Meeting Acute Respiratory Distress Syndrome Criteria Research Articles

Exploration of COVID-19 associated bradycardia using heart rate variability analysis in a case-control study of ARDS patients

BackgroundBradycardia and dysautonomia observed during SARS-Cov2 infection suggests involvement of the autonomic nervous system (ANS). Limited data exists on ANS dysregulation and its association with outcomes in patients with acute respiratory distress syndrome (ARDS) related to COVID-19 (C-ARDS) or other etiologies (NC-ARDS). ObjectivesWe aimed to explore sympathovagal balance, assessed by heart rate variability (HRV), and its clinical prognostic value in C-ARDS compared with NC-ARDS. MethodsA single-center, prospective case-control study was conducted. Consecutive patients meeting ARDS criteria between 2020 and 2022 were included. HRV was assessed using 1-hour electrographic tracing during a stable, daytime period. ResultsTwenty-four patients with C-ARDS and 19 with NC-ARDS were included. Age, sex and ARDS severity were similar between groups. The median heart rate was markedly lower in the C-ARDS group than in the NC-ARDS group (60 [53–72] versus 101 [91–112] bpm, p<.001). Most of HRV parameters were significantly increased in patients with C-ARDS. HRV correlated with heart rate only in patients with C-ARDS. A positive correlation was found between the low-to high-frequency ratio (LF/HF) and length of intensive care unit stay (r = 0.576, p<.001). ConclusionThis study confirmed that C-ARDS was associated with marked bradycardia and severe ANS impairment, suggesting a sympathovagal imbalance with vagal overtone. Poor outcomes appeared to be more related to sympathetic rather than parasympathetic hyperactivation.

28: BIOMARKER-BASED RISK STRATIFICATION IN PEDIATRIC SEPSIS FROM A LOW-MIDDLE-INCOME COUNTRY

Introduction: Most biomarker studies of sepsis and acute respiratory distress syndrome (ARDS) originate from high-income countries per World Bank classification, whereas mortality risk is higher in low- and middle-income countries. In children, the second iteration of the Pediatric Sepsis Biomarker Risk Model (PERSEVERE-II) has been validated in multiple North American pediatric intensive care units (PICUs) for prognosis, with areas under the receiver operating characteristic (AUROC) curve of > 0.80 for discriminating 28-day mortality. Given differences in epidemiology, we assessed the performance of PERSEVERE-II in septic children from Pakistan, a low-middle income country, as well as the utility of other select biomarkers. Methods: This was a prospective cohort study of children (age < 18 years) from Aga Khan University Hospital (AKUH) meeting modified pediatric Sepsis-3 criteria (pSOFA ≥ 2 and lactate > 2) between 11/2020 and 2/2022. Plasma was collected < 24 hours of PICU admission and biomarkers measured via single- and multiplex ELISAs. The AUROC for PERSEVERE-II to discriminate 28-day mortality was determined. Additional biomarkers were compared between PERSEVERE-II risk strata (low, medium, and high mortality risk), between survivors and non-survivors, and between those with and without ARDS. Projecting 15% mortality, 73 subjects were needed to detect AUROC > 0.80 at α = 0.05 and power = 0.90. Results: We enrolled 86 subjects with 20 (23%) 28-day non-survivors. PERSEVERE-II discriminated mortality with an AUROC of 0.83 (95% CI 0.72 to 0.94). Non-survivors had higher plasma angiopoietin-2 (ANG2), soluble thrombomodulin (sTM), and plasminogen activator inhibitor 1 (PAI1; all rank-sum p < 0.05), with increasing ANG2 across worsening PERSEVERE-II risk strata. Children who met ARDS criteria within 96 hours had elevated soluble receptor for advanced glycation end-products (sRAGE) and surfactant protein D (SPD; both rank-sum p < 0.05). Conclusions: PERSEVERE-II performs well in septic children from AKUH, representing the first validation of PERSEVERE-II in a low-middle income country. ANG2, sTM, and PAI1 were elevated in non-survivors, and sRAGE and SPD elevated in subjects with ARDS, suggesting a biomarker profile comparable to that of adult and pediatric sepsis and ARDS from high income countries.

Clinical characteristics, respiratory management, and determinants of oxygenation in COVID-19 ARDS: A prospective cohort study.

