Use of nalbuphine as a substitute for butorphanol in combination with dexmedetomidine and tiletamine/zolazepam: a randomized non-inferiority trial

Abstract

Objectives: The goal of this study was to determine whether a drug combination using nalbuphine with dexmedetomidine and tiletamine/zolazepam is non-inferior to one that uses butorphanol.

Methods: All healthy cats presenting solely for gonadectomy to two trap-neuter-return mobile clinic days were randomly assigned to induction with a combination of tiletamine/zolazepam 3 mg/kg, dexmedetomidine 7.5 µg/kg and either butorphanol or nalbuphine at 0.15 mg/kg. All participants were blinded to the identity of the combinations. The primary endpoint was clinician satisfaction, comprised of the mean of four satisfaction ratings on a 7-point Likert scale (highly dissatisfied through to highly satisfied) recorded for induction, maintenance of anesthesia, surgery and recovery. Exploratory endpoints included each individual score, number of injections, duration of induction, duration of recovery and need for reversal agent. To assess non-inferiority for the primary endpoint and individual scores, the difference and 95% confidence intervals (CIs) of the difference between the mean clinical scores for the nalbuphine and butorphanol-based combinations were calculated and compared with a prespecified non-inferiority margin of 20% (1.4 points).

Results: Seventy-two cats were enrolled, 36 in each group. The mean ± SD composite score for the combination with nalbuphine was 6.06 ± 0.59 (95% CI 5.86-6.25) points, while the combination with butorphanol was 6.22 ± 0.62 (95% CI 6.01-6.43). The difference between mean scores was 0.17 (-0.12 to 0.45), which did not exceed the prespecified boundary of 1.4, establishing the non-inferiority of nalbuphine. No individual clinical score for nalbuphine was inferior to butorphanol, and there were no significant differences for any secondary endpoints.

Conclusions and relevance: The clinical experience of the nalbuphine-based combination was non-inferior to the butorphanol-based combination. Nalbuphine is an effective substitute for butorphanol, providing another option if butorphanol is unavailable due to shortage, controlled status or cost, without requiring a change in anesthetic workflow.

Keywords: Nalbuphine; anesthetic protocol; butorphanol; clinical satisfaction score; controlled substance; drug substitution; field medicine; non-inferiority.

Figure 1

Graph of the 95% confidence interval for the difference in the mean of the composite satisfaction score (mean of the 7-point induction, anesthesia, surgery and recovery scores) of the nalbuphine-based combination as compared with the butorphanol-based combination. Scores correspond to a 7-point Likert scale, where 1 is highly dissatisfied and 7 is highly satisfied. The predefined clinically meaningful difference was set at −1.4 points (20%)

Figure 2

Graph of the 95% confidence interval for the differences of the means of the 7-point satisfaction scores of a nalbuphine-based combination as compared with a butorphanol-based combination for the secondary endpoints. (a) Induction score; (b) anesthesia score; (c) surgery score; (d) recovery score. Scores correspond to a 7-point Likert scale, where 1 is highly dissatisfied and 7 is highly satisfied. The predefined clinically meaningful difference was set at −1.4 points (20%)