Respiratory System Compliance Research Articles

Physiological effects and safety of bed verticalization in patients with acute respiratory distress syndrome

BackgroundTrunk inclination in patients with Acute Respiratory Distress Syndrome (ARDS) in the supine position has gained scientific interest due to its effects on respiratory physiology, including mechanics, oxygenation, ventilation distribution, and efficiency. Changing from flat supine to semi-recumbent increases driving pressure due to decreased respiratory system compliance. Positional adjustments also deteriorate ventilatory efficiency for CO2 removal, particularly in COVID-19-associated ARDS (C-ARDS), indicating likely lung parenchyma overdistension. Tilting the trunk reduces chest wall compliance and, to a lesser extent, lung compliance and transpulmonary driving pressure, with significant hemodynamic and gas exchange implications.MethodsA prospective, pilot physiological study was conducted on early ARDS patients in two ICUs at CHU Clermont-Ferrand, France. The protocol involved 30-min step gradual verticalization from a 30° semi-seated position (baseline) to different levels of inclination (0°, 30°, 60°, and 90°), before returning to the baseline position. Measurements included tidal volume, positive end-expiratory pressure (PEEP), esophageal pressures, and pulmonary artery catheter data. The primary endpoint was the variation in transpulmonary driving pressure through the verticalization procedure.ResultsFrom May 2020 through January 2021, 30 patients were included. Transpulmonary driving pressure increased slightly from baseline (median and interquartile range [IQR], 9 [5–11] cmH2O) to the 90° position (10 [7–14] cmH2O; P < 10–2 for the overall effect of position in mixed model). End-expiratory lung volume increased with verticalization, in parallel to decreases in alveolar strain and increased arterial oxygenation. Verticalization was associated with decreased cardiac output and stroke volume, and increased norepinephrine doses and serum lactate levels, prompting interruption of the procedure in two patients. There were no other adverse events such as falls or equipment accidental removals.ConclusionsVerticalization to 90° is feasible in ARDS patients, improving EELV and oxygenation up to 30°, likely due to alveolar recruitment and blood flow redistribution. However, there is a risk of overdistension and hemodynamic instability beyond 30°, necessitating individualized bed angles based on clinical situations.Trial registration ClinicalTrials.gov registration number NCT04371016, April 24, 2020.

Previous Coronavirus Disease-2019 Infection and Lung Mechanics in Surgical Patients: A Hospital Registry Study.

Long-term pulmonary complications have been reported after a coronavirus disease-2019 (COVID-19). We hypothesized that a history of COVID-19 is associated with a measurable decrease in baseline respiratory system compliance in patients undergoing general anesthesia. In this hospital registry study, we included adult patients undergoing general anesthesia between January 2020 and March 2022 at a tertiary health care network in Massachusetts. We excluded patients with an American Society of Anesthesiologists physical status >IV, laryngoscopic surgeries, and patients who arrived intubated. The primary exposure was a history of COVID-19. The primary outcome was baseline respiratory system compliance (mL/cmH2O). Effects of severity of infection, surges (Alpha1, Alpha2, Delta, and Omicron), patient demographics, and time between infection and assessment of compliance were investigated. A total of 19,921 patients were included. Approximately 1386 (7.0%) patients had a history of COVID-19. A history of COVID-19 at any time before surgery was associated with a measurably lower baseline respiratory system compliance (ratio of meansadj = 0.96; 95% confidence interval [CI], 0.94-0.97; P < .001; adjusted compliance difference: -1.6 mL/cmH2O). The association was more pronounced in patients with a severe form of COVID-19 (ratio of meansadj = 0.95; 95% CI, 0.90-0.99; P = .02, adjusted compliance difference: -2 mL/cmH2O). Alpha1, Alpha2, and Delta surges, but not Omicron, led to a lower baseline respiratory system compliance (P < .001, P = .02, and P < .001). The Delta surge effect was magnified in Hispanic ethnicity (P-for-interaction = 0.003; ratio of meansadj = 0.83; 95% CI, 0.74-0.93; P = .001; adjusted compliance difference: -4.6 mL/cmH2O). A history of COVID-19 infection during Alpha1, Alpha2, and Delta surges was associated with a measurably lower baseline respiratory system compliance.

Immediate Clinical Complications Occurring During Membrane Change in Patients on Veno-Venous Extracorporeal Membrane Oxygenation.

