Influence of Fractional Inspired Oxygen Tension on Lung Perfusion Distribution, Regional Ventilation, and Lung Volume during Mechanical Ventilation of Supine Healthy Swine.

BACKGROUND: Lower fractional inspired oxygen tension (Fio2) during general anesthesia can reduce lung atelectasis. The objectives are to evaluate the effect of two Fio2 (0.4 and 1) during low positive end-expiratory pressure (PEEP) ventilation over lung perfusion distribution, volume, and regional ventilation. These variables were evaluated at two PEEP levels and unilateral lung atelectasis. METHODS: In this exploratory study, 10 healthy female piglets (32.3 ± 3.4 kg) underwent mechanical ventilation in two atelectasis models: (1) bilateral gravitational atelectasis (n = 6), induced by changes in PEEP and Fio2 in three combinations: high PEEP with low Fio2 (Fio2 = 0.4), zero PEEP (PEEP0) with low Fio2 (Fio2 = 0.4), and PEEP0 with high Fio2 (Fio2 = 1); and (2) unilateral atelectasis (n = 6), induced by left bronchial occlusion, with the left lung aerated (Fio2 = 0.21) and low aerated (Fio2 = 1; n = 5 for this step). Measurements were conducted after 10 min in each step, encompassing assessment of respiratory mechanics, oxygenation, and hemodynamics; lung ventilation and perfusion by electrical impedance tomography; and lung aeration and perfusion by computed tomography. RESULTS: During bilateral gravitational atelectasis, PEEP reduction increased atelectasis in dorsal regions, decreased respiratory compliance, and distributed lung ventilation to ventral regions with a parallel shift of perfusion to the same areas. With PEEP0, there were no differences between low and high Fio2 in respiratory compliance (23.9 ± 6.5 ml/cm H2O vs. 21.9 ± 5.0; P = 0.441), regional ventilation, and regional perfusion, despite higher lung collapse (18.6 ± 7.6% vs. 32.7 ± 14.5%; P = 0.045) with high Fio2. During unilateral lung atelectasis, the deaerated lung had a lower shunt (19.3 ± 3.6% vs. 25.3 ± 5.5%; P = 0.045) and lower computed tomography perfusion to the left lung (8.8 ± 1.8% vs. 23.8 ± 7.1%; P = 0.007). CONCLUSIONS: PEEP0 with low Fio2, compared with high Fio2, did not produce significant changes in respiratory system compliance, regional lung ventilation, and perfusion despite significantly lower lung collapse. After left bronchial occlusion, the shrinkage of the parenchyma with Fio2 = 1 enhanced hypoxic pulmonary vasoconstriction, reducing intrapulmonary shunt and perfusion of the nonventilated areas.

Pendelluft in hypoxemic patients resuming spontaneous breathing: proportional modes versus pressure support ventilation.

BACKGROUND: Internal redistribution of gas, referred to as pendelluft, is a new potential mechanism of effort-dependent lung injury. Neurally-adjusted ventilatory assist (NAVA) and proportional assist ventilation (PAV +) follow the patient's respiratory effort and improve synchrony compared with pressure support ventilation (PSV). Whether these modes could prevent the development of pendelluft compared with PSV is unknown. We aimed to compare pendelluft magnitude during PAV + and NAVA versus PSV in patients with resolving acute respiratory distress syndrome (ARDS). METHODS: Patients received either NAVA, PAV + , or PSV in a crossover trial for 20-min using comparable assistance levels after controlled ventilation (> 72 h). We assessed pendelluft (the percentage of lost volume from the non-dependent lung region displaced to the dependent region during inspiration), drive (as the delta esophageal swing of the first 100 ms [ΔPes 100 ms]) and inspiratory effort (as the esophageal pressure-time product per minute [PTPmin]). We performed repeated measures analysis with post-hoc tests and mixed-effects models. RESULTS: Twenty patients mechanically ventilated for 9 [5-14] days were monitored. Despite matching for a similar tidal volume, respiratory drive and inspiratory effort were slightly higher with NAVA and PAV + compared with PSV (ΔPes 100 ms of -2.8 [-3.8--1.9] cm H2O, -3.6 [-3.9--2.4] cm H2O and -2.1 [-2.5--1.1] cm H2O, respectively, p < 0.001 for both comparisons; PTPmin of 155 [118-209] cm H2O s/min, 197 [145-269] cm H2O s/min, and 134 [93-169] cm H2O s/min, respectively, p < 0.001 for both comparisons). Pendelluft magnitude was higher in NAVA (12 ± 7%) and PAV + (13 ± 7%) compared with PSV (8 ± 6%), p < 0.001. Pendelluft magnitude was strongly associated with respiratory drive (ß = -2.771, p-value < 0.001) and inspiratory effort (ß = 0.026, p < 0.001), independent of the ventilatory mode. A higher magnitude of pendelluft in proportional modes compared with PSV existed after adjusting for PTPmin (ß = 2.606, p = 0.010 for NAVA, and ß = 3.360, p = 0.004 for PAV +), and only for PAV + when adjusted for respiratory drive (ß = 2.643, p = 0.009 for PAV +). CONCLUSIONS: Pendelluft magnitude is associated with respiratory drive and inspiratory effort. Proportional modes do not prevent its occurrence in resolving ARDS compared with PSV.

