Extracorporeal carbon dioxide removal requirements for ultraprotective mechanical ventilation: Mathematical model predictions

Extracorporeal carbon dioxide (CO 2 ) removal (ECCO 2 R) facilitates the use of low tidal volumes during protective or ultraprotective mechanical ventilation when managing patients with acute respiratory distress syndrome (ARDS); however, the rate of ECCO 2 R required to avoid hypercapnia remains unclear. We calculated ECCO 2 R rate requirements to maintain arterial partial pressure of CO 2 (PaCO 2 ) at clinically desirable levels in mechanically ventilated ARDS patients using a six‐compartment mathematical model of CO 2 and oxygen (O 2 ) biochemistry and whole‐body transport with the inclusion of an ECCO 2 R device for extracorporeal veno‐venous removal of CO 2 . The model assumes steady state conditions. Model compartments were lung capillary blood, arterial blood, venous blood, post‐ECCO 2 R venous blood, interstitial fluid and tissue cells, with CO 2 and O 2 distribution within each compartment; biochemistry included equilibrium among bicarbonate and non‐bicarbonate buffers and CO 2 and O 2 binding to hemoglobin to elucidate Bohr and Haldane effects. O 2 consumption and CO 2 production rates were assumed proportional to predicted body weight (PBW) and adjusted to achieve reported arterial partial pressure of O 2 and a PaCO 2 level of 46 mmHg at a tidal volume of 7.6 mL/kg PBW in the absence of an ECCO 2 R device based on average data from LUNG SAFE. Model calculations showed that ECCO 2 R rates required to achieve mild permissive hypercapnia (PaCO 2 of 46 mmHg) at a ventilation frequency or respiratory rate of 20.8/min during mechanical ventilation increased when tidal volumes decreased from 7.6 to 3 mL/kg PBW. Higher ECCO2R rates were required to achieve normocapnia (PaCO2 of 40 mmHg). Model calculations also showed that required ECCO2R rates were lower when ventilation frequencies were increased from 20.8/min to 26/min. The current mathematical model predicts that ECCO2R rates resulting in clinically desirable PaCO2 levels at tidal volumes of 5‐6 mL/kg PBW can likely be achieved in mechanically ventilated ARDS patients with current technologies; use of ultraprotective tidal volumes (3‐4 mL/kg PBW) may be challenging unless high mechanical ventilation frequencies are used.