What are the different drugs used for postpartum hemorrhage (PPH) management?

Drugs for Postpartum Hemorrhage Management

The management of postpartum hemorrhage (PPH) requires a systematic approach with uterotonics as first-line treatment, followed by tranexamic acid within 3 hours of birth, and additional pharmacological and mechanical interventions as needed. 1

Definition of PPH

• PPH is defined as blood loss ≥500 mL after vaginal birth or ≥1000 mL after cesarean section, or any blood loss sufficient to compromise hemodynamic stability 2, 1
• PPH is the leading cause of maternal mortality globally, with most deaths occurring within the first 24 hours after birth 2

First-Line Treatment: Uterotonics

Oxytocin

• First-line uterotonic for both prevention and treatment of PPH 3, 4, 5
• Dosage: 5-10 IU slow IV or IM injection, followed by maintenance infusion not exceeding a cumulative dose of 40 IU 3, 4
• For prevention: Administer 5-10 IU at the time of shoulder release or immediately postpartum 2
• For treatment: Initial dose of 5-10 IU slow IV or IM, followed by infusion 4
• Mechanism: Binds to G protein-coupled receptors in the uterus, but subject to desensitization with repeated or prolonged administration 5

Second-Line Uterotonics (when oxytocin fails)

Methylergonovine (Ergot alkaloid)

• Dosage: 0.2 mg IM 6
• Should be administered within 30 minutes of PPH diagnosis if oxytocin fails 4
• Contraindicated in patients with hypertension and cardiovascular disease 6, 5

Carboprost tromethamine (Prostaglandin F2α)

• Indicated for PPH due to uterine atony that has not responded to conventional management 7
• Prior treatment should include IV oxytocin, uterine massage, and (unless contraindicated) intramuscular ergot preparations 7
• Dosage: 250 μg IM, may be repeated at 15-90 minute intervals up to a maximum of 8 doses 7
• Contraindicated in patients with active cardiac, pulmonary, renal, or hepatic disease 5

Antifibrinolytic Treatment

Tranexamic Acid (TXA)

• WHO strongly recommends early use of intravenous TXA (within 3 hours of birth) for clinically diagnosed PPH 2, 1
• Dosage: 1 g (100 mg/mL) IV at 1 mL/min (over 10 minutes) 2, 1
• A second dose of 1 g IV should be given if bleeding continues after 30 minutes or restarts within 24 hours 2, 1
• Must be administered within 3 hours of birth, as effectiveness decreases by approximately 10% for every 15-minute delay 2, 1
• Should not be given beyond 3 hours after birth due to potential harm 2, 1
• Indicated regardless of cause of bleeding (uterine atony or trauma) 2

Comprehensive PPH Management Algorithm

1. Prevention: Active management of third stage of labor with oxytocin 5-10 IU slow IV/IM immediately after delivery 2, 3, 8

2. Initial Assessment: When PPH is diagnosed:

   • Perform manual uterine examination 4
   • Visually assess lower genital tract 4
   • Perform uterine massage 4
   • Place blood collection bag to measure ongoing loss 4

3. First-line Treatment:

   • Administer oxytocin 5-10 IU slow IV/IM, followed by maintenance infusion (not exceeding 40 IU total) 3, 4
   • Begin fluid resuscitation if bleeding persists 4

4. Second-line Treatment (if bleeding continues after 30 minutes):

   • Administer second-line uterotonics (methylergonovine or carboprost) 7, 6, 4
   • Administer tranexamic acid 1 g IV over 10 minutes (within 3 hours of birth) 2, 1
   • Consider second dose of tranexamic acid if bleeding continues after 30 minutes or restarts within 24 hours 2, 1

5. Third-line Treatment:

   • Consider intrauterine balloon tamponade 4
   • Prepare for possible surgical or radiological intervention if pharmacological management fails 4

Important Considerations

• Maintain hemoglobin concentration >8 g/dL and fibrinogen level ≥2 g/L 4
• Administer oxygen in cases of severe PPH 4
• Prevent and treat hypothermia by warming infusion solutions and blood products 4
• Consider massive transfusion protocols for blood loss exceeding 1,500 mL 8
• Avoid methylergonovine in patients with hypertension or cardiovascular disease 2, 5
• Slow injection of all uterotonics is strongly recommended to minimize cardiovascular side effects 5

Pitfalls to Avoid

• Delaying tranexamic acid administration beyond 3 hours after birth (ineffective and potentially harmful) 2, 1
• Continuing with the same uterotonic when it fails to control bleeding (switch to a drug with different mechanism of action) 5
• Performing manual removal of placenta outside specialized structures (except in cases of severe, uncontrollable PPH) 2
• Using methylergonovine in patients with hypertension (risk of severe hypertensive crisis) 2, 5