Higher Lung Compliance Research Articles

Intubation Time, Lung Mechanics and Outcome in COVID-19 Patients Suffering Acute Respiratory Distress Syndrome: A Single-Center Study.

We examined the effect of intubation time and the lung mechanics on clinical outcomes in coronavirus disease 2019 (COVID-19) patients. Based on the patient's hospital admission, intubation time was defined as early (≤ 2 days) or late (> 2 days). Patients were further divided into three groups; early (≤ 3 days), late (4 - 6 days), and very late (> 6 days) intubated. A total of 194 patients were included; 66.5% male, median age 65 years. Fifty-eight patients (29.9%) were intubated early and 136 (70.1%) late. Early intubated patients revealed lower mortality (44.8% vs. 72%, P < 0.001), were younger (60 vs. 67, P = 0.002), had lower sequential organ failure assessment (SOFA) scores (6 vs. 8, P = 0.002) and higher lung compliance on admission days 1, 6 and 12 (42 vs. 36, P = 0.006; 40 vs. 33, P < 0.001; and 37.5 vs. 32, P < 0.001, respectively). Older age (adjusted odds ratio (aOR) = 1.15, P < 0.001), intubation time (aOR = 1.15, P = 0.004), high SOFA scores (aOR = 1.81, P < 0.001), low partial pressure of oxygen (PaO2)/fractional inspired oxygen tension (FiO2) ratio (aOR = 0.96, P = 0.001), and low lung compliance on admission days 1 and 12 (aOR = 1.12, P = 0.012 and aOR = 1.14, P < 0.001, respectively) were associated with higher mortality. Very late and late intubated patients had higher mortality rates than patients intubated early (78.4% vs. 63.4% vs. 44.6%, respectively, P < 0.001). Among COVID-19 intubated patients, age, late intubation, high SOFA scores, low PaO2/FiO2 ratio, and low lung compliance are associated with higher intensive care unit (ICU) mortality.

Trajectories of hypoxemia and pulmonary mechanics of COVID-19 ARDS in the NorthCARDS dataset

BackgroundUnderstanding heterogeneity seen in patients with COVIDARDS and comparing to non-COVIDARDS may inform tailored treatments.MethodsA multidisciplinary team of frontline clinicians and data scientists worked to create the Northwell COVIDARDS dataset (NorthCARDS) leveraging over 11,542 COVID-19 hospital admissions. The data was then summarized to examine descriptive differences based on clinically meaningful categories of lung compliance, and to examine trends in oxygenation.FindingsOf the 1536 COVIDARDS patients in the NorthCARDS dataset, there were 531 (34.6%) who had very low lung compliance (< 20 ml/cmH2O), 970 (63.2%) with low-normal compliance (20–50 ml/cmH2O), and 35 (2.2%) with high lung compliance (> 50 ml/cmH2O). The very low compliance group had double the median time to intubation compared to the low-normal group (107.3 h (IQR 25.8, 239.2) vs. 39.5 h (IQR 5.4, 91.6)). Overall, 68.8% (n = 1057) of the patients died during hospitalization. In comparison to non-COVIDARDS reports, there were less patients in the high compliance category (2.2% vs. 12%, compliance ≥ 50 mL/cmH20), and more patients with P/F ≤ 150 (59.8% vs. 45.6%). There is a statistically significant correlation between compliance and P/F ratio. The Oxygenation Index is the highest in the very low compliance group (12.51, SD(6.15)), and lowest in high compliance group (8.78, SD(4.93)).ConclusionsThe respiratory system compliance distribution of COVIDARDS is similar to non-COVIDARDS. In some patients, there may be a relation between time to intubation and duration of high levels of supplemental oxygen treatment on trajectory of lung compliance.