Dynamic relative regional lung strain estimated by computed tomography and electrical impedance tomography in ARDS patients.

BACKGROUND: In the acute distress respiratory syndrome (ARDS), specific lung regions can be exposed to excessive strain due to heterogeneous disease, gravity-dependent lung collapse and injurious mechanical ventilation. Computed tomography (CT) is the gold standard for regional strain assessment. An alternative tool could be the electrical impedance tomography (EIT). We aimed to determine whether EIT-based methods can predict the dynamic relative regional strain (DRRS) between two levels of end-expiratory pressure (PEEP) in gravity-non-dependent and dependent lung regions. METHODS: Fourteen ARDS patients underwent CT and EIT acquisitions (at end-inspiratory and end-expiratory) at two levels of PEEP: a low-PEEP based on ARDS-net strategy and a high-PEEP titrated according to EIT. Three EIT-based methods for DRRS were compared to relative CT-based strain: (1) the change of the ratio between EIT ventilation and end-expiratory lung impedance in arbitrary units ([ΔZAU low-PEEP/EELIAU low-PEEP]/[ΔZAU high-PEEP/EELIAU high-PEEP]), (2) the change of ΔZ/EELI ratio calibrated to mL ([ΔZml low-PEEP/EELIml low-PEEP]/[ΔZml high-PEEP/EELIml high-PEEP]) using CT data, and (3) the relative change of ∆ZAU (∆ZAU low-PEEP/∆ZAU high-PEEP). We performed linear regressions analysis and calculated bias and limits of agreement to assess the performance of DRRS by EIT in comparison with CT. RESULTS: The DRRS assessed by (ΔZml low-PEEP/EELIml low-PEEP)/(ΔZml high-PEEP/EELIml high-PEEP) and ∆ZAU low-PEEP/∆ZAU high-PEEP showed good relationship and agreement with the CT method (R2 of 0.9050 and 0.8679, respectively, in non-dependent region; R2 of 0.8373 and 0.6588, respectively, in dependent region; biases ranging from - 0.11 to 0.51 and limits of agreement ranging from - 0.73 to 1.16 for both methods and lung regions). Conversely, DRRS based on EELIAU ([ΔZAU low-PEEP/EELIAU low-PEEP]/[ΔZAU high-PEEP/EELIAU high-PEEP]) exhibited a weak negative relationship and poor agreement with the CT method for both non-dependent and dependent regions (R2 ~ 0.3; bias of 3.11 and 2.08, and limits of agreement of - 2.13 to 8.34 and from - 1.49 to 5.64, respectively). CONCLUSION: Changes in DRRS during a PEEP trial in ARDS patients could be monitored using EIT, based on changes in ΔZmL/EELIml and ∆ZAU. The relative change ∆ZAU offers the advantage of not requiring CT data for calibration.

Pronation Reveals a Heterogeneous Response of Global and Regional Respiratory Mechanics in Patients With Acute Hypoxemic Respiratory Failure.

