Venovenous extracorporeal CO 2 removal to support ultraprotective ventilation in moderate-severe acute respiratory distress syndrome: A systematic review and meta-analysis of the literature
Restricted accessResearch articleFirst published online July, 2023
Venovenous extracorporeal CO 2 removal to support ultraprotective ventilation in moderate-severe acute respiratory distress syndrome: A systematic review and meta-analysis of the literature
A strategy that limits tidal volumes and inspiratory pressures, improves outcomes in patients with the acute respiratory distress syndrome (ARDS). Extracorporeal carbon dioxide removal (ECCO2R) may facilitate ultra-protective ventilation. We conducted a systematic review and meta-analysis to evaluate the efficacy and safety of venovenous ECCO2R in supporting ultra-protective ventilation in moderate-to-severe ARDS.
Methods
MEDLINE and EMBASE were interrogated for studies (2000–2021) reporting venovenous ECCO2R use in patients with moderate-to-severe ARDS. Studies reporting ≥10 adult patients in English language journals were included. Ventilatory parameters after 24 h of initiating ECCO2R, device characteristics, and safety outcomes were collected. The primary outcome measure was the change in driving pressure at 24 h of ECCO2R therapy in relation to baseline. Secondary outcomes included change in tidal volume, gas exchange, and safety data.
Results
Ten studies reporting 421 patients (PaO2:FiO2 141.03 mmHg) were included. Extracorporeal blood flow rates ranged from 0.35-1.5 L/min. Random effects modelling indicated a 3.56 cmH2O reduction (95%-CI: 3.22–3.91) in driving pressure from baseline (p < .001) and a 1.89 mL/kg (95%-CI: 1.75–2.02, p < .001) reduction in tidal volume. Oxygenation, respiratory rate and PEEP remained unchanged. No significant interactions between driving pressure reduction and baseline driving pressure, partial pressure of arterial carbon dioxide or PaO2:FiO2 ratio were identified in metaregression analysis. Bleeding and haemolysis were the commonest complications of therapy.
Conclusions
Venovenous ECCO2R permitted significant reductions in ∆P in patients with moderate-to-severe ARDS. Heterogeneity amongst studies and devices, a paucity of randomised controlled trials, and variable safety reporting calls for standardisation of outcome reporting. Prospective evaluation of optimal device operation and anticoagulation in high quality studies is required before further recommendations can be made.
BellaniGLaffeyJGPhamT, et al.Epidemiology, patterns of care, and mortality for patients with acute respiratory distress syndrome in intensive care units in 50 countries. JAMA2016; 315(8): 788–800.
2.
StapletonRDWangBMHudsonLD, et al.Causes and timing of death in patients with ARDS. Chest2005; 128(2): 525–532.
3.
Acute Respiratory Distress SyndromeNBrowerRGMatthayMA, et al.Ventilation with lower tidal volumes as compared with traditional tidal volumes for acute lung injury and the acute respiratory distress syndrome. N Engl J Med2000; 342(18): 1301–1308.
4.
SutherasanYVargasMPelosiP. Protective mechanical ventilation in the non-injured lung: review and meta-analysis. Crit Care2014; 18(2): 211.
5.
AmatoMBMeadeMOSlutskyAS, et al.Driving pressure and survival in the acute respiratory distress syndrome. N Engl J Med2015; 372(8): 747–755.
6.
BugedoGRetamalJBruhnA. Driving pressure: a marker of severity, a safety limit, or a goal for mechanical ventilation?Crit Care2017; 21(1): 199.
7.
Serpa NetoASchmidtMAzevedoLC, et al.Associations between ventilator settings during extracorporeal membrane oxygenation for refractory hypoxemia and outcome in patients with acute respiratory distress syndrome: a pooled individual patient data analysis: mechanical ventilation during ECMO. Intensive Care Med2016; 42(11): 1672–1684.
8.
ParharKKSZjadewiczKSooA, et al.Epidemiology, mechanical power, and 3-year outcomes in acute respiratory distress syndrome patients using standardized screening. an observational cohort study. Ann Am Thorac Soc2019; 16(10): 1263–1272.
9.
AoyamaHPettenuzzoTAoyamaK, et al.Association of driving pressure with mortality among ventilated patients with acute respiratory distress syndrome: a systematic review and meta-analysis. Crit Care Med2018; 46(2): 300–306.
10.
GattinoniLTonettiTCressoniM, et al.Ventilator-related causes of lung injury: the mechanical power. Intensive Care Med2016; 42(10): 1567–1575.
