Mortality In Respiratory Distress Syndrome Research Articles

788: Can we achieve low tidal volume ventilation in pregnant women with acute respiratory distress syndrome?

Lung protective low-tidal volume ventilation (LTVV) has been shown to decrease mortality in Acute Respiratory Distress Syndrome (ARDS). ARDS occurs more frequently in pregnancy, yet changes in respiratory physiology during pregnancy and concern for fetal-acid base status may interfere with LTVV strategy. This study assessed use of LTVV in pregnancy and identified maternal and fetal outcomes of mechanically ventilated pregnant patients with ARDS. This is a retrospective cohort study of women with ARDS who were mechanically ventilated for greater than 24 hours between January 2012 and February 2017 at a tertiary care center. ARDS was defined clinically, and LTVV was defined as weighted daily average tidal volume ≤8 mL/kg of ideal body weight. Pregnant patients (N=23) had 128 days of ventilation, and non-pregnant patients (N=681) had 3,174 days. Demographic, pregnancy and fetal outcome data were collected on pregnant patients. Compliance with LTVV was stratified by trimester, and groups compared with chi-squared analysis. We had no maternal deaths and extracorporeal membrane oxygenation (ECMO) was used in 8.7% of patients (N=2). Causes of ARDS included sepsis, pneumonia, and asthma exacerbation. Obstetric complications occurred frequently, with 21.7% (N=5) experiencing preeclampsia, and 50.0% (N=11) delivering preterm. Mean infant birth weight was 2348g ± 14.6. There were 3 perinatal demises (2 intrauterine, 1 neonatal). In pregnant and non-pregnant patients respectively, weighted average daily tidal volume was 7.8 ml/kg ±1.2 and 7.27 ml/kg ±1.55, and overall LTVV use was 87.0% and 81.9%. LTVV was utilized in 93.3% of patients in the first, 85.1% in the second, and 71.0% in the third trimester. Use of LTVV in the third trimester was significantly less than the first and second (p=0.05). Pregnant patients with ARDS encountered significant adverse maternal and fetal outcomes, with half delivering preterm and over 20% developing preeclampsia. LTVV use was comparable between pregnant and non-pregnant patients, but was utilized more frequently in the first and second trimesters compared to the third. Given the significant morbidity seen with ARDS in pregnancy, additional multi-center studies are needed to evaluate factors associated with increased utilization of LTVV, and the effect of LTVV on maternal and fetal outcomes.

Effect of airway pressure release ventilation on mortality in pediatric severe acute respiratory distress syndrome - A retrospective comparative analysis

Background : Acute respiratory distress syndrome (ARDS) in pediatric ICU contribute to up to 75% mortality which can be up to 90% in high risk patients. Despite of much advance in different ventilation strategies mortality remains unacceptably high. This suggests the need to define the role of newer management approaches. Airway pressure release ventilation (APRV) mode is a new strategy which looks promising in ARDS as shown in studies conducted on animals and adult patients. But its benefit has not been defined in pediatric patients with severe ARDS. Methods : This research was a retrospective comparative study using data from case files. The study period (Jan 2009 to December 2015) covered three years before the initiation of use of APRV mode to three years after its implementation. The study sample included all consecutive patients with ARDS in PICU of a tertiary care hospital during the study period. Patients admitted during APRV use period received APRV after failure of routine modes of ventilation(treatment group/APRV group) and patients admitted during pre-APRV use period received and continued on other modes of ventilation (control group/Non-APRV group). As the patients in treatment group naturally had severe ARDS; we included only severe ARDS cases in control group (equal in number to treatment group) to justify comparison. Case files were reviewed and data were recorded in terms of mortality, length of ICU stay, PaO2/FiO2 (PF) Ratio, lung injury score (LIS), PELOD score and demography. These were compared in two groups based on who received versus who did not receive APRV mode. Results : A total of 24 children in each group were analysed. Baseline PELOD score, age and gender distribution were comparable in both groups. PF Ratio were 67.21±9.74 in APRV versus 91.65(8.68) in non-APRV group (p value 0.01). Improvement in PF ratio after implication of APRV was statistically significant (mean difference of 14.36; p value=0.001). Duration of PF ratio 999], p value of 0.001. The covariates which were significantly associated with mortality were baseline PF ratio and PELOD scores. Conclusion : Use of APRV mode in pediatric severe ARDS used as rescue treatment achieved improved oxygenation and was associated with lower in hospital mortality.

Macrolide therapy is associated with reduced mortality in acute respiratory distress syndrome (ARDS) patients.