IN-HOSPITAL MORTALITY IN MECHANICALLY VENTILATED PATIENTS WITH COVID-19 WITH DIFFERENT ARDS PHENOTYPES

TOPIC: Chest Infections TYPE: Original Investigations PURPOSE: The purpose of the study is to investigate the in-hospital mortality of mechanically ventilated, COVID-19 (i.e., severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2)) patients with high lung compliance (i.e., atypical acute respiratory distress syndrome (ARDS)) compared to those with low lung compliance (i.e., classic ARDS). METHODS: It is a retrospective cohort study of patients older than 18 years diagnosed with COVID-19 infection that required mechanical ventilation (MV) for at least 24 hours between January 20, 2020, and April 30, 2020. Atypical ARDS was defined as driving pressure is less than 15 cm H2O throughout the period of MV, suggesting compliant lung based on the currently available evidence (Amato, Marcelo BP, et al., 2015). If it was impossible to maintain driving pressure less than 15 cm H2O for more than two days, the case was defined as classic ARDS with low compliance. Patients who required mechanical ventilation not more than 24 hours or expired within 24 hours since intubated and those transferred to another hospital were excluded. Patients who received remdesivir were also excluded because 95% of the patients did not receive it during their index hospitalization. The outcome was adjusted by age, sex, days of onset to ICU, the severity of illness estimated by APACHE score, and severity of ARDS based on PaO2/FiO2 ratio. RESULTS: A total of 60 patients that required mechanical ventilation for COVID-19 induced ARDS during the study period were reviewed per inclusion and exclusion criteria. In-hospital mortality of 30 patients of the atypical ARDS group was 50% during the index hospitalization whereas it was 53 % for 30 patients of the classic ARDS group (p=0.80) when both were treated with the same ARDS protocol, including low tidal volume and higher PEEP. The average duration of mechanical ventilation, length of ICU and hospital stay was 10.23, 12.33, and 12.93 days for the atypical ARDS group, respectively, compared to 16.57, 18.33, and 19.33 for the classic ARDS group (p=0.003, 0.011, and 0.004, respectively). The classic ARDS group required prone positioning (67% vs. 37%;p=0.02) and use of paralytics (73% vs. 43%;p=0.018) more frequently compared to the atypical ARDS group. CONCLUSIONS: In this retrospective cohort study of 60 patients that required mechanical ventilation for COVID-19 induced ARDS between January 20, 2020, and April 30, 2020, in-hospital mortality was not significantly different between the atypical ARDS group and the classic ARDS group. However, the duration of mechanical ventilation, length of ICU and hospital stay was significantly shorter in the atypical ARDS group compared to the classic ARDS group. CLINICAL IMPLICATIONS: The difference in the duration of mechanical ventilation between the two groups may suggest a different pathophysiologic process and a need for a different approach to COVID-induced ARDS depending on lung compliance. DISCLOSURES: No relevant relationships by Mariam Charkviani, source=Web Response No relevant relationships by Chul Won Chung, source=Web Response No relevant relationships by Harvey Friedman, source=Web Response No relevant relationships by Jooseob Lee, source=Web Response No relevant relationships by Guillermo Rodriguez-Nava, source=Web Response No relevant relationships by Daniela Trelles Garcia, source=Web Response No relevant relationships by Maria Yanez-Bello, source=Web Response

A CASE OF NINE WEEKS ON VENO-VENOUS EXTRACORPOREAL MEMBRANE OXYGENATION FOR COVID-19

TOPIC: Critical Care TYPE: Medical Student/Resident Case Reports INTRODUCTION: COVID-19 was declared a public health emergency by the World Health Organization in January 2020. The development of acute respiratory distress syndrome (ARDS) due to COVID-19 has high mortality. We present a case of 9 weeks of veno-venous extracorporeal membrane oxygenation (VV ECMO) for COVID-19 ARDS. CASE PRESENTATION: A 47-year-old male with a positive COVID-19 test 5 days prior to admission presented to the emergency department with dyspnea. He was severely hypoxemic prompting admission to the intensive care unit and treatment with high flow nasal canula, glucocorticoids, inhaled nitric oxide and remdesivir. He remained hypoxemic requiring intubation. His hypoxemia worsened despite maximal ventilatory support, proning and paralysis. He was evaluated and considered a candidate for VV ECMO. His cannulation strategy included right femoral vein drainage and right internal jugular (IJ) return cannulas. Anticoagulation for the ECMO circuit was held at 5 days due to bloody secretions and hematochezia. He was started on early nutritional supplementation with high protein tube feeds. Physical therapy included tilting to an upright position with a special bed and passive range of motion exercises. His course was complicated by prolonged respiratory failure requiring tracheostomy, nosocomial pneumonias, bilateral pneumothoraces, right IJ line associated venous thrombosis and bacteremia with native mitral valve endocarditis. At 60 days, his lung compliance began to improve. His ECMO gas sweep and delivered fractional oxygen percentage were incrementally decreased as his native lung gas exchange improved. He was decannulated after 65 days on ECMO. He had continued improvement in physical and respiratory function, including tracheostomy decannulation. He was discharged home after 12 weeks on 1-liter nasal cannula and currently uses oxygen with exertion with minimal dyspnea. DISCUSSION: VV ECMO in traditional ARDS has shown to improve mortality in patients with respiratory failure. Respiratory failure in patients with COVID-19 ARDS tends to be more protracted than traditional ARDS. COVID-19 ARDS patients have higher lung compliance, ventilatory ratio and lung recruitment early in the course. They can have persistent lung diffusion and radiologic abnormalities at 3 months with lingering pulmonary effects post-infection. COVID-19 ARDS patients who require ECMO eventually lose lung compliance. Improvement in tidal volume is the first sign of lung recovery in traditional and COVID-19 ARDS. CONCLUSIONS: VV ECMO is a viable option for the management of COVID-19 ARDS. Longer ECMO support in COVID-19 patients is expected given the difference in lung physiology compared to traditional ARDS and further research into VV ECMO and COVID-19 ARDS is needed. REFERENCE #1: Combes, Alain et al. "ECMO for severe ARDS: systematic review and individual patient data meta-analysis." Intensive care medicine vol. 46,11 (2020): 2048-2057. REFERENCE #2: Haudebourg, Anne-Fleur et al. "Respiratory Mechanics of COVID-19- versus Non-COVID-19-associated Acute Respiratory Distress Syndrome." American journal of respiratory and critical care medicine vol. 202,2 (2020): 287-290. REFERENCE #3: Combes, Alain et al. "Extracorporeal Membrane Oxygenation for Severe Acute Respiratory Distress Syndrome." The New England journal of medicine vol. 378,21 (2018): 1965-1975. DISCLOSURES: No relevant relationships by Kathy Chan, source=Web Response No relevant relationships by Hekmat Nasiri, source=Web Response No relevant relationships by Sudhir Rajan, source=Web Response