PurposeTo identify determinants of oxygenation over time in patients with COVID-19 acute respiratory distress syndrome (ARDS); and to analyze their characteristics according to Berlin definition categories.Materials and methodsProspective cohort study including consecutive mechanically ventilated patients admitted between 3/20/2020–10/31/2020 with ARDS. Epidemiological and clinical data on admission; outcomes; ventilation, respiratory mechanics and oxygenation variables were registered on days 1, 3 and 7 for the entire population and for ARDS categories.Results1525 patients aged 61 ± 13, 69% male, met ARDS criteria; most frequent comorbidities were obesity, hypertension, diabetes and respiratory disease. On admission, 331(21%), 849(56%) and 345(23%) patients had mild, moderate and severe ARDS; all received lung-protective ventilation (mean tidal volumes between 6.3 and 6.7 mL/kg PBW) and intermediate PEEP levels (10–11 cmH2O). PaO2/FiO2, plateau pressure, static compliance, driving pressure, ventilation ratio, pH and D-dimer >2 mg/L remained significantly different among the ARDS categories over time. In-hospital mortality was, respectively, 55%, 58% and 70% (p < 0.000). Independent predictors of changes of PaO2/FiO2 over time were BMI; preexistent respiratory disease; D-dimer >2 mg/L; day 1-PEEP, and day 1-ventilatory ratio.ConclusionHypoxemia in patients with COVID-19-related ARDS is associated with comorbidities, deadspace and activated coagulation markers, and disease severity—reflected by the PEEP level required.

Hyperoxaemia and hypoxaemia are associated with harm in patients with ARDS

BackgroundOxygen therapy is routinely administered to mechanically ventilated patients. However, there remains uncertainty about the optimal oxygen titration target in patients with the acute respiratory distress syndrome (ARDS).MethodsProspectively identified adult patients meeting the Berlin definition of ARDS between 1st January 2014 and 13th December 2016 were analyzed. Oxygen exposure variables were collected at 6-hourly intervals. The primary exposure was the average time-weighted partial pressure of arterial oxygen (PaO2) calculated over a maximum of 7 days from meeting ARDS criteria. The primary outcome was ICU mortality. Univariable and multivariable logistic regression analyses were performed to assess the impact of exposure variables on clinical outcomes. Results are presented as odds ratio [95% confidence interval].Results202 patients were included in the final analysis. Overall ICU mortality was 31%. The average time-weighted PaO2 during the first 7 days of ARDS was similar between non-survivors and survivors (11.3 kPa [10.2, 12.5] (84.8 mmHg [76.5, 93.8]) vs. 11.9 kPa [10.9, 12.6] (89.3 mmHg [81.8, 94.5]); p = 0.08). In univariable and multivariable analysis, average time-weighted PaO2 demonstrated a U-shaped relationship with ICU mortality. There was a similar relationship identified with hospital mortality.ConclusionsIn patients with ARDS, the predicted probability of both ICU and hospital mortality was lowest when the average time-weighted PaO2 was between 12.5 and 14 kPa (93.8–105.0 mmHg), suggesting this is a reasonable oxygenation target for clinicians to aim for.

A Quick Review on the Multisystem Effects of Prone Position in Acute Respiratory Distress Syndrome (ARDS) Including COVID-19.

Objective:The purpose of this review is to highlight the multisystem effects of prone position in ARDS patients with a focus on current findings regarding its use in COVID-19 patients.Methods:Two reviewers comprehensively searched PubMed database for literature regarding pathophysiology and efficacy of prone position in ARDS patients as well as specific data regarding this approach in COVID-19 patients.Conclusion:Prone positioning is well-documented to improve oxygenation and cardiac function in ARDS patients and might confer increased survival, with benefits that outweigh risks such as facial edema, endotracheal tube displacement, and intraabdominal organ dysfunction in obese patients. Severe COVID-19 pneumonia, while meeting ARDS criteria, differs from typical ARDS in several ways. Data would suggest that advantages of prone position would become limited after significant disease progression and fibrosis. The use of this technique in COVID-19 requires prolonged sessions that are unprecedented in the treatment of ARDS patients. New data regarding COVID-19 pathophysiology and patients continues to evolve daily. More frequently, patients are proned while maintaining spontaneous breathing—the results of this intervention are an area for future studies. There is more to learn about the appropriate use of prone position in COVID-19 patients. The multisystem risks and benefits require clinicians to adopt a patient centered decision-making algorithm when employing this technique in COVID-19 patients.Level of evidence:NA

COVID-19 and Acute Respiratory Distress Syndrome. Impact of corticosteroid treatment and predictors of poor outcome.