The clinical tolerance of extracorporeal membrane oxygenation (ECMO) membrane changes in acute respiratory distress syndrome (ARDS) patients under veno-venous ECMO (VV-ECMO) has not been reported. The aim of this study was to describe the tolerance of membrane change. Patients requiring VV-ECMO were retrospectively included between March 2020 and May 2022. In case of membrane dysfunction or an increase in hemolysis markers or an alteration in gas exchange, a membrane change was performed. The primary outcome was a composite measure defined as the occurrence of at least one of the following events within 1 hour of membrane change: severe hypoxemia, hemodynamic collapse, bradycardia, arrhythmia, cardiac arrest, and death. During the study period, 70 patients required a VV-ECMO, 29 (41%) of whom died. Thirty-two patients required a membrane change for a total of 56 changes. The primary outcome occurred for 33 (59%) changes. Arterial desaturation <80% occurred for all complicated membrane changes and cardiac arrest concerned nine changes (16%). Low tidal volume (VT), respiratory system compliance (Crs), PaO2, and high ECMO blood flow (QECMO) were associated with poor tolerance of membrane change. Threshold values of 130 ml for VT, 9.3 cm H2O for Crs, 72 mm Hg for PaO2, and 3.65 L/minute for QECMO best determined the risk of poor tolerance of membrane change.

The Impact of Increased PEEP on Hemodynamics, Respiratory Mechanics, and Oxygenation in Pediatric ARDS.

PEEP is a cornerstone treatment for children with pediatric ARDS. Unfortunately, its titration is often performed solely by evaluating oxygen saturation, which can lead to inadequate PEEP level settings and consequent adverse effects. This study aimed to assess the impact of increasing PEEP on hemodynamics, respiratory system mechanics, and oxygenation in children with ARDS. Children receiving mechanical ventilation and on pressure-controlled volume-guaranteed mode were prospectively assessed for inclusion. PEEP was sequentially changed to 5, 12, 10, 8 cm H2O, and again to 5 cm H2O. After 10 min at each PEEP level, hemodynamic, ventilatory, and oxygenation variables were collected. A total of 31 subjects were included, with median age and weight of 6 months and 6.3 kg, respectively. The main reasons for pediatric ICU admission were respiratory failure caused by acute viral bronchiolitis (45%) and community-acquired pneumonia (32%). Most subjects had mild or moderate ARDS (45% and 42%, respectively), with a median (interquartile range) oxygenation index of 8.4 (5.8-12.7). Oxygen saturation improved significantly when PEEP was increased. However, although no significant changes in blood pressure were observed, the median cardiac index at PEEP of 12 cm H2O was significantly lower than that observed at any other PEEP level (P = .001). Fourteen participants (45%) experienced a reduction in cardiac index of > 10% when PEEP was increased to 12 cm H2O. Also, the estimated oxygen delivery was significantly lower, at 12 cm H2O PEEP. Finally, respiratory system compliance significantly reduced when PEEP was increased. At a PEEP of 12 cm H2O, static compliance had a median reduction of 25% in relation to the initial assessment (PEEP of 5 cm H2O). Although it may improve arterial oxygen saturation, inappropriately high PEEP levels may reduce cardiac output, oxygen delivery, and respiratory system compliance in pediatric subjects with ARDS with low potential for lung recruitability.

Breath-by-breath assessment of acute pulmonary edema using electrical impedance tomography, spirometry and volumetric capnography in a sheep (Ovis Aries) model.

The bedside diagnosis of acute pulmonary edema is challenging. This study evaluated the breath-by-breath information from electrical impedance tomography (EIT), respiratory mechanics and volumetric capnography (VCap) to assess acute pulmonary edema induced by xylazine administration in anesthetized sheep. To determine the ability and efficiency of each monitoring modality in detecting changes in lung function associated with onset of pulmonary edema. Twenty healthy ewes were anesthetized, positioned in sternal (prone) recumbency and instrumented. Synchronized recordings of EIT, spirometry and VCap were performed for 60 s prior to start of injection, during xylazine injection over 60 s (0-60 s) and continuously for 1 min (60-120 s) after the end of injection. After visual assessment of the recorded mean variables, statistical analysis was performed using a mixed effect model for repeated measures with Bonferroni's correction for multiple comparisons, to determine at which breath after start of injection the variable was significantly different from baseline. A significant change over time was defined as an adjusted p < 0.05. All statistics were performed using GraphPad Prism 0.1.0. Electrical impedance tomography showed significant changes from baseline in all but two variables. These changes were observed simultaneously during xylazine injection at 48 s and were consistent with development of edema in dependent lung (decreased end-expiratory lung impedance, ventilation in centro-ventral and ventral lung region) and shift of ventilation into non-dependent lung (decreased non-dependent silent spaces and increased center of ventilation ventral to dorsal and increased ventilation in centro-dorsal and dorsal lung region). All changes in lung mechanics also occurred during injection, including decreased dynamic respiratory system compliance and increased peak expiratory flow, peak inspiratory pressure and airway resistance at 48, 54 and 60 s, respectively. Changes in VCap variables were delayed with all occurring after completion of the injection. In this model of pulmonary edema, EIT detected significant and rapid change in all assessed variables of lung function with changes in regional ventilation indicative of pulmonary edema. Volumetric capnography complemented the EIT findings, while respiratory mechanics were not specific to lung edema. Thus, EIT offers the most comprehensive method for pulmonary edema evaluation, including the assessment of ventilation distribution, thereby enhancing diagnostic capabilities.

