Critical Care Medicine[JOURNAL]
Sun
200 papers
Determining ICU Staff's Conceptions, Opinions, Views, Experiences, and Reflection (DISCOVER) of Brain Death-Results From a Swiss Multicenter Survey.
Grzonka P, Berger S, Tisljar K … +6 more , Hunziker S, Fisch U, Schumann R, Nebiker M, Cioccari L, Sutter R
Crit Care Med · 2026 Jun · PMID 42289099 · Publisher ↗
OBJECTIVES: To assess perceptions, beliefs, and conceptual understanding of brain death among ICU professionals at three Swiss hospitals and to examine their associations with personal, educational, and professional expe...
OBJECTIVES: To assess perceptions, beliefs, and conceptual understanding of brain death among ICU professionals at three Swiss hospitals and to examine their associations with personal, educational, and professional experiences. DESIGN: Cross-sectional questionnaire-based survey. SETTING: Multicenter survey at three Swiss care centers. SUBJECTS: ICU healthcare professionals (i.e., physicians and nurses). INTERVENTIONS: None. MEASUREMENTS AND MAIN RESULTS: Questionnaires assessed demographics, religious beliefs, professional experience, exposure to brain death cases, knowledge of diagnostic criteria, and emotional and ethical attitudes using closed-ended and semi-open questions, Likert scales (1 = "very unsure," "absolutely not" to 10 = "very sure," "absolutely"), and checklists. Endpoints were (primary) perceptions, beliefs, conceptual understanding of brain death, and (secondary) interprofessional differences and associations/correlations with personal, educational, social, and professional factors. Among 338 ICU professionals (78.1% nurses, 74% women), key diagnostic brain death criteria were well recognized, although misconceptions about nonessential tests persisted. Self-perceived understanding and approval were high (both median Likert scores, 9; interquartile range [IQR], 8-10), while agreement that a brain-dead patient is not a patient but a corpse was much lower (median, 1; IQR, 1-4). Physicians showed greater approval than nurses (p = 0.003) and were more likely to equate brain death with circulatory death (p < 0.001). Understanding increased with ICU experience (ρ = 0.194) and age (ρ = 0.213; both p < 0.001) and was higher among those with prior exposure to brain death or its diagnostics (both p < 0.001). No significant associations were found for sex, religious beliefs, parenthood, or bereavement. CONCLUSIONS: Although Swiss ICU professionals generally endorse and understand the brain death concept, our data indicate specific areas for improvement in conceptual clarity, particularly among nurses and less experienced professionals. In contrast to personal/philosophical influences, clinical exposure increases understanding and alignment with definitions, underscoring the need for targeted interdisciplinary education.
Perceived Inappropriateness of Intensive Care Treatment Among Clinicians: A Cross-Sectional Nationwide Survey on the Prevalence, Associated Factors, and Outcomes.
Hesselink G, Ramakers B, Fikkers BG … +7 more , Jongstra R, van Dijk D, Vloet L, Bakhshi-Raiez F, Benoit DD, Zegers M, Perceived Inappropriateness of Care Netherlands-Intensive Care Unit (PICNL-ICU) Study Group
Crit Care Med · 2026 Jun · PMID 42283554 · Publisher ↗
OBJECTIVES: To evaluate the prevalence and reasons for perceived inappropriateness of care (PIC) among ICU clinicians, to identify organizational, clinician, and work-related characteristics associated with PIC, and to d...
OBJECTIVES: To evaluate the prevalence and reasons for perceived inappropriateness of care (PIC) among ICU clinicians, to identify organizational, clinician, and work-related characteristics associated with PIC, and to determine if PIC is associated with adverse patient outcomes within 6 months post-ICU. DESIGN: Single-day cross-sectional survey, supplemented with follow-up data. SETTING AND PATIENTS: Physicians and nurses from 47 Dutch ICUs and 525 patients who were treated in the ICU on the survey day. INTERVENTIONS: None. MEASUREMENTS AND MAIN RESULTS: PIC (i.e., a patient situation in which care provision conflicts with a clinician's personal values or professional judgment) and other relevant variables were collected through questionnaires and the National Intensive Care Evaluation registry. A total of 1058 physicians and nurses (response rate, 72%) and 215 of the 397 eligible patients (54.2%) completed the survey. Among clinicians, 276 (26%) reported PIC for at least one patient. Clinicians mostly referred to distributive injustice (n = 181; 70%) and disproportionality of care (66%). Being a nurse (adjusted odds ratio [aOR], 1.78; 95% CI, 1.37-2.33; p < 0.001) and working in a culture that avoids end-of-life decisions (aOR, 1.92; 95% CI, 1.51-2.45; p < 0.001) were associated with higher PIC risk. Larger ICU bed capacity (aOR, 0.97; 95% CI, 0.94-0.99; p = 0.004) and mutual respect within interdisciplinary teams (aOR, 0.84; 95% CI, 0.70-1.00; p = 0.045) were protective. PIC reported by multiple clinicians was independently associated with increased risk of death (aOR, 3.86; 95% CI, 1.23-12.16; p = 0.02) and the combined outcome (i.e., death, severely frail, or not living at home anymore; aOR, 2.91; 95% CI, 1.14-7.42; p = 0.03). CONCLUSIONS: PIC is common in the ICU, inversely associated with a supportive ethical work environment, and should be regarded as a legitimate concern that warrants team reflection, as it is a prognostic marker of poor patient outcomes.
Positive Pleural Fluid Cultures in the ICU: A 10-Year Population-Based Cohort Study of Prevalence, Microbial Characteristics, and Clinical Associations.
Arge SI, Frambo SP, Nielsen FM … +4 more , Rasmussen BS, Nielsen HL, Søgaard KK, Schjørring OL
Crit Care Med · 2026 Jun · PMID 42283551 · Publisher ↗
OBJECTIVE: Pleural effusions are common in the ICU, often requiring drainage. Although fluid cultures are frequently obtained, pleural microbial findings in ICU patients remain poorly characterized. The current study aim...
