Estimation of the minimum effective dose of tramadol for postoperative analgesia in infants using the continual reassessment method

Abstract

Tramadol is a potent analgesic. However, the analgesia efficacy of tramadol, particularly its minimum effective dose (MED), is not clear. The aim of this study is to find MED of tramadol for postoperative analgesia in infants. The continual reassessment method (CRM) was performed to find MED. Infants undergoing surgeries were included in the 3 phases of this series. In each phase, 24 participants were allocated a different tramadol dose. Pain intensity was measured by face, legs, activity, cry, consolability (FLACC) measurement at 3-hour intervals. Tramadol was considered ineffective if the FLACC score was higher than 4 in 10 at anytime. In phase 1, seven dose levels were used within the range 0.1-0.4 mg·kg(-1)·h(-1). Phase 1 was insufficient to identify the MED, and we increased the dose to 0.4-0.8 mg·kg(-1)·h(-1) in phase 2. Phase 2 was insufficient to identify the MED. In phase 3, local anesthetic wound infiltration was introduced, and the tramadol dose levels tested were the same as in phase 1. The successful analgesia probability of tramadol 0.4 mg·kg(-1)·h(-1) was 82.1% (95% CI, 0.742-0.925) in phase 1. In phase 2, it was 84.7% (95% CI, 0.789-0.991) with the dose 0.8 mg·kg(-1)·h(-1). Phase 1 and phase 2 were insufficient to identify the MED. In phase 3, the successful analgesia probability for dose 0.35 mg·kg(-1)·h(-1) was 96.7% (95% CI, 0.853-0.997).We have demonstrated that tramadol provides insufficient analgesia for surgeries considered to cause moderate-to-severe postoperative pain in infants if used as the sole analgesic, and that local anesthetic wound infiltration enhances the efficacy of tramadol.