Journal of Intensive Care最新文献

Background: Acute pulmonary edema (APE) is a rare complication of subarachnoid hemorrhage (SAH) that is associated with increased morbidity and poor clinical outcomes. There is limited literature addressing the incidence and risk factors of this complication, highlighting the need for further investigation as undertaken in the present study.

Methods: The 2016 to 2021 National Inpatient Sample (NIS) was used to identify adult inpatients with a primary diagnosis of non-traumatic SAH. Univariate and multivariable analyses adjusting for patient demographics, and comorbidity status, were used to characterize statistical associations with APE.

Results: A total of 42,141 patients were identified as having SAH from 2016 to 2021. Of these patients, 960 patients (2.3%) were found to have APE. APE was associated with increased length of stay (20.0 ± 18.9 days vs. 11.6 ± 14.3, p < 0.001), increased total costs ($503,671.3 ± 647,729.9 vs. $238,724.6 ± 328,062.1, p < 0.001), increased number of days from admission to first procedure (3.5 ± 7.3 vs. 1.9 ± 4.9, p < 0.001), increased Elixhauser comorbidity index ≥ 3 (77.5% vs. 66.0%, p < 0.001), and increased mortality (40.2% vs. 22.5%, p < 0.001). After controlling for confounding factors, independent risk factors for APE in patients with non-traumatic SAH included: Coagulopathies (adjusted Odds Ratio [aOR]: 1.57, 95% confidence interval [CI] 1.31-1.89, p < 0.001), Fluid and Electrolyte Disorders (aOR: 2.54, CI 2.13-3.03, p < 0.001), Liver Disease (aOR: 1.37, CI 1.07-1.76, p = 0.013), Obesity (aOR: 1.47, CI 1.19-1.81, p = 0.003), Pulmonary Circulatory Disorder (aOR: 1.72, CI 1.31-2.26, p = 0.001), and Weight Loss (aOR: 1.67, CI 1.36-2.04, p < 0.001).

Conclusion: APE after SAH is associated with increased complicated hospital course. Neurosurgeons and Neurocritical care medical professionals should be aware of the comorbidities and factors associated with increased APE after SAH to improve patient outcomes.

Background: Prone positioning improves outcomes in patients with acute respiratory distress syndrome (ARDS), but the optimal duration in critical care settings remains uncertain. This study aims to evaluate the investigates the impact of prone ventilation duration on clinical outcomes.

Methods: This retrospective study was conducted on ARDS patients admitted to the intensive care unit (ICU), Nanfang hospital of Southern Medical University, who received prone positioning. Patients were categorized into two groups: the prolonged prone positioning (PPP) (≥ 16 h) group and the standard prone positioning (SPP) (< 16 h) group. Propensity score matching (PSM) was employed to balance baseline characteristics. Cox proportional hazards, regression models were utilized to evaluate the association between the prone duration and clinical outcomes. Kaplan-Meier survival curves were generated to compare 28-day mortality, with log-rank tests analyzing differences. Restricted cubic spline (RCS) were applied to investigate the time-response between prone duration, PaCO₂, PaO₂, positive end-expiratory pressure, response rate, and 28-day mortality. In addition, the incidence of prone position-related complications was assessed in both groups.

Results: A total of 234 patients with ARDS were included, with an overall 28-day mortality of 49.1% (115/234). After PSM, 81 matched pairs were compared. The PPP group had lower 28-day mortality (46.9% vs. 53.1%; hazard ratios (HR): 0.53; 95% CI 0.32-0.85; P = 0.033) and improved prone positioning response rate [70.5% vs. 60.5%; odds ratio (OR): 1.46; 95% CI 1.23-1.89; P = 0.025]. RCS analysis suggested a reduction in mortality with prone durations ≥ 16 h, and longer durations correlated with better prone response. However, no significant association was found between PPP and reduced ICU or hospital length of stay. RCS analysis indicated a gradual decrease in 28-day mortality with increasing duration of prone positioning, and longer duration were associated with a higher likelihood of a prone response. There were no significant differences in prone ventilation-related complications between the two groups.

