Journal of Intensive Care最新文献

Objectives: To summarize the evidence on the accuracy of tests evaluating readiness for liberation from mechanical ventilation in the adult population.

Materials and methods: Searches were conducted in MEDLINE, Embase, CENTRAL, and CINAHL, with additional publications identified through conference proceedings and contact with experts. Systematic reviews (SRs) were independently assessed for inclusion, data extraction, and risk of bias, without language or date restrictions. Included SRs focused on adults diagnosed with ventilatory failure requiring invasive support for more than 24 h. Successful weaning was considered being alive in absence of ventilatory support 72 h following liberation from mechanical ventilation.

Results: Ten SRs examining the diagnostic accuracy of 23 readiness tests were included. These tests were conducted before, during, or after spontaneous breathing trials using various methods, such as pressure support, T-piece and continuous positive airway pressure. Among these, lung ultrasound score (sensitivity 0.94, 95% CI 0.59-0.99; specificity 0.87, 95% CI 0.62-0.97), diaphragmatic rapid shallow breathing index (sensitivity 0.84, 95% CI 0.76-0.90; specificity 0.87, 95% CI 0.79-0.92), venous oxygen saturation (sensitivity 0.83, 95% CI 0.74-0.90; specificity 0.88, 95% CI 0.83-0.92), and brain natriuretic peptide (sensitivity 0.88, 95% CI 0.83-0.92; specificity 0.82, 95% CI 0.73-0.89), showed high to moderate diagnostic capacity for ruling in and ruling out weaning failure. The remaining tests (e.g., cuff leak test, cough peak flow, P0.1, RSBI, MIP, DE, DTF, DTF-RSBI, EeDT, and EiDT) demonstrated weak diagnostic accuracy. In the SRs, risk of bias ranged from low to high.

Conclusions: The accuracy of tests used to assess readiness for withdrawing ventilatory support in adults varies considerably. Physicians should integrate the results of physiological, ultrasound, and paraclinical measures to minimize uncertainty in deciding which patients should progress toward ventilator weaning, always considering individual patient needs to ensure personalized healthcare.

Background: Pulse oximetry is essential for continuous oxygen monitoring in intensive care, yet its accuracy declines in patients with low peripheral perfusion, risking both unrecognised hypoxaemia and inappropriate oxygen therapy. The perfusion index (PFI) reflects peripheral blood flow and is often reduced in critically ill patients with impaired microcirculation. Simple bedside strategies to restore PFI and improve SpO₂ accuracy remain underexplored.

Methods: In this prospective quasi-experimental study, 46 adult ICU patients with arterial catheters and baseline PFI < 1.0 underwent localised peripheral warming using a wrist-forearm heating pad for 15 min. The warming pad maintained a surface temperature of 54 °C, with directly measured skin-interface temperatures of 41-42 °C. SpO₂, PFI, and arterial oxygen saturation (SaO₂) were measured immediately before and after the intervention. The primary outcome was the change in PFI; the secondary outcome was the improvement in SpO₂ accuracy (SpO₂-SaO₂ bias).

Results: Thermal intervention increased PFI from a median (IQR) of 0.56 (0.34-0.78) to 3.59 (2.45-4.77) (p < 0.001; Hedges' g = 2.43). The pre-intervention SpO₂-SaO₂ bias was 4.09% (95% limits of agreement 0.61-7.56%), which decreased to 0.00% (- 1.22-1.23%) after warming. Improvements were consistent across subgroups and unrelated to cardiac index, vasoactive use, or skin pigmentation.

Conclusions: A brief, localised thermal intervention markedly improves peripheral perfusion and restores pulse-oximetry accuracy to within the clinically acceptable ± 2% range in critically ill patients with low PFI. However, ceiling effects at SpO₂ values near 100% and the pre-post design limit the strength of causal inference. This simple, non-invasive technique can be readily integrated into ICU practice to enhance the reliability of oxygen monitoring and reduce the risk of undetected hypoxaemia or hyperoxaemia.

Background: Persistent immune checkpoint activation is a recognized feature of critical coronavirus disease 2019 (COVID-19). However, the temporal behavior and clinical utility of soluble programmed death-ligand 1 (sPD-L1) remain unclear. We investigated the longitudinal changes in sPD-L1, its relationship with organ dysfunction markers, and their prognostic value when combined with machine learning (ML) models.

Methods: In this single-center observational study, we included 40 adults with severe COVID-19 pneumonia admitted to the intensive care unit (ICU) (April 2021-December 2022), and 23 healthy volunteers as controls. We measured plasma sPD-L1 on ICU day 1, 5, 7, 14, and 21. Routine biochemistry, complete blood counts, and arterial blood gas analyses were conducted in parallel. Cox regression was used to identify independent predictors of hospital mortality, the primary outcome. Eight ML classifiers were trained using admission variables and sPD-L1 levels from ICU day 1, 5, and 7. Discrimination was assessed using stratified fivefold cross-validation, and feature importance was evaluated using Shapley Additive Explanations (SHAP).

Results: Of 40 patients, 10 died during hospitalization. Overall, sPD-L1 levels declined during the ICU stay but remained persistently high in non-survivors. ICU day 5 and 7 values differed significantly between survivors and non-survivors (p = 0.023 and 0.001, respectively). In multivariable Cox analysis, ICU day 7 sPD-L1 levels and arterial lactate levels on admission independently predicted mortality. ICU day 7 sPD-L1 levels correlated positively with creatinine, C-reactive protein, and fibrinogen levels (all p < 0.05) in cross-sectional correlation analyses. Among ML models, the support vector machine achieved the highest discriminative accuracy (mean area under the curve = 0.917). ICU day 5 sPD-L1 was designated as the primary predictor of mortality based on SHAP analysis, with lactate contributing minimally.

Conclusion: Sustained sPD-L1 elevation during the first ICU week is strongly associated with early organ dysfunction and independently predicts death in critical COVID-19. Incorporating serial sPD-L1 measurements into bedside ML models significantly enhances risk discrimination. These findings support sPD-L1 as an integrative biomarker of the immune-renal-coagulation interplay, warranting validation in larger multicenter cohorts and exploration as a potential companion marker for immune-modulatory interventions.

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.