Enhanced extracorporeal carbon dioxide removal by acidification and metabolic control

Background: Extracorporeal carbon dioxide removal (ECCO2R) promotes protective ventilation in patients with acute respiratory failure, but devices with high CO2 extraction capacity are required for clinically relevant impact. This study evaluates three novel low-flow techniques based on dialysate acidification, also combined with renal replacement therapy, and metabolic control. Methods: Eight swine were connected to a low-flow (350 mL/min) extracorporeal circuit including a dialyzer with a closed-loop dialysate circuit, and two membrane lungs on blood (MLb) and dialysate (MLd), respectively. The following 2-hour steps were performed: 1) MLb-start (MLb ventilated); 2) MLbd-start (MLb and MLd ventilated); 3) HLac (lactic acid infusion before MLd); 4) HCl-NaLac (hydrochloric acid infusion before MLd combined with renal replacement therapy and reinfusion of sodium lactate); 5) HCl-βHB-NaLac (hydrochloric acid infusion before MLd combined with renal replacement therapy and reinfusion of sodium lactate and sodium 3-hydroxybutyrate). Caloric and fluid inputs, temperature, blood glucose and arterial carbon dioxide pressure were kept constant. Results: The total MLs CO2 removal in HLac (130±25 mL/min), HCl-NaLac (130±21 mL/min) and HCl-βHB-NaLac (124±18 mL/min) were higher compared with MLbd-start (81±15 mL/min, P<0.05) and MLb-start (55±7 mL/min, P<0.05). Minute ventilation in HLac (4.3±0.9 L/min), HCl-NaLac (3.6±0.8 L/min) and HCl-βHB-NaLac (3.6±0.8 L/min) were lower compared to MLb-start (6.2±1.1 L/min, P<0.05) and MLbd-start (5.8±2.1 L/min, P<0.05). Arterial pH was 7.40±0.03 at MLb-start and decreased only during HCl-βHB-NaLac (7.35±0.03, P<0.05). No relevant changes in electrolyte concentrations, hemodynamics and significant adverse events were detected. Conclusions: The three techniques achieved a significant extracorporeal CO2 removal allowing a relevant reduction in minute ventilation with a sufficient safety profile.