Intensive Care Medicine Experimental最新文献

{"title":"Pancreatic stone protein versus conventional biomarkers for prognostic discrimination in sepsis: a meta-analysis of paired AUC comparisons.","authors":"Gabriele Melegari, Valerio Valente, Federica Arturi, Ilaria Pacini, Eros Pilia, Alessandro Belletti, Andrea Tognù, Elisabetta Bertellini, Alberto Barbieri","doi":"10.1186/s40635-026-00990-6","DOIUrl":"10.1186/s40635-026-00990-6","url":null,"abstract":"<p><strong>Background: </strong>Pancreatic stone protein (PSP) has been proposed as a prognostic biomarker in sepsis, but its comparative performance versus C-reactive protein (CRP) and procalcitonin (PCT) remains uncertain.</p><p><strong>Methods: </strong>We performed a meta-analysis of direct within-study paired AUC comparisons between PSP and CRP and/or PCT in critically ill adults with sepsis, septic shock, or acute infection-related conditions in whom sepsis development or clinically relevant adverse outcomes were prospectively evaluated. Differences in AUC (ΔAUC) were pooled using random-effects models. The principal conservative analysis included one comparison per independent cohort and comparator.</p><p><strong>Results: </strong>Seven studies comprising 803 unique participants contributed 21 paired comparisons. In the principal conservative analysis, PSP showed a higher prognostic AUC than CRP, with a pooled ΔAUC of 0.179 (95% CI 0.095-0.262; p < 0.001), although between-cohort heterogeneity was substantial (I² = 81.65%). Compared with PCT, the pooled ΔAUC was 0.153 (95% CI 0.114-0.193; p < 0.001), with no observed heterogeneity (I² = 0.00%). The mortality-only sensitivity analysis showed a similar pooled effect for PSP versus CRP (ΔAUC 0.17, 95% CI 0.08-0.26), with substantial heterogeneity persisting, and for PSP versus PCT (ΔAUC 0.153, 95% CI 0.114-0.193), with no observed heterogeneity. Exclusion of the clinically distinct intra-abdominal infection cohort (Michailides et al.) likewise did not materially change the PSP-versus CRP estimate (ΔAUC 0.166, 95% CI 0.077-0.256). The direction and approximate magnitude of the pooled effects were also preserved across alternative assumptions for the within-study correlation.</p><p><strong>Conclusions: </strong>Available comparative evidence suggests that PSP may have greater prognostic discrimination than CRP and PCT. The findings were broadly maintained across sensitivity analyses, but the limited number of independent cohorts and substantial heterogeneity in the CRP comparison warrant caution. Further prospective studies are required to confirm these findings and establish their clinical relevance.</p><p><strong>Trial registration: </strong>This systematic review was prospectively registered in the International Prospective Register of Systematic Reviews (PROSPERO; CRD420261340301).</p>","PeriodicalId":13750,"journal":{"name":"Intensive Care Medicine Experimental","volume":"14 1","pages":""},"PeriodicalIF":2.9,"publicationDate":"2026-10-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13683286/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149227402","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":"Mechanical ventilation-associated AKI: toward a multimodal and kidney-protective ventilatory framework.","authors":"Ying Gao, Yipeng Fang, Silvia De Rosa, Michele Salvagno, Lina Zhao, Keliang Xie, Fabio Silvio Taccone","doi":"10.1186/s40635-026-00979-1","DOIUrl":"10.1186/s40635-026-00979-1","url":null,"abstract":"<p><p>Mechanical ventilation-associated acute kidney injury (AKI) represents a complex manifestation of lung-kidney cross-talk driven by hemodynamic alterations, neurohumoral activation, systemic inflammation and disturbances in gas exchange and acid-base homeostasis. Beyond static ventilatory settings, increasing evidence suggests that dynamic fluctuations in airway and perfusion parameters, including static driving pressure (ΔP), positive end-expiratory pressure (PEEP), mean airway pressure (P_mean), and effective renal perfusion pressure (eRPP) may substantially influence renal vulnerability during mechanical ventilation. This comprehensive narrative review synthesizes current mechanistic and clinical evidence on the relationship between mechanical ventilation and AKI and proposes an integrated framework for future research on the interplay between ventilatory stress, venous congestion, renal