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A newborn girl presented to the hospital on the first day of life because of respiratory failure. She was born at home at 37 weeks' gestation with minimal prenatal care and was found to be small for gestational age. The patient was found to have partial sternal agenesis and sternal cleft, cutis aplasia, left facial hemangioma, micrognathia, wide-spaced nipples, and low-set ears. The mother's and baby's urine toxicology screening were positive for amphetamines. Chest radiographs on admission showed bilateral hazy opacities. CT scan of the chest showed an absent sternum with midline chest wall concavity. The patient was monitored preoperatively in the cardiac ICU for risks of arrythmia, respiratory failure, altered cardiac output, and acute cardiopulmonary decompensation. [ABSTRACT FROM AUTHOR]

A 20-year-old patient with cystic fibrosis (CF) complicated by pansinusitis, pancreatic insufficiency, and diabetes presented to the local ED after an episode of large-volume hemoptysis at home. At baseline, she had advanced lung disease (FEV 1 , 0.97 L; 31% predicted) and upper lobe-predominant fibrocavitary changes. She was intermittently followed at a regional lung transplant center. She was previously evaluated for transplant but was not listed at the time of this presentation because of nontuberculous mycobacteria infection. She had never used tobacco, without reports of recreational inhaled drug use. Her mother had CF, and one of her brothers died in 2018 at age 24 of respiratory failure resulting from the disease. [ABSTRACT FROM AUTHOR]

Respiratory failure is a common and potentially life-threatening complication of neuromuscular diseases. Prompt recognition and accurate diagnosis of new or worsening chronic neuromuscular disease have important clinical management and prognostic implications. In this article, we present an approach to the acute presentation of undifferentiated neuromuscular respiratory failure in the ICU and guidance for determination and respiratory management of the underlying disorder. [ABSTRACT FROM AUTHOR]

Bone marrow mesenchymal stem cell (BM-MSC)-derived extracellular vesicles (ExoFlo) convey the immunomodulatory and regenerative properties of intact BM-MSCs. This study aimed to determine the safety and efficacy of ExoFlo as treatment for moderate to severe ARDS in patients with severe COVID-19. Do two doses of ExoFlo safely reduce mortality in COVID-19-associated moderate to severe ARDS compared with placebo? A prospective phase 2 multicenter double-anonymized randomized placebo-controlled dosing trial was conducted at five sites across the United States with infusions of placebo, 10 mL of ExoFlo, or 15 mL of ExoFlo on days 1 and 4. Patients (N = 102) with COVID-19-associated moderate to severe ARDS were enrolled and randomized to treatment. Adverse events were documented throughout the study. The primary outcome measure was all-cause 60-day mortality rate. Secondary outcomes included time to death (overall mortality); the incidence of treatment-emergent serious adverse events; proportion of discharged patients at 7, 30, and 60 days; time to hospital discharge; and ventilation-free days. No treatment-related adverse events were reported. Mortality (60-day) in the intention-to-treat population was reduced with 15 mL ExoFlo mixed with 85 mL normal saline (ExoFlo-15) compared with placebo (not significant, χ2, P =.1343). For the post hoc subgroup analyses, 60-day mortality was decreased with ExoFlo-15 compared with placebo (relative risk, 0.385; 95% CI, 0.159-0.931; P =.0340; n = 50). With ExoFlo-15, a relative risk of 0.423 (95% CI, 0.173-1.032; P =.0588; n = 24) was determined for participants aged 18 to 65 years with moderate to severe ARDS. Ventilation-free days improved with ExoFlo-15 (P =.0455; n = 50) for all participants aged 18 to 65 years. The 15 mL dose of ExoFlo was found to be safe in patients with severe or critical COVID-19-associated respiratory failure. In participants aged 18 to 65 years, the risk reduction in 60-day mortality was further improved from subjects of all ages in the intention-to-treat population after two doses of 15 mL of ExoFlo compared with placebo. ClinicalTrials.gov; No.: NCT04493242; URL: www.clinicaltrials.gov. [Display omitted] [ABSTRACT FROM AUTHOR]

Safe and timely liberation from venovenous extracorporeal membrane oxygenation (ECMO) would be expected to reduce the duration of ECMO, the risk of complications, and costs. However, how to liberate patients from venovenous ECMO effectively remains understudied. What is the current state of the evidence on liberation from venovenous ECMO? We systematically searched for relevant publications on liberation from venovenous ECMO in Medline and EMBASE. Citations were included if the manuscripts provided any of the following: criteria for readiness for liberation, a liberation protocol, or a definition of successful decannulation or decannulation failure. We included randomized trials, observational trials, narrative reviews, guidelines, editorials, and commentaries. We excluded single case reports and citations where the full text was unavailable. We screened 1,467 citations to identify 39 key publications on liberation from venovenous ECMO. We then summarized the data into five main topics: current strategies used for liberation, criteria used to define readiness for liberation, conducting liberation trials, criteria used to proceed with decannulation, and parameters used to predict decannulation outcomes. Practices on liberation from venovenous ECMO are heterogeneous and are influenced strongly by clinician preference. Additional research on liberation thresholds is needed to define optimal liberation strategies and to close existing knowledge gaps in essential topics on liberation from venovenous ECMO. [ABSTRACT FROM AUTHOR]

An 80-year-old man came to the ED with fever, hematuria, and overall discomfort for 1 week. His medical history included a superficial urothelial carcinoma of the bladder for which he was adjunctively treated with intravesical Mycobacterium bovis BCG (bacillus Calmette-Guérin) immunotherapy for several months. The patient was admitted to the hospital and was initially treated with cephalosporins for a suspected complicated urinary tract infection, but his symptoms did not improve. Ten days after the initial admission, the patient developed hypoxemic respiratory failure during an episode of fever and cold chills and was admitted to the ICU. [ABSTRACT FROM AUTHOR]

