Treatment of Hyperemesis Gravidarum
Start with dietary modifications and vitamin B6, then escalate systematically through doxylamine-pyridoxine combination, metoclopramide, ondansetron, and reserve corticosteroids as last resort, while ensuring IV hydration and thiamine supplementation for all hospitalized patients. 1
Initial Assessment and Stabilization
Before initiating treatment, assess severity using the PUQE score and check for dehydration, ketonuria, and electrolyte abnormalities 1. Approximately 50% of patients will have abnormal liver function tests (AST/ALT), though rarely exceeding 1,000 U/L 1.
For any patient requiring hospitalization:
- Immediate IV fluid resuscitation to correct dehydration 1
- Electrolyte replacement, particularly potassium and magnesium 1
- Thiamine supplementation (vitamin B1) is mandatory to prevent Wernicke's encephalopathy 1, 2
- Check liver function tests, electrolyte panel, and urinalysis for ketonuria 1
Stepwise Pharmacologic Treatment Algorithm
First-Line Therapy
Doxylamine combined with pyridoxine (vitamin B6) is the preferred initial antiemetic and is safe throughout pregnancy and breastfeeding 1. This combination is recommended by the American College of Obstetricians and Gynecologists as first-line for both mild nausea/vomiting and hyperemesis gravidarum 1.
Alternative first-line options with similar safety profiles include 1:
- Promethazine (antihistamine)
- Cyclizine (antihistamine)
- Prochlorperazine (phenothiazine)
- Chlorpromazine (phenothiazine)
For very mild cases, vitamin B6 alone may suffice 1.
Second-Line Therapy
Metoclopramide is the preferred second-line agent when first-line antihistamines fail, causing less drowsiness, dizziness, and dystonia compared to promethazine in hospitalized patients 1. It is compatible throughout pregnancy and breastfeeding 1.
Ondansetron should be reserved as second-line therapy due to concerns about congenital heart defects when used before 10 weeks gestation, though recent data suggest this risk is low 1. The American College of Obstetricians and Gynecologists recommends using ondansetron on a case-by-case basis before 10 weeks of pregnancy 1. It is compatible throughout pregnancy and breastfeeding after this period 1.
Important caveat: Meta-analysis of 25 studies shows no significant efficacy difference among metoclopramide, ondansetron, and promethazine 1, so choice can be individualized based on timing and side effect profile.
Third-Line Therapy (Refractory Cases)
Methylprednisolone should be reserved as last resort for severe hyperemesis gravidarum failing other therapies 1.
Dosing protocol 1:
- 16 mg IV every 8 hours for up to 3 days
- Then taper over 2 weeks to lowest effective dose
- Maximum duration: 6 weeks
Use with extreme caution in first trimester due to slight increased risk of cleft palate when given before 10 weeks gestation 1.
Alternative refractory-case medications include olanzapine and gabapentin 1, 3.
Non-Pharmacologic Interventions
Dietary modifications should be implemented alongside pharmacotherapy 1:
- Small, frequent, bland meals
- BRAT diet (bananas, rice, applesauce, toast)
- High-protein, low-fat meals
- Avoidance of specific food triggers and strong odors
- Ginger supplementation 1
Monitoring During Treatment
Monitor for QT interval prolongation, especially with ondansetron in patients with electrolyte abnormalities 1.
Withdraw phenothiazines or metoclopramide immediately if extrapyramidal symptoms develop 1.
Regular assessment should include 1:
- Hydration status and electrolyte balance
- PUQE score for symptom control
- Fetal growth monitoring, especially with insufficient gestational weight gain
- Monthly fetal growth scans from viability in severe cases
Advanced Nutritional Support
For severe cases with persistent weight loss despite maximal antiemetic therapy, consider 1, 3:
- Enteral nutrition
- Parenteral nutrition
- Multidisciplinary team involvement (obstetricians, gastroenterologists, nutritionists)
Critical Pitfalls to Avoid
Do not delay thiamine supplementation in any hospitalized patient—Wernicke's encephalopathy is preventable but devastating 1, 2.
Do not assume persistent liver abnormalities are from hyperemesis gravidarum—if liver chemistry remains abnormal despite symptom resolution, investigate alternative etiologies 1.
Do not withhold antiemetic therapy due to teratogenicity concerns—abundant data support the safety of antihistamines, phenothiazines, and metoclopramide in early pregnancy 2.
Patient Counseling
Inform patients that 1:
- Symptoms typically resolve by week 16-20 in most cases (80%), though 10% experience symptoms throughout pregnancy
- Recurrence risk in subsequent pregnancies is high (40-92%)
- Untreated hyperemesis gravidarum is associated with low birth weight, small for gestational age infants, and premature delivery