Project description:OBJECTIVES:Low tidal volume (= tidal volume ? 6?mL/kg, predicted body weight) ventilation using volume control benefits patients with acute respiratory distress syndrome. Airway pressure release ventilation is an alternative to low tidal volume-volume control ventilation, but the release breaths generated are variable and can exceed tidal volume breaths of low tidal volume-volume control. We evaluate the application of a low tidal volume-compatible airway pressure release ventilation protocol that manages release volumes on both clinical and feasibility endpoints. DESIGN:We designed a prospective randomized trial in patients with acute hypoxemic respiratory failure. We randomized patients to low tidal volume-volume control, low tidal volume-airway pressure release ventilation, and traditional airway pressure release ventilation with a planned enrollment of 246 patients. The study was stopped early because of low enrollment and inability to consistently achieve tidal volumes less than 6.5?mL/kg in the low tidal volume-airway pressure release ventilation arm. Although the primary clinical study endpoint was PaO2/FIO2 on study day 3, we highlight the feasibility outcomes related to tidal volumes in both arms. SETTING:Four Intermountain Healthcare tertiary ICUs. PATIENTS:Adult ICU patients with hypoxemic respiratory failure anticipated to require prolonged mechanical ventilation. INTERVENTIONS:Low tidal volume-volume control, airway pressure release ventilation, and low tidal volume-airway pressure release ventilation. MEASUREMENTS AND MAIN RESULTS:We observed wide variability and higher tidal (release for airway pressure release ventilation) volumes in both airway pressure release ventilation (8.6?mL/kg; 95% CI, 7.8-9.6) and low tidal volume-airway pressure release ventilation (8.0; 95% CI, 7.3-8.9) than volume control (6.8; 95% CI, 6.2-7.5; p = 0.005) with no difference between airway pressure release ventilation and low tidal volume-airway pressure release ventilation (p = 0.58). Recognizing the limitations of small sample size, we observed no difference in 52 patients in day 3 PaO2/ FIO2 (p = 0.92). We also observed no significant difference between arms in sedation, vasoactive medications, or occurrence of pneumothorax. CONCLUSIONS:Airway pressure release ventilation resulted in release volumes often exceeding 12?mL/kg despite a protocol designed to target low tidal volume ventilation. Current airway pressure release ventilation protocols are unable to achieve consistent and reproducible delivery of low tidal volume ventilation goals. A large-scale efficacy trial of low tidal volume-airway pressure release ventilation is not feasible at this time in the absence of an explicit, generalizable, and reproducible low tidal volume-airway pressure release ventilation protocol.
Project description:BackgroundImproper mechanical ventilation can exacerbate acute lung damage, causing a secondary ventilator-induced lung injury (VILI). We hypothesized that VILI can be reduced by modifying specific components of the ventilation waveform (mechanical breath), and we studied the impact of airway pressure release ventilation (APRV) and controlled mandatory ventilation (CMV) on the lung micro-anatomy (alveoli and conducting airways). The distribution of gas during inspiration and expiration and the strain generated during mechanical ventilation in the micro-anatomy (micro-strain) were calculated.Study designRats were anesthetized, surgically prepared, and randomized into 1 uninjured control group (n = 2) and 4 groups with lung injury: APRV 75% (n = 2), time at expiration (TLow) set to terminate appropriately at 75% of peak expiratory flow rate (PEFR); APRV 10% (n = 2), TLow set to terminate inappropriately at 10% of PEFR; CMV with PEEP 5 cm H2O (PEEP 5; n = 2); or PEEP 16 cm H2O (PEEP 16; n = 2). Lung injury was induced in the experimental groups by Tween lavage and ventilated with their respective settings. Lungs were fixed at peak inspiration and end expiration for standard histology. Conducting airway and alveolar air space areas were quantified and conducting airway micro-strain was calculated.ResultsAll lung injury groups redistributed inspired gas away from alveoli into the conducting airways. The APRV 75% minimized gas redistribution and micro-strain in the conducting airways and provided the alveolar air space occupancy most similar to control at both inspiration and expiration.ConclusionsIn an injured lung, APRV 75% maintained micro-anatomic gas distribution similar to that of the normal lung. The lung protection demonstrated in previous studies using APRV 75% may be due to a more homogeneous distribution of gas at the micro-anatomic level as well as a reduction in conducting airway micro-strain.
