What is the management approach for a pregnant female patient with hyperemesis gravidarum?

Management of Hyperemesis Gravidarum

Start with immediate IV fluid resuscitation, thiamine supplementation, and stepwise antiemetic therapy beginning with doxylamine-pyridoxine, escalating to metoclopramide or ondansetron for moderate-severe cases, and reserving corticosteroids only for refractory cases that fail all other therapies. 1

Initial Assessment and Stabilization

Diagnostic Workup

• Assess severity using the Motherisk Pregnancy-Unique Quantification of Emesis (PUQE) score, which quantifies duration of nausea, frequency of vomiting, and retching episodes over 12 hours 1, 2
• Document weight loss ≥5% of pre-pregnancy weight, signs of dehydration (dry mucous membranes, tachycardia, orthostatic hypotension), and perform neurologic examination for confusion, ataxia, or eye movement abnormalities suggesting Wernicke's encephalopathy 1
• Order electrolyte panel (particularly potassium and magnesium), liver function tests (AST/ALT elevated in 50% of cases, rarely >1,000 U/L), urinalysis for ketonuria, and thyroid function tests (TSH, free T4) as biochemical hyperthyroidism occurs commonly 3, 1
• Perform abdominal ultrasonography to detect multiple gestations, molar pregnancy, and rule out hepatobiliary causes like cholecystitis 1

Immediate Stabilization

• Begin IV fluid resuscitation immediately—this alone often improves liver chemistry abnormalities 1
• Replace electrolytes with particular attention to potassium ≥3.0 mmol/L and magnesium 1
• Administer thiamine 200-300 mg IV daily for at least 3-5 days if the patient cannot tolerate oral intake or has had prolonged vomiting (>7-8 weeks), as thiamine stores can be completely exhausted after only 20 days of inadequate intake 1
• For mild cases tolerating oral intake, give thiamine 300 mg orally daily plus vitamin B compound strong 2 tablets three times daily 1

Critical pitfall: Never start IV dextrose before thiamine administration, as this precipitates Wernicke's encephalopathy in thiamine-depleted patients 1

Stepwise Pharmacologic Management

First-Line Therapy

• Doxylamine 10-20 mg combined with pyridoxine (vitamin B6) 10-20 mg every 6-8 hours is the preferred initial antiemetic, safe throughout pregnancy and breastfeeding 1
• Alternative first-line agents include other antihistamines (promethazine, cyclizine) or phenothiazines (prochlorperazine, chlorpromazine), all with similar safety profiles 1
• Vitamin B6 monotherapy at 10-25 mg every 8 hours may be sufficient for mild cases 1
• Ginger supplementation 250 mg capsule four times daily can be added 1

Second-Line Therapy

• Metoclopramide 5-10 mg orally or IV every 6-8 hours is the preferred second-line agent when antihistamines fail, with less drowsiness and fewer discontinuations than promethazine 1
• Meta-analysis of 33,000 first-trimester exposures shows no increased risk of major congenital defects (OR 1.14,99% CI 0.93-1.38) 1
• Ondansetron should be reserved as second-line therapy and used cautiously before 10 weeks gestation due to concerns about congenital heart defects, though recent data suggest the risk is low 1
• Both metoclopramide and ondansetron are compatible throughout pregnancy and breastfeeding 1
• Monitor QT interval with ondansetron, especially in patients with electrolyte abnormalities 1

Important caveat: Withdraw phenothiazines or metoclopramide immediately if extrapyramidal symptoms (dystonia, akathisia) develop 1

Third-Line Therapy for Refractory Cases

• Methylprednisolone is reserved as last resort for severe hyperemesis that fails both ondansetron and metoclopramide: 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
• Use with caution before 10 weeks gestation due to slight increased risk of cleft palate, though this risk is less concerning after first trimester 1
• Methylprednisolone reduces rehospitalization rates in severe refractory cases 1

Alternative Agents for Exceptional Cases

• Olanzapine may be considered only in exceptional refractory cases after exhausting guideline-directed therapy, based on oncology data showing 70% of patients with no emesis 1
• Mirtazapine has been described in case studies for refractory HG, acting on multiple receptor systems to produce antiemetic and appetite-stimulating effects without increased risk of birth defects 4
• Gabapentin is mentioned as an alternative pharmacotherapeutic for refractory cases 1

