Extracorporeal membrane oxygenation (ECMO) and extracorporeal carbon dioxide removal (ECCO2R) provide respiratory support aimed at gaining time to allow patient’s recovery from hypoxemic and/or hypercapnic respiratory failure, respectively.1 However, in recent years, very few new oxygenators have been developed.2–4 In this report, we describe a newly designed oxygenator, a component of the MOBYBOX (Hemovent, Aachen, Germany). This oxygenator has a membrane lung surface area of 1.6 m2 consisting of typical polymethylpentene fibers. The fibers are arranged in a stacked design with perpendicular blood flow in theory characterized by a low-pressure difference across the oxygenator. The corners of the oxygenator have been sealed, and the blood flow is directed in a helical fashion into the fiber bundle to eliminate stagnant regions and optimize washout. Limited stagnation was achieved by means of computational flow dynamics (CFD) in silico. Recent long-term sheep experiments revealed a high carbon dioxide (CO2) removal capacity.5 The aim of the current animal study was to evaluate the pressure gradient across the oxygenator and the gas exchange performance within a blood flow rate (BFR) range of 1–4 L/min, typically used in clinical practice for ECMO and ECCO2R.
The study was approved by the Animal Research Committee of Uppsala University in Sweden (ethical approval number: C77/16). Pigs were treated as previously described, targeting severe hypercapnia in the baseline conditions.6,7 A 23Fr/38 cm femoral draining cannula and a 19Fr/15 cm jugular return cannula were placed ultrasound guided. BFR of up to 4 L/min was technically possible while treating pigs with a body weight of 43–47 kg. CO2 removal and oxygen transfer were calculated, as previously described.6,7 Experiments were performed in blood flow steps of 1 L/min from 1 to 4 L/min. Regarding the variability in partial pressure of carbon dioxide (PCO2) level entering the oxygenator and to allow comparisons independent of CO2 level, CO2 removal was normalized to 45 mm Hg before the oxygenator, as previously described.6,7
The pressure drop across the oxygenator was on average 5 ± 1 mm Hg (BFR 1 L/min), 9 ± 1 mm Hg (BFR 2 L/min), 13 ± 2 mm Hg (BFR 3 L/min), and 19 ± 4 mm Hg (BFR 4 L/min). Figure 1A and B demonstrate the PCO2 level pre- and post-oxygenator within each blood flow range, with the corresponding arterial partial pressure of carbon dioxide (PaCO2) values. All PCO2 levels show a substantially decrease with 10 L/min compared to 2 L/min sweep gas flow while using pure oxygen as the sweep gas. Normalization of PaCO2 toward a physiologic level was achieved with BFRs of 3 L/min and above with higher sweep gas flow rates, despite very high baseline PaCO2 values (122 ± 43 mm Hg). Figure 2A demonstrates normalized CO2 removal rates with 2 and 10 L/min of sweep gas flow. For better comparison of the efficiency of the oxygenator, normalized CO2 removal was calculated by normalizing the PCO2 before the membrane lung to 45 mm Hg, as previously described.6,7 CO2 removal increases with increasing BFRs, reaching a maximum of 283 ml CO2/min with a BFR of 4 L/min and a sweep gas flow rate of 10 L/min (normalized). Oxygen transfer increases from 63 ml/min (BFR 1 L/min, sweep gas flow 10 L/min) to 213 ml/min (BFR 4 L/min, sweep gas flow rate 10 L/min). Of note, baseline saturation in the pigs was 90–95%. In contrast to CO2 removal, no difference between sweep gas flow rates of 2 and 10 L/min was noted for oxygen transfer under all BFR conditions.
The current study demonstrates in a porcine model that the oxygenator under study 1) is of very low resistance, reaching a maximum of 19 mm Hg at a BFR of 4 L/min, 2) has a high normalized CO2 removal rate, reaching a maximum of 283 ml CO2/min at high sweep gas flow rates, and 3) has a high oxygen transfer capacity, which is independent of the sweep gas flow rate used.
