Journal of Intensive Care最新文献

Background: The ratio of central venous-to-arterial carbon dioxide content difference to arterial-to-venous oxygen content difference (C_v-aCO₂/C_a-vO₂) and central venous-to-arterial carbon dioxide tension difference (P_v-aCO₂) are indicators for monitoring anaerobic metabolism and tissue perfusion in shock. We hypothesized that significant differences in patient outcomes exist across different C_v-aCO₂/C_a-vO₂ and P_v-aCO₂ groups during the early stages of shock resuscitation and that these two indicators reflect microcirculatory perfusion in septic shock patients.

Methods: This single-center, prospective, observational, cohort, exploratory, pilot study involved newly diagnosed patients with septic shock admitted to intensive care unit (ICU) between May 2023 and August 2024. We classified patients into four groups based on their C_v-aCO₂/C_a-vO₂ and P_v-aCO₂ levels at 6 h post-ICU admission (T6), monitored sublingual microcirculation, and followed them for 28 days. The grouping is as follows: Group A is C_v-aCO₂/C_a-vO₂ ≤ 1 and P_v-aCO₂ < 6 mmHg; Group B is C_v-aCO₂/C_a-vO₂ ≤ 1 and P_v-aCO₂ ≥ 6 mmHg; Group C is C_v-aCO₂/C_a-vO₂ > 1 and P_v-aCO₂ < 6 mmHg; and Group D is C_v-aCO₂/C_a-vO₂ > 1 and P_v-aCO₂ ≥ 6 mmHg.

Results: 105 patients were included in the study. The 28-day mortality differed significantly among the four groups of patients (A:8.3%, B:19%, C:30%, and D:46.7%, p < 0.05). The Kaplan-Meier curves for the four groups revealed significant differences in the 28-day survival probabilities. (p = 0.014). Multivariate Cox regression revealed that the independent risk factors for 28-day mortality were age [hazard ratio (HR) = 1.05, 95% confidence interval (95% CI) = 1.02-1.09, p = 0.001], C_v-aCO₂/C_a-vO₂ (HR = 1.67, 95% CI = 1.03-2.69, p = 0.036), and P_v-aCO₂ (HR = 1.13, 95% CI = 1.00-1.27, p = 0.043). There were significant differences among the four groups in terms of the proportion of perfused vessels for all (PPV), proportion of perfused vessels for d < 20 μm (sPPV), microvascular flow index (MFI), and heterogeneity index (HI) values (p < 0.001); correlations were observed for C_v-aCO₂/C_a-vO₂, P_v-aCO₂, and sPPV (r = -0.49, p < 0.001, R² = 0.19; r = -0.22, p = 0.028, R² = 0.08).

Conclusions: The combined assessment of C_v-aCO₂/C_a-vO₂

Background: Delirium, a neuropsychiatric disorder characterized by disturbances in attention, cognition, and awareness, is a common complication among intensive care unit (ICU) patients. Several predictive models have been developed that aim to identify patients at high risk of delirium. PRE-DELIRIC (PREdiction of DELIRium in ICu) and its recalibrated version, have been externally validated in several studies, but modest sample sizes have meant uncertainty remains, particularly in patient subgroups. Of particular relevance to our population (as a tertiary liver disease centre), performance in patients with liver disease has not been specifically assessed.

Methods: This retrospective cohort study evaluated the PRE-DELIRIC model using data from 3312 adult ICU patients at Cambridge University Hospital, between February 2017 and September 2021. Delirium was primarily defined as either a positive Confusion Assessment Method for the ICU (CAM-ICU) or any new administration of antipsychotic medication. Predictive performance was assessed according to discrimination, measured by the area under the receiver operating characteristic (AUROC) and precision-recall curves; and calibration, as quantified by calibration slope and intercept. We also conducted subgroup analyses in patients with liver disease, sedated patients, and across varying opioid dosing.

