Reduction In Tidal Volume Research Articles

Contribution of electrical impedance tomography to personalize positive end-expiratory pressure under ECCO2R

Extracorporeal Carbon Dioxide Removal (ECCO2R) is used in acute respiratory distress syndrome (ARDS) patients to facilitate lung-protective ventilatory strategies. Electrical Impedance Tomography (EIT) allows individual, non-invasive, real-time, bedside, radiation-free imaging of the lungs, providing global and regional dynamic lung analyses. To provide new insights for future ECCO2R research in ARDS, we propose a potential application of EIT to personalize End-Expiratory Pressure (PEEP) following each reduction in tidal volume (VT), as demonstrated in an illustrative case. A 72-year-old male with COVID-19 was admitted to the ICU for moderate ARDS. Monitoring with EIT was started to determine the optimal PEEP value (PEEPEIT), defined as the intersection of the collapse and overdistention curves, after each reduction in VT during ECCO2R. The identified PEEPEIT values were notably low (< 10 cmH2O). The decrease in VT associated with PEEPEIT levels resulted in improved lung compliance, reduced driving pressure and a more uniform ventilation pattern. Despite current Randomized Controlled Trials showing that ultra-protective ventilation with ECCO2R does not improve survival, the applicability of universal ultra-protective ventilation settings for all patients remains a subject of debate. Inappropriately set PEEP levels can lead to alveolar collapse or overdistension, potentially negating the benefits of VT reduction. EIT facilitates real-time monitoring of derecruitment associated with VT reduction, guiding physicians in determining the optimal PEEP value after each decrease in tidal volume. This original description of using EIT under ECCO2R to adjust PEEP at a level compromising between recruitability and overdistention could be a crucial element for future research on ECCO2R.

Respiratory Safety Pharmacological Testing with Single Intravenous Administration of Caffeine in Sprague-Dawley Rats.

As caffeine consumption continues to increase, both positive and negative effects are becoming evident. Caffeine directly affects the cardiovascular system, including heart function and rate. Thus, understanding the current respiratory safety pharmacological responses is of utmost importance. To elucidate the respiratory safety pharmacological characteristics of caffeine, male Sprague-Dawley rats, aged 6 weeks, were intravenously administered doses of 0, 2, 6, and 20 mg/kg of caffeine. Respiratory rate, tidal volume, and minute volume were subsequently measured. In this study, we observed a significant increase in respiratory rate and minute volume, but a remarkable reduction in tidal volume following the intravenous administration of caffeine at doses exceeding 6 mg/kg. These changes were evident within the timeframe of 0.25 to 1.5 h. The data we have collected can serve as valuable foundational scientific information for future research on caffeine, encompassing absorption, distribution, metabolism, excretion, and pharmacological core-battery experiments.

Extracorporeal Carbon Dioxide Removal With the Hemolung in Patients With Acute-on-Chronic Respiratory Failure: A Multicenter Retrospective Cohort Study.

Extracorporeal carbon dioxide removal (ECCO2R) devices are increasingly used in treating acute-on-chronic respiratory failure caused by chronic lung diseases. There are no large studies that investigated safety, efficacy, and the independent association of prognostic variables to survival that could define the role of ECCO2R devices in such patients. This multicenter, multinational, retrospective study investigated the efficacy, safety of a single ECCO2R device (Hemolung) in patients with acute on chronic respiratory failure and identified variables independently associated with intensive care unit (ICU) survival. The primary outcome was improvement in blood gasses with the use of Hemolung. Secondary outcomes included reduction in tidal volume, respiratory rate, minute ventilation, survival to ICU discharge, and complication profile. Multivariable regression analysis was used to identify variables that are independently associated with ICU survival. A total of 62 patients were included. There was a significant improvement in pH and partial pressure of carbon dioxide in arterial blood (PaCO2) along with a reduction in respiratory rate, tidal volume, and minute ventilation with Hemolung therapy. The complication profile did not differ between survivors and nonsurvivors. Multivariable analysis identified the duration of Hemolung therapy to be independently associated with survival to ICU discharge (adjusted odds ratio = 1.21; 95% confidence interval [CI] = 1.040-1.518; p = 0.01).

The Effect of Lower Tidal Volume Ventilation Facilitated by Extracorporeal Carbon Dioxide Removal Compared With Conventional Lung Protective Ventilation on Cardiac Function.