ABSTRACTObjectivesTo assess the impact of corticosteroids on inflammatory and respiratory parameters of patients with COVID-19 and acute respiratory distress syndrome (ARDS).MethodsLongitudinal, retrospective, observational study conducted in an ICU of a second level hospital. Adult patients with COVID-19 were included. Baseline characteristics, data on SARS-CoV-2 infection, treatment received, evolution of respiratory and inflammatory parameters, and ICU and hospital stay and mortality were analyzed.ResultsA total of 27 patients were included, 63% men, median age: 68.4 (51.8, 72.2) years. All patients met ARDS criteria and received MV and corticosteroids. After corticosteroids treatment we observed a reduction in the O2 A-a gradient [day 0: 322 (249, 425); day 3: 169 (129.5, 239.5) p<0.001; day 5: 144 (127.5, 228.0) p<0.001; day 7: 192 (120, 261) p=0.002] and an increase in the pO2/FiO2 ratio on days 3 and 5, but not on day 7 [day 0: 129 (100, 168); day 3: 193 (140, 236) p=0.002; day 5: 183 (141, 255) p=0.004; day 7: 170 (116, 251) p=0.057]. CRP also decreased on days 3 and 5 and increased again on day 7 [day 0: 16 (8.6, 24); day 3: 3.4 (1.7, 10.2) p<0.001; day 5: 4.1 (1.4, 10.2) p<0.001; day 7: 13.5 (6.8, 17.3) p=0.063]. Persistence of moderate ARDS on day 7 was related to a greater risk of poor outcome (OR 6.417 [1.091-37.735], p=0.040)ConclusionCorticosteroids appears to reduce the inflammation and temporarily improve the oxygenation in COVID-19 and ARDS patients. Persistence of ARDS after 7 days treatment is a predictor of poor outcome.

Clinical Significance of Timing of Intubation in Critically Ill Patients with COVID-19: A Multi-Center Retrospective Study.

The effect of intubation timing on the prognosis of critically ill patients with coronavirus 2019 (COVID-19) is not yet well understood. We investigated whether early intubation is associated with the survival of COVID-19 patients with acute respiratory distress syndrome (ARDS). This multicenter, retrospective, observational study was done on 47 adult COVID-19 patients with ARDS who were admitted to the intensive care unit (ICU) in Daegu, Korea between February 17 and April 23, 2020. Clinical characteristics and in-hospital mortality were compared between the early intubation and initially non-intubated groups, and between the early and late intubation groups, respectively. Of the 47 patients studied, 23 (48.9%) were intubated on the day of meeting ARDS criteria (early intubation), while 24 (51.1%) were not initially intubated. Eight patients were never intubated during the in-hospital course. Median follow-up duration was 46 days, and 21 patients (44.7%) died in the hospital. No significant difference in in-hospital mortality rate was noted between the early group and initially non-intubated groups (56.5% vs. 33.3%, p = 0.110). Furthermore, the risk of in-hospital death in the early intubation group was not significantly different compared to the initially non-intubated group on multivariate adjusted analysis (p = 0.385). Results were similar between early and late intubation in the subgroup analysis of 39 patients treated with mechanical ventilation. In conclusion, in this study of critically ill COVID-19 patients with ARDS, early intubation was not associated with improved survival. This result may help in the efficient allocation of limited medical resources, such as ventilators.

Etiologies, diagnostic work-up and outcomes of acute respiratory distress syndrome with no common risk factor: a prospective multicenter study

BackgroundPatients meeting the Berlin definition for the acute respiratory distress syndrome (ARDS) might lack exposure to one or more “common” risk factors and exhibit different clinical phenotype and outcomes. We aimed to compare the clinical presentation and outcome of ARDS patients with or without risk factors, the impact on hospital mortality, and to assess the diagnostic work-up performed. The current study is an ancillary analysis of an international, multicenter, prospective cohort study (the Large Observational Study to Understand the Global Impact of Severe Acute Respiratory Failure, LUNG SAFE). Patients meeting ARDS criteria within 2 days of acute hypoxemic respiratory failure onset were included in the study and categorized as having risk factors or not. Outcomes were compared using propensity score matching.ResultsAmong 2813 patients, 234 (8.3% [7.3–9.3]) had no ARDS risk factor identified. These were older, had more frequent chronic diseases and presented with less severe SOFA and non-pulmonary SOFA scores (p < 0.001). Compared to other ARDS, CT scan (32.1 vs 23.9%, p < 0.001) and open lung biopsy (2.6 vs 0.2%, p < 0.001) were slightly more frequent but left heart filling pressures assessment was not (69.4 vs 68.4%, p > 0.99). Among ARDS with no risk factor, 45 patients (19.2%) had a specific diagnosis made. As compared to others, patients having ARDS with no risk factor had a lower ICU but not hospital mortality (34.6 vs 40.0%; p = 0.12). A matched cohort analysis confirmed the lack of significant difference in mortality.ConclusionEight percent of ARDS patients have no identified risk factor, 80% of whom have no etiological diagnosis made. The outcome of ARDS with no risk factor was comparable to other ARDS but few had a comprehensive diagnostic work-up, potentially leading to missed curable diseases.Trial registration clinicaltrials.gov Identifier: NCT02010073

National survey of outcomes and practices in acute respiratory distress syndrome in Singapore.

