Prevention of Postpartum Hemorrhage in Patients With Severe Preeclampsia Using Carbetocin Versus Misoprostol
Condition: Severe Pre-eclampsia, Postpartum Condition or Complication
MeSH terms: Pre-Eclampsia; Eclampsia
Study type: Interventional
Phase: Phase 3

Summary: 
      We aim to compare carbetocin with misoprostol for the prevention of postpartum hemorrhage in
      patients with severe preeclampsia. The primary outcome is postpartum haemorrhage (blood loss
      of ≥ 500 ml) while our Secondary outcomes include use of additional uterotonics, need for
      blood transfusion, maternal adverse drug reaction, maternal complications and maternal death
    

Detailed description: 
      We conducted a prospective non-randomized study at Department of Obstetrics and Gynecology,
      Benha University Hospital, since March 2013 till June 2015, after approval of the study
      protocol by the Local Ethical Committee. A written informed consent was obtained from
      eligible women before induction or at early stage of labour.

      Women with singleton pregnancies of more than 28 weeks' gestation who are admitted to
      hospital with severe preeclampsia and candidates for vaginal delivery were eligible for the
      study. Preeclampsia is labelled as severe in the presence of any of the following
      abnormalities.

        1. Persistent cerebral or visual disturbances or cerebral edema.

        2. Persistent epigastric pain with nausea or vomiting, or both.

        3. Systolic ≥160 mmHg or diastolic ≥110 mmHg on 2 occasions at least 6 h apart with the
           patient at bed rest.

        4. Proteinuria of ≥5 g on 24-hour urine collection. Urine dipsticks are not accurate for
           this purpose.

        5. Oliguria (˂500 mL in 24 hours).

        6. Pulmonary edema.

        7. Thrombocytopenia.

      Our exclusion criteria are HELLP syndrome, eclampsia, abruptio placentae, malpresentation,
      polyhydramnios, previous uterine scar, chorioamnionitis and multiple pregnancies. All
      patients were in stable condition (no evidence of maternal hemodynamic instability or fetal
      distress) and their management afterwards followed the standards accepted in our country and
      established guidelines for the management of hypertensive disorders of pregnancy. For
      hypertensive crisis the first drug used was hydralazine (5 mg IV every 15 minutes to a
      maximum total dose of 20 mg) and, if this was ineffective, Nifedipine (Epilat): 10 to 20 mg
      orally / 30 min (max 50 mg), Then 10-20 mg /4-6 h (max 120 mg/day) or labetalol (20 mg IV
      every 10 minutes to a maximum total dose of 300 mg). No patient needed additional treatment
      for their symptoms or developed antepartum complications that required admission to the
      intensive care unit. All patients were evaluated hourly and received magnesium sulphate to
      prevent eclampsia during the pregnancy and for a minimum of 24 hours postpartum.

      The patients (60) were divided into two groups, Group A (30) received a single dose of
      carbetocin (100 μg in 1 mL ampoule, Pabal) while Group B (30) received misoprostol (600 μg, 3
      tables) sublingually after the delivery of the anterior shoulder of the baby.

      The third stage of labour is managed as usual by clamping and cutting of umbilical cord,
      waiting for signs of placental separation and delivering the placenta by controlled cord
      traction.

      Duration of the 3rd stage of labour is calculated. Patient is kept in labor room under
      observation for a period of 1 h and any complaint such as nausea, vomiting, fever, headache,
      chills, diarrhoea and shivering is noted. In cases of uterine atony (determined by physical
      examination and continuous postpartum bleeding) uterus is massaged and additional uterotonics
      were given and noted (oxytocin and/or prostaglandin, at the discretion of the attending
      physician). Any requirement for manual removal of the placenta or blood transfusion is also
      recorded.

      The following laboratory assessments (hemoglobin, hematocrit, platelets, and renal and liver
      function tests) are performed in every patient on admission and postpartum. Vital signs
      (blood pressure, heart rate, respiratory rate) and urine output are measured every hour until
      at least 24 hours after delivery.

      Measurement of blood loss A clean plastic lined absorbent drape is placed under the woman's
      buttocks to collect all the blood lost after delivery of the baby and drainage of the
      amniotic fluid. The drape is changed as many times as needed. The woman stays on the drape or
      asked to wear a pad over the next 60 minutes. In the case of severe haemorrhage, we follow
      the usual guidelines for management of postpartum haemorrhage, and the supplemental treatment
      is registered. All drapes and pads are weighed on an electronic scale and the known dry
      weight of the linen is subtracted. As 1 ml of blood weighs close to 1 g, the balance in grams
      is assumed to be the total blood loss in ml.

      Haemoglobin concentration is measured before, 2 hours and 24 hours after delivery.

      The rate of haemorrhage at labour third phase is determined by observation estimation
      considering the amount of blood under the patient. The rate of haemoglobin and haematocrit
      are measured at hospitalization and also 2 h, 24 h after delivery and then are recorded. At
      this interval, the patients are evaluated in terms of possible complications of administered
      drugs such as vomiting, diarrhoea, shivering, pyrexia, and headache).

      All patients have the Foley catheter in situ for 24 hours after delivery and the amount of
      urine was monitored hourly.

      This study has no external funding source. No author had any potential relationships that may
      pose conflict of interest.

      Outcome measures Our primary outcome measure is postpartum haemorrhage, defined as a blood
      loss of ≥ 500 ml. We analyse the blood loss, change in haemoglobin concentration between
      admission and discharge. While secondary outcomes include use of additional uterotonics, need
      for blood transfusion, maternal adverse drug reaction (such as headache, vomiting, abdominal
      pain, pruritus, tacky or bradycardia), sever maternal complications (such as seizures or need
      for ICU admission) and maternal death.
    

Intervention name(s): misoprostol; carbetocin
Intervention type(s): Drug; Drug
Intervention description(s): given after the delivery of the anterior shoulder of the baby.; given after delivery of anterior shoulder
Other intervention name(s): misoprost; cytotec; misotec; pabal
Intervention MeSH terms: Misoprostol; Carbetocin
Allocation: Randomized
Intervention model: Single Group Assignment
Masking: Single (Participant)
Primary purpose: Prevention
Keywords: carbetocin, misoprostol, pre-eclampsia, pph