Journal of Intensive Care最新文献

Background: Intensive care unit (ICU) readmission is a widely recognized marker of patient outcomes and organizational performance. Early ICU readmission-commonly defined as a return to the ICU within 48 h or 2 full calendar days-has been posited as a quality indicator. However, its appropriateness as a quality indicator remains debatable, and evidence from Japan is limited.

Methods: We conducted a retrospective nationwide cohort study in Japan using data from the Diagnosis Procedure Combination database linked with the Hospital Bed Function Report from 2018 through 2023. Adults who were discharged alive after their initial ICU stay, with available Sequential Organ Failure Assessment (SOFA) scores at ICU admission and discharge were included. The primary outcome was early ICU readmission, defined as readmission to the ICU within ≤ 2 full calendar days after the initial ICU discharge. All ICU readmissions (early and late combined) during the same hospitalization were also assessed. Patient- and hospital-level predictors were evaluated using multilevel logistic regression. Between-hospital variability was quantified using intraclass correlation coefficients (ICC) and median odds ratios (MOR).

Results: Of 552,545 eligible patients across 401 hospitals, 22,112 patients (4.0%) underwent ICU readmission; 4728 patients (0.9%) required early readmission. The temporal distribution lacked an early peak, with 32.8% of readmissions occurring ≥ 14 days and 12.2% occurring ≥ 30 days after the initial ICU discharge. Early readmission was associated with higher Charlson Comorbidity Index values, emergency surgery, and elevated SOFA scores at ICU discharge, particularly residual respiratory and circulatory dysfunction. SOFA scores at ICU admission and ICU stay ≥ 7 days were not predictive of early readmission. Intermediate care transfer conferred protection against early but not overall readmission. Hospital-level variation was substantial (ICC, 14-15%; MOR, approximately 2.0) and persisted after adjusting for patient- and hospital-level factors.

Conclusions: In Japan, early ICU readmissions are less frequent than in most Western countries and often occur long after discharge. Discharge severity scores, rather than disease severity at admission, served as the key predictors of readmission. Persistent unexplained hospital-level variations suggest that the ICU readmission rate alone is insufficient as a standalone indicator of the quality of care.

Sepsis is a significant global health issue, with high morbidity, mortality, and economic burden. Its definition has evolved, with the latest Sepsis-3 criteria emphasizing life-threatening organ dysfunction due to a dysregulated host response. Endothelial dysfunction plays a critical role in sepsis pathogenesis, characterized by increased permeability and inflammatory responses. Human serum albumin, the most abundant protein in the bloodstream, is essential for maintaining oncotic pressure and endothelial integrity. This narrative review provides an overview of endothelial changes during sepsis and their impact on organ damage. We also explore the role of albumin administration in managing endothelial dysfunction in sepsis and discuss the available preclinical and clinical evidence.

Septic shock driven by endotoxemia is associated with high mortality despite advances in supportive care. Polymyxin B hemoperfusion (PMX-HP) selectively removes circulating endotoxin and has shown variable efficacy in randomized trials. While earlier studies, such as EUPHAS, suggested benefit, subsequent trials, including ABDO-MIX and EUPHRATES, yielded neutral results, partly due to heterogeneous patient selection. The recently completed TIGRIS trial addressed these limitations by enrolling septic shock patients with intermediate endotoxin activity (EAA: 0.60-0.89) and high multiple organ dysfunction syndrome (MODS > 9) using a Bayesian design. In 151 evaluable patients, PMX-HP achieved the primary endpoint, with a 95.3% posterior probability of 28-day survival benefit (adjusted odds ratio [OR]: 0.67; absolute risk reduction [ARR] 6.4%). At 90 days, mortality reduction was greater (ARR: 17.4%; adjusted OR: 0.54; > 99% posterior probability of benefit), corresponding to a number needed to treat of 8.1. These results support the targeted use of PMX-HP in a biomarker-defined subgroup and may facilitate broader regulatory approval.

Background: Among patients with sepsis admitted to the intensive care unit (ICU), a substantial proportion require mechanical ventilation, and a subset eventually undergo tracheostomy. Early identification of patients at high risk for tracheostomy may facilitate timely decision-making and improve clinical communication.