A 37-year-old woman with a medical history of myasthenia gravis resulting in progressive respiratory failure requiring continuous mechanical ventilation via tracheostomy, as well as multiple cardiac arrests leading to severe anoxic brain injury, was brought to the hospital from a nursing home because of difficulties with ventilation and oxygenation. On presentation to the ED, the patient was found to be agitated and tachypneic on a ventilator, generating low tidal volumes despite elevated peak airway pressures. Before the current presentation, the patient had been mechanically ventilated at a long-term acute care facility for the past 5 years. More recently, staff has noted intermittent loss of tidal volumes, temporarily responding to overinflation of tracheostomy cuff. Additionally, the tracheostomy tube was exchanged for an extra-long tracheostomy tube to improve tidal volumes; however, the problem persisted, prompting the current presentation. [ABSTRACT FROM AUTHOR]

A 37-year-old man attended a medical clinic at the confluence of the Appalachian and the St. Lawrence Valley after 2 weeks of coughing greenish sputum and progressive dyspnea on exertion. In addition, he reported fatigue, fevers, and chills. He had quit smoking a year earlier and was not a drug user. He recently had spent most of his free time outdoors, mountain biking, but had not travelled outside of Canada. Medical history was unremarkable. He did not take any medication. Upper airway samples taken for SARS-CoV-2 proved negative; he was prescribed cefprozil and doxycycline for presumed community-acquired pneumonia. He returned to the emergency room 1 week later with mild hypoxemia, persisting fever, and a chest radiography consistent with lobar pneumonia. The patient was admitted to his local community hospital, and broad-spectrum antibiotics were added to the regimen. Unfortunately, his condition deteriorated over the following week, and he experienced hypoxic respiratory failure for which he required mechanical ventilation before his transfer to our medical center. [ABSTRACT FROM AUTHOR]

A 52-year-old White man, who currently smokes, was admitted to the medical ICU with worsening shortness of breath. The patient was dyspneic for a month and had been clinically diagnosed with COPD by his primary care doctor and started on bronchodilators and supplemental oxygen. He had no known medical history or recent illness. His dyspnea worsened rapidly over the next month, prompting admission to the medical ICU. He was on high-flow oxygen followed by noninvasive positive pressure ventilation and then mechanical ventilation. He denied cough, fever, night sweats, or weight loss at the time of admission. There was no history of work-related or occupational exposures, drug intake, or recent travel. Review of systems was negative for arthralgia, myalgia, or skin rash. [ABSTRACT FROM AUTHOR]

Prone positioning is an immediately accessible, readily implementable intervention that was proposed initially as a method for improvement in gas exchange > 50 years ago. Initially implemented clinically as an empiric therapy for refractory hypoxemia, multiple clinical trials were performed on the use of prone positioning in various respiratory conditions, cumulating in the landmark Proning Severe ARDS Patients trial, which demonstrated mortality benefit in patients with severe ARDS. After this trial and the corresponding meta-analysis, expert consensus and societal guidelines recommended the use of prone positioning for the management of severe ARDS. The ongoing COVID-19 pandemic has brought prone positioning to the forefront of medicine, including widespread implementation of prone positioning in awake, spontaneously breathing, nonintubated patients with acute hypoxemic respiratory failure. Multiple clinical trials now have been performed to investigate the safety and effectiveness of prone positioning in these patients and have enhanced our understanding of the effects of the prone position in respiratory failure. In this review, we discuss the physiologic features, clinical outcome data, practical considerations, and lingering questions of prone positioning. [ABSTRACT FROM AUTHOR]

Background: Asthma exacerbations with respiratory failure (AERF) are associated with hospital mortality of 7% to 15%. Extracorporeal membrane oxygenation (ECMO) has been used as salvage therapy for refractory AERF, but controlled studies showing its association with mortality have not been performed.Research Question: Is treatment with ECMO associated with lower mortality in refractory AERF compared with standard care?Study Design and Methods: This is a retrospective, epidemiologic, observational cohort study using a national, administrative data set from 2010 to 2020 that includes 25% of US hospitalizations. People were included if they were admitted to an ECMO-capable hospital with an asthma exacerbation, and were treated with short-acting bronchodilators, systemic corticosteroids, and invasive ventilation. People were excluded for age < 18 years, no ICU stay, nonasthma chronic lung disease, COVID-19, or multiple admissions. The main exposure was ECMO vs No ECMO. The primary outcome was hospital mortality. Key secondary outcomes were ICU length of stay (LOS), hospital LOS, time receiving invasive ventilation, and total hospital costs.Results: The study analyzed 13,714 patients with AERF, including 127 with ECMO and 13,587 with No ECMO. ECMO was associated with reduced mortality in the covariate-adjusted (OR, 0.33; 95% CI, 0.17-0.64; P = .001), propensity score-adjusted (OR, 0.36; 95% CI, 0.16-0.81; P = .01), and propensity score-matched models (OR, 0.48; 95% CI, 0.24-0.98; P = .04) vs No ECMO. Sensitivity analyses showed that mortality reduction related to ECMO ranged from OR 0.34 to 0.61. ECMO was also associated with increased hospital costs in all three models (P < .0001 for all) vs No ECMO, but not with decreased ICU LOS, hospital LOS, or time receiving invasive ventilation.Interpretation: ECMO was associated with lower mortality and higher hospital costs, suggesting that it may be an important salvage therapy for refractory AERF following confirmatory clinical trials. [ABSTRACT FROM AUTHOR]

