Changes in shunt, ventilation/perfusion mismatch, and lung aeration with PEEP in patients with ARDS: a prospective single-arm interventional study.
ABSTRACT: BACKGROUND:Several studies have found only a weak to moderate correlation between oxygenation and lung aeration in response to changes in PEEP. This study aimed to investigate the association between changes in shunt, low and high ventilation/perfusion (V/Q) mismatch, and computed tomography-measured lung aeration following an increase in PEEP in patients with ARDS. METHODS:In this preliminary study, 12 ARDS patients were subjected to recruitment maneuvers followed by setting PEEP at 5 and then either 15 or 20?cmH2O. Lung aeration was measured by computed tomography. Values of pulmonary shunt and low and high V/Q mismatch were calculated by a model-based method from measurements of oxygenation, ventilation, and metabolism taken at different inspired oxygen levels and an arterial blood gas sample. RESULTS:Increasing PEEP resulted in reduced values of pulmonary shunt and the percentage of non-aerated tissue, and an increased percentage of normally aerated tissue (p?
Project description:BACKGROUND:In contrast to conventional mandatory ventilation, a new ventilation mode, expiratory ventilation assistance (EVA), linearises the expiratory tracheal pressure decline. OBJECTIVE:We hypothesised that due to a recruiting effect, linearised expiration oxygenates better than volume controlled ventilation (VCV). We compared the EVA with VCV mode with regard to gas exchange, ventilation volumes and pressures and lung aeration in a model of peri-operative mandatory ventilation in healthy pigs. DESIGN:Controlled interventional trial. SETTING:Animal operating facility at a university medical centre. ANIMALS:A total of 16 German Landrace hybrid pigs. INTERVENTION:The lungs of anaesthetised pigs were ventilated with the EVA mode (n=9) or VCV (control, n=7) for 5?h with positive end-expiratory pressure of 5?cmH2O and tidal volume of 8?ml?kg. The respiratory rate was adjusted for a target end-tidal CO2 of 4.7 to 6?kPa. MAIN OUTCOME MEASURES:Tracheal pressure, minute volume and arterial blood gases were recorded repeatedly. Computed thoracic tomography was performed to quantify the percentages of normally and poorly aerated lung tissue. RESULTS:Two animals in the EVA group were excluded due to unstable ventilation (n=1) or unstable FiO2 delivery (n=1). Mean tracheal pressure and PaO2 were higher in the EVA group compared with control (mean tracheal pressure: 11.6?±?0.4 versus 9.0?±?0.3?cmH2O, P?<?0.001 and PaO2: 19.2?±?0.7 versus 17.5?±?0.4?kPa, P?=?0.002) with comparable peak inspiratory tracheal pressure (18.3?±?0.9 versus 18.0?±?1.2?cmH2O, P?>?0.99). Minute volume was lower in the EVA group compared with control (5.5?±?0.2 versus 7.0?±?1.0?l?min, P?=?0.02) with normoventilation in both groups (PaCO2 5.4?±?0.3 versus 5.5?±?0.3?kPa, P?>?0.99). In the EVA group, the percentage of normally aerated lung tissue was higher (81.0?±?3.6 versus 75.8?±?3.0%, P?=?0.017) and of poorly aerated lung tissue lower (9.5?±?3.3 versus 15.7?±?3.5%, P?=?0.002) compared with control. CONCLUSION:EVA ventilation improves lung aeration via elevated mean tracheal pressure and consequently improves arterial oxygenation at unaltered positive end-expiratory pressure (PEEP) and peak inspiratory pressure (PIP). These findings suggest the EVA mode is a new approach for protective lung ventilation.