Methods: We conducted a nationwide, retrospective study using the Japanese Intensive care PAtient Database (JIPAD). Adult patients with sepsis (Sequential Organ Failure Assessment score of ≥ 2, excluding viral pneumonia) who required mechanical ventilation between 2018 and 2022 were included. The primary outcome was tracheostomy within 14 days of ICU admission. Seventy-five variables available within 24 h of ICU admission were collected. Using least absolute shrinkage and selection operator (LASSO) regression with tenfold cross-validation, we selected predictors to build a multivariable logistic regression model (Sepsis Tracheostomy early Prediction [STeP] model). A simplified scoring system (STeP score) was also derived. Predictive performance was assessed using the area under the curve (AUC) of the receiver operating characteristic (ROC) in a temporally independent validation cohort.

Results: Among 7357 eligible patients (training: 5374; validation: 1983), 1013 (13.8%) underwent tracheostomy. The STeP model, based on 8 LASSO-selected variables, demonstrated good discrimination (AUC: 0.76 in training, 0.74 in validation). The simplified STeP score (range, 0-17), derived from the same predictors, achieved an AUC of 0.73 in the validation cohort. Patients were stratified into low (≤ 2 points), moderate (3-6 points), and high (≥ 7 points) risk groups for tracheostomy, with corresponding tracheostomy rates of 4.0%, 13.6%, and 27.1%, respectively.

Conclusions: We developed and validated a robust prediction model and simplified risk score (STeP score) for tracheostomy within 14 days in ICU patients with sepsis. Early risk stratification using variables available within 24 h may support timely tracheostomy planning. A web-based calculator is publicly available to facilitate bedside implementation.

Background: External ventricular drain (EVD)-associated infections are a significant cause of morbidity and mortality. Nosocomial meningitis (NM) poses diagnostic challenges, and its prognosis heavily relies on the timely initiation of treatment. The aim of this study was to investigate the epidemiology of NM and risk factors in ICU patients.

Methods: We conducted a retrospective single-center cohort study of adult patients who received an EVD in a French ICU between 2018 and 2022. Patients were classified into those with NM or without meningitis based on biological and microbiological criteria. We assessed risk factors related to the patient, the device, and the primary pathology, treatment regimens, length of stay, and survival.

Results: Of 275 patients with EVD, 32 (11.6%) developed NM. Patients with meningitis had longer ICU stays (median 42.5 vs. 29 days; p = 0.019), though in-hospital mortality was similar between groups (29.5% vs. 21.9%; p = 0.668). A pathogen was identified in 75% of episodes. Significant risk factors associated with NM included CSF leakage at the insertion site (OR 3.47; 95% CI, 1.53-7.86; p = 0.002), longer drainage duration (OR 1.07 per day; 95% CI, 1.04-1.12; p < 0.001), β-lactam allergy (OR 6.83; 95% CI, 1.73-26.92; p = 0.002), and a cytochemical profile consistent with infection (leukocytes > 100/mm³, CSF-to-serum glucose ratio < 0.5, and protein > 1 g/) in the cerebrospinal fluid (OR 3.87; 95% CI 1.67-8.97; p < 0.001). We proposed a predictive model derived from these identified factors with an AUC-ROC curve of 0.89 (95% CI, 0.83-0.94) with a negative predictive value of 96.8%.

Conclusion: Key risk factors included β-lactam allergy, CSF leakage, prolonged drainage, and cerebrospinal biological profile. This predictive model, derived from these factors, could be used for the early detection and treatment of NM.

