Hyperemesis Gravidarum: Clinical Management Presentation
Definition & Epidemiology
Hyperemesis gravidarum is severe, intractable nausea and vomiting in pregnancy characterized by persistent vomiting, ≥5% weight loss from pre-pregnancy weight, dehydration, and ketonuria, affecting 0.3-2% of pregnancies. 1
- Symptoms typically begin before 22 weeks gestation 1
- Resolution occurs by week 16 in >50% of patients and by week 20 in 80% 1, 2
- 10% experience symptoms throughout entire pregnancy 1, 2
- Recurrence risk in subsequent pregnancies: 40-92% 2
Initial Assessment & Stabilization
Immediate IV fluid resuscitation to correct dehydration is the cornerstone of acute management, as this alone often improves associated liver enzyme abnormalities. 1, 2
Critical Laboratory Workup
- Electrolyte panel with particular attention to potassium and magnesium 1, 2
- Liver function tests (50% will have elevated AST/ALT, rarely >1,000 U/L) 1
- Urinalysis for ketonuria 1, 2
- Thyroid function tests (hyperthyroidism associated with HG) 1
- Abdominal ultrasound to detect multiple/molar pregnancies and rule out hepatobiliary causes 1, 2
Severity Assessment
- Use PUQE (Pregnancy-Unique Quantification of Emesis) score serially to track severity 1, 2
- Physical exam focusing on signs of dehydration and neurologic examination for neuropathy or vitamin deficiency 1
Thiamine Supplementation: Non-Negotiable
Start thiamine 100 mg daily for minimum 7 days, then 50 mg daily maintenance until adequate oral intake is established to prevent Wernicke encephalopathy. 2
Critical Dosing Algorithm
- Oral intake tolerated: Thiamine 300 mg daily orally PLUS vitamin B compound strong 2 tablets three times daily 1
- Persistent vomiting or cannot tolerate oral: Switch immediately to IV thiamine 200-300 mg daily for at least 3-5 days 1, 2
- Suspected/confirmed Wernicke encephalopathy: Thiamine 500 mg IV three times daily (1,500 mg total daily) 1
Why This Matters
- Pregnancy increases thiamine requirements 1
- HG depletes thiamine stores within 7-8 weeks of persistent vomiting 1
- Thiamine reserves can be completely exhausted after only 20 days of inadequate oral intake 1
- IV/IM route preferred for acute presentations as oral absorption is unreliable 1
Stepwise Pharmacologic Management
First-Line: Doxylamine-Pyridoxine Combination
The American College of Obstetricians and Gynecologists recommends doxylamine-pyridoxine combination as the preferred initial antiemetic for both mild nausea/vomiting of pregnancy and hyperemesis gravidarum. 1, 2
- Dosing: Doxylamine 10-20 mg + Pyridoxine (Vitamin B6) 10-25 mg every 8 hours 1
- Safe throughout pregnancy and breastfeeding 1, 2
- Alternative first-line agents: promethazine, cyclizine, prochlorperazine, chlorpromazine (all share similar safety profiles) 1, 2
Second-Line: Metoclopramide (Preferred) or Ondansetron
Metoclopramide is the preferred second-line agent when first-line antihistamines fail, with less drowsiness, dizziness, dystonia, and fewer discontinuations compared to promethazine. 1, 2
- Compatible throughout pregnancy and breastfeeding 1
- Withdraw immediately if extrapyramidal symptoms develop 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, 2
- Use on a case-by-case basis before 10 weeks of pregnancy 1, 2
- Monitor for QT interval prolongation, especially with electrolyte abnormalities 1
Third-Line: Methylprednisolone (Last Resort Only)
Methylprednisolone should be reserved as last resort for severe hyperemesis gravidarum that fails other therapies. 1, 2
- Dosing protocol: 16 mg IV every 8 hours for up to 3 days, then taper over 2 weeks to lowest effective dose, maximum duration 6 weeks 1, 2
- Use with caution in first trimester due to slight increased risk of cleft palate when given before 10 weeks gestation 1, 2
- Reduces rehospitalization rates in severe refractory cases 1
Dietary & Non-Pharmacologic Interventions
Small, frequent, bland meals (BRAT diet: bananas, rice, applesauce, toast) with high-protein, low-fat content and avoidance of specific food triggers and strong odors. 1
- Ginger supplementation: 250 mg capsule four times daily 1
- Advance diet slowly over days in patients at risk of refeeding syndrome 1
When to Escalate Care
Indications for Hospitalization & Continuous Therapy
- Frequent vomiting (≥5-7 episodes daily) despite maximal antiemetics 1
- Progressive weight loss ≥5% of pre-pregnancy weight 1
- Inability to maintain oral intake of 1,000 kcal/day for several days 1
- Persistent ketonuria despite outpatient management 1
Enteral Feeding Considerations
- Nasojejunal feeding preferred over nasogastric due to better tolerance 1
- Reserve for patients who have failed to maintain adequate nutrition despite maximal medical therapy 1
- Consider before escalating to total parenteral nutrition 1
Total Parenteral Nutrition
- Reserved for most intractable cases where other treatment modalities have failed 1
- Minimum 2.5 mg/day thiamine in PN formulation, but provide 200-300 mg daily for HG specifically 1
Critical Monitoring Parameters
Objective Markers of Clinical Improvement
- Weight stabilization or gain (not continued loss) 1
- Sustained oral intake 1
- Reduced vomiting frequency 1
- Resolution of ketonuria 1
- Normalization of electrolytes 1
- Improved functional capacity 1
Ongoing Surveillance
- Hydration status and electrolyte balance regularly 1, 2
- PUQE score every 1-2 weeks during acute phase 1
- Fetal growth monitoring, especially with insufficient gestational weight gain 1, 2
- Monthly fetal growth scans from viability in severe cases 1, 2
- Check thiamine status (RBC or whole blood thiamine diphosphate) every trimester 1
Common Pitfalls to Avoid
Do not use PRN or intermittent dosing for severe refractory cases—switch to around-the-clock scheduled antiemetic administration. 1
- Do not skip the stepwise approach and jump directly to corticosteroids or olanzapine 1
- Do not continue escalating promethazine doses when side effects emerge—switch to metoclopramide instead 2
- Do not withhold treatment due to teratogenicity concerns with first-line agents (antihistamines, phenothiazines, metoclopramide have abundant safety data) 3
- Persistent liver chemistry abnormalities despite symptom resolution should prompt investigation for another etiology 1
Multidisciplinary Management for Severe Cases
Severe cases require involvement of obstetricians, gastroenterologists, nutritionists, and mental health professionals, preferably managed at tertiary care centers with multidisciplinary teams experienced in high-risk pregnancies. 1, 2
- Mental health support is important as anxiety and depression are common with severe HG 1
- Coordinate care early to prevent progression from mild nausea/vomiting to hyperemesis gravidarum 1
Maternal & Fetal Outcomes
Untreated hyperemesis gravidarum is associated with low birth weight, small for gestational age infants, premature delivery, and decreased maternal quality of life. 1