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Sulfanilamide in Obstetrics and Gynecology
522
AMERICAN JOURNAL OF OBSTETRICS AND GYNECOI.OGY
with carbon dioxide; tlwt of' the barrn:turatcc; l·ann.ot: a V<'I'Y important point in relation to resuseitatiou. The chief inference to be drawn is that only sueh nareoties as arc of relatively brief action are justitia hle in labor, ~nd then only in the early stages. In the later stages anesthetics aloue should be nsed; :for anesthetics are drugs of brief action and have relatively slight depressive effects upon respiration. gyen 1rith anesthetics precautions mnst be taken against asphyxia. Particularly in the use of nitrous oxide, the percentage of oxygen with which the gas is mixed should not be allowed to fall belo>v 15 per cent.~ Otherwise asphyxial effects, immediate or delayed, effects essentially like those of carbon monoxide asphyxia, ma:-r result. 9 Bven with these limitations much may be done to diminish suffering. But the science of pharmacology affords no means of rendering childbirth free from even the slightest discomfort or recollection in the mothers except at the cost of man:-· dead or damaged habie~l. Yande/1 Hendel'.~on.
Sulfanilamide in Obstetrics and Gynecology IIE:M.OTHERAPY in the treatment of infections has received a C tremendous impetus during the past three years. At no time in medical history has such a promising drug as sulfanilamide and its related compounds been placed in the hands of the medical profession for this purpose. Experience, however, has amply demonstrated a wide variety of toxic symptoms that may occur following its use, some of which are no contraindication to the continuance of the therapy while others less often offer a definite indication to stop the administration of the drug. Exhaustive research in bacteriologic, immunologic, chemical, pharmacologic and therapeutic fields is necessary before we understand some of the most fundamental actions of the drug. Sulfanilamide is absorbed as rapidly or even more rapidly when taken by mouth than when administered subcutaneously and absorption is more rapid when given on an empty stomach. It is rapidly distributed throughout all maternal and fetal tissues including the placenta, liquor amnii, colostrum and milk. The drug is eliminated from the body almost entirely by the kidneys. No definite deleterious effects on the fetus have as yet been described. In general, treatment is more successful if the patient is hospitalized as the drug is tolerated better >vith the patient confined to bed and dosage can be more accurately controlled. Toxic signs and symptoms are also recognized earlier than in ambulatory patients. It is usually advisable to give sodium bicarbonate by mouth at the same time to prevent the possible development of an acidosis. There is usually no contraindication to other necessary medication at the same time, but its therapeutic action should not mask possible toxic s:vmptoms. Because of the rapid absorption and prompt excretion, a 8Ea.stm
N. J.: Ibid. 31: 663, 1936.
•aoumne, a.
B.: Medicine 11>: 129, 1936.
EDITORIALS
523
satisfactory blood concentration can only be maintained by fractionating the daily dose and administering the drug every four hours. Medical history has again repeated itself in that with the discovery of a new therapeutic agent the clinical application has far exceeded the indications of proved value. Our present understanding which may be radically modified in the fntnrl' suggests the following indications, manner of use and control in our field. a. In puerperal and postabortal infection accurate bacteriologic examination of the lochia is an essential prerequisite to treatment. This may be done by examining the lochia obtained from within the uterus or if this is impossible a sample may be obtained by a simple vaginal S\vab. If a hemolytic streptocorrm; is present in the material examined a diagnosis can usually be made in from twelve to eighteen hours. This is necessary because onl:v from 1 to 2 per cent of patients classified as morbid in a well-conducted obstetric service are found to have a heta hemolytic streptococcus in the lochia while an additional 2 to 3 per rent may harbor an alpha prime strain. Bven in institutions where only the more seriously ill patients suffering from puerperal infection are admitted usually not more than one-third are found to have hemolytic streptococ•cus infections. Experienc·c to date indicates that sulfanilamide iH of definite value only in the treatment of puerperal infection due to a hemolytic streptoc-occus and has hut little if any