In a simulation setting, we demonstrated that more proximal arterial cannula tip positioning within the aorta improves VA ECMO blood perfusion to the aortic arch branches. This finding was present even during low levels of support when the cannula tip was placed in P4. We also found much higher perfusion of blood from VA ECMO to the brachiocephalic artery (BCA) during P4 at 90% support compared to all other positions, thereby demonstrating the capacity to reduce the incidence of differential hypoxia.
Differential hypoxia is a common and potentially catastrophic complication caused by the competing flow dynamics between native left ventricular ejection and perfusion from the VA ECMO circuit. In a single center study that involved 720 ECMO patients, Rupprecht et al. reported an incidence rate of 8.8% for complications arising due to upper body hypoxia . This was the second most frequent complication they observed and often required intervention to improve upper body oxygen saturation levels. Differential hypoxia is associated with poor perfusion of oxygenated blood to the brain. For example, Pozzebon et al. reported cerebral desaturation (defined as < 60% oxygen saturation for > 5% ECMO duration) in 43 (74%) ECMO patients using near-infrared spectroscopy applied to the patients’ foreheads . Moreover, 18 (42%) of these patients went on to develop acute cerebral complications such as stroke and brain death. However, patients with no cerebral de-saturation experienced no acute cerebral complications. Clinical interventions for improving cerebral oxygenation include relocation of the arterial cannula to more proximal locations such as the right subclavian artery and also changing the VA ECMO circuit to a VA-Venous configuration [5, 6, 17–19]. Changing the VA ECMO circuit configuration in this manner is a common method of treating differential hypoxia but involves an additional cannulation site, which can increase the risk of bleeding. It is clear that current clinical practices in peripheral VA ECMO are not systematically structured to prevent differential hypoxia.
Perfusion of blood from VA ECMO to the brachiocephalic artery (BCA) has not been seen in previous simulation studies unless maximum cannula flow rates were used [7, 8, 11]. These studies showed that high cannula flow rates (4 L/min and above) were required to establish a mixing zone in the aortic arch whilst a cannula flow rate of 5 L/min was required to adequately perfuse the BCA with blood from the VA ECMO circuit. In our study, however, the BCA received oxygenated blood even during lower levels (50%) of support when placed in P4. Additionally, during 90% VA ECMO support and P4, blood from the cannula was homogenously distributed throughout the entirety of the aorta.
Despite not modelling the coronary arteries in this model, blood from VA ECMO appeared to reach the aortic valve during P4 at 90% support. Therefore, perfusion of the coronary vessels was likely achieved during this scenario. In other CFD and in-vitro based studies, the potential for improved coronary perfusion with blood from the ECMO circuit was not observed, even at high ECMO flow rates (> 4.5 L/min) [7–9, 11, 20, 21]. For example, Hoeper et al demonstrated that clinical VA ECMO support with an arterial cannula tip placed within the common iliac artery and a flow rate of 4.5 L/min (similar to P1 during our 90% support case) resulted in a mixing zone in the aortic arch, identified using CT . These results, which agree with those obtained in our simulation study, concluded that despite maximal increases in cannula flow rates (and for typically positioned cannulae), the ascending aorta and coronary arteries do not receive oxygenated blood from the VA ECMO circuit thereby potentially resulting in cardiac hypoxia and inadequate conditions for cardiac recovery. An advanced arterial cannula tip has been attempted clinically as described by Rodriguez and Maharajh who implemented this technique in two pediatric patients . In their study, a 19 Fr drainage cannula was used in an off-label manner in place of an arterial cannula because there are no commercially available arterial cannulae capable of proximal positioning. The cannula tip was advanced until the tip lay distal to the left subclavian artery (similar to P4 in our study) and a flow rate of 83 ml/kg/min was used. Both patients showed no signs of differential hypoxia during ECMO support and showed improved hemodynamics and saturations.
An important implication of our results is the use of P4 in cases of ECPR where maximizing cerebral perfusion is a priority . Despite the high cannula blood flow rate during 90% support (4.5 L/min), in P1 only 12% of the flow to the BCA consisted of blood from VA ECMO. This is concerning as P1 reflects the most common arterial tip position used in current clinical practice . Instead, our results demonstrated much higher cerebral perfusion of oxygenated blood to the BCA is possible at P4 with the added benefit of possible coronary perfusion at 90% support. This is particularly important in cardiogenic shock after acute myocardial infarction and in the setting of ischemic heart disease. Therefore, cannula tip position may be an important factor in preventing not only neurological injury in patients treated with ECPR but also cardiac injury.
While placement of the cannula in P4 resulted in increased oxygenated VA ECMO perfusion of the aortic arch vessels in our study, there was a decrease in the proportion of VA ECMO blood reaching all other vessels. In particular, VA ECMO perfusion of the two common iliac vessels decreased by more than half with P4 compared to P1 during 50% VA ECMO support. This is supported by numerical results from Bongert et al. who showed that advancing the cannula tip from the femoral artery to the abdominal aorta resulted in lower perfusion of blood from VA ECMO to the lower limbs .
We also found advancing the cannula caused a minor increase in afterload compared to other cannula positions. Only a maximum increase of 6 mmHg was observed in P3 compared to P1. However, a slight decrease in MAP between P3 and P4 was found for all levels of support. This can be attributed to an increase in total flow to the lower branches (from LV and VA ECMO) and a decrease in total flow to the arch branches in P3.
An increase in arterial cannula insertion length may cause concern due to increased cannula resistance. However, the maximum pressure-drop observed was 160 mmHg (P4 at 90% support). This pressure-drop can be achieved by clinically used VA ECMO pumps by increasing pump speed accordingly as usually done when using arterial cannulas of smaller diameter . For example, Stephens et al. demonstrated that a 15 Fr arterial cannula was able to provide targeted full ECMO support with a pressure drop of 282 mmHg across the cannula .
Various studies have previously investigated mixing zone location during VA ECMO using a CFD model [7–11]. However, these studies primarily involved variation of VA ECMO flow rates with a constant cannula position throughout. Cannulas were placed more distal to P1 from our study but tip placement was still within a common iliac artery. Comparison of results between our study (during P1) and Stevens et al. show good agreement at 50% support . However, their exclusion of major vessels such as the SMA and IMA result in a much higher mixing zone location at 80% support. Nezami et al. used an idealized geometry which contained all the major vessels used in our study, and showed good agreement with respect to mixing zone locations and vessel perfusion at al support levels when our cannula was placed in P1 . In both aforementioned papers, however, cannula length was excluded from their models and was addressed as a limitation.
We assumed the aortic walls to be rigid in our simulations. Incorporating wall deformability would require much higher computational power than was feasible for the number of simulations conducted. However, Nezami et al. included wall deformability and their mixing zone results showed negligible difference to simulations conducted with rigid vessel walls . Secondly, the resistance and compliance parameters used in the Windkessel model reflect healthy patient conditions. Thus, any differences in these parameters associated with the heart failure state or vasopressor drugs were not simulated. Additionally, cardiac chamber pressure volume relations and autonomic nervous system autoregulatory mechanisms such as the baroreflex were not modelled in this study. Thus, cardiac and vascular changes in response to VA ECMO implementation were not simulated. Lastly, the results produced in this study have not been validated using in-vivo or in-vitro data. Therefore, all results should be interpreted with caution until experimental or clinical validation is performed.