It is now well known-Schafer, Moore, and others-that adrenalin possesses the property of constricting the smaller vessels of a part into which it is injected. Such a part is seen to be blanched and anemic, as though emptied of blood by constriction or cold. Now, when adrenalin combined with B eucaine is injected, several verv notable effects are produced. By the retardation of the blood flow the eucaine remains in the area. injected, and is not washed away at once by the blood stream into the general circulation. From this it follows that its effects on the nerves of the part are intensified and prolonged to a large extent, and, therefore, if combined with adrenalin, less of the drug is required to produce a full effect. Moreover, as it is thus retained in the tissues locally for a long time, often hours, it only reaches the circulation, and through it the higher nerve centres very slowly, if it ever reaches them at all in the form of Beucaine. For there is reason to believe (Braun) that before it is parted with by the local tissue elements it is altered in their protoplasm into other compounds innocuous to the nerve centres. At any rate, it has been found, experimentally, that a dose of cocaine capable of rapidly killing an animal if injected alone, is quite harmless if combined with adrenalin.

A knowledge of these facts enables us on the one hand to employ less of the drug when adrenalin is added, seeing that its analgesic action is thereby intensified, and on the other justifies us in increasing the area of injection, and, if necessary, the amount of eucaine, seeing that its general toxic effects are restrained or abolished. As a matter of fact, I have several times. injected more than 6 grains of B eucaine, combined with adrenalin, in adults where large areas had to be dealt with, no ill effects being noted. Of course it is necessary to be very careful with a new drug, and I prefer to regard 6 grains as the maximum, especially as in practice it suffices for the largest operations. To utilize these data in clinical work we have to keep in view several questions.

1. How to reach on the proximal side of our area of operation the nerve branches supplying it, and how to saturate them as far as possible with the solution containing the drugs mentioned.

2. How far we can dilute the latter so as (without forfeiting their potency) to have enough of the medium to carry the active agents to all the parts required, even if extensive.

3. How to maintain the analgesia long enough for any ordinary operation without being obliged to infiltrate further, as in the older methods (Schleich).

1. The first of these questions is mainly an anatomical one, best met by considering the course and distribution of all the possible nerves which supply a part. There are, of course, gaps

in our knowledge of the ultimate distribution of many nerves, notably of those supplying the parietal peritoneum; but these are being steadily filled up by the anatomists (vide Ramstrom, Dogiel, Timofejew).

In reaching the nerves of a part hollow needles of varying length are thrust into their immediate neighborhood or across their course at some distance from the area of operation, and thus the fluid injected through them is carried as near to them as possible. We can also make use of fascial planes and areolar spaces, along which the fluid will pass easily. For instance, in removing the vermiform appendix in the stage of quiescence we have to deal with the skin, muscles, parietal peritoneum, and its reflexion to form the mesenteriolum of the vermiform appendix. To render the skin and areolar tissues insensitive is a simple matter. We have only to inject a somewhat larger area of these than we are likely to cut (local analgesia). The muscles are not quite so easy to deal with. Here we enter a very long, blunt, hollow needle through the skin already infiltrated about two inches outside the line of incision at its lower end and push it slowly upwards between the layers of the muscles, injecting slowly as we go until we have nearly reached the costal margin and used 10 c. cm. of fluid. From the upper end, in the same line, the needle is now pushed downwards through the deeper layers as near the peritoneum as possible, using another 10 c.cm. We thus cross the line of the nerves supplying both muscles and peritoneum (Ramstrom). In some cases I have injected the subperitoneal tissues underneath the cecum and appendix, either from above the iliac crest or from below Poupart's ligament, just inside the anterior iliac spine. I had done this previously on the cadaver with blue injecting fluid, and been surprised at the way the fluid spread along the iliac fossa.

This is simply an illustration of how the nerves of a part can be reached ("regional analgesia "). For the groin no better guide can be taken than some diagrams published a propos of the subject by Cushing. These are especially valuable for radical cure of hernia and for removal of testicle, of which I have had several cases in markedly phthisical patients, whose lungs would hardly have tolerated either chloroform or ether.

As to abdominal organs, it appears almost certain (Lennander) that they are per se insensitive to pain so far as they are independent of the parietal peritoneum in any of its reflexions. For instance, I have watched a patient's face while inserting a trochar in several directions deeply into the liver, and it showed complete indifference. When asked, he stated that he felt nothing. The incision through the abdominal wall had been previously made under eucaine. Again, I have several times divided the vermiform appendix with the actual cautery without pain, though

the analgesic fluid had only been applied for the parietes. But a drag on the mesenteriolum or on adhesions about the vermiform appendix is felt as griping unless the injection have reached them.

It is plain, then, that our injection must in every case be carried out with special reference to the nerves of the part (regional analgesia).

2. The strength of the B eucaine solution has only been settled after much practical experience. We must, on the one hand, keep within the safe dose of the drugs, and on the other have at our disposal a large enough quantity of the fluid medium to render it possible to spread the analgesic agents over large areas. If we suppose 6 grains of B eucaine to be about the full dose when combined with adrenalin, a good deal of fluid will be required. My own experience (now a long one) leads me to the conclusion that for ordinary surgical work the following solution answers well:

The actual strength of adrenalin in this solution is one in two hundred thousand (1:200,000).

All this quantity of fluid can be used in an ordinary case if necessary, and is quite sufficient for most. But I have often injected twice as much when large areas had to be dealt with, and have seen no ill results from the 6 grains of eucaine or 20 minims of adrenalin. The latter amount corresponds to just about 1 mg. of adrenalin, namely 20 minims circa 1 c.cm. of 1 pro mille solution.