effect on puerperal infections due to the other usual organisms associated wiih snrh infections. Adequate dosage ( 6 to S g-m. per day) in divided doses ea1'ly in the disease is essential if the infeetion is sel"ious. b. Pyelitis before, during, or after labor. Again accurate bacteriologic examination of the urine is necessary prior to treatment. If total fluid intake is restricted to 2,000 e.c. per day, a satisfactory concentration of the drug may usually be attained by the administration of 3 to 5 gm. daily in divided doses. Oood results are frequently obtained in in:fecticms due to the colon-aerogencs g-roup of organisms so often associated with such infections. Staphylococcns albus and a1ue1ts organisms may al1;o often be quickly eliminated from the urine. Urinary tract infections due to nonhemolytic streptococci and some of the other gram-positive organisms are usually treated more successfully by mandelic acid therapy. Smaller doses than mentioned above may be used successfully to sterilize the urine following the subsidence of the acute infection. c. Gonorrhea. No chemotherapeutie agent used before the introduction of sulfanilamide has yielded anything like as satisfactory results in the treatment of this infection. Clinical experience to date has indicated certain facts that must be taken into consideration in order to obtain the best results. The treatment shonld not be started as a rule before the elapse of at least eight to ten days after the initial onset of the disease. A chronic gonorrhea is often more easily cured than the acute disease. Bacteriologic studies by enltural methods offer the only sound method of rontrolling the treatment and determining when a <·ure is established. It is quite possible that the diseharge may cease and clinical symptoms disappear Hoon after starting treatment b1d the rJonococc1tS may still l1e present in the loeal secretions. Thus, a state of
524
AMERICAN JOl:RXAT" OF OBSTE'l'RICS A?-:D GYXECOI,OGY
chronic canier could in this way hP t•stahlishell, whieh may be a possible, serious menaf:C 1o society. The drug- must he administen·d ill adequate dosage from the start or iht· llwrap,r and until repeated culboth from tures beeomc negative. There i:-; tlcfiuite eviclcn!'e to (•linical findings and from labomtor.'· data that the gonococcus may gradually be induced to grow in the prcscnec of incr·easing coneentrations of the drug, the phenomenon o [ becoming '·sulfanilamide fast." It is readily understandable how this can take plaee in the patient if low dosage is employed. The ideal dosage has not as yet hcen determined; however, present information suggestH that the initial daily dose should approximate 5 gm. The drug slloul(l lw eontillued possibly with d{·C'reased dosage until tlu·ee negath·e (•Hltnres at two-day i ntet·vals ]urn; been obtained. Determination of '· ~-m·e'' pnrel~- by f'liniral methods and smear interpretation is of very dnhious val ne. .. Permanent <·m·o .. r·riteria must depend hn·gely on repeated negative (·ultures at monthl~· intervals following sulfanilamide t bernpy. To sum np, it may be elaimetl that this new drug constitutes a valuable and noteworth~- addition to the materia mediea, but further research is ueeessary to dPtermine its action and limitation~:! as well as proper dosage. Certain unfortunate results whieh have aceornpanied its employment. largely in unskilled hands, should rail for that caution which is so e:-;sential for :safe and iille(•f•;;:-sfnl results. ---R. G. Dour;las.
Announcement American Association of Obstetricians, Gynecologists and Abdom.in.a.l Surgeons Annual J'ounda.ticm Prize The ~A..merican Association of Obstetricians, Gynecologists and Abdominal Surgeons announces that the annual Foundation Prize for this year will be $100.00. Those eligible include only (1) interns, residents, or graduate students in Obstetrics, Gynecology and Abdominal Surgery, and (2) physicians (M.D. degree) who are actually practicing or teaching Obstetrics, Gyneeology or Abdominal Surgery. Competing manuscripts mnRt ( 1) be presented in trizJlicatc under de plume to the Secretary of the Association before June 1, (2) nom a be limited to 5,000 words and such illustrations as are necessary for a clear exposition of the thesis, and ( 8) be typewritten (double-spaced) on one side of the sheets, with ample margins. The successful thesis must be presented at the next annual (September) meeting of the Association, without expense to the Association and in conformity with its regulations. For further details, address Dr .•Tames R. Bloss, Secretary, 418 lith Street, Huntington, W. Va.
