Gangrene of the upper extremity following intra-arterial injection of drugs. A case report and review of the literature.

A case of inadvertent intra-arterial self-injection of crushed codeine tablets in an 37-year-old man, resulting in gangrene of an upper extremity, is presented. The problem studied was whether the gangrene was caused by the codeine or by one of the excipients found in the tablets. The cause of the gangrene was investigated in an experimental study. Each of the components of the tablet (codeine, lactose, gelatin, carboxymethyl cellulose, calcium stearate, talc, and microcrystalline cellulose) was injected into the femoral arteries of dogs. The results of the study clearly demonstrate that the unique component producing the gangrene was the micro-crystalline cellulose, while the injection of pure codeine was harmless. To date, the only reported deleterious effects of intravascular injection of micro-crystalline cellulose have been pulmonary embolism and granulomatosis. Some examples of drugs that include microcrystalline cellulose are methadone, methaqualone, oxcycodone, acetaminophen, aspirin with codeine, propoxyphene napsylate, meprobamate, and phenobarbital. Recently, the vulnerability of drug addicts who habitually inject drugs into veins to the accidental injection of an artery has been noted, and it seems likely that in the future the problem of intra-arterial injection will increase in severity. The literature of the last 40 years is reviewed, and a list of drugs known to have produced gangrene when injected intra-arterially is cited.

Tissue injuries associated with parenteral propylhexedrine abuse.

Propylhexedrine, the active ingredient in Benzedrex Inhalers, is extracted from the wicks of the inhalers by drug abusers for intravenous injection to provide a "desirable high." Six representative cases treated over a one-year period are presented to exemplify the potential for soft tissue injury. Because the actual constituents of the injected material prepared from the inhalers were not established, solutions were prepared from Benzedrex Inhalers according to the formula provided by one of the patients. The extract was then subjected to vigorous qualitative and quantitative analyses; the presence of essentially pure propylhexedrine hydrochloride was confirmed in varying concentrations. To examine the progression of injury following injection of the prepared extract, the ears of 12 New Zealand white rabbits were injected either intra-arterially or subcutaneously. The opposite ear of each rabbit served as a control. Both clinical and pathologic observations demonstrated injury consistent with intense local vasoconstriction. Injury did not appear to relate to impurities in the solution or other embolic phenomena. Finally, the laboratory findings are discussed with regard to the clinical examples. In sum, the insult to tissue from intravascular or local injection with propylhexedrine appears to respond, although poorly, to efforts to reverse the intense pharmacologic vasoconstriction.