Project description:During one-lung ventilation (OLV), titrating the positive end-expiratory pressure (PEEP) to target a low driving pressure (?P) could reduce postoperative pulmonary complications. However, it is unclear how to conduct PEEP titration: by stepwise increase starting from zero PEEP (PEEPINCREMENTAL) or by stepwise decrease after a lung recruiting manoeuvre (PEEPDECREMENTAL). In this randomized trial, we compared the physiological effects of these two PEEP titration strategies on respiratory mechanics, ventilation/perfusion mismatch and gas exchange. Patients undergoing video-assisted thoracoscopic surgery in OLV were randomly assigned to a PEEPINCREMENTAL or PEEPDECREMENTAL strategy to match the lowest ?P. In the PEEPINCREMENTAL group, PEEP was stepwise titrated from ZEEP up to 16 cm H2O, whereas in the PEEPDECREMENTAL group PEEP was decrementally titrated, starting from 16 cm H2O, immediately after a lung recruiting manoeuvre. Respiratory mechanics, ventilation/perfusion mismatch and blood gas analyses were recorded at baseline, after PEEP titration and at the end of surgery. Sixty patients were included in the study. After PEEP titration, shunt decreased similarly in both groups, from 50 [39-55]% to 35 [28-42]% in the PEEPINCREMENTAL and from 45 [37-58]% to 33 [25-45]% in the PEEPDECREMENTAL group (both p?<?0.001 vs baseline). The resulting ?P, however, was lower in the PEEPDECREMENTAL than in the PEEPINCREMENTAL group (8 [7-11] vs 10 [9-11] cm H2O; p?=?0.03). In the PEEPDECREMENTAL group the PaO2/ FIO2 ratio increased significantly after intervention (from 140 [99-176] to 186 [152-243], p?<?0.001). Both the PEEPINCREMENTAL and the PEEPDECREMENTAL strategies were able to decrease intraoperative shunt, but only PEEPDECREMENTAL improved oxygenation and lowered intraoperative ?P.Clinical trial number NCT03635281; August 2018; "retrospectively registered".
Project description:<h4>Introduction</h4>The advantages of physiologically variable ventilation (PVV) based on a spontaneous breathing pattern have been demonstrated in several respiratory conditions. However, its potential benefits in chronic obstructive pulmonary disease (COPD) have not yet been characterized. We used an experimental model of COPD to compare respiratory function outcomes after 6 h of PVV versus conventional pressure-controlled ventilation (PCV).<h4>Materials and methods</h4>Rabbits received nebulized elastase and lipopolysaccharide throughout 4 weeks. After 30 days, animals were anesthetized, tracheotomized, and randomized to receive 6 h of physiologically variable (<i>n</i> = 8) or conventional PCV (<i>n</i> = 7). Blood gases, respiratory mechanics, and chest fluoroscopy were assessed hourly.<h4>Results</h4>After 6 h of ventilation, animals receiving variable ventilation demonstrated significantly higher oxygenation index (PaO<sub>2</sub>/FiO<sub>2</sub> 441 ± 37 (mean ± standard deviation) <i>versus</i> 354 ± 61 mmHg, <i>p</i> < 0.001) and lower respiratory elastance (359 ± 36 <i>versus</i> 463 ± 81 cmH<sub>2</sub>O/L, <i>p</i> < 0.01) than animals receiving PCV. Animals ventilated with the variable mode also presented less lung derecruitment (decrease in lung aerated area, -3.4 ± 9.9 <i>versus</i> -17.9 ± 6.7%, <i>p</i> < 0.01) and intrapulmonary shunt fraction (9.6 ± 4.1 <i>versus</i> 17.0 ± 5.8%, <i>p</i> < 0.01).<h4>Conclusion</h4>PVV applied to a model of COPD improved oxygenation, respiratory mechanics, lung aeration, and intrapulmonary shunt fraction compared to conventional ventilation. A reduction in alveolar derecruitment and lung tissue stress leading to better aeration and gas exchange may explain the benefits of PVV.
Project description:The prone position is used to improve gas exchange in patients with acute respiratory distress syndrome. However, the regional mechanism by which the prone position improves gas exchange in acutely injured lungs is still incompletely defined.We used positron emission tomography imaging of [(13)N]nitrogen to assess the regional distribution of pulmonary shunt, aeration, perfusion, and ventilation in seven surfactant-depleted sheep in supine and prone positions.In the supine position, the dorsal lung regions had a high shunt fraction, high perfusion, and poor aeration. The prone position was associated with an increase in lung gas content and with a more uniform distribution of aeration, as the increase in aeration in dorsal lung regions was not offset by loss of aeration in ventral regions. Consequently, the shunt fraction decreased in dorsal regions in the prone position without a concomitant impairment of gas exchange in ventral regions, thus leading to a significant increase in the fraction of pulmonary perfusion participating in gas exchange. In addition, the vertical distribution of specific alveolar ventilation became more uniform in the prone position. A biphasic relation between regional shunt fraction and gas fraction showed low shunt for values of gas fraction higher than a threshold, and a steep linear increase in shunt for lower values of gas fraction.In a surfactant-deficient model of lung injury, the prone position improved gas exchange by restoring aeration and decreasing shunt while preserving perfusion in dorsal lung regions, and by making the distribution of ventilation more uniform.
