Case Reports Maternal Death Related to Misoprostol Overdose Alexandra Henriques, MD, Alexandre V. Lourenc ¸o, MD, Ana Ribeirinho, MD, Helena Ferreira, MD, and Luís M. Grac ¸a, MD, PhD BACKGROUND: Misoprostol is an important drug in ob- stetrics and gynecology because of its uterotonic and cer- vical-ripening activities. The side effects are dose-related, usually transitory, and well tolerated. The toxic dosage in humans is unknown, and there is no specific antidote. CASE: An adolescent developed upper gastrointestinal bleeding after self-medication with misoprostol orally (12 mg) to cause abortion. She presented with multiorgan failure, acute abdominal signs, and hemodynamic insta- bility. Emergency laparotomy showed gastric and esoph- ageal necrosis. After several episodes of cardiac arrest, and despite resuscitation efforts, the patient died. CONCLUSION: Temporal relationship (48 hours after the beginning of medication) strongly suggests that mi- soprostol was the agent directly involved in the maternal death. The mechanism implicating misoprostol in gastro- intestinal ischemia and necrosis is unknown. (Obstet Gynecol 2007;109:489–90) M isoprostol is a prostaglandin E 1 analogue ap- proved by the Food and Drug Administration to be taken orally for the prevention and treatment of gastric ulcers associated with nonsteroidal anti-inflam- matory drugs. 1 Recommended dosage in the adult is 200 mcg, orally, four times per day. The drug is important in obstetrics and gynecology because of its uterotonic and cervical-ripening actions. The side effects are dose- related, normally transitory, and well tolerated. The maximal ingested dose reported in the liter- ature was 6 mg, 2 taken with trifluoperazine by a woman 31 weeks pregnant. Manifestations of toxicity included hypertonic uterine contractions with fetal distress and death, hyperthermia, rhabdomyolysis, hypoxemia, respiratory alkalosis, and metabolic aci- dosis. The toxic dosage in humans is unknown and there is no specific antidote. We describe a case of fatal intoxication with misoprostol. CASE An adolescent nullipara with indeterminate gestational age, was admitted in the Department of Intensive Care Medicine of our hospital with complications of misoprostol overdose. The teenager self-medicated for 2 days with misoprostol 800 mcg, oral every 2 hours, with nocturnal interval (she took a total of 60 tablets or 12 mg) with abortive intention. Besides vaginal bleeding she developed severe upper gas- trointestinal bleeding and had cardiac arrest just after hospital admission. The laboratory analysis showed acute renal failure (urea 159 mg/dL, creatinine 4.1 mg/dL), rhabdomyolysis (creatine kinase 12,905 units/L) and consumption coagulopathy (ac- tivated partial thromboplastin time 51.2/27.5 seconds, pro- thrombin time 22/11 seconds, platelet count dropping from 431 to 104  10 9 /L and also excluded poisoning or other type of drug abuse. She presented severe hemodynamic instability and acute abdominal signs (board-like abdominal rigidity and absence of bowel sounds), without evidence of active upper gastrointestinal bleeding. Pelvic examination showed an opened cervix with fetid bloody uterine discharge. Ultrasound scan revealed scant conception products in the uterus and a large quantity of free fluid in the pelvic cavity. The patient had multiorgan failure: renal failure, heart failure due to diastolic dysfunction, respiratory failure (pa- tient needed mechanical ventilation), and hepatic failure (alanine transaminase 266 units/L, aspartate transaminase 469 units/L). Hemoglobin levels were quickly dropping from 15.4 to 9.8 g/dL. Hemodynamic instability was refractory to resus- citation measures. With the possible diagnosis of internal bleeding from an ectopic pregnancy or uterine rupture, emergency laparotomy was performed. An intact pregnant uterus was found; there was no evidence of ectopic preg- nancy. The peritoneal cavity was filled with abundant serohematic, purulent, fetid fluid. An extensive necrosis of From the Department of Obstetrics, Gynecology and Reproductive Medicine, Santa Maria University Hospital, Lisbon, Portugal. Presented as a poster at the 20th European Congress of Perinatal Medicine, Prague, Czech Republic, May 24 –27, 2006. Corresponding author: Alexandra Henriques, MD, Departamento de Obstetrí- cia, Ginecologia e Medicina da Reproduçáo Hospital Universitário de Santa Maria, Av. Prof. Egas Moniz, 1649-035 Lisboa, Portugal; e-mail: alexandra.henriques@gmail.com. © 2007 by The American College of Obstetricians and Gynecologists. Published by Lippincott Williams & Wilkins. ISSN: 0029-7844/07 VOL. 109, NO. 2, PART 2, FEBRUARY 2007 OBSTETRICS & GYNECOLOGY 489