Irreversible Ischemic Hand Following Intraarterial Injection of Zolpidem Powder
Ming-Yang Chang, M.D., and Ja-Liang Lin, M.D. -- Journal of Toxicology, CLINICAL TOXICOLOGY, Vol. 41, No. 7, pp. 1025-1028, 2003
CASE REPORT
A 24-yr-old woman was admitted to Chang Gung Memorial Hospital with a painful cyanotic right hand 2 days after she injected a crushed zolpidem tablet into her radial artery. The patient had suffered from severe insomnia for 1 month. Seeking to maximize the effectiveness of the hypnotics she was taking, she learned a method of intravenous injection of tablets from a friend. The patient crushed a 10mg zolpidem tablet into powder, mixed it with 2mL of hot water, waited until it cooled, and then injected the mixture into a blood vessel on the volar aspect of the right wrist. She experienced severe pain in the right hand immediately after the injection, and all the fingers of her right fingers gradually turned black. On questioning, the patient reported that she aspirated bright red prior to the injection. The patient had previously enjoyed good health, and she denied any major systemic disease or history of recreational drug abuse.
Her vital signs were temperature 36C, respiration 19 breaths per min, pulse 129 beats per min, and blood pressure 163=115 mmHg. Her right hand was mottled, cool, and tender; all five digits of the right hand were cyanotic. Delayed capillary refilling and poor sensation to touch of these fingertips were observed. The area around the injection site was not discolored and the right hand was only slightly swollen. The rest of the physical examination was normal. Routine blood count and biochemistry tests were unremarkable. Emergent right upper limb arteriography revealed patent ulnar and radial arteries. The arteries in the hand appeared normal but duplex scanning showed reduced blood flow in the right interphalangeal arteries. The patient was treated promptly with a continuous intravenous heparin infusion titrated to an activated partial thrombin time between one and a half to two times the control value. Additionally, the right hand was elevated and opiates were given for pain control. Cyanosis of the five digits resolved partially after 3 days of treatment, but gangrene gradually developed in the first four fingertips (Fig. 1). The patient was further treated with nifedipine, parenteral oxacillin, and prostaglandin El intravenous infusion. One episode of hyperbaric oxygen therapy was administered. Nevertheless, the patient’s condition failed to improve, and she discharged herself against medical advice 1 month later, with the first four digits of the right hand continuing to suffer from gangrene.
Discussion (abridged):
Vascular occlusion of digits may result in tissue ischemia and subsequent digital necrosis and gangrene. Treiman et al. reported that almost 50% of severe cases required digital amputation following intraarterial injection (3).
The patient reported here accidentally injected one crushed zolpidem tablet into her radial artery, causing severe ischemia and digital gangrene. According to the manufacturer, zolpidem tablets contain zolpidem hemotartrate, microcrystalline cellulose, monohydrated lactose, and sodium carboxymethylamidon. The microcrystalline cellulose, which is an approved structural element in tablets for oral use in humans, is a solid embolic agent for the permanent occlusion of blood vessels in canine renal arterial systems (8). Microcrystalline cellulose spheres are insoluble in water and most organic solvents; they travel to vessels with diameters approximating their own, and larger vessels were occluded by bead aggregation (8). Since our patient was refractory to heparinization and vasodilators, we suspect that microvascular embolization related to the microcrystalline cellulose may have contributed to this irreversible ischemic process.
Microcrystalline cellulose is used also in the preparation of codeine, pentazocine, methadone, oxcycodone, and phenobarbital tablets. Goldberg et al. reported gangrene of the upper extremity after an intraarterial injection of crushed codeine tablets (9).
The results demonstrated that the unique component producing the gangrene was the microcrystalline cellulose, while the injection of pure codeine was harmless. Furthermore, pulmonary microcrystalline cellulose deposition from intravenous injection of codeine tablets has been reported in a patient receiving parenteral nutrition (10).