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ORIGINAL RESEARCH |
From the Department of Obstetrics and Gynecology, Kaplan Medical Center, Rehovot, Israel. Affiliated with the Hebrew University and Hadassah, Jerusalem, Israel.
Address reprint requests to: Alon Ben-Arie, MD Department of Obstetrics and Gynecology Kaplan Medical Center 76100 Rehovot Israel E-mail: alon5360{at}zahav.net.il
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Abstract |
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Methods: Ninety women admitted for terminations of pregnancy at 17–24 weeks’ gestation had transcervical catheters inserted and extraovular PGE2 administered. Success rates were recorded, measured by induction of abortion within 24 hours, need for a complement uterine curettage, and complications.
Results: The technique induced abortion in 67 women (74.4%). The induction-to-abortion median interval was 12 hours (7 and 22 hours, fifth and 95th percentiles, respectively). Thirty-seven women needed uterine curettages because of incomplete abortions or excessive uterine bleeding after fetal and placenta expulsion. One woman had shivering, weakness, and nausea attributed to systemic absorption of PG, and nine women developed systemic inflammatory response syndrome associated with transcervical catheter insertion. Two of those women had septic shock, one of whom deteriorated to a life-threatening situation.
Conclusion: Transcervical catheter insertion for extraovular PG administration is effective for inducing second-trimester abortions. Although the method is considered safe, with generally few mild, treatable complications, we observed a high rate of systemic inflammatory response syndrome, bacteremia, and sepsis caused by transcervical catheter insertion before PG administration. A reconsideration of this method’s safety is warranted.
Induction of second-trimester abortion by intravenous (IV) infusion of prostaglandins (PG) was introduced in 1970.1,2 Its high incidence of adverse effects was reduced by introducing PGE2 and PGF2
near the myometrium. Prostaglandins are administered intra-amniotically or transcervically into the extraovular space.3,4 The advantage of the extraovular route includes a low rate of major complications and possible immediate discontinuation of the drug when adverse effects appear, which cannot be done with the intra-amniotic method.3,5
Efficacy and safety of extraovular PGE2 was evaluated prospectively, after a case in which transcervical catheter insertion caused transient bacteremia and systemic inflammatory response syndrome. This complication includes a variety of clinical conditions that are essentially infectious, but also encompasses noninfectious entities such as burns and pancreatitis when fever and organ hypoperfusion might be present, as with sepsis. Patients with sepsis syndrome are a subset of patients with systemic inflammatory response syndrome, and the terms are interchangeable.6 Clinical diagnoses of systemic inflammatory response syndrome are made when patients have two or more signs of systemic inflammation in the settings of disorders that cause endothelial inflammation without other known causes. Criteria for systemic inflammatory response syndrome include temperature above 38C or below 36C, heart rate elevated above 90 beats per minute, tachypnea over 20 breaths per minute, hyperventilation indicated by arterial carbon dioxide pressure under 32 mmHg, or altered white blood cell (WBC) count of over 12,000 cells per milliliter or under 4000 cells per milliliter.7 In women with known infections, those signs also constitute evidence of sepsis.
Cytokines, produced by interaction between infecting agents and the host’s immune system, are responsible for clinical manifestations of systemic inflammatory response syndrome.6 We report this syndrome associated with extraovular pregnancy termination, heretofore unreported in the medical literature according to a MEDLINE search from 1966 to 1998 using the search terms "pregnancy," "midtrimester abortion," "extraovular," "prostaglandins," "sepsis," "bacteremia," and "complication."
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Patients and Methods |
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. Otherwise, women (90 cases) were scheduled for transcervical extraovular PGE2. After cleansing the vagina and cervix with povidine solution and prophylactic antibiotic (IV cefonicid 1 g), an extraovular Foley balloon catheter (16 F) was inserted. The balloon was inflated with 20 mL of fluid and normal saline was infused slowly through the catheter into the extraovular space at a rate of 20 mL/hour. During the next 2 hours, if there was no evidence of bleeding and the woman was well, PGE2 was given at 500 µg/hour at a concentration of 10 µg/mL. Vital signs and bleeding through the catheter were recorded every 30 minutes during the first 2 hours, then every hour until abortion was complete. The induction-to-abortion interval was recorded as time from catheter insertion to spontaneous placenta expulsion or to uterine curettage. Analgesia with meperidine or continuous epidural block was given according to women’s wishes. During the first 24 hours, women received no additional abortifacient agents.