IntroductionIn the past 20 years, our understanding of acute respiratory distress syndrome (ARDS) management has improved, but the worldwide incidence and current outcomes are unclear. The reported incidence is highly variable, and no studies specifically characterise ARDS epidemiology in Asia. This observation study aims to determine the incidence, mortality and management practices of ARDS in a high income South East Asian country.MethodsWe conducted a prospective, population based observational study in 6 public hospitals. During a one month period, we identified all ARDS patients admitted to public hospital intensive care units (ICU) in Singapore, according to the Berlin definition. Demographic information, clinical management data and ICU outcome data was collected.ResultsA total of 904 adult patients were admitted to ICU during the study period and 15 patients met ARDS criteria. The unadjusted incidence of ARDS was 4.5 cases per 100,000 population, accounting for 1.25% of all ICU patients. Most patients were male (75%), Chinese (62%), had pneumonia (73%), and were admitted to a Medical ICU (56%). Management strategies varied across all ICUs. In-hospital mortality was 40% and median length of ICU stay was 7 days.ConclusionThe incidence of ARDS in a developed S.E Asia country is comparable to reported rates in European studies.

Hydrocortisone treatment in early sepsis-associated acute respiratory distress syndrome: results of a randomized controlled trial.

BackgroundAuthors of recent meta-analyses have reported that prolonged glucocorticoid treatment is associated with significant improvements in patients with severe pneumonia or acute respiratory distress syndrome (ARDS) of multifactorial etiology. A prospective randomized trial limited to patients with sepsis-associated ARDS is lacking. The objective of our study was to evaluate the efficacy of hydrocortisone treatment in sepsis-associated ARDS.MethodsIn this double-blind, single-center (Siriraj Hospital, Bangkok), randomized, placebo-controlled trial, we recruited adult patients with severe sepsis within 12 h of their meeting ARDS criteria. Patients were randomly assigned (1:1 ratio) to receive either hydrocortisone 50 mg every 6 h or placebo. The primary endpoint was 28-day all-cause mortality; secondary endpoints included survival without organ support on day 28.ResultsOver the course of 4 years, 197 patients were randomized to either hydrocortisone (n = 98) or placebo (n = 99) and were included in this intention-to-treat analysis. The treatment group had significant improvement in the ratio of partial pressure of oxygen in arterial blood to fraction of inspired oxygen and lung injury score (p = 0.01), and similar timing to removal of vital organ support (HR 0.74, 95 % CI 0.51–1.07; p = 0.107). After adjustment for significant covariates, day 28 survival was similar for the whole group (HR 0.80, 95 % CI 0.46–1.41; p = 0.44) and for the larger subgroup (n = 126) with Acute Physiology and Chronic Health Evaluation II score <25 (HR 0.57, 95 % CI 0.24–1.36; p = 0.20). With the exception of hyperglycemia (80.6 % vs. 67.7 %; p = 0.04), the rate of adverse events was similar. Hyperglycemia had no impact on outcome.ConclusionsIn sepsis-associated ARDS, hydrocortisone treatment was associated with a significant improvement in pulmonary physiology, but without a significant survival benefit.Trial registrationClinicalTrials.gov identifier NCT01284452. Registered on 18 January 2011.

Ventilation practices in subarachnoid hemorrhage: a cohort study exploring the use of lung protective ventilation.

