Intravenous tramadol: Effects, nociceptive properties, and pharmacokinetics in horses

Objective To determine the optimal dose, serum concentrations and analgesic effects of intravenous (IV) tramadol in the horse. Study design Two-phase blinded, randomized, prospective crossover trial. Animals Seven horses (median age 22.5 years and mean weight 565 kg). Methods Horses were treated every 20 minutes with incremental doses of tramadol HCl (0.1-1.6 mg kg^-1) or with saline. Heart rate, respiratory rate, step frequency, head height, and sweating, trembling, borborygmus and head nodding scores were recorded before and up to 6 hours after treatment. In a second study, hoof withdrawal and skin twitch reflex latencies (HWRL and STRL) to a thermal stimulus were determined 5 and 30 minutes, and 1, 2, 4 and 6 hours after bolus IV tramadol (2.0 mg kg ^-1) or vehicle. Blood samples were taken to determine pharmacokinetics. Results Compared to saline, tramadol caused no change in heart rate, step frequency or sweating score. Respiratory rate, head height, and head nodding and trembling scores were transiently but significantly increased and borborygmus score was decreased by high doses of tramadol. Following cumulative IV administration of 3.1 mg kg^-1 and bolus IV administration of 2 mg kg^-1, the elimination half-life of tramadol was 1.91 ± 0.33 and 2.1 ± 0.9 hours, respectively. Baseline HWRL and STRL were 4.16 ± 1.0 and 3.06 ± 0.99 seconds, respectively, and were not significantly prolonged by tramadol. Conclusion and clinical relevance IV tramadol at cumulative doses of up to 3.1 mg kg^-1 produced minimal transient side effects but 2.0 mg kg^-1 did not provide analgesia, as determined by response to a thermal nociceptive stimulus.