Lower tidal volume ventilation (targeting 3 mL/kg predicted body weight, PBW) facilitated by extracorporeal carbon dioxide removal (ECCO2R) has been investigated as a potential therapy for acute hypoxemic respiratory failure (AHRF) in the pRotective vEntilation with veno-venouS lung assisT in respiratory failure (REST) trial. We investigated the effect of this strategy on cardiac function, and in particular the right ventricle. Substudy of the REST trial. Nine U.K. ICUs. Patients with AHRF (Pao2/Fio2 < 150 mm Hg [20 kPa]). Transthoracic echocardiography and N-terminal pro-B-type natriuretic peptide (NT-proBNP) measurements were collected at baseline and postrandomization in patients randomized to ECCO2R or usual care. The primary outcome measures were a difference in tricuspid annular plane systolic excursion (TAPSE) on postrandomization echocardiogram and difference in NT-proBNP postrandomization. There were 21 patients included in the echocardiography cohort (ECCO2R, n = 13; usual care, n = 8). Patient characteristics were similar in both groups at baseline. Median (interquartile range) tidal volumes were lower in the ECCO2R group compared with the usual care group postrandomization; 3.6 (3.1-4.2) mL/kg PBW versus 5.2 (4.9-5.7) mL/kg PBW, respectively (p = 0.01). There was no difference in the primary outcome measure of mean (sd) TAPSE in the ECCO2R and usual care groups postrandomization; 21.3 (5.4) mm versus 20.1 (3.2) mm, respectively (p = 0.60). There were 75 patients included in the NT-proBNP cohort (ECCO2R, n = 36; usual care, n = 39). Patient characteristics were similar in both groups at baseline. Median (interquartile range [IQR]) tidal volumes were lower in the ECCO2R group than the usual care group postrandomization; 3.8 (3.3-4.2) mL/kg PBW versus 6.7 (5.8-8.1) mL/kg PBW, respectively (p < 0.0001). There was no difference in median (IQR) NT-proBNP postrandomization; 1121 (241-5370) pg/mL versus 1393 (723-4332) pg/mL in the ECCO2R and usual care groups, respectively (p = 0.30). In patients with AHRF, a reduction in tidal volume facilitated by ECCO2R, did not modify cardiac function.

Factors associated with decreased compliance after on-site extracorporeal membrane oxygenation cannulation for acute respiratory distress syndrome: A retrospective, observational cohort study

BackgroundExtracorporeal membrane oxygenation (ECMO) for acute respiratory distress syndrome (ARDS) is systematically associated with decreased respiratory system compliance (CRS). It remains unclear whether transportation to the referral ECMO center, changes in ventilatory mode or settings to achieve ultra-protective ventilation, or the natural evolution of ARDS drives this change in respiratory mechanics. Herein, we assessed the precise moment when CRS decreases after ECMO cannulation and identified factors associated with decreased CRS. MethodsTo rule out the effect of transportation and the different modes of ventilation on CRS, we conducted a retrospective, single-center, observational cohort study from January 2013 to May 2020, on 22 patients with severe ARDS requiring on-site ECMO and ventilated in pressure-controlled mode to achieve ultra-protective ventilation. CRS was assessed at different time points ranging from 12 h before ECMO cannulation to 72 h after ECMO cannulation. The primary outcome was the relative change in CRS between 3 h before and 3 h after ECMO cannulation. The secondary outcomes included variables associated with the relative changes in CRS within the first 3 h after ECMO cannulation and the relative changes in CRS at each time point. ResultsCRS decreased within the first 3 h after ECMO cannulation (−28.3%, 95% confidence interval [CI]: −38.8 to −17.9, P<0.001), while the decrease was mild before and after these first 3 h after ECMO cannulation. To achieve ultra-protective ventilation, respiratory rate decreased in the mean by –13 breaths/min (95% CI: −15 to −11) and driving pressure by −8.3 cmH2O (95% CI: −11.2 to −5.3), resulting in decreased tidal volume by −3.3 mL/kg of predicted body weight (95% CI: −3.9 to −2.6) as compared to before ECMO cannulation (P <0.001 for all). Plateau pressure reduction, driving pressure reduction, and tidal volume reduction were significantly associated with decreased CRS after ECMO cannulation, whereas neither respiratory rate, positive end-expiratory pressure, inspired fraction of oxygen, fluid balance, nor mean airway pressure was associated with decreased CRS. ConclusionsDecreased driving pressure resulting in lower tidal volume to achieve ultra-protective ventilation after ECMO cannulation was associated with a marked decrease in CRS in ARDS patients with on-site ECMO cannulation.

