Michael Lu MD , Callie Drohan MD , William Bain MD , Faraaz A. Shah MD, MPH , Matthew Bittner MD , John Evankovich MD , Niall T. Prendergast MD , Matthew Hensley MD, MPH , Tomeka L. Suber MD, PhD , Meghan Fitzpatrick MD , Raj Ramanan MD , Holt Murray MD , Caitlin Schaefer MPH , Shulin Qin MD, PhD , Xiaohong Wang MD , Yingze Zhang PhD , Seyed M. Nouraie MD, PhD , Heather Gentry BS , Cathy Murray RN , Asha Patel MS , Georgios D. Kitsios MD, PhD
{"title":"Trajectories of Host-Response Subphenotypes in Patients With COVID-19 Across the Spectrum of Respiratory Support","authors":"Michael Lu MD , Callie Drohan MD , William Bain MD , Faraaz A. Shah MD, MPH , Matthew Bittner MD , John Evankovich MD , Niall T. Prendergast MD , Matthew Hensley MD, MPH , Tomeka L. Suber MD, PhD , Meghan Fitzpatrick MD , Raj Ramanan MD , Holt Murray MD , Caitlin Schaefer MPH , Shulin Qin MD, PhD , Xiaohong Wang MD , Yingze Zhang PhD , Seyed M. Nouraie MD, PhD , Heather Gentry BS , Cathy Murray RN , Asha Patel MS , Georgios D. Kitsios MD, PhD","doi":"10.1016/j.chstcc.2023.100018","DOIUrl":"https://doi.org/10.1016/j.chstcc.2023.100018","url":null,"abstract":"<div><h3>Background</h3><p>Hospitalized patients with severe COVID-19 follow heterogeneous clinical trajectories, requiring different levels of respiratory support and experiencing diverse clinical outcomes. Differences in host immune responses to SARS-CoV-2 infection may account for the heterogeneous clinical course, but we have limited data on the dynamic evolution of systemic biomarkers and related subphenotypes. Improved understanding of the dynamic transitions of host subphenotypes in COVID-19 may allow for improved patient selection for targeted therapies.</p></div><div><h3>Research Question</h3><p>We examined the trajectories of host-response profiles in severe COVID-19 and evaluated their prognostic impact on clinical outcomes.</p></div><div><h3>Study Design and Methods</h3><p>In this prospective observational study, we enrolled 323 inpatients with COVID-19 receiving different levels of baseline respiratory support: (1) low-flow oxygen (37%), (2) noninvasive ventilation (NIV) or high-flow oxygen (HFO; 29%), (3) invasive mechanical ventilation (27%), and (4) extracorporeal membrane oxygenation (7%). We collected plasma samples on enrollment and at days 5 and 10 to measure host-response biomarkers. We classified patients by inflammatory subphenotypes using two validated predictive models. We examined clinical, biomarker, and subphenotype trajectories and outcomes during hospitalization.</p></div><div><h3>Results</h3><p>IL-6, procalcitonin, and angiopoietin 2 persistently were elevated in patients receiving higher levels of respiratory support, whereas soluble receptor of advanced glycation end products (sRAGE) levels displayed the inverse pattern. Patients receiving NIV or HFO at baseline showed the most dynamic clinical trajectory, with 24% eventually requiring intubation and exhibiting worse 60-day mortality than patients receiving invasive mechanical ventilation at baseline (67% vs 35%; <em>P</em> < .0001). sRAGE levels predicted NIV failure and worse 60-day mortality for patients receiving NIV or HFO, whereas IL-6 levels were predictive in all patients regardless of level of support (<em>P</em> < .01). Patients classified to a hyperinflammatory subphenotype at baseline (< 10%) showed worse 60-day survival (<em>P</em> < .0001) and 50% of them remained classified as hyperinflammatory at 5 days after enrollment.</p></div><div><h3>Interpretation</h3><p>Longitudinal study of the systemic host response in COVID-19 revealed substantial and predictive interindividual variability influenced by baseline levels of respiratory support.</p></div>","PeriodicalId":93934,"journal":{"name":"CHEST critical care","volume":"1 3","pages":"Article 100018"},"PeriodicalIF":0.0,"publicationDate":"2023-09-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.sciencedirect.com/science/article/pii/S2949788423000187/pdfft?md5=9831b339fd99d8c2e852d50ec6a947bc&pid=1-s2.0-S2949788423000187-main.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"92026697","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