Heatstroke is characterized by systemic inflammation, immune dysregulation, and multiorgan failure, in which mitochondrial damage in leukocytes plays a pivotal role. This review examines the mechanisms by which heat stress induces leukocyte mitochondrial dysfunction and its downstream effects on immunity, coagulation, and organ integrity. Exposure to heat stress activates leukocytes through damage-associated molecular patterns (DAMPs), triggering the release of proinflammatory cytokines, reactive oxygen species (ROS), and neutrophil extracellular traps (NETs). These responses disrupt endothelial integrity, promote microvascular thrombosis, and contribute to the development of disseminated intravascular coagulation (DIC). Prolonged heat exposure further shifts the immune landscape toward immunosuppression, marked by monocyte deactivation and lymphocyte apoptosis. Mitochondrial dysfunction is central to this biphasic immune response. Heat stress reduces mitochondrial membrane potential, increases ROS production, and promotes the release of mitochondrial DNA and cytochrome c, amplifying inflammation and initiating cell death pathways, including apoptosis, pyroptosis, and ferroptosis. Biomarkers such as reduced mitochondrial membrane potential (ΔΨm), elevated mitochondrial ROS, cytochrome c, circulating mitochondrial DNA (mtDNA), and altered expression of mitophagy regulators (e.g., PINK1 and Parkin) provide insights into mitochondrial integrity and function in leukocytes. In addition to immune disruption, mitochondrial injury exacerbates coagulation abnormalities by promoting platelet activation and endothelial dysfunction, fostering a prothrombotic environment. In the microcirculation, leukocyte adhesion, NET formation, and endothelial damage create a self-amplifying cycle of ischemia and inflammation, ultimately leading to organ dysfunction, including hepatic failure, acute kidney injury, acute lung injury, and gastrointestinal barrier breakdown. Therapeutic strategies aimed at preserving mitochondrial function include antioxidants (e.g., N-acetylcysteine and MitoQ), mitochondrial biogenesis inducers (e.g., PGC-1α activators), and mitophagy enhancers. Understanding the central role of leukocyte mitochondrial damage in heat stress provides a foundation for the development of targeted diagnostics and interventions to prevent organ failure and improve clinical outcomes.

Background: Limited data are available on risk stratification in patients undergoing weaning from percutaneous ventricular assist devices (PVADs). We aimed to identify factors associated with adverse events following PVAD weaning and to construct a predictive scoring system.

Methods: This study was a secondary analysis of the UNLOADERS-PVAD study, an observational registry involving three participating institutions in Japan. Consecutive patients with cardiogenic shock who received PVAD support were analyzed for 13 clinical and nine hemodynamic factors assessed immediately prior to PVAD explantation, using the least absolute shrinkage and selection operator (LASSO) method. Risk factors associated with 30-day events, defined as all-cause mortality or reintroduction of mechanical circulatory support after PVAD weaning, were identified.

Results: Among 304 patients, four clinical factors (female sex, renal replacement therapy, use of multiple vasopressors and/or inotropes, and elevated lactate levels) and three hemodynamic factors (elevated heart rate, elevated pulmonary artery wedge pressure, and lower cardiac power output) immediately prior to PVAD explantation were selected to construct a predictive scoring system for 30-day event risk. This score stratified 30-day event risk linearly and demonstrated good predictive accuracy (area under the curve: 0.786; 95% CI 0.712-0.860).

Conclusions: Four clinical and three hemodynamic factors were significantly associated with 30-day events following PVAD weaning, leading to the development of the UNLOADERS-PVAD Weaning Score. This scoring system facilitates accurate risk stratification before PVAD weaning, guiding clinical decisions regarding further interventions.

Trial registration: UMIN000052966.

Background: Sleep disturbances are common in critically ill patients and increase delirium risk, leading to worse outcomes. Non-pharmacologic sleep interventions show mixed results, with limited randomized controlled trial (RCT) data in surgical ICU populations.

Methods: We conducted a prospective, single-blind randomized controlled trial in a surgical ICU to evaluate a multicomponent sleep enhancement protocol vs. usual care in patients aged ≥ 65 years with expected ICU stays > 24 h. The intervention included environmental modifications (noise and light reduction, closed doors, alarm adjustments) and patient-specific measures (earplugs, eye masks). Delirium incidence over 7 days was assessed using the Thai version of CAM-ICU by blinded evaluators. Sleep quality was measured daily with the Richards-Campbell Sleep Questionnaire (RCSQ). Bayesian methods estimated treatment effects and posterior probabilities of benefit.

Results: Of 177 patients analyzed (89 intervention, 88 control), delirium occurred in 10.1% of the intervention group vs. 17.0% in controls (Bayesian OR 0.55; 95% credible interval [CrI] 0.22-1.31; posterior probability of benefit 90.6%). In a predefined high-risk subgroup, delirium incidence was 14.0% vs. 30.0% (OR 0.38; 95% CrI 0.12-1.83; posterior probability of benefit 95.7%). Sleep quality scores and clinical outcomes did not differ significantly. Adherence was high for environmental modifications but moderate for earplugs and eye masks.