Thoracoabdominal asynchrony in a virtual preterm infant: computational modeling and analysis.

Thoracoabdominal asynchrony (TAA), the asynchronous volume changes between the rib cage and abdomen during breathing, is associated with respiratory distress, progressive lung volume loss, and chronic lung disease in the newborn infant. Preterm infants are prone to TAA risk factors such as weak intercostal muscles, surfactant deficiency, and a flaccid chest wall. The causes of TAA in this fragile population are not fully understood and, to date, the assessment of TAA has not included a mechanistic modeling framework to explore the role these risk factors play in breathing dynamics and how TAA can be resolved. We present a dynamic compartmental model of pulmonary mechanics that simulates TAA in the preterm infant under various adverse clinical conditions, including high chest wall compliance, applied inspiratory resistive loads, bronchopulmonary dysplasia, anesthesia-induced intercostal muscle deactivation, weakened costal diaphragm, impaired lung compliance, and upper airway obstruction. Sensitivity analyses performed to screen and rank model parameter influence on model TAA and respiratory volume outputs show that risk factors are additive so that maximal TAA occurs in a virtual preterm infant with multiple adverse conditions, and addressing risk factors individually causes incremental changes in TAA. An abruptly obstructed upper airway caused immediate nearly paradoxical breathing and tidal volume reduction despite greater effort. In most simulations, increased TAA occurred together with decreased tidal volume. Simulated indices of TAA are consistent with published experimental studies and clinically observed pathophysiology, motivating further investigation into the use of computational modeling for assessing and managing TAA.NEW & NOTEWORTHY A novel model of thoracoabdominal asynchrony incorporates literature-derived mechanics and simulates the impact of risk factors on a virtual preterm infant. Sensitivity analyses were performed to determine the influence of model parameters on TAA and respiratory volume. Predicted phase angles are consistent with prior experimental and clinical results, and influential parameters are associated with clinical scenarios that significantly alter phase angle, motivating further investigation into the use of computational modeling for assessing and managing thoracoabdominal asynchrony.

Correlation between inhibition of lung surfactant function in vitro and rapid reduction in tidal volume following exposure to plant protection products in mice.

Currently, testing of acute inhalation toxicity in animals is required for regulation of pesticide active ingredients and formulated plant protection products. The main outcome of the regulatory tests is “lethal concentration 50″ (LC50), i.e. the concentration that will kill 50% of the exposed animals. However, ongoing work aims to identify New Approach Methods (NAMs) to replace animal experiments. To this end, we studied 11 plant protection products, sold in the European Union (EU), for their ability to inhibit lung surfactant function in vitro in the constrained drop surfactometer (CDS). In vivo, inhibition of lung surfactant function can lead to alveolar collapse and reduction of tidal volume. Therefore, we also assessed changes in breathing patterns of mice during exposure to the same products. Six of the eleven products inhibited lung surfactant function, and six products reduced tidal volume in mice. In vitro inhibition of lung surfactant function predicted reduction in tidal volume in exposed mice with a sensitivity of 67% and a specificity of 60%. Two products were labelled as “harmful if inhaled”, both inhibited surfactant function in vitro and reduced tidal volume in mice. Lung surfactant function inhibition in vitro predicted reduction in tidal volume for plant protection products to a lesser degree than for previously tested substances. This could owe to the requirement for rigorous testing of plant protection products prior to approval that might have selected against substances that could potentially inhibit lung surfactant, e.g. due to severe adverse effects during inhalation.

Breathing stability during sleep and during hypercapnia is dependent on the retrotrapezoid nucleus in adult mice