Macrolides have been associated with favorable immunological effects in various inflammatory disease states. We investigated the association between macrolide therapy and mortality in patients with the acute respiratory distress syndrome (ARDS). This was an unplanned secondary analysis of patients with ARDS within a large prospective observational study of critically ill patients in the intensive care units (ICUs) of two university-affiliated hospitals in the Netherlands. The exposure of interest was low-dose macrolide use prescribed for another reason than infection; we excluded patients who received high-dose macrolides for an infection. The primary endpoint was 30-day mortality. The association between macrolide therapy and mortality was determined in the whole cohort, as well as in a propensity score matched cohort; the association was compared between pulmonary versus non-pulmonary ARDS, and between two biological phenotypes based on plasma levels of 20 biomarkers. In total, 873 patients with ARDS were analyzed, of whom 158 patients (18%) received macrolide therapy during stay in ICU for a median duration of 3 (interquartile range, 1-4) days. Erythromycin was the most frequent prescribed macrolide (97%). Macrolide therapy was associated with reduced 30-day mortality in the whole cohort [22.8% vs. 31.6%; crude odds ratio (OR), 0.64 (interquartile range, 0.43-0.96), P=0.03]. The association in the propensity score matched cohort remained significant [22.8% vs. 32.9%; OR, 0.62 (interquartile range, 0.39-0.96), P=0.03]. Propensity matched associations with mortality were different in patients with non-pulmonary ARDS vs. pulmonary ARDS and also varied by biological phenotype. These data together show that low-dose macrolide therapy prescribed for another reason than infection is associated with decreased mortality in patients with ARDS.

The impacts of baseline ventilator parameters on hospital mortality in acute respiratory distress syndrome treated with venovenous extracorporeal membrane oxygenation: a retrospective cohort study

BackgroundVenovenous extracorporeal membrane oxygenation (VV-ECMO) is a valuable life support in acute respiratory distress syndrome (ARDS) in adult patients. However, the success of VV-ECMO is known to be influenced by the baseline settings of mechanical ventilation (MV) before its institution. This study was aimed at identifying the baseline ventilator parameters which were independently associated with hospital mortality in non-trauma patients receiving VV-ECMO for severe ARDS.MethodsThis retrospective study included 106 non-trauma patients (mean age: 53 years) who received VV-ECMO for ARDS in a single medical center from 2007 to 2016. The indication of VV-ECMO was severe hypoxemia (PaO2/ FiO2 ratio < 70 mmHg) under pressure-controlled MV with peak inspiratory pressure (PIP) > 35 cmH2O, positive end-expiratory pressure (PEEP) > 5 cmH2O, and FiO2 > 0.8. Important demographic and clinical data before and during VV-ECMO were collected for analysis of hospital mortality.ResultsThe causes of ARDS were bacterial pneumonia (n = 41), viral pneumonia (n = 24), aspiration pneumonitis (n = 3), and others (n = 38). The median duration of MV before ECMO institution was 3 days and the overall hospital mortality was 53% (n = 56). The medians of PaO2/ FiO2 ratio, PIP, PEEP, and dynamic pulmonary compliance (PCdyn) at the beginning of MV were 84 mmHg, 32 cmH2O, 10 cmH2O, and 21 mL/cmH2O, respectively. However, before the beginning of VV-ECMO, the medians of PaO2/ FiO2 ratio, PIP, PEEP, and PCdyn became 69 mmHg, 36 cmH2O, 14 cmH2O, and 19 mL/cmH2O, respectively. The escalation of PIP and the declines in PaO2/ FiO2 ratio and PCdyn were significantly correlated with the duration of MV before ECMO institution. Finally, the duration of MV (OR: 1.184, 95% CI: 1.079–1.565, p < 0.001) was found to be the only baseline ventilator parameter that independently affected the hospital mortality in these ECMO-treated patients.ConclusionSince the duration of MV before ECMO institution was strongly correlated to the outcome of adult respiratory ECMO, medical centers are suggested to find a suitable prognosticating tool to determine the starting point of respiratory ECMO among their candidates with different duration of MV.Trial registrationThis study reported a health care intervention on human participants and was retrospectively registered. The Chang Gung Medical Foundation Institutional Review Board approved the study (no. 201601483B0) on November 23, 2016. All of the data were extracted from December 1, 2016, to January 31, 2017.

