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Monoethanolamine oleate
MONOETHANOLAMINE A NEW CHEMICAL
FOR THE OBLITERATION
OLEATE* OF VARICOSE
VEINS
NATHANIEL E. MEYER, M.D. NEW
YORK
T
HE use of sodium morrhuate for the injection of varicose veins has been widely adopted because of its superiority over most of the other agents. Its advantages were listed as foIIows: I. It is practicahy paimess. 2. There is diminished likelihood of sIough when smaII amounts are infihrated during an injection. 3. Its efhcacy is at least comparabIe to the other agents in producing a firm thrombus. However, there have been appearing in the Iiterature repeated reports of aIIergic manifestations foIIowing the use of sodium morrhuate. These manifestations vary from mild erythema to severe generalized urticaria and even anaphylactic shock. There are probabIy many more of these cases that never reach the Iiterature. The author has observed numerous such reactions to morrhuate, especially of the urticaria1 variety. Conversation with other physicians has reveaIed that these reactions are not uncommon. Upon considering the composition of sodium morrhuate, the reason for this high incidence of aIIergic reaction becomes obvious. Its exact composition, even in the purified form, is unknown. It is virtuaIIy impossibIe to remove al1 the fish proteins which are present, in smaI1 amounts to be sure, but sufficient to cause hypersensitivity in aIIergic subjects. MonoethanoIamine oIeate has been synthesized in the chemica1 Iaboratory and is of known composition. As the name implies, it is a soap of monoethanoIamine and oIeic acid. The structura1 formuIa is CH,(CH2)KH=CH(CHJrCO-NHCH,(CHz)OH. Th e compound is a yeIIow* From the Out-Patient
Department
CITY
ish viscid liquid, soIubIe in water. Its viscosity in a 5 per cent solution is somewhat less than sodium morrhuate. Monoethanolamine oleate has been tested in the bioIogic Iaboratory. The minimum IethaI dose intravenously in rabbits is I 30 mg. per kiIo, as compared to IOO to 125 mg. per kiIo in sodium morrhuate. In the chemica1 and bioIogic Iaboratory the compound was found to be satisfactory and at Ieast as safe as the older solutions. There remained the proof of clinical trial. Forty-three consecutive cases were injected with the solution. Of these fifteen were males and twenty-eight femaIes. A tota of 345 injections were given. The technique used was virtuaIIy the same as with sodium morrhuate. SingIe injections were given once a week and the amount of thrombosis noted the foIlowing week. The patients were questioned for any possibIe reactions. The initial injection was usualIy I to 2 C.C. The thrombosis was noted the foIIowing week and the amount of subsequent injection reguIated as required by the individual patient and the size of the vein. No tourniquets were used except in cases where there was a faiIure of or insuffrcient thrombosis. For statistical purposes, the resulting thromboses were divided into the foIlowing cIasses : Class o: Failure of thrombosis. CIass I : Thrombosis up to one-haIf inch. CIass 2: From one-half inch to 2 inches. Class 3: Over 2 inches or with chemica1 phIebitis, but with no tendency to break down. CIass 4: Ascending chemical phlebitis. Thromboses in Class 2 were considered optimum. WhiIe CIasses 3 and 4 produced good end-resuIts, we felt that they were of Lincoln Hospital,
628
New York City.
New
SERIES VOL.XL, No. s
Meyer-MonoethanoIamine
undesirabIe because discomfort often prevented the patient from doing his usual work, so that treatment could no Ionger be considered ambulatory. The thromboses ,produced were as follows : Unrecorded : 3 injections CIass 0: 1 I injections 27 injections (Note: Most CIass I: of these resulted from the smaI1 amount used in the initia1 injection.) CIass 2: 284 injections CIass 3: I 6 injections 2 injections CIass 4: There were no sloughs in spite of the fact that on numerous occasions smaI1 amounts were infiltrated. There was no evidence of aIIergic reaction in any of the patients. The voIume of solution injected varied from I to 5 c.c., the usua1 amount required being from 2 to 3 C.C. Of the 345 injections, 287,were from 2 to 3 c.c., and 203 from 2.5 to 3 C.C. At one time we ran short of the oIeate, and substituted sodium morrhuate temporarily in many of the cases. FolIowing the morrhuate injections there resuIted two cases of urticaria. One patient refused further treatment. In the other case treatment was continued with the oleate, and the urticarial symptoms subsided. After two weeks a smaI1 amount of sodium morrhuate was again injected with return of the urticaria.
