Dataset Information

Effects of positive end-expiratory pressure and recruitment maneuvers in a ventilator-induced injury mouse model.

ABSTRACT:

Background

Positive-pressure mechanical ventilation is an essential therapeutic intervention, yet it causes the clinical syndrome known as ventilator-induced lung injury. Various lung protective mechanical ventilation strategies have attempted to reduce or prevent ventilator-induced lung injury but few modalities have proven effective. A model that isolates the contribution of mechanical ventilation on the development of acute lung injury is needed to better understand biologic mechanisms that lead to ventilator-induced lung injury.

Objectives

To evaluate the effects of positive end-expiratory pressure and recruitment maneuvers in reducing lung injury in a ventilator-induced lung injury murine model in short- and longer-term ventilation.

Methods

5-12 week-old female BALB/c mice (n = 85) were anesthetized, placed on mechanical ventilation for either 2 hrs or 4 hrs with either low tidal volume (8 ml/kg) or high tidal volume (15 ml/kg) with or without positive end-expiratory pressure and recruitment maneuvers.

Results

Alteration of the alveolar-capillary barrier was noted at 2 hrs of high tidal volume ventilation. Standardized histology scores, influx of bronchoalveolar lavage albumin, proinflammatory cytokines, and absolute neutrophils were significantly higher in the high-tidal volume ventilation group at 4 hours of ventilation. Application of positive end-expiratory pressure resulted in significantly decreased standardized histology scores and bronchoalveolar absolute neutrophil counts at low- and high-tidal volume ventilation, respectively. Recruitment maneuvers were essential to maintain pulmonary compliance at both 2 and 4 hrs of ventilation.

Conclusions

Signs of ventilator-induced lung injury are evident soon after high tidal volume ventilation (as early as 2 hours) and lung injury worsens with longer-term ventilation (4 hrs). Application of positive end-expiratory pressure and recruitment maneuvers are protective against worsening VILI across all time points. Dynamic compliance can be used guide the frequency of recruitment maneuvers to help ameloriate ventilator-induced lung injury.

SUBMITTER: Cagle LA

PROVIDER: S-EPMC5675408 | biostudies-literature | 2017

REPOSITORIES: biostudies-literature

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Publications

Effects of positive end-expiratory pressure and recruitment maneuvers in a ventilator-induced injury mouse model.

Cagle Laura A LA Franzi Lisa M LM Linderholm Angela L AL Last Jerold A JA Adams Jason Y JY Harper Richart W RW Kenyon Nicholas J NJ

PloS one 20171107 11

<h4>Background</h4>Positive-pressure mechanical ventilation is an essential therapeutic intervention, yet it causes the clinical syndrome known as ventilator-induced lung injury. Various lung protective mechanical ventilation strategies have attempted to reduce or prevent ventilator-induced lung injury but few modalities have proven effective. A model that isolates the contribution of mechanical ventilation on the development of acute lung injury is needed to better understand biologic mechanism ...[more]

PMID: 29112971

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Project description:ImportanceAn intraoperative higher level of positive end-expiratory positive pressure (PEEP) with alveolar recruitment maneuvers improves respiratory function in obese patients undergoing surgery, but the effect on clinical outcomes is uncertain.ObjectiveTo determine whether a higher level of PEEP with alveolar recruitment maneuvers decreases postoperative pulmonary complications in obese patients undergoing surgery compared with a lower level of PEEP.Design, setting, and participantsRandomized clinical trial of 2013 adults with body mass indices of 35 or greater and substantial risk for postoperative pulmonary complications who were undergoing noncardiac, nonneurological surgery under general anesthesia. The trial was conducted at 77 sites in 23 countries from July 2014-February 2018; final follow-up: May 2018.InterventionsPatients were randomized to the high level of PEEP group (n = 989), consisting of a PEEP level of 12 cm H2O with alveolar recruitment maneuvers (a stepwise increase of tidal volume and eventually PEEP) or to the low level of PEEP group (n = 987), consisting of a PEEP level of 4 cm H2O. All patients received volume-controlled ventilation with a tidal volume of 7 mL/kg of predicted body weight.Main outcomes and measuresThe primary outcome was a composite of pulmonary complications within the first 5 postoperative days, including respiratory failure, acute respiratory distress syndrome, bronchospasm, new pulmonary infiltrates, pulmonary infection, aspiration pneumonitis, pleural effusion, atelectasis, cardiopulmonary edema, and pneumothorax. Among the 9 prespecified secondary outcomes, 3 were intraoperative complications, including hypoxemia (oxygen desaturation with Spo2 ≤92% for >1 minute).ResultsAmong 2013 adults who were randomized, 1976 (98.2%) completed the trial (mean age, 48.8 years; 1381 [69.9%] women; 1778 [90.1%] underwent abdominal operations). In the intention-to-treat analysis, the primary outcome occurred in 211 of 989 patients (21.3%) in the high level of PEEP group compared with 233 of 987 patients (23.6%) in the low level of PEEP group (difference, -2.3% [95% CI, -5.9% to 1.4%]; risk ratio, 0.93 [95% CI, 0.83 to 1.04]; P = .23). Among the 9 prespecified secondary outcomes, 6 were not significantly different between the high and low level of PEEP groups, and 3 were significantly different, including fewer patients with hypoxemia (5.0% in the high level of PEEP group vs 13.6% in the low level of PEEP group; difference, -8.6% [95% CI, -11.1% to 6.1%]; P < .001).Conclusions and relevanceAmong obese patients undergoing surgery under general anesthesia, an intraoperative mechanical ventilation strategy with a higher level of PEEP and alveolar recruitment maneuvers, compared with a strategy with a lower level of PEEP, did not reduce postoperative pulmonary complications.Trial registrationClinicalTrials.gov Identifier: NCT02148692.

