Limiting Overdistention or Collapse When Mechanically Ventilating Injured Lungs: A Randomized Study in a Porcine Model.

Rationale: It is unknown whether preventing overdistention or collapse is more important when titrating positive end-expiratory pressure (PEEP) in acute respiratory distress syndrome (ARDS). Objectives: To compare PEEP targeting minimal overdistention or minimal collapse or using a compromise between collapse and overdistention in a randomized trial and to assess the impact on respiratory mechanics, gas exchange, inflammation, and hemodynamics. Methods: In a porcine model of ARDS, lung collapse and overdistention were estimated using electrical impedance tomography during a decremental PEEP titration. Pigs were randomized to three groups and ventilated for 12 hours: PEEP set at ⩽3% of overdistention (low overdistention), ⩽3% of collapse (low collapse), and the crossing point of collapse and overdistention. Measurements and Main Results: Thirty-six pigs (12 per group) were included. Median (interquartile range) values of PEEP were 7 (6-8), 11 (10-11), and 15 (12-16) cm H2O in the three groups (P < 0.001). With low overdistension, 6 (50%) pigs died, whereas survival was 100% in both other groups. Cause of death was hemodynamic in nature, with high transpulmonary vascular gradient and high epinephrine requirements. Compared with the other groups, pigs surviving with low overdistension had worse respiratory mechanics and gas exchange during the entire protocol. Minimal differences existed between crossing-point and low-collapse animals in physiological parameters, but postmortem alveolar density was more homogeneous in the crossing-point group. Inflammatory markers were not significantly different. Conclusions: PEEP to minimize overdistention resulted in high mortality in an animal model of ARDS. Minimizing collapse or choosing a compromise between collapse and overdistention may result in less lung injury, with potential benefits of the compromise approach.

Expiratory Muscle Activity Counteracts Positive End-Expiratory Pressure and Is Associated with Fentanyl Dose in Patients with Acute Respiratory Distress Syndrome.

Rationale: Hypoxemia during mechanical ventilation might be worsened by expiratory muscle activity, which reduces end-expiratory lung volume through lung collapse. A proposed mechanism of benefit of neuromuscular blockade in acute respiratory distress syndrome (ARDS) is the abolition of expiratory efforts. This may contribute to the restoration of lung volumes. The prevalence of this phenomenon, however, is unknown. Objectives: To investigate the incidence and amount of end-expiratory lung impedance (EELI) increase after the administration of neuromuscular blocking agents (NMBAs), clinical factors associated with this phenomenon, its impact on regional lung ventilation, and any association with changes in pleural pressure. Methods: We included mechanically ventilated patients with ARDS monitored with electrical impedance tomography (EIT) who received NMBAs in one of two centers. We measured changes in EELI, a surrogate for end-expiratory lung volume, before and after NMBA administration. In an additional 10 patients, we investigated the characteristic signatures of expiratory muscle activity depicted by EIT and esophageal catheters simultaneously. Clinical factors associated with EELI changes were assessed. Measurements and Main Results: We included 46 patients, half of whom showed an increase in EELI of >10% of the corresponding Vt (46.2%; IQR, 23.9-60.9%). The degree of EELI increase correlated positively with fentanyl dosage and negatively with changes in end-expiratory pleural pressures. This suggests that expiratory muscle activity might exert strong counter-effects against positive end-expiratory pressure that are possibly aggravated by fentanyl. Conclusions: Administration of NMBAs during EIT monitoring revealed activity of expiratory muscles in half of patients with ARDS. The resultant increase in EELI had a dose-response relationship with fentanyl dosage. This suggests a potential side effect of fentanyl during protective ventilation.

High Mechanical Power and Driving Pressures are Associated With Postoperative Respiratory Failure Independent From Patients' Respiratory System Mechanics.

