Methergine (Methylergonovine) and Carboprost in Obstetric Anaesthesia

METHERGINE (Methylergonovine Maleate)

Drug Class

Mechanism of Action

• Uterine smooth muscle: intense and prolonged uterotonic contractions - both the fundus and lower segment contract tonically
• Vascular smooth muscle: diffuse vasoconstriction via alpha-1 adrenergic and serotonergic pathways, raising both systemic and pulmonary vascular resistance
• The uterus at term is far more sensitive to ergot than the non-pregnant uterus, due to increasing dominance of alpha-1 receptors as pregnancy progresses

Indications (Obstetric)

• Postpartum haemorrhage (PPH) due to uterine atony - used as second-line after oxytocin fails
• Prevention and treatment of postpartum/post-abortion uterine haemorrhage
• Subinvolution of the uterus

Dose & Route

• 0.2 mg IM (standard dose) - repeated every 20 minutes as needed
• IV: only as dilute slow infusion over 10 minutes (NEVER as rapid IV bolus - causes severe hypertension)
• Oral: 0.2 mg every 6-8 hours (postpartum maintenance)

Duration of Action

• IM: onset 2-5 min, duration 2-4 hours (prolonged tonic contraction)
• IV: onset within 1 min, shorter but intense effect
• Ergot alkaloids as a class produce effects lasting 2-4 hours

Contraindications

• Hypertension (any degree - absolute contraindication due to vasoconstrictor effect)
• Pre-eclampsia / eclampsia
• Cardiovascular disease: coronary artery disease, angina, peripheral vascular disease
• Pulmonary hypertension - increases PA pressures further
• Mitral stenosis / aortic stenosis - worsens by increasing SVR
• Sepsis / febrile states
• Ergot hypersensitivity
• Induction of labour or before delivery of placenta (risk of trapped placenta, fetal asphyxia)
• Hepatic or renal impairment (reduced drug clearance)

Anaesthetic Considerations

1. Haemodynamic crisis if given IV bolus: Rapid IV injection causes severe hypertension, coronary artery vasospasm, and risk of MI or stroke - always give IM or slow IV infusion over 10 min
2. Contraindicated with vasopressors: Do not combine with ergometrine/methergine when vasopressors (phenylephrine, ephedrine) are already on board - additive vasoconstriction
3. Cardiac patients: Both methylergonovine and carboprost tromethamine increase pulmonary and systemic vascular resistance - these drugs can worsen conditions with elevated PA pressures (pulmonary hypertension, mitral stenosis) and worsen regurgitant lesions that benefit from low SVR
4. Interaction with volatile agents: Volatile anaesthetic agents at >0.5 MAC relax the uterus and can counteract uterotonic therapy; reduce to 0.5 MAC for caesarean section
5. Neuraxial anaesthesia: Spinal/epidural blocks decrease SVR - when methergine is given concurrently, the net haemodynamic effect depends on the relative magnitude; monitor BP closely
6. Nausea/vomiting: Common; have antiemetics ready (ondansetron, metoclopramide)

CARBOPROST TROMETHAMINE (Hemabate, 15-methyl PGF2α)

Drug Class

Mechanism of Action

• Binds prostaglandin FP receptors on uterine smooth muscle → activates IP3/DAG signalling → sustained myometrial contractions
• Stimulates both fundal and lower uterine segment contractions
• Also contracts bronchial smooth muscle → bronchoconstriction
• Increases pulmonary and systemic vascular resistance
• Stimulates GI smooth muscle → nausea, vomiting, diarrhea
• Increases cervical ripening

Indications (Obstetric)

• Refractory PPH due to uterine atony (after oxytocin and ergometrine have failed - third-line or concurrent second-line agent)
• Mid-trimester abortion (15-methyl PGF2α is highly effective for second-trimester termination)
• Cervical ripening (less common; other prostaglandins preferred)

Dose & Route

• 0.25 mg IM initially
• Repeat every 15 to 90 minutes based on clinical response
• Maximum total dose: 2 mg (8 doses)
• Can also be given intramyometrially (direct injection) in theatre settings

Duration of Action

• Onset: 15-20 minutes (IM)
• Duration: approximately 1-2 hours per dose; the 15-methyl modification makes it significantly more resistant to metabolic degradation than native PGF2α, extending its action

Contraindications

• Asthma (absolute contraindication - causes severe bronchoconstriction; can precipitate life-threatening bronchospasm)
• Pulmonary hypertension - increases PA pressures further
• Active cardiovascular disease
• Hepatic disease (metabolised in the liver)
• Renal disease
• Active pelvic inflammatory disease
• Hypersensitivity to prostaglandins

Anaesthetic Considerations

1. Bronchoconstriction: The most critical anaesthetic concern. In ventilated patients (general anaesthesia for caesarean), carboprost can cause sudden severe bronchospasm - monitor airway pressures, have bronchodilators (salbutamol, ipratropium) immediately available
2. Pulmonary and SVR rise: Like methylergonovine, carboprost increases both pulmonary and systemic vascular resistance - dangerous in patients with pulmonary hypertension, mitral stenosis, or Eisenmenger syndrome
3. Haemodynamic monitoring: In cardiac disease patients, the haemodynamic consequences of this agent can be lethal - use with extreme caution and full monitoring
4. GI effects: Nausea, vomiting, and diarrhoea are common - antiemetic cover is important, especially under neuraxial anaesthesia where vomiting during spinal block is distressing
5. Fever: Pyrexia is a recognised side effect - can confound postoperative assessment
6. Ventilated patients: If bronchospasm occurs intraoperatively, increase FiO2, use bronchodilators, consider deepening anaesthesia with propofol or ketamine (ketamine has bronchodilator properties), and avoid carboprost in known asthmatics
7. Interaction with oxytocin: Carboprost is additive with oxytocin in uterotonic effect; titrate total uterotonic load carefully to avoid tetanic uterine contraction and impaired uteroplacental perfusion

Comparison Table

Key Shared Anaesthetic Concerns

• Both agents increase pulmonary vascular resistance - avoid in pulmonary hypertension, Eisenmenger syndrome, severe mitral stenosis
• Both are second-line uterotonics after oxytocin fails
• Both augment uterine tone - if volatile agents are in use at >0.5 MAC they will counteract uterotonic therapy; reduce to 0.5 MAC
• Ensure IV access, vasopressors, and resuscitation equipment are ready before administration
• In cardiac-compromised patients, consider invasive monitoring (arterial line) before giving either agent

• Morgan and Mikhail's Clinical Anesthesiology, 7th Edition, pp. 1590-1591
• Creasy & Resnik's Maternal-Fetal Medicine, Tables 70.4 and 70.5, pp. 1730-1733
• Katzung's Basic and Clinical Pharmacology, 16th Edition, pp. 461-462