Journal of Intensive Care最新文献

The 2024 revised edition of the Japanese Clinical Practice Guidelines for Management of Sepsis and Septic Shock (J-SSCG 2024) is published by the Japanese Society of Intensive Care Medicine and the Japanese Association for Acute Medicine. This is the fourth revision since the first edition was published in 2012. The purpose of the guidelines is to assist healthcare providers in making appropriate decisions in the treatment of sepsis and septic shock, leading to improved patient outcomes. We aimed to create guidelines that are easy to understand and use for physicians who recognize sepsis and provide initial management, specialized physicians who take over the treatment, and multidisciplinary healthcare providers, including nurses, physical therapists, clinical engineers, and pharmacists. The J-SSCG 2024 covers the following nine areas: diagnosis of sepsis and source control, antimicrobial therapy, initial resuscitation, blood purification, disseminated intravascular coagulation, adjunctive therapy, post-intensive care syndrome, patient and family care, and pediatrics. In these areas, we extracted 78 important clinical issues. The GRADE (Grading of Recommendations Assessment, Development and Evaluation) method was adopted for making recommendations, and the modified Delphi method was used to determine recommendations by voting from all committee members. As a result, 42 GRADE-based recommendations, 7 good practice statements, and 22 information-to-background questions were created as responses to clinical questions. We also described 12 future research questions.

Background: Shift work is common in healthcare, especially in emergency and intensive care, to maintain the quality of patient care. Night shifts are linked to health risks such as cardiovascular disease, metabolic disorders, and poor mental health. It has been suggested that inflammatory responses due to the disruption of circadian rhythm may contribute to health risks, but the detailed mechanisms remain unclear. This study aimed to analyze changes in gene expression in whole blood of healthcare workers before and after a night shift and investigate the molecular pathogenesis of these changes and their impact on health.

Methods: This was a single-center, prospective, observational study of four medical doctors working night shifts in the emergency department. Blood samples from the subjects were collected before and after the night shift, and RNA sequencing was performed to analyze changes in gene expression in whole blood. The data obtained were analyzed via Ingenuity Pathway Analysis (IPA) core analysis that included canonical pathway analysis, upstream regulator analysis, and functional network analysis. RNA bulk deconvolution was performed to estimate the relative abundance of immune cells. The IPA analysis match feature was also used to assess similarities of gene expression patterns with other diseases.

Results: We identified 302 upregulated and 78 downregulated genes (p < 0.05, |log2-fold change|> 0.5) as genes whose expression changed after the night shift. Canonical pathway analysis revealed that Toll-like receptors and other innate immune response pathways were activated. Upstream regulator analysis and functional network analysis also consistently indicated a predicted activation of innate immune and inflammatory responses. RNA bulk deconvolution showed changes in the proportions of several immune cells. IPA analysis match indicated that gene expression patterns after night shifts were highly correlated with several diseases, including major depressive disorder, in terms of immune and inflammatory responses.

Conclusion: The results revealed that innate immune and inflammatory responses are elicited after night shifts in healthcare workers and that gene expression patterns correlate with several diseases in terms of immune and inflammatory responses. These findings suggest that shift work may affect health risks through innate immune and inflammatory responses.

We commend the authors for their insightful study on inspiratory muscle training (IMT) in mechanically ventilated patients with difficult weaning, highlighting the robust use of maximum inspiratory pressure (MIP) as a key outcome. We suggest that a lower baseline maximum inspiratory pressure cutoff could better target patients with significant inspiratory dysfunction, improving the study's precision. Additionally, alternative imputation techniques, such as multiple imputation, could strengthen the handling of missing data. While the sample size calculation was appropriate, the unbalanced group sizes raise concerns about generalisability. Future research could benefit from subgroup analyses, individual response curves, and further investigation into the unexpected adverse effects observed in the low-intensity group to refine the inspiratory muscle training protocols.

Background: Sepsis is a critical condition associated with high morbidity and mortality, emphasizing the need for reliable biomarkers for its diagnosis and prognosis. This study uses advanced immunological techniques to evaluate monocytic CD39 (mCD39) expression as a potential marker in sepsis.