Low tidal volume ventilation use remains low in patients with acute respiratory distress syndrome at a single center

PurposeLow tidal volume ventilation (LTVV) reduces mortality in acute respiratory distress syndrome (ARDS) patients. Understanding local barriers to LTVV use at a former ARDS Network hospital may provide new insight to improve LTVV implementation. MethodsA cohort of 214 randomly selected adults met the Berlin definition of ARDS at Harborview Medical Center between 2008 and 2012. The primary outcome was the receipt of LTVV (tidal volume of ≤6.5mL/kg predicted body weight) within 48h of ARDS onset. We constructed a multivariable logistic regression model to identify factors associated with the outcome. ResultsOnly 27% of patients received tidal volumes of ≤6.5mL/kg PBW within 48h of ARDS onset. Increasing plateau pressure (OR 1.11; 95% CI 1.03 to 1.19; p-value<0.01) was positively associated with LTVV use while increasing PaO2:FIO2 ratio was negatively associated (OR 0.75; 95% CI 0.57 to 0.98; p-value 0.03). Physicians documented an ARDS diagnosis in only 21% of the cohort. Neither patient height nor gender was associated with LTVV use. ConclusionsMost ARDS patients did not receive LTVV despite implementation of a protocol. ARDS was also recognized in a minority of patients, suggesting an opportunity for improvement of care.

Understanding patient outcomes after acute respiratory distress syndrome: identifying subtypes of physical, cognitive and mental health outcomes

PurposeWith improving short-term mortality in acute respiratory distress syndrome (ARDS), understanding survivors’ posthospitalisation outcomes is increasingly important. However, little is known regarding associations among physical, cognitive and mental health outcomes....

Disassociating Lung Mechanics and Oxygenation in Pediatric Acute Respiratory Distress Syndrome.

Both oxygenation and peak inspiratory pressure are associated with mortality in pediatric acute respiratory distress syndrome. Since oxygenation and respiratory mechanics are linked, it is difficult to identify which variables, pressure or oxygenation, are independently associated with outcome. We aimed to determine whether respiratory mechanics (peak inspiratory pressure, positive end-expiratory pressure, ΔP [PIP minus PEEP], tidal volume, dynamic compliance [Cdyn]) or oxygenation (PaO2/FIO2) was associated with mortality. Prospective, observational, cohort study. University affiliated PICU. Mechanically ventilated children with acute respiratory distress syndrome (Berlin). None. Peak inspiratory pressure, positive end-expiratory pressure, ΔP, tidal volume, Cdyn, and PaO2/FIO2 were collected at acute respiratory distress syndrome onset and at 24 hours in 352 children between 2011 and 2016. At acute respiratory distress syndrome onset, neither mechanical variables nor PaO2/FIO2 were associated with mortality. At 24 hours, peak inspiratory pressure, positive end-expiratory pressure, ΔP were higher, and Cdyn and PaO2/FIO2 lower, in nonsurvivors. In multivariable logistic regression, PaO2/FIO2 at 24 hours and ΔPaO2/FIO2 (change in PaO2/FIO2 over the first 24 hr) were associated with mortality, whereas pressure variables were not. Both oxygenation and pressure variables were associated with duration of ventilation in multivariable competing risk regression. Improvements in oxygenation, but not in respiratory mechanics, were associated with lower mortality in pediatric acute respiratory distress syndrome. Future trials of mechanical ventilation in children should focus on oxygenation (higher PaO2/FIO2) rather than lower peak inspiratory pressure or ΔP, as oxygenation was more consistently associated with outcome.

External validation of a biomarker and clinical prediction model for hospital mortality in acute respiratory distress syndrome.

Mortality prediction in ARDS is important for prognostication and risk stratification. However, no prediction models have been independently validated. A combination of two biomarkers with age and APACHE III was superior in predicting mortality in the NHLBI ARDSNet ALVEOLI trial. We validated this prediction tool in two clinical trials and an observational cohort. The validation cohorts included 849 patients from the NHLBI ARDSNet Fluid and Catheter Treatment Trial (FACTT), 144 patients from a clinical trial of sivelestat for ARDS (STRIVE), and 545 ARDS patients from the VALID observational cohort study. To evaluate the performance of the prediction model, the area under the receiver operating characteristic curve (AUC), model discrimination, and calibration were assessed, and recalibration methods were applied. The biomarker/clinical prediction model performed well in all cohorts. Performance was better in the clinical trials with an AUC of 0.74 (95% CI 0.70-0.79) in FACTT, compared to 0.72 (95% CI 0.67-0.77) in VALID, a more heterogeneous observational cohort. The AUC was 0.73 (95% CI 0.70-0.76) when FACTT and VALID were combined. We validated a mortality prediction model for ARDS that includes age, APACHE III, surfactant protein D, and interleukin-8 in a variety of clinical settings. Although the model performance as measured by AUC was lower than in the original model derivation cohort, the biomarker/clinical model still performed well and may be useful for risk assessment for clinical trial enrollment, an issue of increasing importance as ARDS mortality declines, and better methods are needed for selection of the most severely ill patients for inclusion.

