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March 2017 Vol. 4 No. 3

In This Issue 

Miso Fever

by Kara Johnson, DNP, RNC-OB, CNS

Why does your postpartum hemorrhage patient have a fever? The answer might surprise you.

Postpartum hemorrhage has a high rate of maternal morbidity and mortality. In the past several years there has been increased focus on developing hospital protocols for risk assessment, prevention, and treatment of postpartum hemorrhage. Misoprostol (Cytotec) is commonly used to prevent or to treat postpartum hemorrhage. Fever and shivering are common side effects of medications that are prostaglandins, such as misoprostol. There have been an increasing number of reported cases of transient high fevers after sublingual or oral misoprostol administration.

Oxytocin is the first line medication for prophylaxis and treatment of postpartum hemorrhage. The California Quality Care Collaborative (CMQCC) recommends choosing a standard second line treatment uterotonic medication between Methergine 0.2 mg IM, Hemabate 250 mcg IM, and misoprostol 600 mcg oral or 800 mcg sublingual (Lyndon, Lagrew, Shields, Main, & Cape, 2015). The World Health Organization (WHO, 2012) also recommends either Methergine or misoprostol 800 mcg sublingual as second line uterotonic medication for the treatment of postpartum hemorrhage. Methergine should be avoided in hypertensive patients and Hemabate should be avoided in patients with asthma. An advantage of Methergine given the intramuscular route is that it has a quick onset of 2-5 minutes (Lyndon, Lagrew, Shields, Main, & Cape, 2015). Fever and severe diarrhea are common with Hemabate so hospitals may choose Hemabate as a 3rd or 4th line medication in their protocols.

The three routes that misoprostol can be administered for postpartum hemorrhage are sublingual, oral, and rectal. Occurrence of pyrexia (fever greater than 38 degrees Celsius) with misoprostol is route dependent and possibly dose dependent. The incidence of fever based on route is sublingual 15%, oral 11%, and rectal 4% (Elati & Weeks, 2012). Sublingual administration has the shortest onset so is often preferred in acute postpartum hemorrhage, but has a chalky texture and is difficult for the patient to take sublingually. With rectal administration plasma concentrations are maintained for a longer period. A systematic review found an overall five-fold increase in pyrexia with misoprostol, which was dose-related and greatest with the sublingual route and least with the rectal route (Hofmeyr, Gülmezoglu, Novikova, & Lawrie, 2013). Hyperpyrexia (body temperature of 40°C or more) is a serious adverse event which can be life threatening.

Misoprostol administered prophylactically with oxytocin does not reduce the rate of postpartum hemorrhage risk and increases the rate of adverse events such as fever, shivering, and nausea (Ghout, et al., 2016) As a result, sublingual or oral misoprostol should be avoided unless treating postpartum hemorrhage.

The abrupt onset also makes it difficult to determine whether the maternal fever is caused by the misoprostol or if it is related to infection (chorioamnionitis). For this reason it is important to let the pediatric provider know if maternal fever develops after delivery and if the patient was given misoprostol.

Key Points

  • Talk with the leaders and providers at your facility to ensure all are in agreement on a standardized postpartum hemorrhage protocol.
  • Consider administering Methergine 0.2 mg IM as a second line medication if patient is not hypertensive.
  • Misoprostol administration for preventing postpartum hemorrhage does not reduce the rate of postpartum hemorrhage and should be avoided unless treating postpartum hemorrhage.
  • Consider administering misoprostol the rectal route to decrease incidence of fever taking into consideration that it has a slower onset, but plasma concentrations are maintained for a longer period.
  • Notify pediatric provider if mother was given misoprostol and develops fever when determining presence of infection or chorioamnionitis.


Elati, A. & Weeks, A. (2012). Risk of fever after misoprostol for the prevention of postpartum hemorrhage: A meta-analysis. Obstetrics & Gynecology, 120(5), 1140-1148.

Ghout , I., Goffinet, F., Salomon , L.J., Fort, J., Javoise, S., Bussieres, L., Aegerter, P., & Rozenberg, .P. (2016). Active management of the third stage of labor with a combination of oxytocin and misoprostol to prevent postpartum hemorrhage: A randomized controlled trial. Obstetrics and Gynecology, 128(4), 805-811.

Hofmeyr, G.J., Gülmezoglu, A.M., Novikova, N., Lawrie, T.A. (2013). Postpartum misoprostol for preventing maternal mortality and morbidity. Cochrane Database of Systematic Reviews, 7, 1-109.

doi: 10.1002/14651858.CD008982.pub2.

Lyndon, A., Lagrew, D., Shields, L., Main, E., & Cape, V. (2015). Improving healthcare response to

obstetric hemorrhage (California Maternal Quality Care Collaborative toolkit to transform maternity care) Developed under contract #11-10006 with the California Department of Public Health; Maternal, Child and Adolescent Health Division; Published by the California Maternal Quality Care Collaborative, 3/17/15.

World Health Organization (2012). WHO recommendations for the prevention and treatment of postpartum haemorrhage. WHO: Geneva.

Thanks to all the contributors to Every Woman, Every Baby in 2016,

Oregon AWHONN has won the Section Challenge once again!

This year, we won for raising the most in charitable donations.

One lucky winner from those who donated will be chosen to receive

complimentary registration for the 2017 AWHONN Convention in New Orleans, LA.

The winner will be announced in next month's newsletter.

Upcoming Events

South Willamette Valley Chapter Meeting

Advanced Fetal Monitoring: Issues in Safety, Choice and Consensus

Mid-Willamette Valley Chapter Meeting

Perinatal Mood Disorders

Presented by Sheryl Combs, NP

May 22, 2017, 1:30 - 3:30 PM

Salem Hospital

Flyer coming soon...

Oregon AWHONN Abstract Writing Webinar

Wednesday, Jun 9 at 5:00 PM - 6:00 PM

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