What is the treatment for hyperemesis gravidarum?

Treatment of Hyperemesis Gravidarum

Immediate Stabilization

Begin with IV fluid resuscitation to correct dehydration and replace electrolytes, focusing particularly on potassium and magnesium levels, as this often improves associated liver enzyme abnormalities. 1, 2

• Start thiamine supplementation immediately: 100 mg daily orally for minimum 7 days, then 50 mg daily maintenance until adequate oral intake is established 2
• If vomiting persists or patient cannot tolerate oral intake, switch immediately to IV thiamine 200-300 mg daily to prevent Wernicke's encephalopathy 1, 2
• Check electrolyte panel, liver function tests (approximately 50% will have abnormal AST/ALT), and urinalysis for ketonuria 1
• Assess severity using the Pregnancy-Unique Quantification of Emesis (PUQE) score 1, 2
• Perform abdominal ultrasonography to detect multiple or molar pregnancies and rule out hepatobiliary causes 1, 2

Stepwise Pharmacologic Algorithm

First-Line: Doxylamine-Pyridoxine Combination

The American College of Obstetricians and Gynecologists recommends doxylamine 10-20 mg combined with pyridoxine (vitamin B6) 10-20 mg as the preferred initial antiemetic, safe throughout pregnancy and breastfeeding. 1, 2

• Alternative first-line agents include other antihistamines (promethazine, cyclizine) and phenothiazines (prochlorperazine, chlorpromazine), all sharing similar safety profiles 1
• Ginger supplementation 250 mg capsule four times daily may be added 1

Second-Line: Metoclopramide (Preferred) or Ondansetron

Metoclopramide is the preferred second-line agent when first-line antihistamines fail, causing less drowsiness, dizziness, dystonia, and fewer discontinuations compared to promethazine in hospitalized patients. 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
• Both metoclopramide and ondansetron are compatible throughout pregnancy and breastfeeding 1
• Monitor for QT interval prolongation with ondansetron, especially in patients with electrolyte abnormalities 1

Third-Line: Methylprednisolone (Last Resort Only)

Reserve methylprednisolone for severe hyperemesis gravidarum that fails both first-line and second-line therapies, using 16 mg IV every 8 hours for up to 3 days, then taper over 2 weeks to lowest effective dose, with maximum duration of 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
• Methylprednisolone reduces rehospitalization rates in severe refractory cases 1

Dietary and Non-Pharmacologic Interventions

• Small, frequent, bland meals using the BRAT diet (bananas, rice, applesauce, toast), advancing slowly over days 1
• High-protein, low-fat meals with avoidance of specific food triggers and strong odors 1

Advanced Nutritional Support for Refractory Cases

Consider enteral feeding via nasojejunal tube (preferred over nasogastric due to better tolerance) for patients with ≥5-7 vomiting episodes daily despite maximal antiemetics, progressive weight loss ≥5% of pre-pregnancy weight, or inability to maintain oral intake of 1000 kcal/day for several days. 1

• Reserve total parenteral nutrition only after nasojejunal feeding fails 1
• When initiating refeeding, start slowly to prevent refeeding syndrome 1

Critical Monitoring Parameters

• Regular assessment of hydration status and electrolyte balance using PUQE score 1, 2
• Monthly fetal growth monitoring scans from viability in severe cases 1, 2
• Check thiamine status (RBC or whole blood thiamine diphosphate) every trimester, particularly in patients with inadequate weight gain 1
• Objective markers of improvement include sustained oral intake, weight stabilization or gain (not continued loss), reduced vomiting frequency, resolution of ketonuria, and normalization of electrolytes 1

Common Pitfalls to Avoid

• Do not use PRN or intermittent antiemetic dosing in refractory cases—switch to around-the-clock scheduled administration 1
• Withdraw phenothiazines or metoclopramide immediately if extrapyramidal symptoms develop 1, 2
• Do not withhold thiamine supplementation—pregnancy itself increases thiamine requirements, and hyperemesis rapidly depletes stores within 7-8 weeks of persistent vomiting 1
• Persistent liver chemistry abnormalities despite symptom resolution should prompt investigation for another etiology 1

Multidisciplinary Management

• Severe cases require involvement of obstetricians, gastroenterologists, nutritionists, and mental health professionals, preferably managed at tertiary care centers with multidisciplinary teams experienced in high-risk pregnancies 1, 2
• Mental health support is important as anxiety and depression are common with severe hyperemesis gravidarum 1

Expected Clinical 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
• 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