Predicted body weight relationships for protective ventilation \u2013 unisex proposals from pre-term through to adult

BackgroundThe lung-protective ventilation bundle has been shown to reduce mortality in adult acute respiratory distress syndrome (ARDS). This concept has expanded to other areas of acute adult ventilation and is recommended for pediatric ventilation. A component of lung-protective ventilation relies on a prediction of lean body weight from height. The predicted body weight (PBW) relationship employed in the ARDS Network trial is considered valid only for adults, with a dedicated formula required for each sex. No agreed PBW formula applies to smaller body sizes. This analysis investigated whether it might be practical to derive a unisex PBW formula spanning all body sizes, while retaining relevance to established adult protective ventilation practice.MethodsHistoric population-based growth charts were adopted as a reference for lean body weight, from pre-term infant through to adult median weight. The traditional ARDSNet PBW formulae acted as the reference for prevailing protective ventilation practice. Error limits for derived PBW models were relative to these references.ResultsThe ARDSNet PBW formulae typically predict weights heavier than the population median, therefore no single relationship could satisfy both references. Four alternate piecewise-linear lean body-weight predictive formulae were presented for consideration, each with different balance between the objectives.ConclusionsThe ‘PBWuf + MBW’ model is proposed as an appropriate compromise between prevailing practice and simplification, while also better representing lean adult body-weight. This model applies the ARDSNet ‘female’ formula to both adult sexes, while providing a tight fit to median body weight at smaller statures down to pre-term. The ‘PBWmf + MBW’ model retains consistency with current practice over the adult range, while adding prediction for small statures.

P241 Validation of APPS tool to predict mortality in moderate and severe acute respiratory distress syndrome

Introduction: A prediction tool that was developed by Villar et al. in Spain called ‘APPS’ tool was shown to accurately predict in-hospital mortality in moderate and severe Acute Respiratory Syndrome (ARDS) patients on lung-protective ventilation. A simple 9-point score that utilized the variables of age, PaO2/FiO2 ratio and Plateau pressure measured at 24 hours after diagnosis of ARDS divided patients into groups of low, moderate and high mortality risk. We have attempted to validate APPS tool to correlate mortality in a cohort of ARDS patients at a tertiary care hospital in the US.

Mortality in Pediatric Acute Respiratory Distress Syndrome: A Systematic Review and Meta-Analysis.

Sparse and conflicting evidence exists regarding mortality risk from pediatric acute respiratory distress syndrome (ARDS). We aimed to determine the pooled mortality in pediatric ARDS and to describe its trend over time. MEDLINE, EMBASE, and Web of Science were searched from 1960 to August 2015. Keywords or medical subject headings (MESH) terms used included "respiratory distress syndrome, adult," "acute lung injury," "acute respiratory insufficiency," "acute hypoxemic respiratory failure," "pediatrics," and "child." Study inclusion criteria were (1) pediatric patients aged 0 days to 18 years, (2) sufficient baseline data described in the pediatric ARDS group, and (3) mortality data. Randomized controlled trials (RCTs) and prospective observational studies were eligible. Data on study characteristics, patient demographics, measures of oxygenation, and mortality were extracted using a standard data extraction form. Independent authors conducted the search, applied the selection criteria, and extracted the data. Methodological quality of studies was assessed. Meta-analysis using a random-effects model was performed to obtain pooled estimates of mortality. Meta-regression was performed to analyze variables contributing to change in mortality over time. Eight RCTs and 21 observational studies (n = 2274 patients) were included. Pooled mortality rate was 24% (95% confidence interval [CI]: 19-31). There was a decrease in mortality rates over 3 epochs (≤2000, 2001-2009, and ≥2010: 40% [95% CI: 24-59], 35% [95% CI: 21-51], and 18% [95% CI: 12-26], respectively, P < .001). Observational studies reported a higher mortality rate than RCTs (27% [95% CI: 24-29] versus 16% [95% CI: 12-20], P < .001). Earlier year of publication was an independent factor associated with mortality. Overall mortality rate in pediatric ARDS is approximately 24%. Studies conducted and published later were associated with better survival.

Pediatric Acute Respiratory Distress Syndrome in Pediatric Allogeneic Hematopoietic Stem Cell Transplants: A Multicenter Study.