Right Ventricular Strain Is Common in Intubated COVID-19 Patients and Does Not Reflect Severity of Respiratory Illness.

Background:Right ventricular (RV) dysfunction is common and associated with worse outcomes in patients with coronavirus disease 2019 (COVID-19). In non-COVID-19 acute respiratory distress syndrome, RV dysfunction develops due to pulmonary hypoxic vasoconstriction, inflammation, and alveolar overdistension or atelectasis. Although similar pathogenic mechanisms may induce RV dysfunction in COVID-19, other COVID-19-specific pathology, such as pulmonary endothelialitis, thrombosis, or myocarditis, may also affect RV function. We quantified RV dysfunction by echocardiographic strain analysis and investigated its correlation with disease severity, ventilatory parameters, biomarkers, and imaging findings in critically ill COVID-19 patients.Methods:We determined RV free wall longitudinal strain (FWLS) in 32 patients receiving mechanical ventilation for COVID-19-associated respiratory failure. Demographics, comorbid conditions, ventilatory parameters, medications, and laboratory findings were extracted from the medical record. Chest imaging was assessed to determine the severity of lung disease and the presence of pulmonary embolism.Results:Abnormal FWLS was present in 66% of mechanically ventilated COVID-19 patients and was associated with higher lung compliance (39.6 vs 29.4 mL/cmH2O, P = 0.016), lower airway plateau pressures (21 vs 24 cmH2O, P = 0.043), lower tidal volume ventilation (5.74 vs 6.17 cc/kg, P = 0.031), and reduced left ventricular function. FWLS correlated negatively with age (r = −0.414, P = 0.018) and with serum troponin (r = 0.402, P = 0.034). Patients with abnormal RV strain did not exhibit decreased oxygenation or increased disease severity based on inflammatory markers, vasopressor requirements, or chest imaging findings.Conclusions:RV dysfunction is common among critically ill COVID-19 patients and is not related to abnormal lung mechanics or ventilatory pressures. Instead, patients with abnormal FWLS had more favorable lung compliance. RV dysfunction may be secondary to diffuse intravascular micro- and macro-thrombosis or direct myocardial damage.Trial Registration:National Institutes of Health #NCT04306393. Registered 10 March 2020, https://clinicaltrials.gov/ct2/show/NCT04306393