Background: The inhaled vasodilators nitric oxide and epoprostenol may be initiated to improve oxygenation in mechanically ventilated patients with severe acute respiratory failure (ARF); however, practice patterns and head-to-head comparisons of effectiveness are unclear.Research Question: What are the practice patterns and comparative effectiveness for inhaled nitric oxide and epoprostenol in severe ARF?Study Design and Methods: Using a large US database (Premier Healthcare Database), we identified adult patients with ARF or ARDS who were mechanically ventilated and started on inhaled nitric oxide, epoprostenol, or both. Leveraging large hospital variation in the choice of initial inhaled vasodilator, we compared the effectiveness of inhaled nitric oxide with that of epoprostenol by limiting analysis to patients admitted to hospitals that exclusively used either inhaled nitric oxide or epoprostenol. The primary outcome of successful extubation was modeled using multivariate Fine-Grey competing risk (death or hospice discharge) time-to-event models.Results: Among 11,200 patients (303 hospitals), 6,366 patients (56.8%) received inhaled nitric oxide first, 4,720 patients (42.1%) received inhaled epoprostenol first, and 114 patients (1.0%) received both therapies on the same day. One hundred four hospitals (34.3%; 1,666 patients) exclusively used nitric oxide and 118 hospitals (38.9%; 1,812 patients) exclusively used epoprostenol. No differences were found in the likelihood of successful extubation between patients admitted to nitric oxide-only hospitals vs those admitted to epoprostenol-only hospitals (subdistribution hazard ratio, 0.97; 95% CI, 0.80-1.18). Also no differences were found in total hospital costs or death. Results were robust to multiple sensitivity analyses.Interpretation: Large variation exists in the use of initial inhaled vasodilator for respiratory failure across US hospitals. Comparative effectiveness analyses identified no differences in outcomes based on inhaled vasodilator type. [ABSTRACT FROM AUTHOR]

A 40-year-old Asian man with COPD presented to the ER with an acute exacerbation and type 2 respiratory failure. He was intubated and placed on the mechanical ventilator. He had a tobacco smoking history of 30 pack-years. Otherwise, he had no other significant medical or social history. The family history was non contributory. His physical development was normal. [ABSTRACT FROM AUTHOR]

Case Presentation: A 63-year-old Japanese woman with no medical history presented as an outside hospital transfer for further management of acute hypoxemic respiratory failure. Per her family, the patient had developed a rash and intermittent shortness of breath 2 months prior to hospital presentation. The rash was described as an erythematous maculopapular rash located on her proximal arms, chest, and upper eyelids. She saw her primary care physician, who prescribed a course of oral and topical corticosteroids. Despite these symptoms, the patient had an excellent functional status and exercised several times per week without muscle weakness. Two months following the initial presentation, the patient progressively became lethargic, prompting her son to bring her to the hospital for admission and evaluation. While in the hospital, the patient had progressive shortness of breath and developed worsening hypoxemic respiratory failure. Despite broad-spectrum antibiotics, her hypoxemia worsened, requiring intubation. She was subsequently started on 80 mg of IV methylprednisolone three times daily and transferred to our institution for further management. The patient arrived from the outside hospital receiving deep sedation and paralysis. Despite maximal ventilator settings, the patient remained hypoxemic and developed shock requiring multiple vasopressors. [ABSTRACT FROM AUTHOR]

Background: Little is known about rates of invasive procedures and associated complications after lung cancer screening (LCS) in nontrial settings.Research Question: What are the frequency of invasive procedures, complication rates, and factors associated with complications in a national sample of veterans screened for lung cancer?Study Design and Methods: We conducted a retrospective cohort analysis of veterans who underwent LCS in any Veterans Health Administration (VA) facility between 2013 and 2019 and identified veterans who underwent invasive procedures within 10 months of initial LCS. The primary outcome was presence of a complication within 10 days after an invasive procedure. We conducted hierarchical mixed-effects logistic regression analyses to determine patient- and facility-level factors associated with complications resulting from an invasive procedure.Results: Our cohort of 82,641 veterans who underwent LCS was older, more racially diverse, and had more comorbidities than National Lung Screening Trial (NLST) participants. Overall, 1,741 veterans (2.1%) underwent an invasive procedure after initial screening, including 856 (42.3%) bronchoscopies, 490 (24.2%) transthoracic needle biopsies, and 423 (20.9%) thoracic surgeries. Among veterans who underwent procedures, 151 (8.7%) experienced a major complication (eg, respiratory failure, prolonged hospitalization) and an additional 203 (11.7%) experienced an intermediate complication (eg, pneumothorax, pleural effusion). Veterans who underwent thoracic surgery (OR, 7.70; 95% CI, 5.48-10.81), underwent multiple nonsurgical procedures (OR, 1.49; 95% CI, 1.15-1.92), or carried a dementia diagnosis (OR, 3.91; 95% CI, 1.79-8.52) were more likely to experience complications. Invasive procedures were performed less often than in the NLST (2.1% vs 4.2%), but veterans were more likely to experience complications after each type of procedure.Interpretation: These findings may reflect a higher threshold to perform procedures in veteran populations with multiple comorbidities and higher risks of complications. Future work should focus on optimizing the identification of patients whose chance of benefit likely outweighs the complication risks. [ABSTRACT FROM AUTHOR]

Background: Mechanical ventilation (MV) via tracheostomy is performed commonly for patients who are in long-term acute care hospitals (LTACHs) after respiratory failure. However, the outcome of MV in COVID-19-associated respiratory failure in LTACHs is not known.Research Question: What is the ventilator liberation rate of patients who have received tracheostomy with COVID-19-associated respiratory failure compared with those with respiratory failure unrelated to COVID-19 in LTACHs?Study Design and Methods: In this retrospective cohort study, we examined mechanically ventilated patients discharged between June 2020 and March 2021. Of 242 discharges, 165 patients who had undergone tracheostomy arrived and were considered for ventilator liberation. One hundred twenty-eight patients did not have COVID-19 and 37 patients were admitted for COVID-19.Results: The primary outcome of the study was ventilator liberation; secondary outcomes were functional recovery, length of stay (LOS) at the LTACH, and discharge disposition. After controlling for demographics, the number of comorbidities, hemodialysis, vasopressor need, thrombocytopenia, and the LOS at the short-term acute care hospital, our results indicated that patients with COVID-19 showed a higher adjusted ventilator liberation rate of 91.4% vs 56.0% in those without COVID-19. Functional ability was assessed with the change of Functional Status Score for the Intensive Care Unit (FSS-ICU) between admission and discharge. The adjusted mean change in FSS-ICU was significantly higher in the COVID-19 group than in the non-COVID-19 group: 9.49 (95% CI, 7.38-11.6) vs 2.08 (95% CI, 1.05-3.11), respectively (P < .001). Patients with COVID-19 experienced a shorter adjusted LOS at the LTACH with an adjusted hazard ratio of 1.57 (95% CI, 1.0-2.46; P = .05) compared with patients without COVID-19. We did not observe significant differences between the two groups regarding discharge location, but a trend toward need for lower level of care was found in patients with COVID-19.Interpretation: Our study suggests that patients with COVID-19 requiring MV and tracheostomy have a higher chance for recovery than those without COVID-19. [ABSTRACT FROM AUTHOR]

