Cognitive and psychiatric morbidity is common and potentially modifiable after acute lung injury (ALI). However, practical measures of neuropsychological function for use in multicenter trials are ...lacking.
To determine whether a validated telephone-based neuropsychological test battery is feasible in a multicenter trial. To determine the frequency and risk factors for long-term neuropsychological impairment.
As an adjunct study to the Acute Respiratory Distress Syndrome Clinical Trials Network Fluid and Catheter Treatment Trial, we assessed neuropsychological function at 2 and 12 months post-hospital discharge.
Of 406 eligible survivors, we approached 261 to participate and 213 consented. We tested 122 subjects at least once, including 102 subjects at 12 months. Memory, verbal fluency, and executive function were impaired in 13% (12 of 92), 16% (15 of 96), and 49% (37 of 76) of long-term survivors. Long-term cognitive impairment was present in 41 of the 75 (55%) survivors who completed cognitive testing. Depression, post-traumatic stress disorder, or anxiety was present in 36% (37 of 102), 39% (40 of 102), and 62% (63 of 102) of long-term survivors. Enrollment in a conservative fluid-management strategy (P = 0.005) was associated with cognitive impairment and lower partial pressure of arterial oxygen during the trial was associated with cognitive (P = 0.02) and psychiatric impairment (P = 0.02).
Neuropsychological function can be assessed by telephone in a multicenter trial. Long-term neuropsychological impairment is common in survivors of ALI. Hypoxemia is a risk factor for long-term neuropsychological impairment. Fluid management strategy is a potential risk factor for long-term cognitive impairment; however, given the select population studied and an unclear mechanism, this finding requires confirmation.
Although critical for host defense, innate immune cells are also pathologic drivers of acute respiratory distress syndrome (ARDS). Innate immune dynamics during Coronavirus Disease 2019 (COVID-19) ...ARDS, compared to ARDS from other respiratory pathogens, is unclear. Moreover, mechanisms underlying the beneficial effects of dexamethasone during severe COVID-19 remain elusive. Using single-cell RNA sequencing and plasma proteomics, we discovered that, compared to bacterial ARDS, COVID-19 was associated with expansion of distinct neutrophil states characterized by interferon (IFN) and prostaglandin signaling. Dexamethasone during severe COVID-19 affected circulating neutrophils, altered IFN
neutrophils, downregulated interferon-stimulated genes and activated IL-1R2
neutrophils. Dexamethasone also expanded immunosuppressive immature neutrophils and remodeled cellular interactions by changing neutrophils from information receivers into information providers. Male patients had higher proportions of IFN
neutrophils and preferential steroid-induced immature neutrophil expansion, potentially affecting outcomes. Our single-cell atlas (see 'Data availability' section) defines COVID-19-enriched neutrophil states and molecular mechanisms of dexamethasone action to develop targeted immunotherapies for severe COVID-19.
Previous trials suggesting that high-frequency oscillatory ventilation (HFOV) reduced mortality among adults with the acute respiratory distress syndrome (ARDS) were limited by the use of outdated ...comparator ventilation strategies and small sample sizes.
In a multicenter, randomized, controlled trial conducted at 39 intensive care units in five countries, we randomly assigned adults with new-onset, moderate-to-severe ARDS to HFOV targeting lung recruitment or to a control ventilation strategy targeting lung recruitment with the use of low tidal volumes and high positive end-expiratory pressure. The primary outcome was the rate of in-hospital death from any cause.
