In vivo testing of the low-flow CO2 removal application of a compact, platform respiratory device

Abstract

Background: Non-invasive and lung-protective ventilation techniques may improve outcomes for patients with an acute exacerbation of chronic obstructive pulmonary disease or moderate acute respiratory distress syndrome by reducing airway pressures. These less invasive techniques can fail due to hypercapnia and require transitioning patients to invasive mechanical ventilation. Extracorporeal CO₂ removal devices remove CO₂ independent of the lungs thereby controlling the hypercapnia and permitting non-invasive or lung-protective ventilation techniques. We are developing the Modular Extracorporeal Lung Assist System as a platform technology capable of providing three levels of respiratory assist: adult and pediatric full respiratory support and adult low-flow CO₂ removal. The objective of this study was to evaluate the in vivo performance of our device to achieve low-flow CO₂ removal.

Methods: The Modular Extracorporeal Lung Assist System was connected to 6 healthy sheep via a 15.5 Fr dual-lumen catheter placed in the external jugular vein. The animals were recovered and tethered within a pen while supported by the device for 7 days. The pump speed was set to achieve a targeted blood flow of 500 mL/min. The extracorporeal CO₂ removal rate was measured daily at a sweep gas independent regime. Hematological parameters were measured pre-operatively and regularly throughout the study. Histopathological samples of the end organs were taken at the end of each study.

Results: All animals survived the surgery and generally tolerated the device well. One animal required early termination due to a pulmonary embolism. Intra-device thrombus formation occurred in a single animal due to improper anticoagulation. The average CO₂ removal rate (normalized to an inlet pCO₂ of 45 mmHg) was 75.6 ± 4.7 mL/min and did not significantly change over the course of the study (p > 0.05). No signs of consistent hemolysis or end organ damage were observed.

Conclusion: These in vivo results indicate positive performance of the Modular Extracorporeal Lung Assist System as a low-flow CO₂ removal device.

Keywords: Carbon dioxide; Extracorporeal CO2 removal; Hypercapnia.

Fig. 1

Prototype of the adult low-flow ECCO₂R ModELAS device showing the blood and gas flow pathways (a). All three respiratory assist applications utilize an identical pumping compartment. Cannulation and HFM bundle size differentiate each respiratory assist configuration. Photograph of a study animal wearing the holstered device (b)

Fig. 2

Raw and normalized CO₂ removal rates (a) and daily extracorporeal blood flow rate (b). When compared to the POD 0 data, neither parameter significantly changed over duration of the study (p > 0.05). ^an = 5, ^bn = 4

Fig. 3

Plasma-free hemoglobin generated during the adult low-flow ECCO₂R ModELAS in vivo study. Legend: ● animal 1; ■ animal 2; ▲ animal 3; ▼ animal trial 4; ♦ animal 5; ○ animal 6

Fig. 4

(a) Images of the explanted hollow fiber membrane bundle inlet (top row) and outlet (bottom row) faces and the (b) impeller top (top row) and bottom (bottom row) pivots. The animal 2 (right) bundle and pivots had significant thrombus formation due to low ACT. All other animals were free of significant thrombi (left)