sulprostone and Uterine-Hemorrhage

This article outlines the current modalities of pregnancy termination, as well as their risks and complications, in 3 phases of pregnancy: 1) up to 49 days past the last menstrual period, 2) 8-15 weeks, and 3) 16-24 weeks. Before 8 weeks of pregnancy, suction dilatation and curettage (D and C) is the preferred method. However, a medical approach, possibly self-administered, is viewed as more satisfactory and requires only an improvement in side effects. From 8-15 weeks' gestation, suction D and C and dilatation and evacuation (D and E) are the methods of choice. The use of laminaria tents improves both the facility and safety of these procedures in nulliparous patients and perhaps in multiparous patients. Priming of the cervix with prostaglandin could further decrease the difficulty and risks of these procedures. The use of a hydrogel compound is especially worthy of consideration. There is controversy about the preferred method between 16-20 weeks' gestation. D and E appears to have fewer complications and to be more cost-effective than hypertonic saline injection. Urea-prostaglandin has fewer and less severe complications than saline injection, and seems to be more cost-effective than saline injection in terms of duration of hospitalization. The high frequency of failure and side effects, combined with the possibility of expulsion of a live fetus, make prostaglandin-only injection less desirable. After 20 weeks' gestation, urea-prostaglandin injection is probably the safer method. Given the rapid increase in complications with passing weeks, any delay in providing late abortion services should be avoided. 2nd trimester pregnancy terminations, especially those after 18 weeks' gestation, are associated with increased mortality and morbidity and should be performed at specialized centers where providers are better equipped to manage complications.

Topics: 16,16-Dimethylprostaglandin E2; Abortifacient Agents; Abortion, Induced; Alprostadil; Amnion; Anesthesia; Animals; Arbaprostil; Bacterial Infections; Carboprost; Cervix Uteri; Dilatation and Curettage; Dinoprost; Dinoprostone; Female; Humans; Hypertonic Solutions; Oxytocin; Pregnancy; Pregnancy Trimester, First; Pregnancy Trimester, Second; Progestins; Prostaglandins E; Prostaglandins E, Synthetic; Prostaglandins F; Pulmonary Embolism; Risk; Saline Solution, Hypertonic; Time Factors; Urea; Uterine Hemorrhage; Uterine Perforation

RU486 (mifepristone) followed by a prostaglandin (PG) analogue has been marketed in France since April 1990 as a medical alternative to surgery for early pregnancy termination. By law, the drug is used only in the centres approved for voluntary pregnancy termination, and its distribution is strictly controlled. Before being marketed, it was distributed to more than 20,000 women, as part of a training programme for the prescribers. Analysis confirmed an efficacy rate of 95.3%. Failures included incomplete ovular expulsion (2.8%), premature vacuum aspiration (0.7%) and ongoing pregnancy (1.2%). Pelvic pain and malaise were reported as side-effects in 1.6 and 1.2% of the cases respectively. Infectious complications were reported in 0.2% of the cases. Three severe adverse events (one of which was fatal) occurred, including myocardial infarction and ventricular arhythmia, in the hours following PG administration and justify a careful medical monitoring in the centre 3-4 h after administration of PG. For this reason, a trial was undertaken to evaluate the efficacy of an oral form of a PGE1 analogue (misoprostol). When RU486 was followed 36-48 h later by 400 micrograms of misoprostol, the efficacy rate was 96.9%, indicating an efficacy equivalent to that obtained with the other PG analogues. The distribution procedures were adequately followed by the prescribers and by the patients. In summary, RU486 constitutes a safe and efficient medical means of pregnancy termination, provided that the manufacturer's recommendations are properly followed.

Topics: Abdominal Pain; Abortion, Induced; Adult; Alprostadil; Contraindications; Dinoprostone; Female; France; Humans; Hypotension; Mifepristone; Misoprostol; Myocardial Infarction; Pilot Projects; Pregnancy; Uterine Hemorrhage