Immunodeficiency is both a preexisting condition and a risk factor for mortality in pediatric acute respiratory distress syndrome. We describe a series of pediatric allogeneic hematopoietic stem cell transplant patients with pediatric acute respiratory distress syndrome based on the recent Pediatric Acute Lung Injury Consensus Conference guidelines with the objective to better define survival of this population. Secondary analysis of a retrospective database. Twelve U.S. pediatric centers. Pediatric allogeneic hematopoietic stem cell transplant recipients requiring mechanical ventilation. None. During the first week of mechanical ventilation, patients were categorized as: no pediatric acute respiratory distress syndrome or mild, moderate, or severe pediatric acute respiratory distress syndrome based on oxygenation index or oxygen saturation index. Univariable logistic regression evaluated the association between pediatric acute respiratory distress syndrome and PICU mortality. A total of 91.5% of the 211 patients met criteria for pediatric acute respiratory distress syndrome using the Pediatric Acute Lung Injury Consensus Conference definition: 61.1% were severe, 27.5% moderate, and 11.4% mild. Overall survival was 39.3%. Survival decreased with worsening pediatric acute respiratory distress syndrome: no pediatric acute respiratory distress syndrome 66.7%, mild 63.6%, odds ratio = 1.1 (95% CI, 0.3-4.2; p = 0.84), moderate 52.8%, odds ratio = 1.8 (95% CI, 0.6-5.5; p = 0.31), and severe 24.6%, odds ratio = 6.1 (95% CI, 2.1-17.8; p < 0.001). Nonsurvivors were more likely to have multiple consecutive days at moderate and severe pediatric acute respiratory distress syndrome (p < 0.001). Moderate and severe patients had longer PICU length of stay (p = 0.01) and longer mechanical ventilation course (p = 0.02) when compared with those with mild or no pediatric acute respiratory distress syndrome. Nonsurvivors had a higher median maximum oxygenation index than survivors at 28.6 (interquartile range, 15.5-49.9) versus 15.0 (interquartile range, 8.4-29.6) (p < 0.0001). In this multicenter cohort, the majority of pediatric allogeneic hematopoietic stem cell transplant patients with respiratory failure met oxygenation criteria for pediatric acute respiratory distress syndrome based on the Pediatric Acute Lung Injury Consensus Conference definition within the first week of invasive mechanical ventilation. Length of invasive mechanical ventilation, length of PICU stay, and mortality increased as the severity of pediatric acute respiratory distress syndrome worsened.

Nanomedicine for the Treatment of Acute Respiratory Distress Syndrome. The 2016 ATS Bear Cage Award-winning Proposal.

After dozens of clinical trials, there are still no Food and Drug Administration-approved drugs that improve mortality in acute respiratory distress syndrome (ARDS). These poor results may be caused in part by three unique pharmacological challenges presented by ARDS: (1) Patients with ARDS are fragile because of concomitant multiple organ dysfunction, so they do not tolerate off-target side effects of drugs; (2) inhaled drug delivery is impeded by the column of proteinaceous fluid covering the injured alveoli; and (3) ARDS is heterogeneous in its underlying pathophysiology, so targeting one pathway is unlikely to improve most patients. To address these three pharmacological problems, I present the development of pulmonary endothelium-targeted liposomes (PELs). PELs are approximately 100-nm drug carriers coated with antibodies that bind to the pulmonary capillary endothelium. In model organisms, intravenously injected PELs strongly concentrate drugs in alveoli, even in animal models displaying severe, spatially heterogeneous pathology similar to severe ARDS. By concentrating drugs in inflamed alveoli, PELs solve pharmacological challenge (1) above. By being obligate intravenous medications, they solve challenge (2). Finally, because PELs can be loaded with at least three drugs, they can solve challenge (3) with combination drug therapy. My colleagues and I are currently testing PELs loaded with numerous candidate drugs in mouse models of ARDS, and we are testing drug distribution in live pigs and ex vivo human lungs. We aim to use such preclinical validation to move PELs into a partnership with industry, and then to patients.

Pulmonary Arterial Compliance in Acute Respiratory Distress Syndrome: Clinical Determinants and Association With Outcome From the Fluid and Catheter Treatment Trial Cohort.

Pulmonary vascular dysfunction is associated with adverse prognosis in patients with the acute respiratory distress syndrome; however, the prognostic impact of pulmonary arterial compliance in acute respiratory distress syndrome is not established. We performed a retrospective analysis of 363 subjects with acute respiratory distress syndrome who had complete baseline right heart catheterization data from the Fluid and Catheter Treatment Trial to test whether pulmonary arterial compliance at baseline and over the course of treatment predicted mortality. Baseline pulmonary arterial compliance (hazard ratio, 1.18 per interquartile range of 1/pulmonary arterial compliance; 95% CI, 1.02-1.37; p = 0.03) and pulmonary vascular resistance (hazard ratio, 1.28 per interquartile range; 95% CI, 1.07-1.53; p = 0.006) both modestly predicted 60-day mortality. Baseline pulmonary arterial compliance remained predictive of mortality when pulmonary vascular resistance was in the normal range (p = 0.02). Between day 0 and day 3, pulmonary arterial compliance increased in acute respiratory distress syndrome survivors and remained unchanged in nonsurvivors, whereas pulmonary vascular resistance did not change in either group. The resistance-compliance product (resistance-compliance time) increased in survivors compared with nonsurvivors, suggesting improvements in right ventricular load. Baseline measures of pulmonary arterial compliance and pulmonary vascular resistance predict mortality in acute respiratory distress syndrome, and pulmonary arterial compliance remains predictive even when pulmonary vascular resistance is normal. Pulmonary arterial compliance and right ventricular load improve over time in acute respiratory distress syndrome survivors. Future studies should assess the impact of right ventricular protective acute respiratory distress syndrome treatment on right ventricular afterload and outcome.