Successful abortion was defined as fetal expulsion. If an abortion was not imminent after 24 hours, the catheter was withdrawn and an alternative procedure of intra-amniotic PGF2 injection or oxytocin augmentation was chosen by the attending physician. Abortion was complete if placenta and fetal membranes were delivered spontaneously within 1 hour of fetal expulsion. If they were not delivered or when excessive bleeding was noted, uterine curettage under general anesthesia was done. Complications of catheter insertion (bleeding, rigor, pyrexia, sepsis), PGE2 administration, and those after abortion (excessive uterine bleeding or febrile morbidity) were evaluated.
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Results |
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), within 2 hours of transcervical catheter insertion with saline infusion and before PGE2, women had severe rigor followed by pyrexia. They each had at least two inclusion criteria for systemic inflammatory response syndrome.
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and had an uneventful abortion. Her blood and amniotic fluid cultures were negative. Thirty-seven women (41.1%) had incomplete abortions that necessitated uterine curettage. In three women, postprocedure complications included febrile morbidity (at least two temperature measurements above 38C) suspected and treated as endometritis. Two women had excessive uterine bleeding, which necessitated blood transfusions, and one needed uterine curettage a week after abortion, because of bleeding from retained cotyledon in her uterus.
Ten Foley catheters taken directly from their sterile wrappings and ten tubes that contained normal saline infused through catheters were sent for culture because they were suspected of being the source of the infections. Results of those tests were negative.
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Discussion |
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Dilation and evacuation seems to be the best method. Its most important advantages are short duration of abortion on an ambulatory basis and very low complication rate.11,12 However, some physicians limit its use to 20 weeks’ gestation and genetic terminations, whenever it is important to secure a malformed fetus without injury. Shulman et al13 showed that prenatal diagnosis can be achieved reliably using dilation and evacuation.
In many medical centers around the world, PG instillation is very popular. Among the abortifacient compounds available, intra-amniotic or extraovular PGE2 or PGF2 are most commonly used.3,5,10,14,15 Studies that compared those two methods have not shown superiority of one over the other, with a uniform success rate of 80–95% for aborting within 24 hours of induction.3,5,14,16 A higher incidence of gastrointestinal side effects and other drug hypersensitivity reactions are associated with the intra-amniotic method,10,14 and a higher rate of infection, indicated by postprocedure pyrexia, is reported for the extraovular route.5,17 Lurie et al14 compared 81 cases of abortion induction by the extraovular PGE2 to 131 women treated by intra-amniotic PGF2 instillation. A complication rate of 9.8% was found in both groups, without significantly more infections, hemorrhages, or drug reactions in either group. Many studies on series of women treated with extraovular PG reported total complication rates of 10–15%, with no major complications.3,5,14,17 Major complications associated with second-trimester abortions, such as uterine rupture or sepsis, have been reported only as case reports.18–20
The present series shows the accepted efficacy of extraovular PGE2, including an acceptable success rate and a short median induction-to-abortion interval (12 hours), a factor associated with a low complication rate.15 Although the total complication rate (20%) was only slightly higher than others reported, we encountered a heretofore unreported cluster of potentially serious complications after transcervical balloon catheter insertion and before the start of PGE2.
Bacteremia was proved by positive blood culture in two women, confirming the infectious nature of the systemic inflammatory response syndrome in those cases and indicating that infection could be the main cause of symptoms in the other cases. Only one blood culture was positive, so those two cases met the criteria for transient bacteremia, which was probably caused by transcervical catheter insertion and saline infusion. Transient bacteremia on its own cannot be considered serious; however, cases in which sepsis developed without evidence of bactermia indicate its potential danger. In a multianalysis of studies that concerned sepsis in more than 1000 patients, fewer than half of them had proved bacteremia. There was no difference in their prognoses regardless of whether bacteremia was found.7
There are several possible explanations for why this complication has not been reported. It is possible that definition of systemic inflammatory response syndrome is exceedingly sensitive; therefore, we included mild cases that were omitted by others. Unfortunately, in our series septic shock developed in two cases, one of whom required hospitalization in the intensive care unit. Another possibility could be underreporting of complications associated with the procedure, but the most likely explanation is that we waited 2 hours from transcervical catheter insertion to PGE2 administration, which might not be common practice. The delay helped us differentiate between systemic inflammatory response syndrome caused by transient bacteremia associated with catheter insertion, and similar symptoms and signs (rigor, tachycardia, dyspnea) that are essentially adverse effects of PG.
Since the first case of systemic inflammatory response syndrome, the procedure was revised to emphasize thorough cleansing of the vagina and cervix with povidine solution and administration of prophylactic antibiotics. Also, a search for possible contamination in the equipment used found nothing. In light of our findings, a reconsideration of this method’s safety is warranted.