11.
MariniJJJaberS. Dynamic predictors of VILI risk: beyond the driving pressure. Intensive Care Med2016; 42(10): 1597–1600.
12.
ProttiAMaraffiTMilesiM, et al.Role of strain rate in the pathogenesis of ventilator-induced lung edema. Crit Care Med2016; 44(9): e838–e845.
13.
RichardJCMarqueSGrosA, et al.Feasibility and safety of ultra-low tidal volume ventilation without extracorporeal circulation in moderately severe and severe ARDS patients. Intensive Care Med2019; 45(11): 1590–1598.
14.
QuintelMBusanaMGattinoniL. Breathing and ventilation during extracorporeal membrane oxygenation: how to find the balance between rest and load. Am J Respir Crit Care Med2019; 200(8): 954–956.
15.
VadaszIHubmayrRDNinN, et al.Hypercapnia: a nonpermissive environment for the lung. Am J Respir Cel Mol Biol2012; 46(4): 417–421.
16.
CurleyGContrerasMMNicholAD, et al.Hypercapnia and acidosis in sepsis: a double-edged sword?Anesthesiology2010; 112(2): 462–472.
17.
Mekontso DessapABoissierFCharronC, et al.Acute cor pulmonale during protective ventilation for acute respiratory distress syndrome: prevalence, predictors, and clinical impact. Intensive Care Med2016; 42(5): 862–870.
18.
CoveMEMacLarenGFederspielWJ, et al.Bench to bedside review: extracorporeal carbon dioxide removal, past present and future. Crit Care2012; 16(5): 232.
19.
AbramsDBacchettaMBrodieD. When the momentum has gone: what will be the role of extracorporeal lung support in the future?Curr Opin Crit Care2018; 24(1): 23–28.
20.
SchmidtPRitscherLDongEN, et al.Identification of determinants required for agonistic and inverse agonistic ligand properties at the ADP receptor P2Y12. Mol Pharmacol2013; 83(1): 256–266.
21.
CombesAHajageDCapellierG, et al.Extracorporeal membrane oxygenation for severe acute respiratory distress syndrome. N Engl J Med2018; 378(21): 1965–1975.
22.
AraosJAlegriaLGarciaP, et al.Near-apneic ventilation decreases lung injury and fibroproliferation in an acute respiratory distress syndrome model with extracorporeal membrane oxygenation. Am J Respir Crit Care Med2019; 199(5): 603–612.
23.
FicialBVasquesFZhangJ, et al.Physiological Basis of Extracorporeal Membrane Oxygenation and Extracorporeal Carbon Dioxide Removal in Respiratory Failure. Membranes (Basel)2021; 11(3).
SchmidtMTachonGDevilliersC, et al.Blood oxygenation and decarboxylation determinants during venovenous ECMO for respiratory failure in adults. Intensive Care Med2013; 39(5): 838–846.
26.
KaragiannidisCStrassmannSBrodieD, et al.Impact of membrane lung surface area and blood flow on extracorporeal CO2 removal during severe respiratory acidosis. Intensive Care Med Exp2017; 5(1): 34.
27.
StrassmannSMertenMSchaferS, et al.Impact of sweep gas flow on extracorporeal CO2 removal (ECCO2R). Intensive Care Med Exp2019; 7(1): 17.
28.
MorelliADel SorboLPesentiA, et al.Extracorporeal carbon dioxide removal (ECCO2R) in patients with acute respiratory failure. Intensive Care Med2017; 43(4): 519–530.
29.
GiraudRBanfiCAssoulineB, et al.The use of extracorporeal CO2 removal in acute respiratory failure. Ann Intensive Care2021; 11(1): 43.
30.
DeniauBRicardJDMessikaJ, et al.Use of extracorporeal carbon dioxide removal (ECCO2R) in 239 intensive care units: results from a French national survey. Intensive Care Med2016; 42(4): 624–625.
31.
GattinoniLKolobowTTomlinsonT, et al.Low-frequency positive pressure ventilation with extracorporeal carbon dioxide removal (LFPPV-ECCO2R): an experimental study. Anesth Analg1978; 57(4): 470–477.
32.
LiberatiAAltmanDGTetzlaffJ, et al.The PRISMA statement for reporting systematic reviews and meta-analyses of studies that evaluate healthcare interventions: explanation and elaboration. BMJ2009; 339: b2700.
33.
