Document vy9p894rKgkpyX73EejmrRB7Y

VoL S Erythoridine, try, u. 15. ind Unaracteri5 (May) 1939. a of Erythrinn rncol. & Exper. ideation of the Jrythrina Crista ;razol Fractures uly) 1940. Beta-erythroidin trazol Therapy, plating estbesiIty, the en) ex- ence mection ill ordi- ?en and or ten- blood articular ; circumlend the na, solusolutions T)t sopressor hich sub- id Elimi;vhen was nowledge July, 1947 ANESTHESIA XXVII. NARCOSIS WITH VINYL CHLORIDE *f Robert H. Oster, Ph.D., C. Jelleff Carr, Ph.D., and John C. Krantz, Jr., Ph.D., with the technical assistance of Mart Jane Sauerwald, B.A. Baltimore, Md. Received for publication December 13, 1946 In our studies on various volatile organic compounds available as in halation anesthetics, our attention was directed to vinyl chloride. Vinyl chloride is an industrial chemical used in the synthesis of many organic compounds. The substance is a gas which boils at --18 C. It is soluble in the etherial solvents and its vapors are combustible. Vinyl chloride was suggested as an anesthetic by Patty, et aL (1) and tried on human subjects by Schaumann (2). Patty's experiments on guinea pigs revealed that the action of vinyl chloride was similar to that of ethyl chloride and less harmful than either chloroform or car bon tetrachloride. According to Schaumann the narcotic limiting con centration for man is 7 to 10 per cent; 12 per cent is dangerous. In our studies, planned to give a first approximation of the anesthetic syn drome of vinyl chloride, we suggest that this compound not be used as an anesthetic in man. Chemotherapeutic Considerations: There is a dictum in pharmacology (3) that potency and unsaturation parallel each other among analo gous organic compounds. This holds for ethane and its more potent analogue, ethylene. It is also true for ethyl ether and its more potent analogue, divinyl ether. Therefore, one might expect that vinyl chlo ride would be a more potent anesthetic than its analogue, ethyl chloride. This relationship, however, appears not to obtain between these two chlorinated hydrocarbons. With ethyl chloride, 3.6 to 4.5 volumes per cent (4) are required for anesthesia with 20 mg. per cent in the blood. Schaumann (2) used 7 to 10 volumes per cent of vinyl chloride to pro duce anesthesia and found 17 to 20 mg. per cent in the blood. Our ob servations in dogs conform well to the indication of these data, namely, that there is little difference in potency between the saturated and the unsaturated analogues, and actually ethyl chloride appears to be the more potent. * From the Departments of Pharmacology and Physiology, Schools of Medicine and Den tistry, University of Maryland, Baltimore, Maryland. t The expense of this investigation was defrayed partially by a grant from the Ohio Chemical and Manufacturing Company of Cleveland, Ohio. 359 24929001 BFG36454 360 R. H. Oster, C. .T. Carr and J. C. Kraxtz, Ju. Vol. 8 Observation Anesthesias in Dogs: Two dogs were anesthetized with vinyl chloride * using mixtures of the gas and oxygen. For induction the concentration of the gas momentarily was allowed to jun.to 50 vol umes per cent aud then reduced to 7 volumes per cent. Induction was rapid. There was continuous "crowing" even under deep anesthesia. There was much salivation. Abdominal relaxation was good, but the legs showed rigidity and incoordinated leg movements throughout the anesthesia. The recovery period was prompt but accompanied by violent excitation. In a third dog anesthesia was produced using 25 volumes per cent momentarily, and a similar syndrome ensued. Blood Pressure in Dogs: Four dogs were prepared for blood pres sure tracings by caiuiulatiug the femoral artery. The operation was performed under monocainc hydrochloride local anesthesia. After a normal blood pressure tracing had been obtained, the animals were anesthetized with vinyl chloride-oxygen mixtures, using 10 volumes per cent of the former. In all 4 cases the magnitude of the blood pressure remained