Intensive Care Medicine Experimental最新文献

Introduction: Spontaneous breathing may have both protective and negative effects in patients with ARDS, according to the severity of lung injury. Scarce evidence is available for physicians to safely guide the transition from controlled to assisted ventilation of ARDS patients. We aimed at describing variations of V/Q matching, measured with electrical impedance tomography (EIT), in patients recovering from ARDS, ventilated with different levels of pressure support.

Methods: We performed a single-centre prospective observational study (Clinicaltrial.gov: NCT05781802), including adult mechanically ventilated patients admitted to the ICU with a diagnosis of ARDS according to the Berlin definition. The period of interest for the study was the transitioning phase from controlled to pressure support ventilation (PSV), and two observations were conducted. Data collection occurred at high and low pressure support, with each patient serving as his own control. The two conditions were defined according to a P0.1 threshold of 2 cmH2O (i.e. P0.1 < 2 cmH2O was considered "High PS" and P0.1 > 2 cmH2O was considered "Low PS"). The primary outcome was V/Q matching at the two different conditions.

Results: We included a total of 15 patients receiving pressure support ventilation, after a median of 3 days of protective controlled ventilation. The median age was 69 y.o., and P/F at ICU admission was 132 [125-150] mmHg. The ΔPsupport difference between the two observations was 10 [10-10] cmH2O; pCO2 was 41 [37-47] mmHg at high support and 45 [41-50] mmHg at low support (P < 0.05), while tidal volume decreased (10.4 [9.8-11.9] ml/kg high; 8 [7.1-9] ml/kg low, P < 0.01). V/Q matching did not significantly differ from high pressure support (56.1% [46.4-69]) to low-pressure support (61.7% [56.7-69.5], P = 0.847). Still, nine patients improved V/Q matching at lower support, and the improvement between the two study steps was correlated with a higher PEEP level (ρ = 0.539, P = 0.038).

Conclusions: Reducing the level of pressure support determined a redistribution of ventilation that did not, on average, result in improved V/Q matching compared to higher support. Our data underline the need for personalized settings during the transition from controlled to assisted mechanical ventilation in patients recovering from ARDS.

Lung ultrasound has become an indispensable tool in the management of acute respiratory failure, offering real-time, radiation-free bedside imaging. Its portability, repeatability, and high sensitivity for detecting pulmonary abnormalities have made it particularly valuable in critical care settings, especially during the Coronavirus disease 2019 pandemic. This narrative review explores the evolving role of lung ultrasound, examining both its established clinical applications and recent advances in artificial intelligence and imaging analysis. These developments emphasize the growing importance of lung ultrasound not only as a diagnostic tool but also as a platform for innovation, with artificial intelligence-driven approaches to further enhance its clinical utility.

Background: Various serum biomarkers and scoring systems are currently employed to manage septic critically ill patients. However, a paucity of biomarker evidence facilitates sepsis identification or prognosis. Mannose-binding lectin (MBL) is the main circulating protein in innate immunity. It acts as a broad-spectrum recognition molecule that binds most pathogens, along with their breakdown products and cell debris. We report results of an original approach dosing molecular patterns captured by FcMBL, an engineered version of MBL, in patients with septic shock. This study aimed at evaluating molecular patterns kinetics to assess their potential contribution to the clinical management of critically ill patients suffering from septic shock.

Results: This monocentric, prospective, observational study was conducted on adults admitted to the intensive care unit (ICU) for septic shock. Using magnetic microbeads coated with FcMBL, we quantified molecular patterns captured in blood and analyzed their kinetics for 5 days. Pathogen-associated molecular patterns (PAMP) levels were sampled at 6-h intervals over the first 24 h of ICU admission, then at 12 h intervals on Day 2, and then daily through Day 5. To align the data from the real time of admission to the ICU, the "Serial Measurements" module in MedCalc^® software enabled the incorporation of advanced methods, such as mixed models. Outcomes were the persistence of sepsis after Day 5 and adherence to routine sepsis metrics. Thirty-nine patients were included in the study. At Day 5, 21 patients had recovered from sepsis with a sequential organ failure assessment (SOFA) score < 2, while 18 were not. The initial values of PAMP yielded a median concentration of 5 ng/mL. The peak concentration was observed at 9 ng/mL, with a median delay of 24 h. Significant differences were observed in kinetic curves according to the SOFA score at Day 5, with a notable delay in time to peak (Tmax) for the prolonged sepsis group (Hour 48) compared to the short-term sepsis group (Hour 18) (p < 0.001). Compared to standard biomarkers, Tmax PAMP was the most discriminative factor for an unfavorable outcome.