Results: Delirium occurred in 32.9% of patients. Overall, PRE-DELIRIC demonstrated moderate-to-good discriminative performance (AUROC 0.74; 95% CI 0.72-0.76); but the model significantly underpredicted delirium incidence for those patients predicted to have moderate-to-high delirium risk (PRE-DELIRIC score 0.2-0.6); and overpredicted for those predicted to be at very high risk (PRE-DELIRIC score > 0.6). Among patients with liver disease (41.6% delirium incidence), discrimination was similar to the overall cohort (AUROC 0.73; 95% CI 0.66-0.81), but calibration was poor, with significant under-prediction of delirium. Discrimination was significantly poorer in both sedated patients and patients receiving high opioid dosing.

Conclusion: This is the largest validation study of the PRE-DELIRIC model to date, and the first to specifically consider patients with liver disease. We found moderate-to-good discriminative predictive performance both overall and in liver disease patients, but calibration was only moderate overall, and significantly under-predicted risk in patients with liver disease. Recalibration of the model and further subgroup-specific adjustments may enhance its utility in clinical practice.

A recent meta-analysis of randomized controlled trials (with pre-specified methods and the largest sample to date) found that prophylactic diuretics significantly reduce acute kidney injury (AKI) incidence in high-risk patients but provide no benefit in treating established AKI. These findings challenge current AKI management guidelines, which generally discourage prophylactic diuretic use. However, given heterogeneity among trials and some risk of bias, caution is advised before generally altering clinical practice until further research confirms these findings.

Background: Disseminated intravascular coagulation (DIC) is characterized by systemic coagulation activation, anticoagulation pathway impairment, and persistent fibrinolysis suppression, resulting in widespread microvascular thrombosis, followed by hemorrhagic consumption coagulopathy and multiple organ dysfunction syndrome. This article aimed to provide a comprehensive and updated DIC overview.

Main body: The International Society on Thrombosis and Hemostasis provides definitions, underlying disorders, diagnostic algorithms, and management guidelines for DIC. Two clinical features of DIC are hemorrhagic consumption coagulopathy, characterized by oozing and difficult-to-control bleeding, and microvascular thrombosis, leading to dysfunctions in multiple vital organs. Histones derived from cellular damage play central roles in the innate-immune-based coagulation model, comprising the initiation, amplification, propagation, and reinforcement phases, which, if dysregulated, develop into DIC. Thus, the innate immune-mediated pathogenic pathways in DIC have become clear. Cell death, damage-associated molecular patterns (including histones), crosstalk between hypoxic inflammation and coagulation, and the serine protease network (comprising coagulation and fibrinolysis, the Kallikrein-Kinin system, and complement pathways) play major roles in DIC pathogenesis. Conversely, these pathogenic pathways and DIC synergistically contribute to organ dysfunction, leading to poor prognoses. Effective DIC management requires treating the underlying condition, along with substitution therapies and, in some cases, antifibrinolytics. Anticoagulant use has been extensively debated; however, the selection of optimal target patients could optimize their application and improve patient outcomes in the near future.

Conclusions: This review provides an updated overview of DIC, aiming to help readers understand various aspects of DIC today.

Diarrhea is common in critically ill patients and can lead to malnutrition, electrolyte imbalance, and dehydration. While its direct impact on outcomes, such as mortality or intensive care unit (ICU) stay, remains unclear due to inconsistent definitions, it often results from drug-induced causes, such as antibiotics and antacids. These agents can also contribute to dysbiosis and increase the risk of infections including Clostridioides difficile infections (CDI) and ventilator-associated pneumonia (VAP).Probiotics, defined as live beneficial microorganisms, can counteract dysbiosis by modulating immune responses, restoring microbial balance, and reducing intestinal inflammation. Evidence suggests that probiotics may help prevent diarrhea and secondary infections. Clinical trials and meta-analyses have shown that probiotics may reduce the incidence of VAP, length of ICU stay, duration of mechanical ventilation, and potential in-hospital mortality in critically ill patients.However, evaluating probiotic efficacy remains challenging due to the lack of standardized markers and the influence of confounding factors like antacid use. In a randomized controlled trial, synbiotic therapy was associated with improved fecal microbiota and reduced infections; however, the role of antacids was not addressed.Probiotics are generally safe, although rare adverse events, such as probiotic-associated bacteremia, have been reported, particularly in immunocompromised individuals.The 2024 Japanese Critical Care Nutrition Guidelines included a systematic review and meta-analysis supporting the potential benefits of probiotics in critically ill patients. However, due to significant heterogeneity in strains, dosing, duration, and concurrent antibiotic/antacid use, a weak recommendation (GRADE 2C; low certainty) was issued.Future research should focus on the standardized evaluation of diarrhea and microbiota changes, the use of objective markers-such as fecal pH and short-chain fatty acid levels-and clarification of the interactions of probiotics with other medications. Comprehensive bowel management, including the cautious use of antibiotics and antacids, may be essential to fully recognize the therapeutic potential of probiotics in critical care settings.