Project description:BackgroundThe Lung Open Ventilation Study (LOV Study) compared a low tidal volume strategy with an experimental strategy combining low tidal volume, lung recruitment maneuvers, and higher plateau and positive end-expiratory pressures (PEEP) in adults with acute respiratory distress syndrome (ARDS). Herein, we compared sedative, opioid, and neuromuscular blocker (NMB) use among patients managed with the intervention and control strategies and clinicians' assessment of comfort in both groups.MethodsThis was an observational substudy of the LOV Study, a randomized trial conducted in 30 intensive care units in Canada, Australia, and Saudi Arabia. In 16 centers, we recorded daily doses of sedatives, opioids, and NMBs and surveyed bedside clinicians about their own comfort with the assigned ventilator strategy and their perceptions of patient comfort. We compared characteristics and outcomes of patients who did and did not receive NMBs.ResultsStudy groups received similar sedative, opioid, and NMB dosing on days 1, 3, and 7. Patient comfort as assessed by clinicians was not different in the two groups: 93% perceived patients had no/minimal discomfort. In addition, 92% of clinicians were comfortable with the assigned ventilation strategy without significant differences between the two groups. When clinicians expressed discomfort, more expressed discomfort about PEEP levels in the intervention vs control group (2.9% vs 0.7%, P <0.0001), and more perceived patient discomfort among controls (6.0% vs 4.3%, P = 0.049). On multivariable analysis, the strongest associations with NMB use were higher plateau pressure (hazard ratio (HR) 1.15; 95% confidence interval (CI) 1.07 to 1.23; P = 0.0002) and higher daily sedative dose (HR 1.03; 95% CI 1.02 to 1.05; P <0.0001). Patients receiving NMBs had more barotrauma, longer durations of mechanical ventilation and hospital stay, and higher mortality.ConclusionsIn the LOV Study, high PEEP, low tidal volume ventilation did not increase sedative, opioid, or NMB doses in adults with ARDS, compared with a lower PEEP strategy, and appeared at least as comfortable for patients. NMB use may reflect worse lung injury, as these patients had more barotrauma, longer durations of ventilation, and higher mortality.Trial registrationClinicalTrials.gov Identifier NCT00182195.

Project description:BackgroundPositive end-expiratory pressure (PEEP) has been demonstrated to decrease ventilator-induced lung injury in patients under mechanical ventilation (MV) for acute respiratory failure. Recently, some studies have proposed some beneficial effects of PEEP in ventilated patients without lung injury. The influence of PEEP on respiratory mechanics in children is not well known. Our aim was to determine the effects on respiratory mechanics of setting PEEP at 5 cmH2O in anesthetized healthy children.MethodsPatients younger than 15 years old without history of lung injury scheduled for elective surgery gave informed consent and were enrolled in the study. After usual care for general anesthesia, patients were placed on volume controlled MV. Two sets of respiratory mechanics studies were performed using inspiratory and expiratory breath hold, with PEEP 0 and 5 cmH2O. The maximum inspiratory and expiratory flow (QI and QE) as well as peak inspiratory pressure (PIP), plateau pressure (PPL) and total PEEP (tPEEP) were measured. Respiratory system compliance (CRS), inspiratory and expiratory resistances (RawI and RawE) and time constants (KTI and KTE) were calculated. Data were expressed as median and interquartile range (IQR). Wilcoxon sign test and Spearman's analysis were used. Significance was set at P < 0.05.ResultsWe included 30 patients, median age 39 (15-61.3) months old, 60% male. When PEEP increased, PIP increased from 12 (11,14) to 15.5 (14,18), and CRS increased from 0.9 (0.9,1.2) to 1.2 (0.9,1.4) mL·kg- 1·cmH2O- 1; additionally, when PEEP increased, driving pressure decreased from 6.8 (5.9,8.1) to 5.8 (4.7,7.1) cmH2O, and QE decreased from 13.8 (11.8,18.7) to 11.7 (9.1,13.5) L·min- 1 (all P < 0.01). There were no significant changes in resistance and QI.ConclusionsAnalysis of respiratory mechanics in anesthetized healthy children shows that PEEP at 5 cmH2O places the respiratory system in a better position in the P/V curve. A better understanding of lung mechanics may lead to changes in the traditional ventilatory approach, limiting injury associated with MV.