Physiological and clinical effects of trunk inclination adjustment in patients with respiratory failure: a scoping review and narrative synthesis

BackgroundAdjusting trunk inclination from a semi-recumbent position to a supine-flat position or vice versa in patients with respiratory failure significantly affects numerous aspects of respiratory physiology including respiratory mechanics, oxygenation, end-expiratory lung volume, and ventilatory efficiency. Despite these observed effects, the current clinical evidence regarding this positioning manoeuvre is limited. This study undertakes a scoping review of patients with respiratory failure undergoing mechanical ventilation to assess the effect of trunk inclination on physiological lung parameters.MethodsThe PubMed, Cochrane, and Scopus databases were systematically searched from 2003 to 2023. Interventions: Changes in trunk inclination. Measurements: Four domains were evaluated in this study: 1) respiratory mechanics, 2) ventilation distribution, 3) oxygenation, and 4) ventilatory efficiency.ResultsAfter searching the three databases and removing duplicates, 220 studies were screened. Of these, 37 were assessed in detail, and 13 were included in the final analysis, comprising 274 patients. All selected studies were experimental, and assessed respiratory mechanics, ventilation distribution, oxygenation, and ventilatory efficiency, primarily within 60 min post postural change.ConclusionIn patients with acute respiratory failure, transitioning from a supine to a semi-recumbent position leads to decreased respiratory system compliance and increased airway driving pressure. Additionally, C-ARDS patients experienced an improvement in ventilatory efficiency, which resulted in lower PaCO2 levels. Improvements in oxygenation were observed in a few patients and only in those who exhibited an increase in EELV upon moving to a semi-recumbent position. Therefore, the trunk inclination angle must be accurately reported in patients with respiratory failure under mechanical ventilation.

Physiological and clinical effects of trunk inclination adjustment in patients with respiratory failure: a scoping review and narrative synthesis

BackgroundAdjusting trunk inclination from a semi-recumbent position to a supine-flat position or vice versa in patients with respiratory failure significantly affects numerous aspects of respiratory physiology including respiratory mechanics, oxygenation, end-expiratory lung volume, and ventilatory efficiency. Despite these observed effects, the current clinical evidence regarding this positioning manoeuvre is limited. This study undertakes a scoping review of patients with respiratory failure undergoing mechanical ventilation to assess the effect of trunk inclination on physiological lung parameters.MethodsThe PubMed, Cochrane, and Scopus databases were systematically searched from 2003 to 2023. Interventions: Changes in trunk inclination. Measurements: Four domains were evaluated in this study: 1) respiratory mechanics, 2) ventilation distribution, 3) oxygenation, and 4) ventilatory efficiency.ResultsAfter searching the three databases and removing duplicates, 220 studies were screened. Of these, 37 were assessed in detail, and 13 were included in the final analysis, comprising 274 patients. All selected studies were experimental, and assessed respiratory mechanics, ventilation distribution, oxygenation, and ventilatory efficiency, primarily within 60 min post postural change.ConclusionIn patients with acute respiratory failure, transitioning from a supine to a semi-recumbent position leads to decreased respiratory system compliance and increased airway driving pressure. Additionally, C-ARDS patients experienced an improvement in ventilatory efficiency, which resulted in lower PaCO2 levels. Improvements in oxygenation were observed in a few patients and only in those who exhibited an increase in EELV upon moving to a semi-recumbent position. Therefore, the trunk inclination angle must be accurately reported in patients with respiratory failure under mechanical ventilation.

Early and late effects of volatile sedation with sevoflurane on respiratory mechanics of critically ill COPD patients

