THE EFFECTS OF HYALURONIDASE ON LOCAL-ANESTHESIA - A PROSPECTIVE, RANDOMIZED, CONTROLLED, DOUBLE-BLIND-STUDY

Hyaluronidase, an enzyme that breaks down intercellular cement, has been advocated as an additive to local anesthetics because it allows injected solutions to spread and penetrate tissues. Because epinephrine is commonly used in conjunction with local anesthetics, the combined effects of both hyaluronidase and epinephrine were studied in a prospective, controlled, double-blind manner. The forearms of volunteers ranging in number from 15 to 23 were injected with 0.5 ml of lidocaine to which graded doses of hyaluronidase and epinephrine had been added. At various intervals after injection, the areas of anesthesia were measured. From these data, the time to reach peak area of anesthesia (onset), the size of the peak area of anesthesia, and the time until disappearance of anesthesia (duration) were computed and analyzed. We found that epinephrine has a more profound effect on the onset, area, and duration of anesthesia than hyaluronidase. Epinephrine delayed the time to reach peak area of anesthesia (onset) relative to lidocaine alone more than hyaluronidase (0.28 h versus 0.04 h). When both agents were used together, the effect was subtractive (0.28 - 0.04 = 0.24 h, compared with 0.22 h observed). This suggests a negative interaction (inhibition) because hyaluronidase decreased the epinephrine effect by 21 percent. Concerning the size of peak area of anesthesia, epinephrine increased the area relative to lidocaine alone more than hyaluronidase (626 versus 221 mm(2)). When both agents were used together, the effect was additive (626 + 221 = 847 mm(2), compared with 848 mm(2) observed). This suggests that the two agents acted independently of each other in relation to area of anesthesia. As for duration of anesthesia, epinephrine increased the duration of anesthesia relative to lidocaine alone by 150 percent, whereas hyaluronidase had no effect. The combined effect was the same as that produced by epinephrine alone. The clinical implications of these findings are that epinephrine and hyaluronidase, administered separately or together with lidocaine, appear to produce effects on the onset, size, and duration of anesthesia that may be adapted to achieve specific goals for specific surgical procedures. The evidence for (1) independent action of the agents in increasing the area of anesthesia and (2) inhibition by hyaluronidase of the epinephrine effect on the onset of anesthesia suggests the presence of receptor mechanisms at the tissue and/or the cellular level.