Project description:Current recommendations suggest the use of positive end-expiratory pressures (PEEP) to assist very preterm infants to develop a functional residual capacity (FRC) and establish gas exchange at birth. However, maintaining a consistent PEEP is difficult and so the lungs are exposed to changing distending pressures after birth, which can affect respiratory function. Our aim was to determine how changing PEEP levels alters the distribution of ventilation within the lung. Preterm rabbit pups (28 days gestation) were delivered and mechanically ventilated with one of three strategies, whereby PEEP was changed in sequence; 0-5-10-5-0 cmH2O, 5-10-0-5-0 cmH2O or 10-5-0-10-0 cmH2O. Phase contrast X-ray imaging was used to analyse the distribution of ventilation in the upper left (UL), upper right (UR), lower left (LL) and lower right (LR) quadrants of the lung. Initiating ventilation with 10PEEP resulted in a uniform increase in FRC throughout the lung whereas initiating ventilation with 5PEEP or 0PEEP preferentially aerated the UR than both lower quadrants (p<0.05). Consequently, the relative distribution of incoming VT was preferentially directed into the lower lobes at low PEEP, primarily due to the loss of FRC in those lobes. Following ventilation at 10PEEP, the distribution of air at end-inflation was uniform across all quadrants and remained so regardless of the PEEP level. Uniform distribution of ventilation can be achieved by initiating ventilation with a high PEEP. After the lungs have aerated, small and stepped reductions in PEEP result in more uniform changes in ventilation.
Project description:Uncertainty persists regarding the optimal ventilatory strategy in trauma patients developing acute respiratory distress syndrome (ARDS). This work aims to assess the effects of two mechanical ventilation strategies with high positive end-expiratory pressure (PEEP) in experimental ARDS following blunt chest trauma.Twenty-six juvenile pigs were anesthetized, tracheotomized and mechanically ventilated. A contusion was applied to the right chest using a bolt-shot device. Ninety minutes after contusion, animals were randomized to two different ventilation modes, applied for 24 h: Twelve pigs received conventional pressure-controlled ventilation with moderately low tidal volumes (VT, 8 ml/kg) and empirically chosen high external PEEP (16 cmH2O) and are referred to as the HP-CMV-group. The other group (n = 14) underwent high-frequency inverse-ratio pressure-controlled ventilation (HFPPV) involving respiratory rate of 65 breaths · min(-1), inspiratory-to-expiratory-ratio 2:1, development of intrinsic PEEP and recruitment maneuvers, compatible with the rationale of the Open Lung Concept. Hemodynamics, gas exchange and respiratory mechanics were monitored during 24 h. Computed tomography and histology were analyzed in subgroups.Comparing changes which occurred from randomization (90 min after chest trauma) over the 24-h treatment period, groups differed statistically significantly (all P values for group effect <0.001, General Linear Model analysis) for the following parameters (values are mean ± SD for randomization vs. 24-h): PaO2 (100% O2) (HFPPV 186 ± 82 vs. 450 ± 59 mmHg; HP-CMV 249 ± 73 vs. 243 ± 81 mmHg), venous admixture (HFPPV 34 ± 9.8 vs. 11.2 ± 3.7%; HP-CMV 33.9 ± 10.5 vs. 21.8 ± 7.2%), PaCO2 (HFPPV 46.9 ± 6.8 vs. 33.1 ± 2.4 mmHg; HP-CMV 46.3 ± 11.9 vs. 59.7 ± 18.3 mmHg) and normally aerated lung mass (HFPPV 42.8 ± 11.8 vs. 74.6 ± 10.0 %; HP-CMV 40.7 ± 8.6 vs. 53.4 ± 11.6%). Improvements occurring after recruitment in the HFPPV-group persisted throughout the study. Peak airway pressure and VT did not differ significantly. HFPPV animals had lower atelectasis and inflammation scores in gravity-dependent lung areas.In this model of ARDS following unilateral blunt chest trauma, HFPPV ventilation improved respiratory function and fulfilled relevant ventilation endpoints for trauma patients, i.e. restoration of oxygenation and lung aeration while avoiding hypercapnia and respiratory acidosis.