Background: Eupneic breathing during sleep is determined by the chemical drive arising from central and peripheral chemoreceptors. The retrotrapezoid nucleus (RTN) contains chemoreceptor neurons that are proposed to be critical for ventilatory responses to CO 2 . RTN chemoreceptor neurons can be identified by expression of transcripts for Neuromedin B ( Nmb + ). We hypothesized that the ablation of RTN Nmb + neurons cause alveolar hypoventilation at rest and breathing instability during sleep. Normally, in intact subjects, increasing respiratory drive with hypercapnia produces a robust and more stable breathing pattern compared to resting condition. We furhter hypothesized that in the absence of RTN, hypercapnia will not increase breathing stability and the ventilatory response to CO 2 will be impaired. Methods: Bilateral microinjections of a designer cell-ablation virus, AAV5-Flex-Casp3-TEVP, were placed in the RTN in heterozygous Cre-positive (RTN lesion) and Cre-negative (controls) Nmb-Cre mice and EEG/neck EMG electrodes were implanted. One month later, mice were tested in an unrestrained plethysmography chamber for breathing and sleep/wake recordings in normoxic conditions. Mice were exposed to hyperoxic hypercapnia (F I CO 2 up to 0.09) to assess the central respiratory CO 2 chemoreflex after RTN lesion. Arterial blood gases were also collected in unrestrained unanesthetized conditions. Values are presented as mean ±SD. Results: Ablation of the RTN was complete (&lt;1% of total RTN Nmb + neurons remaining in RTN lesion group) and selective based on counts of neighboring catecholaminergic and serotonergic neurons. Arterial PCO 2 was increased in RTN-lesion mice (n=6) compared to controls (n=7) (49 ± 5 vs. 39 ± 3 mmHg, p&lt;0.001) and arterial PO 2 was reduced (75 ± 11 vs. 89 ± 7 mmHg, p=0.019). Minute-ventilation was reduced in RTN-lesion mice (n=13) compared to control (n=13) (1.7 ± 0.4 vs. 2.4 ± 0.3 mL/min/g, p&lt;0.0001) due to a reduction in tidal volume that was most evident during NREM sleep. Breathing variability was increased in RTN-lesion mice (n=9) compared to controls (n=10) during NREM (22 ± 5 vs. 10 ± 1% of inter-breath variability, p&lt;0.001) and REM sleep (37 ± 8 vs. 25 ±7 % of inter-breath variability, p&lt;0.01) but not during wakefulness (28 ± 9 vs. 21 ±10 % of inter-breath variability, p=0.32). The ventilatory response to CO 2 was attenuated in RTN lesion mice compared to controls (3.2 ±1 vs. 10.4 ±2 mL/min/g at FICO2 0.09, p&lt;0.0001).Finally, during hypercapnia, breathing was more variable in RTN-lesion mice (23 ±10 vs. 3.1 ±0.4 % of inter-breath variability, p&lt;0.0001) compared to control. Summary and conclusion: In sum, RTN neurons contribute to resting alveolar ventilation and eupneic breathing, especially during sleep. The hypercapnic ventilatory response is severely blunted and hypercapnia does not increase breathing stability in the absence of RTN. We conclude that breathing stability during sleep and during hypercapnia is dependent on the RTN. This work is funded by National Institutes of Health, R01HL148004 to Stephen BG Abbott and R01HL108609 to Douglas A Bayliss. This is the full abstract presented at the American Physiology Summit 2023 meeting and is only available in HTML format. There are no additional versions or additional content available for this abstract. Physiology was not involved in the peer review process.

Effects of 2 modes of positive pressure ventilation on respiratory mechanics and gas exchange in foals.

Continuous positive airway pressure (CPAP) and pressure support ventilation (PSV) can improve respiratory mechanics and gas exchange, but different airway pressures have not been compared in foals. Assess the effect of different airway pressures during CPAP and PSV have on respiratory function in healthy foals with pharmacologically induced respiratory insufficiency. We hypothesized that increased airway pressures would improve respiratory mechanics and increased positive end-expiratory pressure (PEEP) would be associated with hypercapnia. Six healthy foals from a university teaching herd. A prospective, 2-phase, 2-treatment, randomized cross-over study design was used to evaluate sequential interventions in sedated foals using 2 protocols (CPAP and PSV). Outcome measures included arterial blood gases, spirometry, volumetric capnography, lung volume and aeration assessed using computed tomography (CT). Sedation and dorsal recumbency were associated with significant reductions in arterial oxygen pressure (PaO2 ), respiratory rate, and tidal volume. Continuous positive airway pressure was associated with improved PaO2 , without concurrent hypercapnia. Volumetric capnography identified improved ventilation:perfusion (V/Q) matching and increased carbon dioxide elimination during ventilation, and spirometry identified decreased respiratory rate and increased tidal volume. Peak inspiratory pressure was moderately associated with PaO2 and lung volume. Improved pulmonary aeration was evident in CT images, and lung volume was increased, particularly during CPAP. Both CPAP and PSV improved lung mechanics and gas exchange in healthy foals with induced respiratory insufficiency.

Instrumental dead space: A glass ceiling for extremely low birth weight preterm infants? A dead space washout bench study.