perfusion, and inflammatory injury. Emerging bedside tools such as renal Doppler indices, venous excess ultrasound score (VExUS), and kidney injury biomarkers are discussed as components of an integrated physiologic approach for early recognition and risk stratification of ventilator-associated AKI. We further propose a multimodal conceptual framework integrating respiratory mechanics, congestion assessment, perfusion monitoring, and biomarkers to support individualized kidney-protective ventilation strategies. Future research should prioritize standardized physiologic monitoring, time-varying exposure analyses, causal mediation approaches, and prospective multicenter studies to better define renal-protective ventilatory targets and advance precision critical care.</p>","PeriodicalId":13750,"journal":{"name":"Intensive Care Medicine Experimental","volume":"14 1","pages":""},"PeriodicalIF":2.9,"publicationDate":"2026-10-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13675160/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149206957","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":"Esophageal resonance Raman spectroscopy tracks mixed venous oxygenation in experimental shock and hypoxemia.","authors":"Tysen DeWaard, Bonne L Keijer, Franklin Ducatez, Cassidy Ferron, Jason Zhang, Yifeng Peng, Padraic Romfh, John N Kheir","doi":"10.1186/s40635-026-00989-z","DOIUrl":"10.1186/s40635-026-00989-z","url":null,"abstract":"<p><strong>Introduction: </strong>Mixed venous oxygen saturation (SvO₂) reflects the balance between systemic oxygen delivery and consumption and is widely used as an indicator of tissue oxygenation in critically ill patients. However, its measurement requires invasive venous access. We evaluated whether a customized probe applied to the esophageal mucosa could provide a continuous measurement of regional capillary hemoglobin oxygen saturation (S_EsO₂) that tracks changes in mixed venous oxygen saturation for early detection of experimental shock with minimal invasiveness.</p><p><strong>Methods: </strong>A miniaturized 405 nm resonance Raman spectroscopy (RRS) probe was developed to quantify esophageal regional capillary hemoglobin saturation (S_EsO₂) based on spectral decomposition of oxy- and deoxy-hemoglobin Raman peaks. Two rat models were investigated: progressive hemorrhage (n = 12) and graded hypoxia (n = 9). At each stage, SvO₂, S_EsO₂, arterial oxygen saturation (SaO₂), and serum lactate were measured. Tracking ability and diagnostic accuracy compared to SvO₂ and transabdominal near-infrared spectroscopy (NIRS) were evaluated using linear mixed-effects models (animal random intercepts), (cluster-bootstrapped) receiver operating characteristic curve (ROC) analyses, and Pearson correlation.</p><p><strong>Results: </strong>In both models, baseline S_EsO₂ was ~20% higher than SvO₂, consistent with a regional capillary measurement distinct from mixed venous blood. In hemorrhage, LME showed S_EsO₂ was positively associated with SvO₂ (β = 0.53, 95% CI 0.43-0.62; p < 0.0001) and inversely associated with lactate (β = -0.15, 95% CI -0.18 to -0.12; p < 0.0001). In ROC analysis, S_EsO₂ discriminated SvO₂ < 40% with AUC 0.98 (95% CI 0.95-1.00). For transabdominal NIRS, the AUC was 0.82 (95% CI 0.70-0.95). During graded hypoxia, S_EsO₂ was also positively associated with SvO₂ (β = 0.51, 95% CI 0.43-0.60; p < 0.0001) and inversely associated with lactate (β = -0.11, 95% CI -0.13 to -0.09; p < 0.0001). Discrimination of S_EsO₂ for SvO₂ < 40% was AUC 0.92 (95% CI 0.82-1.00). Transabdominal NIRS demonstrated discrimination with high uncertainty (AUC 0.56, 95% CI 0.23-1.00).</p><p><strong>Conclusions: </strong>Esophageal RRS enables molecularly specific measurement of regional capillary hemoglobin oxygen saturation and thereby tracks SvO₂ across distinct experimental shock paradigms. These preclinical findings support further investigation of esophageal RRS as a potential minimally invasive monitoring approach for detection of systemic oxygen imbalance.