Project description:OBJECTIVE:Critical organ shortages have resulted in ex vivo lung perfusion gaining clinical acceptance for lung evaluation and rehabilitation to expand the use of donation after circulatory death organs for lung transplantation. We hypothesized that an innovative use of airway pressure release ventilation during ex vivo lung perfusion improves lung function after transplantation. METHODS:Two groups (n = 4 animals/group) of porcine donation after circulatory death donor lungs were procured after hypoxic cardiac arrest and a 2-hour period of warm ischemia, followed by a 4-hour period of ex vivo lung perfusion rehabilitation with standard conventional volume-based ventilation or pressure-based airway pressure release ventilation. Left lungs were subsequently transplanted into recipient animals and reperfused for 4 hours. Blood gases for partial pressure of oxygen/inspired oxygen fraction ratios, airway pressures for calculation of compliance, and percent wet weight gain during ex vivo lung perfusion and reperfusion were measured. RESULTS:Airway pressure release ventilation during ex vivo lung perfusion significantly improved left lung oxygenation at 2 hours (561.5 ± 83.9 mm Hg vs 341.1 ± 136.1 mm Hg) and 4 hours (569.1 ± 18.3 mm Hg vs 463.5 ± 78.4 mm Hg). Likewise, compliance was significantly higher at 2 hours (26.0 ± 5.2 mL/cm H2O vs 15.0 ± 4.6 mL/cm H2O) and 4 hours (30.6 ± 1.3 mL/cm H2O vs 17.7 ± 5.9 mL/cm H2O) after transplantation. Finally, airway pressure release ventilation significantly reduced lung edema development on ex vivo lung perfusion on the basis of percentage of weight gain (36.9% ± 14.6% vs 73.9% ± 4.9%). There was no difference in additional edema accumulation 4 hours after reperfusion. CONCLUSIONS:Pressure-directed airway pressure release ventilation strategy during ex vivo lung perfusion improves the rehabilitation of severely injured donation after circulatory death lungs. After transplant, these lungs demonstrate superior lung-specific oxygenation and dynamic compliance compared with lungs ventilated with standard conventional ventilation. This strategy, if implemented into clinical ex vivo lung perfusion protocols, could advance the field of donation after circulatory death lung rehabilitation to expand the lung donor pool.
Project description:Background:To investigate the effects of high-frequency oscillatory ventilation (HFOV) or airway pressure release ventilation (APRV) as a rescue therapy on children with moderate and severe acute respiratory distress syndrome (ARDS). Methods:We retrospectively enrolled 47 children with ARDS who were transitioned from synchronized intermittent mandatory ventilation (SIMV) to either HFOV or APRV for 48 h or longer after failure of SIMV. The parameters of demographic data, arterial blood gases, ventilator settings, oxygenation index (OI), and PaO2/FiO2 (PF) ratio during the first 48 h of HFOV and APRV were recorded. Results:There was no significant difference between the HFOV and APRV groups with survival rates of 60% and 72.7%, respectively. Compared to pre-transition, the mean airway pressures at 2 and 48 h after transition were higher in both groups (P<0.01), and the PF ratio at 2 and 48 h in both modes was significantly improved (P<0.001). PF ratio and PaCO2 have significant differences at 48 h between two groups. The OI at 2 h after transition had no improvement in either group and was substantially lower at 48 h relative to the pre-transition level (P<0.001) in both groups. At 48 h after the transition to both HFOV and APRV, the survivors had lower mean airway pressures, higher PF ratios, and a lower OIs than non-survivors (P<0.01). Conclusions:There was no significant difference on the survival rates of HFOV and APRV application as a rescue therapy for ARDS, but improved oxygenation at 48 h reliably discriminated survivors from non-survivors in both groups.
