Intensive Care Medicine Experimental最新文献

Background: Individualised bedside adjustment of mechanical ventilation is a standard strategy in acute coma neurocritical care patients. This involves customising positive end-expiratory pressure (PEEP), which could improve ventilation homogeneity and arterial oxygenation. This study aimed to determine whether PEEP titrated by electrical impedance tomography (EIT) results in different lung ventilation homogeneity when compared to standard PEEP of 5 cmH₂O in mechanically ventilated patients with healthy lungs.

Methods: In this prospective single-centre study, we evaluated 55 acute adult neurocritical care patients starting controlled ventilation with PEEPs close to 5 cmH₂O. Next, the optimal PEEP was identified by EIT-guided decremental PEEP titration, probing PEEP levels between 9 and 2 cmH₂O and finding the minimal amount of collapse and overdistension. EIT-derived parameters of ventilation homogeneity were evaluated before and after the PEEP titration and after the adjustment of PEEP to its optimal value. Non-EIT-based parameters, such as peripheral capillary Hb saturation (SpO₂) and end-tidal pressure of CO₂, were recorded hourly and analysed before PEEP titration and after PEEP adjustment.

Results: The mean PEEP value before titration was 4.75 ± 0.94 cmH₂O (ranging from 3 to max 8 cmH₂O), 4.29 ± 1.24 cmH₂O after titration and before PEEP adjustment, and 4.26 ± 1.5 cmH₂O after PEEP adjustment. No statistically significant differences in ventilation homogeneity were observed due to the adjustment of PEEP found by PEEP titration. We also found non-significant changes in non-EIT-based parameters following the PEEP titration and subsequent PEEP adjustment, except for the mean arterial pressure, which dropped statistically significantly (with a mean difference of 3.2 mmHg, 95% CI 0.45 to 6.0 cmH₂O, p < 0.001).

Conclusion: Adjusting PEEP to values derived from PEEP titration guided by EIT does not provide any significant changes in ventilation homogeneity as assessed by EIT to ventilated patients with healthy lungs, provided the change in PEEP does not exceed three cmH₂O. Thus, a reduction in PEEP determined through PEEP titration that is not greater than 3 cmH₂O from an initial value of 5 cmH₂O is unlikely to affect ventilation homogeneity significantly, which could benefit mechanically ventilated neurocritical care patients.

Background: Infusion of exogenous catecholamines (i.e., norepinephrine [NE] and dobutamine) is a recommended treatment for septic shock with myocardial dysfunction. However, sustained catecholamine infusion is linked to cardiac toxicity and impaired responsiveness. Several pre-clinical and clinical studies have investigated the use of alternative vasopressors in the treatment of septic shock, with limited benefits and generally no effect on mortality. Apelin-13 (APL-13) is an endogenous positive inotrope and vasoactive peptide and has been demonstrated cardioprotective with vasomodulator and sparing life effects in animal models of septic shock. A primary objective of this study was to evaluate the NE-sparing effect of APL-13 infusion in an experimental sepsis-induced hypotension.

Methods: For this goal, sepsis was induced by cecal ligation and puncture (CLP) in male rats and the arterial blood pressure (BP) monitored continuously via a carotid catheter. Monitoring, fluid resuscitation and experimental treatments were performed on conscious animals. Based on pilot assays, normal saline fluid resuscitation (2.5 mL/Kg/h) was initiated 3 h post-CLP and maintained up to the endpoint. Thus, titrated doses of NE, with or without fixed-doses of APL-13 or the apelin receptor antagonist F13A co-infusion were started when 20% decrease of systolic BP (SBP) from baseline was achieved, to restore SBP values ≥ 115 ± 1.5 mmHg (baseline average ± SEM).

