Journal of Intensive Care最新文献

Background: Remimazolam, a benzodiazepine, was first approved in 2020 for general anesthesia and procedural sedation but has not for sedation in the intensive care units. As other sedatives used in intensive care units have disadvantages such as propofol infusion syndrome and hypotension, an alternative sedative would be desired.

Main body: Remimazolam was developed as a soft drug that is designed to be rapidly metabolized to the inactive chemical, CNS7054. In humans, it is mainly metabolized by the non-specific esterase, carboxylesterase 1, in the liver, not in the blood, unlike the ultrashort-acting soft drug remifentanil. Remimazolam is a short-acting drug. The context-sensitive decrement time, which describes how the accumulated drug affects the decay curve of the drug concentration after its infusion ends, of remimazolam is similar to that of propofol. Remimazolam binds the benzodiazepine site of the gamma-aminobutyric acid type A receptors, and does not directly activate the gamma-aminobutyric acid type A receptors. Benzodiazepines are not effective in the absence of gamma-aminobutyric acid. Although hypotension appears less frequent, it can occur during remimazolam administration. Delayed emergence can occur after remimazolam infusion due to its accumulation. To prevent delayed emergence, excessive doses should be avoided. A dose of the competitive antagonist flumazenil can cause re-sedation after administration. The impact of delirium after prolonged sedation is unknown. The remimazolam concentration at steady-state is approximately 10% higher in males than in females, > 20% in obese patients than in normal weight patients, and approximately 20% higher in American Society of Anesthesiologists physical status III/IV patients than in I/II patients. The infusion rate should may be reduced in these patients. A study has shown that the required dose is higher in children than in adults.

Conclusions: Remimazolam could be an alternative sedative in intensive care units. Because remimazolam is short-acting, it accumulates during prolonged infusions. Infusion rate should be titrated based on patient characteristics, including sex, body mass index, and physical status. Benzodiazepine tolerance should be considered before and during remimazolam infusion. Similar to other sedatives, concurrent use of additional hypnotics and analgesics may help maintain the desired sedation in intensive care units.

Background: Few studies have examined the prognostic impact of high fever after decannulation from veno-venous (V-V) extracorporeal membrane oxygenation (ECMO) in patients with severe acute respiratory distress syndrome (ARDS). We aimed to investigate the incidence and prognostic significance of post-decannulation high fever in this population, exploring its association with mortality, stratified by the presence of infectious complications at decannulation.

Methods: This study was a post hoc analysis of a multicenter retrospective registry that included adult patients with severe ARDS who were successfully weaned off V-V ECMO between 2012 and 2022 across 24 institutions in Japan. High fever was defined as a core body temperature of ≥ 39.0 °C within 3 days after ECMO decannulation. The primary outcome was 90-day in-hospital mortality. Cox proportional hazards models were used to examine the association between post-decannulation high fever and mortality. As a subgroup analysis, we evaluated this association according to the presence or absence of infectious complications.

Results: Among 522 patients, 121 (23.2%) developed high fever within 3 days after ECMO decannulation. In the overall cohort, 90-day in-hospital mortality did not differ significantly between the high-fever and no-fever groups (19.0% vs. 13.7%, p = 0.372). Multivariable analysis showed no statistically significant association between high fever and mortality (hazard ratio [HR] 0.92, 95% confidence interval [CI] 0.55-1.56, p = 0.770). Subgroup analyses revealed opposite associations depending on infection status. High fever was associated with reduced mortality in patients with infection (HR 0.33, 95% CI 0.12-0.89, p = 0.045) but increased mortality in those without (HR 2.25, 95% CI 1.23-4.11, p = 0.011).

Conclusions: Post-decannulation high fever occurs in nearly one-fourth of patients with severe ARDS treated with V-V ECMO. Its association with mortality appears to differ depending on the infection status at decannulation, underscoring the importance of carefully assessing infectious complications.

Background: Quality indicators (QIs) support measurement and improvement of ICU care; however, until 2017 there was no comprehensive, evidence-based QI set tailored to frontline adult ICU practice in Japan. Because evidence and practice evolve, periodic updating is required. We developed a Japanese ICU QI set in 2017-2018 and conducted a formal re-evaluation in 2025 to confirm current validity and update the core set.

