS were enrolled and we compared SIMV + PS with A/C. Identical sedation, analgesia and ventilation strategies were performed. The co-primary outcomes were early (≤72 h) partial pressure of arterial oxygen to fraction of inspired oxygen (PaO2/FiO2) and incidence of delirium. The secondary outcomes were all-cause in-hospital mortality, dosages of analgesics and sedatives, incidence of patient-ventilator asynchrony, and duration of mechanical ventilation and hospital stay. We screened 2,684 patients and 40 patients were enrolled in our study. In SIMV + PS, early (≤72 h) PaO2/FiO2 was greater improved than that at baseline and that in A/C (P<0.05) with lower positive end-expiratory pressure (PEEP) (8.7±3.0 vs. 10.3±3.2, P<0.001) and FiO2 (58%±18% vs. 67%±19%, P<0.001). We found more SIMV + PS success (defined as SIMV + PS successfully applied without switching to A/C) (100.0% vs. 16.7%, P<0.001), less male (46.3% vs. 85.7%, P=0.015) and pulmonary etiology of ARDS (53.8% vs. 92.9%, P=0.015), and lower PEEP (9.1±3.1 vs. 10.3±3.3, P=0.004) and FiO2 (58%±19% vs. 71%±19%, P<0.001) in survival patients. However, there were no significant differences in incidence of delirium and mortality, dosages of analgesics and sedatives, incidence of patient-ventilator asynchrony, duration of mechanical ventilation and hospital stay (P>0.05). In patients with moderate ARDS, SIMV + PS can safely and effectively improve oxygenation, but does not decrease mortality, incidence of delirium and patient-ventilator asynchrony, dosages of analgesics and sedatives, and duration of mechanical ventilation and hospital stay.

Effects of inhaled anesthetics sevoflurane and isoflurane on lung morphofunction and biological markers in experimental pulmonary and extrapulmonary acute respiratory distress syndrome

Experimental and clinical studies have shown that volatile anesthetics modulate the inflammatory process, which may be beneficial in the context of acute respiratory distress syndrome (ARDS). Furthermore, these agents may also protect type II epithelial cells minimizing the impairment on surfactant production. There are various triggers for ARDS, and differences in the initial insult combined with underlying conditions may result in the activation of different inflammatory mechanisms. Based on the aforementioned, we hypothesized that sevoflurane and isoflurane may act differently depending on the etiology of ARDS.

Acute Respiratory Distress Syndrome With and Without Extracorporeal Membrane Oxygenation: A Score Matched Study

Acute respiratory distress syndrome (ARDS) is a life-threatening medical condition. Extracorporeal membrane oxygenation (ECMO) is a salvage therapy for patients with ARDS and refractory hypoxia. This study compared the characteristics and outcomes of ARDS patients who did or did not receive ECMO matched with Acute Physiology and Chronic Health Evaluation II (APACHE II) score and age. This retrospective, case-control study enrolled patients with ARDS admitted to the intensive care unit of a tertiary referral hospital between January 2007 and December 2012. Overall, 216 patients with ARDS-81 receiving ECMO (ECMO group) and 135 not receiving ECMO (non-ECMO group)-were enrolled in this study. Patients were paired when the difference in their APACHE II scores was within 3 points and their age difference was 3 years. In total, 126 patients could not be matched and were thus excluded. Eventually, of the 90 patients with ARDS enrolled in this study, 45 ECMO group patients were matched with 45 non-ECMO group patients. The demographic data, reasons for intensive care unit admission, and laboratory variables were evaluated. The primary etiology of ARDS was infection (72.2%). The APACHE II score and age-matched group receiving ECMO therapy had higher inhospital survival rates. Moreover, the patients receiving ECMO therapy had significantly lower 6-month mortality rates than did the non-ECMO group. Patients with ARDS who received ECMO treatment had higher inhospital survival rates than did those with a similar disease severity and at a similar age who did not receive ECMO.

