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      Bench to bedside review: Extracorporeal carbon dioxide removal, past present and future

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          Abstract

          Acute respiratory distress syndrome (ARDS) has a substantial mortality rate and annually affects more than 140,000 people in the USA alone. Standard management includes lung protective ventilation but this impairs carbon dioxide clearance and may lead to right heart dysfunction or increased intracranial pressure. Extracorporeal carbon dioxide removal has the potential to optimize lung protective ventilation by uncoupling oxygenation and carbon dioxide clearance. The aim of this article is to review the carbon dioxide removal strategies that are likely to be widely available in the near future. Relevant published literature was identified using PubMed and Medline searches. Queries were performed by using the search terms ECCOR, AVCO2R, VVCO2R, respiratory dialysis, and by combining carbon dioxide removal and ARDS. The only search limitation imposed was English language. Additional articles were identified from reference lists in the studies that were reviewed. Several novel strategies to achieve carbon dioxide removal were identified, some of which are already commercially available whereas others are in advanced stages of development.

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          Has mortality from acute respiratory distress syndrome decreased over time?: A systematic review.

          Jason Phua, Joan Badia, Neill K. J. Adhikari … (2009)
          It is commonly stated that mortality from acute respiratory distress syndrome (ARDS) and acute lung injury (ALI) is decreasing. To systematically review the literature assessing ARDS mortality over time and to determine patient- and study-level factors independently associated with mortality. We searched multiple databases (MEDLINE, EMBASE, CINAHL, Cochrane CENTRAL) for prospective observational studies or randomized controlled trials (RCTs) published during the period 1984 to 2006 that enrolled 50 or more patients with ALI/ARDS and reported mortality. We pooled mortality estimates using random-effects meta-analysis and examined mortality trends before and after 1994 (when a consensus definition of ALI/ARDS was published) and factors associated with mortality using meta-regression models. Of 4,966 studies, 89 met inclusion criteria (53 observational, 36 RCTs). There was a total of 18,900 patients (mean age 51.6 years; 39% female). Overall pooled weighted mortality was 44.3% (95% confidence interval [CI], 41.8-46.9). Mortality decreased with time in observational studies conducted before 1994; no temporal associations with mortality were demonstrated in RCTs (any time) or observational studies (after 1994). Pooled mortality from 1994 to 2006 was 44.0% (95% CI, 40.1-47.5) for observational studies, and 36.2% (95% CI, 32.1-40.5) for RCTs. Meta-regression identified study type (observational versus RCT, odds ratio, 1.36; 95% CI, 1.08-1.73) and patient age (odds ratio per additional 10 yr, 1.27; 95% CI, 1.07-1.50) as the only factors associated with mortality. A decrease in ARDS mortality was only seen in observational studies from 1984 to 1993. Mortality did not decrease between 1994 (when a consensus definition was published) and 2006, and is lower in RCTs than observational studies.
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            Tidal volume lower than 6 ml/kg enhances lung protection: role of extracorporeal carbon dioxide removal.

            Pier Paolo Terragni, Lorenzo Del Sorbo, Luciana Mascia … (2009)
            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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              Randomized clinical trial of pressure-controlled inverse ratio ventilation and extracorporeal CO2 removal for adult respiratory distress syndrome.

              T Clemmer, A.-B. Morris, Andrea T East … (1994)
              The impact of a new therapy that includes pressure-controlled inverse ratio ventilation followed by extracorporeal CO2 removal on the survival of patients with severe ARDS was evaluated in a randomized controlled clinical trial. Computerized protocols generated around-the-clock instructions for management of arterial oxygenation to assure equivalent intensity of care for patients randomized to the new therapy limb and those randomized to the control, mechanical ventilation limb. We randomized 40 patients with severe ARDS who met the ECMO entry criteria. The main outcome measure was survival at 30 days after randomization. Survival was not significantly different in the 19 mechanical ventilation (42%) and 21 new therapy (extracorporeal) (33%) patients (p = 0.8). All deaths occurred within 30 days of randomization. Overall patient survival was 38% (15 of 40) and was about four times that expected from historical data (p = 0.0002). Extracorporeal treatment group survival was not significantly different from other published survival rates after extracorporeal CO2 removal. Mechanical ventilation patient group survival was significantly higher than the 12% derived from published data (p = 0.0001). Protocols controlled care 86% of the time. Average PaO2 was 59 mm Hg in both treatment groups. Intensity of care required to maintain arterial oxygenation was similar in both groups (2.6 and 2.6 PEEP changes/day; 4.3 and 5.0 FIO2 changes/day). We conclude that there was no significant difference in survival between the mechanical ventilation and the extracorporeal CO2 removal groups. We do not recommend extracorporeal support as a therapy for ARDS. Extracorporeal support for ARDS should be restricted to controlled clinical trials.
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                Author and article information

                Journal
                Journal ID (nlm-ta): Crit Care
                Journal ID (iso-abbrev): Crit Care
                Title: Critical Care
                Publisher: BioMed Central
                ISSN (Print): 1364-8535
                ISSN (Electronic): 1466-609X
                Publication date (Print): 2012
                Publication date (Electronic): 21 September 2012
                Publication date PMC-release: 21 September 2013
                Volume: 16
                Issue: 5
                Page: 232
                Affiliations
                [1 ]Clinical Research, Research, Investigation and Systems Modeling of Acute Illness (CRISMA) Center, Department of Crit Care Med, University of Pittsburgh School of Medicine, 603 Scaife Hall, 3550 Terrace Street, Pittsburgh, PA 15261, USA
                [2 ]Cardiothoracic Intensive Care Unit, National University Health System, 5 Lower Kent Ridge Road, Singapore, 119074
                [3 ]Paediatric Intensive Care Unit, Royal Children's Hospital, Flemington Rd, Melbourne, VIC 3052, Australia
                [4 ]McGowan Institute of Regenerative Medicine, University of Pittsburgh, Room 218, McGowan Building, 3025 East Carson Street, Pittsburgh, PA 15203, USA
                [5 ]Department of Bioengineering and Department of Chemical Engineering, University of Pittsburgh, 3700 O'Hara Street, Pittsburgh, PA 15261, USA
                Article
                Publisher ID: cc11356
                DOI: 10.1186/cc11356
                PMC ID: 3682237
                PubMed ID: 23014710
                SO-VID: 00842be3-f45a-489e-a439-c1fdaec2e956
                Copyright © Copyright ©2012 BioMed Central Ltd
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                Subject: Review

                ScienceOpen disciplines: Emergency medicine & Trauma
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                ScienceOpen disciplines: Emergency medicine & Trauma

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