Critical Care Medicine最新文献

Objectives: Globally, the burden of sepsis is highest in malaria endemic areas of sub-Saharan Africa. The influence of malaria on biological heterogeneity inherent to sepsis in this setting is poorly understood. We sought to determine shared and distinct features of the host response in malarial and non-malarial sepsis in sub-Saharan Africa.

Design and setting: Analysis of Olink proteomic data from prospective observational cohort studies of sepsis conducted at public hospitals in Uganda (discovery cohort [Entebbe, urban], n = 238; validation cohort [Tororo, rural], n = 253).

Patients: Adults (age ≥ 18 yr) hospitalized with sepsis.

Interventions: None.

Measurements and main results: The frequency of malaria-associated (malarial) sepsis was 20% in the discovery cohort and 28% in the validation cohort. In both cohorts, a shared host response was predominant, with less than or equal to 8% of proteins differentially expressed (Benjamini-Hochberg-adjusted p ≤ 0.05) between malarial and non-malarial sepsis, after adjustment for demographic variables and HIV and tuberculosis coinfection. In both cohorts, malarial sepsis was associated with increased expression of immunosuppressive proteins (interleukin-10, leukocyte immunoglobulin-like receptor B1, killer cell immunoglobulin-like receptor 3DL1), including those associated with Tcell exhaustion and apoptosis (lymphocyte activation gene 3, T cell immunoglobulin and mucin domain containing 4). A classifier model including these immunosuppressive proteins showed reasonable discrimination (area under the receiver operating characteristic curves, 0.73 [95% CI, 0.65-0.81] and 0.72 [0.65-0.79]) and calibration (Brier scores 0.14 and 0.18) for stratification of malarial sepsis in the discovery and validation cohorts, respectively.

Conclusions: Host responses are largely conserved in malarial and non-malarial sepsis but may be distinguished by a signature of relative immunosuppression in the former. Further investigations are needed to differentiate mechanisms of malarial and non-malarial sepsis, with the goal of informing pathogen-stratified and pathogen-agnostic treatment strategies.

Objectives: Length of stay (LOS) models support evaluating ICU care; however, current benchmarking models fail to consider differences in LOS between surviving and nonsurviving patients, which can lead to biased predictions toward the surviving population. We aim to develop a model addressing this as well as documentation bias to improve ICU benchmarking.

Design: The Critical Care Outcomes Prediction Model (CCOPM) LOS uses patient characteristics, vitals, and laboratories during the first 24 hours of ICU admission to predict LOS in the hospital and ICU using a deep learning framework for modeling time to events with competing risk. Data was randomly divided into training, validation, and test (hold out) sets in a 2:1:1 ratio.

Setting: Electronic ICU Research Institute database from participating tele-critical care programs.

Patients: Six hundred sixty-nine thousand eight hundred seventy-six ICU admissions pertaining to 628,815 patients from 329 ICUs in 194 U.S. hospitals, from 2017 to 2019.

Interventions: None.

Measurements and main results: Model performance was assessed using the coefficient of determination (R2), concordance index, mean absolute error, and calibration. For individual stays in the test set, the ICU LOS model presented R2 = 0.29 and 0.23 for surviving and nonsurviving populations, respectively, at the individual level and R2 = 0.48 and 0.23 at the ICU level. Conversely, hospital LOS model presented R2 = 0.46 and 0.52 at the individual level and R2 = 0.71 and 0.64 at the ICU level. In the subset of the test set containing predictions from Acute Physiology and Chronic Health Evaluation (APACHE) IVb, R2 of ICU LOS for surviving and nonsurviving populations was, respectively, 0.30 and 0.23 for the CCOPM and 0.16 and zero for APACHE IVb. For hospital LOS, the values were R2 = 0.39 and 0.40 for the CCOPM and 0.27 and zero for APACHE IVb.

Conclusions: This novel LOS model represents a step forward in achieving more equitable benchmarking across diverse ICU settings with varying risk profiles.

Objectives: Sepsis is a life-threatening condition characterized by a dysregulated host response to infection. Despite decades of clinical trials, there are no specific treatments; care of the nearly 50 million annual cases worldwide is limited to antimicrobials and supportive measures. A primary prevention strategy may therefore be of value. We hypothesized that higher premorbid omega-3 fatty acid levels would be associated with a reduced incidence of sepsis.

Design: Population-based cohort study.

Setting: Retrospective data from the United Kingdom (U.K. Biobank).

Patients: Two hundred seventy-three thousand three hundred twenty-five participants from the U.K. Biobank.

