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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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          Abstract

          Background

          Mechanical ventilation with a tidal volume (V T) of 6 mL/kg/predicted body weight (PBW), to maintain plateau pressure (P plat) lower than 30 cmH 2O, 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 V T combined with extracorporeal carbon dioxide removal (ECCO 2R).

          Methods

          In fifteen patients with moderate ARDS, V T was reduced from baseline to 4 mL/kg PBW while PEEP was increased to target a plateau pressure – (P plat) between 23 and 25 cmH 2O. Low-flow ECCO 2R was initiated when respiratory acidosis developed (pH < 7.25, PaCO 2 > 60 mmHg). Ventilation parameters (V T, respiratory rate, PEEP), respiratory compliance (C RS), driving pressure (DeltaP = V T/C RS), arterial blood gases, and ECCO 2R system operational characteristics were collected during the period of ultra-protective ventilation. Patients were weaned from ECCO 2R when PaO 2/FiO 2 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 ECCO 2R were also collected.

          Results

          During the 2 h run in phase, V T 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, ECCO 2R with an average blood flow of 435 mL/min and sweep gas flow of 10 L/min was effective at correcting pH and PaCO 2 to within 10 % of baseline values. PEEP values tended to increase at V T of 4 mL/kg from 12.2 to 14.5 cmH 2O, 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 cmH 2O; 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).

          Conclusions

          The low-flow ECCO 2R system safely facilitates a low volume, low pressure ultra-protective mechanical ventilation strategy in patients with moderate ARDS.

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          Most cited references14

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          Positive end-expiratory pressure setting in adults with acute lung injury and acute respiratory distress syndrome: a randomized controlled trial.

          The need for lung protection is universally accepted, but the optimal level of positive end-expiratory pressure (PEEP) in patients with acute lung injury (ALI) or acute respiratory distress syndrome remains debated. To compare the effect on outcome of a strategy for setting PEEP aimed at increasing alveolar recruitment while limiting hyperinflation to one aimed at minimizing alveolar distension in patients with ALI. A multicenter randomized controlled trial of 767 adults (mean [SD] age, 59.9 [15.4] years) with ALI conducted in 37 intensive care units in France from September 2002 to December 2005. Tidal volume was set at 6 mL/kg of predicted body weight in both strategies. Patients were randomly assigned to a moderate PEEP strategy (5-9 cm H(2)O) (minimal distension strategy; n = 382) or to a level of PEEP set to reach a plateau pressure of 28 to 30 cm H(2)O (increased recruitment strategy; n = 385). The primary end point was mortality at 28 days. Secondary end points were hospital mortality at 60 days, ventilator-free days, and organ failure-free days at 28 days. The 28-day mortality rate in the minimal distension group was 31.2% (n = 119) vs 27.8% (n = 107) in the increased recruitment group (relative risk, 1.12 [95% confidence interval, 0.90-1.40]; P = .31). The hospital mortality rate in the minimal distension group was 39.0% (n = 149) vs 35.4% (n = 136) in the increased recruitment group (relative risk, 1.10 [95% confidence interval, 0.92-1.32]; P = .30). The increased recruitment group compared with the minimal distension group had a higher median number of ventilator-free days (7 [interquartile range {IQR}, 0-19] vs 3 [IQR, 0-17]; P = .04) and organ failure-free days (6 [IQR, 0-18] vs 2 [IQR, 0-16]; P = .04). This strategy also was associated with higher compliance values, better oxygenation, less use of adjunctive therapies, and larger fluid requirements. A strategy for setting PEEP aimed at increasing alveolar recruitment while limiting hyperinflation did not significantly reduce mortality. However, it did improve lung function and reduced the duration of mechanical ventilation and the duration of organ failure. clinicaltrials.gov Identifier: NCT00188058.
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            Tidal hyperinflation during low tidal volume ventilation in acute respiratory distress syndrome.

            Tidal volume and plateau pressure limitation decreases mortality in acute respiratory distress syndrome. Computed tomography demonstrated a small, normally aerated compartment on the top of poorly aerated and nonaerated compartments that may be hyperinflated by tidal inflation. We hypothesized that despite tidal volume and plateau pressure limitation, patients with a larger nonaerated compartment are exposed to tidal hyperinflation of the normally aerated compartment. Pulmonary computed tomography at end-expiration and end-inspiration was obtained in 30 patients ventilated with a low tidal volume (6 ml/kg predicted body weight). Cluster analysis identified 20 patients in whom tidal inflation occurred largely in the normally aerated compartment (69.9 +/- 6.9%; "more protected"), and 10 patients in whom tidal inflation occurred largely within the hyperinflated compartments (63.0 +/- 12.7%; "less protected"). The nonaerated compartment was smaller and the normally aerated compartment was larger in the more protected patients than in the less protected patients (p = 0.01). Pulmonary cytokines were lower in the more protected patients than in the less protected patients (p < 0.05). Ventilator-free days were 7 +/- 8 and 1 +/- 2 d in the more protected and less protected patients, respectively (p = 0.01). Plateau pressure ranged between 25 and 26 cm H(2)O in the more protected patients and between 28 and 30 cm H(2)O in the less protected patients (p = 0.006). Limiting tidal volume to 6 ml/kg predicted body weight and plateau pressure to 30 cm H(2)O may not be sufficient in patients characterized by a larger nonaerated compartment.
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              Tidal volume lower than 6 ml/kg enhances lung protection: role of extracorporeal carbon dioxide removal.

