The Effects of Hyaluronidase on the Efficacy and on the Pain of Administration of 1% Lidocaine

Abstract

Despite current clinical practice, there is no objective evidence to demonstrate the efficacy or pain on injection when hyaluronidase is added to lidocaine as an anesthetic combination for local anesthesia. To evaluate the usefulness of hyaluronidase added to lidocaine in affecting pain on injection and effectiveness of local anesthesia, a prospective, randomized, double blind study comparing 1% lidocaine preparations with and without hyaluronidase (15 U/cc) was conducted. A paired experiment was done with each subject receiving both treatments. Solutions of these local anesthetics were prepared. A 0.5-cc intradermal injection of each was administered to the dorsum of the nondominant hand of 25 volunteers. After showing study participants a standard pain with a peripheral nerve stimulator, pain of anesthetic infiltration was rated by the subject using a visual analog scale. The amount of tissue deformation on injection was assessed. The area of anesthetized skin surrounding each injection was measured at 1/2, 1, 2 1/2, 4 1/2, 8, and 12 minutes after injection. The area of anesthesia achieved by 1% lidocaine infiltration can be significantly enhanced by the addition of hyaluronidase at a concentration of 15 U/cc (p = 0.0003). This raises the pH of the anesthetic to a slightly more physiologic level (6.33 versus 6.20) and makes the pH closer to the pK of the lidocaine. In addition, the hyaluronidase additive significantly decreases the amount of tissue distortion (p < 0.0001) without decreasing the efficacy of anesthetic action (p = 0.01). However, adding hyaluronidase to 1% lidocaine significantly increased the pain on injection (p = 0.0002). The injections of small amounts of hyaluronidase-containing solutions in this experiment did not produce any visible effects at 5 to 7 days after injection; however, the effect of hyaluronidase upon wound healing was not studied.

Pain Levels after Local Anaesthetic with or without Hyaluronidase in Carpal Tunnel Release: A Randomised Controlled Trial

“…The addition of hyaluronidase can also significantly enhance the area of anaesthesia achieved by local anaesthetic infiltration, decreasing the amount of tissue distortion without decreasing its efficacy. This has been noted in previous papers which observed increased surface area of local anaesthesia with the addition of hyaluronidase [22, 23]. …”

Bee Venom Pretreatment Has Both an Antinociceptive and Anti-Inflammatory Effect on Carrageenan-Induced Inflammation.

“…These include: histamine, which acts directly on primary afferent nociceptive endings; phospholipase A 2 , which activates arachidonic acid metabolism to produce prostanoids which in turn act directly on primary afferents; and hyaluronidase, which has been shown to cause pain following injection into the skin [23,29]. In the present study, while subcutaneous injection of BV into the hindlimb did not produce detectable nociceptive behavior or hyperalgesia in the hindpaw region (as did direct intraplantar injection; see also ref [6]), we did observe some redness in the injection site.…”

Clinical Trial for Safety Evaluation of Hyaluronidase as Diffusion Enhancing Adjuvant for Infiltration Analgesia of Skin with Lidocaine

“…Some authors postulate that HAase causes less tissue distortion. 20 This could be an explanation for the better diffusion conditions and greater efficacy of co-applied lidocaine, but also for the inhibition of wound healing. Because of the great individual variation, clinical wound-healing studies on healthy volunteers have been found useful for comparative investigations, because although the wounds are artificial, the population is homogeneous.…”