Journal of Intensive Care最新文献

Background: Traumatic brain injury (TBI) is a major public health concern associated with substantial morbidity and mortality. In Japan, carbazochrome sodium sulfonate (CSS) is widely used, often in combination with tranexamic acid (TXA), for the management of various types of bleeding; however, studies on the effectiveness of CSS in TBI are scarce. Therefore, this study aimed to investigate the association between the use of CSS plus TXA versus TXA alone and the clinical outcomes in patients with TBI.

Methods: This observational study was conducted using data retrieved from the Japanese Diagnosis Procedure Combination database between July 2010 and March 2022. We enrolled adult patients aged ≥ 16 years diagnosed with TBI who received TXA on the day of admission. Patients with chronic subdural hematoma, suspected TBI diagnosis, or severe extracranial trauma were excluded. The exposure was CSS plus TXA administration on the day of admission, with TXA monotherapy assigned as the control. The primary outcome was 28-day in-hospital mortality, and the secondary outcomes were 7-day in-hospital mortality, overall in-hospital mortality, consciousness at discharge, and length of hospital stay. We used propensity-score overlap weighting to balance patient characteristics between the groups.

Results: This study included 150,026 patients. Of these, 17,212 (11.5%) received TXA alone, and 132,814 (88.5%) received CSS plus TXA. After propensity score overlap weighting, the primary outcome did not differ significantly between the TXA-only and CSS plus TXA groups (11.7% vs. 11.9%; risk difference, 0.1%; 95% CI - 0.4 to 0.7%). The secondary outcomes were also comparable between the two groups. However, the subgroup analysis restricted to unarousable patients (Japan Coma Scale 100-300) revealed a significant reduction in the 7-day mortality in the CSS plus TXA group.

Conclusions: Combined treatment with CSS and TXA was not associated with better clinical outcomes in terms of in-hospital mortality, consciousness at discharge, or length of hospital stay in hospitalized adult patients with TBI compared with TXA therapy alone. Routine use of CSS may not be recommended.

In this comment, we aim to offer some perspective on the work of Raffenot et al. entitled "Risk factors for nosocomial meningitis in patients with external ventricular drainages". After highlighting the main findings of their study, we discuss the predictive model as well as the disease definition they used.

Background: The effect of different spontaneous breathing trial (SBT) methods on lung volume and ventilation distribution has not been well clarified in post-cardiac surgery patients.

Methods: In this prospective observational study, patients underwent 30 min of pressure-support ventilation (PSV)-SBT [PS 8 cmH₂O, zero positive end-expiratory pressure (ZEEP)], followed by a 30-min T-piece trial if tolerated. Electrical impedance tomography (EIT) was used to continuously monitor regional lung ventilation and end-expiratory lung volume (EELV) at baseline, PSV-SBT 3 min, PSV-SBT 30 min, T-piece SBT 3 min and T-piece SBT 30 min. EELV_loss = [VT_baseline/tidal impedance variation (TIV)_baseline] × ΔEELI. EELV_{loss PSV} was defined as volume loss at 30 min of PSV-SBT and EELV_{loss T-piece} was defined as volume loss during T-piece SBT.

Results: In 60 patients who complied with both SBT steps, 43 succeeded (71.7%) and 17 failed (28.3%) the T-piece SBT. Compared to the success group, the failure group exhibited a higher incidence of pendelluft (52.9% vs. 23.3%, p = 0.045) and significantly greater EELV_loss at T-piece SBT 30 min (623[459,746] ml vs. 511[376,702]ml, p = 0.003). However, the success group showed greater EELV_{loss PSV} than the failure group (322[247,459] ml vs. 199[166, 269] ml, p < 0.001), which was an abnormal pattern. Notably, the failure group had lower TIV (2102[1769,2562] vs. 2742[2153,3872], p = 0.005) and a higher respiratory rate (RR) than baseline at PSV-SBT 30 min (20[17,24] vs. 16[12,18], p < 0.001). Furthermore, we classified all patients into two groups based on the predominant reduction of volume loss: P-volume loss group (N = 37, EELV_{loss PSV} > EELV_{loss T-piece}) and T-volume loss group (N = 23, EELV_{loss T-piece} > EELV_{loss PSV}). In addition, the T-volume loss group had a higher weaning failure rate than the P-volume loss group (52.2% [12/23] vs. 13.5% [5/37], p < 0.001) and was associated with reduced baseline dorsal ventilation (39%[37%,43%] vs. 44%[41%,50%], p = 0.023). ROC analysis suggested that a dorsal ventilation threshold of 40.5% was associated with T-volume loss.

Conclusions: The successful weaning patients had a higher reduction of EELV_{loss PSV} and a lower reduction of EELV_{loss T-piece}. In the weaning failure patients, the paradox of lower EELV_{loss PSV} that was accompanied by a high RR and low VT might be associated with air trapping. Attention should be paid to using EELV_{loss PSV} to identify weaning failure.