Conclusions: PPP (≥ 16 h) is associated with reduced 28-day mortality and improved response rates in ICU patients with ARDS, without increasing complication risks. Prospective studies are needed to further validate these results.

Background: Sepsis is a leading cause of death in intensive care units (ICU). Sepsis survivors are often left with significant morbidity, termed post-intensive care syndrome (PICS), impacting post-sepsis life. The aim was to present detailed data on the prognostic and functional long-term outcomes of ICU patients with sepsis in Japan, which is currently lacking and therefore prevents development of targeted solutions.

Methods: A multicenter prospective study, involving 21 ICUs in 20 tertiary hospitals in Japan, included all consecutive adult ICU patients between November 2020 and April 2022, and diagnosed with sepsis at ICU admission (Sepsis 3). Follow-ups were performed at 3, 6, and 12 months after hospital discharge by telephone and mail. Primary outcome was death or incidence of PICS, defined by any of physical dysfunction (Barthel Index ≤ 90), cognitive dysfunction (Short Memory Questionnaire < 40), or mental disorder (any subscales for anxiety or depression of Hospital Anxiety and Depression Scale ≥ 8, or Impact of Event Scale-Revised ≥ 25). Secondary outcomes included Quality of Life (QOL), employment, and use of hospital, emergency, rehabilitation, and psychiatric services. A multivariable analysis investigated independent factors associated with each dysfunction at each follow-up.

Results: A total of 339 patients were included (median age 74 [67-82] years, 60% male, 77% septic shock, and a median SOFA of 9 [6-12]). Mortality was 23% at hospital discharge, increasing to 37% at 12 months. The rate of death for those who met PICS Criteria at hospital discharge was 89%, with a death or PICS incidence of 73%, 64%, and 65% at 3, 6, and 12 months, respectively. Limited improvements in QOL and return to work (44%), high rates of hospital readmissions (40%), frequent emergency service usage (31%), and low utilization of rehabilitation and psychiatric services (15% and 7%) were identified over the first year. The incidence of any PICS-related dysfunction was consistently an independent factor for the incidence of the same dysfunction at the following follow-ups.

Conclusions: This multicenter study identified the distinct realities of post-sepsis life in Japanese ICU patients, highlighting the unique challenges in improving their functions and returning to daily life. Trial Registration University Hospital Medical Information Network UMIN000041433.

Background: Although experts recommend intravenous fluid (IVF) for patients with rhabdomyolysis to prevent renal injury, the optimal IVF volume remains unknown because excessive IVF may lead to organ edema, resulting in organ injury. This study aimed to investigate the association between IVF volume and the composite outcome of hemodialysis dependence or in-hospital death in patients with rhabdomyolysis.

Methods: We retrospectively identified patients with rhabdomyolysis admitted to intensive care units and tertiary-care hospitals from July 2010 to March 2022 using the Japanese Diagnosis Procedure Combination database. We divided the patients into those who received at least 3500 mL/day of IVF within 3 days of admission and those who did not. This threshold was defined based on the findings of previous studies. We compared the composite outcome, including hemodialysis dependence at discharge and in-hospital death, between the groups using propensity score overlap weighting.

Results: We identified 5392 eligible patients. Of those, 1677 (31.1%) received ≥ 3500 mL/day of IVF, and 3715 (68.9%) received < 3500 mL/day of IVF; the total volumes of IVF within 3 days of admission were 11,039 mL and 4054 mL, respectively. Propensity-score overlap weighting created balanced cohorts, which did not show significant difference in primary composite outcome between the groups (3.4% vs. 3.9%; risk difference [RD] - 0.4, 95% confidence interval [CI] - 1.8 to 0.9, P = 0.53). The proportion of hemodialysis dependence was lower in the IVF ≥ 3500 mL/day group than those in the < 3500 mL/day group (0.4% vs. 1.3%; RD - 0.9, 95% CI - 1.6 to - 0.2, P = 0.02).

