Shibata Yuuka, Sagara Yumeka, Yokooji Tomoharu, Taogoshi Takanori, Tanaka Maiko, Hide Michihiro, Matsuo Hiroaki
Department of Pharmaceutical Services, Hiroshima University Hospital.
School of Pharmaceutical Sciences, Hiroshima University.
Biol Pharm Bull. 2018;41(6):951-956. doi: 10.1248/bpb.b18-00105.
Inadvertent leakage of noncytotoxic agents causes severe tissue injury. In this study, we macroscopically and histopathologically evaluated the extent of skin injury caused by extravasation of hyperosmolar or vasopressor agents in rats. Rats were intradermally administered saline (100 µL), the hyperosmolar agents mannitol (5-20 mg/100 µL) and glucose (5-50 mg/100 µL), or the vasopressors dopamine (2 mg/100 µL), adrenaline (0.1 mg/100 µL), and noradrenaline (0.1 mg/100 µL). Lesion size (erythema, induration, ulceration, and necrosis) was monitored after agent injection. Skin tissue biopsies were evaluated at 24 h after agent injection. Mannitol and glucose induced severe lesions in a concentration (and osmolarity)-dependent manner. Mannitol and glucose at 10-20% (w/v) induced inflammation, and lesions healed within 3-6 d. In contrast, ≥25% (w/v) glucose elicited severe skin lesions with ulceration and necrosis within 24 h, which healed gradually 16-22 d after injection. The severity of extravasation injury caused by vasopressors varied. Adrenaline and noradrenaline induced severe injury with ulceration and necrosis, which healed over 23.3 and 18.3 d, respectively. In contrast, dopamine induced erythema and induration, and damage duration was only 5.7 d. In conclusion, mannitol and glucose at osmolarities of 549-1098 and 833-1110 mOsm/L, respectively, can be classified as "irritants," while ≥1388 mOsm/L glucose can be classified as a "vesicant." As for vasopressors, adrenaline and noradrenaline can be classified as "vesicants" whereas dopamine can be classified as an "irritant."
非细胞毒性药物的意外渗漏会导致严重的组织损伤。在本研究中，我们从宏观和组织病理学角度评估了高渗剂或血管升压药在大鼠体内外渗引起的皮肤损伤程度。给大鼠皮内注射生理盐水（100 μL）、高渗剂甘露醇（5 - 20 mg/100 μL）和葡萄糖（5 - 50 mg/100 μL），或血管升压药多巴胺（2 mg/100 μL）、肾上腺素（0.1 mg/100 μL）和去甲肾上腺素（0.1 mg/100 μL）。注射药物后监测损伤大小（红斑、硬结、溃疡和坏死）。在注射药物后24小时对皮肤组织活检进行评估。甘露醇和葡萄糖以浓度（和渗透压）依赖性方式诱导严重损伤。10 - 20%（w/v）的甘露醇和葡萄糖引起炎症，损伤在3 - 6天内愈合。相比之下，≥25%（w/v）的葡萄糖在24小时内引发严重的皮肤溃疡和坏死损伤，注射后16 - 22天逐渐愈合。血管升压药引起的外渗损伤严重程度各不相同。肾上腺素和去甲肾上腺素引起严重损伤，伴有溃疡和坏死，分别在23.3天和18.3天愈合。相比之下，多巴胺引起红斑和硬结，损伤持续时间仅为5.7天。总之，渗透压分别为549 - 1098和833 - 1110 mOsm/L的甘露醇和葡萄糖可归类为“刺激剂”，而≥1388 mOsm/L的葡萄糖可归类为“发泡剂”。至于血管升压药，肾上腺素和去甲肾上腺素可归类为“发泡剂”，而多巴胺可归类为“刺激剂”。