Conclusions: Molecular pattern levels captured by FcMBL during septic shock exhibited large inter-patient variability, suggesting values depend on numerous parameters. The signal's kinetics demonstrated predictive value and may contribute to clinical management.

Trial registration: clinicaltrials, NCT03457038, Registered 15 October 2017, https://clinicaltrials.gov/study/NCT03457038.

Introduction: CO₂-derived variables, veno-arterial CO₂ content gradient (ΔCCO₂) and the ratio of ΔCCO₂ with arterio-venous oxygen difference (AV-DO₂) (ΔCCO2/AV-DO₂), may have a potential role as indicators of low cardiac output and anaerobic metabolism, respectively. We sought to describe and evaluate the association of CO₂-derived variables with patients' outcomes in the post cardiopulmonary bypass (CPB) period in children.

Methods: Prospective, single-center, study enrolling children post-CPB with paired arterial and venous blood gases for determination of lactate, O₂ extraction, ΔCCO₂, and ΔCCO₂/AV-DO₂ at admission (H0), and at 6 (H6), 12 (H12) and 24 (H24) hours. Different clinical patterns were defined based on the presence of an anaerobic context or a hypoperfusion context, using both O₂ and CO₂-derived variables. The presence of anaerobic metabolism was defined with a lactate > 2 mmol/l and ΔCCO₂/AV-DO₂ > 1.8; the presence of hypoperfusion was defined with an O₂ extraction > 30% and ΔCCO₂ > 6 mL. The potential association of duration of amine support and mechanical ventilation was tested with CO₂-derived variables and specific clinical patterns.

Results: A total of 51 patients with a median age of 36 (IQR 11-85) months were included. Median admission ΔCCO₂ was 9.3 mL (IQR 5.6-11.4) with 72% above 6 mL. Median ΔCCO₂/AV-DO₂ was 2.1 (IQR 1.5-2.4) with 58% above 1.8. Admission ΔCCO₂ showed a significant association with the duration of mechanical ventilation (R2 21.6, p value = 0.001) but not with the duration of vasoactive support. Neither H0 ΔCCO₂ nor H0 ΔCCO₂/AV-DO₂ improved outcome prediction by a model including lactate and O₂ extraction. Anaerobic metabolism context showed a significant association with prolonged vasoactive support [28.4 (CI 95% 12.2-44.6) p = 0.001] and mechanical ventilation duration [1.4 (95% CI 0.62-2.3) p = 0.003]. In hypoperfusion context, neither duration of vasoactive support nor mechanical ventilation appeared different in the subgroups analysis.

Conclusion: CO₂-derived variables may improve outcome prediction after cardiac surgery in pediatric patients. Further evaluation in larger multicentered trials is necessary to improve its validation.

Background: Critically ill patients frequently experience profound skeletal muscle (SM) wasting, to which early detection and effective clinical management remain significant challenges. Ultrasonography (US) provides early objective information about SM compared with usual functional tests. The characteristics of the optimal nutritional support are controversial. This observational study aimed to characterize the SM changes through US in the first week after Intensive Care Unit (ICU) admission and to evaluate the potential interference factors with a focus on nutritional support.

Results: A total of 95 patients (age 55.7 ± 16.01 years, 70.5% male) were included. All the ultrasound SM measures tendentially reduced after admission: quadriceps muscle layer thickness (QMLT) 10.03% (0.38 ± 0.73 cm), rectus femoris cross-sectional area (RF-CSA) 10.48% (0.50 ± 1.38 cm²), RF pennation angle (RF-PA) 0.94 ± 4.14 º, RF echogenicity (RF-EG) 1.05 ± 22.33 in echo-intensity gray scale and RF shear wave elastography (RF-SWE) 0.13 ± 1.25 m/s and 3.96 ± 28.10 kPa. A significant association between nutritional risk at baseline and SM changes (QMLT 0.194, p = 0.079 and RF-CSA 0.25, p = 0.027) was observed and confirmed in a linear regression model (1.257 and p = 0.011). No significant associations were found between SM changes and nutritional support.

Conclusion: Present findings demonstrate a marked reduction in the SM ultrasound measures evaluated in the first week after ICU admission, mainly in patients at nutritional risk. More evidence on optimal nutritional strategies to attenuate SM wasting is warranted.

Background: Despite advances in treatment, critically ill COVID-19 patients requiring intensive care unit (ICU) admission continue to comprise a substantial proportion of cases. However, the factors influencing poor prognosis in this population remain poorly understood. To address this knowledge gap, we conducted a prospective analysis of serum neutralizing activity against SARS-CoV-2 in 49 non-selected, critically ill COVID-19 patients enrolled in the multicenter SEVARVIR cohort between October 2022 and May 2024.