Conclusions: This retrospective database study found that IVF ≥ 3500 mL/day for patients with rhabdomyolysis was not associated with a reduction in the composite outcome but was associated with a reduction in hemodialysis dependence at discharge. The optimal IVF volume still remains unknown, and further studies are warranted.

Background: Treatment effect of high-dose intravenous selenium remains controversial in patients with sepsis or septic shock. Here, we reanalyzed data from the randomized placebo-controlled trial of Sodium Selenite and Procalcitonin Guided Antimicrobial Therapy in Severe Sepsis (SISPCT) to reveal possible treatment differences according to established sepsis phenotypes.

Methods: In this secondary data analysis of the SISPCT trial all 1089 patients of the original study were included. Patients were assigned to one of the four phenotypes by comparing patient variables with the Sepsis Endotyping in Emergency Care (SENECA) validation cohort. Survival analyses were performed using Kaplan-Meier and log-rank tests.

Results: No robust effect of selenium on mortality and other outcome parameters could be determined in any sepsis phenotype. Phenotype frequencies were markedly different in our study cohort compared to previous reports (α: 2.2%, β: 6.3%, γ: 68.0%, δ: 23.4%). Differences in mortality between the respective phenotypes were not significant overall; however, 28-day mortality showed a lower mortality for the α- (20.8%) and β-phenotype (20.3%), followed by the γ- (27.1%), and δ-phenotype (28.5%).

Conclusions: Application of the four sepsis phenotypes to the SISPCT study cohort showed discrete but non-significant mortality differences within 28 days. However, beneficial treatment effects of high-dose intravenous selenium were still not detectable after categorizing the SISPCT study cohort according to four phenotype criteria.

Background: Sepsis is a life-threatening condition often associated with metabolic and acid-base imbalances. Alactic base excess (ABE) has emerged as a novel biomarker to assess metabolic disturbances in critically ill sepsis patients, but its prognostic value remains underexplored. We aimed to investigate the relationship between ABE and 30-day/90-day ICU all-cause mortality in a large sepsis cohort in the intensive care unit (ICU) setting.

Methods: This study utilised data from a large US ICU sepsis cohort. ABE was calculated as the sum of lactate and base excess (BE) values from the first day of ICU admission. Patients were divided into quartiles based on ABE values. Kaplan-Meier survival analysis, Cox proportional hazards models, and restricted cubic spline analyses were used to examine the associations between ABE and mortality outcomes. The predictive performance of ABE combined with the SOFA score was assessed using the area under the curve, Net Reclassification Improvement, and Integrated Discrimination Improvement.

Results: 17,099 patients with sepsis were included in this analysis, with median (IQR) age of 67.82 (56.80, 78.04) years and 59.7% males. Our analysis revealed a U-shaped association between ABE and 30-day and 90-day ICU all-cause mortality. Both the lowest (Q1) and highest (Q4) quartiles of ABE were linked to increased mortality risks, with 30-day mortality showing HRs of 1.27 (95% CI 1.13-1.44) for Q1 and 1.17 (95% CI 1.06-1.31) for Q4, while 90-day mortality showed HRs of 1.28 (95% CI 1.16-1.44) for Q1, 1.12 (95% CI 1.02-1.23) for Q2, and 1.22 (95% CI 1.11-1.34) for Q4. ABE demonstrated superior predictive performance for mortality compared to BE and lactate. Incorporating ABE into the SOFA score improved predictive performance, emphasizing ABE's value in better risk stratification. The identified thresholds (2.5 mmol/L for 30-day mortality and 2.2 mmol/L for 90-day mortality) indicate optimal ABE levels that may be associated with improved survival outcomes.

Conclusions: ABE demonstrated a U-shaped association with 30-day and 90-day ICU all-cause mortality in critically ill sepsis patients, suggesting its superiority over BE and lactate as a predictive biomarker. Incorporating ABE with the SOFA score may further enhance prognostic predictions. Further studies are needed to determine whether ABE should serve solely as a biomarker for monitoring the clinical course or could also be considered a potential therapeutic target.

