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BackgroundThe renin-angiotensin system (RAS) plays a role in the pathogenesis of ARDS, Angiotensin II (Ang-II) contributing to the pathogenesis of inflammation and fibrogenesis. Angiotensin-(1-7) (Ang-(1-7)) may antagonize the effects of Ang-II. This study was aimed at evaluating the potential for Ang-(1-7) to reduce injury, inflammation and fibrosis in an experimental model of ARDS in the acute and late phases.MethodsMale Sprague Dawley rats underwent an instillation of 0.1 M hydrochloric acid (HCl, 2.5 ml/kg) into the right bronchus. In an acute ARDS study, acid-injured rats were subjected to high stretch mechanical ventilation (18 ml/kg) for 5 h and randomized to receive an intravenous infusion of either vehicle (saline), Ang-(1-7) at low dose(0.27 μg/kg/h) (ALD), or high dose (60 μg/kg/h) (AHD) starting simultaneously with injury or 2 h afterwards. Arterial blood gas analysis and bronchoalveolar lavage (BAL) were performed to assess the injury. For the late ARDS study, after HCl instillation rats were randomized to either vehicle or high dose Ang-(1-7) (300 μg/kg/day) infused by mini osmotic pumps for two weeks, and lung hydroxyproline content measured.ResultsIn the acute ARDS study, Ang-(1-7) led to a significant improvement in oxygenation (PaO2/FiO2 : vehicle 359 ± 86; ALD 436 ± 72; AHD 44 442 ± 56; ANOVA p = 0.007) and reduced white blood cells counts (vehicle 4,519 ± 2,234; ALD 2,496 ± 621; AHD 2,744 ± 119/mm3; ANOVA p = 0.004). Only treatment with high dose Ang-(1-7) reduced inflammatory cell numbers in BAL (vehicle 127 ± 34; AHD 96 ± 34/ μl; p = 0.033). Interestingly also delayed administration of Ang-(1-7) was effective in reducing injury. In later ARDS, Ang-(1-7) decreased hydroxyproline content (649 ± 202 and 1,117 ± 297 μg/lung; p < 0.05).ConclusionsAngiotensin-(1-7), decreased the severity of acute lung injury and inflammation induced by combined acid aspiration and high stretch ventilation. Furthermore, continuous infusion of Ang-(1-7) reduced lung fibrosis 2 weeks following acid aspiration injury. These results call for further research on Ang-(1-7) as possible therapy for ARDS.

Editor’s Perspective What We Already Know about This Topic What This Article Tells Us That Is New Background Driving pressure, the difference between plateau pressure and positive end-expiratory pressure (PEEP), is closely associated with increased mortality in patients with acute respiratory distress syndrome (ARDS). Although this relationship has been demonstrated during controlled mechanical ventilation, plateau pressure is often not measured during spontaneous breathing because of concerns about validity. The objective of the present study is to verify whether driving pressure and respiratory system compliance are independently associated with increased mortality during assisted ventilation (i.e., pressure support ventilation). Methods This is a retrospective cohort study conducted on 154 patients with ARDS in whom plateau pressure during the first three days of assisted ventilation was available. Associations between driving pressure, respiratory system compliance, and survival were assessed by univariable and multivariable analysis. In patients who underwent a computed tomography scan (n = 23) during the stage of assisted ventilation, the quantity of aerated lung was compared with respiratory system compliance measured on the same date. Results In contrast to controlled mechanical ventilation, plateau pressure during assisted ventilation was higher than the sum of PEEP and pressure support (peak pressure). Driving pressure was higher (11 [9–14] vs. 10 [8–11] cm H2O; P = 0.004); compliance was lower (40 [30–50] vs. 51 [42–61] ml · cm H2O-1; P &lt; 0.001); and peak pressure was similar, in nonsurvivors versus survivors. Lower respiratory system compliance (odds ratio, 0.92 [0.88–0.96]) and higher driving pressure (odds ratio, 1.34 [1.12–1.61]) were each independently associated with increased risk of death. Respiratory system compliance was correlated with the aerated lung volume (n = 23, r = 0.69, P &lt; 0.0001). Conclusions In patients with ARDS, plateau pressure, driving pressure, and respiratory system compliance can be measured during assisted ventilation, and both higher driving pressure and lower compliance are associated with increased mortality.

