Intensive Care Medicine Experimental最新文献

Introduction: Venous congestion is a major contributor to organ dysfunction in critically ill and perioperative patients. While Doppler-based ultrasound strategies such as VExUS are the focus of growing clinical and research interest, the common femoral vein (CFV) is a promising, easily accessible alternative window for assessing right heart function and volume status.

Objective: To map and synthesize current evidence on the use of common femoral vein (CFV) Doppler ultrasound to assess venous congestion, right heart function, and intravascular volume status in adult patients across perioperative, critical care, heart failure, and emergency care settings.

Design: Scoping review conducted according to the PRISMA-ScR guideline.

Review methods: PubMed, Embase, Scopus, and the Cochrane Library were searched from inception to August 2025. We charted clinical setting, CFV Doppler/diameter parameters, acquisition protocol details, reference standards (invasive pressures and imaging-based surrogates), and reported associations with hemodynamic measures and clinical outcomes. Two reviewers independently screened records and extracted data.

Results: Nineteen observational studies (n = 2146) were included. CFV pulsatility or waveform morphology was assessed in 10/19 studies; 5/19 reported quantitative pulsatility indices or retrograde-flow thresholds, 5/19 evaluated femoral vein diameter/collapsibility, and 1/19 proposed derived indices. Most studies compared CFV measures with invasive central venous pressure (CVP) or echocardiographic surrogates; when correlation coefficients were reported, associations were weak-to-moderate (e.g., r = 0.66 for CFV diameter vs CVP; r = - 0.476 for minimum velocity vs CVP). Only a minority of studies assessed clinical outcomes, and abnormal CFV patterns were variably associated with postoperative complications, including acute kidney injury, delirium and, in ICU cohorts, longer ICU length of stay or mortality. Acquisition protocols and waveform interpretation criteria varied across studies, with heterogeneous definitions and thresholds.

Conclusions: CFV Doppler is a feasible and accessible tool for congestion assessment, with promising correlations to invasive measures. However, variability in acquisition protocols, waveform definitions, and thresholds limits its current applicability. Standardization and prospective validation in high-risk populations are needed.

Background: Dexmedetomidine (DEX) is increasingly used in the intensive care unit for sedation and also serves as an adjuvant in general anesthesia and in procedural sedations. We tested whether dexmedetomidine at different concentrations influences the activity of the neuromuscular junction at the diaphragm and whether DEX has an impact on the action of rocuronium at the diaphragm as well as the reversal of the neuromuscular block by sugammadex.

Methods: 20 male Wistar rat phrenic nerve-hemidiaphragm system was used for our experiments. The concentration-response characteristics of DEX and rocuronium were quantified as the depression of the force amplitude of single twitches (ST) in response to electrical stimulation of the phrenic nerve. Rocuronium concentration-response curves were obtained with 0, 1, and 2.67 μg/ml DEX concentration. After a single dose of rocuronium, sugammadex doses were given until additional doses of sugammadex were not accompanied by a further increase in ST force amplitude. The concentration-response curve of sugammadex was also measured in the presence of 1 μg/ml DEX concentration.

Results: DEX at different doses negligibly reduces the force of the contractions and the contractility of the diaphragm. The EC50 of rocuronium [7.74 µM (6.99-8.57)] did not change significantly [7.18 µM (6.58-7.84); p = 0.27] with the addition of DEX 1 µg/ml. At 2.67 µg/ml DEX concentration, the ED50 of rocuronium was significantly reduced [6.37 µM (5.69-7.13); p = 0.015]. With 1 µg/ml DEX concentration, the EC50 of the sugammadex [2.04 µM (1.94-2.14)] needed for the reversal of rocuronium-induced neuromuscular blockade was significantly increased [2.45 µM (2.39-2.51); p < 0.01].

Conclusions: DEX at clinically administered doses does not significantly influence the function of the neuromuscular junction at the diaphragm. Under routine dosing conditions, the action of the neuromuscular blocking agents and their reversal by sugammadex are also not modified by DEX.

Background: Cardiac arrest (CA) is a major cause of mortality and morbidity. Accurate prediction of neurological outcome and survival remains challenging. In this context, our study aimed to explore novel molecular biomarkers that could provide additional insights into the pathophysiology of brain injury after CA and potentially distinguish patients with no brain injury (CPC 1) from those with any degree of neurological damage from moderate injury up to death (CPC 2-5), and complement existing prognostic tools.