OBJECTIVES: Experimental models suggest that prone position and positive end-expiratory pressure (PEEP) homogenize ventral-dorsal ventilation distribution and regional respiratory compliance. However, this response still needs confirmation on humans. Therefore, this study aimed to assess the changes in global and regional respiratory mechanics in supine and prone positions over a range of PEEP levels in acute respiratory distress syndrome (ARDS) patients. DESIGN: A prospective cohort study. PATIENTS: Twenty-two intubated patients with ARDS caused by COVID-19 pneumonia. INTERVENTIONS: Electrical impedance tomography and esophageal manometry were applied during PEEP titrations from 20 cm H2O to 6 cm H2O in supine and prone positions. MEASUREMENTS: Global respiratory system compliance (Crs), chest wall compliance, regional lung compliance, ventilation distribution in supine and prone positions. MAIN RESULTS: Compared with supine position, the maximum level of Crs changed after prone position in 59% of ARDS patients (n = 13), of which the Crs decreased in 32% (n = 7) and increased in 27% (n = 6). To reach maximum Crs after pronation, PEEP was changed in 45% of the patients by at least 4 cm H2O. After pronation, the ventilation and compliance of the dorsal region did not consistently change in the entire sample of patients, increasing specifically in a subgroup of patients who showed a positive change in Crs when transitioning from supine to prone position. These combined changes in ventilation and compliance suggest dorsal recruitment postpronation. In addition, the subgroup with increased Crs postpronation demonstrated the most pronounced difference between dorsal and ventral ventilation distribution from supine to prone position (p = 0.01), indicating heterogeneous ventilation distribution in prone position. CONCLUSIONS: Prone position modifies global respiratory compliance in most patients with ARDS. Only a subgroup of patients with a positive change in Crs postpronation presented a consistent improvement in dorsal ventilation and compliance. These data suggest that the response to pronation on global and regional mechanics can vary among ARDS patients, with some patients presenting more dorsal lung recruitment than others.

Electrical Impedance Tomography Identifies Evolution of Regional Perfusion in a Porcine Model of Acute Respiratory Distress Syndrome.

BACKGROUND: Bedside electrical impedance tomography could be useful to visualize evolving pulmonary perfusion distributions when acute respiratory distress syndrome worsens or in response to ventilatory and positional therapies. In experimental acute respiratory distress syndrome, this study evaluated the agreement of electrical impedance tomography and dynamic contrast-enhanced computed tomography perfusion distributions at two injury time points and in response to increased positive end-expiratory pressure (PEEP) and prone position. METHODS: Eleven mechanically ventilated (VT 8 ml · kg-1) Yorkshire pigs (five male, six female) received bronchial hydrochloric acid (3.5 ml · kg-1) to invoke lung injury. Electrical impedance tomography and computed tomography perfusion images were obtained at 2 h (early injury) and 24 h (late injury) after injury in supine position with PEEP 5 and 10 cm H2O. In eight animals, electrical impedance tomography and computed tomography perfusion imaging were also conducted in the prone position. Electrical impedance tomography perfusion (QEIT) and computed tomography perfusion (QCT) values (as percentages of image total) were compared in eight vertical regions across injury stages, levels of PEEP, and body positions using mixed-effects linear regression. The primary outcome was agreement between QEIT and QCT, defined using limits of agreement and Pearson correlation coefficient. RESULTS: Pao2/Fio2 decreased over the course of the experiment (healthy to early injury, -253 [95% CI, -317 to -189]; early to late injury, -88 [95% CI, -151 to -24]). The limits of agreement between QEIT and QCT were -4.66% and 4.73% for the middle 50% quantile of average regional perfusion, and the correlation coefficient was 0.88 (95% CI, 0.86 to 0.90]; P < 0.001). Electrical impedance tomography and computed tomography showed similar perfusion redistributions over injury stages and in response to increased PEEP. QEIT redistributions after positional therapy underestimated QCT in ventral regions and overestimated QCT in dorsal regions. CONCLUSIONS: Electrical impedance tomography closely approximated computed tomography perfusion measures in experimental acute respiratory distress syndrome, in the supine position, over injury progression and with increased PEEP. Further validation is needed to determine the accuracy of electrical impedance tomography in measuring perfusion redistributions after positional changes.

Modulation of pulmonary blood flow in patients with acute respiratory failure.

