What are the treatment options for hyperemesis gravidarum?

Treatment of Hyperemesis Gravidarum

Start with doxylamine-pyridoxine combination as first-line pharmacologic therapy, escalate to metoclopramide if this fails, reserve ondansetron for second-line use (with caution before 10 weeks), and use corticosteroids only as last resort for severe refractory cases—while simultaneously providing IV hydration, thiamine supplementation, and electrolyte replacement for all patients requiring hospitalization. 1

Initial Stabilization and Assessment

Immediate Interventions

• Provide IV fluid resuscitation immediately to correct dehydration, which often improves associated liver chemistry abnormalities 1
• Administer thiamine 200-300 mg IV daily to prevent Wernicke's encephalopathy, particularly critical as thiamine stores can be depleted within 7-8 weeks of persistent vomiting 1
• Replace electrolytes with particular attention to potassium and magnesium levels 1

Diagnostic Workup

• Check electrolyte panel, liver function tests (approximately 50% will have abnormal AST/ALT), and urinalysis for ketonuria 1
• Assess severity using the PUQE (Pregnancy-Unique Quantification of Emesis) score 1, 2
• Screen for thyroid dysfunction as hyperemesis can cause biochemical hyperthyroidism 2
• Confirm weight loss ≥5% of pre-pregnancy weight 1

Stepwise Pharmacologic Algorithm

First-Line: Antihistamine-Pyridoxine Combination

Doxylamine combined with pyridoxine (vitamin B6) is the preferred initial antiemetic for hyperemesis gravidarum, safe throughout pregnancy and breastfeeding 1

Alternative first-line agents with similar safety profiles include:

• Promethazine (antihistamine) 1
• Cyclizine (antihistamine) 1
• Prochlorperazine (phenothiazine) 1
• Chlorpromazine (phenothiazine) 1

Critical caveat: Withdraw phenothiazines immediately if extrapyramidal symptoms develop 1

Second-Line: Prokinetic or Serotonin Antagonist

Metoclopramide is the preferred second-line agent when antihistamines fail, causing less drowsiness, dizziness, and dystonia compared to promethazine in hospitalized patients 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. The American College of Obstetricians and Gynecologists recommends using ondansetron on a case-by-case basis before 10 weeks 1.

Important monitoring: Watch for QT interval prolongation with ondansetron, especially in patients with electrolyte abnormalities 1

Third-Line: Corticosteroids (Last Resort Only)

Methylprednisolone should be reserved for severe hyperemesis that fails other therapies 1

Dosing protocol:

• 16 mg IV every 8 hours for up to 3 days 1
• Then taper over 2 weeks to lowest effective dose 1
• Maximum duration 6 weeks 1

Use with extreme caution in first trimester due to slight increased risk of cleft palate when given before 10 weeks 1

Alternative Refractory Therapies

For cases unresponsive to standard antiemetics, consider:

• Olanzapine 1, 3
• Gabapentin 1, 3
• Mirtazapine (acts on multiple receptor systems including histaminergic and serotonergic, with antiemetic and appetite-stimulating effects) 4

Thiamine Dosing Protocol

Oral Thiamine (Mild-Moderate Cases)

• 300 mg orally daily plus vitamin B compound strong: 2 tablets three times daily 1
• Continue until vomiting resolves and oral intake is adequate 1

IV Thiamine (Severe Cases or Inability to Tolerate Oral)

• Switch immediately to IV thiamine 200-300 mg daily if vomiting persists or patient cannot tolerate oral intake 1
• Continue for at least 3-5 days, then switch to oral maintenance (50-100 mg daily) once vomiting is controlled 1

Suspected Wernicke's Encephalopathy

• Thiamine 500 mg IV three times daily (1,500 mg total daily dose) 1

Critical timing: Pregnancy increases thiamine requirements, and reserves can be completely exhausted after only 20 days of inadequate oral intake 1

Non-Pharmacologic Interventions

• Small, frequent, bland meals 1
• BRAT diet (bananas, rice, applesauce, toast) 1
• High-protein, low-fat meals 1
• Avoidance of specific food triggers and strong odors 1
• Ginger supplementation 1, 5

Nutritional Support for Refractory Cases

When to Consider Advanced Nutrition

• Persistent weight loss despite maximizing antiemetics 3
• Inability to tolerate oral intake for prolonged periods 3

Options

• Enteral nutrition (tube feeding) 3, 6
• Parenteral nutrition with minimum 2.5 mg/day thiamine in PN formulation, but provide 200-300 mg daily for hyperemesis specifically 1

Monitoring Requirements

• Regular assessment of hydration status and electrolyte balance 1, 2
• Ongoing PUQE score evaluation 1, 2
• Check thiamine status (RBC or whole blood thiamine diphosphate) every trimester 1
• Monthly fetal growth monitoring scans from viability in severe cases with insufficient gestational weight gain 1, 2
• Monitor for persistent liver chemistry abnormalities, which should prompt investigation for another etiology 1

Prognosis and Patient Education

• Symptoms typically resolve by week 16 in >50% of patients and by week 20 in 80%, though 10% may experience symptoms throughout pregnancy 1
• Recurrence risk is 40-92% in subsequent pregnancies 1
• Untreated hyperemesis is associated with low birth weight, small for gestational age infants, and premature delivery 1

Multidisciplinary Care Coordination

Severe cases require coordination among obstetricians, gastroenterologists, nutritionists, and mental health professionals, preferably at tertiary care centers with multidisciplinary teams experienced in high-risk pregnancies 1, 7