Methods: This a substudy of the SEVARVIR prospective multicenter observational cohort study (NCT05162508). We included 49 critically ill COVID-19 patients hospitalized in four French intensive care units between October 2022 and May 2024 from the 827 patients enrolled in the multicenter, prospective SEVARVIR study. Serum neutralizing titers of authentic SARS-CoV-2 isolates were measured using the S-Fuse assay and patients categorized as neutralizers if they had an anti-spike serum neutralization titer against the infecting variant > 15 and non-neutralizers if ≤ 15. Full-length SARS-CoV-2 genomes from all included patients were sequenced by means of next-generation sequencing.

Results: Median age was 73 years (59-75) and 34.7% of patients (n = 17/49) were female. Half of the patients (53.1%, n = 26/49) had immunosuppressive comorbidities. A large proportion of individuals lacked the capacity to neutralize their infecting variant (57.1%, n = 28/49). Neutralizing titers were significantly higher in 28-day survivors than in deceased patients (p = 0.0212) and neutralizers had a significantly lower 28-day mortality than non-neutralizers (5.0%, n = 1/21 vs. 32.1%, n = 9/28; p = 0.0312). Nine out of the ten patients who succumbed to the disease within 28 days of admission had undetectable serum neutralizing capacity, which was significantly more prevalent than in survivors (p = 0.03), irrespective of immunosuppression status. The sole patient who died despite having detectable neutralizing antibodies against SARS-CoV-2, was found to have anti-interferon auto-antibodies.

Conclusion: These findings underscore the potential benefits of early therapeutic interventions aimed at enhancing neutralization, which may improve survival outcomes in both immunocompetent and immunocompromised critically ill COVID-19 patients.

Background: Fluid overload in critically ill patients has been associated with muscle edema, decreased tissue quality, and the development of intensive care unit-acquired weakness (ICU-AW). Continuous renal replacement therapy (CRRT) with ultrafiltration (UF) contributes to removing excess extracellular fluid. This study aimed to evaluate whether UF is associated with changes in muscle ultrasound parameters and strength in critically ill patients.

Methods: Critically ill patients with resolved hypoperfusion undergoing CRRT with fluid removal via UF were prospectively enrolled and compared with a control group without UF. Muscle ultrasound assessments included rectus femoris and vastus intermedius thickness, echogenicity, and subcutaneous tissue. Global muscle strength was assessed using the Medical Research Council Sum Score (MRC-SS). Assessments were performed at CRRT initiation (T1) and again 36 h later (T2).

Results: Twenty-eight patients were enrolled, 18 in the UF group and 10 patients in the control group. All ultrasonographic variables measured were different between the UF and control groups. In the UF group, median rectus femoris thickness decreased from 1.74 to 1.57 cm (p = 0.03), vastus intermedius from 1.14 to 0.95 cm (p < 0.01), echogenicity from 91.7 to 78.3 grayscale units (p < 0.01), and subcutaneous tissue thickness from 1.98 to 1.79 cm (p < 0.01). MRC-SS increased from 45.0 to 49.0 points (p = 0.05). A positive correlation was found between UF volume (mL/kg) and MRC-SS at T2 (ρ = 0.71, p < 0.01), and a negative correlation between UF volume and change in muscle echogenicity (ρ = - 0.49, p = 0.039). ROC curve analysis identified that a UF volume ≥ 82 mL/kg was associated with MRC-SS > 48 points obtaining an AUC of 0.982 (95% CI: 0.928-1.000), sensitivity 92.9%, and specificity 100%.

Conclusion: Ultrafiltration was associated with changes in muscle echogenicity and subcutaneous tissue as well as an increase in MRC scoring at follow-up. These results suggest a potential relationship between fluid balance and muscle ultrasound parameters. No causal inferences can be drawn; therefore, further studies are needed.

The vascular waterfall phenomenon, rooted in Starling resistor principles, describes how blood flow becomes independent of downstream pressure when intraluminal pressure falls below a critical closing pressure (Pcrit). This review first introduces the classic arterial vascular waterfall, where local Pcrit enables organ-specific autoregulation of blood flow despite varying metabolic demands. Building on this framework, we extend the concept to the venous side, where similar mechanisms govern venous return and protect against congestion. The pulmonary vascular waterfall serves as a prototype, illustrating how alveolar pressures redefine downstream limits, shaping the effects of mechanical ventilation and positive end-expiratory pressure (PEEP). In valveless venous beds such as the hepatic veins, a reverse vascular waterfall may occur when elevated downstream pressure, typically right atrial pressure, causes brief, localized backflow buffered by vessel collapse and the emergence of a new Pcrit. These mechanisms explain organ-specific vulnerabilities to venous congestion: organs with effective venous waterfalls, such as the liver and intestine, can partially buffer overload, whereas the kidney, lacking such protection, is highly susceptible to venous pressure-dependent injury. Clinical implications include refined approaches to PEEP titration, fluid management balancing responsiveness with tolerance, and congestion assessment through Doppler ultrasound. Reframing congestion as a dynamic Starling resistor process explains why similar CVP elevations produce heterogeneous organ effects and provides a mechanistic basis for individualized, physiology-guided critical care.