Results: A reduction in mean NE dose was observed with APL-13 but not F13A co-infusion at pre-determined treatment time of 4.5 ± 0.5 h (17.37 ± 1.74 µg/Kg/h [APL-13] vs. 25.64 ± 2.61 µg/Kg/h [Control NE] vs. 28.60 ± 4.79 µg/Kg/min [F13A], P = 0.0491). A 60% decrease in NE infusion rate over time was observed with APL-13 co-infusion, (p = 0.008 vs NE alone), while F13A co-infusion increased the NE infusion rate over time by 218% (p = 0.003 vs NE + APL-13). Associated improvements in cardiac function are likely mediated by (i) enhanced left ventricular end-diastolic volume (0.18 ± 0.02 mL [Control NE] vs. 0.30 ± 0.03 mL [APL-13], P = 0.0051), stroke volume (0.11 ± 0.01 mL [Control NE] vs. 0.21 ± 0.01 mL [APL-13], P < 0.001) and cardiac output (67.57 ± 8.63 mL/min [Control NE] vs. 112.20 ± 8.53 mL/min [APL-13], P = 0.0036), and (ii) a reduced effective arterial elastance (920.6 ± 81.4 mmHg/mL/min [Control NE] vs. 497.633.44 mmHg/mL/min. [APL-13], P = 0.0002). APL-13 administration was also associated with a decrease in lactate levels compared to animals only receiving NE (7.08 ± 0.40 [Control NE] vs. 4.78 ± 0.60 [APL-13], P < 0.01).

Conclusion: APL-13 exhibits NE-sparing benefits in the treatment of sepsis-induced shock, potentially reducing deleterious effects of prolonged exogenous catecholamine administration.

Background: IL-6 is a pleiotropic cytokine modulating inflammation and metabolic pathways. Its proinflammatory effect plays a significant role in organ failure pathogenesis, commonly elevated in systemic inflammatory conditions. Extracorporeal blood purification devices, such as the Advanced Organ Support (ADVOS) multi hemodialysis system, might offer potential in mitigating IL-6's detrimental effects, yet its efficacy remains unreported.

Methods: We conducted a proof-of-concept in vitro study to assess the ADVOS multi system's efficacy in eliminating IL-6. Varying concentrations of IL-6 were introduced into a swine blood model and treated with ADVOS multi for up to 12 h, employing different blood and concentrate flow rates. IL-6 reduction rate, clearance, and dynamics in blood and dialysate were analyzed.

Results: IL-6 clearance rates of 0.70 L/h and 0.42 L/h were observed in 4 and 12-h experiments, respectively. No significant differences were noted across different initial concentrations. Reduction rates ranged between 40 and 46% within the first 4 h, increasing up to 72% over 12 h, with minimal impact from flow rate variations. Our findings suggest that an IL-6-albumin interaction and convective filtration are implicated in in vitro IL-6 elimination with ADVOS multi.

Conclusions: This study demonstrates for the first time an efficient and continuous in vitro removal of IL-6 by ADVOS multi at low blood flow rates. Initial concentration-dependent removal transitions to more consistent elimination over time. Further clinical investigations are imperative for comprehensive data acquisition.

Rationale: Mechanical power (MP) is a summary variable incorporating all causes of ventilator-induced-lung-injury (VILI). We expressed MP as the ratio between observed and normal expected values (MP_ratio).

Objective: To define a threshold value of MP_ratio leading to the development of VILI.

Methods: In a population of 82 healthy pigs, a threshold of MP_ratio for VILI, as assessed by histological variables and confirmed by using unsupervised cluster analysis was 4.5. The population was divided into two groups with MP_ratio above or below the threshold.

Measurements and main results: We measured physiological variables every six hours. At the end of the experiment, we measured lung weight and wet-to-dry ratio to quantify edema. Histological samples were analyzed for alveolar ruptures, inflammation, alveolar edema, atelectasis. An MP_ratio threshold of 4.5 was associated with worse injury, lung weight, wet-to-dry ratio and fluid balance (all p < 0.001). After 48 h, in the two MP_ratio clusters (above or below 4.5), respiratory system elastance, mean pulmonary artery pressure and physiological dead space differed by 32%, 36% and 22%, respectively (all p < 0.001), being worse in the high MP_ratio group. Also, the changes in driving pressure, lung elastance, pulmonary artery occlusion pressure, central venous pressure differed by 17%, 64%, 8%, 25%, respectively (all p < 0.001).

Limitations: The main limitation of this study is its retrospective design. In addition, the computation for the expected MP in pigs is based on arbitrary criteria. Different values of expected MP may change the absolute value of MP ratio but will not change the concept of the existence of an injury threshold.

