- Email: [email protected]
Maternal deaths associated with an intrauterine device
Maternal deaths associated with an intrauterine device C.
D.
Tucson,
CHRISTIAN,
M.D.
Arizona
Five midtrimester maternal deaths and several severe cases of sepsis associated more commonly with the shield type of intrauterine decice are presented. The apparent development of generalized sepsis before localized signs or symptoms are made known is a feature of greatest concern. The question of whether this pattern is associated with a certain type of device and the management of intrauterine devices in the pregnant uterus are discussed.
1 T IS THE P u RP o s E of this communication to report two maternal deaths and make reference to three others (as well as several severely septic midtrimester abortions) in which a pattern of pathophysiology is surfacing that appears to be associated more commonly with a particular intrauterine device. These cases are being referred to rather than completely detailed because of a sense of urgency to express the author’s concern regarding the possible problems with this particular device. The Family Planning Evaluation Branch, Bureau of Epidemiology, Center for Disease Control, has devised and has the preliminary tabulations1 from a thoughtful questionnaire which will add immeasurably to our understanding of the epidemiology of serious infections associated with intrauterine devices. By the protocol of the questionnaire (reporting only the immediately prior six months), however, four
of the five maternal deaths noted below apparently would not be included in those data. The number of cases mentioned below is in no way meant to imply any statistical validity since no meaningful data base of numbers of insertions is available, and therefore no inferences regarding incidence should be drawn. Likewise, it should not be concluded that a shield-type device is the only device that may be associated with such problems. Maternal deaths Case 1 (Arizona). The patient, a Sl-year-old woman, gravida 3, para 2, had a Dalkon Shield* inserted on October 8 (last menstrual period November 20). An intrauterine pregnancy was diagnosed, and the patient was followed prenatally. The intrauterine device was left in place. On March 27, the patient reported a flulike syndrome which she stated that two of her children also had. She additionally mentioned a sense of lower abdominal fullness. On March 28, she noted one episode of transient shaking chills. At 0400 hours on March 29, she developed unremitting shaking chills and a scant amount of vaginal bleeding and fever. She was admitted with a temperature of 103O F., jaundice, and an acutely ill appearance. At the time of admission, the patient was noted to bleed freely from venipuncture sites. At that time, the hematocrit was 35 per cent; pro-
From the Department of Obstetrics and Gynecology, Arizona Medical Center, The University of Arizona. Received 1973.
for
Revised
January
Accepted
publication
February
December
24,
31, 1974. II,
1974.
Reprint requests: Dr. C. D. Christian, Department of Obstetrics-Gynecology, University of Arizona Medical Center, Tucson, Arizona 85724.
*A. Virginia
141
H. Robins ?3220.
Co..
1407
Cummings
Dr..
Richmond.
442
Junr 15. 1974 .Am. J, matet. Gynccol.
Christian
thromhin time, greater than 230 seconds; partial thromboplastin time, over 200 seconds; clotting time, over 60 minutes; fibrinogen, less than 15 mg. per cent; and platelets, 105,000. Shortly after admission, she was delivered of a fetus of approximately 19 weeks’ gestational age, and a curettage followed. Hypotension developed with systolic pressures in the 60 to 100 mm. Hg range. Despite all measures, the patient developed anuria with a rising creatinine 32 hours after admission. At this time, the platelet count was 20,000; partial thrombopiastin timr was 180 seconds, and urinary fibrin split products were reported as 3,164. At 2012. hours on October 30, the patient died 72 hours after the first flulike symptoms. Pathologic diagnoses were: postseptic abortion, septicemia (blood cultures were negative, the uterine cultures revealed “pseudomonas”), disseminated intravascular coagulopathy, rrtroperitoneal hemorrhage, bilateral adrenal hemorrhage, pulmonary edema and hemorrhage, tubular degeneration of the in the heart, and
