Kohno Emiko, Murase Saori, Matsuyama Kenji, Okamura Noboru
Department of Hospital Pharmacy, Kansai Medical University Takii Hospital, 10-15 Fumizono-cho, Moriguchi, Osaka 570-8507, Japan.
Int J Med Sci. 2009 Aug 6;6(5):218-23. doi: 10.7150/ijms.6.218.
Phlebitis caused by intravenous infusion of antineoplastic agents is one of the critical problems when anticancer therapy is prolonged. We have already reported that both rapid infusion and dilution of the injection solution were effective methods for reducing phlebitis caused by vinorelbine (VNR) in rabbits. The aim of this study was to explore other practical methods for preventing phlebitis caused by VNR and doxorubicin (DXR) in a rabbit model. VNR is often used with cisplatin, and dexamethasone (DEX) has been co-administered for prevention of cisplatin-induced nausea. DXR is used with prednisolone (PSL) in the CHOP regimen for the treatment of non-Hodgkin's lymphoma. Therefore, the present study investigated the prevention of phlebitis due to VNR with DEX and that due to DXR with PSL.
VNR and DXR were diluted with normal saline to prepare test solutions at concentrations of 0.6 mg/mL and 1.4 mg/mL, respectively. Each test solution was infused into the auricular veins of rabbits. Two days after VNR infusion and three days after DXR infusion, the veins were evaluated histopathologically. The effect of DEX on VNR-induced phlebitis was evaluated by infusion of DEX before or after VNR. The effect of PSL on DXR-induced phlebitis was similarly evaluated by co-infusion of PSL.
The histopathological features of phlebitis caused by the antineoplastic agents differed between VNR and DXR: VNR did not cause the loss of venous endothelial cells, but caused inflammatory cell infiltration, edema, and epidermal degeneration. In contrast, DXR caused the loss of venous endothelial cells and chrondrocyte necrosis. Pre-treatment and post-treatment with DEX significantly decreased VNR-induced phlebitis compared with the control group and pre-treatment was particularly effective. Co-infusion of PSL also significantly decreased phlebitis caused by DXR, but its effect was less marked.
The present findings suggested that pre-treatment with DEX may be a useful method for preventing phlebitis due to VNR, and that co-infusion of PSL has the potential to prevent phlebitis caused by DXR.
在抗癌治疗延长期间，静脉输注抗肿瘤药物引起的静脉炎是一个关键问题。我们已经报道，快速输注和稀释注射溶液是减少兔长春瑞滨（VNR）引起的静脉炎的有效方法。本研究的目的是在兔模型中探索预防VNR和多柔比星（DXR）引起的静脉炎的其他实用方法。VNR常与顺铂联合使用，地塞米松（DEX）已被联合使用以预防顺铂引起的恶心。DXR在CHOP方案中与泼尼松龙（PSL）联合用于治疗非霍奇金淋巴瘤。因此，本研究调查了DEX预防VNR引起的静脉炎以及PSL预防DXR引起的静脉炎的情况。
将VNR和DXR用生理盐水稀释，分别制备浓度为0.6mg/mL和1.4mg/mL的测试溶液。将每种测试溶液注入兔耳静脉。在输注VNR后两天和输注DXR后三天，对静脉进行组织病理学评估。通过在VNR之前或之后输注DEX来评估DEX对VNR诱导的静脉炎的影响。通过联合输注PSL以类似方式评估PSL对DXR诱导的静脉炎的影响。
VNR和DXR引起的静脉炎的组织病理学特征不同：VNR未导致静脉内皮细胞丢失，但引起炎症细胞浸润、水肿和表皮变性。相比之下，DXR导致静脉内皮细胞丢失和软骨细胞坏死。与对照组相比，DEX预处理和后处理均显著降低了VNR诱导的静脉炎，且预处理尤为有效。联合输注PSL也显著降低了DXR引起的静脉炎，但其效果不太明显。
本研究结果表明，DEX预处理可能是预防VNR引起的静脉炎的有用方法，联合输注PSL有可能预防DXR引起的静脉炎。
