risks before conception so they can seek treatment early and advocate for evaluation if they experience worrisome symptoms. Because 41% of patients with internal hernias presented with abdominal pain, it is important for patients to be encouraged to seek immediate evaluation when they experience symptoms.8 A multidisciplinary approach using Maternal Fetal Medicine, Bariatric Surgery, and Intensive Care teams should be utilized for evaluation and treatment. Radiologic evaluation with computed tomography scan should be reviewed by bariatric surgeons or radiologists with specialized expertise in this area.8 The decision of whether to evacuate the uterus and how to accomplish this should be based on the clinical condition of the patient. The benefits of uterine evacuation to facilitate autotransfusion in cases of shock must be weighed against the potential to prolong the pregnancy and the ability to perform intrauterine resuscitation. In cases of hemodynamic instability with an unripened cervix, the hysterotomy at the time of exploratory laparotomy allowed for the most expeditious way to accomplish uterine evacuation. Patients with this surgical history and presenting for evaluation of abdominal pain should undergo a multidisciplinary approach including bariatric surgical consultation with appropriate imaging early in the evaluation process.


Anaphylaxis to Buccal Misoprostol for Labor Induction

anesthetic agents are more common triggers for anaphylaxis, induction agents are also a rare cause.

Corina Schoen, MD, Sara Campbell, MD, Amber Maratas, MD, and Cheung Kim, MD BACKGROUND: Misoprostol is a commonly used agent for induction of labor. Anaphylactic reactions are infrequent but possible complications of drugs administered to the pregnant patient. Although antibiotics, latex, and

1. Nguyen NT, Masoomi H, Magno CP, Nguyen XT, Laugenour K, Lane J. Trends in use of bariatric surgery, 2003-2008. J Am Coll Surg 2011;213:261–6. 2. Weintraub AY, Levy A, Mazor M, Sheiner E. Effect of bariatric surgery on pregnancy outcome. Int J Gynaecol Obstet 2008;103: 246–51. 3. Capella RF, Iannace VA, Capella JF. Bowel obstruction after open and laparoscopic gastric bypass surgery for morbid obesity. J Am Coll Surg 2006;203:328–35. 4. Loar PV, Sanchez-Ramos L, Kaunitz AM, Kerwin AJ, Diaz J. Maternal death caused by midgut volvulus after bariatric surgery. Am J Obstet Gynecol 2005;193:1748–9. 5. La Marca A, Giulini S, Tirelli A, Bertucci E, Marsella T, Xella S, et al. Anti-Müllerian hormone measurement on any day of the menstrual cycle strongly predicts ovarian response in assisted reproductive technology. Hum Reprod 2011;22:766–71. 6. Moore KA, Ouyang DW, Whang EE. Maternal and fetal deaths after gastric bypass surgery for morbid obesity. N Engl J Med 2004;351:721–2. 7. Graubard Z, Graham KM, Schein M. Small-bowel obstruction in pregnancy after Scopinaro weight reduction operation: a case report. S Afr Med J 1988;72:127–8. 8. Higa KD, Ho T, Boone KB. Internal hernias after laparoscopic Roux-en-Y gastric bypass: incidence, treatment and prevention. Obes Surg 2003;13:350–4. 9. Wax JR, Pinette MG, Cartin A. Roux–en-Y gastric bypassassociated bowel obstruction complicating pregnancy–an obstetrician’s map to the clinical minefield. Am J Obstet Gynecol 2013; 208:265–71.

CASE: A 21-year-old woman received buccal misoprostol as a ripening agent for postdate labor induction and experienced anaphylaxis and tachysystole. Prompt administration of epinephrine and emergent cesarean delivery allowed for the safe delivery of the neonate and minimal maternal morbidity. CONCLUSION: When inducing labor, prompt identification and treatment of anaphylaxis and hypersensitivity reactions are necessary to prevent maternal and neonatal morbidity and mortality. Health care providers must be aware of uncommon reactions to medications used to induce labor. (Obstet Gynecol 2014;124:466–8)

From the Departments of Obstetrics and Gynecology and Family Medicine, Thomas Jefferson University Hospital, Philadelphia, Pennsylvania. Corresponding author: Corina Schoen, MD, Department of Obstetrics and Gynecology, Thomas Jefferson University Hospital, 833 Chestnut Street, 1st floor, Philadelphia, PA 19107; e-mail: [email protected]. Financial Disclosure The authors did not report any potential conflicts of interest. © 2014 by The American College of Obstetricians and Gynecologists. Published by Lippincott Williams & Wilkins. ISSN: 0029-7844/14


Schoen et al

Anaphylaxis to Buccal Misoprostol

DOI: 10.1097/AOG.0000000000000268


naphylactic reactions to medications are uncommon in pregnancy. An epidemiologic study of women giving birth in Texas found a rate of 2.7 anaphylactic reactions per 100,000 deliveries.1 Most cases of anaphylactic reaction during pregnancy involve exposures to antibiotics (particularly penicillins or cephalosporins) and latex.2 Much less frequently, agents


for inducing labor cause anaphylaxis.3 We report a case of buccal misoprostol as a cause of anaphylaxis during labor induction.