Association between chronic exposure to air pollution and mortality in the acute respiratory distress syndrome

The impact of chronic exposure to air pollution and outcomes in the acute respiratory distress syndrome (ARDS) is unknown. The Nationwide Inpatient Sample (NIS) from 2011 was utilized for this analysis. The NIS is a national database that captures 20% of all US in-patient hospitalizations from 47 states. Patients with ARDS who underwent mechanical ventilation from the highest 15 ozone pollution cities were compared with the rest of the country. Secondary analyses assessed outcomes of ARDS patients for ozone pollution and particulate matter pollution on a continuous scale by county of residence. A total of 8,023,590 hospital admissions from the 2011 NIS sample were analyzed. There were 93,950 patients who underwent mechanical ventilation for ARDS included in the study. Patients treated in high ozone regions had significantly higher unadjusted hospital mortality (34.9% versus 30.8%, p < 0.01) than patients in cities with control levels of ozone. After controlling for all variables in the model, treatment in a hospital located in a high ozone pollution area was associated with an increased odds of in-hospital mortality (OR 1.11, 95% CI 1.08–1.15, p < 0.01). After adjustment for all variables in the model, for each increase in ozone exposure by 0.01 ppm the OR for death was 1.07 (95% CI 1.06–1.08, p < 0.01). Similarly, for each increase in particulate matter exposure by 10 μg/m3, the OR for death was 1.08 (95% CI 1.02–1.16, p < 0.01).Chronic exposure to both ozone and particulate matter pollution is associated with higher rates of mortality in ARDS. These preliminary findings need to be confirmed by further detailed studies.

Hemodynamic effects of lung recruitment maneuvers in acute respiratory distress syndrome

BackgroundClinical trials have, so far, failed to establish clear beneficial outcomes of recruitment maneuvers (RMs) on patient mortality in acute respiratory distress syndrome (ARDS), and the effects of RMs on the cardiovascular system remain poorly understood.MethodsA computational model with highly integrated pulmonary and cardiovascular systems was configured to replicate static and dynamic cardio-pulmonary data from clinical trials. Recruitment maneuvers (RMs) were executed in 23 individual in-silico patients with varying levels of ARDS severity and initial cardiac output. Multiple clinical variables were recorded and analyzed, including arterial oxygenation, cardiac output, peripheral oxygen delivery and alveolar strain.ResultsThe maximal recruitment strategy (MRS) maneuver, which implements gradual increments of positive end expiratory pressure (PEEP) followed by PEEP titration, produced improvements in PF ratio, carbon dioxide elimination and dynamic strain in all 23 in-silico patients considered. Reduced cardiac output in the moderate and mild in silico ARDS patients produced significant drops in oxygen delivery during the RM (average decrease of 423 ml min−1 and 526 ml min−1, respectively). In the in-silico patients with severe ARDS, however, significantly improved gas-exchange led to an average increase of 89 ml min−1 in oxygen delivery during the RM, despite a simultaneous fall in cardiac output of more than 3 l min−1 on average. Post RM increases in oxygen delivery were observed only for the in silico patients with severe ARDS. In patients with high baseline cardiac outputs (>6.5 l min−1), oxygen delivery never fell below 700 ml min−1.ConclusionsOur results support the hypothesis that patients with severe ARDS and significant numbers of alveolar units available for recruitment may benefit more from RMs. Our results also indicate that a higher than normal initial cardiac output may provide protection against the potentially negative effects of high intrathoracic pressures associated with RMs on cardiac function. Results from in silico patients with mild or moderate ARDS suggest that the detrimental effects of RMs on cardiac output can potentially outweigh the positive effects of alveolar recruitment on oxygenation, resulting in overall reductions in tissue oxygen delivery.