kidneys, petechial hemorrhages glomerular intracapillary clots. Case 2 (Texas). The patient, a 24-year-old woman, gravida 3, para 2, had a shield-type device inserted on January 6 with no subsequent complaints (last menstrual period April 22). The pregnancy proceded without difficulty with the intrauterine device in place until August 18 when she noted a scant cocoa-colored vaginal discharge. Six hours prior to admission, a sort’ throat and painful right ear developed, and a temperature elevation to 104O F. was noted along with nausea and vomiting. Shortly after admission at 2300 hours on March 20, there was a small amount of uterine cramping and scant vaginal bleeding. Prior to the six hours before admission, the patient had no complaints 01 symptoms of illness other than the scant brownish discharge. On admission. the patient appeared acutely ill; temperature, 102O F.; pulse, 120 beats per minute; blood pressure. 90/40 mm. Hg; respirations, 36. Examination revealed pharyngitis, and a throat culture was obtained. Pelvic examination revealed 5 C.C. of dark menstrual-type blood in the vagina. There was no active bleeding and no purulent discharge. The uterus was enlarged to about a 15 week’s gestation size, nontender, and freely mobile. No adnexal masses were noted. The uterine cramping progressed, and at 0630 hours on .4ugust 21, the patient aborted. Digital
examination
of
the
uterus
at
that
time
revealed
no remaining tissue. There was minimal bleeding; the uterus contracted vvelt. and there was no clinical evidence of intrauterine infection. The device was passed with the products of conception. The hypotension present since admission (80/40) improved to ( 100/6Oj, and she became more alert. At 1400 hours on August 21 a shocklike picture again developed, and despite all measures for treatment of gram-negative sepsis thr patient died at 0250 hours on August 22. 1972, some 31 hours after the first symptoms of a sore throat and painful right ear. Pathological diagnoses were: Aborted material ~-fetus 13.5 cttr. crown-heel length. placenta rcvealing “heavy colonies of bacilli within the villi, some suggesting clustering within the loose stroma and others suggesting that they blood v~essels.” Autopsyystatus abortion bilateral
fill the chorionic post incomplete device also present, acute myocarditis
with intrauterine adrenal petechiac,
with acute cardiac edema. Etiology considered to be
Case 3 to sepsis membrane a loop-type
failure, and acute pulmonary by pathologic diagnosis wa\; gram-negative septicemia. (Colorado). Maternal death secondary following premature rupturr of the in thr second trimester occurred with device in place.:’
Case 4 (North Carolina). Maternal secondary to sepsis in the midtrimester with a shield-type device in place:
death occurred
Case 5 (West Virginia). Maternal death in the midtrimester (20 weeks) secondary to septic shock and disseminated intravascular coa,gulation secondary to septic abortion occurred with a shield-type drvice in place. The patirnt had scant vaginal bleeding, no cramping, and no other symptoms on the day prior to admission. On admission. she had a tcmpcraturc of 104O F. She spontaneously aborted and died in :36 hortrs.~ Severely
ill patients
with
septic
abortions
Case 1 (Arizona). A 3 I -year-old v\ Oman, gravida 4, pata 2, abortuses 1, had a shield-type device in place for over one year. She became pregnant, and at 16 weeks was admitted with blood pressure 88/50, pulse 120 to 140, temperature 38.6O C., and profuse vaginal bleeding. She was treated for septic and hemorrhagic shock; the uterus was emptied, and she survived with no residual problems. (:rrvical culture grew ant\ alpha hcrnolytic streptococri; t\\ o blood cttlture\: revealed no growth.