TacconeFSMalfertheinerMVFerrariF, et al.Extracorporeal CO2 removal in critically ill patients: a systematic review. Minerva Anestesiol2017; 83(7): 762–772.
34.
CombesAPeekGJHajageD, et al.ECMO for severe ARDS: systematic review and individual patient data meta-analysis. Intensive Care Med2020; 46(11): 2048–2057.
35.
BernardGRArtigasABrighamKL, et al.The American-European Consensus conference on ARDS. Definitions, mechanisms, relevant outcomes, and clinical trial coordination. Am J Respir Crit Care Med1994; 149(3 Pt 1): 818–824.
36.
ForceADTRanieriVMRubenfeldGD, et al.Acute respiratory distress syndrome: the Berlin definition. JAMA2012; 307(23): 2526–2533.
37.
MullerTLubnowMPhilippA, et al.Extracorporeal pumpless interventional lung assist in clinical practice: determinants of efficacy. Eur Respir J2009; 33(3): 551–558.
38.
HermannARissKSchellongowskiP, et al.A novel pump-driven veno-venous gas exchange system during extracorporeal CO2-removal. Intensive Care Med2015; 41(10): 1773–1780.
39.
FischerSSimonARWelteT, et al.Bridge to lung transplantation with the novel pumpless interventional lung assist device NovaLung. J Thorac Cardiovasc Surg2006; 131(3): 719–723.
40.
BeinTWeberFPhilippA, et al.A new pumpless extracorporeal interventional lung assist in critical hypoxemia/hypercapnia. Crit Care Med2006; 34(5): 1372–1377.
41.
KuoIAkpaBS. Validity of the lipid sink as a mechanism for the reversal of local anesthetic systemic toxicity: a physiologically based pharmacokinetic model study. Anesthesiology2013; 118(6): 1350–1361.
42.
HigginsJPTLiTDeeksJJChoosing effect measures and computing estimates of effect. In: Higgins JPT, Thomas J, Chandler J, Cumpston M, Li T, Page MJ, Welch VA (editors).. In Cochrane Handbook for Systematic Reviews of Interventionsversion 6.3(updated February 2022). Cochrane, 2022. Available from www.training.cochrane.org/handbook
43.
DerSimonianRLairdN. Meta-analysis in clinical trials. Control Clin Trials1986; 7(3): 177–188.
44.
MillerJJ. The inverse of the freeman–Tukey double arcsine transformation. The Am Statistician1978; 32(4): 138.
45.
ClopperCJPearsonES. The use of confidence or fiducial limits illustrated in the case of the binomial. Biometrika1934; 26(4): 404–413.
46.
IorioASpencerFAFalavignaM, et al.Use of GRADE for assessment of evidence about prognosis: rating confidence in estimates of event rates in broad categories of patients. BMJ2015; 350: h870.
47.
TerragniPPDel SorboLMasciaL, et al.Tidal volume lower than 6 ml/kg enhances lung protection: role of extracorporeal carbon dioxide removal. Anesthesiology2009; 111(4): 826–835.
48.
McNameeJJGilliesMABarrettNA, et al.Effect of lower tidal volume ventilation facilitated by extracorporeal carbon dioxide removal vs standard care ventilation on 90-day mortality in patients with acute hypoxemic respiratory failure: the REST randomized clinical trial. JAMA2021.
49.
AugyJLAissaouiNRichardC, et al.A 2-year multicenter, observational, prospective, cohort study on extracorporeal CO2 removal in a large metropolis area. J Intensive Care2019; 7: 45.
50.
WiniszewskiHAptelFBelonF, et al.Daily use of extracorporeal CO2 removal in a critical care unit: indications and results. J Intensive Care2018; 6: 36.
51.
PeperstraeteHElootSDepuydtP, et al.Low flow extracorporeal CO2 removal in ARDS patients: a prospective short-term crossover pilot study. BMC Anesthesiol2017; 17(1): 155.
52.
CombesAFanelliVPhamT, et al.European society of intensive care medicine trials g, the “strategy of ultra-protective lung ventilation with extracorporeal CORfN-OmtsAi. Feasibility and safety of extracorporeal CO2 removal to enhance protective ventilation in acute respiratory distress syndrome: the SUPERNOVA study. Intensive Care Med2019; 45(5): 592–600.
53.
GoursaudSValetteXDupeyratJ, et al.Ultraprotective ventilation allowed by extracorporeal CO2 removal improves the right ventricular function in acute respiratory distress syndrome patients: a quasi-experimental pilot study. Ann Intensive Care2021; 11(1): 3.