Methods: This prospective observational cohort study included 206 participants from the First Affiliated Hospital, Zhejiang University School of Medicine between April 2022 and September 2023. Participants were categorized into four groups: healthy donors, patients with mild infections, post-cardiac surgery patients (non-infectious inflammation), and sepsis patients. Peripheral Blood Mononuclear Cells were analyzed using mass cytometry time-of-flight (CyTOF) with a 42-marker immune panel and flow cytometry targeting monocytes. Statistical analyses included ROC curves for diagnostic and prognostic performance and Kaplan-Meier survival analysis for prognostic evaluation.

Results: Sepsis patients exhibited significantly lower monocytic CD39 expression than mild infection and post-surgery groups (p < 0.05). The diagnostic performance analysis revealed that mCD39 effectively distinguished sepsis from mild infection (AUC = 0.877) and non-infectious inflammation (AUC = 0.935). Prognostic analysis identified low mCD39 expression as a strong predictor of short-term survival, with a 7-day survival AUC of 0.85 (p = 0.037). Kaplan-Meier analysis showed that sepsis patients with low mCD39 expression had significantly lower 28-day survival rates (56.7% vs. 80.6%, p = 0.016).

Conclusions: Low CD39 expression on monocytes might serve as a potential diagnostic biomarker and a strong predictor of poor prognosis in sepsis patients.

Background: Sepsis is characterized by organ dysfunction as a response to infection and is one of the leading causes of mortality and loss of health. The heterogeneous nature of sepsis, along with ethnic differences in susceptibility, challenges a thorough understanding of its etiology. This study aimed to propose prediction models by leveraging genetic-risk scores and clinical variables that can assist in risk stratification of patients.

Methods: A total of 1,403 patients from Taiwan, diagnosed with sepsis, were utilized. Genome-wide survival analysis was conducted, with death within 28 days from sepsis onset, as the primary event to report significantly associated SNPs. A polygenic risk score (PRS-sepsis) was constructed via clumping and thresholding method which was added to clinical-only models to generate better performing prognostic models for identifying high-risk patients. Kaplan-Meier analysis was conducted using PRS-sepsis.

Results: A total of five single-nucleotide-polymorphisms (SNPs) reached genome-wide significance (p < 5e-8), and 86 SNPs reached suggestive significance (p < 1e-5). The prognostic model using PRS-sepsis showed significantly improved performance with c-index [confidence interval (CI)] of 0.79 [0.62-0.96] and area under receiver operating characteristic curve (AUROC) [CI] of 0.78 [0.75-0.80], in comparison to clinical-only prognostic models (c-index [CI] = 0.63 [0.45- 0.81], AUROC [CI] = 0.61 [0.58-0.64]). The ethnic specificity was established for our proposed models by comparing it with models generated using significant SNPs from prior European studies (c-index [CI] = 0.63 [0.42-0.85], AUROC [CI] = 0.60 [0.58-0.63]). Kaplan-Meier plots showed that patient groups with higher PRSs have inferior survival probability compared to those with lower PRSs.

Conclusions: This study proposed genetic-risk models specific for Taiwanese populations that outperformed clinical-only models. Also it established a strong racial-effect on the underlying genetics of sepsis-related mortality. The model can potentially be used in real clinical setting for deciding precise treatment courses for patients at high-risk thereby reducing the possibility of worse outcomes.

Background: Lipoproteins and their component apolipoproteins play an important role in sepsis. However, little is known with regard to the association and causal contribution of these proteins to mortality in patients of different ancestries following septic shock. The objective of this study was to determine whether lipoprotein and apolipoprotein levels, and related genetic variants, are associated with clinical outcomes in septic shock.

Methods: We investigated the association between lipoprotein and apolipoprotein levels at the point of admission to the intensive care unit and in-hospital mortality in 687 Japan patients diagnosed with septic shock. For each clinically significant candidate protein, we extracted haplotype tag single nucleotide polymorphisms (SNPs) of the corresponding gene and examined the association of the candidate gene variants with 28-day mortality and organ dysfunction. We tested for replication in a Caucasian septic shock cohort (Vasopressin and Septic Shock Trial, VASST, n = 474). To determine whether the candidate lipoprotein causally contributed to septic shock outcome, we used a Mendelian randomization analysis based on polygenic scores generated from a genome-wide association study (GWAS) in the Japan cohort.

