NEW YORK (Reuters Health) – Women in Ecuador have a particularly high rate of fever and shivering with sublingual misoprostol – but whether this is due to altitude, genetics, or some other cause is still not clear.

The fevers resolved within hours after treatment, leaving no long-term side effects, according to a report in BJOG: An International Journal of Obstetrics and Gynaecology that was published online April 20.

Although the prostaglandin E1 derivative misoprostol is commonly used for postpartum hemorrhage, high fevers have raised concerns about its safety.

In a recent multicenter trial, one site — a tertiary hospital in Quito, Ecuador – had a 35.6% rate of high fevers (40 degrees C or higher) with postpartum administration of sublingual misoprostol (800 mcg). Rates of high fever at the other three hospitals in that study and at another five hospitals in a companion trial ranged from 0% to 9.5% (see Reuters Health report, January 6, 2010).

The dramatically higher risk in Quito led Jill Durocher, from Gynuity Health Projects, New York, and colleagues to conduct a post hoc analysis of side effects in the 163 women at the Ecuadorian site.

The rate of shivering was also higher in Ecuador (89.6%) than at hospitals in Burkina Faso, Egypt, Turkey, and Vietnam (7.1% – 75.8%).

The 58 cases of high fever in Ecuador were treated with oral acetaminophen, cool compresses, and IV aspirin.

Severe shivering – uncontrollable shaking that made it difficult to speak or control movement – occurred in 28% of women with high fever and in 3% of those without. In the women with higher fevers, shivering generally started within 20 minutes. Temperature peaked 1 to 2 hours after misoprostol administration and then declined gradually over 3 hours. In general, temperatures stayed above 40 degrees C for less than 2 hours, and fell below 38 degrees C (100.4 degrees F) within 6 hours.

Transient delirium or altered sensorium occurred more often with high fever (13.8% vs 3.2%). Otherwise, high fever did not result in additional health complications, the authors report.

About half of women who had shivering and fever described them as intolerable, regardless of the degree of fever.

Nevertheless, the occurrence of high fever did not affect the time to discharge or likelihood of being in good condition at discharge.

Infection had no obvious role in these fevers. The only risk factors the research team could identify were previous postpartum hemorrhage (10.3% vs 1.9% in those without high fever) and placental expulsion within 15 minutes (82.8% vs 65.7%, respectively). Durocher’s team theorizes that the flood of endogenous and exogenous prostaglandins related to rapid placental expulsion could contribute to the high fever.

They also suggest that Ecuador’s high altitude may play a role, pointing out that the hypoxic environment typically leads to larger placental size.

They also propose that “a genetic variation permits misoprostol, a PGE1 analogue, to activate the endogenous fever mechanism that is typically triggered by PGE2. If this is the case, the high rate of fever among Ecuadorian women may represent a high frequency of a variant allele in this homogeneous population.”

Reference:

BJOG 2010.