Br.J. Anaesth. (1975), 47, 923
SURFACE ANAESTHETIC PROPERTIES OF THE NEW LOCAL ANAESTHETIC AMIDE ETIDOCAINE (DURANEST): A laboratory evaluation S. B. A. AKERMAN SUMMARY
Etidocaine (Duranest) is a new local anaesthetic amide, which seems to combine favourable properties such as rapidity of onset, a high incidence of satisfactory anaesthesia and a long duration of action in peripheral nerve blocks and extradural anaesthesia (Adams, Kronberg and Takman, 1972; Lund, Cwik and Pagdanganan, 1973; Bridenbaugh et al., 1973). Studies in animals (Adams, Kronberg and Takman, 1972) and man (Scott, Jebson and Boyes, 1973) suggest that the toxicity of etidocaine is intermediate to that of lignocaine and the long-acting local anaesthetic agents bupivacaine and amethocaine. As far as we know, there are no reports of studies of etidocaine as a topical local anaesthetic agent. The present study in experimental animals was undertaken to elucidate the surface local anaesthetic properties of etidocaine and to compare these with those of amethocaine, bupivacaine and lignocaine. Methods were used which made it possible to evaluate both the relative anaesthetic potency of the new compound and its safety following administration to different mucous surfaces. A new technique was developed for a more detailed study on the effects of the application of etidocaine to the respiratory tract, there being a need for an agent that has a better therapeutic ratio than a drug such as amethocaine, since toxic effects are common (Adriani and Campbell, S. B. A. AKERMAN, PH.D., Research and Development Laboratories, Astra Lakemedel AB, S-151 85 Sodertalje, Sweden.
1956; Axelsson, 1960) because of the rapid absorption of local anaesthetic agents from this site of application. MATERIAL AND METHODS
Corneal anaesthesia was studied in rabbits (New Zealand White, 1.8-3.0 kg) by the application of 0.25 ml of the solutions to the conjunctival sac for 0.5 min. Frequency, latency period and duration of block of the corneal reflex to pin-pricking were recorded. The topical anaesthetic effect of the different compounds on the nasal mucosa was studied in the rabbit according to the method of Nieschultz, Hoffman and Popendiker (1958). One-half ml of the test solution was applied to one nostril by a polyethylene catheter with an occluded tip and multiple side perforations. A small brush was introduced into the nostril at regular intervals after the application, and the block of the sneeze reflex was recorded. A new technique (Akerman and Haegerstam, unpublished) using guineapigs (Dunkin-Hartley, 260350 g), was developed for the assessment of surface anaesthesia of the respiratory tract. The animals were anaesthetized with 0.6 ml of 1.0% pentobarbitone sodium (Mebumalum NFN) given into the peritoneum. An incision was made between two tracheal rings through which a specially designed polyethylene catheter was inserted about 2 cm into the trachea and fixed. After recovery from the operation the cough reflex was provoked by inserting a plastic tube, sealed and perforated at the end, through the fixed catheter and moving the tube up and down in the
Downloaded from http://bja.oxfordjournals.org/ at Cornell University Library on June 23, 2015
The surface local anaesthetic properties of the new local anaesthetic amide etidocaine (Duranest) were studied in experimental animals. Etidocaine produced topical local anaesthesia of high intensity, rapid onset and with a comparatively long duration of action following corneal, intxanasal and intratracheal application. The surface anaesthetic activity of etidocaine was substantially greater than that of lignocaine, similar to that of bupivacaine but less than that of amethocaine. When applied to the mucous surfaces of the nose and the respiratory tract, etidocaine was less toxic than amethocaine and bupivacaine but more toxic than lignocaine. The data justify a clinical evaluation of etidocaine as a surface anaesthetic.
