High respiratory effort may be common in invasively ventilated patients receiving pressure support ventilation, but its epidemiologic characteristics are unclear.
Research Question
What are the epidemiologic characteristics of high respiratory efforts in critically ill patients, does agreement exist between high respiratory drive and high respiratory effort, what are clinician responses during such events, and what is the relationship between those with clinical parameters and outcomes?
Study Design and Methods
This clinician-masked, prospective, observational study in 2 centers measured the drop in airway pressure during the first 100 ms of an inspiratory effort with an occluded airway (P0.1), a validated noninvasive measure of respiratory drive, in patients receiving pressure support ventilation for > 24 hours. We also measured estimated respiratory muscle pressure (ePmusc), a validated surrogate of inspiratory effort. We measured ePmusc and P0.1 twice daily.
Results
Of 528 ventilated patients, 80 patients received pressure support ventilation for > 24 hours. Among them, 33 patients (41%) exhibited high respiratory effort, which was more common in COVID-19 ARDS, with 19 of such patients (58%) reached the predefined threshold vs 14 patients (27%) in the non-COVID-19 cohort (OR, 5.0; 95% CI, 1.9-14.9; P = .001). Moreover, 36% of P0.1 values were ≥ 4 cm H2O, indicating high respiratory drive. Moderate agreement was found between ePmusc and P0.1 measurements (intraclass correlation coefficient, 0.65), suggesting significant discrepancies between those 2 parameters. Clinician-directed management based on usual clinical observations (but masked to P0.1 and ePmusc) rarely changed in the presence of high respiratory effort. Higher ePmusc and its concomitant elevation with P0.1 were associated with worse blood gas parameters and respiratory mechanics. A concomitant elevation of both ePmusc and P0.1 was associated independently with a decreased likelihood of being alive and ventilator-free up to day 28 (OR, 0.26; 95% CI, 0.06-0.87; P = .037).
Interpretation
In this study, many critical care patients receiving invasive pressure support ventilation exhibited high respiratory efforts. In these patients, adjustments to ventilator settings were uncommon, despite association with worse clinical parameters and outcomes.
{"title":"High Respiratory Effort During Invasive Pressure Support Ventilation","authors":"Anis Chaba MD , Joanna W.Y. Chow MBBS , Atthaphong Phongphithakchai MD , Wisam Al-Bassam MD , Fumitaka Yanase PhD , Zachary O’Brien MBBS , Glenn Eastwood PhD , Ahmad Bassam MD , Stefanos Hadzakis MD , Sofia Spano MD , Akinori Maeda MD , Lucinda Roberts MD , Rinaldo Bellomo PhD , Ary Serpa Neto PhD","doi":"10.1016/j.chstcc.2025.100147","DOIUrl":"10.1016/j.chstcc.2025.100147","url":null,"abstract":"<div><h3>Background</h3><div>High respiratory effort may be common in invasively ventilated patients receiving pressure support ventilation, but its epidemiologic characteristics are unclear.</div></div><div><h3>Research Question</h3><div>What are the epidemiologic characteristics of high respiratory efforts in critically ill patients, does agreement exist between high respiratory drive and high respiratory effort, what are clinician responses during such events, and what is the relationship between those with clinical parameters and outcomes?</div></div><div><h3>Study Design and Methods</h3><div>This clinician-masked, prospective, observational study in 2 centers measured the drop in airway pressure during the first 100 ms of an inspiratory effort with an occluded airway (P<sub>0.1</sub>), a validated noninvasive measure of respiratory drive, in patients receiving pressure support ventilation for > 24 hours. We also measured estimated respiratory muscle pressure (<sub>e</sub>P<sub>musc</sub>), a validated surrogate of inspiratory effort. We measured <sub>e</sub>P<sub>musc</sub> and P<sub>0.1</sub> twice daily.