VT Ventilation Research Articles

Lung (extracorporeal CO2 removal) and renal (continuous renal replacement therapy) support: the role of ultraprotective strategy in Covid 19 and non-Covid 19 ARDS. A case-control study

BackgroundPreliminary studies suggest that moderate ARDS and acute renal failure might benefit from extracorporeal CO2 removal (ECCO2R) coupled with CRRT. However, evidence is limited and potential for this coupled treatment may need to be explored. The aim of the present study was to evaluate whether a protective driving pressure was obtained applying low-flow ECCO2-R plus CRRT in patients affected by moderate ARDS with COVID-19 compared to an historical group without COVID-19.MethodsA case-control study has been conducted comparing a group of consecutive moderate ARDS patients presenting AKI and affected by COVID-19, who needed low-flow ECCO2-R plus CRRT to achieve an ultra-protective ventilatory strategy, with historical group without COVID-19 that matched for clinical presentation and underwent the same ultra-protective treatment. VT was set at 6 mL/kg predicted body weight then ECCO2R was assessed to facilitate ultra-protective low VT ventilation to preserve safe Pplat and low driving pressure.ResultsECCO2R+CRRT reduced the driving pressure from 17 (14-18) to 11.5 (10-15) cmH2O (p<0.0004) in the fourteen ARDS patients by decreasing VT from 6.7 ml/kg PBW (6.1-6.9) to 5.1 (4.2-5.6) after 1 hour (p <0.0001). In the ARDS patients with COVID-19, the driving pressure reduction was more effective from baseline 18 (14-24) cmH2O to 11 (10-15) cmH2O (p<0.004), compared to the control group from 15 (13-17) to 12(10-16) cmH2O (p< 0.03), after one hour. ECCO2R+CRRT did not affected 28 days mortality in the two groups, while we observed a shorter duration of mechanical ventilation (19 {7-29} vs 24 {22-38} days; p=0.24) and ICU length of stay (19 {7-29} vs 24 {22-78} days; p=0.25) in moderate ARDS patients with COVID-19 compared to control group.ConclusionsIn moderate ARDS patients with or without COVID-19 disease, ECCO2R+CRRT may be and effective supportive treatment to reach protective values of driving pressure unless severe oxygenation defects arise requiring ECMO therapy initiation.

Effects of tidal volume on physiology and clinical outcomes in patients with one‑lung ventilation undergoing surgery: A meta‑analysis of randomized controlled trials.

There is no detailed study on how tidal volume (VT) affects patients during one-lung ventilation (OLV). The present study conducted a meta-analysis to assess the effect of VT on physiology and clinical outcomes in OLV patients. Databases until February 2023 were retrieved from PubMed, Cochrane Library and Web of Science. Randomized controlled trials comparing the application of low and high VT ventilation in adults with OLV were performed. Demographic variables, VT, physiology, and clinical outcomes were retrieved. The random-effects model calculated the summary of odds ratios with 95% confidence intervals (CI) and mean difference with standard deviation. A total of 12 studies involving a total of 876 participants met the inclusion criteria. Low VT ventilation was associated with decreased risk of acute lung injury [relative risk 0.50, 95% CI (0.28, 0.88), P=0.02]. Low VT ventilation decreased the driving pressure (ΔP) and peak pressure (Ppeak) and improved arterial oxygen pressure (PaO2)/fraction of inspired oxygen (FiO2). Furthermore, the present study suggested that a significant difference in blood IL-6 was observed between low and high VT ventilation [mean difference, -35.51 pg/ml, 95% CI (-66.47, -4.54 pg/ml), P=0.02]. A decrease in the length of stay at the hospital occurred in the low VT group when set to 4-5 ml/kg. In the OLV patients, low VT ventilation decreased the risk of acute lung injury, blood IL-6, ΔP and Ppeak, and improved PaO2/FiO2. Furthermore, when low VT was set to 4-5 ml/kg, the length of stay at the hospital decreased.

Flow-Limited and Reverse-Triggered Ventilator Dyssynchrony Are Associated With Increased Tidal and Dynamic Transpulmonary Pressure.