On the recommendation of the data monitoring committee, we stopped the trial after 548 of a planned 1200 patients had undergone randomization. The two study groups were well matched at baseline. The HFOV group underwent HFOV for a median of 3 days (interquartile range, 2 to 8); in addition, 34 of 273 patients (12%) in the control group received HFOV for refractory hypoxemia. In-hospital mortality was 47% in the HFOV group, as compared with 35% in the control group (relative risk of death with HFOV, 1.33; 95% confidence interval, 1.09 to 1.64; P=0.005). This finding was independent of baseline abnormalities in oxygenation or respiratory compliance. Patients in the HFOV group received higher doses of midazolam than did patients in the control group (199 mg per day interquartile range, 100 to 382 vs. 141 mg per day interquartile range, 68 to 240, P<0.001), and more patients in the HFOV group than in the control group received neuromuscular blockers (83% vs. 68%, P<0.001). In addition, more patients in the HFOV group received vasoactive drugs (91% vs. 84%, P=0.01) and received them for a longer period than did patients in the control group (5 days vs. 3 days, P=0.01).
In adults with moderate-to-severe ARDS, early application of HFOV, as compared with a ventilation strategy of low tidal volume and high positive end-expiratory pressure, does not reduce, and may increase, in-hospital mortality. (Funded by the Canadian Institutes of Health Research; Current Controlled Trials numbers, ISRCTN42992782 and ISRCTN87124254, and ClinicalTrials.gov numbers, NCT00474656 and NCT01506401.).
A personalized mechanical ventilation approach for patients with adult respiratory distress syndrome (ARDS) based on lung physiology and morphology, ARDS etiology, lung imaging, and biological ...phenotypes may improve ventilation practice and outcome. However, additional research is warranted before personalized mechanical ventilation strategies can be applied at the bedside. Ventilatory parameters should be titrated based on close monitoring of targeted physiologic variables and individualized goals. Although low tidal volume (V
) is a standard of care, further individualization of V
may necessitate the evaluation of lung volume reserve (e.g., inspiratory capacity). Low driving pressures provide a target for clinicians to adjust V
and possibly to optimize positive end-expiratory pressure (PEEP), while maintaining plateau pressures below safety thresholds. Esophageal pressure monitoring allows estimation of transpulmonary pressure, but its use requires technical skill and correct physiologic interpretation for clinical application at the bedside. Mechanical power considers ventilatory parameters as a whole in the optimization of ventilation setting, but further studies are necessary to assess its clinical relevance. The identification of recruitability in patients with ARDS is essential to titrate and individualize PEEP. To define gas-exchange targets for individual patients, clinicians should consider issues related to oxygen transport and dead space. In this review, we discuss the rationale for personalized approaches to mechanical ventilation for patients with ARDS, the role of lung imaging, phenotype identification, physiologically based individualized approaches to ventilation, and a future research agenda.
Coronavirus disease 2019 (COVID-19) is a serious illness caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) and in severe cases associated with acute respiratory distress syndrome ...(ARDS).
To describe the clinical characteristics of patients with ARDS-COVID-19.
This study involved 197 male Egyptian participants, among them111 COVID-19 patients presented with ARDS, 60 COVID-19 patients presented with non-ARDS, and 26 Non-COVID-19 patients. We reported the analysis results of clinical and laboratory information, including blood routine tests, blood biochemistry parameters aspartate aminotransferase (AST), alanine aminotransferase (ALT), creatinine and C-reactive protein (CRP), thrombotic activity (D-dimer) and serum ferritin and lactate dehydrogenase (LDH).
The levels of hemoglobin, AST, creatinine, monocyte count, monocyte %, RBC count, TLC, and platelet count were not significantly different among the groups. The lymphopenia and increased CRP, ALT, D-dimer, ferritin, and LDH were observed in patients with ARDS-COVID-19.
COVID-19 patients with ARDS presented with lymphopenia, increased thrombotic activity, increased CRP, LDH, and ferritin levels. The results revealed that CRP, D-dimer, LDH levels, and lymphopenia have a significant association with the COVID-19 severity and can be used as biomarkers to predict the disease severity.