When ventilating extremely low birth weight infants, clinicians face the problem of instrumental dead space, which is often larger than tidal volume. Hence, aggressive ventilation is necessary to achieve CO2 removal. Continuous tracheal gas insufflation can wash out CO2 from dead space and might also have an impact on O2 and water vapor transport. The objective of this bench study is to test the impact of instrumental dead space on the transport of CO2 , O2 , and water vapor and the ability of continuous tracheal gas insufflation to remedy this problem during small tidal volume ventilation. A test-lung located in an incubator at 37°C was ventilated with pressure levels needed to reach different tidal volumes from 1.5to 5 mL. End-tidal CO2 at the test-lung exit, O2 concentration, and relative humidity in the test-lung were measured for each tidal volume with and without a 0.2 L/min continuous tracheal gas insufflation flow. CO2 clearance was improved by continuous tracheal gas insufflation allowing a 28%-44% of tidal volume reduction. With continuous tracheal gas insufflation, time to reach desired O2 concentration was reduced from 20% to 80% and relative humidity was restored. These results are inversely related to tidal volume and are particularly critical below 3 mL. For the smallest tidal volumes, reduction of instrumental dead space seems mandatory for CO2 , O2 , and water vapor transfer. Continuous tracheal gas insufflation improved CO2 clearance, time to reach desired O2 concentration and humidification of airways and, thus, may be an option to protect lung development.

Long term feasibility of ultraprotective lung ventilation with low-flow extracorporeal carbon dioxide removal in ARDS patients.

To explore the feasibility of long-term application of ultraprotective ventilation with low flow ECCO2R support in moderate-severe ARDS patients and the reduction of mechanical power (MP) compared to lung protective ventilation. ARDS patients with PaO2/FiO2 < 200, PEEP of 10 cmH2O, tidal volume 6 ml/Kg of predicted body weight (PBW), plateau pressure > 24 cmH2O, MP > 17 J/min were prospectively enrolled. After 2 h tidal volume was reduced to 4-5 ml/kg, respiratory rate (RR) and PEEP were changed to maintain similar minute ventilation and mean airway pressure (MAP) to those obtained at baseline. After 2 h, ECCO2R support was started, RR was decreased and PEEP was increased to maintain similar PaCO2 and MAP, respectively. The only reduction of tidal volume with the increase in RR did not decrease MP. The application of low flow ECCO2R support allowed a reduction of RR from 25 [24-30] to 11 [9-14] bpm and MP from 18 [13-23] to 8 [7-11] J/min. During the following 5 days no changes in mechanics variables and gas exchange occurred. The application of low flow ECCO2R support with ultraprotective ventilation was feasible minimizing the MP without deterioration in oxygenation in ARDS patients.

The impact of reduction in intensity of mechanical ventilation upon venovenous ECMO initiation on radiographically assessed lung edema scores: A retrospective observational study.

BackgroundPatients with severe acute respiratory distress syndrome (ARDS) typically receive ultra-protective ventilation after extracorporeal membrane oxygenation (ECMO) is initiated. While the benefit of ECMO appears to derive from supporting “lung rest”, reductions in the intensity of mechanical ventilation, principally tidal volume limitation, may manifest radiologically. This study evaluated the relative changes in radiographic assessment of lung edema (RALE) score upon venovenous ECMO initiation in patients with severe ARDS.MethodsDigital chest x-rays (CXR) performed at baseline immediately before initiation of ECMO, and at intervals post (median 1.1, 2.1, and 9.6 days) were reviewed in 39 Adult ARDS patients. One hundred fifty-six digital images were scored by two independent, blinded radiologists according to the RALE (Radiographic Assessment of Lung Edema) scoring criteria. Ventilatory data, ECMO parameters and fluid balance were recorded at corresponding time points. Multivariable analysis was performed analyzing the change in RALE score over time relative to baseline.ResultsThe RALE score demonstrated excellent inter-rater agreement in this novel application in an ECMO cohort. Mean RALE scores increased from 28 (22–37) at baseline to 35 (26–42) (p < 0.001) on D1 of ECMO; increasing RALE was associated with higher baseline APACHE III scores [ß value +0.19 (0.08, 0.30) p = 0.001], and greater reductions in tidal volume [ß value −2.08 (−3.07, −1.10) p < 0.001] after ECMO initiation. Duration of mechanical ventilation, and ECMO support did not differ between survivors and non-survivors.ConclusionsThe magnitude of reductions in delivered tidal volumes correlated with increasing RALE scores (radiographic worsening) in ARDS patients receiving ECMO. Implications for patient centered outcomes remain unclear. There is a need to define appropriate ventilator settings on venovenous ECMO, counterbalancing the risks vs. benefits of optimal “lung rest” against potential atelectrauma.

