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Feasibility and safety of low-flow extracorporeal carbon dioxide removal to facilitate ultra-protective ventilation in patients with moderate acute respiratory distress sindrome.

ABSTRACT: Mechanical ventilation with a tidal volume (VT) of 6 mL/kg/predicted body weight (PBW), to maintain plateau pressure (Pplat) lower than 30 cmH2O, does not completely avoid the risk of ventilator induced lung injury (VILI). The aim of this study was to evaluate safety and feasibility of a ventilation strategy consisting of very low VT combined with extracorporeal carbon dioxide removal (ECCO2R).In fifteen patients with moderate ARDS, VT was reduced from baseline to 4 mL/kg PBW while PEEP was increased to target a plateau pressure--(Pplat) between 23 and 25 cmH2O. Low-flow ECCO2R was initiated when respiratory acidosis developed (pH < 7.25, PaCO2 > 60 mmHg). Ventilation parameters (VT, respiratory rate, PEEP), respiratory compliance (CRS), driving pressure (DeltaP = VT/CRS), arterial blood gases, and ECCO2R system operational characteristics were collected during the period of ultra-protective ventilation. Patients were weaned from ECCO2R when PaO2/FiO2 was higher than 200 and could tolerate conventional ventilation settings. Complications, mortality at day 28, need for prone positioning and extracorporeal membrane oxygenation, and data on weaning from both MV and ECCO2R were also collected.During the 2 h run in phase, VT reduction from baseline (6.2 mL/kg PBW) to approximately 4 mL/kg PBW caused respiratory acidosis (pH < 7.25) in all fifteen patients. At steady state, ECCO2R with an average blood flow of 435 mL/min and sweep gas flow of 10 L/min was effective at correcting pH and PaCO2 to within 10 % of baseline values. PEEP values tended to increase at VT of 4 mL/kg from 12.2 to 14.5 cmH2O, but this change was not statistically significant. Driving pressure was significantly reduced during the first two days compared to baseline (from 13.9 to 11.6 cmH2O; p < 0.05) and there were no significant differences in the values of respiratory system compliance. Rescue therapies for life threatening hypoxemia such as prone position and ECMO were necessary in four and two patients, respectively. Only two study-related adverse events were observed (intravascular hemolysis and femoral catheter kinking).The low-flow ECCO2R system safely facilitates a low volume, low pressure ultra-protective mechanical ventilation strategy in patients with moderate ARDS.

SUBMITTER: Fanelli V

PROVIDER: S-EPMC4748548 | biostudies-other | 2016

REPOSITORIES: biostudies-other

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Project description:Background:Tidal hyperinflation can still occur with mechanical ventilation using low tidal volume (LVT) (6?mL/kg predicted body weight (PBW)) in acute respiratory distress syndrome (ARDS), despite a well-demonstrated reduction in mortality. Methods:Retrospective chart review from August 2012 to October 2014. Inclusion: Age >18years, PaO2/FiO2<200 with bilateral pulmonary infiltrates, absent heart failure, and ultra-protective mechanical ventilation (UPMV) defined as tidal volume (VT) <6?mL/kg PBW. Exclusion: UPMV use for <24?h. Demographics, admission Acute Physiology and Chronic Health Evaluation II (APACHE II) scores, arterial blood gas, serum bicarbonate, ventilator parameters for pre-, during, and post-UPMV periods including modes, VT, peak inspiratory pressure (PIP), plateau pressure (Pplat), driving pressure, etc. were gathered. We compared lab and ventilator data for pre-, during, and post-UPMV periods. Results:Fifteen patients (male:female?=?7:8, age 42.13?±?11.29 years) satisfied criteria, APACHEII 20.6?±?7.1, mean days in intensive care unit and hospitalization were 18.5?±?8.85 and 20.81?±?9.78 days, 9 (60%) received paralysis and 7 (46.67%) required inotropes. Eleven patients had echocardiogram, 7 (63.64%) demonstrated right ventricular volume or pressure overload. Eleven patients (73.33%) survived. During-UPMV, VT ranged 2-5?mL/kg PBW(3.99?±?0.73), the arterial partial pressure of carbon dioxide (PaCO2) was higher than pre-UPMV values (84.81?±?18.95 cmH2O vs. 69.16?±?33.09 cmH2O), but pH was comparable and none received extracorporeal carbon dioxide removal (ECCO2-R). The positive end-expiratory pressure (14.18?±?7.56 vs. 12.31?±?6.84 cmH2O), PIP (38.21?±?12.89 vs. 32.59?±?9.88), and mean airway pressures (19.98?±?7.61 vs. 17.48?±?6.7?cm H2O) were higher during UPMV, but Pplat and PaO2/FiO2 were comparable during- and pre-UPMV. Driving pressure was observed to be higher in those who died than who survived (24.18?±?12.36 vs. 13.42?±?3.25). Conclusion:UPMV alone may be a safe alternative option for ARDS patients in centers without ECCO2-R.