Acute respiratory distress syndrome (ARDS) is common following aneurysmal subarachnoid hemorrhage (SAH), but the influence of mechanical ventilator settings on its development is unclear. We sought to determine adherence to lung protective thresholds in ventilated patients with SAH and describe the association between ventilator settings and subsequent development of ARDS. We conducted a retrospective cohort study of consecutive patients receiving mechanical ventilation within 72 h of SAH at a single academic center. Ventilator settings and blood gas data were collected twice daily for the first 7 days of ventilation along with ICU and hospital outcomes. Lung protective ventilation was defined as follows: tidal volume ≤8 mL/kg of predicted body weight, positive end-expiratory pressure (PEEP) ≥5 cm H(2)O, and peak or plateau pressure ≤30 cm H(2)O. The development of ARDS was ascertained retrospectively by PaO(2)/FiO(2) ≤300 with new bilateral lung opacities on chest X-ray within one day of hypoxemia. We identified 62 patients who underwent early mechanical ventilation following SAH. PS and Continuous Positive Airway Pressure were common ventilator modes with a median tidal volume of 7.8 mL/kg [interquartile range 6.8-8.8], median peak pressure of 14 cm H(2)O [IQR 12-17], and median PEEP of 5 cm H(2)O [IQR 5-6]. Adherence to tidal volumes ≤8 mL/kg was seen in 64 % of all observations and peak pressures <30 cm H(2)O were 94 % of all observations. All three lung protective criteria were seen in 58 % of all observations. Thirty-one patients (50 %) were determined to have ARDS. ARDS patients were more frequently ventilated with a peak pressure >30 cm H(2)O (11.3 % of ARDS ventilation days vs. 0 % of non-ARDS ventilation days; p < 0.01). Initial tidal volume was not associated with subsequent development of ARDS in univariate (p = 0.6) or multivariate analysis (p = 0.49). Only the number of ARDS risk factors was independently associated with the development of ARDS (Adjusted Odds Ratio 2.8 per additional risk factor [95 % CI 1.2-6.5]). Patients with SAH requiring mechanical ventilation frequently breathe spontaneously, generating tidal volumes above usual protective thresholds regardless of meeting ARDS criteria. In patients with SAH, the presence of an additional ARDS risk factor should prompt close screening for the development of ARDS and consideration of adjustment of ventilator settings to meet lung protective thresholds.

EARLY AIRWAY PRESSURE RELEASE VENTILATION PREVENTS ARDS—A NOVEL PREVENTIVE APPROACH TO LUNG INJURY

Acute respiratory distress syndrome (ARDS) afflicts 200,000 patients annually with a mortality rate of 30% to 60% despite wide use of low tidal volume (LTV) ventilation, the present standard of care. High-permeability alveolar edema and instability occur early in the development of ARDS, before clinical signs of lung injury, and represent potential targets for therapy. We hypothesize that early application of a protective ventilation strategy (airway pressure release ventilation [APRV]) will stabilize alveoli and reduce alveolar edema, preventing the development of ARDS. Yorkshire pigs (30-40 kg) were anesthetized and subjected to two-hit injury: (a) intestinal ischemia-reperfusion, (b) peritoneal sepsis, or sham surgery. Following surgery, pigs were randomized into APRV (n = 4), according to current published guidelines for APRV; LTV ventilation (n = 3), using the current published ARDS Network guidelines (6 mL/kg); or sham (n = 5). The clinical care of all pigs was administered per the Surviving Sepsis Campaign guidelines. Animals were killed, and necropsy performed at 48 h. Arterial blood gases were measured to assess for the development of clinical lung injury. Lung tissue epithelial cadherin (E-cadherin) was measured to assess alveolar permeability. Bronchoalveolar lavage fluid (BALF) surfactant protein A was measured to assess alveolar stability. Lung edema content and histopathology were analyzed at 48 h. Airway pressure release ventilation pigs did not develop ARDS. In contrast, pigs in the LTV ventilation met ARDS criteria (PaO2/FIO2 ratio) (APRV: baseline = 471 ± 16; 48 h = 392 ± 8; vs. LTV ventilation: baseline = 551 ± 28; 48 h = 138 ± 88; P < 0.001). Airway pressure release ventilation preserved alveolar epithelial integrity demonstrated by higher levels of E-cadherin in lung tissue as compared with LTV ventilation (P < 0.05). Surfactant protein A levels were higher in BALF from the APRV group, suggesting APRV preserved alveolar stability. Quantitative histologic scoring showed improvements in all stigmata of ARDS in the APRV group versus the LTV ventilation (P < 0.05). Airway pressure release ventilation had significantly lower lung edema (wet-dry weight) than LTV ventilation (P < 0.05). Protective ventilation with APRV immediately following injury prevents development of ARDS. Reduction in lung edema, preservation of lung E-cadherin, and surfactant protein A abundance in BALF suggest that APRV attenuates lung permeability, edema, and surfactant degradation. Protective ventilation could change the clinical paradigm from supportive care for ARDS with LTV ventilation to preventing development of ARDS with APRV.

59 The Pediatric Alien Study: Incidence and Outcome of the Acute Respiratory Distress Syndrome in Children

IntroductionThe incidence and outcome of the acute respiratory distress syndrome (ARDS) in children is not well known, especially under current ventilatory practices. The goal of this study was to determine...

