Evaluation of risk of injury by extravasation of hyperosmolar and vasopressor agents in a rat model

Abstract

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 (100µL), the hyperosmolar agents mannitol (5–20mg/100µL) and glucose (5–50mg/100µL), or the vasopressors dopamine (2mg/100µL), adrenaline (0.1mg/100µL), and noradrenaline (0.1mg/100µL). Lesion size (erythema, induration, ulceration, and necrosis) was monitored after agent injection. Skin tissue biopsies were evaluated at 24h 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 3–6d. In contrast, ≥25% (w/v) glucose elicited severe skin lesions with ulceration and necrosis within 24h, which healed gradually 16–22d 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 18.3d, respectively. In contrast, dopamine induced erythema and induration, and damage duration was only 5.7d. In conclusion, mannitol and glucose at osmolarities of 549–1098 and 833–1110mOsm/L, respectively, can be classified as “irritants,” while ≥1388mOsm/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.”