BackgroundThe objective was to compare sevoflurane, a volatile sedation agent with potential bronchodilatory properties, with propofol on respiratory mechanics in critically ill patients with COPD exacerbation.MethodsProspective study in an ICU enrolling critically ill intubated patients with severe COPD exacerbation and comparing propofol and sevoflurane after 1:1 randomisation. Respiratory system mechanics (airway resistance, PEEPi, trapped volume, ventilatory ratio and respiratory system compliance), gas exchange, vitals, safety and outcome were measured at inclusion and then until H48. Total airway resistance change from baseline to H48 in both sevoflurane and propofol groups was the main endpoint.ResultsSixteen patients were enrolled and were sedated for 126 h(61–228) in the propofol group and 207 h(171–216) in the sevoflurane group. At baseline, airway resistance was 21.6cmH2O/l/s(19.8–21.6) in the propofol group and 20.4cmH2O/l/s(18.6–26.4) in the sevoflurane group, (p = 0.73); trapped volume was 260 ml(176–290) in the propofol group and 73 ml(35–126) in the sevoflurane group, p = 0.02. Intrinsic PEEP was 1.5cmH2O(1–3) in both groups after external PEEP optimization. There was neither early (H4) or late (H48) significant difference in airway resistance and respiratory mechanics parameters between the two groups.ConclusionsIn critically ill patients intubated with COPD exacerbation, there was no significant difference in respiratory mechanics between sevoflurane and propofol from inclusion to H4 and H48.

Digital Twins of Acute Hypoxemic Respiratory Failure Patients Suggest a Mechanistic Basis for Success and Failure of Noninvasive Ventilation

Objectives: To clarify the mechanistic basis for the success or failure of noninvasive ventilation (NIV) in acute hypoxemic respiratory failure (AHRF). Design: We created digital twins based on mechanistic computational models of individual patients with AHRF. Setting: Interdisciplinary Collaboration in Systems Medicine Research Network. Subjects: We used individual patient data from 30 moderate-to-severe AHRF patients who had failed high-flow nasal cannula (HFNC) therapy and subsequently underwent a trial of NIV. Interventions: Using the digital twins, we evaluated lung mechanics, quantified the separate contributions of external support and patient respiratory effort to lung injury indices, and investigated their relative impact on NIV success or failure. Measurements and Main Results: In digital twins of patients who successfully completed/failed NIV, after 2 hours of the trial the mean (sd) of the change in total lung stress was –10.9 (6.2)/–0.35 (3.38) cm H2O, mechanical power –13.4 (12.2)/–1.0 (5.4) J/min, and total lung strain 0.02 (0.24)/0.16 (0.30). In the digital twins, positive end-expiratory pressure (PEEP) produced by HFNC was similar to that set during NIV. In digital twins of patients who failed NIV vs. those who succeeded, intrinsic PEEP was 3.5 (0.6) vs. 2.3 (0.8) cm H2O, inspiratory pressure support was 8.3 (5.9) vs. 22.3 (7.2) cm H2O, and tidal volume was 10.9 (1.2) vs. 9.4 (1.8) mL/kg. In digital twins, successful NIV increased respiratory system compliance +25.0 (16.4) mL/cm H2O, lowered inspiratory muscle pressure –9.7 (9.6) cm H2O, and reduced the contribution of patient spontaneous breathing to total driving pressure by 57.0%. Conclusions: In digital twins of AHRF patients, successful NIV improved lung mechanics, lowering respiratory effort and indices associated with lung injury. NIV failed in patients for whom only low levels of positive inspiratory pressure support could be applied without risking patient self-inflicted lung injury due to excessive tidal volumes.

Continuous estimation of respiratory system compliance and airway resistance during pressure-controlled ventilation without end-inspiration occlusion

BackgroundAssessing mechanical properties of the respiratory system (Cst) during mechanical ventilation necessitates an end-inspiration flow of zero, which requires an end-inspiratory occlusion maneuver. This lung model study aimed to observe the effect of airflow obstruction on the accuracy of respiratory mechanical properties during pressure-controlled ventilation (PCV) by analyzing dynamic signals.MethodsA Hamilton C3 ventilator was attached to a lung simulator that mimics lung mechanics in healthy, acute respiratory distress syndrome (ARDS) and chronic obstructive pulmonary disease (COPD) models. PCV and volume-controlled ventilation (VCV) were applied with tidal volume (VT) values of 5.0, 7.0, and 10.0 ml/kg. Performance characteristics and respiratory mechanics were assessed and were calibrated by virtual extrapolation using expiratory time constant (RCexp).ResultsDuring PCV ventilation, drive pressure (DP) was significantly increased in the ARDS model. Peak inspiratory flow (PIF) and peak expiratory flow (PEF) gradually declined with increasing severity of airflow obstruction, while DP, end-inspiration flow (EIF), and inspiratory cycling ratio (EIF/PIF%) increased. Similar estimated values of Crs and airway resistance (Raw) during PCV and VCV ventilation were obtained in healthy adult and mild obstructive models, and the calculated errors did not exceed 5%. An underestimation of Crs and an overestimation of Raw were observed in the severe obstruction model.ConclusionUsing the modified dynamic signal analysis approach, respiratory system properties (Crs and Raw) could be accurately estimated in patients with non-severe airflow obstruction in the PCV mode.

