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

Abstract

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&#xa0;units of canine FDP, and 8&#xa0;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.