OBJECTIVES: High mechanical power and driving pressure (ΔP) have been associated with postoperative respiratory failure (PRF) and may be important parameters guiding mechanical ventilation. However, it remains unclear whether high mechanical power and ΔP merely reflect patients with poor respiratory system mechanics at risk of PRF. We investigated the effect of mechanical power and ΔP on PRF in cohorts after exact matching by patients' baseline respiratory system compliance. DESIGN: Hospital registry study. SETTING: Academic hospital in New England. PATIENTS: Adult patients undergoing general anesthesia between 2008 and 2020. INTERVENTION: None. MEASUREMENTS AND MAIN RESULTS: The primary exposure was high (≥ 6.7 J/min, cohort median) versus low mechanical power and the key-secondary exposure was high (≥ 15.0 cm H 2 O) versus low ΔP. The primary endpoint was PRF (reintubation or unplanned noninvasive ventilation within seven days). Among 97,555 included patients, 4,030 (4.1%) developed PRF. In adjusted analyses, high intraoperative mechanical power and ΔP were associated with higher odds of PRF (adjusted odds ratio [aOR] 1.37 [95% CI, 1.25-1.50]; p < 0.001 and aOR 1.45 [95% CI, 1.31-1.60]; p < 0.001, respectively). There was large variability in applied ventilatory parameters, dependent on the anesthesia provider. This facilitated matching of 63,612 (mechanical power cohort) and 53,260 (ΔP cohort) patients, yielding identical baseline standardized respiratory system compliance (standardized difference [SDiff] = 0.00) with distinctly different mechanical power (9.4 [2.4] vs 4.9 [1.3] J/min; SDiff = -2.33) and ΔP (19.3 [4.1] vs 11.9 [2.1] cm H 2 O; SDiff = -2.27). After matching, high mechanical power and ΔP remained associated with higher risk of PRF (aOR 1.30 [95% CI, 1.17-1.45]; p < 0.001 and aOR 1.28 [95% CI, 1.12-1.46]; p < 0.001, respectively). CONCLUSIONS: High mechanical power and ΔP are associated with PRF independent of patient's baseline respiratory system compliance. Our findings support utilization of these parameters for titrating mechanical ventilation in the operating room and ICU.

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.

Linking Acute Physiology to Outcomes in the ICU: Challenges and Solutions for Research.

ICU clinicians rely on bedside physiological measurements to inform many routine clinical decisions. Because deranged physiology is usually associated with poor clinical outcomes, it is tempting to hypothesize that manipulating and intervening on physiological parameters might improve outcomes for patients. However, testing these hypotheses through mathematical models of the relationship between physiology and outcomes presents a number of important methodological challenges. These models reflect the theories of the researcher and can therefore be heavily influenced by one's assumptions and background beliefs. Model building must therefore be approached with great care and forethought, because failure to consider relevant sources of measurement error, confounding, coupling, and time dependency or failure to assess the direction of causality for associations of interest before modeling may give rise to spurious results. This paper outlines the main challenges in analyzing and interpreting these models and offers potential solutions to address these challenges.

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.

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.

Repeated endo-tracheal tube disconnection generates pulmonary edema in a model of volume overload: an experimental study.

BACKGROUND: An abrupt lung deflation in rodents results in lung injury through vascular mechanisms. Ventilator disconnections during endo-tracheal suctioning in humans often cause cardio-respiratory instability. Whether repeated disconnections or lung deflations cause lung injury or oedema is not known and was tested here in a porcine large animal model. METHODS: Yorkshire pigs (~ 12 weeks) were studied in three series. First, we compared PEEP abruptly deflated from 26 cmH2O or from PEEP 5 cmH2O to zero. Second, pigs were randomly crossed over to receive rapid versus gradual PEEP removal from 20 cmH2O. Third, pigs with relative volume overload, were ventilated with PEEP 15 cmH2O and randomized to repeated ETT disconnections (15 s every 15 min) or no disconnection for 3 h. Hemodynamics, pulmonary variables were monitored, and lung histology and bronchoalveolar lavage studied. RESULTS: As compared to PEEP 5 cmH2O, abrupt deflation from PEEP 26 cmH2O increased PVR, lowered oxygenation, and increased lung wet-to-dry ratio. From PEEP 20 cmH2O, gradual versus abrupt deflation mitigated the changes in oxygenation and vascular resistance. From PEEP 15, repeated disconnections in presence of fluid loading led to reduced compliance, lower oxygenation, higher pulmonary artery pressure, higher lung wet-to-dry ratio, higher lung injury score and increased oedema on morphometry, compared to no disconnects. CONCLUSION: Single abrupt deflation from high PEEP, and repeated short deflations from moderate PEEP cause pulmonary oedema, impaired oxygenation, and increased PVR, in this large animal model, thus replicating our previous finding from rodents. Rapid deflation may thus be a clinically relevant cause of impaired lung function, which may be attenuated by gradual pressure release.

Intraoperative open lung condition and postoperative pulmonary complications. A secondary analysis of iPROVE and iPROVE-O2 trials.