Dynamic inflation prevents and standardized lung recruitment reverts volume loss associated with percutaneous tracheostomy during volume control ventilation: results from a Neuro-ICU population.

To determine how percutaneous tracheostomy (PT) impacts on respiratory system compliance (Crs) and end-expiratory lung volume (EELV)during volume control ventilation and to test whether a recruitment maneuver (RM) at the end of PT may reverse lung derecruitment. This is a single center, prospective, applied physiology study. 25 patients with acute brain injury who underwent PT were studied. Patients were ventilated in volume control ventilation. Electrical impedance tomography (EIT) monitoring and respiratory mechanics measurements were performed in three steps: (a) baseline, (b) after PT, and (c) after a standardized RM (10 sighs of 30 cmH2O lasting 3s each within 1min). End-expiratory lung impedance (EELI) was used as a surrogate of EELV. PT determined a significant EELI loss (mean reduction of 432 arbitrary units p = 0.049) leading to a reduction in Crs (55 ± 13 vs. 62 ± 13 mL/cmH2O; p < 0.001) as compared to baseline. RM was able to revert EELI loss and restore Crs (68 ± 15 vs. 55 ± 13 mL/cmH2O; p < 0.001). In a subgroup of patients (N = 8, 31%), we observed a gradual but progressive increase in EELI. In this subgroup, patients did not experience a decrease of Crs after PT as compared to patients without dynamic inflation. Dynamic inflation did not cause hemodynamic impairment nor raising of intracranial pressure. We propose a novel and explorative hyperinflation risk index (HRI) formula. Volume control ventilation did not prevent the PT-induced lung derecruitment. RM could restore the baseline lung volume and mechanics. Dynamic inflation is common during PT, it can be monitored real-time by EIT and anticipated by HRI. The presence of dynamic inflation during PT may prevent lung derecruitment.

Mechanical and morphological characterization of the emphysematous lung tissue

Irreversible alveolar airspace enlargement is the main characteristic of pulmonary emphysema, which has been extensively studied using animal models. While the alterations in lung mechanics associated with these morphological changes have been documented in the literature, the study of the mechanical behavior of parenchymal tissue from emphysematous lungs has been poorly investigated. In this work, we characterize the mechanical and morphological properties of lung tissue in elastase-induced emphysema rat models under varying severity conditions. We analyze the non-linear tissue behavior using suitable hyperelastic constitutive models that enable to compare different non-linear responses in terms of hyperelastic material parameters. We further analyze the effect of the elastase dose on alveolar morphology and tissue material parameters and study their connection with respiratory-system mechanical parameters. Our results show that while the lung mechanical function is not significantly influenced by the elastase treatment, the tissue mechanical behavior and alveolar morphology are markedly affected by it. We further show a strong association between alveolar enlargement and tissue softening, not evidenced by respiratory-system compliance. Our findings highlight the importance of understanding tissue mechanics in emphysematous lungs, as changes in tissue properties could detect the early stages of emphysema remodeling. Statement of significanceGas exchange is vital for life and strongly relies on the mechanical function of the lungs. Pulmonary emphysema is a prevalent respiratory disease where alveolar walls are damaged, causing alveolar enlargement that induces harmful changes in the mechanical response of the lungs. In this work, we study how the mechanical properties of lung tissue change during emphysema. Our results from animal models show that tissue properties are more sensitive to alveolar enlargement due to emphysema than other mechanical properties that describe the function of the whole respiratory system.

Effect of prone positioning ventilation on pulmonary function in neonates during venous-arterial extracorporeal membrane oxygenation.

The use of extracorporeal membrane oxygenation (ECMO) technology has significantly decreased mortality rates associated with neonatal pulmonary hypertension and respiratory failure. Prone positioning ventilation (PPV) is a commonly used technique in critically ill infants, designed to improve thoracic pressure gradients, re-expand dorsal lung segments, and increase oxygenation in approximately 70-80% of patients suffering from acute respiratory distress syndrome. This study aimed to evaluate the effects of PPV on pulmonary function in neonates undergoing venous-arterial extracorporeal membrane oxygenation (VA-ECMO). We conducted a retrospective analysis of clinical data from 17 neonates who received ECMO support in our institution, divided into two groups based on ventilation strategy: ECMO with PPV (ECMO-PPV, n=8) and ECMO with supine positioning ventilation (ECMO-SPV, n=9). Parameters such as the P/F ratio [arterial oxygen partial pressure (PaO2)/fraction of inspired oxygen (FiO2)], oxygenation index (OI), respiratory system compliance (Crs), and airway resistance (RAW) were collected and analyzed at baseline, and at 1, 2, and 3 days post-ECMO initiation. In the ECMO-PPV group, these parameters were also assessed 3 days pre-treatment and 2 hours post-treatment initiation. Initial comparisons between ECMO-PPV and ECMO-SPV groups showed no significant difference in PaO2/FiO2, OI, Crs, or RAW. Throughout the ECMO treatment, both groups demonstrated gradual improvements in PaO2/FiO2 and Crs, and reductions in OI and RAW. Notably, by day 3, the ECMO-PPV group exhibited significant improvements in Crs and RAW compared to the ECMO-SPV group (P<0.05). Specifically, in the ECMO-PPV group, Crs significantly increased and RAW decreased after 2 hours of initiating PPV, with these changes becoming statistically significant by day 3 (Crs P=0.03, RAW P=0.03). No severe PPV-related complications were noted. PPV during neonatal ECMO may improve respiratory compliance and reduce RAW, potentially aiding lung recovery. Our findings suggest PPV as a viable strategy for neonates under ECMO support.