Methods: We used a modified RAND/UCLA appropriateness method. First, an initial list of candidate QIs was generated through a systematic literature review and major clinical guidelines. Next, a multidisciplinary panel of 14 Japanese experts (including intensivists, a nurse, a physiotherapist, and a clinical engineer) rated the appropriateness of these indicators using a nine-point Likert scale (Round 1). Following Round 1, a face-to-face consensus meeting was held to discuss, refine, add, or delete indicators based on scientific evidence, clinical importance, and feasibility, followed by Round 2 to finalize the 2018 consensus set. In 2025 (Round 3), the panel re-rated all indicators from the 2018 set using the same rating and classification framework and also rated newly proposed indicators reflecting contemporary practice.

Results: The systematic review yielded 44 initial candidate QIs. After the two-round rating process and the expert panel meeting, a 2018 consensus set of 38 QIs was established (13 structure indicators, 10 process indicators, and 15 outcome indicators). In Round 3 (2025), 37 indicators remained Appropriate, whereas one indicator was reclassified as Uncertain and was not retained in the updated core set. One newly proposed indicator was rated Appropriate and added, resulting in an updated 2025 core set of 38 indicators. All selected indicators were deemed appropriate and relevant for the Japanese ICU setting by the expert panel.

Conclusions: Using a rigorous modified RAND/UCLA appropriateness method and a 2025 re-evaluation, we developed and updated a feasible, contextually adapted Japanese ICU QI set. The updated core set, with operational definitions and specified data sources, provides a foundation for national benchmarking and continuous quality improvement in Japanese ICUs. 330 words.

Background: Despite advances in post-cardiac arrest (CA) care, mortality rates remain high. Intestinal dysfunction following CA is associated with adverse clinical outcomes. While laxatives might be a potential therapeutic strategy for restoring intestinal function, there is currently a lack of evidence.

Objective: This study aims to explore the safety and efficacy of laxatives as therapeutic agents for intestinal function recovery in CA, while further assessing the most suitable types of laxatives for this clinical context.

Methods: Utilizing the MIMIC-IV database, we conducted a retrospective cohort study categorizing patients into laxative and non-laxative groups. Propensity score matching (PSM) was applied to balance baseline characteristics. We classified confounders into prehospital and hospitalization categories, establishing three hierarchical adjustment models. Through multivariable Cox and logistic regression analyses, we assessed 30-day and extended mortality risks while evaluating laxative-associated safety outcomes. Time-dependent Cox regression analysis was utilized to assess the time-varying effect of laxative administration. Furthermore, we also comparatively analyzed the risk-benefit profiles of commonly used laxatives.

Results: 2604 patients were eligible for this study. After PSM, a total of 898 patients were average divided into two groups. Patients in the laxative group demonstrated a statistically significant reduction in 30-day mortality risk compared to the non-laxative group (HR = 0.686, 95%CI [0.550-0.855], P = 0.001). After applying time-dependent Cox regression analysis, the results remain consistent (HR = - 0.771 + 0.632 × ln[day + 1], 95%CI [0.528-0.835], P = 0.001). Meanwhile, laxative did not increase the risk of sepsis and Clostridium difficile infection but improved the bowel sounds recovery and increased the ICU-free day. Further subgroup analysis revealed that the use of docusate sodium (HR = 0.753, 95%CI [0.566-1.000], P = 0.050) may be associated with a decreased mortality risk.

Conclusion: Early using laxative to improve intestinal function is associated with improved survival outcomes. However, clinical application may be guided by the bowel sounds recovery and demonstrated tolerance to enteral feeding. This still requires further studies to confirm.

Background: Traumatic brain injury (TBI) is a major cause of trauma-related deaths. Systemic glucose and lactate levels reflect secondary metabolic derangements over time; however, most prognostic models rely on admission values. This study compared static and longitudinal indices of glucose, lactate, and their ratio in relation to ICU mortality.