The ALIEN study: incidence and outcome of acute respiratory distress syndrome in the era of lung protective ventilation

While our understanding of the pathogenesis and management of acute respiratory distress syndrome (ARDS) has improved over the past decade, estimates of its incidence have been controversial. The goal of this study was to examine ARDS incidence and outcome under current lung protective ventilatory support practices before and after the diagnosis of ARDS. This was a 1-year prospective, multicenter, observational study in 13 geographical areas of Spain (serving a population of 3.55 million at least 18years of age) between November 2008 and October 2009. Subjects comprised all consecutive patients meeting American-European Consensus Criteria for ARDS. Data on ventilatory management, gas exchange, hemodynamics, and organ dysfunction were collected. A total of 255 mechanically ventilated patients fulfilled the ARDS definition, representing an incidence of 7.2/100,000population/year. Pneumonia and sepsis were the most common causes of ARDS. At the time of meeting ARDS criteria, mean PaO(2)/FiO(2) was 114±40mmHg, mean tidal volume was 7.2±1.1ml/kg predicted body weight, mean plateau pressure was 26±5cmH(2)O, and mean positive end-expiratory pressure (PEEP) was 9.3±2.4cmH(2)O. Overall ARDS intensive care unit (ICU) and hospital mortality was 42.7% (95%CI 37.7-47.8) and 47.8% (95%CI 42.8-53.0), respectively. This is the first study to prospectively estimate the ARDS incidence during the routine application of lung protective ventilation. Our findings support previous estimates in Europe and are an order of magnitude lower than those reported in the USA and Australia. Despite use of lung protective ventilation, overall ICU and hospital mortality of ARDS patients is still higher than 40%.

Optimal duration of a sustained inflation recruitment maneuver in ARDS patients

To measure the dynamics of recruitment and the hemodynamic status during a sustained inflation recruitment maneuver (RM) in order to determine the optimal duration of RM in acute respiratory distress syndrome (ARDS) patients. This prospective study was conducted in a 12-bed intensive care unit (ICU) in a general hospital. A 40cmH(2)O sustained inflation RM maintained for 30s was performed in 50 sedated ventilated patients within the first 24h of meeting ARDS criteria. Invasive arterial pressures, heart rate, and SpO(2) were measured at 10-s intervals during the RM. The volume increase during the RM was measured by integration of the flow required to maintain the pressure at 40cmH(2)O, which provides an estimation of the volume recruited during the RM. Raw data were corrected for gas consumption and fitted with an exponential curve in order to determine an individual time constant for the volume increase. The average volume increase and time constant were 210±198mL and 2.3±1.3s, respectively. Heart rate, diastolic arterial pressure, and SpO(2) did not change during or after the RM. Systolic and mean arterial pressures were maintained at 10s, decreased significantly at 20 and 30s during the RM, and recovered to the pre-RM value 30s after the end of the RM (ANOVA, p<0.01). In early-onset ARDS patients, most of the recruitment occurs during the first 10s of a sustained inflation RM. However, hemodynamic impairment is significant after the tenth second of RM.

Ovine Smoke/Burn ARDS Model: A New Ventilator-Controlled Smoke Delivery System

Our current ovine smoke/burn acute respiratory distress syndrome (ARDS) model utilizes a manual bee smoker. This smoke delivery system lacks standardization and reproducibility, with 20% of sheep failing to meet ARDS criteria. Time to reach ARDS criteria and survival time are also variable. The mild volutrauma (15 mL/kg) applied after smoke/burn injury may also fail to induce ARDS within 24 h. We hypothesized that these inconsistencies were associated with the bee smoker and the mild volutrauma. In the current study, we addressed these problems to improve the consistency of the smoke/burn ARDS model. Adult female sheep (n = 10) were given a 40% total body surface area third degree cutaneous burn and 48 breaths (4 × 12) of cotton smoke under general anesthesia. A modified ventilator was then used to deliver a precise and consistent smoke volume (tidal volume) to the sheep. Additional barotrauma was induced by pressure control ventilation (40 cm H(2)0). When ARDS criteria (PaO(2)/FiO(2) < 200) were met, the ARDS Network low tidal volume ventilation protocol (6-8 mL/kg ideal body weight) was used. Carboxyhemoglobin levels were 81.4% ± 5.6% immediately following smoke injury. All sheep met ARDS criteria within 24 h (12.5 ± 4.9 h). Mean survival time post-injury was 62.1 ± 26.4 h. White blood cells and granulocytes were significantly elevated at 24 h post-smoke/burn injury. Lung tissue at necropsy was consistent with ARDS. The refinements made to the original ovine smoke/burn ARDS model produce a more reliable time to ARDS onset, injury severity, and time of death.

