Journal of Intensive Care最新文献

Background: Lipoproteins and their component apolipoproteins play an important role in sepsis. However, little is known with regard to the association and causal contribution of these proteins to mortality in patients of different ancestries following septic shock. The objective of this study was to determine whether lipoprotein and apolipoprotein levels, and related genetic variants, are associated with clinical outcomes in septic shock.

Methods: We investigated the association between lipoprotein and apolipoprotein levels at the point of admission to the intensive care unit and in-hospital mortality in 687 Japan patients diagnosed with septic shock. For each clinically significant candidate protein, we extracted haplotype tag single nucleotide polymorphisms (SNPs) of the corresponding gene and examined the association of the candidate gene variants with 28-day mortality and organ dysfunction. We tested for replication in a Caucasian septic shock cohort (Vasopressin and Septic Shock Trial, VASST, n = 474). To determine whether the candidate lipoprotein causally contributed to septic shock outcome, we used a Mendelian randomization analysis based on polygenic scores generated from a genome-wide association study (GWAS) in the Japan cohort.

Results: In the Japan cohort, low apolipoprotein A-II levels were associated with increased septic shock mortality (adjusted odds ratio, 1.05; 95%CI, 1.02-1.09; P < 0.001). For a haplotype tag SNP of the corresponding ApoA2 gene, rs6413453 GG carriers had significantly higher 28-day mortality (adjusted hazard ratio [aHR], 1.79; 95% confidence interval [CI], 1.06-3.04; P = 0.029) and significantly fewer days free of cardiovascular, respiratory, renal and neurologic dysfunction than AG/AA carriers. This result was replicated in the Caucasian septic shock cohort (28-day mortality: aHR, 1.65; 95% CI, 1.02-2.68; P = 0.041). Mendelian randomization using 9 SNPs from an apolipoprotein A-II GWAS suggested that genetically decreased levels of apolipoprotein A-II were a causal factor for increased mortality in septic shock (odds ratio for mortality due to a 1 mg/dL decrease in apolipoprotein A-II is 1.05 [95% CI; 1.01-1.03, P = 0.0022]).

Conclusions: In septic shock, apolipoprotein A-II levels and ApoA2 genetic variations are important factors associated with outcome.

Purpose: Acute respiratory distress syndrome (ARDS) is a prevalent respiratory condition associated with significant mortality. Current literature on ARDS epidemiology reports a wide range of incidence (7.2-78.9/100,000 population/year), hospital mortality (32-51%), and associated costs ($8476-$547,974). We have analyzed epidemiological trends of mechanically ventilated ARDS (MV-ARDS) in Spain from 2000 to 2022 using the Minimum Basic Data Set (MBDS), focusing on MV-ARDS incidence, associated mortality, and economic impact.

Methods: We conducted a nationwide, population-based retrospective study of all hospitalizations for MV-ARDS in Spanish hospitals-from January 1, 2000 to December 31, 2022-using MBDS records, with an estimated coverage of 99.5%. The study reports MV-ARDS incidence per 100,000 population/year, hospital mortality rate, and mean cost per patient. We also considered the effect of COVID-19 on MV-ARDS epidemiology.

Results: We analyzed 93,192 records of patients with a new diagnosis of MV-ARDS during the study period. MV-ARDS incidence ranged from 2.96 to 20.14/100,000 population-years, peaking in 2021. Mortality ranged between 38.0 and 55.0%, showing a declining trend, while the cost per patient increased, stabilizing ~€30,000-€40,000 after reaching a peak of €42,812 in 2011. During the COVID-19 pandemic, hospital stay lengthened (p < 0.001), while hospital mortality decreased (p < 0.001). There was an increased proportion of patients with obesity and diabetes mellitus, with fungal or viral etiologies.

Conclusion: This is the largest epidemiological study on ARDS in Europe. MV-ARDS incidence has stabilized in recent years, with mortality showing a declining trend. ARDS-related costs have increased nearly fourfold. MBDS data could enhance ARDS understanding and guide future studies.

Background: Neurological outcomes after out-of-hospital cardiac arrest (OHCA) depend on multiple factors, including the patient's baseline condition and post-arrest management. The SLANT, developed specifically for OHCA survivors treated with targeted temperature management (TTM), requires further validation, particularly in Asian populations.

Methods: This multicenter retrospective cohort study analyzed data from 2016 to 2023, examining demographics, pre-arrest conditions, resuscitation events, and laboratory biomarkers following TTM. The primary outcome was defined as a poor neurological outcome at hospital discharge. Model performance was assessed using the area under the receiver operating characteristic curve. Multivariate logistic regression analysis was used to analyze the included variables.

