Cardiopulmonary Effects and Pharmacokinetics of Dexmedetomidine Used as an Adjunctive Analgesic to Regional Anesthesia of the Oral Cavity with Levobupivacaine in Dogs

Simple Summary The modern approach to multimodal analgesia is based on the use of various types of analgesics before, during, and after surgery, including local anesthetics, such as levobupivacaine. Dexmedetomidine is used as an adjunctive analgesic to enhance the efficacy and duration of local anesthetics, but its use may be associated with dose-related adverse effects, such as hypertension and bradycardia. The primary aim of the study was to investigate the cardiopulmonary effects of dexmedetomidine administered perineurally as an adjunctive analgesic to regional anesthesia of the upper and lower jaw with levobupivacaine in anesthetized dogs. The secondary aim of the study was to investigate the pharmacokinetics of dexmedetomidine to explain the changes in cardiopulmonary parameters due to dexmedetomidine administration. Infraorbital administration was associated with faster absorption of dexmedetomidine, while application into the submucosa near the inferior alveolar nerve resulted in better bioavailability and faster elimination. Perineural administration of dexmedetomidine was associated with lower plasma concentration compared to intravenous administration and may be preferable because it induces a less pronounced cardiovascular response in terms of hypertension and bradycardia. This study investigated the cardiopulmonary effects and pharmacokinetics of dexmedetomidine (DEX) used as an adjunctive analgesic for regional anesthesia of the oral cavity with levobupivacaine in anesthetized dogs. Forty dogs were randomly assigned to four groups of 10 dogs. All dogs received levobupivacaine (4 blocks) with DEX IO (infraorbital block, n = 10) or IA (inferior alveolar block, n = 10) or placebo (PLC; n = 10) or DEX (n = 10) was injected intravenously (IV) after administration of levobupivacaine. The dose of DEX was always 0.5 mu g/kg. Cardiopulmonary parameters were recorded, and blood was drawn for the quantification of DEX in plasma using LC-MS/MS. Heart rate was lower in all LB + DEX groups, while mean arterial pressure (MAP) was higher in the LB + DEX IV and LB + DEX IA groups compared to the LB + PLC IV group. Compared to DEX IV, IO and IA administration resulted in lower MAP up to 2 min after application. Absorption of DEX was faster at IO administration (C-max and T-max were 0.47 +/- 0.08 ng/mL and 7.22 +/- 1.28 min and 0.76 +/- 0.09 ng/mL and 7.50 +/- 1.63 min for the IO and IA block, respectively). The IA administration resulted in better bioavailability and faster elimination (t(1/2) was 63.44 +/- 24.15 min and 23.78 +/- 3.78 min for the IO and IA block, respectively). Perineural administration of DEX may be preferable because of the less pronounced cardiovascular response compared to IV administration.