Misoprostol is widely used in daily practice for induction of labor and cervical dilatation prior to intrauterine procedures, including dilatation and curettage or hysteroscopy. Anaphylactic shock to intravaginal misoprostol can occur not only in pregnant women, as reported in 2 previous cases, but also in a non-pregnant, perimenopausal woman, as in the case described herein. A 49-year-old woman received vaginal misoprostol for cervical ripening prior to hysteroscopic myomectomy and experienced anaphylactic shock. Two 400 μg doses of misoprostol 6 hours apart caused uncontrolled shaking and high fever followed by shock. In conclusion, the possibility of anaphylactic shock should be considered in patients with sudden hypotension following misoprostol administration. Prompt identification and management are crucial to prevent morbidity and mortality following an anaphylactic shock to misoprostol.
Misoprostol, a prostaglandin E1 analog, is commonly used in obstetrics/gynecology clinics for various purposes, including induction of labor and dilatation of the cervix prior to intrauterine procedures, including dilatation and curettage or hysteroscopy [
A para 2, 49-year-old woman presented with menorrhagia. Transvaginal sonography revealed 2 submucosal myomas of 3 cm each. A hysteroscopic myomectomy was planned after the administration of 3 doses of monthly gonadotrophin-releasing hormone agonists to decrease the size of the myomas. The patient's body mass index was 22.2 kg/m2. She was taking antihypertensive drugs and denied any known drug or nondrug allergies. She had undergone an aneurysm clipping for subarachnoid hemorrhage 18 months ago and laparoscopic cholecystectomy for acute cholecystitis 16 months ago in our hospital. On admission, her vital signs were normal, including a blood pressure of 142/80 mmHg, a pulse rate of 80 beats per minute, and a body temperature of 36.9°C. Misoprostol (Cytotec®, G.D. Searle LLC, Skokie, IL, USA) 400 μg was administered vaginally at 12:00 AM and 6:00 AM for cervical ripening prior to hysteroscopic myomectomy. Approximately 5 minutes after the second dose of vaginal misoprostol, the patient experienced uncontrolled shaking for 20 minutes; however, she did not complain of this because she thought it was just a common adverse effect of misoprostol. We routinely explain the possible adverse effects of misoprostol, including abdominal pain, vaginal bleeding, diarrhea, fever, and shivering to patients before administration of misoprostol. At 8:00 AM, the patient's body temperature was 39.0°C, and accompanying mild shivering was noted. Hydration with 300 mL of normal saline and 1 g of propacetamol hydrochloride (Denogan®, Yungjin Pharm. Co, Ltd., Seoul, Korea) was provided intravenously to control fever. At 9:30 AM, her body temperature decreased to 37.8°C, and whole-body plethora was noted. At 9:30 AM, her blood pressure decreased abruptly to 65/40 mmHg and pulse rate increased to 125 beats per minute immediately after the induction of general endotracheal anesthesia before the start of the hysteroscopic operation. Arterial cord blood gas analysis showed a pH of 7.27 and a base deficit of −1.6 mmol/L. Oxygen saturation (SaO2) was 98.9% (under mask O2 volume, 2 L), and the patient had a prolonged expiratory phase and a respiratory rate of 16 cycles/min, accompanied by generalized erythema, tachycardia, and hypotension. A physical examination revealed facial flushing, generalized edema, and a normal lung without evidence of oropharyngeal edema (
Clinical features of generalized edema caused by anaphylactic shock to intravaginal misoprostol. (A) Facial and neck edema. (B) Hand edema at 20 hours after the onset of anaphylactic shock.
Chest X-ray and chest computed tomography findings. (A) Chest X-ray showing interstitial pulmonary edema without cardiomegaly or pleural effusion. (B) An axial, contrast-enhanced computed tomography scan showing alveolar and interstitial pulmonary edema without evidence of pulmonary embolism.
The Institutional Review Board of Ewha Womans University waived the approval for this case report and we obtained the patient's informed consent for its publication.
Among immunological reactions, the immediate type refers to a type 1 anaphylactic reaction, which is due to biologically active materials that are released from mast cells sensitized by specific immunoglobulin E antibodies. An allergic reaction occurs in the skin (urticaria/angioedema), respiratory and gastrointestinal tracts, or cardiovascular system, shortly after exposure to an allergen. The characteristic symptoms are shortness of breath, bronchospasms, soft-tissue swelling, edema, hypotension, itching, redness of the skin, wheezing, nausea, vomiting, diarrhea, cramps, and, in some cases, shock [
According to studies about pharmacological mechanisms of misoprostol, it is generally known that misoprostol suppresses immune reactions that occur during the late phase of cutaneous allergic reactions and has a protective effect against allergic disease. However, contrary to previous studies, Babakhin et al. [
Madaan et al. [
In the case of the subject of this case report, an allergic skin test for misoprostol could not be performed due to the patient's refusal. However, symptoms such as severe shivering immediately after misoprostol insertion, as well as generalized erythema, facial flushing, generalized edema, and hypotension that occurred later, correspond to an immediate-type immunologic reaction.
Other drugs that were administered to the patient included anesthetic drugs and denogan (paracetamol). The patient had received local and systemic anesthetic drugs several years before but had not experienced an allergic reaction. Paracetamol is a non-opioid analgesic and a non-steroidal anti-inflammatory drug that is used worldwide for analgesic and fever reduction purposes, and it is also known to cause hypotension as an allergic reaction. However, since most of these allergic reactions are associated with chronic use and overdose and acute side effects of this IV formulation have not been evaluated in many studies, the basis for such an association is weak [
We report the first case of anaphylactic shock to vaginal misoprostol in a non-pregnant woman. The possibility of anaphylactic shock should be considered in patients with sudden hypotension following misoprostol administration and prompt identification and management are crucial to prevent morbidity and mortality following anaphylactic shock to misoprostol.
Theoretically, we assume that a single dose of misoprostol could be safer than multiple doses for preventing sensitization to misoprostol. The risk of sensitization and the resulting anaphylactic shock to misoprostol can decrease with the use of a mechanical cervical dilator, such as laminaria, after the initial dose of misoprostol instead of a repeat dose for cervical dilation and ripening. Prompt identification along with determination of urinary and serum histamine levels and plasma tryptase levels as well as prompt management including the use of epinephrine and intravenous fluids are crucial to prevent morbidity and mortality following an anaphylactic shock to misoprostol. Adjunctive measures include airway protection and the use of antihistamines, steroids, and beta agonists. Patients taking beta-blockers may require additional measures [
We should keep in mind that even a frequently used drug can cause anaphylactic shock, which is a rare, life-threatening, emergent situation. Therefore, obstetricians and gynecologists should be well acquainted with the possibility of anaphylactic shock to misoprostol.
This work was supported by a research grant from the National Research Foundation of Korea (NRF-2015R1C1A1A02038010).