Volume Number
119 4
Case 2 (Arizona). A 26year-old woman, gravida 6, para 4, abortuses I, was 16 weeks pregnant with a shield-type device in place. She presented with headache, nausea and vomiting, fever, chills, and low abdominal discomfort. She was treated for septic shock, and the uterus was emptied. She survived. Bacteriologic diagnosis was gram-negative sepsis. Case 3 (Arizona). A 24-year-old woman, gravida 2, para 1, had a 19 weeks’ gestation with a loop-type device in place. She presented with fever and uterine cramping. She was treated for sepsis, and the uterus was emptied. She survived. The cervical cultures grew hemolytic streptococci. Case 4 (Texas). A 3 l-year-old woman, gravida 3, para 2, had a shield-type device for two years prior to pregnancy with the device in place. At 15 to 16 weeks, she developed a fever of 103O F. and a brownish vaginal discharge. The uterus was emptied, and the device was removed. She was treated for sepsis and survived. Pathologic examination of the products of conception revealed large numbers of bacilli within the blood vessels of the villi.” Case 5 (Texas). A 24-year-old woman, gravida 3, para 1, was pregnant with a shield-type device in place. She had an uneventful pregnancy until 18 to 20 weeks when she developed a fever of 103O F. and uterine cramping. The uterus was emptied, and she was treated for sepsis. She developed septic shock and disseminated intravascular coagulopathy. She survived but required two additional admissions for uterine bleeding and endometritis.2 Case 6 (Massachusetts). This patient became pregnant with a shield-type device in place. In the midtrimester, she developed gram-negative sepsis and disseminated intravascular coagulopathy-she survived.” Case 7 (Pennsylvania). The patient became pregnant with a shield-type device in place. In the midtrimester, she developed gram-negative sepsis with disseminated intravascular coagulopathy and shock lung-she survived.7 These cases have certain similarities that raise several questions. 1. Is this a relatively new clinical situation that develops with intrauterine devices or certain types of uterine devices? The Food and Drug Administrations report on intrauterine devices of January, 1968, gave the results of Dr. Roger Scott’s survey of Fel-
Maternal
deaths
and IUD
443
lows of the American College of Obstetricians and Gynecologists and listed 12 deaths associated with intrauterine devices. Two of these were maternal deaths and were both proved to be secondary to amniotic fluid embolism following midtrimester abortions, and in both cases the devices (one a loop-type device, the other a coil type) had perforated the uterus. There were included in those data no cases with the pattern that seems to be evolving in the situations previously mentioned. 2. What is the true incidence of pregnancy with various devices, and once known what is the true incidence of problems such as we are reporting in those pregnancies? It is important that these types of data be known with as much accuracy as possible so that we may assess the relative risk to the population and to any patient as an individual. 3. If a patient becomes pregnant with a device in place, should it be removed? There is, of course, difference of opinion in this regard but knowledge of these cases has modified our behavior in two ways. If the strings are visible, we remove the device. We have not as yet advocated aborting such patients unless they so desire, but a very effective argument could be mounted for such an approach. Second, at least until further data are available, we have discontinued the use of the shield-type device. The greatest concern is the rather insidious yet rapid manner in which these patients become ill. In three of the five noted maternal deaths, the first symptoms, which were disarmingly innocuous in and of themselves, occurred within 31 to 72 hours of death from sepsis and the sequalae of sepsis. It appears that the iniection becomes generalized at about the same time as or before there are any localizing signs, and therefore the margin of safety that time ordinarily provides in treating such infections is not present. One wonders if there may be something about the design of the shield-type device that allows vascular dissemination of infection that might otherwise be locally contained. In this regard, it is easy to visualize that the pronglike protrusions on the periphery of
444
Christian
the device could make this apparent difference in the incidence of such problems when compared to the smooth-surfaced devices. Such conjecture is just that, and certainly no experimental data exist to say that any particular design is more or less likely to be associated with dissemination of infection. This all invites the much larger question of whether there should not be more rigid evaluation and control of medical devices. Certainly, if there were five botulism deaths from one type of mushroom soup, the Food
and Drug Administration would do more than put out a questionnaire. Any pregnancy associated with an intrauterine device must be followed most circumspectly. and we must be constantly alert to the slightest symptom or complaint. Painless dark bro\\n spotting is common to most of the reported cases, but symptoms as apparently unrelated as sore throat, painful ear. or Au heralded the fatal sepsis in certain of the patients.
REFERENCES
1.
Kahn, H. S., and Tyler, C. W.: Joint I.U.D. Study-Preliminary Tabulations, October 20, 1973. ‘2. Des Rosiers, J. L.: Personal communication. Ii. Bowes, W. A., Jr.: Personal communication. 4. McCoy, J. B.: Personal communication. 5. Poole, T. R.: Personal communication.
6. 7. 8.
Reid, D. E.: Personal communication. Rogers, R. E.: Personal communication. Advisory Committee on Obstetrics and Gynecology, Hellman, L. M., Chairman: Report on Intrauterine Contraceptive Devices, Washington, D. C., 1968, Department of Health, Education. and Welfare.
