Barbiturate Poisoning

Barbiturate Poisoning SIDNEY KAYE, Ph.D. Richmond, Virginia

The widespread use of barbiturates makes it appropriate that all physicians be reminded of barbiturate poisoning.

BARBITURIC ACID derivatives THE comprise an important and valuable

group of central nervous system depressants. Over 2,000 tons are sold yearly in the United States of America alone. It is hence no wonder that it is found in almost every home, and that more people die from their over-dosage than from any other single drug. Its first member was synthesized by Fisher in 1903 and was called barbital (Veronal) which is a diethyl barbiturate. The next to be synthesized was phenobarbital (Luminal) which is an ethyl, phenyl derivative. In the following years, many hundreds of new derivatives have been produced but barbital and especially phenobarbital still enjoy a deserved preference for many purposes. The chief advantage of several of the newer members of this group is their quicker onset of action and a shorter duration of action. Synonyms: Sleeping pills, goof balls, yellow jackets, red devils, etc. Uses: Sedation, hypnotic, anesthesia, preoperative. Properties: odorless, bitter, white crystalline powder, acidic, insoluble in water, soluble as the sodium salt. MLD: Varies from about 1 to 6 Gm. 150 lb. man depending upon the derivative poThis is one of periodic articles on common poisonings which will be published in the Monthly from rime to rime, it is prepared by Dr. Kaye in collaboration with the Richmond Poison Information Center.

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tency. Short acting ones are more potent; longer acting less potent. Remarks: Long Duration (18-24 hours), barbital, phenobarbital, found in blood and urine even up to one week later. Intermediate (8-12 hours) amobarbital (Amytal), diallylbarbituric acid (Dial), butethal (Neonal), aprobarbital (Alurate), probarbital (ipral), butibarbital (Butisol), vinbarbital (Delvinal). Short Duration (3-6 hours), pentobarbital (Nembutal), secobarbital (Seconal) hexethal (Ortal), isobutylallyl barbituric acid (Sandoptal), cyclobarbital (Phanodorn). Ultra-Short (1/2-2 hours), thiopental (Pentothal), hexobarbital (Evipal), thioamylal (Surital). (Rapidly removed from blood within several hours.) High incidence of suicides. Barbiturates are synergistic and increases in toxicity in combination with alcohol intoxication, chlorpromazine (Thorazine) reserprine or other depressants. Acute Signs and Symptoms: Depression, amnesia, lowered body temperature, depressed circulation (marked fall in blood pressure), respiratory embarrassment, decreased response of respiratory center to carbon dioxide (Cheyne-Stokes), anoxia, cyanosis, limbs are flaccid, retention of urine is common, constriction or dilatation of pupils, corneal reflexes may be absent, ataxia, deep coma, possible shock, cold extremities, death due to respiratory arrest (frequently associated with marked cardio-vascular depression) or pneumonia. Chronic Signs and Symptoms: Skin rash, slurred speech, cyanosis, amnesia, anorexia, emotional instability, ataxia constipation. Identification: Urine, gastric lavage or blood are specimens of choice:

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Acid-ether extraction group. (1) 100 ml. of urine are placed into a large separatory funnel. Test urine with litmus paper to make certain it is slightly acid. if it is not, add one to two drops of sulfuric acid, and again retest. The urine is gently shaken for several minutes with 200 ml. of ether. These layers are then allowed to settle. Separate the layers, and discard the urine. The ether (upper layer) is filtered through two layers of coarse grade filter paper to remove traces of water. The ether filtrate is collected into a Pyrex evaporating dish. This is then evaporated to dryness on a water bath. (Keep away from open flame.) If residue is tarry yellow-brown (most times it is), add 15 ml. of chloroform and swirl and stir to dissolve residue. Then add a small pinch (size of match head) of activated animal charcoal. Again swirl and stir. This charcoal will absorb much of the yellow organic impurities that might interfere with the test. Filter and collect the clear chloroform into a small container. Gently evaporate to about 1-2 ml. Several drops are transferred to a micro test tube, or a micro spot plate. Add two drops of cobalt acetate (1% in absolute methyl alcohol). Mix well by swirling. Stratify (overlay) with three drops of isopropyl amine (5% in absolute methyl alcohol). A blue-violet interface or diffuse color indicates the presence of a barbiturate. Test may be used directly on powders or tablets. (Dilantin Doriden, and other ureides also give a positive test.) Phenobarbital requires cobalt acetate and isopropyl amine to turn blue, whereas, the other members of group turns blue upon the addition of only cobalt acetate, which however intensifies on addition of isopropyl amine and turns it lilac. This is a good means to differentiate phenobarbital from the others especially in tablets. (2) Extract 5 ml. of blood (slightly acidi fled with 1 drop of 5 % sulfuric acid), with 25 ml. of chloroform. Collect the chloroform VOLUME 88, MARCH, 1961

layer and shake out with 5 ml. sodium hydroxide 0.5 N. Save the sodium hydroxide layer and centrifuge to remove any adhering drops of chloroform. Read with a Spectrophotometer plotting the absorption curve in the ultraviolet range. Barbiturates have a characteristic ultraviolet absorption spectra with a maximum density at 255 mµ and a minimum at 235 mµ. Quantitative determinations can be calculated from the reading obtained at 255 mµ, and comparing with a standard graph. This test is sensitive to 2 micrograms/5 ml. blood. The exceptions are pentothal (maximum density 300 mµ and minimum density 260 mµ), and Butisol. Evipal or Mebaral whose maximum density is 243 mµ and minimum density is 230 mµ. (3a) Barbiturate derivatives may be further confirmed by shifting pH to 10.5 with ammonium chloride and re-examine the ultra-violet range as in above test 2. A new maximum is produced at 240 mµ. Butisol, Evipal or Mebaral do not produce any change with a shift in pH by adding ammonium chloride. (3b) Paper chromatography will assist in identification. (4) Some capsules may be suggestive by color. Pentobarbital: Yellow or brown Delvinal: Brown Seconal: Red Amytal: Blue Tuinal: Blue and red Treatment: Gastric lavage with water and tannin or activated charcoal. Cathartics. Avoid emetics if patient is depressed. Antibiotics prophylactically to prevent secondary infection especially when in coma. Hemodialysis (artificial kidney) if available will hasten elimination and recovery. If respiration is normal, color good, and twitching and corneal reflexes present, it may be advisable to “let patient sleep it off” watching to prevent aspiration and for the pos

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sible development of respiratory difficulties. Keep air passages open, prevent aspiration. Artificial respiration and oxygen therapy with 5% - 7% carbon dioxide as needed. To combat respiratory depression, artificial respiration and oxygen usually may be effective and sufficient. The use of picrotoxin, metrazol or other strong analeptics is now believed to be ineffective and perhaps dangerous for patients in deep depression, and unnecessary for mild cases. Ritalin, Megimide (Bemegride), each have been reported with good results. If in shock, norepinephrine; fluids or blood are effective, if not contraindicated by pulmonary edema. Maintain body heat, water and electrolyte balance. Fluids and catheterization as needed.

Coma may persist for several days with the long acting barbiturates. Prognosis is good if you can prevent anoxia and pneumonia. Careful nursing is essential!! If levels are high (long acting derivative), and artificial kidney is not available, an exchange transfusion may be beneficial, especially for children. REFERENCES Kaye, Sidney, Handbook of Emergency Toxicology: A guide for the identification, diagnosis and treatment of poisonings. C. C. Thomas, publishers, 2nd Edition, 1960, Springfield, Illinois. 404 North 12th Street Richmond, Virginia VIRGINIA MEDICAL MONTHLY

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