An Early PEEP/FiO2 Trial Identifies Different Degrees of Lung Injury in Patients with Acute Respiratory Distress Syndrome

Current American-European Consensus Conference definitions for acute lung injury (ALI) and acute respiratory distress syndrome (ARDS) are inadequate for inclusion into clinical trials due to the lack of standardization for measuring the oxygenation defect. We questioned whether an early assessment of oxygenation on specific ventilator settings would identify patients with established ARDS (persisting over 24 h). At the time of meeting ARDS criteria (Day 0) and 24 hours later (Day 1), arterial blood gases were obtained on standard ventilator settings, Vt 7 ml/kg predicted body weight plus the following positive end-expiratory pressure (PEEP) and Fi(O(2)) settings in sequence: (1) PEEP >or= 5 cm H(2)O and Fi(O(2)) >or= 0.5, (2) PEEP >or= 5 cm H(2)O and Fi(O(2)) 1.0, (3) PEEP >or= 10 cm H(2)O and Fi(O(2))>or=0.5, and (4) PEEP >or= 10 cm H(2)O and Fi(O(2)) 1.0. One hundred seventy patients meeting ARDS criteria (Pa(O(2))/Fi(O(2)) 128 +/- 33 mm Hg) were enrolled. Overall hospital mortality was 34.1%. The standard ventilator settings that best identified patients with established ARDS and predicted differences in intensive care unit (ICU) mortality were PEEP >or= 10 cm H(2)O and Fi(O(2)) >or= 0.5 at Day 1 (P = 0.0001). Only 99 (58.2%) patients continued to meet ARDS criteria (Pa(O(2))/Fi(O(2)), 155.8 +/- 29.8 mm Hg; ICU mortality, 45.5%), whereas 55 patients were reclassified as having ALI (Pa(O(2))/Fi(O(2)), 246.5 +/- 25.6 mm Hg; ICU mortality, 20%) and 16 patients as having acute respiratory failure (Pa(O(2))/Fi(O(2)), 370 +/- 54 mm Hg; ICU mortality, 6.3%) (P = 0.0001) on these settings. Patients meeting current American-European Consensus Conference ARDS criteria may have highly variable levels of lung injury and outcomes. A systematic method of assessing severity of lung injury is required for enrollment of patients with ARDS into randomized controlled trials. Clinical trial registered with www.clinicaltrials.gov (NCT 00435110).

High-Frequency Percussive Ventilation With Systemic Heparin Improves Short-Term Survival in a LD100 Sheep Model of Acute Respiratory Distress Syndrome

We undertook an assessment of high-frequency percussive ventilation (HFPV) and systemic heparin on survival in our LD100 sheep model of smoke/burn-induced acute respiratory distress syndrome (ARDS). This was a prospective controlled outcomes study in a large animal critical care laboratory. ARDS was induced in 13 sheep by a combination of 48 cotton smoke breaths and 40% full-thickness cutaneous burn (LD100) followed by mechanical ventilation (15 ml/kg tidal volume). After meeting ARDS criteria (PaO2/FiO2 < 200), the sheep were divided into high-frequency percussive ventilation (HFPV; n = 7) or volume-controlled mechanical ventilation (VCMV; n = 6) groups. Both groups received systemic heparin to achieve an ACT 180-300 seconds. HFPV was managed with the Volumetric Diffusive Respiration Ventilator (Percussionaire Corp., Sandpoint, ID). The VCMV group was managed with up to 10 ml/kg tidal volume. Arterial blood gases and ventilator settings were monitored every 6 hours after onset of ARDS. HFPV did not affect sheep hemodynamics. Survival 84 hours after smoke and burn injury was significantly greater in the HFPV (7/7, 100%) compared with the VCMV group (3/6, 50%, P < .05). PaCO2 was significantly greater in VCMV group at 36, 48, and 72 hours after smoke and burn injury. PaO2/FiO2 after 36 hours of smoke and burn injury in the HFPV group was improved compared with the VCMV group, but no statistical difference was found. In the VCMV group, peak airway pressure was decreased to 19.7 +/- 2.2 cm H2O at 36 hours from 29 +/- 2.8 at 24 hours as the tidal volume changed from 15 ml/kg to 10 ml/kg and then gradually increased to 39 +/- 5.6 cm H2O at 72 hours. In the HFPV group, peak inspiratory pressure kept constant at a level of 30 cmH2O. In our smoke/burn-induced LD100 sheep model of ARDS, volume-controlled mechanical ventilation with systemic heparin achieved a 50% survival whereas HFPV with systemic heparin achieved 100% survival at 60 hours after the onset of ARDS.