Project description:Mechanical ventilation (MV) represents a lifesaving treatment for patients with respiratory failure, but it could be harmful through the development of ventilator-induced lung injury (VILI). In patients with acute respiratory distress syndrome (ARDS), protective MV strategies with low tidal volume to minimize VILI have been demonstrated to reduce lung injury and mortality. However, they can be limited by the emergence of uncontrolled hypercapnia. Similarly, in COPD patients, noninvasive MV failure often is associated with a progressive rise in arterial CO2 and need for endotracheal intubation, with higher risk of hospital mortality. Minimally invasive extracorporeal CO2 removal systems (ECCO2R) theoretically can remove the entire amount of the CO2 produced in the body per minute. In ARDS patients, ECCO2R may further reduce the risk of VILI ensuring ultraprotective MV and avoiding hypercapnia. In patients with exacerbation of COPD, ECCO2R may help to avoid intubation or facilitate weaning from invasive MV. In intensive care unit, concomitant renal and respiratory failure with MV is one of the strongest risk factors for hospital mortality. Combining ECCO2R and renal replacement therapy may support respiratory and renal functions and limit the side effects of MV. However, the need for systemic anticoagulation and the related risk of bleeding still represent a concern for a wider application of ECCO2R devices. In conclusion, ECCO2R is an effective support therapy to MV to limit its invasiveness and side effects, but its efficacy and safety must be proven in well-designed clinical trials. Objectives This chapter will:1 Explain the physiology of CO2 removal during extracorporeal support.2 Describe potential clinical applications of extracorporeal CO2 removal systems (ECCO2R) support therapy in patients with acute respiratory distress syndrome (ARDS) and chronic obstructive pulmonary disease (COPD) as well as in those with acute kidney injury requiring renal replacement therapy.

Project description:BACKGROUND:Extracorporeal carbon-dioxide removal (ECCO2R) might allow ultraprotective mechanical ventilation with lower tidal volume (VT) (<?6 ml/kg predicted body weight), plateau pressure (Pplat) (<?30 cmH2O), and driving pressure to limit ventilator-induced lung injury. This study was undertaken to assess the feasibility and safety of ECCO2R managed with a renal replacement therapy (RRT) platform to enable very low tidal volume ventilation of patients with mild-to-moderate acute respiratory distress syndrome (ARDS). METHODS:Twenty patients with mild (n?=?8) or moderate (n?=?12) ARDS were included. VT was gradually lowered from 6 to 5, 4.5, and 4 ml/kg, and PEEP adjusted to reach 23???Pplat???25 cmH2O. Standalone ECCO2R (no hemofilter associated with the RRT platform) was initiated when arterial PaCO2 increased by >?20% from its initial value. Ventilation parameters (VT, respiratory rate, PEEP), respiratory system compliance, Pplat and driving pressure, arterial blood gases, and ECCO2R-system operational characteristics were collected during at least 24 h of very low tidal volume ventilation. Complications, day-28 mortality, need for adjuvant therapies, and data on weaning off ECCO2R and mechanical ventilation were also recorded. RESULTS:While VT was reduced from 6 to 4 ml/kg and Pplat kept <?25 cmH2O, PEEP was significantly increased from 13.4?±?3.6 cmH2O at baseline to 15.0?±?3.4 cmH2O, and the driving pressure was significantly reduced from 13.0?±?4.8 to 7.9?±?3.2 cmH2O (both p?<?0.05). The PaO2/FiO2 ratio and respiratory-system compliance were not modified after VT reduction. Mild respiratory acidosis occurred, with mean PaCO2 increasing from 43?±?8 to 53?±?9 mmHg and mean pH decreasing from 7.39?±?0.1 to 7.32?±?0.10 from baseline to 4 ml/kg VT, while the respiratory rate was not altered. Mean extracorporeal blood flow, sweep-gas flow, and CO2 removal were 421?±?40 ml/min, 10?±?0.3 L/min, and 51?±?26 ml/min, respectively. Mean treatment duration was 31?±?22 h. Day-28 mortality was 15%. CONCLUSIONS:A low-flow ECCO2R device managed with an RRT platform easily and safely enabled very low tidal volume ventilation with moderate increase in PaCO2 in patients with mild-to-moderate ARDS. TRIAL REGISTRATION:ClinicalTrials.gov, NCT02606240. Registered on 17 November 2015.

