The respiratory quotient (RQ) reflects metabolic substrate utilization and is traditionally measured using indirect calorimetry techniques, e.g. Douglas bag, which are technically demanding and not always feasible in clinical practice. The alveolar gas equation (AGE) provides a theoretical relationship between oxygen tension, carbon dioxide tension and RQ and may be rearranged to estimate RQ using standard respiratory measurements. This study aimed to validate a novel method for estimating RQ by reversing the alveolar gas equation. In this prospective experimental study, twelve anesthetized, mechanically ventilated pigs were studied under steady-state conditions. RQ was determined using two methods: (1) reference measurement via Douglas bag collection using Haldane transformation (RQref), and (2) calculation from the rearranged alveolar gas equation using inspired and expired gas measurements (RQcalc). Agreement between methods was assessed using paired t-tests, Bland-Altman analysis with bootstrap confidence intervals, and linear regression. Mean RQref was 0.877 (95
Abstract Background Septic shock induces skeletal muscle wasting and neuromuscular dysfunction, contributing to ICU-acquired weakness (ICUAW) and poor recovery after critical illness. Conventional ultrasound primarily captures structural changes but provides limited insight into early muscle mechanical alterations or their relationships with clinical factors. Shear-wave elastography (SWE) enables non-invasive assessment of muscle stiffness, but its performance in critically ill patients remains poorly understood. Methods In this prospective study, adults with septic shock requiring invasive ventilation underwent daily muscle ultrasound during the first five ICU days. Rectus femoris muscle cross-sectional area, echogenicity and SWE-derived shear modulus (SM RF ) were assessed bilaterally using conventional ultrasound and shear-wave elastography in both longitudinal and transverse orientations at two anatomical sites within the rectus femoris . An exploratory anisotropy estimate was derived from the transverse-to-longitudinal stiffness ratio. ICUAW was evaluated at the time of extubation. Associations between ultrasound markers and clinical variables were explored using correlation and regression analyses. Results Twenty-seven patients (66.7% male, mean age 61 ± 12 years) were analysed (125 sessions, 4,971 images). Rectus femoris cross-sectional area declined from 3.90 cm² on Day 1 to 2.97 cm² by Day 5 (− 21%, p < 0.01), while echogenicity remained stable. Shear modulus (SM RF ) demonstrated region- and orientation-dependent behaviour. At the lower-third region, longitudinal SM RF remained relatively stable (7.08 to 7.72 kPa), whereas transverse SM RF declined significantly (15.20 to 12.30 kPa, p = 0.009), resulting in dynamic changes in the transverse-to-longitudinal stiffness ratio. Muscle atrophy trajectories were similar in patients with and without ICUAW, and no significant between-group differences in SM RF measures were identified. Higher illness severity (SOFA score, β = 18.18, p = 0.003) and cumulative fluid balance (β = 3.32, p = 0.002) were associated with increases in longitudinal SM RF . Greater early caloric intake (β = 0.076, p = 0.006) and increases in echogenicity (β = −0.91, p = 0.027) were associated with changes in transverse SM RF . Conclusions Rapid muscle loss during early septic shock was accompanied by distinct, site- and direction-specific stiffness changes. Dual-plane SWE identified early mechanical changes, although these measures did not discriminate ICUAW status in this cohort. Associations with clinical variables suggest that SWE may help capture early physiological muscle changes in critical illness.
