PURPOSE: Passive leg raising (PLR) increases intrathoracic blood volume by redistributing blood from the lower to the upper body area. While inspiratory effort is hypothesized to have a similar effect due to pressure differences between the intrathoracic and extrathoracic cavities, direct evidence is scarce. Therefore, this study evaluated whether excessive inspiratory effort increases intrathoracic blood volume using end-expiratory lung impedance (EELI). METHODS: Volunteers, fitted with electrical impedance tomography (EIT) belts, underwent a spontaneous breathing procedure in the supine position (control step). They breathed through a specialized face mask with separated inspiration and expiration routes (one-way valves) and their EELI was continuously recorded. First, PLR was performed. Subsequently, resistors (3-mm and 2-mm) were sequentially added to the mask's inspiration route, requiring volunteers to increase inspiratory effort. A reference EELI was established during spontaneous breathing, and changes in EELI (ΔEELI) were calculated for each step (control, PLR, 3-mm, and 2-mm). ΔEELI values were compared using the Friedman test and Wilcoxon signed-rank test with Holm's P value adjustment. RESULTS: Across 11 participants, the mean ΔEELI decreased by 13, 18, and 19 units for PLR, 3-mm, and 2-mm resistors, respectively. The Friedman test and Wilcoxon signed-rank test revealed significant differences between the control and each aforementioned intervention. CONCLUSION: PLR and increased inspiratory effort augment thoracic blood volume, thereby reducing EELI. REGISTRATION: UMIN000054238. April/23/2024.

BACKGROUND: Currently, clinical indicators for evaluating endothelial permeability in sepsis are unavailable. Endothelium-derived extracellular vesicles (EDEVs) are emerging as biomarkers of endothelial injury. Platelet endothelial cell adhesion molecule (PECAM) and vascular endothelial (VE)-cadherin are constitutively expressed endothelial intercellular adhesion molecules that regulate intercellular adhesion and permeability. Herein, we investigated the possible association between EDEVs expressing intercellular adhesion molecules (PECAM+ or VE-cadherin+ EDEVs) and endothelial permeability and sepsis severity. METHODS: Human umbilical vein endothelial cells (HUVECs) were stimulated with tumor necrosis factor alpha (TNF-α) directly or after pretreatment with permeability-modifying reagents such as angiopoietin-1, prostacyclin, or vascular endothelial growth factor (VEGF) to alter TNF-α-induced endothelial hyperpermeability. Endothelial permeability was measured using the dextran assay or transendothelial electrical resistance. Additionally, a prospective cross-sectional observational study was conducted to analyze circulating EDEV levels in patients with sepsis. EDEVs were examined in HUVEC culture supernatants or patient plasma (nonsepsis, n = 30; sepsis, n = 30; septic shock, n = 42) using flow cytometry. The Wilcoxon rank-sum test was used for comparisons between 2 groups. Comparisons among 3 or more groups were performed using the Steel-Dwass test. Spearman's test was used for correlation analysis. Statistical significance was set at P < .05. RESULTS: TNF-α stimulation of HUVECs significantly increased EDEV release and endothelial permeability. Pretreatment with angiopoietin-1 or prostacyclin suppressed the TNF-α-induced increase in endothelial permeability and inhibited the release of PECAM+ and VE-cadherin+ EDEVs. In contrast, pretreatment with VEGF increased TNF-α-induced endothelial permeability and the release of PECAM+ and VE-cadherin+ EDEVs. However, pretreatment with permeability-modifying reagents did not affect the release of EDEVs expressing inflammatory stimulus-inducible endothelial adhesion molecules such as E-selectin, intracellular adhesion molecule-1, or vascular cell adhesion molecule-1. The number of PECAM+ EDEVs on admission in the septic-shock group (232 [124, 590]/μL) was significantly higher (P = .043) than that in the sepsis group (138 [77,267]/μL), with an average treatment effect of 98/μL (95% confidence interval [CI], 2-270/μL), and the number of VE-cadherin+ EDEVs in the septic-shock group (173 [76,339]/μL) was also significantly higher (P = .004) than that in the sepsis group (81 [42,159]/μL), with an average treatment effect (ATE) of 79/μL (95% CI, 19-171/μL); these EDEV levels remained elevated until day 5. CONCLUSIONS: EDEVs expressing intercellular adhesion molecules (PECAM+ or VE-cadherin+ EDEVs) may reflect increased endothelial permeability and could be valuable diagnostic and prognostic markers for sepsis.