D.
Tucson,
CHRISTIAN,
M.D.
Arizona
Five midtrimester maternal deaths and several severe cases of sepsis associated more commonly with the shield type of intrauterine decice are presented. The apparent development of generalized sepsis before localized signs or symptoms are made known is a feature of greatest concern. The question of whether this pattern is associated with a certain type of device and the management of intrauterine devices in the pregnant uterus are discussed.
1 T IS THE P u RP o s E of this communication to report two maternal deaths and make reference to three others (as well as several severely septic midtrimester abortions) in which a pattern of pathophysiology is surfacing that appears to be associated more commonly with a particular intrauterine device. These cases are being referred to rather than completely detailed because of a sense of urgency to express the author’s concern regarding the possible problems with this particular device. The Family Planning Evaluation Branch, Bureau of Epidemiology, Center for Disease Control, has devised and has the preliminary tabulations1 from a thoughtful questionnaire which will add immeasurably to our understanding of the epidemiology of serious infections associated with intrauterine devices. By the protocol of the questionnaire (reporting only the immediately prior six months), however, four
of the five maternal deaths noted below apparently would not be included in those data. The number of cases mentioned below is in no way meant to imply any statistical validity since no meaningful data base of numbers of insertions is available, and therefore no inferences regarding incidence should be drawn. Likewise, it should not be concluded that a shield-type device is the only device that may be associated with such problems. Maternal deaths Case 1 (Arizona). The patient, a Sl-year-old woman, gravida 3, para 2, had a Dalkon Shield* inserted on October 8 (last menstrual period November 20). An intrauterine pregnancy was diagnosed, and the patient was followed prenatally. The intrauterine device was left in place. On March 27, the patient reported a flulike syndrome which she stated that two of her children also had. She additionally mentioned a sense of lower abdominal fullness. On March 28, she noted one episode of transient shaking chills. At 0400 hours on March 29, she developed unremitting shaking chills and a scant amount of vaginal bleeding and fever. She was admitted with a temperature of 103O F., jaundice, and an acutely ill appearance. At the time of admission, the patient was noted to bleed freely from venipuncture sites. At that time, the hematocrit was 35 per cent; pro-
From the Department of Obstetrics and Gynecology, Arizona Medical Center, The University of Arizona. Received 1973.
for
Revised
January
Accepted
publication
February
December
24,
31, 1974. II,
1974.
Reprint requests: Dr. C. D. Christian, Department of Obstetrics-Gynecology, University of Arizona Medical Center, Tucson, Arizona 85724.
*A. Virginia
141
H. Robins ?3220.
Co..
1407
Cummings
Dr..
Richmond.
442
Junr 15. 1974 .Am. J, matet. Gynccol.
Christian
thromhin time, greater than 230 seconds; partial thromboplastin time, over 200 seconds; clotting time, over 60 minutes; fibrinogen, less than 15 mg. per cent; and platelets, 105,000. Shortly after admission, she was delivered of a fetus of approximately 19 weeks’ gestational age, and a curettage followed. Hypotension developed with systolic pressures in the 60 to 100 mm. Hg range. Despite all measures, the patient developed anuria with a rising creatinine 32 hours after admission. At this time, the platelet count was 20,000; partial thrombopiastin timr was 180 seconds, and urinary fibrin split products were reported as 3,164. At 2012. hours on October 30, the patient died 72 hours after the first flulike symptoms. Pathologic diagnoses were: postseptic abortion, septicemia (blood cultures were negative, the uterine cultures revealed “pseudomonas”), disseminated intravascular coagulopathy, rrtroperitoneal hemorrhage, bilateral adrenal hemorrhage, pulmonary edema and hemorrhage, tubular degeneration of the in the heart, and