OBJECTIVE: Pleural effusions are common in the ICU, often requiring drainage. Although fluid cultures are frequently obtained, pleural microbial findings in ICU patients remain poorly characterized. The current study aimed to assess prevalence and microbial characteristics of positive pleural fluid cultures in ICU patients, assessing positive cultures' associations with clinical assessments and 90-day mortality. DESIGN: Retrospective population-based cohort study of pleural fluid cultures in ICU. The primary outcome was the proportion of first pleural fluid cultures yielding positive microbial growth, secondary outcome was 90-day all-cause mortality. Using multiple regression, we assessed associations between suspected pleural infection and parapneumonic effusion, respectively, and the risk of a positive culture, as well as associations between a positive culture and 90-day mortality. SETTING: Data from eight ICUs comprising the entire North Denmark Region from March 1, 2013, to February 28, 2023, were obtained from the regional microbiological database, administrative databases, and through review of electronic medical records. PATIENTS: All adult patients who underwent pleural fluid culturing in any of the eight ICUs within the inclusion period. INTERVENTIONS: None. MEASUREMENTS AND MAIN RESULTS: A total of 1251 patients were included, of whom 51 (4.1%) had a positive first pleural culture. Suspected pleural infection was associated with a higher positive culture risk (adjusted risk ratio [RR]: 4.88; 95% CI, 2.70-8.83). No such association was observed for parapneumonic effusions (adjusted RR: 1.41; 95% CI, 0.83-2.38). A positive culture was associated with increased 90-day mortality (adjusted RR: 1.35; 95% CI, 1.04-1.73). CONCLUSIONS: In this 10-year cohort study of ICU patients undergoing pleural drainage, the risk of positive pleural fluid cultures was low. Suspected pleural infection significantly increased the likelihood of a positive culture, suggesting that culturing may be most useful in these cases. A positive pleural culture was associated with increased 90-day mortality underscoring its potential clinical significance.
Correlation Between Quantitative Pupillometry and Other Markers for Neuroprognostication of Comatose Patients After Cardiac Arrest: A Bicentric Study.
Benghanem S, Novy J, Cariou A … +2 more , Ben-Hamouda N, Rossetti AO
Crit Care Med · 2026 Jun · PMID 42274301 · Publisher ↗
OBJECTIVES: The prognostic role of quantitative pupillometry in comatose patients after cardiac arrest (CA) has been recently described, but data on quantitative pupillary light reflex (qPLR) are limited, especially in a...
OBJECTIVES: The prognostic role of quantitative pupillometry in comatose patients after cardiac arrest (CA) has been recently described, but data on quantitative pupillary light reflex (qPLR) are limited, especially in a multimodal approach and regarding good outcome. We assessed qPLR correlations with clinical features, electroencephalogram (EEG), somatosensory evoked potentials (SSEPs), and neuron-specific enolase (NSE), as well as qPLR prognostic values toward poor and good outcomes. DESIGN, SETTINGS, AND PATIENTS: Bicentric study (Centre Hospitalier Universitaire Vaudois, Lausanne, Switzerland and Cochin Hospital, Paris, France), analyzing prospective registries of comatose adults with pupillometry parameters obtained during the first 48-72 hours after CA. Neurological Pupil index (NPi), lowest (minimum qPLR), and highest values (maximum qPLR) of qPLR were collected. Predictive performances in terms of Cerebral Performance Categories (CPCs) level at 3 months (good outcome: CPC 1-2) were calculated. INTERVENTIONS: None. MEASUREMENTS AND MAIN RESULTS: Between 2020 and 2024, 442 patients were included. Minimum and maximum qPLRs were significantly lower in case of early myoclonus ( p < 0.001), bilateral N20 SSEP absence ( p < 0.001), unreactive EEG ( p < 0.001), and epileptiform EEG ( p = 0.03 and 0.05). qPLR was also significantly lower with suppressed EEG, compared with discontinuous and continuous background ( p < 0.001). Serum NSE level at 48 hours was significantly correlated with minimum (Spearman Rho = -0.283; p < 0.001) and maximum qPLRs ( R = -0.444; p < 0.001). Minimum qPLR less than 2% (96.4% specificity, 23.6% sensitivity), maximum qPLR less than 13% (96.4% specificity, 19.0% sensitivity), and NPi less than or equal to 2 (99% specificity, 34% sensitivity) robustly correlated with poor outcome. Notably, qualitative PLR had higher sensitivity than minimum and maximum qPLRs (38.9 vs. 23.6 and 19.0%, respectively; p < 0.001) with comparable specificity. A minimum qPLR greater than 9.5% (83.2% specificity, 31.1% sensitivity) and a maximum qPLR greater than 25.5% (62.2% specificity, 65.5% sensitivity) correlated with good outcome. CONCLUSIONS: In comatose patients after CA, qPLR is tightly correlated with other prognostic markers; low qPLR and NPi less than or equal to 2 appeared highly specific for poor outcome, but performances do not exceed that of clinical PLR. Finally, high qPLR remained limited in predicting a good outcome.
Clinical Prediction Models for Prognostication After Out-of-Hospital Cardiac Arrest: A Systematic Review and Meta-Analysis.
Niznick N, Sadeghirad B, Rochwerg B … +9 more , Tran A, Jung RG, Fantaneanu TA, Boyd JG, Sekhon MS, Hirsch KG, Nolan JP, Sandroni C, Fernando SM
Crit Care Med · 2026 Jun · PMID 42274294 · Publisher ↗
OBJECTIVES: Summarize the prognostic performance of existing clinical prediction models (CPMs) for neuroprognostication after out-of-hospital cardiac arrest (OHCA). DATA SOURCES: We searched Medline and Embase databases...
OBJECTIVES: Summarize the prognostic performance of existing clinical prediction models (CPMs) for neuroprognostication after out-of-hospital cardiac arrest (OHCA). DATA SOURCES: We searched Medline and Embase databases from inception to June 1, 2025. STUDY SELECTION: We selected English-language studies that included adults with OHCA and evaluated a CPM for the prediction of poor functional outcome. We excluded derivation cohorts for prognostic scores and excluded models without at least two external validation cohorts. DATA EXTRACTION: Two authors performed citation screening and data extraction. Where possible, we pooled the sensitivity and specificity of poor functional outcome, and the area under the receiver operating characteristic curve (AUROC) values for each CPM. We assessed risk of bias using the Prediction model study Risk of Bias Assessment Tool, and rated the certainty of evidence using the Grading of Recommendations, Assessment, Development, and Evaluation. DATA SYNTHESIS: We included 39 observational cohorts (95,037 patients) evaluating 11 different CPMs, with the two most common scores being the OHCA and Cardiac Arrest Hospital Prognosis (CAHP) scores. An OHCA score greater than or equal to 17 had a pooled sensitivity of 81.8% (95% CI, 65.8-91.4%) and specificity of 74.2% (95% CI, 58.8-85.3%), while a score of greater than or equal to 32 had a pooled sensitivity of 64.9% (95% CI, 44.0-81.3%) and specificity of 89.5% (95% CI, 75.9-95.8%) for poor functional outcome (low certainty). A CAHP score greater than or equal to 150 had a pooled sensitivity of 81.3% (95% CI, 77.7-84.4%) and specificity of 77.0% (95% CI, 70.6-82.4%) for poor functional outcome (moderate certainty). Pooled AUROCs across the 11 CPMs varied from 0.75 to 0.88, with substantial heterogeneity. CONCLUSIONS: CPMs for neuroprognostication after OHCA demonstrate only moderate accuracy, with substantial heterogeneity across validation cohorts. These limitations restrict their clinical utility, particularly for irreversible decisions such as withdrawal of life-sustaining therapy.