Conclusions: The concept of MP_ratio is a physiological and intuitive way to quantify the risk of ventilator-induced lung injury. Our results suggest that a mechanical power ratio > 4.5 MP_ratio in healthy lungs subjected to 48 h of mechanical ventilation appears to be a threshold for the development of ventilator-induced lung injury, as indicated by the convergence of histological, physiological, and anatomical alterations. In humans and in lungs that are already injured, this threshold is likely to be different.

For decades, left ventricular ejection fraction (LVEF < 35%) has been a mainstay for identifying heart failure (HF) patients most likely to benefit from an implantable cardioverter defibrillator (ICD). However, LVEF is a poor predictor of sudden cardiac death (SCD) and ignores 50% of HF patients with mildly reduced and preserved LVEF. The current international guidelines for primary prophylaxis ICD therapy are inadequate. Instead of LVEF, which is not a good measure of LV contractility or hemodynamic characterization, we hypothesize ventriculo-arterial (VA) coupling combined with fragmented QRS (fQRS) will improve risk stratification and patient suitability for an ICD. Quantifying cardiac and aortic mechanics, and predicting active arrhythmogenic substrate, from varying fQRS morphologies, may help to stratify ischemic and non-ischemic patients with different functional capacities and predisposition for lethal arrhythmias. We propose HF patients with a low physiological reserve may not benefit from ICD therapy, whereas those patients with higher reserves and extensive arrhythmogenic substrate may benefit. Our hypothesis combining VA coupling with fQRS changes has the potential to widen HF patient participation (low and high LVEF) and advance personalized medicine for HF patients at high risk of SCD.

Purpose: Currently, there is no marker of efficacy of red blood cell (RBC) transfusion. This study describes the impact of RBC transfusion on mitochondrial oxygen tension (mitoPO₂) and mitochondrial oxygen consumption (mitoVO₂) in critically ill patients with anemia.

Methods: Critically ill patients with a hemoglobin concentration < 10 g/dL, for whom a single RBC unit had been ordered, were included. MitoPO₂ was measured with the COMET device immediately before RBC transfusion, 0.5 h, 1 h, 3 h, and 24 h after RBC transfusion. MitoVO₂ was calculated from dynamic mitoPO₂ measurements during cessation of local oxygen supply.

Results: Sixty-three patients participated, median age 64.0 (interquartile range (IQR) 52.3-72.8) years, median hemoglobin concentration before transfusion 7.4 (IQR 7.1-7.7) g/dL. Median mitoPO₂ values were 55.0 (IQR 49.6-63.0) mmHg before RBC transfusion, 51.0 (IQR 41.5-61.2) directly after and 67.3 (IQR 41.6-83.7) at 24 h after RBC transfusion. Median mitoVO₂ values were 3.3 (IQR 2.1-5.9) mmHg/s before RBC transfusion, 3.7 (IQR 2.0-5.1) mmHg/s directly after, and 3.1 (IQR 2.5-4.8) mmHg/s 24 h after RBC transfusion. In the higher Hb concentration group (> 7 g/dL), we saw a dissociation of the effect of RBC transfusion on mitoPO₂ versus on mitoVO₂ values. MitoPO₂ and mitoVO₂ values were not associated with commonly used parameters of tissue perfusion and oxygenation.

Conclusion: RBC transfusion did not alter mitoPO₂ and mitoVO₂ in critically ill patients with anemia. MitoPO₂ and mitoVO₂ values were not notably associated with Hb concentrations, parameters of severity of illness and markers of tissue perfusion or oxygenation. Given the high baseline value, it cannot be excluded nor confirmed whether RBC can improve low mitoPO₂. Trial registration number NCT03092297 (registered 27 March 2017).

Background: People with type 2 diabetes mellitus treated with sodium-glucose transporter-2 inhibitors (SGLT2i) have lower rates of acute kidney injury (AKI). Sepsis is responsible for the majority of AKI in critically ill patients. This study investigated whether SGLT2i is renoprotective in an ovine model of Gram-negative septic AKI.

Methods: Sixteen healthy merino ewes were surgically instrumented to enable measurement of mean arterial pressure, cardiac output, renal blood flow, renal cortical and medullary perfusion, and oxygenation. After a 5-day recovery period, sepsis was induced via slow and continuous intravenous infusion of live Escherichia coli. Twenty-three hours later, sheep were randomized to receive an intravenous bolus of 0.2 mg/kg empagliflozin (n = 8) or a fluid-matched vehicle (n = 8).