</div></div><div><h3>Results</h3><div>Of 528 ventilated patients, 80 patients received pressure support ventilation for > 24 hours. Among them, 33 patients (41%) exhibited high respiratory effort, which was more common in COVID-19 ARDS, with 19 of such patients (58%) reached the predefined threshold vs 14 patients (27%) in the non-COVID-19 cohort (OR, 5.0; 95% CI, 1.9-14.9; <em>P</em> = .001). Moreover, 36% of P<sub>0.1</sub> values were ≥ 4 cm H<sub>2</sub>O, indicating high respiratory drive. Moderate agreement was found between <sub>e</sub>P<sub>musc</sub> and P<sub>0.1</sub> measurements (intraclass correlation coefficient, 0.65), suggesting significant discrepancies between those 2 parameters. Clinician-directed management based on usual clinical observations (but masked to P<sub>0.1</sub> and <sub>e</sub>P<sub>musc</sub>) rarely changed in the presence of high respiratory effort. Higher <sub>e</sub>P<sub>musc</sub> and its concomitant elevation with P<sub>0.1</sub> were associated with worse blood gas parameters and respiratory mechanics. A concomitant elevation of both <sub>e</sub>P<sub>musc</sub> and P<sub>0.1</sub> was associated independently with a decreased likelihood of being alive and ventilator-free up to day 28 (OR, 0.26; 95% CI, 0.06-0.87; <em>P</em> = .037).</div></div><div><h3>Interpretation</h3><div>In this study, many critical care patients receiving invasive pressure support ventilation exhibited high respiratory efforts. In these patients, adjustments to ventilator settings were uncommon, despite association with worse clinical parameters and outcomes.</div></div>","PeriodicalId":93934,"journal":{"name":"CHEST critical care","volume":"3 2","pages":"Article 100147"},"PeriodicalIF":0.0,"publicationDate":"2025-03-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144146831","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}
Pub Date : 2025-03-05DOI: 10.1016/j.chstcc.2025.100145
Robin L. Goossen MD , Daan F.L. Filippini MD , Relin van Vliet MD , Laura A. Buiteman-Kruizinga RN, PhD , Markus W. Hollmann MD, PhD , Sheila N. Myatra MD , Ary Serpa Neto MD, PhD , Peter E. Spronk MD, PhD , Meta C.E. van der Woude MD, PhD , Marcus J. Schultz MD, PhD , David M.P. van Meenen MD, PhD , Frederique Paulus PhD , Lieuwe D.J. Bos MD, PhD , Practice of Ventilation and Adjunctive Therapies in ICU Patients With COVID-19 Investigators
Background
In patients with ARDS, positive end-expiratory pressure (PEEP) titration remains a challenge and recommendations are not in agreement. In mechanically ventilated patients with COVID-19, subphenotypes based on different respiratory trajectories have been identified, but their heterogeneity in response to PEEP/Fio2 strategy remains understudied.
Research Question
Can these previously determined subphenotypes be detected early in the course of mechanical ventilation, and do these subphenotypes moderate the association between PEEP and Fio2 ventilation strategy and mortality?
Study Design and Methods
Retrospective analysis of invasively ventilated patients with COVID-19. Patients were categorized into 2 treatment groups: high PEEP/low Fio2 strategy and low PEEP/high Fio2 strategy. To replicate previously described longitudinal respiratory subphenotypes, hereafter named the low-power or high-power subphenotype, a prediction model was created. The primary outcome was the interaction between PEEP/Fio2 strategy and subphenotype, with mortality as the dependent variable.
Results
Of the 1,464 patients included in this analysis, 361 patients (25%) were allocated into the high PEEP/low Fio2 strategy and 1,103 patients (75%) were allocated into the low PEEP/high Fio2 strategy. A prediction model consisting of respiratory data of the first 2 days of invasive ventilation (area under the receiver operating characteristics curve, 0.88) assigned 908 patients (62%) to the low-power subphenotype and 556 patients (38%) to the high-power subphenotype. The high-power subphenotype was characterized by higher minute volume, mechanical power, ventilatory ratio, and driving pressure. The association between PEEP/Fio2 ventilation strategy and ICU mortality was moderated by the subphenotype (P = .03), with high PEEP/low Fio2 ventilation being associated with lower mortality in the low-power subphenotype (OR, 0.46; 95% CI, 0.31-0.67; P < .001) and not in the high-power subphenotype (OR, 0.85; 95% CI, 0.57-1.28; P = .44).
Interpretation
In this study, high PEEP/low Fio2 ventilation was associated with improved mortality only in one of the subphenotypes, suggesting that such subphenotypes influence heterogeneity of PEEP and Fio2 effect and should be considered in personalized ventilation strategies.