Ventilator dyssynchrony may be associated with increased delivered tidal volumes (V t s) and dynamic transpulmonary pressure (ΔP L,dyn ), surrogate markers of lung stress and strain, despite low V t ventilation. However, it is unknown which types of ventilator dyssynchrony are most likely to increase these metrics or if specific ventilation or sedation strategies can mitigate this potential. A prospective cohort analysis to delineate the association between ten types of breaths and delivered V t , ΔP L,dyn , and transpulmonary mechanical energy. Patients admitted to the medical ICU. Over 580,000 breaths from 35 patients with acute respiratory distress syndrome (ARDS) or ARDS risk factors. None. Patients received continuous esophageal manometry. Ventilator dyssynchrony was identified using a machine learning algorithm. Mixed-effect models predicted V t , ΔP L,dyn , and transpulmonary mechanical energy for each type of ventilator dyssynchrony while controlling for repeated measures. Finally, we described how V t , positive end-expiratory pressure (PEEP), and sedation (Richmond Agitation-Sedation Scale) strategies modify ventilator dyssynchrony's association with these surrogate markers of lung stress and strain. Double-triggered breaths were associated with the most significant increase in V t , ΔP L,dyn , and transpulmonary mechanical energy. However, flow-limited, early reverse-triggered, and early ventilator-terminated breaths were also associated with significant increases in V t , ΔP L,dyn , and energy. The potential of a ventilator dyssynchrony type to increase V t , ΔP L,dyn , or energy clustered similarly. Increasing set V t may be associated with a disproportionate increase in high-volume and high-energy ventilation from double-triggered breaths, but PEEP and sedation do not clinically modify the interaction between ventilator dyssynchrony and surrogate markers of lung stress and strain. Double-triggered, flow-limited, early reverse-triggered, and early ventilator-terminated breaths are associated with increases in V t , ΔP L,dyn , and energy. As flow-limited breaths are more than twice as common as double-triggered breaths, further work is needed to determine the interaction of ventilator dyssynchrony frequency to cause clinically meaningful changes in patient outcomes.

Respiratory variation in the internal jugular vein does not predict fluid responsiveness in the prone position during adolescent idiopathic scoliosis surgery: a prospective cohort study

BackgroundRespiratory variation in the internal jugular vein (IJVV) has not shown promising results in predicting volume responsiveness in ventilated patients with low tidal volume (Vt) in prone position. We aimed to determine whether the baseline respiratory variation in the IJVV value measured by ultrasound might predict fluid responsiveness in patients with adolescent idiopathic scoliosis (AIS) undergoing posterior spinal fusion (PSF) with low Vt.MethodsAccording to the fluid responsiveness results, the included patients were divided into two groups: those who responded to volume expansion, denoted the responder group, and those who did not respond, denoted the non-responder group. The primary outcome was determination of the value of baseline IJVV in predicting fluid responsiveness (≥15% increases in stroke volume index (SVI) after 7 ml·kg-1 colloid administration) in patients with AIS undergoing PSF during low Vt ventilation. Secondary outcomes were estimation of the diagnostic performance of pulse pressure variation (PPV), stroke volume variation (SVV), and the combination of IJVV and PPV in predicting fluid responsiveness in this surgical setting. The ability of each parameter to predict fluid responsiveness was assessed using a receiver operating characteristic curve.ResultsFifty-six patients were included, 36 (64.29%) of whom were deemed fluid responsive. No significant difference in baseline IJVV was found between responders and non-responders (25.89% vs. 23.66%, p = 0.73), and no correlation was detected between baseline IJVV and the increase in SVI after volume expansion (r = 0.14, p = 0.40). A baseline IJVV greater than 32.00%, SVV greater than 14.30%, PPV greater than 11.00%, and a combination of IJVV and PPV greater than 64.00% had utility in identifying fluid responsiveness, with a sensitivity of 33.33%, 77.78%, 55.56%, and 55.56%, respectively, and a specificity of 80.00%, 50.00%, 65.00%, and 65.00%, respectively. The area under the receiver operating characteristic curve for the baseline values of IJVV, SVV, PPV, and the combination of IJVV and PPV was 0.52 (95% CI, 0.38–0.65, p=0.83), 0.54 (95% CI, 0.40–0.67, p=0.67), 0.58 (95% CI, 0.45–0.71, p=0.31), and 0.57 (95% CI, 0.43–0.71, p=0.37), respectively.ConclusionsUltrasonic-derived IJVV lacked accuracy in predicting fluid responsiveness in patients with AIS undergoing PSF during low Vt ventilation. In addition, the baseline values of PPV, SVV, and the combination of IJVV and PPV did not predict fluid responsiveness in this surgical setting.Trail registrationThis trial was registered at www.chictr.org (ChiCTR2200064947) on 24/10/2022. All data were collected through chart review.

Effects of tidal volume challenge on the reliability of plethysmography variability index in hepatobiliary and pancreatic surgeries: a prospective interventional study

BackgroundThe plethysmography variability index (PVI) is a non-invasive, real-time, and automated parameter for evaluating fluid responsiveness, but it does not reliably predict fluid responsiveness during low tidal volume (VT) ventilation. We hypothesized that in a ‘tidal volume challenge’ with a transient increase in tidal volume from 6 to 8 ml Kg− 1, the changes in PVI could predict fluid responsiveness reliably.MethodWe performed a prospective interventional study in adult patients undergoing hepatobiliary or pancreatic tumor resections and receiving controlled low VT ventilation. The values for PVI, perfusion index, stroke volume variation, and stroke volume index (SVI) were recorded at baseline VT of 6 ml Kg− 1, 1 min after the VT challenge (8 ml Kg− 1), 1 min after VT 6 ml Kg− 1 reduced back again, and then 5 min after crystalloid fluid bolus 6 ml kg− 1 (actual body weight) administered over 10 min. The fluid responders were identified by SVI rise ≥ 10% after the fluid bolus.ResultsThe area under the receiver operating characteristic curve for PVI value change (ΔPVI6–8) after increasing VT from 6 to 8 ml Kg− 1 was 0.86 (95% confidence interval, 0.76–0.96), P < 0.001, 95% sensitivity, 68% specificity, and with best cut-off value of absolute change (ΔPVI6–8) = 2.5%.ConclusionIn hepatobiliary and pancreatic surgeries, tidal volume challenge improves the reliability of PVI for predicting fluid responsiveness and changes in PVI values obtained after tidal volume challenge are comparable to the changes in SVI.