The Effects of Dasatinib in Experimental Acute Respiratory Distress Syndrome Depend on Dose and Etiology

Background/Aims: Evidence suggests that tyrosine-kinase inhibitors may attenuate lung inflammation and fibrosis in experimental acute respiratory distress syndrome (ARDS). We hypothesized that dasatinib, a tyrosine-kinase inhibitor, might act differently depending on the ARDS etiology and the dose. Methods: C57/BL6 mice were divided to be pre-treated with dasatinib (1mg/kg or 10mg/kg) or vehicle (1% dimethyl-sulfoxide) by oral gavage. Thirty-minutes after pre-treatment, mice were subdivided into control (C) or ARDS groups. ARDS animals received Escherichia coli lipopolysaccharide intratracheally (ARDSp) or intraperitoneally (ARDSexp). A new dose of dasatinib or vehicle was administered at 6 and 24h. Results: Forty-eight hours after ARDS induction, dasatinib 1mg/kg yielded: improved lung morphofunction and reduced cells expressing toll-like receptor (TLR)-4 in lung, independent of ARDS etiology; reduced neutrophil and levels of interleukin (IL)-6, IL-10 and transforming growth factor (TGF)-β in ARDSp. The higher dose of dasatinib caused no changes in lung mechanics, diffuse alveolar damage, neutrophil, or cells expressing TLR4, but increased IL-6, vascular endothelial growth factor (VEGF), and cells expressing Fas receptor in lung in ARDSp. In ARDSexp, it improved lung morphofunction, increased VEGF, and reduced cells expressing TLR4. Conclusion: Dasatinib may have therapeutic potential in ARDS independent of etiology, but careful dose monitoring is required.

Prone positioning in acute respiratory distress syndrome after abdominal surgery

Prone positioning has been used for many years as an alveolar recruitment strategy in acute respiratory distress syndrome (ARDS). Prone positioning in ARDS improves oxygenation and demonstrated recently its effectiveness on prognosis. Extrapulmonary etiologies of ARDS include abdominal emergencies. In cases of severe hypoxemia in the early postoperative period, intensivists discuss prone positioning based on the risk/benefit ratio.

0427. Respiratory effects of noisy ventilation depend on the etiology of acute respiratory distress syndrome

Healthy biological systems are characterized by intrinsic variability of their function, including the respiratory system. However, during pathological conditions, as observed in acute respiratory distress syndrome (ARDS), this biological variability can be lost, and the institution of variable ventilation (noisy, VV) may lead to morphofunctional improvement compared with conventional ventilation (CV). However, it is not known if this beneficial effect is dependent on the etiology of ARDS. In pulmonary ARDS (ARDSp) there is a predominance of lung tissue consolidation, whereas extrapulmonary ARDS (ARDSexp) is associated with alveolar collapse.

Effects of Bone Marrow–Derived Mononuclear Cells From Healthy or Acute Respiratory Distress Syndrome Donors on Recipient Lung-Injured Mice

The advantage of using autologous bone marrow-derived mononuclear cells to treat acute respiratory distress syndrome patients is to prevent immunological rejection. However, bone marrow-derived mononuclear cells may be altered by different acute respiratory distress syndrome etiologies, resulting in questionable efficacy and thus limited clinical application. We aimed to investigate the effects of bone marrow-derived mononuclear cells obtained from healthy and acute respiratory distress syndrome donors on pulmonary and extrapulmonary acute respiratory distress syndrome. Prospective, randomized, controlled experimental study. University research laboratory. Two hundred and twenty-five C57BL/6 mice. Acute respiratory distress syndrome was induced by Escherichia coli lipopolysaccharide intratracheally (ARDSp) or intraperitoneally (ARDSexp). Control mice (Healthy) received saline solution intratracheally (Cp) or intraperitoneally (Cexp). After 24 hours, whole bone marrow cells were analyzed in vitro: 1) colony-forming unit-fibroblasts and 2) hematopoietic stem cells, neutrophils, T helper lymphocytes, B lymphocytes, and nonhematopoietic precursors. After cell characterization, all groups received saline or bone marrow-derived mononuclear cells (2 × 10), obtained from Cp, Cexp, ARDSp, and ARDSexp donor mice, IV, on day 1. On day 1, in ARDSp, different patterns of colony formation were found, with nonstromal cells (mainly neutrophils) predominating over fibroblastoid colonies. In ARDSexp, irregular colony-forming unit-fibroblasts morphology with dispersed proliferating colonies and a greater number of hematopoietic stem cells were observed. In ARDSp, colony-forming unit-fibroblasts count was higher but not measurable in ARDSexp. In ARDSp, monocytes and T lymphocytes were increased and hematopoietic precursor cells reduced, with no significant changes in ARDSexp. On day 7, bone marrow-derived mononuclear cells improved survival and attenuated changes in lung mechanics, alveolar collapse, inflammation, pulmonary fibrosis, and apoptosis in the lung and distal organs, regardless of donor type. Bone marrow-derived mononuclear cells from ARDSp and ARDSexp donors showed different characteristics but were as effective as cells obtained from healthy donors in reducing inflammation and remodeling, suggesting the utility of autologous transplant of bone marrow-derived mononuclear cells in the clinical setting.