For over two decades, dilation and evacuation has been successful with minimal complications, and it should be the preferred method for the early half of second-trimester abortions. For those toward the end of the second trimester, and when it is important to secure a malformed fetus for genetic evaluation, the optimal safe, efficient method of abortion, with a short induction-to-abortion interval and minimal emotional burden on women, has yet to be found.
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Footnotes |
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Received November 30, 1999. Received in revised form April 21, 2000. Accepted May 18, 2000.
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References |
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. Lancet 1970;1:157–9.[Medline]2. Roth-Brandel U, Bygdeman M, Wiqvist N, Bergstrom S. Prostaglandins for induction of therapeutic abortion. Lancet 1970;1:190–1.
3. Lauersen NH, Wilson KH. Continuous extraovular administration of prostaglandin F2 for midtrimester abortion. Am J Obstet Gynecol 1974;120:273–80.[Medline]
4. Embrey MP, Hillier K. Therapeutic abortion by intrauterine instillation of prostaglandins. BMJ 1971;1:588–90.
5. Atad J, Lissak A, Sorokin Y, Bornstein J, Auslender R, Rofe A, et al. Continuous extraovular prostaglandin F2 instillation for second-trimester pregnancy termination. Isr J Med Sci 1985;21:935–9.[Medline]
6. Young LS. Sepsis syndrome. In: Mandell GL, Bennet JE, Dolin R, eds. Principles and practice of infectious diseases. New York: Churchill Livingstone, 1995:690–5.
7. Bone RC. Toward an epidemiology and natural history of SIRS (systemic infammatory response syndrome). JAMA 1992;268: 3452–5.[Abstract]
8. American College of Obstetricians and Gynecologists. Methods of midtrimester abortion. Washington, DC: American College of Obstetricians and Gynecologists, 1987:1–4.
9. Rayburn WF, Laferla JJ. Mid-gestational abortion for medical or genetic indications. Clin Obstet Gynecol 1986;13:71–82.
10. Castadot RG. Pregnancy termination: Techniques, risks, and complications and their management. Fertil Steril 1986;45:5–17.[Medline]
11. Grimes DA, Schulz KF, Cates W, Tyler CW. Midtrimester abortion by dilatation and evacuation: A safe and practical alternative. N Engl J Med 1977;296:1141–5.[Abstract]
12. Grimes DA, Hulka JF, McCutchen ME. Midtrimester abortion by dilatation and evacuation versus intra-amniotic instillation of prostaglandin F2 A randomized clinical trial. Am J Obstet Gynecol 1980;137:785–90.[Medline]
13. Shulman LP, Ling FW, Meyers CM, Shanklin DR, Simpson JL, Elias S. Dilatation and evacuation for second-trimester genetic pregnancy termination. Obstet Gynecol 1990;75:1037–40.
14. Lurie S, Katz Z, Vaclav I. Midtrimester induction of abortion: Comparison of extraovular prostaglandin E2 and intra-amniotic prostaglandin F2. Contraception 1993;47:475–81.[Medline]
15. Lipitz S, Grisaru D, Libshiz A, Rotstein Z, Schiff E, Lidor A, et al Intra-amniotic prostaglandin F2 for pregancy termination in the second and early third trimesters of pregnancy. J Reprod Med 1997;42:235–8.[Medline]
16. Hill NC, Selinger M, Fergusen J, MacKenzie IZ. Mid-trimester termination of pregnancy with 16,16-dimethyl-trans-delta-2-PGE1 vaginal pessaries: A comparison with intra- and extra-amniotic prostaglandin E2 administration. Int J Gynaecol Obstet 1991;35:337–40.[Medline]
17. Abramovici H, Bornstein J, Ben David Y, Yishai D, Rofe A, Atad J. Double-balloon instillation device for second-trimester abortion. Outcome in 340 consecutive cases. J Reprod Med 1995;40:56–62.[Medline]
18. Ishikawa Y, Uneki K, Fukui H, Futakawa K, Ogawa T. A technique for the induction of labor by the extraovular administration of prostaglandin F2. Int J Gynaecol Obstet 1976;14:439–44.[Medline]
19. Jasnosz KM, Shakir AM, Perper JA. Fatal Clostridium perfringens and Escherichia coli sepsis following urea-instillation abortion. Am J Forensic Med Pathol 1993;4:151–4.
20. Lurie S, Hagay Z, Borenstein R. Extraovular PGE2 and oxytocinimplicated uterine rupture during midtrimester termination of pregnancy. Adv Contracep 1993;9:331–3.
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