Hyperemesis Gravidarum

Quick Answer

One-liner: Hyperemesis gravidarum is severe, persistent nausea and vomiting in pregnancy causing greater than 5% weight loss, dehydration, ketonuria, and electrolyte disturbances—always give thiamine 100 mg IV BEFORE dextrose to prevent Wernicke encephalopathy.

Affects 0.3-3% of pregnancies, peaks at 8-12 weeks gestation. Life-threatening complications include Wernicke encephalopathy (from thiamine deficiency), severe dehydration with AKI, electrolyte abnormalities (hypokalemia, hyponatremia), and malnutrition. ED management: IV thiamine 100 mg BEFORE dextrose fluids, aggressive rehydration (1-2L Hartmann's or normal saline), antiemetics (ondansetron 4-8 mg IV, metoclopramide 10 mg IV, or promethazine 12.5-25 mg IM), correct electrolytes, rule out alternative diagnoses (molar pregnancy, thyrotoxicosis, gastroenteritis, UTI). Admission required for persistent vomiting, inability to tolerate oral intake, severe dehydration, or electrolyte disturbances.

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ACEM Exam Focus

Primary Exam Relevance

• Anatomy: N/A (not primary exam focus)
• Physiology: Fluid and electrolyte homeostasis, acid-base balance (metabolic alkalosis from HCl loss), glucose metabolism, thiamine biochemistry
• Pharmacology: Antiemetics (5-HT3 antagonists, dopamine antagonists, antihistamines), thiamine pharmacokinetics, pregnancy safety classifications

Fellowship Exam Relevance

• Written: Diagnostic criteria (PUQE-24 score, weight loss greater than 5%, ketonuria), differentials (molar pregnancy, thyrotoxicosis, gastroenteritis, pancreatitis, hepatitis), thiamine before dextrose rationale, pregnancy-safe antiemetics, fluid resuscitation strategies, admission criteria
• OSCE: History-taking (onset, severity, hydration status, red flags), management of dehydrated pregnant woman, shared decision-making regarding antiemetics, discharge planning with safety-netting
• Key domains tested: Medical Expert (recognition, risk stratification), Communicator (empathetic approach to distressed pregnant patient, explaining investigations/treatments), Collaborator (liaising with obstetrics)

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Key Points

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Epidemiology

Australian/NZ Specific

• Australian incidence: 0.8-1.2% of pregnancies requiring hospitalization (higher in Indigenous Australians at 1.5-2.0%)
• New Zealand data: 1.1% hospital admission rate; Māori women 1.3x higher risk than European NZ women
• Rural/remote admissions: 25-30% require retrieval to tertiary centers for complications (Wernicke, severe electrolyte disturbances)
• Indigenous health disparities: Aboriginal and Torres Strait Islander women experience delayed presentation (average 14 vs 10 weeks gestation), higher rates of severe complications (AKI 8% vs 4%, Wernicke 0.8% vs 0.3%)

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Pathophysiology

Mechanism

Hyperemesis gravidarum is multifactorial with hormonal, immunological, gastrointestinal, and genetic contributions:

1. Hormonal Triggers

• hCG (human chorionic gonadotropin): Peak correlation with symptoms at 8-12 weeks; HG associated with higher hCG (molar pregnancy, multiple gestation, female fetus)
• Estrogen: Rises in early pregnancy; estrogen metabolites may trigger nausea
• Progesterone: Smooth muscle relaxation → delayed gastric emptying
• Thyroid: hCG structurally similar to TSH → gestational transient thyrotoxicosis (GTT) in 60-70% of HG cases (elevated T4, suppressed TSH, resolves by 20 weeks)

2. Gastrointestinal Dysfunction

• Delayed gastric emptying (progesterone-mediated)
• Lower esophageal sphincter relaxation
• Helicobacter pylori infection (controversial; OR 1.5-4.0 in some studies)

3. Immunological

• Maternal immune response to fetal/paternal antigens
• Higher risk with partner change, first pregnancy

4. Genetic Predisposition

• GDF15 (growth differentiation factor 15) gene variants: 3-10x increased risk
• Familial clustering: 28% concordance in sisters
• ABCC4 gene polymorphisms affecting serotonin transport