Interventions: None.

Measurements and main results: Our exposure was baseline estimated omega-3 index (eO3I), modeled both categorically in quartiles, and continuously with restricted cubic splines. Our outcome measure was hospital admission with an International Classification of Diseases, 10th Edition code consistent with sepsis. The median (interquartile range) baseline eO3I was 6.0% (4.8-7.3%). Over a mean follow-up period of 13 years, 9241 participants experienced hospitalization with sepsis. In our adjusted model, compared with the lowest eO3I quartile, participants had lower risks of sepsis incidence in the second quartile (hazard ratio [HR], 0.88; 95% CI, 0.86-0.91; p < 0.001), third quartile (HR, 0.80; 95% CI, 0.78-0.83; p < 0.001), and fourth quartile (HR, 0.75; 95% CI, 0.73-0.77; p < 0.001). When analyzed as a continuous variable, increasing eO3I was associated with a decreasing risk of sepsis (p < 0.001).

Conclusions: In this population-based cohort study, baseline eO3I was inversely associated with subsequent sepsis incidence. Given that omega-3 levels can be increased with dietary supplementation, primary prevention should be explored to mitigate the burden of sepsis.

Objectives: This study aimed to evaluate the effectiveness of a pharmacist-led intervention in decreasing the overuse of stress ulcer prophylaxis (SUP) compared with the usual care for adult patients in Chinese ICUs.

Design: Pragmatic, multicenter, stepped-wedge, cluster-randomized controlled trial.

Setting: Twenty-six ICUs in China from October 2022 to March 2023.

Patients: We enrolled 2199 patients 18 years old or older who were newly admitted to the participating ICUs.

Interventions: Using the Medical Research Council framework for developing and evaluating complex intervention measures, a multidisciplinary team (Scenarios, Improving and Refining Interventions, Constructing, Refining and Testing Research Theories, Incorporating Stakeholders, Identifying Important Uncertainties, and Economics Considerations) designed a multifaceted intervention.

Measurements and main results: The primary outcomes were the proportion of patients receiving SUP and that with overt gastrointestinal bleeding. We conducted intention-to-treat analyses using generalized linear mixed models to adjust for potential confounders (age, sex, and acute physiology and chronic health evaluation II score) with random effects for the site. The proportion of patients receiving SUP in the intervention group was lower than that in the control group (45.5% vs. 49.5%; odds ratio [OR], 0.81; 95% CI, 0.68-0.96; p = 0.017). The proportion of patients with overt gastrointestinal bleeding was similar (3.7% vs. 4.0%; OR, 1.05; 95% CI, 0.65-2.85; p = 0.81).

Conclusions: The pharmacist-led intervention reduced the proportion of patients receiving SUP in the ICUs, without significantly affecting the proportion of patients with overt gastrointestinal bleeding. These findings will help guide ICU medical decision-making.

Objectives: Balancing oxygen requirements, neurologic outcomes, and systemic complications from transfusions in traumatic brain injury (TBI) patients is challenging. This review compares liberal and restrictive transfusion strategies in TBI patients.

Data sources: Electronic databases were searched from inception to October 2024.

Study selection: We included randomized controlled trials comparing liberal and restrictive transfusion strategies in TBI patients.

Data extraction: Data were extracted by two reviewers using predefined forms.

Data synthesis: We included five studies with 1,533 patients: 769 (50.2%) in the liberal transfusion group and 764 (49.8%) in the restrictive group. There were no significant differences between groups favorable Glasgow Outcome Scale (risk ratio [RR], 1.16; 95% CI, 1.00-1.34), although a leave-one-out analysis demonstrated significance in this endpoint (RR, 1.24; 95% CI, 1.06-1.45). No significant difference was found regarding hospital mortality (RR, 0.98; 95% CI, 0.76-1.27), mortality at follow-up (RR, 1.03; 95% CI, 0.82-1.28), mortality in the ICU (RR, 1.00; 95% CI, 0.73-1.37), infection rates (RR, 1.08; 95% CI, 0.95-1.23), thromboembolic events (RR, 1.79; 95% CI, 0.74-4.31), hospital length of stay (LOS) (mean difference [MD], -1.45; 95% CI, -4.85 to 1.96), or ICU LOS (MD, -0.47; 95% CI, -3.84 to 2.91). The liberal transfusion strategy group had a significantly higher prevalence of acute respiratory distress syndrome (RR, 1.78; 95% CI, 1.06-2.98) and received more blood units per patient (MD, 2.62; 95% CI, 1.90-3.33).

