Summary
The synthetic colloids, dextran and hydroxyethyl starch, have only recently enjoyed widespread use in critically ill veterinary patients. Plasma proteins normally provide colloid oncotic pressure and, thereby, are the primary force responsible for retaining fluid within the vasculature. Abnormally low plasma protein concentrations, common in the critically ill patient, are associated with excessive fluid loss from capillaries and development of peripheral or pulmonary edema. Infusion of colloid solutions decreases the potential for and severity of edema in hypooncotic states. Dextran and hydroxyethyl starch solutions also provide other positive hemodynamic benefits and are a preferable alternative to crystalloid usage in the resuscitation of selected patients from hypotensive and hypovolemic states. Potential side effects of synthetic colloid infusion include anaphylactoid reactions, increased risk of bleeding, interference with cross matching, and acute renal failure. Knowledge of the mechanisms responsible for these adverse effects minimizes their occurrence.
SUMMARY Amiloride and DIDS (4,4-diisothiocyanato-stilbene-2,2 '-disulfonic acid) have been used to lower intracellular pH and increase thermosensitivity of malignant cells. We previously observed adverse reactions after injection of these drugs in canines and hypothesized that reactions may be mediated by amiloride-induced histamine release. This study was designed to define an amiloride infusion rate unlikely to cause adverse effects in dogs. Plasma concentrations of amiloride were quantified to assess whether infusions in this study produced amiloride concentrations within the range known to produce thermosensitization in vitro. Anesthetized dogs received intravenous amiloride infusions during multiple sessions on different days. The infusion was divided into 1) a loading infusion of either 100,200,300,400,500, or 600 p,g/kg/min given for 25 min and 2) a maintenance infusion of 7.4 pg/kg/min started immediately after the loading infusion and lasting for 2 hr. Infusion resulted in histamine release, and hypotension (240% decrease from baseline) occurred in dogs given amiloride at rates 2500 pg/kg/min. Hypotension appeared to be associated with more rapid amiloride infusion but not with peak plasma concentration. Plasma amiloride concentrations were less than in vitro concentrations shown to produce thermosensitivity.
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