Journal of Intensive Care最新文献

Background: Extracorporeal membrane oxygenation (ECMO) might be required as a treatment option in patients with critical pulmonary embolism (PE). However, the clinical features and outcomes of the use of ECMO for critical acute PE are still limited. The present study aimed to clarify the clinical characteristics, management strategies and outcomes of patients with acute PE requiring ECMO in the current era using data from a large-scale observational database.

Methods: We analyzed the data of the COMMAND VTE Registry-2: a physician-initiated, multicenter, retrospective cohort study enrolling consecutive patients with acute symptomatic venous thromboembolism (VTE). Among 2035 patients with acute symptomatic PE, there were 76 patients (3.7%) requiring ECMO.

Results: Overall, the mean age was 58.4 years, and 34 patients (44.7%) were men. Cardiac arrest or circulatory collapse at diagnosis was reported in 67 patients (88.2%). The 30-day incidence of all-cause death was 30.3%, which were all PE-related deaths. The 30-day incidence of major bleeding was 54.0%, and the vast majority of bleedings were procedure site-related bleeding events and surgery-related bleeding (22.4%). The 30-day incidence of all-cause death was 6.3% in 16 patients with surgical intervention, 43.8% in 16 patients with catheter intervention, 25.0% in 16 patients with thrombolytic therapy, and 39.3% in 28 patients with anticoagulation only.

Conclusions: The current large real-world VTE registry in Japan revealed clinical features and outcomes of critical acute PE requiring ECMO in the current era, which suggested several unmet needs for future clinical trials.

Background: There was no study to investigate the association between the national surge of Coronavirus disease 2019 (COVID-19) patients and the mortality of mechanically ventilated COVID-19 patients. The aim of this study was to assess the association between mortality in mechanically ventilated COVID-19 patients and two distinct national COVID-19 surge indices: (1) the daily number of newly confirmed COVID-19 cases, representing overall medical demands and (2) the total number of critically ill COVID-19 patients, reflecting critical care demands.

Methods: We analyzed the patient data registered in a national database of mechanically ventilated COVID-19 patients between February 6, 2020, and May 16, 2023, combined with the data officially published by the Japanese government. Multivariable logistic regression analysis was performed to evaluate the association of these two indices with COVID-19 mortality. A generalized linear mixed effect model was used to examine the relationships between the variation in the impact of critical care demands across hospitals and the variation in baseline risk across hospitals.

Results: The data of 8327 patients from 264 centers in Japan were analyzed. The overall mortality rate was 24% (1990/8327). The critical care demands, but not overall medical demands, were independently associated with the mortality (OR, 1.11; 95% CI 1.07-1.16; p < 0.001). This effect of critical care demands on the mortality was more pronounced in hospitals with higher baseline risk (r = 0.67).

Conclusions: The national critical care demands were independently associated with the mortality of COVID-19 patients requiring mechanical ventilation. This effect was more pronounced in hospitals with higher baseline risk.

The increase in the incidence of antibiotic-resistant bacteria poses a global public health threat. According to a 2019 WHO report, approximately 1.27 million deaths were attributed to antibiotic-resistant bacteria, with many cases linked to specific bacterial species, such as drug-resistant Pseudomonas aeruginosa and Staphylococcus aureus. By 2050, the number of deaths caused by these bacteria is predicted to surpass that caused by cancer. In response to this serious situation, phage therapy, an alternative to antibiotic treatment, has gained attention. Phage therapy involves the use of viruses that target specific bacteria to treat infections. This method has proven effective in multiple clinical cases, particularly for patients with severe infections caused by multidrug-resistant bacteria. For example, there are reports of patients with systemic infections caused by multidrug-resistant Acinetobacter who recovered following phage administration and patients infected with panresistant Pseudomonas aeruginosa who were cured by phage therapy. A key feature of phage therapy is its high specificity. Phages infect only specific bacteria and eliminate them. However, this specificity can also be a disadvantage, as careful selection of the appropriate phage for the target bacteria is needed. Additionally, bacteria can develop resistance to phages, potentially reducing treatment effectiveness over time. Efforts are underway to select, combine, and improve phages to address these challenges. In Belgium, a national phage bank has been established, and in the United States, the University of California, San Diego, has founded Innovative Phage Applications and Therapeutics (IPATH), marking significant progress toward the clinical application of phage therapy in the country. As a result, phage therapy is emerging as a component of personalized medicine, offering a new treatment option against antibiotic-resistant bacteria. The clinical application of phage therapy is particularly important in life-saving treatments for patients with severe bacterial infections, and its use in conjunction with antibiotics could enhance therapeutic outcomes. Continued research and development of this therapy could provide hope for many more patients in the future.

