Intensive Care Medicine Experimental最新文献

{"title":"Physiology, imaging and proteomics of non-ventilated vs. non-perfused lung injury: an experimental study.","authors":"Anna Damia, Ines Marongiu, Elena Spinelli, Francesco Damarco, Clarissa Uslenghi, Giovanni Lorenzo Rumi, Michele Battistin, Caterina Lonati, Alessandra Maria Storaci, Gianluca Lopez, Maria Rosaria De Filippo, Fabiana Madotto, Cristina Banfi, Alice Mallia, Lorenzo Rosso, Valentina Vaira, Tommaso Mauri","doi":"10.1186/s40635-025-00772-6","DOIUrl":"10.1186/s40635-025-00772-6","url":null,"abstract":"<p><strong>Background: </strong>The exclusion of one lung from ventilation or pulmonary artery perfusion triggers pathological mechanisms that can lead to lung injury. Although the final effect is similar for both insults, the underlying mechanisms may differ. Primary aim of this study was to compare severity of lung injury between non-ventilated (NVLI) and non-perfused (NPLI) lung injury. Secondary aims were to compare physiologic, imaging and proteomic signatures of NVLI vs NPLI.</p><p><strong>Methods: </strong>Sedated and paralyzed healthy female piglets (weight = 36 ± 5 kg) were mechanically ventilated for 24 h after left pulmonary artery ligation (NPLI group, n = 11) or exclusion from ventilation of the left lung (NVLI group, n = 10). Physiological data including electrical impedance tomography imaging of regional ventilation and perfusion were collected. Histological scoring was performed blindly as well as proteomic analysis of broncho-alveolar lavage (BAL) fluids and lung tissue samples at the end of the experiment.</p><p><strong>Results: </strong>The left lung of both groups received similarly low fraction (< 20%) of blood flow. The left side of the NPLI group was characterized by ventilation distributed only to the dead space and high ventilation/perfusion compartments, while the left lung of the NVLI group was characterized by perfusion only to the shunt compartment. The left lung of the NVLI group showed severe pulmonary vascular dysfunction (pulmonary vascular resistance > 2000 dyne/s/cm^-5), while the left lung of the NPLI group was ventilated with raising inspiratory stress (driving pressure > 20 cmH₂O at the end of the experiment and progressive decline in left lung compliance). The histologic lung injury score was higher for the left lung of the NVLI group compared to the left lung of the NPLI (left histological score: 10.3 ± 2.0 vs 6.4 ± 1.6, p < 0.0001), and pro-inflammatory alveolar cytokines were similarly more expressed in the left lung of the NVLI versus NPLI group (IL-1β: 418 ± 416 vs 53 ± 71, p < 0.001; IL-6: 406 ± 455 vs 99 ± 93, p = 0.036). Proteomic analysis showed signature specific for the two injuries, with two proteins, namely PRDX5 and DCTN1, being upregulated in NVLI left lung compared with the left NPLI lung. The right lung developed injury only in the NVLI group (right histological score: 5.5 ± 1.9 vs 3.0 ± 0.7, p < 0.001).</p><p><strong>Conclusions: </strong>Lung injury is more severe in terms of lung histological score in the collapsed lung of the NVLI group and involves also contralateral areas. At the mechanistic level, NVLI has specific physiologic mechanisms like vascular dysfunction and inflammation and presents unique proteomic profile in comparison to NPLI.</p>","PeriodicalId":13750,"journal":{"name":"Intensive Care Medicine Experimental","volume":"13 1","pages":"63"},"PeriodicalIF":2.8,"publicationDate":"2025-06-23","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12185848/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144475111","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":"Left ventricular systolic longitudinal strain in mechanically ventilated patients in the intensive care unit: assessment of global and chamber reproducibility.","authors":"Matías Pécora, Piero Pastorini, Roberto Farolini, Gastón Burghi, F Javier Hurtado","doi":"10.1186/s40635-025-00770-8","DOIUrl":"10.1186/s40635-025-00770-8","url":null,"abstract":"<p><strong>Introduction: </strong>In the intensive care unit (ICU), left ventricular systolic function is traditionally assessed by measuring the left ventricular ejection fraction (LVEF). Recently, left ventricular global systolic longitudinal strain (SL-S) has emerged as a more sensitive marker of myocardial function in this setting. However, obtaining high-quality echocardiographic images remains a significant challenge, particularly in patients undergoing invasive mechanical ventilation (IMV), and data on the feasibility and reproducibility of these measurements in critically ill patients are limited.