Postpartum hemorrhage (PPH) is an obstetric emergency and a leading cause of maternal mortality. It directly impacts maternal and infant safety as well as the quality of obstetric care. With the rising number of high-risk pregnancies—such as placenta previa, placenta accreta, and scarred uteri—the difficulty of precise clinical prevention and treatment has increased significantly. To address this, Obstetrics and Gynecology Network invited Professor Zhang Yan from The Affiliated Hospital of Qingdao University to analyze the precision selection of drugs, optimal timing of administration, and practical protocols for managing placenta-related refractory hemorrhage.
Expert Profile
Zhang Yan, Professor
Director of Obstetrics, Shinan District Campus, The Affiliated Hospital of Qingdao University
MD, Associate Chief Physician
Professor Zhang graduated from Qingdao University, majoring in Clinical Obstetrics and Gynecology. She served as a visiting scholar in Reproductive Medicine at the University of California, San Diego (UCSD). Currently, she serves as the Deputy Chairman of the Obstetric Safety and Rapid Response Committee of the Shandong Maternal and Child Health Association, and the Deputy Chairman of the Postpartum Rehabilitation Committee of the Shandong Rehabilitation Medicine Association. She is also a committee member of the Obstetrics and Gynecology Branch of the Qingdao Medical Association.
With years of dedication to clinical obstetrics, teaching, and research, Professor Zhang possesses extensive clinical experience and strong research capabilities. She specializes in perinatal care, high-risk pregnancy, and the diagnosis and treatment of placenta-related diseases. She has participated in two national-level scientific research projects, co-authored one monograph, published several SCI papers, and received the Third Prize of the Shandong Provincial Science and Technology Innovation Achievement Award.
Q: Drawing from your experience in high-risk pregnancy and placenta-related diseases, how should clinicians precisely select uterotonics and hemostatic agents for different types of PPH? What are the key determinants for timing prophylactic versus therapeutic medication?
Professor Zhang Yan:
High-risk pregnancies complicated by placenta-related diseases, such as placenta previa and accreta, represent a high-risk group for postpartum hemorrhage. This type of bleeding mostly occurs during cesarean sections, though it can occasionally happen after vaginal delivery. Clinically, we must precisely select uterotonics and hemostatics based on the mode of delivery and the type of bleeding, while strictly adhering to the timing of administration.
Part 1: Precision Selection of Uterotonics and Hemostatics
First-Line Uterotonics (Prophylactic Preferred)
Oxytocin is the first-line uterotonic recommended by domestic and international guidelines for preventing all types of postpartum hemorrhage. During a cesarean section, it is routinely administered via intramuscular injection into the uterine body combined with intravenous drip immediately after fetal delivery. For vaginal deliveries, oxytocin is initiated upon entry into the third stage of labor to strengthen uterine contractions. Most patients with placenta previa achieve controllable bleeding and enhanced uterine tone with oxytocin alone, requiring no additional drugs.
Second-Line Uterotonics (Therapeutic Reserve)
Second-line uterotonics should be prepared routinely before surgery for cases where oxytocin proves insufficient. These include Methylergometrine, Carboprost Tromethamine, and Carboprost Suppositories. Carboprost Tromethamine is widely used clinically due to its strong and rapid onset; it can be repeated every 15 minutes and is the preferred drug for atonic bleeding caused by placental adhesion or accreta. Carboprost Suppositories are convenient to administer and are often combined with Carboprost Tromethamine to enhance overall uterine contractility. Methylergometrine shows significant efficacy for the lower uterine segment, making it the preferred second-line option in some institutions.
Hemostatic Agents (Combination Therapy)
Tranexamic Acid is the core hemostatic agent. As an antifibrinolytic, it is suitable for moderate-to-severe postpartum hemorrhage. It is recommended to administer it via rapid intravenous infusion within 30 minutes of bleeding onset to inhibit the fibrinolytic system and reduce blood loss. It is particularly effective for placenta-related refractory hemorrhage.
Part 2: Timing Judgment for Prophylactic vs. Therapeutic Use
Postpartum hemorrhage progresses rapidly, and there is no absolute boundary between prophylactic and therapeutic medication. The core principle is early assessment, strict monitoring, and timely escalation to avoid missing the optimal intervention window.
Timing of Prophylactic Medication
For cesarean sections, oxytocin should be initiated immediately upon fetal delivery. For vaginal deliveries, it should be used routinely upon entry into the third stage of labor. This applies to patients with no obvious bleeding, a clear uterine outline, and fair uterine tone, aiming to prevent atony and reduce placental site bleeding.
Indications for Initiating Therapeutic Medication
If the following situations occur, immediately stop simple prophylactic medication and escalate to second-line uterotonics combined with hemostatics:
• During Cesarean Section: The uterus is soft and boggy with an unclear outline, and bleeding in the surgical field continues to increase unresponsive to oxytocin.
• After Vaginal Delivery: Blood loss continues to increase, fundal massage yields no effective uterine tone, or there is delayed/detained placental separation.
• Early Signs of Shock: Maternal thirst, agitation, tachycardia, oliguria, or an abnormal shock index.
• Warning: Be vigilant against "trickling" (slow, steady) bleeding. This type is easily overlooked but can induce Disseminated Intravascular Coagulation (DIC).
