Management of Hyperemesis Gravidarum
Begin immediate IV fluid resuscitation with thiamine supplementation, followed by stepwise antiemetic therapy starting with doxylamine-pyridoxine, escalating to metoclopramide, then ondansetron, and reserving corticosteroids for refractory cases. 1
Initial Stabilization
Administer IV fluids immediately to correct dehydration, which typically improves associated liver enzyme abnormalities that occur in approximately 50% of patients. 1, 2
Start thiamine 100 mg daily for minimum 7 days, then 50 mg daily maintenance until adequate oral intake is established to prevent Wernicke encephalopathy. 1 If vomiting persists or the patient cannot tolerate oral intake, switch immediately to IV thiamine 200-300 mg daily. 1, 2 This is critical because pregnancy increases thiamine requirements, and hyperemesis can deplete stores within 7-8 weeks of persistent vomiting. 2
Replace electrolytes with particular attention to potassium and magnesium levels, as these are commonly depleted. 1, 2
Diagnostic Assessment
Check the following laboratory tests: 1, 2
- Electrolyte panel
- Liver function tests (AST/ALT elevated in ~50% of cases, rarely >1,000 U/L)
- Urinalysis for ketonuria
- Thyroid function tests (TSH, free T4) to screen for biochemical hyperthyroidism
Assess severity using the Pregnancy-Unique Quantification of Emesis (PUQE) score, which evaluates duration of nausea, frequency of vomiting, and frequency of retching over a 12-hour period. 3, 1
Perform abdominal ultrasonography to detect multiple or molar pregnancies and rule out hepatobiliary causes. 1, 2
Stepwise Antiemetic Therapy
First-Line: Doxylamine-Pyridoxine
The doxylamine-pyridoxine combination is the preferred initial antiemetic, safe throughout pregnancy and breastfeeding. 1, 2 This is recommended by the American College of Obstetricians and Gynecologists as first-line for both mild nausea/vomiting and hyperemesis gravidarum. 2
Alternative first-line agents include other antihistamines (promethazine, cyclizine) and phenothiazines (prochlorperazine, chlorpromazine), all with similar safety profiles. 2
Second-Line: Metoclopramide
Metoclopramide is the preferred second-line agent when first-line antihistamines fail, with similar efficacy to promethazine but fewer side effects including less drowsiness, dizziness, and dystonia. 1, 2 It is compatible throughout pregnancy and breastfeeding. 2
Withdraw metoclopramide immediately if extrapyramidal symptoms develop. 2
Second-Line Alternative: Ondansetron
Ondansetron should be reserved as second-line therapy and used on a case-by-case basis before 10 weeks gestation due to concerns about congenital heart defects, though recent data suggest the risk is low. 1, 2 It is compatible throughout pregnancy and breastfeeding after the first trimester. 2
Monitor for QT interval prolongation, especially in patients with electrolyte abnormalities. 2
Third-Line: Corticosteroids
Methylprednisolone should be reserved as last resort 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. 2
Use with caution in first trimester due to slight increased risk of cleft palate when given before 10 weeks gestation. 1, 2
Refractory Cases
For cases unresponsive to standard antiemetics, consider alternative pharmacotherapeutics: 4
- Olanzapine
- Mirtazapine
- Gabapentin
Severe cases with persistent weight loss may require hospitalization for enteral or parenteral nutrition. 2, 4 For patients on total parenteral nutrition, provide thiamine 200-300 mg daily given the increased metabolic demands. 2
Common Pitfalls to Avoid
Do not delay thiamine supplementation, as Wernicke encephalopathy can develop rapidly and is a serious neurological complication. 1, 5
Do not assume all antiemetics have equal efficacy—while meta-analysis shows no significant difference among metoclopramide, ondansetron, and promethazine, medication selection should be based on safety profile and gestational age. 1, 2
Do not overlook persistent liver chemistry abnormalities despite symptom resolution, as this should prompt investigation for another etiology. 2
Monitoring and Follow-Up
Regularly assess hydration status, electrolyte balance, and symptom control using PUQE score. 1, 2
Monitor fetal growth, especially if maternal weight gain is insufficient, with monthly fetal growth scans from viability in severe cases. 3, 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
Multidisciplinary Approach
Severe cases require involvement of obstetricians, gastroenterologists, nutritionists, and mental health professionals for comprehensive management. 1, 2
Patient Counseling
Educate patients that symptoms resolve by week 16 in >50% of cases and by week 20 in 80%, though 10% experience symptoms throughout pregnancy. 1, 2
Inform patients of the high recurrence risk (40-92%) in subsequent pregnancies. 1, 2