Development of a sedation assessment scale for comparing the sedative effects of alfaxalone-hydromorphone and ketamine-midazolam-hydromorphone for intravenous catheterization in the domestic rat (Rattus norvegicus)

Abstract Background Sedation is commonly performed in rats to facilitate diagnostic and minimally invasive procedures. No sedative drugs are labeled for use in this species and there are few reports comparing efficacies of different sedation protocols. The study aim was to compare two intramuscular sedation protocols for intravenous catheterization and initial development of a sedation assessment scale. Methods Following ethics approval and informed consent, a convenience sample of clinically healthy adult rats (n = 13 females, n = 12 males) scheduled for neutering was recruited. Rats were randomized to 2 treatment groups: intramuscular alfaxalone (5 mg/kg)-hydromorphone (0.2 mg/kg) (AH, n = 12) or ketamine (20 mg/kg)-midazolam (0.5 mg/kg)-hydromorphone (0.2 mg/kg) (KMH, n = 13). Catheter placement was attempted 20 minutes post-injection. A sedation scale was developed by 2 observers blinded to treatment. Study outcomes: sedation quality, response to catheter placement, heart and respiratory rates. Results Measurable sedation was present at 5 minutes post-injection in both groups. Peak sedation was earlier with AH (5 minutes) than KMH (15-20 minutes). At 20 minutes, sedation scores with AH were lower than KMH. Heart rate was reduced in both groups compared to baseline, with no difference between groups. Up to 15 minutes, respiratory rate was lower with AH than KMH. More rats in the AH (10/12) than KMH (4/13) group responded to catheter placement. The sedation scale showed excellent internal consistency (Cronbach's alpha = 0.88). Conclusions and clinical relevance Measurable sedation was achieved with both protocols but the temporal profile differed, so that window of opportunity to perform procedures is shorter with AH than KMH. The sedation scale was able to discriminate between different sedation protocols, illustrating construct validity, and shows promise for further development.