Pulse Pressure Variation During Passive Leg Raising to Assess Preload Responsiveness: Influence of Inspiratory Effort During Pressure Support Ventilation.
Caplan M, Pradignac L, Djerada Z … +14 more , Pierre A, Préau S, Ticos O, Thery G, Goury A, Passouant O, Sage M, Ficheux CA, Charon L, Boustani E, Mourvillier B, Bertrand M, Teboul JL, Hamzaoui O
Crit Care Med · 2026 Jun · PMID 42267876 · Publisher ↗
OBJECTIVES: Passive leg raising (PLR) is reliable to assess preload responsiveness in spontaneously breathing patients, but it requires cardiac output (CO) measurements. Recent studies suggested that a decrease in pulse...
OBJECTIVES: Passive leg raising (PLR) is reliable to assess preload responsiveness in spontaneously breathing patients, but it requires cardiac output (CO) measurements. Recent studies suggested that a decrease in pulse pressure variation (PPV) during PLR or an increase in pulse pressure (PP) during PLR could assess preload responsiveness, defined by a PLR-induced increase in CO. Our objective was to investigate whether PLR-induced changes in PPV and in PP assess preload responsiveness during pressure support ventilation (PSV). DESIGN: Prospective study. SETTING: Two ICUs of French university hospitals. PATIENTS: Critically ill patients receiving PSV and requiring assessment of preload responsiveness. INTERVENTIONS: Hemodynamic and transthoracic echocardiography variables were collected before and within 1 minute of PLR. PLR-induced changes in PPV and PP were calculated as the difference between PPV during PLR and PPV before PLR and the difference between PP during PLR and PP before PLR, respectively. Preload responsiveness was defined as an increase greater than or equal to 12% in the velocity-time integral of the subaortic flow during PLR. The population was subdivided according to the median value of airway occlusion pressure at 100 ms (P0.1), as an estimate of the inspiratory effort. MEASUREMENTS AND MAIN RESULTS: Thirty-four patients were included. Their median Simplified Acute Physiology Score II was 52 (42-65). Fourteen (41%) were defined as preload responders. Unlike baseline PPV and PLR-induced change in PP, PLR-induced change in PPV was associated with preload responsiveness (area under the receiver operating characteristic curve [AUROC], 0.76; p = 0.026; cutoff value, -3%). In patients with lower inspiratory effort (P0.1 < 2.3 cm H2O), PLR-induced change in PPV had a greater ability to assess preload responsiveness (AUROC, 0.90; p = 0.050; cutoff value, -3%) than in patients with higher inspiratory effort (AUROC, 0.61; p = 0.480). CONCLUSIONS: During PSV, PLR-induced changes in PPV assess preload responsiveness, primarily in patients with lower inspiratory effort reflected by P0.1. This simple test can predict the CO response to fluid administration without requiring direct CO measurement.
International Validation of Temperature-Trajectory Sepsis Subphenotypes With Longitudinal Immune and Coagulation Patterns and Its Implications for Immunoglobulin Therapy.
Wang L, Pei F, Gu B … +5 more , Navya TR, Long H, Guan X, Wu J, Bhavani SV
Crit Care Med · 2026 Jun · PMID 42267870 · Publisher ↗
OBJECTIVES: Sepsis remains a major challenge in the ICU. Given the limitations of the one-size-fits-all strategy, precision medicine approaches are needed to identify distinct sepsis subtypes that may respond to differen...
OBJECTIVES: Sepsis remains a major challenge in the ICU. Given the limitations of the one-size-fits-all strategy, precision medicine approaches are needed to identify distinct sepsis subtypes that may respond to different treatments. This study aimed to validate a temperature-trajectory model of sepsis developed in U.S. centers in a non-U.S. cohort from China, to characterize longitudinal immune and coagulation profiles, and to explore their potential value in guiding immunotherapy. DESIGN: This study validated a previously developed sepsis temperature-trajectory model, delineated longitudinal immune and coagulation dynamics across distinct subphenotypes, and, after propensity score matching, examined the heterogeneous effects of immunoglobulin treatment. SETTING: Retrospective data from a tertiary-care hospital ICU in China. PATIENTS: Adult ICU patients with suspected infection. INTERVENTIONS: None. MEASUREMENTS AND MAIN RESULTS: Clinical and microbiological characteristics were compared across subphenotypes, and the interaction between subphenotype and immunoglobulin therapy on 30-day mortality was assessed. In total, 2478 patients were included and classified into four subphenotypes: hyperthermic slow resolvers (567; 23%), hyperthermic fast resolvers (397; 16%), normothermic (780; 31%), and hypothermic (HT, 734; 30%). The HT subphenotype exhibited the highest mortality rate (25%), consistent with previous findings. In longitudinal immune and coagulation profiling, the HT subphenotype exhibited the lowest inflammatory response (low and rapidly declining C-reactive protein and rapidly declining interleukin-6), suppressed immunity (persistently low lymphocyte counts and monocyte human leukocyte antigen-DR), and coagulation abnormalities (persistently prolonged prothrombin time and activated partial thromboplastin time; the lowest platelet counts, fibrinogen, and hemoglobin; and the highest rate and dose of RBC transfusion). Immunoglobulin therapy showed heterogeneous effects across different subphenotypes, with patients in the HT subphenotype showing a consistent direction of benefit (primary subtyping: hazard ratio, 0.47; p = 0.03). CONCLUSIONS: The temperature-trajectory subphenotypes were validated in an international cohort. Patients in the HT subphenotype exhibited the highest mortality and showed persistent immune dysfunction and coagulopathy. Furthermore, different subphenotypes demonstrated distinct responses to immunoglobulin therapy.
Comparison of Intensive Versus Conventional Glycemic Control Targets: An Updated Systematic Review and Meta-Analysis of the 2024 Society of Critical Care Medicine Guidelines on Glycemic Control for Critically Ill Adults.