EFFECT OF GENDER ON THE TREATMENT RESPONSES TO RAPAMYCIN ON THE PROGRESSION OF EMPHYSEMA IN CIGARETTE SMOKE-EXPOSED MICE

SESSION TITLE: Obstructive Lung Disease Posters SESSION TYPE: Original Investigation Posters PRESENTED ON: October 18-21, 2020 PURPOSE: Emphysema is characterized by the permanent enlargement of distal airspaces. Current therapies focus on symptom relief as little can halt disease progression. Given its role in cell aging/damage, the mTOR pathway has been studied with respect to emphysema. While inhibition of this pathway with rapamycin has been shown to delay progression of cigarette-smoke (CS) induced emphysema, effects of gender have not been examined. We aim to characterize the effects of rapamycin on the progression of CS induced lung injury in male and female mice. METHODS: A prospective study of 151 mice (C57B/6 strain) was conducted. The mice were separated into two cohorts: CS exposure vs. no CS exposure. The CS exposed group was stratified based on gender and treatment with rapamycin (CS-D) or a vehicle (CS-V) whereas the no CS exposure group was stratified by gender alone. Mice were sacrificed at 0, 3 and 5 months to obtain alveolar histologic data (chord length [Lm]) and pre-mortem physiologic data by Scireq Flexivent (total lung capacity [TLC], static compliance [Cst], dynamic compliance [Cdy], and Pressure-Volume [PV] loops). Statistical analysis was performed by Mann-Whitney t-test and Kruskall-Wallis test using PRISM GraphPad software with a p < 0.05 considered significant. RESULTS: Male CS-V mice had a higher lung compliance at 3 months compared to male CS-D mice as seen on the PV loops. Ventilator data showed male CS-V mice to have a higher average TLC (1.56mL vs 1.43mL; p= 0.002) and Cst (0.11 mL/cmH2O vs 0.09 mL/cmH2O; p = 0.002) at 3 months compared to male CS-D mice. This difference in ventilator parameters did not persist at 5 months and were not different between CS-V and CS-D mice (p > 0.05). On histology, CS-V mice had longer Lm than non-CS exposed mice over the 5 month study period with the largest difference at 5 months (75.12 um vs 66.28 um; p= 0.003). Male CS-V mice had longer Lm than CS-D mice at 3 months (69.59 um vs 65.47 um; p= 0.016), but not at 5 months. No significant differences in Lm were seen between CS-V and CS-D mice at 3 and 5 months in the female group. CONCLUSIONS: Protection against CS induced emphysema by treatment with rapamycin is highly gender dependent. Males benefit significantly with rapamycin treatment while females do not. This therapeutic effect is not durable over long/chronic CS exposure. CLINICAL IMPLICATIONS: Rapamycin may be a viable option for temporarily delaying the progression of CS-induced emphysema, though further investigation into the mechanisms by which gender influences the progression of CS-induced emphysema related to the biology of mTOR and aging are needed. DISCLOSURES: No relevant relationships by Marie Burdick, source=Web Response No relevant relationships by Kranthikiran Earasi, source=Web Response No relevant relationships by Mu He, source=Web Response No relevant relationships by Jamie MacLeod, source=Web Response No relevant relationships by Lukasz Myc, source=Web Response No relevant relationships by Zaid Obaida, source=Web Response No relevant relationships Added 05/30/2020 by Yun Shim, source=Web Response, value=Intellectual property rights Removed 06/01/2020 by Yun Shim, source=Web Response No relevant relationships Added 05/30/2020 by Yun Shim, source=Web Response, value=Salary Removed 06/01/2020 by Yun Shim, source=Web Response No relevant relationships by Chunzi Song, source=Web Response No relevant relationships by Zhimin Zhang, source=Web Response

Using the Systems Engineering Initiative for Patient Safety (SEIPS) model to describe critical care nursing during the SARS-CoV-2 pandemic (2020).

Using the Systems Engineering Initiative for Patient Safety (SEIPS) model to describe critical care nursing during the SARS-CoV-2 pandemic (2020).

Lung developmental arrest caused by PDGF-A deletion: consequences for the adult mouse lung.

PDGF-A is a key contributor to lung development in mice. Its expression is needed for secondary septation of the alveoli and deletion of the gene leads to abnormally enlarged alveolar air spaces in mice. In humans, the same phenotype is the hallmark of bronchopulmonary dysplasia (BPD), a disease that affects premature babies and may have long lasting consequences in adulthood. So far, the knowledge regarding adult effects of developmental arrest in the lung is limited. This is attributable to few follow-up studies of BPD survivors and lack of good experimental models that could help predict the outcomes of this early age disease for the adult individual. In this study, we used the constitutive lung-specific Pdgfa deletion mouse model to analyze the consequences of developmental lung defects in adult mice. We assessed lung morphology, physiology, cellular content, ECM composition and proteomics data in mature mice, that perinatally exhibited lungs with a BPD-like morphology. Histological and physiological analyses both revealed that enlarged alveolar air spaces remained until adulthood, resulting in higher lung compliance and higher respiratory volume in knockout mice. Still, no or only small differences were seen in cellular, ECM and protein content when comparing knockout and control mice. Taken together, our results indicate that Pdgfa deletion-induced lung developmental arrest has consequences for the adult lung at the morphological and functional level. In addition, these mice can reach adulthood with a BPD-like phenotype, which makes them a robust model to further investigate the pathophysiological progression of the disease and test putative regenerative therapies.

