Journal of Intensive Care最新文献

Background: Extracorporeal membrane oxygenation (ECMO) for infectious causes of refractory cardiopulmonary failure is established as appropriate therapy in high-income countries. Its use in low- and middle-income nations for tropical infections is not well-studied, however, perhaps because most of these countries have not been historically able to offer ECMO support. Tropical infections remain an important cause of global morbidity and mortality, but the role of ECMO is poorly described.

Methods: We identified a list of viral, bacterial, fungal, and parasitic infections that qualified as tropical infectious diseases. These included infections that were either a World Health Organization (WHO) designated Neglected Tropical Disease (NTD) or an infectious disease with a higher prevalence in the Tropics than elsewhere. We conducted a comprehensive review of existing literature regarding ECMO use to support these infections.

Results: Multiple viral, bacterial, fungal, and parasitic tropical infections have been supported by ECMO with varying success. leptospirosis, melioidosis, and tuberculosis are conditions suitable for venovenous ECMO support with frequent use in the literature and reported survival as high as 84% in Leptospirosis. Venoarterial ECMO has been successfully used in American trypanosomiasis-related cardiogenic shock as a bridge to transplant, with one center reporting a 71% survival rate. Dengue and malaria have been successfully supported with both venovenous and venoarterial ECMO. Mortality is relatively high (> 65%) in patients who receive ECMO for Middle Eastern Respiratory Syndrome. ECMO has also supported Echinococcal infections perioperatively. There are multiple tropical infections where ECMO use has not been published.

Conclusion: As the use of ECMO expands globally, more patients with tropical infections may require ECMO in both endemic and non-endemic settings. We present a scoping review on the evidence base of ECMO use to support tropical infectious diseases, with data regarding feasibility in specific disease processes as well as clinical considerations for tropical diseases on the ECMO circuit.

Background: Although inhaled nitric oxide (iNO) is used as a rescue therapy in patients with acute respiratory distress syndrome (ARDS), its impact on patient-centered outcomes remains uncertain. To address this gap, we conducted a systematic review of randomized controlled trials (RCTs) to test the hypothesis that the addition of iNO to standard care improves survival in adult patients with ARDS.

Methods: We searched PubMed, Embase, Cochrane Library, ClinicalTrials.gov, and WHO ICTRP for RCTs evaluating iNO in adult patients with ARDS through October 28, 2025. The primary outcome was mortality at the longest follow-up. Secondary outcomes included acute kidney injury (AKI), receipt of renal replacement therapy (RRT), duration of mechanical ventilation, length of intensive care unit stay, length of hospital stay, receipt of extracorporeal membrane oxygenation (ECMO), mean pulmonary artery pressure, partial pressure of arterial oxygen/fraction of inspiratory oxygen (PaO₂/FiO₂) ratio, elevated methemoglobin concentrations (> 5%), elevated nitrogen dioxide concentrations (> 3 ppm), extubation, and reintubation. We pooled data using a random-effects model, assessed the risk of bias with the Cochrane RoB 2 tool, and graded certainty with the GRADE approach.

Results: We included 11 RCTs comprising 1302 patients. Only one study was of low risk of bias. iNO therapy may result in no difference in mortality at the longest follow-up (relative risk [RR], 1.07; 95% confidence interval [CI], 0.93-1.23; I² = 0%; low certainty). iNO may improve PaO₂/FiO₂ ratio slightly (mean difference, 15.03 mmHg; 95% CI, 6.19-23.86; I² = 0%; low certainty). The evidence is very uncertain about the effect on ECMO use (RR, 0.45; 95% CI, 0.10-2.17; I² = 45%; very low certainty). iNO may increase the need for RRT (RR, 1.56; 95% CI, 1.17-2.08; I² = 0%; low certainty). No clear differences were observed in other secondary outcomes. No study reported data on reintubation.

Conclusions: Although iNO may improve oxygenation slightly, it may not confer survival or other patient-centered benefits and may increase the need for RRT. High-quality randomized evidence is needed to guide the optimal patient selection for this therapeutic option.

