Efficiency in Extracorporeal Membrane Oxygenation—Cellular Deposits on Polymethypentene Membranes Increase Resistance to Blood Flow and Reduce Gas Exchange Capacity KARLA LEHLE,* ALOIS PHILIPP,* OTTO GLEICH,† ANDREAS HOLZAMER,* THOMAS M¨ ULLER,‡ THOMAS BEIN,§ AND CHRISTOF SCHMID* Bioline-coated polymethylpentene (PMP) membrane oxy- genators (MO) are used for extracorporeal membrane ox- ygenation (ECMO) to improve gas exchange in patients with severe acute respiratory distress syndrome (ARDS). However, in some patients, long-term durability is limited due to fibrous and cellular accumulations on the gas exchange surface which can increase resistance to blood flow and diffusion path. These surface deposits of PMP MO after removal were studied with scanning electron and fluorescence microscopy techniques. Three of 31 patients supported by a PMP MO in an ECMO setting required a replacement of the oxygenator after a mean support interval of 11  7 days due to an increase in flow resistance and an impairment of the gas exchange capacity. The membrane surface of the MO was covered with a fibrous network with imbedded platelets and red blood cells. A membranous structure composed of single cells and clusters of cells covered large areas of the PMP fibers. We assume that these cellular deposits lower the effi- cacy of ECMO. The identification of these cells could be a key for future therapeutic interventions and improvements in the development of MO. ASAIO Journal 2008; 54:612– 617. M embrane oxygenators (MO) are integral components for extracorporeal circulation (ECC) in open heart surgery, as well as for mechanical assist systems such as extracorporeal mem- brane oxygenation (ECMO) and interventional lung assist (iLA), which are successfully applied in the management of acute respiratory distress syndrome (ARDS). 1–3 In open heart surgery, ECC is applied for a brief period only, whereas ECMO and iLA are long-term treatment modalities which may be employed for several weeks. 4,5 Most of the ECC components are not suitable for long-term ECMO treatment. In fact, ECMO requires particularly en- hanced biocompatibility such as heparin-coating, low blood flow resistance, and long-term durability. The current devel- opment in ECC technology concentrates on high-performance microporous polypropylene (PPL) capillary MO and nonmi- croporous poly 4-methyl-1-pentene (PMP) diffusion capillary MO, 6 where the molecular structure of PPL and PMP directly affects the physical characteristics of the gas exchange. 7–9 The wall of the plasma-tight PMP membrane consists of a highly porous support matrix and a thin tight membrane on the blood side of the matrix, which constitutes a solid barrier between blood and gas. The homogenous tight membrane and the complete separation of blood and gas phases obviously pro- vide a better biocompatibility with less blood trauma. The crossing of microbubbles caused by a lowered pressure on the blood side compared to the gas side, as well as a plasma leakage does not occur due to the tightness of the membrane. 9 Recent improvements and device innovations in ECMO tech- nology favor the application of MO with PMP capillaries. 10 –15 The PMP MO is highly resistant to plasma leakage and has an acceptable function durability, allowing long-term extracorpo- real application. 13,14 However, despite heparin-coating and continuous systemic low-dose heparin infusion, these MOs can occasionally require early replacement, due to cellular and thrombotic deposits in the blood path with a consecutive increase in blood flow resistance and a consecutive reduction in the gas exchange capacity. 16 Methods Study Design Patients with severe ARDS, who could not be stabilized with standard treatment protocols, were treated with femoro-jugular venovenous ECMO using an optimized ECMO-Set (CE li- censed for use of 14 days in Europe and also approved for Canada while the approval for China still is pending) consist- ing of a Quadrox PLS (Permanent Life Support Set) MO, and a Rotaflow RF 32 centrifugal blood pump (Maquet Cardiopul- monary AG, Hirrlingen, Germany). All components of the ECMO-Set, including the tubing and cannulas are tip to tip coated with heparin (Bioline, Maquet). The MO has a gas exchange area of 1.8 m 2 and is composed of poly-(4-methyl- 1-pentene) capillary fabrics (Membrane, Membrana GmbH, Wuppertal, Germany) for the gas exchange. The recom- mended blood flow rate is 0.5–7.0 L/min. Our ECMO-Set has a very low priming volume of 600 ml. The priming process consisted of 300 ml colloid expander (Gelatinpolysuccinat, Braun, Melsungen, Germany) and 300 ml normal saline with- out any additional drugs, In all patients, systemic low-dose heparin infusion was administered to maintain a partial throm- boplastin time of 50 – 60 seconds (= 1.5 to 2 fold of normal value). If our ARDS patients required volume substitution at the intensive care unit (ICU), it consisted mainly of crystalloids. At From the Departments of *Cardiothoracic Surgery, †ENT, ‡Internal Medicine, and §Anesthesiology, University of Regensburg, Regens- burg, Germany. Submitted for consideration May 2008; accepted for publication in revised form July 2008. Reprint Requests: Dr. Karla Lehle, Department of Cardiothoracic Surgery, University of Regensburg, Franz-Josef-Strauss-Allee 11, D-93042 Regens- burg, Germany. Email: karla.lehle@klinik.uni-regensburg.de. DOI: 10.1097/MAT.0b013e318186a807 ASAIO Journal 2008 612