Background: Pulmonary vascular microthrombi are a proposed mechanism of COVID-19 respiratory failure. We hypothesized that early administration of tissue plasminogen activator (tPA) followed by therapeutic heparin would improve pulmonary function in these patients.Research Question: Does tPA improve pulmonary function in severe COVID-19 respiratory failure, and is it safe?Study Design and Methods: Adults with COVID-19-induced respiratory failure were randomized from May14, 2020 through March 3, 2021, in two phases. Phase 1 (n = 36) comprised a control group (standard-of-care treatment) vs a tPA bolus (50-mg tPA IV bolus followed by 7 days of heparin; goal activated partial thromboplastin time [aPTT], 60-80 s) group. Phase 2 (n = 14) comprised a control group vs a tPA drip (50-mg tPA IV bolus, followed by tPA drip 2 mg/h plus heparin 500 units/h over 24 h, then heparin to maintain aPTT of 60-80 s for 7 days) group. Patients were excluded from enrollment if they had not undergone a neurologic examination or cross-sectional brain imaging within the previous 4.5 h to rule out stroke and potential for hemorrhagic conversion. The primary outcome was Pao2 to Fio2 ratio improvement from baseline at 48 h after randomization. Secondary outcomes included Pao2 to Fio2 ratio improvement of > 50% or Pao2 to Fio2 ratio of ≥ 200 at 48 h (composite outcome), ventilator-free days (VFD), and mortality.Results: Fifty patients were randomized: 17 in the control group and 19 in the tPA bolus group in phase 1 and eight in the control group and six in the tPA drip group in phase 2. No severe bleeding events occurred. In the tPA bolus group, the Pao2 to Fio2 ratio values were significantly (P < .017) higher than baseline at 6 through 168 h after randomization; the control group showed no significant improvements. Among patients receiving a tPA bolus, the percent change of Pao2 to Fio2 ratio at 48 h (16.9% control [interquartile range (IQR), -8.3% to 36.8%] vs 29.8% tPA bolus [IQR, 4.5%-88.7%]; P = .11), the composite outcome (11.8% vs 47.4%; P = .03), VFD (0.0 [IQR, 0.0-9.0] vs 12.0 [IQR, 0.0-19.0]; P = .11), and in-hospital mortality (41.2% vs 21.1%; P = .19) did not reach statistically significant differences when compared with those of control participants. The patients who received a tPA drip did not experience benefit.Interpretation: The combination of tPA bolus plus heparin is safe in severe COVID-19 respiratory failure. A phase 3 study is warranted given the improvements in oxygenation and promising observations in VFD and mortality.Trial Registry: ClinicalTrials.gov; No.: NCT04357730; URL: www.clinicaltrials.gov. [ABSTRACT FROM AUTHOR]

Hepatic hydrothorax can be present in 5% to 15% of patients with underlying cirrhosis and portal hypertension, often reflecting advanced liver disease. Its impact can be variable, because patients may have small pleural effusions and minimal pulmonary symptoms or massive pleural effusions and respiratory failure. Management of hepatic hydrothorax can be difficult because these patients often have a number of comorbidities and potential for complications. Minimal high-quality data are available for guidance specifically related to hepatic hydrothorax, potentially resulting in pulmonary or critical care physician struggling for best management options. We therefore provide a Case-based presentation with management options based on currently available data and opinion. We discuss the role of pleural interventions, including thoracentesis, tube thoracostomy, indwelling tunneled pleural catheter, pleurodesis, and surgical interventions. In general, we recommend that management be conducted within a multidisciplinary team including pulmonology, hepatology, and transplant surgery. Patients with refractory hepatic hydrothorax that are not transplant candidates should be managed with palliative intent; we suggest indwelling tunneled pleural catheter placement unless otherwise contraindicated. For patients with unclear or incomplete hepatology treatment plans or those unable to undergo more definitive procedures, we recommend serial thoracentesis. In patients who are transplant candidates, we often consider serial thoracentesis as a standard treatment, while also evaluating the role indwelling tunneled pleural catheter placement may play within the course of disease and transplant evaluation. [ABSTRACT FROM AUTHOR]

Background: Sarcoidosis-related hospitalizations have been increasing in the past decade. There is a paucity of data on mortality trends over time in patients with pulmonary sarcoidosis and respiratory failure who are hospitalized.Research Question: What are the national temporal trends over time in hospitalization and inpatient mortality rates in patients with pulmonary sarcoidosis and respiratory failure hospitalized in the United States between 2007 and 2018?Study Design and Methods: Hospitalization data between 2007 and 2018 were extracted from the National Inpatient Sample for subjects with pulmonary sarcoidosis. Inpatient mortality was stratified by age, respiratory failure, mechanical ventilation (MV), hospital location, and setting (rural vs urban, academic vs nonacademic). A Cochran-Armitage test for trend was used to assess the linear trend in mortality, respiratory failure, and need for MV.Results: Hospitalizations in patients with pulmonary sarcoidosis increased from 258.5 per 1,000,000 hospitalizations in 2007 to 705.7 per 1,000,000 in 2018. Hospitalizations for respiratory failure increased ninefold from 25.9 to 239.4 per 1,000,000 hospitalizations, and the need for MV increased threefold from 9.4 per 1,000,000 in 2007 to 29.4 per 1,000,000 in 2018. All-cause inpatient mortality was 2.6%; however, mortality was 13 times higher in patients with respiratory failure (10.6% vs 0.8%) and 26 times higher in patients who required MV (31.2% vs 1.2%). Inpatient mortality associated with respiratory failure declined 50% from 17.2% in 2007 to 6.6% in 2018. Independent inpatient mortality predictors were older age (adjusted hazard ratio [aHR], 1.025), respiratory failure (aHR, 3.12), need for MV (aHR, 6.01), pulmonary hypertension (pHTN; aHR, 1.44), pulmonary embolism (aHR, 1.61), and frailty (aHR, 3.10).Interpretation: Hospitalizations for respiratory failure in patients with pulmonary sarcoidosis are increasing; however, inpatient mortality from respiratory failure has declined. Older age, respiratory failure, pHTN, and frailty are important predictors of inpatient mortality in patients with pulmonary sarcoidosis who are hospitalized. [ABSTRACT FROM AUTHOR]

