Intensive Care Medicine Experimental最新文献

{"title":"Can patient-derived in vitro models improve clinical translation in critical care research when used before animal studies?","authors":"Alexandre Pierre, Raphael Favory, Steve Lancel, Sebastien Preau","doi":"10.1186/s40635-025-00814-z","DOIUrl":"https://doi.org/10.1186/s40635-025-00814-z","url":null,"abstract":"<p><strong>Background: </strong>Translational failure remains a major barrier in critical illness research, with preclinical findings from animal models often failing to replicate in human trials.</p><p><strong>Hypothesis: </strong>we hypothesize that the integration of advanced in vitro models derived from human cells-particularly those from ICU patients-prior to animal studies will enhance clinical translation in critical care research.</p><p><strong>Main text: </strong>These emerging human-relevant platforms-such as organ-on-chip microfluidic systems-recapitulate key aspects of human physiology and pathology that animal models often cannot, thereby avoiding interspecies differences, capturing patient-specific variability, and enabling the study of disease phenotypes and endotypes. We propose that advanced in vitro models should be used first to gain mechanistic insights and assess efficacy in a human-relevant setting, while subsequent animal studies would then serve to evaluate systemic effects and safety before translation to patients. By leveraging such complementary strengths, an integrated in vitro-in vivo pipeline could better bridge the bench-to-bedside gap. This approach aligns with 3Rs principles by refining and reducing animal use (screening therapeutics in human models to focus subsequent animal experiments), and potentially replacing certain animal tests pending rigorous validation and regulatory acceptance. Implementation will require regulatory support, as well as training and funding to overcome technical barriers. This hypothesis is testable through analyses of past translational failures to determine whether human in vitro models could have predicted outcomes, and through prospective studies comparing drug development pipelines with and without an in vitro prescreening step to assess improvements in clinical success rates.</p><p><strong>Conclusions: </strong>By harnessing the strengths of both model systems, this two-step strategy could help bridge the translational gap in critical care, improve therapeutic development, and accelerate precision medicine in sepsis and other critical illnesses.</p>","PeriodicalId":13750,"journal":{"name":"Intensive Care Medicine Experimental","volume":"13 1","pages":"102"},"PeriodicalIF":2.8,"publicationDate":"2025-10-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145292056","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":"Electrochemical skin conductance is associated with peripheral tissue hypoperfusion in septic patients.","authors":"Jérémie Joffre, Tomas Urbina, Vincent Bonny, Louai Missri, Juliette Bernier, Lisa Raia, Jean-Luc Baudel, Eric Maury, Hafid Ait-Oufella","doi":"10.1186/s40635-025-00813-0","DOIUrl":"https://doi.org/10.1186/s40635-025-00813-0","url":null,"abstract":"<p><strong>Background: </strong>Autonomic nervous system (ANS) dysfunction contributes to the pathophysiology of sepsis. However, studies using reliable methods for ANS activity monitoring and evaluating its association with outcomes in sepsis patients are scarce. The Sudoscan^® device offers a non-invasive method to evaluate sympathetic function by measuring electrochemical skin conductance (ESC), but its clinical relevance in sepsis remains unclear. This study aimed to assess autonomic sympathetic activity in septic patients using the Sudoscan^® technology and explore its relationship with peripheral perfusion and outcomes.</p><p><strong>Methods: </strong>This prospective, observational, single-center study included 97 consecutive adult ICU septic patients without or with shock. Sudoscan^® measurements were performed at admission and serially for 72 h, alongside standard hemodynamic and peripheral perfusion assessments (e.g., knee capillary refill time [CRT], mottling, cardiac output). Associations between ESC (\"sudoscore\"), clinical parameters, and mortality at day-28 were analyzed.