In 1943, during research studies concerning the pharmacological activity of glycerol on abnormal foci, its hemorrhagiparous effect appeared as a serious handicap. Various hemostyptic substances were tested without sufficient effect. At this time, a new product, to which a hemostatic effect was attributed, appeared on the market. It was a very weak solution (around 1/10,000) of octanol in saline. We could find no therapeutic effect for it. However, we were studying butanol and other higher aliphatic alcohols with lipoidic properties, and we decided to test butanol for its antihemorrhagic activity, hoping that it might counteract the undesirable hemorrhagiparous effect of glycerol. It did and we have since added butanol to glycerol for this purpose.

We observed the remarkable hemostatic effect of butanol years later in a patient with severe hemorrhage, to whom doses of 10 cc. of a 6.5% solution were given intravenously. Hemorrhage stopped in a few minutes. Since then, we have successfully applied butanol clinically in hemorrhages of various origins.

As an antihemorrhagic agent, butanol is administered either parenterally as a 6.5% solution in saline, or orally as 6.5% solution in water. The route of administration—intravenous, intramuscular, subcutaneous or oral is chosen according to the severity of the hemorrhage. Doses of 5-20 cc. are given and repeated, if necessary, at intervals of a few minutes. Since butanol is not at all toxic in these large doses, we usually give them with good results in severe emergencies. The following cases illustrate the styptic effect.

R. E., a 64-year old man with an extensive ulcerated epidermoid carcinoma of the floor of the mouth and large bilateral cervical metastases, had received intensive radiotherapy. Occasionally, there was a small amount of bleeding from the oral lesion, but a sudden hemorrhage of about 500 cc. of blood during a half hour period occurred late at night while the patient was at home. Pressure, applied to the floor of the mouth, was of value but bleeding recurred immediately upon release. Oxidized gauze, adrenalin soaked gauze, vitamin K and vitamin C in large quantities were of no value. n Butanol solution in saline was finally obtained and 5 cc. injected intravenously. Bleeding ceased during the injection. A second equally severe hemorrhage occurred one week later and again could not be adequately controlled by pressure or oxidized gauze. 10 cc. of n butanol solution administered intramuscularly stopped the bleeding within 2-3 minutes. Three hours later, the floor of the mouth was carefully examined preliminary to right external carotid artery ligation, and the lesion was found to be free of bleeding. Despite the ligation, bleeding later recurred but was controlled each time by n butanol administered orally.

S. S., a 30-year old man, had an adenocarcinoma involving the right maxillary sinus with cervical metastases. During the period of observation, this patient experienced a profuse hemorrhage from nose and mouth. Blood flowed at the rate of approximately 5-6 cc. per minute, and pressure gave little or no relief. 5 cc. of n butanol in saline solution was injected intravenously and within two minutes, the profuse hemorrhage ceased and did not recur at that time. On several other occasions, bleeding was controlled following the administration of oral doses of 5-10 cc. of 6.5% n butanol solution in water.

A. M., a 36-year old man, had multiple pulmonary metastases from a primary malignant melanoma of the left foot. On several occasions, hemoptysis occurred and during three of these episodes bleeding was profuse. 5 cc. of n butanol in saline administered intramuscularly stopped two of these episodes rapidly, but in the third, an injection of 10 cc. intravenously was needed ten minutes after an initial intramuscular dose. Although the intramuscular injection was ineffective, the bleeding was halted within two minutes after intravenous administration.

In a report in 1951 in "Angiology," (193) we presented the following statistics concerning the control of hemorrhage in cancer cases:

Group I Untreated

Group II n Butanol

Number of cases observed

256

344

Number of cases with profuse hemorrhage

18

25

Percent of cases with profuse hemorrhage

7

7

Number of deaths attributed to hemorrhage

12

1

Percent of deaths in cases with profuse hemorrhage *

67

4

* Death attributed directly to hemorrhage.

Since then, these results have been consistently confirmed.

Additional progress was achieved with organic acids added to butanol in adequate amounts. Completely non toxic in the dosages used, they were observed to enhance the hemostatic effect of butanol. This hemostatic effect has been confirmed many times, particularly in Europe where, following our research, butanol has been widely used as a hemostyptic agent.

A hemostatic effect was also evident when butanol was used with the principal aim of controlling pain in postoperative cases. The hemostatic effect was especially important in cases where pathological bleeding usually represented a major complication, either because of the impossibility of obtaining hemostasis during operation or because the surgical wound could not be kept aseptic, as in tonsillectomy, prostatectomy and plastic surgery of the nose. In a study on the use of butanol for postoperative care in tonsillectomies, B. Welt has been able to show a preventive effect, and more important, a hemostatic one if hemorrhage occurs. (187) (Fig. 91) In prostatic surgery, the amount of bleeding was so reduced, that of a group of 40 cases, only one needed transfusion while in a similar number of controls, 8 had to have transfusions. (189)

Still more impressive results have been noted in pathological hemorrhages following plastic surgery, especially of the nose. In a significantly large number of cases, severe hemorrhages tend to occur around the 7th day after operation. We have discussed above the pathogenesis of these hemorrhages and the relationship to the allergic defense mechanism. Such hemorrhages have been difficult to control. The use of antibiotics has only partially reduced their frequency and gravity. S. Scher has obtained very good results with the administration of butanol in such cases, using an injection of 5 cc. of a 6.5% solution of butanol once before surgical intervention and four times daily for two days afterward, followed by oral administration of 15 cc. or one tablespoon four times a day for eight days. No hemorrhages occurred in more than two thousand cases treated. In a few patients who neglected to take the medication, and in whom a hemorrhage appeared, bleeding was rapidly controlled by butanol. (Note 6)