In Vitro Evaluation of the Co‐Administration of Canine Blood Products and Drugs Used in Critical Illness

Objective To analyze the effects of co‐administering various drugs with canine whole blood (WB), canine fresh frozen plasma (FFP), or canine freeze‐dried plasma (FDP), and determine whether alterations to the blood constituents or drugs exist within the admixture. Design In vitro experimental study. Setting Government blood and coagulation research laboratory. Interventions Seven units of commercially acquired canine FFP, 7 units of canine FDP, and 8 units of canine WB were co‐administered with multiple drugs, including fentanyl, midazolam, ketamine, hydromorphone, tranexamic acid (TXA), ampicillin/sulbactam, enrofloxacin, ceftriaxone, and ertapenem, and delivered simultaneously into an IV line via infusion pumps using clinically relevant doses. The resultant solutions were analyzed for coagulation factor activities and fibrinogen concentration. Liquid chromatography–tandem mass spectroscopy was used to assess drug concentration, and impedance aggregometry and cell‐free hemoglobin were used to evaluate platelet function in the WB samples. Measurement and Main Results Platelet function decreased with each drug co‐administered with WB in vitro. Cell‐free hemoglobin increased when ketamine, fentanyl, and midazolam were co‐administered with WB. Drug loss was seen when enrofloxacin was co‐administered with FDP. Drug loss was also seen when hydromorphone was co‐administered with FFP. Sulbactam and ertapenem resulted in drug loss when co‐administered with FDP and FFP. Drug loss was seen when ceftriaxone, fentanyl, and midazolam were co‐administered with each blood product. With each admixture, there were variable changes in coagulation factor activities. A statistically significant decrease in activity <50% was seen only in factors V and VIII when ceftriaxone and enrofloxacin, respectively, were co‐administered with FDP. Conclusions Platelet function will likely be adversely affected by the co‐administration of any of the selected drugs. Co‐administration of ketamine, fentanyl, and midazolam with WB resulted in significant hemolysis and is not recommended. It is reasonable to consider co‐administering ampicillin, TXA, and ketamine with FDP and FFP.