Differential hypoxemia, or Harlequin syndrome, is a critical concern during veno-arterial extracorporeal membrane oxygenation (VA-ECMO), especially when femoral artery cannulation delivers retrograde flow. This phenomenon may impair cerebral oxygenation and promote brain injury. We investigated whether the arterial cannulation site and ventilation strategy influence acute cerebral injury in a rat cardiopulmonary bypass (CPB) model. Forty male Wistar rats were randomized into four groups (n = 10 each) according to the arterial cannulation site (carotid [anterograde, A-CPB] or femoral [retrograde, R-CPB]) and ventilation strategy (normal [NV, 100
Intensive Care Unit–acquired weakness (ICUAW) is a frequent complication that significantly impairs functional recovery in critically ill patients. Fluid overload during critical illness has been associated with adverse outcomes, but its relationship with peripheral muscle quality and strength remains uncertain. This study aimed to evaluate the association between cumulative fluid balance, ultrasound-assessed muscle quality, and muscle strength in critically ill patients. We conducted a retrospective analysis of routinely collected data between May and October 2024 in adult ICU patients who were deeply sedated, mechanically ventilated, and had an ICU length of stay ≥24 hours. Muscle and subcutaneous tissue measurements were obtained using ultrasound of the vastus intermedius and rectus femoris within the first 24 hours of ICU admission (day 1) and at clinical awakening. Muscle quality was assessed at both time points using the Heckmatt scale. Global muscle strength was assessed only at clinical awakening using the Medical Research Council Sum Score (MRC-SS), once patients were able to follow commands. Patients without complete ultrasound measurements at both time points were excluded from the final analysis. Eighty patients were included (mean age 51 ± 14 years; APACHE II score 18 ± 5). The main admission diagnoses were predominantly respiratory and septic conditions. Mean cumulative fluid balance at awakening was 2400 ± 800 mL. From ICU admission to awakening, quadriceps thickness decreased, whereas subcutaneous tissue thickness increased and muscle quality deteriorated, as reflected by higher Heckmatt scores. At awakening, cumulative fluid balance showed a strong inverse correlation with global muscle strength (rho = −0.70, p < 0.001) and a moderate positive correlation with subcutaneous tissue thickness. Muscle quality assessed by the Heckmatt scale was moderately inversely correlated with MRC-SS (rho = −0.43, p< 0.001). In multivariable analysis adjusted for age, disease severity, and duration of mechanical ventilation, cumulative fluid balance remained independently associated with lower muscle strength at awakening. Qualitative muscle ultrasound assessment using the Heckmatt scale provides complementary information to muscle thickness measurements. The observed association between cumulative fluid balance and poorer muscle quality suggests that fluid status should be considered when interpreting qualitative muscle ultrasound findings in critically ill patients.
Early downward temperature drift is a common event of pre-hospital extracorporeal cardiopulmonary resuscitation (e-CPR), since prehospital extracorporeal membrane oxygenation (VA-ECMO) circuits often lack heat-exchangers. However, whether this core body temperature evolution could be detrimental or beneficial compared to strict normothermia in this context remains unclear. Accordingly, in a swine model of refractory cardiac arrest, we compared e-CPR with heat-exchanger-assisted active maintenance of normothermia versus e-CPR with no temperature regulating device. Female pigs underwent ventricular fibrillation with 15 min of no-flow and subsequent e-CPR using VA-ECMO. Animals were randomized (n = 6 per group) to receive either active normothermia (with heat-exchanger connected to the VA-ECMO circuit) or no temperature control (without heat-exchanger). Fluids and vasopressor requirements, hemodynamics, ECMO parameters, blood gases, and ultra early impact on target organs biomarkers were monitored for 120 min after return of spontaneous beating (ROSB). Core temperature was significantly lower in the group without heat-exchanger use (36.1 ± 0.3 vs. 37.5 ± 0.3 °C, p = 0.0002). However, fluid requirements, vasopressor doses, heart rate, arterial pressure, intracranial pressure and ECMO flow were similar between groups. Blood gases and biomarkers (including troponin I, creatinine, ALAT and Protein S100β) showed no relevant differences. Withholding active temperature regulation during early VA-ECMO after refractory cardiac arrest resulted in lower core temperatures but did not significantly affect macrohemodynamics, ECMO flow, fluids/vasopressor needs, or ultra early impact on target organs biomarkers. The short use of simplified ECMO circuits without active temperature management does not appear to result in severe hypothermia or major early hemodynamic instability over a clinically realistic transport like timeframe.
Acute Respiratory Distress Syndrome (ARDS) is marked by spatial heterogeneity in lung structure and mechanical behavior, limiting the ability of global physiologic measurements to guide ventilatory management and prevent ventilator-induced lung injury (VILI). X-ray computed tomography (CT) has emerged as a central imaging modality for characterizing regional differences in lung aeration, deformation, and mechanical properties that underlie such heterogeneity. When combined with quantitative image processing, deformable image registration, and computational modeling, CT enables regional assessment of lung strain, recruitment, and computationally inferred estimates of regional mechanical stress in injured lungs. This review summarizes CT-based methods for the quantitative evaluation of lung mechanical properties in ARDS, including image acquisition, segmentation, aeration analysis, deformable registration, and biomechanical modeling. Experimental and translational evidence is discussed to illustrate how CT has advanced the mechanistic understanding of regional ventilation distribution and deformation patterns that contribute to VILI. Methodological limitations and translational challenges are also discussed. Emerging directions, such as portable, low-dose, and photon counting CT are considered in the context of critically ill patients and their potential use for bedside assessment of lung mechanics. In ARDS, lung structure and mechanics are highly heterogeneous, causing mechanical ventilation to generate uneven regional strains and stresses that are not captured by global respiratory mechanical measurements. Quantitative CT provides a regional view of lung aeration and deformation that helps explain the regional mechanisms underlying VILI. 140-character Tweet: CT imaging shows promise for quantifying regional lung mechanics in ARDS and potential risk factors for ventilator-induced lung injury.