Project description:The use of airway pressure release ventilation (APRV) in very low birth weight infants is limited.To report the authors' institutional experience and to review the current literature regarding the use of APRV in pediatric populations.Neonates <1500 g ventilated using APRV from 2005 to 2006 at McMaster Children's Hospital (Hamilton, Ontario) were retrospectively reviewed. Publications describing APRV in children from 1987 to 2011 were reviewed.Five infants, 24 to 28 weeks' gestational age, were ventilated using APRV. Indications for APRV were refractory hypoxemia (n=3), ventilatory dyssynchrony (n=1) and minimizing sedatives (n=1). All infants appeared to tolerate APRV well with no recorded adverse events. Current pediatric evidence regarding APRV is primarily observational. Published experience reveals that APRV settings in pediatrics often approximate those used in adults, thus deviating from the original guidelines recommended in children. Clinical outcomes, such as oxygenation, ventilation and sedation requirements, are inconsistent.APRV is primarily used as a rescue ventilation mode in children. Neonatal evidence is limited; however, the present study indicates that APRV is feasible in very low birth weight infants. There are unique considerations when applying this mode in small infants. Further research is necessary to confirm whether APRV is a safe and effective ventilation strategy in this population.
Project description:PurposeExperimental animal models of acute respiratory distress syndrome (ARDS) have shown that the updated airway pressure release ventilation (APRV) methodologies may significantly improve oxygenation, maximize lung recruitment, and attenuate lung injury, without circulatory depression. This led us to hypothesize that early application of APRV in patients with ARDS would allow pulmonary function to recover faster and would reduce the duration of mechanical ventilation as compared with low tidal volume lung protective ventilation (LTV).MethodsA total of 138 patients with ARDS who received mechanical ventilation for <48 h between May 2015 to October 2016 while in the critical care medicine unit (ICU) of the West China Hospital of Sichuan University were enrolled in the study. Patients were randomly assigned to receive APRV (n = 71) or LTV (n = 67). The settings for APRV were: high airway pressure (Phigh) set at the last plateau airway pressure (Pplat), not to exceed 30 cmH2O) and low airway pressure ( Plow) set at 5 cmH2O; the release phase (Tlow) setting adjusted to terminate the peak expiratory flow rate to ≥ 50%; release frequency of 10-14 cycles/min. The settings for LTV were: target tidal volume of 6 mL/kg of predicted body weight; Pplat not exceeding 30 cmH2O; positive end-expiratory pressure (PEEP) guided by the PEEP-FiO2 table according to the ARDSnet protocol. The primary outcome was the number of days without mechanical ventilation from enrollment to day 28. The secondary endpoints included oxygenation, Pplat, respiratory system compliance, and patient outcomes.ResultsCompared with the LTV group, patients in the APRV group had a higher median number of ventilator-free days {19 [interquartile range (IQR) 8-22] vs. 2 (IQR 0-15); P < 0.001}. This finding was independent of the coexisting differences in chronic disease. The APRV group had a shorter stay in the ICU (P = 0.003). The ICU mortality rate was 19.7% in the APRV group versus 34.3% in the LTV group (P = 0.053) and was associated with better oxygenation and respiratory system compliance, lower Pplat, and less sedation requirement during the first week following enrollment (P < 0.05, repeated-measures analysis of variance).ConclusionsCompared with LTV, early application of APRV in patients with ARDS improved oxygenation and respiratory system compliance, decreased Pplat and reduced the duration of both mechanical ventilation and ICU stay.