Case Presentation: A 17-year-old previously healthy Taiwanese girl presented with syncope on a background of 1 month of weakness, polyarthritis, and heliotrope rash. Her presentation and investigations, which included an elevated creatine phosphokinase level and diffuse myositis on lower limb MRI, were consistent with juvenile dermatomyositis (JDM). [ABSTRACT FROM AUTHOR]

This document summarizes the work of the COPD Technical Expert Panel working group. For patients with COPD, the most pressing current coverage barriers identified were onerous diagnostic requirements focused on oxygenation (rather than ventilation) and difficulty obtaining bilevel devices with backup rate capabilities. Because of these difficulties, many patients with COPD were instead sometimes prescribed home mechanical ventilators. Critical evidence supports changes to current policies, including randomized controlled trial evidence suggesting a mortality benefit from bilevel positive airway pressure with backup rate and updated clinical practice guidelines from the American Thoracic Society as well as the European Respiratory Society. To achieve optimal access to noninvasive ventilation for patients with COPD, we make the following key recommendations: (1) removal of the need for overnight oximetry testing; (2) the ability to initiate therapy using bilevel devices with backup rate capability; and (3) increased duration of time to meet adherence criteria (ie, a second 90-day trial period) in those patients actively engaged in their care. Clear guidelines based on medical necessity are also included for patients who require initiation of or switch to a home mechanical ventilator. Adoption of these proposed recommendations would result in the right device, for the right type of patient with COPD, at the right time. Finally, we emphasize the need for adequate clinical support during initiation and maintenance of home noninvasive ventilation in such patients. [ABSTRACT FROM AUTHOR]

Background: Ultrasound may be useful to assess the structure, activity, and function of the abdominal muscles in patients who are mechanically ventilated.Research Question: Does measurement of abdominal muscle thickening on ultrasound in patients who are mechanically ventilated provide clinically relevant information about abdominal muscle function and weaning outcomes?Study Design and Methods: This study consisted of two parts, a physiological study conducted in healthy subjects and a prospective observational study in patients who were mechanically ventilated. Abdominal muscle thickness and thickening fraction were measured during cough and expiratory efforts in 20 healthy subjects, and prior to and during a spontaneous breathing trial in 57 patients being ventilated.Results: In healthy subjects, internal oblique and rectus abdominis thickening fraction correlated with pressure generated during expiratory efforts (P < .001). In patients being ventilated, abdominal muscle thickness and thickening fraction were feasible to measure in all patients, and reproducibility was moderately acceptable. During a failed spontaneous breathing trial, thickening fraction of transversus abdominis and internal oblique increased substantially from baseline (13.2% [95% CI, 0.9-24.8] and 7.2% [95% CI, 2.2-13.2], respectively). The combined thickening fraction of transversus abdominis, internal oblique, and rectus abdominis measured during cough was associated with an increased risk of reintubation or reconnection to the ventilator following attempted liberation (OR, 2.1; 95% CI, 1.1-4.4 per 10% decrease in thickening fraction).Interpretation: Abdominal muscle thickening on ultrasound was correlated to the airway pressure generated by expiratory efforts. In patients who were mechanically ventilated, abdominal muscle ultrasound measurements are feasible and moderately reproducible. Among patients who passed a spontaneous breathing trial, reduced abdominal muscle thickening during cough was associated with a high risk of liberation failure.Clinical Trial Registration: ClinicalTrials.gov; No.: NCT03567564; URL: www.clinicaltrials.gov. [ABSTRACT FROM AUTHOR]

Case Presentation: A 57-year-old man who had been intubated and placed on venovenous extracorporeal membrane oxygenation for hypoxemic respiratory failure due to COVID-19 pneumonia was transferred to our facility. He underwent anticoagulation with IV heparin titrated to an anti-Factor Xa goal of 0.1 to 0.3 international unit/mL. Over extracorporeal membrane oxygenation days 13 to 17, his WBC count rose from 17,500 to 47,000 cells/μL. He simultaneously experienced the development of fluid-refractory shock that required multiple vasopressors and received stress-dose hydrocortisone when his WBC was 30,000 cells/μL. He remained afebrile and was started on broad-spectrum antimicrobials that included antifungal and anthelminthic therapy. [ABSTRACT FROM AUTHOR]

Case Presentation: A 58-year-old man presented to the ED with a 1-week history of progressive weight loss, generalized weakness, unsteadiness, and dizziness. In hospital, he experienced a witnessed episode of loss of consciousness with no observable respirations that lasted for 15 minutes. His arterial blood gas demonstrated hypercapnic respiratory failure, and he required mask ventilation and vasoactive medications. Similar episodes occurred several more times over the course of the night that required the patient to be intubated. The paroxysmal episodes persisted necessitating continued invasive ventilatory support and admission to the ICU. The episodes occurred in both awake and asleep states and required the ventilator settings to dictate a minimum rate, but minimal ventilatory support otherwise. Further history revealed other symptomatic complaints of vertigo, dysphagia, and hypophonia that had progressed over a 2-month period. The patient's medical history was pertinent for a diagnosis of prostatic carcinoma 3 years previously that was found to be castrate resistant. He had metastases to his hip, ribs, and thoracic spine. Previous treatments had included bicalutamide, docetaxel, and abiraterone; he was receiving leuprolide therapy on presentation. [ABSTRACT FROM AUTHOR]