Lung mechanical properties distinguish children with asthma with normal and diminished lung function

Children with asthma, even those with severe persistent disease, can have forced expiratory volume in 1second (FEV1 ) values ≥100% of predicted, while others have diminished FEV1 . We sought to characterize the lung mechanical properties underlying these two asthma phenotypes and the mechanisms explaining the paradox of severe asthmatic children, whom when clinically stable can have an FEV1 >100% of predicted, but during an acute bronchospastic episode can experience a life-threatening asthma event. Lung mechanics were evaluated in three groups of children: asthmatics with FEV1 ≥100% (HFEV1 ; n=13), asthmatics with FEV1 ≤80% (LFEV1 ; n=14) and non-asthmatic controls (n=10). A linear mixed model was used to examine the relationship between volume and static transpulmonary pressures obtained at total lung capacity (TLC); actual TLC %of predicted and flow; and static transpulmonary pressure and flow. HFEV1 asthmatics had larger airways (FEV1 z-scores 1.12 vs -2.37; P<.05), greater lung volumes (mean % of predicted TLC 134.8% vs 109.6%; P<.05) and lower airway resistance (mean %of predicted Raw 101.9% vs 199.9%; P<.05) compared to the LFEV1 group. Moreover, HFEV1 asthmatics had significantly reduced elastic recoil pressure (pressure-volume curve shifted upward and to the left) and higher lung compliance (0.21 vs 00.9L/cm H2 O; P<.05) compared to the LFEV1 group. The pressure-flow curves revealed the LFEV1 group to have significantly increased resistance to flow in the upstream segment of the airways at all lung volumes studied compared to HFEV1 . HFEV1 asthmatic children display distinct lung mechanical proprieties compared to their LFEV1 asthmatic peers. With loss of elastic recoil pressure, the HFEV1 group could generate normal FEV1 due to proportionally enlarged airways and reduced airway resistance, while airflow limitation in the LFEV1 is due to increased airway resistance. Loss of elastic recoil and interdependence during acute bronchoconstriction episodes may predispose the HFEV1 group to catastrophic reductions in airflow.

Severe but not moderate hyperoxia of newborn mice causes an emphysematous lung phenotype in adulthood without persisting oxidative stress and inflammation

BackgroundPreterm newborns typically require supplemental oxygen but hyperoxic conditions also damage the premature lung. Oxygen-induced lung damages are mainly studied in newborn mouse models using oxygen concentrations above 75% and looking at short-term effects. Therefore, we aimed at the investigation of long-term effects and their dependency on different oxygen concentrations.MethodsNewborn mice were exposed to moderate vs. severe hyperoxic air conditions (50 vs. 75% O2) for 14 days followed by a longer period of normoxic conditions. Lung-related parameters were collected at an age of 60 or 120 days.ResultsSevere hyperoxia caused lower alveolar density, enlargement of parenchymal air spaces and fragmented elastic fibers as well as higher lung compliance with peak airflow limitations and higher sensitivity to ventilation-mediated damages in later life. However, these long-term lung structural and functional changes did not restrict the voluntary physical activity. Also, they were not accompanied by ongoing inflammatory processes, increased formation of reactive oxygen species (ROS) or altered expressions of antioxidant enzymes (superoxide dismutases, catalase) and lung elasticity-relevant proteins (elastin, pro-surfactant proteins) in adulthood. In contrast to severe hyperoxia, moderate hyperoxia was less lung damaging but also not free of long-term effects (higher lung compliance without peak airflow limitations, increased ROS formation).ConclusionsSevere but not moderate neonatal hyperoxia causes emphysematous lungs without persisting oxidative stress and inflammation in adulthood. As the existing fragmentation of the elastic fibers seems to play a pivotal role, it indicates the usefulness of elastin-protecting compounds in the reduction of long-term oxygen-related lung damages.

Receptor for advanced glycation end-products modulates lung development and lung sensitivity to hyperoxic injury in newborn mice.

The receptor for advanced glycation end-products is mainly expressed in type I alveolar epithelial cells but its importance in lung development and response to neonatal hyperoxia is unclear. Therefore, our study aimed at the analysis of young wildtype and RAGE knockout mice which grew up under normoxic or hyperoxic air conditions for the first 14days followed by a longer period of normoxic conditions. Lung histology, expression of lung-specific proteins, and respiratory mechanics were analyzed when the mice reached an age of 2 or 4months. These analyses indicated less but larger and thicker alveoli in RAGE knockout mice, reverse differences in the mRNA and protein amount of pro-surfactant proteins (pro-SP-B, pro-SP-C) and aquaporin-5, and differences in the amount of elastin and CREB, a pro-survival transcription factor, as well as higher lung compliance. Despite this potential disadvantages, RAGE knockout lungs showed less long-term damages mediated by neonatal hyperoxia. In detail, the hyperoxia-mediated reduction in alveoli, enlargement of airspaces, fragmentation of elastic fibers, and increased lung compliance combined with reduced peak airflows was less pronounced in RAGE knockout mice. In conclusion, RAGE supports the alveolarization but makes the lung more susceptible to hyperoxic injury shortly after birth. Blocking RAGE function could still be a helpful tool in reducing hyperoxia-mediated lung pathologies during alveolarization.

