Management of Hyperemesis Gravidarum in Pregnant Women
Start with doxylamine-pyridoxine combination as first-line therapy, escalate to metoclopramide for moderate symptoms, reserve ondansetron for refractory cases (with caution before 10 weeks), and use methylprednisolone only as a last resort for severe refractory hyperemesis gravidarum. 1
Immediate Assessment and Stabilization
Assess severity using the PUQE score: mild (≤6), moderate (7-12), severe (≥13) to guide treatment intensity. 2, 1
For hyperemesis gravidarum (dehydration, >5% weight loss, ketonuria):
- Administer IV fluid resuscitation to correct dehydration and replace electrolytes, particularly potassium and magnesium. 1
- Start thiamine 100 mg daily for minimum 7 days to prevent Wernicke encephalopathy, then 50 mg daily maintenance until adequate oral intake is established. 1
- If vomiting persists or patient cannot tolerate oral intake, switch to IV thiamine 200-300 mg daily. 1
- Check electrolyte panel, liver function tests, and urinalysis for ketonuria. 1
- Perform abdominal ultrasonography to detect multiple or molar pregnancies and rule out hepatobiliary causes. 1
Stepwise Pharmacologic Management
Mild Symptoms (PUQE ≤6)
Dietary modifications:
- Small, frequent, bland meals following the BRAT diet with high-protein, low-fat focus. 2
First-line pharmacotherapy:
- Vitamin B6 (pyridoxine) 10-25 mg every 8 hours. 2
- Add doxylamine if symptoms persist. 2
- Ginger has demonstrated efficacy for mild symptoms. 3
Moderate Symptoms (PUQE 7-12)
Doxylamine-pyridoxine combination is the preferred initial antiemetic, safe throughout pregnancy and breastfeeding. 1
If first-line therapy fails, escalate to metoclopramide as the preferred second-line agent due to similar efficacy to promethazine but fewer side effects (less drowsiness, dizziness, dystonia). 2, 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 the risk is low. 1 Use on a case-by-case basis before 10 weeks. 1
Severe/Refractory Symptoms (PUQE ≥13)
Methylprednisolone should be reserved as last resort for severe hyperemesis gravidarum that fails other therapies. 1 Use 16 mg IV every 8 hours for up to 3 days, then taper. 1 Exercise caution in the first trimester due to slight increased risk of cleft palate when given before 10 weeks gestation. 1
Critical Pitfall to Avoid
Do not continue escalating promethazine doses when side effects emerge—switch to metoclopramide instead. 1 While phenothiazines including promethazine are endorsed as first-line options, metoclopramide is preferred when escalating beyond initial antihistamine therapy. 1 In head-to-head trials, promethazine caused significantly more drowsiness, dizziness, dystonia, and treatment discontinuations compared to metoclopramide despite equivalent efficacy. 1
Comparative Efficacy Note
Meta-analysis of 25 studies found no significant efficacy difference among commonly used antiemetics (metoclopramide, ondansetron, promethazine). 1, 3 Therefore, medication selection should be based on safety profile, side effect tolerance, and gestational age rather than efficacy alone. 1
Monitoring Requirements
Regular assessments should include:
- Hydration status and electrolyte balance. 1
- Symptom control using PUQE score. 1
- Weight monitoring. 2
- Fetal growth monitoring with monthly scans from viability in severe cases. 1
Expected timeline: Symptoms resolve by week 16 in >50% of patients and by week 20 in 80%, though 10% experience symptoms throughout pregnancy. 1 Recurrence risk in subsequent pregnancies is 40-92%. 1
Multidisciplinary Involvement
Severe cases require involvement of obstetricians, gastroenterologists, nutritionists, and mental health professionals for comprehensive management. 1