Critical care explorations最新文献

{"title":"Access to Limited Critical Care and Risk of Mortality in Rwanda: A Prospective Cohort Study.","authors":"Alex Mezei, Donatien Hitayezu, Tyler Gilman, Jeffrey Bone, Celestin Hategaka, Srinivas Murthy, Marla McKnight, Theogene Twagirumugabe","doi":"10.1097/CCE.0000000000001298","DOIUrl":"10.1097/CCE.0000000000001298","url":null,"abstract":"<p><strong>Importance: </strong>There is a large discrepancy between need and access to critical care in low- and middle-income countries. Little is known about what subgroups of patients are being prioritized for critical care.</p><p><strong>Objectives: </strong>The primary objective was to assess what clinical, demographic, and socioeconomic variables were associated with timely ICU admission. Secondary objectives included determining the rate of ICU admission among patients who met admission criteria, inpatient mortality, and length of stay.</p><p><strong>Design: </strong>Prospective cohort study.</p><p><strong>Setting and participants: </strong>All adult patients meeting ICU admission criteria at the University Teaching Hospital of Butare, Huye, Rwanda.</p><p><strong>Main outcomes and measures: </strong>The primary outcome was the proportion of patients admitted to ICU within 24 hours of being identified as critically ill. A multivariable logistic regression model was used to assess whether clinical, demographic, or socioeconomic factors are associated with timely ICU admission. Secondary outcomes were the proportion of patients admitted to ICU at any time, inpatient mortality, and length of stay.</p><p><strong>Results: </strong>Three hundred eighteen patients were enrolled between January 24, 2024, and June 3, 2024. Eighty-eight (27.7%) were admitted to ICU within 24 hours. Requiring ICU for postoperative recovery (odds ratio [OR], 8.21; 95% CI, 3.64-19.8), obstetric patients (OR, 2.43; 95% CI, 0.92-6.41), and ICU bed availability (OR, 1.26; 95% CI, 1.02-1.55) increased the odds of timely ICU admission in multivariable analysis. Socioeconomic status, gender, and social connections had minimal association with ICU admission, with wide CIs. The inpatient mortality rate was 44.0% and average length of stay was 14 days.</p><p><strong>Conclusions and relevance: </strong>Obstetric and postoperative patients are prioritized for ICU admission. There is a large unmet need for critical care in Rwanda, and mortality among critically ill patients is high.</p>","PeriodicalId":93957,"journal":{"name":"Critical care explorations","volume":"7 8","pages":"e1298"},"PeriodicalIF":2.7,"publicationDate":"2025-08-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12333700/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144796337","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}

{"title":"Life-Supporting Treatment Limitations in Patients Who Die Within 48 Hours After ICU Admission: A French, Multicenter, Observational, Exploratory Study.","authors":"Aurélie Nouvel, Pierre Leprovost, Charlotte Larrat, Xavier Valette, Isabelle Vinatier, Agathe Delbove, David Schnell, Anne Renault, Pauline Cailliez, Maud Jonas, Pauline Guillot, Anthony Lemeur, Jean Reignier, Théophile Lancrey-Javal, Reyes Munoz Calahorro, Soline Bobet, Gauthier Blonz","doi":"10.1097/CCE.0000000000001300","DOIUrl":"10.1097/CCE.0000000000001300","url":null,"abstract":"<p><strong>Importance: </strong>The occurrence of death shortly after ICU admission raises concerns about the appropriateness of providing intensive care to frail patients-many of whom are subsequently subject to decisions to limit life-supporting treatment limitation (LST-L). The proportion of patients who die early and are affected by such limitations remains unknown.</p><p><strong>Objectives: </strong>The primary objective was to determine the proportion of patients with a decision of LST-L among patients who died within 48 hours after ICU admission. We also conducted analyses to identify variables associated with LST-L and collected staff perceptions.</p><p><strong>Design, setting, and participants: </strong>A retrospective, observational, multicenter study with data collected immediately after the patient's death, according to predefined criteria. The study was conducted in 12 ICUs in France. Consecutive patients who died within 48 hours of ICU admission during the study period, in 2022-2023, were included. LST-L decisions were not guided by protocols but were at the discretion of the attending intensivists.</p><p><strong>Main outcomes and measures: </strong>Of 1615 patients admitted to the participating ICUs during the study period, 100 died (6.2%) within 48 hours, including 62 with LST-L.</p><p><strong>Results: </strong>In the LST-L group, age was significantly older (72 yr [64-77.8 yr] vs. 63 yr [59.0-69.8 yr]; p = 0.002), Charlson Comorbidity Index significantly higher (5.5 [2.0-8.0] vs. 4.0 [2.0-5.0]; p < 0.001), and management less invasive compared with the full-care group. By multivariable analysis, male patients were less likely to have LST-L decisions (odds ratio, 0.35; 95% CI, 0.13-0.93; p = 0.03). Most physicians, but a smaller proportion of nurses, perceived LST-L decisions as consensual. For 28 of 100 patients, the intensivist retrospectively deemed the ICU admission not the most suitable option. Patient wishes were rarely considered when making LST-L decisions. Time-limited trials were rarely used. Two-thirds of LST-L decisions were made during on-call hours.</p><p><strong>Conclusions and relevance: </strong>Deaths occurring shortly after ICU admission were usually preceded by LST-L decisions. Efforts are needed to better consider patients' wishes and to strengthen communication between ICU physicians and nursing staff, to ensure appropriate care-even when patients' wishes are unknown and alternatives to ICU admission are not straightforward. Such rare and sometimes unforeseeable cases may also reflect unspoken preferences of patients or their families.</p>","PeriodicalId":93957,"journal":{"name":"Critical care explorations","volume":"7 8","pages":"e1300"},"PeriodicalIF":2.7,"publicationDate":"2025-08-06","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12330360/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144791053","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}