Special Considerations
We must be wary of bleeding caused by soft tissue lacerations. Do not over-focus on uterine tone and placental factors while missing a laceration diagnosis. If the uterus is well-contracted and the placenta is intact but bleeding persists, immediately examine the cervix and vagina, exclude lacerations, and perform timely suturing.
Q: Regarding placenta-related refractory postpartum hemorrhage, could you share some practical clinical experiences regarding the use of potent uterotonics, dosage control, and combination therapy?
Professor Zhang Yan:
Placenta-related refractory postpartum hemorrhage refers to cases involving placental adhesion, partial separation, accreta, or pernicious placenta previa where bleeding remains uncontrolled despite conventional uterotonics and uterine massage. Management requires combining potent uterotonics, hemostatics, and surgical maneuvers. Here are some practical clinical experiences.
Part 1: Potent Uterotonic Use and Dosage Control
Oxytocin (Baseline Maintenance)
For cesarean sections, 20 units are given via intramuscular injection into the uterine body and 10 units via intravenous drip immediately after fetal delivery, maintaining uterine tone throughout. For vaginal deliveries, continuous intravenous infusion of oxytocin is used as baseline maintenance therapy.
Carboprost Tromethamine (Core Potent Agent)
It is administered via intramuscular or direct myometrial injection. It can be repeated every 15 minutes as needed. It is the first choice for active bleeding caused by partial placental separation, accreta, or pernicious placenta previa when oxytocin is ineffective.
Carboprost Suppository (Auxiliary)
Used in combination with Carboprost Tromethamine to enhance the contractile ability of the entire uterine wall, especially suitable for lower uterine segment bleeding. It has high clinical safety and is convenient to operate.
Methylergometrine (Targeted)
It has a significant effect on the lower uterine segment and is suitable for bleeding from the placental implantation site in the lower segment. If there are no contraindications, it can be combined with Carboprost Tromethamine.
Part 2: Combination Therapy Protocols (Practical Clinical Operations)
For Simple Placental Adhesion
Administer Oxytocin via intravenous drip combined with a single dose of Carboprost Tromethamine. Once uterine tone improves, manually remove the placenta under the protection of the medication. Maintain open intravenous access and continuously monitor vital signs.
For Partial Separation or Partial Accreta (The Most Challenging Type)
Administer Oxytocin (IV) + Carboprost Tromethamine (repeatable every 15 minutes) + Carboprost Suppository + Tranexamic Acid (IV). Once uterine tone improves, clean the detached placental tissue under ultrasound guidance. Never perform violent manual removal of the placenta.
For Complete Placenta Accreta (No Separation)
It is strictly forbidden to forcibly strip the placenta. After disinfecting the umbilical cord, reduce it back into the uterine cavity. Administer continuous intravenous Oxytocin + Carboprost Tromethamine + Carboprost Suppository to prevent uterine bleeding. Simultaneously use antibiotics to prevent infection and dynamically monitor the placental expulsion status afterward.
For Pernicious Placenta Previa (Scarred Uterus with Accreta)
Immediately upon fetal delivery, initiate triple therapy: Oxytocin (intramuscular + intravenous) + Carboprost Tromethamine + Tranexamic Acid (within 30 minutes of bleeding). Simultaneously perform surgical hemostasis, including uterine artery ascending branch ligation, B-Lynch compression sutures, and intrauterine balloon tamponade. If necessary, combine with uterine artery interventional embolization.
Part 3: Key Practical Points
Adequate Preoperative Preparation
For high-risk patients, routinely prepare all first- and second-line uterotonics, Tranexamic Acid, and blood products to avoid drug shortages during surgery. Complete ultrasound examinations to evaluate the depth and range of placental invasion and formulate a hysterectomy contingency plan in advance.
Synchronization of Medical and Surgical Treatment
Medical therapy and surgical hemostasis must proceed simultaneously. During cesarean sections, combine with uterine artery ligation and local sutures at the implantation site. After vaginal delivery, combine with intrauterine balloon or gauze packing to enhance hemostatic efficacy with drug support.
Strengthening Multidisciplinary Team Collaboration
Refractory postpartum hemorrhage requires multidisciplinary teamwork. Assign dedicated personnel for medication management, intravenous access establishment, blood preparation, and surgical operations. Ensure robust doctor-patient communication and inform the patient/family about the risk of hysterectomy in advance.
Grasping the Ultimate Rescue Solution
If potent uterotonics, hemostatics, and surgical operations are all ineffective, and massive hemorrhage or signs of DIC appear, a hysterectomy must be performed decisively to save the mother's life.
Summary
This interview series focuses on the precise prevention and standardized treatment of postpartum hemorrhage. Professor Xu Qian clarified the principles of medication safety, stratification, and sequencing from the dual perspectives of obstetric quality control and critical rescue, proposing methods for constructing standardized medication thinking and linkage rescue pathways for overlapping high-risk bleeding. Professor Zhang Yan, grounded in clinical experience with high-risk pregnancy and placental diseases, detailed the precision selection of uterotonics, optimal timing, and practical combination protocols for placenta-related refractory hemorrhage, explaining drug combinations, surgical coordination, and ultimate rescue essentials. Both experts addressed key clinical pain points, integrating quality control standards with frontline experience to provide authoritative, actionable guidance for the precise medication, stratified treatment, and critical management of postpartum hemorrhage, thereby enhancing the capabilities of obstetric staff and safeguarding maternal and infant safety.
Editor: Huo Pan
