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Cobra Venom for Intractable Pain
105()
AMERICA::\ JOURNAL OF' OBSTETRIC:"; AND GYNECOLOGY COMMENT
It is reasonable to assume that the cigarette drain, which was removed forty-eight hours after the vaginal hysterectomy, offererl the hiatus through which the fimbriated extremity of the right Fallopian tube prolapsed. H is also possible that the fimbriae might have become adherent to the gauze uf the drain and been inadvertently pulled through the hiatus when the drain was removed. Torsion of the structure then occurred with resultant edema, venous congestion and hemorrhage. Whether or not endocrine imbalance added to this me~hanical derangement with resultant periodicity of bleeding, we are unable to say.
COBRA VENOM FOR INTRACTABLE PAIN
w.
JOSEPH KELSO, M.D., OKLAHOMA CITY, OKLA. (Fr01n the Gyrvecological Service of the University Hospital)
of the long-continued intractable pain associated with inBECAUSE curable pelvic cancer, and the disappointing results of the anodyne measures usually employed, morphine addiction, nausea, vomiting, insomnia, and euphoria so frequently seen making the use of these analgesic measures unsatisfactory, the author deeided to try cobra venom for the relief of pain. Cobra venom was studied by Dr. Adolph Monae-Lesser in 1929. He observed the relief of pain in a Cuban leper who was bitten by a tropical spider. This experience caused him to study the action of cobra venom. Dr. David I. Macht deserves the credit for a greater part of the physiologic and pharmacologic data which have been obtained from work done in the United States. He has proved conclusively that the venom, like morphine, has its effect on the higher centers of the brain and has no peripheral action at all. Dr. Macht has likewise carried on a biochemical investigation in which he has established the fact that opium derivatives are oxidized from the brain very rapidly, while the venom from the cobra is found unchanged in fresh brain tissue for a much longer period of time. This explains its tardy action and its prolonged anodyne effect in contradistinction to morphine. The latter produces rapid analgesia, but unfortunately the effect is not very lasting. Fortunately cobra venom is not habit forming. In other words, a patient is not likely to beeome addicted to a drug from which he obtains no relief for seventy-two hours after administration.
On the basis of experimen-tal clinical observations made by Dr. Macht and others, I have used this drug on 18 patients, 15 of whom were eonsidered hopeless. CASE REPORTS
A. T., 57 years of age, had a Group IV carcinoma of the cervix and received 7,200 r. units of x-ray. After temporary improvement she developed pain and con· tinued bleeding. Cobra venom was started in August, 1939, by Dr. C. W. Ohl, of Chickasha, Oklahoma. Her malignancy advanced and she continued to bleed on repeated occasions, but in spite of this she has gained weight and has been relieved of pain. This patient continued to be comfortable on 5 mouse units, or 1 c.c. of the cobra venom every third day. T. L. W., 50 years of age, Group III cervical cancer, received x-ray and radium, but after eight months the growth began to progress rapidly and she developed unbearable pain. Cobra venom was begun in August, 1939, under the supervision
KEI"SO:
COBRA VEXOM FOR IKTRACTABLE PAIN
tofil
of Dr. C. M. Cochran, Okemah, Oklahoma. 'Though quantities of anodyne pills had been given, she experienced little relief from pain until cobra venom was ad, ministered. The control of pain was almost 100 per cent. Although she con· tinued to lose weight, she gained in strength and well-being. 0. D., 65 years of age, Group III carcinoma of the cervix, had a pathologic fracture through the neck of the left femur and has obtained 100 per cent relief from her I•ain since the use of the venom, which has been given by Dr. L. R. Wilhite, of Perkins, Oklahoma. Her fracture has united, thfm• is no evidence of bon<> rlestruction, aml at the present time she takes :'5 units weekly and is without pain. N. J., 40 years of age, had a Group III carcinoma of the cervix, receivf'.d radium anti x·ray, but a year later began to have severe pain. She was given cobra venom by Dr. D. B. Collins, of Waurika, Oklahoma. He thought she wa8 obtaining relief from the injections, but later leametl that Rhe was taking papine for eontrol of pain. It is interesting to note that she did eat well and gainenom, she was just as comfortable on !}.; gr. of morphine sulfate as she ha