In a randomized, double-blind study, 30 healthy, nulliparous women of similar gestational age were given intracervical applications of 0.5mg PGE2, 0.05mg Sulprostone or 0.1mg Sulprostone gel in order to soften the cervix prior to curettage for first trimester termination of pregnancy. The preparations were administered 8 hours before curettage. The number of complete and incomplete abortions, ease of passage through the cervical canal, as measured by a tonometer before and 8 hours after the administration of prostaglandin, the degree of pain experienced and the quantity of analgesics required, plus the frequency of systemic side effects were all always assessed by one trialist. With regard to the rate of abortion and cervical softening, the administration of 0.1mg Sulprostone gel proved the most effective method. However, in comparison with the others, it also caused the greatest degree of pain and necessitated the greatest use of analgesics. The softening effect of the prostaglandin E2 gel was significantly less and in this group there were two cases of cervical lesion due to tenaculum laceration. The intracervical application of 0.05mg Sulprostone gel is to be recommended for pre-operative ripening of the cervix before termination of pregnancy in the first trimester, as it effectively dilates the cervix and does not cause systemic side effects or pain in the lower abdomen, enough to make treatment necessary.. In a randomized, double-blind study, 30 healthy, nulliparous women of similar gestational age were given intracervical applications of 0.5 mg prostaglandin E2 (PGE2), 0.05 mg Suplrostone, or 0.1 mg Sulprostone gel in order to soften the cervix prior to curettage for 1st trimester termination of pregnancy. Preparations were administered 8 hours before curettage. The number of complete and incomplete abortions, ease of passage through the cervical canal, as measured by a tonometer before and 8 hours after the administration of PG, the degree of pain experienced, and the quantity of analgesics required, plus the frequency of systemic side effects were all assessed by 1 trialist. With regard to the rate of abortion and cervical softening, the administration of 0.1 mg Sulprostone gel proved the most effective method. However, in comparison with the others, it also caused the greatest degree of pain and necessitated the greatest use of analgesics. The softening effect of the PGE2 gel was significantly less and in this group, there were 2 cases of cervical lesion due to tenaculum laceration. The intracervical application of 0.05 mg Sulprostone gel is to be recommended for preoperative ripening of the cervix before termination of pregnancy in the 1st trimester, as it effectively dilates the cervix and does not cause systemic side effects or pain in the lower abdomen, enough to make treatment necessary.

Topics: Abdomen; Abortion, Induced; Cervix Uteri; Clinical Trials as Topic; Dilatation and Curettage; Dinoprostone; Double-Blind Method; Female; Gels; Humans; Muscle Cramp; Pain, Postoperative; Pregnancy; Pregnancy Trimester, First; Prostaglandins E; Prostaglandins E, Synthetic; Uterine Hemorrhage

Major obstetric hemorrhage is a challenge for anesthesiologists because it remains responsible for over 10% of maternal deaths in high-income countries. A standardized multidisciplinary management, described in locally validated protocols and based on international guidelines is mandatory to prevent these deaths. The first difficulty relies on the systematic underestimation of the bleeding. Collection bags must be used to facilitate the diagnosis and therefore rapid management. The etiologies in antenatal or postpartum must be well-known in order to be treated adequately. A rapid recourse to prostaglandins (sulprostone in France) may reverse uterine atony. Invasive approach with surgery or radiology should be promptly implemented (uterine artery or internal iliac artery ligations±uterus plication) and hysterectomy should then be timely considered. Simultaneously, early and aggressive resuscitation with large-bore venous accesses should be implemented for rapid and massive transfusion (4:4:1 RBC:FFP:platelets ratio), along with an early use of fibrinogen concentrates and tranexamic acid. This transfusion strategy may be then guided by thromboelastography or thromboelastometry and bedside hemoglobin measurements. Activated factor VII remains indicated only before or after hysterectomy in case of uncontrolled bleeding. Management of placentation abnormalities (placenta previa, accreta, increta, percreta) must be well mastered as these etiologies may generate cataclysmic hemorrhages that can be and have to be anticipated.

Topics: Blood Component Transfusion; Combined Modality Therapy; Dinoprostone; Factor VIIa; Female; Fibrinogen; Humans; Hysterectomy; Iliac Artery; Ligation; Maternal Mortality; Operative Blood Salvage; Placenta Accreta; Placenta Previa; Postpartum Hemorrhage; Pregnancy; Pregnancy Complications; Recombinant Proteins; Tranexamic Acid; Uterine Artery; Uterine Artery Embolization; Uterine Hemorrhage; Uterine Inertia

We report the case of a 31-year-old woman who delivered twins by Caesarean section in whom atonic uterine haemorrhage developed 6 h postoperatively. During conservative treatment with the high-dose prostaglandin analogs sulprostone (PGE(2)) and dinoprost (PGF(2alpha)), acute pulmonary oedema and cardiac decompensation developed and, subsequently, the patient suffered cardiopulmonary arrest. After a 2h-period of cardiopulmonary resuscitation (CPR), it was possible to restore and stabilize circulation under the highest dose of catecholamines. Despite 2h of CPR, the patient was discharged from hospital 3 months later without any major physical or neurocognitive deficit.

