Flow-Controlled Ventilation Attenuates Lung Injury in a Porcine Model of Acute Respiratory Distress Syndrome: A Preclinical Randomized Controlled Study.

OBJECTIVES: Lung-protective ventilation for acute respiratory distress syndrome aims for providing sufficient oxygenation and carbon dioxide clearance, while limiting the harmful effects of mechanical ventilation. "Flow-controlled ventilation", providing a constant expiratory flow, has been suggested as a new lung-protective ventilation strategy. The aim of this study was to test whether flow-controlled ventilation attenuates lung injury in an animal model of acute respiratory distress syndrome. DESIGN: Preclinical, randomized controlled animal study. SETTING: Animal research facility. SUBJECTS: Nineteen German landrace hybrid pigs. INTERVENTION: Flow-controlled ventilation (intervention group) or volume-controlled ventilation (control group) with identical tidal volume (7 mL/kg) and positive end-expiratory pressure (9 cm H2O) after inducing acute respiratory distress syndrome with oleic acid. MEASUREMENTS AND MAIN RESULTS: PaO2 and PaCO2, minute volume, tracheal pressure, lung aeration measured via CT, alveolar wall thickness, cell infiltration, and surfactant protein A concentration in bronchoalveolar lavage fluid. Five pigs were excluded leaving n equals to 7 for each group. Compared with control, flow-controlled ventilation elevated PaO2 (154 ± 21 vs 105 ± 9 torr; 20.5 ± 2.8 vs 14.0 ± 1.2 kPa; p = 0.035) and achieved comparable PaCO2 (57 ± 3 vs 54 ± 1 torr; 7.6 ± 0.4 vs 7.1 ± 0.1 kPa; p = 0.37) with a lower minute volume (6.4 ± 0.5 vs 8.7 ± 0.4 L/min; p < 0.001). Inspiratory plateau pressure was comparable in both groups (31 ± 2 vs 34 ± 2 cm H2O; p = 0.16). Flow-controlled ventilation increased normally aerated (24% ± 4% vs 10% ± 2%; p = 0.004) and decreased nonaerated lung volume (23% ± 6% vs 38% ± 5%; p = 0.033) in the dependent lung region. Alveolar walls were thinner (5.5 ± 0.1 vs 7.8 ± 0.2 µm; p < 0.0001), cell infiltration was lower (20 ± 2 vs 32 ± 2 n/field; p < 0.0001), and normalized surfactant protein A concentration was higher with flow-controlled ventilation (1.1 ± 0.04 vs 1.0 ± 0.03; p = 0.039). CONCLUSIONS: Flow-controlled ventilation enhances lung aeration in the dependent lung region and consequently improves gas exchange and attenuates lung injury. Control of the expiratory flow may provide a novel option for lung-protective ventilation.

Flow-controlled ventilation (FCV) improves regional ventilation in obese patients - a randomized controlled crossover trial.

BACKGROUND: In obese patients, high closing capacity and low functional residual capacity increase the risk for expiratory alveolar collapse. Constant expiratory flow, as provided by the new flow-controlled ventilation (FCV) mode, was shown to improve lung recruitment. We hypothesized that lung aeration and respiratory mechanics improve in obese patients during FCV. METHODS: We compared FCV and volume-controlled (VCV) ventilation in 23 obese patients in a randomized crossover setting. Starting with baseline measurements, ventilation settings were kept identical except for the ventilation mode related differences (VCV: inspiration to expiration ratio 1:2 with passive expiration, FCV: inspiration to expiration ratio 1:1 with active, linearized expiration). Primary endpoint of the study was the change of end-expiratory lung volume compared to baseline ventilation. Secondary endpoints were the change of mean lung volume, respiratory mechanics and hemodynamic variables. RESULTS: The loss of end-expiratory lung volume and mean lung volume compared to baseline was lower during FCV compared to VCV (end-expiratory lung volume: FCV, - 126 ± 207 ml; VCV, - 316 ± 254 ml; p < 0.001, mean lung volume: FCV, - 108.2 ± 198.6 ml; VCV, - 315.8 ± 252.1 ml; p < 0.001) and at comparable plateau pressure (baseline, 19.6 ± 3.7; VCV, 20.2 ± 3.4; FCV, 20.2 ± 3.8 cmH2O; p = 0.441), mean tracheal pressure was higher (baseline, 13.1 ± 1.1; VCV, 12.9 ± 1.2; FCV, 14.8 ± 2.2 cmH2O; p < 0.001). All other respiratory and hemodynamic variables were comparable between the ventilation modes. CONCLUSIONS: This study demonstrates that, compared to VCV, FCV improves regional ventilation distribution of the lung at comparable PEEP, tidal volume, PPlat and ventilation frequency. The increase in end-expiratory lung volume during FCV was probably caused by the increased mean tracheal pressure which can be attributed to the linearized expiratory pressure decline. TRIAL REGISTRATION: German Clinical Trials Register: DRKS00014925. Registered 12 July 2018.