Hemodynamic changes in child acute respiratory distress syndrome with airway pressure release ventilation: a case series.

Airway pressure release ventilation (APRV) is widely used in adult critical care settings. However, information on the use of APRV in the pediatric population is limited. All patients admitted to the medical-surgical pediatric intensive care unit with a diagnosis of acute respiratory distress syndrome (ARDS) who received APRV for at least 12 h between 2007 and 2009 were reviewed. Thirteen patients with a variety of etiologies of ARDS were included, with a mean weight of 18.2 ± 15.0 kg, a mean age of 68 ± 57 months and a predicted mortality (based on Pediatric Index of Mortality version 2) of 23.9 ± 13.8%. Patients were placed on APRV for a median of 4 days (range 1-10 days). There was no change in blood gas parameters after 1 h or 12 h of APRV when compared with pre-APRV. There was no statistical difference in hemodynamic parameters, including mean arterial blood pressure, central venous blood pressure and heart rate, while the patients were on APRV. APRV could be safely used in pediatric ARDS patients, without significant hemodynamic compromise or side effects.

Transforming High Risk to High Yield

Transforming High Risk to High Yield

Síndrome de Dificuldade Respiratória Aguda: Casuística de Dois Anos numa Unidade de Cuidados Intensivos

Acute Respiratory Distress Syndrome has a significant incidence and mortality at Intensive Care Units. Therefore, more studies are necessary in order to develop new effective therapeutic strategies. The authors have proposed themselves to characterize Acute Respiratory Distress Syndrome patients admitted to an Intensive Care Unit for 2 years. This was an observational retrospective study of the patients filling the Acute Respiratory Distress Syndrome criteria from the American-European Consensus Conference on ARDS, being excluded those non invasively ventilated. Demographic data, Acute Respiratory Distress Syndrome etiology, comorbidities, Gravity Indices, PaO2/FiO2, ventilator modalities and programmation, pulmonary compliance, days of invasive mechanical ventilation, corticosteroids use, rescue therapies, complications, days at Intensive Care Unit and obits were searched for and were submitted to statistic description and analysis. A 40 patients sample was obtained, with a median age of 72.5 years (interquartile range = 22) and a female:male ratio of ≈1:1.86. Fifty five percent of the Acute Respiratory Distress Syndrome cases had pulmonary etiology. The mean minimal PaO2/FiO2 was 88 mmHg (CI 95%: 78.5-97.6). The mean maximal applied PEEP was 12.4 cmH2O (Standard Deviation 4.12) and the mean maximal used tidal volume was 8.2 mL/ Kg ideal body weight (CI 95%: 7.7-8.6). The median invasive mechanical ventilation days was 10. Forty seven and one half percent of the patients had been administered corticosteroids and 52.5% had been submitted to recruitment maneuvers. The most frequent complication was Ventilator Associated Pneumonia (20%). The median Intensive Care Unit stay was 10.7 days (interquartile range 10.85). The fatality rate was 60%. The probability of the favorable outcome 'non-death in Intensive Care Unit' was 4.4x superior for patients who were administered corticosteroids and 11x superior for patients < 65 years old. Acute Respiratory Distress Syndrome is associated with long hospitalization and significant mortality. New prospective studies will be necessary to endorse the potential benefit of steroid therapy and to identify the subgroups of patients that warrant its use.

Exploring the heterogeneity of effects of corticosteroids on acute respiratory distress syndrome: a systematic review and meta-analysis

IntroductionThe effectiveness of corticosteroid therapy on the mortality of acute respiratory distress syndrome (ARDS) remains under debate. We aimed to explore the grounds for the inconsistent results in previous studies and update the evidence.MethodsWe searched MEDLINE, Cochrane Central Register of Controlled Trials and Web of Science up to December 2013. Eligible studies included randomized clinical trials (RCTs) and cohort studies that reported mortality and that had corticosteroid nonusers for comparison. The effect of corticosteroids on ARDS mortality was assessed by relative risk (RR) and risk difference (RD) for ICU, hospital, and 60-day mortality using a random-effects model.ResultsEight RCTs and 10 cohort studies were included for analysis. In RCTs, corticosteroids had a possible but statistically insignificant effect on ICU mortality (RD, −0.28; 95% confidence interval (CI), −0.53 to −0.03 and RR, 0.55; 95% CI, 0.24 to 1.25) but no effect on 60-day mortality (RD, −0.01; 95% CI, −0.12 to 0.10 and RR, 0.97; 95% CI, 0.75 to 1.26). In cohort studies, corticosteroids had no effect on ICU mortality (RR, 1.05; 95% CI, 0.74 to 1.49) but non-significantly increased 60-day mortality (RR, 1.30; 95% CI, 0.96 to 1.78). In the subgroup analysis by ARDS etiology, corticosteroids significantly increased mortality in influenza-related ARDS (three cohort studies, RR, 2.45, 95% CI, 1.40 to 4.27).ConclusionsThe effects of corticosteroids on the mortality of ARDS differed by duration of outcome measures and etiologies. Corticosteroids did not improve longer-term outcomes and may cause harm in certain subgroups. Current data do not support routine use of corticosteroids in ARDS. More clinical trials are needed to specify the favorable and unfavorable subgroups for corticosteroid therapy.