James McErlane MSc , Philip McCall MD , Jennifer Willder PhD , Colin Berry PhD , Ben Shelley MD
{"title":"Cardiac Biomarkers and Right Ventricular Dysfunction Are Associated Independently With 1-Year Mortality in Patients With COVID-19 Receiving Mechanical Ventilation","authors":"James McErlane MSc , Philip McCall MD , Jennifer Willder PhD , Colin Berry PhD , Ben Shelley MD","doi":"10.1016/j.chstcc.2023.100015","DOIUrl":"https://doi.org/10.1016/j.chstcc.2023.100015","url":null,"abstract":"<div><h3>Background</h3><p>The cardiac biomarkers N-terminal pro-brain natriuretic peptide (NT-proBNP) and troponin frequently are raised in patients with acute COVID-19. As a secondary analysis of the Right Ventricular Dysfunction in Ventilated Patients With COVID-19 study, we sought to determine the association between raised cardiac biomarkers and 1-year mortality in patients with COVID-19 receiving invasive mechanical ventilation (IMV). As an exploratory investigation, we combined point-of-care echocardiography and cardiac biomarker analyses to determine whether the biomarker signal represented a global or regional cardiac injury.</p></div><div><h3>Study Question</h3><p>Are abnormal cardiac biomarker levels associated with 1-year mortality in patients with COVID-19 requiring IMV?</p></div><div><h3>Study Design and Methods</h3><p>In this prospective cardiac biomarker and echocardiography study in patients with COVID-19 across 10 ICUs in the west of Scotland, patients underwent contemporaneous cardiac biomarker testing with point-of-care echocardiography between days 2 and 14 after intubation. Survival analyses was performed using univariable log-rank and multivariable Cox regression.</p></div><div><h3>Results</h3><p>One hundred twenty-one patients were recruited between September 2, 2020, and March 22, 2021. At 1 year, 57.6% of patients (68 of 118) had died. Patients with abnormal NT-proBNP levels and patients with abnormal troponin levels showed a 1-year mortality incidence of 71.4% (50 of 70) and 80.4% (45 of 56), respectively. Both abnormal NT-proBNP and abnormal troponin levels were associated with 1-year mortality (<em>P</em> < .001 for both). Abnormal troponin level was associated with subjective right ventricular dysfunction (RVD; <em>P</em> = .003), and no association with subjective left ventricular dysfunction was found (<em>P</em> = .342). On multivariable analysis, abnormal NT-proBNP level, abnormal troponin level, and subjective RVD were associated independently with 1-year mortality (hazard ratios, 2.82 [95% CI, 1.19-6.67], 2.84 [95% CI, 1.44-5.62], and 2.09 [95% CI, 1.07-4.07], respectively).</p></div><div><h3>Interpretation</h3><p>Abnormal NT-proBNP level, abnormal troponin level, and subjective RVD are associated independently with 1-year mortality in patients with COVID-19 receiving IMV. Cardiac biomarker testing and point-of-care echocardiography are available readily during ICU admission and may identify a group of patients who are at very high risk of poor outcomes.</p></div><div><h3>Trial Registry</h3><p>ClinicalTrials.gov; No.: NCT04764032; URL: <span>www.clinicaltrials.gov</span><svg><path></path></svg></p></div>","PeriodicalId":93934,"journal":{"name":"CHEST critical care","volume":"1 3","pages":"Article 100015"},"PeriodicalIF":0.0,"publicationDate":"2023-09-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"49761511","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Chad H. Hochberg MD, MHS, Mary E. Card MD, Bhavna Seth MD, MHS, David N. Hager MD, PhD, Michelle N. Eakin PhD