{"title":"The Novel Application of Surgiflo and Successful Hemostasis of Refractory Intrapulmonary Hemorrhage in Extracorporeal Membrane Oxygenation.","authors":"Syed H Haq, Riley Pulver, Hoshimjon Begmatov, Candace Downing, Amanda Laird, Sandeep M Patel, Sreenivasa Chanamolu, William Cole","doi":"10.1097/CCE.0000000000001301","DOIUrl":"10.1097/CCE.0000000000001301","url":null,"abstract":"<p><strong>Background: </strong>Intrapulmonary hemorrhage (IPH) is a life-threatening condition associated with specific risk factors including prolonged mechanical ventilation, therapeutic anticoagulation, and notably, mechanical circulatory support (MCS). MCS creates a constellation of conditions that predispose patients to IPH. Given the need for systemic anticoagulation and concomitant critical illness, managing IPH can be challenging. Consequently, extracorporeal membrane oxygenation (ECMO) is accompanied by an increased mortality rate.</p><p><strong>Case summary: </strong>We present a case of a patient on ECMO complicated by severe intrapulmonary bleeding refractory to conventional therapies, but responded to the novel application of Surgiflo (a hemostatic matrix) to achieve hemostasis.</p><p><strong>Conclusions: </strong>Endobronchial application of Surgiflo provides a viable option to manage refractory IPH.</p>","PeriodicalId":93957,"journal":{"name":"Critical care explorations","volume":"7 8","pages":"e1301"},"PeriodicalIF":2.7,"publicationDate":"2025-08-06","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12330348/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144791055","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}

{"title":"Challenges Facing Developers of Diagnostic Tests for Sepsis: A Report From Sepsis Alliance and the Infection Management and Sepsis Collaborative Community.","authors":"Michael T McCurdy, Timothy E Sweeney, Debra Foster, Bobby Reddy, Steven Q Simpson","doi":"10.1097/CCE.0000000000001293","DOIUrl":"10.1097/CCE.0000000000001293","url":null,"abstract":"<p><strong>Objectives: </strong>To characterize regulatory and clinical adoption challenges to developing host-based sepsis diagnostics and to establish a common framework for stakeholders to work together toward potential solutions to these challenges.</p><p><strong>Design: </strong>Expert review, structured interviews, and small group discussions with experienced clinicians and experts in diagnostic test development and regulatory issues.</p><p><strong>Setting: </strong>A series of large and small group conference calls conducted from January 2023 to September 2024, along with a review of the available evidence and scope of the issue.</p><p><strong>Subjects: </strong>A collaborative group of multinational and multidisciplinary sepsis-focused patient advocacy groups, academic research groups, regulatory experts, and executives and clinical leaders from private companies assembled by Sepsis Alliance's Infection Management and Sepsis Collaborative Community.</p><p><strong>Interventions: </strong>The implications of existing regulatory practices surrounding the evaluation of host-based sepsis diagnostics were examined using structured, small group interviews and discussions. The entire expert panel collated the findings of small groups, and consensus was achieved on the most salient points.</p><p><strong>Measurements and main results: </strong>For various reasons, current regulatory practices surrounding host-based sepsis diagnostics pose significant challenges to both regulators and product developers in creating optimal clinical tools. The most important barriers to regulatory approval were considered to be: classification of the diagnostic tests' goals and output, heterogeneity of sepsis presentation and course, and lack of universal definitions of sepsis. Potential solutions to the challenges were informally proposed, but were not explored rigorously at this project phase.</p><p><strong>Conclusions: </strong>A collaborative statement was created outlining the challenges of developing diagnostic tests and devices for sepsis, including existing regulatory requirements surrounding host-based sepsis diagnostics and their implications for ultimate clinical deployment. Characterizing these challenges is a necessary first step to establish a common framework for stakeholders to effectively engage in discussions to develop potential solutions.</p>","PeriodicalId":93957,"journal":{"name":"Critical care explorations","volume":"7 8","pages":"e1293"},"PeriodicalIF":2.7,"publicationDate":"2025-08-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12327582/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144791051","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}

