Case Study
A healthy nulliparous woman was admitted to the delivery suite at 40 weeks’ gestation for induction of labor of a postdates pregnancy. During her pregnancy, she developed gestational diabetes mellitus (GDM), managed with dietary control.
Labor was induced with the application of intravaginal dinoprostone gel. Six hours later, on examination, the cervix was 3 cm dilated, and the patient was contracting every 4–6 minutes. She requested labor analgesia, and an epidural was inserted by the anesthetist, which produced satisfactory analgesia.
Due to slow labor progression, augmentation was required, and the patient underwent artificial rupture of membranes (AROM). Following this, a continuous oxytocin infusion at 2 mU/min was started, which was doubled every 30 minutes until a maximum rate of 32 mU/min was administered. Labor progression remained slow, and 12 hours later, the patient’s cervix was only 6 cm dilated. She also developed a temperature of 38.5°C and was treated with antibiotics for suspected chorioamnionitis.
A decision was made for cesarean delivery for failure to progress in labor, and the patient’s epidural was topped up in the OR. Following delivery of the baby, the obstetrician commented that the uterus was “boggy,” and there was active bleeding. Uterine atony was diagnosed. Oxytocin 5 units was administered intravenously as a bolus, and an infusion of 20 units/liter was started. The uterus remained atonic, and the estimated blood loss exceeded 1,200 ml. As a second-line agent, ergonovine 250 µg diluted in 10 ml normal saline, was given slowly intravenously. The obstetrician continued with uterine massage and administered carboprost 250 µg intramyometrially and misoprostol 1,000 µg rectally.
The patient’s total blood loss was estimated at 2,000 ml, and she was resuscitated with fluid therapy and blood products. Her uterine tone improved, and her bleeding ceased.
Key Points
Patients may experience uterine atony secondary to multiple factors, including prolonged augmented labor, GDM, and chorioamnionitis.
Multiple pharmacologic uterotonics for management of uterine atony may be required, including resuscitative measures for the effective management of postpartum hemorrhage (PPH).
Discussion
Postpartum Hemorrhage and Uterine Atony
The World Health Organization (WHO) defines primary PPH as maternal blood loss of 500 ml or more within 24-hours following birth. PPH is a global problem, with an incidence affecting 2 percent of all deliveries and is responsible for nearly one-quarter of all maternal deaths. Furthermore, the morbidity associated with PPH can be severe and includes hemorrhagic shock, subsequent multiorgan failure, and long-term disability.1
The pathogenesis of PPH includes the four T’s: tone (uterine atony), tissue (retained placenta or clots), thrombin (maternal coagulopathy), and trauma (genital tract). Of these, uterine atony is the most common cause, accountable for approximately 75 percent of PPH cases. Numerous factors are associated with uterine atony, and often a parturient may have multiple predisposing conditions (Table 25.1).
| Overdistension of uterus | Polyhydramnios |
| Multiple gestation | |
| Macrosomia | |
| Uterine muscle exhaustion | Rapid labor |
| Prolonged labor | |
| High parity | |
| Intrapartum oxytocin administration | |
| Intra-amniotic infection | Fever |
| Prolonged rupture of membranes | |
| Functional/anatomic distortion of the uterus | Fibroids |
| Abnormal placentation | |
| Uterine anomalies | |
| Uterine relaxing medications | Halogenated anesthetics |
| Nitroglycerin |
Uterotonics
There is significant evidence2 to suggest that active management of the third stage of labor (AMTSL) versus expectant management is important in reducing PPH, and this is advocated by several international organizations.1, 3, 4 Expectant management is a conservative or more physiologic approach, which awaits the natural separation of the placenta. Conversely, active management requires clinician intervention and encompasses three components following delivery: the administration of prophylactic uterotonic agents, early cord clamping, and controlled traction of the umbilical cord.2
On delivery, contraction of the myometrium is essential to ensure that muscle fibers exert tension on the maternal vessels to cause vasoconstriction and limit excessive bleeding.2 This process can be augmented by the use of uterotonic agents. The WHO guidance advocates that the active management of the third stage of labor, through the administration of prophylactic uterotonics, following all births is mandated, and this includes vaginal births and cesarean deliveries.1
There are three main classes of uterotonic agents in current clinical practice, all with different mechanisms of actions and adverse effects (Figure 25.1, Table 25.2):
Figure 25.1 Schematic illustration of uterotonic mechanisms leading to myometrial cell contraction. Oxytocin binds to the OTR, which leads to an increase in the production of InsP3 and DAG. InsP3 stimulates the release of calcium from internal stores, and this promotes the formation of the calcium–calmodulin complex and ultimately smooth muscle contraction. DAG increases PG synthesis. Prostaglandin analogues bind to the PG receptor, which stimulates synthesis of the OTR. Ergonovine binds to either the 5-HT or α1-receptor, which leads to a rise in intracellular calcium.
