Intensive Care Medicine Experimental最新文献

{"title":"Target-controlled dialysis for antibiotics (TCD-ABx).","authors":"Alexander Dejaco, Christoph Dorn, Constantin Lier, Daniel Fleischmann, Alexander Kratzer, Katharina Habler, Michael Paal, Michael Gruber, Johanna Rosenberger, Martin G Kees","doi":"10.1186/s40635-024-00696-7","DOIUrl":"https://doi.org/10.1186/s40635-024-00696-7","url":null,"abstract":"<p><strong>Background: </strong>Effective antimicrobial therapy is an essential part of intensive care medicine and renal replacement therapy is an important and common intervention which significantly affects the pharmacokinetics of many antimicrobials. This is especially critical for substances with a narrow therapeutic range, creating a dilemma of weighing the risk of toxicity from increased drug exposure against risk of ineffective treatment and promotion of antimicrobial resistance. To address this problem, we investigate a target-controlled dialysis by in vitro experiments - a novel technique in which drug is spiked into the dialysis solution to make use of the physicochemical properties of renal replacement therapy for solute transport, with the goal to reduce the risk of inadequate drug exposure.</p><p><strong>Methods: </strong>Five antibiotics (ceftazidime, meropenem, piperacillin/tazobactam, vancomycin, flucloxacillin) were dialyzed in an in vitro model of continuous veno-venous hemodialysis using 1 L of bovine serum albumin solution as simulated patient plasma compartment. This was done with and without antibiotics in target concentrations added to the dialysis solution, mimicking three clinically relevant scenarios: (i) target-controlled dialysis in a subject with sub-therapeutic drug levels, (ii) target-controlled dialysis in a subject with supra-therapeutic drug levels, and (iii) traditional dialysis of drugs starting at the target concentration. Drug levels were quantified by high-performance liquid chromatography. Additionally, the stability over 24 h of all antibiotics in two typical dialysis solutions was assessed.</p><p><strong>Results: </strong>Our data shows that with target-controlled dialysis, antibiotic concentrations will change in the desired direction towards the target concentration, depending on the patients' unbound drug levels in relation to the concentration in the dialysis solution. The desired target concentrations can be induced and maintained, regardless of the initial concentration. Furthermore, the stability tests revealed only a minor and clinically irrelevant loss in drug concentration (all < 10.2%) after 12 h.</p><p><strong>Conclusions: </strong>We outlined the mechanistic plausibility and provided experimental evidence of the feasibility of the target-controlled dialysis concept, which could help to maintain therapeutic concentrations of many time-dependent antibiotics in critically ill patients under renal replacement therapy. The required stability in dialysis solutions was shown for a set of important antibiotics. The next step will be the prudent application of this concept to patients in clinical trials.</p>","PeriodicalId":13750,"journal":{"name":"Intensive Care Medicine Experimental","volume":"12 1","pages":"108"},"PeriodicalIF":2.8,"publicationDate":"2024-11-26","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142716133","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Assessment of mitochondrial function and its prognostic role in sepsis: a literature review.","authors":"Wagner Nedel, Nathan Ryzewski Strogulski, Afonso Kopczynski, Luis Valmor Portela","doi":"10.1186/s40635-024-00694-9","DOIUrl":"https://doi.org/10.1186/s40635-024-00694-9","url":null,"abstract":"<p><p>Sepsis is characterized by a dysregulated and excessive systemic inflammatory response to infection, associated with vascular and metabolic abnormalities that ultimately lead to organ dysfunction. In immune cells, both non-oxidative and oxidative metabolic rates are closely linked to inflammatory responses. Mitochondria play a central role in supporting these cellular processes by utilizing metabolic substrates and synthesizing ATP through oxygen consumption. To meet fluctuating cellular demands, mitochondria must exhibit adaptive plasticity underlying bioenergetic capacity, biogenesis, fusion, and fission. Given their role as a hub for various cellular functions, mitochondrial alterations induced by sepsis may hold significant pathophysiological implications and impact on clinical outcomes. In patients, mitochondrial DNA concentration, protein expression levels, and bioenergetic profiles can be accessed via tissue biopsies or isolated peripheral blood cells. Clinically, monocytes and lymphocytes serve as promising matrices for evaluating mitochondrial function. These mononuclear cells are highly oxidative, mitochondria-rich, routinely monitored in blood, easy to collect and process, and show a clinical association with immune status. Hence, mitochondrial assessments in immune cells could serve as biomarkers for clinical recovery, immunometabolic status, and responsiveness to oxygen and vasopressor therapies in sepsis. These characteristics underscore mitochondrial parameters in both tissues and immune cells as practical tools for exploring underlying mechanisms and monitoring septic patients in intensive care settings. In this article, we examine pathophysiological aspects, key methods for measuring mitochondrial function, and prominent studies in this field.