Abstract Background Acute lung injury (ALI) after extracorporeal circulation can originate from multiple causes, including transfusion. Despite improvements in blood safety policy, transfusion-related lung injury (TRALI) continues to occur, suggesting an incomplete understanding of its pathogenesis. Objectives To evaluate the association between the composition of the red blood cell unit (RBC) and the onset of ALI after transfusion, defined by a ratio between partial pressure of oxygen (PaO 2 ) and the fraction of inspired oxygen (FiO 2 ) ≤ 300 mmHg in the first 3 days postoperatively. Methods Adults undergoing scheduled cardiac surgery at Nantes University Hospital between September 2016 and March 2021 and requiring transfusion of 1–5 RBC during surgery were included. To determine the exposure of each patient (i.e., total amount of inflammatory proteins received during transfusion), we analyzed the composition (panel of 15 proteins) of each RBC received by the participants. After stimulation of peripheral blood mononuclear cells (PBMC) with supernatant RBC (SN-RBC), NK cell cytotoxicity to pulmonary epithelial cells (Calu_3 cells) was assessed. Finally, we determined the association between SN-RBC composition, patient characteristics, and blood donation preparation methods. Results Over the study period, 161 patients were included, of whom 54 (33.5%) developed ALI within the first 3 days. Patients with ALI had a significantly higher median (IQR) exposure to SDF_1α than non-ALI patients 2.0 × 10 4 (0.0 to 4.2 × 10 4 ) vs. 1.0 × 10 4 (0.0 to 2.7 × 10 4 ) picograms, P = 0.02. In vitro, PBMC coculture with SN-RBC containing high levels of SDF_1α enhanced NKG2D-dependant NKG2A + NK cell cytotoxicity to Calu_3 cells. RBC from female donors or donors with platelet counts higher than 300 × 10 9 /L showed the highest concentration of SDF_1α, as well as RBC prepared by "whole blood filtration". Conclusions High exposure to SDF_1α through transfusion may be associated with the onset of ALI following cardiac surgery. The increase in NKG2D-dependent cytotoxicity of NKG2A + NK cells is a possible explanation for this finding. These results advocate for better characterization of the determinants of RBC composition and for developing new immune strategies to mitigate transfusion side effects.
Sepsis damages endothelial cells through glycocalyx degradation, contributing to organ dysfunction. Glycocalyx repair is essential for recovery, but the underlying mechanisms remain unclear. Rhamnan sulfate (RS), a sulfated polysaccharide with anti-inflammatory properties, may support endothelial glycocalyx repair. In this study, we investigated the glycocalyx repair process and the therapeutic potential of RS using a mouse sepsis model. Sepsis was induced in male C57BL/6 mice by cecal ligation and puncture (CLP). Mice were divided into the RS, control (CTL), and sham groups. RS was orally administered to the RS group, while the CTL group received no treatment after CLP. Sham mice underwent laparotomy only without CLP. Endothelial glycocalyx repair was evaluated using transmission electron microscopy (TEM) and scanning electron microscopy (SEM), and quantitative TEM analysis. Gene expressions of glycocalyx-related enzymes and inflammatory cytokines were assessed in liver and small intestine tissues by quantitative real-time PCR. The 7-day survival rate after CLP was significantly higher in the RS group (55
Abstract Background Sepsis and septic shock are life-threatening syndromes characterized by complex systemic effects, including alterations in tissue oxygenation, mitochondrial function, and organ performance. Despite advances in supportive care, management remains challenging and is largely focused on maintaining adequate perfusion through fluids and vasoactive agents. To better characterize early systemic responses to endotoxemia under different hemodynamic conditions, this study used a swine lipopolysaccharide (LPS)-induced endotoxemia model with graded hypotension exposure. Animals were allocated to a control group (MAP maintained > 80 mmHg) and two LPS-groups defined by different MAP thresholds for initiating hemodynamic support (LPS-1: <80 mmHg; LPS-2: <65 mmHg), with a focus on early mitochondrial and microcirculatory (dys)function. Results LPS administration induced marked systemic responses, including tachycardia, metabolic stress, and organ dysfunction. Microcirculatory alterations were present but quantitatively modest. In vivo mitochondrial oxygen tension (mitoPO 2 ) remained largely preserved or was only transiently affected, whereas mitochondrial oxygen consumption (mitoVO 2 ) was reduced or showed a blunted time course in the epidermis and liver. In contrast, ex vivo analyses revealed increased mitochondrial respiratory flux in peripheral blood mononuclear cells during early endotoxemia. More permissive hypotension was associated with a greater cumulative hypotension burden and stronger renal injury signals, including higher neutrophil gelatinase-associated lipocalin concentrations and reduced renal clearance. Arterial lactate concentrations increased during endotoxemia and were inversely associated with hepatic indocyanine green plasma disappearance rate. Conclusion Early LPS-induced endotoxemia was associated with reduced or blunted mitoVO 2 despite largely preserved mitoPO 2 , consistent with partial uncoupling between mitochondrial oxygen availability and utilization. Microcirculatory alterations were modest and unlikely to fully account for the observed changes in mitoVO 2 . Supportive ex vivo and organ function findings indicated increased mitochondrial respiratory activity and early renal vulnerability under more permissive hypotension. Together these findings highlight that mitoVO 2 is a valuable parameter in combination with mitoPO 2 to probe tissue-level mitochondrial function during early endotoxemia.