Conclusions: Our findings suggest that a liberal transfusion strategy results in better neurologic outcomes than a restrictive approach. Future research should examine the complication profile and the effects of using a 9 g/dL threshold. We advocate for revising current guidelines to establish 9 g/dL as the standard threshold for transfusions in TBI patients.

Objectives: Nelonemdaz is a N-methyl d-aspartate receptor subtype 2B-selective N-methyl-D-aspartate receptor antagonist and a potent free-radical scavenger that might ameliorate hypoxic-ischemic brain injury after out-of-hospital cardiac arrest (OHCA). We investigated the efficacy of nelonemdaz for patients with OHCA.

Design: A double-blind, placebo-controlled, randomized, multicenter phase II trial.

Setting: This trial enrolled 105 patients at five sites in South Korea between November 18, 2018, and February 23, 2023.

Participants: OHCA patients undergoing targeted temperature management.

Interventions: Patients were randomly assigned to high-dose (5250 mg), low-dose (3250 mg), and placebo groups at a 1:1:1 ratio.

Measurements and main results: Patients with a median age of 61 years (82% male) were assigned to the high-dose (n = 37), low-dose (n = 35), and placebo (n = 33) groups. The primary outcome, the serum level of neuron-specific enolase (NSE) at 48-52 hours, was evaluated in 93 patients. There was no difference in serum NSE between high-dose (median and interquartile range; 23.7, 15.0-69.9) and placebo (17.5, 13.6-113.0) groups, or between low-dose (26.6, 16.2-83.4) and placebo groups (all p > 0.05). Brain MRI fractional anisotropy was significantly higher in the high-dose group compared with the placebo group (0.465, 0.449-0.485 vs. 0.441, 0.431-0.464; p = 0.028), but not between low-dose (0.462, 0.439-0.480) and placebo groups (p > 0.05). At day 90, the common odds ratio (95% CI) indicating a numerically favorable shift in the modified Rankin Scale was 1.25 (0.48-3.24) and 1.22 (0.47-3.20) in the high-dose and low-dose groups, respectively, compared with placebo group (all p > 0.05). No serious adverse events were reported.

Conclusions: Nelonemdaz treatment of patients after OHCA did not reduce serum NSE levels compared with controls. Patients treated with high-dose nelonemdaz showed higher brain MRI fractional anisotropy suggesting less cerebral white matter damage.

Objectives: To explore practice variations in the rate and timing of tracheostomy and gastrostomy for adolescent with severe traumatic brain injury (TBI) across trauma center types.

Design: Retrospective cohort study.

Setting: Trauma centers participating in the American College of Surgeons Trauma Quality Improvement Program (2017-2021) included adult (ATC), mixed (MTC), and pediatric trauma centers (PTC).

Patients: Adolescent 14-18 years old with severe TBI (Head Abbreviated Injury Scale: 3-5 and Glasgow Coma Scale: 3-8) requiring mechanical ventilation.

Interventions: None.

Measurements and main results: A multilevel mixed-effect Poisson regression model assessed the association between trauma center type and tracheostomy/gastrostomy rates. Effect sizes for fixed effects were reported as adjusted incidence rate ratio (IRR) with 95% CI. Secondary analyses were performed to assess the association between trauma center types and ventilator-associated pneumonia (VAP). Of 6978 patients, tracheostomy and gastrostomy were performed in 22.5% and 21.3% at ATC, 20.8% and 21.3% at MTC, and 6.9% and 11.1% at PTC, respectively. The median time to tracheostomy was 10 days (interquartile range [IQR], 7-13 d) at ATC, 11 days (IQR, 7-15 d) at MTC, and 15 days (IQR, 11-23 d) at PTC, demonstrating a significantly later timing of tracheostomy at PTC. In the regression model adjusting for potential confounders, treatment at PTC was significantly associated with a decreased likelihood of tracheostomy and gastrostomy placement compared with ATC (adjusted IRR, 0.38; 95% CI, 0.28-0.52; p < 0.001 and adjusted IRR, 0.58; 95% CI, 0.44-0.75; p < 0.001, respectively). There was no significant difference in the occurrence rate of VAP between ATC, MTC, and PTC.

Conclusions: Our results offer insights into the existing current practice variations between ATC, MTC, and PTC in tracheostomy and gastrostomy placement for adolescent with severe TBI. Further research is warranted to examine the impact of these observed disparities on short- and long-term outcomes and to standardize the care process for adolescent patients.