What is the treatment for hyperemesis gravidarum?

Treatment of Hyperemesis Gravidarum

Start with immediate IV fluid resuscitation and electrolyte replacement, followed by thiamine supplementation and a stepwise antiemetic protocol beginning with doxylamine-pyridoxine, escalating to metoclopramide or ondansetron, and reserving corticosteroids for refractory cases. 1, 2

Initial Stabilization

Administer IV fluids immediately to correct dehydration, which often resolves associated liver enzyme abnormalities that occur in approximately 50% of patients. 1, 2

• Replace electrolytes with particular attention to potassium and magnesium levels, as these are commonly depleted. 1, 2
• Check electrolyte panel, liver function tests (AST/ALT rarely exceed 1,000 U/L), and urinalysis for ketonuria. 1
• Perform abdominal ultrasonography to detect multiple or molar pregnancies and rule out hepatobiliary causes. 1, 2
• Assess severity using the Pregnancy-Unique Quantification of Emesis (PUQE) score to guide treatment intensity. 1, 2

Thiamine Supplementation (Critical to Prevent Wernicke's Encephalopathy)

Start thiamine immediately, as pregnancy increases thiamine requirements and hyperemesis depletes stores within 7-8 weeks of persistent vomiting. 1

• For mild-moderate cases with oral tolerance: Thiamine 300 mg orally daily plus vitamin B compound strong (2 tablets three times daily). 1
• For severe cases or inability to tolerate oral intake: Switch immediately to IV thiamine 200-300 mg daily for at least 3-5 days, then oral maintenance (50-100 mg daily) once vomiting controlled. 1, 2
• For suspected Wernicke's encephalopathy: Thiamine 500 mg IV three times daily (1,500 mg total daily dose). 1
• Continue thiamine 100 mg daily for minimum 7 days, then 50 mg daily maintenance until adequate oral intake established. 2

Stepwise Antiemetic Protocol

First-Line: Doxylamine-Pyridoxine

Doxylamine combined with pyridoxine (vitamin B6) is the preferred initial antiemetic, safe throughout pregnancy and breastfeeding. 1, 2

• Alternative first-line agents include antihistamines (promethazine, cyclizine) or phenothiazines (prochlorperazine, chlorpromazine), all with similar safety profiles. 1
• Vitamin B6 (pyridoxine) supplementation alone may be used for mild cases. 1

Second-Line: Metoclopramide 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

• 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 ondansetron on a case-by-case basis before 10 weeks of pregnancy. 1, 2
• Monitor for QT interval prolongation with ondansetron, especially in patients with electrolyte abnormalities. 1
• Both metoclopramide and ondansetron are compatible throughout pregnancy and breastfeeding. 1
• Withdraw phenothiazines or metoclopramide immediately if extrapyramidal symptoms develop. 1

Third-Line: Corticosteroids (Last Resort)

Methylprednisolone should be reserved as last resort for severe hyperemesis 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
• Use with caution in first trimester due to slight increased risk of cleft palate when given before 10 weeks gestation. 1, 2

Alternative Refractory Therapies

For cases unresponsive to standard antiemetics, consider olanzapine, gabapentin, or mirtazapine. 1, 3

• Mirtazapine acts on noradrenergic, serotonergic, histaminergic, and muscarinic receptors to produce antiemetic, sedative, and appetite-stimulating effects, and is not associated with increased risk of birth defects. 4

Non-Pharmacological Interventions

Dietary modifications include small, frequent, bland meals, BRAT diet, high-protein low-fat meals, and avoidance of specific food triggers and strong odors. 1

Nutritional Support for Severe Cases

For persistent weight loss despite maximal antiemetic therapy, consider enteral or parenteral nutrition. 1, 3

• Nasogastric feeding with continuous infusion of iso-osmolar tube-feeding product provides uniformly good symptom relief and avoids more invasive therapy. 5
• For patients on total parenteral nutrition, provide thiamine 200-300 mg daily (not just the standard 2.5 mg/day) given increased metabolic demands. 1

Monitoring and Follow-Up

Regular assessments should include:

• Hydration status and electrolyte balance monitoring. 1, 2
• Symptom control using PUQE score. 1, 2
• Monthly fetal growth monitoring scans from viability in severe cases with insufficient gestational weight gain. 1, 2
• Check thiamine status (RBC or whole blood thiamine diphosphate) every trimester in all hyperemesis patients. 1

Important Clinical Caveats

Symptoms resolve by week 16 in >50% of patients and by week 20 in 80%, though 10% experience symptoms throughout pregnancy. 1, 2

• Recurrence risk in subsequent pregnancies is 40-92%, so counsel patients accordingly. 1, 2
• No significant efficacy difference exists among commonly used antiemetics (metoclopramide, ondansetron, promethazine) based on meta-analysis of 25 studies, so medication selection should be based on safety profile and gestational age. 1, 2
• Persistent liver chemistry abnormalities despite symptom resolution should prompt investigation for another etiology. 1
• Untreated hyperemesis is associated with low birth weight, small for gestational age infants, and premature delivery. 1

Multidisciplinary Care

Severe cases require involvement of obstetricians, gastroenterologists, nutritionists, and mental health professionals for comprehensive management. 1, 2, 3