Premedication and general anesthetic agents decrease plasma concentration of the endocannabinoid anandamide in dogs.

Objective: To determine the effect of premedication followed by isoflurane (ISO) versus sevoflurane (SEVO), length of general anesthesia (GA), and the amount of IV fluid administered on plasma endocannabinoid arachidonoyl ethanolamide (anandamide; AEA) concentrations in dogs undergoing GA.

Methods: This study was an analysis of samples collected during a previously designed prospective, randomized, single-blinded experimental study involving 21 client-owned dogs undergoing GA. Samples were collected from March through October 2021. Dogs were randomized to ISO or SEVO as the inhalant anesthetic. Blood samples collected before and after GA were used to measure plasma AEA concentrations using HPLC-MS-MS. Data included signalment, length of GA (minutes), surgery performed, fluid volume administered (milliliters per kilogram), and treatment with NSAIDs or steroids. Statistical analyses included power analysis, normality testing, and adjusted linear mixed models.

Results: Plasma AEA concentrations significantly decreased after GA in both groups. Least squares mean AEA concentration decreased from 29 to 12.3 ng/mL in the ISO group and from 26.6 to 11.1 ng/mL in the SEVO group. There were no significant differences between groups or associations with anesthesia duration, fluid volume, surgery, or NSAID/steroid use.

Conclusions: Plasma AEA concentrations were significantly reduced after GA in both the ISO and SEVO groups. This reduction may be influenced by other anesthesia agents, such as dexmedetomidine, hydromorphone, and propofol.

Clinical Relevance: This study is the first to highlight a potential interaction between premedication, GA, and endocannabinoid signaling. Further research is needed to explore these findings and their implications for pain management and neuroprotection.