Sirimaturos M, Honarmand K, Long MT … +18 more , Preiser JC, Nagpal AD, Agus MSD, Aldouhan J, Bircher NG, Carpenter DL, Dearness K, Farrington EA, Freire AX, Hirshberg EL, Irving SY, Krinsley JS, Lanspa MJ, Prager R, Srinivasan V, Umpierrez GE, Wax SP, Jacobi J
Crit Care Med · 2026 Jun · PMID 42262517 · Publisher ↗
OBJECTIVES: To perform an updated systematic review and meta-analysis of the efficacy and safety of intensive (INT) vs. conventional (CONV) blood glucose (BG) targets for critically ill adults on insulin infusions. DATA...
OBJECTIVES: To perform an updated systematic review and meta-analysis of the efficacy and safety of intensive (INT) vs. conventional (CONV) blood glucose (BG) targets for critically ill adults on insulin infusions. DATA SOURCES: We conducted a comprehensive search of Embase and OVID Medline databases from inception to October 16, 2023. We manually excluded studies published before 2000 due to potential lack of relevance as glycemic control in the ICU was not routinely practiced before 2000. STUDY SELECTION: We included randomized controlled trials (RCTs) evaluating adult, critically ill patients on insulin infusions comparing INT vs. CONV targets for efficacy and safety outcomes. DATA EXTRACTION: Data were screened and extracted with accuracy confirmed by a second reviewer. Study methodological characteristics, patient population, interventions, and outcome data were recorded. Studies without numerical outcomes were summarized as text statements. DATA SYNTHESIS: Forty-five RCTs were included involving 32,215 patients. No differences were seen between INT and CONV targets for hospital mortality or ICU mortality. INT targets were associated with lower ICU length of stay (LOS), infections, and critical illness polyneuropathy (CIP); however, INT targets demonstrated a 3.6-fold higher risk of severe hypoglycemia. Most of the studies with significant differences contained serious inconsistencies or risk of bias. In the subgroup analyses, INT targets demonstrated favorable neurologic outcomes in neurologic ICU patients, lower ICU LOS in mixed ICU patients, and lower ICU mortality in the cardiac surgery subgroup. CONCLUSIONS: INT BG targets demonstrated mild to moderate improvements in several important morbidity secondary outcomes, including LOS, infections, and CIP, but were associated with a 3.6-fold higher risk of severe hypoglycemia. No differences were seen in ICU or hospital mortality. INT targets should not be routinely used over CONV targets when trying to minimize hypoglycemia as a marker of patient safety. However, as stated in the Society of Critical Care Medicine guidelines, a lower target within the INT range (110-140 mg/dL; 6.1-7.8 mmol/L) may be considered acceptable in select centers where the risk of hypoglycemia is documented to be negligible based on routine assessment and with the use of optimized glycemic management protocols.
Hospital-Level Variation in Early Tracheostomy and Withdrawal of Life-Sustaining Treatment in Severe Traumatic Brain Injury: A Nationwide Analysis.
Katsura M, Ikenoue T, Ambrose C … +3 more , Braschi C, Fukuma S, Matsushima K
Crit Care Med · 2026 Jun · PMID 42262510 · Publisher ↗
OBJECTIVES: Early tracheostomy (ET) in severe traumatic brain injury (TBI) is often considered during periods of prognostic uncertainty and evolving goals of care. We aimed to evaluate the association between hospital-le...
OBJECTIVES: Early tracheostomy (ET) in severe traumatic brain injury (TBI) is often considered during periods of prognostic uncertainty and evolving goals of care. We aimed to evaluate the association between hospital-level tendency for ET and the frequency of withdrawal of life-sustaining treatment (WLST) following tracheostomy in patients with severe TBI. DESIGN: Retrospective cohort study. SETTING: Trauma centers participating in the American College of Surgeons Trauma Quality Improvement Program (2016-2021). PATIENTS: Adult patients 20-89 years old with severe TBI (head Abbreviated Injury Scale: 3-5 and Glasgow Coma Scale: 3-8), who received mechanical ventilation and underwent tracheostomy. INTERVENTIONS: None. MEASUREMENTS AND MAIN RESULTS: A mixed-effects logistic regression model was developed to estimate each hospital's unique risk-adjusted odds ratio (AOR) for ET (≤ 7 d after injury), and hospitals were stratified into low-, medium-, and high-tendency groups based on the AOR for ET. The association between hospital-level tendency for ET and WLST post-tracheostomy was assessed. Among 22,156 patients with severe TBI treated at 417 hospitals, the ET rates were 16.8%, 30.1%, and 47.7% in the low-, medium-, and high-tendency hospitals, respectively. WLST following tracheostomy occurred in 2.6%, 4.8%, and 9.6% of patients 20-39, 40-59, and 60-89 years old, respectively. After multilevel case-mix adjustments, a high hospital-level tendency for ET was associated with increased odds of WLST post-tracheostomy (AOR, 1.35; 95% CI, 1.10-1.66; p = 0.004), with the highest point estimate observed among patients 40-59 years old (AOR, 1.39; 95% CI, 1.01-1.91). CONCLUSIONS: Hospitals with a higher tendency to perform ET had a greater likelihood of WLST following tracheostomy. These findings highlight practice variability in tracheostomy timing that may occur in the setting of prognostic uncertainty early after severe TBI and may influence downstream care pathways.
Continuing Vs. Withholding Home Beta-Blockers at Admission for Suspected Infection: A Target Trial Emulation.
Christian-Miller N, Lee KT, Pashun R … +8 more , Ballut K, Prescott H, Cascino T, Taylor SP, Ansari S, Sjoding MW, Nagle M, Admon AJ
Crit Care Med · 2026 Jun · PMID 42262489 · Publisher ↗
OBJECTIVE: Beta-blockers are commonly prescribed for chronic cardiovascular diseases. Despite potential benefits in septic shock, beta-blockers are often held at hospital admission for patients with suspected infection a...