54.
FitzgeraldMMillarJBlackwoodB, et al.Extracorporeal carbon dioxide removal for patients with acute respiratory failure secondary to the acute respiratory distress syndrome: a systematic review. Crit Care2014; 18(3): 222.
55.
CombesAAuzingerGCapellierG, et al.ECCO2R therapy in the ICU: consensus of a European round table meeting. Crit Care2020; 24(1): 490.
56.
GoligherECCombesABrodieD, et al.Determinants of the effect of extracorporeal carbon dioxide removal in the SUPERNOVA trial: implications for trial design. Intensive Care Med2019; 45(9): 1219–1230.
57.
GoligherECAmatoMBPSlutskyAS. Applying precision medicine to trial design using physiology. extracorporeal CO2 removal for acute respiratory distress syndrome. Am J Respir Crit Care Med2017; 196(5): 558–568.
58.
DasACamporotaLHardmanJG, et al.What links ventilator driving pressure with survival in the acute respiratory distress syndrome? A computational study. Respir Res2019; 20(1): 29.
59.
RozencwajgSGuihotAFranchineauG, et al.Ultra-protective ventilation reduces biotrauma in patients on venovenous extracorporeal membrane oxygenation for severe acute respiratory distress syndrome. Crit Care Med2019; 47(11): 1505–1512.
60.
BeitlerJR. Lung protection in acute respiratory distress syndrome: what should we target?Curr Opin Crit Care2019.
61.
CalfeeCSDelucchiKFamousKR. Reply: next step to understanding subphenotypes of acute respiratory distress syndrome. Am J Respir Crit Care Med2017; 196(6): 796.
62.
BeinTWeber-CarstensSGoldmannA, et al.Lower tidal volume strategy ( approximately 3 ml/kg) combined with extracorporeal CO2 removal versus 'conventional’ protective ventilation (6 ml/kg) in severe ARDS: the prospective randomized Xtravent-study. Intensive Care Med2013; 39(5): 847–856.
63.
ChiuLCTsaiFCHuHC, et al.Survival predictors in acute respiratory distress syndrome with extracorporeal membrane oxygenation. Ann Thorac Surg2015; 99(1): 243–250.
64.
DamlujiAColantuoniEMendez-TellezPA, et al.Short-term mortality prediction for acute lung injury patients: external validation of the acute respiratory distress syndrome network prediction model. Crit Care Med2011; 39(5): 1023–1028.
65.
Writing Group for the Alveolar Recruitment for Acute RespiratoryDistress Syndrome TrialICavalcantiAB, et al.Effect of lung recruitment and titrated positive end-expiratory pressure (PEEP) vs low peep on mortality in patients with acute respiratory distress syndrome: a randomized clinical trial. JAMA2017; 318(14): 1335–1345.
66.
TonnaJEPeltanIDBrownSM, et al.Positive end-expiratory pressure and respiratory rate modify the association of mechanical power and driving pressure with mortality among patients with acute respiratory distress syndrome. Crit Care Explor2021; 3(12): e0583.
67.
CressoniMGottiMChiurazziC, et al.Mechanical power and development of ventilator-induced lung injury. Anesthesiology2016; 124(5): 1100–1108.
68.
GiosaLBusanaMPasticciI, et al.Mechanical power at a glance: a simple surrogate for volume-controlled ventilation. Intensive Care Med Exp2019; 7(1): 61.
69.
MaioloGCollinoFVasquesF, et al.Reclassifying acute respiratory distress syndrome. Am J Respir Crit Care Med2018; 197(12): 1586–1595.
70.
ChiumelloDBrioniM. Severe hypoxemia: which strategy to choose. Crit Care2016; 20(1): 132.
71.
GoligherECCostaELVYarnellCJ, et al.Effect of lowering tidal volume on mortality in ARDS varies with respiratory system elastance. Am J Respir Crit Care Med2021.
72.
SpinelliEMauriTLissoniA, et al.Spontaneous breathing patterns during maximum extracorporeal CO2 removal in subjects with early severe ARDS. Respir Care2020; 65(7): 911–919.
73.
SpinelliEMauriTBeitlerJR, et al.Respiratory drive in the acute respiratory distress syndrome: pathophysiology, monitoring, and therapeutic interventions. Intensive Care Med2020; 46(4): 606–618.
74.