American ~~~~~~~ or surgery
OIeate
629
SUMMARY
A cIinica1 tria1 of a new chemica1, monoethanoIamine oleate, was made on fortythree cases; a tota of 345 injections were given. In every case a good thrombus could be produced either at first or subsequentIy on injection. There were no cases of slough or any evidence of aIIergic reaction, CONCLUSION
MonoethanoIamine oleate is a satisfactory substitute for sodium morrhuate. It is comparable to the morrhuate in its lack of pain, its efficacy in production of thrombosis and prevention of sIough. It is superior to morrhuate because it is of known standard composition, it is more stable in solution, and has Iess tendency to produce aIIergic reactions. The monoethanoIamine oIeate for this study was suppIied through the courtesy of the Abbott Laboratories. REFERENCES
BIE~ELEISEN, J. The evaluation of sodium morrhuate therapy in varicose veins. Surg., GJnec. e? Obst., 57: 696-700,
1934.
FROHMAN, I. G., and BRAND, G. D. Compfications in injections of varicose veins. J. A. M. A., 103: 1088 (Oct. 6) 1934; Ic3: 1794 (Dec. 8) 1934. KEITZER, W. A. J. Michigan Med. Sot., 35: 168-169 (March) 1936. LEWIS, K. M. Anaphylactic shock due to sodium morrhuate. J. A. M. A., 107: r2g8 (Oct. 17) 1936. MCAUSLAND, 8. &it. M. J., I : 430 (Mar. I I) 1933. WELLS, C. A. &it. M. .I., I: 674 (April IS) 1933. ZIMMERMAN,L. M. J. A.M. A., 102: 1216-7 (April 14) 1934.
FOR THE OBLITERATION
OLEATE* OF VARICOSE
VEINS
NATHANIEL E. MEYER, M.D. NEW
YORK
T
HE use of sodium morrhuate for the injection of varicose veins has been widely adopted because of its superiority over most of the other agents. Its advantages were listed as foIIows: I. It is practicahy paimess. 2. There is diminished likelihood of sIough when smaII amounts are infihrated during an injection. 3. Its efhcacy is at least comparabIe to the other agents in producing a firm thrombus. However, there have been appearing in the Iiterature repeated reports of aIIergic manifestations foIIowing the use of sodium morrhuate. These manifestations vary from mild erythema to severe generalized urticaria and even anaphylactic shock. There are probabIy many more of these cases that never reach the Iiterature. The author has observed numerous such reactions to morrhuate, especially of the urticaria1 variety. Conversation with other physicians has reveaIed that these reactions are not uncommon. Upon considering the composition of sodium morrhuate, the reason for this high incidence of aIIergic reaction becomes obvious. Its exact composition, even in the purified form, is unknown. It is virtuaIIy impossibIe to remove al1 the fish proteins which are present, in smaI1 amounts to be sure, but sufficient to cause hypersensitivity in aIIergic subjects. MonoethanoIamine oIeate has been synthesized in the chemica1 Iaboratory and is of known composition. As the name implies, it is a soap of monoethanoIamine and oIeic acid. The structura1 formuIa is CH,(CH2)KH=CH(CHJrCO-NHCH,(CHz)OH. Th e compound is a yeIIow* From the Out-Patient
Department
CITY
ish viscid liquid, soIubIe in water. Its viscosity in a 5 per cent solution is somewhat less than sodium morrhuate. Monoethanolamine oleate has been tested in the bioIogic Iaboratory. The minimum IethaI dose intravenously in rabbits is I 30 mg. per kiIo, as compared to IOO to 125 mg. per kiIo in sodium morrhuate. In the chemica1 and bioIogic Iaboratory the compound was found to be satisfactory and at Ieast as safe as the older solutions. There remained the proof of clinical trial. Forty-three consecutive cases were injected with the solution. Of these fifteen were males and twenty-eight femaIes. A tota of 345 injections were given. The technique used was virtuaIIy the same as with sodium morrhuate. SingIe injections were given once a week and the amount of thrombosis noted the foIlowing week. The patients were questioned for any possibIe reactions. The initial injection was usualIy I to 2 C.C. The thrombosis was noted the foIIowing week and the amount of subsequent injection reguIated as required by the individual patient and the size of the vein. No tourniquets were used except in cases where there was a faiIure of or insuffrcient thrombosis. For statistical purposes, the resulting thromboses were divided into the foIlowing cIasses : Class o: Failure of thrombosis. CIass I : Thrombosis up to one-haIf inch. CIass 2: From one-half inch to 2 inches. Class 3: Over 2 inches or with chemica1 phIebitis, but with no tendency to break down. CIass 4: Ascending chemical phlebitis. Thromboses in Class 2 were considered optimum. WhiIe CIasses 3 and 4 produced good end-resuIts, we felt that they were of Lincoln Hospital,
628
New York City.