kidneys, petechial hemorrhages glomerular intracapillary clots. Case 2 (Texas). The patient, a 24-year-old woman, gravida 3, para 2, had a shield-type device inserted on January 6 with no subsequent complaints (last menstrual period April 22). The pregnancy proceded without difficulty with the intrauterine device in place until August 18 when she noted a scant cocoa-colored vaginal discharge. Six hours prior to admission, a sort’ throat and painful right ear developed, and a temperature elevation to 104O F. was noted along with nausea and vomiting. Shortly after admission at 2300 hours on March 20, there was a small amount of uterine cramping and scant vaginal bleeding. Prior to the six hours before admission, the patient had no complaints 01 symptoms of illness other than the scant brownish discharge. On admission. the patient appeared acutely ill; temperature, 102O F.; pulse, 120 beats per minute; blood pressure. 90/40 mm. Hg; respirations, 36. Examination revealed pharyngitis, and a throat culture was obtained. Pelvic examination revealed 5 C.C. of dark menstrual-type blood in the vagina. There was no active bleeding and no purulent discharge. The uterus was enlarged to about a 15 week’s gestation size, nontender, and freely mobile. No adnexal masses were noted. The uterine cramping progressed, and at 0630 hours on .4ugust 21, the patient aborted. Digital
examination
of
the
uterus
at
that
time
revealed
no remaining tissue. There was minimal bleeding; the uterus contracted vvelt. and there was no clinical evidence of intrauterine infection. The device was passed with the products of conception. The hypotension present since admission (80/40) improved to ( 100/6Oj, and she became more alert. At 1400 hours on August 21 a shocklike picture again developed, and despite all measures for treatment of gram-negative sepsis thr patient died at 0250 hours on August 22. 1972, some 31 hours after the first symptoms of a sore throat and painful right ear. Pathological diagnoses were: Aborted material ~-fetus 13.5 cttr. crown-heel length. placenta rcvealing “heavy colonies of bacilli within the villi, some suggesting clustering within the loose stroma and others suggesting that they blood v~essels.” Autopsyystatus abortion bilateral
fill the chorionic post incomplete device also present, acute myocarditis
with intrauterine adrenal petechiac,
with acute cardiac edema. Etiology considered to be
Case 3 to sepsis membrane a loop-type
failure, and acute pulmonary by pathologic diagnosis wa\; gram-negative septicemia. (Colorado). Maternal death secondary following premature rupturr of the in thr second trimester occurred with device in place.:’
Case 4 (North Carolina). Maternal secondary to sepsis in the midtrimester with a shield-type device in place:
death occurred
Case 5 (West Virginia). Maternal death in the midtrimester (20 weeks) secondary to septic shock and disseminated intravascular coa,gulation secondary to septic abortion occurred with a shield-type drvice in place. The patirnt had scant vaginal bleeding, no cramping, and no other symptoms on the day prior to admission. On admission. she had a tcmpcraturc of 104O F. She spontaneously aborted and died in :36 hortrs.~ Severely
ill patients
with
septic
abortions
Case 1 (Arizona). A 3 I -year-old v\ Oman, gravida 4, pata 2, abortuses 1, had a shield-type device in place for over one year. She became pregnant, and at 16 weeks was admitted with blood pressure 88/50, pulse 120 to 140, temperature 38.6O C., and profuse vaginal bleeding. She was treated for septic and hemorrhagic shock; the uterus was emptied, and she survived with no residual problems. (:rrvical culture grew ant\ alpha hcrnolytic streptococri; t\\ o blood cttlture\: revealed no growth.