OBJECTIVE: Beta-blockers are commonly prescribed for chronic cardiovascular diseases. Despite potential benefits in septic shock, beta-blockers are often held at hospital admission for patients with suspected infection and possible sepsis. We compared the effects of chronic beta-blocker continuation vs. discontinuation on 90-day all-cause mortality among patients admitted from the emergency department with suspected infection. DESIGN: Retrospective cohort study using the target trial emulation framework. We used Cox regression to compare 90-day mortality between treatment groups, with inverse probability of treatment weights to account for baseline differences in sex, race, ethnicity, age, body mass index, presence of a "do not resuscitate" order, comorbidities, and acute illness severity. SETTING: A single large, academic, tertiary care emergency department in the Midwest United States. PATIENTS: Patients 18 years or older on beta-blockers prior to admission hospitalized for suspected infection (defined by orders for blood cultures and broad-spectrum antibiotics). Patients with shock, heart rates less than 40 or greater than 120, or who required an IV beta- or calcium channel blocker at a clinician's discretion were excluded. INTERVENTIONS: Continuation of oral beta-blockers within 48 hours of admission vs. no continuation. MEASUREMENTS AND MAIN RESULTS: Of 4635 eligible patients, 1172 (25.3%) received an oral beta-blocker, whereas 3463 (74.7%) did not receive an oral beta-blocker. Beta-blocker continuation was associated with a reduced risk of all-cause mortality within 90 days of hospital admission (hazard ratio 0.77; 95% CI, 0.61-0.98; p = 0.03) and shorter hospital stay (incidence rate ratio 0.39; 95% CI, 0.38-0.41; p < 0.001). There was no significant association between beta-blocker continuation and in-hospital mortality (odds ratio 0.60; 95% CI, 0.30-1.20; p = 0.15). CONCLUSIONS: Continuation of chronic beta-blockers in a broad population of patients admitted with suspected infection was associated with improved clinical outcomes. Our findings support the need for controlled experimental studies evaluating the role of chronic beta-blocker continuation among patients hospitalized with possible sepsis.
Traumatic Brain Injury Enhances Susceptibility to Lung Bacterial Infection in Mice and Pigs by Modulating the Innate Immune Response.
Seshadri AJ, Alves P, Kim HI … +17 more , Singh A, Harbison J, Hancco I, Nikolaus-Liberum J, Voltarelli V, Meehan WP, Qiu J, Guilhaume-Correa F, Warren K, Nosek N, Sodemann RL, Nedder A, Stippler M, Hauser C, Mannix R, Ghiran I, Otterbein LE
Crit Care Med · 2026 Jun · PMID 42262353 · Publisher ↗
OBJECTIVE: Traumatic brain injury (TBI) leads to immune dysregulation, which predisposes patients to infections. We hypothesized that TBI leads to poor lung bacterial clearance, due at least in part to dysfunctional neut...
OBJECTIVE: Traumatic brain injury (TBI) leads to immune dysregulation, which predisposes patients to infections. We hypothesized that TBI leads to poor lung bacterial clearance, due at least in part to dysfunctional neutrophil (PMN) responses. In this study, we characterized both murine and porcine models of TBI plus lung bacterial inoculation to evaluate the effects of TBI on bacterial clearance, and tested the effects of plasma harvested from human TBI patients on PMN function. DESIGN: C57BL6 mice or Yucatan mini swine underwent sham (anesthesia only) or a mild TBI using standardized methods. Four hours later, mice were inoculated with Staphylococcus aureus. Pigs were inoculated with Actinobacter pleuropneumoniae immediately after TBI. At prespecified timepoints after inoculation (24 hr for mice and 72 hr for pigs), animals were euthanized and bronchoalveolar lavage (BAL) and blood were collected, and lung was harvested for further analyses. Plasma from TBI patients was used to perform in vitro assessment of PMN function. SUBJECTS: C57BL6 mice, Yucatan mini swine, healthy volunteers, and TBI patients. INTERVENTIONS: None. MEASUREMENTS AND MAIN RESULTS: In both animal models, TBI predisposed to poor pulmonary bacterial clearance despite significantly increased PMNs in BAL and blood. In vitro, treatment of PMNs with plasma or plasma-derived extracellular vesicles (EVs) from TBI patients led to increased nondirectional chemokinesis, less reactive oxygen species production, and decreased ability to phagocytose. CONCLUSIONS: TBI leads to decreased bacterial clearance in the lung in models of TBI + bacterial lung infection, despite increased PMN counts in lung and blood. This is secondary to inappropriate PMN function after TBI, which we demonstrated in vitro via multiple functional assays to be caused, in part, by systemic factors in the plasma, including EVs. Further studies are required to understand the link between TBI and PMN dysfunction that leads to increased susceptibility to bacterial lung infection.
The Impact of Centrally Acting Drug Burden at Discharge on Long-Term Outcomes Among ICU Survivors.
Boncyk C, Connell J, Stollings JL … +9 more , Vasilevskis EE, Walsh A, Rengel KF, Jackson J, Orun OM, Raman R, Pandharipande PP, Ely EW, Hughes CG
Crit Care Med · 2026 Jun · PMID 42262347 · Publisher ↗
OBJECTIVES: ICU patients are at increased risk of inappropriate prescribing and high drug burden. These patients also often experience cognitive impairment, physical disability, and increased mortality after discharge. W...
OBJECTIVES: ICU patients are at increased risk of inappropriate prescribing and high drug burden. These patients also often experience cognitive impairment, physical disability, and increased mortality after discharge. We investigated whether drug burden at hospital discharge was associated with worsened cognition, physical disability, and mortality among ICU survivors up to 6 months postdischarge. DESIGN: Substudy of three prospective cohort studies. SETTING: Tertiary academic medical center. PATIENTS: Adult patients with respiratory failure and/or shock discharged alive from the ICU. INTERVENTIONS: None. MEASUREMENTS AND MAIN RESULTS: Drug burden was quantified using drug burden index (DBI) at admission, ICU transfer, and hospital discharge. Cognition was assessed with validated cognitive batteries. We assessed physical disability using Katz activities of daily living (ADL) and Functional Activities Questionnaire (FAQ), and 90-day mortality via chart review and surrogate. Binary logistic regression was used to investigate the association of discharge DBI on cognitive impairment, adjusting for prespecified covariates. Multivariable proportional odds logistic regression was used to investigate the association of discharge DBI on physical disability. Cox proportional hazards regression was used to investigate 90-day mortality. A total of 676 patients were included, 478 patients with cognitive assessment and 490 with physical assessment data. Median DBI increased throughout hospitalization with admission, ICU transfer, and hospital discharge DBI 1.96, 2.42, and 3.08, respectively. We did not find a statistically significant association between hospital discharge DBI and long-term cognitive impairment (odds ratio [OR] 1.25; 95% CI, 0.89-1.76; p = 0.20). There was no association between hospital discharge DBI and Katz activities of daily living (OR 1.08; 95% CI, 0.80-1.44; p = 0.62), FAQ (OR 1.15; 95% CI, 0.89-1.49; p = 0.29), or 90-day mortality (hazard ratio 0.87; 95% CI, 0.61-1.23; p = 0.42). CONCLUSIONS: Within our cohort of ICU survivors, we did not find a significant association of centrally acting drug burden measured by the DBI with long-term cognitive impairment, physical disability, or 90-day mortality.