I have also used 4 grains B eucaine to 100 c.cm., but noted no appreciable increase of analgesia.

I have made several observations on this fluid with Beckmann's apparatus to prove its osmotic tension, and found that it is as nearly as possible isotonic with the blood. If not isotonic such a solution would produce pain on injection, and might also lead to necrosis of the tissues into which it was injected. This was actually the case in the practice of a friend of mine, who used 2 per cent. of eucaine simply dissolved in boiled water without any addition of sodium chloride. The analgesia was excellent, he told me, but necrosis of the injected tissue followed. To test the osmotic tension of a 2 per cent. of B eucaine alone I froze it in the Beckmann's apparatus and showed him that it registered-0.28 C. as against human blood-0.56 C. Hence his trouble.

With the solution given above we have never seen the slightest sign of loss of vitality.

"indifferent" to the tissues.

In short, it was "isotonic" and
It is very easily made. In a Jena

glass beaker, or 7 oz. wide-mouthed flask into which a syringe will go, 31⁄2 oz. (—100 c.cm.) of distilled water is put and boiled. To this is added a powder containing the B eucaine 3 gr. and pure sodium chloride 12 gr. After a couple of minutes' boiling it can be let cool to blood heat, or cooled by standing the flask in cold water. Then 10 drops of the 1 per thousand adrenalin chloride solution of commerce is added, and the solution is ready for use.

The adrenalin solution is best measured by drops from the bottle itself with a loosened stonner. Other ways of measuring are wasteful, and above all expose the fluid to air and light, which soon spoil it, and to septic contamination of the whole bottle, which would be dangerous. If it is dropped as described, and the stopper refastened, the fluid in the bottle will keep good for months in my experience, if left, besides, in its box in the dark. I have often tested these drops with a standard measure, and find about 18 or 20 go to the cubic centimetre. Adrenalin solution should not require boiling. It is already sterile or will not keep. I have sometimes put the drops into the solution while boiling and found that this did not destroy its specific properties, but they seemed to pass off more rapidly than when the drops were added from the bottle direct to the solution at blood heat. Any alkali spoils it at once, hence the Jena glass. The syringes must, of course, be boiled, but not in the usual soda solutions, for the same reason. The needles are best sterilized in alcohol. The ordinary Freienstein's needles fitted into fine caps screwed on to hollow rods, answer all the purposes of limited injections, the finest size being used for the skin, the larger for moderate depths of tissue. But where greater distances have to be reached-for example, the whole length of the inguinal canal-a longer needle is necessary. For this I have devised a needle which so far answers all purposes. Two sizes-1 mm. and 1⁄2 mm. thickare used. Each is 5 in. long. As such a length of fine steel tubing is very flexible and difficult to force through the tissues, especially if blunt (as it should be to avoid injury to vessels), it is so arranged by a little device of my own that it can be set to begin with at a short length until it has entered the tissues, when it can be lengthened up to 41⁄2 in. This is provided for as follows: Each needle is a plain, straight, fine tube slightly bevelled at the distal end or closed blunt with a lateral opening. passed through the lumen of a small section of % in. of the finest rubber catheter (Jaques). This little rubber collar just fits into the screw-cap, which is then screwed up on the straight rod into which the needle runs, the other end of which fits on the svringe. When the cap is screwed down on the rubber the needle is fixed water-tight. When it is unscrewed a turn or two the needle can be drawn out of the hollow rod or pushed in and again fixed.

It is

All these needles should be washed in plain hot water after use, to remove the salt solution, and then be washed in spirit, their stylets being finally replaced in them. The rubber cap should also be removed from them, as it spoils the metal if left long in contact with its bright surface. When thrusting these blunt needles through the skin it is well to prepare the way by a puneture with a large sharp-edged needle through the spot previously anesthetized by the fine needle of the first injection.

3. The duration of the insensibility is secured by the admixture of the adrenalin. Without it sensation is only abolished by eucaine for about fifteen minutes, with it for three or four hours that is, as long as the anemia lasts. But, on the other hand, the analgesia is produced more slowly when adrenalin is employed with the eucaine. It is, therefore, well, before all larger operations, to wait some thirty minutes after injection to allow time for the insensibility to become fully developed. After this the effect appears to deepen for a couple of hours. In one case of operation for a recurrence in the breast involving the removal of a mass of skin as big as half my hand, I had injected two and a half hours before. Sensation was still absolutely abolished, the patient spontaneously expressing her wonder and delight that she had felt no pain at all. She made an interesting remark besides-that is, that she could tell when a knife was used and when a needle by the touch, but both were absolutely painless. Others have said the same, showing it is not anesthesia but analgesia. Waiting for half an hour or so may sometimes be inconvenient, unless the time be utilized for preparation of instruments, etc. In hospital it gives little trouble. Three or four cases can be infiltrated at once, or one after the other, and left in the wards, while some other operation requiring general anesthesia is done. They can then come in in succession.

Waiting has another advantage which places this above the earlier methods of repeated infiltration of eucaine alone. When the latter is employed the operation must be practically done at once. It will then be found that the tissues are still in a state of artificial edema from the amount of fluid injected. This edema may mask the anatomical details unpleasantly for beginners. When, on the other hand, adrenalin has been added to the eucaine solution, and we have waited, say, forty minutes, the artificial edema has disappeared, and we cut through pale and almost bloodless tissues, where the details are very clearly seen. Rapid injection is to be avoided; the sudden distension of the tissues is disagreeable, if not painful. The fluid should not be allowed to become cold, or be used too hot for the same reason. These and other small details will soon be learned by any one who is in earnest and patient.

Of course, all dragging on the parts is to be avoided, lest