ABSTRACT
PURPOSE: Oxytocin is the preferred choice for prophylaxis and treatment of postpartum hemorrhage. Intravenous infusion has been a widely accepted route for Oxytocin administration. However, intravenous bolus route is not a readily preferred route due to apprehensions regarding hypotension that it may cause. This trial compares low dose 3 IU intravenous (IV) bolus Oxytocin along with 7 IU Oxytocin in intravenous infusion to 10IU Oxytocin intravenous infusion during cesarean section. PATIENTS AND METHODS: A total of 250 term pregnant women were randomized to either 3 IU intravenous bolus with 7 IU intravenous infusion of Oxytocin or 10IU of intravenous Oxytocin infusion. The difference in pre- and post-operative hemoglobin levels, tone of the uterus, hemodynamic changes, adverse effects of the drug, need for additional uterotonics and need for blood transfusions were assessed. RESULTS: There was 6.7% less blood loss in the 3 IU IV bolus Oxytocin with 7 IU Oxytocin infusion group in comparison to the Oxytocin infusion group. The tone of the uterus was firmer in IV bolus Oxytocin with Oxytocin infusion group at 5 minutes (p<0.001) than the Oxytocin infusion group. There was no significant difference in the hemodynamic changes, adverse effects or need for blood transfusions. CONCLUSION: Intravenous bolus of 3 IU Oxytocin along with 7 IU infusion of Oxytocin is as safe and more effective than intravenous infusion of 10 IU of Oxytocin during cesarean section in the prevention of postpartum hemorrhage.
ABSTRACT
BACKGROUND: Postpartum hemorrhage is the most common cause of maternal death. Oxytocin is the standard therapy for the prevention of postpartum hemorrhage, but it requires cold storage, which is not available in many countries. In a large trial, we compared a novel formulation of heat-stable carbetocin with oxytocin. METHODS: We enrolled women across 23 sites in 10 countries in a randomized, double-blind, noninferiority trial comparing intramuscular injections of heat-stable carbetocin (at a dose of 100 µg) with oxytocin (at a dose of 10 IU) administered immediately after vaginal birth. Both drugs were kept in cold storage (2 to 8°C) to maintain double-blinding. There were two primary outcomes: the proportion of women with blood loss of at least 500 ml or the use of additional uterotonic agents, and the proportion of women with blood loss of at least 1000 ml. The noninferiority margins for the relative risks of these outcomes were 1.16 and 1.23, respectively. RESULTS: A total of 29,645 women underwent randomization. The frequency of blood loss of at least 500 ml or the use of additional uterotonic agents was 14.5% in the carbetocin group and 14.4% in the oxytocin group (relative risk, 1.01; 95% confidence interval [CI], 0.95 to 1.06), a finding that was consistent with noninferiority. The frequency of blood loss of at least 1000 ml was 1.51% in the carbetocin group and 1.45% in the oxytocin group (relative risk, 1.04; 95% CI, 0.87 to 1.25), with the confidence interval crossing the margin of noninferiority. The use of additional uterotonic agents, interventions to stop bleeding, and adverse effects did not differ significantly between the two groups. CONCLUSIONS: Heat-stable carbetocin was noninferior to oxytocin for the prevention of blood loss of at least 500 ml or the use of additional uterotonic agents. Noninferiority was not shown for the outcome of blood loss of at least 1000 ml; low event rates for this outcome reduced the power of the trial. (Funded by Merck Sharpe & Dohme; CHAMPION Australian New Zealand Clinical Trials Registry number, ACTRN12614000870651 ; EudraCT number, 2014-004445-26 ; and Clinical Trials Registry-India number, CTRI/2016/05/006969 .).
