What are the management options for hyperemesis gravidarum?

Management of Hyperemesis Gravidarum

Begin treatment immediately with vitamin B6 (pyridoxine) 10-25 mg every 8 hours combined with doxylamine as first-line therapy, escalating stepwise through metoclopramide, ondansetron, and ultimately intravenous corticosteroids for refractory cases, while ensuring aggressive hydration and thiamine supplementation to prevent Wernicke's encephalopathy. 1, 2

Initial Assessment and Severity Stratification

Assess severity using the Motherisk Pregnancy-Unique Quantification of Emesis (PUQE) score: mild (≤6), moderate (7-12), severe (≥13). 2, 3 Check for dehydration signs, weight loss ≥5% of pre-pregnancy weight, and ketonuria. 2

Laboratory workup must include:

• Electrolyte panel with particular attention to potassium and magnesium levels 2
• Liver function tests (approximately 50% will have abnormal AST/ALT, rarely >1,000 U/L) 2
• Urinalysis for ketonuria 2
• Abdominal ultrasonography to detect multiple or molar pregnancies 2

Stepwise Treatment Algorithm

Step 1: Non-Pharmacological and First-Line Therapy

Dietary modifications: Small, frequent, bland meals; BRAT diet (bananas, rice, applesauce, toast); high-protein, low-fat meals; avoid specific food triggers and strong odors. 2, 3

First-line pharmacologic therapy: Doxylamine combined with pyridoxine (vitamin B6) 10-25 mg every 8 hours is the preferred initial antiemetic throughout pregnancy and breastfeeding. 2, 3 Alternative first-line agents include promethazine, cyclizine, prochlorperazine, or chlorpromazine, all with similar safety profiles. 2

Step 2: Moderate Cases Requiring Hydration

Immediate intravenous fluid resuscitation to correct dehydration, which often improves liver chemistry abnormalities. 2

Thiamine supplementation (vitamin B1) is mandatory to prevent Wernicke's encephalopathy—this is a critical step that cannot be omitted. 1, 2

Electrolyte replacement with particular focus on potassium (aim for ≥3.0 mmol/L) and magnesium. 2

Step 3: Second-Line Antiemetics

Metoclopramide is the preferred second-line agent when first-line antihistamines fail, with less drowsiness, dizziness, dystonia, and fewer discontinuations compared to promethazine. 2 Withdraw immediately if extrapyramidal symptoms develop. 2

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. 2 Monitor for QT interval prolongation, especially in patients with electrolyte abnormalities. 2 Use on a case-by-case basis before 10 weeks of pregnancy. 2

Step 4: Third-Line Therapy for Refractory Cases

Methylprednisolone (corticosteroids) should be reserved as last resort for severe hyperemesis gravidarum that fails other therapies: 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. 2

Alternative pharmacotherapeutics for refractory cases include olanzapine, gabapentin, and mirtazapine. 2, 4 Mirtazapine acts on noradrenergic, serotonergic, histaminergic, and muscarinic receptors to produce antiemetic and appetite-stimulating effects without independent increased risk of birth defects. 5

Step 5: Nutritional Support for Severe Cases

Enteral or parenteral nutrition may be required for severe cases with persistent weight loss and inability to tolerate oral intake for prolonged periods. 2, 4

Critical Monitoring Parameters

• Regular assessment of hydration status and electrolyte balance 2
• Evaluation of symptom control using PUQE score 2
• Fetal growth monitoring, especially with insufficient gestational weight gain—monthly fetal growth scans from viability in severe cases 2
• Persistent liver chemistry abnormalities despite symptom resolution should prompt investigation for another etiology 2

Important Clinical Pitfalls

Early treatment of nausea and vomiting of pregnancy may reduce progression to hyperemesis gravidarum—do not wait for severe symptoms to develop. 1, 2 Symptoms typically peak at 8-12 weeks and subside by week 20 in 80% of cases, though 10% may experience symptoms throughout pregnancy. 2, 3

Recurrence risk is extremely high (40-92%) in subsequent pregnancies—counsel patients accordingly. 2

No significant efficacy difference exists among commonly used antiemetics (metoclopramide, ondansetron, promethazine) based on meta-analysis of 25 studies, so selection should be based on safety profile and gestational age. 2

Multidisciplinary Coordination

Severe cases require multidisciplinary team involvement including obstetricians, gastroenterologists, nutritionists, and mental health professionals, preferably in a tertiary care center. 1, 2 Most interventions, including computed tomography or ERCP, should not be withheld if deemed necessary. 1