Short-Term and Long-Term Mortality of Pulmonary Embolism Patients Admitted to the ICU in the Netherlands.
Mandigers L, Termorshuizen F, Rietdijk WJR … +4 more , Stenger WJE, Klok FA, de Keizer NF, den Uil CA
Crit Care Med · 2026 Jun · PMID 42262341 · Publisher ↗
OBJECTIVES: To describe the short-term and long-term mortality of pulmonary embolism patients admitted to the ICU. DESIGN: Retrospective cohort study of data from the Netherlands Intensive Care Evaluation registry. SETTI...
OBJECTIVES: To describe the short-term and long-term mortality of pulmonary embolism patients admitted to the ICU. DESIGN: Retrospective cohort study of data from the Netherlands Intensive Care Evaluation registry. SETTING: All ICUs in the Netherlands. PATIENTS: All adult critically ill patients (≥ 18 yr) with pulmonary embolism as ICU admission diagnosis between 2013 and 2023 were included in the study. INTERVENTIONS: None. MEASUREMENTS AND MAIN RESULTS: The primary outcome is hospital mortality for patients with pulmonary embolism admitted to the ICU, as this represents short-term outcomes of pulmonary embolism and its treatment. The secondary outcome was 1-year mortality as a long-term outcome. Next, we compared patient characteristics and outcomes for survivors and nonsurvivors of the hospital admission. Of 10,210 eligible patients, 1,506 patients died (14.6%) during admission. This hospital mortality rate was higher in high-risk pulmonary embolism patients (n = 1372, 25.4%) than in non-high-risk pulmonary embolism patients (n = 134, 2.8%). Multivariable analysis also shows a higher 1-year mortality rate in high-risk pulmonary embolism patients than in non-high-risk pulmonary embolism patients (hazard ratio [HR], 3.98; CI, 3.59-4.40). The 1-year mortality of hospital survivors after hospital discharge is also higher in high-risk pulmonary embolism patients than in non-high-risk pulmonary embolism patients (HR, 1.70; CI, 1.49-1.96). CONCLUSIONS: This nationwide registry study confirmed that high-risk pulmonary embolism patients have a higher mortality than patients with non-high-risk pulmonary embolism admitted to the ICU. The unfavorable difference in mortality risk persists in the first year after hospital discharge. These numbers should be considered when making management decisions in patients with pulmonary embolism.
Diagnostic and Prognostic Value of the Venous Excess Ultrasound Grading System: A Systematic Review and Meta-Analysis.
Klompmaker P, Opschoor K, Dalen JT … +5 more , de Vries R, Balan C, Veelo DP, Vlaar APJ, Tuinman PR
Crit Care Med · 2026 Jun · PMID 42262338 · Publisher ↗
OBJECTIVES: The venous excess ultrasound (VExUS) grading system has gained recognition in acute and critical care medicine as a promising approach to evaluate venous congestion and optimize fluid management. However, the...
OBJECTIVES: The venous excess ultrasound (VExUS) grading system has gained recognition in acute and critical care medicine as a promising approach to evaluate venous congestion and optimize fluid management. However, the diagnostic accuracy and prognostic value of VExUS remain unclear. DATA SOURCES: PubMed, Embase.com, Web of Science (Core Collection), and Wiley/Cochrane Library from inception to May 19, 2025, in accordance with the Preferred Reporting Items for Systematic Reviews and Meta-Analyses guidelines and in collaboration with a medical information specialist. STUDY SELECTION: Study selection was systematically performed by a panel of authors. A total of 32 studies were included, consisting of 3142 patients, with six diagnostic, 22 prognostic studies, and four studies that reported on both diagnostic and prognostic outcomes. DATA EXTRACTION: Relevant data were extracted by two authors, and the corresponding authors were contacted when necessary. DATA SYNTHESIS: For diagnostic studies, no meta-analysis could be performed. Studies suggest moderate to good diagnostic accuracy for detecting increased central venous and right atrial pressures (sensitivity 78-95%, specificity 80-90%). Prognostic studies in cardiac patients found an association between VExUS greater than or equal to 2 and acute kidney injury (AKI; odds ratio [OR], 4.44; 95% CI, 2.34-8.43; moderate certainty) and mortality (OR, 3.17; 95% CI, 1.30-7.75, low certainty). For critically ill patients, no associations between VExUS greater than or equal to 2 and AKI (OR, 1.45; 95% CI, 0.70-2.99; very low certainty) and mortality (OR, 1.25; 95% CI, 0.77-2.03; low certainty) were found. Per-patient analysis showed an association between VExUS 3 and mortality for all patients and an association with AKI for cardiac patients. CONCLUSIONS: Results from this systematic review and meta-analysis suggest that VExUS has moderate to good accuracy to diagnose increased central venous pressure and right atrial pressure. In cardiac patients, higher VExUS grades are associated with AKI and mortality, but in critically ill patients, the association between VExUS grades and outcomes is less clear.
Multimodal Perfusion Assessment in Hemodynamically Unstable Patients: A Concise Definitive Review.
Sanchez-Escalante C, Monnet X
Crit Care Med · 2026 Jun · PMID 42240436 · Publisher ↗
OBJECTIVES: Assessment of tissue perfusion remains a central challenge in the management of hemodynamically unstable patients, as normalization of macrocirculatory variables does not necessarily reflect restoration of ef...
OBJECTIVES: Assessment of tissue perfusion remains a central challenge in the management of hemodynamically unstable patients, as normalization of macrocirculatory variables does not necessarily reflect restoration of effective organ perfusion. This concise definitive review examines contemporary approaches to multimodal perfusion assessment and discusses how available monitoring tools may be integrated into a stepwise, physiology-driven framework to guide escalation of monitoring at the bedside. DATA SOURCES: Relevant physiologic and clinical studies addressing peripheral perfusion assessment, hemodynamic monitoring, and circulatory shock were identified from the peer-reviewed literature and complemented by established physiologic concepts and clinical experience. STUDY SELECTION: Randomized clinical trials, observational studies, physiologic investigations, and narrative and systematic reviews evaluating perfusion monitoring modalities in critically ill patients were considered. DATA EXTRACTION AND DATA SYNTHESIS: Available monitoring tools-including capillary refill time, peripheral perfusion indices, serum lactate, venous oxygenation variables, tissue oxygenation, spectral imaging techniques, and advanced hemodynamic assessments were analyzed with emphasis on physiologic rationale, clinical applicability, strengths, and limitations. These elements were integrated into a pragmatic framework emphasizing dynamic interpretation and proportional escalation of monitoring rather than normalization of isolated variables. CONCLUSIONS: Multimodal perfusion assessment should be interpreted as an integrated physiologic process rather than a search for a single superior marker. Capillary refill time provides a pragmatic clinical anchor, while complementary tools may refine interpretation when physiologic coherence is uncertain. Escalation of monitoring should be guided by patient risk and unresolved uncertainty, supporting individualized, physiology-driven resuscitation while minimizing unnecessary therapeutic escalation.