BACKGROUND: Esophagectomy is a high-risk procedure that can involve serious postoperative complications. There has been an increase in the number of minimally invasive esophagectomies (MIEs) being performed. However, the relationship between intraoperative management and postoperative complications in MIE remains unclear. METHODS: After the institutional review board approval, we enrolled 300 patients who underwent MIE at Tohoku University Hospital between April 2016 and March 2021. The relationships among patient characteristics, intraoperative and perioperative factors, and postoperative complications were retrospectively analyzed. The primary outcome was the relationship between intraoperative fluid volume and anastomotic leakage, and the secondary outcomes included the associations between other perioperative factors and postoperative complications. RESULTS: Among 300 patients, 28 were excluded because of missing data; accordingly, 272 patients were included in the final analysis. The median [interquartile range] operative duration was 599 [545-682] minutes; total intraoperative infusion volume was 3,747 [3,038-4,399] mL; total infusion volume per body weight per hour was 5.48 [4.42-6.73] mL/kg/h; and fluid balance was + 2,648 [2,015-3,263] mL. The postoperative complications included anastomotic leakage in 68 (25%) patients, recurrent nerve palsy in 91 (33%) patients, pneumonia in 62 (23%) patients, cardiac arrhythmia in 13 (5%) patients, acute kidney injury in 5 (2%) patients, and heart failure in 5 (2%) patients. The Cochrane-Armitage trend test indicated significantly increased anastomotic leakage among patients with a relatively high total infusion volume (P = 0.0085). Moreover, anastomotic leakage was associated with male sex but not with peak serum lactate levels. Patients with a longer anesthesia duration or recurrent nerve palsy had a significantly higher incidence of postoperative pneumonia than those without. Further, the incidence of postoperative pneumonia was not associated with the operative duration, total infusion volume, or fluid balance. The operative duration and blood loss were related to the total infusion volume. Acute kidney injury was not associated with the total infusion volume or serum lactate levels. CONCLUSIONS: Among patients who underwent MIE, the total infusion volume was positively correlated with the incidence of anastomotic leakage. Further, postoperative pneumonia was associated with recurrent nerve palsy but not total infusion volume or fluid balance.

The endotracheal tubes (ETTs) used for children have a smaller inner diameter. Accordingly, the resistance across ETT (RETT) is higher. Theoretically, shortening the ETTs can decrease total airway resistance (Rtotal), because Rtotal is sum of RETT and patient's airway resistance. However, the effectiveness of ETT shortening for mechanical ventilation in the clinical setting has not been reported. We assessed the effectiveness of shortening a cuffed ETT for decreasing Rtotal, and increasing tidal volume (TV), and estimated the RETT/Rtotal ratio in children. In anesthetized children in a constant pressure-controlled ventilation setting, Rtotal and TV were measured with a pneumotachometer before and after shortening a cuffed ETT. In a laboratory experiment, the pressure gradient across the original length, shortened length, and the slip joint alone of the ETT were measured. We then determined the RETT/Rtotal ratio using the above results. The clinical study included 22 children. The median ETT percent shortening was 21.7%. Median Rtotal was decreased from 26 to 24 cmH2O/L/s, and median TV was increased by 6% after ETT shortening. The laboratory experiment showed that ETT length and the pressure gradient across ETT are linearly related under a certain flow rate, and approximately 40% of the pressure gradient across the ETT at its original length was generated by the slip joint. Median RETT/Rtotal ratio were calculated as 0.69. The effectiveness of ETT shortening on Rtotal and TV was very limited, because the resistance of the slip joint was very large.

In mechanically ventilated severe acute respiratory distress syndrome patients, spontaneous inspiratory effort generates more negative pressure in the dorsal lung than in the ventral lung. The airflow caused by this pressure difference is called pendelluft, which is a possible mechanisms of patient self-inflicted lung injury. This study aimed to use computer simulation to understand how the endotracheal tube and insufficient ventilatory support contribute to pendelluft. We established two models. In the invasive model, an endotracheal tube was connected to the tracheobronchial tree with 34 outlets grouped into six locations: the right and left upper, lower, and middle lobes. In the non-invasive model, the upper airway, including the glottis, was connected to the tracheobronchial tree. To recreate the inspiratory effort of acute respiratory distress syndrome patients, the lower lobe pressure was set at -13 cmH2O, while the upper and middle lobe pressure was set at -6.4 cmH2O. The inlet pressure was set from 10 to 30 cmH2O to recreate ventilatory support. Using the finite volume method, the total flow rates through each model and toward each lobe were calculated. The invasive model had half the total flow rate of the non-invasive model (1.92 L/s versus 3.73 L/s under 10 cmH2O, respectively). More pendelluft (gas flow into the model from the outlets) was observed in the invasive model than in the non-invasive model. The inlet pressure increase from 10 to 30 cmH2O decreased pendelluft by 11% and 29% in the invasive and non-invasive models, respectively. In the invasive model, a faster jet flowed from the tip of the endotracheal tube toward the lower lobes, consequently entraining gas from the upper and middle lobes. Increasing ventilatory support intensifies the jet from the endotracheal tube, causing a venturi effect at the bifurcation in the tracheobronchial tree. Clinically acceptable ventilatory support cannot completely prevent pendelluft.

Abstract Fluid mechanics shows that high-density gases need more energy while flowing through a endo-tracheal tube. This means that during general anesthesia, high-density gases left less energy for lung inflation under pressure-controlled ventilation (PCV). However, the impact have not been studied. This study investigated the effects of high-density anesthetic gases on tidal volume (TV) in laboratory and clinical settings.In laboratory study, a test lung was ventilated at fixed PCV with 22 different gas compositions (density range, 1.22-2.27 kg/m³) using an Avance® anesthesia machine. The TV of the test lung and the respiratory gas composition were recorded by a pneumotachometer. As a result, the TV of the test lung decreased as the respiratory gas density increased. In clinical study, the change in TV/body weight, accompanied by gas composition change (2% sevoflurane in oxygen and with 0-30-60% of N₂O), was recorded in 30 pediatric patients. Median TV/body weight decreased by 10% when the respiratory gas density increased from 1.41 kg/m³ to 1.70 kg/m³, indicating a significant between-group difference (P&lt;0.0001). In both laboratory and clinical settings, an increase in respiratory gas density decreases the TV during PCV, and it could be well explained by the theory of fluid dynamics.