</p>","PeriodicalId":13750,"journal":{"name":"Intensive Care Medicine Experimental","volume":"14 1","pages":""},"PeriodicalIF":2.9,"publicationDate":"2026-10-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13672757/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149193243","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 impact of intraoperative hemoadsorption during cardiac surgery for infective endocarditis.","authors":"Amin Serradj, Gabriel Saiydoun, Costin Radu, Eric Bergoend, Antonio Fiore, Raphaelle Huguet, Pascal Lim, Cyrus Moini, Thierry Folliguet","doi":"10.1186/s40635-026-00988-0","DOIUrl":"10.1186/s40635-026-00988-0","url":null,"abstract":"<p><strong>Background: </strong>Postoperative sepsis and/or systemic inflammatory response syndrome caused by infective endocarditis (IE) can lead to significant postoperative mortality. Intraoperative hemoadsorption therapy has shown promising results in the treatment of sepsis and dysregulated inflammatory response during cardiac surgery. The aim of this study was to evaluate the effects of intraoperative hemoadsorption in high-risk patients with IE undergoing cardiac surgery.</p><p><strong>Methods: </strong>A total of 176 high-risk patients with IE were enrolled from 10/2020 to 10/2024. Patients with intraoperative hemoadsorption (HA group, n = 93) were compared to patients without hemoadsorption (control, n = 83). The primary endpoint was a composite of 30-day mortality, incidence of vasoplegic syndrome within the first 24 h and 7 days postoperatively, and intensive care (ICU) stay, analyzed using an unmatched hierarchical win-ratio method.</p><p><strong>Results: </strong>There were no differences in baseline characteristics between the groups. The mean hemoadsorption time was 106 ± 61 min in the HA group. Vasoplegic syndrome was more frequent in the control group (49.4% vs. 24.7%, p < 0.001). Importantly, 30-day mortality was also significantly lower with intraoperative hemoadsorption (7.5% vs. 20.5%, p = 0.003). The mean ICU stay was shorter in the HA group (7.8 ± 4.6 vs. 11.5 ± 4.2 days, p < 0.001). The analysis met the primary endpoint in favor of patients receiving intraoperative hemoadsorption (win ratio 3.83; 95% CI 2.55, 5.74; p < 0.001).</p><p><strong>Conclusions: </strong>In high-risk cardiac surgery patients with IE, the intraoperative use of hemoadsorption was associated with a significantly lower incidence of postoperative vasoplegic syndrome and lower overall 30-day mortality. These findings should be interpreted in the context of the study's methodological limitations and confirmed in future randomized controlled trials.</p><p><strong>Trial registration: </strong>This study was approved by the Institutional Review Board (IRB00012919) of the French Society of Thoracic and Cardiovascular Surgery (CERCSFCTCV20251021).</p>","PeriodicalId":13750,"journal":{"name":"Intensive Care Medicine Experimental","volume":"14 1","pages":""},"PeriodicalIF":2.9,"publicationDate":"2026-10-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13669272/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149181667","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":"Bioactive adrenomedullin dynamics and microcirculatory changes in a porcine model of hemorrhagic shock.","authors":"Carolin Vekla, Oliver Hartmann, Sebastian O Decker, Maik von der Forst, Florian Uhle, Alexander Studier-Fischer, Berkin Özdemir, Felix Nickel, Stephan Katzenschlager, Frank Weilbacher, Thorsten Brenner, Erik Popp, Markus A Weigand, Karsten Schmidt, Maximilian Dietrich, Daniel Gruneberg","doi":"10.1186/s40635-026-00976-4","DOIUrl":"10.1186/s40635-026-00976-4","url":null,"abstract":"<p><strong>Background: </strong>Hemorrhagic shock is a leading cause of preventable trauma death, marked by impaired oxygen delivery and endothelial dysfunction. Bioactive adrenomedullin (bio-ADM) regulates endothelial barrier integrity, but its dynamics during hemorrhagic shock and resuscitation remain unclear. This secondary analysis of a porcine hemorrhagic shock model investigated bio-ADM and its association with macro- and microcirculatory parameters during resuscitation. All animals received crystalloid infusion (10 mL/kg/h) from anesthesia induction onward. Shock was induced by blood withdrawal to maintain MAP at 40 ± 5 mmHg for 60 min (T5), before randomization to control (n = 7), fluid (n = 6), or noradrenaline (n = 7) groups, with intervention groups titrated to MAP targets of 65 then 90 mmHg (60 min each). Macrocirculation was assessed via vital signs and pulse contour analysis; microcirculation via hyperspectral imaging (tissue oxygenation, hemoglobin, water index).