Time Course of Mechanical Ventilation Driving Pressure Levels in Pediatric Acute Respiratory Distress Syndrome: Outcomes in a Prospective, Multicenter Cohort Study From Colombia, 2018-2022.

High driving pressure (DP, ratio of tidal volume (Vt) over respiratory system compliance) is a risk for poor outcomes in patients with pediatric acute respiratory distress syndrome (PARDS). We therefore assessed the time course in level of DP (i.e., 24, 48, and 72 hr) after starting mechanical ventilation (MV), and its association with 28-day mortality. Multicenter, prospective study conducted between February 2018 and December 2022. Twelve tertiary care PICUs in Colombia. One hundred eighty-four intubated children with moderate to severe PARDS. None. The median (interquartile range [IQR]) age of the PARDS cohort was 11 (IQR 3-24) months. A total of 129 of 184 patients (70.2%) had a pulmonary etiology leading to PARDS, and 31 of 184 patients (16.8%) died. In the first 24 hours after admission, the plateau pressure in the nonsurvivor group, compared with the survivor group, differed (28.24 [IQR 24.14-32.11] vs. 23.18 [IQR 20.72-27.13] cm H2O, p < 0.01). Of note, children with a Vt less than 8 mL/kg of ideal body weight had lower adjusted odds ratio (aOR [95% CI]) of 28-day mortality (aOR 0.69, [95% CI, 0.55-0.87]; p = 0.02). However, we failed to identify an association between DP level and the oxygenation index (aOR 0.58; 95% CI, 0.21-1.58) at each of time point. In a diagnostic exploratory analysis, we found that DP greater than 15 cm H2O at 72 hours was an explanatory variable for mortality, with area under the receiver operating characteristic curve of 0.83 (95% CI, 0.74-0.89); there was also increased hazard for death with hazard ratio 2.5 (95% CI, 1.07-5.92). DP greater than 15 cm H2O at 72 hours was also associated with longer duration of MV (10 [IQR 7-14] vs. 7 [IQR 5-10] d; p = 0.02). In children with moderate to severe PARDS, a DP greater than 15 cm H2O at 72 hours after the initiation of MV is associated with greater odds of 28-day mortality and a longer duration of MV. DP should be considered a variable worth monitoring during protective ventilation for PARDS.

Effects of positive end-expiratory pressure on pulmonary perfusion distribution and intrapulmonary shunt during one-lung ventilation in pigs A randomized crossover study.

During one-lung ventilation (OLV), positive end-expiratory pressure (PEEP) can improve lung aeration, but might over-distend lung units and increase intrapulmonary shunt. We hypothesized that higher PEEP shifts pulmonary perfusion from the ventilated to the non-ventilated lung, resulting in a U-shaped relationship with intrapulmonary shunt during OLV. In nine anesthetized female pigs, a thoracotomy was performed and intravenous lipopolysaccharide infused to mimic the inflammatory response of thoracic surgery. Animals underwent OLV in supine position with PEEP of 0 cmH2O, 5 cmH2O, titrated to best respiratory system compliance, and 15 cmH2O (PEEP0, PEEP5, PEEPtitr, and PEEP15, respectively, 45 min each, Latin square sequence). Respiratory, hemodynamic, and gas exchange variables were measured. The distributions of perfusion and ventilation were determined by i.v. fluorescent microspheres and computed tomography, respectively. Compared to two lung ventilation, the driving pressure increased with OLV, irrespective of the PEEP level. During OLV, cardiac output was lower at PEEP15 (5.5 ± 1.5 l/min) than PEEP0 (7.6 ± 3 l/min) and PEEP5 (7.4 ± 2.9 l/min; P=0.004), while the intrapulmonary shunt was highest at PEEP0 (PEEP0: 48.1 ± 14.4 %; PEEP5: 42.4 ± 14.8 %; PEEPtitr: 37.8 ± 11.0 %; PEEP15: 39.0 ± 10.7 %; P=0.027). The relative perfusion of the ventilated lung did not differ among PEEP levels (PEEP0: 65.0 ± 10.6 %; PEEP5:68.7 ± 8.7 %; PEEPtitr: 68.2 ± 10.5 %; PEEP15: 58.4 ± 12.8%; P=0.096), but the centers of relative perfusion and ventilation in the ventilated lung shifted from ventral to dorsal, and from cranial to caudal zones with increasing PEEP. In this experimental model of thoracic surgery, higher PEEP during OLV did not shift the perfusion from the ventilated to the non-ventilated lung, thus not increasing intrapulmonary shunt. This study was registered and approved by the Landesdirektion Dresden, Germany (25-5131/496/33).