{"title":"Impact of Extending Beta-Lactam Infusions on IV Access Requirements.","authors":"Kirstin J Kooda, Julia Nelson, Sara E Ausman, Christina G Rivera, Omar M Abu Saleh, Andrew D Rule, Ryan W Stevens, Micaela N Warfield, Yanjun Zhao, Erin F Barreto","doi":"10.1097/CCE.0000000000001299","DOIUrl":"10.1097/CCE.0000000000001299","url":null,"abstract":"<p><p>This study aimed to determine if extended infusion (EI; over > 3 hr) beta-lactam therapy increased IV access requirements compared with traditional dosing (TD; over 30 min). Eighty-six adult ICU patients treated with TD anti-pseudomonal beta-lactams who underwent therapeutic drug monitoring (TDM) were included. Patients who transitioned from TD to EI after TDM (EI group) were matched 1:1 to patients who remained on TD. In the primary analysis, the median (interquartile range) total number of lumens in the 24 hours before TDM compared with the 48 hours after TDM were similar between groups (pre: TD 3 [2-5] vs. EI 4 [3-5]; p = 0.22 and post: TD 3 [2-4] vs. EI 4 [3-5]; p = 0.05). Delivery of beta-lactams via EI was not associated with a need for more IV access. Practical challenges such as access should not limit use of EI beta-lactams when indicated.</p>","PeriodicalId":93957,"journal":{"name":"Critical care explorations","volume":"7 8","pages":"e1299"},"PeriodicalIF":2.7,"publicationDate":"2025-08-04","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12324035/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144777263","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}

{"title":"Outcomes of Venovenous Extracorporeal Membrane Oxygenation for Pneumocystis jirovecii Pneumonia: A Multicenter Retrospective Case Series.","authors":"Aaron M Pulsipher, Kyle Henry, Holenarasipur R Vikram, Michael B Gotway, Rodrigo Cartin-Ceba, Andrew H Limper, Augustine Lee, Bhavesh Patel, Brittany Miller, Emily R Thompson, Ayan Sen, Kealy Ham","doi":"10.1097/CCE.0000000000001296","DOIUrl":"10.1097/CCE.0000000000001296","url":null,"abstract":"<p><p>Pneumocystis jirovecii pneumonia (PCP) is a life-threatening opportunistic infection increasingly recognized among non-HIV immunocompromised patients. In severe cases progressing to acute respiratory distress syndrome, venovenous extracorporeal membrane oxygenation (VV-ECMO) may serve as a rescue therapy. We conducted a retrospective multicenter review of 10 adult patients with proven or probable PCP who received VV-ECMO between 2017 and 2024. Seven of 10 patients survived to discharge, including all three HIV-positive patients and 4 of 7 non-HIV immunocompromised patients. The mean Respiratory ECMO Survival Prediction Score was -1.5, corresponding to a predicted survival of 33-57%. Multiorgan dysfunction was common, including renal failure requiring dialysis in 6 of 10 patients, need for neuromuscular blockade in 8 of 10, and pulmonary vasodilator use in 8 of 10. Despite high acuity and prolonged ECMO support, outcomes were favorable. These findings suggest that VV-ECMO may be a viable salvage therapy for select patients with severe PCP, including those without HIV.</p>","PeriodicalId":93957,"journal":{"name":"Critical care explorations","volume":"7 8","pages":"e1296"},"PeriodicalIF":2.7,"publicationDate":"2025-08-04","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12324008/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144777264","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}