{"title":"Longitudinal Respiratory Subphenotypes and Differences in Response to Positive End-Expiratory Pressure and Fio2 Ventilation Strategy in COVID-19 ARDS","authors":"Robin L. Goossen MD , Daan F.L. Filippini MD , Relin van Vliet MD , Laura A. Buiteman-Kruizinga RN, PhD , Markus W. Hollmann MD, PhD , Sheila N. Myatra MD , Ary Serpa Neto MD, PhD , Peter E. Spronk MD, PhD , Meta C.E. van der Woude MD, PhD , Marcus J. Schultz MD, PhD , David M.P. van Meenen MD, PhD , Frederique Paulus PhD , Lieuwe D.J. Bos MD, PhD , Practice of Ventilation and Adjunctive Therapies in ICU Patients With COVID-19 Investigators","doi":"10.1016/j.chstcc.2025.100145","DOIUrl":"10.1016/j.chstcc.2025.100145","url":null,"abstract":"<div><h3>Background</h3><div>In patients with ARDS, positive end-expiratory pressure (PEEP) titration remains a challenge and recommendations are not in agreement. In mechanically ventilated patients with COVID-19, subphenotypes based on different respiratory trajectories have been identified, but their heterogeneity in response to PEEP/F<span>io</span><sub>2</sub> strategy remains understudied.</div></div><div><h3>Research Question</h3><div>Can these previously determined subphenotypes be detected early in the course of mechanical ventilation, and do these subphenotypes moderate the association between PEEP and F<span>io</span><sub>2</sub> ventilation strategy and mortality?</div></div><div><h3>Study Design and Methods</h3><div>Retrospective analysis of invasively ventilated patients with COVID-19. Patients were categorized into 2 treatment groups: high PEEP/low F<span>io</span><sub>2</sub> strategy and low PEEP/high F<span>io</span><sub>2</sub> strategy. To replicate previously described longitudinal respiratory subphenotypes, hereafter named the <em>low-power</em> or <em>high-power</em> subphenotype, a prediction model was created. The primary outcome was the interaction between PEEP/F<span>io</span><sub>2</sub> strategy and subphenotype, with mortality as the dependent variable.</div></div><div><h3>Results</h3><div>Of the 1,464 patients included in this analysis, 361 patients (25%) were allocated into the high PEEP/low F<span>io</span><sub>2</sub> strategy and 1,103 patients (75%) were allocated into the low PEEP/high F<span>io</span><sub>2</sub> strategy. A prediction model consisting of respiratory data of the first 2 days of invasive ventilation (area under the receiver operating characteristics curve, 0.88) assigned 908 patients (62%) to the low-power subphenotype and 556 patients (38%) to the high-power subphenotype. The high-power subphenotype was characterized by higher minute volume, mechanical power, ventilatory ratio, and driving pressure. The association between PEEP/F<span>io</span><sub>2</sub> ventilation strategy and ICU mortality was moderated by the subphenotype (<em>P = .</em>03), with high PEEP/low F<span>io</span><sub>2</sub> ventilation being associated with lower mortality in the low-power subphenotype (OR, 0.46; 95% CI, 0.31-0.67; <em>P < .</em>001) and not in the high-power subphenotype (OR, 0.85; 95% CI, 0.57-1.28; <em>P = .</em>44).</div></div><div><h3>Interpretation</h3><div>In this study, high PEEP/low F<span>io</span><sub>2</sub> ventilation was associated with improved mortality only in one of the subphenotypes, suggesting that such subphenotypes influence heterogeneity of PEEP and F<span>io</span><sub>2</sub> effect and should be considered in personalized ventilation strategies.</div></div><div><h3>Clinical Trial Registry</h3><div><span><span>ClinicalTrials.gov</span><svg><path></path></svg></span>; No.: NCT05954351; URL: <span><span>www.clinicaltrials.gov</span><svg><path></path></svg></span></div></div>","PeriodicalId":93934,"journal":{"name":"CHEST critical care","volume":"3 2","pages":"Article 100145"},"PeriodicalIF":0.0,"publicationDate":"2025-03-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144166487","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}
Pub Date : 2025-03-03DOI: 10.1016/j.chstcc.2025.100143
Andrew T. Pham MD , Ryan A. Peterson PhD , Suzanne Slaughter MS , Morgan Martin BS , Joseph A. Hippensteel MD , Ellen L. Burnham MD
Background
Delirium commonly occurs in critical illness and is associated with significant morbidity and mortality. Although risk reduction measures can mitigate the risk of delirium, identifying patients in whom delirium will develop remains clinically challenging.
Research Question
In critically ill patients with respiratory failure, are central nervous system (CNS)-related biomarkers measured at admission associated with delirium diagnosis?