{"title":"Adaptation and Uncertainty","authors":"Chad H. Hochberg MD, MHS, Mary E. Card MD, Bhavna Seth MD, MHS, David N. Hager MD, PhD, Michelle N. Eakin PhD","doi":"10.1016/j.chstcc.2023.100008","DOIUrl":"https://doi.org/10.1016/j.chstcc.2023.100008","url":null,"abstract":"<div><h3>Background</h3><p>Prone positioning was widely adopted for use in patients with ARDS from COVID-19. However, proning was also delivered in ways that differed from historical evidence and practice. In implementation research, these changes are referred to as adaptations, and they occur constantly as evidence-based interventions are used in real-world practice. Adaptations can alter the delivered intervention, impacting patient and implementation outcomes.</p></div><div><h3>Research Question</h3><p>How have clinicians adapted prone positioning to COVID-19 ARDS, and what uncertainties remain regarding optimal proning use?</p></div><div><h3>Study Design and Methods</h3><p>We conducted a qualitative study using semi-structured interviews with ICU clinicians from two hospitals in Baltimore, MD, from February to July 2021. We interviewed physicians (MDs), registered nurses (RNs), respiratory therapists (RTs), advanced practice providers (APPs), and physical therapists (PTs) involved with proning mechanically ventilated patients with COVID-19 ARDS. We used thematic analysis of interviews to classify proning adaptations and clinician uncertainties about best practice for prone positioning.</p></div><div><h3>Results</h3><p>Forty ICU clinicians (12 MDs, 4 APPs, 12 RNs, 7 RTs, and 5 PTs) were interviewed. Clinicians described several adaptations to the practice of prone positioning, including earlier proning initiation, extended duration of proning sessions, and less use of concomitant neuromuscular blockade. Clinicians expressed uncertainty regarding the optimal timing of initiation and duration of prone positioning. This uncertainty was viewed as a driver of practice variation. Although prescribers intended to use less deep sedation and paralysis in proned patients compared with historical evidence and practice, this raised concerns regarding patient comfort and safety amongst RNs and RTs.</p></div><div><h3>Interpretation</h3><p>Prone positioning in patients with COVID-19 ARDS has been adapted from historically described practice. Understanding the impact of these adaptations on patient and implementation outcomes and addressing clinician uncertainties are priority areas for future research to optimize the use of prone positioning.</p></div>","PeriodicalId":93934,"journal":{"name":"CHEST critical care","volume":"1 2","pages":"Article 100008"},"PeriodicalIF":0.0,"publicationDate":"2023-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"49778275","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Rama A. Salhi MD, MHS, MSc , Valeria S.M. Valbuena MD , Ashraf Fawzy MD, MPH , Sarah M. Seelye PhD , Theodore J. Iwashyna MD, PhD
{"title":"Impact of Racial Differences in Hypoxia Distribution on the Measured Prevalence of Occult Hypoxemia by Pulse Oximeters","authors":"Rama A. Salhi MD, MHS, MSc , Valeria S.M. Valbuena MD , Ashraf Fawzy MD, MPH , Sarah M. Seelye PhD , Theodore J. Iwashyna MD, PhD","doi":"10.1016/j.chstcc.2023.100011","DOIUrl":"https://doi.org/10.1016/j.chstcc.2023.100011","url":null,"abstract":"<div><h3>Background</h3><p>Racial differences in pulse oximeter accuracy increasingly have become recognized. However, previously published literature has not examined the extent to which underlying racial differences in levels of hypoxemia, such as those arising from differential testing, disease recognition, and treatment, may confound previously observed differences in pulse oximetry measurement.</p></div><div><h3>Research Question</h3><p>The presented study examined the extent to which underlying differences in arterial oxygen saturation (Sa<span>o</span><sub>2</sub>) drive previously observed racial differences in pulse oximetry occult hypoxemia measurement.</p></div><div><h3>Study Design and Methods</h3><p>Analysis was completed as a secondary data analysis of two existing databases. Data were reanalyzed from the previously published Veterans Affairs (VA) Patient Database (2013-2019) and the Extracorporeal Life Support Organization (ELSO) registry (2019-2020). Patients included general ward and critically ill patients. We compared the measured burden of occult hypoxemia (ie, Sa<span>o</span><sub>2</sub> < 88%, with peripheral capillary oxygen saturation ≥ 92%) when standardizing for population-level distributions of Sa<span>o</span><sub>2</sub> vs when standardizing the sensitivity at each Sa<span>o</span><sub>2</sub>.