In the preceding pages we have submitted evidence which shows that a simple intratracheal injection of a solution in a normally breathing rabbit penetrates within a few seconds to the alveoli, chiefly those of the left lower lobe; that absorption is rapid and well maintained; and that the procedure may be repeated effectively a number of times even with a substance like adrenalin which decreases absorption. It was also shown that absorption of adrenalin from the lung could be obtained at a time when double the dose given intramuscularly exerted no blood pressure effect whatever, and that absorption could still take place after the development of pulmonary edema, when there was an undoubted dilution of the injected solution with a serum-containing liquid and when a diminution of the absorptive field had occurred.

The solution injected, after reaching the alveoli, is probably largely taken up by the capillaries of the pulmonary veins. This is indicated by the great rapidity with which an intratracheal injection of adrenalin may cause a rise of blood pressure. In numerous instances, for example, the pressure began to rise less than 5 seconds after the completion of an injection, equaling and even surpassing in rapidity of effect an intramuscular injection. Absorption by the lymphatics probably plays a secondary part, an assumption rendered all themore likely if we consider that lymph nodes are interpolated in the lymphatic pulmonary path, where the bed of the lymph stream becomes greatly widened and the current slowed.

Injection into the lungs, however, offers another advantage due to the vascular arrangement of the absorbing field which could be of value therapeutically. Absorption of liquids injected into the lung probably takes place largely through the capillaries of the pulmonary veins; to a slight extent possibly through the capillaries of the bronchial veins which empty partly into the pulmonary veins, partly into the azygos veins; and probably some absorption occurs also through the lymphatics. By far the larger proportion of the absorbed material will thus be rapidly delivered to the left auricle and then to the left ventricle. At each succeeding systole, as long as absorption continues, a fraction of the drug will be driven into the coronary arteries and be able to affect the musculature of the cardiac pump. This fact ought to render the procedure of intratracheal injection a valuable method when it becomes imperative to stimulate a suddenly failing heart as promptly as possible by drugs of the digitalis group.

Intratracheal injection is perhaps better under the conditions mentioned than the intravenous route, for the surface veins cannot always be entered with promptness and certainty even under fairly normal conditions, and in cases of cardiac weakness the difficulties will be measurably increased, while an intratracheal injection can be carried out with ease. Moreover, it is legitimate to expect that some absorption will take place from the lung alveoli as long as the heart-lung circulation persists, no matter how feebly, and that thus some of the drug will reach the heart to act on this structure itself more promptly perhaps than when the drug is administered successfully through surface veins. As far as the intramuscular route is concerned, we have shown that the intratracheal injection of adrenalin gives prompt though diminished absorption at a time when double the dose intramuscularly exerts no blood pressure effect whatever.

The technical difficulties of giving an intratracheal injection in animals are slight. Tracheotomy as practised by us in the present series of experiments is not necessary, for the injection may be given into the intact trachea without exposure of the trachea. The hypodermic needle is inserted through the skin about 1 cm. below the larynx in a slanting caudad direction; the entrance of the needle into the trachea is readily felt. The injection should not be so rapid that the injected solution fills the entire tracheal lumen, but it should flow down the sides of the trachea. If the lumen is entirely filled, an expiration may drive some of the injected liquid into the larynx causing cough. In our experiments each injection of about 0.5 cc. consumed approximately 5 seconds.

In the human subject no data are available as far as our knowledge goes, but a priori it would seem that an intratracheal injection is almost as simple as in the lower animals. The free hypodermic needle could be inserted into the tracheal lumen immediately below the cricoid cartilage. The needle itself should preferably be connected with the syringe by a short length of rubber tubing to minimize the danger of breaking the needle by a sudden move of the patient. The amount of the solution should not be too small, so that at least a fraction of it may reach the alveoli as promptly as possible; 3 to 5 cc. probably would suffice.

Insertion of the needle in the locality mentioned would puncture the isthmus of the thyroid, but this is of no significance, especially when the procedure is employed in cases of cardiac failure where the gravity of the condition would warrant incurring much heavier risks than a slight bleeding from the thyroidal isthmus.

In conclusion it may be said that the incorporation of drugs by intratracheal injection, while not as generally applicable as other methods, nevertheless has advantages which warrant its use also in human therapeutics.

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