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32: Oxytocin regimens to prevent uterine atony after vaginal delivery: a 3-arm double-blind RCT

      Objective

      Oxytocin use to prevent post partum hemorrhage is a common obstetric intervention but optimal dosing is unknown. We compared 2 higher dose regimens to our routine regimen for vaginal deliveries.

      Study Design

      Double-masked randomized trial of three oxytocin regimens: 80U, 40U or 10U of oxytocin in 500ml crystalloid solution given after delivery as a 1-hour infusion. Any uterotonic or other treatment for hemorrhage could be used as indicated - additional oxytocin was discouraged during the 1-hour infusion. The primary composite outcome was treatment for uterine atony or hemorrhage including additional uterotonics, tamponade, surgical or interventional treatment, or blood transfusion. Secondary outcomes included dose-response and safety. To detect a 33% decrease in the primary outcome (relative to the 10U group) with 80% power and 2-tailed alpha of 0.05, a total of 1800 patients were required. At planned interim review (n=1200), the 40U arm was stopped for futility; enrollment continued in the 10U and 80U dose arms.

      Results

      1798 out of 2869 women were randomized and analyzed; 59% were African-American and 37% nulliparous; mean gestational age was 39 weeks. The groups had similar demographics and risk factors for atony. Results for selected pre-specified outcomes are presented in the table. The relative risk (95% CI) of the primary outcome was 0.93 (0.62-1.40) for the 80U and 0.94 (0.61-1.47) for the 40U group. Treatment with additional oxytocin was less frequent in the 80U compared to 10U group (RR 0.41; 0.19-0.88) as was the frequency of hematocrit drop >6% (0.83; 0.69-0.0.99). No such differences were observed between the 40U and 10U groups. Surgical or other treatments were rare and similar across groups as were safety outcomes.
      TableResults for primary and selected secondary outcomes
      OutcomeIncidence % (or Mean ± SD)P-values for comparisons
      80U (N=658)40U (N=481)10U (N=659)80 vs. 10UTrend
      Primary composite6670.7450.744
      Any Uterotonic6670.5800.578
      Additional oxytocin
      Indicates exact test; EBL=Estimated blood loss
      1230.0180.019
      Methergine
      Indicates exact test; EBL=Estimated blood loss
      4440.6720.673
      Hemabate
      Indicates exact test; EBL=Estimated blood loss
      3330.5330.525
      Blood Transfusion
      Indicates exact test; EBL=Estimated blood loss
      <1<110.5640.559
      20 outcomes
      Hematocrit change (%)−3.9 ± 3.0−4.0 ± 3.0−4.2 ± 2.90.0840.091
      Hematocrit drop >6%2327280.0450.046
      EBL >500cc4560.0700.191
      Safety
      Fluid overload<1000.5000.366
      Pressor treatment1412130.4160.409
      low asterisk Indicates exact test; EBL=Estimated blood loss

      Conclusions

      Compared with our usual 10U oxytocin regimen, higher dose regimens were safe but did not reduce the incidence of the primary composite outcome. Higher dose oxytocin may reduce need for additional oxytocin and incidence of drop in hematocrit > 6%.