Although prevalent in critical care, sepsis-associated acute lung injury (sALI) lacks a clear mechanistic framework and disease-modifying therapies. In this narrative review, we synthesize clinical and experimental data implicating lipid mediators (LMs) as underappreciated drivers of pulmonary barrier failure in sALI. LMs are known activators or sensitizers of transient receptor potential (TRP) channels expressed in non-neuronal lung cells. In endothelial and epithelial compartments, activation of TRP channels elevates intracellular Ca²⁺, increases microvascular permeability, impairs alveolar fluid clearance, and promotes pulmonary edema. Converging metabolomic and translational studies associate accumulation of specific LMs with respiratory failure, providing a mechanistic link between the LMs and TRP-dependent barrier dysfunction. We propose the activation of TRP channels by LMs as a key underlying mechanism of sALI. Clarifying this mechanism, biomarker-guided studies may enable more targeted clinical trials and ultimately improve outcomes in sALI.
Out-of-hospital cardiac arrest is associated with a low rate of favourable neurological recovery, estimated at 8
An adequate endotracheal tube depth is crucial for airway management and effective mechanical ventilation, as both too deep and superficial tube placement can be harmful to the patient. The aim of this study was to evaluate endotracheal tube depth using the ultrasound double twist sign as a new diagnostic tool using a cadaver model. In this diagnostic accuracy study, ultrasounds were performed by 12 sonographers (2 expert and 10 novice users, consisting of residents and specialists) on 3 cadavers. Novice users learned the technique in 15 min. Tubes were randomized to be placed in adequate, deep (tube tip touching main carina) or superficial (cranial edge of cuff touching vocal cords) position. The double twist sign showed an overall success rate of 90.6
Early and adequate source control (SC) is a cornerstone of sepsis management, yet experimental data linking delays in SC to bacterial dissemination and remote organ injury remain limited. We aimed to determine how the timing of surgical SC after polymicrobial abdominal sepsis influences bacterial burden, host inflammatory response, and lung injury. Hemodynamic recovery was assessed as a secondary outcome, and survival as an exploratory outcome. Adult Wistar rats underwent cecal ligation and puncture (CLP) and received standardized fluid resuscitation and meropenem. Surgical SC (cecal resection plus peritoneal lavage) was performed at 6, 12, 18 or 24 h after CLP, or not performed, and outcomes were assessed at 72 h (hemodynamics, lactate, bacterial counts in blood/peritoneal lavage/bronchoalveolar lavage, systemic and pulmonary cytokines, bronchoalveolar lavage cellularity and histology). Surgical SC within 6–12 h was associated with lower bacterial burden across blood, peritoneal lavage, and bronchoalveolar lavage, together with attenuation of systemic and pulmonary inflammatory mediators and reduced lung injury. These biological effects were accompanied by improved mean arterial pressure, lower lactate, and preservation of body weight. Survival analysis suggested a numerically time-dependent pattern according to SC timing; however, these data were exploratory and the study was not powered to detect mortality differences. In this clinically relevant CLP rat model, earlier surgical SC (≤ 12 h) was associated with lower bacterial burden, attenuation of systemic and pulmonary inflammation, reduced sepsis-associated lung injury, and improved physiological recovery. These findings reinforce the importance of timely source control in abdominal sepsis and provide experimental support for avoiding unnecessary delay.
