It is clinically well known that the additive adrenaline improves the anesthetic potency, increases the duration of action, and decreases the risk of systemic toxicity of local anesthetics. The objectives of this study were to demonstrate experimentally the effects of adrenaline on local and serum pharmacokinetics of lidocaine after infiltration anesthesia. Two percent 14C-lidocaine with and without 10 µg/ml of adrenaline was injected into the palatal mucosa of rats and radioactivity in the maxilla and serum was sequentially and quantitatively measured.
This study was approved by the Animal Experiment Committee of The Nippon Dental University, School of Life Dentistry at Tokyo, and all procedures were performed according to the prescribed regulations.
After the injection of 20 µl of 2% 14C-lidocaine and 2% 14C-lidocaine with 10 µg/ml of adrenaline into the right palatal mucosa proximal to the first molar (Fig. 1), radioactivity (dpm) in the maxillary tissue was measured 2, 5, 10, 20, 30, 40, 50 and 60 minutes after the injection (n = 5). The concentration of lidocaine (ng/mg tissue wet weight) was calculated from dpm. Autoradiograms of frontal sections of the maxilla including the injection site were analyzed visually and quantitatively 2, 20, 40 and 60 minutes after the injection to demonstrate the frontally infiltrated area of lidocaine and the amount of lidocaine (n = 5). The radioactivity in the serum was measured from 2 to 720 minutes after the injection of 2% 14C-lidocaine with and without 10 µg/ml of adrenaline (n = 7). Radioactive substances extracted from the maxilla and serum 60 minutes after the injection were analyzed by thin layer chromatography (TLC) (n = 4). The effect of 2% lidocaine with and without 10 µg/ml adrenaline on the lip blood flow was observed by laser Doppler flowmetry (n = 4).
The lidocaine concentration in the palatal mucosa (Fig. 2A, B) and maxillary part (Fig. 2C, D) 2 minutes after the injection of lidocaine with adrenaline was more than twice that when injected alone. The increasing tendency of concentration caused by additive adrenaline was also confirmed in the incisive part (Fig. 2E, F), palatal part (Fig. 2G, H) and maxillary nerve (Fig. 2I, J). The autoradio-graphic analysis showed that lidocaine infiltrated into a wide area covering the palatal mucosa on the right and left sides and the ethmoidal sinuses (Fig. 3). When adrenaline was added, the lidocaine concentrations 2, 20, and 40 minutes after the injection were 1.8, 2.1, and 1.7 times higher respectively than those when administered alone (Fig. 4). The lidocaine concentration in the serum reached the maximum value at 90 minutes after the injection. The serum lidocaine concentration after the injection of lidocaine with adrenaline was significantly lower from 2 to 50 minutes and higher after 60 minutes than that when injected alone (Fig. 5). It was confirmed by TLC that more than 70% of the radioactive substances detected in the maxillary tissue and serum within 60 minutes after the injection was authentic lidocaine (Fig. 6A, B). The upper lip blood flow increased from 15 to 55 minutes after 2% lidocaine injection, and decreased from 10 to 45 minutes after 2% lidocaine with 10 µg/ml of adrenaline (Fig. 7).
These findings demonstrated that following oral infiltration anesthesia, lidocaine in the maxillary tissue diffuses across the palatal mucosa, is absorbed rapidly into the bloodstream because of its vasodilative action, and disappears from the maxilla. When adrenaline is added, however, lidocaine stays in the local site for a long time because of the vasoconstrictive action of adrenaline.