</p><p><strong>Objective: </strong>To assess the feasibility and reproducibility (both global and per chamber) of SL-S and LVEF (both manual and automatic) in ICU patients under IMV.</p><p><strong>Materials and methods: </strong>Thirty ICU patients receiving IMV were randomly selected. The feasibility and reproducibility of SL-S (global and per chamber) and LVEF were assessed using both manual and automatic methods. The analysis was performed using the intraclass correlation coefficient (ICC) with its 95% confidence interval (CI), and Bland-Altman analysis (BA), which reported the mean difference and limits of agreement (lower-upper limits of agreement).</p><p><strong>Results: </strong>SL-S was feasible in 70% of patients and demonstrated excellent intra- and interobserver reproducibility for both manual and automatic methods. Intraobserver reproducibility for automatic SL-S: ICC 0.97 (CI: 0.94-0.99), BA 0.26 (-1.89 to 2.40) and interobserver reproducibility: ICC 0.96 (CI: 0.92-0.98), and BA 0.53 (-2.41 to 3.47). The reproducibility of manual SL-S was comparable to automatic measurements. Additionally, the reproducibility per chamber was excellent. LVEF was feasible in 80% of patients. Manual LVEF (Simpson's biplane) reproducibility demonstrated good reproducibility: intraobserver ICC: 0.82 (CI: 0.48-0.93), BA -5.00 (-19.70 to 9.70); interobserver ICC 0.78 (CI: 0.55-0.91), BA 7.50 (-5.40 to 20.40). Automatic LVEF (auto-LVEF) demonstrated excellent reproducibility: intraobserver ICC: 0.94 (CI: 0.86-0.98), BA -0.95 (-10.02 to 8.13); and interobserver ICC: 0.94 (CI: 0.87-0.97), BA 1.75 (-6.38 to 10.33).</p><p><strong>Conclusion: </strong>SL-S (global and per chamber) and auto-LVEF were feasible and showed excellent reproducibility. LVEF demonstrated the highest feasibility, while SL-S exhibited the greatest reproducibility. These parameters may represent a useful tool in the evaluation of LV function in ICU patients under IMV.</p>","PeriodicalId":13750,"journal":{"name":"Intensive Care Medicine Experimental","volume":"13 1","pages":"62"},"PeriodicalIF":2.8,"publicationDate":"2025-06-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12173981/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144316853","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":"Advancing omics technologies in acute respiratory distress syndrome: paving the way for personalized medicine.","authors":"Lou'i Al-Husinat, Mohammad Araydah, Sarah Al Sharie, Saif Azzam, Denise Battaglini, Arqam Alrababah, Rana Haddad, Khaled Al-Asad, Claudia C Dos Santos, Marcus J Schultz, Fernanda F Cruz, Pedro L Silva, Patricia R M Rocco","doi":"10.1186/s40635-025-00766-4","DOIUrl":"10.1186/s40635-025-00766-4","url":null,"abstract":"<p><p>Despite advances in critical care, acute respiratory distress syndrome (ARDS) remains a potentially life-threatening condition with high mortality. The heterogeneous nature of ARDS, caused by diverse etiologies, poses considerable challenges to accurate diagnosis, treatment, and prognosis. Conventional methods often fail to elucidate the pathophysiology of ARDS, thus limiting therapeutic efficacy. However, recent advances in omics technologies, including genomics, transcriptomics, proteomics, metabolomics, lipidomics, and epigenomics, have provided deeper insights into ARDS mechanisms. Genomic studies have identified genetic variants associated with ARDS susceptibility, such as polymorphisms in genes encoding angiotensin-converting enzyme, surfactant proteins, toll-like receptor 4, interleukin-6, Fas/FasL, and vascular endothelial growth factor, offering potential therapeutic targets. Transcriptomic and proteomic reveal distinct biomarker profiles associated with ARDS pathogenesis, including dysregulated inflammatory signaling, epithelial and endothelial barrier dysfunction, and compromised immune responses. Metabolomics has highlighted biomarkers, such as phenylalanine and choline, aiding in severity assessment, subphenotype stratification, and treatment response prediction. Lipidomics has uncovered disruptions in lipid metabolism, including altered phospholipids, sphingolipids, and eicosanoids, with key lipid species such as lysophosphatidylcholine and ceramide emerging as biomarkers for severity and outcomes. Epigenomics explores DNA methylation, histone modifications, and non-coding RNAs, revealing their role in regulating inflammation, immune responses, and tissue repair in ARDS. These epigenetic changes hold promise for biomarker discovery and personalized therapy. Integrating these omics technologies advances our understanding of ARDS pathophysiology, enabling precision medicine approaches. This review examines the latest advancements in omics research related to ARDS, emphasizing its role in developing personalized diagnostics and therapeutic strategies to improve disease monitoring, prognosis, and treatment outcomes.