</p><p><strong>Results: </strong>Fluid resuscitation improved macrohemodynamics and microcirculatory oxygenation versus control and noradrenaline, which failed to sustain perfusion and impaired microcirculatory oxygenation. Bio-ADM increased after shock induction (p < 0.001), peaking at T9 (120 min of therapy). At T5, levels were comparable among control (16.8 [13.6-18.9] pg/ml), fluid (15.65 [15.43-16.55] pg/ml), and noradrenaline (14.3 [7.85-18.95] pg/ml). Thereafter, bio-ADM continued to rise in control (19.7 [17.4-32.6] pg/ml) and noradrenaline (21.2 [14.4-33.45] pg/ml), while stabilizing in the fluid group (12.05 [10.65-15.18] pg/ml); accordingly, the T5-T9 increase was smaller in the fluid group than in control (p = 0.022) or noradrenaline (p = 0.003). The fluid group received ~3-fold more fluid by T9. Higher bio-ADM correlated with lower MAP, higher lactate, and lower ScvO₂, but not oxygen delivery (DO₂); a higher tissue water index correlated with a smaller rise.</p><p><strong>Conclusions: </strong>Bio-ADM increased during hemorrhagic shock, extending previous observations from cardiogenic and septic shock, and represents a comparatively non-specific marker of endothelial and microcirculatory stress rather than specific to any single shock etiology. Effective resuscitation was associated with stabilization, rather than a clear decrease, of bio-ADM levels, though this coincided with higher fluid administration, and dilution cannot be excluded. Whether bio-ADM offers therapeutic utility to guide resuscitation remains unclear, warranting further prospective evaluation in animal and human studies.</p>","PeriodicalId":13750,"journal":{"name":"Intensive Care Medicine Experimental","volume":"14 1","pages":""},"PeriodicalIF":2.9,"publicationDate":"2026-10-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13661888/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149181676","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 effect of preload on Doppler systolic time in a large emergency department cohort with suspected sepsis.","authors":"Sarah Atwi, Jared Nunnally, Kristen Ugale, So Mi Ko, Jaclyn Bond, Kimberly Boozer, Raymond J Bautista, Catalina Torres, Matthew Sedillo, Daniel Lachner-Piza, Tracy Savery, Melissa Hebscher, Joseph K Eibl, Jon-Emile S Kenny, Korbin Haycock","doi":"10.1186/s40635-026-00987-1","DOIUrl":"10.1186/s40635-026-00987-1","url":null,"abstract":"<p><strong>Background: </strong>Change in the corrected flow time of the common carotid artery (ccFT_Δ) during a preload challenge (PC) is a surrogate for stroke volume change (SV_Δ) to infer preload responsiveness (P_R).</p><p><strong>Methods: </strong>This is a retrospective cohort study comprising patients with suspected sepsis in a large, publicly funded, academic emergency department; no patient health information is linked to the Doppler assessments. Carotid Doppler spectrograms from a wireless, wearable critical care Doppler ultrasound system are analyzed for ccFT_Δ during a PC (either infusion of 300 mL of crystalloid over 3 min or a Trendelenburg maneuver). The primary objectives of this study are to describe the proportion of P_R patients by previously described ccFT_Δ thresholds (i.e., both 4 and 7 ms ccFT_Δ ), describe time-to-peak (TTP) ccFT_Δ, and evaluate the ability of baseline ccFT to detect ccFT_Δ during PC, using both the equations of Wodey and Bazett. Comparisons of related outcomes were adjusted for multiple comparisons using the Holm procedure, baseline ccFT discrimination was quantified using area under the receiver operating characteristic curve, and TTP was estimated using patient-level bootstrap resampling. Threshold-agnostic ccFT_Δ trajectories were additionally explored using unsupervised k-means clustering of patient-level temporal responses for both correction equations.</p><p><strong>Results: </strong>A PC was attempted in 4367 patients and an adequate ccFT_Δ was collected from 4,128 patients (95%). In total, 982,937 Doppler cardiac cycles are included. The median ccFT_Δ was 7.3 milliseconds (ms). 51.9% of patients had a ccFT_Δ ≥ 7 ms, while 68.6% had a ccFT_Δ ≥ 4 ms by the equation of Wodey. For Bazett, these fractions were 61.2% and 73.5%, respectively. For patients identified as P_R based upon either a 4 ms or 7 ms ccFT_Δ threshold, the time-to-peak ccFT_Δ was 27.5 s for both equations. Baseline absolute ccFT did not discriminate P_R from P_UR patients under both correction formulae (AUROC 0.56-0.57).