Critical pitfall: Never skip the stepwise approach and jump directly to olanzapine or other alternative agents—this violates evidence-based guidelines 1

Dietary and Non-Pharmacologic Management

• Start with small, frequent, bland meals using the BRAT diet (bananas, rice, applesauce, toast), advancing slowly over days 1
• Recommend high-protein, low-fat meals and avoidance of specific food triggers and strong odors 1
• Provide emotional support and mental health screening, as anxiety and depression are common with severe HG 1

Management of Severe Refractory Cases

Indications for Hospitalization

• Frequent vomiting ≥5-7 episodes daily despite maximal antiemetics 1
• Progressive weight loss ≥5% of pre-pregnancy weight 1
• Inability to maintain oral intake of 1,000 kcal/day for several days 1
• Persistent ketonuria and electrolyte abnormalities despite outpatient management 1

Continuous Therapy Approach

• Switch from PRN or intermittent dosing to around-the-clock scheduled antiemetic administration—worsening symptoms after twice-weekly IV treatments indicates inadequate continuous coverage 1
• Consider hospitalization for continuous IV therapy with methylprednisolone and scheduled antiemetics 1

Enteral Nutrition Support

• Nasojejunal feeding is preferred over nasogastric feeding due to better tolerance, and should be considered before escalating to total parenteral nutrition 1
• Reserve enteral feeding tubes for patients who have failed to maintain adequate nutrition despite maximal medical therapy, not for those with nausea or food aversions alone 1
• Indications include escalating symptoms with inability to maintain 1,000 kcal/day for several days despite maximal antiemetics 1

Parenteral Nutrition

• Consider total parenteral nutrition for severe cases with persistent weight loss when enteral feeding fails 1, 5
• Provide minimum 200-300 mg thiamine daily in PN formulation given increased metabolic demands and depletion risk 1

Refeeding syndrome prevention: When reintroducing nutrition after prolonged poor intake, start with small frequent meals and advance slowly over days, monitor electrolytes closely, and ensure adequate thiamine supplementation 1

Monitoring and Follow-Up

• Use PUQE score serially to track symptom severity and treatment response every 1-2 weeks during acute phase 1
• Monitor for objective markers of improvement: sustained oral intake, weight stabilization or gain (not continued loss), reduced vomiting frequency, resolution of ketonuria, and normalization of electrolytes 1
• Check thiamine status (RBC or whole blood thiamine diphosphate) every trimester in all HG patients, particularly those with inadequate weight gain 1
• Perform monthly fetal growth monitoring scans from viability in severe cases with insufficient gestational weight gain 1, 2

Special Considerations

Thyroid Dysfunction

• Biochemical hyperthyroidism (undetectable TSH, elevated free T4) is common with HG but rarely requires treatment 3
• The condition is self-limited and resolves as HG improves 3
• Routine thyroid testing is not recommended unless other signs of clinical hyperthyroidism are present 3

Twin Pregnancies

• Twin pregnancies have higher risk of HG due to elevated hCG and estrogen levels 6
• For monochorionic-diamniotic twins, begin routine ultrasound surveillance for twin-twin transfusion syndrome at 16 weeks, continuing every 2 weeks until delivery 2
• Monitor fetal growth more closely if maternal weight gain is insufficient 2

Persistent Liver Abnormalities

• If liver chemistry abnormalities persist despite symptom resolution, investigate for alternative etiology (cholecystitis, hepatitis, HELLP syndrome) 1

Prognosis and Patient Education

• HG typically resolves by week 16-20 in 80% of cases, though 10% may experience symptoms throughout pregnancy 1
• Educate patients about high recurrence risk of 40-92% in subsequent pregnancies 1
• Early aggressive treatment may prevent progression from mild nausea/vomiting to full HG 1
• Untreated HG is associated with low birth weight, small for gestational age infants, and premature delivery 1

Multidisciplinary Approach for Severe Cases

• Involve maternal-fetal medicine, gastroenterology, nutrition services, and mental health professionals for refractory cases 1
• Preferably manage severe cases at tertiary care centers with multidisciplinary teams experienced in high-risk pregnancies 1
• Most interventions, including CT or ERCP, should not be withheld if deemed necessary during pregnancy 1