Intramuscular Versus Intravenous Oxytocin to Prevent Postpartum Hemorrhage at Vaginal Delivery: Randomized Controlled Trial

P ostpartum hemorrhage (PPH) is a leading cause of maternal mortality and has been increasing over the last 15 years in many developed countries. While uterotonic drugs such as oxytocin have been established as useful tools in preventing PPH, the best administration method remains unclear. When given intramuscularly, a uterotonic effect will be obtained in 3 to 7 minutes, with the effect lasting 30 to 60 minutes. Intravenous oxytocin has an effect almost immediately and the plateau concentration is reached at 30 minutes. However, intravenous administration has been associated with hypotension and tachycardia. At these investigators’ medical center, the practice of administering oxytocin 10 international units (IU) intravenously after delivery was changed in 2010 to intramuscular oxytocin, following Royal College of Obstetricians and Gynaecologists guidelines. This randomized, controlled trial, the Labour Oxytocin Route (LabOR) was prompted by concerns from midwives and obstetricians at the study center regarding a perceived rise in PPH after this change in practice was adopted. The LabOR trial aimed to determine whether intravenous oxytocin 10 IU was more effective than intramuscular oxytocin 10 IU at preventing PPH after vaginal delivery. This double-blind, placebo-controlled randomized trial was conducted at a large maternity unit in Ireland between January 4, 2016 and December 13, 2017. The study group included women 18 years or older who were at least 37 weeks’ gestation with a singleton pregnancy and planning a vaginal birth with an actively managed third stage of labor. Women were excluded if they were considered to be at increased risk of PPH or had preexisting cardiovascular disease. Randomization to intramuscular or intravenous oxytocin occurred once the second stage of labor was reached. All patients received both an intramuscular and intravenous injection, with one being the oxytocin and the other saline, depending on the study group to which the woman was randomized. Immediately following delivery, Drug 1-IM was administered intramuscularly into the thigh. Then, Drug 2-IV was administered intravenously through an intravenous cannula over 1 minute. Blood loss was measured by direct collection during delivery, using a gravimetric surgical drape. In addition, sheets, sponges, and pads that contained blood were weighed to determine blood loss volume. The primary outcome was PPH of 500mL or more. Multiple secondary outcomes were studied, including side effects of oxytocin, severe PPH (1000mL or more), need for blood transfusion, admission to a high dependency unit, and changes in hemoglobin and hematocrit values. Of the 1075 randomized for the study, 1035 were ultimately included in the analysis. Of these, 517 were in the intravenous oxytocin group and 518 were in the intramuscular oxytocin group. Analysis was performed on an intention to treat basis. Of the 517 women in the intravenous group, 97 (18.8%) experienced PPH compared with 120 (23.2%) in the intramuscular group [adjusted odds ratio (aOR), 0.75; 95% confidence interval (CI), 0.55-1.03]. While the rate of overall PPH was not significantly different between the 2 groups, the intravenous oxytocin group had a significantly lower incidence of severe PPH than the intramuscular group (4.6% vs. 8.1%; aOR, 0.54; 95% CI, 0.320.91). The need for blood transfusion was also significantly lower in the intravenous group compared with the intramuscular group (1.5% vs. 4.4%; aOR, 0.44; 95% CI, 0.130.70) as was the need for admission to a high dependency unit (1.7% vs. 3.7%; aOR, 0.44; 95% CI, 0.2-0.98). Compared with the intramuscular group, the risk of side effects such as hypotension and tachycardia was similar for the intravenous oxytocin group (4.1% vs. 5.2%; aOR, 0.75; 95% CI, 0.421.35). No significant differences were found between groups for changes in hemoglobin and hematocrit levels. In this randomized, controlled trial, no difference was found in the incidence of PPH, as defined by > 500mL after vaginal delivery, when intravenous or intramuscular oxytocin was administered for the management of the third stage of labor. However, the incidence of severe PPH, need for blood transfusion and admission to a high dependency unit were all reduced when intravenous oxytocin was used compared with intramuscular oxytocin. These study findings would support the use of intravenous oxytocin for managing the third stage of labor.