Project description:BACKGROUND:High positive end-expiratory pressures (PEEP) may induce overdistension/recruitment and affect ventilation-perfusion matching (VQMatch) in mechanically ventilated patients. This study aimed to investigate the association between PEEP-induced lung overdistension/recruitment and VQMatch by electrical impedance tomography (EIT). METHODS:The study was conducted prospectively on 30 adult mechanically ventilated patients: 18/30 with ARDS and 12/30 with high risk for ARDS. EIT measurements were performed at zero end-expiratory pressures (ZEEP) and subsequently at high (12-15 cmH2O) PEEP. The number of overdistended pixels over the number of recruited pixels (O/R ratio) was calculated, and the patients were divided into low O/R (O/R ratio?<?15%) and high O/R groups (O/R ratio???15%). The global inhomogeneity (GI) index was calculated to evaluate the ventilation distribution. Lung perfusion image was calculated from the EIT impedance-time curves caused by 10?ml 10% NaCl injection during a respiratory pause (>?8?s). DeadSpace%, Shunt%, and VQMatch% were calculated based on lung EIT perfusion and ventilation images. RESULTS:Increasing PEEP resulted in recruitment mainly in dorsal regions and overdistension mainly in ventral regions. ?VQMatch% (VQMatch% at high PEEP minus that at ZEEP) was significantly correlated with recruited pixels (r?=?0.468, P?=?0.009), overdistended pixels (r =?-?0.666, P?<?0.001), O/R ratio (r =?-?0.686, P?<?0.001), and ?SpO2 (r?=?0.440, P?=?0.015). Patients in the low O/R ratio group (14/30) had significantly higher Shunt% and lower VQMatch% than those in the high O/R ratio group (16/30) at ZEEP but not at high PEEP. Comparable DeadSpace% was found in both groups. A high PEEP caused a significant improvement of VQMatch%, DeadSpace%, Shunt%, and GI in the low O/R ratio group, but not in the high O/R ratio group. Using O/R ratio of 15% resulted in a sensitivity of 81% and a specificity of 100% for an increase of VQMatch%?>?20% in response to high PEEP. CONCLUSIONS:Change of ventilation-perfusion matching was associated with regional overdistention and recruitment induced by PEEP. A low O/R ratio induced by high PEEP might indicate a more homogeneous ventilation and improvement of VQMatch. TRIAL REGISTRATION:ClinicalTrials.gov, NCT04081155 . Registered on 9 September 2019-retrospectively registered.
Project description:BACKGROUND:Intraoperative driving pressure (?P) is associated with development of postoperative pulmonary complications (PPC). When tidal volume (VT) is kept constant, ?P may change according to positive end-expiratory pressure (PEEP)-induced changes in lung aeration. ?P may decrease if PEEP leads to a recruitment of collapsed lung tissue but will increase if PEEP mainly causes pulmonary overdistension. This study tests the hypothesis that individualized high PEEP, when compared to fixed low PEEP, protects against PPC in patients undergoing open abdominal surgery. METHODS:The "Driving prESsure durIng GeNeral AnesThesIa for Open abdomiNal surgery trial" (DESIGNATION) is an international, multicenter, two-group, double-blind randomized clinical superiority trial. A total of 1468 patients will be randomly assigned to one of the two intraoperative ventilation strategies. Investigators screen patients aged ??18?years and with a body mass index ??40?kg/m2, scheduled for open abdominal surgery and at risk for PPC. Patients either receive an intraoperative ventilation strategy with individualized high PEEP with recruitment maneuvers (RM) ("individualized high PEEP") or one in which PEEP of 5?cm H2O without RM is used ("low PEEP"). In the "individualized high PEEP" group, PEEP is set at the level at which ?P is lowest. In both groups of the trial, VT is kept at 8?mL/kg predicted body weight. The primary endpoint is the occurrence of PPC, recorded as a collapsed composite of adverse pulmonary events. DISCUSSION:DESIGNATION will be the first randomized clinical trial that is adequately powered to compare the effects of individualized high PEEP with RM versus fixed low PEEP without RM on the occurrence of PPC after open abdominal surgery. The results of DESIGNATION will support anesthesiologists in their decisions regarding PEEP settings during open abdominal surgery. TRIAL REGISTRATION:Clinicaltrials.gov, NCT03884543. Registered on 21 March 2019.
