Reactions to Misoprostol: A Case Report

Abstract

Background:

Most of abortions occur before the 13th week of pregnancy. Nowadays, non-surgical approaches for evacuation of uterine have been replaced with surgical ones due to the reduction in bleeding, fewer complications, ease of management, and cost-effectiveness. Misoprostol is a prostaglandin E1 analog that is used for labor induction. It is known as a safe drug with very few side effects.

Case Presentation:

A 29-year-old woman with the gestational age of 11 weeks and 6 days with a diagnosis of cystic hygroma introduced herself to the labor ward. At the time of hospitalization, the patient was conscious. The heart sounds were normal. A vaginal exam indicated no pathological findings. Totally, she received 1000 mg of Misoprostol. Approximately, 2 hours after the last placement of Misoprostol, the patient developed bending and mild cyanosis of fingers and showed tachycardia with a pulse rate of 140 beats/min. Her O₂ saturation decreased to 78%. At this time, the patient had a successful miscarriage. Echocardiography showed an ejection fraction of 55% and normal right ventricular size. The electrocardiogram showed sinus tachycardia. Therefore, she was sent to CCU with a possible diagnosis of embolism. The cardiologist administered a heparin drip of 5000-unit IV stat, and 1000 unit/h heparin and asked for a D-Dimer test. However, the laboratory reported that the patient’s blood sample was hemolyzed and they could only check her hemoglobin which was 4 g/dl. Immediately, the heparin drip was held and the patient received 3 packed cells. Her Hb was 6.5 g/dl. 12 hours later she showed tachycardia, and her O₂ saturation reduced to 70%. She lost her consciousness. Nearly 40 minutes later, she had cardiorespiratory arrest and CPR wasn’t successful and she died.

Conclusions:

In Conclusion, even a frequently used drug such as Misoprostol can cause life-threatening side effects, leading to emergent situations.

Background

Statistics suggest that abortion happens in between 12% and 14% of pregnancies and the vast majority (80%) of them occur before the 13th week of pregnancy. ¹ Evacuation of the uterine cavity is the main purpose of abortion. To achieve this aim, traditional surgical evacuation had been done in the past, however, nowadays, non-surgical approaches such as medical treatments with prostaglandin analogs for evacuation of uterine have been replaced with surgical ones due to the reduction in bleeding, fewer complications, ease of management, and cost-effectiveness. ² Misoprostol is a prostaglandin E1 (PGE1) analog that is mostly used for the prevention and treatment of peptic ulcers. ³ Furthermore, the use of Misoprostol for labor induction is also approved in many countries because of its affordability, molecular stability, ease of administration, and clinical efficacy.^{4 -6} It acts through its effect on the cervix as a ripening and uterotonic agent. ⁷ Misoprostol is known as a safe drug with very few side effects. Its common side effects include diarrhea, abdominal pain, headache, menstrual cramps, nausea, chills, shivering and fever. ⁸ This drug can be administered by oral, buccal, sublingual, or vaginal routes. ³ To the best of our knowledge, there is no report about cardiac reactions to Misoprostol which leads to death. In this case report, we present a case of a 29-year-old pregnant woman who showed cardiovascular complications and passed away after receiving Misoprostol for abortion.

Case Presentation

A 29-year-old G2P1L1 (previous NVD) woman with a gestational age of 11 weeks and 6 days and one prior childbirth (2 years prior to the current pregnancy) with the diagnosis of cystic hygroma introduced herself to the labor ward at 10 p.m. on May 19th, 2021 for legal abortion. She had no remarkable medical history except hypothyroidism. Apart from consuming levothyroxine 50 mcg (every day other than Fridays) for hypothyroidism, she reported no current medications.

Physical examination revealed a blood pressure of 120/80 mmHg, heart rate of 80 beats/min, respiratory rate of 18 breaths/min, temperature of 37°C, and oxygen saturation of 98% in room air. At the time of hospitalization, the patient was conscious and had no dyspnea. The heart sounds were normal with a regular rhythm, and no murmur was found. In lung auscultation, no remarkable finding was detected. Vaginal exam indicated no pathological findings. Uterus fundal height was 12 weeks. No vaginal bleeding was seen and the cervix (CX) was firm. Transvaginal ultrasound showed that the nuchal translucency (NT) was 8 mm which is more than normal size.

Cystic hygroma measuring 8 mm × 20 mm was observed in the neck area. Diffuse generalized edema was seen in the fetus, which favored generalized hydrops fetalis. The pregnancy had a poor prognosis and the length of the cervix was 31 mm.

The laboratory examination results before any interventions were as follows: the CBC (WBC: 12.9, RBC: 4.55, Hb: 13.2 g/dl, HCT: 38.7%, Platelet: 387, Neutrophil: 74, Lymphocyte: 22, Monocyte: 2, Eosinophil: 2, MCHC: 34 g/dl, MCV: 85, PT: 12.5 seconds, INR: 1, PTT: 35 seconds, MCH: 29 pg, ESR: first hour: 22 mm/h, Urea: 17 mg/dl, Cr: 0.6 mg/dl).

The Obstetrician presumed a diagnosis of cystic hygroma and treated her with misoprostol 200 mg vaginally in the admission day at 8:30 p.m. Three hours later, at 11:30 p.m. our patient received 400 more milligrams of misoprostol (200 mg sublingual, 200 mg vaginal). In the next day, at 7:45 a.m. another 400 mg of misoprostol (200 mg sublingual, 200 mg vaginal) were prescribed for her.