Trial registration: PROSPERO (registration number: CRD42024573383).

This study examined a discrepancy that exists between the duration of resuscitative efforts that physicians perceive as appropriate and the duration that laypersons desire. We conducted an online nationwide cross-sectional survey with 323 physicians and 2,667 laypersons. Physicians were significantly more likely than laypersons to consider a duration of ≥ 30 min as appropriate for resuscitation, especially in younger patients (age 0-6:85% vs. 27%; age 7-17:84% vs. 29%; both p < 0.001). Although these responses arise from fundamentally different psychological frames, identifying this discrepancy may provide a conceptual foundation for discussing more appropriate termination-of-resuscitation approaches in real-world clinical settings.

Background: The global rise in the elderly population presents unique challenges in intensive care, including treatment decisions and end-of-life care due to physiological, ethical, and social complexities. However, data on the very elderly remain limited, highlighting the need for real-world, large-scale studies. We aimed to characterize the age-related epidemiology and outcomes of sepsis in Japan using a nationwide administrative claims database.

Method: We conducted a retrospective cohort study using the Japanese Diagnosis Procedure Combination database for fiscal years 2010-2019. Sepsis was defined by infection-related ICD-10 codes, blood culture testing, and administration of antimicrobials within a three-day window around admission to critical care unit. Patients were stratified into 10-year age groups, and logistic regression was used to assess the association between age and in-hospital mortality.

Results: Among 1,880,275 critical care patients with infection-related diagnosis, 511,848 met the sepsis criteria. The median age was 76 years, and 40.0% were aged ≥ 80 years. ICU and hospital mortality increased with age, reaching 9.5% and 24.9%, respectively, in patients aged ≥ 90 years. Compared to patients aged ≤ 29 years, those aged ≥ 90 had an adjusted odds ratio of 4.75 (95% CI 4.37-5.16) for in-hospital mortality. The proportion of patients discharged home declined with age, falling to 29.4% in the ≥ 90 group. Use of organ support, including vasopressors and mechanical ventilation, was inversely related to age.

Conclusions: Sepsis in Japanese critical care units demonstrated substantial age-related differences in epidemiology, treatment, resource utilization, and outcomes. The disproportionately high mortality and reduced treatment intensity among the oldest patients underscore the complex clinical and ethical considerations involved in managing sepsis in aging societies. These findings emphasize the urgent need to adapt sepsis care models and critical care resource planning for the rapidly aging population in Japan and similar nations.

Background: Family members of adults who experience a critical care admission often experience significant strain and emotional distress following discharge. This meta-analysis aimed to synthesise the levels of distress, anxiety, and depression in family members of people who have experienced a critical care admission.

Methods: Medline, PsycINFO, Scopus, CINAHL and Web of Science databases were searched for articles (2000-2024) that measured distress using the Impact of Events Scale-Revised (IES-R), or anxiety or depression using the Hospital Anxiety and Depression Scale subscales (HADS-A and HADS-D) 3 months after critical care. Bayesian meta-analyses estimated the pooled average, and meta-regression examined whether the inclusion of bereaved relatives influenced the pooled outcome estimates. Anxiety and depression models estimated the pooled proportion of participants with HADS scores >7.

Results: Fifty articles were included (45 cohorts). Seventeen studies were from the USA and the median sample size at baseline assessment was 94.0. The pooled estimate of the IES-R at 3 months was 18.16 points [95% credible interval (CrI): 12.26-26.23, 15 studies]. The pooled estimate of the HADS-A at 3 months was 5.98 points (CrI: 5.29-6.73, 35 studies). The estimated proportion of family members with clinically meaningful levels of anxiety (HADS-A > 7) was 0.38 (95% CrI: 0.30-0.47; 11 studies). The pooled estimate of the HADS-D at 3 months was 3.91 points (95% CrI: 3.39-4.50; 33 studies). The estimated proportion of family members with clinically meaningful levels of depression (HADS-D > 7) was 0.20 (95% CrI: 0.15-0.26; 11 studies). Meta-regression found no significant effect of including non-bereaved participants only with the HADS subscales and was not possible due to insufficient studies with the IES-R.

