Abstract

Purpose: The effects of infusion speed and dilution on the severity of phlebitis in rabbits were investigated in order to find an effective method for reducing the phlebitis associated with epirubicin injection. Method: Farmorubicin^® RTU Injection, a commercial formulation containing 2 mg/ml of epirubicin hydrochloride (EB), was diluted either with the same volume of 0.9% saline (S+EB; containing 1 mg/ml of EB) or with a three-fold volume of saline (3S+EB; containing 0.5 mg/ml of EB). S+EB was infused hourly into the ear veins of eight rabbits for 20 min at 10 ml/kg (rapid-infusion group), or 60 min hourly at 3.33 ml/kg (slow-infusion group), and 3S+EB was infused hourly for 60 min at 6.66 ml/kg (dilution group). The dose of EB infused was identical (3.33 mg/kg) in all groups. The infused veins were sampled 3 days after the infusion and examined histopathologically. Result: EB caused general phlebitic changes such as loss of venous endothelial cells, inflammatory cell infiltration, and perivascular edema, as well as chondrocyte necrosis in auricular cartilage near the infused vein. The phlebitic changes observed in the slow-infusion group were significantly more severe than those in the rapid-infusion group. When the same dose (3.33 mg/kg) of EB was infused for the same duration (60 min), the phlebitic changes caused by S+EB (slow-infusion group) were significantly more severe than those by 3S+EB (dilution group). Conclusion: The rapid infusion or dilution may be effective in reducing the severity of phlebitis caused by EB.


Keywords:  Epirubicin   Phlebitis   Rapid infusion   Dilution   Rabbit ear vein