After 1 hour and 45 minutes of the last intravaginal placement of misoprostol, the patient developed bending and a mild Cyanosis of fingers. We asked for checking her Ca, P. The laboratory results were as below: Ca: 10 mg/dl, P: 4.5 mg/dl. Additionally, she showed tachycardia with pulse rate of 140 beats/min. Her O₂ saturation decreased to 78% for a minute and then, after receiving O₂ nasal, it increased to 98%. But, due to detection of tachycardia, cardiac consultation was requested for the patient.

These symptoms began after the last intravaginal administration of misoprostol. At this time, the patient had a miscarriage because of which she lost the fetus and placenta and she had no heavy bleeding or abnormal bleeding.

After that, the patient had been referred to a cardiologist for cardiac monitoring by performing D-dimer test, echocardiography, and electrocardiogram (ECG). Echocardiography showed ejection fraction (EF): 55%, normal right ventricular (RV) size which showed that patient was not at risk of any clots or massive pulmonary embolism (PE). The electrocardiogram (ECG) showed sinus tachycardia (Figure 1). Therefore, the patient was hospitalized with a possible diagnosis of embolism in the cardiac care unit (CCU). The cardiologist administered heparin drip 5000-unit IV stat, and 1000 unit/h heparin and asked for CT- angiography and D-Dimer test (Pt, Ptt, and INR). But the laboratory reported that patient’s blood sample was hemolyzed and they could not analyze it. They only checked her hemoglobin which was 4 g/dl and the CT angiography did not perform because of her Hemodynamic instability. Consequently, the heparin drip was hold and the patient received 3 packed red blood cells.

Figure 1.

Sinus tachycardia a day after receiving Misoprostol.

After blood transfusion, she appeared a little bit icteric and pale, she had no petechiae and purpura, or ecchymosis. At this time, she was transferred to intensive care unit (ICU). Her physician requested color doppler and transvaginal ultrasound for diagnosis of deep vein thrombosis (DVT) and rule out the possibility of uterine remains, uterus rupture, and intra-abdominal free fluid after complete abortion, respectively. Ultrasounds showed no acute DVT or any other anomalies. Transvaginal ultrasound showed no blood in abdominal cavity and the uterus was normal without any rupture. Once more, complete blood count tests were prescribed for her. The results were as follows: WBC: 8.88, Hb: 6.5 g/dl, MCV: 88 fL, PLT: 241000, PT: 19.6 seconds, PTT: 35 seconds, INR: 2.2. Approximately, 12 hours later she went through an episode of tachycardia, and her O₂ saturation reduced to 70%. During all this period, our patient had normal bleeding after her abortion (equal to the amount seen during menstruation). Suddenly, she lost her consciousness. Cardiopulmonary resuscitation (CPR) was performed for the first time at 8:35 a.m. which was successful. Nearly 40 minutes later, she had cardiorespiratory arrest and CPR was conducted for the second time. Unfortunately, she could not survive and she died.

In the autopsy report, it was found that there was no free fluid inside the abdomen, and there were no signs of scars or rupture throughout the uterus. Furthermore, no amniotic fluid cells (Squamous cells) were observed inside the lung parenchymal tissue of our patient.

Discussion and Conclusions

Abortion is known to be one of the most common complications of pregnancy. Missed abortion, which occurs in 15%–20% of clinically diagnosed pregnancies, is the retention of pregnancy products in the uterus for several days or weeks after death of the fetus. ⁹ Various medical and surgical methods have been used to manage missed abortions, among which the doctors generally prefer medical methods over surgical ones for abortion. Medical approaches include prostaglandins, both alone and in combination with other drugs. ¹⁰ Although a number of prostaglandins can be used, prostaglandin E1 (misoprostol) is widely preferred for induction of delivery.^11,12 The most common adverse effects of misoprostol are gastrointestinal, whereas cardiovascular effects rarely occur. ² Most of previous studies found no adverse cardiovascular effects following the use of misoprostol.^{13 -16} However, some studies reported cardiovascular effects related to misoprostol. The French Regional Pharmacovigilance Centre ¹⁷ reported 63 cases of cardiovascular effects related to misoprostol, seven of them being angina, and they have identified some cardiovascular risk factors related to these adverse effects, such as age > 35 years, smoking or high doses of vaginal misoprostol.

We have thoroughly searched the PubMed/Medline using the terms “misoprostol” AND “allergic reactions”/ “Cardiovascular side effects”/ “amniotic fluid embolism”/ “coagulation disorder,” however, we did not find any similar articles which shows any amniotic fluid emboli, cardiac arrest, or coagulation disorder after using misoprostol. Based on the results of autopsy, the definite cause of death of our patient is not completely clear.

Based on the forensic report, it seems that the cause of our patient’s death is multiple organ failure following fulminant disseminated intravascular coagulation (DIC) following micro-embolism or due to drug complications (after administration of Misoprostol).

Our patient survived for about 24 hours after taking misoprostol. Since embolism leads to death in a much shorter period of time, we assume that the cause of our patient’s death was DIC following the reaction caused by taking misoprostol.

In conclusion, we should keep in mind that even a frequently used drug can cause irreparable, life-threatening side effects which can lead to emergent situations. Therefore, obstetricians and gynecologists should be well acquainted with the possibility of coagulations disorder to misoprostol.