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Lung transplantation is a lifesaving intervention for people with advanced lung disease, but it is costly and resource-intensive. To investigate the cost-effectiveness of lung transplantation as a treatment option in pulmonary disease, we must understand costs attributable to end-of-life hospitalizations for end-stage lung disease. What are the costs associated with end-of-life hospitalizations for people with pulmonary disease, and how have these trends changed over time? Adults aged 18 to 74 years with hospitalization data in the Cost and Utilization Project National Inpatient Sample data from 2009 to 2019 with a pulmonary disease admission were included in this analysis. Those with a history of lung transplantation were excluded. International Classification of Diseases codes were used to identify pulmonary disease admissions, complications, and procedures and interventions. Total charges were calculated for hospitalizations and stratified by patient status at time of discharge. Trends in charges over time were assessed by demographic and hospital factors. One hundred nine thousand nine hundred twenty-four (4.1%) hospital admissions for pulmonary disease resulted in in-hospital mortality. Those with obstructive lung disease accounted for 94.1% of hospitalizations and 88.1% cases of in-hospital mortality. Estimated costs for end-of-life hospitalizations were $29,981 on average with wide variation in cost by diagnosis and procedure utilization. Inpatient costs were highest for younger people who received more procedures. Among the most expensive admissions, mechanical ventilation accounted for the greatest proportion of interventions. Significant increases in the use of mechanical ventilation, extracorporeal membrane oxygenation, and dialysis occurred over the time period. The rate of hospital transfers increased with a proportionately greater increase across admissions resulting in in-hospital mortality. Costs accrued during end-of-life hospitalizations vary across people but represent a significant health care cost that can be averted for selected people who undergo lung transplantation. These costs should be considered in studies of cost-effectiveness in lung transplantation. [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]

Lung transplantation (LTx) is the definitive treatment for end-stage lung failure. However, there have been no large, long-term studies on the impact of acute in-hospital stroke in this population. What are the trends, risk factors, and outcomes of acute stroke in patients undergoing LTx in the United States? We identified adult first-time isolated LTx recipients from the United Network for Organ Sharing database, which comprehensively captures every transplant in the United States, between May 2005 and December 2020. Stroke was defined as occurring at any time after LTx but prior to discharge. Multivariable logistic regression with stepwise feature elimination was used to identify risk factors for stroke. Freedom from death in patients with a stroke vs those without a stroke was evaluated with Kaplan-Meier analysis. Cox proportional hazards analysis was used to identify predictors of death at 24 months. Of 28,564 patients (median age, 60 years; 60% male), 653 (2.3%) experienced an acute in-hospital stroke after LTx. Median follow-up was 1.2 (stroke) and 3.0 (non-stroke) years. Annual incidence of stroke increased (1.5% in 2005 to 2.4% in 2020; P for trend =.007), as did lung allocation score and utilization of post-LTx extracorporeal membrane oxygenation (P =.01 and P <.001, respectively). Compared with those without stroke, patients with stroke had lower survival at 1 month (84% vs 98%), 12 months (61% vs 88%), and 24 months (52% vs 80%) (log-rank test, P <.001 for all). In Cox analysis, acute stroke conferred a high hazard of mortality (hazard ratio, 3.01; 95% CI, 2.67-3.41). Post-LTx extracorporeal membrane oxygenation was the strongest risk factor for stroke (adjusted OR, 2.98; 95% CI, 2.19-4.06). Acute in-hospital stroke post-LTx has been increasing over time and is associated with markedly worse short- and long-term survival. As increasingly sicker patients undergo LTx as well as experience stroke, further research on stroke characteristics, prevention, and management strategies is warranted. [Display omitted] [ABSTRACT FROM AUTHOR]