Results: In the Japan cohort, low apolipoprotein A-II levels were associated with increased septic shock mortality (adjusted odds ratio, 1.05; 95%CI, 1.02-1.09; P < 0.001). For a haplotype tag SNP of the corresponding ApoA2 gene, rs6413453 GG carriers had significantly higher 28-day mortality (adjusted hazard ratio [aHR], 1.79; 95% confidence interval [CI], 1.06-3.04; P = 0.029) and significantly fewer days free of cardiovascular, respiratory, renal and neurologic dysfunction than AG/AA carriers. This result was replicated in the Caucasian septic shock cohort (28-day mortality: aHR, 1.65; 95% CI, 1.02-2.68; P = 0.041). Mendelian randomization using 9 SNPs from an apolipoprotein A-II GWAS suggested that genetically decreased levels of apolipoprotein A-II were a causal factor for increased mortality in septic shock (odds ratio for mortality due to a 1 mg/dL decrease in apolipoprotein A-II is 1.05 [95% CI; 1.01-1.03, P = 0.0022]).

Conclusions: In septic shock, apolipoprotein A-II levels and ApoA2 genetic variations are important factors associated with outcome.

Purpose: Acute respiratory distress syndrome (ARDS) is a prevalent respiratory condition associated with significant mortality. Current literature on ARDS epidemiology reports a wide range of incidence (7.2-78.9/100,000 population/year), hospital mortality (32-51%), and associated costs ($8476-$547,974). We have analyzed epidemiological trends of mechanically ventilated ARDS (MV-ARDS) in Spain from 2000 to 2022 using the Minimum Basic Data Set (MBDS), focusing on MV-ARDS incidence, associated mortality, and economic impact.

Methods: We conducted a nationwide, population-based retrospective study of all hospitalizations for MV-ARDS in Spanish hospitals-from January 1, 2000 to December 31, 2022-using MBDS records, with an estimated coverage of 99.5%. The study reports MV-ARDS incidence per 100,000 population/year, hospital mortality rate, and mean cost per patient. We also considered the effect of COVID-19 on MV-ARDS epidemiology.

Results: We analyzed 93,192 records of patients with a new diagnosis of MV-ARDS during the study period. MV-ARDS incidence ranged from 2.96 to 20.14/100,000 population-years, peaking in 2021. Mortality ranged between 38.0 and 55.0%, showing a declining trend, while the cost per patient increased, stabilizing ~€30,000-€40,000 after reaching a peak of €42,812 in 2011. During the COVID-19 pandemic, hospital stay lengthened (p < 0.001), while hospital mortality decreased (p < 0.001). There was an increased proportion of patients with obesity and diabetes mellitus, with fungal or viral etiologies.

Conclusion: This is the largest epidemiological study on ARDS in Europe. MV-ARDS incidence has stabilized in recent years, with mortality showing a declining trend. ARDS-related costs have increased nearly fourfold. MBDS data could enhance ARDS understanding and guide future studies.

Background: Neurological outcomes after out-of-hospital cardiac arrest (OHCA) depend on multiple factors, including the patient's baseline condition and post-arrest management. The SLANT, developed specifically for OHCA survivors treated with targeted temperature management (TTM), requires further validation, particularly in Asian populations.

Methods: This multicenter retrospective cohort study analyzed data from 2016 to 2023, examining demographics, pre-arrest conditions, resuscitation events, and laboratory biomarkers following TTM. The primary outcome was defined as a poor neurological outcome at hospital discharge. Model performance was assessed using the area under the receiver operating characteristic curve. Multivariate logistic regression analysis was used to analyze the included variables.