</p><p><strong>Conclusions: </strong>To our knowledge this is the largest reported dataset of ED patients with suspected sepsis receiving P_R assessments by Doppler ultrasound, comprising nearly 1 million Doppler cardiac cycles obtained from over 4100 ED patients. Both 7 ms and 4 ms ccFT_Δ thresholds described clinically-accepted rates of P_R. The TTP was roughly 30 s into PC and baseline ccFT did not accurately detect ccFT_Δ during PC. Finally, a hypothesis-generating analysis identified four distinct ccFT_Δ trajectories during PC which may represent unique preload response patterns during P_R testing.</p>","PeriodicalId":13750,"journal":{"name":"Intensive Care Medicine Experimental","volume":"14 1","pages":""},"PeriodicalIF":2.9,"publicationDate":"2026-10-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13658765/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149165947","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":"Effect of vasopressin and its analogues on microcirculatory perfusion: a systematic review.","authors":"Judith van Zwol, J G Kruijsse, A A Vidal Itriago, S N T Hemmes, C E van den Brom","doi":"10.1186/s40635-026-00983-5","DOIUrl":"https://doi.org/10.1186/s40635-026-00983-5","url":null,"abstract":"<p><strong>Objective: </strong>Arginine vasopressin (AVP) is a non-adrenergic vasopressor increasingly used in the management of shock. While it restores arterial pressure, its effects on the microcirculation remain uncertain, with potential for reduced regional perfusion and tissue oxygenation. The aim of this systematic review is to evaluate the effects of intravenous AVP and its analogues on microcirculatory perfusion across different haemodynamic conditions and vascular beds.</p><p><strong>Methods: </strong>A systematic search of MEDLINE, EMBASE, and Web of Science was conducted. Animal and human publications evaluating the effects of intravenous AVP or analogues on microcirculatory perfusion assessed with in vivo microcirculatory imaging or flowmetry techniques were included. Publications were grouped by haemodynamic condition and vascular bed.</p><p><strong>Results: </strong>Of 1693 records, 39 publications (31 animal, 7 human, 1 combined) were included, comprising 43 study-units and 152 individual measurements. Overall perfusion was decreased in 33%, unchanged in 48%, and increased in 19% of measurements, compared with baseline, saline, or other vasopressors. By haemodynamic condition, perfusion was decreased/unchanged/increased (n=study-units; % of measurements) in physiological conditions (n = 14: 57/38/4), vasodilatory or septic shock (n = 23: 24/55/21; versus baseline, fluid resuscitation or noradrenaline), haemorrhagic shock (n = 3: 17/17/67; versus baseline, saline or noradrenaline), cardiac dysfunction or arrest (n = 2: 0/67/33; versus adrenaline or noradrenaline) and cirrhosis-related portal hypertension (n = 1: 0/0/100). Across vascular beds: gastrointestinal tract (n = 18: 30/42/27), kidney (n = 9: medulla 77/23/0, cortex 27/64/9), sublingual bed (n = 7: 19/68/13), cerebral cortex (n = 2: 0/67/33), cutaneous bed (n = 6: 42/42/17), and conjunctiva (n = 1, 100/0/0).</p><p><strong>Conclusion: </strong>AVP and its analogues reduced microcirculatory perfusion most consistently under physiological conditions, whereas effects in vasodilatory or septic shock were more heterogeneous. Across vascular beds, the highest proportion of measurements showing reduced perfusion was in the renal medulla. These results highlight the divergent effects of vasopressin across vascular beds and clinical conditions.</p>","PeriodicalId":13750,"journal":{"name":"Intensive Care Medicine Experimental","volume":"14 1","pages":""},"PeriodicalIF":2.9,"publicationDate":"2026-10-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13653856/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149166705","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 impact of ventilation mode on systemic inflammation and organ dysfunction in a porcine model of abdominal sepsis-associated acute respiratory distress syndrome.","authors":"James G Williams, Michaela Kollisch-Singule, Nirmeen Elmadany, Nader M Habashi, Gary F Nieman, Brian M Varisco","doi":"10.1186/s40635-026-00985-3","DOIUrl":"10.1186/s40635-026-00985-3","url":null,"abstract":"<p><strong>Introduction: </strong>Sepsis commonly causes acute respiratory distress syndrome (ARDS), and immune hyperactivation may be a causal link. Ventilator-induced lung injury (VILI) is common in ARDS, and VILI may potentiate organ dysfunction in severe sepsis. We used a porcine model of abdominal sepsis-associated ARDS to test whether ventilation strategy could impact systemic inflammation and organ dysfunction.