Buccal Misoprostol During Cesarean Section for Preventing Postpartum Hemorrhage

Buccal Misoprostol During Cesarean Section for Preventing Postpartum Hemorrhage in Women With Risk Factors for Uterine Atony

Objective: to demonstrate that buccal misoprostol administration during cesarean delivery in women with risk factors for uterine atony decreases the need for additional uterotonic medications, uterine atony and postpartum hemorrhage.

Design: randomized, double-blinded, placebo-controlled trial.

Study Overview

• Status: Completed
• Conditions: Postpartum Hemorrhage
• Intervention / Treatment: Drug: Misoprostol; Drug: Folic Acid

Detailed Description

Patients and methods: 120 pregnant women with risk factors for uterine atony who underwent cesarean delivery were assigned randomly to either 400 mcg misoprostol (n=60) or placebo (n=60) placed in buccal space after umbilical cord clamping. The primary outcome variables were the need for additional uterotonic agents, estimated blood loss and uterine atony.

• Study Type: Interventional
• Enrollment (Actual): 123
• Phase: Phase 4

Contacts and Locations

Study Locations

• Mexico
  • Nuevo León
    • Monterrey, Nuevo León, Mexico, 64460
      • Hospital Universitario Dr. Jose Eleuterio Gonzalez

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: ADULT; OLDER_ADULT; CHILD
• Accepts Healthy Volunteers: Yes
• Genders Eligible for Study: Female

Description

Inclusion Criteria:

• Women who underwent delivery either by elective or emergent cesarean section at 24 week gestation or later with preoperative levels of hemoglobin and hematocrit determined up to 72 hours prior to delivery. The patients must have at least one of the risk factors for uterine atony listed below:

  1. Fetal macrosomia (estimated fetal weight ≥ 4 Kilos) diagnosed by clinical measurement (Johnson´s technique) or ultrasound measurement (Hadlock´s formula).
  2. Polyhydramnios (defined as Phelan´s amniotic fluid index > 24 cm)
  3. Twin or Multiple pregnancy.
  4. Prolonged labour (prolonged active phase > 12 hours) or precipitate labour(cervical dilatation ≥ 10 cm/hour).
  5. Magnesium sulphate or any other tocolytic agent therapy for ≥ 8 hours before cesarean section.
  6. Intravenous oxytocin therapy for at least 4 hours before cesarean section.
  7. Multiparous women (≥ 3 prior abdominal or vaginal deliveries )
  8. Clinical chorioamnionitis was defined as maternal temperature of ≥ 38°C in addition to more than one of the following criteria: fetal tachycardia (> 160 beats per minute), maternal tachycardia (>100 beats per minute, maternal leukocytosis (15,000 cells/mm3), uterine tenderness or foul smelling amniotic fluid.
  9. Known myomatosis, uterine Müllerian malformations or those diagnosed by ultrasound.

Exclusion Criteria:

1. Misoprostol incorrect administration
2. Severe allergic, bleeding disorders (e.g., haemophilia); severe asthma or any other absolute contraindication to misoprostol use.
3. Any bleeding occurred before delivery (abruptio placentae, placenta praevia) or bleeding due to other causes different than uterine atony.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: PREVENTION
• Allocation: RANDOMIZED
• Interventional Model: PARALLEL
• Masking: DOUBLE

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
EXPERIMENTAL: Misoprostol; women with risk factors for uterine atony who underwent cesarean delivery were assigned randomly to 400 mcg misoprostol (2 tablets) (n=60) placed in buccal space after umbilical cord clamping by anesthesiologist. The primary outcome variables were the need for additional uterotonic agents, estimated blood loss and uterine atony.	Drug: Misoprostol; At cord clamping 2 tablets (400 mcg) were placed in the patient´s buccal space by anesthesiologist.; Other Names: Cytotec
PLACEBO_COMPARATOR: Folic Acid; women with risk factors for uterine atony who underwent cesarean delivery were assigned randomly to 10 mg Folic acid (2 tablets) (n=60) placed in buccal space after umbilical cord clamping by anesthesiologist. The primary outcome variables were the need for additional uterotonic agents, estimated blood loss and uterine atony.	Drug: Folic Acid; At cord clamping 2 tablets (10 mg) were placed in the patient´s buccal space by anesthesiologist.; Other Names: Placebo

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Need for Additional Uterotonic Medications	The surgeon requested additional uterotonic agents on the basis of the clinical findings during surgery (e.g. uterine atony or blood loss of at least 1000 mL) Additional oxytocin was considered additional oxytocic intervention for purposes of data analysis.	24 hours

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Uterine Atony	Uterine atony is defined as failure of the uterus to contract adequately following delivery. Recognition of a soft, "boggy" uterus in the setting of excessive postpartum bleeding can alert the attendant to atony and should trigger a series of interventions aimed at achieving tonic sustained uterine contraction.	24 hours
Postpartum Hemorrhage	Defined as: Estimated blood loss ≥1000 mL after cesarean delivery. A substantial fall in the haematocrit e.g. 10% The requirement for a blood transfusion	24 HOURS
Blood Loss		24 hours

Collaborators and Investigators

• Sponsor: Hospital Universitario Dr. Jose E. Gonzalez

Publications and helpful links

General Publications

• Hamm J, Russell Z, Botha T, Carlan SJ, Richichi K. Buccal misoprostol to prevent hemorrhage at cesarean delivery: a randomized study. Am J Obstet Gynecol. 2005 May;192(5):1404-6. doi: 10.1016/j.ajog.2004.12.033.
• Hernandez-Castro F, Lopez-Serna N, Trevino-Salinas EM, Soria-Lopez JA, Sordia-Hernandez LH, Cardenas-Estrada E. Randomized double-blind placebo-controlled trial of buccal misoprostol to reduce the need for additional uterotonic drugs during cesarean delivery. Int J Gynaecol Obstet. 2016 Feb;132(2):184-7. doi: 10.1016/j.ijgo.2015.06.060. Epub 2015 Oct 23.

Study record dates

Study Major Dates

• Study Start: February 1, 2008
• Primary Completion (ACTUAL): December 1, 2013
• Study Completion (ACTUAL): December 1, 2013

Study Registration Dates

• First Submitted: November 16, 2012
• First Submitted That Met QC Criteria: November 26, 2012
• First Posted (ESTIMATE): November 27, 2012

Study Record Updates

• Last Update Posted (ACTUAL): October 11, 2018
• Last Update Submitted That Met QC Criteria: October 9, 2018
• Last Verified: October 1, 2018

More Information

Terms related to this study

• Keywords: Postpartum Hemorrhage; Uterine Atony; Buccal Misoprostol
• Additional Relevant MeSH Terms: Pathologic Processes; Pregnancy Complications; Obstetric Labor Complications; Puerperal Disorders; Uterine Hemorrhage; Hemorrhage; Postpartum Hemorrhage; Physiological Effects of Drugs; Gastrointestinal Agents; Micronutrients; Vitamins; Reproductive Control Agents; Anti-Ulcer Agents; Vitamin B Complex; Hematinics; Abortifacient Agents, Nonsteroidal; Abortifacient Agents; Oxytocics; Misoprostol; Folic Acid
• Other Study ID Numbers: GI07-011