This Month in Anesthesiology

This Month in Anesthesiology

Intraoperative low tidal volume ventilation and the risk of ICD-10 coded delirium and the use for antipsychotic medications

BackgroundLow tidal volume (VT) ventilation and its associated increase in arterial carbon dioxide (PaCO2) may affect postoperative neurologic function. We aimed to test the hypothesis that intraoperative low VT ventilation affect the incidence of postoperative ICD-10 coded delirium and/or the need for antipsychotic medications.MethodsThis is a post-hoc analysis of a large randomized controlled trial evaluating low vs. conventional VT ventilation during major non-cardiothoracic, non-intracranial surgery. The primary outcome was the incidence of ICD-10 delirium and/or the use of antipsychotic medications during hospital stay, and the absolute difference with its 95% confidence interval (CI) was calculated.ResultsWe studied 1206 patients (median age of 64 [55–72] years, 59.0% males, median ARISCAT of 26 [19–37], and 47.6% of ASA 3). ICD-10 coded delirium and /or antipsychotic medication use was diagnosed in 11.2% with similar incidence between low and conventional VT ventilation (11.1% vs. 11.3%; absolute difference, -0.24 [95%CI, -3.82 to 3.32]; p = 0.894). There was no interaction between allocation group and type of surgery.ConclusionIn adult patients undergoing major surgery, low VT ventilation was not associated with increased risk of ICD-10 delirium and/or the use of antipsychotic medications during hospital stay.Trial registrationANZCTR Identifier: ACTRN12614000790640.

Efficacy of using tidal volume challenge to improve the reliability of pulse pressure variation reduced in low tidal volume ventilated critically ill patients with decreased respiratory system compliance

BackgroundThe prediction accuracy of pulse pressure variation (PPV) for fluid responsiveness was proposed to be unreliable in low tidal volume (Vt) ventilation. It was suggested that changes in PPV obtained by transiently increasing Vt to 8 ml/kg accurately predicted fluid responsiveness even in subjects receiving low Vt. We assessed whether the changes in PPV induced by a Vt challenge predicted fluid responsiveness in our critically ill subjects ventilated with low Vt 6 ml/kg.MethodsThis study is a prospective single-center study. PPV and other parameters were measured at a Vt of 6 mL/kg, 8 mL/kg, and after volume expansion. The prediction accuracy of PPV and other parameters for fluid responsiveness before and after tidal volume challenge was also analyzed using receiver operating characteristic (ROC) curves.ResultsThirty-one of the 76 subjects enrolled in the study were responders (41%). Respiratory system compliance of all subjects decreased significantly (26 ± 4.3). The PPV values were significantly higher in the responder group than the non-responder group before (8.8 ± 2.7 vs 6.8 ± 3.1) or after (13.0 ± 1.7 vs 8.5 ± 3.0) Vt challenge. In the receiver operating characteristic curve (ROC) analysis, PPV6 showed unsatisfactory predictive capability with an area under the curve (AUC) of 0.69 (95%CI, 0.57–0.79, p = 0.002) at a Vt of 6 mL/kg. PPV8 andΔPPV6–8 showed good predictive capability with an AUC of 0.90 (95% CI, 0.81–0.96, p < 0.001) and 0.90 (95% CI, 0.80–0.95, P < 0.001) respectively. The corresponding cutoff values were 11% for PPV8 and 2% for ΔPPV6–8.ConclusionsPPV shows a poor operative performance as a predictor of fluid responsiveness in critically ill subjects ventilated with a tidal volume of 6 mL/ kg. Vt challenge could improve the predictive accuracy of PPV to a good but not excellent extent when respiratory system compliance decreased significantly.