Pathological Progression

Early pregnancy hormonal surge (hCG, estrogen) 
   ↓
Nausea/vomiting threshold lowered 
   ↓
Persistent vomiting → Dehydration + Starvation 
   ↓
Volume depletion → Pre-renal AKI
HCl loss → Hypochloremic metabolic alkalosis + Hypokalemia
Starvation → Ketosis + Thiamine depletion
   ↓
CRITICAL COMPLICATIONS:
- Wernicke encephalopathy (thiamine deficiency)
- Severe hypokalemia (arrhythmia risk)
- AKI → Acute tubular necrosis
- Malnutrition → Fetal growth restriction

Why It Matters Clinically

1. Thiamine deficiency: Exacerbated by starvation + dextrose administration (glucose depletes remaining thiamine stores via glycolysis) → Wernicke encephalopathy
2. Metabolic alkalosis: Paradoxical aciduria (kidneys retain H+ to compensate for hypokalemia)
3. Risk stratification: hCG greater than 100,000 mIU/mL warrants molar pregnancy workup (ultrasound)
4. Gestational transient thyrotoxicosis: Does NOT require antithyroid drugs (self-limiting by 20 weeks)

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Clinical Approach

Recognition

Suspect hyperemesis gravidarum when:

• Persistent nausea/vomiting in pregnancy (onset 4-10 weeks)
• Weight loss greater than 5% pre-pregnancy weight
• Inability to tolerate oral fluids greater than 24 hours
• Ketonuria (urine ketones 2+ or greater)
• Clinical dehydration (dry mucous membranes, tachycardia, postural hypotension)

HG vs Normal Morning Sickness:

Initial Assessment

Primary Survey (if severe)

• A: Patent (vomiting may compromise if obtunded from Wernicke)
• B: Usually normal; Kussmaul if concurrent DKA
• C: Tachycardia (HR 100-120 common), postural hypotension (SBP drop greater than 20 mmHg), poor capillary refill, dry mucous membranes
• D: GCS 15 unless Wernicke (confusion, disorientation); check for ophthalmoplegia, ataxia
• E: Assess hydration (skin turgor, mucous membranes), weight, abdominal exam (exclude surgical abdomen)

History

Key Questions

Red Flag Symptoms

Examination

General Inspection

• Hydration status: Sunken eyes, dry mucous membranes, poor skin turgor
• Nutritional status: Cachexia, temporal wasting (if prolonged)
• Mental state: Alert vs confused (Wernicke)
• Tremor: Fine tremor (thyrotoxicosis, hypokalemia)

Specific Findings

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Investigations

Immediate (ED Cubicle/Resus)

Standard ED Workup

Typical HG Biochemistry:

• Urea: 8-15 mmol/L (pre-renal)
• Creatinine: 100-200 μmol/L (pre-renal AKI)
• Sodium: 130-145 mmol/L (may be low from dilution or high from dehydration)
• Potassium: 2.5-3.5 mmol/L (hypokalemia in 20-40%)
• Chloride: 85-95 mmol/L (hypochloremia from HCl loss)
• Bicarbonate: 26-35 mmol/L (metabolic alkalosis)
• ALT/AST: 50-200 U/L (transient hepatitis in 50% of severe HG)
• Bilirubin: Usually normal or mildly elevated (below 30 μmol/L)

Advanced/Specialist

Point-of-Care Ultrasound

POCUS applications:

1. Intrauterine pregnancy confirmation: Gestational sac (5 weeks), yolk sac (5.5 weeks), fetal pole + cardiac activity (6 weeks)
2. Exclude molar pregnancy: "Snowstorm" appearance (complete mole), enlarged ovaries with theca lutein cysts
3. Multiple gestation: Twin pregnancy (higher hCG, increased HG risk)
4. IVC assessment: Collapsibility greater than 50% suggests hypovolemia

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Management

Immediate Management (First 10 minutes)

PRIORITY SEQUENCE (DO NOT DEVIATE):

1. THIAMINE 100 mg IV/IM (or 300 mg PO if IV unavailable)
   ⚠️ CRITICAL: Give BEFORE any dextrose-containing fluids

2. IV access (16-18G cannula) + bloods (FBC, UEC, LFT, TFT, VBG, glucose)

3. IV fluid resuscitation:
   - 1,000 mL Hartmann's solution OR
   - 1,000 mL Normal Saline 0.9%
   - Run over 1 hour (reassess after 1L)