Results: A total of 448 eligible adult patients were included, of whom 77.9% experienced poor neurological outcomes at discharge. The performance of the current cohort was comparable to that of the original SLANT cohort, achieving an area under the curve of 0.797 (95% confidence interval: 0.746-0.849). All five factors of the SLANT score remained statistically significant in predicting poor neurological outcomes. At a cutoff of ≥ 6.5, the SLANT score demonstrated a specificity of 53.5% and positive predictive value (PPV) of 86.9%. Increasing the cutoff value to 8.5 improved the specificity to 66.7% and the PPV to 89.6%.

Conclusion: The SLANT showed high PPV for predicting poor neurological outcomes at discharge in patients with OHCA undergoing TTM across a multicenter Asian cohort. Combining the score with other neurological assessments is recommended for improved neuroprognostication.

Background: Post-intensive care syndrome (PICS) affects the quality of life (QOL) of survivors of critical illness. Although PICS persists for a long time, the longitudinal changes in each component and their interrelationships over time both remain unclear. This multicenter prospective study investigated the 2-year trajectory of PICS and its components as well as factors contributing to deterioration or recovery in mechanically ventilated patients with coronavirus disease 2019 (COVID-19), and also attempted to identify possible countermeasures.

Methods: Patients who survived COVID-19 requiring mechanical ventilation completed questionnaires on the Barthel index, Short-Memory Questionnaire, Hospital Anxiety and Depression Scale, and EuroQol 5 dimensions 5-level every six months over a two-year period. Scores were weighted to account for dropouts, and the trajectory of each functional impairment was evaluated with alluvial diagrams. The prevalence of PICS and factors impairing or restoring function were examined using generalized estimating equations considering trajectories.

Results: Among 334 patients, PICS prevalence rates in the four completed questionnaires were 72.1, 78.5, 77.6, and 82.0%, with cognitive impairment being the most common and lower QOL being noted when multiple impairments coexisted. Physical function and QOL indicated that many patients exhibited consistent trends of either recovery or deterioration. In contrast, cognitive function and mental health revealed considerable variability, with many patients showing fluctuating ratings in the later surveys. Delirium was associated with worse physical and mental health and poor QOL, while prolonged ventilation was associated with poor QOL. Living with family was associated with the recovery of all functions and QOL, while extracorporeal membrane oxygenation (ECMO) was associated with the recovery of cognitive function and mental health.

Conclusions: Critically ill patients had PICS for a long period and followed different trajectories for each impairment component. Based on trajectories, known PICS risk factors such as prolonged ventilation and delirium were associated with impaired recovery, while ECMO and the presence of family were associated with recovery from PICS. In critically ill COVID-19 patients, delirium management and family interventions may play an important role in promoting recovery from PICS.

Trial registration number: UMIN000041276, August 01, 2020.

Background: The triglyceride-glucose (TyG) index is increasingly recognized for its ability to predict cardiovascular and metabolic risks. This study investigated the correlation between the TyG index and the risk of acute kidney injury(AKI) in critical ill patients with acute pancreatitis(AP).

Methods: The Medical Information Mart for Intensive Care IV database was retrospectively searched to identify AP patients hospitalized in the intensive care unit. The primary outcome measure was the incidence of AKI. The secondary endpoint was in-hospital mortality and the rate of renal replacement therapy(RRT) use. Cox regression analysis and restricted cubic spline were used to analyze TyG index association with AKI risk. Kaplan-Meier survival analysis was performed to assess the incidence of endpoints in the different groups.

Results: A total of 848 patients were enrolled. The incidence of AKI was 61.56%.The in-hospital mortality was 11.69%. Kaplan-Meier analysis showed that the TyG index ≥ 8.78 group has a high incidence of AKI and high risk of requiring RRT (P < 0.001). Multivariable Cox regression analysis showed whether TyG index was a continuous variable (HR, 1.65 [95% CI 1.10-2.48], P = 0.015) or a categorical variable (HR, 1.72 [95% CI 1.09-2.79], P = 0.028), and the TyG index was independently associated with the risk of AKI in AP patients. The restricted cubic splines model illustrated the linear relationship between higher TyG index and increased risk of AKI in this specific patient population.

Conclusions: High TyG index is an independent risk factor for AKI in critical ill patients with AP. Assessing the TyG index may be beneficial for early stratification and interventions to improve prognosis.