Advances in Patient Care for Preclinical Extracorporeal Life Support

ABSTRACT

Extracorporeal life support (ECLS) reduces the functional workload requirements of the lungs, heart, or both for days to weeks in patients with reversible life threatening respiratory or cardiac disease. It is estimated that ECLS could have saved close to half of the seriously ill COVID-19 patients for whom mechanical ventilation was not effective if ECLS had been available. Supporting an ECLS patient however requires extensive knowledge and resources, and this is true also in the preclinical space when working with healthy animal models. The most common serious complications in the clinical setting are bleeding and thrombosis, both of which are also seen in preclinical studies performed on healthy sheep. From late 2020 to early 2021, the animal care and clinical laboratory teams made significant advances in supporting preclinical ECLS studies, reducing both mortality and other adverse outcomes significantly by implementing several interventions: 1) improving diagnostic ability to monitor anticoagulation status more accurately with the measurement of activated clotting time (ACT), blood heparin concentration, partial thromboplastin time (PTT), activated partial thromboplastin time (aPTT), plasma free hemoglobin and red blood cell values;2) refining ECLS circuit attachments and optimizing the kennel environment to allow for improved animal comfort while decreasing the risk for canulae or circuit kinking or migration and 3) refining nursing care and monitoring by the inclusion of improved AV system and standardized care protocols. One of the core improvements was supplementing periodic ACT tests with blood heparin concentration. After these refinements, mortality during 7 d in life ECLS studies was reduced from 50% (3/6 animals, study1) to none (0/3 animals, study2) Blood heparin concentration is also beneficial in the management of human patients on ECLS. Facilities performing ECLS studies can benefit from expanding anticoagulation evaluation from simple ACT measurements to a multimodal approach, with blood heparin concentration measurements being especially advantageous. In addition, skilled round-the-clock nursing care of the study animals is vital for success.