Evaluation of Risk of Injury by Extravasation of Hyperosmolar and Vasopressor Agents in a Rat Model

Shibata Yuuka

Sagara Yumeka

Tokooji Tomoharu

Taogoshi Takanori

Tanaka Maiko

Hide Michihiro

Matsuo Hiroaki

Biological and Pharmaceutical Bulletin

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.”

extravasation

vasopressor

hyperosmolar

noncytotoxic

Medical sciences [ 490 ]

eng

The Pharmaceutical Society of Japan

© 2018 The Pharmaceutical Society of Japan

[ISSN] 0918-6158

[ISSN] 1347-5215

[NCID] AA10885497

[DOI] 10.1248/bpb.b18-00105

[DOI] https://doi.org/10.1248/bpb.b18-00105