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Effects of Positive End-Expiratory Pressure and Spontaneous Breathing Activity on Regional Lung Inflammation in Experimental Acute Respiratory Distress Syndrome.

ABSTRACT: OBJECTIVES:To determine the impact of positive end-expiratory pressure during mechanical ventilation with and without spontaneous breathing activity on regional lung inflammation in experimental nonsevere acute respiratory distress syndrome. DESIGN:Laboratory investigation. SETTING:University hospital research facility. SUBJECTS:Twenty-four pigs (28.1-58.2?kg). INTERVENTIONS:In anesthetized animals, intrapleural pressure sensors were placed thoracoscopically in ventral, dorsal, and caudal regions of the left hemithorax. Lung injury was induced with saline lung lavage followed by injurious ventilation in supine position. During airway pressure release ventilation with low tidal volumes, positive end-expiratory pressure was set 4?cm H2O above the level to reach a positive transpulmonary pressure in caudal regions at end-expiration (best-positive end-expiratory pressure). Animals were randomly assigned to one of four groups (n = 6/group; 12?hr): 1) no spontaneous breathing activity and positive end-expiratory pressure = best-positive end-expiratory pressure - 4?cm H2O, 2) no spontaneous breathing activity and positive end-expiratory pressure = best-positive end-expiratory pressure + 4?cm H2O, 3) spontaneous breathing activity and positive end-expiratory pressure = best-positive end-expiratory pressure + 4?cm H2O, 4) spontaneous breathing activity and positive end-expiratory pressure = best-positive end-expiratory pressure - 4?cm H2O. MEASUREMENTS AND MAIN RESULTS:Global lung inflammation assessed by specific [F]fluorodeoxyglucose uptake rate (median [25-75% percentiles], min) was decreased with higher compared with lower positive end-expiratory pressure both without spontaneous breathing activity (0.029 [0.027-0.030] vs 0.044 [0.041-0.065]; p = 0.004) and with spontaneous breathing activity (0.032 [0.028-0.043] vs 0.057 [0.042-0.075]; p = 0.016). Spontaneous breathing activity did not increase global lung inflammation. Lung inflammation in dorsal regions correlated with transpulmonary driving pressure from spontaneous breathing at lower (r = 0.850; p = 0.032) but not higher positive end-expiratory pressure (r = 0.018; p = 0.972). Higher positive end-expiratory pressure resulted in a more homogeneous distribution of aeration and regional transpulmonary pressures at end-expiration along the ventral-dorsal gradient, as well as a shift of the perfusion center toward dependent zones in the presence of spontaneous breathing activity. CONCLUSIONS:In experimental mild-to-moderate acute respiratory distress syndrome, positive end-expiratory pressure levels that stabilize dependent lung regions reduce global lung inflammation during mechanical ventilation, independent from spontaneous breathing activity.

SUBMITTER: Kiss T

PROVIDER: S-EPMC6433156 | biostudies-literature | 2019 Apr

REPOSITORIES: biostudies-literature

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Effects of Positive End-Expiratory Pressure and Spontaneous Breathing Activity on Regional Lung Inflammation in Experimental Acute Respiratory Distress Syndrome.

Kiss Thomas T Bluth Thomas T Braune Anja A Huhle Robert R Denz Axel A Herzog Moritz M Herold Johannes J Vivona Luigi L Millone Marco M Bergamaschi Alice A Andreeff Michael M Scharffenberg Martin M Wittenstein Jakob J Vidal Melo Marcos F MF Koch Thea T Rocco Patricia R M PRM Pelosi Paolo P Kotzerke Jörg J Gama de Abreu Marcelo M

Critical care medicine 20190401 4

<h4>Objectives</h4>To determine the impact of positive end-expiratory pressure during mechanical ventilation with and without spontaneous breathing activity on regional lung inflammation in experimental nonsevere acute respiratory distress syndrome.<h4>Design</h4>Laboratory investigation.<h4>Setting</h4>University hospital research facility.<h4>Subjects</h4>Twenty-four pigs (28.1-58.2 kg).<h4>Interventions</h4>In anesthetized animals, intrapleural pressure sensors were placed thoracoscopically i ...[more]

PMID: 30676338

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Project description:BackgroundWe hypothesized that as CARDS may present different pathophysiological features than classic ARDS, the application of high levels of end-expiratory pressure is questionable. Our first aim was to investigate the effects of 5-15 cmH2O of PEEP on partitioned respiratory mechanics, gas exchange and dead space; secondly, we investigated whether respiratory system compliance and severity of hypoxemia could affect the response to PEEP on partitioned respiratory mechanics, gas exchange and dead space, dividing the population according to the median value of respiratory system compliance and oxygenation. Thirdly, we explored the effects of an additional PEEP selected according to the Empirical PEEP-FiO2 table of the EPVent-2 study on partitioned respiratory mechanics and gas exchange in a subgroup of patients.MethodsSixty-one paralyzed mechanically ventilated patients with a confirmed diagnosis of SARS-CoV-2 were enrolled (age 60 [54-67] years, PaO2/FiO2 113 [79-158] mmHg and PEEP 10 [10-10] cmH2O). Keeping constant tidal volume, respiratory rate and oxygen fraction, two PEEP levels (5 and 15 cmH2O) were selected. In a subgroup of patients an additional PEEP level was applied according to an Empirical PEEP-FiO2 table (empirical PEEP). At each PEEP level gas exchange, partitioned lung mechanics and hemodynamic were collected.ResultsAt 15 cmH2O of PEEP the lung elastance, lung stress and mechanical power were higher compared to 5 cmH2O. The PaO2/FiO2, arterial carbon dioxide and ventilatory ratio increased at 15 cmH2O of PEEP. The arterial-venous oxygen difference and central venous saturation were higher at 15 cmH2O of PEEP. Both the mechanics and gas exchange variables significantly increased although with high heterogeneity. By increasing the PEEP from 5 to 15 cmH2O, the changes in partitioned respiratory mechanics and mechanical power were not related to hypoxemia or respiratory compliance. The empirical PEEP was 18 ± 1 cmH2O. The empirical PEEP significantly increased the PaO2/FiO2 but also driving pressure, lung elastance, lung stress and mechanical power compared to 15 cmH2O of PEEP.ConclusionsIn COVID-19 ARDS during the early phase the effects of raising PEEP are highly variable and cannot easily be predicted by respiratory system characteristics, because of the heterogeneity of the disease.