</p><p><strong>Methods: </strong>Female Yorkshire pigs (6-8 months) underwent ischemia-reperfusion (I/R) injury of the small bowel and fecal clot implantation or sham laparotomy. The abdominal sepsis animals were ventilated with a volume-controlled (VC) mode using the ARDS-Net low tidal volume (LVt) method to set and adjust the mode, and applied at two time points. Late LVt, was applied once PaO₂/FiO₂ was ≤300, and Early LVt was applied immediately following injury. The third lung protective group used the airway pressure release ventilation (APRV) mode set and adjusted with the time-controlled adaptive ventilation (TCAV) method, also applied immediately after injury. Animals were supported for 48 h using standardized resuscitation protocols and euthanized. Physiologic variables, clinical lab data, lung histology, and plasma proteome were assessed.</p><p><strong>Results: </strong>Sham animals showed no evidence of sepsis or ARDS, whereas all experimental animals developed septic shock, requiring fluid resuscitation and vasopressors. Both LVt groups developed ARDS as measured by PaO₂/FiO₂ ratio by the study end (Late LVt: 129.9±16.0; Early LVt: 205.2±24.2), while the Early APRV group did not (429.4±59.4). The Sham and experimental groups all had similar proteomes at baseline. The proteomes diverged over time and ended in three distinct groups: Sham, Late LVt/Early LVt, and Early APRV. The most significantly differentially expressed proteins distinguishing the groups were involved in the immune and inflammatory response, with APRV having the lowest inflammatory signature.</p><p><strong>Conclusion: </strong>In a porcine model of abdominal septic shock we found that animals ventilated with a higher mean airway pressure strategy (APRV) had decreased plasma proteomic signatures of inflammation compared to those ventilated with a conventional low tidal volume strategy. Our findings are hypothesis generating and not directly translatable to the clinical setting. Future studies should focus on further elucidating a link between VILI and its effect on systemic inflammation and organ dysfunction.</p>","PeriodicalId":13750,"journal":{"name":"Intensive Care Medicine Experimental","volume":"14 1","pages":""},"PeriodicalIF":2.9,"publicationDate":"2026-10-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13653911/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149167100","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":"Frontal cortical neuroinflammation and circulating biomarkers following cardiopulmonary bypass in sheep.","authors":"Taku Furukawa, Alemayehu H Jufar, Anton L Trask-Marino, Clive N May, Roger G Evans, Andrew D Cochrane, Bruno Marino, Peter R McCall, Sally G Hood, Jaishankar Raman, Connie Pei Chen Ow, Lars I P Snel, Scott Ayton, Ashenafi Betrie, Linda Cornthwaite, Munenori Kusunoki, Angela Connelly Huf, Dawoud AlMekhled, Emily Hadzajlic, Adam Southon, Rinaldo Bellomo, Lachlan F Miles, Lindsea Booth, Yugeesh R Lankadeva","doi":"10.1186/s40635-026-00986-2","DOIUrl":"https://doi.org/10.1186/s40635-026-00986-2","url":null,"abstract":"<p><strong>Background: </strong>Cerebral hypoxia and neuroinflammation have been implicated in neurocognitive disorders following cardiac surgery, but their postoperative trajectory and relationship with circulating biomarkers are poorly defined. We investigated cerebral tissue oxygenation, neuroinflammation, and plasma biomarkers of neurodegeneration over 4 weeks after cardiopulmonary bypass (CPB) in sheep.</p><p><strong>Methods: </strong>Sixteen adult Merino ewes underwent CPB with a 2-h aortic cross-clamp and recovered for either 48 h (n = 8) or 4 weeks (n = 8). Cerebral tissue oxygenation was monitored. Neuroinflammation was quantified by morphometric analyses of microglia and astrocytes in the frontal cortex in both CPB groups and a naïve control group (n = 8). Plasma neurofilament light chain (NfL) and glial fibrillary acidic protein (GFAP) were measured serially.