BACKGROUND: Impairment of ventilation and perfusion (V/Q) matching is a common mechanism leading to hypoxemia in patients with acute respiratory failure requiring intensive care unit (ICU) admission. While ventilation has been thoroughly investigated, little progress has been made to monitor pulmonary perfusion at the bedside and treat impaired blood distribution. The study aimed to assess real-time changes in regional pulmonary perfusion in response to a therapeutic intervention. METHODS: Single-center prospective study that enrolled adult patients with ARDS caused by SARS-Cov-2 who were sedated, paralyzed, and mechanically ventilated. The distribution of pulmonary perfusion was assessed through electrical impedance tomography (EIT) after the injection of a 10-ml bolus of hypertonic saline. The therapeutic intervention consisted in the administration of inhaled nitric oxide (iNO), as rescue therapy for refractory hypoxemia. Each patient underwent two 15-min steps at 0 and 20 ppm iNO, respectively. At each step, respiratory, gas exchange, and hemodynamic parameters were recorded, and V/Q distribution was measured, with unchanged ventilatory settings. RESULTS: Ten 65 [56-75] years old patients with moderate (40%) and severe (60%) ARDS were studied 10 [4-20] days after intubation. Gas exchange improved at 20 ppm iNO (PaO2/FiO2 from 86 ± 16 to 110 ± 30 mmHg, p = 0.001; venous admixture from 51 ± 8 to 45 ± 7%, p = 0.0045; dead space from 29 ± 8 to 25 ± 6%, p = 0.008). The respiratory system's elastic properties and ventilation distribution were unaltered by iNO. Hemodynamics did not change after gas initiation (cardiac output 7.6 ± 1.9 vs. 7.7 ± 1.9 L/min, p = 0.66). The EIT pixel perfusion maps showed a variety of patterns of changes in pulmonary blood flow, whose increase positively correlated with PaO2/FiO2 increase (R2 = 0.50, p = 0.049). CONCLUSIONS: The assessment of lung perfusion is feasible at the bedside and blood distribution can be modulated with effects that are visualized in vivo. These findings might lay the foundations for testing new therapies aimed at optimizing the regional perfusion in the lungs.

Effect of general anesthesia and controlled mechanical ventilation on pulmonary ventilation distribution assessed by electrical impedance tomography in healthy children.

INTRODUCTION: General anesthesia is associated with the development of atelectasis, which may affect lung ventilation. Electrical impedance tomography (EIT) is a noninvasive imaging tool that allows monitoring in real time the topographical changes in aeration and ventilation. OBJECTIVE: To evaluate the pattern of distribution of pulmonary ventilation through EIT before and after anesthesia induction in pediatric patients without lung disease undergoing nonthoracic surgery. METHODS: This was a prospective observational study including healthy children younger than 5 years who underwent nonthoracic surgery. Monitoring was performed continuously before and throughout the surgical period. Data analysis was divided into 5 periods: induction (spontaneous breathing, SB), ventilation-5min, ventilation-30min, ventilation-late and recovery-SB. In addition to demographic data, mechanical ventilation parameters were also collected. Ventilation impedance (Delta Z) and pulmonary ventilation distribution were analyzed cycle by cycle at the 5 periods. RESULTS: Twenty patients were included, and redistribution of ventilation from the posterior to the anterior region was observed with the beginning of mechanical ventilation: on average, the percentage ventilation distribution in the dorsal region decreased from 54%(IC95%:49-60%) to 49%(IC95%:44-54%). With the restoration of spontaneous breathing, ventilation in the posterior region was restored. CONCLUSION: There were significant pulmonary changes observed during anesthesia and controlled mechanical ventilation in children younger than 5 years, mirroring the findings previously described adults. Monitoring these changes may contribute to guiding the individualized settings of the mechanical ventilator with the goal to prevent postoperative complications.

Inflammatory biomarkers and pendelluft magnitude in ards patients transitioning from controlled to partial support ventilation.