BACKGROUND: The preventive role of an intraoperative recruitment maneuver plus open lung approach (RM + OLA) ventilation on postoperative pulmonary complications (PPC) remains unclear. We aimed at investigating whether an intraoperative open lung condition reduces the risk of developing a composite of PPCs. METHODS: Post hoc analysis of two randomized controlled trials including patients undergoing abdominal surgery. Patients were classified according to the intraoperative lung condition as "open" (OL) or "non-open" (NOL) if PaO2 /FIO2 ratio was ≥ or <400 mmHg, respectively. We used a multivariable logistic regression model that included potential confounders selected with directed acyclic graphs (DAG) using Dagitty software built with variables that were considered clinically relevant based on biological mechanism or evidence from previously published data. PPCs included severe acute respiratory failure, acute respiratory distress syndrome, and pneumonia. RESULTS: A total of 1480 patients were included in the final analysis, with 718 (49%) classified as OL. The rate of severe PPCs during the first seven postoperative days was 6.0% (7.9% in the NOL and 4.4% in the OL group, p = .007). OL was independently associated with a lower risk for severe PPCs during the first 7 and 30 postoperative days [odds ratio of 0.58 (95% CI 0.34-0.99, p = .04) and 0.56 (95% CI 0.34-0.94, p = .03), respectively]. CONCLUSIONS: An intraoperative open lung condition was associated with a reduced risk of developing severe PPCs in intermediate-to-high risk patients undergoing abdominal surgery. TRIAL REGISTRATION: Registered at clinicaltrials.gov NCT02158923 (iPROVE), NCT02776046 (iPROVE-O2).

Positive End-Expiratory Pressure, Pleural Pressure, and Regional Compliance during Pronation: An Experimental Study.

Rationale: The physiological basis of lung protection and the impact of positive end-expiratory pressure (PEEP) during pronation in acute respiratory distress syndrome are not fully elucidated. Objectives: To compare pleural pressure (Ppl) gradient, ventilation distribution, and regional compliance between dependent and nondependent lungs, and investigate the effect of PEEP during supination and pronation. Methods: We used a two-hit model of lung injury (saline lavage and high-volume ventilation) in 14 mechanically ventilated pigs and studied supine and prone positions. Global and regional lung mechanics including Ppl and distribution of ventilation (electrical impedance tomography) were analyzed across PEEP steps from 20 to 3 cm H2O. Two pigs underwent computed tomography scans: tidal recruitment and hyperinflation were calculated. Measurements and Main Results: Pronation improved oxygenation, increased Ppl, thus decreasing transpulmonary pressure for any PEEP, and reduced the dorsal-ventral pleural pressure gradient at PEEP < 10 cm H2O. The distribution of ventilation was homogenized between dependent and nondependent while prone and was less dependent on the PEEP level than while supine. The highest regional compliance was achieved at different PEEP levels in dependent and nondependent regions in supine position (15 and 8 cm H2O), but for similar values in prone position (13 and 12 cm H2O). Tidal recruitment was more evenly distributed (dependent and nondependent), hyperinflation lower, and lungs cephalocaudally longer in the prone position. Conclusions: In this lung injury model, pronation reduces the vertical pleural pressure gradient and homogenizes regional ventilation and compliance between the dependent and nondependent regions. Homogenization is much less dependent on the PEEP level in prone than in supine positon.

Role of Positive End-Expiratory Pressure and Regional Transpulmonary Pressure in Asymmetrical Lung Injury.

Rationale: Asymmetrical lung injury is a frequent clinical presentation. Regional distribution of Vt and positive end-expiratory pressure (PEEP) could result in hyperinflation of the less-injured lung. The validity of esophageal pressure (Pes) is unknown.Objectives: To compare, in asymmetrical lung injury, Pes with directly measured pleural pressures (Ppl) of both sides and investigate how PEEP impacts ventilation distribution and the regional driving transpulmonary pressure (inspiratory - expiratory).Methods: Fourteen mechanically ventilated pigs with lung injury were studied. One lung was blocked while the contralateral one underwent surfactant lavage and injurious ventilation. Airway pressure and Pes were measured, as was Ppl in the dorsal and ventral pleural space adjacent to each lung. Distribution of ventilation was assessed by electrical impedance tomography. PEEP was studied through decremental steps.Measurements and Results: Ventral and dorsal Ppl were similar between the injured and the noninjured lung across all PEEP levels. Dorsal Ppl and Pes were similar. The driving transpulmonary pressure was similar in the two lungs. Vt distribution between lungs was different at zero end-expiratory pressure (≈70% of Vt going in noninjured lung) owing to different respiratory system compliance (8.3 ml/cm H2O noninjured lung vs. 3.7 ml/cm H2O injured lung). PEEP at 10 cm H2O with transpulmonary pressure around zero homogenized Vt distribution opening the lungs. PEEP ≥16 cm H2O equalized distribution of Vt but with overdistension for both lungs.Conclusions: Despite asymmetrical lung injury, Ppl between injured and noninjured lungs is equalized and esophageal pressure is a reliable estimate of dorsal Ppl. Driving transpulmonary pressure is similar for both lungs. Vt distribution results from regional respiratory system compliance. Moderate PEEP homogenizes Vt distribution between lungs without generating hyperinflation.

