Document wrQOq0085YyRyNgj4m5a4JLgD

U R L! 8028 j Reprinted from Anesthesiology, VoL 8, No. 4, pp. 359-361, Jul/, 1947 Printed in U. S. A. 7 THF ANESTHESIA XXVII. NARCOSIS WITH VINYL CtNN L W.ART.\,.a CHLORIDE SEF?4fg4p. 1 fr.._---- RItOoBbEeRrTt Htl.,*TU)s5StTeZrR, PrHh..LDI., C. JELLEFF CaRR, Ph.D., AND JOHN C. KrANTZ, Jr., Pbt;., 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 ehloride, 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 \ V 360 R. H. Oster, C. J. Carr and J. C. Krantz, Jr. 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 run to 50 vol umes per cent and 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 cannulating the femoral artery. The operation was performed under monocaine 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 in 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 used in these studies was prepared for us especially purified by H. B. Smith of Petroleum Chemicals, Inc., Baltimore, Md. It was stabilized with 0.5 per cent of . p-tertiary butyl catechol. The compound was purified as follows: "Vinyl chloride of 97.4% by weight purity containing 2.6% by weight triehlorethylene, 3.5 ppm. of acetylene, and no free acidity was carefully distilled to remove triehlorethylene. 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: None by euprous ammonium chloride test. Free Acidity: None. Ammonia; None. Triehlorethylene: Trace." URL 18029 Anesthesia XXVII 361 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 QRS abnormalities dis appeared but the K amplitude was greatly reduced. * :_v}' *ir-A - Normal Lead II Cham 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. Summary 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 serious 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. REFERENCES 1. Patty, F. A.; Yant, W. P., and Waite, C. P.: Acute Response of Guinea Pigs to Vapors of Some New Organic Compounds, U. S, P. B. Reports 45: 1963, 1930. 2. Schaumann, O. Cited by Lehmann, S. B., and Flury, F.: Toxicology and Hygiene of In dustrial Solvents, Baltimore, Williams and Wilkins, 1943, p. 171. 3. Dyson, G. M.: The Chemistry of Chemotherapy, London, Ernest Benn, Ltd., 1928, p. 48. 4. Adriani, J.: The Pharmacology of Anesthetic Drugs, Springfield, HI., Charles C. Thomas, 1941, p. 33. oco8nan