CASE A 21-year-old primigravid woman was admitted for a postdate induction of labor at 41 weeks of gestation. She reported feeling painful contractions for “days” and reported good fetal movement with no vaginal bleeding or leakage of fluid. Her antenatal course was uncomplicated. She had no previous obstetric, gynecologic, medical, or surgical history. In addition, she was taking no medications and denied any known drug or nondrug allergies. Her social history was noncontributory. On admission, her blood pressure was 103/56 mm Hg, pulse 80 beats per minute, respirations 16 breaths per minute, and temperature 98.1˚F. Fetal heart tracing was Category I with a baseline heart rate of 130 beats per minute, moderate variability, and accelerations. External tocometry indicated she was contracting irregularly, every 2–6 minutes, and she appeared comfortable. Her cervix was 1 cm dilated, 50% effaced, and the fetal vertex was at 23 station. Her Bishop score was 3. Induction of labor was started with 25 micrograms buccal misoprostol at 5:00 PM. At 5:22 PM, the patient reported pruritus and flushing and was given 25 mg diphenhydramine by intravenous push. Uterine tachysystole was evident. As a result of increasing urticaria, an additional 25 mg diphenhydramine was given. Physical examination revealed facial flushing and a normal lung examination without evidence of oropharyngeal edema. She was mildly tachycardic at 110 beats per minute but normotensive. The urticaria rapidly evolved. The fetal tracing remained Category I with a baseline of 160 beats per minute. The patient then was given 0.3 mg 1:1,000 epinephrine intramuscularly for presumed anaphylaxis. After administration of epinephrine, the patient started to report lip tingling and became increasingly tachycardic to 130 beats per minute but remained normotensive. At 5:45 PM the fetal heart tracing began showing variable decelerations and eventual deterioration to fetal bradycardia of 70 beats per minute. There was continued tachysystole, but terbutaline was not given for fear of worsening the maternal tachycardia. Magnesium sulfate also was considered as treatment for the uterine tachysystole, but fetal bradycardia and evolving maternal dyspnea led to the decision for an emergent cesarean delivery, which was performed under general endotracheal anesthesia. Laryngeal edema was noted at laryngoscopy. Immediately before delivery, the fetal heart rate was 80 beats per minute. Incision-to-delivery time was 8 minutes, and the neonate had Apgar scores of 7 at 1 minute and 9 at 5 minutes and was taken to the term nursery. Arterial cord blood gas showed a pH of 7.04 and base deficit of 7.7 mmol/L. The mother remained intubated overnight as a result of her persistent laryngeal edema and was extubated the next day. Serum tryptase level drawn 5 hours after the event was 16 ng/mL (normal 2–10 ng/mL). The remain-

VOL. 124, NO. 2, PART 2, AUGUST 2014

der of her postoperative course was uncomplicated and she and the neonate were discharged home on postoperative day 3.

COMMENT The rates of allergic reactions and anaphylaxis to misoprostol have not been quantified. We performed an English language PubMed search using relevant key words (“misoprostol,” “labor,” “allergy,” and “anaphylaxis”) from 1950 to 2013 and retrieved no results. Using the additional search term “dermatoses,” we

Fig. 1. Algorithm to treat anaphylaxis in pregnancy. *These medications may be used to treat mild to moderate allergic reactions but should never replace epinephrine in the setting of anaphylaxis. Schoen. Anaphylaxis to Buccal Misoprostol. Obstet Gynecol 2014.

