Long-term treatment of patients with respiratory distress syndrome with extracorporeal membrane oxygenation (ECMO) goes along with the risk of thrombotic fibrous and cellular deposits on the gas exchange surface of the device.1,2 This condition often requires an exchange of the membrane oxygenator (MO), which is expensive and clinically dangerous for critically ill patients.
Biochemical markers of coagulation and fibrinolysis seem to indicate the dysfunction of MO devices caused by thrombotic activity.3 However, there is no reliable technical or laboratory approach for direct visualization, quantification, or monitoring of these thrombotic complications in vivo.
In this feasibility study, we describe our first experience of visualization of thrombotic deposits in ECMO devices using advanced multidetector computed tomography (MDCT) under ex vivo conditions.
Materials and Methods
We evaluated the permanent life support (PLS) set with an integrated bioline-coated polymethylpentene oxygenator (MAQUET Cardiopulmonary AG, Hirrlingen, Germany). The technique of extracorporeal lung support has previously been described in detail elsewhere.2 During ECMO treatment, a continuous systemic low-dose heparin infusion was administered to maintain a partial thromboplastin time (PTT) of more than 60 seconds. A plot of the PTT values of the patient is given in Table 1. The MO device reported in this study derives from a patient who could be successfully weaned from ECMO treatment after 8 days. The device showed no clinically obvious dysfunction (device 1). Besides this oxygenator, we examined a second, factory-sealed MO that served as an internal quality control for the applied advanced MDCT three-dimensional (3D)-visualization techniques (device 2).
Both oxygenators were rinsed with regular saline solution (0.9% w/v of NaCl) and then examined by MDCT. After the computed tomography (CT) scan, the used oxygenator (device 1) was anatomically dissected for direct visualization of potential deposits on the diffusion capillaries of the MO device and further analyzed by scanning electron microscopy (SEM) as described previously.2
Multidetector Computed Tomography
Multidetector computed tomography images were acquired using a 128 slice MDCT scanner (Somatom Sensation Flash; Siemens Medical Solutions, Erlangen, Germany). The following scan parameters were used: collimation 128 × 0.6 mm, rotation time 0.28 seconds, pitch 0.6, tube voltage 120 kV, and tube current dose modulated 32–110 mAs. The scans were performed without injection of contrast media into the device. The isotropic secondary 3D volume dataset with 0.6 mm3 voxel size was analyzed using postprocessing software with advanced 3D visualization (syngo.via, version VA11A; Siemens Medical Solutions). We performed 3D visualization using volume rendering techniques (VRTs).
Device 1 showed macroscopically suspicious signs of clot formation. On the VRT 3D model based on the MDCT dataset, the red-coded areas within the gas exchange surface of the device are consistent with fibrous and cellular deposits (Figures 1 and 2). These deposits could be confirmed by anatomical dissection of the device (Figure 3) and using SEM, which showed a meshwork of fibrin strands with accumulation of platelets and red blood cells within the conspicuous red-coded areas of the device (Figure 4).
Device 2 showed no signs of clot formation in MDCT using the same VRT settings as in device 1 (Figures 1 and 2).
It was demonstrated that MDCT with VRT is able to visualize thrombotic deposits in ECMO devices under ex vivo conditions without the need to open the device. Our first results show thrombotic clot formation in an MO device after 8 days of treatment. The presence of these deposits could be confirmed by SEM, a method which is considered to be the gold standard in identification of fibrous and cellular deposits in ECMO devices.2
The nonbiological surface of an extracorporeal circuit leads to a general activation and consumption of procoagulant and anticoagulant components.4 The formation of thrombotic deposits on the gas exchange surface of the ECMO device may induce an increasing resistance in the diffusion capillaries and an increased transmembrane pressure gradient potentially reducing the gas exchange capacity and leading to a malfunction of the device.1
The ECMO device examined in our study showed extensive clot formation in the venous half of the device, despite the stringent anticoagulation of the patient with PTT values of approximately 70 seconds (Table 1). However, the device showed no clinically obvious dysfunction. Further investigations with larger sample sizes are necessary to study the impact of thrombotic deposits detected by MDCT on the oxygenator’s function and the clinical outcome of the patient. Comparative analyses of the MDCT findings of ECMO devices with obvious dysfunction and the findings of patients with uncomplicated ECMO treatment have to be conducted. The description of clot size and volume, the characterization of the distribution of deposits within the oxygenators, as well as the correlation of thrombus size and volume to the findings from blood gas analysis and laboratory values of anticoagulation will be of further interest. This could lead to a better understanding of the impact of clot formation on the function of the device and on the clinical outcome of the patient.
From a more clinical point of view, MDCT is far away from being a routine method for monitoring patients under ECMO treatment. Encouraged by our initial results, numerous further studies have to be conducted, including in vitro experiments, to evaluate the capability of MDCT for detecting thrombotic deposits in oxygenators streamed with blood.
However, MDCT allows direct visualization of the actual thrombus load of a used ECMO device as well as the quantification of the thrombus volume and could, therefore, play a significant role in better understanding the oxygenator thrombosis in modern ECMO treatment.
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2. Lehle K, Philipp A, Gleich O, et al. Efficiency in extracorporeal membrane oxygenation-cellular deposits on polymethylpentene membranes increase resistance to blood flow and reduce gas exchange capacity. ASAIO J. 2008;54:612–617
3. Arnold P, Jackson S, Wallis J, Smith J, Bolton D, Haynes S. Coagulation factor activity during neonatal extra-corporeal membrane oxygenation. Intensive Care Med. 2001;27:1395–1400
4. Oliver WC. Anticoagulation and coagulation management for ECMO. Semin Cardiothorac Vasc Anesth. 2009;13:154–175