Evaluation of the local irritation potential of hypertonic saline–dextran (HSD) in mice and rabbits

Recent questions have renewed concerns regarding possible irritation associated with intravenous (i.v.) injection of 7.5% hypertonic saline (HS) or hypertonic saline-dextran (HSD: 7.5% NaCl and 6% Dextran-70). This study investigated local injection site irritation associated with i.v., paravenous (p.v.), intramuscular (i.m.) and subcutaneous (s.c.) injection of HSD or its individual components. Mice (n=10 per group per time point) and rabbits (n=10 per group per time point) were infused i.v. with the maximum tolerated dose (28 or 20 ml kg(-1), respectively) of HSD, HS, Dextran-70 (D-70) or lactated Ringer's solution (LR). Animals were observed at 1,2 and 4 h after injection and then twice daily until euthanized on day 3 or 14. In irritation studies, 24 rabbits were randomized to receive the four fluids and they were evaluated histologically at 4, 24, 48 or 72 h after i.v., p.v., i.m. or s.c. infusion. The sites were observed immediately after injection, at 4 h and then twice daily until euthanasia. In surviving mice, bruising of the tail was observed in 6/18 and 5/19 animals in the HSD and HS groups, respectively, compared with 0/20 animals in the D-70 or LR groups. Sloughing of the tail was eventually observed in two HSD-infused and three HS-infused mice, compared with none in the other groups. More bruises, hematomas and blebs were observed after i.v. or s.c. injection of HS and D-70 than LR or HSD in the rabbit irritation studies, but the differences among groups were not statistically significant. In the acute toxicity study in rabbits, bruising at the site of injection was observed in 7/20 and 5/14 surviving animals from the HSD and HS groups, respectively, but none was observed in the LR or D-70 groups. These data suggest that, if infused over 5-10 min into a peripheral or central vein, a therapeutic dose of HSD (4 ml kg(-1)) should not induce any greater inflammation on the vein than LR. However, if significant extravasation of hypertonic fluid occurs, the possibility of localized, focal necrosis might be expected to occur.