What is the management of hyperemesis gravidarum?

Management of Hyperemesis Gravidarum

Early treatment of nausea and vomiting in pregnancy with a stepwise pharmacologic approach may prevent progression to hyperemesis gravidarum, starting with vitamin B6 plus doxylamine, escalating to ondansetron or metoclopramide for moderate cases, and reserving corticosteroids only for severe refractory cases. 1

Initial Assessment and Stabilization

Diagnostic Workup

• Assess severity using the Motherisk Pregnancy-Unique Quantification of Emesis (PUQE) score: mild (≤6), moderate (7-12), severe (≥13) 1, 2
• Check electrolyte panel, liver function tests, and urinalysis for ketonuria to identify dehydration and metabolic derangements 2
• Obtain abdominal ultrasonography to detect multiple gestations or molar pregnancy (both associated with elevated hCG and increased hyperemesis risk) 2
• Approximately 50% of patients will have elevated AST/ALT, though rarely >1,000 U/L 2

Immediate Stabilization

• Administer intravenous fluid resuscitation to correct dehydration, which often improves liver chemistry abnormalities 2
• Replace electrolytes with particular attention to potassium and magnesium levels 2
• Start thiamine supplementation immediately: 300 mg daily orally if tolerating oral intake, or 200-300 mg IV daily if not, to prevent Wernicke's encephalopathy 2, 3
  • Thiamine reserves can be completely exhausted after only 20 days of inadequate oral intake 2
  • For suspected Wernicke's encephalopathy, increase to 500 mg IV three times daily 2

Stepwise Pharmacologic Management

First-Line Therapy

Doxylamine-pyridoxine (vitamin B6) combination is the preferred initial antiemetic, safe throughout pregnancy and breastfeeding 2, 1

• Alternative first-line agents include antihistamines (promethazine, cyclizine) or phenothiazines (prochlorperazine, chlorpromazine) 2
• Vitamin B6 alone may be used for mild cases 2
• Treatment should not be withheld based on teratogenicity concerns, as there are abundant safety data for antihistamines and phenothiazines in early pregnancy 3

Second-Line Therapy

Metoclopramide is the preferred second-line agent when first-line antihistamines fail, with less drowsiness, dizziness, and dystonia compared to promethazine 2

• In one study of 146 participants, promethazine caused significantly more drowsiness (RR 0.70), dizziness (RR 0.48), and dystonia (RR 0.31) than metoclopramide 4
• Withdraw metoclopramide or phenothiazines 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

• Use ondansetron on a case-by-case basis before 10 weeks of pregnancy 2
• Monitor for QT interval prolongation with ondansetron, especially in patients with electrolyte abnormalities 2
• Both metoclopramide and ondansetron are compatible throughout pregnancy and breastfeeding 2

Third-Line Therapy for Refractory Cases

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

• Dosing: 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 2
• In one study of 110 participants, corticosteroids decreased readmission rate (RR 0.69) compared to placebo 4

Alternative pharmacotherapeutics for refractory cases include olanzapine, mirtazapine, and gabapentin 2, 5

Non-Pharmacologic Interventions

Dietary Modifications

• Small, frequent, bland meals using the BRAT diet (bananas, rice, applesauce, toast) 2
• High-protein, low-fat meals with avoidance of specific food triggers and strong odors 2
• For patients with adjustable gastric bands, deflation may be necessary to prevent band slippage and nutrient deficiencies 2

Nutritional Support for Severe Cases

Indications for Advanced Nutrition

Severe cases with persistent weight loss (≥5% of pre-pregnancy weight) and inability to tolerate oral intake for prolonged periods require enteral or parenteral nutrition 2, 5

Parenteral Nutrition Guidelines

• Minimum 2.5 mg/day thiamine in PN formulation, but for hyperemesis specifically provide 200-300 mg daily given increased metabolic demands 2
• Check thiamine status (RBC or whole blood thiamine diphosphate) every trimester in all hyperemesis patients, particularly those with inadequate weight gain 2

Monitoring and Follow-Up

Ongoing Assessment

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

Patient Education

• Educate patients about the high recurrence risk (40-92%) in subsequent pregnancies 2
• Inform patients that hyperemesis typically resolves by week 16-20 in 80% of cases, though 10% may experience symptoms throughout pregnancy 2, 1

Multidisciplinary Care

Coordination of care for severe hyperemesis should involve obstetricians, gastroenterologists, nutritionists, and mental health professionals 2, 5

• Preferably managed at tertiary care centers with multidisciplinary teams experienced in high-risk pregnancies 1

Important Caveats

• No significant efficacy difference exists among commonly used antiemetics (metoclopramide, ondansetron, promethazine) based on meta-analysis of 25 studies 2
• Most interventions, including computed tomography or ERCP, should not be withheld if deemed necessary during pregnancy 1
• Untreated hyperemesis is associated with low birth weight, small for gestational age infants, and premature delivery 2
• Early intervention is crucial to prevent progression from mild nausea and vomiting to hyperemesis gravidarum 2, 1