New
SERIES VOL.XL, No. s
Meyer-MonoethanoIamine
undesirabIe because discomfort often prevented the patient from doing his usual work, so that treatment could no Ionger be considered ambulatory. The thromboses ,produced were as follows : Unrecorded : 3 injections CIass 0: 1 I injections 27 injections (Note: Most CIass I: of these resulted from the smaI1 amount used in the initia1 injection.) CIass 2: 284 injections CIass 3: I 6 injections 2 injections CIass 4: There were no sloughs in spite of the fact that on numerous occasions smaI1 amounts were infiltrated. There was no evidence of aIIergic reaction in any of the patients. The voIume of solution injected varied from I to 5 c.c., the usua1 amount required being from 2 to 3 C.C. Of the 345 injections, 287,were from 2 to 3 c.c., and 203 from 2.5 to 3 C.C. At one time we ran short of the oIeate, and substituted sodium morrhuate temporarily in many of the cases. FolIowing the morrhuate injections there resuIted two cases of urticaria. One patient refused further treatment. In the other case treatment was continued with the oleate, and the urticarial symptoms subsided. After two weeks a smaI1 amount of sodium morrhuate was again injected with return of the urticaria.
American ~~~~~~~ or surgery
OIeate
629
SUMMARY
A cIinica1 tria1 of a new chemica1, monoethanoIamine oleate, was made on fortythree cases; a tota of 345 injections were given. In every case a good thrombus could be produced either at first or subsequentIy on injection. There were no cases of slough or any evidence of aIIergic reaction, CONCLUSION
MonoethanoIamine oleate is a satisfactory substitute for sodium morrhuate. It is comparable to the morrhuate in its lack of pain, its efficacy in production of thrombosis and prevention of sIough. It is superior to morrhuate because it is of known standard composition, it is more stable in solution, and has Iess tendency to produce aIIergic reactions. The monoethanoIamine oIeate for this study was suppIied through the courtesy of the Abbott Laboratories. REFERENCES
BIE~ELEISEN, J. The evaluation of sodium morrhuate therapy in varicose veins. Surg., GJnec. e? Obst., 57: 696-700,
1934.
FROHMAN, I. G., and BRAND, G. D. Compfications in injections of varicose veins. J. A. M. A., 103: 1088 (Oct. 6) 1934; Ic3: 1794 (Dec. 8) 1934. KEITZER, W. A. J. Michigan Med. Sot., 35: 168-169 (March) 1936. LEWIS, K. M. Anaphylactic shock due to sodium morrhuate. J. A. M. A., 107: r2g8 (Oct. 17) 1936. MCAUSLAND, 8. &it. M. J., I : 430 (Mar. I I) 1933. WELLS, C. A. &it. M. .I., I: 674 (April IS) 1933. ZIMMERMAN,L. M. J. A.M. A., 102: 1216-7 (April 14) 1934.