Intensive Care Medicine Experimental最新文献

Background: Low systolic blood pressure (SBP) is a key criterion for diagnosing cardiogenic shock (CS) caused by a reduction in stroke volume and cardiac output (CO). The temporal interaction between changes in pressure and flow has not been well described in the development of CS. In a large animal model, we assessed the temporal relationships of SBP, CO, and blood flow in the carotid artery during induction of CS.

Methods: Fifteen adult Danish landrace pigs (median weight 71 kg) underwent CS induction by stepwise injection of polyvinyl alcohol microspheres into the left main coronary artery every 3 min to induce microvascular obstruction. After each injection, CO, SBP, and mixed venous saturation (SvO₂) were recorded simultaneously from a ventricle sheath in the carotid artery and a pulmonary artery catheter in the right internal jugular vein. A Doppler flow probe measured blood flow in the left carotid artery. CS was defined as a ≥ 50% reduction in CO or SvO₂ from baseline, or absolute SvO₂ < 30%.

Results: CS occurred after a mean of 8 (range 5 to 19) boluses of microspheres. SBP declined from 99 (± 15) mmHg to 74 (± 6) mmHg, equal to 74 (± 13)% of the baseline value. CO was reduced to 5.8 (± 0.7) L/min to 2.2 (± 1.3) L/min, equal to 38 (± 23)% and SvO₂ from 63 (± 7)% to 37 (± 7)%, equal to 60 (± 13)% of baseline values. The decrease in CO was due to a reduction to 43 (± 26)% in stroke volume, as heart rate remained unchanged. The carotid artery blood flow was reduced from 285 (± 50) mL/min to 155 (± 56) mL/min, equal to 54% of baseline values. The decline in SvO₂ and CO preceded a reduction in SBP, and after 25% of emboli were given, CO decreased by 24% while SBP was unchanged.

Conclusion: In a porcine model of ischemic myocardial injury, the decrease in blood flow and stroke volume preceded a decline in SBP, suggesting pressure preservation occurs in the presence of hypoperfusion.

Dobutamine is the most commonly used inotropic agent in critically ill patients with impaired cardiac contractility. However, its benefit-risk profile remains debated, and clear, structured guidance for its use is lacking. This hypothesis proposes a pragmatic framework for dobutamine administration to promote rational and consistent clinical and experimental practice. The aim is to propose a rational and reproducible use of inotropic therapy with dobutamine in both clinical and experimental settings in cases of shock with low cardiac output, particularly cardiogenic shock, septic shock with septic cardiomyopathy, and low cardiac output syndrome after cardiac surgery (LCOS). Dobutamine should be prescribed only in the presence of acute circulatory failure with signs of peripheral hypoperfusion and impaired cardiac contractility. A low cardiac index (CI) alone does not mandate inotrope initiation. Echocardiography is essential for initial assessment but should be complemented by continuous cardiac output monitoring for evaluating dose-response. The recommended starting dose is 2.5 μg/kg*min, with stepwise titration based on CI and perfusion markers reassessed every 20 min. A significant CI increase and resolution of hypoperfusion should guide further escalation. Persistent hypoperfusion despite CI improvement may indicate inadequate response and justify cautious dose increases, while continued hypoperfusion with further CI rise suggests a flow-independent deficit, discouraging further titration. Dobutamine should be used with clear indications, guided by a standardized approach integrating continuous hemodynamic and perfusion monitoring. This strategy may help optimize therapeutic benefit while minimizing unnecessary exposure and adverse effects.

Background: Critical illness is known to reduce gut microbiota (GM) diversity, a change associated with adverse outcomes. Among potential mechanisms, splanchnic hypoperfusion may play a key role. Cardiac arrest (CA), characterized by transient global hypoperfusion, provides a relevant model to explore this effect.

Results: We conducted a secondary, propensity score-matched analysis of a cohort study investigating GM changes during early intensive care unit stay. Stool samples were collected at ICU admission (S1) and at least 24 h later (S2). GM profiling was performed using 16S rRNA sequencing. Shannon diversity index and taxonomic composition were compared between CA and non-CA patients. Propensity score matching and generalized linear models (GLM) were used to adjust for confounding. A total of 26 patients were included in this analysis (13 CA, 13 matched controls). At S1, CA patients had significantly lower GM diversity (Shannon index: 3.6 [3.0-3.8] vs. 4.3 [3.9-4.8], p = 0.019). This was confirmed in the GLM (β = - 0.30, SE 0.12, p = 0.022). At S2, diversity remained lower (3.2 [2.7-3.8] vs. 4.0 [3.7-4.3], p = 0.064). While no global compositional shifts were observed between groups, differences in the abundance of specific taxa were noted.