</p>","PeriodicalId":13750,"journal":{"name":"Intensive Care Medicine Experimental","volume":"12 1","pages":"107"},"PeriodicalIF":2.8,"publicationDate":"2024-11-25","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142710054","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Predictors of intradialytic hypotension in critically ill patients undergoing kidney replacement therapy: a systematic review.","authors":"Rafaella Maria C Lyrio, Etienne Macedo, Raghavan Murugan, Arnaldo A da Silva, Tess M Calcagno, Estevão F Sampaio, Rafael H Sassi, Rogério da Hora Passos","doi":"10.1186/s40635-024-00695-8","DOIUrl":"10.1186/s40635-024-00695-8","url":null,"abstract":"<p><strong>Background: </strong>This systematic review aims to identify predictors of intradialytic hypotension (IDH) in critically ill patients undergoing kidney replacement therapy (KRT) for acute kidney injury (AKI).</p><p><strong>Methods: </strong>A comprehensive search of PubMed was conducted from 2002 to April 2024. Studies included critically ill adults undergoing KRT for AKI, excluding pediatric patients, non-critically ill individuals, those with chronic kidney disease, and those not undergoing KRT. The primary outcome was identifying predictive tools for hypotensive episodes during KRT sessions.</p><p><strong>Results: </strong>The review analyzed data from 8 studies involving 2873 patients. Various machine learning models were assessed for their predictive accuracy. The Extreme Gradient Boosting Machine (XGB) model was the top performer with an area under the receiver operating characteristic curve (AUROC) of 0.828 (95% CI 0.796-0.861), closely followed by the deep neural network (DNN) with an AUROC of 0.822 (95% CI 0.789-0.856). All machine learning models outperformed other predictors. The SOCRATE score, which includes cardiovascular SOFA score, index capillary refill, and lactate level, had an AUROC of 0.79 (95% CI 0.69-0.89, p < 0.0001). Peripheral perfusion index (PPI) and heart rate variability (HRV) showed AUROCs of 0.721 (95% CI 0.547-0.857) and 0.761 (95% CI 0.59-0.887), respectively. Pulmonary vascular permeability index (PVPI) and mechanical ventilation also demonstrated significant diagnostic performance. A PVPI ≥ 1.6 at the onset of intermittent hemodialysis (IHD) sessions predicted IDH associated with preload dependence with a sensitivity of 91% (95% CI 59-100%) and specificity of 53% (95% CI 42-63%).</p><p><strong>Conclusion: </strong>This systematic review shows how combining predictive models with clinical indicators can forecast IDH in critically ill AKI patients undergoing KRT, with validation in diverse settings needed to improve accuracy and patient care strategies.</p>","PeriodicalId":13750,"journal":{"name":"Intensive Care Medicine Experimental","volume":"12 1","pages":"106"},"PeriodicalIF":2.8,"publicationDate":"2024-11-21","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11582124/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142681674","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Is passive leg raising clinically useful in predicting intradialytic hypotension?","authors":"Martin Ruste, Jean-Luc Fellahi, Matthias Jacquet-Lagrèze","doi":"10.1186/s40635-024-00683-y","DOIUrl":"10.1186/s40635-024-00683-y","url":null,"abstract":"","PeriodicalId":13750,"journal":{"name":"Intensive Care Medicine Experimental","volume":"12 1","pages":"105"},"PeriodicalIF":2.8,"publicationDate":"2024-11-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11576678/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142675799","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"The development of a C5.0 machine learning model in a limited data set to predict early mortality in patients with ARDS undergoing an initial session of prone positioning.","authors":"David M Hannon, Jaffar David Abbas Syed, Bairbre McNicholas, Michael Madden, John G Laffey","doi":"10.1186/s40635-024-00682-z","DOIUrl":"10.1186/s40635-024-00682-z","url":null,"abstract":"<p><strong>Background: </strong>Acute Respiratory Distress Syndrome (ARDS) has a high morbidity and mortality. One therapy that can decrease mortality is ventilation in the prone position (PP). Patients undergoing PP are amongst the sickest, and there is a need for early identification of patients at particularly high risk of death. These patients may benefit from an in-depth review of treatment or consideration of rescue therapies. We report the development of a machine learning model trained to predict early mortality in patients undergoing prone positioning as part of the management of their ARDS.</p><p><strong>Methods: </strong>Prospectively collected clinical data were analysed retrospectively from a single tertiary ICU. The records of patients who underwent an initial session of prone positioning whilst receiving invasive mechanical ventilation were identified (n = 131). The decision to perform prone positioning was based on the criteria in the PROSEVA study. A C5.0 classifier algorithm with adaptive boosting was trained on data gathered before, during, and after initial proning. Data was split between training (85% of data) and testing (15% of data). Hyperparameter tuning was achieved through a grid-search using a maximal entropy configuration. Predictions for 7-day mortality after initial proning session were made on the training and testing data.