</p><p><strong>Results: </strong>Of the 97 septic patients included, 37% had shock. Mottling was frequent (53%), and mean knee CRT was 3.3 ± 2.5 s. The mean admission Sudoscore was 31.2 ± 21 µS and was significantly higher in patients with peripheral perfusion abnormalities, such as mottling compared to no mottling (35.7 ± 21 vs 28.5 ± 19.5 µS, P = 0.04) and prolonged knee CRT > 5 s compared to CRT < 5 s (44.2 ± 25 vs 29.6 ± 18.6 µS, P = 0.03). Additionally, Sudoscore positively correlated with CRT (P = 0.01, R = 0.27). There was no difference in Sudoscore between patients receiving vasopressors or not, and between patients receiving sedative drugs or not. Longitudinally, the Sudoscore course was significantly lower over the first 72 h in survivors compared to non-survivors (P = 0.04, two-way ANOVA mixed model effect).</p><p><strong>Conclusion: </strong>Electrochemical skin conductance measured via Sudoscan^® may serve as a surrogate marker of autonomic sympathetic hyperactivation during sepsis and is associated with peripheral circulatory impairment. Although admission values were not independently predictive of mortality, elevated and persistently high Sudoscores are associated with death at day 28. Sudoscan^® may offer a non-invasive window into sympathetic activity during septic shock and warrants further investigations.</p>","PeriodicalId":13750,"journal":{"name":"Intensive Care Medicine Experimental","volume":"13 1","pages":"101"},"PeriodicalIF":2.8,"publicationDate":"2025-10-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145292189","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":"Combined mechanical ventilatory and mechanical circulatory support aids pulmonary vascular state in cardiogenic shock.","authors":"Kimberly K Lamberti, Elazer R Edelman, Steven P Keller","doi":"10.1186/s40635-025-00811-2","DOIUrl":"https://doi.org/10.1186/s40635-025-00811-2","url":null,"abstract":"<p><strong>Background: </strong>Percutaneous ventricular assist devices (pVADs) support patients in circulatory failure and increasingly concomitant respiratory failure. The presence of co-existent lung disease creates a management challenge due to cardiopulmonary interactions, especially when there is simultaneous mechanical ventilation and mechanical circulatory support. Enhanced understanding of the combined effects of these devices is necessary to better inform care for circulatory failure patients.</p><p><strong>Methods: </strong>A porcine model of titratable acute cardiogenic shock was used to quantify the effect of pVAD support on cardiac loading states in five intubated animals with positive pressure ventilation and varied intrathoracic pressure. Cardiovascular hemodynamics were assessed across positive end-expiratory pressure (PEEP) ramps in animals in health, health with pVAD, and pVAD-supported cardiogenic shock induced via coronary microembolization.</p><p><strong>Results: </strong>This study employed invasive physiological metrics and assessment of right and left ventricular press-volume loops to recreate classic Frank-Starling curves. Increased intrathoracic pressure altered transmural pressure in the ventricles and the pulmonary vasculature and resulted in decreased venous return and stroke volume while increasing end-diastolic pressure consistent with decreased ventricular compliance. In pVAD-supported cardiogenic shock, elevated PEEP enhanced left ventricular output and increased pulmonary vascular compliance in several animals, contrary to traditional decrements observed with elevated PEEP. The right ventricular functional response aligned with these varied responses in pulmonary vascular state.</p><p><strong>Conclusions: </strong>These results demonstrate that combined used of cardiopulmonary support devices in cardiogenic shock can create variable responses compared to classic physiological understanding. In pVAD-supported cardiogenic shock, an increase in ventilatory PEEP increased unloading from the heart and improved right ventricular function, counter to traditional findings. This demonstrates that combined use of these technologies could be leveraged to optimize a patient's volume status in complex shock and provides promise for management of patients with cardiopulmonary failure requiring simultaneous use of mechanical circulatory support and mechanical ventilation.