Study Design and Methods
We performed a secondary analysis of a cohort of patients with respiratory failure in the medical ICU enrolled at a single medical center. Using serum collected at ICU admission, we measured CNS-related biomarkers including brain-derived neurotrophic factor (BDNF), chitinase-3-like protein 1, glial fibrillary acidic protein, neurofilament light chain (NF-L), neurogranin, S100 calcium-binding protein B, and triggering receptor expressed on myeloid cells 2 via a multiplex immunoassay. The primary outcome was diagnosis of in-hospital delirium, defined using validated methods. Associations between individual biomarkers and delirium diagnosis were examined using multivariable logistic regressions, adjusting for factors known to predispose and precipitate delirium. Secondary outcomes included in-hospital mortality, ventilator-free days, ICU-free days, and hospital-free days.
Results
Serum biomarkers were measured in 100 patients. Delirium occurred in 73% of the cohort. Patients with vs without delirium did not differ significantly in terms of age, sex, comorbidities, severity of illness, or unhealthy alcohol use. After adjustment, NF-L was associated positively with delirium diagnosis (adjusted OR, 1.86; 95% CI, 1.09-3.43), whereas BDNF was associated negatively with delirium (adjusted OR, 0.43; 95% CI, 0.15-0.82). No associations were found between other measured biomarkers and delirium diagnosis. NF-L levels were associated negatively with ICU-free and hospital-free days.
Interpretation
Our results indicate that CNS-related biomarkers measured at ICU admission are associated with delirium diagnosis in critically ill patients. Prospective investigations are necessary to validate the role of these biomarkers in predicting delirium.
{"title":"Association of Central Nervous System-Related Biomarkers With Hospital Delirium in Patients With Respiratory Failure in the ICU","authors":"Andrew T. Pham MD , Ryan A. Peterson PhD , Suzanne Slaughter MS , Morgan Martin BS , Joseph A. Hippensteel MD , Ellen L. Burnham MD","doi":"10.1016/j.chstcc.2025.100143","DOIUrl":"10.1016/j.chstcc.2025.100143","url":null,"abstract":"<div><h3>Background</h3><div>Delirium commonly occurs in critical illness and is associated with significant morbidity and mortality. Although risk reduction measures can mitigate the risk of delirium, identifying patients in whom delirium will develop remains clinically challenging.</div></div><div><h3>Research Question</h3><div>In critically ill patients with respiratory failure, are central nervous system (CNS)-related biomarkers measured at admission associated with delirium diagnosis?</div></div><div><h3>Study Design and Methods</h3><div>We performed a secondary analysis of a cohort of patients with respiratory failure in the medical ICU enrolled at a single medical center. Using serum collected at ICU admission, we measured CNS-related biomarkers including brain-derived neurotrophic factor (BDNF), chitinase-3-like protein 1, glial fibrillary acidic protein, neurofilament light chain (NF-L), neurogranin, S100 calcium-binding protein B, and triggering receptor expressed on myeloid cells 2 via a multiplex immunoassay. The primary outcome was diagnosis of in-hospital delirium, defined using validated methods. Associations between individual biomarkers and delirium diagnosis were examined using multivariable logistic regressions, adjusting for factors known to predispose and precipitate delirium. Secondary outcomes included in-hospital mortality, ventilator-free days, ICU-free days, and hospital-free days.</div></div><div><h3>Results</h3><div>Serum biomarkers were measured in 100 patients. Delirium occurred in 73% of the cohort. Patients with vs without delirium did not differ significantly in terms of age, sex, comorbidities, severity of illness, or unhealthy alcohol use. After adjustment, NF-L was associated positively with delirium diagnosis (adjusted OR, 1.86; 95% CI, 1.09-3.43), whereas BDNF was associated negatively with delirium (adjusted OR, 0.43; 95% CI, 0.15-0.82). No associations were found between other measured biomarkers and delirium diagnosis. NF-L levels were associated negatively with ICU-free and hospital-free days.</div></div><div><h3>Interpretation</h3><div>Our results indicate that CNS-related biomarkers measured at ICU admission are associated with delirium diagnosis in critically ill patients. Prospective investigations are necessary to validate the role of these biomarkers in predicting delirium.</div></div>","PeriodicalId":93934,"journal":{"name":"CHEST critical care","volume":"3 2","pages":"Article 100143"},"PeriodicalIF":0.0,"publicationDate":"2025-03-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144070637","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}
Pub Date : 2025-03-03DOI: 10.1016/j.chstcc.2025.100144
Emily A. Vail MD , Varun K. Goyal MD , Ashley C. McGinity MD , Todd Sarge MD , Julie K. Heimbach MD , Arthur R. Mielke MD, MPH , Allison J. Tompeck MD , Carolina B. Maciel MD , Katharina M. Busl MD , Thomas M. Leventhal MD , Devang K. Sanghavi MBBS, MD , Rishi Kumar MD , Philip M. Sommer MD , Kim M. Olthoff MD , Niels D. Martin MD , Samuel T. Windham MD , Rita N. Bakhru MD
United States organ procurement organizations increasingly are centralizing the management and recovery of organs from deceased donors into dedicated donor care units (DCUs) with growing evidence of effectiveness. This paradigm shift offers logistical advantages, but introduces new considerations for intensivists responsible for the safe, effective, and efficient management of deceased potential organ donors. In this How I Do It article, intensivist leaders of 12 US DCUs collaborating in the Donor Care Unit Network for Optimizing Recovery group describe best practices for delivering care and organ recovery from deceased donors after brain death and circulatory death in hospital-based donor care units. Specific considerations include donor transfers, clinical donor management, performance assessment, and quality improvement.