</p><p><strong>Results: </strong>Compared with pre-CPB baseline, cerebral tissue oxygenation did not change significantly in the 48-h or 4-week period. In the 48-h post-CPB group, microglial soma sphericity was reduced (0.79 ± 0.04 vs. 0.83 ± 0.02, P = 0.018) compared with naïve controls, indicating microglial activation. Astrocytic GFAP-positive area was also elevated (17 ± 2% vs. 10 ± 2%, P = 0.026). In the 4-week post-CPB group, these measures did not differ significantly from naïve controls. Plasma NfL rose from 138 [96-185] pg/mL at baseline to 198 [149-265] pg/mL at 48 h (P = 0.0007), while GFAP peaked at the end of CPB (14.4 [4.7-32.4] vs. 3.0 [1.3-4.5] pg/mL, P < 0.0001) and normalised by 48 h.</p><p><strong>Conclusions: </strong>CPB induced neuroinflammation characterised by frontal cortical microglial activation and astrogliosis, accompanied by temporal elevations in plasma GFAP and NfL. These findings identify microglial activation as a response to CPB in the setting of preserved tissue oxygenation and provide preliminary evidence of an association between perioperative neuroinflammatory changes and circulating biomarkers GFAP and NfL, supporting further investigation.</p>","PeriodicalId":13750,"journal":{"name":"Intensive Care Medicine Experimental","volume":"14 1","pages":""},"PeriodicalIF":2.9,"publicationDate":"2026-10-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13653855/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149165528","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":"Impact of side hole design of drainage cannulas on flow velocity and predilection sites for low-flow areas in veno-venous ECMO circuits.","authors":"Markus Bongert, Vincent Marciniak, Wolfram Windisch, Christian Karagiannidis","doi":"10.1186/s40635-026-00980-8","DOIUrl":"10.1186/s40635-026-00980-8","url":null,"abstract":"<p><strong>Background: </strong>Veno-Venous Extracorporeal Membrane Oxygenation (VV-ECMO) (VV-ECMO) and Veno-Artial Extracorporeal Membrane Oxygenation (VA-ECMO) have become evidence-based therapy options for patients with most severe heart and/or lung failure. Cannulas continue to play a central role as the direct interface between patients and extracorporeal circulation. However, severe side-effects, such as coagulation and haemolysis, may result not only from a blood pump but also from inappropriate cannula design.</p><p><strong>Methods: </strong>Based on the multi-stage lighthouse design of a draining ECMO cannula, the area of the side holes was varied in both shape and size in the distal and proximal directions. Using a Computer-Aided Design (CAD)- Model of cannulas (19,21,23 French (Fr)) appropriate simulation models were created in the non-reactive plenum. The resultant numerical 3D simulations are based on physiological boundary conditions and on the flows covering different ECMO-flow rates.</p><p><strong>Results: </strong>The current cannula design reveals no-flow zones, which induce thrombus formation, especially when using blood-flow rates below 2 L/min. New geometric cannula design variants revealed an improvement in pressure loss, but at the expense of pronounced no-flow zones in the distal region. During drainage, the largest proportion of the total volume flow drains through the proximal row of side holes. Here, the pressure and thus the flow for both, immediately drops to the level of the surrounding plenum. This means that risk areas for haemostasis develop more distally. The direct influence of the design is evident in the proximally exponentially reduced side holes. They significantly reduce the extent of the no-flow zones. Simulations of the reference cannula showed that suction to the vessel wall and thus closure of some side holes contributes to an overall improvement in flow within the cannula.</p><p><strong>Conclusions: </strong>When reducing the blood-flow rate in ECMO therapy, stagnation areas may develop within the drainage cannula. The geometry of the side holes has an important impact. A comparison of the different designs shows that distal growth of the side hole area results in improved flow behaviour.</p>","PeriodicalId":13750,"journal":{"name":"Intensive Care Medicine Experimental","volume":"14 1","pages":""},"PeriodicalIF":2.9,"publicationDate":"2026-10-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13653020/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149147622","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}