1052
AMERICAX JOURNAL OF OBI'TF.TR!Cfi Al'\D OYNECOLOUY
awl she wa~ n,]mitted for intrathe!•.ul akohol i1• injections, whieh were done on twn different oer.a,;ions without relief. i':4he •ras then giwn cohm wnom and obtained eornplete relief, in spite of a ra.pi1l 1levdopment of a huge mass in the right si1le of the ab,Jomen. Following the rPlief of pain the eontradurP re,;por),(Je(! to diathermy tm<1 massage. V. \V., a 62-year-old woman, had. seven• pain sixteen months after treatment for an atlvaneetl, Group III, unrlifferentiatetl malignaney of the een-ix and body of the uterus. She was givt'n cobra wnom hy Dr. C. E. Northwtt. of Ponca City, Oklahoma, an1l he reports that she ohtaim:d most ~atisfal'tory results, and that it waR Jmne,~Ps Rary for hrr to u~e any other <1rug;-; for tlw rPlie£ of pain. n. L., a ili-year·ohl woman who ha<1 a Group IV carcinoma of the cervical stump, ohtaine<1 no reg1·eRsion from x-ray series. ).H the growth continued she develope<] pain, requiring morphine for rt>lief. She \VHs given ,·obra venom with no appr('ciable relief. Two akoholic in,iertions wrn: then given into thr spinal canal, with relirf for twpnt~·-four hours following thr fir"t, and sixteen hours following the serono. Shr is no\\' up and about following· a hilateral chunlotomy and is eompletl'ly fr'l. Her relief is P~timate
Encouraged by the results obtained in the relief of pain in pelvic malignancies, I decided to try the remedy in the following cases: Mrs. H., a nurse's mother, agel'tieulosis of the colon for many years and now had a malignancy of the redum and lowet· sigmoid, with eonstan't pain. She vomits after the administnttion of morphine ]Jut can tolerate small closes of hyoscine, morphine, anrl cadoid compound. She haH taken 20 ampoules of eobra venom in a ~pan of fourteen days without any apparent r(•lief. L. S., a 14-year-ol
The above brief case reports seem to warrant a continued trial of this therapeutic agent. The cobra venom is supplied in 1 c.c. ampoules, each representing 5 mouse units. It was given intramuscularly. The initial dose was % c·.r., with succeeding daily doses of 1 <'.<'. until relief was obtained, or until 10 ampoules were given. It should be noted that in 12 of the cases reported the estimated relief of pain ranged from 85 to 100 per cent. '\Vhile there were no Sl'l'ious untoward sequelae, there were definite local and systemic reactions encountered. manifested by
BROt:GHER:
10G3
'L'PBOOVARL\:'\ .\BRCERS
transitory shock and cerebrovascular disturhanees. The use of rohra venom should be limited to carefully chosen eases and its effects closdy observed until its physiologic action is better known to the clinieiun and its ultimate results more el<'arl~' df'fhwd. Maoht, D. I.: Ann. Int. Med. 11: 1824, HI ilK. Oayle, R. F., l!nd. Willia·ms, ,J. ]1[.: South. M. J. 31: 188, 1938. Macht, D. I.: M. He~. 144: 537, 19:3ti. Idem: Am. ,J. PhyRiol. 116: 101, 19:36. Ru.therford, R. ;V.: Xew Englanr. Biol. & Me1l, 42: 4:13, Hl:39. Maoht, D. I.: Proe. Nat. Aca
PREGNANCY COMPLICATED BY TUBOOVARIAN ABSCESS JOHX
C.
BROLTGHER,
M.D .. F.A.C.S ..
VANCOl'VER, WASH.
T HE
early i!iagnosis of pregnancy has heen greatly fadlitated h,v the Aschheim· ZonnE'k test. A negative following a pot'itiw test would indicate death of the fetu~. The following ca~E' report demonftratt>~ ~ueh finding-~ romplicated b~· th~· clE'velopment of a large abclominal tumor. Mrs. X .. married, aged 22 years, primipara, 1·onsultecl mE' Sept. 2Cl, 1\!:38. Hl'r laAt regular menstrual period began July 5, JH:\8. On August 1 she had hail a light menstrual flow lasting two days. Starting again August 27 she continueil to flow for Sl'ventf'en 1lays, using 4 to (i pad~ daily. An ;\~ehheim·Zondek test which hacl been mane September 10 was positi\·e. Family history rrvealed three eases of tuhert'ulo~is, no cliabetPR or cancer. ME'n~es began at 12 years nf age, regular, twenty·one-cla.v c,vde, lasting six days, moderate flow, no dot:.; or leucorrhea, slight pain. An appenlll'rtomy for ruptnrrd appendix wa~ donp in 1925. General health had been poor for eight or nint' yPar~. As an a,]ole~rent she had had various attacks of cystitis and at one time nephritis with albumin. Examina· tion had revealeil a pehic tumor hut her father woultl not permit an operation. ]hn•in.
hln'f'1ivflr·ln
flf 1
'l'PtrA\.7Al'hul
11tt~ron!'l.