{"title":"Best Practices for Hospital-Based Donor Care Unit Operations","authors":"Emily A. Vail MD , Varun K. Goyal MD , Ashley C. McGinity MD , Todd Sarge MD , Julie K. Heimbach MD , Arthur R. Mielke MD, MPH , Allison J. Tompeck MD , Carolina B. Maciel MD , Katharina M. Busl MD , Thomas M. Leventhal MD , Devang K. Sanghavi MBBS, MD , Rishi Kumar MD , Philip M. Sommer MD , Kim M. Olthoff MD , Niels D. Martin MD , Samuel T. Windham MD , Rita N. Bakhru MD","doi":"10.1016/j.chstcc.2025.100144","DOIUrl":"10.1016/j.chstcc.2025.100144","url":null,"abstract":"<div><div>United States organ procurement organizations increasingly are centralizing the management and recovery of organs from deceased donors into dedicated donor care units (DCUs) with growing evidence of effectiveness. This paradigm shift offers logistical advantages, but introduces new considerations for intensivists responsible for the safe, effective, and efficient management of deceased potential organ donors. In this How I Do It article, intensivist leaders of 12 US DCUs collaborating in the Donor Care Unit Network for Optimizing Recovery group describe best practices for delivering care and organ recovery from deceased donors after brain death and circulatory death in hospital-based donor care units. Specific considerations include donor transfers, clinical donor management, performance assessment, and quality improvement.</div></div>","PeriodicalId":93934,"journal":{"name":"CHEST critical care","volume":"3 2","pages":"Article 100144"},"PeriodicalIF":0.0,"publicationDate":"2025-03-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144124084","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}
Pub Date : 2025-03-01DOI: 10.1016/j.chstcc.2024.100117
F. Linzee Mabrey MD, MSc , Thomas R. Martin MD , Carolyn S. Calfee MD , Kathleen D. Liu MD , Benjamin LaCombe BS , Lamorna Brown-Swigart PhD , Andrea Discacciati PhD , Martin Eklund PhD , Susan R. Heckbert MD , Michael A. Matthay MD , Laura Esserman MD , Mark M. Wurfel MD, PhD
Background
Cluster of differentiation 14 (CD14)-dependent innate immunity contributes to poor outcomes in COVID-19 pneumonia.
Research Question
What are the clinical and biological effects of a blocking anti-CD14 monoclonal antibody (IC14) for treatment of severe COVID-19 pneumonia and what is the usefulness of a biomarker of CD14 pathway activation in predicting outcome?
Study Design And Methods
We report a preplanned secondary analysis of the Investigation of Serial Studies to Predict Your Therapeutic Response With Imaging and Molecular Analysis to Coronavirus Disease of 2019 (I-SPY COVID) trial, which enrolled hospitalized patients with severe COVID-19 pneumonia who required high-level respiratory support at 19 medical centers in the United States. Participants were randomized to receive either IV IC14 (4 mg/kg on day 1, then 2 mg/kg on days 2-4; n = 67) or standard care (n = 76). Primary end points included time to recovery, defined as the first 2-day period with ≤ 6 L/min of oxygen, and mortality. In predefined secondary analyses, we tested the association between IC14 treatment and mortality in patients with high or low baseline plasma presepsin, a biomarker of CD14 pathway activity, and the effects of IC14 on plasma biomarkers of pharmacodynamics, injury, and inflammation.
