Classification of Skin Injury Risk Caused by Extravasation of Electrolyte Solutions or Infusions in a Rat Model

Abstract

Cytotoxic agents are classified according to the severity of skin injury after extravasation. However, injuries caused by extravasation of noncytotoxic agents have not been sufficiently investigated, although the risk of extravasation is mentioned in medical safety information published by the Japan Council for Quality Health Care. Therefore, in this study, we focused on noncytotoxic electrolyte solutions and infusions and evaluated skin injuries during leakage using extravasation model rats. Rats were anesthetized and intradermally injected with 100 µL of an electrolyte solution or infusion. Injection lesions were macroscopically and histopathologically evaluated for extravasation injuries. Each electrolyte solution and infusion were classified into three categories (vesicants, irritants, and non-tissue-damaging agents) depending on the degree of skin injury. Similar to saline, 0.3% potassium chloride and 0.6% magnesium sulfate showed almost no injury, and 3% sodium chloride and BFLUID ® caused erythema and induration. Erythema, induration, and ulceration were observed with the following: 10% sodium chloride, 2% calcium chloride, 8.5% calcium gluconate, 12.3% magnesium sulfate, MAGSENT ® , FESIN ® , and Intralipos ® . The duration of damage with these agents was markedly prolonged. Electrolyte solutions and infusions can be classified into vesicants (10% sodium chloride, 2% calcium chloride, 8.5% calcium gluconate, 12.3% magnesium sulfate, MAGSENT ® , FESIN ® , and Intralipos ® ), irritants (3% sodium chloride and BFLUID ® ), and non-tissue-damaging agents (0.3% potassium chloride and 0.6% magnesium sulfate) according to their composition. The characteristic symptoms and severity of each drug extravasation revealed in this study will provide basic information for preparation of guidelines for treatment of extravasation.

Profiles and Outcomes of Skin Injuries Caused by Injectable Drug Extravasation

“…Several studies have reported skin injuries caused by PPN extravasation. In a previous study on laboratory animals, Taogoshi et al4 reported that PPN extravasation resulted in significant changes, such as erythema and induration, but not in histopathological changes, such as necrosis, making PPN comparable to irritants. In contrast, Ersoy and Tasargol23 examined an intensive care unit patient with a cardiac disease and reported a case of refractory skin necrosis and bullous skin lesions caused by PPN extravasation.…”

“…25 Calcium chloride extravasation is attributed to calcium calcification. In a laboratory animal study, Taogoshi et al 4 suggested that calcium chloride extravasation causes tissue necrosis and phlebitis, making the properties of calcium chloride comparable to those of vesicants. Also, Lin et al 26 studied patients who had postoperative hypocalcemia after parathyroidectomy and reported 4 cases of injection site skin injuries caused by calcium chloride administration.…”

“…Previous studies have suggested that hyperosmotic drugs, vasoconstrictors, and infusions containing certain electrolytes may cause skin injuries comparable to those caused by vesicants. 3,4 Furthermore, several studies have evaluated the severity of skin injuries associated with extravasation and their outcomes in clinical practice. [5][6][7] However, most are single-center studies and lack external validity.…”

“…The potential for skin injury associated with extravasation of noncytotoxic drugs has also been studied in recent years. Previous studies have suggested that hyperosmotic drugs, vasoconstrictors, and infusions containing certain electrolytes may cause skin injuries comparable to those caused by vesicants 3,4…”

An Explorative Study on Calcium Electroporation for Low-risk Basal Cell Carcinoma

“…In our patient, the severe and large ulceration healed within 11 months after careful wound care leaving a large scar under the breast. No skin biopsies were taken, but skin necrosis and prolonged ulceration after calcium chloride infusion is usually caused by tissue calcification (calcinosis cutis) ( 25 ). This serious side effect has not previously been reported after CaEP and was not seen in other patients during the study.…”