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Patients with reflex sympathetic dystrophy, who received transient pain relief from stellate ganglion blocks or lumbar sympathetic blocks and had abnormal isolated cold stress tests, were enrolled in a study to determine the efficacy of intravenous regional bretylium. Each patient received two control treatments (0.5% lidocaine) and two treatments with 0.5% lidocaine and bretylium 1.5 mg/kg in a randomized, double-blind fashion. A standard intravenous regional technique was used with a 300-mm Hg tourniquet pressure for 20 min. Patients kept a daily record of pain relief (0 = no relief, 100% = complete relief). A decrease in pain of more than 30% was considered clinically significant. Therefore, once the patient's pain relief was less than 30%, the next intravenous regional treatment was performed. Bretylium and lidocaine provided more than 30% pain relief for a mean of 20.0 (± 17.5) days, whereas lidocaine alone provided relief for only 2.7 (± 3.7) days (Mann-Whitney U-test, P < 0.001). A mean temperature increase in the treated limb of +2.64 ± 3.41°C above the baseline temperature was noted after bretylium administration, whereas after control treatments the change was −0.086 ± 1.30°C (Mann-Whitney U-test, P < 0.02). We conclude that the combination of bretylium and lidocaine is significantly more effective than lidocaine alone when an intravenous block is used to treat reflex sympathetic dystrophy.