Hypoxia is encountered frequently in the ICU as a result of a wide range of pathologic characteristics. The oxygen-hemoglobin dissociation curve describes hemoglobin's affinity for a given P o 2 and factors affecting uptake and offload. Research in manipulating this relationship between hemoglobin and oxygen is sparing. Voxelotor is a hemoglobin oxygen-affinity modulator that is approved by the US Food and Drug Association for use in the management of sickle cell disease. We present two patients without sickle cell disease who underwent treatment with this novel agent to assist with chronic hypoxia and weaning of mechanical support. [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: In recent decades, the incidence of multidrug-resistant (MDR) and extended-spectrum β-lactamase (ESBL) gram-negative (GN) bacteria has increased progressively among lung transplantation (LT) recipients. A prompt diagnosis, prevention, and management of these pathogens remain the cornerstone for successful organ transplantation.Research Question: What are the incidence of MDR and ESBL GN bacteria within the first 30 days after LT and related risk of in-hospital mortality? What are the potential clinical predictors of isolation of MDR and ESBL GN bacteria?Study Design and Methods: All consecutive LT recipients admitted to the ICU of the University Hospital of Padua (February 2016-December 2021) were screened retrospectively. Only adult patients undergoing the first bilateral LT and not requiring invasive mechanical ventilation, extracorporeal membrane oxygenation, or both before surgery were included. MDR and ESBL GN bacteria were identified using in vitro susceptibility tests and were isolated from the respiratory tract, blood, urine, rectal swab, or surgical wound or drainage according to a routine protocol.Results: One hundred fifty-three LT recipients were screened, and 132 were considered for analysis. Median age was 52 years (interquartile range, 41-60 years) and 46 patients (35%) were women. MDR and ESBL GN bacteria were identified in 45 patients (34%), and 60% of patients demonstrated clinically relevant infection. Pseudomonas aeruginosa (n = 22 [49%]) and Klebsiella pneumoniae (n = 17 [38%]) were frequently isolated after LT from the respiratory tract (n = 21 [47%]) and multiple sites (n = 18 [40%]). Previous recipient-related colonization (hazard ratio [HR], 2.48 [95% CI, 1.04-5.90]; P = .04) and empirical exposure to broad-spectrum antibiotics (HR, 6.94 [95% CI, 2.93-16.46]; P < .01) were independent predictors of isolation of MDR and ESBL GN bacteria. In-hospital mortality of the MDR and ESBL group was 27% (HR, 6.38 [95% CI, 1.98-20.63]; P < .01).Interpretation: The incidence of MDR and ESBL GN bacteria after LT was 34%, and in-hospital mortality was six times greater. Previous recipient-related colonization and empirical exposure to broad-spectrum antibiotics were clinical predictors of isolation of MDR and ESBL GN bacteria. [ABSTRACT FROM AUTHOR]

Case Presentation: A 13-year-old male patient with intermittent asthma and joint hypermobility presented to the ED in acute hypoxemic respiratory distress. He reported experiencing cough, increased work of breathing, and worsening chest pain for 3 days before presentation. He also reported fatigue and decreased appetite for 2 weeks. He had no known fever, myalgias, or recent weight loss. His medical history included two hospitalizations during early childhood for viral respiratory illnesses, one of which required intubation at 8 months of age. He had a gastrostomy tube placed shortly after his hospitalization because of failure to thrive secondary to aspiration based on a swallow study. His weight gain and growth improved with adequate nutrition, and his gastrostomy tube was removed at 2 years of age. His newborn screen, which included immunoreactive trypsinogen, was normal. He was noted to have hypermobile joints on physical examination at a clinic visit in childhood, but his examination results were not concerning for a hypermobility syndrome, and further diagnosis was not pursued. His parents endorsed that he has been a "healthy child" overall other than the occasional cough, which was attributed to asthma. His lifestyle was described as sedentary; he did not play any sports or have any unusual hobbies. He did not take any daily medications and no environmental exposures were reported. There was no family history of pulmonary, autoimmune, or connective tissue disease. [ABSTRACT FROM AUTHOR]