Lung Compliance and Outcomes in Patients With Acute Respiratory Distress Syndrome Receiving ECMO

Limited data are available regarding mechanical ventilation strategies in patients with acute respiratory distress syndrome receiving extracorporeal membrane oxygenation (ECMO). A retrospective analysis of acute respiratory distress syndrome patients on ECMO was conducted in 9 hospitals in Korea. Data on ventilator settings (pre-ECMO and 0, 4, 24, and 48 hours after ECMO) were collected. Based on the effect of the duration and intensity of mechanical ventilator on outcomes, time-weighted average values were calculated for ventilator parameters. The 56 patients included in the study had a mean age of 55.5 years. The hospital and 6-month mortality rates were 48.1% and 54.0%, respectively, with a median ECMO duration of 9.4 days. After initiation of ECMO, peak inspiratory pressure, above positive end-expiratory pressure, tidal volume, and respiration rate were reduced, while lung compliance did not change significantly. Before and during ECMO support, tidal volume and lung compliance were higher in 6-month survivors than in nonsurvivors. In Cox proportional models, both lung compliance (odds ratio, 0.961; 95% confidence interval, 0.928 to 0.995) and time-weighted average-lung compliance (odds ratio, 0.943; 95% confidence interval, 0.903 to 0.986) were significantly associated with 6-month mortality. Kaplan-Meier curves revealed that patients with higher lung compliance before ECMO had a longer survival time at the 6-month follow-up than did those with lower lung compliance. Lung compliance, whether before or during ECMO, may be an important predictor of outcome in acute respiratory distress syndrome patients receiving ECMO. However, this result requires confirmation in larger clinical studies.

Evaluation of the effects of dexmedetomidine infusion on oxygenation and lung mechanics in morbidly obese patients with restrictive lung disease

BackgroundDexmedetomidine infusion improves oxygenation and lung mechanics in patients with chronic obstructive lung disease; however, its effect in patients with restrictive lung disease has not been thoroughly investigated yet. The aim of this work was to evaluate the effects of dexmedetomidine infusion on oxygenation and lung mechanics in morbidly obese patients with restrictive lung disease.MethodsForty-two morbidly obese patients scheduled for bariatric surgery were included in the study. Patients were randomized to receive either dexmedetomidine infusion at a bolus dose of 1mcg/Kg followed by infusion at 1 mcg/Kg/hour for 90 min (Dexmedetomidine group), or normal saline infusion (Control group). Both groups were compared with regard to: oxygenation {P/F ratio: PaO2/fraction of inspired oxygen (FiO2)}, lung compliance, dead space, plateau pressure, blood pressure, and heart rate.ResultsDexmedetomidine group showed significant improvement of the PaO2/FiO2 ratio, and higher lung compliance compared to control group by the end of drug infusion. Dexmedetomidine group demonstrated decreased dead space, plateau pressure, blood pressure, and heart rate compared to control group by the end of drug infusion.ConclusionA 90-min dexmedetomidine infusion resulted in moderate improvement in oxygenation and lung mechanics in morbidly obese patients with restrictive lung disease.Trial registrationclinicaltrials.gov: NCT02843698 on 20 July 2016.

Re: Retrogradein situversus antegrade pulmonary preservation in clinical lung transplantation: a single-centre experience

Historically, grafts were preserved by means of autoperfusion with extracorporeal circulation, topical cooling or donor core cooling. In the 1980s, the standard lung preservation method was single pulmonary artery flush perfusion, using modified Euro-Collins solution at 4°C [1]. However, reperfusion injury remained a significant factor for morbidity and early mortality after lung transplant. Since the early years of lung preservation strategies, some advances have emerged in transplant teams, such as adding prostaglandin E2 to prevent counteract temperature and potassium-induced vasoconstriction. The use of low potassium dextran glucose solutions shows better overall lung function, superior early oxygenation, higher lung compliance, lower incidence of severe primary graft dysfunction and 30-day mortality [2]. As Gohrbandt et al. point out, the route to administer the preservation solution may also have an impact on early lung graft performance [3]. Anterograde flush initiating the infusion through the pulmonary artery with pulmonary vein drainage was the traditional approach for many years [4]. This technique, however, presents a number of limitations. Flushing the pulmonary artery leaves the bronchial tissue to be preserved by topical cooling alone, raising the complication from the bronchial suture. Also, clots and fat or brain tissue emboli, especially in donors with major trauma and multiple bone fractures, may hamper uniform flushing and cooling and, therefore, impair graft function upon reperfusion. Adding a retrograde flush, whereby the preservation solution is administered via the left atrial appendage or four pulmonary veins into the pulmonary venous system and drained through the pulmonary artery, has the potential to flush not only pulmonary vessels, but also the bronchial network, contributing to the adequate perfusion of the tracheobronchial submucosa tissue, and also limiting the effect of hypothermic pulmonary arterial vasoconstriction. On the other hand, less ventilated areas, such as the posterior segments of lower lobes, are better flushed. Also residual blood and harmful constituents and any possible microthrombi that may obstruct the pulmonary vessels are washed out. The evidence from clinical series of this technique is limited [5]; authors such as Gohrbandt et al. show us that there are no clinical benefits of retrograde lung preservation alone and that it may cause or prolong mechanical ventilation and primary graft dysfunction at 72 h and prolong ICU stay [3]. On the other hand, some evidence has been published, showing that biphasic lung preservation is not only clinically feasible [6], but also related with better early oxygenation ratio, lower mean airway pressure and chest radiography score [7, 8]. Many transplant teams have now adopted a biphasic technique with an antegrade flush through the pulmonary artery followed by a retrograde flush through each of the pulmonary veins after heart excision with the lung still ventilated inside the cadaver. However, there is lack of controlled randomized studies.