Background: The heterogeneity of host responses in sepsis has hindered efforts to develop targeted therapies for this large patient population. Although growing evidence has identified sepsis endotypes based on the microarray data, studies using RNA-seq data-which offers higher sensitivity and a broader dynamic range-remain limited. We hypothesized that integrating RNA-seq data from patients with sepsis would reveal molecular endotypes with distinct biological and clinical signatures.

Methods: In this meta-analysis, we systematically searched for publicly available RNA-seq datasets of sepsis. Using identified datasets, we applied a consensus clustering algorithm to identify distinct endotypes. To characterize the biological differences between these endotypes, we performed gene-set enrichment analysis and immune cell deconvolution. Next, we investigated the association between these endotypes and mortality risks. We finally developed gene classifiers for endotype stratification and validated our endotype classification by applying these classifiers to an external cohort.

Results: A total of 280 adults with sepsis from four datasets were included in this analysis. Using an unsupervised approach, we identified three distinct endotypes: coagulopathic (n = 83, 30%), inflammatory (n = 118, 42%), and adaptive endotype (n = 79, 28%). The coagulopathic endotype exhibited upregulated coagulation signaling, along with an increased monocyte and neutrophil composition, although the adaptive endotype demonstrated enhanced adaptive immune cell responses, marked by elevated T and B cell compositions. The inflammatory endotype was characterized by upregulated TNF-α/NF-κB signaling and IL-6/JAK/STAT3 pathways with an increased neutrophil composition. Patients with the coagulopathic endotype had a significantly higher risk of mortality than those with the adaptive endotype (30% vs. 16%, odds ratio 2.19, 95% confidence interval 1.04-4.78, p = 0.04). To enable the practical application of these findings, we developed endotype classification models and identified 14 gene classifiers. In a validation cohort of 123 patients, we consistently identified these three endotypes. Furthermore, the mortality risk pattern was reproduced, with the coagulopathic endotype showing greater mortality risk than the adaptive endotype (34% vs 18%, p = 0.10).

Conclusions: This multicohort RNA-seq meta-analysis identified three biologically and clinically distinct sepsis endotypes characterized by coagulopathic, adaptive, and inflammatory responses. This endotype-based approach to patient stratification may facilitate the development of more precise therapeutic strategies for sepsis.

Background: Minimizing relative hypotension, or mean arterial pressure (MAP) deficit, by targeting patients' own pre-illness MAP (individualized MAP) during vasopressor therapy is a potential strategy to improve outcomes among ICU patients with shock. We conducted a prospective, open label, parallel-group, pilot RCT to assess feasibility and safety of this intervention compared to standard care.

Methods: Thirty-seven eligible patients, aged 40 years or older and receiving vasopressor support for shock, were randomly allocated to individualized MAP target (N = 17) or standard MAP target (N = 20) at two multidisciplinary ICUs in Australia and Ireland. Pre-specified endpoints were time-weighted average MAP-deficit (i.e., percentage difference between patients' pre-illness MAP and achieved-MAP), percentage time spent with > 20% MAP-deficit, major adverse kidney events (MAKE-14), 14-day and 90-day all-cause mortality, and cardiovascular adverse events within 28 days of randomization. All comparisons of efficacy outcomes were exploratory.