Methods: This retrospective single-center study analyzed 479 non-diabetic adult patients with TBI admitted to a German university ICU (2013-2023). After 1:2 severity-balanced, outcome-stratified propensity score matching, 229 patients (150 survivors, 79 non-survivors) were included. Indices comprised admission values, means, clearance, time-weighted averages, variability, and dysglycemic burden. Outcome was ICU mortality, assessed using regression, mixed-effects modeling, and ROC analysis.

Results: Longitudinal indices showed stronger associations. Time-weighted average lactate was the best independent predictor (OR 14.70, 95% CI [5.41-39.98], p < 0.001, AUC 0.73). Time-weighted average glucose-lactate ratio also independently predicted ICU mortality (OR 0.75, 95% CI [0.66-0.86], p < 0.001). Non-survivors exhibited persistently higher glucose, lactate and lower ratios, with lactate significantly elevated on all first ten ICU days (all p < 0.05). Admission values, clearance and variability were not predictive after adjustment.

Conclusions: In critically ill non-diabetic patients with TBI, longitudinal time-weighted average lactate significantly outperformed admission values and glucose metrics for predicting ICU mortality in a severity-balanced cohort; the glucose-lactate ratio was associated but did not surpass lactate. These findings underscore the importance of longitudinal monitoring and support prioritizing lactate in multiparametric prognostic model to account for secondary injuries. Prospective validation is warranted to confirm external validity and assess therapeutic implications.

Background: Tracheal intubation in critically ill adults is frequently complicated by severe physiological adverse events, particularly cardiovascular instability. Although fentanyl is commonly used for induction, observational data suggest that its use may increase the risk of post-intubation hypotension. However, the overall randomized evidence remains unclear. In this systematic review and meta-analysis of randomized controlled trials (RCTs), we hypothesized that induction regimens including fentanyl or its analogs would increase the risk of peri-intubation cardiovascular instability in critically ill patients.

Methods: We comprehensively searched PubMed, Embase, the Cochrane Library, ClinicalTrials.gov, and the WHO ICTRP from inception through October 31, 2025. Eligible studies were RCTs comparing an induction regimen including fentanyl or its analogs with one without them in critically ill adults undergoing tracheal intubation. The primary outcome was peri-intubation cardiovascular instability. Secondary outcomes included peri-intubation hypoxemia, successful intubation on the first attempt, duration of mechanical ventilation, ICU length of stay, and mortality. Random-effects meta-analyses were performed for all outcomes. Trial sequential analysis (TSA) was conducted for the primary outcome. Certainty of evidence was assessed using the GRADE approach.

Results: We included five RCTs and 515 participants. Two studies were judged to be low risk of bias, two raised some concerns, and one was at high risk of bias. Comparators included various induction agents and placebo. Definitions of peri-intubation cardiovascular instability also varied. The evidence was very uncertain regarding the effect of fentanyl on the risk of peri-intubation cardiovascular instability (risk ratio, 1.41; 95% confidence interval, 0.83-2.40; risk difference, 9.2% more; 95% confidence interval, 3.8% fewer to 31.3% more; very low certainty). In TSA, the required information size (n = 5586) was not reached, indicating the lack of statistical power. The certainty of evidence for pooled secondary outcomes was generally low or very low.

Conclusions: The effect of fentanyl on peri-intubation cardiovascular instability remains highly uncertain, with pooled estimates compatible with substantial harm, substantial benefit, or no effect. Current randomized evidence is insufficient to guide routine clinical practice, given their very low or low certainty and susceptibility to random error.

Trial registration: PROSPERO (registration number: CRD420251241214).

Background: Sepsis is a critical determinant of mortality in critical patients. Antithrombin (AT) plays a pivotal role as a serine protease inhibitor with dual anticoagulant and anti-inflammatory functions, yet its precise role in prognostic stratification remains undefined. This study aimed to investigate the association between AT activity and clinical outcomes in sepsis and to identify critical prognostic thresholds.

