OBJECTIVE: To synthesize available evidence on intravenous (IV) oxytocin dosing regimens for the prevention of postpartum hemorrhage (PPH) at cesarean section (CS). DATA SOURCES: We searched Medline/OVID, Embase, Global Index Medicus, CINAHL, CENTRAL, ClinicalTrials.gov, and ICTRP for eligible studies published until Feb 2020. STUDY ELIGIBILITY CRITERIA: We included any randomized or non-randomized study published in peer-reviewed journals that compared at least two different dosing regimens of IV oxytocin for PPH prevention in women undergoing CS. STUDY APPRAISAL AND SYNTHESIS METHODS: Two authors independently assessed eligibility, extracted data, and assessed risk of bias. Primary outcome was incidence of PPH >/= 1000 mL. Other review outcomes included use of additional uterotonics, blood loss, and adverse maternal events. Data were analyzed based on type of IV administration (bolus only, infusion only, bolus plus infusion) and oxytocin dose. Meta-analysis was performed using randomized trials and reported using risk ratios or mean difference with 95% confidence intervals. GRADE was used to rate the certainty of evidence. Findings from dose-finding trials and non-randomized studies were reported narratively. RESULTS: Thirty-five studies (7,333 women) met our inclusion criteria, including 30 randomized trials and five non-randomized studies. There were limited data from trials for most outcomes, and results were not conclusive. Compared to bolus plus infusion regimens, bolus only regimens probably result in slightly higher mean blood loss (MD 52 mL, 95% CI 0.4-104 mL, moderate certainty). Amongst bolus plus infusion regimens, initial bolus doses < 5 IU may reduce nausea (RR 0.26, 95% CI 0.11-0.63, low certainty) as compared to 5-9 IU. Total oxytocin doses 5-9 IU versus 10-19 IU may increase use of additional uterotonics (RR 13.00, 95% CI 1.75-96.37, low certainty). Effects on other outcomes were generally inconclusive. CONCLUSION: There are limited data comparing IV oxytocin regimens for PPH prevention at CS. Bolus plus infusion regimens may lead to minor reductions in mean blood loss, and initial bolus doses of < 5 IU may minimize nausea. Bolus only regimens of 10 IU versus 5 IU may decrease use of additional uterotonics, however further comparative trials are required to understand effects on other key outcomes, particularly hypotension.
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