{"title":"Outcomes of Venovenous Extracorporeal Membrane Oxygenation for <i>Pneumocystis jirovecii</i> Pneumonia: A Multicenter Retrospective Case Series.","authors":"Aaron M Pulsipher, Kyle Henry, Holenarasipur R Vikram, Michael B Gotway, Rodrigo Cartin-Ceba, Andrew H Limper, Augustine Lee, Bhavesh Patel, Brittany Miller, Emily R Thompson, Ayan Sen, Kealy Ham","doi":"10.1097/CCE.0000000000001296","DOIUrl":"10.1097/CCE.0000000000001296","url":null,"abstract":"<p><p><i>Pneumocystis jirovecii</i> pneumonia (PCP) is a life-threatening opportunistic infection increasingly recognized among non-HIV immunocompromised patients. In severe cases progressing to acute respiratory distress syndrome, venovenous extracorporeal membrane oxygenation (VV-ECMO) may serve as a rescue therapy. We conducted a retrospective multicenter review of 10 adult patients with proven or probable PCP who received VV-ECMO between 2017 and 2024. Seven of 10 patients survived to discharge, including all three HIV-positive patients and 4 of 7 non-HIV immunocompromised patients. The mean Respiratory ECMO Survival Prediction Score was -1.5, corresponding to a predicted survival of 33-57%. Multiorgan dysfunction was common, including renal failure requiring dialysis in 6 of 10 patients, need for neuromuscular blockade in 8 of 10, and pulmonary vasodilator use in 8 of 10. Despite high acuity and prolonged ECMO support, outcomes were favorable. These findings suggest that VV-ECMO may be a viable salvage therapy for select patients with severe PCP, including those without HIV.</p>","PeriodicalId":93957,"journal":{"name":"Critical care explorations","volume":"7 8","pages":"e1296"},"PeriodicalIF":2.7,"publicationDate":"2025-08-04","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12324008/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144791054","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}

{"title":"Impact of Extending Beta-Lactam Infusions on IV Access Requirements.","authors":"Kirstin J Kooda, Julia Nelson, Sara E Ausman, Christina G Rivera, Omar M Abu Saleh, Andrew D Rule, Ryan W Stevens, Micaela N Warfield, Yanjun Zhao, Erin F Barreto","doi":"10.1097/CCE.0000000000001299","DOIUrl":"10.1097/CCE.0000000000001299","url":null,"abstract":"<p><p>This study aimed to determine if extended infusion (EI; over > 3 hr) beta-lactam therapy increased IV access requirements compared with traditional dosing (TD; over 30 min). Eighty-six adult ICU patients treated with TD anti-pseudomonal beta-lactams who underwent therapeutic drug monitoring (TDM) were included. Patients who transitioned from TD to EI after TDM (EI group) were matched 1:1 to patients who remained on TD. In the primary analysis, the median (interquartile range) total number of lumens in the 24 hours before TDM compared with the 48 hours after TDM were similar between groups (pre: TD 3 [2-5] vs. EI 4 [3-5]; <i>p</i> = 0.22 and post: TD 3 [2-4] vs. EI 4 [3-5]; <i>p</i> = 0.05). Delivery of beta-lactams via EI was not associated with a need for more IV access. Practical challenges such as access should not limit use of EI beta-lactams when indicated.</p>","PeriodicalId":93957,"journal":{"name":"Critical care explorations","volume":"7 8","pages":"e1299"},"PeriodicalIF":2.7,"publicationDate":"2025-08-04","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12324035/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144791052","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}