Background: The resting of the respiratory musculature after undergoing the spontaneous breathing trial (SBT) to prevent extubation failures in critically ill patients needs to be studied further.Research Question: Is the reconnection to mechanical ventilation (MV) for 1 h after a successful SBT able to reduce the risk of reintubation?Study Design and Methods: Randomized clinical trial conducted in four ICUs between August 2018 and July 2019. Candidates for tracheal extubation who met all screening criteria for weaning were included. After achieving success in the SBT using a T-tube, the patients were randomized to the following groups: direct extubation (DE) or extubation after reconnection to MV for 1 h (R1h). The primary outcome was reintubation within 48 h.Results: Among the 336 patients studied (women, 41.1%; median age, 59 years [interquartile range, 45-70 years]), 12.9% (22/171) in the R1h group required reintubation within 48 h vs 18.2% (30/165) in the DE group (risk difference, 5.3 [95% CI, -2.49 to 13.12]; P = .18). No differences were found in mortality, length of ICU or hospital stay, causes of reintubation, or signs of extubation failure. A prespecified exploratory analysis showed that among the 233 patients (69.3%) who were ventilated for more than 72 h, the incidence of reintubation was 12.7% (15/118) in the R1h group compared with 22.6% (26/115) observed in the DE group (P = .04).Interpretation: Reconnection to MV after a successful SBT, compared with DE, did not result in a statistically significant reduction in the risk of reintubation in mechanically ventilated patients. Subgroup exploratory findings suggest that the strategy may benefit patients who were ventilated for more than 72 h, which should be confirmed in further studies.Trial Registry: Brazilian Clinical Trials Registry; No.: RBR-3x8nxn; URL: www.ensaiosclinicos.gov.br. [ABSTRACT FROM AUTHOR]

Background: Despite the frequency and cost of hospitalizations for acute respiratory failure (ARF), the literature regarding the impact of hospital safety net burden on outcomes of these hospitalizations is sparse.Research Question: How does safety net burden impact outcomes of ARF hospitalizations such as mortality, tracheostomy, and resource use?Study Design and Methods: This was a retrospective cohort study using the National Inpatient Sample 2007-2017. All patients hospitalized with a primary diagnosis of ARF were tabulated using the International Classification of Diseases 9th and 10th Revision codes, and safety net burden was calculated using previously published methodology. High- and low-burden hospitals were generated from proportions of Medicaid and uninsured patients. Trends were analyzed using a nonparametric rank-based test, whereas multivariate logistic and linear regression models were used to establish associations of safety net burden with key clinical outcomes.Results: Of an estimated 8,941,334 hospitalizations with a primary diagnosis of ARF, 33.9% were categorized as occurring at low-burden hospitals (LBHs) and 31.6% were categorized as occurring at high-burden hospitals (HBHs). In-hospital mortality significantly decreased at HBHs (22.8%-12.6%; nonparametric trend [nptrend] < .001) and LBHs (22.0%-10.9%; nptrend < .001) over the study period, as did tracheostomy placement (HBH, 5.6%-1.3%; LBH, 3.5%-0.8%; all nptrend <.001). After adjustment for patient and hospital factors, an HBH was associated with increased odds of mortality (adjusted OR [AOR], 1.11; 95% CI, 1.10-1.12) and tracheostomy use (AOR, 1.33; 95% CI, 1.29-1.37), as well as greater hospitalization costs (β coefficient, +$1,083; 95% CI, $882-$1,294) and longer lengths of stay (β coefficient, +3.3 days; 95% CI, 3.2-3.3 days).Interpretation: After accounting for differences between patient cohorts, high safety net burden was associated independently with inferior clinical outcomes and increased costs after ARF hospitalizations. These findings emphasize the need for health care reform to ameliorate disparities within these safety net centers, which treat our most vulnerable populations. [ABSTRACT FROM AUTHOR]

Background: Although resuscitation with IV fluids is the cornerstone of sepsis management, consensus regarding their association with improvement in clinical outcomes is lacking.Research Question: Is there a difference in the incidence of respiratory failure in patients with sepsis who received guideline-recommended initial IV fluid bolus of 30 mL/kg or more conservative resuscitation of less than 30 mL/kg?Study Design and Methods: This was a retrospective analysis of prospectively collected clinical data conducted at an academic medical center in Omaha, Nebraska. We abstracted data from 214 patients with sepsis admitted to a single academic medical center between June 2017 and June 2018. Patients were stratified by receipt of guideline-recommended fluid bolus. The primary outcome was respiratory failure defined as an increase in oxygen flow rate or more intense oxygenation and ventilation support; oxygen requirement and volume were measured at admission, 6 h, 12 h, 24 h, and at discharge. Subgroup analyses were conducted in high-risk patients with congestive heart failure (CHF) as well as those with chronic kidney disease (CKD).Results: A total of 62 patients (29.0%) received appropriate bolus treatment. The overall rate of respiratory failure was not statistically different between patients who received appropriate bolus or did not (40.3% vs 36.8%; P = .634). Likewise, no differences were observed in time to respiratory failure (P = .645) or risk of respiratory failure (adjusted hazard ratio, 1.1 [95% CI, 0.7-1.7]; P = .774). Results were similar within the high-risk CHF and CKD subgroups.Interpretation: In this single-center retrospective study, we found that by broadly defining respiratory failure as an increase in oxygen requirements, a conservative initial IV fluid resuscitation strategy did not correlate with decreased rates of hypoxemic respiratory failure. [ABSTRACT FROM AUTHOR]