Sedation is essential in intensive care units (ICUs) for invasive procedures and mechanical ventilation; however, commonly used agents are limited by hemodynamic instability, delayed recovery of consciousness, and delirium. Remimazolam, an ultra-short-acting benzodiazepine, introduced in 2020, is rapid metabolized by hepatic carboxylesterase 1 and enables predictable recovery after prolonged administration, suggesting potential advantages for sedation in critical illness despite limited ICU-specific evidence. A narrative review was conducted based on evidence derived from randomized controlled trials, meta-analyses, and observational studies, which indicated that remimazolam provides sedation efficacy comparable to that of conventional hypnotics across surgical anesthesia, procedural sedation, and ICU settings. Multiple meta-analyses have suggested that remimazolam is associated with favorable hemodynamic tolerance and does not increase the incidence of postoperative or ICU delirium compared with propofol or other sedative agents. Delirium risk appears to be more strongly influenced by patient severity, surgical characteristics, and sedation depth than by hypnotic choice alone, although the heterogeneity across studies may partly reflect differences in delirium diagnostic tools. In ICU patients requiring mechanical ventilation, remimazolam demonstrated safety and efficacy comparable to those of propofol or midazolam, with acceptable hemodynamic stability and no consistent signs of increased mortality. Several studies have also suggested that the predictable recovery profile associated with flumazenil may facilitate ventilator weaning or recovery of consciousness, although the interpretation of recovery outcomes requires caution, particularly in studies involving routine flumazenil administration. Pharmacokinetic data in ICU populations remain limited but suggest preserved dose linearity with reduced clearance in patients with severe hepatic dysfunction. Remimazolam may be a promising sedative option for critically ill patients, offering a predictable recovery and generally favorable hemodynamic profiles. However, its optimal role in ICU sedation requires confirmation through high-quality international multicenter studies, particularly regarding prolonged mechanical ventilation, neurocognitive outcomes, and cost-effectiveness.

Ventilator-induced lung injury and diaphragm dysfunction are well-recognized complications of mechanical ventilation and commonly attributed to inadequate ventilator settings. Excessive or insufficient assistance and the patient's own respiratory effort are increasingly acknowledged as important factors in the pathogenesis of these injuries. Therefore, monitoring respiratory effort at the bedside is a highly relevant strategy to identify and prevent potentially injurious breathing patterns. Esophageal manometry remains the reference standard for assessing respiratory effort, but its technical complexity limits routine clinical use. Placement and calibration of the esophageal balloon are time-consuming and require specific expertise. Moreover, the invasive nature of the procedure precludes visual confirmation and leads to uncertainty about correct positioning, reducing confidence in the validity of measurements. Innovative noninvasive and continuous monitoring techniques are emerging as more accessible and scalable alternatives, enabling assessment of respiratory effort without impacting so much on clinical workflow. This narrative review provides an in-depth overview of three noninvasive techniques that are reshaping continuous respiratory effort monitoring: (1) Surface electromyography (sEMG) now enables continuous monitoring of respiratory muscle activity and derivation of continuous effort estimation using electrodes placed on the torso of the patient. (2) Computational modeling offers dynamic, patient-specific effort estimation from ventilator waveforms. (3) Assessment of diaphragm thickening fraction, derived from high-resolution ultrasound, provides a straightforward surrogate for effort, driven by widely available acquisition devices. Together, these innovations promise to make respiratory muscle monitoring less labor-intensive and more clinically sustainable-paving the way for broader implementation of diaphragm-protective ventilation strategies in critical care.

Remimazolam, an ultra-short-acting benzodiazepine rapidly metabolized by carboxylesterase-1, was developed as a promising alternative for ICU sedation. It was anticipated to overcome the unpredictable accumulation associated with midazolam and the hemodynamic/metabolic risks of propofol, offering superior hemodynamic stability and potential benefits in reducing postoperative delirium. Its ultra-short, predictable half-life positioned it as an ideal candidate for facile titration in critically ill patients. However, the trajectory of remimazolam's development for long-term ICU sedation faced a critical setback in Japan. Based on results from the ONO-2745-04 Phase II trial conducted on mechanically ventilated postoperative patients, the development program for the ICU indication was halted in 2013. The central safety concern was the unexpected pharmacokinetic failure observed in a subset of patients receiving continuous infusion for 24 h or longer. Specifically, this subgroup exhibited plasma concentrations of the parent drug far exceeding predicted levels, resulting in significantly delayed awakening and recover. This observation directly challenged the fundamental non-accumulating advantage of the drug. The mechanism is hypothesized to be compromised carboxylesterase-1 activity due to severe critical illness, systemic inflammation, or organ dysfunction-conditions that impair the very non-organ-dependent clearance pathway the drug relies upon. While international experience continues to validate the safe and effective use of remimazolam for short-to-medium-term ICU sedation, the Japanese experience serves as a critical clinical warning. It underscores that even drugs with inherently favorable pharmacokinetic profiles are susceptible to unpredictable parent drug accumulation in the highly heterogeneous and physiologically compromised ICU population during prolonged infusion. Therefore, extreme caution and individualized dosing strategies are warranted for remimazolam use in critically ill patients, especially those with severe systemic dysfunction.

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.