Multimodal Uterotonics at the Time of Cesarean Section in Laboring Patients
Condition: Uterine Atony With Hemorrhage
MeSH terms: Uterine Inertia; Hemorrhage
Study type: Interventional
Phase: Phase 4

Summary: 
      Postpartum hemorrhage remains a leading cause of maternal morbidity and mortality worldwide,
      even in high income countries. Uterine atony is estimated to cause 70-80% of postpartum
      hemorrhage. Prolonged labor and augmented labor are known risk factors for postpartum
      hemorrhage. In attempts to reduce the incidence of postpartum hemorrhage, particularly in
      patients with known risks factors, it is essential to optimize preventative practices in
      order to reduce the rates postpartum hemorrhage.

      Although oxytocin is considered the first line therapy for preventing and treating uterine
      atony, early consideration of additional prophylactic uterotonic agents may be indicated in
      women with prior oxytocin exposure given oxytocin receptor desensitization and down
      regulation.

      As such, investigators sought to examine whether multimodal prophylactic uterotonics
      (standard oxytocin + methylergonovine), in patients who are increased risk of developing
      postpartum hemorrhage (specifically laboring patients who ultimately require a cesarean
      section) would benefit from the addition of prophylactic uterotonics. The clinical rational
      for administration of multimodal prophylactic uterotonics at the time of cesarean delivery in
      laboring patients is three-fold: to decrease the incidence of uterine atony, to decrease the
      incidence of postpartum hemorrhage, decrease the number of uterotonics required at the time
      of cesarean section.

      The primary outcome will be to evaluate the need for additional uterotonic agents
      (Methylergonovine, Carboprost, Misoprostol) at the time of delivery.

      Secondary outcomes will include the incidence of postpartum hemorrhage (quantitative blood
      loss >1 liter), surgical assessment of uterine tone four minutes following delivery of the
      placenta, preoperative and postoperative hemoglobin, the need for a blood transfusion,
      intensive care unit admission, uterine infection (endometritis).
    

Detailed description: 
      All patients who meet eligibility for the study will be consented during their clinic visit
      or upon arrival to labor and delivery. If patients elect to participate in the study,
      enrollment in the study will be noted in their sticky note in EPIC (electronic medical
      record) which will be ready available to all members of the health care team. If patients
      during the labor process require a cesarean section, the anesthesiologist will pick up a
      sealed envelope (which will contain the allocation sequence and group assignment). A
      randomization block design with mixed block sizes will be used to generate the allocation
      sequence by using the nQuery Advisor computer software.

      The sealed envelopes will be readily available to the anesthesiologist and kept in the
      anesthesia workroom. Following delivery of the infant, the patient will receive the standard
      oxytocin infusion. Following administration of the oxytocin infusion, the patient will be
      given either methylergonovine 0.2 mg IM (intramuscular) or placebo (1 ml of normal saline,
      intramuscular). This will be drawn up and administered by the anesthesiologist. The
      obstetrician (delivering provider performing the cesarean section) will be blinded to the
      group assignment. Documentation of the drug will be recorded in epic in the medication
      administration record.

      The delivering provider will be responsible for determining and relaying to the
      anesthesiologist whether additional uterotonics are needed throughout the procedure.
      Additional uterotonics will be given in accordance to the current guidelines outlined by the
      American Congress of Obstetricians and Gynecologists (ACOG). The delivery provider will
      assess uterine tone at 4 minutes (satisfactory versus unsatisfactory). The registered nurse
      will be responsible for setting up a timer to let the OB provider know when 4 minutes have
      passed. Nursing will call out once the 4 minutes have passed and the OB provider will state
      whether adequate tone was noted. The anesthesiologist will be responsible for documenting
      whether a placebo/study drug was given and uterine tone after 4 minutes. This documentation
      will be placed back into the sealed envelope by the anesthesiologist and placed in the
      anesthesia workroom. Nicole Masse (primary investigator) will be responsible for storing
      folders in a secured, locked file cabinet within the Maternal Fetal Medicine offices.

      As routinely done at the time of cesarean delivery, the registered nurse will be responsible
      for measuring and documenting the quantitative blood loss. As routinely performed on all are
      patients who undergo a vaginal or cesarean delivery, preoperative hemoglobin and
      postoperative day one hemoglobin levels will be collected.

      In the event a postpartum hemorrhage was to occur, the obstetrician will then be un-blinded
      as management of a postpartum hemorrhage will be driven by whether normal saline or
      methergine was given as part of the study.

      The primary outcome, the need for additional uterotonics, will be assessed in the operating
      room. Other outcome which will be assessed in the operating room include uterine tone and
      quantitative blood loss. Outcomes which will be assessed in the immediate postpartum period
      include: postpartum hemoglobin values, need for a blood transfusion, admission to the
      intensive care unit, endometritis).

      No long-term follow will be needed.
    

Intervention name(s): Methylergonovine; Normal Saline (placebo)
Intervention type(s): Drug; Drug
Intervention description(s): 0.2 mg of intramuscular methylergonovine at the time of cesarean section following standard IV oxytocin infusion.; 1 ml of normal saline intramuscular at the time of cesarean section following standard IV oxytocin infusion
Other intervention name(s): Methergine; Saline
Intervention MeSH terms: Methylergonovine
Allocation: Randomized
Intervention model: Parallel Assignment
Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
Primary purpose: Prevention
Keywords: Methergine; Uterine Atony