Effect of individualized PEEP titration guided by intratidal compliance profile analysis on regional ventilation assessed by electrical impedance tomography - a randomized controlled trial.

BACKGROUND: The application of positive end-expiratory pressure (PEEP) may reduce dynamic strain during mechanical ventilation. Although numerous approaches for PEEP titration have been proposed, there is no accepted strategy for titrating optimal PEEP. By analyzing intratidal compliance profiles, PEEP may be individually titrated for patients. METHODS: After obtaining informed consent, 60 consecutive patients undergoing general anesthesia were randomly allocated to mechanical ventilation with PEEP 5 cmH2O (control group) or PEEP individually titrated, guided by an analysis of the intratidal compliance profile (intervention group). The primary endpoint was the frequency of each nonlinear intratidal compliance (CRS) profile of the respiratory system (horizontal, increasing, decreasing, and mixed). The secondary endpoints measured were respiratory mechanics, hemodynamic variables, and regional ventilation, which was assessed via electrical impedance tomography. RESULTS: The frequencies of the CRS profiles were comparable between the groups. Besides PEEP [control: 5.0 (0.0), intervention: 5.8 (1.1) cmH2O, p < 0.001], the respiratory and hemodynamic variables were comparable between the two groups. The compliance profile analysis showed no significant differences between the two groups. The loss of ventral and dorsal regional ventilation was higher in the control [ventral: 41.0 (16.3)%; dorsal: 25.9 (13.8)%] than in the intervention group [ventral: 29.3 (17.6)%; dorsal: 16.4 (12.7)%; p (ventral) = 0.039, p (dorsal) = 0.028]. CONCLUSIONS: Unfavorable compliance profiles indicating tidal derecruitment were found less often than in earlier studies. Individualized PEEP titration resulted in slightly higher PEEP. A slight global increase in aeration associated with this was indicated by regional gain and loss analysis. Differences in dorsal to ventral ventilation distribution were not found. TRIAL REGISTRATION: This clinical trial was registered at the German Register for Clinical Trials (DRKS00008924) on August 10, 2015.

Dependency of respiratory system mechanics on positive end-expiratory pressure and recruitment maneuvers in lung healthy pediatric patients-A randomized crossover study.

BACKGROUND: The lungs of pediatric patients are subjected to tidal derecruitment during mechanical ventilation and in contrast to adult patients this unfavorable condition cannot be resolved with small c increases. This raises the question if higher end-expiratory pressure increases or recruitment maneuvers may resolve tidal derecruitment in pediatric patients. AIMS: We hypothesized that higher PEEP resolves tidal derecruitment in pediatric patients and that recruitment maneuvers between the pressure changes support the improvement of respiratory system mechanics. METHODS: The effects of end-expiratory pressure changes from 3 to 7 cmH2 O and vice versa without and with intermediate recruitment maneuvers on respiratory system mechanics and regional ventilation were investigated in 57 mechanically ventilated pediatric patients. The intratidal respiratory system compliance was determined from volume and pressure data before and after PEEP changes and categorized to indicate tidal derecruitment. RESULTS: Tidal derecruitment occurred comparably frequently at PEEP 3 cmH2 O without (13 out of 14 cases) and with recruitment maneuver (14 out of 14 cases) and at PEEP 7 cmH2 O without (13 out of 14 cases) and with recruitment maneuver (13 out of 15 cases). CONCLUSIONS: We conclude that contrary to our hypothesis, PEEP up to 7 cmH2 O is not sufficient to resolve tidal derecruitment and that recruitment maneuvers may be dispensable in mechanically ventilated pediatric patients.

Glottic visibility for laryngeal surgery: Tritube vs. microlaryngeal tube: A randomised controlled trial.