</p>","PeriodicalId":13750,"journal":{"name":"Intensive Care Medicine Experimental","volume":"13 1","pages":"61"},"PeriodicalIF":2.8,"publicationDate":"2025-06-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12165931/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144283796","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":"Prediction of lung overdistension during mechanical ventilation using micro-RNA and gene expression.","authors":"Cecilia López-Martínez, Paula Martín-Vicente, Laura Amado-Rodríguez, Inés López-Alonso, Margarita Fernández-Rodríguez, Adrián González-López, Pablo Martínez-Camblor, Juan Gómez, Andrew J Boyle, Cecilia M O'Kane, Daniel F McAuley, James N Tsoporis, Claudia Dos Santos, Guillermo M Albaiceta","doi":"10.1186/s40635-025-00768-2","DOIUrl":"10.1186/s40635-025-00768-2","url":null,"abstract":"<p><strong>Background: </strong>Overstretching of lung parenchyma may lead to injury, especially during mechanical ventilation. To date, there are no specific biomarkers of lung stretch, but transcriptomic signatures have not been explored. Our objective was to identify stretch-specific signatures using micro-RNA and gene expression.</p><p><strong>Methods: </strong>Data on micro-RNA and RNA expression in response to stretch in experimental models were systematically pooled. Signatures were identified as those micro-RNAs or genes with differential expression in samples from stretched cells or tissues, and optimized using a greedy algorithm. Expression data was used to calculate transcriptomic scores. The accuracy of these scores was validated in animal models of lung injury, ex vivo mechanically ventilated human lungs, and bronchoalveolar lavage fluid (BALF, n = 7) and in serum samples (n = 31) of mechanically ventilated patients.</p><p><strong>Results: </strong>Six micro-RNAs (mir-383, mir-877, mir-130b; mir-146b, mir-181b, and mir-26b) were differentially expressed in stretched cell cultures (n = 24). Amongst the genes regulated by these micro-RNAs, a 451-gene signature was identified in vitro (n = 106) and refined using data from animal models (n = 143) to obtain a 6-gene signature (Lims1, Atp6v1c1, Dedd, Bclb7, Ppp1r2 and F3). Transcriptomic scores were significantly higher in samples submitted to stretch or injurious mechanical ventilation. The microRNA and RNA signatures were validated in human tissue, BALF and serum, with areas under the ROC curve between 0.7 and 1 to identify lung overdistention.</p><p><strong>Conclusions: </strong>Lung cell stretch induces the expression of specific micro-RNA and genes. The potential of these signatures to identify lung stretch in a clinical setting must be explored.</p>","PeriodicalId":13750,"journal":{"name":"Intensive Care Medicine Experimental","volume":"13 1","pages":"60"},"PeriodicalIF":2.8,"publicationDate":"2025-06-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12145361/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144247752","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":"Intensive care infection score: ICIS discriminates between infected and uninfected critically ill patients in routine intensive care unit practice.","authors":"Emre Deniz, Stefanie Klatte, Nilgün Tekin-Bubenheim, Mathias Zimmermann","doi":"10.1186/s40635-025-00767-3","DOIUrl":"10.1186/s40635-025-00767-3","url":null,"abstract":"<p><strong>Background: </strong>Diagnosis of infectious inflammation is challenging as acute phase protein expression is nonspecific, limiting the utility of well-established biomarkers, such as procalcitonin (PCT) and C-reactive protein (CRP). The emergent blood cell-derived Intensive Care Infection Score (ICIS) is an innovative approach for the sensitive and specific diagnosis of infection in intensive care unit (ICU) patients. This study aimed to confirm the suitability of routine ICIS use in various ICU settings.