Case Presentation: A 27-year-old man was hospitalized in the burn unit after sustaining an acute inhalational injury and facial burns after an accidental occupational exposure to an industrial disinfectant consisting of a mixture of hydrogen peroxide (15%-30%), acetic acid (5%-15%), and peracetic acid (5%-15%). He demonstrated cough, shortness of breath, and hoarseness of voice at presentation that had developed 6 h after exposure. In addition to the inhalational injury of the vocal cords and lower airways on bronchoscopy (Fig 1), the patient also was diagnosed with acute inhalational pneumonitis based on the findings of hypoxemic respiratory failure and bilateral perihilar airspace opacities on chest radiography (Fig 2). He required intubation and mechanical ventilation initially for 2 days for upper airway edema and was discharged 19 days after exposure with resolution of hypoxemia and reduction of airspace opacities on chest radiography. However, symptoms of productive cough and shortness of breath on exertion persisted, and he was rehospitalized 27 days after exposure. He was a nonsmoker with no prior history of atopy, asthma, or lung disease. His medical history was remarkable for hypertension and severe obesity with a BMI of 34.7 kg/m2. [ABSTRACT FROM AUTHOR]

Case Presentation: A 43-year-old man urgently was referred to the hospital complaining of rapidly worsening dyspnea and right-side chest wall discomfort for 1 hour. Two hours later, he experienced acute respiratory failure that subsequently required intubation and invasive mechanical ventilation, thus he was transferred to ICU. He had no fever, weight loss, or bleeding tendency. He was previously healthy with no history of trauma and was not currently on any medication. [ABSTRACT FROM AUTHOR]

A 65-year-old man was admitted to the ICU for septic shock due to pneumonia. He remained on mechanical ventilation for 96 hours. His shock resolved, and he no longer required IV vasopressor therapy. His vital signs included a BP of 105/70 mm Hg, heart rate 85 beats/min, respiratory rate 22 breaths/min, and oxygen saturation 95%. His ventilator settings were volume control/assist control with a positive end-expiratory pressure of 5 and an Fio2 set to 40%. On these setting his blood gas showed an Pao2 of 75 mm Hg. He was following simple commands and had minimal tracheobronchial secretions. He was placed on a spontaneous breathing trial with a spontaneous mode of ventilation and pressure support of 7/5. He remained hemodynamically stable and showed no distress through the procedure, so he was extubated to 6 L oxygen by nasal cannula. Eighteen hours later, the patient was found to have increased work of breathing, with use of accessory respiratory muscles. A blood gas showed an elevated level of CO2, so the patient was reintubated. After intubation, the patient again appeared comfortable on minimal ventilator settings. Chest radiography before reintubation showed no new parenchymal process, but an elevated left diaphragm. After a thorough workup, it was determined that diaphragmatic weakness was the most likely reason for respiratory failure. The team questioned whether there was a way to have detected this before extubation. [ABSTRACT FROM AUTHOR]

The relatively low number of patients assessed does not afford the opportunity to be confident in excluding that there may be a small but significant link to any of these other factors for VTE in patients with COVID-19. The impact of our findings on our practice has been to order ultrasound screening in patients with COVID-19 in our ICUs, and to treat those with positive test results with full-dose IV UFH. To the Editor: Many studies indicate that severe coronavirus disease 2019 (COVID-19) infection is associated with a hypercoagulable state, as evidenced by pathologic findings from lung autopsies.[1] Procoagulant antiphospholipid antibodies have also been reported in patients with COVID-19.[2] We sought to determine the prevalence of DVT in patients with COVID-19 and ARDS within our ICUs. [Extracted from the article]

Given the general utility of lung ultrasound for the evaluation of respiratory failure in acutely ill patients, it is logical to consider its specific advantages in coronavirus disease 2019-related pulmonary disease. The authors, representing the extensive experience of the North American and European coronavirus disease 2019 epicenters, present an ultrasound scanning protocol and report on the common associated ultrasound findings. [ABSTRACT FROM AUTHOR]

Lung ultrasonography (LUS), an imaging modality quickly performed, interpreted, and integrated by the treating physician at the bedside, is a particularly useful tool for acutely ill patients. In the evaluation of a patient with respiratory failure in the ICU or ED, LUS is superior to chest radiograph and generally comparable with CT imaging and reduces the need for patient transport and radiation exposure. This article will provide a concise review of LUS as it pertains to respiratory failure in general and will include examples of relevant ultrasound images and video clips from critically ill patients. [ABSTRACT FROM AUTHOR]

When and how do I qualify inpatients with acute on chronic hypercapnic respiratory failure for home noninvasive positive-pressure ventilation at the time of discharge? A 44-year-old woman with morbid obesity (BMI, 48) was brought to the hospital by her boyfriend for 1 day of confusion and reduced alertness. She had a history of chronic dyspnea on exertion and 10-pack-years of smoking. She also had history of well-treated diabetes and hypertension. In the ER, she was found to be somnolent but arousable and following commands appropriately. Her oxygen saturation was 86% on room air, and arterial blood gases indicated a pH of 7.16 with a Paco2 of 87 mm Hg, a Pao2 of 60 mm Hg, and a bicarbonate of 42 mEq/L. Chest radiograph showed mild pulmonary vascular congestion. She was started on continuous bilevel positive airway pressure and medical therapy, with clinical improvement. [ABSTRACT FROM AUTHOR]

Background: There is an increasing demand for home mechanical ventilation (HMV) in patients with chronic respiratory insufficiency. At present, noninvasive ventilation is exclusively initiated in a clinical setting at all four centers for HMV in the Netherlands. In addition to its high societal costs and patient discomfort, commencing HMV is often delayed because of a lack of hospital bed capacity.Research Question: Is HMV initiation at home, using a telemonitoring approach, noninferior to in-hospital initiation in a nationwide study?Study Design and Methods: We conducted a nationwide, randomized controlled noninferiority trial, in which every HMV center recruited 24 patients (home [n = 12] vs hospital [n = 12]) with a neuromuscular disease or thoracic cage disorder, all with an indication to start HMV. Change in arterial CO2 (Paco2) over a 6-month period was considered the primary outcome, and quality of life and costs were assessed as secondary outcomes.Results: A total of 96 patients were randomized, most of them diagnosed with neuromuscular disease. We found a significant improvement in Paco2 within both groups (home: from 6.1 to 5.6 kPa [P < .01]; hospital: from 6.3 to 5.6 kPa [P < .01]), with no significant differences between groups. Health-related quality of life showed significant improvement on various subscales; however, no significant differences were observed between the home and hospital groups. From a societal perspective, a cost reduction of more than €3,200 ($3,793) per patient was evident in the home group.Interpretation: This nationwide, multicenter study shows that HMV initiation at home is noninferior to hospital initiation, as it shows the same improvement in gas exchange and health-related quality of life. In fact, from a patient's perspective, it might even be a more attractive approach. In addition, starting at home saves over €3,200 ($3,793) per patient over a 6-month period.Trial Registry: ClinicalTrials.gov; No.: NCT03203577; URL: www.clinicaltrials.gov. [ABSTRACT FROM AUTHOR]