by p~:~~~~ie~, -a~,i·l~a·cl·b-eE'~--gi~~~ tl;;;.~irl -f~1: ·-w~~lm;:s~--~;,} f;;;;~~~-·- .Sl!~-];~d-h~;;;
trouhle1l with lwa,lacheR, vertigo, blurring of vi~ion, and '{lOor appetite. She ha eomplained of ''soreness in oyarie~,'' imligestion, ana eon~tipation. Physieal •'xamination in my offire Rept. 2:1, 1931'1, revealed a n('rvous, tall, pale, a~thenic• inc1ividual, appearing to he ahout :\(1 yPars of age, w<>ight 11:! poun
AMERICA::\ JOURNAL OF' OBSTETRIC:"; AND GYNECOLOGY COMMENT
It is reasonable to assume that the cigarette drain, which was removed forty-eight hours after the vaginal hysterectomy, offererl the hiatus through which the fimbriated extremity of the right Fallopian tube prolapsed. H is also possible that the fimbriae might have become adherent to the gauze uf the drain and been inadvertently pulled through the hiatus when the drain was removed. Torsion of the structure then occurred with resultant edema, venous congestion and hemorrhage. Whether or not endocrine imbalance added to this me~hanical derangement with resultant periodicity of bleeding, we are unable to say.
COBRA VENOM FOR INTRACTABLE PAIN
w.
JOSEPH KELSO, M.D., OKLAHOMA CITY, OKLA. (Fr01n the Gyrvecological Service of the University Hospital)
of the long-continued intractable pain associated with inBECAUSE curable pelvic cancer, and the disappointing results of the anodyne measures usually employed, morphine addiction, nausea, vomiting, insomnia, and euphoria so frequently seen making the use of these analgesic measures unsatisfactory, the author deeided to try cobra venom for the relief of pain. Cobra venom was studied by Dr. Adolph Monae-Lesser in 1929. He observed the relief of pain in a Cuban leper who was bitten by a tropical spider. This experience caused him to study the action of cobra venom. Dr. David I. Macht deserves the credit for a greater part of the physiologic and pharmacologic data which have been obtained from work done in the United States. He has proved conclusively that the venom, like morphine, has its effect on the higher centers of the brain and has no peripheral action at all. Dr. Macht has likewise carried on a biochemical investigation in which he has established the fact that opium derivatives are oxidized from the brain very rapidly, while the venom from the cobra is found unchanged in fresh brain tissue for a much longer period of time. This explains its tardy action and its prolonged anodyne effect in contradistinction to morphine. The latter produces rapid analgesia, but unfortunately the effect is not very lasting. Fortunately cobra venom is not habit forming. In other words, a patient is not likely to beeome addicted to a drug from which he obtains no relief for seventy-two hours after administration.
On the basis of experimen-tal clinical observations made by Dr. Macht and others, I have used this drug on 18 patients, 15 of whom were eonsidered hopeless. CASE REPORTS
A. T., 57 years of age, had a Group IV carcinoma of the cervix and received 7,200 r. units of x-ray. After temporary improvement she developed pain and con· tinued bleeding. Cobra venom was started in August, 1939, by Dr. C. W. Ohl, of Chickasha, Oklahoma. Her malignancy advanced and she continued to bleed on repeated occasions, but in spite of this she has gained weight and has been relieved of pain. This patient continued to be comfortable on 5 mouse units, or 1 c.c. of the cobra venom every third day. T. L. W., 50 years of age, Group III cervical cancer, received x-ray and radium, but after eight months the growth began to progress rapidly and she developed unbearable pain. Cobra venom was begun in August, 1939, under the supervision
KEI"SO:
COBRA VEXOM FOR IKTRACTABLE PAIN
tofil
of Dr. C. M. Cochran, Okemah, Oklahoma. 'Though quantities of anodyne pills had been given, she experienced little relief from pain until cobra venom was ad, ministered. The control of pain was almost 100 per cent. Although she con· tinued to lose weight, she gained in strength and well-being. 0. D., 65 years of age, Group III carcinoma of the cervix, had a pathologic fracture through the neck of the left femur and has obtained 100 per cent relief from her I•ain since the use of the venom, which has been given by Dr. L. R. Wilhite, of Perkins, Oklahoma. Her fracture has united, thfm• is no evidence of bon<> rlestruction, aml at the present time she takes :'5 units weekly and is without pain. N. J., 40 years of age, had a Group III carcinoma of the cervix, receivf'.d radium anti x·ray, but a year later began to have severe pain. She was given cobra venom by Dr. D. B. Collins, of Waurika, Oklahoma. He thought she wa8 obtaining relief from the injections, but later leametl that Rhe was taking papine for eontrol of pain. It is interesting to note that she did eat well and gaine