The transition from controlled to partial support ventilation is a challenge in acute respiratory distress syndrome (ARDS) patients due to the risks of patient-self-inflicted lung injury. The magnitude of tidal volume (VT) and intrapulmonary dyssynchrony (pendelluft) are suggested mechanisms of lung injury. We conducted a prospective, observational, physiological study in a tertiary academic intensive care unit. ARDS patients transitioning from controlled to partial support ventilation were included. On these, we evaluated the association between changes in inflammatory biomarkers and esophageal pressure swing (ΔPes), transpulmonary driving pressure (ΔPL), VT, and pendelluft. Pendelluft was defined as the percentage of the tidal volume that moves from the non-dependent to the dependent lung region during inspiration, and its frequency at different thresholds (- 15, - 20 and - 25%) was also registered. Blood concentrations of inflammatory biomarkers (IL-6, IL-8, TNF-α, ANGPT2, RAGE, IL-18, Caspase-1) were measured before (T0) and after 4-h (T4) of partial support ventilation. Pendelluft, ΔPes, ΔPL and VT were recorded. Nine out of twenty-four patients (37.5%) showed a pendelluft mean ≥ 10%. The mean values of ΔPes, ΔPL, and VT were - 8.4 [- 6.7; - 10.2] cmH2O, 15.2 [12.3-16.5] cmH2O and 8.1 [7.3-8.9] m/kg PBW, respectively. Significant associations were observed between the frequency of high-magnitude pendelluft and IL-8, IL-18, and Caspase-1 changes (T0/T4 ratio). These results suggest that the frequency of high magnitude pendelluft may be a potential determinant of inflammatory response related to inspiratory efforts in ARDS patients transitioning to partial support ventilation. Future studies are needed to confirm these results.

Phrenic Nerve Block and Respiratory Effort in Pigs and Critically Ill Patients with Acute Lung Injury.

BACKGROUND: Strong spontaneous inspiratory efforts can be difficult to control and prohibit protective mechanical ventilation. Instead of using deep sedation and neuromuscular blockade, the authors hypothesized that perineural administration of lidocaine around the phrenic nerve would reduce tidal volume (VT) and peak transpulmonary pressure in spontaneously breathing patients with acute respiratory distress syndrome. METHODS: An established animal model of acute respiratory distress syndrome with six female pigs was used in a proof-of-concept study. The authors then evaluated this technique in nine mechanically ventilated patients under pressure support exhibiting driving pressure greater than 15 cm H2O or VT greater than 10 ml/kg of predicted body weight. Esophageal and transpulmonary pressures, electrical activity of the diaphragm, and electrical impedance tomography were measured in pigs and patients. Ultrasound imaging and a nerve stimulator were used to identify the phrenic nerve, and perineural lidocaine was administered sequentially around the left and right phrenic nerves. RESULTS: Results are presented as median [interquartile range, 25th to 75th percentiles]. In pigs, VT decreased from 7.4 ml/kg [7.2 to 8.4] to 5.9 ml/kg [5.5 to 6.6] (P < 0.001), as did peak transpulmonary pressure (25.8 cm H2O [20.2 to 27.2] to 17.7 cm H2O [13.8 to 18.8]; P < 0.001) and driving pressure (28.7 cm H2O [20.4 to 30.8] to 19.4 cm H2O [15.2 to 22.9]; P < 0.001). Ventilation in the most dependent part decreased from 29.3% [26.4 to 29.5] to 20.1% [15.3 to 20.8] (P < 0.001). In patients, VT decreased (8.2 ml/ kg [7.9 to 11.1] to 6.0 ml/ kg [5.7 to 6.7]; P < 0.001), as did driving pressure (24.7 cm H2O [20.4 to 34.5] to 18.4 cm H2O [16.8 to 20.7]; P < 0.001). Esophageal pressure, peak transpulmonary pressure, and electrical activity of the diaphragm also decreased. Dependent ventilation only slightly decreased from 11.5% [8.5 to 12.6] to 7.9% [5.3 to 8.6] (P = 0.005). Respiratory rate did not vary. Variables recovered 1 to 12.7 h [6.7 to 13.7] after phrenic nerve block. CONCLUSIONS: Phrenic nerve block is feasible, lasts around 12 h, and reduces VT and driving pressure without changing respiratory rate in patients under assisted ventilation.

Diminishing Efficacy of Prone Positioning With Late Application in Evolving Lung Injury.