Apneustic anesthesia ventilation improves pulmonary function in anesthetized bottlenose dolphins (Tursiops truncatus).

Use of mechanical ventilation during general anesthesia is a necessary practice in the anesthetization of small cetaceans as spontaneous ventilation fails to provide adequate gas exchange. Currently available methods of ventilation do not account for the intermittent breathing strategy of representative species within this infraorder of fully aquatic mammals and may have a significant effect on cardiac and respiratory physiology. To understand the impact of mechanical ventilation on cardiopulmonary function in one small species of cetacean, the bottlenose dolphin (Tursiops truncatus), we compared controlled mechanical ventilation (CMV) to a novel ventilation method known as apneustic anesthesia ventilation (AAV). AAV simulates the normal inspiratory breath-hold pattern of dolphins. Ten anesthetic procedures (dental procedure, n = 9; bronchoscopy, n = 2) were performed on nine dolphins (age range: 10-42 years; mean = 32 years; median = 37 years; female = 3, 40%; male = 6, 60%). In a cross-over study design, dolphins were instrumented and randomly assigned to AAV or CMV as the initial mode of ventilation, then switched to the alternate mode. Baseline cardiopulmonary data were collected and again after 30 min on each mode of ventilation. Cardiac index, stroke volume index, systemic vascular resistance, alveolar dead space, alveolar-arterial oxygen tension gradient, arterial oxygen content, oxygen delivery index, and dynamic respiratory system compliance index were calculated at each of the four time points. During AAV, dolphins had higher arterial oxygen tension, higher mean airway pressure, reduced alveolar dead space ventilation and lower alveolar-arterial oxygen difference. Cardiovascular performance was not statistically different between the two modes. Our study suggests AAV, which more closely resembles the conscious intermittent respiratory pattern phenotype of dolphins, improves ventilation and pulmonary function in the anesthetized dolphin. Future studies should evaluate the cardiopulmonary effects of neutral buoyancy and cardiopulmonary sparing drug protocols to reduce the need for hemodynamic support of current protocols.

Prediction and simulation of PEEP setting effects with machine learning models

ObjectiveTo establish a new machine learning-based method to adjust positive end-expiratory pressure (PEEP) using only already routinely measured data. DesignRetrospective observational study. SettingIntensive care unit (ICU). Patients or participants51811 mechanically ventilated patients in multiple ICUs in the USA (data from MIMIC-III and eICU databases). InterventionsNo interventions. Main variables of interestSuccess parameters of ventilation (arterial partial pressures of oxygen and carbon dioxide and respiratory system compliance) ResultsThe multi-tasking neural network model performed significantly best for all target tasks in the primary test set. The model predicts arterial partial pressures of oxygen and carbon dioxide and respiratory system compliance about 45 min into the future with mean absolute percentage errors of about 21.7%, 10.0% and 15.8%, respectively. The proposed use of the model was demonstrated in case scenarios, where we simulated possible effects of PEEP adjustments for individual cases. ConclusionsOur study implies that machine learning approach to PEEP titration is a promising new method which comes with no extra cost once the infrastructure is in place. Availability of databases with most recent ICU patient data is crucial for the refinement of prediction performance.

The Respiratory Mechanics of COVID-19 Acute Respiratory Distress Syndrome-Lessons Learned?

Acute respiratory distress syndrome (ARDS) is a well-defined clinical entity characterized by the acute onset of diffuse pulmonary injury and hypoxemia not explained by fluid overload. The COVID-19 pandemic brought about an unprecedented volume of patients with ARDS and challenged our understanding and clinical approach to treatment of this clinical syndrome. Unique to COVID-19 ARDS is the disruption and dysregulation of the pulmonary vascular compartment caused by the SARS-CoV-2 virus, which is a significant cause of hypoxemia in these patients. As a result, gas exchange does not necessarily correlate with respiratory system compliance and mechanics in COVID-19 ARDS as it does with other etiologies. The purpose of this review is to relate the mechanics of COVID-19 ARDS to its underlying pathophysiologic mechanisms and outline the lessons we have learned in the management of this clinic syndrome.

