What is the appropriate management for a pregnant female diagnosed with hyperemesis gravidarum?

Management of Hyperemesis Gravidarum

Immediate Stabilization

Begin with aggressive IV fluid resuscitation to correct dehydration, which will often improve associated liver enzyme abnormalities, and replace electrolytes with particular attention to potassium and magnesium levels. 1, 2

• Check electrolyte panel, liver function tests (expect AST/ALT elevation in ~50% of cases, rarely >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 and track serially 1
• Conduct neurologic examination for confusion, ataxia, or eye movement abnormalities suggesting Wernicke's encephalopathy 1

Critical Thiamine Supplementation

Start thiamine 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 1, 2
• For suspected or confirmed Wernicke's encephalopathy, escalate to thiamine 500 mg IV three times daily (1,500 mg total daily dose) 1
• Pregnancy depletes thiamine stores within 7-8 weeks of persistent vomiting, with complete exhaustion possible after only 20 days of inadequate intake 1

Stepwise Pharmacologic Management

First-Line Therapy

Doxylamine 10-20 mg combined with pyridoxine (vitamin B6) 10-20 mg every 8 hours is 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 with similar safety profiles 1, 2
• Vitamin B6 (pyridoxine) monotherapy at 10-25 mg every 8 hours may be used for mild cases 1
• Ginger supplementation 250 mg capsule four times daily may be considered 1

Second-Line Therapy

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
• 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 Therapy

Methylprednisolone should be reserved as last resort for severe refractory hyperemesis gravidarum that fails other therapies: 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
• Methylprednisolone reduces rehospitalization rates in severe refractory cases 1

Non-Pharmacologic Interventions

• Small, frequent, bland meals (BRAT diet: bananas, rice, applesauce, toast) 1
• High-protein, low-fat meals 1
• Avoidance of specific food triggers and strong odors 1
• Advance diet slowly over days in patients at risk of refeeding syndrome 1

Management of Refractory Cases

For patients with worsening symptoms despite treatment, switch from PRN or intermittent dosing to around-the-clock scheduled antiemetic administration. 1

• Consider hospitalization for continuous therapy with IV methylprednisolone and enteral feeding via nasojejunal tube (preferred over nasogastric due to better tolerance) 1
• Enteral feeding should be considered 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 1,000 kcal/day for several days 1
• Reserve total parenteral nutrition for patients who fail enteral feeding 1
• For patients on TPN, provide thiamine 200-300 mg daily given increased metabolic demands 1

Monitoring and Follow-Up

• Regular assessment of hydration status and electrolyte balance 1, 2
• Serial PUQE scores to track symptom severity 1, 2
• Fetal growth monitoring, with monthly 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
• Weight stabilization or gain (not continued loss) is a critical marker of clinical improvement 1
• Resolution of ketonuria and normalization of electrolytes confirm true clinical improvement 1

Multidisciplinary Care

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 Course and Prognosis

• 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, and premature delivery 1

Critical Pitfalls to Avoid

• Never withhold thiamine supplementation—start immediately in all cases to prevent Wernicke's encephalopathy 1, 2
• Withdraw phenothiazines or metoclopramide immediately if extrapyramidal symptoms develop 1
• Do not skip the stepwise approach and jump directly to corticosteroids or alternative agents like olanzapine 1
• Persistent liver chemistry abnormalities despite symptom resolution should prompt investigation for another etiology 1
• For patients with adjustable gastric bands, deflation may be necessary to prevent band slippage and nutrient deficiencies 1