Project description:BACKGROUND:Percutaneous dilatational tracheotomy (PDT) may lead to transient impairment of pulmonary function due to suboptimal ventilation, loss of positive end-expiratory pressure (PEEP) and repetitive suction maneuvers during the procedure. Possible changes in regional lung aeration were investigated using electrical impedance tomography (EIT), an increasingly implied instrument for bedside monitoring of pulmonary aeration. METHODS:With local ethics committee approval, after obtaining written informed consent 29 patients scheduled for elective PDT under bronchoscopic control were studied during mechanical ventilation in supine position. Anesthetized patients were monitored with a 16-electrode EIT monitor for 2 min at four time points: (a) before and (b) after initiation of neuromuscular blockade (NMB), (c) after dilatational tracheostomy (PDT) and (d) after a standardized recruitment maneuver (RM) following surgery, respectively. Possible changes in lung aeration were detected by changes in end-expiratory lung impedance (? EELI). Global and regional ventilation was characterized by analysis of tidal impedance variation. RESULTS:While NMB had no detectable effect on EELI, PDT led to significantly reduced EELI in dorsal lung regions as compared to baseline, suggesting reduced regional aeration. This effect could be reversed by a standardized RM. Mean delta EELI from baseline (SE) was: NMB -?47?±?62; PDT -?490?±?180; RM -?89?±?176, values shown as arbitrary units (a.u.). Analysis of regional tidal impedance variation, a robust measure of regional ventilation, did not show significant changes in ventilation distribution. CONCLUSION:Though changes of EELI might suggest temporary loss of aeration in dorsal lung regions, PDT does not lead to significant changes in either regional ventilation distribution or oxygenation.
Project description:INTRODUCTION: Atelectasis is a common finding in acute lung injury, leading to increased shunt and hypoxemia. Current treatment strategies aim to recruit alveoli for gas exchange. Improvement in oxygenation is commonly used to detect recruitment, although the assumption that gas exchange parameters adequately represent the mechanical process of alveolar opening has not been proven so far. The aim of this study was to investigate whether commonly used measures of lung mechanics better detect lung tissue collapse and changes in lung aeration after a recruitment maneuver as compared to measures of gas exchange METHODS: In eight anesthetized and mechanically ventilated pigs, acute lung injury was induced by saline lavage and a recruitment maneuver was performed by inflating the lungs three times with a pressure of 45 cmH2O for 40 s with a constant positive end-expiratory pressure of 10 cmH2O. The association of gas exchange and lung mechanics parameters with the amount and the changes in aerated and nonaerated lung volumes induced by this specific recruitment maneuver was investigated by multi slice CT scan analysis of the whole lung. RESULTS: Nonaerated lung correlated with shunt fraction (r = 0.68) and respiratory system compliance (r = 0.59). The arterial partial oxygen pressure (PaO2) and the respiratory system compliance correlated with poorly aerated lung volume (r = 0.57 and 0.72, respectively). The recruitment maneuver caused a decrease in nonaerated lung volume, an increase in normally and poorly aerated lung, but no change in the distribution of a tidal breath to differently aerated lung volumes. The fractional changes in PaO2, arterial partial carbon dioxide pressure (PaCO2) and venous admixture after the recruitment maneuver did not correlate with the changes in lung volumes. Alveolar recruitment correlated only with changes in the plateau pressure (r = 0.89), respiratory system compliance (r = 0.82) and parameters obtained from the pressure-volume curve. CONCLUSION: A recruitment maneuver by repeatedly hyperinflating the lungs led to an increase of poorly aerated and a decrease of nonaerated lung mainly. Changes in aerated and nonaerated lung volumes were adequately represented by respiratory compliance but not by changes in oxygenation or shunt.