Conclusions: Among elderly surgical ICU patients, a multicomponent, non-pharmacologic sleep enhancement protocol was associated with a high posterior probability of reducing delirium during the early ICU period, despite no measurable improvement in subjective sleep quality. The findings are hypothesis-generating; given the protocol's simplicity and low risk, confirmation in larger multicenter trials with objective sleep measures and strategies to optimize adherence is warranted.

Trial registration: This study was registered with the Thai Clinical Trials Registry (TCTR: https://www.thaiclinicaltrials.org ) under the registration number TCTR20221129003, with the registration date of 29 November 2022. TCTR20221129003.

Background: Acute Kidney Injury (AKI) is common in patients admitted to the intensive care unit (ICU) for severe SARS-CoV-2 pneumonia and is associated with a worse prognosis. Mechanical ventilation has been identified as a risk factor for renal damage in COVID-19. However, few studies have examined the specific ventilatory settings involved. We hypothesized that positive end-expiratory pressure (PEEP) may contribute to the onset of AKI. Our primary objective was to assess the relationship between PEEP levels and the development of AKI in critically ill patients with COVID-19-related ARDS.

Methods: We conducted an ancillary analysis of the international, prospective, multicenter COVID-ICU study, which included 4244 COVID-19 ICU patients across 149 intensive care units. For our study, only patients who underwent mechanical ventilation for at least 48 h and had normal renal function before intubation were included. The primary outcome was AKI, defined according to Kidney Disease Improving Global Outcomes (KDIGO) criteria. A multivariable logistic regression model was used to evaluate the association between PEEP levels and the development of AKI (KDIGO score > 1).

Results: A total of 1,066 patients were included in the analysis. Among them, 510 (48%) developed AKI within the first 5 days after intubation. After multivariable adjustment, higher daily mean PEEP levels, averaged over the first 3 days of mechanical ventilation and treated as a continuous variable, were independently associated with the development of AKI (odds ratio [OR] 1.10; 95% confidence interval [CI] 1.05-1.16). A PEEP level exceeding 15.2 cmH₂O was significantly associated with the occurrence of AKI.

Conclusion: In patients with COVID-19-related ARDS patients, higher PEEP levels within the first 5 days after intubation were independently associated with AKI. These findings underscore the importance of ventilatory strategies to balance oxygenation and kidney protection.

Background: Urosepsis has a reported mortality rate of up to 13.5%, and approximately 38% of affected patients require intubation. This study evaluated the association between the timing of intubation and in-hospital mortality among patients with urosepsis.

Methods: We conducted a multicenter retrospective cohort study using the Australian and New Zealand Intensive Care Registry Adult Patient Database. Adult ICU patients (≥ 16 years) with a primary diagnosis of urosepsis admitted between 1 January 2018 and 1 April 2023 were included. Patients were classified into early (≤ 24 h from ICU admission) or delayed (> 24 h) intubation groups. The primary outcome was in-hospital mortality. Secondary outcomes included ICU and hospital lengths of stay (LOS), mortality at 6, and 12 months. Outcomes were analyzed using multivariable logistic or linear regression models.

Results: Of 1,235 patients across 151 sites, 983 patients (79.6%) received early intubation. In-hospital mortality was similar between early and delayed intubation groups (19.2% vs. 17.5%, p = 0.52). Early intubation was not associated with in-hospital mortality (adjusted odds ratio [OR] = 0.76; 95% confidence intervals [95% CI] 0.51-1.13). Patients with early intubation had shorter ICU LOS (adjusted point estimate = -2.94 days; 95% CI -3.90 to -1.98) but not hospital LOS. There was no association between early intubation and mortality at 6 months (adjusted OR = 0.76; 95% CI 0.53-1.10) and 12 months (adjusted OR = 0.75; 95% CI 0.53-1.06).

Conclusions: Early intubation within the first 24 h after ICU admission was not associated with reduced in-hospital or long-term mortality among patients with urosepsis.

Trial registration: Alfred Hospital Ethics Committee (Reference 762/24) and the Australian and New Zealand Intensive Care Society (ANZICS) Centre for Outcome and Resource Evaluation Management Committee.