M. Nuskowski2, M. DEsai2, A. Tongut2, K. Ramakrishnan1 1University of Tennessee Health Sciences Center, Surgery, Memphis, TN, USA 2Children’s National Medical Center, Washington, DC, USA
Introduction:
Anticoagulation is critical to maintain integrity of Extracorporeal life support (ECLS) circuits. Heparin is the current standard of care and has many drawbacks. Hence an alternative is required. The objective of this study was to investigate the potential synergistic utility of a combination of gaseous nitric oxide (gNO)- intravenous Cangrelor as an effective pharmacological option for the prevention of thrombosis in ECLS circuits.
Methods:
This was an animal experiment to test proof of concept. 10 newborn lambs were placed on ECLS. 5 of them were administered a combination of gaseous nitric oxide (gNO)- intravenous Cangrelor. The remaining 5 were not administered any anticoagulation medication. The primary end-point was duration of ECLS without clot formation. ECLS was continued for a maximum of 12 hours (720 minutes) or until one of the following surrogates of thrombosis occurred. a. The ECLS pump stopped spontaneously without obvious non-thrombotic mechanical reasons
b. The difference between the pre- and post- oxygenator pressure reached 100 mmHg.
c. There was clot formation visualized in the circuit.
Results:
The experiments were completed in accordance with the protocol in 8 animals. 2 animals, one in each group, died before initiation of ECLS. The mean duration of ECLS were 210 minutes (standard deviation 269.44 minutes) in the control group and 502 minutes (standard deviation 265.38 minutes/) in the experimental group. This difference did not reach statistical significance (p= 0.17). The peak trans-oxygenator pressure difference was 43 mm Hg (standard deviation 23 mm Hg) in the control group and 62 mm Hg (standard deviation 71 mm Hg) in the experimental group. This difference also did not reach statistical significance (p=.64).
None of the animals in the control group reached the maximum duration of ECLS support, while 2 animals in the experimental group were supported up to 12 hours without clot formation. Clot formation was seen as early as within 30 minutes of commencing ECLS in the control group. In the two experimental animals where clot formation was seen, the clots developed in the cannulae before initiation of ECLS and commencement of gNO and Cangrelor infusion. The cannulae were flushed in both these animals before commencement of ECLS, but the pumps stopped due to massive clots after 390 minutes and 180 minutes respectively. In the first animal, clots were seen in the oxygenator and the arterial cannula while in the second animal, an obstructive clot was seen in the venous cannula, and nowhere else.
Conclusion:
A combination of gNO and Cangrelor is effective in preventing clot formation in an animal model of ECLS. However, the combination therapy is effective only when administered before initiation of clot formation. The efficacy Cangrelor bolus prior to cannulation to prevent initiation of clot formation in the cannulae needs to be explored.