NOVEL STRATEGIES TO IMPLEMENT EXTRACORPOREAL LIFE SUPPORT TECHNIQUES

Extracorporeal techniques are the ultimate resources for critically ill patients with life threating respiratory or cardiac failure, maintaining tissue oxygenation for days to weeks by supporting the lungs, the heart, or both. We focused our interest on novel strategies to implement this technology in order to guarantee safer and more efficient extracorporeal life support. The first approach was a novel regional anticoagulation strategy based on ion-exchange resins, which aimed at avoiding the risks related to systemic anticoagulation. In this experiment, conducted on a swine model, we were able to reduce the concentration of ionized calcium in the extracorporeal circuit, thus inhibiting its coagulation activity, while having an extracorporeal blood flow of 500mL/min. On the other hand, by re-infusing calcium in the systemic circulation, we were able to maintain a normal coagulation function in our in vivo model. Secondly, we devised a thermodilution technique to quantify recirculation flow in a membrane lung, a step needed in order to reduce the amount of oxygenated blood flowing back into the extracorporeal circuit. We built an in vitro setup mimicking a patient undergoing veno-venous ExtraCorporeal Membrane Oxygenation (vv-ECMO) to measure the recirculation fraction, which was computed as the ratio between the areas under the curve of temperature traces recorded on the drainage line and at reinfusion line. We found that our thermodilution technique provided a punctual measurement of the fraction of oxygenated blood recirculating into the membrane lung. Thirdly, we tested sodium hydroxide (NaOH) as an alternative medium to clear carbon dioxyde (CO2) in a membrane lung, comparing its efficacy and efficiency against those of various fresh gas flows. Despite its limitations for clinical practice, this strategy shows that NaOH solutions have a high CO2 absorbing capacity. The partial pressure of CO2 (pCO2) of the alkaline sweep fluid was persistently very close to 0 mmHg, as the added CO2 was instantly hydrated and dissociated to bicarbonate and carbonate. This optimized the transmembrane pCO2 gradient, increasing the efficiency of extracorporeal CO2 removal. The last experiment of this cycle aimed at understanding the relevance of haematocrit (HCT) during extracorporeal CO2 removal. In our in vitro study, we kept inlet pCO2 stable, blood flow at membrane lung at 250 mL/min, and sweep gas flow at 5 L/min according with membrane lung characteristics. We showed that variations in HCT corresponded to variations in the amount of removed CO2 (V̇CO2). Specifically, in our study, an increase of HCT by 20% determined a rise in V̇CO2 of 15% compared to treatment baseline. Overall, starting from physiology, we tackled some open issues of extracorporeal life support. Our results are promising and expand the fund of knowledge on extracorporeal techniques. The next steps will require further studies in order to take our findings from the bench to the bedside.