Innover sans toxicité: à la recherche d’un anesthésique local plus sécuritaire

Abstract

The search for an ‘‘ideal’’ local anesthetic for perioperative anesthesia and analgesia has continued for more than a century. The ideal local anesthetic is an agent with a rapid onset and desirable duration of action that is capable of producing reversible and selective blockade of sensory nerve conduction without risks of local (neurotoxic and myotoxic) or systemic (neurological and cardiovascular) toxicity. Since Koller’s introduction of cocaine as a surgical anesthetic in 1884, several hundred compounds have been tested and found to produce local anesthetic effects. The chemical structures of these agents are diverse and include amino esters (procaine analogues), aminoamides (lidocaine analogues), alcohols (benzyl alcohol), and phenol. However, only a handful of these agents are of clinical value, and the search for the ‘‘ideal’’ local anesthetic continues. For decades, systemic local anesthetic toxicity has received much attention due to the relatively large quantity of local anesthetic administered when performing regional anesthesia. Given the advent of ultrasound-guided regional anesthesia, it is now possible to deposit local anesthetic in close proximity to the desired neurological structure with great precision. Therefore, most regional anesthesia experts are capable of producing successful and desirable effects using substantially reduced quantities of local anesthetic. Furthermore, the ability to visualize the anatomic surroundings in a dynamic manner allows the spread of local anesthetic to take place with a greatly reduced risk of accidental intravascular injection. Although the evidence is still pending, it is likely that this advance in technology holds great promise for reducing the incidence of systemic toxicity. Barrington et al. reported an incidence of systemic anesthetic toxicity to be 0.98 per 1,000 blocks. Our anxiety about the risk of systemic toxicity to local anesthetics has been reduced in recent years by the introduction of the ‘‘lipid sink’’ idea. Prior to this innovation, serious systemic toxic reaction to long-acting local anesthetic drugs was associated with a very poor patient outcome. With the advent of ultrasound-guided regional anesthesia, experts in regional anesthesia have become aware and concerned about the emerging evidence that intraneural injection is a common occurrence during performance of regional anesthesia. In addition, studies have demonstrated that commonly used local anesthetics can cause injury to Schwann cells, disrupt the blood-nerve barrier, decrease neural blood flow with associated ischemia, and disrupt cell membrane integrity. Fortunately, the longterm clinical significance of neurotoxicity without direct needle trauma remains rare. Nevertheless, any drug deposited in the perineural region must be clearly evaluated for its local neurotoxicity. Dextromethorphan has been used as a cough suppressant for decades. Both the parent drug and its metabolite are voltage-dependent sodium channel antagonists, equating them in most ways with local anesthetics. Their local anesthetic properties have been demonstrated in various regional anesthesia techniques, including cutaneous infiltration, peripheral nerve blockade, and intrathecal anesthesia. In this issue of the Journal, Chen et al. undertook an intriguing step to determine and evaluate the systemic toxicity in rodents of dextromethorphan and its metabolite, dextrorphan. After demonstrating the local anesthetic properties of these two agents in their animal models, they administered equipotent doses of these new V. H. Y. Ip, MB B. C. H. Tsui, MD (&) Department of Anesthesiology and Pain Medicine, University of Alberta Hospital, 8-120 Clinical Sciences Building, Edmonton, AB T6G 2G3, Canada e-mail: btsui@ualberta.ca