EMG for Uterotonic Efficiency Estimation
Condition: Postpartum Hemorrhage
MeSH terms: Postpartum Hemorrhage; Hemorrhage
Study type: Interventional

Summary: 
      Studies found conflicting results on efficacy of uterotonic agents used to prevent and treat
      uterine atony, the most common cause of postpartum hemorrhage. Uterine EMG can be used to
      objectively assess myometrial contractility and, consequently, efficacy of different
      uterotonics.

      The investigators are planning a single-center, randomized, open-label trial to compare
      uterine EMG parameters in women receiving oxytocin vs. those receiving carbetocin after
      cesarean delivery.
    

Detailed description: 
      RATIONALE

      Postpartum hemorrhage is the leading cause of maternal mortality worldwide. In the Western
      world the estimated risk of life threatening postpartum hemorrhage is 2 on 1000 births. Most
      frequently (up to 90% of cases of postpartum hemorrhage) it is a consequence of uterine atony
      or inappropriate uterine contraction. In clinical practice preventing postpartum hemorrhage
      is key and routinely, different prophylactic uterotonic drugs are used. The first-line
      recommended drug for postpartum hemorrhage prevention is oxytocin. However, a recent Cochrane
      meta-analysis concluded that the most effective drugs (compared to oxytocin) to prevent
      postpartum hemorrhage of 500 ml or more are ergometrine with oxytocin, misoprostol with
      oxytocin and carbetocin.

      Carbetocin is a synthetic heat-stable analogue of oxytocin, with a longer half-life. It
      shares the same mechanism of action and the same side-effects as oxytocin. The recommended
      dose of carbetocin is 100 μg, which is equivalent to 10 μg (5 IU) of oxytocin. In the WHO
      carbetocin multicenter, double-blind, randomized trial, the intramuscular administration of
      100 μg of heat-stable carbetocin was discovered to be noninferior to the administration of 10
      IU of oxytocin for the prevention of postpartum hemorrhage after vaginal birth. Some studies
      have found carbetocin to be an effective prophylactic agent with a favourable side effect
      profile for the third stage of labour in caesarean sections, reducing the use of additional
      uterotonic agents, blood and recovery time. Moreover, carbetocin was found to be effective in
      reducing the need for additional uterotonic use and postpartum blood transfusion in women at
      increased risk of postpartum hemorrhage undergoing cesarean delivery. In one study,
      carbetocin was also found to be more effective than oxytocin in preventing postpartum
      hemorrhage in twin pregnancies delivered by cesarean section.

      Uterine contractions in pregnancy, labour and postpartum can be detected using
      electromyography. Myometrial contractility can be objectively and non-invasively assessed in
      vivo by monitoring uterine electromyography (EMG), as uterine contractions are the result of
      the electrical activity generated and propagated in the myometrium.

      To our knowledge, no study has reported oxytocin or carbetocin effects using postpartum
      electromyography.

      OBJECTIVE The objective of the study is to compare efficacy and objectively quantify the
      effect of carbetocin (Pabal ®) with electromyography compared to the standard uterotonic
      oxytocin (Syntocinon ®) for postpartum hemorrhage prevention.

      METHODS Single-center, randomized, open-label trial.

      After signed informed consent, the cesarean section will be performed. All the patients will
      receive 5 IU of oxytocin bolus and a single oxytocin infusion (10 IU). Subsequently patients
      will be transferred to high dependency unit and allocated randomly into one of two groups:

        1. Carbetocin group Patients will receive a single dose of carbetocin 100 mcg (Pabal ®). An
           electromyogram of the uterus will be performed and a blood sample will be obtained.
           After 2-3 hours another electromyogram will follow, as well as a visual and quantified
           estimation of blood loss.

        2. Oxytocin group Patients will receive 5 IU of oxytocin (Syntocinon ®) as a 250 ml 0.9%
           NaCl infusion. An electromyogram of the uterus will be performed and a blood sample will
           be obtained. After 2-3 hours another electromyogram will follow, as well as a visual and
           quantified estimation of blood loss.

      Another blood sample will be routinely obtained 24 hours after the caesarean section.

      Statistical analysis

      From previous EMG studies, there has been reported difference in means of EMG PS peak
      frequency in labor vs. non-labor patients of (0.56 - 0.44 = 0.12 Hz), and a standard
      deviation of 0.15 Hz. Using power of 0.80, and an α - 0.05, with t-test, gives a desired
      sample size of 26 per group minimum.

      All data will be analyzed according to a pre-established statistical plan. Statistical
      analyses will be performed with SPSS software (version 24.0; IBM Corporation, Armonk, New
      York).

      Data will be entered as numerical or categorical, as appropriate. Shapiro-Wilk test will be
      used to assess normality of distribution. Parametric statistics will be carried out for
      normally distributed variables; for non-normal distribution, nonparametric statistics will be
      used. Data with normal distribution will be described using minimum, maximum and mean with
      standard deviation. Data with non-normal distribution will be shown using minimum, maximum,
      median, and interquartile range (IQR). Comparisons will be carried out between the study
      groups using independent Student's t test or Mann-Whitney U test for continuous and with
      Chi-square test for categorical variables.
    

Intervention name(s): Carbetocin; Oxytocin
Intervention type(s): Drug; Drug
Intervention description(s): Patients will receive a single dose of carbetocin 100 mcg (Pabal ®) at admission to high dependency obstetric unit after cesarean section.; Patients will receive 5 units of oxytocin ( Syntocinon ®) as a 250 ml 0.9% NaCl infusion at admission to high dependency obstetric unit after cesarean section.
Intervention MeSH terms: Oxytocin; Carbetocin
Allocation: Randomized
Intervention model: Parallel Assignment
Masking: None (Open Label)
Primary purpose: Treatment
Keywords: electohysterography; postpartum hemorrhage; uterine electromyography