Methods: Whole blood samples collected 48 h after return of spontaneous circulation were analyzed by RNA sequencing in a subgroup of 50 CA patients from the monocenter North Pole cohort, and by quantitative PCR in 233 patients from the same cohort as well as in 511 patients from the multicenter TTM trial. The association of gene expression changes with 6-month neurological outcome (assessed by the Cerebral Performance Category (CPC) score) and survival was studied.

Results: In a discovery phase with a subset of 50 patients from the North Pole cohort (25 CPC 1 and 25 CPC 5), direct RNA sequencing identified the solute carrier family 2 member 1 (SLC2A1), a gene encoding a major glucose transporter at the blood-brain barrier (GLUT1), as significantly upregulated in CPC 5 patients (dead with severe neurological impairment) compared to survivors without neurological sequelae (CPC 1). This upregulation was confirmed by quantitative PCR and extended to the entire North Pole cohort (p < 0.001). SLC2A1 was an independent predictor of neurological sequelae or death in this cohort. In the TTM trial, SLC2A1 was also upregulated in patients with neurological sequelae or death (p < 0.001) and was an independent predictor of neurological sequelae or death, providing an incremental predictive value to a baseline clinical model (odds ratio = 2.06, 95% confidence interval 1.31-3.4, p = 2.82E-03, and likelihood ratio test p < 0.001).

Conclusion: Blood level of SLC2A1 is a tentative blood biomarker that may aid in neurological outcome prediction after CA and also provide new insights into post-CA injury mechanisms.

The achieved technological maturity of electrical impedance tomography (EIT) and the clinical need of the information provided by this functional imaging method has intensified research activities on the medical use of chest EIT. The recent years have witnessed an accelerated research covering not only the experimental setting but also the clinical environment with the major focus on mechanically ventilated patients, both in the perioperative period or as part of the intensive care treatment. Patients of all age groups are being included in clinical investigations and studies using EIT. The major objectives for use of EIT are the monitoring of regional lung and cardiovascular function, identification of adverse events (pneumothorax, alveolar overdistension and collapse, pulmonary embolism) and guidance for individualised therapy (selection of ventilator setting, positioning and physical therapy). Our review describes the most recent achievements of experimental and clinical research on chest EIT. The provided information helps to identify the current hot topics in EIT research and to guide further improvements of EIT technology and applications that are still needed to enforce the establishment of chest EIT in routine patient care.

Background: In mechanically ventilated patients with acute respiratory distress syndrome (ARDS) it is of great importance to prevent ventilator-induced lung injury (VILI) using lung protective ventilation. VILI has been associated with a high mechanical power (MP). Flow-controlled ventilation (FCV) could play a role in decreasing the risk of VILI by lowering the MP and preventing atelectrauma by a controlled expiration.

Objectives: To assess the difference in MP between FCV and pressure-controlled ventilation (PCV). Secondary aims were to explore the effect of FCV in terms of ventilation distribution and homogeneity, measured by electrical impedance tomography (EIT).

Methods: Randomized crossover physiological pilot study in ICU patients with a moderate to severe ARDS. Patients were randomized between 90 min of FCV followed by 90 min of PCV, or vice versa. Intratracheal and esophageal pressure, airway flow and EIT were measured continuously, and hemodynamics and venous and arterial blood gases were obtained repeatedly. Pressure-volume loops were constructed for the calculation of the MP.

Results: In 10 patients, optimized FCV (compliance-guided driving pressure) versus PCV resulted in a similar MP (12.6 vs. 14.8 J/min; p = 0.302). A stable gas exchange at similar minute volumes was obtained. Optimized FCV resulted in increased tidal ventilation of the mid-ventral to dorsal regions compared to PCV, but EIT demonstrated a trend towards overdistension especially of the non-dependent lung regions. Because of this trend towards overdistension, severe hypercapnia in one patient, and inability to apply FCV as intended, the study was stopped early due to safety concerns.

Conclusions: Optimized FCV compared with PCV resulted in a similar MP and tends towards overdistension in patients with moderate to severe ARDS.

Trial registration: Clinicaltrials.gov identifier: NCT06051188. Registered 22 September 2023.