Dynamic driving pressure associated mortality in acute respiratory distress syndrome with extracorporeal membrane oxygenation

BackgroundThe survival predictors and optimal mechanical ventilator settings in patients with severe acute respiratory distress syndrome (ARDS) undergoing extracorporeal membrane oxygenation (ECMO) are uncertain. This study was designed to investigate the influences of clinical variables and mechanical ventilation settings on the outcomes for severe ARDS patients receiving ECMO.MethodsWe reviewed severe ARDS patients who received ECMO due to refractory hypoxemia from May 2006 to October 2015. Serial mechanical ventilator settings before and after ECMO and factors associated with survival were analyzed.ResultsA total of 158 severe ARDS patients received ECMO were finally analyzed. Overall intensive care unit (ICU) mortality was 55.1%. After ECMO initiation, tidal volume, peak inspiratory pressure and dynamic driving pressure were decreased, while positive end-expiratory pressure levels were relative maintained. After ECMO initiation, nonsurvivors had significantly higher dynamic driving pressure until day 7 than survivors. Cox proportional hazards regression model revealed that immunocompromised [hazard ratio 1.957; 95% confidence interval (CI) 1.216–3.147; p = 0.006], Acute Physiology and Chronic Health Evaluation (APACHE) II score (hazard ratio 1.039; 95% CI 1.005–1.073; p = 0.023), ARDS duration before ECMO (hazard ratio 1.002; 95% CI 1.000–1.003; p = 0.029) and mean dynamic driving pressure from day 1 to 3 on ECMO (hazard ratio 1.070; 95% CI 1.026–1.116; p = 0.002) were independently associated with ICU mortality.ConclusionsFor severe ARDS patients receiving ECMO, immunocompromised status, APACHE II score and the duration of ARDS before ECMO initiation were significantly associated with ICU survival. Higher dynamic driving pressure during first 3 days of ECMO support was also independently associated with increased ICU mortality.

Circulating Activated Protein C in Thrombophilia Carriers

Background: Inherited thrombophilias are genetic disorders in which mutation carriers have an elevated risk of venous thromboembolism through abnormalities in the coagulation cascade. These abnormalities all lead to increased thrombin generation. The mutations, of which factor V Leiden and prothrombin G20210A are the most common, therefore likely increase thrombin mediated protein C activation in plasma. Previous findings have however been inconsistent.Increased activation of protein C in inherited thrombophilia would be interesting in light of various unexplained phenotypes described in thrombophilia carriers. Examples of such phenotypes include improved fertility, increased risk of miscarriage, protection from diabetic nephropathy, decreased susceptibility to and mortality from sepsis and decreased mortality in acute respiratory distress syndrome. These do not appear directly related to increased coagulation in carriers.Activated protein C (APC) possesses a wide range of signaling functions and interactions with multiple pathways. These result in anti-apoptotic, anti-inflammatory, gene-expression, regenerative and endothelial stabilizing effects. Such properties can easily be thought to play a role in the above described phenotypes. APC has indeed been shown to possess beneficial properties in numerous animal injury models. Due to its pleiotropic nature, APC might be a promising candidate for further research into the unexplained phenotypes observed in inherited thrombophilia.Aim: To investigate if plasma APC concentrations are higher in thrombophilia carriers as compared to non-carriers.Methods: We performed a cross-sectional observational study comparing the APC plasma levels of factor V Leiden and prothrombin G20210A mutation hetero- and homozygotes with non-carriers. Exclusion criteria comprised use of anticoagulant medication and recent venous thrombosis or risk factors for venous thrombosis. We measured APC using a recently developed highly sensitive oligonucleotide-based capture assay, with a limit of detection of 0.022 ng/ml and the ability to quantify APC upward of 0.116 ng/ml (lower limit of quantification) (Müller et al., 2012). In addition we determined APC-protein C inhibitor complex (APC-PCI) as a secondary measure of protein C activation, and prothrombin fragment 1+2 (F1+2) concentration as a measure of thrombin generation using immunoassays. Parametric and non-parametric descriptive and inferential statistics were applied as appropriate.Results: We included 19 thrombophilia carriers and 18 non-carriers (Table 1). APC was detectable in 47% of carriers and in 39% of non-carriers (p = 0.74). APC was above the lower limit of quantification in only 19% of all subjects, with no difference between the groups (Figure 1). The median APC-PCI concentration in carriers and non-carriers were 5 AU (IQR 3.5-10.5) vs. 5 AU (IQR 3.0-8.0) (p = 0.338); and mean F1+2 concentrations were 266 pmol/L and 194 pmol/L in carriers and non-carriers respectively (p = 0.075).Discussion: We did not find increased circulating APC concentrations in thrombophilia carriers. Given the low number of subjects with quantifiable APC in the study, elevated APC levels in carriers versus non-carriers cannot be fully excluded. Local elevation at the site of thrombin formation still seems plausible, and our data do show a trend towards increased thrombin generation in thrombophilia carriers. However, we also show that systemic concentrations are generally below 0.116 ng/ml, which is an order of magnitude lower than concentrations previously reported as physiological levels. A prominent role for APC in non-coagulation related thrombophilia phenotypes might therefore be questioned.ReferencesMüller, J. et al. (2012). Journal of Thrombosis and Haemostasis: JTH, 10(3), 390-8. [Display omitted] [Display omitted] DisclosuresMiddeldorp:Boehringer Ingelheim: Consultancy; GSK: Consultancy, Honoraria; Aspen: Consultancy, Honoraria; BMS/Pfizer: Consultancy, Honoraria; Bayer: Consultancy; Daiichi Sankyo: Consultancy, Honoraria; Sanquin: Consultancy.