Background: Anthropometric measurements are crucial in pediatric critical care, but the impact of height on ICU outcomes is underexplored despite a substantial number of short-for-age children in ICUs. Previous studies suggest that short stature increases the risk of poor clinical outcomes. This study examines the relationship between short stature and ICU outcomes.

Methods: We conducted a retrospective cohort study using a Japanese nationwide database (the Japanese Intensive Care Patient Database; JIPAD), which included pediatric patients under 16 years admitted to ICUs from April 2015 to March 2020. Height standard deviation scores (SD scores) were calculated based on age and sex. Short-stature patients were defined as height SD score <  - 2. The primary outcome was all-cause ICU mortality, and the secondary outcome was the length of stay in ICU.

Results: Out of 6,377 pediatric patients, 27.2% were classified as having short stature. The ICU mortality rate was significantly higher in the short-stature group compared to the normal-height group (3.6% vs. 1.4%, p < 0.01). Multivariable logistic regression showed that short stature was independently associated with increased ICU mortality (OR = 2.73, 95% CI 1.81-4.11). Additionally, the Fine-Gray subdistribution hazards model indicated that short stature was associated with a lower chance of ICU discharge for each additional day (HR 0.85, 95% CI 0.81-0.90, p < 0.01).

Conclusions: Short stature is a significant risk factor for increased ICU mortality and prolonged ICU stay in critically ill children. Height should be considered in risk assessments and management strategies in pediatric intensive care to improve outcomes.

Objective: To verify whether the bleeding risk assessment guidelines from the 9th American College of Chest Physicians (ACCP) are prognostic for respiratory intensive care unit (RICU) patients and to explore risk factors for hemorrhages, we conducted a secondary data analysis based on our previously published cohort study of venous thromboembolism.

Patients and methods: We performed a secondary data analysis on the single-center prospective cohort from our previous study. Patients admitted to the RICU at Beijing Chao-Yang Hospital from August 1, 2014 to December 31, 2020 were included and followed up until discharge.

Results: The study enrolled 931 patients, of which 715 (76.8%) were at high risk of bleeding, while the remaining were at low risk. Of the total, 9.2% (86/931) suffered major bleeding, and no significant difference was found between the two risk groups (p = 0.601). High-risk patients had poor outcomes, including higher mortality and longer stays. Independent risk factors for major bleeding were APACHE II score ≥ 15; invasive pulmonary aspergillosis; therapeutic dose of anticoagulants; extracorporeal membrane oxygenation; and continuous renal replacement therapy. Blood transfusion not related to bleeding appeared to be an independent protective factor for major bleeding (OR 0.099, 95% CI 0.045-0.218, p < 0.001).

Conclusion: Bleeding risk assessment models from the 9th ACCP guidelines may not be suitable for patients in RICU. Building a bleeding risk assessment model that is suitable for patients in all RICUs remains a challenge. Trial registration ClinicalTrials.gov: NCT02213978.