Results
IC14 treatment did not improve time to recovery or 28-day mortality in the overall population, and the trial was stopped because of meeting futility criteria for the time-to-recovery end point. However, a predefined subgroup analysis showed that IC14 treatment was associated with a numerical reduction in 28-day mortality in participants with high (above median) baseline presepsin levels (n = 47; hazard ratio for mortality [HRm], 0.52; 95% credible interval, 0.22-1.22; posterior probability [Pr] HRm < 1 (Pr(HRm < 1 | data)) = 0.93). IC14 treatment increased plasma sCD14, a pharmacodynamic marker, and decreased plasma inflammatory biomarkers, including IL-8, receptor for advanced glycation end products, vascular endothelial growth factor, and presepsin.
Interpretation
Although IC14 treatment did not improve overall clinical outcomes, this new secondary analysis showed that IC14 produced the expected pharmacodynamic and biological effects and that baseline plasma presepsin concentrations may identify patients likely to respond to IC14 treatment. Further trials are needed to determine the efficacy of IC14 treatment in acute lung injury and the value of presepsin to identify patients most likely to respond.
{"title":"Anti-CD14 Treatment in Patients With Severe COVID-19 Clinical and Biological Effects in a Phase 2 Randomized Open-Label Adaptive Platform Clinical Trial","authors":"F. Linzee Mabrey MD, MSc , Thomas R. Martin MD , Carolyn S. Calfee MD , Kathleen D. Liu MD , Benjamin LaCombe BS , Lamorna Brown-Swigart PhD , Andrea Discacciati PhD , Martin Eklund PhD , Susan R. Heckbert MD , Michael A. Matthay MD , Laura Esserman MD , Mark M. Wurfel MD, PhD","doi":"10.1016/j.chstcc.2024.100117","DOIUrl":"10.1016/j.chstcc.2024.100117","url":null,"abstract":"<div><h3>Background</h3><div>Cluster of differentiation 14 (CD14)-dependent innate immunity contributes to poor outcomes in COVID-19 pneumonia.</div></div><div><h3>Research Question</h3><div>What are the clinical and biological effects of a blocking anti-CD14 monoclonal antibody (IC14) for treatment of severe COVID-19 pneumonia and what is the usefulness of a biomarker of CD14 pathway activation in predicting outcome?</div></div><div><h3>Study Design And Methods</h3><div>We report a preplanned secondary analysis of the Investigation of Serial Studies to Predict Your Therapeutic Response With Imaging and Molecular Analysis to Coronavirus Disease of 2019 (I-SPY COVID) trial, which enrolled hospitalized patients with severe COVID-19 pneumonia who required high-level respiratory support at 19 medical centers in the United States. Participants were randomized to receive either IV IC14 (4 mg/kg on day 1, then 2 mg/kg on days 2-4; n = 67) or standard care (n = 76). Primary end points included time to recovery, defined as the first 2-day period with ≤ 6 L/min of oxygen, and mortality. In predefined secondary analyses, we tested the association between IC14 treatment and mortality in patients with high or low baseline plasma presepsin, a biomarker of CD14 pathway activity, and the effects of IC14 on plasma biomarkers of pharmacodynamics, injury, and inflammation.</div></div><div><h3>Results</h3><div>IC14 treatment did not improve time to recovery or 28-day mortality in the overall population, and the trial was stopped because of meeting futility criteria for the time-to-recovery end point. However, a predefined subgroup analysis showed that IC14 treatment was associated with a numerical reduction in 28-day mortality in participants with high (above median) baseline presepsin levels (n = 47; hazard ratio for mortality [HRm], 0.52; 95% credible interval, 0.22-1.22; posterior probability [Pr] HRm < 1 (Pr(HRm < 1 | data)) = 0.93). IC14 treatment increased plasma sCD14, a pharmacodynamic marker, and decreased plasma inflammatory biomarkers, including IL-8, receptor for advanced glycation end products, vascular endothelial growth factor, and presepsin.