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ObjectiveTo explore what triggers an elevated body temperature of ≥40.0°C in some women given misoprostol, a prostaglandin E1 analogue, for postpartum haemorrhage (PPH).DesignPost hoc analysis.SettingOne tertiary-level hospital in Quito, Ecuador.PopulationA cohort of 58 women with a fever of above 40°C following treatment with sublingual misoprostol (800 micrograms) for PPH.MethodsSide effects were documented for 163 Ecuadorian women given sublingual misoprostol to treat their PPH. Women’s body temperatures were measured, and if they had a fever of ≥40.0°C, measurements were taken hourly until the fever subsided. Temperature trends were analysed, and the possible physiological mechanisms by which postpartum misoprostol produces a high fever were explored.Main outcome measuresThe onset, duration, peak temperatures, and treatments administered for cases with a high fever.ResultsFifty-eight of 163 women (35.6%) treated with misoprostol experienced a fever of ≥40.0°C. High fevers followed a predictable pattern, often preceded by moderate/severe shivering within 20 minutes of treatment. Body temperatures peaked 1–2 hours post-treatment, and gradually declined over 3 hours. Fevers were transient and did not lead to any hospitalisation. Baseline characteristics were comparable among women who did and did not develop a high fever, except for known previous PPH and time to placental expulsion.ConclusionsAn unexpectedly high rate of elevated body temperature of ≥40.0°C was documented in Ecuador following sublingually administered misoprostol. It is unclear why temperatures ≥40.0°C occurred with a greater frequency in Ecuador than in other study populations using similar treatment regimens for PPH. Pharmacogenetic studies may shed further light on variations in individuals’ responses to misoprostol.

BackgroundShivering and fever are common side effects of misoprostol. An unexpectedly high rate of fever above 40°C was documented among Ecuadorian women given treatment with 800mcg of sublingual misoprostol to manage postpartum hemorrhage (PPH) (36%). Much lower rates have been reported elsewhere (0-9%).MethodsFrom February to July 2010, an open-label pilot study was conducted in Quito, Ecuador to determine whether a lower dose--600mcg sublingual misoprostol--would result in a lower incidence of high fever (≥40°C). Rates of shivering and fever with 600mcg sublingual regimen were compared to previously documented rates in Ecuador following PPH treatment with 800mcg sublingual misoprostol.ResultsThe 600mcg dose resulted in a 55% lower rate of high fever compared with the 800mcg regimen (8/50; 16% vs. 58/163; 36%; relative risk 0.45 95% CI 0.23-0.88). Only one woman had severe shivering following the 600mcg dose compared with 19 women in the 800mcg cohort (2% vs. 12%; relative risk 0.17 (0.02-1.25)). No cases of delirium/altered sensorium were reported with the 600mcg dose and women’s assessment of severity/tolerability of shivering and fever was better with the lower dose.Conclusions600mcg sublingual misoprostol was found to decrease the occurrence of high fever among Ecuadorian women when given to treat PPH. This study however was not powered to examine the efficacy of this treatment regimen and cannot be recommended at this time. Future research is needed to confirm whether other populations, outside of Quito, Ecuador, experience unusually high rates of elevated body temperature following sublingual administration of misoprostol for treatment of PPH. If indeed similar trends are found elsewhere, larger trials to confirm the efficacy of lower dosages may be justified.Trial RegistrationClinical trials.gov, Registry No. NCT01080846

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