</p><p><strong>Results: </strong>The model demonstrated good performance in predicting 7-day mortality (AUROC: 0.89 training, 0.78 testing). Seven variables were used for prediction. Sensitivity was 0.80 and specificity was 0.67 on the testing data set. Patients predicted to survive had 13.3% mortality, while those predicted to die had 66.67% mortality. Among patients in whom the model predicted patient would survive to day 7 based on their response, mortality at day 7 was 13.3%. Conversely, if the model predicted the patient would not survive to day 7, mortality was 66.67%.</p><p><strong>Conclusions: </strong>This proof-of-concept study shows that with a limited data set, a C5.0 classifier can predict 7-day mortality from a number of variables, including the response to initial proning, and identify a cohort at significantly higher risk of death. This can help identify patients failing conventional therapies who may benefit from a thorough review of their management, including consideration of rescue treatments, such as extracorporeal membrane oxygenation. This study shows the potential of a machine learning model to identify ARDS patients at high risk of early mortality following PP. This information can guide clinicians in tailoring treatment strategies and considering rescue therapies. Further validation in larger cohorts is needed.</p>","PeriodicalId":13750,"journal":{"name":"Intensive Care Medicine Experimental","volume":"12 1","pages":"103"},"PeriodicalIF":2.8,"publicationDate":"2024-11-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11564488/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142619845","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Largely ignored-but pathogenetically significant: ambient temperature in rodent sepsis models.","authors":"Reinhard Bauer","doi":"10.1186/s40635-024-00693-w","DOIUrl":"10.1186/s40635-024-00693-w","url":null,"abstract":"","PeriodicalId":13750,"journal":{"name":"Intensive Care Medicine Experimental","volume":"12 1","pages":"104"},"PeriodicalIF":2.8,"publicationDate":"2024-11-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11564610/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142619843","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"A new method to predict return of spontaneous circulation by peripheral intravenous analysis during cardiopulmonary resuscitation: a rat model pilot study.","authors":"Claudius Balzer, Susan S Eagle, Franz J Baudenbacher, Matthias L Riess","doi":"10.1186/s40635-024-00679-8","DOIUrl":"10.1186/s40635-024-00679-8","url":null,"abstract":"<p><strong>Background: </strong>Enhancing venous return during cardiopulmonary resuscitation (CPR) can lead to better hemodynamics and improved outcome after cardiac arrest (CA). Peripheral Intravenous Analysis (PIVA) provides feedback on venous flow changes and may indicate an increase in venous return and cardiac output during CPR. We hypothesize PIVA can serve as an early indicator of increased venous return, preceding end-tidal CO₂ (etCO₂) increase, before the return of spontaneous circulation (ROSC) in a rat model of CA and CPR.</p><p><strong>Results: </strong>Eight male Wistar rats were intubated and ventilated, and etCO₂ was measured. Vessels were cannulated in the tail vein, femoral vein, femoral artery, and central venous and connected to pressure transducers. Ventilation was discontinued to achieve asphyxial CA. After 8 min, CPR began with ventilation, epinephrine, and automated chest compressions 200 times per minute until mean arterial pressure increased to 120 mmHg. Waveforms were recorded and analyzed. PIVA was calculated using a Fourier transformation of venous waveforms. Data are mean ± SE. Maximum PIVA values occurred in the tail vein 34.7 ± 2.9 s before ROSC, with subsequent PIVA peaks in femoral vein and centrally at 30.9 ± 5.4 and 25.1 ± 5.0 s, respectively. All PIVA peaks preceded etCO₂ increase (21.5 ± 3.2 s before ROSC).</p><p><strong>Conclusion: </strong>PIVA consistently detected venous pressure changes prior to changes in etCO₂. This suggests that PIVA has the potential to serve as an important indicator of venous return and cardiac output during CPR, and also as a predictor of ROSC.</p>","PeriodicalId":13750,"journal":{"name":"Intensive Care Medicine Experimental","volume":"12 1","pages":"102"},"PeriodicalIF":2.8,"publicationDate":"2024-11-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11557784/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142619841","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"The pressure gradient for venous return and its derivatives are ambiguous measures.","authors":"Jon-Emile S Kenny, Per Werner Moller","doi":"10.1186/s40635-024-00692-x","DOIUrl":"10.1186/s40635-024-00692-x","url":null,"abstract":"","PeriodicalId":13750,"journal":{"name":"Intensive Care Medicine Experimental","volume":"12 1","pages":"101"},"PeriodicalIF":2.8,"publicationDate":"2024-11-11","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11551081/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142619848","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Thermoregulation