Sepsis remains a leading cause of death worldwide, characterized by a dysregulated host response to infection that results in organ dysfunction. Extracorporeal blood purification (EBP) therapies traditionally aim to remove circulating mediators involved in this pathological response, although novel technologies that can remove cells and even living pathogens have recently been developed. Despite their growing clinical use, robust evidence supporting EBP in septic shock as an adjuvant therapy is lacking, and several knowledge gaps hinder their effective and safe application. This narrative review critically examines these gaps from both mechanistic and clinical perspectives. Key issues include the dynamic and compartmentalized nature of the immune response, the unclear roles of specific cytokines, and the potential removal of protective anti-inflammatory mediators. Broad-spectrum adsorption may induce unintended immunomodulatory effects, including desorption and altered leukocyte trafficking. Selective approaches, such as endotoxin removal with polymyxin B hemoadsorption, face challenges related to dose, patient stratification, and the limitations of endotoxin activity assays. Therapeutic plasma exchange offers the potential to restore homeostasis but raises questions regarding optimal regimens, replacement fluids, and the risk of unintended drug clearance. The heterogeneity of trial designs, insufficient patient phenotyping, and variability in treatment protocols have led to inconclusive or conflicting clinical outcomes, including some trials suggesting potential harm. This review underscores the need for better mechanistic understanding, real-time immune monitoring, and ideally targeted clinical trial designs to define which patients might benefit from EBP and when. Ultimately, the path to effective application of EBP in sepsis lies in individualized therapy guided by immune profiling, biomarker-driven stratification, and rigorous evaluation in high-quality randomized controlled trials.

Background: The concurrent application of extracorporeal carbon dioxide removal (ECCO₂R) and continuous renal replacement therapy (CRRT) delivers essential respiratory and renal support. However, the use of bicarbonate (HCO₃⁻) in substitution solution increases the external HCO₃⁻ load and affect the carbon dioxide removal rate (VCO₂). This study aims to investigate the influence of low bicarbonate substitution solution on VCO₂ within the combined ECCO₂R-CRRT system.

Methods: This crossover study was conducted with hypercapnic pigs and patients with acute respiratory distress syndrome (ARDS). In pigs, we tested two extracorporeal blood flow rates (200 and 350 mL/min) alongside three continuous veno-venous hemofiltration (CVVH) strategies: a control group receiving ECCO₂R alone without CVVH, a low HCO₃⁻ group receiving ECCO₂R combined with CVVH (HCO₃⁻ concentration of 16 mmol/L at a substitution rate of 30 mL/kg/h), and a normal HCO₃⁻ group (HCO₃⁻ concentration of 25 mmol/L). Respiratory variables, hemodynamic parameters, and VCO₂ were measured 30 min after each intervention. In ARDS patients, we also assessed ECCO₂R combined with these CVVH strategies. The primary endpoint was the comparison of VCO₂ among the three groups in both the pig and patient.

Results: This study involved 12 hypercapnic pigs. At a blood flow rate of 200 mL/min, the VCO₂ were significantly different among groups (P = 0.029). The VCO₂ in the low HCO₃⁻ group (51.7 ± 6.0 mL/min) was significantly higher than that in the normal HCO₃⁻ group (46.1 ± 2.9 mL/min) and comparable to the control group (50.3 ± 5.4 mL/min). However, at a blood flow rate of 350 mL/min, VCO₂ values were similar across all three groups. In 10 ARDS patients with a mean age of 64 ± 8 years, the PaCO₂ was 60.0 ± 4.7 mmHg prior to ECCO₂R. At a blood flow rate of 293 ± 59 mL/min, VCO₂ did not change significantly in the low HCO₃⁻ group (77.0 ± 16.2 mL/min) compared to the control group (75.2 ± 15.9 mL/min), a decrease was noted in the normal HCO₃⁻ group (69.9 ± 16.6 mL/min, P < 0.010).

Conclusion: A low bicarbonate concentration of 16 mmol/L in the substitution solution may optimize CO₂ elimination in the ECCO₂R-CRRT system, especially at lower extracorporeal blood flow rates.