THE ORAL, RECTAL AND INTRAVENOUS ADMINISTRATION OF SODIUM ISO-AMYL-ETHYL-BARBITURATE (SODIUM AMYTAL)

¹ From the Department of Pharmacology, The Lilly Research Laboratories

In comparison with iso-amyl-ethyl barbituric acid (amytal) sodium iso-amyl-ethyl barbiturate (sodium amytal) is more rapid in producing symptoms of ataxia and narcosis. Amytal when given orally, produced symptoms of ataxia in fifteen to seventeen minutes in cats and dogs. Sodium amytal given orally in capsules produced symptoms of ataxia in eight minutes and light sleep in twenty minutes. The duration of sleep with sodium amytal given orally in hypnotic and anesthetic doses is also less than with amytal. The average oral minimal effective hypnotic dose (light sleep) of sodium amytal appeared to be 20 to 25 per cent of the m.l.d. (table 8). The average oral m.l.d. of sodium amytal was taken to be 125 mgm. per kilogram. The amytal content of sodium amytal is about 90.21 per cent. The calculated oral m.l.d. of sodium amytal based on the oral m.l.d. of amytal would be approximately 112 mgm. per kilogram. This is in close agreement with Swanson and Page (2) who reported the oral m.l.d. for cats as 110 mgm. per kilogram.

Eddy (1) found that to produce stupor amounting to anesthesia it required at least 50 per cent of the average fatal dose of most of the barbituric acids and with a few compounds 60 per cent was required. Our average oral minimal anesthetic dose was found to be approximately 55 per cent of the m.l.d. (table 8). This anesthetic dose was further determined by actually placing several dogs on the operating table, the right carotid artery and trachea exposed, cannulae inserted, and kymographic tracings made of the blood pressure and respiration. An abdominal incision was made large enough for a hand to reach the various internal organs. The effect of traction and mauling of these organs was shown on the blood pressure and respiration.

Sodium amytal given by rectum produced symptoms of ataxia appearing on the average in five minutes and hypnosis (light sleep) in fifteen to twenty minutes. The average duration of sleep by rectum in hypnotic and anesthetic doses was less than twenty four hours. The average rectal minimal effective hypnotic dose (light sleep) appeared to be 20 to 25 per cent of the m.l.d. The average rectal m.l.d. was found to be 200 mgm. per kilogram. The average rectal anesthetic dose was found to be approximately 55 per cent of the m.l.d. as shown in table 8. This was further determined by operation, exposing right carotid artery and trachea, inserting cannula and traction and mauling of internal organs.

Sodium amytal given intravenously produced symptoms of ataxia, hypnosis, narcosis and anesthesia almost immediately during and following the injection. In anesthetic doses some dogs were asleep before the completion of the injection. The rate of injection found to be safe for hypnosis and anesthesia in more than three hundred and fifty dogs without a single death was 1 cc. per one minute of a 10 per cent solution of sodium amytal. Forty milligram doses per kilogram if injected in less than thirty seconds will produce death. The average intravenous minimal hypnotic dose (light sleep) appeared to be 20 to 25 per cent of the m.l.d. The average intravenous m.l.d. was found to be 70 to 75 mgm. per kilogram. The average intravenous anesthetic dose seemed to be approximately 55 per cent of the m.l.d. as shown in table 10. This was further substantiated by operation, recording blood pressure, respiration and traction and mauling of the internal organs. The safety of the intravenous administration of sodium amytal is controlled by the speed or rate of injection.