Conclusion: CA is associated with reduced GM diversity in the first few days of intensive care unit admission compared to non-CA patients, supporting a role for splanchnic hypoperfusion in GM modulation. Further research should investigate clinical consequences and evaluate microbiota-targeted interventions in this high-risk population.

Background: Hypernatremia, a common electrolyte disorder in critically ill patients, induces a hyperosmotic state linked to increased mortality and metabolic stress. While loop diuretics such as furosemide are used for fluid management, their main effect is water excretion, often worsening hypernatremia. This study aimed to determine whether free water infusion enhances sodium excretion when combined with furosemide after a sodium chloride bolus. We also hypothesized that hyperosmolar hypernatremia stimulates protein degradation and urea synthesis.

Results: Fourteen pigs (seven per group) received a sodium chloride bolus to induce hypernatremia (plasma Na⁺ > 150 mmol/L). One group received furosemide alone, while the other received furosemide plus free water to maintain normo-osmolality. Renal and metabolic parameters were analyzed over five hours. Free water infusion significantly lowered plasma sodium levels (134 ± 4 vs. 150 ± 4 mmol/L, p = 1.2e-14) and increased total sodium excretion (99 ± 20 vs. 70 ± 18 mmol, p = 0.00056) and urine output (1860 ± 220 vs. 1200 ± 160 mL, p = 2.47e-05). Fractional sodium excretion was higher with free water (5.3 ± 1.1% vs. 3.5 ± 2.2%, p = 0.012). Plasma glutamine was elevated in the no-water group (1305 ± 209 vs. 1084 ± 110 µmol/L, p = 0.029), indicating greater metabolic stress.

Conclusions: These results suggest that free water infusion enhances sodium clearance and reduces hypernatremia-induced metabolic alterations, supporting its potential role in fluid management strategies.

Background and aims: Acute pulmonary thromboembolism (PE) may require haemodynamic supportive therapies while appropriate therapies for clot burden reduction are pursued. This scoping review aims to identify the non-mechanical haemodynamic support interventions that have been investigated for the management of acute PE, and to map the available evidence for each intervention.

Methods: An iterative search of MEDLINE, Embase, CINAHL and the Cochrane Library was performed to map all available animal studies, case-series, observational studies, human trials, systematic reviews and meta-analyses that investigate any non-mechanical haemodynamic support in acute PE.

Results: 6,362 unique articles were screened and of the 132 studies that met the eligibility criteria, 98 were animal studies, 31 human studies, and 3 were systematic reviews. Among all studies 57 different agents were found, including 16 among the human studies. 6 agents were investigated across 7 human randomised controlled trials (RCTs) and included inhaled nitric oxide, fluid, furosemide, diclofenac, sildenafil, and epoprostenol, but were limited to intermediate-risk PE and none demonstrated a mortality benefit from the intervention tested.

Conclusion: The evidence to guide clinical practice in the non-mechanical haemodynamic support of PE is severely limited. However, there are numerous candidate agents that could be further investigated. The high-risk group are an understudied population.

Transcranial ultrasound is gaining widespread recognition as a useful bedside monitoring tool and non-invasive diagnostic device in the critically ill patient. The capabilities of transcranial ultrasound are themselves ever-increasing, and this, combined with improved physiological understanding, affords insights into pathophysiological processes often concealed from the bedside critical care clinician. Transcranial ultrasound remains unique in regard to its non-invasive, rapid, and critically composite blood flow velocity-centric (not pressure-centric) information. The mobility of transcranial ultrasound devices is of particular value to the largely immobile critically ill patient requiring multiple organ supportive therapies. In this review, we discuss some important origins of more modern composite techniques and highlight relevant major key concepts, whilst noting exciting frontier possibilities.

Background: Histones released in response to cellular injury are important mediators of organ failure and death in sepsis. Preclinical studies demonstrate that neutralization of histones in sepsis is associated with improved outcome. M6229 is a low-anticoagulant heparin able to neutralize histones. We aimed to evaluate the safety, tolerability, pharmacokinetics and pharmacodynamics of M6229 in critically ill patients with sepsis.

Methods: This was a first-in-human, phase I, monocenter trial in patients with sepsis admitted to the intensive care unit (ICU). Patients received a single 6 h intravenous infusion of M6229. A modified continual reassessment method (mCRM) with escalation overdose control was used for dose-escalation. The model was based on the probability of activated partial thromboplastin time (aPTT) being above 90 s (i.e., dose limiting pharmacologic event, DLPE). Three cohorts were studied (1: 0.15 mg/kg/h; 2: 0.45 mg/kg/h; 3: 0.90 mg/kg/h).