In sepsis, inflammation, and nutrient deficiencies endanger cellular homeostasis and survival. Autophagy is primarily a mechanism of cellular survival under fasting conditions. However, autophagy-dependent cell death, known as autophagic cell death, is proinflammatory and can exacerbate sepsis. Autophagy also regulates various types of non-inflammatory and inflammatory cell deaths. Non-inflammatory apoptosis tends to suppress inflammation, however, inflammatory necroptosis, pyroptosis, ferroptosis, and autophagic cell death lead to the release of inflammatory cytokines and damage-associated molecular patterns (DAMPs) and amplify inflammation. The selection of cell death mechanisms is complex and often involves a mixture of various styles. Similarly, protective autophagy and lethal autophagy may be triggered simultaneously in cells. How cells balance the regulatory mechanisms of these processes is an area of interest that is still under investigation. Therapies aimed at modulating autophagy are considered promising. Enhancing autophagy helps clear and recycle damaged organelles and reduce the burden of inflammatory processes while inhibiting excessive autophagy, which could prevent autophagic cell death. In this review, we introduce recent advances in research and the complex regulatory system of autophagy in sepsis.

Background: Interferon gamma‑1b has been proposed to treat critical illness-induced immunosuppression. We aimed to determine the effects on 90-day outcomes and the cost-effectiveness of interferon gamma‑1b compared to placebo in mechanically ventilated critically ill patients.

Methods: A cost-effectiveness analysis (CEA) was embedded in the "PREV-HAP trial", a multicenter, placebo‑controlled, randomized trial, which randomly assigned critically ill adults under mechanical ventilation to receive interferon gamma or placebo. The CEA compared interferon-gamma with placebo using a collective perspective at a 90-day time horizon. The primary outcome was the incremental cost-effectiveness ratio (ICER) expressed in terms of adjusted cost per adjusted Quality-Adjusted Life-Years (QALYs) gained. QALYs were estimated from the responses of patients and proxy respondents to the health-related quality of life questionnaire EQ-5D-3L.

Results: The 109 patients in the PREV-HAP trial were included in the CEA. At day 90, all-cause mortality rates were 23.6% in the interferon group and 25% in the placebo group (Odds Ratio (OR) = 0.88 (0.40 -1.93) p = 0.67). The difference in the mean adjusted costs per patient at 90 days was €-1.638 (95%CI €-17.534 to €11.968) in favor of interferon gamma-1b. The mean difference in adjusted QALYs between interferon gamma-1b and the placebo group was + 0.019 (95%CI -0.005 to 0.043). The probability that interferon gamma-1b was cost-effective ranged from 0.60 to 0.71 for a willingness to pay a QALY between €20k and €150k for the base case analysis.

Conclusion: Early administration of interferon gamma might be cost-effective in critically ill patients supporting the realization of other studies on this treatment. However, the generalization of the findings should be considered cautiously, given the small sample size due to the premature end of PREV-HAP. Trial registration ClinicalTrials.gov Identifier: NCT04793568, Registration date: 2021-02-24.

Background: Sepsis is a leading cause of acute kidney injury requiring continuous kidney replacement therapy (CKRT) and CKRT can alter drug pharmacokinetics (PK). Cefepime is used commonly in critically ill children and is cleared by CKRT, yet data regarding cefepime PK and pharmacodynamic (PD) target attainment in children receiving CKRT are scarce, so we performed Monte Carlo simulations (MCS) of cefepime dosing strategies in children receiving CKRT.

Methods: We developed a CKRT "module" in the precision dosing software Edsim++. The module was added into a pediatric cefepime PK model. 1000-fold MCS were performed using six dosing strategies in patients aged 2-25 years and ≥ 10 kg with differing residual kidney function (estimated glomerular filtration rate of 5 vs 30 mL/min/1.73 m²), CKRT prescriptions, (standard-dose total effluent flow of 2500 mL/h/1.73 m² vs high-dose of 8000 mL/h/1.73 m²), and fluid accumulation (0-30%). Probability of target attainment (PTA) was defined by percentage of patients with free concentrations exceeding bacterial minimum inhibitory concentration (MIC) for 100% of the dosing interval (100% fT > 1xMIC) and 4xMIC using an MIC of 8 mg/L for Pseudomonas aeruginosa.

Results: Assuming standard-dose dialysis and minimal kidney function, > 90% PTA was achieved for 100% fT > 1x MIC with continuous infusions (CI) of 100-150 mg/kg/day (max 4/6 g) and 4-h infusions of 50 mg/kg (max 2 g), but > 90% PTA for 100% fT > 4x MIC was only achieved by 150 mg/kg CI. Decreased PTA was seen with less frequent dosing, shorter infusions, higher-dose CKRT, and higher residual kidney function.