Reported Practices in End-of-Life Decision-Making During Extracorporeal Life Support (ENSURE)-Results From an International European Chapter of the Extracorporeal Life Support Organization Survey.
Swol J, Supady A, Fleig M … +4 more , Kelly-Geyer J, Hoskote A, Thiagarajan RR, Polito A
Crit Care Med · 2026 Jun · PMID 42240435 · Publisher ↗
OBJECTIVES: The ENd-of-life deciSion-making dURing Extracorporeal life support (ENSURE) survey aimed to assess current clinical practices and perspectives on end-of-life decisions for patients on extracorporeal life supp...
OBJECTIVES: The ENd-of-life deciSion-making dURing Extracorporeal life support (ENSURE) survey aimed to assess current clinical practices and perspectives on end-of-life decisions for patients on extracorporeal life support (ECLS) across Europe. Understanding the challenges surrounding ECLS withdrawal may help mitigate moral distress in this complex decision-making process. DESIGN: The survey covered 20 questions to be assessed online and was composed of two sections: the first dealt with general questions on hospital details, ICU profile, ECLS provision, and participants' profession, and the second part was designed to elicit clinical questions, institutional protocols, management, and palliative care provision. For most of the questions, multiple-choice answers were provided. SETTING: The survey was translated into 31 native European languages and captured respondents' actual practices, institutional protocols, management approaches, and palliative care provision related to ECLS discontinuation. PATIENTS: Critically ill patients on ECLS when treatment goals are no longer achievable. INTERVENTIONS: None. MEASUREMENTS AND MAIN RESULTS: Responses from 570 participants across 28 European countries showed that physicians (99%), nurses (63%), and relatives (54%) are commonly involved in ECLS end-of-life discussions. Although 49% of institutions offer clinical ethics committee access and 12% provide clinical ethicists, 24% lack any ethics support for challenging decisions. When ECLS goals fail, 41% of respondents reported discontinuing ECLS with comfort care, with Northern and Western Europeans most likely to report this practice (54% and 59%). Southern and Eastern Europeans more often reported limiting life-sustaining treatments without stopping ECLS (42% and 46%). Differences could also be observed for professionals with different religious backgrounds. CONCLUSIONS: The ENSURE survey highlights significant regional and cultural variations in reported ECLS discontinuation practices across Europe, likely influenced by clinicians' diverse backgrounds and institutional contexts. These differences, alongside limited ethics and palliative care support, underscore the need for structured interventions to enhance consistency and reduce moral distress in end-of-life decision-making for ECLS patients.
Implementation of a Remote Respiratory Therapy in a Donor Center ICU Using a Telecritical Care Platform.
Ghio M, Pavlichko H, Patel A … +6 more , Acero-Webb JA, Howley B, Brown E, O'Neill K, Pascual JL, Martin ND
Crit Care Med · 2026 Jun · PMID 42240434 · Publisher ↗
OBJECTIVES: To evaluate the feasibility, safety, and operational impact of delivering comprehensive remote telecritical care respiratory therapy (eRT), including full ventilator management, in a dedicated brain-dead dono...
OBJECTIVES: To evaluate the feasibility, safety, and operational impact of delivering comprehensive remote telecritical care respiratory therapy (eRT), including full ventilator management, in a dedicated brain-dead donor care ICU. DESIGN: Prospective observational study conducted over a 12-month period (from October 2023 to October 2024). SETTING: An eight-bed brain-dead donor care ICU utilizing a telecritical care platform with real-time audiovisual monitoring and remote ventilator interface capability. SUBJECTS: Organ donors (n = 182) managed during the study period. INTERVENTIONS: All respiratory therapy (RT) care, including ventilator management and procedural support, was delivered remotely. In-person RT support was available as needed. MEASUREMENTS AND MAIN RESULTS: Procedural workload, in-person RT utilization, safety events, donor outcomes, and full-time equivalent (FTE) labor requirements were recorded. eRT completed 3872 respiratory procedures, totaling 1782 hours of remote care. In-person RT support was required for 119 hours (6.1%), primarily for transport and advanced airway interventions. No airway losses, emergency RT activations, cardiac arrests, or delays in care occurred. Remote RT support resulted in an estimated savings of 2.2 FTEs and $306,952 in avoided labor costs. A total of 520 organs were procured, with an observed-to-expected recovery ratio of 1.19. CONCLUSIONS: Comprehensive remote RT, including full ventilator management, was safely and effectively implemented in a donor care ICU. This model substantially reduced bedside staffing requirements while maintaining favorable donor outcomes, supporting broader adoption and highlighting the need for regulatory pathways enabling secure remote ventilator access.
Incidence and Outcomes of Refractory Septic Shock per Consensus Clinical Criteria: A Multicohort Retrospective Study.
Bauer SR, Wieruszewski PM, Khanna AK … +13 more , Leone M, Barreto EF, Dugar S, Sacha GL, Mourany L, Gunsalus PR, Milinovich A, Reddy AJ, Kane-Gill SL, Tarabichi Y, Wang X, Dalton JE, Vachharajani V
Crit Care Med · 2026 Jun · PMID 42240423 · Full text
OBJECTIVES: Consensus clinical criteria for refractory septic shock were recently developed, but the incidence and outcomes with these criteria are unknown. There were two aims: 1) to describe the incidence of refractory...