Six methods to determine expiratory time constants in mechanically ventilated patients: a prospective observational physiology study

BackgroundExpiratory time constant (τ) objectively assesses the speed of exhalation and can guide adjustments of the respiratory rate and the I:E ratio with the goal of achieving complete exhalation. Multiple methods of obtaining τ are available, but they have not been compared. The purpose of this study was to compare six different methods to obtain τ and to test if the exponentially decaying flow corresponds to the measured time constants.MethodsIn this prospective study, pressure, flow, and volume waveforms of 30 postoperative patients undergoing volume (VCV) and pressure-controlled ventilation (PCV) were obtained using a data acquisition device and analyzed. τ was measured as the first 63% of the exhaled tidal volume (VT) and compared to the calculated τ as the product of expiratory resistance (RE) and respiratory system compliance (CRS), or τ derived from passive flow/volume waveforms using previously published equations as proposed by Aerts, Brunner, Guttmann, and Lourens. We tested if the duration of exponentially decaying flow during exhalation corresponded to the duration of the predicted second and third τ, based on multiples of the first measured τ.ResultsMean (95% CI) measured τ was 0.59 (0.57–0.62) s and 0.60 (0.58–0.63) s for PCV and VCV (p = 0.45), respectively. Aerts method showed the shortest values of all methods for both modes: 0.57 (0.54–0.59) s for PCV and 0.58 (0.55–0.61) s for VCV. Calculated (CRS * RE) and Brunner’s τ were identical with mean τ of 0.64 (0.61–0.67) s for PCV and 0.66 (0.63–069) s for VCV. Mean Guttmann’s τ was 0.64 (0.61–0.68) in PCV and 0.65 (0.62–0.69) in VCV. Comparison of each τ method between PCV and VCV was not significant. Predicted time to exhale 95% of the VT (i.e., 3*τ) was 1.77 (1.70–1.84) s for PCV and 1.80 (1.73–1.88) s for VCV, which was significantly longer than measured values: 1.27 (1.22–1.32) for PCV and 1.30 (1.25–1.35) s for VCV (p < 0.0001). The first, the second and the third measured τ were progressively shorter: 0.6, 0.4 and 0.3 s, in both ventilation modes (p < 0.0001).ConclusionAll six methods to determine τ show similar values and are feasible in postoperative mechanically ventilated patients in both PCV and VCV modes.

Effect of end-inspiratory pause duration on respiratory system compliance calculation in mechanically ventilated dogs with healthy lungs

ObjectiveTo compare respiratory system compliance (CRS), expressed per kilogram of bodyweight (CRSBW), calculated without end-inspiratory pause (EIP) and after three EIP times (0.2, 0.5 and 1 seconds) with that after 3 second EIP (considered the reference EIP for static CRS) and to determine the EIP times that provided CRSBW values in acceptable agreement with static CRSBW during controlled mechanical ventilation (CMV) in anaesthetized dogs. Study designProspective, randomized, nonblinded, crossover clinical study. AnimalsA group of 24 client-owned dogs with healthy lungs undergoing surgery in lateral recumbency. MethodsDuring CMV in dogs undergoing general anaesthesia, five EIPs [0 (no EIP), 0.2, 0.5, 1 and 3 seconds] were consecutively applied in random order. Tidal volume (Vt) was set at 10 mL kg–1 and positive end-expiratory pressure (PEEP) was not applied. Respiratory rate and inspiratory time were established according to each EIP time, setting EIP between 0 and 50% of the inspiratory time. The CRSBW was calculated as [expired Vt/(plateau pressure – PEEP)]/bodyweight and recorded every 15 seconds for 2 minutes after a 5 minute equilibration period with each EIP. One-way anova for repeated measures and the Bland–Altman analysis were used to compare CRSBW and evaluate agreement between EIP times, respectively. ResultsThe CRSBW was significantly greater as the EIP time increased up to 1 second (p < 0.05). In the Bland–Altman analysis, none of the tested EIPs (0, 0.2, 0.5 and 1 seconds) provided 95% confidence intervals for limits of agreement within the maximum allowed difference considered for acceptable agreement with 3 second EIP. Conclusionsand clinical relevance An EIP ≤ to 1 second does not provide a CRSBW value in acceptable agreement with static CRSBW in healthy dogs. Besides, the application of an EIP ≤ to 0.5 seconds underestimates the static CRSBW to an increasing extent as the EIP time decreases.