Project description:Background: The pathophysiological effects of positive end-expiratory pressure (PEEP) on respiratory mechanics, lung recruitment, and intracranial pressure (ICP) in acute brain-injured patients have not been completely elucidated. The primary aim of this study was to assess the effects of PEEP augmentation on respiratory mechanics, quantitative computed lung tomography (qCT) findings, and its relationship with ICP modifications. Secondary aims included the assessment of the correlations between different factors (respiratory mechanics and qCT features) with the changes of ICP and how these factors at baseline may predict ICP response after greater PEEP levels. Methods: A prospective, observational study included mechanically ventilated patients with acute brain injury requiring invasive ICP and who underwent two-PEEP levels lung CT scan. Respiratory system compliance (Crs), arterial partial pressure of carbon dioxide (PaCO2), mean arterial pressure (MAP), data from qCT and ICP were obtained at PEEP 5 and 15 cmH2O. Results: Sixteen examinations (double PEEP lung CT and neuromonitoring) in 15 patients were analyzed. The median age of the patients was 54 years (interquartile range, IQR = 39-65) and 53% were men. The median Glasgow Coma Scale (GCS) at intensive care unit (ICU) admission was 8 (IQR = 3-12). Median alveolar recruitment was 2.5% of total lung weight (-1.5 to 4.7). PEEP from 5 to 15 cmH2O increased ICP [median values from 14.0 (11.2-17.5) to 23.5 (19.5-26.8) mmHg, p < 0.001, respectively]. The amount of recruited lung tissue on CT was inversely correlated with the change (Δ) in ICP (rho = -0.78; p = 0.0006). Additionally, ΔCrs (rho = -0.77, p = 0.008), ΔPaCO2 (rho = 0.81, p = 0.0003), and ΔMAP (rho = -0.64, p = 0.009) were correlated with ΔICP. Baseline Crs was not predictive of ICP response to PEEP. Conclusions: The main factors associated with increased ICP after PEEP augmentation included reduced Crs, lower MAP and lung recruitment, and increased PaCO2, but none of these factors was able to predict, at baseline, ICP response to PEEP. To assess the potential benefits of increased PEEP in patients with acute brain injury, hemodynamic status, respiratory mechanics, and lung morphology should be taken into account.

Project description:IntroductionOne potential mechanism of ventilator-induced lung injury (VILI) is due to shear stresses associated with alveolar instability (recruitment/derecruitment). It has been postulated that the optimal combination of tidal volume (Vt) and positive end-expiratory pressure (PEEP) stabilizes alveoli, thus diminishing recruitment/derecruitment and reducing VILI. In this study we directly visualized the effect of Vt and PEEP on alveolar mechanics and correlated alveolar stability with lung injury.MethodsIn vivo microscopy was utilized in a surfactant deactivation porcine ARDS model to observe the effects of Vt and PEEP on alveolar mechanics. In phase I (n = 3), nine combinations of Vt and PEEP were evaluated to determine which combination resulted in the most and least alveolar instability. In phase II (n = 6), data from phase I were utilized to separate animals into two groups based on the combination of Vt and PEEP that caused the most alveolar stability (high Vt [15 cc/kg] plus low PEEP [5 cmH2O]) and least alveolar stability (low Vt [6 cc/kg] and plus PEEP [20 cmH2O]). The animals were ventilated for three hours following lung injury, with in vivo alveolar stability measured and VILI assessed by lung function, blood gases, morphometrically, and by changes in inflammatory mediators.ResultsHigh Vt/low PEEP resulted in the most alveolar instability and lung injury, as indicated by lung function and morphometric analysis of lung tissue. Low Vt/high PEEP stabilized alveoli, improved oxygenation, and reduced lung injury. There were no significant differences between groups in plasma or bronchoalveolar lavage cytokines or proteases.ConclusionA ventilatory strategy employing high Vt and low PEEP causes alveolar instability, and to our knowledge this is the first study to confirm this finding by direct visualization. These studies demonstrate that low Vt and high PEEP work synergistically to stabilize alveoli, although increased PEEP is more effective at stabilizing alveoli than reduced Vt. In this animal model of ARDS, alveolar instability results in lung injury (VILI) with minimal changes in plasma and bronchoalveolar lavage cytokines and proteases. This suggests that the mechanism of lung injury in the high Vt/low PEEP group was mechanical, not inflammatory in nature.

Dataset Information

Effects of positive end-expiratory pressure and recruitment maneuvers in a ventilator-induced injury mouse model.

Background

Objectives

Methods

Results

Conclusions

Publications

Effects of positive end-expiratory pressure and recruitment maneuvers in a ventilator-induced injury mouse model.

Similar Datasets

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