ObjectiveTo investigate neurologic outcome of patients with cardiac arrest with refractory status epilepticus (RSE) treated with a standardized aggressive protocol with antiepileptic drugs and anesthetics compared to patients with other EEG patterns.MethodsIn the prospective cohort study, 166 consecutive patients with cardiac arrest in coma were stratified according to 4 independent EEG patterns (benign, RSE, generalized periodic discharges [GPDs], malignant nonepileptiform) and multimodal prognostic indicators. Primary outcomes were survival and cerebral performance category (CPC) at 6 months.ResultsRSE occurred in 36 patients (21.7%) and was treated with an aggressive standardized protocol as long as multimodal prognostic indicators were not unfavorable. RSE started after 3 ± 2.3 days after cardiac arrest and lasted 4.7 ± 4.3 days. A benign EEG pattern was recorded in 76 patients (45.8%); a periodic pattern (GPDs) was seen in 13 patients (7.8%); and a malignant nonepileptiform EEG pattern was recorded in 41 patients (24.7%). The 4 EEG patterns were highly associated with different prognostic indicators (low-flow time, clinical motor seizures, N20 responses, neuron-specific enolase, neuroimaging). Survival and good neurologic outcome (CPC 1 or 2) at 6 months were 72.4% and 71.1% for benign EEG pattern, 54.3% and 44.4% for RSE, 15.4% and 0% for GPDs, and 2.4% and 0% for malignant nonepileptiform EEG pattern, respectively.ConclusionsAggressive and prolonged treatment of RSE may be justified in patients with cardiac arrest with favorable multimodal prognostic indicators.

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Background: Pendelluft, the movement of gas within different lung regions, is present in animal models of assisted mechanical ventilation and associated with lung overstretching. Due to rebreathing of CO 2 as compared to fresh gas, pendelluft might reduce ventilatory efficiency possibly exacerbating patient's respiratory workload during weaning. Our aim was to measure pendelluft by electrical impedance tomography (EIT) in patients who failed a spontaneous breathing trial (SBT).Methods: This is an observational study conducted in a general intensive care unit of a tertiary-level teaching hospital. EIT signal was recorded in 20 patients while pressure support (PS) ventilation was progressively reduced from clinical level (baseline) to 2 cmH 2 O, as in an SBT; four ventral-to-dorsal lung regions of interest were identified for pendelluft measurement. A regional gas movement (> 6 mL) occurring in a direction opposite to the global EIT signal was considered diagnostic for high pendelluft.Results: Eight patients out of 20 (40%) were classified as high-pendelluft; baseline clinical characteristics did not differ between high-and low-pendelluft patients. At PS reduction, pendelluft and EtCO 2 increased more in the highpendelluft group (p < .001 and .011, respectively). The volume of gas subject to pendelluft moved almost completely from the ventral towards the dorsal lung regions, while the opposite movement was minimal (16.3 [10:32.8] vs. 0 [0:1.8] mL, p = .001). In a subgroup of patients, increased pendelluft volumes positively correlated with markers of respiratory distress such as increased respiratory rate, p0.1, and EtCO 2 . Conclusions: Occult pendelluft can be measured by EIT, and is frequently present in patients failing an SBT. When present, pendelluft increases with the reduction of ventilator support and is associated with increased EtCO 2 , suggesting a reduction of the ability to eliminate CO 2 .

Objective. We will describe our clinical experience using electrical impedance tomography (EIT) in the management of mechanical ventilation in patients with acute respiratory failure and to determine to which extent EIT-guided positive end-expiratory pressure (PEEP) setting differed from clinically set values. Approach. We conducted a retrospective, observational cohort study performed in a hub centre for the treatment of acute respiratory failure and veno-venous extracorporeal membrane oxygenation (ECMO). Main results. Between January 2017 and December 2019, EIT was performed 54 times in 41 patients, not feasible only in one case because of signal instability. More than 50% was on veno-venous ECMO support. In 16 cases (30%), EIT was used for monitoring mechanical ventilation, i.e. to evaluate recruitability or sigh setting. In 37 cases (70%), EIT was used to set PEEP both with incremental (11 cases in nine patients) and decremental (26 cases, 18 patients) PEEP trial. Clinical PEEP before the decremental PEEP trial (PEEPPRE) was 14.1 ± 3.4 cmH2O and clinical PEEP set by clinicians after the PEEP trial (PEEPPOST) was 13.6 ± 3.1 (p = ns). EIT analyses demonstrated that more hypoxic patients were higher derecruited when compared to less hypoxic patients that were, on the contrary, more overdistended (p < 0.05). No acute effects of PEEP adjustment based on EIT on respiratory mechanics or regional EIT parameters modification were observed. Significance. The variability of EIT findings in our population confirmed the need to provide ventilation settings individually tailored and EIT was confirmed to be an optimal useful clinical bedside noninvasive tool to provide real-time monitoring of the PEEP effect and ventilation distribution.

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