Conclusions: Our new CKRT-module was successfully added to an existing cefepime PK model for MCS in young patients on CKRT. When targeting 100% fT > 4xMIC or using higher-dose CKRT, CI would allow for higher PTA than intermittent dosing.

Background: Heatstroke is a life-threatening condition characterized by severe hyperthermia and multiple organ dysfunction. Both normal saline (NS) and lactated Ringer's solution (LR) are commonly used for cooling and volume resuscitation in heatstroke patients; however, their specific impacts on patient outcomes during heatstroke management are poorly understood. Given that the systemic inflammatory response and multiple-organ damage caused by heat toxicity are the main pathophysiological features of heatstroke, the aim of this study was to evaluate the effects of NS and LR on the production of inflammatory cytokines and the functional and structural integrity of renal and cardiac tissues in a rat model of heatstroke.

Methods: Fifty-five male Sprague‒Dawley rats were randomly divided into four groups: cold NS or LR infusion postheatstroke (4 ℃, 4 ml/100 g, over 10 min) and NS or LR infusion without heatstroke induction (control groups). Vital signs, arterial blood gases, inflammatory cytokines, and renal and cardiac function indicators, such as serum creatinine and cTnI, were monitored after treatment. Tissue samples were analysed via HE staining, electron microscopy, and fluorescence staining for apoptosis markers, and protein lysates were used for Western blotting of pyroptosis-related proteins.

Results: Compared with LR-treated heatstroke rats, NS-treated heatstroke rats presented lower mean arterial pressures, worsened metabolic acidosis, and higher levels of IL-6 and TNF-α in both the serum and tissue. These rats also presented increased serum creatinine, troponin, catecholamines, and NGAL and reduced renal clearance. Histological and ultrastructural analyses revealed more severe tissue damage in NS-treated rats, with increased apoptosis and increased expression of NLRP3/caspase-1/GSDMD signalling molecules. Similar differences were not observed between the control groups receiving either NS or LR infusion. One NS-treated heatstroke rat died within 24 h, whereas all the LR-treated and control rats survived.

Conclusions: NS resuscitation in heat-exposed rats significantly promotes metabolic acidosis and the inflammatory response, leading to greater functional and structural organ damage than does LR. These findings underscore the necessity of selecting appropriate resuscitation fluids for heatstroke management to minimize organ damage and improve outcomes.

Background: Disorders of consciousness (DoC) are frequently encountered in both, acute and chronic brain injuries. In many countries, early withdrawal of life-sustaining treatments is common practice for these patients even though the accuracy of predicting recovery is debated and delayed recovery can be seen. In this review, we will discuss theoretical concepts of consciousness and pathophysiology, explore effective strategies for management, and discuss the accurate prediction of long-term clinical outcomes. We will also address research challenges.

Main text: DoC are characterized by alterations in arousal and/or content, being classified as coma, unresponsive wakefulness syndrome/vegetative state, minimally conscious state, and confusional state. Patients with willful modulation of brain activity detectable by functional MRI or EEG but not by behavioral examination is a state also known as covert consciousness or cognitive motor dissociation. This state may be as common as every 4th or 5th patient without behavioral evidence of verbal command following and has been identified as an independent predictor of long-term functional recovery. Underlying mechanisms are uncertain but intact arousal and thalamocortical projections maybe be essential. Insights into the mechanisms underlying DoC will be of major importance as these will provide a framework to conceptualize treatment approaches, including medical, mechanical, or electoral brain stimulation.

Conclusions: We are beginning to gain insights into the underlying mechanisms of DoC, identifying novel advanced prognostication tools to improve the accuracy of recovery predictions, and are starting to conceptualize targeted treatments to support the recovery of DoC patients. It is essential to determine how these advancements can be implemented and benefit DoC patients across a range of clinical settings and global societal systems. The Curing Coma Campaign has highlighted major gaps knowledge and provides a roadmap to advance the field of coma science with the goal to support the recovery of patients with DoC.