What is the management for hyperemesis gravidarum (severe morning sickness) grade 3?

Management of Hyperemesis Gravidarum Grade 3

Immediate Stabilization and Hospitalization

For grade 3 (severe) hyperemesis gravidarum, immediate hospitalization is required with aggressive intravenous fluid resuscitation, thiamine supplementation to prevent Wernicke's encephalopathy, electrolyte replacement, and escalation to third-line antiemetics including corticosteroids if first and second-line agents have failed. 1

Initial Resuscitation Protocol

• Intravenous fluid resuscitation is the cornerstone of acute management to correct dehydration, which often improves associated liver chemistry abnormalities that occur in 40-50% of severe cases 1
• Thiamine 200-300 mg IV daily must be started immediately for at least 3-5 days before any glucose-containing fluids to prevent Wernicke's encephalopathy, as thiamine stores can be completely exhausted after only 20 days of inadequate oral intake 1
  • If neurologic signs are present (confusion, ataxia, eye movement abnormalities), increase to thiamine 500 mg IV three times daily (1,500 mg total) 1
• Electrolyte replacement with particular attention to potassium and magnesium levels, as hypokalemia is common and dangerous 1

Pharmacologic Management Algorithm

First-Line Antiemetics:

• Doxylamine 10-20 mg combined with pyridoxine (vitamin B6) 10-20 mg is the preferred initial antiemetic, safe throughout pregnancy and breastfeeding 1
• Alternative first-line agents include promethazine, cyclizine, prochlorperazine, or chlorpromazine if doxylamine-pyridoxine fails 1

Second-Line Antiemetics (if first-line fails):

• Metoclopramide is the preferred second-line agent with less drowsiness and fewer discontinuations compared to promethazine 1
• Ondansetron can be used as second-line therapy, though use caution before 10 weeks gestation due to concerns about congenital heart defects (though recent data suggest low risk) 1
• Switch from PRN dosing to around-the-clock scheduled antiemetic administration rather than intermittent dosing for better symptom control 1

Third-Line Therapy for Severe Refractory Cases:

• Methylprednisolone 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
• This reduces rehospitalization rates in severe refractory cases 1
• Use with caution in first trimester due to slight increased risk of cleft palate when given before 10 weeks gestation 1

Alternative Pharmacotherapeutics for Refractory Cases:

• Olanzapine, mirtazapine, or gabapentin may be considered when standard antiemetics fail 1, 2

Nutritional Support

• If unable to maintain oral intake of 1000 kcal/day for several days despite maximal antiemetics, or if progressive weight loss ≥5% of pre-pregnancy weight continues, consider enteral feeding 1
• Nasojejunal feeding is preferred over nasogastric due to better tolerance 1
• For patients at risk of refeeding syndrome (prolonged poor intake), start with small, frequent meals (BRAT diet: bananas, rice, applesauce, toast) and advance slowly over days 1
• Total parenteral nutrition should be reserved for patients who fail enteral feeding, with thiamine 200-300 mg daily in the formulation 1

Monitoring Requirements

• Check liver function tests as approximately 50% will have abnormal AST and ALT 1
• Monitor for QT interval prolongation, especially with ondansetron, particularly in patients with electrolyte abnormalities 1
• Serial PUQE (Pregnancy-Unique Quantification of Emesis) scores to track symptom severity and treatment response 1
• Check thiamine status (RBC or whole blood thiamine diphosphate) every trimester, particularly with inadequate weight gain or continued weight loss 1
• Monthly fetal growth monitoring scans from viability in severe cases 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

Special Considerations

• For patients with adjustable gastric bands, deflate the band to prevent band slippage and nutrient deficiencies 3, 1
• Screen for thyroid dysfunction as hyperemesis can be associated with biochemical hyperthyroidism 1
• Rule out alternative diagnoses with abdominal ultrasound (gallstones, cholecystitis) if liver enzymes remain elevated despite symptom improvement 1

Multidisciplinary Care

• Involve maternal-fetal medicine, gastroenterology, nutrition services, and mental health professionals for severe refractory cases, preferably at tertiary care centers with multidisciplinary teams experienced in high-risk pregnancies 1
• Mental health support is important as anxiety and depression are common with severe hyperemesis 1

Critical Pitfalls to Avoid

• Never give glucose-containing IV fluids before thiamine supplementation to prevent precipitating Wernicke's encephalopathy 1
• Withdraw phenothiazines or metoclopramide immediately if extrapyramidal symptoms develop 1
• Do not use PRN antiemetic dosing in severe cases—switch to scheduled around-the-clock administration 1
• Do not delay enteral feeding if patient has frequent vomiting (≥5-7 episodes daily) despite maximal antiemetics, progressive weight loss, or inability to maintain 1000 kcal/day 1

Prognosis

• Symptoms typically resolve by week 16-20 in 80% of cases, though 10% may experience symptoms throughout pregnancy 1
• Recurrence risk is 40-92% in subsequent pregnancies 1
• Untreated hyperemesis is associated with low birth weight, small for gestational age infants, and premature delivery 1