Results: A total of 448 eligible adult patients were included, of whom 77.9% experienced poor neurological outcomes at discharge. The performance of the current cohort was comparable to that of the original SLANT cohort, achieving an area under the curve of 0.797 (95% confidence interval: 0.746-0.849). All five factors of the SLANT score remained statistically significant in predicting poor neurological outcomes. At a cutoff of ≥ 6.5, the SLANT score demonstrated a specificity of 53.5% and positive predictive value (PPV) of 86.9%. Increasing the cutoff value to 8.5 improved the specificity to 66.7% and the PPV to 89.6%.

Conclusion: The SLANT showed high PPV for predicting poor neurological outcomes at discharge in patients with OHCA undergoing TTM across a multicenter Asian cohort. Combining the score with other neurological assessments is recommended for improved neuroprognostication.

Background: Post-intensive care syndrome (PICS) affects the quality of life (QOL) of survivors of critical illness. Although PICS persists for a long time, the longitudinal changes in each component and their interrelationships over time both remain unclear. This multicenter prospective study investigated the 2-year trajectory of PICS and its components as well as factors contributing to deterioration or recovery in mechanically ventilated patients with coronavirus disease 2019 (COVID-19), and also attempted to identify possible countermeasures.

Methods: Patients who survived COVID-19 requiring mechanical ventilation completed questionnaires on the Barthel index, Short-Memory Questionnaire, Hospital Anxiety and Depression Scale, and EuroQol 5 dimensions 5-level every six months over a two-year period. Scores were weighted to account for dropouts, and the trajectory of each functional impairment was evaluated with alluvial diagrams. The prevalence of PICS and factors impairing or restoring function were examined using generalized estimating equations considering trajectories.

Results: Among 334 patients, PICS prevalence rates in the four completed questionnaires were 72.1, 78.5, 77.6, and 82.0%, with cognitive impairment being the most common and lower QOL being noted when multiple impairments coexisted. Physical function and QOL indicated that many patients exhibited consistent trends of either recovery or deterioration. In contrast, cognitive function and mental health revealed considerable variability, with many patients showing fluctuating ratings in the later surveys. Delirium was associated with worse physical and mental health and poor QOL, while prolonged ventilation was associated with poor QOL. Living with family was associated with the recovery of all functions and QOL, while extracorporeal membrane oxygenation (ECMO) was associated with the recovery of cognitive function and mental health.

Conclusions: Critically ill patients had PICS for a long period and followed different trajectories for each impairment component. Based on trajectories, known PICS risk factors such as prolonged ventilation and delirium were associated with impaired recovery, while ECMO and the presence of family were associated with recovery from PICS. In critically ill COVID-19 patients, delirium management and family interventions may play an important role in promoting recovery from PICS.

Trial registration number: UMIN000041276, August 01, 2020.

Background: The triglyceride-glucose (TyG) index is increasingly recognized for its ability to predict cardiovascular and metabolic risks. This study investigated the correlation between the TyG index and the risk of acute kidney injury(AKI) in critical ill patients with acute pancreatitis(AP).

Methods: The Medical Information Mart for Intensive Care IV database was retrospectively searched to identify AP patients hospitalized in the intensive care unit. The primary outcome measure was the incidence of AKI. The secondary endpoint was in-hospital mortality and the rate of renal replacement therapy(RRT) use. Cox regression analysis and restricted cubic spline were used to analyze TyG index association with AKI risk. Kaplan-Meier survival analysis was performed to assess the incidence of endpoints in the different groups.

Results: A total of 848 patients were enrolled. The incidence of AKI was 61.56%.The in-hospital mortality was 11.69%. Kaplan-Meier analysis showed that the TyG index ≥ 8.78 group has a high incidence of AKI and high risk of requiring RRT (P < 0.001). Multivariable Cox regression analysis showed whether TyG index was a continuous variable (HR, 1.65 [95% CI 1.10-2.48], P = 0.015) or a categorical variable (HR, 1.72 [95% CI 1.09-2.79], P = 0.028), and the TyG index was independently associated with the risk of AKI in AP patients. The restricted cubic splines model illustrated the linear relationship between higher TyG index and increased risk of AKI in this specific patient population.

Conclusions: High TyG index is an independent risk factor for AKI in critical ill patients with AP. Assessing the TyG index may be beneficial for early stratification and interventions to improve prognosis.