924
BRITISH JOURNAL OF ANAESTHESIA
RESULTS
Corneal application. As indicated by the minimum concentrations required for complete block of the corneal reflex to pin-pricking, the local anaesthetic activity increased in the following order: lignocaine, etidocaine, bupivacaine and amethocaine (fig. 1). The blocks produced by etidocaine were of longer duration (PP>0.01). The blocks produced by amethocaine had durations which were longer than those of both etidocaine (P
SURFACE ANAESTHETIC PROPERTIES OF THE NEW LOCAL ANAESTHETIC AMIDE ETIDOCAINE (DURANEST): A laboratory evaluation S. B. A. AKERMAN SUMMARY
Etidocaine (Duranest) is a new local anaesthetic amide, which seems to combine favourable properties such as rapidity of onset, a high incidence of satisfactory anaesthesia and a long duration of action in peripheral nerve blocks and extradural anaesthesia (Adams, Kronberg and Takman, 1972; Lund, Cwik and Pagdanganan, 1973; Bridenbaugh et al., 1973). Studies in animals (Adams, Kronberg and Takman, 1972) and man (Scott, Jebson and Boyes, 1973) suggest that the toxicity of etidocaine is intermediate to that of lignocaine and the long-acting local anaesthetic agents bupivacaine and amethocaine. As far as we know, there are no reports of studies of etidocaine as a topical local anaesthetic agent. The present study in experimental animals was undertaken to elucidate the surface local anaesthetic properties of etidocaine and to compare these with those of amethocaine, bupivacaine and lignocaine. Methods were used which made it possible to evaluate both the relative anaesthetic potency of the new compound and its safety following administration to different mucous surfaces. A new technique was developed for a more detailed study on the effects of the application of etidocaine to the respiratory tract, there being a need for an agent that has a better therapeutic ratio than a drug such as amethocaine, since toxic effects are common (Adriani and Campbell, S. B. A. AKERMAN, PH.D., Research and Development Laboratories, Astra Lakemedel AB, S-151 85 Sodertalje, Sweden.
1956; Axelsson, 1960) because of the rapid absorption of local anaesthetic agents from this site of application. MATERIAL AND METHODS
Corneal anaesthesia was studied in rabbits (New Zealand White, 1.8-3.0 kg) by the application of 0.25 ml of the solutions to the conjunctival sac for 0.5 min. Frequency, latency period and duration of block of the corneal reflex to pin-pricking were recorded. The topical anaesthetic effect of the different compounds on the nasal mucosa was studied in the rabbit according to the method of Nieschultz, Hoffman and Popendiker (1958). One-half ml of the test solution was applied to one nostril by a polyethylene catheter with an occluded tip and multiple side perforations. A small brush was introduced into the nostril at regular intervals after the application, and the block of the sneeze reflex was recorded. A new technique (Akerman and Haegerstam, unpublished) using guineapigs (Dunkin-Hartley, 260350 g), was developed for the assessment of surface anaesthesia of the respiratory tract. The animals were anaesthetized with 0.6 ml of 1.0% pentobarbitone sodium (Mebumalum NFN) given into the peritoneum. An incision was made between two tracheal rings through which a specially designed polyethylene catheter was inserted about 2 cm into the trachea and fixed. After recovery from the operation the cough reflex was provoked by inserting a plastic tube, sealed and perforated at the end, through the fixed catheter and moving the tube up and down in the
Downloaded from http://bja.oxfordjournals.org/ at Cornell University Library on June 23, 2015
The surface local anaesthetic properties of the new local anaesthetic amide etidocaine (Duranest) were studied in experimental animals. Etidocaine produced topical local anaesthesia of high intensity, rapid onset and with a comparatively long duration of action following corneal, intxanasal and intratracheal application. The surface anaesthetic activity of etidocaine was substantially greater than that of lignocaine, similar to that of bupivacaine but less than that of amethocaine. When applied to the mucous surfaces of the nose and the respiratory tract, etidocaine was less toxic than amethocaine and bupivacaine but more toxic than lignocaine. The data justify a clinical evaluation of etidocaine as a surface anaesthetic.
924
BRITISH JOURNAL OF ANAESTHESIA
RESULTS
Corneal application. As indicated by the minimum concentrations required for complete block of the corneal reflex to pin-pricking, the local anaesthetic activity increased in the following order: lignocaine, etidocaine, bupivacaine and amethocaine (fig. 1). The blocks produced by etidocaine were of longer duration (PP>0.01). The blocks produced by amethocaine had durations which were longer than those of both etidocaine (P