</p>","PeriodicalId":13750,"journal":{"name":"Intensive Care Medicine Experimental","volume":"13 1","pages":"100"},"PeriodicalIF":2.8,"publicationDate":"2025-10-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145292031","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":"Lipid emulsion in blood increases extraction of amitriptyline in liposome augmented peritoneal dialysis in rats chronically dosed with amitriptyline: could nanoparticles mitigate the limitations to dialysis in intoxication?","authors":"Justin Koh, Matthew Quance, Martyn Harvey, Debra Chalmers, Grant Cave","doi":"10.1186/s40635-025-00812-1","DOIUrl":"10.1186/s40635-025-00812-1","url":null,"abstract":"<p><strong>Background: </strong>The reach of dialysis in toxicology is limited by two factors, high toxicant volume of distribution and low dialytic extraction of protein bound toxicants in blood. Therapeutic actions for lipid emulsion as antidote are thought involve a \"lipid shuttle\", whereby lipid droplets in the circulation \"shuttle\" lipophilic toxicants with \"boarding\" in well perfused heart and brain tissue with high toxicant concentrations and \"exit\" to biologically inert slower equilibrating sites such as muscle or adipose where toxicant concentrations are lower. Such a mechanism raises the conceptual possibility of an extracorporeal \"exit\" potentially mitigating toxicity through increased drug clearance. In experimental models drug binding nanoparticles in dialysate have been shown to mitigate the problem of blood proteins binding toxicant. We investigated whether the addition of intravenous lipid emulsion would increase extraction of amitriptyline into nanoparticle augmented peritoneal dialysate in rats orally dosed with amitriptyline for 1 week.</p><p><strong>Methods: </strong>Rats were dosed with amitriptyline in drinking water for a week. On the day of the experiment, anaesthetised rats received either an initial bolus then infusion of lipid emulsion for one hour, or a bolus of saline at the initiation of the experiment equal to the total volume of lipid emulsion given. After a 50 min equilibration period, a 10 min pH gradient nanoparticle augmented peritoneal dialysis dwell was undertaken. Animals were humanely euthanised at the end of the experiment. Blood was sampled 0, 10, 45 and 60 min and peritoneal dialysate was analysed for amitriptyline concentration.</p><p><strong>Results: </strong>There were no significant differences in baseline physiology, initial amitriptyline blood concentration, nor pulse and blood pressure at any time between groups. Time weighted individual subject mean blood amitriptyline concentrations (median (IQR)); control 104 (87-125) nmol/l, lipid 219 (148-357) nmol/L, p = 0.03 and dialysate amitriptyline concentration; control 31(14-52) nmol/L, lipid 105 (62-185) nmol/L, p = 0.03 were greater in animals given intravenous lipid emulsion.</p><p><strong>Conclusion: </strong>These are the first data to our knowledge showing experimental support for the approach of simultaneously decreasing volume of distribution with an intravascular nanoparticle in conjunction with a drug binding particle in dialysate. Further work in this area is warranted.</p>","PeriodicalId":13750,"journal":{"name":"Intensive Care Medicine Experimental","volume":"13 1","pages":"99"},"PeriodicalIF":2.8,"publicationDate":"2025-09-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12484478/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145199299","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":"Development and validation of a machine learning model for early prediction of intensive care unit acquired weakness.","authors":"Felipe Kenji Nakano, Nathalie Van Aerde, Grégoire Coppens, Ilse Vanhorebeek, Celine Vens, Greet Van den Berghe, Fabian Güiza Grandas","doi":"10.1186/s40635-025-00810-3","DOIUrl":"10.1186/s40635-025-00810-3","url":null,"abstract":"<p><strong>Background: </strong>Early identification of potential high cost and high need patients on the ICU may assist in the development of targeted protocols, which allows proper resource utilization and initialization of preventive care. Weakness acquired in the ICU developed within the first week is an independent predictor of both short and long-term adverse outcomes, nonetheless early prediction is challenging. We aimed to develop and validate a machine learning model for ICU acquired-weakness (ICU-AW), using data readily available within the first 24 h of ICU admission.