Results: The median MAP-deficit and percentage time with > 20% MAP-deficit with individualized MAP vs. standard MAP were 7% [interquartile range: 2-16] vs. 18% [9-23] (p = 0.048), and 8% [0-43] vs. 53% [14-75] (p = 0.03), respectively. MAKE-14 (2/17 (12%) vs. 4/20 (20%), p = 0.67), 14-day mortality (1/17 (6%) vs. 3/20 (15%), p = 0.61), 90-day mortality (2/17 (12%) vs. 4/20 (20%), p = 0.67) and cardiovascular adverse events were similar for both groups.

Conclusions: This pilot RCT demonstrated that an individualized MAP target strategy was feasible to implement. No adverse safety signals were evident. These data and study procedures helped inform the design of a definitive RCT on the question of individualized MAP targets among critically ill patients with shock.

Study registration: ACTRN12618000571279.

Objective: This study investigates the impact of four laxatives-Senna, Docusate Sodium, Polyethylene Glycol, and Lactulose on 28-day mortality, ICU-free days, ventilator-free days, bowel recovery, and Clostridium difficile (C-diff) infection in critically ill sepsis patients to identify optimal bowel management strategies for improving survival and recovery.

Methods: Using the MIMIC-IV database (v3.1), we analyzed 7163 ICU sepsis patients (median age: 67.5 years; 63% male), assessing 28-day mortality, ICU-free days, vasopressor-free days, ventilator-free days, bowel sound recovery, and C-diff incidence, with propensity score matching and multivariable adjustments for confounders, alongside subgroup analyses by sex, age, Charlson Comorbidity Index, and Sequential Organ Failure Assessment score.

Results: Docusate Sodium was associated with significantly lower 28-day mortality (adjusted HR: 0.43; 95% CI 0.36-0.52), more ICU-free days, and better bowel recovery compared to Senna, while Lactulose was linked to higher mortality (adjusted HR: 1.82; 95% CI 1.45-2.27), fewer ICU-free days, and increased C. difficile risk, with subgroup analyses confirming these trends across sex, age, and comorbidity strata.

Conclusion: Docusate sodium appears to be a safer and more effective bowel management option for critically ill patients with sepsis. In contrast, the association between lactulose use and adverse outcomes may primarily reflect the severity of underlying liver disease rather than a direct drug effect. These findings underscore the importance of individualized laxative selection based on patients' clinical context in critical care practice.

Background: Acute respiratory distress syndrome (ARDS) remains a significant clinical challenge, and its pathogenesis is not fully understood. Proteomic analyses of plasma and bronchoalveolar lavage fluid (BALF) in patients with ARDS have been performed to uncover diagnostic and prognostic markers, although previous studies have not adequately focused on longitudinal comparison of biomarkers. This study aimed to elucidate the proteomic profiles of patients with ARDS in the acute and subacute phases to better understand the pathophysiological progression of ARDS.

Methods: This was a single-center, prospective, observational study of adult patients with ARDS in whom plasma and BALF samples were collected in the acute and subacute phases of ARDS and comprehensive proteins were identified and analyzed by mass spectrometry.

Results: Plasma and BALF were collected from 21 ARDS patients and plasma from 24 healthy donors, from which 694 plasma proteins and 2017 BALF proteins were analyzed. Processes related to coagulation and complement commonly activated in plasma and BALF were more pronounced in the acute phase than in the subacute phase. In BALF in the acute phase, pathways related to humoral and immune responses were activated, whereas processes related to chaperones and protein folding were suppressed. IPA analysis showed that B cell receptor signaling was most activated, whereas heat shock protein 90 (HSP90) chaperone cycle, protein folding, and other pathways associated with cellular stress responses and proper protein processing were suppressed. The most activated upstream regulator was interferon gamma (IFN-γ) and the most suppressed was notch receptor 1 (NOTCH1).

Conclusions: The proteomics of plasma and BALF from patients with ARDS were compared in both the acute and subacute phases. In BALF in the acute phase, humoral immunity, mainly B-cell receptor signaling, was activated, whereas the HSP90 cycle and protein folding mechanisms were inactivated.