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Anaphylaxis to Buccal Misoprostol


found a case report that describes a lichenoid drug eruption that occurred 2 months after 800 micrograms misoprostol vaginally was used to induce a firsttrimester abortion.4 When we expanded our search to include all languages, we found one case (in French) of anaphylaxis and myocardial myocytic necrosis with the concurrent use of diclofenac and misoprostol.5 To our knowledge, even with the frequent use of misoprostol for second-trimester losses and third-trimester induction of labor, there are no other reported cases of acute anaphylaxis. This case is consistent with a moderate-to-severe (Class 3 on the Ring and Messmer Scale) IgEmediated hypersensitivity reaction characterized by pruritus, flushing, urticaria, tachycardia, dyspnea, and laryngeal edema.6 Tryptase is a protease found almost exclusively in mast cells. An increase in serum levels is highly sensitive for identifying mast cell activation. Elevated tryptase levels can be used to confirm an IgE-mediated allergic reaction compared with a nonallergic anaphylactic event, which is not controlled by immunologic mechanisms. The optimal time to draw a serum tryptase level is 1–4 hours after the acute event and compare it with a control specimen taken at least 24 hours afterward. False-negative tryptase levels have been reported, so skin testing should be strongly encouraged if the clinical suspicion is high. In this case, the increase in tryptase drawn 5 hours after the event confirmed an IgE-mediated reaction. Usually tryptase levels will peak at 1 hour and decline linearly with a half-life of 2 hours.6 The patient’s tryptase level was just above the upper limit of normal; however, the sample was drawn well after the expected peak. We can infer that at 1 hour, her tryptase level would have been even higher, diagnosing this reaction as a hypersensitivity reaction, although optimally testing should have been initiated sooner. Only three cases previously have reported anaphylaxis secondary to the use of a progesterone induction agent during labor.3 These cases all were associated with intracervical placement of dinoprostone gel and were followed by respiratory distress, tetanic contractions, and fetal distress. Our literature search recovered no reported cases of anaphylaxis caused by misoprostol by any administration method during labor induction. Oxytocin, another frequently used induction agent, is rarely associated with allergic reactions in women who have a latex allergy. This


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Anaphylaxis to Buccal Misoprostol

may be secondary to the homology in the protein sequence between oxytocin and the latex antigen, palatin.7 Timely appropriate treatment of anaphylaxis is critical to optimize maternal and perinatal outcomes (Fig. 1). Hepner and colleagues2 reviewed a series of anaphylaxis cases in pregnancy and found that neonatal deaths and neurologic morbidity (eg, seizure-like activity, brain damage, hypoxic encephalopathy) may be attributed to incorrect dosing or delayed administration of epinephrine. Epinephrine is more effective than other vasoconstrictors in increasing systemic vascular resistance and improving cardiac output, uteroplacental perfusion, and ultimately fetal perfusion and oxygenation.8 Treating physicians must also consider immediate delivery (10–15 minutes) in these cases. There were no cases in the series that had a poor neonatal outcome when cesarean delivery was performed within this time frame. However, in 50% of the cases with a poor neonatal outcome, the cesarean delivery was delayed (time from anaphylactic event to delivery 30–120 minutes). Therefore, prompt correction of maternal perfusion and immediate delivery remains the most effective means of ensuring fetal perfusion and a good pregnancy outcome. REFERENCES 1. Mulla ZD, Ebrahim MS, Gonzalez JL. Anaphylaxis in the obstetric patient: analysis of a statewide hospital discharge database. Ann Allergy Asthma Immunol 2010;104:55–9. 2. Hepner DL, Castells M, Mouton-Faivre C, Dewachter P. Anaphylaxis in the clinical setting of obstetric anesthesia: a literature review. Anesth Analg 2013;117:1357–67. 3. Cusick W, Leuci D, Viscarello RR, Rodis JF. Anaphylactoid syndrome of pregnancy after intracervical dinoprostone for cervical ripening: a report of 3 cases. J Reprod Med 2005;50: 225–8. 4. Cruz MJ, Duarte AF, Baudrier T, Cunha AP, Barreto F, Azevedo F. Lichenoid drug eruption induced by misoprostol. Contact Dermatitis 2009;61:240–2. 5. Meuleman C, Jourdain P, Bellorini M, Guillard N, Loiret J, Thebault B, et al. Anaphylactic shock and myocytic necrosis after treatment with Artotec [in French]. Arch Mal Coeur Vaiss 2002;95:1230–3. 6. Kroigaard M, Garvey LH, Gillberg L, Johansson SG, Mosbech H, Florvaag E, et al. Scandinavian clinical practice guidelines on the diagnosis, management and follow-up of anaphylaxis during anaesthesia. Acta Anaesthesiol Scand 2007;51:655–70. 7. Ogata J, Minami K. Synthetic oxytocin and latex allergy. Br J Anaesth 2007;98:845–6. 8. Simons FE, Schatz M. Anaphylaxis during pregnancy. J Allergy Clin Immunol 2012;130:597–606.


Anaphylaxis to buccal misoprostol for labor induction.

Misoprostol is a commonly used agent for induction of labor. Anaphylactic reactions are infrequent but possible complications of drugs administered to...
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