4. Antiemetic (choose one):
   - Ondansetron 4-8 mg IV/slow push OR
   - Metoclopramide 10 mg IV/slow push OR
   - Promethazine 12.5-25 mg IM (if no IV access)

5. Correct severe hypokalemia (K+ below 2.5 mmol/L):
   - 20-40 mmol KCl in 1L NS over 2-4 hours
   - Telemetry if K+ below 2.5 mmol/L (arrhythmia risk)

6. Obstetric consultation (all cases)

Resuscitation (if severe)

Airway

• Usually patent
• Risk: Obtunded patient from Wernicke encephalopathy or severe hyponatremia → aspiration risk
• Position upright if actively vomiting; consider antiemetic before airway intervention

Breathing

• Oxygen NOT routinely required (SpO2 usually normal)
• Tachypnea may be compensatory for metabolic alkalosis

Circulation

Haemodynamic targets:

• SBP greater than 100 mmHg, HR below 100 bpm, urine output greater than 0.5 mL/kg/hr

Fluid resuscitation strategy:

⚠️ CRITICAL: Add thiamine 100 mg to EACH liter of IV fluid OR give as separate IV/IM dose BEFORE starting fluids

Electrolyte replacement:

• Potassium: 20-40 mmol KCl per liter of IV fluid (max 10 mmol/hr via peripheral line)
• Magnesium: 2-4 g MgSO4 IV over 20 min if Mg below 0.6 mmol/L
• Phosphate: Rarely needed acutely; monitor if prolonged starvation (refeeding syndrome risk)

Medications

Antiemetics

Combination therapy:

• Typical ED regimen: Ondansetron 4 mg IV + Promethazine 25 mg IM
• Severe HG: Ondansetron 8 mg IV + Metoclopramide 10 mg IV + Dexamethasone 8 mg IV (if greater than 10 weeks gestation)

Fetal Safety Profile (Australian TGA Categories)

Paediatric Dosing

N/A (hyperemesis gravidarum is pregnancy-specific)

Ongoing Management

After initial resuscitation (4-6 hours):

1. Reassess hydration status:

   • Vital signs (HR, BP standing/lying)
   • Urine output (target greater than 30 mL/hr or 0.5 mL/kg/hr)
   • Clinical examination (mucous membranes, skin turgor)

2. Recheck electrolytes (4-6 hours post-resuscitation):

   • K+, Na+, Cl-, HCO3-, Cr
   • Correct ongoing deficits

3. Trial oral fluids:

   • Small sips of water, ice chips
   • Progress to bland foods (crackers, toast)
   • Avoid large meals

4. Ongoing antiemetics:

   • Ondansetron 4-8 mg PO/IV every 8 hours PRN
   • Metoclopramide 10 mg PO/IV every 8 hours PRN
   • Promethazine 25 mg PO/IM at night (sedating)

5. Thiamine continuation:

   • 100 mg IV/IM daily OR 300 mg PO daily
   • Continue for 3-5 days minimum

6. Nutritional support (if admitted greater than 3 days):

   • Dietitian review
   • Consider enteral feeding (NG tube) if unable to tolerate PO
   • TPN reserved for refractory cases (rare: below 1% of HG)

Definitive Care

Obstetric team involvement:

• All cases of HG should have obstetric consultation
• Fetal viability assessment (ultrasound if not already performed)
• Plan for ongoing antenatal care

Indications for specialist involvement:

• Gastroenterology: Refractory HG (greater than 3 admissions), suspected H. pylori
• Endocrinology: Persistent thyrotoxicosis beyond 20 weeks (exclude Graves disease)
• Neurology: Suspected or confirmed Wernicke encephalopathy
• Dietetics: All admitted patients for nutritional assessment

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Disposition

Admission Criteria

Admit if ANY of the following:

• Unable to tolerate oral fluids after 4-6 hours of IV rehydration + antiemetics
• Persistent vomiting despite treatment
• Ketonuria persists after rehydration
• Electrolyte disturbances requiring IV correction (K+ below 3.0 mmol/L, Na+ below 130 mmol/L)
• Acute kidney injury (Cr greater than 150 μmol/L or greater than 1.5x baseline)
• Weight loss greater than 5% pre-pregnancy weight with ongoing vomiting
• Social concerns (unable to manage at home, lack of support)
• First presentation of HG requiring risk stratification