The very low resistance of the oxygenator may offer the possibility of using it as a passive system driven by natural pressure gradients.8 At least in theory, very low resistance oxygenators offer the possibility to drive passive systems either arteriovenous or by bypassing the lung from the pulmonal artery to the left atrium. Pumpless systems are in general less traumatic in regard of thrombocyte function and may offer some beneficial effects under certain circumstances. Regarding the gas exchange performance, normalizing the CO2 elimination rate to 45 mm Hg pre-oxygenator, values can be more easily compared with previous measurements in similar experiments.6,7 Our previous extracorporeal carbon dioxide removal (ECCO2R) experiments in pigs demonstrated normalized CO2 removal rates of up to 81.1 ± 9.6 mm Hg using membrane lungs with a comparable stacked design (Quadrox, Gettinge, Rastatt, Germany; 1.3 m2). In regard to these data, the current oxygenator provides a higher CO2 removal capacity, making applications in low blood flow ranges potentially quite attractive. Of note, the sweep gas flow rate has a strong impact on CO2 removal capacity, even higher than previously demonstrated.7 This can be explained by the design of the oxygenator. With increasing sweep gas flow rates, the cylindrical fiber geometry facilitates a steady recruitment of additional effective gas exchange fiber sections. The cylindrical fiber deck has a larger portion of shorter fibers in contact with blood, which enhances CO2 removal. In addition, the inflow geometry promotes blood distribution to these fibers in the outer area of the cylinder. In general, the dependency of oxygen and CO2 transfer on sweep gas flow rates clearly differs between oxygenators due to the internal design. Additionally, it has recently been shown that in three contemporary oxygenators, an increased blood flow exhibited lower flow path parameters resulting in less efficient use of the gas exchange.9 Finally, although the blood flow is directed in a helical fashion into the fiber bundle to eliminate stagnant regions and optimize washout, only long-term applications may convincingly demonstrate biocompatibility, especially at low blood flow ranges. In addition, we focus in this Letter on the new oxygenator, while not ignoring that pumps also play a crucial role in blood trauma and hemolysis as recently demonstrated.10,11
The current study has limitations related to the porcine model used and the calculated CO2 removal. These limitations have been extensively discussed in the previous publications on veno-venous-ECCO2R using a very similar set up for these animal experiments.6,7 However, the authors would like to point out that calculation of CO2 removal by blood gas analysis is always an approximation, being reliable in some CO2 ranges and maybe somewhat more inappropriate at more extreme CO2 values. Nevertheless, the approximation seems to be reliable across a wide range of CO2 values typically observed in daily clinical practice.
In conclusion, the current brief report demonstrates the low resistance and high CO2 removal capacity of this new oxygenator, across a wide blood range of blood flows in this porcine model.
1. Karagiannidis C, Brodie D, Strassmann S, et al. Extracorporeal membrane oxygenation: Evolving epidemiology and mortality. Intensive Care Med. 2016; 42:889–896
2. Yeager T, Roy S. Evolution of gas permeable membranes for extracorporeal membrane oxygenation. Artif Organs. 2017; 41:700–709
3. Kaesler A, Rosen M, Schlanstein PC, et al. How computational modeling can help to predict gas transfer in artificial lungs early during development. ASAIO J. 2020; 66:683–690
4. Borchardt R, Schlanstein P, Mager I, Arens J, Schmitz-Rode T, Steinseifer U. In vitro performance testing of a pediatric oxygenator with an integrated pulsatile pump. ASAIO J. 2012; 58:420–425
5. Karagiannidis C, Joost T, Strassmann S, et al. Safety and efficacy of a novel pneumatic-driven ECMO device. Ann Thorac Surg. 2020; pii:S0003-4975(20)30253-8
6. Karagiannidis C, Strassmann S, Brodie D, et al. Impact of membrane lung surface area and blood flow on extracorporeal CO2 removal during severe respiratory acidosis. Intensive Care Med Exp. 2017; 5:34
7. Strassmann S, Merten M, Schäfer S, et al. Impact of sweep gas flow on extracorporeal CO2 removal (ECCO2R). Intensive Care Med Exp. 2019; 7:17
8. Müller T, Lubnow M, Philipp A, et al. Extracorporeal pumpless interventional lung assist in clinical practice: Determinants of efficacy. Eur Respir J. 2009; 33:551–558
9. Hendrix RH, Yeung AK, Ganushchak YM, Weerwind PW. The effect of flow and pressure on the intraoxygenator flow path of different contemporary oxygenators: An in vitro trial. Perfusion. 2020. 267659119899883, Epub ahead of print
10. Maul TM, Aspenleiter M, Palmer D, Sharma MS, Viegas ML, Wearden PD. Impact of circuit size on coagulation and hemolysis complications in pediatric extracorporeal membrane oxygenation. ASAIO J. 2020; 66:1048–1053
11. Appelt H, Philipp A, Mueller T, et al. Factors associated with hemolysis during extracorporeal membrane oxygenation (ECMO)-Comparison of VA- versus VV ECMO. PLoS One. 2020; 15:e0227793