OBJECTIVES: Consensus clinical criteria for refractory septic shock were recently developed, but the incidence and outcomes with these criteria are unknown. There were two aims: 1) to describe the incidence of refractory septic shock and 2) to assess outcomes of patients with septic shock meeting refractory septic shock criteria compared with those who did not. DESIGN: Multicohort, retrospective study. For aim 1, a descriptive epidemiologic study was designed to ascertain the cumulative incidence of refractory septic shock in patients with septic shock. For aim 2, a cohort study was conducted to compare hospital mortality between patients meeting refractory septic shock clinical criteria compared with those who did not. SETTING: Large U.S. health system from 2012 to 2024. PATIENTS: Adults (age ≥ 18 yr) meeting both Centers for Disease Control and Prevention Adult Sepsis Event and Sepsis-3 clinical criteria for septic shock. Patients with missing hospital discharge disposition and incomplete vasopressor dosage information were excluded. INTERVENTIONS: None. MEASUREMENTS AND MAIN RESULTS: Clinical criteria for refractory septic shock were operationalized as concomitant occurrence of norepinephrine (base) equivalent greater than 0.5 µg/kg/min and lactate greater than 2 mmol/L. Risk-adjusted hospital mortality was assessed with a generalized linear mixed-effects model with a random effect for hospital and fixed effects for age, sex, Elixhauser Comorbidity Index, and Sequential Organ Failure Assessment (original description, without cardiovascular component). Of 35,914 patients assessed, 15,732 patients with septic shock were included. Refractory septic shock occurred in 3423 patients (21.8%), with a cumulative incidence of 218 cases (95% CI, 211-224) per 1000 patients with septic shock. Hospital mortality with refractory septic shock was 64.4%, and risk-adjusted hospital mortality odds were 4.87-fold higher (95% CI, 4.46-5.31) compared with patients without refractory septic shock. CONCLUSIONS: Clinical criteria for refractory septic shock were fulfilled in about one in five patients with septic shock and associated with substantially higher mortality.
Epidemiology and Outcomes Among Adults With Severe Community-Acquired Bacterial Pneumonia Hospitalized in the United States, 2021-2024.
Zilberberg MD, Greenberg M, Nathanson BH … +3 more , Andan QE, Curt V, Shorr AF
Crit Care Med · 2026 Jun · PMID 42233741 · Publisher ↗
OBJECTIVES: To examine post-pandemic population, treatment, and outcomes of severe community-acquired bacterial pneumonia (sCABP) as identified via two common definitions, and to compare these two groups. DESIGN: A retro...
OBJECTIVES: To examine post-pandemic population, treatment, and outcomes of severe community-acquired bacterial pneumonia (sCABP) as identified via two common definitions, and to compare these two groups. DESIGN: A retrospective quasi-cohort study within Premier Healthcare Database, 2021-2024. SETTING: 849 U.S. acute care hospitals (253 reporting microbiology data). PATIENTS: Adults hospitalized with sCABP, as defined by the need for ICU (ICU-sCABP) or by the American Thoracic Society (ATS) major criteria. INTERVENTIONS: None. MEASUREMENTS AND MAIN RESULTS: Among 67,439 patients who met either definition of sCABP (24.5% of all CAPB admissions), 51.2% met ICU-sCABP and 78.0% ATS-sCABP definitions. The groups were similar with respect to age, gender, and race, and the burden of chronic illness. While similar proportions in both groups required vasopressors (17.0% ICU-sCABP vs. 15.8% ATS-sCABP), fewer in the ICU-sCABP than the ATS-sCABP received mechanical ventilation (MV, 51.9% vs. 91.0%). Noninvasive positive pressure ventilation predominated in both (27.9% ICU-sCABP vs. 65.6% ATS-sCABP), while invasive MV (IMV) was used in under ¼ of all patients in either group. Among patients with a known pathogen (n = 851 ICU-sCABP and n = 959 ATS-sCABP), the distribution of organisms was similar. Staphylococcus aureus (30.2% ICU-sCABP and 31.7% ATS-sCABP) and Pseudomonas aeruginosa (24.5% ICU-sCABP vs. 27.0% ATS-sCABP) were most common. Streptococcus pneumoniae caused 11.0% of ICU-sCABP and 9.8% of ATS-sCABP. Antibiotics classes used were similar as well. Hospital mortality (15.6% ICU-sCABP vs. 15.0% ATS-sCABP), 30-day readmission (14.8% ICU-sCABP vs. 15.7% ATS-sCABP), median hospital length of stay (LOS, 7 d for each), median ICU LOS (3 d for each), and median MV duration (3 d for each) were also similar. CONCLUSIONS: The two commonly used sCABP definitions identify a similar population of patients, which is large and resource-intensive. MV practices have evolved since the pandemic, with much less IMV used. Despite these changes, mortality risk from sCABP remains unacceptably high.
Myelin Basic Protein Expressing Microparticles Predict Neurologic Morbidity Risk From Acute Carbon Monoxide Poisoning.
Bhat AR, Sethuraman K, Arya AK … +10 more , Cha YS, Liang Y, Walia D, Imtiyaz Z, Lee Y, Moayedi S, Sward D, Chew A, Badjatia N, Thom SR
Crit Care Med · 2026 Jun · PMID 42233740 · Publisher ↗
OBJECTIVE: Identify a biomarker in blood obtained at hospital admission that estimates the neurologic morbidity risk for carbon monoxide (CO) poisoning. DESIGN: Observational cohort study and murine model. SETTING: Retro...
OBJECTIVE: Identify a biomarker in blood obtained at hospital admission that estimates the neurologic morbidity risk for carbon monoxide (CO) poisoning. DESIGN: Observational cohort study and murine model. SETTING: Retrospective and prospective data from two emergency departments and laboratory investigations. PATIENTS: This study compared 114 CO-poisoned patients (57 retrospective, 57 prospective) with 89 samples from age and sex matched controls. INTERVENTIONS: None. MEASUREMENTS AND MAIN RESULTS: We hypothesized that microparticles (MPs) bearing myelin basic protein (MBP) in blood at hospital presentation predicted neurologic sequelae (NS) risk. MBP-MPs/μL in 89 controls subjects was 19 + 12 (sd), the value was 88 + 43 (n = 77, p < 0.001 vs. control) in CO patients who recovered by 1 month based on Global Deterioration Scale (GDS) score = 1, and 146 + 62 (p < 0.001 vs. control and CO-recovered groups) in 37 CO patients with NS at 1 month (GDS > 1). In a murine CO-poisoning model, the risk from brain-derived MBP-MPs was due to sensitizing peripheral lymphocytes. This event, concurrent with neutrophil-mediated blood-brain barrier disruption, triggered neuroinflammation. This also occurred in naive mice injected with MBP-MPs isolated from CO-exposed mice, but not MBP-MPs from controls. Mice rendered immunologically tolerant to MBP, those with ligated cervical lymphatics to block MBP-MPs release to the circulation, neutropenic mice and those treated with human recombinant plasma gelsolin to lyse inflammatory MPs did not exhibit neuroinflammation. CONCLUSIONS: MBP-MPs are an index for adverse outcome risk in CO-poisoned patients because they initiate an adaptive immune response.
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