Table 25.2 Uterotonic Drugs, Administration Methods, Doses, Onset Time, Duration of Action, Side Effects, and Major Contraindications
| Uterotonic drug | Administration | Onset | Duration of action | Side effects | Major contraindications |
|---|---|---|---|---|---|
| Oxytocin | IV slow bolus: 5 units over 1 minute (can repeat for a second dose) | IV: <1 minute | IV: 20 minutes | Reduction in SVR (hypotension, tachycardia, arrhythmia) | Hypotension |
| IV continuous infusion: 20–40 units (rate as per local policy or clinical scenario) | IM: 3–5 minutes | IM: 30–90 minutes | Nausea and vomiting | Hemodynamic instability | |
| IM: 5–10 units | |||||
| Carbetocin | IV slow bolus: 100 µg over 1 minute | IV: 2 minutes | IV: 60 minutes | Reduction in SVR (hypotension, tachycardia, arrhythmia) | Hypotension |
| IM: 100 µg | IM: 2 minutes | IM: 120 minutes | Nausea and vomiting | Hemodynamic instability | |
| Ergonovine maleate | IV: 200–250 µg, slow, diluted over 1 minute | IV: <1 minute | IV: 45 minutes | Hypertension | Hypertension (pregnancy induced, preeclampsia, or preexisting) |
| Nausea and vomiting | |||||
| M: 200–250 µg (can repeat second dose after 2 hours) | 2–3 minutes | 3 hours | Increased risk of retained placenta | Myocardial ischemia | |
| Porphyria | |||||
| Methylergonovine | IM: 200 µg | As per ergonovine maleate | |||
| IV: 200 µg, slow, diluted, over 1 minute | |||||
| Carboprost tromethamine | IM: 250 µg | IM: 3–5 minutes | IM: 60–120 minutes | Bronchospasm | Asthma |
| (15-methyl PGF2α) | Intramyometrial: 250 µg (unlicensed use) (Can repeat every 15 minutes; total of 8 doses; 2 mg maximum) | IMM: No data | IMM: No data | Nausea and vomiting | Caution in hepatic, renal, or cardiac disease |
| Headaches | |||||
| Shivering | |||||
| Misoprostol | PO, SL, PV or PR: 600–1,000 µg | PO: 8 minutes | PO:120 minutes | Pyrexia | |
| (PGE1 analogue) | SL: 11 minutes | SL: 180 minutes | Diarrhea | ||
| PV: 20 minutes | PV: 240 minutes | Nausea and vomiting | |||
| PR: 100 minutes | PR: 240 minutes | (All side effects less with PR) | |||
| Syntometrine | IM: oxytocin 5 units + ergonovine 500 µg | As per oxytocin and ergonovine | |||
Oxytocin and Its Analogues
Oxytocin is an endogenous hormone synthesized primarily in the hypothalamus and secreted by the posterior lobe of the pituitary gland. It has several roles in the process of reproduction and childbirth, but its effects on myometrial contractility in the peripartum period are of utmost significance. As a result, synthetic oxytocin can be administered exogenously for labor induction, augmentation, and prophylaxis or treatment of PPH. Due to its short duration of action, oxytocin is commonly delivered as a continuous IV infusion.
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