Topics: Adult; Cardiopulmonary Resuscitation; Cesarean Section; Dinoprost; Dinoprostone; Female; Heart Arrest; Heart Failure; Heart Massage; Humans; Oxytocics; Postoperative Hemorrhage; Pregnancy; Pulmonary Edema; Uterine Contraction; Uterine Hemorrhage

In 2115 women seeking voluntary termination of pregnancy after 49 days of amenorrhea or less, we studied the effect of a single 600-mg dose of mifepristone (RU 486), followed 36 to 48 hours later by the administration of one of two prostaglandin analogues, either gemeprost (1 mg by vaginal suppository) or sulprostone (0.25, 0.375, or 0.5 mg by intramuscular injection). The women were monitored for four hours after prostaglandin administration. Efficacy was indicated by the complete expulsion of the conceptus without the need of an additional procedure. All other results were considered failures, and the pregnancy was then terminated by a surgical method. The overall efficacy rate was 96.0 percent (95 percent confidence interval, 95.0 to 96.8). The failures included persisting pregnancies (1.0 percent), incomplete expulsions (2.1 percent), and the need for hemostatic procedure (0.9 percent). The mean time to expulsion was significantly shorter when sulprostone was given in the high dose (4.5 hours) than when it was given in the two lower doses (13.1 and 19.3 hours) or when gemeprost was given (22.7 hours). The mean duration of uterine bleeding was 8.9 days (range, 1 to 35); one woman received a blood transfusion. Most women had transient abdominal pain after receiving prostaglandin, but there were few other side effects. We conclude that the administration of mifepristone followed by a small dose of a prostaglandin analogue is an effective and safe method for the early termination of pregnancy.

Topics: Abortifacient Agents; Abortifacient Agents, Nonsteroidal; Abortion, Induced; Alprostadil; Dinoprostone; Drug Evaluation; Female; Humans; Mifepristone; Pregnancy; Retrospective Studies; Time Factors; Uterine Hemorrhage

Sulprostone (Nalador-Schering) was used on 25 cases of bleeding caused by post-partum atonia that did not respond to conventional uterotonic treatment. The good results obtained led to the use of the drug whenever it was necessary to prevent haemorrhage independent of the risk factors that might cause its onset.

Topics: Dinoprostone; Drug Evaluation; Female; Humans; Pregnancy; Puerperal Disorders; Uterine Hemorrhage; Uterine Inertia

Sulprostone in a new prostaglandin E2 (PGE2) derivative (16-phenoxy methylsulfonyl-amide PGE2) can be used for pregnancy termination and can also be used to avoid hysterectomy in cases of heavy bleeding due to uterine atony. This study examines the effects of intravenous sulprostone on uterine blood flow by studying the color of the uterus during hysterotomy in the 2nd trimester. 12 multiparous patients in the 2nd trimester of pregnancy (age 36 +or- 2 years old, gravida 5 +or- 0.6, para 3 +or- 0.4) underwent hysterotomy and tubal ligation. A color photograph of the uterus was taken and a sulprostone drip (5 mcg/minute in isotonic saline) was started in 9 patients, the other 3 serving as controls. During the tubal ligation surgery, more pictures were taken at 3, 5, 10, 15, and 20 minutes. A fixed microballoon method recorded intrauterine pressure while a Gretag D 23 densitometry analyzed color intensity at 5 points of the photographs. The average of 5 readings was used for further analyses. A significant change in the blue color was observed (p 0.05). 3 independent outsiders who had no knowledge of the times the pictures were taken were able to distinguish the pictures which had been taken after 15-20 minutes of sulprostone exposure. Uterine contractile response to sulprostone was close to the maximum after 15-20 minutes of infusion. A slight increase of cyclic uterine activity was observed, as was a very pronounced increase in resting pressure. This study shows that intravenous sulprostone infusion resulted in a uterine contracture response and a change in the color of the uterine surface. It justifies the use of sulprostone for severe postpartum hemorrhage.

Topics: Abortion, Legal; Adult; Dinoprostone; Female; Humans; Hysterectomy; Pregnancy; Pregnancy Trimester, Second; Prostaglandins E, Synthetic; Regional Blood Flow; Uterine Hemorrhage; Uterus