High fever after sublingual administration of misoprostol for treatment of post‐partum haemorrhage: a hospital‐based, prospective observational study in Argentina

Abstract

objective To characterise the occurrence of fever (≥38.0°C) after treatment for post-partum haemorrhage (PPH) with sublingual misoprostol 800 mcg in Latin America, where elevated rates of misoprostol's thermoregulatory effects and recipients' increased susceptibility to high fever have been documented.methods A prospective observational study in hospitals in Argentina enrolled consenting women with atonic PPH after vaginal delivery, eligible to receive misoprostol. Corporal temperature was assessed at 30, 60, 90 and 120 min post-treatment; other effects were recorded. The incidence of high fever ≥ 40.0°C (primary outcome) was compared to the rate observed previously in Ecuador. Logistic regressions were performed to identify clinical and population-based predictors of misoprostolinduced fever.results Transient shivering and fever were experienced by 75.5% (37/49) of treated participants and described as acceptable by three-quarters of women interviewed (35/47). The high fever rate was 12.2% (6/49), [95% Confidence Interval (CI) 4.6, 24.8], compared to Ecuador's rate following misoprostol treatment (35.6% (58/163) [95% CI 28.3, 43.5], P = 0.002). Significant predictors of misoprostolinduced fever (model dependent) were as follows: pre-delivery haemoglobin < 11.0g/dl, rapid placental expulsion, and higher age of the woman. No serious outcomes were reported prior to discharge.conclusions Misoprostol to treat PPH in Argentina resulted in a significantly lower rate of high fever than in Ecuador, although both are notably higher than rates seen elsewhere. A greater understanding of misoprostol's side effects and factors involved in their occurrence, including genetics, will help alleviate concerns. The onset of shivering may be the simplest way to know if fever can also be expected.keywords misoprostol, fever, post-partum haemorrhage, sublingual, Argentina, Latin America Sustainable Development Goals (SDGs): SDG 3 (good health and well-being), SDG 17 (partnerships for the goals)

Prostaglandins for Postpartum Hemorrhage: Pharmacology, Application, and Current Opinion

“…A large multicenter study [44] reported an unusually high rate of fever >40°C (36%) in Ecuadorian women who received 800 μg of misoprostol sublingually compared with other participants (0-9%) who received the same regimen. Since the incidence of fever varies greatly in different populations, there is hypothesis that genetic factors may play a role in misoprostol-induced fever [45]. Some studies [46] suggest that genetic variability in ABCC4 and the resultant higher level of misoprostol acid in the brain lead to hyperpyrexia in pregnant women.…”

“…However, this is not the only influence on postnatal fever. There appear also to be other effects that could be genetic or cultural [44,45]. Clinically, it is worth noting that fever as the side effect of misoprostol and fever caused by postpartum infection need to be distinguished more carefully [83].…”

Corticotrophins, corticosteroids, and prostaglandins

“…Women who were in active labor and did not have an allergy to a prostaglandin or had a planned caesarean section were able to participate in the study. Four 200 μg of misoprostol were placed under the tongue if their hemorrhage bleeding reached 500 mL ( Durocher et al, 2020 ) [A]. Participants' temperature was checked in 30-min intervals.…”

What do healthcare providers think of the quality of uterotonics? A mixed-methods systematic review

“…This perception can affect prescription behaviour, potentially leading to repeated administration, changing to other less effective uterotonics and the use of combinations of different types of uterotonics 27. This behaviour can expose women to excessive doses of oxytocin and misoprostol, and associated adverse events including maternal and perinatal death 14 16 28–30. In theory, women exposed to repeated doses of degradation products from deteriorated drugs could also develop toxicity-related adverse effects.…”