Role of inflammation and apoptosis in right ventricular dysfunction induced by injurious mechanical ventilation in rats

To investigate whether myocardial inflammation and apoptosis are involved in right ventricular dysfunction (RVD) induced by injurious mechanical ventilation with high tidal volume (VT) in rats. Total 30 adult male SD rats were randomly divided into the control group (CON group), the low VT ventilation group (LVT group) and the injurious mechanical ventilation group (HVT group), with 10 rats in each group. The CON group was maintained spontaneous breathing, the LVT group and HVT group were ventilated with different VT 6 mL/kg and 20 mL/kg for 4 hours, respectively. The right jugular vein and the left carotid artery were catheterized and connected with the PowerLab biological signal acquisition and analysis system to record heart rate (HR), mean arterial pressure (MAP), right ventricular systolic pressure (RVSP), the maximum rate of rising of right ventricular pressure (+dp/dt max). Echocardiography was performed to measure left ventricular end-diastolic diameter (LVEDd), right ventricular end-diastolic diameter (RVEDd), tricuspid annulus plane systolic migration (TAPSE) and myocardial performance index (MPI). The rats were sacrified by cervical dislocation. Specimens of right ventricle tissues were taken for hematoxylin-eosin (HE) staining, and morphological changes of right ventricle tissues were observed under light microscope. Real time reverse transcription-polymerase chain reaction (RT-PCR) and Western blotting were used to detect the mRNA and protein expressions of interleukin-6 (IL-6), tumor necrosis factor-α (TNF-α), caspase-3, apoptosis-related proteins Bax and Bcl-2. HR, MAP, +dp/dt max gradually decreased, while RVSP gradually increased in different group with the increase of VT ventilation. There was no significant difference between the CON group and LVT group. However, there was a statistically significant difference with respect to these index in HVT group as compared to CON group and LVT group [HR (bpm): 397.6±5.7 vs. 433.0±4.8, 441.6±7.8; MAP (mmHg, 1 mmHg ≈ 0.133 kPa): 102.0±2.4 vs. 108.5±2.2, 110.6±2.1; +dp/dt max (mmHg/s): 2 357.65±62.80 vs. 2 661.27±55.62, 2 679.43±75.13; RVSP (mmHg): 28.8±1.0 vs. 22.6±10.8, 21.9±0.4; all P < 0.05]. Echocardiography findings showed that RVEDd/LVEDd and MPI gradually increased, TAPSE gradually decreased in different group with the increase of VT ventilation. There was no significant difference between the LVT group and CON group. However, there was a statistically significant difference with respect to these indexes in HVT group as compared to the CON group and LVT group [RVEDd/LVEDd: 0.36±0.02 vs. 0.26±0.01, 0.23±0.02; MPI: 1.23±0.03 vs. 0.84±0.04, 0.86±0.03; TAPSE (mm): 1.65±0.03 vs. 1.88±0.02, 1.91±0.04; all P < 0.05]. Histopathological observation of the right ventricle tissue showed that myocardial cells of the rats in the CON group were orderly arranged and uniformed in size. In the LVT group, there was a small amount of inflammatory cell infiltration in the myocardial interstitium, while in the HVT group, the myocardial cell arrangement was obviously disordered, the structure was obviously damaged, and more inflammatory cell infiltration was found. RT-PCR and Western blotting analysis showed that the mRNA and protein expressions of IL-6, TNF-α, caspase-3 and Bax in HVT group were significantly higher than those in the LVT group and CON group [mRNA expression (2-ΔΔCt): IL-6 were 1.97±0.07 vs. 1.09±0.02, 1.02±0.03, TNF-α were 1.69±0.10 vs. 1.10±0.03, 1.05±0.04, caspase-3 were 1.82±0.09 vs. 1.08±0.02, 1.06±0.03, Bax were 2.19±0.14 vs. 1.07±0.03, 1.04±0.03; protein expression (gray value): IL-6 were 0.64±0.02 vs. 0.38±0.03, 0.31±0.04, TNF-α were 0.50±0.04 vs. 0.16±0.01, 0.15±0.01, caspase-3 were 0.58±0.02 vs. 0.29±0.01, 0.25±0.02, Bax were 0.50±0.03 vs. 0.21±0.01, 0.26±0.02; all P < 0.05], and the mRNA and protein expressions of Bcl-2 in the HVT group were lower than those in the LVT group and CON group [mRNA expression (2-ΔΔCt): 1.23±0.05 vs. 1.43±0.05, 1.50±0.08; protein expression (gray value): 0.42±0.02 vs. 0.62±0.03, 0.65±0.03, all P < 0.05]. Myocardial inflammation and apoptosis may be involved in RVD induced by injurious mechanical ventilation.

Does Wim Hof Method Improve Breathing Economy during Exercise?

(1) Background: Breathing economy during endurance sports plays a major role in performance. Poor breathing economy is mainly characterized by excessive breathing frequency (BF) and low tidal volume (VT) due to shallow breathing. The purpose of this study was to evaluate whether a 4 week intervention based on the Wim Hof breathing method (WHBM) would improve breathing economy during exercise in adolescent runners. (2) Methods: 19 adolescent (16.6 ± 1.53 years) middle- and long-distance runners (11 boys and 8 girls) participated in the study. Participants were randomly divided into experimental (n = 11) and control groups (n = 8). The study was set in the transition period between competitive race seasons and both groups had a similar training program in terms of running volume and intensity over the course of the study. The experimental group performed breathing exercises every day (~20 min/day) for 4 weeks. The control group did not perform any kind of breathing exercise. The breathing exercises consisted of three sets of controlled hyperventilation and consecutive maximum breath holds. Before and after the intervention, participants performed incremental cycle ergometer testing sessions consisting of two minute stages at 1, 2, 3, and 4 W·kg−1 with breath-by-breath metabolic analysis. During the testing sessions, BF, VT, and minute ventilation (VE) were assessed and compared. (3) Results: There were no statistically significant differences (p > 0.05) in BF, VT, or VE between experimental and control groups before or after the intervention. A nonsignificant small-to-large effect for an increase in VE and BF in both groups following the 4 week intervention period was observed, possibly due to a reduction in training volume and intensity owing to the down period between competitive seasons. (4) Conclusions: The 4 week intervention of WHBM did not appear to alter parameters of breathing economy during a maximal graded exercise test in adolescent runners.