VaporidiKAkoumianakiETeliasI, et al.Respiratory drive in critically Ill Patients. Pathophysiology and clinical implications. Am J Respir Crit Care Med2020; 201(1): 20–32.
75.
FranchineauGBrechotNHekimianG, et al.Prone positioning monitored by electrical impedance tomography in patients with severe acute respiratory distress syndrome on veno-venous ECMO. Ann Intensive Care2020; 10(1): 12.
76.
CharronCRepesseXBouferracheK, et al.PaCO2 and alveolar dead space are more relevant than PaO2/FiO2 ratio in monitoring the respiratory response to prone position in ARDS patients: a physiological study. Crit Care2011; 15(4): R175.
77.
GattinoniLVagginelliFCarlessoE, et al.Decrease in PaCO2 with prone position is predictive of improved outcome in acute respiratory distress syndrome. Crit Care Med2003; 31(12): 2727–2733.
78.
Vieillard-BaronACharronCCailleV, et al.Prone positioning unloads the right ventricle in severe ARDS. Chest2007; 132(5): 1440–1446.
79.
TiruvoipatiRPeekG. Extracorporeal carbon dioxide removal vs standard care ventilation effect on 90-day mortality in patients with acute hypoxemic respiratory failure. JAMA2022; 327(1): 83–84.
80.
EthgenOGoldsteinJHarenskiK, et al.A preliminary cost-effectiveness analysis of lung protective ventilation with extra corporeal carbon dioxide removal (ECCO2R) in the management of acute respiratory distress syndrome (ARDS). J Crit Care2021; 63: 45–53.
81.
PoonWHRamanathanKLingRR, et al.Prone positioning during venovenous extracorporeal membrane oxygenation for acute respiratory distress syndrome: a systematic review and meta-analysis. Crit Care2021; 25(1): 292.
82.
MustafaAKAlexanderPJJoshiDJ, et al.Extracorporeal membrane oxygenation for patients with COVID-19 in severe respiratory failure. JAMA Surg2020; 155(10): 990–992.
83.
Figueroa VillalbaCABroganTVMcMullanDM, et al.Conversion from activated clotting time to Anti-Xa Heparin activity assay for heparin monitoring during extracorporeal membrane oxygenation. Crit Care Med2020.
84.
CombesATonettiTFanelliV, et al.Efficacy and safety of lower versus higher CO2 extraction devices to allow ultraprotective ventilation: secondary analysis of the SUPERNOVA study. Thorax2019; 74(12): 1179–1181.
85.
KiKKPassmoreMRChanCHH, et al.Low flow rate alters haemostatic parameters in an ex-vivo extracorporeal membrane oxygenation circuit. Intensive Care Med Exp2019; 7(1): 51.
86.
SchneiderSWNuscheleSWixforthA, et al.Shear-induced unfolding triggers adhesion of von Willebrand factor fibers. Proc Natl Acad Sci U S A2007; 104(19): 7899–7903.
87.
Gross-HardtSHesselmannFArensJ, et al.Low-flow assessment of current ECMO/ECCO2R rotary blood pumps and the potential effect on hemocompatibility. Crit Care2019; 23(1): 348.
88.
HeilmannCGeisenUBeyersdorfF, et al.Acquired von Willebrand syndrome in patients with ventricular assist device or total artificial heart. Thromb Haemost2010; 103(5): 962–967.
89.
HeilmannCGeisenUBeyersdorfF, et al.Acquired von Willebrand syndrome in patients with extracorporeal life support (ECLS). Intensive Care Med2012; 38(1): 62–68.
90.
HeilmannCTrummerGBeyersdorfF, et al.Acquired Von Willebrand syndrome in patients on long-term support with HeartMate II. Eur J Cardiothorac Surg2017; 51(3): 587–590.
91.
WuJPadenBEBorovetzHS, et al.Computational fluid dynamics analysis of blade tip clearances on hemodynamic performance and blood damage in a centrifugal ventricular assist device. Artif Organs2010; 34(5): 402–411.
92.
MorimontPHabranSDesaiveT, et al.Extracorporeal CO2 removal and regional citrate anticoagulation in an experimental model of hypercapnic acidosis. Artif Organs2019; 43(8): 719–727.
93.
BarbaroRPOdetolaFOKidwellKM, et al.Association of hospital-level volume of extracorporeal membrane oxygenation cases and mortality. Analysis of the extracorporeal life support organization registry. Am J Respir Crit Care Med2015; 191(8): 894–901.
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