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Introduction: Acute respiratory distress syndrome (ARDS) is an important cause of respiratory failure and continues to be associated with high hospital mortality rates. Numerous therapeutic interventions have been employed to improve outcomes, including inhaled epoprostenol; however, only low tidal volume ventilation has been consistently shown to have a survival benefit. Methods: We performed a retrospective analysis of consecutive patients with ARDS treated with inhaled epoprostenol between January 1st 2004 and June 30th 2012. Hospital survivors were compared to non-survivors to identify predictors of mortality. A scoring system was then developed to predict which patients with ARDS receiving inhaled epoprostenol are more likely to survive. Results: Among the cohort (n = 216) there were 80 (37%) hospital survivors and 136 (63%) hospital non-survivors. Both baseline characteristics and process of care variables were associated with outcome. Logistic regression revealed 5 variables associated with hospital outcome: cumulative fluid balance during treatment with epoprostenol, aspiration as the etiology of ARDS, trauma as the etiology of ARDS, presence of both pulmonary and non-pulmonary sources of sepsis, and an international normalized ratio (INR) > 1.5. A scoring system was then developed as follows: etiology for ARDS other than aspiration or trauma (4 points), presence of both pulmonary and non-pulmonary sources of sepsis (3 points), cumulative fluid balance during treatment with inhaled epoprostenol > 4 liters (2 points) and INR > 1.5 (2 points). Among patients with fewer than 5 points, the hospital mortality was 37.4% compared to 81.8% for those with greater than 7 points (p < 0.001). This system had moderate predictive power at segregating survivors from non-survivors. Conclusions: While the use of inhaled epoprostenol in ARDS remains a therapeutic challenge, a simple score may facilitate more accurate identification of patients less likely to survive on inhaled epoprostenol and for whom more advanced therapies should be attempted.

Outcome of acute respiratory distress syndrome patients treated with extracorporeal membrane oxygenation and brought to a referral center

PurposePatients with severe acute respiratory distress syndrome (ARDS) are candidates for extracorporeal membrane oxygenation (ECMO) therapy. The evaluation of organ severity is difficult in patients considered for cannulation in a distant hospital. This study was designed to identify early factors associated with hospital mortality in ARDS patients treated with ECMO and retrieved from referring hospitals.MethodsData from 85 consecutive ARDS patients equipped with ECMO by our mobile team and consequently admitted to our ICU were prospectively collected and analyzed.ResultsThe main ARDS etiologies were community-acquired bacterial pneumonia (35 %), influenza pneumonia (23 %) (with 12 patients having been treated during the first half of the study period), and nosocomial pneumonia (14 %). The median (interquartile range) time between contact from the referring hospital and patient cannulation was 3 (1–4) h. ECMO was venovenous in 77 (91 %) patients. No complications occurred during transport by our mobile unit. Forty-eight patients died at the hospital (56 %). Based on a multivariate logistic regression, a score including age, SOFA score, and a diagnosis of influenza pneumonia was constructed. The probability of hospital mortality following ECMO initiation was 40 % in the 0–2 score class (n = 58) and 93 % in the 3–4 score class (n = 27). Patients with an influenza pneumonia diagnosis and a SOFA score before ECMO of less than 12 had a mortality rate of 22 %.ConclusionsAge, SOFA score, and a diagnosis of influenza may be used to accurately evaluate the risk of death in ARDS patients considered for retrieval under ECMO from distant hospitals.