Background: Sepsis is a life-threatening condition with a high mortality rate in intensive care unit (ICU). However, rapid and accurate diagnostic criteria are still lacking. This pilot study explored the role of METRNL as a novel biomarker for sepsis by focusing on its diagnostic potential and rapid secretion mechanism.

Methods: METRNL levels were measured in cell and animal models of sepsis. Serum samples from 107 sepsis patients and 95 non-septic controls in ICU were collected. Diagnostic performance of METRNL, Procalcitonin (PCT) and C-reactive protein (CRP) were assessed using ROC analysis. Endothelial cell-specific Metrnl gene knockout mice (EC-Metrnl^-/- mice) were used to identify the source of METRNL secretion. Chemical inhibitors and RNA interference were used to explore the secretion pathways.

Results: In lipopolysaccharide (LPS)-induced cell and mouse models of sepsis, METRNL levels significantly increased in a dose- and time-dependent manner. Similarly, in the cecal ligation and puncture mouse models, serum METRNL levels were elevated over time and correlated with sepsis severity. In animals, serum METRNL increased within 1 h post-modeling, preceding PCT and CRP. Clinically, sepsis patients had significantly higher serum METRNL levels. ROC analysis showed area under the curves [95% confidence intervals] of 0.943 [0.91-0.975] for METRNL, 0.955 [0.929-0.981] for PCT and 0.873 [0.825-0.921] for CRP. At the optimal cutoff value, METRNL (91.6%) exhibited relatively greater diagnostic specificity than PCT (88.4%) and CRP (69.5%). EC-Metrnl^-/- reduced majority of serum Metrnl levels in sepsis mouse models. Inhibition of the endoplasmic reticulum-Golgi (ER-Golgi) pathway through chemical inhibitors or RNA interference significantly reduced METRNL levels in the supernatant of sepsis cell models compared to control groups. Similar results were obtained with Toll-like receptor 4 (TLR4) and ERK inhibitors.

Conclusions: This pilot study demonstrates that METRNL is a novel potential biomarker for sepsis with diagnostic capability comparable to that of PCT. Serum METRNL rapidly increased during the early phase of sepsis. Mechanistically, it mainly originates from the endothelium during sepsis, and TLR4-ERK signaling mediates the rapid secretion of METRNL via the classical ER-Golgi pathway in response to LPS stimulation.

Nutrition therapy is important in the management of critically ill patients and is continuously evolving as new evidence emerges. The Japanese Critical Care Nutrition Guideline 2024 (JCCNG 2024) is specific to Japan and is the latest set of clinical practice guidelines for nutrition therapy in critical care that was revised from JCCNG 2016 by the Japanese Society of Intensive Care Medicine. An English version of these guidelines was created based on the contents of the original Japanese version. These guidelines were developed to help health care providers understand and provide nutrition therapy that will improve the outcomes of children and adults admitted to intensive care units or requiring intensive care, regardless of the disease. The intended users of these guidelines are all healthcare professionals involved in intensive care, including those who are not familiar with nutrition therapy. JCCNG 2024 consists of 37 clinical questions and 24 recommendations, covering immunomodulation therapy, nutrition therapy for special conditions, and nutrition therapy for children. These guidelines were developed in accordance with the Grading of Recommendations, Assessment, Development and Evaluation (GRADE) system by experts from various healthcare professionals related to nutrition therapy and/or critical care. All GRADE-based recommendations, good practice statements (GPS), future research questions, and answers to background questions were finalized by consensus using the modified Delphi method. Strong recommendations for adults include early enteral nutrition (EN) within 48 h and the provision of pre/synbiotics. Weak recommendations for adults include the use of a nutrition protocol, EN rather than parenteral nutrition, the provision of higher protein doses, post-pyloric EN, continuous EN, omega-3 fatty acid-enriched EN, the provision of probiotics, and indirect calorimetry use. Weak recommendations for children include early EN within 48 h, bolus EN, and energy/protein-dense EN formulas. A nutritional assessment is recommended by GPS for both adults and children. JCCNG 2024 will be disseminated through educational activities mainly by the JCCNG Committee at various scientific meetings and seminars. Since studies on nutritional treatment for critically ill patients are being reported worldwide, these guidelines will be revised in 4 to 6 years. We hope that these guidelines will be used in clinical practice for critically ill patients and in future research.

