Intensive Care Medicine Experimental最新文献

Background: Cardiopulmonary bypass (CPB) is integral to the conduct of cardiac surgery but is associated with postoperative acute kidney injury (AKI). Dexmedetomidine, an α₂-adrenoceptor agonist with anti-inflammatory and sympatholytic properties, has putative renoprotective effects. In a recent meta-analysis, dexmedetomidine during CPB reduced AKI; conversely, a large, randomised trial reported an increase in postoperative AKI. Further, we found increased renal tubular injury in sheep receiving dexmedetomidine during CPB. Here, we aimed to determine whether dexmedetomidine during CPB induces changes in renal vascular reactivity or endothelial integrity that could explain focal renal tubular injury.

Methods: Fourteen instrumented Merino ewes underwent 2 h of non-pulsatile CPB (flow 70 mL/kg/min; MAP 65-75 mmHg; cooled by 3 °C) under standardised propofol-fentanyl-sevoflurane anaesthesia. Animals were randomly allocated to dexmedetomidine (0.4-0.8 µg/kg/h, n = 7) or fluid-matched saline (n = 7) from induction of anesthesia to end-CPB. Arterial pressure, renal blood flow, cortical and medullary perfusion and PO₂ were measured in vivo (n = 7/group). Post-CPB, renal interlobar arteries were isolated for wire myography. Due to standardisation failures, in vitro analyses of dose-response curves for phenylephrine were performed in n = 6 per group, while endothelial-dependent and independent relaxation responses were performed in n = 7 per group. Endothelial histology of CPB arteries was compared with arteries from a separate cohort of healthy Merino ewes (n = 7).

Results: In vitro functional investigations demonstrated that interlobar arteries from dexmedetomidine-treated sheep exhibited a 2.3-fold increase in phenylephrine sensitivity (pEC₅₀ 5.82 ± 0.27 vs. 5.45 ± 0.23; p = 0.034), with unchanged maximal contraction. Endothelium-dependent and independent relaxations were similar between groups, though inhibitor studies indicated a shift towards cyclooxygenase-mediated dilation under dexmedetomidine. Histology revealed intact endothelial architecture and no damage to endothelial integrity in all groups.

Conclusions: Perioperative dexmedetomidine during CPB enhanced α₁-adrenergic vasoconstrictor sensitivity in renal interlobar arteries without disrupting endothelial integrity or compromising renal blood flow or intrarenal perfusion. The enhanced vasoreactivity may contribute to focal renal ischaemia and tubular injury during CPB, which cannot be detected by in vivo measurements of global and regional kidney perfusion and oxygenation. Further investigation is warranted to elucidate the pathways through which dexmedetomidine contributes to renal tubular injury during CPB.

Background: Cardiac arrest (CA) remains a leading cause of mortality and long-term neurological disability. In cases of refractory CA, extracorporeal cardiopulmonary resuscitation (ECPR) may be implemented as a salvage therapy to mitigate hypoxic-ischemic brain injury and improve outcomes. However, the optimal target temperature in the specific context of ECPR remains uncertain. The objective of this study was to evaluate the impact of hypothermia on brain function using a controlled experimental model of ECPR.

Methods: Twelve pigs were subjected to 5 min of untreated ventricular fibrillation, followed by 25 min of conventional cardiopulmonary resuscitation (CPR). At 30 min, veno-arterial extracorporeal membrane oxygenation support was initiated, and defibrillation attempts were performed until the achievement of return of spontaneous circulation (ROSC). Following ROSC, animals were randomly assigned to one of two groups: hypothermia (HT), targeting a core body temperature of 33-34 °C, or controlled normothermia (NT), targeting 37-38 °C. All animals underwent continuous multimodal neurological and cardiovascular monitoring. Blood samples were collected at predefined time points to assess circulating biomarkers of organ injury. The primary outcome was the change of brain tissue oxygen tension (PbtO₂) over time. Other neurological and hemodynamical parameters were treated as secondary analyses. At 12 h post-ROSC, animals were euthanized via intracardiac injection of potassium chloride. Brain tissues were immediately harvested and appropriately stored for molecular analyses.

Results: A total of 12 pigs were included in the study, with six animals allocated to each group. Baseline characteristics were comparable between the groups and ROSC was achieved in all animals. Throughout the experiment, PbtO₂ gradually declined and intracranial pressure (ICP) increased in both groups; however, no significant differences were observed between groups. Similarly, there were no significant differences in cerebral metabolites, cortical activity, or gene expression in either frontal or parietal brain tissues. Notably, neurofilament light chain (NfL) concentrations were significantly lower at the end of the observation period in the HT group compared to NT (p = 0.04), while neuron-specific enolase (NSE) and glial fibrillary acidic protein (GFAP) levels did not differ significantly between the two groups.

Conclusions: HT did not improve cerebral perfusion or metabolic parameters in this refractory cardiac arrest ECPR model; the early decrease in NfL levels requires cautious interpretation and further investigation.

Background: Sepsis-associated encephalopathy (SAE) is a common complication of sepsis, contributing to poor outcomes and increased mortality. Early detection remains challenging due to the absence of observable direct brain injury. Transcranial Doppler (TCD) ultrasonography provides a non-invasive, bedside tool for assessing cerebral hemodynamics and may help identify patients at risk. SAE was defined as new-onset delirium (positive CAM-ICU) or unexplained coma (GCS < 8) not attributable to structural or metabolic causes. This study aimed to evaluate the role of TCD in predicting the incidence and prognosis of SAE in septic patients admitted to the ICU.

Methods: This prospective cohort study included 93 patients with sepsis. Demographic, clinical, and laboratory data were recorded upon admission. Daily TCD was performed for seven consecutive days to measure the pulsatility index (PI) and resistive index (RI). Neurological dysfunction was assessed daily using the Confusion Assessment Method for the ICU (CAM-ICU) and the Glasgow Coma Scale (GCS).

Results: A total of 93 patients were included, of whom 44 (47.3%) developed SAE. SAE patients showed greater illness severity, with higher median SOFA (6 [5-7] vs. 5 [3-6], p < 0.001) and APACHE II (14 [12-17] vs. 11 [9-14], p < 0.001) scores, and higher 28-day mortality (61.4% vs. 22.4%, p < 0.001). The median PI and RI were consistently higher in SAE patients across all study days, while the mean flow velocity (mFV) was lower. PI on day 1 had the best accuracy for predicting SAE, with a cutoff ≥ 1.30 (AUC: 0.963, sensitivity 95.45%, specificity 100%). RI on day 3 was also highly predictive (AUC: 0.971, cutoff ≥ 0.67, sensitivity 95.45%, specificity 95.92%).

Conclusions: In this sample of septic patients, PI and RI are strong predictors of SAE, with PI serving as a reliable early indicator of both SAE and mortality. Trial Preregistration The study was registered in the Pan African Clinical Trials Registry: PACTR202410707982429, date: 7/10/2024.

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.