A high positive end-expiratory pressure, low tidal volume ventilatory strategy improves outcome in persistent acute respiratory distress syndrome: A randomized, controlled trial*

It has been shown in a two-center study that high positive end-expiratory pressure (PEEP) and low tidal volume (LTV) improved outcome in ARDS. However, that study involved patients with underlying diseases unique to the study area, was conducted at only two centers, and enrolled a small number of patients. We similarly hypothesized that a ventilatory strategy based on PEEP above the lower inflection point of the pressure volume curve of the respiratory system (Pflex) set on day 1 with a low tidal volume would result in improved outcome in patients with severe and persistent acute respiratory distress syndrome (ARDS). Randomized, controlled clinical trial. Network of eight Spanish multidisciplinary intensive care units (ICUs) under the acronym of ARIES (Acute Respiratory Insufficiency: España Study). All consecutive patients admitted into participating Spanish ICUs from March 1999 to March 2001 with a diagnosis of ARDS were considered for the study. If 24 hrs after meeting ARDS criteria, the Pao2/Fio2 remained < or =200 mm Hg on standard ventilator settings, patients were randomized into two groups: control and Pflex/LTV. In the control group, tidal volume was 9-11 mL/kg of predicted body weight (PBW) and PEEP > or =5 cm H2O. In the Pflex/LTV group, tidal volume was 5-8 mL/kg PBW and PEEP was set on day 1 at Pflex + 2 cm H2O. In both groups, Fio2 was set to maintain arterial oxygen saturation >90% and Pao2 70-100 mm Hg, and respiratory rate was adjusted to maintain Paco2 between 35 and 50 mm Hg. The study was stopped early based on an efficacy stopping rule as described in the methods. Of 103 patients who were enrolled (50 control and 53 Pflex), eight patients (five in control, three in Pflex) were excluded from the final evaluation because the random group assignment was not performed in one center according to protocol. Main outcome measures were ICU and hospital mortality, ventilator-free days, and nonpulmonary organ dysfunction. ICU mortality (24 of 45 [53.3%] vs. 16 of 50 [32%], p = .040), hospital mortality (25 of 45 [55.5%] vs. 17 of 50 [34%], p = .041), and ventilator-free days at day 28 (6.02 +/- 7.95 in control and 10.90 +/- 9.45 in Pflex/LTV, p = .008) all favored Pflex/LTV. The mean difference in the number of additional organ failures postrandomization was higher in the control group (p < .001). A mechanical ventilation strategy with a PEEP level set on day 1 above Pflex and a low tidal volume compared with a strategy with a higher tidal volume and relatively low PEEP has a beneficial impact on outcome in patients with severe and persistent ARDS.

Simple vs complex radionuclide methods of assessing capillary protein permeability for diagnosing acute respiratory distress syndrome

Purpose Using injection of gallium Ga 67 transferrin, technetium Tc 99m red cells, probes over the lungs, and blood samples, a pulmonary leak index (PLI) and pulmonary transcapillary escape rate (PTCER) for transferrin can be measured. This may help differentiating between cardiogenic pulmonary edema (CPE) and permeability (noncardiogenic) pulmonary edema of the acute respiratory distress syndrome (ARDS). The purpose of the study was to evaluate the relative importance of red cell labeling, blood sampling, and probe measurements in this assessment. Materials and Methods Analysis of radionuclide data obtained in consecutive patients with radiographic evidence for pulmonary edema, classified as ARDS (n = 13), CPE (n = 8), or mixed (n = 5), was performed. The latter patients met ARDS criteria except for a high pulmonary capillary wedge pressure. Results The PLI, PTCER, and the 67Ga-lung/blood radioactivity increase (without 99mTc–red cell data) were specific and sensitive indices to differentiate ARDS/mixed from CPE. The blood transcapillary escape rate (TER) of 67Ga-transferrin was about 2- to 6-fold higher in ARDS and mixed than in CPE. The TER had similar diagnostic value as the PLI, PTCER, and the 67Ga-lung/blood radioactivity ratio increase. Conclusions The diagnostic value of the simple blood TER of 67Ga-transferrin is similar to that of complex methods, using 99mTc–red cells and probe measurements over the lungs, because the complex methods largely depend on the blood TER. Simplification of the method without red cell labeling and probes may facilitate bedside use to diagnose permeability edema of ARDS, particularly in the absence of a pulmonary artery catheter.