The addition of epinephrine to proxymetacaine or oxybuprocaine solution increases the depth and duration of cutaneous analgesia in rats

Background: The aim of this experiment was to investigate the interaction between epinephrine and 2 local anesthetics (proxymetacaine or oxybuprocaine) using subcutaneous injections under the hairy skin, thereby simulating infiltration blocks. Methods: Using a rat model of cutaneous trunci muscle reflex in response to local skin pinpricks, the anesthetic properties of proxymetacaine and oxybuprocaine alone and in combination with epinephrine as an infiltrative anesthetic were tested. Isobolographic analysis was used for the analgesic interactions between adjuvant epinephrine and the local anesthetics. Lidocaine was used as a control group. Results: Oxybuprocaine, proxymetacaine, and lidocaine elicited a dosedependent block to pinpricks. On the 50% effective dose (ED50) basis, their relative potencies were proxymetacaine [0.126 (0.113-0.141) μmol] greater than oxybuprocaine [0.208 (0.192-0.226) μmol] greater than lidocaine [6.331 (5.662-7.079) μmol] (P < 0.01 for each comparison). On an equipotent basis (ED25, ED50, and ED75), sensory block duration elicited by oxybuprocaine or proxymetacaine was greater than that elicited by lidocaine (P < 0.01). Coadministration of proxymetacaine, oxybuprocaine, or lidocaine with epinephrine produced a synergistic analgesic effect and prolonged the cutaneous analgesic effect. After adding epinephrine, oxybuprocaine was much faster, reaching its maximal blockade, than proxymetacaine or lidocaine (P < 0.01). Conclusions: We concluded that proxymetacaine and oxybuprocaine were more potent and produced greater duration of nociceptive block than lidocaine. The use of epinephrine augmented the potency and prolonged the duration of proxymetacaine, oxybuprocaine, and lidocaine as an infiltrative anesthetic.