</p></div><div><h3>Results</h3><p>Black patients showed a higher likelihood of occult hypoxemia when compared with White patients in both data sources (Veterans Affairs Patient Database, 18.8% vs 14.9%; Extracorporeal Life Support Organization registry, 14.6% vs 7.0%). The distribution of Sa<span>o</span><sub>2</sub>, to an extent, does change the measured occult hypoxemia rates; however, large racial differences were persistent after standardizing based on underlying Sa<span>o</span><sub>2</sub> distributions.</p></div><div><h3>Interpretation</h3><p>Underlying differences in Sa<span>o</span><sub>2</sub> distributions were observed in the analyzed data. Such differences point to ongoing differentials in care; however, even when accounting for Sa<span>o</span><sub>2</sub> distributions, differential detection of hypoxemia by race persisted in pulse oximeters in contemporary use.</p></div>","PeriodicalId":93934,"journal":{"name":"CHEST critical care","volume":"1 2","pages":"Article 100011"},"PeriodicalIF":0.0,"publicationDate":"2023-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"49778161","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Regis Goulart Rosa MD, PhD, Sérgio Renato da Rosa Decker MD
{"title":"Unveiling Critical Care Resiliency","authors":"Regis Goulart Rosa MD, PhD, Sérgio Renato da Rosa Decker MD","doi":"10.1016/j.chstcc.2023.100006","DOIUrl":"https://doi.org/10.1016/j.chstcc.2023.100006","url":null,"abstract":"","PeriodicalId":93934,"journal":{"name":"CHEST critical care","volume":"1 2","pages":"Article 100006"},"PeriodicalIF":0.0,"publicationDate":"2023-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"49778163","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Christopher K. Schott MD , Erin Wetherbee MD , Rahul Khosla MD , Robert Nathanson MD , Jason P. Williams MD , Michael J. Mader MS , Elizabeth K. Haro MPH , Dean Kellogg III MD , Abraham Rodriguez DO , Kevin C. Proud MD , Jeremy S. Boyd MD , Brian Bales MD , Harald Sauthoff MD , Zahir Basrai MD , Dana Resop MD , Brian P. Lucas MD , Marcos I. Restrepo MD, PhD , Nilam J. Soni MD
{"title":"Current Use, Training, and Barriers to Point-of-Care Ultrasound Use in ICUs in the Department of Veterans Affairs","authors":"Christopher K. Schott MD , Erin Wetherbee MD , Rahul Khosla MD , Robert Nathanson MD , Jason P. Williams MD , Michael J. Mader MS , Elizabeth K. Haro MPH , Dean Kellogg III MD , Abraham Rodriguez DO , Kevin C. Proud MD , Jeremy S. Boyd MD , Brian Bales MD , Harald Sauthoff MD , Zahir Basrai MD , Dana Resop MD , Brian P. Lucas MD , Marcos I. Restrepo MD, PhD , Nilam J. Soni MD","doi":"10.1016/j.chstcc.2023.100012","DOIUrl":"https://doi.org/10.1016/j.chstcc.2023.100012","url":null,"abstract":"<div><h3>Background</h3><p>Point-of-care ultrasound (POCUS) has become an integral part of critical care medicine for procedural guidance, bedside diagnostics, and assessing response to treatment. Multiple critical care societies recommend POCUS use, and POCUS training has been a requirement for critical care fellowship since 2012. Yet, current practice patterns of POCUS use in ICUs are not well known.</p></div><div><h3>Research Question</h3><p>This study aimed to characterize current POCUS use, training needs, and barriers to use among intensivists.</p></div><div><h3>Study Design and Methods</h3><p>A prospective observational study of all Veterans Affairs (VA) medical centers was conducted between June 2019 and March 2020 using a web-based survey of all chiefs of staff and ICU chiefs. These data were compared with those from a similar survey conducted in 2015.</p></div><div><h3>Results</h3><p>Chiefs of staff and ICU chiefs from 130 VA medical centers were surveyed with 100% and 94% response rates, respectively. At least one physician currently uses POCUS in 93% of ICUs, and 62% of individual physicians were estimated to be using POCUS. The most common POCUS applications were procedural guidance (59%), cardiac ultrasound (55%), and thoracic ultrasound (56%) . Most chiefs (80%) reported teaching POCUS to trainees in their ICU. The most frequently reported barriers to POCUS use were lack of trained providers (48%), lack of funding for training (45%), lack of training opportunities (37%), and lack of image archiving (34%). From 2015 through 2020, POCUS use increased across most applications and an increase in desire for training was seen.