</p><p><strong>Methods: </strong>Patients from the EPaNIC trial (NCT00512122, N = 4640) who were assessed for muscle weakness at day 9 (IQR 8-13), after ICU-admission, using the Medical Research Council (MRC) sum. Patients are diagnosed with ICU-AW if their MRC is higher than 48. The final subset contains N = 600. Our models were internally validated using 100 repetitions of fivefold cross validation. We compared three predictive models: (i) a random forest and (ii) a logistic regression model built using descriptors available at day 1, (iii) a random forest using only APACHE II as a descriptor. Both random forests contain 150 trees.</p><p><strong>Results: </strong>The training set comprised 600 patients where the incidence of ICU-AW was 38.6% (232/600). The AUROC of the random forest with all descriptors and the logistic regression were 76% and 74%, respectively. The random forest (RF) achieved a specificity of 62% and a sensitivity 79%, whereas the logistic regression yielded 69% and 68%, respectively. The RF identified APACHE II, creatinine, SOFA PaO2/FiO2, bilirubin, BMI, age, glycemia upon admission, morning glycemia and sepsis as the most relevant descriptors. Lastly, the RF also presented very good calibration and clinical usefulness for a wide range of risk thresholds.</p><p><strong>Conclusions: </strong>Machine learning models, especially random forests, can be used to predict if patients are at risk of developing ICU-AW, using data available within 24 h of admission. This tool allows prognostication early in an adult general critically ill patient population, with the potential to detect high cost and high need patients who benefit from different levels of care.</p>","PeriodicalId":13750,"journal":{"name":"Intensive Care Medicine Experimental","volume":"13 1","pages":"98"},"PeriodicalIF":2.8,"publicationDate":"2025-09-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12484466/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145199308","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":"Correspondence about the article \"Left ventricular systolic longitudinal strain in mechanically ventilated patients in the intensive care unit: assessment of global and chamber reproducibility\"-author's reply.","authors":"Matías Pécora, Piero Pastorini, Roberto Farolini, Gastón Burghi, F Javier Hurtado","doi":"10.1186/s40635-025-00789-x","DOIUrl":"10.1186/s40635-025-00789-x","url":null,"abstract":"","PeriodicalId":13750,"journal":{"name":"Intensive Care Medicine Experimental","volume":"13 1","pages":"97"},"PeriodicalIF":2.8,"publicationDate":"2025-09-25","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12463789/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145137303","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 mannitol on diuresis and acid-base equilibrium in critically ill patients.","authors":"Davide Chiumello, Clara Aiello, Tommaso Pozzi, Francesca Panina, Alessandra Muscas, Simone Mancusi, Silvia Coppola","doi":"10.1186/s40635-025-00807-y","DOIUrl":"10.1186/s40635-025-00807-y","url":null,"abstract":"<p><strong>Background: </strong>Mannitol is the most commonly used osmotic diuretic, but its effect on plasma and urine electrolytes and on acid-base equilibrium have not been well investigated. The aim of this study was to evaluate the short-term effects of mannitol on diuresis and plasma and urine acid-base equilibrium in a group of critically ill patients according to the Stewart approach.</p><p><strong>Results: </strong>Prospective observational study enrolling all consecutive sedated and mechanically ventilated patients requiring mannitol infusion for clinical purpose. Plasma and urine acid-base variables and electrolytes were measured before mannitol infusion and every 60 and 30 min, respectively, following the infusion of 1 g/kg of ideal body weight of mannitol. Forty-two patients were enrolled. Diuresis increased significantly 30 min after the mannitol infusion was completed and remained significantly higher as compared with T₀. Plasma sodium and chloride concentrations and plasma SID significantly decreased after mannitol infusion ended; urine sodium and chloride concentration remained unchanged, while urine ammonium increased increasing urine SID.