Welding Fume Instillation in Isolated Perfused Mouse Lungs-Effects of Zinc- and Copper-Containing Welding Fumes.

Zinc- and copper-containing welding fumes can cause systemic inflammation after exposure in humans. Recent ex vivo studies have shown that the observed inflammation originates from exposed immune cells. In vitro studies identified the soluble fraction of metal particles as the main effectors. Isolated perfused mouse lungs (IPLs) were perfused and ventilated for 270 min. Lungs were instilled with saline solution (control), welding fume particle suspension (WFs) or the soluble fraction of the welding fumes (SF-WFs). Bronchoalveolar lavage fluid (BALF) and perfusate samples were analyzed for cytokine levels and lung tissue mRNA expression levels were analyzed via RT-PCR. All lungs instilled with WFs did not complete the experiments due to a fatal reduction in tidal volume. Accordingly, IL-6 and MPO levels were significantly higher in BALF of WF lungs compared to the control. IL-6 and MPO mRNA expression levels were also increased for WFs. Lungs instilled with SF-WFs only showed mild reactions in tidal volume, with BALF and mRNA expression levels not significantly differing from the control. Zinc- and copper-containing welding fume particles adversely affect IPLs when instilled, as evidenced by the fatal loss in tidal volume and increased cytokine expression and secretion. The effects are mainly caused by the particles, not by the soluble fraction.

Prediction of exhaled carbon dioxide concentration using a computer-simulated person that included alveolar gas exchange.

Accurate prediction of inhaled CO2 concentration and alveolar gas exchange efficiency would improve the prediction of CO2 concentrations around the human body, which is essential for advanced ventilation design in buildings. We therefore, developed a computer-simulated person (CSP) that included a computational fluid dynamics approach. The CSP simulates metabolic heat production at the skin surface and carbon dioxide (CO2 ) gas exchange at the alveoli during the transient breathing cycle. This makes it possible to predict the CO2 distribution around the human body. The numerical model of the CO2 gas exchange mechanism includes both the upper and lower airways and makes it possible to calculate the alveolar CO2 partial pressure; this improves the prediction accuracy. We used the CSP to predict emission rates of metabolically generated CO2 exhaled by a person and assumed that the tidal volume will be unconsciously reduced as a result of exposure to poor indoor air quality. A reduction in tidal volume resulted in a decrease in CO2 emission rates of the same magnitude as was observed in our published experimental data. We also observed that the predicted inhaled CO2 concentration depended on the flow pattern around the human body, as would be expected.

Paradoxical response to chest wall loading predicts a favorable mechanical response to reduction in tidal volume or PEEP

BackgroundChest wall loading has been shown to paradoxically improve respiratory system compliance (CRS) in patients with moderate to severe acute respiratory distress syndrome (ARDS). The most likely, albeit unconfirmed, mechanism is relief of end-tidal overdistension in ‘baby lungs’ of low-capacity. The purpose of this study was to define how small changes of tidal volume (VT) and positive end-expiratory pressure (PEEP) affect CRS (and its associated airway pressures) in patients with ARDS who demonstrate a paradoxical response to chest wall loading. We hypothesized that small reductions of VT or PEEP would alleviate overdistension and favorably affect CRS and conversely, that small increases of VT or PEEP would worsen CRS.MethodsProspective, multi-center physiologic study of seventeen patients with moderate to severe ARDS who demonstrated paradoxical responses to chest wall loading. All patients received mechanical ventilation in volume control mode and were passively ventilated. Airway pressures were measured before and after decreasing/increasing VT by 1 ml/kg predicted body weight and decreasing/increasing PEEP by 2.5 cmH2O.ResultsDecreasing either VT or PEEP improved CRS in all patients. Driving pressure (DP) decreased by a mean of 4.9 cmH2O (supine) and by 4.3 cmH2O (prone) after decreasing VT, and by a mean of 2.9 cmH2O (supine) and 2.2 cmH2O (prone) after decreasing PEEP. CRS increased by a mean of 3.1 ml/cmH2O (supine) and by 2.5 ml/cmH2O (prone) after decreasing VT. CRS increased by a mean of 5.2 ml/cmH2O (supine) and 3.6 ml/cmH2O (prone) after decreasing PEEP (P < 0.01 for all). Small increments of either VT or PEEP worsened CRS in the majority of patients.ConclusionPatients with a paradoxical response to chest wall loading demonstrate uniform improvement in both DP and CRS following a reduction in either VT or PEEP, findings in keeping with prior evidence suggesting its presence is a sign of end-tidal overdistension. The presence of ‘paradox’ should prompt re-evaluation of modifiable determinants of end-tidal overdistension, including VT, PEEP, and body position.