</p></div><div><h3>Interpretation</h3><p>POCUS use increased across VA ICUs between 2015 and 2020, but significant gaps remain. Without a deliberate investment in POCUS training and infrastructure for physicians in practice, institutions are unlikely to benefit fully from standardized POCUS use in ICUs.</p></div>","PeriodicalId":93934,"journal":{"name":"CHEST critical care","volume":"1 2","pages":"Article 100012"},"PeriodicalIF":0.0,"publicationDate":"2023-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"49778165","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Kevin W. Gibbs MD , Adit A. Ginde MD, MPH , Matthew E. Prekker MD, MPH , Kevin P. Seitz MD, MSc , Susan B. Stempek PA, MBA , Caleb Taylor MD, MPH , Sheetal Gandotra MD , Heath White DO, MS , Daniel Resnick-Ault MD , Akram Khan MD , Amira Mohmed MD , Jason C. Brainard MD , Daniel G. Fein MD , Neil R. Aggarwal MD , Micah R. Whitson MD , Stephen J. Halliday MD, MSc , John P. Gaillard MD , Veronika Blinder DO , Brian E. Driver MD , Jessica A. Palakshappa MD, MS , Jonathan D. Casey MD, MSc
{"title":"Protocol and Statistical Analysis Plan for the Pragmatic Trial Examining Oxygenation Prior to Intubation of Preoxygenation With Noninvasive Ventilation vs Oxygen Mask in Critically Ill Adults","authors":"Kevin W. Gibbs MD , Adit A. Ginde MD, MPH , Matthew E. Prekker MD, MPH , Kevin P. Seitz MD, MSc , Susan B. Stempek PA, MBA , Caleb Taylor MD, MPH , Sheetal Gandotra MD , Heath White DO, MS , Daniel Resnick-Ault MD , Akram Khan MD , Amira Mohmed MD , Jason C. Brainard MD , Daniel G. Fein MD , Neil R. Aggarwal MD , Micah R. Whitson MD , Stephen J. Halliday MD, MSc , John P. Gaillard MD , Veronika Blinder DO , Brian E. Driver MD , Jessica A. Palakshappa MD, MS , Jonathan D. Casey MD, MSc","doi":"10.1016/j.chstcc.2023.100014","DOIUrl":"https://doi.org/10.1016/j.chstcc.2023.100014","url":null,"abstract":"<div><h3>Background</h3><p>Hypoxemia is a common and life-threatening complication during emergency tracheal intubation of critically ill adults. The administration of supplemental oxygen before the procedure (ie, preoxygenation) decreases the risk of hypoxemia during intubation.</p></div><div><h3>Research Question</h3><p>Does preoxygenation with noninvasive ventilation prevent hypoxemia during tracheal intubation of critically ill adults compared with preoxygenation with an oxygen mask?</p></div><div><h3>Study Design and Methods</h3><p>The Pragmatic Trial Examining Oxygenation Prior to Intubation (PREOXI) is a prospective, multicenter, nonmasked randomized comparative effectiveness trial being conducted in seven EDs and 17 ICUs across the United States. The trial compares preoxygenation with noninvasive ventilation vs oxygen mask among 1,300 critically ill adults undergoing emergency tracheal intubation. Eligible patients are randomized in a 1:1 ratio to receive either noninvasive ventilation or an oxygen mask before induction. The primary outcome is the incidence of hypoxemia, defined as a peripheral oxygen saturation of < 85% between induction and 2 min after intubation. The secondary outcome is the lowest oxygen saturation between induction and 2 min after intubation. Enrollment began on March 10, 2022, and is expected to conclude in 2023.</p></div><div><h3>Interpretation</h3><p>The PREOXI investigation will provide important data on the comparative effectiveness of preoxygenation with noninvasive ventilation vs oxygen mask for the prevention of hypoxemia during emergency tracheal intubation. Specifying the protocol and statistical analysis plan before the conclusion of enrollment increases the rigor, reproducibility, and interpretability of the trial.</p></div><div><h3>Trial Registry</h3><p>ClinicalTrials.gov; No.: NCT05267652; URL: <span>www.clinicaltrials.gov</span><svg><path></path></svg></p></div>","PeriodicalId":93934,"journal":{"name":"CHEST critical care","volume":"1 2","pages":"Article 100014"},"PeriodicalIF":0.0,"publicationDate":"2023-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"49778166","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}