Conclusions: Levels of distress, anxiety and depression appear to be comparable between individuals who experience a critical care admission and their family members. An estimated 38% and 20% of family members have clinically important levels of anxiety and depression, respectively. PROSPERO registration: CRD42022302735.

Background: The pharmacokinetics of prolonged remimazolam infusion in patients undergoing long-term mechanical ventilation remain unclear. This study aimed to evaluate the pharmacokinetics of remimazolam administered continuously for 24 h.

Methods: This open-label pharmacokinetic analysis enrolled patients requiring mechanical ventilation into two groups: the surgical group, which received remimazolam during and after surgery, and the medical ICU group, which received remimazolam in the intensive care unit (ICU). Remimazolam was administered at a fixed rate of 0.1 mg/kg/h for ≥ 24 h, and blood samples were collected at regular intervals. Plasma remimazolam concentrations were measured by tandem mass spectrometry.

Results: Twenty patients (10 in each group) completed the study. The median duration of remimazolam infusion was 24.0 h in the surgical group and 102.0 h in the medical ICU group. The steady-state plasma concentrations in both the surgical and medical ICU groups exhibited modest intrasubject variability (4.46-32.73%) and moderate intersubject variability (16.45-31.71%), with all values falling within clinically acceptable intermediate ranges. The plasma remimazolam concentration at the end of infusion was 130.7 ng/mL (95% confidence interval [CI] 115.2-146.1) in the surgical group and 134.3 ng/mL (95% CI 98.7-170.0) in the medical ICU group. Noncompartmental analysis showed that the clearance was 54.3 L/h (95% CI 47.6-61.8) and 55.6 L/h (95% CI 42.8-72.1) (P = 0.856), while the volume of distribution at steady state was 284 L (95% CI 215-376) and 316 L (95% CI 142-707) (P = 0.780), with no statistically significant differences between the groups.

Conclusions: In this preliminary study, both the surgical ICU group (approximately 24 h) and the medical ICU group (beyond 24 h) showed no evidence of time-dependent accumulation of plasma remimazolam, indicating a generally stable pharmacokinetic profile under the examined conditions.

Trial registration: In compliance with the Japanese Clinical Trials Act, the study was classified as a Specified Clinical Trial owing to the use of unapproved pharmaceuticals, which were reviewed by a certified review board (CRB) and registered in the Japan Registry of Clinical Trials (jRCTs041200076) on December 15, 2020.

Background: Blood pressure management is crucial in critical care, but relationships between pressure patterns and outcomes remain incompletely understood. We analyzed minute-by-minute blood pressure data to develop and validate a novel index quantifying hypotensive exposure burden.

Methods: In this retrospective study using the Salzburg Intensive Care Database, 11,059 ICU admissions with continuous invasive arterial monitoring were analyzed. Heatmaps were constructed from high-resolution hemodynamic data to visualize relationships between blood pressure thresholds (52-120 mmHg), exposure durations (5 min-5 h), and mortality. The Hypotensive Exposure Duration Index (HEDI) was developed to quantify cumulative hypotensive burden by integrating exposure across multiple MAP thresholds. HEDI's prognostic value was evaluated through nine machine learning algorithms. External validation using the eICU database assessed HEDI's consistency across different populations.

Results: Non-survivors showed significantly higher HEDI compared to survivors (0.47 [-0.20, 1.43] vs. -0.15 [-0.41, 0.27], p < 0.001). HEDI demonstrated increasing predictive capability, with AUC values rising from 0.624 at 24 h to 0.700 at 72 h post-admission. The Extra Trees classifier achieved exceptional performance (test AUC: 0.843), with HEDI ranking among the top predictive features. Both internal cross-validation and external validation confirmed the model's robustness, demonstrating HEDI's prognostic value across different patient populations, including both patients with and without vasopressor use.

Conclusions: HEDI effectively quantifies cumulative hypotensive burden in critically ill patients, demonstrating significant predictive ability for ICU mortality validated across diverse populations.

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.