Severe covid-19 pneumonia has posed critical challenges for the research and medical communities. Older age, male sex, and comorbidities increase the risk for severe disease. For people hospitalized ...with covid-19, 15-30% will go on to develop covid-19 associated acute respiratory distress syndrome (CARDS). Autopsy studies of patients who died of severe SARS CoV-2 infection reveal presence of diffuse alveolar damage consistent with ARDS but with a higher thrombus burden in pulmonary capillaries. When used appropriately, high flow nasal cannula (HFNC) may allow CARDS patients to avoid intubation, and does not increase risk for disease transmission. During invasive mechanical ventilation, low tidal volume ventilation and positive end expiratory pressure (PEEP) titration to optimize oxygenation are recommended. Dexamethasone treatment improves mortality for the treatment of severe and critical covid-19, while remdesivir may have modest benefit in time to recovery in patients with severe disease but shows no statistically significant benefit in mortality or other clinical outcomes. Covid-19 survivors, especially patients with ARDS, are at high risk for long term physical and mental impairments, and an interdisciplinary approach is essential for critical illness recovery.
There have been few detailed, in-person interviews and examinations to obtain follow-up data on 5-year outcomes among survivors of the acute respiratory distress syndrome (ARDS).
We evaluated 109 ...survivors of ARDS at 3, 6, and 12 months and at 2, 3, 4, and 5 years after discharge from the intensive care unit. At each visit, patients were interviewed and examined; underwent pulmonary-function tests, the 6-minute walk test, resting and exercise oximetry, chest imaging, and a quality-of-life evaluation; and reported their use of health care services.
At 5 years, the median 6-minute walk distance was 436 m (76% of predicted distance) and the Physical Component Score on the Medical Outcomes Study 36-Item Short-Form Health Survey was 41 (mean norm score matched for age and sex, 50). With respect to this score, younger patients had a greater rate of recovery than older patients, but neither group returned to normal predicted levels of physical function at 5 years. Pulmonary function was normal to near-normal. A constellation of other physical and psychological problems developed or persisted in patients and family caregivers for up to 5 years. Patients with more coexisting illnesses incurred greater 5-year costs.
Exercise limitation, physical and psychological sequelae, decreased physical quality of life, and increased costs and use of health care services are important legacies of severe lung injury.
Estimates of the incidence of the acute respiratory distress syndrome (ARDS) in high- and middle-income countries vary from 10.1 to 86.2 per 100,000 person-years in the general population. The ...epidemiology of ARDS has not been reported for a low-income country at the level of the population, hospital, or intensive care unit (ICU). The Berlin definition may not allow identification of ARDS in resource-constrained settings.
To estimate the incidence and outcomes of ARDS at a Rwandan referral hospital using the Kigali modification of the Berlin definition: without requirement for positive end-expiratory pressure, hypoxia cutoff of SpO2/FiO2 less than or equal to 315, and bilateral opacities on lung ultrasound or chest radiograph.
We screened every adult patient for hypoxia at a public referral hospital in Rwanda for 6 weeks. For every patient with hypoxia, we collected data on demographics and ARDS risk factors, performed lung ultrasonography, and evaluated chest radiography when available.
Forty-two (4.0%) of 1,046 hospital admissions met criteria for ARDS. Using various prespecified cutoffs for the SpO2/FiO2 ratio resulted in almost identical hospital incidence values. Median age for patients with ARDS was 37 years, and infection was the most common risk factor (44.1%). Only 30.9% of patients with ARDS were admitted to an ICU, and hospital mortality was 50.0%. Using traditional Berlin criteria, no patients would have met criteria for ARDS.
ARDS seems to be a common and fatal syndrome in a hospital in Rwanda, with few patients admitted to an ICU. The Berlin definition is likely to underestimate the impact of ARDS in low-income countries, where resources to meet the definition requirements are lacking. Although the Kigali modification requires validation before widespread use, we hope this study stimulates further work in refining an ARDS definition that can be consistently used in all settings.
Noninvasive ventilation (NIV) is increasingly used in patients with acute respiratory distress syndrome (ARDS). The evidence supporting NIV use in patients with ARDS remains relatively sparse.
To ...determine whether, during NIV, the categorization of ARDS severity based on the Pa
/Fi
Berlin criteria is useful.