1052
AMERICAX JOURNAL OF OBI'TF.TR!Cfi Al'\D OYNECOLOUY
awl she wa~ n,]mitted for intrathe!•.ul akohol i1• injections, whieh were done on twn different oer.a,;ions without relief. i':4he •ras then giwn cohm wnom and obtained eornplete relief, in spite of a ra.pi1l 1levdopment of a huge mass in the right si1le of the ab,Jomen. Following the rPlief of pain the eontradurP re,;por),(Je(! to diathermy tm<1 massage. V. \V., a 62-year-old woman, had. seven• pain sixteen months after treatment for an atlvaneetl, Group III, unrlifferentiatetl malignaney of the een-ix and body of the uterus. She was givt'n cobra wnom hy Dr. C. E. Northwtt. of Ponca City, Oklahoma, an1l he reports that she ohtaim:d most ~atisfal'tory results, and that it waR Jmne,~Ps Rary for hrr to u~e any other <1rug;-; for tlw rPlie£ of pain. n. L., a ili-year·ohl woman who ha<1 a Group IV carcinoma of the cervical stump, ohtaine<1 no reg1·eRsion from x-ray series. ).H the growth continued she develope<] pain, requiring morphine for rt>lief. She \VHs given ,·obra venom with no appr('ciable relief. Two akoholic in,iertions wrn: then given into thr spinal canal, with relirf for twpnt~·-four hours following thr fir"t, and sixteen hours following the serono. Shr is no\\' up and about following· a hilateral chunlotomy and is eompletl'ly fr'l. Her relief is P~timate
Encouraged by the results obtained in the relief of pain in pelvic malignancies, I decided to try the remedy in the following cases: Mrs. H., a nurse's mother, age
The above brief case reports seem to warrant a continued trial of this therapeutic agent. The cobra venom is supplied in 1 c.c. ampoules, each representing 5 mouse units. It was given intramuscularly. The initial dose was % c·.r., with succeeding daily doses of 1 <'.<'. until relief was obtained, or until 10 ampoules were given. It should be noted that in 12 of the cases reported the estimated relief of pain ranged from 85 to 100 per cent. '\Vhile there were no Sl'l'ious untoward sequelae, there were definite local and systemic reactions encountered. manifested by
BROt:GHER:
10G3
'L'PBOOVARL\:'\ .\BRCERS
transitory shock and cerebrovascular disturhanees. The use of rohra venom should be limited to carefully chosen eases and its effects closdy observed until its physiologic action is better known to the clinieiun and its ultimate results more el<'arl~' df'fhwd. Maoht, D. I.: Ann. Int. Med. 11: 1824, HI ilK. Oayle, R. F., l!nd. Willia·ms, ,J. ]1[.: South. M. J. 31: 188, 1938. Macht, D. I.: M. He~. 144: 537, 19:3ti. Idem: Am. ,J. PhyRiol. 116: 101, 19:36. Ru.therford, R. ;V.: Xew Englan
PREGNANCY COMPLICATED BY TUBOOVARIAN ABSCESS JOHX
C.
BROLTGHER,
M.D .. F.A.C.S ..
VANCOl'VER, WASH.
T HE
early i!iagnosis of pregnancy has heen greatly fadlitated h,v the Aschheim· ZonnE'k test. A negative following a pot'itiw test would indicate death of the fetu~. The following ca~E' report demonftratt>~ ~ueh finding-~ romplicated b~· th~· clE'velopment of a large abclominal tumor. Mrs. X .. married, aged 22 years, primipara, 1·onsultecl mE' Sept. 2Cl, 1\!:38. Hl'r laAt regular menstrual period began July 5, JH:\8. On August 1 she had hail a light menstrual flow lasting two days. Starting again August 27 she continueil to flow for Sl'ventf'en 1lays, using 4 to (i pad~ daily. An ;\~ehheim·Zondek test which hacl been mane September 10 was positi\·e. Family history rrvealed three eases of tuhert'ulo~is, no cliabetPR or cancer. ME'n~es began at 12 years nf age, regular, twenty·one-cla.v c,vde, lasting six days, moderate flow, no dot:.; or leucorrhea, slight pain. An appenlll'rtomy for ruptnrrd appendix wa~ donp in 1925. General health had been poor for eight or nint' yPar~. As an a,]ole~rent she had had various attacks of cystitis and at one time nephritis with albumin. Examina· tion had revealeil a pehic tumor hut her father woultl not permit an operation. ]hn•in.
hln'f'1ivflr·ln
flf 1
'l'PtrA\.7Al'hul
11tt~ron!'l.
by p~:~~~~ie~, -a~,i·l~a·cl·b-eE'~--gi~~~ tl;;;.~irl -f~1: ·-w~~lm;:s~--~;,} f;;;;~~~-·- .Sl!~-];~d-h~;;;
trouhle1l with lwa,lacheR, vertigo, blurring of vi~ion, and '{lOor appetite. She ha