Background: The "Personalized Mechanical Ventilation Guided by Lung UltraSound in Patients with Acute Respiratory Distress Syndrome" (PEGASUS) study aims to evaluate personalized mechanical ventilation (MV) in patients with acute respiratory distress syndrome (ARDS) compared to the standard of care. However, misclassification and misaligned MV strategies were shown to be harmful. We therefore aimed to assess the interobserver agreement of lung ultrasound (LUS) between the local investigator and an expert panel in classifying ARDS subphenotypes alongside protocol adherence and safety endpoints, as a pilot phase of the ongoing PEGASUS study.

Methods: The first 80 mechanically ventilated patients with moderate-to-severe ARDS were enrolled in the ongoing PEGASUS study, a randomized clinical trial (RCT), and were included in the pilot phase. Focal or non-focal subphenotypes were classified using a LUS. Positive end-expiratory pressures (PEEP), tidal volumes (VT), the application of recruitment manoeuvres, and proning were performed according to randomization arm and subphenotype. Safety limits for MV followed current guidelines. Agreement in subphenotype classification between local investigators and a panel of three experts was evaluated using Cohen's κ coefficient.

Results: In 68 out of 80 exams, the images were of sufficient quality for assessment. The interobserver agreement for the lung morphology had a Cohen's kappa of 0.72 (95% CI 0.53-0.9) and accuracy of 88% between local investigator and the expert panel. Misclassification occurred in 8/68 exams (11.8%). Among these 8 misclassified cases, 6 (75%) also showed disagreement between experts due to different LUS scores of the anterior regions. Tidal volume and PEEP were generally set according to the protocol. An exception was the TV in the non-focal ARDS patients randomized to personalized MV, where the median (6.2 ml/kg/PBW) was above the target range (4-6 ml/kg/PBW). Patients exceeding safety limits of MV were low.

Conclusion: In the pilot phase of an ongoing international subphenotype-targeted RCT, we found that local investigators' assessments agreed with expert panel consensus assessments in the large majority of cases, and nearly always when the expert panel assessment was unanimous. Protocol adherence was sufficient, but tidal volume in the non-focal subphenotype deserves attention during continuation of the study.

Trial registration: The study was registered on clinicaltrial.gov (ID: NCT05492344, date 2022-08-05).

Background: Sepsis-associated acute kidney injury (SA-AKI) is a common and severe complication in critically ill patients, but the association between hypoxemia and renal dysfunction remains uncertain.

Method: We retrospectively analyzed 2292 patients with SA-AKI from the MIMIC-IV database and stratified them into four groups based on their highest arterial partial pressure of oxygen (PO₂) within 24 h of admission: < 60 mmHg, ≥ 60 to < 80 mmHg, ≥ 80 to  < 100 mmHg, and ≥ 100 mmHg. Associations between PO₂ and renal injury markers (serum creatinine [SCr] and blood urea nitrogen [BUN]) were evaluated using multivariable regression analyses, and survival outcomes were compared with Kaplan-Meier methods. To explore mechanistic pathways, a murine model was established with four experimental conditions: normoxia, hypoxia (10% O₂), lipopolysaccharide (LPS)-induced sepsis, and combined sepsis plus hypoxia. Serum biochemical parameters, histological injury, and protein expression of hypoxia-inducible factor-1α (HIF-1α) were measured at 6, 24, and 48 h. Mitochondrial autophagy was assessed by LC3 and TOMM20 immunofluorescence colocalization.

Result: Patients with lower PO₂ had higher illness severity and unadjusted BUN and SCr levels, multivariable analyses revealed no independent association between PO₂ and renal injury markers. Survival differed significantly across groups, with the ≥ 100 mmHg group showing the best outcomes (log-rank P < 0.001). In animal experiments, sepsis groups developed increased SCr and BUN at 24 and 48 h, but combined hypoxia did not exacerbate these parameters compared to sepsis alone. Histological analysis revealed severe tubular injury with no significant aggravation in the sepsis-plus hypoxia group. HIF-1α expression was lowest in sepsis-only kidneys but markedly upregulated in the sepsis-plus-hypoxia group at 6 h. Immunofluorescence demonstrated less colocalization of LC3 and TOMM20 in the sepsis-only group than in sepsis-plus-hypoxia mice, suggesting more efficient mitophagy with hypoxemia.