BACKGROUND: Good visibility is essential for successful laryngeal surgery. A Tritube with outer diameter 4.4 mm, combined with flow-controlled ventilation (FCV), enables ventilation by active expiration with a sealed trachea and may improve laryngeal visibility. OBJECTIVES: We hypothesised that a Tritube with FCV would provide better laryngeal visibility and surgical conditions for laryngeal surgery than a conventional microlaryngeal tube (MLT) with volume-controlled ventilation (VCV). DESIGN: Randomised, controlled trial. SETTING: University Medical Centre. PATIENTS: A total of 55 consecutive patients (>18 years) undergoing elective laryngeal surgery were assessed for participation, providing 40 evaluable data sets with 20 per group. INTERVENTIONS: Random allocation to intubation with Tritube and ventilation with FCV (Tritube-FCV group) or intubation with MLT 6.0 and ventilation with VCV (MLT-VCV) as control. Tidal volumes of 7 ml kg predicted body weight, and positive end-expiratory pressure of 7 cmH2O were standardised between groups. MAIN OUTCOME MEASURES: Primary endpoint was the tube-related concealment of laryngeal structures, measured on videolaryngoscopic photographs by appropriate software. Secondary endpoints were surgical conditions (categorical four-point rating scale), respiratory variables and change of end-expiratory lung volume from atmospheric airway pressure to ventilation with positive end-expiratory pressure. Data are presented as median [IQR]. RESULTS: There was less concealment of laryngeal structures with the Tritube than with the MLT; 7 [6 to 9] vs. 22 [18 to 27] %, (P < 0.001). Surgical conditions were rated comparably (P = 0.06). A subgroup of residents in training perceived surgical conditions to be better with the Tritube compared with the MLT (P = 0.006). Respiratory system compliance with the Tritube was higher at 61 [52 to 71] vs. 46 [41 to 51] ml cmH2O (P < 0.001), plateau pressure was lower at 14 [13 to 15] vs. 17 [16 to 18] cmH2O (P < 0.001), and change of end-expiratory lung volume was higher at 681 [463 to 849] vs. 414 [194 to 604] ml, (P = 0.023) for Tritube-FCV compared with MLT-VCV. CONCLUSION: During laryngeal surgery a Tritube improves visibility of the surgical site but not surgical conditions when compared with a MLT 6.0. FCV improves lung aeration and respiratory system compliance compared with VCV. TRIAL REGISTRY NUMBER: DRKS00013097.

Dorsal recruitment with flow-controlled expiration (FLEX): an experimental study in mechanically ventilated lung-healthy and lung-injured pigs.

BACKGROUND: Concepts for optimizing mechanical ventilation focus mainly on modifying the inspiratory phase. We propose flow-controlled expiration (FLEX) as an additional means for lung protective ventilation and hypothesize that it is capable of recruiting dependent areas of the lungs. This study investigates potential recruiting effects of FLEX using models of mechanically ventilated pigs before and after induction of lung injury with oleic acid. METHODS: Seven pigs in the supine position were ventilated with tidal volume 8 ml·kg- 1 and positive end-expiratory pressure (PEEP) set to maintain partial pressure of oxygen in arterial blood (paO2) at ≥ 60 mmHg and monitored with electrical impedance tomography (EIT). Two ventilation sequences were recorded - one before and one after induction of lung injury. Each sequence comprised 2 min of conventional volume-controlled ventilation (VCV), 2 min of VCV with FLEX and 1 min again of conventional VCV. Analysis of the EIT recordings comprised global and ventral and dorsal baseline levels of impedance curves, end-expiratory no-flow periods, tidal variation in ventral and dorsal areas, and regional ventilation delay index. RESULTS: With FLEX, the duration of the end-expiratory zero flow intervals was significantly shortened (VCV 1.4 ± 0.3 s; FLEX 0.7 ± 0.1 s, p < 0.001), functional residual capacity was significantly elevated in both conditions of the lungs (global: healthy, increase of 87 ± 12 ml, p < 0.001; injured, increase of 115 ± 44 ml, p < 0.001; ventral: healthy, increase of 64 ± 11 ml, p < 0.001; injured, increase of 83 ± 22 ml, p < 0.001; dorsal: healthy, increase of 23 ± 5 ml, p < 0.001; injured, increase of 32 ± 26 ml, p = 0.02), and ventilation was shifted from ventral to dorsal areas (dorsal increase: healthy, 1 ± 0.5%, p < 0.01; dorsal increase: injured, 6 ± 2%, p < 0.01), compared to conventional VCV. Recruiting effects of FLEX persisted during conventional VCV following FLEX ventilation mostly in the injured but also in the healthy lungs. CONCLUSIONS: FLEX shifts regional ventilation towards dependent lung areas in healthy and in injured pig lungs. The recruiting capabilities of FLEX may be mainly responsible for lung-protective effects observed in an earlier study.

