Acute Intravenous Toxicity Study of Hypertonic Saline/Dextran 70 (Trade Name) and its Constituents in New Zealand White Rabbits

摘要

The acute toxicity following intravenous administration of a proposed resuscitation fluid, hypertonic saline/ Dextran 70 (HSD), was evaluated in male and female New Zealand White rabbits. Animals received a single intravenous dose of HSD, 20 ml/kg over a 5-minute period, in an attempt to define maximum tolerated dosage. Equal volumes of each HSD component, 7.5% hypertonic saline (HS) and 6% Dextran 70 (D70) in normal saline, and Ringer's lactate (RL)/ were also evaluated. The animals in each group were divided into two subgroups according to necropsy, either Day 3 or Day 14 after dosing. Blood samples were collected for serum chemistry and hematologic analyses at necropsy on Day 3, and on Day 13. Observations were made at 1,2, and 4 hours after administration on the day of dosing and twice daily thereafter. HS produced death within 12 minutes of the start of injection in 6 of 20 rabbits. Compared to the control animals receiving RL, the HS and HSD groups exhibited increased incidence of bruising of the injected ear, inactivity, disorientation, and tremors. These data suggest that the lethality of HS was due to an acute hemodynamic effect of the volume administered, and that the rabbit was less sensitive to HSD or D70 than to HS. Since the proposed therapeutic dose of HSD is only 4 ml/kg, these findings indicate minimal adverse effects should be anticipated with the therapeutic administration of HSD. (aw)