John J. Bonica

THE TOXICITY OF SOME LOCAL ANESTHETICS AFTER APPLICATION ON DIFFERENT MUCOUS MEMBRANES AND ITS RELATION TO ANESTHETIC ACTION ON THE NASAL MUCOSA OF THE RABBIT

The toxicities of tetracaine, cocaine, lidocaine and α-n-propylamino-2-methylpropionanilide (L 67 Astra) have been compared in rabbits after intravenous, intratracheal, intranasal and intravesical application. The efficiency of these compounds as topical anesthetics has also been estimated on the nasal mucosa of rabbits. The very rapid rate of absorption of tetracaine is illustrated by the LD50 being nearly equal for the i.v. and intratracheal routes of administration. Lidocaine and L 67 in the concentrations used were only about one-fourth to one-fifth as toxic by the intratracheal as compared to the intravenous route. Cocaine toxicity occupied a place between tetracaine and lidocaine when applied on the mucous membranes. A comparison of the topical anesthetic effects of the different compounds showed that tetracaine is about 10 times (cocaine about 2 to 3 times) as efficient as lidocaine and L 67 if the EC50s are compared. However, if duration of anesthesia is taken into account 1% solutions of tetracaine and cocaine are comparable to 2% lidocaine and L 67. By comparing the toxicities and anesthetic efficiencies by the nasal route the relative safety of the different compounds has been discussed.

A COMPARATIVE STUDY OF HEXYLCAINE, PROCAINE, AND LIDOCAINE WITH SPECIFIC ATTENTION TO TISSUE IRRITATION

The authors question the use of Hexylcaine in conduction anesthesia. Their studies demonstrate the irritative properties of this drug.

ANAESTHETIC POTENCY IN EPIDURAL ANALGESIA

IN an extensive literature on epidural analgesia there appears to be some difference of opinion as to the intensity of nerve block produced by different drugs, perhaps partly attributable to the fact that many patients are given light narcosis in addition to nerve block, nowadays, which may conceal differences of drug action. In quoting a few of the many authorities, the following drugs are listed according to the original authors assessment of the relative strengths as regards sensory and motor block, independent of duration, although the actual concentrations used by the different observers varied.

A STATISTICAL EVALUATION OF THE RELATIONSHIPS AMONG LOCAL ANESTHETIC ACTIVITY, IRRITANCY AND SYSTEMIC TOXICITY

Correlation studies were carried out between local anesthetic activity and systemic toxicity and between the former and irritancy. A very high correlation coefficient (r = 0.97) was found between the log of the Threshold Anesthetic Concentration5 (TAC5) of 25 compounds tested by intraspinal injection and the log of their LD50, determined by intravenous injection in mice. A significant correlation (r = 0.74) was also found between the log of the TAC5 of 61 compounds tested by intradermal injection in guinea pigs and the log of the LD50 determrned by intravenous injection in mice. A much lower correlation coefficient (r = 0.43) was obtained between the log of tile Threshold Irritant Concentration4 (TIC4) of 54 compounds deternlined by intradermal injection in rabbits (trypan blue method) and the log of the TAC5 determined by intradermal injection in guinea pigs. These results suggest that a similar mechanism is responsible for the local anesthetic and the lethal effects of local anesthetics. A different mechanism appears to be responsible for local irritation, although in some cases, activity and irritancy may be modified in the same direction by certain structural changes in local anesthetic compounds.