Project description:BackgroundThe study objective was to compare titration of positive end-expiratory pressure (PEEP) with electrical impedance tomography (EIT) and with ventilator-embedded pressure-volume loop in severe acute respiratory distress syndrome (ARDS).MethodsWe have designed a prospective study with historical control group. Twenty-four severe ARDS patients (arterial oxygen partial pressure to fractional inspired oxygen ratio, PaO2/FiO2 < 100 mmHg) were included in the EIT group and examined prospectively. Data from another 31 severe ARDS patients were evaluated retrospectively (control group). All patients were receiving medical care under identical general support guidelines and protective mechanical ventilation. The PEEP level selected in the EIT group was the intercept point of cumulated collapse and overdistension percentages curves. In the control group, optimal PEEP was selected 2 cmH2O above the lower inflection point on the static pressure-volume curve.ResultsPatients in the EIT group were younger (P < 0.05), and their mean plateau pressure was 1.5 cmH2O higher (P < 0.01). No differences in other baseline parameters such as APACHE II score, PaO2/FiO2, initial PEEP, driving pressure, tidal volume, and respiratory system compliance were found. Two hours after the first PEEP titration, significantly higher PEEP, compliance, and lower driving pressure were found in the EIT group (P < 0.01). Hospital survival rates were 66.7% (16 of 24 patients) in the EIT group and 48.4% (15 of 31) in the control group. Identical rates were found regarding the weaning success rate: 66.7% in the EIT group and 48.4% in the control group.ConclusionIn severe ARDS patients, it was feasible and safe to guide PEEP titration with EIT at the bedside. As compared with pressure-volume curve, the EIT-guided PEEP titration may be associated with improved oxygenation, compliance, driving pressure, and weaning success rate. The findings encourage further randomized control study with a larger sample size and potentially less bias in the baseline data. Trial Registration NCT03112512.

Project description:BackgroundIn acute respiratory distress syndrome (ARDS), response to positive end-expiratory pressure (PEEP) is variable according to different degrees of lung recruitability. The search for a tool to individualize PEEP based on patients' individual response is warranted. End-expiratory lung volume (EELV) assessment by nitrogen washing-washout aids bedside estimation of PEEP-induced alveolar recruitment and may therefore help titrate PEEP on patient's individual recruitability. We designed a randomized trial to test whether an individualized PEEP setting protocol driven by EELV measurement may improve a composite clinical outcome in patients with moderate-to-severe ARDS (IPERPEEP trial).MethodsIPERPEEP is an open-label, multicenter, randomized trial that will be conducted in 10 intensive care units in Italy and will enroll 132 ARDS patients showing PaO2/FiO2 ratio ≤ 150 mmHg within 24 h from endotracheal intubation while on mechanical ventilation with PEEP 5 cmH2O. To standardize lung volumes at study initiation, all patients will undergo mechanical ventilation with tidal volume of 6 ml/kg of predicted body weight and PEEP set to obtain a plateau pressure within 28 and 30 cmH2O for 30 min (EXPRESS PEEP). Afterwards, a 5-step decremental PEEP trial will be conducted (EXPRESS PEEP to PEEP 5 cmH2O), and EELV will be measured at each step. Recruitment-to-inflation ratio will be calculated for each PEEP range from EELV difference. Patients will be then randomized to receive mechanical ventilation with PEEP set according to the optimal recruitment observed in the PEEP trial (IPERPEEP arm) trial or to achieve a plateau pressure of 28-30 cmH2O (control arm, EXPRESS strategy). In both groups, tidal volume size, use of prone positioning and neuromuscular blocking agents, and weaning from PEEP and from mechanical ventilation will be standardized. The primary endpoint of the study is a composite clinical outcome incorporating in-ICU mortality, 60-day ventilator-free days, and serum interleukin-6 concentration over the course of the initial 72 h of treatment.DiscussionThe IPERPEEP study is a randomized trial powered to elucidate whether an individualized PEEP setting protocol based on bedside assessment of lung recruitability can improve a composite clinical outcome during moderate-to-severe ARDS.Trial registrationClinicalTrials.gov NCT04012073 . Registered 9 July 2019.

Dataset Information

Effects of Positive End-Expiratory Pressure and Spontaneous Breathing Activity on Regional Lung Inflammation in Experimental Acute Respiratory Distress Syndrome.

Publications

Effects of Positive End-Expiratory Pressure and Spontaneous Breathing Activity on Regional Lung Inflammation in Experimental Acute Respiratory Distress Syndrome.

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