Functional and morphologic dysfunctions in the airways of rats submitted to an experimental model of obesity-exacerbated asthma

The obesity-exacerbated asthma phenotype is characterized by more severe asthma symptoms and glucocorticoid resistance. The aim of this study was to standardize an obesity-exacerbated asthma model by a high glycemic level index (HGLI) diet and ovalbumin (OVA) sensitization and challenges in Wistar rats. Animals were divided into groups: control (Ctrl), obese (Ob), asthmatic (Asth), obese asthmatic (Ob + Asth) and obese asthmatic treated with dexamethasone (Ob + Asth + Dexa), and in vivo and in vitro functional and morphological parameters were measured. After HGLI consumption, there was an increase in body weight, fasting blood glucose, abdominal circumferences, body mass index and adiposity index. Respiratory function showed a reduction in pulmonary tidal volume and ventilation. In isolated tracheas, carbachol showed an increase in contractile efficacy in the Ob, Ob + Asth and Ob + Asth + Dexa, but mostly on Ob + Asth. Histological analysis of lungs showed peribronchovascular inflammation and smooth muscle hypertrophy and extracellular remodeling on Ob + Asth and Ob + Asth + Dexa. An obesity-exacerbated asthma model was successfully established. Therefore, this model allows further molecular investigations and the search for new therapies for the treatment and relief of symptoms of patients with obesity-induced resistant asthma.

Venovenous extracorporeal CO2 removal to support ultraprotective ventilation in moderate-severe acute respiratory distress syndrome: A systematic review and meta-analysis of the literature.

A strategy that limits tidal volumes and inspiratory pressures, improves outcomes in patients with the acute respiratory distress syndrome (ARDS). Extracorporeal carbon dioxide removal (ECCO2R) may facilitate ultra-protective ventilation. We conducted a systematic review and meta-analysis to evaluate the efficacy and safety of venovenous ECCO2R in supporting ultra-protective ventilation in moderate-to-severe ARDS. MEDLINE and EMBASE were interrogated for studies (2000-2021) reporting venovenous ECCO2R use in patients with moderate-to-severe ARDS. Studies reporting ≥10 adult patients in English language journals were included. Ventilatory parameters after 24h of initiating ECCO2R, device characteristics, and safety outcomes were collected. The primary outcome measure was the change in driving pressure at 24h of ECCO2R therapy in relation to baseline. Secondary outcomes included change in tidal volume, gas exchange, and safety data. Ten studies reporting 421 patients (PaO2:FiO2 141.03mmHg) were included. Extracorporeal blood flow rates ranged from 0.35-1.5L/min. Random effects modelling indicated a 3.56cmH2O reduction (95%-CI: 3.22-3.91) in driving pressure from baseline (p < .001) and a 1.89mL/kg (95%-CI: 1.75-2.02, p < .001) reduction in tidal volume. Oxygenation, respiratory rate and PEEP remained unchanged. No significant interactions between driving pressure reduction and baseline driving pressure, partial pressure of arterial carbon dioxide or PaO2:FiO2 ratio were identified in metaregression analysis. Bleeding and haemolysis were the commonest complications of therapy. Venovenous ECCO2R permitted significant reductions in ∆P in patients with moderate-to-severe ARDS. Heterogeneity amongst studies and devices, a paucity of randomised controlled trials, and variable safety reporting calls for standardisation of outcome reporting. Prospective evaluation of optimal device operation and anticoagulation in high quality studies is required before further recommendations can be made.

A case requiring re-thoracotomy due to a significant reduction of tidal volume after commencement of chest tube drainage under pressure control ventilation following lower lobectomy

BackgroundThe use of pressure-controlled ventilation (PCV) during one lung ventilation (OLV) has been popular to avoid high airway pressure. We experienced a case of a significant reduction of tidal volume (TV) after commencement of chest tube drainage under PCV following lower lobectomy, which required re-thoracotomy to evaluate the degree of air leak.Case presentationA 70-year-old man was scheduled for a lower lobectomy. OLV was managed by PCV. The driving pressure was set at 15–20 cmH2O with 4 cmH2O of positive end-expiratory pressure (PEEP). A chest drainage tube was placed after completion of lobectomy. To switch OLV to two lung ventilation (TLV), PCV settings were changed to the driving pressure at 10 cmH2O with 4 cmH2O of PEEP, which generated 450 ml of TV. Immediately after applying drainage (−10 cmH2O), TV decreased down to 250 ml. To maintain 450 ml of TV, PCV was switched to volume-controlled ventilation with 450 ml of TV, which raised the plateau pressure close to 24 cmH2O. Re-thoracotomy was done; however, significant findings were not detected.ConclusionsWe experienced a case of a significant reduction of TV immediately after chest tube drainage following lower lobectomy. Probably, negative intrapleural pressure increased the residual volume, which might have significantly affected the limited lung volume after lobectomy, resulting in decreasing TV during PCV.

