Therapeutics

1. In hemorrhage - to restore the blood volume to normal and thus permit the maintenance of arterial pressure. Probably not over 1200 c.c. should be given at one time. Bernheim cites a case of exsanguination in which, after 2000 c.c. of saline, salt solution instead of blood flowed from the incision made for transfusion. He advises that with saline if there is a fall in blood-pressure after a preliminary rise further saline is dangerous.

2. In cholera - to restore the volume of the blood and supply liquid to the tissues. Rogers has found a hypertonic fluid best, as it checks the transudation of fluid into the intestines.

3. In toxemic conditions - to promote kidney activity, with the idea of carrying out the poison. In uremia, saline infusion is sometimes employed after considerable blood-letting, though ordinarily in kidney cases the saline is given by rectum instead of intravenously. If there is salt retention, sodium bicarbonate or potassium acetate may be substituted for the sodium chloride. Levin considered bleeding followed by infusion a useless procedure in toxemic conditions, for he could obtain no appreciable effect from it in artificially produced toxemias. In strychnine poisoning Delbert has prevented toxic symptoms by the use of saline infusion.

4. In severe collapse or shock - a small saline infusion of about 500 c.c, given slowly and containing epinephrine or pituitary liquid, may promote the maintenance of blood-pressure. A large infusion merely favors the production of edema. In post-operative collapse, the saline may replace blood lost in the operation, but care must be used not to administer too great a quantity.

Saline By Hypodermoclysis And Enema

After hemorrhage, absorption from the rectum is especially rapid, and one or two quarts may be given by enema without expulsion. Under ordinary conditions, too, hot saline by rectum regularly shows a prompt effect upon the kidneys. Even by hypodermoclysis over the abdomen, in the axillary line, in the thighs or beneath the breasts, as much as a pint (500 c.c.) of saline may be used in some cases in about ten or fifteen minutes, or double this amount in half or one hour, During major operations Lane keeps up a supply of fluid by a needle in the subcutaneous tissue of each side of the chest about at the anterior axillary line, the so-called "axillary sup."

Contraindications - any form of edema, but especially that of the lungs, and that resulting from sodium chloride retention, as in nephritis.

Toxicology

Chills and fever have been reported following saline infusions. They have been attributed to the products of dead bacteria in the water used. Several cases of death have occurred from the use, by rectum or intravenously, of concentrated solutions of sodium chloride in mistake for normal saline. (See Sodium Chloride, under Alkalies.)

Remedies Which Lower Blood-Pressure

These we are able to divide into three classes:

(a) Cardiac depressants.

(b) Arterial dilators.

(c) Measures for decreasing the volume of blood.

The Cardiac Depressants Aconite

Aconitum (aconite, monkshood) is the dried tuberous root of Aconitum napellus (Fam. Ranunculaceae), collected in autumn, and yielding when assayed not less than 0.5 per cent. of aconitine. It is a European herb, extensively cultivated as a garden flower.

Constituents

Several alkaloids, of which aconitine is the essential active one. Aconine, present in minute quantity, is said to be a cardiac stimulant, while benzaconine, picraconitine, and aconitic acid are inert.

Preparations And Doses

The preparations on the market are exceedingly variable, many of them having been found almost inert. They deteriorate rapidly on keeping. The Pharmacopoeia requires a biologic assay.

Aconite, assaying not less than 0.5 per cent. of ether-soluble alkaloids, 1 grain (0.06 gm.).

Fluidextract, 1 minim (0.06 c.c.).

Tincture, 10 per cent., 10 minims (0.06 c.c.).

Aconitine, dose, 1/400 grain (0.15 mg.), is insoluble in water and soluble in oil or alcohol. It is one of the most powerful poisons known. As marketed, it is highly variable, some specimens having been found a hundred times as strong as others.

Pharmacologic Action

Skin

Following the application to the skin of an oily or alcoholic solution of aconite there are tingling, pricking, and smarting of the part. This is not accompanied by the phenomena of counterirritation, i. e., general irritation of the tissues, with redness and warmth, as after ammonia or mustard, for aconite is not a general protoplasmic irritant, but a selective drug. The primary stimulation of the nerve-endings is followed by depression, which shows in numbness and diminished appreciation of pain and touch, i. e., partial local anesthesia. Since the drug is highly selective, these effects on nerve-endings are also seen from large doses of the drug acting systemically, as when it is administered by mouth. Short and Salisbury could get no cutaneous anesthesia from a 3 per cent. solution of aconitine; and it may be that the stimulating effect is the essential one.

Alimentary Tract

The taste is bitter, and from even a very dilute solution (1: 500,000 of aconitine), the mouth, lips, and tongue may feel a pricking and biting sensation, followed by numbness. The saliva is increased at first largely reflexly, as the result of the presence of an offending substance in the mouth, but partly from direct stimulation of the secretory nerve-endings; these are later depressed, the mouth becoming dry from the absence of saliva. Squibb's test for aconite is to hold 1 dram (4 c.c.) of a solution of 1: 70 of the tincture in the anterior part of the mouth for one minute, then discharge it. A distinct tingling will be apparent in ten to fifteen minutes.

In the stomach and intestines the unpleasant local action may result in nausea, vomiting, and catharsis, but such effects are unusual from therapeutic doses. After absorption, the vomiting center may show increased sensitiveness, as from digitalis; but in practice vomiting is rare, for, unlike digitalis, aconite is seldom employed in full doses for long periods.

Absorption is rapid through mucous membranes. From oily or alcoholic preparations it is also fairly rapid through the skin, hence liniments must be employed with caution. The drug causes too much pain for hypodermatic use.