Epidemiology, ventilation management and outcome in patients receiving intensive care after non–thoracic surgery – Insights from the LAS VEGAS study

Introduction and objectivesInformation about epidemiology, ventilation management and outcome in postoperative intensive care unit (ICU) patients remains scarce. The objective was to test whether postoperative ventilation differs from that in the operation room. Material and methodsThis was a substudy of the worldwide observational LAS VEGAS study, including patients undergoing non–thoracic surgeries. Of 146 study sites participating in the LAS VEGAS study, 117 (80%) sites reported on the postoperative ICU course, including ventilation and complications. The coprimary outcomes were two key elements of ventilator management, i.e., tidal volume (VT) and positive end–expiratory pressure (PEEP). Secondary outcomes included the proportion of patients receiving low VT ventilation (LTVV, defined as ventilation with a median VT < 8.0 ml/kg PBW), and the proportion of patients developing postoperative pulmonary complications (PPC), including ARDS, pneumothorax, pneumonia and need for escalation of ventilatory support, ICU and hospital length of stay, and mortality at day 28. ResultsOf 653 patients who were admitted to the ICU after surgery, 274 (42%) patients received invasive postoperative ventilation. Median postoperative VT was 8.4 [7.3–9.8] ml/kg predicted body weight (PBW), PEEP was 5 [5–5] cm H2O, statistically significant but not meaningfully different from median intraoperative VT (8.1 [7.3–8.9] ml/kg PBW; P < 0.001) and PEEP (4 [2–5] cm H2O; P < 0.001). The proportion of patients receiving LTVV after surgery was 41%. The PPC rate was 10%. Length of stay in ICU and hospital was independent of development of a PPC, but hospital mortality was higher in patients who developed a PPC (24 versus 4%; P < 0.001). ConclusionsIn this observational study of patients undergoing non–thoracic surgeries, postoperative ventilation was not meaningfully different from that in the operating room. Like in the operating room, there is room for improved use of LTVV. Development of PPC is associated with mortality.

Constant Vt Ventilation and Surfactant Dysfunction: An Overlooked Cause of Ventilator-induced Lung Injury.

Ventilator-induced lung injury (VILI) is currently ascribed to volutrauma and/or atelectrauma, but the effect of constant Vt ventilation (CVtV) has received little attention. This Perspective summarizes the literature documenting that CVtV causes VILI and reviews the mechanisms by which it occurs. Surfactant is continuously inactivated, depleted, displaced, or desorbed as a function of the duration of ventilation, the Vt, the level of positive end-expiratory pressure (PEEP), and possibly the respiratory rate. Accordingly, surfactant must be continuously replenished, and secretion primarily depends on intermittent delivery of large ventilatory excursions. The surfactant abnormalities resulting from CVtV result in atelectasis and VILI. Although surfactant secretion is reduced by the absence of intermittent deep breaths, continuous administration of large Vts depletes surfactant and impairs subsequent secretion. Low or normal lung volumes result in desorption of surfactant. PEEP can be protective by reducing surface film collapse and subsequent film rupture on reexpansion, and/or by reducing surfactant displacement into the airways, but PEEP can also downregulate surfactant release. The effect of CVtV on surfactant is complex. If attention is not paid to facilitating surfactant secretion and limiting its inactivation, depletion, desorption, or displacement, surface tension will increase and atelectasis and VILI will occur.

Ability of Carotid Corrected Flow Time to Predict Fluid Responsiveness in Patients Mechanically Ventilated Using Low Tidal Volume after Surgery.