and survival during sepsis: insights from the cecal ligation and puncture experimental model.","authors":"Luis H A Costa, Isis P Trajano, Patricia Passaglia, Luiz G S Branco","doi":"10.1186/s40635-024-00687-8","DOIUrl":"10.1186/s40635-024-00687-8","url":null,"abstract":"<p><strong>Background: </strong>Sepsis remains a major global health concern due to its high prevalence and mortality. Changes in body temperature (Tb), such as hypothermia or fever, are diagnostic indicators and play a crucial role in the pathophysiology of sepsis. This study aims to characterize the thermoregulatory mechanisms during sepsis using the cecal ligation and puncture (CLP) model and explore how sepsis severity and ambient temperature (Ta) influence Tb regulation and mortality. Rats were subjected to mild or severe sepsis by CLP while housed at thermoneutral (28 °C) or subthermoneutral (22 °C) Ta, and their Tb was monitored for 12 h. Blood and hypothalamus were collected for cytokines and prostaglandin E₂ (PGE₂) analysis.</p><p><strong>Results: </strong>At 28 °C, febrile response magnitude correlated with sepsis severity and inflammatory response, with tail vasoconstriction as the primary heat retention mechanism. At 22 °C, Tb was maintained during mild sepsis but dropped during severe sepsis, linked to reduced UCP1 expression in brown adipose tissue and less effective vasoconstriction. Despite differences in thermoregulatory responses, both Ta conditions induced a persistent inflammatory response and increased hypothalamic PGE₂ production. Notably, mortality in severe sepsis was significantly higher at 28 °C (80%) compared to 22 °C (0%).</p><p><strong>Conclusions: </strong>Our findings reveal that ambient temperature and the inflammatory burden critically influence thermoregulation and survival during early sepsis. These results emphasize the importance of considering environmental factors in preclinical sepsis studies. Although rodents in experimental settings are often adapted to cold environments, these conditions may not fully translate to human sepsis, where cold adaptation is rare. Thus, researchers should carefully consider these variables when designing experiments and interpreting translational implications.</p>","PeriodicalId":13750,"journal":{"name":"Intensive Care Medicine Experimental","volume":"12 1","pages":"100"},"PeriodicalIF":2.8,"publicationDate":"2024-11-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11551088/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142619851","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Mitochondrial DNA in plasma and long-term physical recovery of critically ill patients: an observational study.","authors":"Maryory Galvis-Pedraza, Lise F E Beumeler, Elisabeth C van der Slikke, E Christiaan Boerma, Tim van Zutphen","doi":"10.1186/s40635-024-00690-z","DOIUrl":"10.1186/s40635-024-00690-z","url":null,"abstract":"<p><strong>Background: </strong>Post-intensive care syndrome (PICS) poses a notable public health concern, with survivors of critical illness experiencing long-term physical, psychological, and cognitive challenges. Mitochondrial dysfunction has gained attention for its potential involvement in PICS. However, the long-term impact of mitochondrial status on patient recovery remains uncertain. A single-centre retrospective analysis was conducted in Leeuwarden, the Netherlands, between May and November 2019, within a mixed ICU survivor cohort. Patients were assessed for mitochondrial markers (mtDNA damage represented by the presence of mtDNA fragmentation and mitochondrial DNA levels evaluated by the ratio of mtDNA and nuclear DNA), clinical factors, and long-term outcomes measured by the physical functioning (PF) domain of health-related quality of life.</p><p><strong>Results: </strong>A total of 43 patients were included in this study divided into recovery and non-recovery groups based on age-adjusted PF scores at 12 months post-ICU. Nineteen patients scored below these thresholds. No significant differences in mitochondrial markers between groups were identified. Furthermore, no significant correlations were found between mtDNA levels and mtDNA damage at baseline and 12 months with PF scores. However, mtDNA levels decreased over time in the recovery (p-value <  < 0.01) and non-recovery groups (p-value < 0.01).</p><p><strong>Conclusion: </strong>No significant correlation was found between mitochondrial markers and physical functioning scores. This study underscores the multifactorial nature of PICS and the need for a comprehensive understanding of its metabolic and cellular components. While mitochondrial markers may play a role in PICS, they operate within a framework influenced by various factors. This exploratory study serves as a foundation for future investigations aimed at developing targeted interventions to enhance the quality of life for ICU survivors grappling with PICS.</p>","PeriodicalId":13750,"journal":{"name":"Intensive Care Medicine Experimental","volume":"12 1","pages":"99"},"PeriodicalIF":2.8,"publicationDate":"2024-11-06","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11541963/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142590827","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}