within normal limits during anesthesia. There was definite evidence of cardiac irregularity, however, such as intermittent tachy cardia, extraventricular systoles and vagal beats. These irregularities disappeared upon changing the anesthetic to ethyl ether. These cardiac disturbances confirmed our stethoscopic observations on the unoperated dogs. Electrocardiographic Studies in Dogs: Six dogs were anesthetized with vinyl chloride-oxygen mixtures, using 10 volumes per cent of the former. Electrocardiographic records, lead II, were made at light surgical anesthesia, surgical anesthesia and threatened respiratory col lapse. All of the animals manifested marked changes in cardiac rhythm in surgical anesthesia. Marked tachycardia followed by bradycardia was typical- In 2 of the 6 animals the R-spike was inverted during surgical anesthesia and in 1, evidence of incipient ventricular fibrilla tion obtained. Inversion of the R-spike with bradycardia is shown iu the record from dog 6, lead II, chart 1. Abnormalities in the QRS complex were found in all 6 dogs varying from sinus arrhythmia and transitory extreme left axis deviation to very serious conditions including auriculoventricular block, ventricular * The vinyl chloride tued In these studies was prepared for ns esperiallj purified by II. B. Smith of Petroleum Chemicals, Ine., Baltimore, Md. It was stabilized with 0.5 per rent of p-tertiary butyl catechol. The compound was purified as follows: " Yinjl chloride of 97.4% by weight parity containing 2.6% by weight triclilorethylene, 15 ppm. of acetylene, and no free aridity was carefnlly distilled to remove trirbloretbylene. The distilled vinyl chloride was washed with cuprous ammonium chloride, phosphoric acid, and dried over pelleted potassium hydroxide. The purified vinyl chloride was found to have the following specifications: Acetylene: Nous by cuprous ammonium chloride tost. Free Aridity: None. Ammonia: None. Tricblorcthylcne: Trace." rinnssrfaE& BFG36455 July, 1947- Axesthesia XXVII 3G1 cl tachycardia^ ventricular multifocal extra systoles, and inversion of the T-wave with elevated.ST segments in lead II. As anesthesia pro gressed toward respiratory failure, most of the QES abnormalities dis appeared but the R amplitude was greatly reduced. ent esvas ra ere per ure lite hyties liac d '.zed the ight coltlim i*dia ring ma il in 1 to nlnr it. B. nl of vlene, ylene. !, and e tbe Normal Lead IX Chjutt 1 Vinyl Chloride Anesthesia Lead II Two dogs under ethyl chloride anesthesia and the same experi mental conditions showed a lowering of blood pressure and progressive bradycardia without arrhythmias. In 1 animal a brief period of left axis deviation appeared during the induction phase. . SuMMABY AND CONCLUSIONS 1. Vinyl chloride has been studied as an anesthetic in the dog. 2. The anesthetic syndrome is marked by incoordinated muscular activity in the extremities. 3. In 6 dogs cardiac arrhythmias of a serions nature were observed. It is our opinion that, as an anesthetic in the dog, vinyl chloride is unsafe and that its use in man is unwarranted. BEFEBEXCES 1. l*atty, P. A.; Taut, W. P, and Waite, C. P.: Acute Besponse of Guinea Pigs to Vapors of Some Xew Organic Compounds, U. S. P. H. Keports 45: 1963, 1930. 2. Schamnann, O. Cited by TAmmi, K. B., and FInry, F.: Toxicology and Hygiene of In dustrial Solvents, Baltimore, Williams and Wilkins, 1943, p. 171. 3. Dyson, G. AL: The Chemistry of Chemotherapy, London, Ernest Benn, Ltd, 1928, p. 48. 4. Adrian!, J.: The Pharmacology of Anesthetic Drags, Springfield, HL, Charles C. Thomas, 1941, p. 33. The Scientific Assembly of Tub American Medical Associa tion will be held in Chicago in 1948. Anyone who wishes to appear on the Program of the Section on Anesthesiology should submit titles of papers to the Secretary, Dr. John S. Lundy, 102 Seeoml Avenue Southwest, Rochester, Minn., as soou as possible. 24323003 bFG36456 )) o C.O A *o yi jo ?o <i J if) -0 02 *? i a o a> )) S'O> Vj >9 *