</div></div><div><h3>Interpretation</h3><div>Although IC14 treatment did not improve overall clinical outcomes, this new secondary analysis showed that IC14 produced the expected pharmacodynamic and biological effects and that baseline plasma presepsin concentrations may identify patients likely to respond to IC14 treatment. Further trials are needed to determine the efficacy of IC14 treatment in acute lung injury and the value of presepsin to identify patients most likely to respond.</div></div><div><h3>Clinical Trial Registry</h3><div><span><span>ClinicalTrials.gov</span><svg><path></path></svg></span>; No.: NCT04488081; URL: <span><span>www.clinicaltrials.gov</span><svg><path></path></svg></span></div></div>","PeriodicalId":93934,"journal":{"name":"CHEST critical care","volume":"3 1","pages":"Article 100117"},"PeriodicalIF":0.0,"publicationDate":"2025-03-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143611142","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}
Pub Date : 2025-03-01DOI: 10.1016/j.chstcc.2024.100121
Theogene Twagirumugabe MD, PhD
{"title":"The New Global Definition of ARDS","authors":"Theogene Twagirumugabe MD, PhD","doi":"10.1016/j.chstcc.2024.100121","DOIUrl":"10.1016/j.chstcc.2024.100121","url":null,"abstract":"","PeriodicalId":93934,"journal":{"name":"CHEST critical care","volume":"3 1","pages":"Article 100121"},"PeriodicalIF":0.0,"publicationDate":"2025-03-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143610862","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}
Pub Date : 2025-03-01DOI: 10.1016/j.chstcc.2024.100124
Theodore J. Iwashyna MD, PhD , Elizabeth M. Viglianti MD, MPH , Jennifer Cano MPH , Sarah Seelye PhD , Nicholas A. Bosch MD , Lisa D. Burry PhD , Bijan Teja MD , David N. Juurlink MD, PhD , Henry T. Stelfox MD, PhD , Downing Lu MD, MPH , Andrea D. Hill PhD , Allan J. Walkey MD , Hannah Wunsch MD
Background
Little is known about whether the choice of opioid influences long-term outcomes for critically ill patients.
Research Question
To determine whether initiation of IV morphine or hydromorphone during mechanical ventilation (MV) is associated with reduced opioid use after discharge relative to fentanyl.
Study Design and Methods
This was a retrospective cohort study of 14,197 veterans who underwent MV in 116 Veterans Administration hospitals (2014-2020) and who received fentanyl, morphine, or hydromorphone as the initial and only IV opioid during their first 2 days in the ICU. The primary outcome was persistent opioid use in the year after hospital discharge.
Results
Overall, 11,903 patients (83.8%) received fentanyl, 1,156 patients (8.1%) received morphine, and 1,138 patients (8.0%) received hydromorphone as the initial and only IV opioid during the first 2 days in the ICU. The median patient age was 67 years (interquartile range, 61-72 years). Persistent opioid use in the year after discharge was more common with hydromorphone (16.5%) vs fentanyl (12.0%; adjusted OR [aOR], 1.25; 95% CI, 1.00-1.56), but not with morphine (15.7%) vs fentanyl (aOR, 1.12; 95% CI, 0.91-1.39). Stratified by prior persistent opioid use, the association between opioid initially received in the ICU and an increased risk of persistent use in the following year was present only among individuals without this history for both morphine and hydromorphine compared with fentanyl (morphine: aOR, 1.44 [95% CI, 1.07-1.94]; hydromorphone: aOR, 1.51 [95% CI, 1.12-2.04]).
Interpretation
Among patients in the ICU who received MV, persistent opioid use in the year after hospital discharge was more frequent among patients initially exposed to IV morphine or hydromorphone compared with fentanyl, but only among those without a prior history of persistent opioid use. The choice of initial opioid may have long-term consequences for patients. Further research is needed to confirm these exploratory findings.