Results: Empagliflozin treatment did not significantly reduce renal medullary hypoperfusion or hypoxia, improve kidney function, or induce histological changes. Renal cortical oxygenation during the intervention period was 47.6 ± 5.9 mmHg in the empagliflozin group compared with 40.6 ± 8.2 mmHg in the placebo group (P = 0.16). Renal medullary oxygenation was 28.0 ± 18.5 mmHg in the empagliflozin compared with 25.7 ± 16.3 mmHg (P = 0.82). Empagliflozin treatment did not result in significant between-group differences in renal blood flow, kidney function, or renal histopathological changes.

Conclusion: In a large mammalian model of septic AKI, a single dose of empagliflozin did not improve renal microcirculatory perfusion, oxygenation, kidney function, or histopathology.

Purpose: Tracheostomized patients often present with muscle weakness, altered consciousness, or swallowing difficulties. Hence, the literature is scarce regarding the challenging management of tracheostomy weaning. There is a need to strengthen the understanding of respiratory mechanisms with the different tracheostomy tube modalities that compose this weaning pathway. We aimed to evaluate the impact of these modalities on the work of breathing (WOB), total positive end-expiratory pressure (PEEPtot), and tidal volume (V_T).

Methods: With a three-dimensional (3D) printed head mimicking human upper airways, we added a tracheal extension, and pierced to allow insertion of a size 7.0 tracheostomy cannula. The whole was connected to an artificial lung. Three lung mechanics were simulated (normal, obstructive and restrictive). We compared five different tracheostomy tube modalities to a control scenario in which the tube was capped and the cuff was deflated.

Results: A marginal difference was observed on the WOB within conditions with a slight increase + 0.004 [95% CI (0.003-0.004); p < 0.001] when the cuff was inflated in the normal and restrictive models and a slight decrease in the obstructive model. The highest PEEPtot that was reached was + 1 cmH₂O [95% CI (1-1.1); p < 0.001] with high-flow therapy (HFT) with the cuff inflated in the obstructive model. We observed a statistically significant reduction in V_T [up to - 57 mL 95% CI (- 60 to - 54); p < 0.001] when the cuff was inflated, in both the normal and obstructive models.

Conclusions: Our results support the use of conditions that involve cuff deflation. Intermediate modalities with the cuff deflated produced similar results than cannula capping.

Excessive tidal stretching may initiate damage or retard healing after lung injury. However, it is seldom considered whether intracycle power and ventilatory forces of lesser magnitude than those required to cross an injury threshold might stimulate or accelerate beneficial adaptive responses. Acute lung injury is a dynamic process that may exhibit phase-dependent reparative responses to mechanical stress broadly similar to physical training, body trauma or sepsis. We propose that lower stress may not always be better through all phases of ARDS; moderately high tidal airway pressures that stay below the threshold of global injury may have potential to speed healing of the injured lung.

Background: The spatiotemporal progression and patterns of tissue deformation in ventilator-induced lung injury (VILI) remain understudied. Our aim was to identify lung clusters based on their regional mechanical behavior over space and time in lungs subjected to VILI using machine-learning techniques.

Results: Ten anesthetized pigs (27 ± 2 kg) were studied. Eight subjects were analyzed. End-inspiratory and end-expiratory lung computed tomography scans were performed at the beginning and after 12 h of one-hit VILI model. Regional image-based biomechanical analysis was used to determine end-expiratory aeration, tidal recruitment, and volumetric strain for both early and late stages. Clustering analysis was performed using principal component analysis and K-Means algorithms. We identified three different clusters of lung tissue: Stable, Recruitable Unstable, and Non-Recruitable Unstable. End-expiratory aeration, tidal recruitment, and volumetric strain were significantly different between clusters at early stage. At late stage, we found a step loss of end-expiratory aeration among clusters, lowest in Stable, followed by Unstable Recruitable, and highest in the Unstable Non-Recruitable cluster. Volumetric strain remaining unchanged in the Stable cluster, with slight increases in the Recruitable cluster, and strong reduction in the Unstable Non-Recruitable cluster.

Conclusions: VILI is a regional and dynamic phenomenon. Using unbiased machine-learning techniques we can identify the coexistence of three functional lung tissue compartments with different spatiotemporal regional biomechanical behavior.