What is the treatment for hyperemesis gravidarum?

Treatment of Hyperemesis Gravidarum

Start with doxylamine-pyridoxine combination as first-line pharmacologic therapy, escalate to metoclopramide if this fails, reserve ondansetron as second-line (with caution before 10 weeks gestation), and use methylprednisolone only as a last resort for severe refractory cases—all while ensuring immediate IV hydration, electrolyte replacement, and thiamine supplementation to prevent Wernicke's encephalopathy. 1, 2

Initial Stabilization (First 24-48 Hours)

Immediate interventions must address life-threatening complications:

• IV fluid resuscitation to correct dehydration, which often improves associated liver enzyme abnormalities seen in 40-50% of patients 1, 2
• Electrolyte replacement with particular attention to potassium and magnesium levels, as hypokalemia is common and dangerous 1, 2
• 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 to prevent Wernicke's encephalopathy, which can develop after only 20 days of inadequate intake 1, 2
  • For suspected Wernicke's encephalopathy (confusion, ataxia, eye movement abnormalities), give thiamine 500 mg IV three times daily 1

Diagnostic workup during stabilization:

• Electrolyte panel, liver function tests (AST/ALT elevated in ~50% of cases), urinalysis for ketonuria 1, 2
• Abdominal ultrasonography to detect multiple/molar pregnancies and rule out hepatobiliary causes 1, 2
• Assess severity using Pregnancy-Unique Quantification of Emesis (PUQE) score for tracking response to treatment 1, 2

Stepwise Pharmacologic Algorithm

First-Line: Doxylamine-Pyridoxine

Doxylamine 10-20 mg combined with pyridoxine (vitamin B6) 10-20 mg 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), all with similar safety profiles 1
• Vitamin B6 supplementation alone may be used for mild cases 1
• Ginger 250 mg capsule four times daily may be added as adjunctive therapy 1

Second-Line: Metoclopramide (Preferred) or Ondansetron

When first-line antihistamines fail, metoclopramide is the preferred second-line agent due to 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

• Use ondansetron on a case-by-case basis before 10 weeks of pregnancy 1, 2
• Monitor for QT interval prolongation with ondansetron, especially in patients with electrolyte abnormalities 1
• Both metoclopramide and ondansetron are compatible throughout pregnancy and breastfeeding 1

Important caveat: Meta-analysis of 25 studies shows no significant efficacy difference among commonly used antiemetics (metoclopramide, ondansetron, promethazine), so medication selection should be based on safety profile and gestational age 1, 2

Third-Line: Methylprednisolone (Last Resort Only)

Reserve methylprednisolone 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 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 including 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

If symptoms worsen despite treatment or patient cannot maintain 1000 kcal/day:

• Switch from PRN or intermittent dosing to around-the-clock scheduled antiemetic administration 1
• Consider hospitalization for continuous IV therapy 1
• Nasojejunal feeding is preferred over nasogastric feeding due to better tolerance, and should be considered before escalating to total parenteral nutrition 1

Indications for enteral feeding:

• Frequent vomiting (≥5-7 episodes daily) despite maximal antiemetics
• Progressive weight loss ≥5% of pre-pregnancy weight
• Inability to maintain oral intake of 1000 kcal/day for several days 1

Alternative pharmacotherapeutics for refractory cases:

• Olanzapine and gabapentin may be considered 1, 3

Critical Pitfalls to Avoid

• Withdraw phenothiazines or metoclopramide immediately if extrapyramidal symptoms develop 1, 2
• Do not use PRN dosing in refractory cases—switch to scheduled around-the-clock administration 1
• Do not delay thiamine supplementation—pregnancy increases thiamine requirements and hyperemesis rapidly depletes stores within 7-8 weeks 1
• Do not continue escalating promethazine doses when side effects emerge—switch to metoclopramide instead 2

Monitoring and Follow-Up

Regular assessments should include:

• Hydration status and electrolyte balance 1, 2
• Symptom control using PUQE score serially to track trajectory 1, 2
• Weight stabilization or gain (not continued loss) is a critical marker of clinical improvement 1
• Resolution of ketonuria and normalization of electrolytes 1
• Fetal growth monitoring, with monthly fetal growth scans from viability in severe cases 1, 2

Expected timeline:

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

Multidisciplinary Management

Severe cases require involvement of:

• Obstetricians or maternal-fetal medicine specialists
• Gastroenterologists
• Nutritionists
• Mental health professionals (anxiety and depression are common with severe hyperemesis) 1, 2, 3

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