+Adjuvants, Substitutes and Safeguards.+ The numerous disadvantages in the general use of this most efficient but most treacherous local anesthetic have operated so strongly that efforts have constantly been made to find a substance which, when used with it, would correct its toxic effects. The desirability of employing large quantities of an anesthetic solution so as to enable the operator to infiltrate large areas of tissue has led to the method of preparing very dilute solutions and mixing them with various chemical substances which in themselves would act as mild anesthetics and at the same time increase the diffusibility of the cocaine. With any of these substances, cocaine still remains toxic and the quantity injected must be kept account of when an operation of any extent is being performed even though the solution be never so mild. A valuable preventive to this absorption is found in the application of a constricting band or tourniquet to impede the return circulation and allow the washing out of much of the drug before the obstruction is removed. It is evident that no method has yet been devised whereby the use of cocaine is rendered safe and it is for this reason that chemists throughout the world have sought to produce either a new anesthetic drug or to evolve a drug synthetically, from cocaine, minus its toxicity. This has been done, but cocaine still has its adherents because of its superior qualities. Quinine and urea hydrochloride is one of the new substitutes which has found much favor. Among the synthetic derivatives may be mentioned alypin, novocaine, stovaine, betaeucaine, tropacocaine, anesthesin, subcutin and many others. Each of these has its advocates and all of them have some advantage over cocaine; they have disadvantages as well, which, however, in the hands of skilled operators, may be overcome. +Quinine and Urea Hydrochloride.+ Among the quinine salts and combinations, the above has found most favor. It consists of a molecule of quinine hydrochloride and one of urea. It occurs as a fine crystalline powder and is readily soluble in water, forming an acid solution. This substance is one of the most recent and best substitutes for cocaine, being capable of a wide range of usefulness and practically devoid of any toxicity. It causes redness on being injected and, in strong solutions, may delay healing considerably, this constituting the main disadvantage to its use. After the use of this anesthetic, primary union is not usual.