Bench and mathematical modeling of the effects of breathing a helium/oxygen mixture on expiratory time constants in the presence of heterogeneous airway obstructions

BackgroundExpiratory time constants are used to quantify emptying of the lung as a whole, and emptying of individual lung compartments. Breathing low-density helium/oxygen mixtures may modify regional time constants so as to redistribute ventilation, potentially reducing gas trapping and hyperinflation for patients with obstructive lung disease. In the present work, bench and mathematical models of the lung were used to study the influence of heterogeneous patterns of obstruction on compartmental and whole-lung time constants.MethodsA two-compartment mechanical test lung was used with the resistance in one compartment held constant, and a series of increasing resistances placed in the opposite compartment. Measurements were made over a range of lung compliances during ventilation with air or with a 78/22% mixture of helium/oxygen. The resistance imposed by the breathing circuit was assessed for both gases. Experimental results were compared with predictions of a mathematical model applied to the test lung and breathing circuit. In addition, compartmental and whole-lung time constants were compared with those reported by the ventilator.ResultsTime constants were greater for larger minute ventilation, and were reduced by substituting helium/oxygen in place of air. Notably, where time constants were long due to high lung compliance (i.e. low elasticity), helium/oxygen improved expiratory flow even for a low level of resistance representative of healthy, adult airways. In such circumstances, the resistance imposed by the external breathing circuit was significant. Mathematical predictions were in agreement with experimental results. Time constants reported by the ventilator were well-correlated with those determined for the whole-lung and for the low-resistance compartment, but poorly correlated with time constants determined for the high-resistance compartment.ConclusionsIt was concluded that breathing a low-density gas mixture, such as helium/oxygen, can improve expiratory flow from an obstructed lung compartment, but that such improvements will not necessarily affect time constants measured by the ventilator. Further research is required to determine if alternative measurements made at the ventilator level are predictive of regional changes in ventilation. It is anticipated that such efforts will be aided by continued development of mathematical models to include pertinent physiological and pathophysiological phenomena that are difficult to reproduce in mechanical test systems.

Effect of spontaneous breathing on ventilator-induced lung injury in mechanically ventilated healthy rabbits: a randomized, controlled, experimental study

IntroductionVentilator-induced lung injury (VILI), one of the most serious complications of mechanical ventilation (MV), can impact patients' clinical prognoses. Compared to control ventilation, preserving spontaneous breathing can improve many physiological features in ventilated patients, such as gas distribution, cardiac performance, and ventilation-perfusion matching. However, the effect of spontaneous breathing on VILI is unknown. The goal of this study was to compare the effects of spontaneous breathing and control ventilation on lung injury in mechanically-ventilated healthy rabbits.MethodsSixteen healthy New Zealand white rabbits were randomly placed into a spontaneous breathing group (SB Group) and a control ventilation group (CV Group). Both groups were ventilated for eight hours using biphasic positive airway pressure (BIPAP) with similar ventilator parameters: inspiration pressure (PI) resulting in a tidal volume (VT) of 10 to 15 ml/kg, inspiratory-to-expiratory ratio of 1:1, positive end-expiration pressure (PEEP) of 2 cmH2O, and FiO2 of 0.5. Inflammatory markers in blood serum, lung homogenates and bronchoalveolar lavage fluid (BALF), total protein levels in BALF, mRNA expressions of selected cytokines in lung tissue, and lung injury histopathology scores were determined.ResultsAnimals remained hemodynamically stable throughout the entire experiment. After eight hours of MV, compared to the CV Group, the SB Group had lower PaCO2 values and ratios of dead space to tidal volume, and higher lung compliance. The levels of cytokines in blood serum and BALF in both groups were similar, but spontaneous breathing led to significantly lower cytokine mRNA expressions in lung tissues and lower lung injury histological scores.ConclusionsPreserving spontaneous breathing can not only improve ventilatory function, but can also attenuate selected markers of VILI in the mechanically-ventilated healthy lung.