Background: In 2019, the United States experienced a nationwide outbreak of e-cigarette, or vaping, product use-associated lung injury (EVALI). More than one-half of these patients required admission to an ICU.Research Question: What are the recent literature and expert opinions which inform the diagnosis and management of patients with critical illness with EVALI?Study Design and Methods: To synthesize information critical to pulmonary/critical care specialists in the care of patients with EVALI, this study examined data available from patients hospitalized with EVALI between August 2019 and January 2020; reviewed the clinical course and critical care experience with those patients admitted to the ICU; and compiled opinion of national experts.Results: Of the 2,708 patients with confirmed or probable EVALI requiring hospitalization as of January 21, 2020, a total of 1,604 (59.2%) had data available on ICU admission; of these, 705 (44.0%) were admitted to the ICU and are included in this analysis. The majority of ICU patients required respiratory support (88.5%) and in severe cases required intubation (36.1%) or extracorporeal membrane oxygenation (6.7%). The majority (93.0%) of these ICU patients survived to discharge. Review of the clinical course and expert opinion provided insight into: imaging; considerations for bronchoscopy; medical treatment, including use of empiric antibiotics, antiviral agents, and corticosteroids; respiratory support, including considerations for intubation, positioning maneuvers, and extracorporeal membrane oxygenation; and patient outcomes.Interpretation: Review of the clinical course of patients with EVALI requiring ICU admission and compilation of expert opinion provided critical insight into pulmonary/critical care-specific considerations for this patient population. Because a large proportion of patients hospitalized with EVALI required ICU admission, it is important to remain prepared to care for patients with EVALI. [ABSTRACT FROM AUTHOR]

Extracorporeal membrane oxygenation (ECMO) increasingly is being used to support acute respiratory failure and for bridging to lung transplantation. Bleeding and thrombosis are common complications in the acute setting, but the literature describing long-term ECMO complications is limited, and no previous reports have been made of delayed central venous strictures resulting from remote ECMO bridging. Herein, we describe a patient who demonstrated complete inferior vena cava obstruction resulting from venovenous ECMO bridge to lung transplantation 5 years previously. The severe stricture and secondary thrombosis were managed with inferior vena cava angioplasty, stenting, thrombectomy, and thrombolysis, leading to clinical improvement. This case highlights the need for awareness and monitoring for long-term vascular complications in a growing population of patients who have received ECMO support. [ABSTRACT FROM AUTHOR]

Background: Pulse oximeters may produce less accurate results in non-White patients.Research Question: Do pulse oximeters detect arterial hypoxemia less effectively in Black, Hispanic, and/or Asian patients than in White patients in respiratory failure and about to undergo extracorporeal membrane oxygenation (ECMO)?Study Design and Methods: Data on adult patients with respiratory failure readings 6 h before ECMO were provided by the Extracorporeal Life Support Organization registry. Data was collected from 324 centers between January 2019 and July 2020. Our primary analysis was of rates of occult hypoxemia-low arterial oxygen saturation (Sao2 ≤ 88%) on arterial blood gas measurement despite a pulse oximetry reading in the range of 92% to 96%.Results: The rate of pre-ECMO occult hypoxemia, that is, arterial oxygen saturation (Sao2) ≤ 88%, was 10.2% (95% CI, 6.2%-15.3%) for 186 White patients with peripheral oxygen saturation (Spo2) of 92% to 96%; 21.5% (95% CI, 11.3%-35.3%) for 51 Black patients (P = .031 vs White); 8.6% (95% CI, 3.2%-17.7%) for 70 Hispanic patients (P = .693 vs White); and 9.2% (95% CI, 3.5%-19.0%) for 65 Asian patients (P = .820 vs White). Black patients with respiratory failure had a statistically significantly higher risk of occult hypoxemia with an OR of 2.57 (95% CI, 1.12-5.92) compared with White patients (P = .026). The risk of occult hypoxemia for Hispanic and Asian patients was equivalent to that of White patients. In a secondary analysis of patients with Sao2 ≤ 88% despite Spo2 > 96%, Black patients had more than three times the risk compared with White patients (OR, 3.52; 95% CI, 1.12-11.10; P = .032).Interpretation: Compared with White patients, the prevalence of occult hypoxemia was higher in Black patients than in White patients about to undergo ECMO for respiratory failure, but it was comparable in Hispanic and Asian patients compared with White patients. [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]

