Analgesic effects and pharmacokinetics of a low dose of ketamine preoperatively administered epidurally or intravenously

Objectives: The aim of this study was to compare the analgesic effects and pharmacokinetics of epidural versus intravenous administration of low doses of ketamine. Methods: 45 patients scheduled for selective gastrectomy were randomly assigned into 3 groups: 0.5 mg/kg ketamine administered epidurally (Kepi group), 0.5 mg/kg ketamine administered intravenously (Kiv group), or 10 ml normal saline administered epidurally (Ctr group). Analgesic effects were evaluated using Visual Analog Scale (VAS) pain scores at rest, time to first request for analgesic (TFA), and subsequent morphine consumption. The plasma concentration of ketamine was measured with high performance liquid chromatography (HPLC) in the Kepi and Kiv groups. The elimination half-life of ketamine was calculated. Results: Patients in the Kepi group had significantly lower VAS pain scores, longer TFA, and lower morphine consumption than patients in the Kiv or Ctr groups. Compared with intravenous administration, epidural administration of ketamine resulted in higher plasma concentrations from 90 minutes to 48 hours after injection, and much longer elimination half-life of ketamine, but a lower maximum plasma concentration of ketamine. Conclusion: The results suggest that epidural administration of a low dose of ketamine provides more effective analgesic effects as seen post-operatively than intravenous administration. The prolonged half-life and high plasma sustained concentration of epidural ketamine might account for the difference in analgesic effects.