Background: Erythropoietin (EPO), a glycoprotein hormone primarily produced in the kidneys, plays pleiotropic roles in hematopoietic and non-hematopoietic system. However, the clinical relevance of circulating EPO in sepsis progression and outcomes remains contentious and requires further elucidation.

Methods: Participants were categorized into three groups on the basis of EPO tertiles. The primary outcome was 28-day mortality. Multivariate Cox proportional regression analysis and restricted cubic spline regression were employed to evaluate the association between EPO levels and 28-day mortality in sepsis patients. Subgroup analyses were also conducted. Causal mediation analysis was conducted to explore the potential mediating role of EPO in the relationship between lactate and 28-day mortality.

Results: A total of 267 patients (65.17% male) were included in the study. The 28-day and hospital mortality rates were 23.22 and 31.20%, respectively. Multivariate Cox regression revealed significantly higher 28-day and hospital mortality in the highest EPO tertile compared to the lowest (HR 2.93, 95% CI 1.20-7.22; HR 2.47, 95% CI 1.05-5.81, respectively). Restricted cubic spline analysis demonstrated a progressively increasing mortality risk with elevated EPO levels. Subgroup analyses confirmed the consistency and stability of the effect size and direction across different subgroups. Moreover, causal intermediary analysis revealed that the association between lactate and 28-day mortality was partially mediated by EPO, with a mediation ratio of 12.59%.

Conclusions: Elevated EPO levels in patients with sepsis are correlated with unfavorable prognoses and may function as a prognostic biomarker for adverse outcomes.

Background: The gut has long been hypothesized to be the "motor" of critical illness, propagating inflammation and playing a key role in multiple organ dysfunction. However, the exact mechanisms through which impaired gut integrity potentially contribute to worsened clinical outcome remain to be elucidated. Critical elements of gut dysregulation including intestinal hyperpermeability and a perturbed microbiome are now recognized as potential therapeutic targets in critical care.

Main body: The gut is a finely tuned ecosystem comprising ~ 40 trillion microorganisms, a single cell layer intestinal epithelia that separates the host from the microbiome and its products, and the mucosal immune system that actively communicates in a bidirectional manner. Under basal conditions, these elements cooperate to maintain a finely balanced homeostasis benefitting both the host and its internal microbial community. Tight junctions between adjacent epithelial cells selectively transport essential molecules while preventing translocation of pathogens. However, critical illness disrupts gut barrier function leading to increased gut permeability, epithelial apoptosis, and immune activation. This disruption is further exacerbated by a shift in the microbiome toward a "pathobiome" dominated by pathogenic microbes with increased expression of virulence factors, which intensifies systemic inflammation and accelerates organ dysfunction. Research has highlighted several potential therapeutic targets to restore gut integrity in the host, including the regulation of epithelial cell function, modulation of tight junction proteins, and inhibition of epithelial apoptosis. Additionally, microbiome-targeted therapies, such as prebiotics, probiotics, fecal microbiota transplantation, and selective decontamination of the digestive tract have also been extensively investigated to promote restoration of gut homeostasis in critically ill patients. Future research is needed to validate the potential efficacy of these interventions in clinical settings and to determine if the gut can be targeted in an individualized fashion.

Conclusion: Increased gut permeability and a disrupted microbiome are common in critical illness, potentially driving dysregulated systemic inflammation and organ dysfunction. Therapeutic strategies to modulate gut permeability and restore the composition of microbiome hold promise as novel treatments for critically ill patients.