The PRESERVE mortality risk score and analysis of long-term outcomes after extracorporeal membrane oxygenation for severe acute respiratory distress syndrome

PurposeThis study was designed to identify factors associated with death by 6 months post-intensive care unit (ICU) discharge and to develop a practical mortality risk score for extracorporeal membrane oxygenation (ECMO)-treated acute respiratory distress syndrome (ARDS) patients. We also assessed long-term survivors’ health-related quality of life (HRQL), respiratory symptoms, and anxiety, depression and post-traumatic stress disorder (PTSD) frequencies.MethodsData from 140 ECMO-treated ARDS patients admitted to three French ICUs (2008–2012) were analyzed. ICU survivors contacted >6 months post-ICU discharge were assessed for HRQL, psychological and PTSD status.ResultsMain ARDS etiologies were bacterial (45 %), influenza A[H1N1] (26 %) and post-operative (17 %) pneumonias. Six months post-ICU discharge, 84 (60 %) patients were still alive. Based on multivariable logistic regression analysis, the PRESERVE (PRedicting dEath for SEvere ARDS on VV-ECMO) score (0–14 points) was constructed with eight pre-ECMO parameters, i.e. age, body mass index, immunocompromised status, prone positioning, days of mechanical ventilation, sepsis-related organ failure assessment, plateau pressure andpositive end-expiratory pressure. Six-month post-ECMO initiation cumulative probabilities of survival were 97, 79, 54 and 16 % for PRESERVE classes 0–2, 3–4, 5–6 and ≥7 (p < 0.001), respectively. HRQL evaluation in 80 % of the 6-month survivors revealed satisfactory mental health but persistent physical and emotional-related difficulties, with anxiety, depression or PTSD symptoms reported, by 34, 25 or 16 %, respectively.ConclusionsThe PRESERVE score might help ICU physicians select appropriate candidates for ECMO among severe ARDS patients. Future studies should also focus on physical and psychosocial rehabilitation that could lead to improved HRQL in this population.Electronic supplementary materialThe online version of this article (doi:10.1007/s00134-013-3037-2) contains supplementary material, which is available to authorized users.

Acute respiratory distress syndrome in patients with hematological malignancies

BackgroundWe investigated the clinical course and mortality of acute respiratory distress syndrome (ARDS) in patients with hematological malignancies.MethodsSixty-eight patients with hematological malignancies and ARDS admitted to medical intensive care unit (ICU) of a university hospital were analyzed semi-prospectively in the study.ResultsThe most common etiology of ARDS was pneumonia. The ratio of partial pressure of oxygen in arterial blood to fractional concentration of inspired oxygen (PO2/FiO2) was 104 (74–165). Ten patients (15%) received non-invasive mechanical ventilation (NIV), 21 (31%) received invasive mechanical ventilation (MV), and 36 (53%) received both NIV and invasive MV. ICU mortality was 77% in the cohort. None of the variables with relevance to the underlying hematological disease was associated with mortality. The presence of two or more organ failures was the only independent risk factor for mortality (P = 0.045), whereas NIV was associated with low mortality (P = 0.001). The Kaplan–Meier curve of mortality, with respect to the type of MV support, demonstrated that NIV was associated with the lowest mortality (P < 0.001).ConclusionThe mortality of ARDS in critically ill patients with hematological malignancies is quite high. The presence of multi-organ failure is independently associated with high mortality whereas the use of NIV is independently associated with low mortality.

Acute Respiratory Distress Syndrome after Onyx Embolization of Arteriovenous Malformation

Purpose. We report a case of a 60-year-old male who underwent sequential Onyx embolizations of a cerebral arteriovenous malformation (AVM) which we implicate as the most likely etiology of subsequent acute respiratory distress syndrome (ARDS). Methods. Case report and literature review. Results. Shortly after the second Onyx embolization procedure, the patient declined from respiratory failure secondary to pulmonary edema. Clinical entities typically responsible for pulmonary edema including cardiac failure, renal failure, iatrogenic volume overload, negative-pressure pulmonary edema, and infectious etiologies were evaluated and excluded. The patient required mechanical ventilatory support for several days, delaying operative resection. The patient met clinical and radiographic criteria for ARDS. After excluding other etiologies of ARDS, we postulate that ARDS developed as a result of Onyx administration. The Onyx copolymer is dissolved in dimethyl sulfoxide (DMSO), a solvent excreted through the lungs and has been implicated in transient pulmonary side effects. Additionally, a direct toxic effect of the Onyx copolymer is postulated. Conclusion. Onyx embolization and DMSO toxicity are implicated as the etiology of ARDS given the lack of other inciting factors and the close temporal relationship. A strong physiologic rationale provides further support. Clinicians should consider this uncommon but important complication.