Extracorporeal arteriovenous CO₂ removal for severe respiratory failure: high versus low dose heparin

Objective: In prior studies, we established the safety and feasibility of percutaneous arteriovenous CO₂ removal (AVCO₂R) for severe respiratory failure using high dose heparin to minimize thrombosis with activated clotting times (ACT) > 300 sec (sheep) and > 260 sec (humans). We conducted a prospective randomized study of AVCO₂R utilizing a new, commercially available, heparin-coated oxygenator comparing low dose heparin (< 200 sec) with high dose heparin (> 300 sec). Methods: Adult Suffolk ewes (n=10) received a combination cotton smoke inhalation (36 breaths) and cutaneous flame burn (40% TBSA III°) injury, with volume controlled mechanical ventilation. When animals met entry criteria for AEDS (P/F ratio < 200) they were re-anesthetized, systemically anticoagulated (200 IU/kg bovine lung heparin) and underwent cannulation of the left carotid artery (percutaneous 10-12F) and left jugular vein (percutaneous 14F). The AVCO₂R circuit included a Trillium® Biopassive Surface coated, low resistance membrane gas exchanger (Affinity, Avecor Cardiovascular, Plymouth, MN). Animals randomly received LOW DOSE (n=5, ACT < 200 sec) or HIGH DOSE heparin (n=5, ACT > 300 sec). ACT was measured hourly while prothrombin time, activated partial thromboplastin time, fibrinogen, FDP, and platelets were measured every 12 hours. Results: For the HIGH DOSE group, ACT values ranged from 336 ± 81 to 448 ± 100 sec with an overall average of 415 ± 27 sec. The LOW DOSE ACT ranged from 173 ± 8 to 241 ± 39 sec with an overall average of 192 ± 6 sec. Mean flow through the oxygenator was similar in both groups, ranging from 813 ± 150 ml/min to 922 ± 138 ml/min and from 862 ± 115 ml/min to 932 ± 84 ml/min in the HIGH and LOW dose groups, respectively. Coagulation parameters, measured by prothrombin time, activated partial thromboplastin time, fibrinogen and FDP remained within physiologic range for both groups and no difference between groups was observed. No evidence of thrombosis or hemorrhage was observed from the cannulation sites or systemically. Conclusion: Low dose systemic heparin (ACT < 200 sec) with a heparin-coated oxygenator does not increase thrombogenicity during AVCO ₂R for ARDS.