Postpartum Hemorrhage
Conditions
Keywords
Buccal Misoprostol, Uterine Atony, Postpartum Hemorrhage
Brief summary
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.
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.
Interventions
DRUGMisoprostol
At cord clamping 2 tablets (400 mcg) were placed in the patient´s buccal space by anesthesiologist.
DRUGFolic Acid
At cord clamping 2 tablets (10 mg) were placed in the patient´s buccal space by anesthesiologist.
Sponsors
Hospital Universitario Dr. Jose E. Gonzalez
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
PREVENTION
Masking
DOUBLE (Subject, Investigator)
Eligibility
Sex/Gender
FEMALE
Healthy volunteers
Yes
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.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Need for Additional Uterotonic Medications | 24 hours | 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. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Uterine Atony | 24 hours | 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. |
| Postpartum Hemorrhage | 24 HOURS | 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 |
| Blood Loss | 24 hours | — |
Countries
Mexico
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| Misoprostol women with risk factors for uterine atony who underwent cesarean delivery 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.
Misoprostol | 62 |
| Folic Acid women with risk factors for uterine atony who underwent cesarean delivery 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.
Placebo | 61 |
| Total | 123 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 |
|---|---|---|---|
| Overall Study | Protocol Violation | 1 | 1 |
| Overall Study | Uterine artery injury | 1 | 0 |
Baseline characteristics
| Characteristic | Misoprostol | Folic Acid | Total |
|---|---|---|---|
| Age, Categorical <=18 years | 7 Participants | 4 Participants | 11 Participants |
| Age, Categorical >=65 years | 0 Participants | 0 Participants | 0 Participants |
| Age, Categorical Between 18 and 65 years | 55 Participants | 57 Participants | 112 Participants |
| Age, Continuous | 24.05 years STANDARD_DEVIATION 5.32 | 25.18 years STANDARD_DEVIATION 6.29 | 24.62 years STANDARD_DEVIATION 5.83 |
| Region of Enrollment Mexico | 62 participants | 61 participants | 123 participants |
| Sex: Female, Male Female | 62 Participants | 61 Participants | 123 Participants |
| Sex: Female, Male Male | 0 Participants | 0 Participants | 0 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | — / — | — / — |
| other Total, other adverse events | 0 / 60 | 0 / 60 |
| serious Total, serious adverse events | 0 / 60 | 0 / 60 |
Outcome results
Primary
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.
Time frame: 24 hours
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Misoprostol | Need for Additional Uterotonic Medications | 10 percentage of participants |
| Folic Acid | Need for Additional Uterotonic Medications | 40 percentage of participants |
p-value: <0.01Fisher Exact
Secondary
Blood Loss
Time frame: 24 hours
| Arm | Measure | Value (MEDIAN) | Dispersion |
|---|---|---|---|
| Misoprostol | Blood Loss | 470 mL | Standard Deviation 149.91 |
| Folic Acid | Blood Loss | 653.33 mL | Standard Deviation 342.21 |
p-value: 0.007Kruskal-Wallis
Secondary
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
Time frame: 24 HOURS
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Misoprostol | Postpartum Hemorrhage | 6.6 percentage of patients |
| Folic Acid | Postpartum Hemorrhage | 20 percentage of patients |
p-value: 0.058Fisher Exact
Secondary
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.
Time frame: 24 hours
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Misoprostol | Uterine Atony | 8.3 percentage of participants |
| Folic Acid | Uterine Atony | 25 percentage of participants |
p-value: 0.026Fisher Exact