              Tidal hyperinflation may occur in patients with acute respiratory distress syndrome who are ventilated with a tidal volume (VT) of 6 ml/kg of predicted body weight develop a plateau pressure (PPLAT) of 28 < or = PPLAT < or = 30 cm H2O. The authors verified whether VT lower than 6 ml/kg may enhance lung protection and that consequent respiratory acidosis may be managed by extracorporeal carbon dioxide removal. PPLAT, lung morphology computed tomography, and pulmonary inflammatory cytokines (bronchoalveolar lavage) were assessed in 32 patients ventilated with a VT of 6 ml/kg. Data are provided as mean +/- SD or median and interquartile (25th and 75th percentile) range. In patients with 28 < or = PPLAT < or = 30 cm H2O (n = 10), VT was reduced from 6.3 +/- 0.2 to 4.2 +/- 0.3 ml/kg, and PPLAT decreased from 29.1 +/- 1.2 to 25.0 +/- 1.2 cm H2O (P < 0.001); consequent respiratory acidosis (Paco2 from 48.4 +/- 8.7 to 73.6 +/- 11.1 mmHg and pH from 7.36 +/- 0.03 to 7.20 +/- 0.02; P < 0.001) was managed by extracorporeal carbon dioxide removal. Lung function, morphology, and pulmonary inflammatory cytokines were also assessed after 72 h. Extracorporeal assist normalized Paco2 (50.4 +/- 8.2 mmHg) and pH (7.32 +/- 0.03) and allowed use of VT lower than 6 ml/kg for 144 (84-168) h. The improvement of morphological markers of lung protection and the reduction of pulmonary cytokines concentration (P < 0.01) were observed after 72 h of ventilation with VT lower than 6 ml/kg. No patient-related complications were observed. VT lower than 6 ml/Kg enhanced lung protection. Respiratory acidosis consequent to low VT ventilation was safely and efficiently managed by extracorporeal carbon dioxide removal.
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                Author and article information

                Contributors
                +39-011 633 4005 , vito.fanelli@unito.it
                Journal
                Crit Care
                Critical Care
                BioMed Central (London )
                1364-8535
                1466-609X
                10 February 2016
                10 February 2016
                2015
                : 20
                : 36
                Affiliations
                [ ]Department of Anesthesia and Critical Care - AOU Città della Salute e della Scienza di Torino, University of Turin, Corso Dogliotti 14, 10126 Torino, Italy
                [ ]Dipartimento di Anestesia e Rianimazione, Ospedale Policlinico Umberto I, Sapienza Università di Roma, Rome, Italy
                [ ]Servei de Medicina Intensiva, Hospital de Sant Pau, Barcelona, Spain
                [ ]Department of Anesthesiology, Emergency and Intensive Care Medicine, University Medical Center Göttingen, Göttingen, Germany
                [ ]ALung Technologies, Pittsburgh, USA
                [ ]Service de Réanimation Médicale, iCAN, Institute of Cardiometabolism and Nutrition, Hôpital de la Pitié-Salpêtrière, Assistance Publique-Hôpitaux de Paris, Paris, France
                Article
                1211
                10.1186/s13054-016-1211-y
                4748548
                26861596
                90d25b17-59ed-49bd-b36a-160b4fd91662
                © Fanelli et al. 2016

                Open AccessThis article is distributed under the terms of the Creative Commons Attribution 4.0 International License ( http://creativecommons.org/licenses/by/4.0/), which permits unrestricted use, distribution, and reproduction in any medium, provided you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made. The Creative Commons Public Domain Dedication waiver ( http://creativecommons.org/publicdomain/zero/1.0/) applies to the data made available in this article, unless otherwise stated.

                History
                : 28 September 2015
                : 31 January 2016
                Categories
                Research
                Custom metadata
                © The Author(s) 2016

                Emergency medicine & Trauma
                acute respiratory distress syndrome,protective mechanical ventilation,extracorporeal carbon dioxide removal,extracorporeal membrane oxygenation,positive end-expiratory pressure,driving pressure,ventilator-induced lung injury

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