Predicting fluid responsiveness in patients under mechanical ventilation with low tidal volume (VT) is challenging. This study evaluated the ability of carotid corrected flow time (FTc) assessed by ultrasound for predicting the fluid responsiveness during low VT ventilation. Patients under postoperative mechanical ventilation and clinically diagnosed with hypovolemia were enrolled. Carotid FTc and pulse pressure variation (PPV) were measured at VT of 6 and 10 mL/kg predicted body weight (PBW). FTc was calculated using both Bazett’s (FTcB) and Wodey’s (FTcW) formulas. Fluid responsiveness was defined as a ≥15% increase in the stroke volume index assessed by FloTrac/Vigileo monitor after administration of 8 mL/kg of balanced crystalloid. Among 36 patients, 16 (44.4%) were fluid responders. The areas under the receiver operating characteristic curves (AUROCs) for the FTcB at VT of 6 and 10 mL/kg PBW were 0.897 (95% confidence interval [95% CI]: 0.750–0.973) and 0.895 (95% CI: 0.748–0.972), respectively. The AUROCs for the FTcW at VT of 6 and 10 mL/kg PBW were 0.875 (95% CI: 0.722–0.961) and 0.891 (95% CI: 0.744–0.970), respectively. However, PPV at VT of 6 mL/kg PBW (AUROC: 0.714, 95% CI: 0.539–0.852) showed significantly lower accuracy than that of PPV at VT of 10 mL/kg PBW (AUROC: 0.867, 95% CI: 0.712–0.957; p = 0.034). Carotid FTc can predict fluid responsiveness better than PPV during low VT ventilation. However, further studies using automated continuous monitoring system are needed before its clinical use.

YAP expression in endothelial cells prevents ventilator-induced lung injury.

Ventilator-induced lung injury is associated with an increase in mortality in patients with respiratory dysfunction, although mechanical ventilation is an essential intervention implemented in the intensive care unit. Intrinsic molecular mechanisms for minimizing lung inflammatory injury during mechanical ventilation remain poorly defined. We hypothesize that Yes-associated protein (YAP) expression in endothelial cells protects the lung against ventilator-induced injury. Wild-type and endothelial-specific YAP-deficient mice were subjected to a low (7 mL/kg) or high (21 mL/kg) tidal volume (VT) ventilation for 4 h. Infiltration of inflammatory cells into the lung, vascular permeability, lung histopathology, and the levels of inflammatory cytokines were measured. Here, we showed that mechanical ventilation with high VT upregulated YAP protein expression in pulmonary endothelial cells. Endothelial-specific YAP knockout mice following high VT ventilation exhibited increased neutrophil counts and protein content in bronchoalveolar lavage fluid, Evans blue leakage, and histological lung injury compared with wild-type littermate controls. Deletion of YAP in endothelial cells exaggerated vascular endothelial (VE)-cadherin phosphorylation, downregulation of vascular endothelial protein tyrosine phosphatase (VE-PTP), and dissociation of VE-cadherin and catenins following mechanical ventilation. Importantly, exogenous expression of wild-type VE-PTP in the pulmonary vasculature rescued YAP ablation-induced increases in neutrophil counts and protein content in bronchoalveolar lavage fluid, vascular leakage, and histological lung injury as well as VE-cadherin phosphorylation and dissociation from catenins following ventilation. These data demonstrate that YAP expression in endothelial cells suppresses lung inflammatory response and edema formation by modulating VE-PTP-mediated VE-cadherin phosphorylation and thus plays a protective role in ventilator-induced lung injury.

Predicting Fluid Responsiveness Using Change in Pulse Pressure Variation and Stroke Volume Variation after Tidal Volume Challenge in Postoperative Patients Receiving Lung Protective Ventilation

Background: Lung protective ventilation with low tidal volume (VT) is beneficial in patients with intermediate to high risk of post-operative pulmonary complications. However, during low VT ventilation, pulse pressure variation (PPV) and stroke volume variation (SVV) do not predict fluid responsiveness. Objective: To determine whether changes in PPV and SVV after transient increases in VT could predict fluid responsiveness. Materials and Methods: The authors recorded 20 measurements from 15 patients experiencing post-operative acute circulatory failure. The authors performed a VT challenge by transient increasing VT from 6 to 8 mL/kg (VT₆-₈), 8 to 10 mL/kg (VT₈-₁₀), and 6 to 10 mL/kg (VT₆-₁₀) of patients’ predicted body weight. The change in PPV (∆PPV) at VT₆-₈ (∆PPV₆-₈), VT₈-₁₀ (∆PPV₈-₁₀), VT₆-₁₀ (∆PPV₆-₁₀), and the change in SVV (∆SVV) at VT₆-₈ (∆SVV₆-₈), VT₈-₁₀ (∆SVV₈-₁₀), and VT₆-₁₀ (∆SVV₆-₁₀) were recorded. Patients were classified as fluid responders if there was an increase in stroke volume of more than 10% after a fluid bolus. Results: Following the VT challenge, ∆PPV and ∆SVV failed to predict fluid responsiveness, with areas under the receiver operating characteristic curves (with 95% confidence intervals) of 0.49 (0.23 to 0.74), 0.54 (0.29 to 0.79), 0.52 (0.28 to 0.77) for ∆PPV₆-₈, ∆PPV₈-₁₀, and ∆PPV₆-₁₀, and 0.55 (0.30 to 0.80), 0.55 (0.31 to 0.80), and 0.59 (0.34 to 0.84) for ∆SVV₆-₈, ∆SVV₈-₁₀, and ∆SVV₆-₁₀, respectively. Conclusion: Changes in PPV and SVV after the VT challenge did not predict fluid responsiveness in post-operative patients with low VT ventilation. Trial registration: Thai Clinical Trials Registry, TCTR 20190808003 Keywords: Pulse pressure variation, Stroke volume variation, Fluid responsiveness, Tidal volume challenge

Combined Mesenchymal Stromal Cell Therapy and Extracorporeal Membrane Oxygenation in Acute Respiratory Distress Syndrome. A Randomized Controlled Trial in Sheep.