Methods: We conducted a retrospective cohort study of 222 septic patients from the MIMIC-IV and MIMIC-III databases. AT activity was measured within the first 24 h following sepsis diagnosis, with the primary outcome defined as 28-day all-cause mortality. For preliminary description, AT activity was categorized into tertiles. The primary analysis utilized restricted cubic splines (RCS) to model the dose-response relationship and identify risk thresholds. Multivariable Cox regression models were employed to adjust for demographics, comorbidities, and SOFA score. Subgroup and survival analyses were performed to evaluate effect modification and visualize outcome differences across threshold-defined risk groups. To visually compare survival outcomes between patient groups defined by the RCS-derived risk thresholds, we generated Kaplan-Meier curves and employed log-rank tests.

Results: A non-linear relationship between AT activity and 28-day mortality was identified, with a marked increase in risk observed below approximately 55% in the overall cohort. Patients with AT activity < 55% had significantly higher 28-day mortality (34.2% vs. 14.4%, p = 0.001), ICU mortality (33.3% vs. 9.0%, p < 0.001), and incidences of disseminated intravascular coagulation (DIC) (22.5% vs. 3.6%, p < 0.001) and acute kidney injury (AKI) (78.4% vs. 62.2%, p = 0.013). Subgroup analysis revealed a significant interaction with hypertension. In the hypertensive subgroup, a similarly elevated risk zone was observed below approximately 64% AT activity. Hypertensive patients below this level had markedly increased 28-day mortality (42.3% vs. 9.62%, p < 0.001), ICU mortality (38.5% vs. 5.77%, p < 0.001), and incidences of DIC (19.2% vs. 1.92%, p < 0.001).

Conclusion: Reduced AT activity was significantly associated with higher mortality and organ dysfunction in sepsis. Risk thresholds were observed at approximately 55% for the overall cohort and 64% among hypertensive patients. Patients below these levels exhibited significantly increased mortality and higher incidences of DIC and AKI. These findings support AT activity as a prognostic biomarker for risk stratification and highlight its potential to inform future management strategies for high-risk patients.

Infections are frequent after cardiac arrest and materially affect post-ICU care and outcomes. Diagnostic uncertainty is heightened by post-cardiac arrest syndrome (PCAS)-hypoxic-ischemic brain injury, myocardial dysfunction, systemic ischemia-reperfusion injury, and immune dysregulation-and by sedation and targeted temperature management (TTM), which can mask clinical signs and modulate host defenses. Pneumonia predominates; bloodstream infection and intra-abdominal or hepatobiliary infections are under-recognized, especially in device-dependent or extracorporeal membrane oxygenation (ECMO)-treated patients. Conventional biomarkers such as C-reactive protein and procalcitonin show reduced infection specificity early after return of spontaneous circulation; therefore, single timepoint cutoffs are unreliable, and serial trajectories interpreted with clinical examination, microbiology, and imaging are preferred. Risk scores (e.g., Sequential Organ Failure Assessment [SOFA], Clinical Pulmonary Infection Score [CPIS]) may support stratification but are insufficient for definitive diagnosis. Observational cohorts report higher pneumonia rates with TTM, and temperature control can blunt fever and leukocytosis and alter cytokine and biomarker kinetics, complicating timely recognition. Prevention should emphasize protocolized bundles, including hand hygiene and asepsis, head-of-bed elevation, structured oral care per local policy, minimization of sedation with spontaneous breathing trials, and early removal of unnecessary devices, within an antimicrobial stewardship framework that supports early de-escalation once cultures and trajectories clarify etiology. Procalcitonin-guided early discontinuation reduces antibiotic exposure in general critical-care populations; in PCAS, use should prioritize serial trends integrated with clinical context rather than single thresholds. No fixed algorithm is prescribed; instead, practical considerations are presented to guide diagnostic practice, emphasizing early microbiological sampling and imaging, integration of serial biomarker trajectories with clinical assessment, and timely de-escalation as the clinical picture clarifies, without endorsing single-test cutoffs. Priorities include quantifying infection-attributable morbidity and mortality; developing and validating PCAS-specific biomarkers and composite decision tools, including electronic health record-based early warning models; evaluating short post-intubation prophylaxis in selected high-risk patients; optimizing TTM parameters (target temperature, duration, rewarming rate); and systematically characterizing under-recognized infections. A protocol-driven, multimodal program that integrates prevention, standardized diagnostics, and stewardship is required to deliver timely, appropriate therapy and improve outcomes after cardiac arrest.