Improved lung recruitment and oxygenation during mandatory ventilation with a new expiratory ventilation assistance device: A controlled interventional trial in healthy pigs.

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 ±â€Š0.4 versus 9.0 ±â€Š0.3 cmH2O, P < 0.001 and PaO2: 19.2 ±â€Š0.7 versus 17.5 ±â€Š0.4 kPa, P = 0.002) with comparable peak inspiratory tracheal pressure (18.3 ±â€Š0.9 versus 18.0 ±â€Š1.2 cmH2O, P > 0.99). Minute volume was lower in the EVA group compared with control (5.5 ±â€Š0.2 versus 7.0 ±â€Š1.0 l min, P = 0.02) with normoventilation in both groups (PaCO2 5.4 ±â€Š0.3 versus 5.5 ±â€Š0.3 kPa, P > 0.99). In the EVA group, the percentage of normally aerated lung tissue was higher (81.0 ±â€Š3.6 versus 75.8 ±â€Š3.0%, P = 0.017) and of poorly aerated lung tissue lower (9.5 ±â€Š3.3 versus 15.7 ±â€Š3.5%, 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.

Application of the Novel Ventilation Mode FLow-Controlled EXpiration (FLEX): A Crossover Proof-of-Principle Study in Lung-Healthy Patients.

BACKGROUND: Traditionally, mechanical ventilation is achieved via active lung inflation during inspiration and passive lung emptying during expiration. By contrast, the novel FLEX (FLow-controlled EXpiration) ventilator mode actively decreases the rate of lung emptying. We investigated whether FLEX can be used during intraoperative mechanical ventilation of lung-healthy patients. METHODS: In 30 adult patients scheduled for neurosurgical procedures, we studied respiratory system mechanics, regional ventilation, oxygenation, and hemodynamics during ventilation with and without FLEX at positive end-expiratory pressure (PEEP) of 5 and 7 cm H2O. The FLEX system was integrated into the expiratory limb and modified the expiratory flow profile by continuously changing expiratory resistance according to a computer-controlled algorithm. RESULTS: Mean airway pressure increased with PEEP by 1.9 cm H2O and with FLEX by 1 cm H2O (all P < .001). The expiratory peak flow was 42% lower with FLEX than without FLEX (P < .001). FLEX caused significant shifts in aeration from ventral to the dorsal lung regions. Respiratory mechanics, end-tidal carbon dioxide partial pressure, oxygenation, and hemodynamics were independent from FLEX and PEEP. We observed no critical incidents or FLEX malfunctions in any measurement that would have required an intervention or termination of the FLEX mode. CONCLUSIONS: FLEX can be used in lung-healthy patients who are mechanically ventilated during general anesthesia. FLEX improves the homogeneous distribution of ventilation in the lungs.

Lung area estimation using functional tidal electrical impedance variation images and active contouring.

Objective.Electrical impedance tomography is a valuable tool for monitoring global and regional lung mechanics. To evaluate the recorded data, an accurate estimate of the lung area is crucial.Approach.We present two novel methods for estimating the lung area using functional tidal images or active contouring methods. A convolutional neural network was trained to determine, whether or not the heart region was visible within tidal images. In addition, the effects of lung area mirroring were investigated. The performance of the methods and the effects of mirroring were evaluated via a score based on the impedance magnitudes and their standard deviations in functional tidal images.Main results.Our analyses showed that the method based on functional tidal images provided the best estimate of the lung area. Mirroring of the lung area had an impact on the accuracy of area estimation for both methods. The achieved accuracy of the neural network's classification was 94%. For images without a visible heart area, the subtraction of a heart template proved to be a pragmatic approach with good results.Significance.In summary, we developed a routine for estimation of the lung area combined with estimation of the heart area in electrical impedance tomography images.