OBJECTIVES: It is not known how lung injury progression during mechanical ventilation modifies pulmonary responses to prone positioning. We compared the effects of prone positioning on regional lung aeration in late versus early stages of lung injury. DESIGN: Prospective, longitudinal imaging study. SETTING: Research imaging facility at The University of Pennsylvania (Philadelphia, PA) and Medical and Surgical ICUs at Massachusetts General Hospital (Boston, MA). SUBJECTS: Anesthetized swine and patients with acute respiratory distress syndrome (acute respiratory distress syndrome). INTERVENTIONS: Lung injury was induced by bronchial hydrochloric acid (3.5 mL/kg) in 10 ventilated Yorkshire pigs and worsened by supine nonprotective ventilation for 24 hours. Whole-lung CT was performed 2 hours after hydrochloric acid (Day 1) in both prone and supine positions and repeated at 24 hours (Day 2). Prone and supine images were registered (superimposed) in pairs to measure the effects of positioning on the aeration of each tissue unit. Two patients with early acute respiratory distress syndrome were compared with two patients with late acute respiratory distress syndrome, using electrical impedance tomography to measure the effects of body position on regional lung mechanics. MEASUREMENTS AND MAIN RESULTS: Gas exchange and respiratory mechanics worsened over 24 hours, indicating lung injury progression. On Day 1, prone positioning reinflated 18.9% ± 5.2% of lung mass in the posterior lung regions. On Day 2, position-associated dorsal reinflation was reduced to 7.3% ± 1.5% (p < 0.05 vs Day 1). Prone positioning decreased aeration in the anterior lungs on both days. Although prone positioning improved posterior lung compliance in the early acute respiratory distress syndrome patients, it had no effect in late acute respiratory distress syndrome subjects. CONCLUSIONS: The effects of prone positioning on lung aeration may depend on the stage of lung injury and duration of prior ventilation; this may limit the clinical efficacy of this treatment if applied late.

Ventilatory Variables and Mechanical Power in Patients with Acute Respiratory Distress Syndrome.

Rationale: Mortality in acute respiratory distress syndrome (ARDS) has decreased after the adoption of lung-protective strategies. Lower Vt, lower driving pressure (ΔP), lower respiratory rates (RR), and higher end-expiratory pressure have all been suggested as key components of lung protection strategies. A unifying theoretical explanation has been proposed that attributes lung injury to the energy transfer rate (mechanical power) from the ventilator to the patient, calculated from a combination of several ventilator variables.Objectives: To assess the impact of mechanical power on mortality in patients with ARDS as compared with that of primary ventilator variables such as the ΔP, Vt, and RR.Methods: We obtained data on ventilatory variables and mechanical power from a pooled database of patients with ARDS who had participated in six randomized clinical trials of protective mechanical ventilation and one large observational cohort of patients with ARDS. The primary outcome was mortality at 28 days or 60 days.Measurements and Main Results: We included 4,549 patients (38% women; mean age, 55 ± 23 yr). The average mechanical power was 0.32 ± 0.14 J · min-1 · kg-1 of predicted body weight, the ΔP was 15.0 ± 5.8 cm H2O, and the RR was 25.7 ± 7.4 breaths/min. The driving pressure, RR, and mechanical power were significant predictors of mortality in adjusted analyses. The impact of the ΔP on mortality was four times as large as that of the RR.Conclusions: Mechanical power was associated with mortality during controlled mechanical ventilation in ARDS, but a simpler model using only the ΔP and RR was equivalent.

High Pleural Pressure Prevents Alveolar Overdistension and Hemodynamic Collapse in Acute Respiratory Distress Syndrome with Class III Obesity. A Clinical Trial.