</p><p><strong>Methods: </strong>This retrospective study included 115 patients from three ICUs. Seventy-five patients were diagnosed as infected and 40 as uninfected. ICIS, CRP, and PCT were compared to routine clinical assessment to evaluate their effectiveness in predicting infection in critically ill patients.</p><p><strong>Results: </strong>ICIS was superior to CRP and PCT in discriminating infection from no infection on day 1 in the ICU. In receiver operating characteristic curve analysis, ICIS exhibited an AUC = 0.984, sensitivity of 90.7%, specificity of 97.5%, positive predictive value (PPV) of 97.7% and negative predictive value (NPV) of 89.9%, by the best cutoff value of 3. CRP gave an AUC = 0.727, PPV of 70.0% and NPV of 67.8% by best cutoff value of 8.3 mg/L with a sensitivity of 74.7% and specificity of 62.5%. The best cutoff value of 0.9 ng/mL was calculated for PCT with an AUC = 0.812, PPV of 84.4%, NPV of 70.3%, sensitivity of 69.3% and specificity of 85.0%.</p><p><strong>Conclusions: </strong>ICIS outperformed CRP and PCT in identifying infection in critically ill patients across different ICU settings on the first day in the ICU. The high NPV emphasizes the potential of ICIS as an adjuvant tool to rule out infections thereby facilitating the reduction of antibiotic overuse and consequently limiting antimicrobial resistance (AMR) development. ICIS appears suitable for routine implementation in various ICU settings.</p>","PeriodicalId":13750,"journal":{"name":"Intensive Care Medicine Experimental","volume":"13 1","pages":"58"},"PeriodicalIF":2.8,"publicationDate":"2025-06-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12141177/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144225387","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":"Sub-phenotyping in critical care: a valuable strategy or methodologically fragile path?","authors":"Jim M Smit, Annemijn H Jonkman, Jesse H Krijthe","doi":"10.1186/s40635-025-00769-1","DOIUrl":"10.1186/s40635-025-00769-1","url":null,"abstract":"","PeriodicalId":13750,"journal":{"name":"Intensive Care Medicine Experimental","volume":"13 1","pages":"59"},"PeriodicalIF":2.8,"publicationDate":"2025-06-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12141183/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144234012","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":"In vitro and in vivo muscle mass and strength during the first week of critical illness.","authors":"Wout J Claassen, Isabel M van Ruijven, Marloes van den Berg, Rianne J Baelde, Alexcia Fortes Monteiro, Rajvi M N Balesar, Sylvia W Hania, Donald L van der Peet, Peter J M Weijs, Coen A C Ottenheijm, Sandra N Stapel","doi":"10.1186/s40635-025-00755-7","DOIUrl":"10.1186/s40635-025-00755-7","url":null,"abstract":"<p><strong>Background: </strong>Loss of muscle mass and strength is provoked by critical illness. Our primary aim was to study the development of muscle atrophy and weakness in vitro in isolated myofibers and in vivo muscle mass and in vitro muscle strength during the first week of critical illness. Furthermore, we explored how in vitro muscle strength compares to healthy controls. Finally, we studied correlations between in vitro muscle mass and strength and in vivo muscle mass in critically ill patients.</p><p><strong>Methods: </strong>We performed a secondary analysis using data from a randomized controlled trial. We studied contractile force of single myofibers isolated from muscle biopsies around admission (day 1-3) and around 1 week after inclusion (day 8-10). Furthermore, we studied myofiber cross-sectional area (CSA), proportion of fast-twitch myofibers, bio-electrical impedance analysis-derived fat-free mass index (FFMI), ultrasound-derived quadriceps muscle layer thickness (QMLT) and diaphragm thickness. In the control group, only contractile force outcomes were available.</p><p><strong>Results: </strong>In total, ten ICU patients had two muscle biopsies taken. Maximum force of both fast and slow-twitch myofibers was reduced at day 8-10 compared to day 1-3, even though there were no differences in normalized force and calcium sensitivity. FFM and QMLT did not change over time, nor were there differences between groups. Compared to healthy controls, maximum force of myofibers was lower in the ICU group at day 8-10 in both slow and fast-twitch myofibers, while the calcium sensitivity of force was lower in slow-twitch myofibers. We found a significant correlation between myofiber CSA vs. FFMI (r = 0.68) and maximum force of the fast-twitch fibers vs. QMLT (r = 0.72).