{"title":"Characteristics and Outcomes of Patients Receiving Volatile Anesthetics in Near-Fatal Asthma: A Retrospective Observational Cohort Study.","authors":"Christopher Remmington, Luigi Camporota, Daniel Taylor, Angelo Sousa, Barnaby Sanderson, Guy Glover","doi":"10.1097/CCE.0000000000001295","DOIUrl":"10.1097/CCE.0000000000001295","url":null,"abstract":"<p><strong>Importance and objectives: </strong>Inhaled volatile anesthetics are employed as rescue therapy in near-fatal asthma, despite limited evidence. This study aims to describe the characteristics, management, and outcomes of mechanically ventilated adult patients with near-fatal asthma, stratified by the use of volatile anesthetic therapy.</p><p><strong>Design: </strong>Retrospective single-center observational cohort study.</p><p><strong>Setting: </strong>Tertiary critical care and extracorporeal membrane oxygenation (ECMO) unit.</p><p><strong>Participants: </strong>Adults 16 years old or older receiving mechanical ventilation (MV) for greater than or equal to 24 hours and/or ECMO between January 2016 and August 2023 for near-fatal asthma.</p><p><strong>Main outcomes and measures: </strong>We recorded demographics, disease severity tidal volumes, and ventilator settings, by treatment over the first 100 hours. Outcomes were duration of ECMO and MV, ICU length of stay, 90-day mortality, and adverse drug reaction.</p><p><strong>Results: </strong>Sixty-two patients were included (62.9% female), with a median (interquartile range [IQR]) age of 45 years (29-51 yr). Median (IQR) pH 7.13 (6.93-7.23), Paco2 12.9 kPa (8.7-16.2 kPa), and tidal volume 178 mL (50-300 mL). Most patients received IV bronchodilators and 32 (51.6%) required ECMO. Thirty-eight patients (61.3%) were treated with volatile anesthetics. Volatile patients had worse ventilation and blood gas parameters before treatment, more barotrauma, and were more likely to be receiving ECMO. Despite this, improvements in tidal volume occurred in the volatile group (mean increase, 204 mL [83.9%]; 95% CI, 110-298; p < 0.001). Median (IQR) duration of MV and ICU length of stay in volatile and no volatile patients were 10 days (8-16 d) vs. 5 days (3-10 d; p = 0.001) and 15 days (13-20 d) vs. 9 days (7-14 d; p = 0.001), respectively. ICU and 90-day mortality in volatile and no volatile patients were 5.3% vs. 4.2%.</p><p><strong>Conclusions and relevance: </strong>The use of inhaled volatile anesthetics for near-fatal asthma, including during ECMO, appears to be feasible and safe, and with favorable clinical outcomes; however, no conclusions regarding efficacy can be directly inferred.</p>","PeriodicalId":93957,"journal":{"name":"Critical care explorations","volume":"7 8","pages":"e1295"},"PeriodicalIF":2.7,"publicationDate":"2025-07-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12316345/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144755446","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}

{"title":"Comparative Evaluation of Lipopolysaccharide Administration Methods to Induce Acute Lung Injury in Murine Models: Efficacy, Consistency, and Technical Considerations.","authors":"Eva Kuhar, Duncan J Stewart, Doreen Engelberts, Forough Jahandideh, Matthew S Jeffers, Julie Khang, Haibo Zhang, Arnold S Kristof, Bernard Thébaud, Arul Vadivel, Dean A Fergusson, Manoj M Lalu","doi":"10.1097/CCE.0000000000001292","DOIUrl":"10.1097/CCE.0000000000001292","url":null,"abstract":"<p><strong>Context: </strong>Direct preclinical lipopolysaccharide acute lung injury (ALI) models are commonly used to study acute respiratory distress syndrome. Differences in lipopolysaccharide delivery methods may impact lung injury severity and reproducibility.</p><p><strong>Hypothesis: </strong>We hypothesized that the severity and variability of ALI outcomes in mice would differ depending on the technique of lipopolysaccharide administration.</p><p><strong>Methods and models: </strong>Male and female C57BL/6 mice were administered lipopolysaccharide (2.25 mg/kg) via four methods: 1) intratracheal intubation; 2) intranasal; 3) surgical transtracheal by either needle puncture; or 4) by catheter. ALI severity and variability were assessed at 72 hours post-lipopolysaccharide via histological scoring and bronchoalveolar lavage fluid (BALF) analysis (total protein, cell counts, interleukin-6 [IL-6]). The relative distribution of Evans Blue dye was also assessed for each model (lungs vs. stomach).</p><p><strong>Results: </strong>Distinct lung injury patterns were observed between the four methods. The transtracheal with catheter method demonstrated significantly greater lung injury scores than the intratracheal intubation and intranasal techniques. Both transtracheal methods produced greater alveolar neutrophil counts, increased proteinaceous debris, fewer hyaline membranes, and lower variability than non-surgical techniques. The transtracheal with catheter method produced higher BALF total cell counts and IL-6 levels than intratracheal intubation. Transtracheal methods also resulted in more localized Evans Blue dye distribution in the lungs. Male mice exhibited more severe lung injury scores and higher BALF protein concentrations than females.</p><p><strong>Interpretation and conclusions: </strong>This study demonstrates that the choice of technique to administer lipopolysaccharide impacts injury severity, phenotype, and variability. The surgical transtracheal with catheter technique produced the most robust and least variable ALI phenotype; however, this technique is associated with increased procedural complexity. Our results will allow researchers to tailor their model choice to align with their specific study objectives.</p>","PeriodicalId":93957,"journal":{"name":"Critical care explorations","volume":"7 8","pages":"e1292"},"PeriodicalIF":2.7,"publicationDate":"2025-07-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12306704/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144736097","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}