Trans-ECMO thermodilution to measure recirculation during veno-venous Extracorporeal Membrane Oxygenation: an experimental animal study
by Mattia Busana
Date of Examination:2025-12-08
Date of issue:2025-12-02
Advisor:Prof. Dr. Onnen Mörer
Referee:Prof. Dr. Onnen Mörer
Referee:PD Dr. Aschraf El-Essawi
Persistent Address:
http://dx.doi.org/10.53846/goediss-11639
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Abstract
English
ARDS is a syndrome responsible for an impressive morbidity and mortality. In the most severe cases, the lung function is so compromised that the oxygenation and decarboxylation provided are simply no more compatible with life. In other cases, the lung mechanics is so deranged that it is not possible to guarantee a sufficient gas exchange without directly injuring the lungs through the mechanical ventilation, the so-called VILI. In these selected cases, V-V ECMO is indicated as a last resort. V-V ECMO can provide an artificial and extracorporeal source of gas exchange allowing to uncouple the need of gas exchange of the patient from the minute ventilation provided by the ventilator. Unfortunately, the performance of the V-V ECMO can sometimes be unsatisfactorily. Many factors may be responsible, but a very important factor is, without doubt, the recirculation. Indeed, as in V-V ECMO the drainage and the return cannula lie in the same (central) venous district, there will always be a flow of blood from the return cannula that gets drained back into the ECMO device, instead of reaching the systemic circulation. Understanding the factors promoting the recirculation would be key to avoid it, as 100% recirculation implies the complete futility of the extracorporeal therapy. Unfortunately, recirculation is a phenomenon hard to study and, until now, most of the studies have been of computational nature, or using proprietary techniques. Recently, Cipulli and coworkers, however, showed in an in vitro study that a modification of a simple thermodilution technique, TET, applied on the extracorporeal circuit, can non-invasively and precisely estimate the recirculation fraction at the bedside. In this work, we applied the very same technique for the first time in vivo, in an animal study, to evaluate whether measuring the recirculation with TET is feasible outside an in vitro study and if the technique allows to measure the phenomenon at the bedside over time; to understand which are the determinants of the recirculation and if its values can be used in a mathematical algorithm to estimate the mixed venous oxygen content and saturation. Indeed, the gas composition in the pulmonary artery during V-V ECMO remains elusive if the patient is not equipped with a pulmonary artery catheter. We studied 8 large pigs of 65 kg of weight. They were anesthetized, intubated and mechanically ventilated. Then they were instrumented with a standard set of intravascular catheters for the administration of drugs, fluids, blood sampling and measurements. The V-V ECMO was established with the cannulation of the femoral and jugular vein. A baseline measurement was acquired. The ARDS was induced in 4 animals with intratracheal instillations of hydrochloric acid and in 4 animals with the intravenous injection of oleic acid. The model was considered satisfactorily by a PaO2/FiO2 of 150 mmHg. After reaching the desired severity of the disease, the SGF was turned on and a set of measurements was acquired every 4 hours for 23 hours. At the end of the experiment the animals were sacrificed and the autopsy performed. The recirculation was studied throughout the duration of the experiment by TET. ARDS was reached in all cases with both oleic and hydrochloric acid, and, despite the widely different methodology of application, the models were remarkably similar. Of note, ARDS induced with oleic acid was characterized by a more pronounced vascular permeability., However, it was more difficult to control. Recirculation was present in variable extent during the experiment. Some animals showed an elevated recirculation fraction throughout the experiment, while others showed very little recirculation. The proximity of the tip of the cannulas was not a relevant anatomical factor associated to the development of recirculation. Among the physiological factors, the most significant was the ratio between the extracorporeal blood flow and the cardiac output of the subject, which we named ExtraCorporeal Support fraction (ECSF). In other words, the higher the blood flow with respect to the cardiac output the higher the recirculation fraction. Using the value of recirculation we algorithmically estimated the mixed venous blood composition. We were able to estimate with a high degree of accuracy the mixed venous oxygen content and, to a lesser extent, even the mixed venous oxygen saturation. The results of this study have a series of consequences. Firstly, we demonstrated that TET is easy, cost-effective and, above all, easy applicable at bedside. This is relevant, as the recirculation phenomenon has been elusive to quantify. Measuring it allowed to uncover some responsible variables and its consequences over the extracorporeal therapy. The fact that the ECSF is such a relevant variable is very important: indeed, while trying to improve the oxygenation performance of the ECMO, the clinician often increases the ECBF, with the aim to “treating” extracorporeally a larger fraction of the cardiac output. However, our study shows in vivo that this action also increases the recirculation, decreasing the effectiveness of the ECMO. Being able to measure the recirculation allows to directly find the ECMO setup that delivers the best performance in each individual patient. Furthermore, being able to estimate the mixed venous oxygen content and saturation is potentially very important. The use of the pulmonary artery catheter is becoming increasingly rare, but this leaves the doctor blind to the composition of the blood in the pulmonary artery. Nevertheless, the oxygenation (and decarboxylation, for that matter) of the blood entering the pulmonary circulation is key to setup the ventilator during V-V ECMO. The better the mixed venous blood is oxygenated and decarboxylated, the more the patient is independent from the mechanical ventilation. We strongly believe that optimizing the gas exchange during V-V ECMO should be done by measuring the blood gas composition distal to the provided extracorporeal therapy, but before the mechanical ventilation takes place. Only by doing so the extracorporeal therapy and the ventilation can be understood independently and tweaked, if needed, accordingly. Overall, recirculation is a pivotal variable for managing V-V ECMO. This insight allows V-V ECMO to be approached with greater precision rather than as an enigmatic "black box", ultimately enhancing patient safety.
Keywords: ARDS; ECMO; Respiratory medicine; Recirculation