AMERICAN JOURNAL OF OBSTETRICS AND GYNECOI.OGY
with carbon dioxide; tlwt of' the barrn:turatcc; l·ann.ot: a V<'I'Y important point in relation to resuseitatiou. The chief inference to be drawn is that only sueh nareoties as arc of relatively brief action are justitia hle in labor, ~nd then only in the early stages. In the later stages anesthetics aloue should be nsed; :for anesthetics are drugs of brief action and have relatively slight depressive effects upon respiration. gyen 1rith anesthetics precautions mnst be taken against asphyxia. Particularly in the use of nitrous oxide, the percentage of oxygen with which the gas is mixed should not be allowed to fall belo>v 15 per cent.~ Otherwise asphyxial effects, immediate or delayed, effects essentially like those of carbon monoxide asphyxia, ma:-r result. 9 Bven with these limitations much may be done to diminish suffering. But the science of pharmacology affords no means of rendering childbirth free from even the slightest discomfort or recollection in the mothers except at the cost of man:-· dead or damaged habie~l. Yande/1 Hendel'.~on.
Sulfanilamide in Obstetrics and Gynecology IIE:M.OTHERAPY in the treatment of infections has received a C tremendous impetus during the past three years. At no time in medical history has such a promising drug as sulfanilamide and its related compounds been placed in the hands of the medical profession for this purpose. Experience, however, has amply demonstrated a wide variety of toxic symptoms that may occur following its use, some of which are no contraindication to the continuance of the therapy while others less often offer a definite indication to stop the administration of the drug. Exhaustive research in bacteriologic, immunologic, chemical, pharmacologic and therapeutic fields is necessary before we understand some of the most fundamental actions of the drug. Sulfanilamide is absorbed as rapidly or even more rapidly when taken by mouth than when administered subcutaneously and absorption is more rapid when given on an empty stomach. It is rapidly distributed throughout all maternal and fetal tissues including the placenta, liquor amnii, colostrum and milk. The drug is eliminated from the body almost entirely by the kidneys. No definite deleterious effects on the fetus have as yet been described. In general, treatment is more successful if the patient is hospitalized as the drug is tolerated better >vith the patient confined to bed and dosage can be more accurately controlled. Toxic signs and symptoms are also recognized earlier than in ambulatory patients. It is usually advisable to give sodium bicarbonate by mouth at the same time to prevent the possible development of an acidosis. There is usually no contraindication to other necessary medication at the same time, but its therapeutic action should not mask possible toxic s:vmptoms. Because of the rapid absorption and prompt excretion, a 8Ea.stm
N. J.: Ibid. 31: 663, 1936.
•aoumne, a.
B.: Medicine 11>: 129, 1936.
EDITORIALS
523
satisfactory blood concentration can only be maintained by fractionating the daily dose and administering the drug every four hours. Medical history has again repeated itself in that with the discovery of a new therapeutic agent the clinical application has far exceeded the indications of proved value. Our present understanding which may be radically modified in the fntnrl' suggests the following indications, manner of use and control in our field. a. In puerperal and postabortal infection accurate bacteriologic examination of the lochia is an essential prerequisite to treatment. This may be done by examining the lochia obtained from within the uterus or if this is impossible a sample may be obtained by a simple vaginal S\vab. If a hemolytic streptocorrm; is present in the material examined a diagnosis can usually be made in from twelve to eighteen hours. This is necessary because onl:v from 1 to 2 per cent of patients classified as morbid in a well-conducted obstetric service are found to have a heta hemolytic streptococcus in the lochia while an additional 2 to 3 per rent may harbor an alpha prime strain. Bven in institutions where only the more seriously ill patients suffering from puerperal infection are admitted usually not more than one-third are found to have hemolytic streptococ•cus infections. Experienc·c to date indicates that sulfanilamide iH of definite value only in the treatment of puerperal infection due to a hemolytic streptoc-occus and has hut little if any effect on puerperal infections due to the other usual