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

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 misoprostol-induced 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 misoprostol-induced 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.

OBJECTIF: Caractériser la survenue de fièvre (≥ 38,0°C) après traitement d'une hémorragie post-partum (HPP) avec du misoprostol sublingual à 800 mcg en Amérique latine, où des taux élevés d'effets thermorégulateurs du misoprostol et une sensibilité accrue des receveurs à une forte fièvre ont été documentés. MÉTHODES: Une étude observationnelle prospective dans des hôpitaux en Argentine a recruté des femmes consentantes atteintes d'HPP atonique après un accouchement vaginal éligibles pour recevoir du misoprostol. La température corporelle a été évaluée 30, 60, 90 et 120 minutes après le traitement; d'autres effets ont été enregistrés. L'incidence d'une fièvre élevée ≥40,0°C (critère principal) a été comparée au taux observé précédemment en Equateur. Des régressions logistiques ont été effectuées pour identifier les prédicteurs cliniques et ceux basés sur la population de la fièvre induite par le misoprostol . RÉSULTATS: Des frissons transitoires et de la fièvre ont été ressentis par 75% (37/49) des participantes traitées et décrits comme acceptables par les trois quarts des femmes interrogées (35/47). Le taux de fièvre élevé était de 12% (6/49), [intervalle de confiance (IC) à 95%: 4,6, 24,8] contre 35,6% en Equateur après traitement au misoprostol (58/163) [IC95%: 28,3, 43,5], p = 0,002). Les prédicteurs significatifs de la fièvre induite par le misoprostol (selon le modèle) étaient: hémoglobine avant l'accouchement <11,0 g/dL, expulsion placentaire rapide et âge plus élevé de la femme. Aucun résultat sévère n'a été signalé avant le sortie d'hôpital. CONCLUSIONS: Le misoprostol pour traiter l'HPP en Argentine a entraîné un taux de fièvre élevée significativement plus bas qu'en Equateur, bien que les taux dans les deux pays soient notablement plus élevés que les taux observés ailleurs. Une meilleure compréhension des effets secondaires du misoprostol et des facteurs impliqués dans leur apparition, y compris la génétique, aidera à atténuer les inquiétudes. L'apparition de frissons peut être le moyen le plus simple de savoir si l'on peut également s'attendre à de la fièvre.

Does route matter? Impact of route of oxytocin administration on postpartum bleeding: A double-blind, randomized controlled trial.

OBJECTIVE: We assessed the impact of intravenous (IV) infusion versus intramuscular (IM) oxytocin on postpartum blood loss and rates of postpartum hemorrhage (PPH) when administered during the third stage of labor. While oxytocin is recommended for prevention of PPH, few double-blind studies have compared outcomes by routes of administration. METHODS: A double-blind, placebo-controlled randomized trial was conducted at a hospital in Argentina. Participants were assigned to receive 10 IU oxytocin via IV infusion or IM injection and a matching saline ampoule for the other route after vaginal birth. Blood loss was measured using a calibrated receptacle for a 1-hour minimum. Shock index (SI) was also calculated, based on vital signs measurements, and additional interventions were recorded. Primary outcomes included: the frequency of blood loss ≥500ml and mean blood loss. RESULTS: 239 (IV infusion) and 241 (IM) women were enrolled with comparable baseline characteristics. Mean blood loss was 43ml less in the IV infusion group (p = 0.161). Rates of blood loss ≥500ml were similar (IV infusion = 21%; IM = 24%, p = 0.362). Women in the IV infusion group received significantly fewer additional uterotonics (5%), than women in the IM group (12%, p = 0.007). Women with PPH in the IM group experienced a larger increase in SI after delivery, which may have influenced recourse to additional interventions. CONCLUSIONS: The route of oxytocin administration for PPH prevention did not significantly impact measured blood loss after vaginal birth. However, differences were observed in recourse to additional uterotonics, favoring IV infusion over IM. In settings where IV lines are routinely placed, oxytocin infusion may be preferable to IM injection.

A systematic review of the relationship between blood loss and clinical signs.

INTRODUCTION: This systematic review examines the relationship between blood loss and clinical signs and explores its use to trigger clinical interventions in the management of obstetric haemorrhage. METHODS: A systematic review of the literature was carried out using a comprehensive search strategy to identify studies presenting data on the relationship of clinical signs & symptoms and blood loss. Methodological quality was assessed using the STROBE checklist and the general guidelines of MOOSE. RESULTS: 30 studies were included and five were performed in women with pregnancy-related haemorrhage (other studies were carried in non-obstetric populations). Heart rate (HR), systolic blood pressure (SBP) and shock index were the parameters most frequently studied. An association between blood loss and HR changes was observed in 22 out of 24 studies, and between blood loss and SBP was observed in 17 out of 23 studies. An association was found in all papers reporting on the relationship of shock index and blood loss. Seven studies have used Receiver Operating Characteristic Curves to determine the accuracy of clinical signs in predicting blood loss. In those studies the AUC ranged from 0.56 to 0.74 for HR, from 0.56 to 0.79 for SBP and from 0.77 to 0.84 for shock index. In some studies, HR, SBP and shock index were associated with increased mortality. CONCLUSION: We found a substantial variability in the relationship between blood loss and clinical signs, making it difficult to establish specific cut-off points for clinical signs that could be used as triggers for clinical interventions. However, the shock index can be an accurate indicator of compensatory changes in the cardiovascular system due to blood loss. Considering that most of the evidence included in this systematic review is derived from studies in non-obstetric populations, further research on the use of the shock index in obstetric populations is needed.

Dose and side effects of sublingual misoprostol for treatment of postpartum hemorrhage: what difference do they make?

BACKGROUND: Shivering 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%). METHODS: From 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. RESULTS: The 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. CONCLUSIONS: 600mcg 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 REGISTRATION: Clinical trials.gov, Registry No. NCT01080846.

Oral misoprostol for the management of incomplete abortion in Ecuador.

OBJECTIVE: To assess the feasibility of introducing misoprostol for the treatment of incomplete abortion in Quito, Ecuador. METHODS: In a randomized prospective study conducted at a large tertiary-level maternity hospital and a private secondary-level clinic between November 2006 and November 2007, women with incomplete abortion were treated with either 600 µg of oral misoprostol (n=122) or manual vacuum aspiration (MVA) (n=120). All participants were requested to return for follow-up care on day 7 to determine the success of the treatment and to document their satisfaction with the method and the adverse effects experienced. RESULTS: Sixteen percent of women (39/242) did not return for their follow-up visit and their outcomes are unknown. Among those who did return, 94% (100/106) of women showed successful completion of abortion after treatment with misoprostol, as compared with 100% (97/97) of women treated with MVA. Most women described their adverse effects after treatment as tolerable (misoprostol, 95%; MVA, 91%). Nearly all women reported being satisfied with their treatment (196/203); there were no differences among the women's reports of satisfaction according to treatment received. CONCLUSION: An oral dose of 600 µg of misoprostol was found to be an acceptable and effective non-surgical option for treating incomplete abortion. Clinical trials.gov NCT00674232.