Background: Treatment of hypoxemic respiratory failure (HRF) and ARDS is complex. Standardized management of HRF and ARDS may improve adherence to evidence-informed practice and improve outcomes.Research Question: What is the effect of standardized treatment compared with usual care on survival of patients with HRF and ARDS?Study Design and Methods: MEDLINE, EMBASE, Cochrane, CINAHL, Scopus, and Web-of-Science were searched (inception to 2018). Included studies were randomized clinical trials or quasi-experimental studies that examined the effect of standardized treatment (care-protocol, care-pathway, or bundle) compared with usual treatment among mechanically ventilated adult patients admitted to an ICU with HRF or ARDS. Study characteristics, pathway components, and patient outcomes were abstracted independently by two reviewers.Results: From 15,932 unique citations, 14 studies were included in the systematic review (three randomized clinical trials and 11 quasi-experimental studies). Twelve studies (including 5,767 patients) were included in the meta-analysis. Standardized management of HRF was associated with a 23% relative reduction in mortality (relative risk, 0.77; 95% CI, 0.65-0.91; I2, 70%; P = .002). In studies targeting patients with ARDS (n = 8), a 21% pooled mortality reduction was observed (relative risk, 0.79; 95% CI, 0.71-0.88; I2, 3.1%). Standardized management was associated with increased 28-day ventilator-free days (weighted mean difference, 3.48 days; 95% CI, 2.43-4.54 days; P < .001). Standardized management was also associated with a reduction in tidal volume (weighted mean difference, -1.80 mL/kg predicted body weight; 95% CI, -2.80 to -0.80 mL/kg predicted body weight; P < .001). Meta-regression demonstrated that the reduction in mortality was associated with provision of lower tidal volume (P = .045).Interpretation: When compared with usual treatment, standardized treatment of patients with HRF and ARDS is associated with increased ventilator-free days, lower tidal volume ventilation, and lower mortality. ICUs should consider the use of standardized treatment to improve the processes and outcomes of care for patients with HRF and ARDS.Clinical Trial Registration: PROSPERO; No.: CRD42019099921; URL: www.crd.york.ac.uk/prospero/. [ABSTRACT FROM AUTHOR]

The coronavirus disease 2019 pandemic will be remembered for the rapidity with which it spread, the morbidity and mortality associated with it, and the paucity of evidence-based management guidelines. One of the major concerns of hospitals was to limit spread of infection to health-care workers. Because the virus is spread mainly by respiratory droplets and aerosolized particles, procedures that may potentially disperse viral particles, the so-called "aerosol-generating procedures" were avoided whenever possible. Included in this category were noninvasive ventilation (NIV), high-flow nasal cannula (HFNC), and awake (nonintubated) proning. Accordingly, at many health-care facilities, patients who had increasing oxygen requirements were emergently intubated and mechanically ventilated to avoid exposure to aerosol-generating procedures. With experience, physicians realized that mortality of invasively ventilated patients was high and it was not easy to extubate many of these patients. This raised the concern that HFNC and NIV were being underutilized to avoid intubation and to facilitate extubation. In this article, we attempt to separate fact from fiction and perception from reality pertaining to the aerosol dispersion with NIV, HFNC, and awake proning. We describe precautions that hospitals and health-care providers must take to mitigate risks with these devices. Finally, we take a practical approach in describing how we use the three techniques, including the common indications, contraindications, and practical aspects of application. [ABSTRACT FROM AUTHOR]

Background: Studies have demonstrated that high-flow nasal cannula (HFNC) prevents intubation in acute hypoxic respiratory failure when compared with conventional oxygen therapy (COT). However, the data examining routine HFNC use in the immediate postoperative period are less clear.Research Question: Is routine HFNC use superior to COT or noninvasive ventilation (NIV) use in preventing intubation in patients postoperatively?Study Design and Methods: We comprehensively searched databases (PubMed, Embase, Web of Science) to identify randomized controlled trials (RCTs) that compared the effect of HFNC use with that of COT or NIV in the immediate postoperative period on reintubation, escalation of respiratory support, hospital mortality, ICU and hospital length of stay (LOS), postoperative hypoxemia, and treatment complications. We assessed individual study risk of bias (RoB) by using the revised Cochrane RoB 2 tool and rated certainty in outcomes by using the Grading of Recommendations Assessment, Development and Evaluation framework.Results: We included 11 RCTs enrolling 2,201 patients. Ten compared HFNC with COT and one with NIV. Compared with COT use, HFNC use in the postoperative period was associated with a lower reintubation rate (relative risk [RR], 0.32; 95% CI, 0.12-0.88; absolute risk reduction [ARR], 2.9%; moderate certainty) and decreased escalation of respiratory support (RR, 0.54; 95% CI, 0.31-0.94; ARR, 5.8%; very low certainty). Post hoc subgroup analysis suggested that this effect was driven by patients who were obese and/or at high risk (subgroup differences, P = .06). We did not find differences in any of the other stated outcomes between HFNC and COT. HFNC was also no different from NIV in reintubation rate, respiratory therapy failure, or ICU LOS.Interpretation: With evidence of moderate certainty, prophylactic HFNC reduces reintubation and escalation of respiratory support compared with COT in the immediate postoperative period after cardiothoracic surgery. This effect is likely driven by patients who are at high risk and/or obese. These findings support postoperative prophylactic HFNC use in the patients who are at high risk and/or obese undergoing cardiothoracic surgery. [ABSTRACT FROM AUTHOR]