Rationale: Obesity is characterized by elevated pleural pressure (Ppl) and worsening atelectasis during mechanical ventilation in patients with acute respiratory distress syndrome (ARDS).Objectives: To determine the effects of a lung recruitment maneuver (LRM) in the presence of elevated Ppl on hemodynamics, left and right ventricular pressure, and pulmonary vascular resistance. We hypothesized that elevated Ppl protects the cardiovascular system against high airway pressure and prevents lung overdistension.Methods: First, an interventional crossover trial in adult subjects with ARDS and a body mass index ≥ 35 kg/m2 (n = 21) was performed to explore the hemodynamic consequences of the LRM. Second, cardiovascular function was studied during low and high positive end-expiratory pressure (PEEP) in a model of swine with ARDS and high Ppl (n = 9) versus healthy swine with normal Ppl (n = 6).Measurements and Main Results: Subjects with ARDS and obesity (body mass index = 57 ± 12 kg/m2) after LRM required an increase in PEEP of 8 (95% confidence interval [95% CI], 7-10) cm H2O above traditional ARDS Network settings to improve lung function, oxygenation and [Formula: see text]/[Formula: see text] matching, without impairment of hemodynamics or right heart function. ARDS swine with high Ppl demonstrated unchanged transmural left ventricular pressure and systemic blood pressure after the LRM protocol. Pulmonary arterial hypertension decreased (8 [95% CI, 13-4] mm Hg), as did vascular resistance (1.5 [95% CI, 2.2-0.9] Wood units) and transmural right ventricular pressure (10 [95% CI, 15-6] mm Hg) during exhalation. LRM and PEEP decreased pulmonary vascular resistance and normalized the [Formula: see text]/[Formula: see text] ratio.Conclusions: High airway pressure is required to recruit lung atelectasis in patients with ARDS and class III obesity but causes minimal overdistension. In addition, patients with ARDS and class III obesity hemodynamically tolerate LRM with high airway pressure.Clinical trial registered with www.clinicaltrials.gov (NCT02503241).

Estimation of changes in cyclic lung strain by electrical impedance tomography: Proof-of-concept study.

RATIONALE: Cyclic strain may be a determinant of ventilator-induced lung injury. The standard for strain assessment is the computed tomography (CT), which does not allow continuous monitoring and exposes to radiation. Electrical impedance tomography (EIT) is able to monitor changes in regional lung ventilation. In addition, there is a correlation between mechanical deformation of materials and detectable changes in its electrical impedance, making EIT a potential surrogate for cyclic lung strain measured by CT (StrainCT ). OBJECTIVES: To compare the global StrainCT with the change in electrical impedance (ΔZ). METHODS: Acute respiratory distress syndrome patients under mechanical ventilation (VT 6 mL/kg ideal body weight with positive end-expiratory pressure 5 [PEEP 5] and best PEEP according to EIT) underwent whole-lung CT at end-inspiration and end-expiration. Biomechanical analysis was used to construct 3D maps and determine StrainCT at different levels of PEEP. CT and EIT acquisitions were performed simultaneously. Multilevel analysis was employed to determine the causal association between StrainCT and ΔZ. Linear regression models were used to predict the change in lung StrainCT between different PEEP levels based on the change in ΔZ. MAIN RESULTS: StrainCT was positively and independently associated with ΔZ at global level (P < .01). Furthermore, the change in StrainCT (between PEEP 5 and Best PEEP) was accurately predicted by the change in ΔZ (R2 0.855, P < .001 at global level) with a high agreement between predicted and measured StrainCT . CONCLUSIONS: The change in electrical impedance may provide a noninvasive assessment of global cyclic strain, without radiation at bedside.

High Concentrations of Nitric Oxide Inhalation Therapy in Pregnant Patients With Severe Coronavirus Disease 2019 (COVID-19).

BACKGROUND: Rescue therapies to treat or prevent progression of coronavirus disease 2019 (COVID-19) hypoxic respiratory failure in pregnant patients are lacking. METHOD: To treat pregnant patients meeting criteria for severe or critical COVID-19 with high-dose (160-200 ppm) nitric oxide by mask twice daily and report on their clinical response. EXPERIENCE: Six pregnant patients were admitted with severe or critical COVID-19 at Massachusetts General Hospital from April to June 2020 and received inhalational nitric oxide therapy. All patients tested positive for severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection. A total of 39 treatments was administered. An improvement in cardiopulmonary function was observed after commencing nitric oxide gas, as evidenced by an increase in systemic oxygenation in each administration session among those with evidence of baseline hypoxemia and reduction of tachypnea in all patients in each session. Three patients delivered a total of four neonates during hospitalization. At 28-day follow-up, all three patients were home and their newborns were in good condition. Three of the six patients remain pregnant after hospital discharge. Five patients had two negative test results on nasopharyngeal swab for SARS-CoV-2 within 28 days from admission. CONCLUSION: Nitric oxide at 160-200 ppm is easy to use, appears to be well tolerated, and might be of benefit in pregnant patients with COVID-19 with hypoxic respiratory failure.