The LUNG SAFE (Large Observational Study to Understand the Global Impact of Severe Acute Respiratory Failure) study described the management of patients with ARDS. This substudy examines the current practice of NIV use in ARDS, the utility of the Pa
/Fi
ratio in classifying patients receiving NIV, and the impact of NIV on outcome.
Of 2,813 patients with ARDS, 436 (15.5%) were managed with NIV on Days 1 and 2 following fulfillment of diagnostic criteria. Classification of ARDS severity based on Pa
/Fi
ratio was associated with an increase in intensity of ventilatory support, NIV failure, and intensive care unit (ICU) mortality. NIV failure occurred in 22.2% of mild, 42.3% of moderate, and 47.1% of patients with severe ARDS. Hospital mortality in patients with NIV success and failure was 16.1% and 45.4%, respectively. NIV use was independently associated with increased ICU (hazard ratio, 1.446 95% confidence interval, 1.159-1.805), but not hospital, mortality. In a propensity matched analysis, ICU mortality was higher in NIV than invasively ventilated patients with a Pa
/Fi
lower than 150 mm Hg.
NIV was used in 15% of patients with ARDS, irrespective of severity category. NIV seems to be associated with higher ICU mortality in patients with a Pa
/Fi
lower than 150 mm Hg. Clinical trial registered with www.clinicaltrials.gov (NCT 02010073).
Patients with COVID-19 can develop acute respiratory distress syndrome (ARDS), which is associated with high mortality. The aim of this study was to examine the functional and morphological features ...of COVID-19-associated ARDS and to compare these with the characteristics of ARDS unrelated to COVID-19.
This prospective observational study was done at seven hospitals in Italy. We enrolled consecutive, mechanically ventilated patients with laboratory-confirmed COVID-19 and who met Berlin criteria for ARDS, who were admitted to the intensive care unit (ICU) between March 9 and March 22, 2020. All patients were sedated, paralysed, and ventilated in volume-control mode with standard ICU ventilators. Static respiratory system compliance, the ratio of partial pressure of arterial oxygen to fractional concentration of oxygen in inspired air, ventilatory ratio (a surrogate of dead space), and D-dimer concentrations were measured within 24 h of ICU admission. Lung CT scans and CT angiograms were done when clinically indicated. A dataset for ARDS unrelated to COVID-19 was created from previous ARDS studies. Survival to day 28 was assessed.
Between March 9 and March 22, 2020, 301 patients with COVID-19 met the Berlin criteria for ARDS at participating hospitals. Median static compliance was 41 mL/cm H
O (33-52), which was 28% higher than in the cohort of patients with ARDS unrelated to COVID-19 (32 mL/cm H
O 25-43; p<0·0001). 17 (6%) of 297 patients with COVID-19-associated ARDS had compliances greater than the 95th percentile of the classical ARDS cohort. Total lung weight did not differ between the two cohorts. CT pulmonary angiograms (obtained in 23 8% patients with COVID-19-related ARDS) showed that 15 (94%) of 16 patients with D-dimer concentrations greater than the median had bilateral areas of hypoperfusion, consistent with thromboembolic disease. Patients with D-dimer concentrations equal to or less than the median had ventilatory ratios lower than those of patients with D-dimer concentrations greater than the median (1·66 1·32-1·95 vs 1·90 1·50-2·33; p=0·0001). Patients with static compliance equal to or less than the median and D-dimer concentrations greater than the median had markedly increased 28-day mortality compared with other patient subgroups (40 56% of 71 with high D-dimers and low compliance vs 18 27% of 67 with low D-dimers and high compliance, 13 22% of 60 with low D-dimers and low compliance, and 22 35% of 63 with high D-dimers and high compliance, all p=0·0001).
Patients with COVID-19-associated ARDS have a form of injury that, in many aspects, is similar to that of those with ARDS unrelated to COVID-19. Notably, patients with COVID-19-related ARDS who have a reduction in respiratory system compliance together with increased D-dimer concentrations have high mortality rates.
None.
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