What is the treatment for hyperemesis gravidarum?

Treatment of Hyperemesis Gravidarum

Start with IV fluid resuscitation and electrolyte replacement, immediately initiate thiamine 100 mg daily (or 200-300 mg IV if vomiting persists), and use doxylamine-pyridoxine as first-line antiemetic, escalating to metoclopramide if needed, with ondansetron reserved for second-line therapy and corticosteroids only as last resort. 1

Initial Stabilization

Immediate interventions are critical to prevent life-threatening complications:

• Administer IV fluid resuscitation to correct dehydration, which typically improves associated liver enzyme abnormalities 1
• Replace electrolytes with particular attention to potassium and magnesium levels, as deficiencies are common and dangerous 1
• Check electrolyte panel, liver function tests (approximately 50% will have abnormal AST/ALT, though rarely >1,000 U/L), and urinalysis for ketonuria 1, 2
• Assess severity using the Pregnancy-Unique Quantification of Emesis (PUQE) score to guide treatment intensity 1, 2
• Perform abdominal ultrasonography to detect multiple or molar pregnancies and rule out hepatobiliary causes 1

Thiamine Supplementation: Critical for Preventing Wernicke Encephalopathy

Thiamine depletion occurs rapidly—within 7-8 days of persistent vomiting—making immediate supplementation non-negotiable:

• 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
• For suspected or confirmed Wernicke's encephalopathy, escalate to thiamine 500 mg IV three times daily (1,500 mg total daily dose) 2
• Pregnancy itself increases thiamine requirements, and reserves can be completely exhausted after only 20 days of inadequate intake 2

Stepwise Pharmacologic Management

First-Line: Doxylamine-Pyridoxine Combination

The American College of Obstetricians and Gynecologists recommends doxylamine-pyridoxine as the preferred initial antiemetic:

• This combination is safe throughout pregnancy and breastfeeding 1, 2
• Alternative first-line agents include other antihistamines (promethazine, cyclizine) and phenothiazines (prochlorperazine, chlorpromazine), all with similar safety profiles 2
• Vitamin B6 (pyridoxine) alone may be suggested for mild cases 2

Second-Line: Metoclopramide (Preferred) or Ondansetron

When first-line antihistamines fail, escalate systematically:

• Metoclopramide is the preferred second-line agent with similar efficacy to promethazine but significantly fewer side effects—less drowsiness, dizziness, dystonia, and fewer treatment discontinuations in hospitalized patients 1, 3
• 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
• Both metoclopramide and ondansetron are compatible throughout pregnancy and breastfeeding 2
• A Cochrane meta-analysis of 25 studies found no significant efficacy difference among metoclopramide, ondansetron, and promethazine, so medication selection should be based on safety profile, side effect tolerance, and gestational age 1, 3

Critical pitfall: Do not continue escalating promethazine doses when side effects emerge—switch to metoclopramide instead 1

Third-Line: Corticosteroids (Last Resort Only)

Methylprednisolone should be reserved for severe hyperemesis gravidarum that fails other therapies:

• 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
• Corticosteroids decrease readmission rates (RR 0.69,95% CI 0.50-0.94) but do not clearly reduce hospital stay duration 3

Alternative Pharmacotherapies for Refractory Cases

When standard antiemetics fail, consider:

• Mirtazapine, olanzapine, and gabapentin are alternative pharmacotherapeutics for refractory hyperemesis gravidarum 2, 4
• These should be considered only after maximizing typical antiemetics and in consultation with multidisciplinary team 4

Safety Monitoring and Side Effect Management

Withdraw medications immediately if specific complications develop:

• Stop phenothiazines or metoclopramide immediately if extrapyramidal symptoms develop 1, 2
• Monitor for QT interval prolongation, especially with ondansetron, particularly in patients with electrolyte abnormalities 2
• Promethazine causes significantly more drowsiness, dizziness, and dystonia compared to metoclopramide in head-to-head trials 1, 3

Nutritional Support for Severe Cases

When oral intake remains inadequate despite maximal antiemetic therapy:

• Severe cases with persistent weight loss may require hospitalization for IV hydration, enteral or parenteral nutrition 2, 4
• For patients on total parenteral nutrition, provide thiamine 200-300 mg daily given the increased metabolic demands and depletion risk 2
• For patients with adjustable gastric bands, deflation may be necessary to prevent band slippage and nutrient deficiencies 2

Monitoring and Follow-Up

Regular assessments prevent complications and guide treatment adjustments:

• Monitor hydration status, electrolyte balance, and symptom control using PUQE score 1, 2
• Check thiamine status (RBC or whole blood thiamine diphosphate) every trimester in all hyperemesis gravidarum patients, particularly those with inadequate weight gain or continued weight loss 2
• Perform monthly fetal growth monitoring scans from viability in severe cases 1, 2
• If liver chemistry abnormalities persist despite symptom resolution, investigate for another etiology 2

Prognosis and Patient Counseling

Set realistic expectations about disease course:

• 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% 1, 2
• Untreated hyperemesis gravidarum is associated with low birth weight, small for gestational age infants, premature delivery, and decreased maternal quality of life 2

Multidisciplinary Management

Severe cases require coordinated care:

• Involve obstetricians, gastroenterologists, nutritionists, and mental health professionals for comprehensive management of severe cases 1, 2, 4
• Consider midwife-led outpatient care, which is associated with fewer hours of hospital admission (MD -33.20,95% CI -46.91 to -19.49) compared to routine inpatient admission 3