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).

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.

Electrical impedance tomography in pediatric patients with COVID-19, the first reports.

INTRODUCTION: Electrical impedance tomography (EIT) is a noninvasive, radiation-free, bedside tool to monitor ventilation distribution in real time. OBJECTIVE: To evaluate, in pediatric COVID-19 patients, the ventilation distribution using EIT and compare it to thoracic computed tomography (TCT) or chest radiograph results obtained in these patients. METHODS: This was a prospective, observational clinical study including pediatric patients admitted to the intensive care unit of a private hospital. The patients monitored with EIT tested positive for COVID-19 and were submitted to the previously mentioned radiation exams. EIT monitoring lasted 15 min and no sedation was used. RESULTS: Six patients were included in this study. The main differences observed in the EIT were in the right-left distribution and were compatible with the morphological changes found in the TCT or radiograph images due to COVID-19 infection. CONCLUSION: We conclude that EIT is ready to investigate the ventilatory profile present at different lung diseases, including COVID-19, and might postpone or mitigate the need of repeated ionizing radiation exams in the pediatric population, although larger pediatric cohorts comparing to standard radiological imaging are needed.

A lung rescue team improves survival in obesity with acute respiratory distress syndrome.

BACKGROUND: Limited data exist regarding ventilation in patients with class III obesity [body mass index (BMI) > 40 kg/m2] and acute respiratory distress syndrome (ARDS). The aim of the present study was to determine whether an individualized titration of mechanical ventilation according to cardiopulmonary physiology reduces the mortality in patients with class III obesity and ARDS. METHODS: In this retrospective study, we enrolled adults admitted to the ICU from 2012 to 2017 who had class III obesity and ARDS and received mechanical ventilation for > 48 h. Enrolled patients were divided in two cohorts: one cohort (2012-2014) had ventilator settings determined by the ARDSnet table for lower positive end-expiratory pressure/higher inspiratory fraction of oxygen (standard protocol-based cohort); the other cohort (2015-2017) had ventilator settings determined by an individualized protocol established by a lung rescue team (lung rescue team cohort). The lung rescue team used lung recruitment maneuvers, esophageal manometry, and hemodynamic monitoring. RESULTS: The standard protocol-based cohort included 70 patients (BMI = 49 ± 9 kg/m2), and the lung rescue team cohort included 50 patients (BMI = 54 ± 13 kg/m2). Patients in the standard protocol-based cohort compared to lung rescue team cohort had almost double the risk of dying at 28 days [31% versus 16%, P = 0.012; hazard ratio (HR) 0.32; 95% confidence interval (CI95%) 0.13-0.78] and 3 months (41% versus 22%, P = 0.006; HR 0.35; CI95% 0.16-0.74), and this effect persisted at 6 months and 1 year (incidence of death unchanged 41% versus 22%, P = 0.006; HR 0.35; CI95% 0.16-0.74). CONCLUSION: Individualized titration of mechanical ventilation by a lung rescue team was associated with decreased mortality compared to use of an ARDSnet table.

Lung Recruitment in Obese Patients with Acute Respiratory Distress Syndrome.