Volume Number
119 4
Case 2 (Arizona). A 26year-old woman, gravida 6, para 4, abortuses I, was 16 weeks pregnant with a shield-type device in place. She presented with headache, nausea and vomiting, fever, chills, and low abdominal discomfort. She was treated for septic shock, and the uterus was emptied. She survived. Bacteriologic diagnosis was gram-negative sepsis. Case 3 (Arizona). A 24-year-old woman, gravida 2, para 1, had a 19 weeks’ gestation with a loop-type device in place. She presented with fever and uterine cramping. She was treated for sepsis, and the uterus was emptied. She survived. The cervical cultures grew hemolytic streptococci. Case 4 (Texas). A 3 l-year-old woman, gravida 3, para 2, had a shield-type device for two years prior to pregnancy with the device in place. At 15 to 16 weeks, she developed a fever of 103O F. and a brownish vaginal discharge. The uterus was emptied, and the device was removed. She was treated for sepsis and survived. Pathologic examination of the products of conception revealed large numbers of bacilli within the blood vessels of the villi.” Case 5 (Texas). A 24-year-old woman, gravida 3, para 1, was pregnant with a shield-type device in place. She had an uneventful pregnancy until 18 to 20 weeks when she developed a fever of 103O F. and uterine cramping. The uterus was emptied, and she was treated for sepsis. She developed septic shock and disseminated intravascular coagulopathy. She survived but required two additional admissions for uterine bleeding and endometritis.2 Case 6 (Massachusetts). This patient became pregnant with a shield-type device in place. In the midtrimester, she developed gram-negative sepsis and disseminated intravascular coagulopathy-she survived.” Case 7 (Pennsylvania). The patient became pregnant with a shield-type device in place. In the midtrimester, she developed gram-negative sepsis with disseminated intravascular coagulopathy and shock lung-she survived.7 These cases have certain similarities that raise several questions. 1. Is this a relatively new clinical situation that develops with intrauterine devices or certain types of uterine devices? The Food and Drug Administrations report on intrauterine devices of January, 1968, gave the results of Dr. Roger Scott’s survey of Fel-
Maternal
deaths
and IUD
443
lows of the American College of Obstetricians and Gynecologists and listed 12 deaths associated with intrauterine devices. Two of these were maternal deaths and were both proved to be secondary to amniotic fluid embolism following midtrimester abortions, and in both cases the devices (one a loop-type device, the other a coil type) had perforated the uterus. There were included in those data no cases with the pattern that seems to be evolving in the situations previously mentioned. 2. What is the true incidence of pregnancy with various devices, and once known what is the true incidence of problems such as we are reporting in those pregnancies? It is important that these types of data be known with as much accuracy as possible so that we may assess the relative risk to the population and to any patient as an individual. 3. If a patient becomes pregnant with a device in place, should it be removed? There is, of course, difference of opinion in this regard but knowledge of these cases has modified our behavior in two ways. If the strings are visible, we remove the device. We have not as yet advocated aborting such patients unless they so desire, but a very effective argument could be mounted for such an approach. Second, at least until further data are available, we have discontinued the use of the shield-type device. The greatest concern is the rather insidious yet rapid manner in which these patients become ill. In three of the five noted maternal deaths, the first symptoms, which were disarmingly innocuous in and of themselves, occurred within 31 to 72 hours of death from sepsis and the sequalae of sepsis. It appears that the iniection becomes generalized at about the same time as or before there are any localizing signs, and therefore the margin of safety that time ordinarily provides in treating such infections is not present. One wonders if there may be something about the design of the shield-type device that allows vascular dissemination of infection that might otherwise be locally contained. In this regard, it is easy to visualize that the pronglike protrusions on the periphery of
444
Christian
the device could make this apparent difference in the incidence of such problems when compared to the smooth-surfaced devices. Such conjecture is just that, and certainly no experimental data exist to say that any particular design is more or less likely to be associated with dissemination of infection. This all invites the much larger question of whether there should not be more rigid evaluation and control of medical devices. Certainly, if there were five botulism deaths from one type of mushroom soup, the Food
and Drug Administration would do more than put out a questionnaire. Any pregnancy associated with an intrauterine device must be followed most circumspectly. and we must be constantly alert to the slightest symptom or complaint. Painless dark bro\\n spotting is common to most of the reported cases, but symptoms as apparently unrelated as sore throat, painful ear. or Au heralded the fatal sepsis in certain of the patients.
REFERENCES
1.
Kahn, H. S., and Tyler, C. W.: Joint I.U.D. Study-Preliminary Tabulations, October 20, 1973. ‘2. Des Rosiers, J. L.: Personal communication. Ii. Bowes, W. A., Jr.: Personal communication. 4. McCoy, J. B.: Personal communication. 5. Poole, T. R.: Personal communication.
6. 7. 8.
Reid, D. E.: Personal communication. Rogers, R. E.: Personal communication. Advisory Committee on Obstetrics and Gynecology, Hellman, L. M., Chairman: Report on Intrauterine Contraceptive Devices, Washington, D. C., 1968, Department of Health, Education. and Welfare.