organisms associated wiih snrh infections. Adequate dosage ( 6 to S g-m. per day) in divided doses ea1'ly in the disease is essential if the infeetion is sel"ious. b. Pyelitis before, during, or after labor. Again accurate bacteriologic examination of the urine is necessary prior to treatment. If total fluid intake is restricted to 2,000 e.c. per day, a satisfactory concentration of the drug may usually be attained by the administration of 3 to 5 gm. daily in divided doses. Oood results are frequently obtained in in:fecticms due to the colon-aerogencs g-roup of organisms so often associated with such infections. Staphylococcns albus and a1ue1ts organisms may al1;o often be quickly eliminated from the urine. Urinary tract infections due to nonhemolytic streptococci and some of the other gram-positive organisms are usually treated more successfully by mandelic acid therapy. Smaller doses than mentioned above may be used successfully to sterilize the urine following the subsidence of the acute infection. c. Gonorrhea. No chemotherapeutie agent used before the introduction of sulfanilamide has yielded anything like as satisfactory results in the treatment of this infection. Clinical experience to date has indicated certain facts that must be taken into consideration in order to obtain the best results. The treatment shonld not be started as a rule before the elapse of at least eight to ten days after the initial onset of the disease. A chronic gonorrhea is often more easily cured than the acute disease. Bacteriologic studies by enltural methods offer the only sound method of rontrolling the treatment and determining when a <·ure is established. It is quite possible that the diseharge may cease and clinical symptoms disappear Hoon after starting treatment b1d the rJonococc1tS may still l1e present in the loeal secretions. Thus, a state of
524
AMERICAN JOl:RXAT" OF OBSTE'l'RICS A?-:D GYXECOI,OGY
chronic canier could in this way hP t•stahlishell, whieh may be a possible, serious menaf:C 1o society. The drug- must he administen·d ill adequate dosage from the start or iht· llwrap,r and until repeated culboth from tures beeomc negative. There i:-; tlcfiuite eviclcn!'e to (•linical findings and from labomtor.'· data that the gonococcus may gradually be induced to grow in the prcscnec of incr·easing coneentrations of the drug, the phenomenon o [ becoming '·sulfanilamide fast." It is readily understandable how this can take plaee in the patient if low dosage is employed. The ideal dosage has not as yet hcen determined; however, present information suggestH that the initial daily dose should approximate 5 gm. The drug slloul(l lw eontillued possibly with d{·C'reased dosage until tlu·ee negath·e (•Hltnres at two-day i ntet·vals ]urn; been obtained. Determination of '· ~-m·e'' pnrel~- by f'liniral methods and smear interpretation is of very dnhious val ne. .. Permanent <·m·o .. r·riteria must depend hn·gely on repeated negative (·ultures at monthl~· intervals following sulfanilamide t bernpy. To sum np, it may be elaimetl that this new drug constitutes a valuable and noteworth~- addition to the materia mediea, but further research is ueeessary to dPtermine its action and limitation~:! as well as proper dosage. Certain unfortunate results whieh have aceornpanied its employment. largely in unskilled hands, should rail for that caution which is so e:-;sential for :safe and iille(•f•;;:-sfnl results. ---R. G. Dour;las.
Announcement American Association of Obstetricians, Gynecologists and Abdom.in.a.l Surgeons Annual J'ounda.ticm Prize The ~A..merican Association of Obstetricians, Gynecologists and Abdominal Surgeons announces that the annual Foundation Prize for this year will be $100.00. Those eligible include only (1) interns, residents, or graduate students in Obstetrics, Gynecology and Abdominal Surgery, and (2) physicians (M.D. degree) who are actually practicing or teaching Obstetrics, Gyneeology or Abdominal Surgery. Competing manuscripts mnRt ( 1) be presented in trizJlicatc under de plume to the Secretary of the Association before June 1, (2) nom a be limited to 5,000 words and such illustrations as are necessary for a clear exposition of the thesis, and ( 8) be typewritten (double-spaced) on one side of the sheets, with ample margins. The successful thesis must be presented at the next annual (September) meeting of the Association, without expense to the Association and in conformity with its regulations. For further details, address Dr .•Tames R. Bloss, Secretary, 418 lith Street, Huntington, W. Va.