Project description:Acute respiratory distress syndrome (ARDS) continues to have significant mortality and morbidity. The only intervention proven to reduce mortality is the use of lung-protective mechanical ventilation strategies, although such a strategy may lead to problematic hypercapnia. Extracorporeal carbon dioxide removal (ECCO?R) devices allow uncoupling of ventilation from oxygenation, thereby removing carbon dioxide and facilitating lower tidal volume ventilation. We performed a systematic review to assess efficacy, complication rates, and utility of ECCO?R devices. We included randomised controlled trials (RCTs), case-control studies and case series with 10 or more patients. We searched MEDLINE, Embase, LILACS (Literatura Latino Americana em Ciências da Saúde), and ISI Web of Science, in addition to grey literature and clinical trials registries. Data were independently extracted by two reviewers against predefined criteria and agreement was reached by consensus. Outcomes of interest included mortality, intensive care and hospital lengths of stay, respiratory parameters and complications. The review included 14 studies with 495 patients (two RCTs and 12 observational studies). Arteriovenous ECCO?R was used in seven studies, and venovenous ECCO?R in seven studies. Available evidence suggests no mortality benefit to ECCO?R, although post hoc analysis of data from the most recent RCT showed an improvement in ventilator-free days in more severe ARDS. Organ failure-free days or ICU stay have not been shown to decrease with ECCOvR. Carbon dioxide removal was widely demonstrated as feasible, facilitating the use of lower tidal volume ventilation. Complication rates varied greatly across the included studies, representing technological advances. There was a general paucity of high-quality data and significant variation in both practice and technology used among studies, which confounded analysis. ECCO?R is a rapidly evolving technology and is an efficacious treatment to enable protective lung ventilation. Evidence for a positive effect on mortality and other important clinical outcomes is lacking. Rapid technological advances have led to major changes in these devices and together with variation in study design have limited applicability of analysis. Further well-designed adequately powered RCTs are needed.

Project description:BackgroundUltra-lung-protective ventilation may be useful during veno-venous extracorporeal membrane oxygenation (vv-ECMO) for severe acute respiratory distress syndrome (ARDS) to minimize ventilator-induced lung injury and to facilitate lung recovery. The objective was to compare pulmonary and systemic biotrauma evaluated by numerous biomarkers of inflammation, epithelial, endothelial injuries, and lung repair according to two ventilator strategies on vv-ECMO.MethodsThis is a prospective randomized controlled study. Patients were randomized to receive during 48 h either ultra-lung-protective ventilation combining very low tidal volume (1-2 mL/kg of predicted body weight), low respiratory rate (5-10 cycles per minute), positive expiratory transpulmonary pressure, and 16 h of prone position or lung-protective-ventilation which followed the ECMO arm of the EOLIA trial (control group).ResultsThe primary outcome was the alveolar concentrations of interleukin-1-beta, interleukin-6, interleukin-8, surfactant protein D, and blood concentrations of serum advanced glycation end products and angiopoietin-2 48 h after randomization. Enrollment was stopped for futility after the inclusion of 39 patients. Tidal volume, respiratory rate, minute ventilation, plateau pressure, and mechanical power were significantly lower in the ultra-lung-protective group. None of the concentrations of the pre-specified biomarkers differed between the two groups 48 h after randomization. However, a trend to higher 60-day mortality was observed in the ultra-lung-protective group compared to the control group (45 vs 17%, p = 0.06).ConclusionsDespite a significant reduction in the mechanical power, ultra-lung-protective ventilation during 48 h did not reduce biotrauma in patients with vv-ECMO-supported ARDS. The impact of this ventilation strategy on clinical outcomes warrants further investigation. Trial registration Clinical trial registered with www.Clinicaltrialsgov ( NCT03918603 ). Registered 17 April 2019.

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Feasibility and safety of low-flow extracorporeal carbon dioxide removal to facilitate ultra-protective ventilation in patients with moderate acute respiratory distress sindrome.

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