What is the treatment for hyperemesis gravidarum?

Treatment of Hyperemesis Gravidarum

Start with IV fluid resuscitation and electrolyte replacement, immediately begin thiamine 100 mg daily (or 200-300 mg IV if vomiting persists), and initiate doxylamine-pyridoxine as first-line antiemetic therapy. 1

Initial Stabilization

Fluid and Electrolyte Management:

• Administer IV fluids to correct dehydration, which typically improves associated liver enzyme abnormalities 1
• Replace electrolytes with particular attention to potassium and magnesium levels 1, 2
• Check electrolyte panel, liver function tests (approximately 50% will have abnormal AST/ALT), and urinalysis for ketonuria 1, 2

Thiamine Supplementation (Critical):

• Start thiamine 100 mg orally daily for minimum 7 days, then 50 mg daily maintenance until adequate oral intake is established 1
• If vomiting persists or patient cannot tolerate oral intake, switch immediately to IV thiamine 200-300 mg daily 1, 2
• This prevents Wernicke encephalopathy, as pregnancy increases thiamine requirements and hyperemesis depletes stores within 7-8 weeks 2
• For suspected Wernicke's encephalopathy, escalate to thiamine 500 mg IV three times daily (1,500 mg total) 2

Diagnostic Workup:

• 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 1, 2

Stepwise Pharmacologic Management

First-Line Antiemetic:

• Doxylamine-pyridoxine combination is the preferred initial antiemetic, safe throughout pregnancy and breastfeeding 1, 2
• Alternative first-line agents include other antihistamines (promethazine, cyclizine) or phenothiazines (prochlorperazine, chlorpromazine) with similar safety profiles 2

Second-Line Therapy:

• Metoclopramide is the preferred second-line agent when first-line antihistamines fail 1, 2
• In head-to-head comparison with promethazine in hospitalized patients, metoclopramide showed similar efficacy but significantly fewer side effects (less drowsiness, dizziness, dystonia, and treatment discontinuations) 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
• The American College of Obstetricians and Gynecologists recommends using ondansetron on a case-by-case basis before 10 weeks of pregnancy 1, 2

Important Caveat on Antiemetic Selection:

• Meta-analysis of 25 studies found no significant efficacy difference among commonly used antiemetics (metoclopramide, ondansetron, promethazine) 1, 2
• Therefore, medication selection should be based on safety profile and gestational age rather than efficacy alone 1

Third-Line Therapy (Last Resort):

• Methylprednisolone should be reserved 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 2
• 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 refractory to typical antiemetics, consider mirtazapine, olanzapine, or gabapentin 2, 3

Non-Pharmacologic Interventions

• Small, frequent, bland meals; BRAT diet; high-protein, low-fat meals 2
• Avoidance of specific food triggers and strong odors 2
• Ginger supplementation may provide benefit 2, 4

Monitoring and Follow-Up

Regular Assessments:

• Monitor hydration status and electrolyte balance 2
• Evaluate symptom control using PUQE score 1, 2
• Check thiamine status (RBC or whole blood thiamine diphosphate) every trimester, particularly in patients with inadequate weight gain 2
• Perform monthly fetal growth monitoring scans from viability in severe cases 2

Expected Timeline:

• Symptoms resolve by week 16 in >50% of patients and by week 20 in 80% 1, 2
• 10% experience symptoms throughout pregnancy 1, 2
• Recurrence risk in subsequent pregnancies is 40-92% 1, 2

Severe/Refractory Cases

Nutritional Support:

• For persistent weight loss despite maximal antiemetic therapy, consider enteral or parenteral nutrition 2, 3
• For patients on total parenteral nutrition, provide thiamine 200-300 mg daily (not just the standard 2.5 mg/day) given increased metabolic demands 2

Multidisciplinary Management:

• Severe cases require involvement of obstetricians, gastroenterologists, nutritionists, and mental health professionals 1, 2

Critical Pitfalls to Avoid

• Do not withhold thiamine supplementation—start immediately on presentation to prevent Wernicke encephalopathy 1, 2, 5
• Withdraw phenothiazines or metoclopramide immediately if extrapyramidal symptoms develop 1, 2
• Do not continue escalating promethazine doses when side effects emerge—switch to metoclopramide instead 1
• If liver chemistry abnormalities persist despite symptom resolution, investigate for another etiology 2
• Monitor QT interval with ondansetron, especially in patients with electrolyte abnormalities 2