Rationale: Mesenchymal stromal cell (MSC) therapy is a promising intervention for acute respiratory distress syndrome (ARDS), although trials to date have not investigated its use alongside extracorporeal membrane oxygenation (ECMO). Recent preclinical studies have suggested that combining these interventions may attenuate the efficacy of ECMO.Objectives: To determine the safety and efficacy of MSC therapy in a model of ARDS and ECMO.Methods: ARDS was induced in 14 sheep, after which they were established on venovenous ECMO. Subsequently, they received either endobronchial induced pluripotent stem cell-derived human MSCs (hMSCs) (n = 7) or cell-free carrier vehicle (vehicle control; n = 7). During ECMO, a low Vt ventilation strategy was employed in addition to protocolized hemodynamic support. Animals were monitored and supported for 24 hours. Lung tissue, bronchoalveolar fluid, and plasma were analyzed, in addition to continuous respiratory and hemodynamic monitoring.Measurements and Main Results: The administration of hMSCs did not improve oxygenation (PaO2/FiO2 mean difference = -146 mm Hg; P = 0.076) or pulmonary function. However, histological evidence of lung injury (lung injury score mean difference = -0.07; P = 0.04) and BAL IL-8 were reduced. In addition, hMSC-treated animals had a significantly lower cumulative requirement for vasopressor. Despite endobronchial administration, animals treated with hMSCs had a significant elevation in transmembrane oxygenator pressure gradients. This was accompanied by more pulmonary artery thromboses and adherent hMSCs found on explanted oxygenator fibers.Conclusions: Endobronchial hMSC therapy in an ovine model of ARDS and ECMO can impair membrane oxygenator function and does not improve oxygenation. These data do not recommend the safe use of hMSCs during venovenous ECMO.

Dose of budesonide with surfactant affects lung and systemic inflammation after normal and injurious ventilation in preterm lambs.

Background:The addition of budesonide (Bud) 0.25 mg/kg to surfactant decreased the lung and systemic responses to mechanical ventilation in preterm sheep, and the rates and severity of bronchopulmonary dysplasia (BPD) in preterm infants.Hypothesis:Lower budesonide concentrations in surfactant will decrease injury while decreasing systemic corticosteroid exposure.Methods:Preterm lambs received either: 1) protective tidal volume (VT) ventilation with surfactant from birth or 2) injurious VT ventilation for 15 minutes then surfactant treatment. Lambs were further assigned to surfactant mixed with: i) Saline, ii) Bud 0.25 mg/kg, iii) Bud 0.1 mg/kg, or iv) Bud 0.04 mg/kg. All lambs were then ventilated with protective VT for 6 hours.Results:Plasma Bud levels were proportional to the dose received, and decreased throughout ventilation. In both protective and injurious VT ventilation, less than 4% of Bud remained in the lung at 6 h. Some of the improvements in physiology and markers of injury with Bud 0.25 mg/kg were also found with 0.1 mg/kg, whereas 0.04 mg/kg had only minimal effects.Conclusion:Lower doses of Bud were less effective at decreasing lung and systemic inflammation from mechanical ventilation. The plasma Bud levels were proportional to dose given and the majority left the lung.

Intraoperative ventilation strategies to prevent postoperative pulmonary complications: a network meta-analysis of randomised controlled trials

BackgroundThe debate on lung-protective ventilation strategies for surgical patients is ongoing. Evidence suggests that the use of low tidal volume VT improves clinical outcomes. However, the optimal levels of PEEP and recruitment manoeuvre (RM) strategies incorporated into low VT ventilation remain unclear. MethodsSeveral electronic databases were searched to identify RCTs that focused on comparison between low VT strategy and conventional mechanical ventilation (CMV), or between two different low VT strategies in surgical patients. The primary outcome was postoperative pulmonary complications (PPCs). The secondary outcomes were atelectasis, pneumonia, acute respiratory distress syndrome, and short-term mortality. Bayesian network meta-analyses were performed using WinBUGS. The odds ratios (ORs) and corresponding 95% credible intervals (CrIs) were estimated. ResultsCompared with CMV, low VT ventilation with moderate-to-high PEEP reduced the risk of PPCs (moderate PEEP [5–8 cm H2O]: OR 0.50 [95% CrI: 0.28, 0.89]; moderate PEEP+RMs: 0.39 [0.19, 0.78]; and high PEEP [≥9 cm H2O]+RMs: 0.34 [0.14, 0.79]). Low VT ventilation with moderate-to-high PEEP and RMs also specifically reduced the risk of atelectasis compared with CMV (moderate PEEP+RMs: OR 0.36 [95% CrI: 0.16, 0.87]; and high PEEP+RMs: 0.41 [0.15, 0.97]), whilst low VT ventilation with moderate PEEP was superior to CMV in reducing the risk of pneumonia (OR 0.46 [95% CrI: 0.15, 0.94]). ConclusionsThe combination of low VT ventilation and moderate-to-high PEEP (≥5 cm H2O) seems to confer lung protection in surgical patients undergoing general anaesthesia. Clinical trial registrationPROSPERO (CRD42019144561)

Surfactant plus budesonide decreases lung and systemic responses to injurious ventilation in preterm sheep.