A Rationale for Safe Ventilation with Inhalation Injury: An Editorial Review.

Lung injury from smoke inhalation manifests as airway and parenchymal damage, at times leading to the acute respiratory distress syndrome. From the beginning of this millennium, the approach to mechanical ventilation in the patient with ARDS was based on reduction of tidal volume to 6 milliliters/kilogram of ideal body weight, maintaining a ceiling of plateau pressure, and titration of driving pressure (plateau pressure minus PEEP). Beyond these broad constraints, there is little specification for the mechanics of ventilator settings, consideration of the metabolic impact of the disease process on the patient, or interaction of patient disease and ventilator settings. Various studies suggest that inhomogeneity of lung injury, which increases the risk of regional lung trauma from mechanical ventilation, may be found in the patient with smoke inhalation. We now appreciate that energy transfer principles may affect optimal ventilator management and come into play in damaged heterogenous lungs. Mechanical ventilation in the patient with inhalation injury should consider various factors. Self-injurious respiratory demand by the patient can be reduced using analgesia and sedation. Dynamic factors beginning with rate management can reduce the incidence of potentially damaging ventilation. Moreover, preclinical study is underway to examine the flow of gas based on the ventilator mode selected, which may also be a factor triggering regional lung injury.

Diaphragmatic Activity and Respiratory Function Following C3 or C6 Unilateral Spinal Cord Contusion in Mice.

Simple SummaryTetraplegia is one of the most devastating conditions that an individual can sustain and affects more than 2.5 million people worldwide. Tetraplegia not only affects mobility but also impacts spontaneous breathing such that survivors can be rendered ventilator dependent and have increased mortality. Although no treatment can restore respiratory function after tetraplegia, there is a need for more exploratory studies defining therapeutic approaches to ameliorate respiratory decline in tetraplegia. Here, we studied two models of tetraplegia mimicking human forms of injury, using spinal cord contusion in mice, either above the third cervical metameric segment (C3 model) or below the sixth cervical metameric segment (C6 model) innervation of the phrenic nerves. These nerves are responsible for contraction of the diaphragm, the main inspiratory muscle. Using measurements of spontaneous breathing and muscle activity of the diaphragm, we found reduced diaphragmatic activity in both models, but only the C3 model led to reduced spontaneous breathing similar to what is seen in humans with tetraplegia. Moreover, we found a decline in basal contractility of the diaphragm in the C3 model only. We conclude that the C3 model is an appropriate model to explore interventions aimed at restoring breathing following tetraplegia.The majority of spinal cord injuries (SCIs) are cervical (cSCI), leading to a marked reduction in respiratory capacity. We aimed to investigate the effect of hemicontusion models of cSCI on both diaphragm activity and respiratory function to serve as preclinical models of cervical SCI. Since phrenic motoneuron pools are located at the C3–C5 spinal level, we investigated two models of preclinical cSCI mimicking human forms of injury, namely, one above (C3 hemicontusion—C3HC) and one below phrenic motoneuron pools (C6HC) in wild-type swiss OF-1 mice, and we compared their effects on respiratory function using whole-body plethysmography and on diaphragm activity using electromyography (EMG). At 7 days post-surgery, both C3HC and C6HC damaged spinal cord integrity above the lesion level, suggesting that C6HC potentially alters C5 motoneurons. Although both models led to decreased diaphragmatic EMG activity in the injured hemidiaphragm compared to the intact one (−46% and −26% in C3HC and C6HC, respectively, both p = 0.02), only C3HC led to a significant reduction in tidal volume and minute ventilation compared to sham surgery (−25% and −20% vs. baseline). Moreover, changes in EMG amplitude between respiratory bursts were observed post-C3HC, reflecting a change in phrenic motoneuronal excitability. Hence, C3HC and C6HC models induced alteration in respiratory function proportionally to injury level, and the C3HC model is a more appropriate model for interventional studies aiming to restore respiratory function in cSCI.