</p><p><strong>Conclusions: </strong>During the first week of critical illness, maximum force declined over time, while no other in vitro parameters changed. We found a moderate correlation between myofiber CSA vs. FFMI and maximum force of the fast-twitch fibers vs. QMLT.</p>","PeriodicalId":13750,"journal":{"name":"Intensive Care Medicine Experimental","volume":"13 1","pages":"57"},"PeriodicalIF":2.8,"publicationDate":"2025-06-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12133653/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144215741","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":"Explainable machine learning models for mortality prediction in patients with sepsis in tertiary care hospital ICU in low- to middle-income countries.","authors":"Saumya Diwan, Vinay Gandhi, Esha Baidya Kayal, Puneet Khanna, Amit Mehndiratta","doi":"10.1186/s40635-025-00765-5","DOIUrl":"10.1186/s40635-025-00765-5","url":null,"abstract":"<p><strong>Introduction: </strong>Mortality in sepsis patients remains a challenging condition due to its complex nature. It is an even more prevalent health problem in low- and middle-income countries demanding costly treatment and management. This study proposes an explainable artificial intelligence-based approach towards mortality prediction for patients with sepsis admitted to intensive care unit (ICU).</p><p><strong>Methods: </strong>A total of 500 patients (N = 500, male: female = 262:238, age = 45.96 ± 20.92 years) with sepsis were analyzed retrospectively. We utilize SHapley Additive exPlanations (SHAP) method to gain insights into the preliminary model's learnings regarding the wide array of demographic, clinical, radiological, and laboratory features. The clinical insights were used for feature selection to fetch the top t = 80% feature spread as well as to derive empirical findings from feature dependence plots which could find application in periphery hospital settings. Four machine learning algorithms, Random Forest, XGBoost, Extra Trees and Gradient Boosting classifiers were trained for the binary classification task (discharge from ICU and death in ICU) with the selected influential feature set.</p><p><strong>Results: </strong>The Extra Trees Classifier showed the best overall performance with AUROC score: 0.87 (95% CI 0.80-0.93), Accuracy: 0.79 (95% CI 0.71-0.86), F1 score: 0.78 (95% CI 0.69-0.86), Precision: 0.88 (95% CI 0.78-0.98) and Recall: 0.70 (95% CI 0.57-0.82). All four models perform significantly well on dataset with AUROC scores ranging from 0.81 (CI 0.73-0.89) to 0.87 (CI 0.80-0.93) and F1 scores ranging 0.74 (CI 0.64-0.83) to 0.78 (CI 0.69-0.86) on the hold-out test set and were stable over fivefold cross-validation prior to testing.</p><p><strong>Conclusions: </strong>The proposed approach could provide preemptive estimations into prognostication and outcome prediction of patients with sepsis in low-resource settings. This will aid in clinical decision-making, resource allocation and research for new treatment modalities.</p>","PeriodicalId":13750,"journal":{"name":"Intensive Care Medicine Experimental","volume":"13 1","pages":"56"},"PeriodicalIF":2.8,"publicationDate":"2025-06-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12133658/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144208504","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":"Determination of pK_A of nonvolatile weak acids in plasma of healthy volunteers and critically ill patients.","authors":"Martin Krbec, Serena Brusatori, Petr Waldauf, Alberto Zanella, Francesco Zadek, Victor van Bochove, František Duška, Thomas Langer, Paul Elbers","doi":"10.1186/s40635-025-00762-8","DOIUrl":"10.1186/s40635-025-00762-8","url":null,"abstract":"<p><strong>Background: </strong>The dissociation constant of nonvolatile weak acids in plasma (K_A), expressed as pK_A, is essential for electroneutrality-based acid-base analysis. To date, its normal value in human plasma has been determined in only one study involving eight healthy volunteers. We hypothesized that pK_A would differ in ICU patients, whose plasma protein composition is altered by disease and medication, and that changes in protein charge-rather than undetected strong acids-could account for the unexplained anions observed in sepsis.