Serum concentrations of lidocaine and its metabolites after prolonged infusion in healthy horses

Lidocaine continuous-rate infusions (CRI) are the most commonly used prokinetic in equine practice for the treatment of post-operative ileus and are also increasingly being used in pain management, such as in cases of severe laminitis, and are often used for prolonged durations. To date only limited time/concentration relationships of lidocaine administered as a short term (24hours) CRI to horses are reported. This study examined the time/concentration profile of lidocaine and its active metabolites (GX, MEGX) during a 96 hour lidocaine infusion in eight mature healthy horses. Serum lidocaine concentrations reached steady state by three hours and did not accumulate thereafter. The serum concentration of lidocaine was above the target therapeutic concentration (980ng/ml) only at 6 and 48 hours. The serum lidocaine concentration did not reach the range described as potentially causing toxicity (>1850ng/ml). The MEGX metabolite did not accumulate over time, while the GX metabolite accumulated significantly up to 48 hours and then remained constant. The serum concentrations of lidocaine, MEGX and GX were below the limit of detection within 24 hours of discontinuation of the infusion. None of the horses developed any signs of lidocaine toxicity during the study. It was concluded that the metabolism of lidocaine was not significantly impaired by prolonged infusion, contrasting with studies in dogs and humans. No adverse effects were observed in this study, which with the lack of lidocaine accumulation suggests that prolonged infusions are safe. However the accumulation of GX, a potentially toxic active metabolite, is cause for concern.