Background: Decannulation from venovenous extracorporeal membrane oxygenation (ECMO) at the earliest and safest possible time may improve outcomes and reduce cost. Yet, no prospective studies have compared weaning strategies for liberation from ECMO.Research Question: Is a protocolized daily assessment of readiness to liberate from venovenous ECMO safe and feasible?Study Design and Methods: We conducted a prospective, single-arm safety and feasibility study of a protocol for daily assessment of readiness to liberate from venovenous ECMO among consecutive adult patients receiving venovenous ECMO across four ICUs at a single center between June 20, 2020, and November 24, 2020. The ECMO-free protocol included three phases: (1) the safety screening, (2) non-ECMO Fio2 titration, and (3) the ECMO-free trial. Enrollment, interventions, and data collection were performed prospectively by trained study staff.Results: Twenty-six patients received the ECMO-free protocol on 385 patient-days. The safety screening was passed during a total of 59 ECMO-free daily assessments (15.3%) among 20 patients. Every passed safety screening proceeded to an ECMO-free trial. Twenty-eight passed ECMO-free trials (47.5%) occurred among 16 patients (61.5%). No missed safety screenings, protocol deviations, or adverse events occurred. Of the 16 patients who passed an ECMO-free trial, 14 patients (87.5%) were decannulated. Among decannulated patients, 12 patients (85.7%) were decannulated on the same day as a passed ECMO-free trial, 6 patients (42.9%) were decannulated on the first day that they passed an ECMO-free trial, and 6 patients (42.9%) passed an ECMO-free trial at least twice consecutively before decannulation. The median time from first passed ECMO-free trial to decannulation was 2 days (interquartile range, 0-3 days).Interpretation: The ECMO-free protocol is feasible and may identify patients for decannulation earlier than gradual approaches to weaning. [ABSTRACT FROM AUTHOR]

Background: Although specific interventions previously demonstrated benefit in patients with ARDS, use of these interventions is inconsistent, and patient mortality remains high. The impact of variability in center management practices on ARDS mortality rates remains unknown.Research Question: What is the impact of treatment variability on mortality in patients with moderate to severe ARDS in the United States?Study Design and Methods: We conducted a multicenter, observational cohort study of mechanically ventilated adults with ARDS and Pao2 to Fio2 ratio of ≤ 150 with positive end-expiratory pressure of ≥ 5 cm H2O, who were admitted to 29 US centers between October 1, 2016, and April 30, 2017. The primary outcome was 28-day in-hospital mortality. Center variation in ventilator management, adjunctive therapy use, and mortality also were assessed.Results: A total of 2,466 patients were enrolled. Median baseline Pao2 to Fio2 ratio was 105 (interquartile range, 78.0-129.0). In-hospital 28-day mortality was 40.7%. Initial adherence to lung protective ventilation (LPV; tidal volume, ≤ 6.5 mL/kg predicted body weight; plateau pressure, or when unavailable, peak inspiratory pressure, ≤ 30 mm H2O) was 31.4% and varied between centers (0%-65%), as did rates of adjunctive therapy use (27.1%-96.4%), methods used (neuromuscular blockade, prone positioning, systemic steroids, pulmonary vasodilators, and extracorporeal support), and mortality (16.7%-73.3%). Center standardized mortality ratios (SMRs), calculated using baseline patient-level characteristics to derive expected mortality rate, ranged from 0.33 to 1.98. Of the treatment-level factors explored, only center adherence to early LPV was correlated with SMR.Interpretation: Substantial center-to-center variability exists in ARDS management, suggesting that further opportunities for improving ARDS outcomes exist. Early adherence to LPV was associated with lower center mortality and may be a surrogate for overall quality of care processes. Future collaboration is needed to identify additional treatment-level factors influencing center-level outcomes.Trial Registry: ClinicalTrials.gov; No.: NCT03021824; 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]

Severe pulmonary edema, secondary to left ventricular afterload increment, is a common problem occurring in patients receiving venoarterial extracorporeal membrane oxygenation. No consensus is currently available for its management, but several devices/procedures have been described, including an Impella device (Abiomed), balloon atrial septostomy, intraaortic balloon counterpulsation, or an additional venous cannula, as possible adjuncts. We report the feasibility and efficacy of the atrial flow regulator device (Occlutech) for left ventricular unloading in a 58-year-old patient receiving extracorporeal membrane oxygenation. However, the benefits of this device relative to simple balloon atrial septostomy need to be further investigated. [ABSTRACT FROM AUTHOR]