PaO2/FiO2 Deterioration During Stable Extracorporeal Membrane Oxygenation Associates With Protracted Recovery and Increased Mortality in Severe Acute Respiratory Distress Syndrome

During extracorporeal membrane oxygenation (ECMO), arterial oxygen partial pressure to fractional inspired oxygen (PaO2/FiO2; PF ratio reflects native and artificial lung blood oxygenation). In this study we analyzed PF ratio during ECMO support and its association with clinical outcome. This was a single-center observational study ofadult patients (n= 81) undergoing veno-venous ECMO support for severe acute respiratory distress syndrome. In 37 patients (46%) PF ratio decreased from ECMO-day 1 to ECMO-day 7 (PF ratio deterioration [PF-d];-37 ± 6.1 mm Hg), whereas in 44 patients PF ratio improved (PF-i; 65 ± 10.8 mm Hg). PF-d group required prolonged ECMO (median 21 days [interquartile range (IQR)]:14-35 days] versus 13 days [IQR: 10-20 days]) and invasive mechanical ventilation (median 33 days [IQR: 24-52 days] versus 26 days [IQR: 22-34 days]), longer intensive care unit (median 44 days [IQR: 32-74 days] versus 30 days [IQR: 25-47 days]), and hospital (median 66 days [IQR: 39-95 days] versus 36 days [IQR: 28-54 days]) lengths of stay, with higher hospital mortality rates (48.7% versus 22.7%). ECMO oxygenation did notexplain PF ratio variation that remained stable in PF-d and decreased in PF-i (198 ± 12.7 mL/min versus 171± 8.8 mL/min). Pre-ECMO PF ratio, neuromuscular blockade, and prone position, as well as ventilatory variables did not differ between groups. The PF-d group was older (49 ± 2.1 years versus 41 ± 1.8 years) and presented lower Respiratory Extracorporeal Membrane Oxygenation Survival Prediction (RESP) scores (0.57 ± 0.63 versus 2.2 ± 0.52). With the use of logistic regression, PF ratio variation remained an independent predictor of hospital mortality after adjusting for age or RESP score. In severe acute respiratory distress syndrome, PF ratio deterioration during stable ECMO associates with protracted recovery and increased mortality, not accounted for by patient baseline characteristics, acute respiratory distress syndrome severity, or pre-ECMO management.

Early detection of right ventricular dysfunction using transthoracic echocardiography in ARDS: a more objective approach.

Right ventricular (RV) dysfunction is an independent predictor of morbidity and mortality in acute respiratory distress syndrome (ARDS). Our goal was to describe morphologic changes in the RV using objective measures on transthoracic echocardiography (TTE) that occur following ARDS. We retrospectively measured changes in the following RV parameters from a pre-ARDS TTE to an ARDS TTE: tricuspid annular plane systolic excursion (TAPSE), myocardial performance index (MPI), fractional area change (FAC), systolic pulmonary artery pressure (SPAP), peak tricuspid regurgitant (TR) velocity, and septal shift. Over 24months, 14 patients met inclusion/exclusion criteria. Mean TAPSE decreased from 22.4mm pre-ARDS to 16.3mm during ARDS, P<.001. Mean MPI increased from 0.19 to 0.38, P=.001. Mean FAC decreased from 60.8% to 41.2%, P=.003. Peak TR velocity increased from 2.67m/s pre-ARDS to 3.31m/s during ARDS, P=.02. SPAP and septal shift demonstrated trends but not statistically different between pre-ARDS and ARDS states. TAPSE correlated with ARDS severity (PaO2 /FiO2 ratios), P=.004, and was lower among 30-day nonsurvivors compared with survivors, P=.002. Mild RV dysfunction is common after ARDS onset. RV morphologic changes coupled with dysfunction can be detected noninvasively through TTE changes with TAPSE, MPI, and FAC. Mild RV dysfunction by TAPSE is associated with ARDS severity and mortality.