Background: Sepsis-associated encephalopathy (SAE) may be worsened by early systemic insults. We aimed to investigate the association of early systemic insults with outcomes of critically ill patients with severe SAE.

Methods: We performed a retrospective analysis using data from the French OUTCOMEREA prospective multicenter database. We included patients hospitalized in intensive care unit (ICU) for at least 48 h with severe SAE (defined by a score on the Glasgow Coma Scale (GCS) ≤ 13 and severe sepsis or septic shock (SEPSIS 2.0 criteria)) requiring invasive ventilation and who had no primary brain injury. We analyzed early systemic insults (abnormal glycemia (< 3 mmol/L or ≥ 11 mmol/L), hypotension (diastolic blood pressure ≤ 50 mmHg), temperature abnormalities (< 36 °C or ≥ 38.3 °C), anemia (hematocrit < 21%), dysnatremia (< 135 mmol/L or ≥ 145 mmol/L), oxygenation abnormalities (PaO₂ < 60 or > 200 mmHg), carbon dioxide abnormalities (< 35 mmHg or ≥ 45 mmHg), and the impact of their correction at day 3 on day-28 mortality and awakening, defined as a recovery of GCS > 13.

Results: We included 995 patients with severe SAE, of whom 883 (89%) exhibited at least one early systemic insult that persisted through day 3. Compared to non-survivors, survivors had significantly less early systemic insults (hypoglycemia, hypotension, hypothermia, and anemia) within the first 48 h of ICU admission. The absence of correction of the following systemic insults at day 3 was independently associated with mortality: blood pressure (adjusted hazard ratio (aHR) = 1.77, 95% confidence interval (CI) 1.34-2.34), oxygenation (aHR = 1.78, 95% CI 1.20-2.63), temperature (aHR = 1.46, 95% CI 1.12-1.91) and glycemia (aHR = 1.41, 95% CI 1.10-1.80). Persistent abnormal blood pressure, temperature and glycemia at day 3 were associated with decreased chances of awakening.

Conclusions: In patients with severe SAE, the persistence of systemic insults within the first three days of ICU admission is associated with increased mortality and decreased chances of awakening.

Background: Interleukin-6 (IL-6) is a cytokine that predicts clinical outcomes in critically ill patients, including those with sepsis. Elderly patients have blunted and easily dysregulated host responses to infection, which may influence IL-6 kinetics and alter the association between IL-6 levels and clinical outcomes.

Methods: This retrospective observational study included patients aged ≥ 16 years who were admitted to the intensive care unit at Chiba University Hospital. The patients were categorized into two groups: non-elderly (< 70 years) and elderly (≥ 70 years). Associations between log-transformed blood IL-6 levels and 28-day in-hospital mortality (primary outcome) and multiple organ dysfunction (MOD) on days 3 and 7 (secondary outcomes) were examined.

Results: The non-elderly and elderly groups included 272 and 247 patients, respectively. There were no significant differences in the Sequential Organ Failure Assessment score, components of the APACHE II score (Acute physiology score and Chronic health points), MOD at baseline, or any of the outcome measures between the groups. In the non-elderly group, univariate Cox regression analysis showed a significant association between IL-6 levels and mortality (hazard ratio [HR] 1.71, 95% confidence interval [CI] 1.25-2.37, P < 0.001). This association remained significant after adjusting for sex, body mass index, steroid use prior to sepsis onset, and number of chronic organ dysfunctions (HR 1.66, 95% CI 1.20-2.32, P = 0.002). However, no significant association was observed in the elderly group in either the univariate (P = 0.69) or multivariable analyses (P = 0.77). Multivariable logistic regression analysis of MOD on days 3 and 7 revealed significant associations between MOD and IL-6 levels in both groups.

Conclusions: Blood IL-6 levels were significantly associated with mortality in non-elderly patients with sepsis, but not in elderly patients. IL-6 levels were associated with MOD in both groups. Therefore, IL-6 levels should be interpreted with caution when predicting mortality in elderly patients with sepsis.

Trial registration: Not applicable.

The incidence of heat-related illnesses and heatstroke continues to rise amidst global warming. Hyperthermia triggers inflammation, coagulation, and progressive multiorgan dysfunction, and, at levels above 40 °C, can even lead to cell death. Blood cells, particularly granulocytes and platelets, are highly sensitive to heat, which promotes proinflammatory and procoagulant changes. Key factors in heatstroke pathophysiology involve mitochondrial thermal damage and excessive oxidative stress, which drive apoptosis and necrosis. While the kinetics of cellular damage from heat have been extensively studied, the mechanisms driving heat-induced organ damage and death are not yet fully understood. Converse to hyperthermia, hypothermia is generally protective, as seen in therapeutic hypothermia. However, accidental hypothermia presents another environmental threat due to arrhythmias, cardiac arrest, and coagulopathy. From a cellular physiology perspective, hypothermia generally supports mitochondrial homeostasis and enhances cell preservation, aiding whole-body recovery following resuscitation. This review summarizes recent findings on temperature-related cellular damage and preservation and suggests future research directions for understanding the tempo-physiologic axis.