PROTEIN INHIBITION OF SURFACTANT DURING MECHANICAL VENTILATION OF ISOLATED RAT LUNGS

This study tested the hypothesis that material leaking into the airspace from the vasculature during ventilation interferes with surfactant function and contributes to decreases in lung compliance. Rats were euthanized and the lungs were isolated either with or without flushing of the vasculature, followed by mechanical ventilation and analysis of lung compliance and lung lavage analysis. Flushed lungs had higher lung compliance compared to the non-flushed lungs. This was associated with lower protein concentrations and improved surfactant activity. It is concluded that during mechanical ventilation, leakage of proteins results in surfactant inhibition and thereby contribute to decreased lung compliance.

Effectiveness of mask ventilation in a training mannikin. A comparison between the Oxylator EM100 and the bag-valve device

The demands for an optimal ventilation apparatus are that it can be easily handled, achieves a sufficiently high ventilation volume, and minimizes gastric inflation. Our aim was therefore to carry out a study in a training mannikin to find out whether the Oxylator EM100, compared with the bag, obtains improved ventilation and a decrease in gastric inflation. In a randomized crossover study, 72 subjects were selected (24 physicians, 44 nurses and 4 auxiliary nurses), chosen from the operating theatre, emergency department and intensive care unit of two hospitals. We used the Ambu®-Bag Mark III with mask No. 4, the Oxylator EM100 with a pressure setting of 35 cm H 2O run in the manual setting, the Ambu®-Man C mannikin as well as the Ambu®-CPR computer program. The resuscitation cycles of the standard two-rescuer's adult procedure lasted 3 min each, with a 3-min pause between the crossover procedure. The participants could improve their ventilatory volume with the Oxylator EM100 by 635 ml (95% confidence interval 578–692 ml) compared with the bag ventilation. The number of subjects who could attain a mean ventilatory volume of 800 ml or more increased from 15% to 98.6% ( P<0.001). Compared with the bag, the increase of adequate respirations (≥800 ml) obtained by the Oxylator EM100 for the individual participants amounted to a median of 91% ( P<0.001). Moreover, conventional ventilation caused in 42% one or several instances of gastric inflation, whereas no such reactions occurred with the Oxylator EM100. The Oxylator EM100 showed significantly better results in the mannikin than the bag. Of most importance is a significant lowering of gastric inflation and less so a marked increase in ventilatory volume. Our trial procedure with a relatively high lung compliance and a high oesophageal sphincter opening simulated favorable conditions. Owing to a large in vivo variability of these magnitudes, a direct testing in real patients with circulatory arrest is indicated.

Laryngeal mask airway and the ASA difficult airway algorithm.

Laryngeal mask airway and the ASA difficult airway algorithm.

Quantification of the Jet Function of a Jet Stylet

The concept and use of a as an additional safety measure during tracheal extubation of patients in whom subsequent ventilation and/or reintubation of the trachea may be difficult has recently been described. If ventilation through a could provide for effective gas exchange, it would allow additional time to assess the need for reintubation of the trachea. We determined the tidal volumes (measured by integrating a pneumotachograph flow signal) that 50-psi ventilation, at an inspiratory to expiratory time ratio of 1:1 (unit of time = 1 s), could deliver through small, medium, and large Sheridan tube exchangers into an in vitro lung model that had lung compliances of 50 and 30 mL/cm H2O (six experimental permutations). The tidal volume (VT) produced during ventilation was moderately dependent on air entrainment (measured by a volume spirometer), with the contribution to total VT ranging from 0% to 31%; the amount of air entrainment was confirmed by excellent correlation between the alveolar oxygen concentration (FAO2) measured by an oxygen analyzer and the FAO2 calculated from entrained and total VT. Decreased lung compliance caused decreased VT and end-expiratory volume for all six experimental conditions. The largest VT and minute ventilation (VE) generated were 1680 mL and 51.6 L/min (large tube exchanger, high lung compliance) and the lowest VT and VE were 440 mL and 13.2 L/min (small tube exchanger, low lung compliance), respectively. These findings validate the term jet stylet for all three tube exchangers as even the smallest tube exchanger, coupled with a low lung compliance, can provide a VE consistent with total ventilatory support for most clinical situations.