{"title":"Initial Opioid Exposure in the ICU and 1-Year Opioid-Related Outcomes in Patients Who Are Mechanically Ventilated","authors":"Theodore J. Iwashyna MD, PhD , Elizabeth M. Viglianti MD, MPH , Jennifer Cano MPH , Sarah Seelye PhD , Nicholas A. Bosch MD , Lisa D. Burry PhD , Bijan Teja MD , David N. Juurlink MD, PhD , Henry T. Stelfox MD, PhD , Downing Lu MD, MPH , Andrea D. Hill PhD , Allan J. Walkey MD , Hannah Wunsch MD","doi":"10.1016/j.chstcc.2024.100124","DOIUrl":"10.1016/j.chstcc.2024.100124","url":null,"abstract":"<div><h3>Background</h3><div>Little is known about whether the choice of opioid influences long-term outcomes for critically ill patients.</div></div><div><h3>Research Question</h3><div>To determine whether initiation of IV morphine or hydromorphone during mechanical ventilation (MV) is associated with reduced opioid use after discharge relative to fentanyl.</div></div><div><h3>Study Design and Methods</h3><div>This was a retrospective cohort study of 14,197 veterans who underwent MV in 116 Veterans Administration hospitals (2014-2020) and who received fentanyl, morphine, or hydromorphone as the initial and only IV opioid during their first 2 days in the ICU. The primary outcome was persistent opioid use in the year after hospital discharge.</div></div><div><h3>Results</h3><div>Overall, 11,903 patients (83.8%) received fentanyl, 1,156 patients (8.1%) received morphine, and 1,138 patients (8.0%) received hydromorphone as the initial and only IV opioid during the first 2 days in the ICU. The median patient age was 67 years (interquartile range, 61-72 years). Persistent opioid use in the year after discharge was more common with hydromorphone (16.5%) vs fentanyl (12.0%; adjusted OR [aOR], 1.25; 95% CI, 1.00-1.56), but not with morphine (15.7%) vs fentanyl (aOR, 1.12; 95% CI, 0.91-1.39). Stratified by prior persistent opioid use, the association between opioid initially received in the ICU and an increased risk of persistent use in the following year was present only among individuals without this history for both morphine and hydromorphine compared with fentanyl (morphine: aOR, 1.44 [95% CI, 1.07-1.94]; hydromorphone: aOR, 1.51 [95% CI, 1.12-2.04]).</div></div><div><h3>Interpretation</h3><div>Among patients in the ICU who received MV, persistent opioid use in the year after hospital discharge was more frequent among patients initially exposed to IV morphine or hydromorphone compared with fentanyl, but only among those without a prior history of persistent opioid use. The choice of initial opioid may have long-term consequences for patients. Further research is needed to confirm these exploratory findings.</div></div>","PeriodicalId":93934,"journal":{"name":"CHEST critical care","volume":"3 1","pages":"Article 100124"},"PeriodicalIF":0.0,"publicationDate":"2025-03-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143510988","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}
Pub Date : 2025-02-19DOI: 10.1016/j.chstcc.2025.100142
Evelyn Sloan DPT , Selina M. Parry PhD , Alisha A. da Silva BPhysio, AdvRes (Hons) , Catherine L. Granger PhD , Zoe Fehlberg MPH , Owen Gustafson PhD , Catherine Voutier MInfoMgmt , Camille E. Short PhD , Marlena Klaic PhD
Background
Survivors of the ICU can experience physical, mental, and cognitive impairments, limiting activities and societal participation. Limited evidence supports the effectiveness of complex interventions after hospitalization, raising questions regarding how these interventions are developed and evaluated. Recommendations from implementation science and complex intervention research may provide further insight.
Research Question
What methods have informed the development and evaluation of complex interventions after hospitalization for survivors of the ICU. How have implementability (acceptability, fidelity, and feasibility) and efficacy been considered in the development and evaluation of these interventions?
Study Design and Methods
Studies were included if they developed or evaluated, or both, a complex, structured intervention after hospitalization aimed at improving recovery outcomes for survivors of the ICU. MEDLINE, Embase, PsycINFO, CINAHL, and PEDro were searched through June 4, 2024. Extracted data included intervention development processes; intervention description; and if and how acceptability or satisfaction, fidelity, feasibility, and efficacy were evaluated. Synthesis methods included deductive analysis and scoring using the Template for Intervention Description and Reporting (TIDieR) and the National Institutes of Health’s Treatment Fidelity Framework. Quality appraisal was completed using the applicable Johanna Briggs Institute (JBI) guidelines.
Results
Seventy-one publications were included involving 62 unique patient cohorts. Twelve studies (19%) used intervention development frameworks, whereas 24 studies (39%) engaged stakeholders in development processes. The median TIDieR score was 16 (interquartile range [IQR], 14-20) of 24. Twenty-two studies (35%) evaluated patient acceptability, of which 2 studies also evaluated clinician acceptability. Median treatment fidelity score was 6 (IQR, 6-9) of 21 with training, delivery, receipt, and enactment domains described poorly. The median consent rate was 48% (IQR, 34%-68%). Thirteen of the 22 studies (59%) designed to test efficacy achieved their sample size. Eight studies (13%) evaluated cost and 20 studies (34% of studies delivering interventions) reported safety. The median JBI score was 61% (IQR, 50%-70%).
Interpretation
Few studies reported applying theory-informed methods or engaging stakeholders in intervention development. Treatment fidelity focused on delivery with little description of receipt or enactment. Future efforts may consider applying implementation science theory and complex intervention approaches.
Clinical Trial Registration
International Prospective Register of Systematic Reviews; No.: CRD42023444648; URL: https://www.crd.york.ac.uk/prospero/
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