Background: Hepatic encephalopathy (HE) is a severe complication of acute hepatic failure requiring urgent critical care management. Branched-chain amino acids (BCAAs) such as leucine, isoleucine, and valine have been investigated as potential treatments to improve outcomes in patients with acute HE. However, the effectiveness of BCAA administration during the acute phase remains unclear. This study aimed to evaluate the effect of intravenous BCAA (IV-BCAA) treatment on clinical outcomes in patients with acute HE by systematically reviewing and analyzing randomized controlled trials (RCTs).

Methods: We conducted a comprehensive literature search of MEDLINE, the Cochrane Central Register of Controlled Trials, and Igaku Chuo Zasshi (ICHUSHI), a Japanese database for medical literature. We included RCTs involving adult patients with acute HE who received IV-BCAA or placebo during the acute phase after admission (< 7 days). Two reviewers independently screened the citations and extracted data. The primary "critical" outcomes were mortality from any cause and improvement in disturbance of consciousness. The secondary "important" outcome included the incidence of complications such as nausea and diarrhea. Risk ratios (RRs) were calculated using random effects models with inverse variance weighting.

Results: Among the 2073 screened records, four met the criteria for quantitative analysis. The analysis included 219 patients: 109 received IV-BCAA, and 110 received placebo. Improvement in the disturbance of consciousness and mortality were not significantly different between the two groups (RR, 1.26; 95% confidence interval [CI], 0.96-1.66; RR, 0.90; 95% CI 0.70-1.16, respectively). Following IV-BCAA administration, the absolute differences of improvement in the disturbance of consciousness and mortality were 118 more per 1000 (95% CI 18 fewer-300 more) and 55 fewer per 1000 (95% CI 165 fewer-88 more), respectively. No significant differences were observed in the incidence of nausea or diarrhea between the two groups.

Conclusions: Our meta-analysis demonstrates that all outcomes were not significantly different between IV-BCAA treatment and placebo for acute HE. Further RCTs are required to better understand IV-BCAA treatment potential in patients with HE.

Sepsis often leads to vasoplegia and a hyperdynamic cardiac state, with treatment focused on restoring vascular tone. However, sepsis can also cause reversible myocardial dysfunction, particularly in the elderly with pre-existing heart conditions. The Surviving Sepsis Campaign Guidelines recommend using dobutamine with norepinephrine or epinephrine alone for patients with septic shock with cardiac dysfunction and persistent hypoperfusion despite adequate fluid resuscitation and stable blood pressure. However, the definition of cardiac dysfunction and hypoperfusion in these guidelines remains controversial, leading to varied clinical interpretations. Cardiac dysfunction with persistent hypoperfusion despite restoring adequate preload and afterload is often considered a cardiogenic shock. Therefore, sepsis complicated by new-onset myocardial dysfunction or worsening of underlying myocardial dysfunction due to sepsis-induced cardiomyopathy, resulting in cardiogenic shock, can be defined as "Sepsis-induced cardiogenic shock (SICS)". SICS is known to be associated with significantly higher mortality. A history of cardiac dysfunction is a strong predictor of SICS, highlighting the need for precise diagnosis and management given the aging population and rising cardiovascular disease prevalence. Therefore, SICS might benefit from early invasive hemodynamic monitoring with a pulmonary artery catheter (PAC), unlike those with septic shock alone. While routine PAC monitoring for all septic patients is impractical, echocardiography could be a useful screening tool for high-risk individuals. If echocardiography indicates cardiogenic shock, PAC might be warranted for continuous monitoring. The role of inotropes in SICS remains uncertain. Mechanical circulatory support (MCS) might be considered for severe cases, as high-dose vasopressors and inotropes are associated with worse outcomes. Correct patient selection is the key to improving outcomes with MCS. Engaging a cardiogenic shock team for a multidisciplinary approach can be beneficial. In summary, addressing the evidence gaps in SICS diagnosis and management is crucial. Echocardiography for screening, advanced monitoring with PAC, and careful patient selection for MCS are important for optimal patient care.