Mechanical ventilation from birth with normal tidal volumes (VT) causes lung injury and systemic responses in preterm sheep. The addition of budesonide to surfactant therapy decreases these injury markers. Budesonide and surfactant will decrease the injury from injurious VT ventilation in preterm sheep. Lambs at 126 ± 1 day gestational age were ventilated from birth with either: 1) Normal VT [surfactant 200 mg/kg before ventilation, positive end expiratory pressure (PEEP) 5 cmH2O, VT 8 mL/kg] or 2) Injury VT (high pressure, 100% oxygen, no PEEP) for 15 min, then further randomized to surfactant + saline or surfactant + 0.25 mg/kg budesonide with Normal VT for 6 h. Lung function and lung, liver, and brain tissues were evaluated for indicators of injury. Injury VT + saline caused significant injury and systemic responses, and Injury VT + budesonide improved lung physiology. Budesonide decreased lung inflammation and decreased pro-inflammatory cytokine mRNA in the lung, liver, and brain to levels similar to Normal VT + saline. Budesonide was present in plasma within 15 min of treatment in both ventilation groups, and less than 5% of the budesonide remained in the lung at 6 h. mRNA sequencing of liver and periventricular white matter demonstrated multiple pathways altered by both Injury VT and budesonide and the combination exposure. In lambs receiving Injury VT, the addition of budesonide to surfactant improved lung physiology and decreased pro-inflammatory cytokine responses in the lung, liver, and brain to levels similar to lambs receiving Normal VT.

Role and mechanism of Ly6Chigh monocyte in ventilator-induced lung injury in mice

To investigate the role and mechanism of Ly6Chigh monocyte in mice with ventilator-induced lung injury (VILI). Forty-eight healthy male SPF C57BL/6 mice were divided into spontaneous breathing group (n = 8), normal tidal volume (VT) group (VT was 8 mL/kg, n = 8), and high VT group (VT was 20 mL/kg, n = 32). The mice in the high VT group were subdivided into 1, 2, 3 and 4 hours subgroups, with 8 mice in each subgroup. All mice underwent direct tracheal intubation, those in the spontaneous breathing group maintained spontaneous breathing, and those in the normal VT group and high VT group were mechanically ventilated with different VT. After ventilation for 4 hours, bronchoalveolar lavage fluid (BALF) was collected to determine total protein, and the levels of inflammatory factors including tumor necrosis factor-α (TNF-α) and interleukin-1β (IL-1β) were determined by enzyme-linked immune sorbent assay (ELISA). The lung tissues were harvested to determine the wet/dry (W/D) ratio, and lung tissue injury was assessed in terms of lung histopathologic examination after hematoxylin-eosin (HE) staining under the light microscope. The protein expressions of monocyte chemotactic protein-1 (MCP-1) and CC-chemokine receptor 2 (CCR2) in lung tissues were determined by Western Blot. Flow cytometry was used to detect the proportion of Ly6Chigh monocyte in lung tissue. The histopathology of lung tissue structures was normal in the spontaneous breathing group and the normal VT group. Inflammatory reaction began to appear at 2 hours of high VT ventilation, and inflammatory reaction was gradually aggravated with the time extension. Compared with the spontaneous breathing group, the total protein, TNF-α, and IL-1β levels in BALF, the lung W/D ratio and MCP-1 expression were increased from 2 hours of high VT ventilation [total protein in BALF (g/L): 1.05±0.13 vs. 0.58±0.11, TNF-α in BALF (ng/L): 116.86±16.14 vs. 38.27±8.00, IL-1β in BALF (ng/L): 178.98±10.41 vs. 117.56±23.40, lung W/D ratio: 5.76±0.27 vs. 4.98±0.39, MCP-1/GAPDH: 0.87±0.19 vs. 0.29±0.12, all P < 0.05], and CCR2 expression and the proportion of Ly6Chigh monocyte was significantly increased from 3 hours of high VT ventilation [CCR2/GAPDH: 0.84±0.19 vs. 0.24±0.11, Ly6Chigh monocyte proportion: (9.01±2.47)% vs. (1.06±0.35)%, both P < 0.05], and they all showed an increased tendency with the time extension. There was no significant difference in the parameters mentioned above among the spontaneous breathing group, normal VT group and high VT ventilation 1-hour group. Ly6Chigh monocytes are involved in VILI, which aggravate VILI by activating the MCP-1/CCR2 axis.