</p><p><strong>Conclusions: </strong>Since the end of the infusion, mannitol promoted a significant increase in diuresis, with a reduction in plasma electrolytes due to volume expansion, and a slight decrease in arterial pH due to dilutional acidosis. Kidney relative excretion pattern was unmodified during the study.</p>","PeriodicalId":13750,"journal":{"name":"Intensive Care Medicine Experimental","volume":"13 1","pages":"96"},"PeriodicalIF":2.8,"publicationDate":"2025-09-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12440839/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145069428","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":"Total liquid ventilation in a porcine model of severe acute respiratory distress syndrome using a new generation of liquid ventilator.","authors":"Naoto Watanabe, Antoine Bois, Fanny Lidouren, Yara Abi Zeid Daou, Ali Jendoubi, Baptiste Gaborieau, Mathéo Richard, Mathieu Nadeau, Fabrice Paublant, Mickaël Libardi, Sandrine Perrotto, Bijan Ghaleh, Etienne Fortin-Pellerin, Philippe Micheau, Patrick Bruneval, Matthias Kohlhauer, Jean-Damien Ricard, Renaud Tissier","doi":"10.1186/s40635-025-00799-9","DOIUrl":"10.1186/s40635-025-00799-9","url":null,"abstract":"<p><strong>Background: </strong>Total liquid ventilation (TLV) has been experimentally proposed as an alternative treatment for the management of Acute Respiratory Distress Syndrome (ARDS). Recent technological advances have led to the evaluation of a TLV prototype in patients resuscitated after cardiac arrest. Here, our goal was to determine whether a derived version of this prototype, so-called LV4B (liquid ventilation for breathing), could be used for normothermic TLV in a swine model of severe ARDS.</p><p><strong>Methods: </strong>Swine were anesthetized and instrumented for respiratory and hemodynamic evaluation. ARDS was induced by one or two administrations of oleic acid (0.1 mg/kg), until reaching a PaO2/FiO2 ratio < 100 mmHg. After ARDS induction, animals were allocated to undergo 60 min of either gas ventilation continuation (Control group) or TLV using a prototype that continuously controls respiratory rate (RR), liquid tidal volume (LqVt) and end-expiratory liquid volume (EELqV, respectively). Perfluorooctyl bromide was used as breathable liquid.</p><p><strong>Results: </strong>After ARDS induction and group allocation, 2/5 animals (40%) survived in the Control groups versus 5/5 in the TLV group (100%). In the Control group, premature deaths were related to sustained hypoxemia (PaO₂ < 50 mmHg) with hemodynamic failure. Surviving animals presented a trend toward better oxygenation in TLV versus Control, without achieving statistical significance due to the low number of survivors in the Control group. PaCO₂, blood pH, lactate levels, or pulmonary and systemic hemodynamics were not different between groups in survivors. In the TLV group, the average LqVt, EELqV, and respiratory rate (RR) were 12.6 ± 0.4 mL/kg, 22.9 ± 2.9 mL/kg, and 5.3 ± 0.5 breath/min (mean ± SEM) at the end of the procedure, respectively. In all animals, pulmonary debris were washed out from the lung and collected by the TLV device throughout the procedure. After necropsy, histopathological examination demonstrated a significantly lower extent of inflammatory and congestion lesions in TLV versus Control.</p><p><strong>Conclusions: </strong>TLV with a liquid ventilator controlling EELqV, RR and LqVt is feasible and safe in large animals in a severe model of ARDS. This opens promising perspectives and warrants further investigation, including prolonged treatment durations and long-term follow-up.</p>","PeriodicalId":13750,"journal":{"name":"Intensive Care Medicine Experimental","volume":"13 1","pages":"95"},"PeriodicalIF":2.8,"publicationDate":"2025-09-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12436666/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145069433","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":"Gas as medicine: the case for hydrogen gas as a therapeutic agent for critical illness.","authors":"Lakhmir S Chawla","doi":"10.1186/s40635-025-00798-w","DOIUrl":"10.1186/s40635-025-00798-w","url":null,"abstract":"<p><p>Molecular hydrogen gas (HG), administered through inhalation or as hydrogen-rich fluids (HRF), has demonstrated antioxidant, anti-inflammatory, antiapoptotic, cytoprotective, and beneficial