Conclusions: These clinical and experimental findings indicate that hypoxemia was not independently associated with aggravated renal injury in SA-AKI and may activate HIF-1α and promote adaptive mitophagy. This challenges the conventionally held belief that hypoxemia is uniformly detrimental to renal function during sepsis.

Background: Acute pulmonary embolism (PE) is a leading cause of cardiovascular death, primarily due to abrupt increased pulmonary vascular resistance (PVR) leading to acute right ventricular (RV) failure. Ketone bodies, especially 3-hydroxybutyrate (3-OHB), have shown potential to increase cardiac output (CO) and reduce PVR in pulmonary hypertension, suggesting possible benefits in PE. We hypothesized that 3-OHB would induce pulmonary vasorelaxation and increase CO in a porcine model of acute PE.

Methods: We conducted a randomized, controlled, assessor-blinded study in a porcine model of acute PE. Acute PE was induced, followed by a 3-h infusion of 3-OHB (0.22 g/kg/h, n = 8) or control (isovolumic saline of equimolar tonicity) (n = 8). Hemodynamic parameters were monitored hourly including right heart catheterization and RV pressure-volume loop acquisition. Primary outcome was the difference in CO during 3 h. Ex vivo effects on isolated pulmonary arteries were tested using wire myography.

Results: Compared with control infusion, 3-OHB did not increase CO significantly (between-group difference: 0.7 [-0.2 to 1.6] L/min, p = 0.131). However, 3-OHB treatment lowered the PVR/systemic vascular resistance (SVR) ratio (-0.05 [-0.09; -0.01], p = 0.046) and increased pulmonary artery pulsatility index (5 [2-8], p = 0.006). Ex vivo, 3-OHB caused vasorelaxation in pre-contracted pulmonary arteries (p < 0.0001).

Conclusions: 3-OHB reduced PVR/SVR ratio, while CO was not significantly increased in a porcine model of acute PE. The present findings demonstrated potential hemodynamic effects in PE. Further studies are needed to explore the translational potential of ketone body therapy in humans with PE.

Background: Uncontrolled hemorrhagic shock (UHS) is prevalent in military operations, disaster relief, and traffic accidents at high altitudes. Due to reduced tolerance to resuscitation fluids and prolonged evacuation times, its management poses substantial challenges. Whether 4-phenylbutyric acid (PBA) can protect vital organ function and extend the golden period for UHS at high altitudes remains unclear.

Methods: Rats airlifted from Chongqing to Lhasa were used to establish a UHS model. The experiment consisted of three parts: Part 1 investigated PBA's effect on extending the golden period (prehospital treatment window). Specifically, using a high-altitude rat model of UHS, we observe the duration that PBA + LR maintains mean arterial pressure (MAP) at 50-60 mmHg without definitive hemostasis; Parts 2 and 3 involve hypotensive maintenance of MAP at 50-60 mmHg for 1 and 2 h, respectively, prior to definitive hemostasis, simulating 1-h and 2-h prehospital phases. After hypotensive maintenance, definitive hemostasis is performed. Parameters including vital organ injury markers, blood gas profiles, and survival rates were assessed.

Results: In Part 1, PBA (20 mg/kg) reduced blood loss by 13.3% (from 53.6 ± 2.4% to 45.28 ± 3.4%) and resuscitation fluid volume by 28% compared to LR alone. PBA (20 mg/kg) prolonged the duration of sustained hypotensive resuscitation by 243% (from 39 ± 4.6 min to 134 ± 10.6 min) compared to LR, stabilized hemodynamics, and improved 2-h survival from 12.5% to 62.5%. In Part 2, 20 mg/kg PBA attenuated vital organ damage, increased 72-h survival from 18.7% (LR group) to 50% (20 mg/kg PBA group), and meanwhile reduced blood loss by 7.7% and resuscitation fluid volume by 16.3% compared to LR alone. In Part 3, despite extending hypotensive resuscitation to 2 h, PBA still significantly ameliorated organ function, reduced blood loss, decreased fluid administration, and enhanced 72-h survival in rats from 0% (LR group) to 31.25% (20 mg/kg PBA group).

Conclusion: PBA administration during hypotensive resuscitation protects vital organs (heart, liver, kidney), reduces pulmonary and cerebral edema incidence, and significantly extends the golden period for UHS at high altitudes.