Project description:Mortality in acute respiratory distress syndrome (ARDS) remains unacceptably high at approximately 39%. One of the only treatments is supportive: mechanical ventilation. However, improperly set mechanical ventilation can further increase the risk of death in patients with ARDS. Recent studies suggest that ventilation-induced lung injury (VILI) is caused by exaggerated regional lung strain, particularly in areas of alveolar instability subject to tidal recruitment/derecruitment and stress-multiplication. Thus, it is reasonable to expect that if a ventilation strategy can maintain stable lung inflation and homogeneity, regional dynamic strain would be reduced and VILI attenuated. A time-controlled adaptive ventilation (TCAV) method was developed to minimize dynamic alveolar strain by adjusting the delivered breath according to the mechanical characteristics of the lung. The goal of this review is to describe how the TCAV method impacts pathophysiology and protects lungs with, or at high risk of, acute lung injury. We present work from our group and others that identifies novel mechanisms of VILI in the alveolar microenvironment and demonstrates that the TCAV method can reduce VILI in translational animal ARDS models and mortality in surgical/trauma patients. Our TCAV method utilizes the airway pressure release ventilation (APRV) mode and is based on opening and collapsing time constants, which reflect the viscoelastic properties of the terminal airspaces. Time-controlled adaptive ventilation uses inspiratory and expiratory time to (1) gradually "nudge" alveoli and alveolar ducts open with an extended inspiratory duration and (2) prevent alveolar collapse using a brief (sub-second) expiratory duration that does not allow time for alveolar collapse. The new paradigm in TCAV is configuring each breath guided by the previous one, which achieves real-time titration of ventilator settings and minimizes instability induced tissue damage. This novel methodology changes the current approach to mechanical ventilation, from arbitrary to personalized and adaptive. The outcome of this approach is an open and stable lung with reduced regional strain and greater lung protection.
Project description:BackgroundAirway pressure release ventilation (APRV) is widely available on mechanical ventilators and has been proposed as an early intervention to prevent lung injury or as a rescue therapy in the management of refractory hypoxemia. Driving pressure ([Formula: see text]) has been identified in numerous studies as a key indicator of ventilator-induced-lung-injury that needs to be carefully controlled. [Formula: see text] delivered by the ventilator in APRV is not directly measurable in dynamic conditions, and there is no "gold standard" method for its estimation.MethodsWe used a computational simulator matched to data from 90 patients with acute respiratory distress syndrome (ARDS) to evaluate the accuracy of three "at-the-bedside" methods for estimating ventilator [Formula: see text] during APRV.ResultsLevels of [Formula: see text] delivered by the ventilator in APRV were generally within safe limits, but in some cases exceeded levels specified by protective ventilation strategies. A formula based on estimating the intrinsic positive end expiratory pressure present at the end of the APRV release provided the most accurate estimates of [Formula: see text]. A second formula based on assuming that expiratory flow, volume and pressure decay mono-exponentially, and a third method that requires temporarily switching to volume-controlled ventilation, also provided accurate estimates of true [Formula: see text].ConclusionsLevels of [Formula: see text] delivered by the ventilator during APRV can potentially exceed levels specified by standard protective ventilation strategies, highlighting the need for careful monitoring. Our results show that [Formula: see text] delivered by the ventilator during APRV can be accurately estimated at the bedside using simple formulae that are based on readily available measurements.
Project description:BACKGROUND:Primary blast lung injury (PBLI) presents as a syndrome of respiratory distress and haemoptysis resulting from explosive shock wave exposure and is a frequent cause of mortality and morbidity in both military conflicts and terrorist attacks. The optimal mode of mechanical ventilation for managing PBLI is not currently known, and clinical trials in humans are impossible due to the sporadic and violent nature of the disease. METHODS:A high-fidelity multi-organ computational simulator of PBLI pathophysiology was configured to replicate data from 14 PBLI casualties from the conflict in Afghanistan. Adaptive and responsive ventilatory protocols implementing low tidal volume (LTV) ventilation and airway pressure release ventilation (APRV) were applied to each simulated patient for 24 h, allowing direct quantitative comparison of their effects on gas exchange, ventilatory parameters, haemodynamics, extravascular lung water and indices of ventilator-induced lung injury. RESULTS:The simulated patients responded well to both ventilation strategies. Post 24-h investigation period, the APRV arm had similar PF ratios (137 mmHg vs 157 mmHg), lower sub-injury threshold levels of mechanical power (11.9 J/min vs 20.7 J/min) and lower levels of extravascular lung water (501 ml vs 600 ml) compared to conventional LTV. Driving pressure was higher in the APRV group (11.9 cmH2O vs 8.6 cmH2O), but still significantly less than levels associated with increased mortality. CONCLUSIONS:Appropriate use of APRV may offer casualties with PBLI important mortality-related benefits and should be considered for management of this challenging patient group.