Sepsis, a dysregulated host response to infection leading to organ failure, remains a leading cause of death worldwide, reflecting the failure to translate preclinical findings into clinical therapies. This translational gap is partly driven by substantial variability and limited reproducibility of preclinical models, particularly the cecal ligation and puncture (CLP) model, widely regarded as the gold standard among experimental sepsis models. Although multiple biological and methodological variables influence outcomes, their relative contributions remain incompletely defined, and standardized approaches for integrated immune and hematopoietic profiling are lacking. We established and validated a standardized experimental and analytical framework for CLP-induced sepsis, enabling controlled disease severity and integrated assessment of local and systemic immune responses. A total of 88 C57BL/6 mice underwent mid-grade sepsis (target survival 70
Background Low-titer group O whole blood (LTOWB) is increasingly used for hemorrhagic resuscitation in trauma and critical care, but the phenotype of platelets maintained within refrigerated LTOWB remains incompletely characterized. Because platelet activation may influence not only hemostatic competence but also transfusion-related inflammatory and pulmonary responses in critically ill patients, we assessed platelet surface markers in LTOWB in comparison with standard platelet concentrates and examined their evolution during 8 days of cold storage.Methods LTOWB units prepared from qualified group O donors were stored under refrigerated conditions and studied at day 0 and day 8. Platelet phenotype was assessed by flow cytometry using CD41, CD62P, and CD63 under basal conditions and after thrombin receptor-activating peptide (TRAP) stimulation. LTOWB was compared with apheresis platelet concentrates (APC) and buffy coat-derived platelet concentrates (BC-PC).Results Compared with APC and BC-PC, LTOWB showed a broader distribution of CD41-positive events and a modestly lower median CD41 signal. Basal CD62P in LTOWB was lower than in APC but higher than in BC-PC, whereas basal CD63 in LTOWB was higher than in both comparator products. Between day 0 and day 8, basal CD62P and CD63 increased in LTOWB. TRAP induced marked upregulation of CD62P and CD63 at both time points; stimulated CD63 was lower at day 8 than at day 0, whereas stimulated CD62P remained high.Conclusion Cold-stored LTOWB displays a distinct platelet activation phenotype characterized by progressive basal activation during refrigerated storage together with persistent agonist-inducible responses through day 8. These findings justify further functional and translational studies integrating platelet, endothelial, and lung-injury readouts to determine whether this storage-associated phenotype has consequences for microvascular hemostasis, immunothrombosis, or transfusion-associated pulmonary complications after hemorrhagic resuscitation.
Sepsis is a syndrome of systemic inflammatory reaction caused by a severe infection, leading to multiorgan damage and a high mortality rate. In recent years, several studies have shown that decoy receptor 3 (DcR3) is positively correlated with the severity of infection, and its high specificity and sensitivity in the diagnosis of sepsis is expected to serve as a novel marker for sepsis. This meta-analysis aims to evaluate the diagnostic accuracy of decoy receptor 3 (DcR3) for sepsis in the intensive care unit (ICU) setting. We conducted a comprehensive search in six databases, extracting data independently.Studies were included if they assessed the diagnostic accuracy of DcR3 for sepsis in the intensive care unit (ICU). A meta-analysis was performed using a random-effects model to calculate pooled sensitivity, specificity, and area under the curve (AUC). Four records assessing 681 patients were included in this meta-analysis. In distinguishing sepsis from normal controls, DcR3 demonstrated exceptional discriminatory power with an AUC of 0.99. The pooled sensitivity was 0.98 (95
Abstract Background Withholding and withdrawing life-sustaining therapy (LST) is common in European ICUs but significant variations exist. Behaviour artificial intelligence technology (BAIT) may help standardize the ethical dilemma to continue or withdraw LST for patients already admitted to the ICU. Methods Several sessions with intensivists of an academic medical centre and a large urban teaching hospital were held to determine the criteria influencing the process. A discrete choice experiment was conducted during which 25 hypothetical cases were presented to the participants. For each case the participants had to decide whether they would continue, continue with a time limited trial of one week, or withdraw LST. The results of the experiment were used to develop a multinomial logistic regression model that was incorporated in a web-based decision-support system. Results Thirty-six participants (intensivists and fellows in intensive care medicine) completed the experiment. The estimated model consisted of twelve covariates and showed good model fit (McFadden’s ρ 2 0.25). The most important covariates were age, patient values, expected cardiovascular and pulmonary impairment after ICU discharge and frailty at admission. The BAIT system lets intensivists view expected decisions based on documented criteria and uses color-coding to show the magnitude of the effect and its direction (i.e. to continue or withdraw LST). Conclusions We developed a BAIT system that may support clinicians facing the dilemma of continuing or withdrawing LST by elucidating the key criteria involved in assessing medical futility.