mitochondrial effects in critical illness. Preclinical studies and human clinical studies consistently endorse hydrogen gas as safe, with mechanisms of action linked to vital molecular pathways, such as reductions in both oxidative stress and inflammation with beneficial effects on mitochondria. In preclinical studies, HG has been shown to improve outcomes in conditions such as sepsis, acute lung injury, hepatic injury, pancreatitis, cardiac arrest, traumatic injury, acute kidney injury, and brain injury. HG has been given to human subjects across multiple disease states and has a good safety profile with encouraging clinical effects. Given its accessibility, safety, and low-cost, hydrogen gas therapy should be assessed in adequately powered clinical trials in critical illness.</p>","PeriodicalId":13750,"journal":{"name":"Intensive Care Medicine Experimental","volume":"13 1","pages":"94"},"PeriodicalIF":2.8,"publicationDate":"2025-09-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12431974/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145040054","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":"Regional venous-to-arterial carbon dioxide pressure and content differences during endotoxemic shock: influence of hydrogen ion accumulation vs. Haldane effect.","authors":"Gustavo A Ospina-Tascón, Daniel De Backer, José L Aldana, Alberto F García Marín, Luis E Calderón, Julián Chica, Gustavo García-Gallardo, Nicolás Orozco, Jihad Mallat","doi":"10.1186/s40635-025-00805-0","DOIUrl":"10.1186/s40635-025-00805-0","url":null,"abstract":"<p><strong>Background: </strong>The relationship between carbon dioxide pressures (PCO₂) and contents (CCO₂) is linked to the Haldane effect. Nevertheless, under shock conditions, hydrogen ion accumulation might strongly influence the discrepancies between PCO₂ and CCO₂. This study aims to evaluate the impact of hydrogen ion accumulation and hemoglobin oxygen saturation (Haldane effect) on PCO₂:CCO₂ relationships during induction and resuscitation of endotoxemic shock.</p><p><strong>Methods: </strong>Shock was induced by an escalating dose of lipopolysaccharide in 12 female Landrace pigs. Norepinephrine was then started to maintain mean arterial pressure ≥ 75 mmHg, while successive fluid boluses were administered targeting arterial lactate < 2.0 mmol·L^-1 or decreases > 10% per 30 min. Mesenteric venous and arterial PCO₂ were measured at baseline, time of shock, and then, every hour for 6 h, while their respective CCO₂ were computed using the Douglas equation. Mesenteric venous-to-arterial PCO₂ and CCO₂ differences (i.e., ΔPCO₂ and ΔCCO₂), and then, their absolute arithmetic differences (i.e., [|ΔPCO₂ - ΔCCO₂|]) were calculated. Discrepancies in [|ΔPCO₂ - ΔCCO₂|] between adjacent measurement time points (i.e., ∆-[|ΔPCO₂ - ΔCCO₂|]) were compared with the variations in mesenteric venous O₂ saturation (∆-S_vmesO₂) and arterial-to-mesenteric venous pH (∆-pH_a-vmes). In addition, arterial and venous CCO₂ values were recalculated, maintaining baseline pH (Def_pH) or SO₂ values (Def_SO2) to then quantify the impact of pH and S_vmesO₂ on the PCO₂:CCO₂ relationship.</p><p><strong>Results: </strong>Variations in ∆-[|∆PCO₂ - ∆CCO₂|]) were paralleled by ∆-pH_a-vmes (R² = 0.56, p < 0.001), while poorly correlated with ∆-S_vmesO₂ (R² = 0.15, p < 0.001). When variations in pH were not included in CCO₂ calculations (i.e., Def_pH-CCO₂), both arterial and mesenteric venous CCO₂ disagreed in ranges from 21.8 to 50.4% and 15.3 to 47.6%, respectively. Conversely, overestimation of CCO₂ was almost null when variations in SvmesO₂ were not assumed (Def_SvmesO2). Calculations under Def_pH-CCO₂ conditions revealed an almost linear relationship between PCO₂ and CCO₂, contrasting with a non-linear relationship when pH variations were acknowledged.</p><p><strong>Conclusions: </strong>Regional splanchnic PCO₂:CCO₂ relationship was mostly influenced by hydrogen ion accumulation rather than the Haldane effect during development and resusc","PeriodicalId":13750,"journal":{"name":"Intensive Care Medicine Experimental","volume":"13 1","pages":"93"},"PeriodicalIF":2.8,"publicationDate":"2025-09-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12417345/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145023217","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}