</p><p><strong>Methods: </strong>Using CO₂ tonometry, we determined pK_A and total weak nonvolatile acids (A_TOT) in plasma from 30 healthy volunteers and two ICU cohorts (27 postoperative and 30 septic patients). Additionally, we calculated the strong ion gap in plasma and protein-free serum filtrates from 10 healthy volunteers and 20 septic patients.</p><p><strong>Results: </strong>In healthy volunteers, pK_A was 7.55 ± 0.16 (K_A = 2.8 × 10⁻⁸) and A_TOT was 15.9 ± 3.0 mmol/L (0.222 ± 0.043 mmol/g of TP). In postoperative and septic patients, A_TOT was significantly reduced (10.1 ± 5.4 and 11.9 ± 4.0 mmol/L, p < 0.001), but pK_A and A_TOT/TP remained unchanged, yielding an average pK_A of 7.55 ± 0.35 (K_A = 2.8 × 10⁻⁸) and A_TOT/TP of 0.230 ± 0.097 mmol/g. We found elevated strong ion gap in both plasma and protein-free filtrates of septic patients, which confirms the presence of unmeasured low-molecular-weight anions.</p><p><strong>Conclusion: </strong>Our findings confirm stable pK_A and A_TOT/TP values in human plasma in both health and disease, supporting the Staempfli-Constable model for clinical acid-base diagnostics. Unexplained anions in sepsis are attributed to low molecular weight strong ions rather than alterations in plasma protein dissociation.</p>","PeriodicalId":13750,"journal":{"name":"Intensive Care Medicine Experimental","volume":"13 1","pages":"54"},"PeriodicalIF":2.8,"publicationDate":"2025-06-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12130371/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144199021","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":"Accelerometer-based vibration analysis and oxygenator thrombosis in venovenous ECMO: an experimental porcine model.","authors":"Lars Prag Antonsen, Svein Aslak Landsverk, Per Steinar Halvorsen, Amrit Thiara, Didrik Lilja, Naimahmed Nesaragi, Andreas Espinoza","doi":"10.1186/s40635-025-00763-7","DOIUrl":"10.1186/s40635-025-00763-7","url":null,"abstract":"<p><strong>Background: </strong>Oxygenator thrombosis is a potentially life-threatening complication during venovenous extracorporeal membrane oxygenation (VV ECMO). It can cause blood flow obstruction, impaired gas exchange, hematologic abnormalities, or sudden ECMO flow cessation. Early detection and timely circuit exchange is critical yet challenging. Acute clot formation necessitates immediate circuit replacement, while premature replacement risks unnecessary procedural harm and increased costs. No reliable method exists to detect early oxygenator thrombosis. Strategies include visual inspection, monitoring the pressure difference across the oxygenator (ΔP_oxy), gas exchange evaluation, and blood tests. In the present animal study, we aimed to evaluate the feasibility of accelerometer-based vibration analysis as a real-time and non-invasive method for detecting oxygenator thrombosis during VV ECMO. We hypothesized that accelerometer signals would change concurrently with or precede increases in ΔP_oxy.</p><p><strong>Methods: </strong>The study was performed on anesthetized and mechanically ventilated pigs (n = 7) on VV ECMO. Hemodynamic parameters, ECMO circuit pressures, and signals from an accelerometer attached to the ECMO oxygenator were continuously recorded at different pump speeds, and after anticoagulation reversal to promote thrombosis within the ECMO oxygenator.</p><p><strong>Results: </strong>The primary finding of this study was a significant increase in the accelerometer signal's Root Mean Squared (RMS_oxy) 15 min after anticoagulation reversal, with no rpm adjustment and without corresponding changes in ΔP_oxy. Variations in RMS_oxy associated with high ECMO pump speed and circuit flow were discernible from those observed following anticoagulation reversal.</p><p><strong>Conclusion: </strong>The present animal study demonstrates the feasibility of accelerometer-based vibration analysis as a real-time and non-invasive method for detecting vibrations associated with reversal of anticoagulation and potential oxygenator thrombosis during VV ECMO.</p>","PeriodicalId":13750,"journal":{"name":"Intensive Care Medicine Experimental","volume":"13 1","pages":"55"},"PeriodicalIF":2.8,"publicationDate":"2025-06-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12130417/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144208503","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}