Results: Ten patients were included. The aPTT increased proportionally with increasing dosages of M6229 and decreased rapidly after infusion cessation. One DLPE occurred (aPTT of 100 s). Based on the mCRM model and data safety monitoring board recommendations, the maximum tolerated dose was defined as 0.9 mg/kg/h for a 6 h infusion of M6229. No serious adverse events were related to study drug infusion. An increase in QTc was probably related to infusion in one patient. M6229 showed close to dose-proportional pharmacokinetics. Total histone H3 and H2b plasma levels increased during and/or in the hours after M6229 infusion in all patients. In four out of five patients with plasma samples positive for histone H3, proteolytic cleavage was observed after infusion start. A decrease in sequential organ failure assessment score was observed in the days after infusion in 70% of patients.

Conclusions: M6229 was deemed safe to use in critically ill sepsis patients. Our results suggest intravascular neutralization of histones by M6229. Future clinical studies need to confirm our findings and the efficacy of M6229.

Background: Artificial intelligence (AI) has emerged as a promising tool for decision support in managing acute respiratory failure, yet its real-world clinical impact remains unclear. This scoping review identifies clinically validated AI-driven tools in this domain, focusing on the reporting of key evaluation quality measures that are a prerequisite for broader deployment.

Eligibility criteria: Studies were included if they compared a clinical, human factors, or health systems-related outcome of an AI-driven intervention to a control group in adult patients with acute respiratory failure. Studies were excluded if they lacked a machine learning model, compared models trained on the same dataset, assessed only model performance, or evaluated models in simulated settings. A systematic literature search was conducted in PubMed, CINAHL, and EmBase, from inception until January 2025. Each abstract was independently screened by two reviewers. One reviewer extracted data and performed quality assessment, following the DECIDE-AI framework for early-stage clinical evaluation of AI-based decision support systems.

Results: Of 5,987 citations, six studies met eligibility. The studies, conducted between 2012 and 2024 in Taiwan, Italy, and the U.S., included 40-2,536 patients. Four studies (67%) focused on predicting weaning from mechanical ventilation. Three (50%) of the studies demonstrated a statistically significant and clinically meaningful outcome. Studies met a median of 3.5 (IQR: 2.25-6.25) of the 17 DECIDE-AI criteria. None reported AI-related errors, malfunctions, or algorithmic fairness considerations. Only one study (17%) described user characteristics and adherence, while two (33%) assessed human-computer agreement and usability.

Conclusions: Our review identified six studies evaluating AI-driven decision support tools for acute respiratory failure, with most focusing on predicting weaning from mechanical ventilation. However, methodological rigor for early clinical evaluation was inconsistent, with studies meeting few of the DECIDE-AI criteria. Notably, critical aspects such as error reporting, algorithmic fairness, and user adherence were largely unaddressed. Further high-quality assessments of reliability, usability, and real-world implementation are essential to realize the potential of these tools to transform patient care.

Background: Acute respiratory distress syndrome (ARDS) is characterised by significant morphological heterogeneity. Morphological sub-phenotyping can potentially be used to personalise mechanical ventilation. Current methods to classify lung injury as focal or diffuse rely on subjective image interpretation, which risks misclassification and suboptimal treatment. This study aimed to investigate the morphological appearance features of lung injury objectively. The focal index, an objective quantitative tool, was introduced to assess focality in lung injury.

Methods: In this single-centre retrospective study, we included lung computed tomography (CT) scans from COVID-19 ARDS patients on invasive mechanical ventilation, classified as diffuse lung injury. CT data were analysed to extract regional Hounsfield Unit (HU) profiles across nine predefined lung areas. The focal index was derived by quantifying the non-overlapping area under HU distribution curves between the apical ventral and diaphragmatic dorsal regions. Correlations with lung weight, gas volume, and ventilatory settings were assessed. For validation, at least two experienced ICU consultants assessed the same images and determined whether ARDS was of a diffuse or focal type. The experts classified 36 out of 37 patients as diffuse ARDS, with substantial interobserver agreement (k = 0.65, 95% CI 0.02-1.00).

Results: The focal index demonstrated a wide range (25-175; mean 95.5 ± standard deviation 42.8), correlating significantly with the dorsal diaphragmatic non-aerated area (r = 0.67, p < 0.01) and with total gas volume (r = - 0.36, p = 0.03). There was no significant influence of ventilatory settings on the focal index.

Conclusions: The analysis suggested diffuse lung injury includes a spectrum of focality rather than a binary classification. The focal index provides an objective method to quantify the focality of lung injury in ARDS. Further studies are needed to validate the focal index across diverse ARDS aetiologies and establish its clinical application threshold for guiding personalised ventilation strategies.