BACKGROUND: Obese patients are characterized by normal chest-wall elastance and high pleural pressure and have been excluded from trials assessing best strategies to set positive end-expiratory pressure (PEEP) in acute respiratory distress syndrome (ARDS). The authors hypothesized that severely obese patients with ARDS present with a high degree of lung collapse, reversible by titrated PEEP preceded by a lung recruitment maneuver. METHODS: Severely obese ARDS patients were enrolled in a physiologic crossover study evaluating the effects of three PEEP titration strategies applied in the following order: (1) PEEPARDSNET: the low PEEP/FIO2 ARDSnet table; (2) PEEPINCREMENTAL: PEEP levels set to determine a positive end-expiratory transpulmonary pressure; and (3) PEEPDECREMENTAL: PEEP levels set to determine the lowest respiratory system elastance during a decremental PEEP trial following a recruitment maneuver on respiratory mechanics, regional lung collapse, and overdistension according to electrical impedance tomography and gas exchange. RESULTS: Fourteen patients underwent the study procedures. At PEEPARDSNET (13 ± 1 cm H2O) end-expiratory transpulmonary pressure was negative (-5 ± 5 cm H2O), lung elastance was 27 ± 12 cm H2O/L, and PaO2/FIO2 was 194 ± 111 mmHg. Compared to PEEPARDSNET, at PEEPINCREMENTAL level (22 ± 3 cm H2O) lung volume increased (977 ± 708 ml), lung elastance decreased (23 ± 7 cm H2O/l), lung collapse decreased (18 ± 10%), and ventilation homogeneity increased thus rising oxygenation (251 ± 105 mmHg), despite higher overdistension levels (16 ± 12%), all values P < 0.05 versus PEEPARDSnet. Setting PEEP according to a PEEPDECREMENTAL trial after a recruitment maneuver (21 ± 4 cm H2O, P = 0.99 vs. PEEPINCREMENTAL) further lowered lung elastance (19 ± 6 cm H2O/l) and increased oxygenation (329 ± 82 mmHg) while reducing lung collapse (9 ± 2%) and overdistension (11 ± 2%), all values P < 0.05 versus PEEPARDSnet and PEEPINCREMENTAL. All patients were maintained on titrated PEEP levels up to 24 h without hemodynamic or ventilation related complications. CONCLUSIONS: Among the PEEP titration strategies tested, setting PEEP according to a PEEPDECREMENTAL trial preceded by a recruitment maneuver obtained the best lung function by decreasing lung overdistension and collapse, restoring lung elastance, and oxygenation suggesting lung tissue recruitment.

Impact of spontaneous breathing during mechanical ventilation in acute respiratory distress syndrome.

PURPOSE OF REVIEW: Facilitating spontaneous breathing has been traditionally recommended during mechanical ventilation in acute respiratory distress syndrome (ARDS). However, early, short-term use of neuromuscular blockade appears to improve survival, and spontaneous effort has been shown to potentiate lung injury in animal and clinical studies. The purpose of this review is to describe the beneficial and deleterious effects of spontaneous breathing in ARDS, explain potential mechanisms for harm, and provide contemporary suggestions for clinical management. RECENT FINDINGS: Gentle spontaneous effort can improve lung function and prevent diaphragm atrophy. However, accumulating evidence indicates that spontaneous effort may cause or worsen lung and diaphragm injury, especially if the ARDS is severe or spontaneous effort is vigorous. Recently, such effort-dependent lung injury has been termed patient self-inflicted lung injury (P-SILI). Finally, several approaches to minimize P-SILI while maintaining some diaphragm activity (e.g. partial neuromuscular blockade, high PEEP) appear promising. SUMMARY: We update and summarize the role of spontaneous breathing during mechanical ventilation in ARDS, which can be beneficial or deleterious, depending on the strength of spontaneous activity and severity of lung injury. Future studies are needed to determine ventilator strategies that minimize injury but maintaining some diaphragm activity.

Heterogeneous effects of alveolar recruitment in acute respiratory distress syndrome: a machine learning reanalysis of the Alveolar Recruitment for Acute Respiratory Distress Syndrome Trial.

BACKGROUND: Despite a robust physiological rationale, recruitment manoeuvres with PEEP titration were associated with harm in the Alveolar Recruitment for Acute Respiratory Distress Syndrome Trial (ART). We sought to investigate the potential heterogeneity in treatment effects in patients enrolled in the ART, using a machine learning approach. METHODS: The primary outcome was hospital mortality. Patients were clustered using baseline clinical and physiological data using the k-means for mixed large data method. The heterogeneity in treatment effect between clusters was investigated using Bayesian methods. We further investigated whether baseline driving pressure could modulate the association between treatment arm, cluster, and mortality. RESULTS: Data from all 1010 patients enrolled in the ART were analysed. Partitioning suggested that three clusters were present in the ART population. The largest cluster (Cluster 1) was characterised by patients with pneumonia and requiring vasopressor support. Recruitment manoeuvres with PEEP titration were associated with higher mortality in Cluster 1 (probability of harm of >98%), but this association was absent in Clusters 2 and 3 (probability of harm of 45% and 68%, respectively). Higher baseline driving pressure was associated with a progressive reduction in the association between alveolar recruitment with PEEP titration and mortality. CONCLUSIONS: Recruitment manoeuvre with PEEP titration may be harmful in acute respiratory distress syndrome (ARDS) patients with pneumonia or requiring vasopressor support. Driving pressure appears to modulate the association between the ART study intervention, aetiology of ARDS, and mortality. This machine learning approach may help tailor future RCTs. CLINICAL TRIAL REGISTRATION: NCT01374022.