Pathogenesis of gangrene following intra-arterial injection of drugs: a new hypothesis.

We have demonstrated the toxicity of diazepam and the safety of ketamine hydrochloride following intra-arterial injection in an anaesthetized animal model. The pathogenesis of gangrene following intra-arterial injection of drugs is unclear. Clinical reports and this experiment suggest that it only follows injection of highly membrane-soluble drugs. Early swelling and disruption of capillary endothelial cells were demonstrated after intra-arterial injection of diazepam and thiopentone. We believe that a theory of pathogenesis based on this finding is consistent not only with our experimental findings, but with known in vitro effects of membrane soluble drugs on cell membranes and the clinical features following intra-arterial injections in both human subjects and in animals.