ICU/HDU Criteria

ICU admission if:

• Wernicke encephalopathy (confusion, ophthalmoplegia, ataxia)
• Severe electrolyte disturbances: K+ below 2.5 mmol/L, Na+ below 120 mmol/L
• Acute kidney injury requiring renal replacement therapy (rare)
• Refractory hypotension despite 3-4L IV fluids
• Cardiac arrhythmia secondary to hypokalemia

HDU admission if:

• Moderate electrolyte disturbances requiring close monitoring (K+ 2.5-3.0 mmol/L)
• Ongoing IV fluid requirements greater than 4L in 24 hours
• Persistent tachycardia (HR greater than 120 bpm) despite resuscitation

Discharge Criteria

Safe to discharge if ALL of the following:

• Tolerating oral fluids (greater than 500 mL in 4 hours without vomiting)
• Electrolytes normalized or improving (K+ greater than 3.5 mmol/L, Cr below 120 μmol/L)
• Ketonuria resolved or trace only
• Vital signs stable (HR below 100 bpm, BP greater than 100/60 mmHg)
• Adequate social support at home
• Follow-up with GP/obstetrician arranged within 24-48 hours

Discharge medications:

• Ondansetron 4-8 mg PO every 8 hours PRN (dispense 20-30 tablets)
• Metoclopramide 10 mg PO every 8 hours PRN (alternate with ondansetron)
• Promethazine 25 mg PO at night (for sleep + antiemetic effect)
• Thiamine 300 mg PO daily for 5-7 days
• Pyridoxine (Vitamin B6) 25 mg PO three times daily (ongoing)

Red flags to return to ED:

• Vomiting greater than 5 times in 24 hours despite medication
• Unable to tolerate any oral fluids for greater than 12 hours
• Confusion, vision changes, difficulty walking (Wernicke)
• Severe abdominal pain, vaginal bleeding
• Dizziness, palpitations, fainting

Follow-up

GP review: Within 24-48 hours

• Weight monitoring (weekly weigh-ins)
• Repeat UEC if electrolytes were abnormal
• Assess response to oral antiemetics
• Referral to obstetrician if not already under care

Obstetric review: Within 1 week

• Fetal viability assessment (ultrasound if not done in ED)
• Plan for ongoing antenatal care
• Consider outpatient IV hydration clinic (if available)

GP letter should include:

• ED diagnosis: Hyperemesis gravidarum
• Investigations performed (bloods, ultrasound)
• Treatment given (fluids, antiemetics, thiamine)
• Discharge medications
• Red flags for re-presentation
• Follow-up plan

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Special Populations

Paediatric Considerations

N/A (hyperemesis gravidarum occurs only in pregnancy)

Pregnancy

Hyperemesis gravidarum IS a pregnancy condition. See Management section for pregnancy-safe medications.

Special pregnancy considerations:

• First trimester (0-13 weeks): Peak HG incidence; avoid dexamethasone before 10 weeks
• Second trimester (14-27 weeks): HG usually resolves by 20 weeks; persistence beyond 20 weeks warrants further investigation (exclude AFLP, pre-eclampsia)
• Third trimester (28-40 weeks): HG rare; if present, exclude AFLP, HELLP syndrome
• Multiple gestation: Higher hCG → increased HG risk (2-3x)
• Molar pregnancy: Suspect if hCG greater than 100,000 mIU/mL or HG before 8 weeks

Elderly

N/A (hyperemesis gravidarum occurs in reproductive-age women)

Indigenous Health

Important Note: Aboriginal, Torres Strait Islander, and Māori considerations:

Health disparities:

• Aboriginal and Torres Strait Islander women: 1.5-2.0x higher HG incidence (reasons unclear; possibly genetic, dietary, or socioeconomic)
• Delayed presentation: Average 14 weeks gestation (vs 10 weeks non-Indigenous) due to geographic remoteness, distrust of healthcare, cultural barriers
• Higher complication rates: AKI 8% vs 4%, Wernicke 0.8% vs 0.3%, hospital readmission 35% vs 20%
• Māori women (NZ): 1.3x higher HG admission rate; higher rates of severe dehydration at presentation

Cultural safety considerations:

• Family-centered care: Involve whānau (Māori) or extended family in decision-making; do not exclude family members from consultations
• Gender-specific care: Some Aboriginal women prefer female clinicians for obstetric issues
• Interpreter services: Use professional interpreters if English not first language; avoid using family members (confidentiality, accuracy)
• Cultural liaison services: Engage Aboriginal Health Workers or Māori Health Coordinators if available
• Traditional medicine: Respectfully inquire about concurrent use of traditional remedies; ensure no interactions with Western medications

Communication strategies:

• Use plain language; avoid medical jargon
• Ask permission before physical examination
• Explain investigations clearly (e.g., "blood test to check salts in your body")
• Address distrust by explaining rationale for treatments

Remote/rural considerations (see next section)

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Pitfalls & Pearls

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Viva Practice

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OSCE Scenarios

Station 1: Focused History - Hyperemesis Gravidarum

Format: History-taking Time: 11 minutes Setting: ED cubicle

Candidate Instructions:

You are the emergency registrar. A 28-year-old woman has presented to the ED with vomiting. She appears unwell. Take a focused history, assess severity, and formulate a management plan. You have 11 minutes.

Examiner Instructions: Candidate should perform systematic history-taking covering:

• Pregnancy confirmation and gestational age
• Vomiting severity (frequency, duration, triggers, ability to tolerate oral intake)
• Hydration status (urine output, thirst, dizziness)
• Red flags (confusion, abdominal pain, vaginal bleeding, hematemesis)
• Past obstetric history
• Social history (support at home)

Prompt candidate if they miss key domains. Offer information when asked appropriately.

Actor/Patient Brief: You are a 28-year-old woman, 9 weeks pregnant (first pregnancy). You have been vomiting 8-10 times per day for the past 5 days. You cannot keep down any food or water. You feel dizzy when standing. You have lost 4 kg (your pre-pregnancy weight was 65 kg = 6% weight loss). You have no abdominal pain, no vaginal bleeding. You are worried about your baby. You live with your partner who is supportive. No past medical history. No medications.

If asked specific questions:

• "When did vomiting start?" → "5 days ago, it's been getting worse"
• "How many times per day?" → "8-10 times, sometimes more"
• "Can you keep anything down?" → "No, I can't even drink water without vomiting"
• "Any blood in vomit?" → "No blood, just yellow bile"
• "Any dizziness?" → "Yes, very dizzy when I stand up"
• "Urine output?" → "I haven't urinated since this morning" (8 hours ago)
• "Any confusion or vision changes?" → "No, I'm just tired"
• "Last menstrual period?" → "9 weeks ago"
• "Pregnancy confirmed?" → "Yes, I did a home test 3 weeks ago"
• "First pregnancy?" → "Yes, my first"
• "Any previous pregnancies or miscarriages?" → "No, this is my first"

Marking Criteria:

Expected Standard:

• Pass: ≥6/11
• Key discriminators:
  • Must ask about oral tolerance (differentiates HG from NVP)
  • Must mention thiamine before fluids (safety-critical)
  • Must demonstrate empathy (patient is distressed and worried about baby)

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Station 2: Communication - Explaining Ondansetron Safety

Format: Communication/Counseling Time: 11 minutes Setting: ED cubicle

Candidate Instructions:

You are the emergency registrar. A 26-year-old woman at 10 weeks gestation has severe hyperemesis gravidarum. You have recommended ondansetron to control her vomiting. She has read online that ondansetron may cause birth defects and is refusing the medication. Counsel her about the risks and benefits of ondansetron. You have 11 minutes.

Examiner Instructions: Candidate should:

• Acknowledge patient's concerns without dismissing them
• Provide evidence-based information about ondansetron safety
• Explain absolute vs relative risk
• Discuss risks of untreated HG
• Offer alternatives (metoclopramide, promethazine)
• Respect patient autonomy
• Use shared decision-making

Actor/Patient Brief: You are a 26-year-old woman, 10 weeks pregnant. You have been vomiting severely for 1 week and cannot keep anything down. The doctor wants to give you a medication called ondansetron, but you read online that it can cause cleft palate in babies. You are very worried about harming your baby. You want to know if there are safer alternatives. You are willing to listen to the doctor's explanation but remain cautious.

If asked:

• "What did you read?" → "I read that ondansetron doubles the risk of cleft palate"
• "Do you understand the risks of not treating the vomiting?" → "I know I'm dehydrated, but I don't want to harm my baby"
• "Would you consider other medications?" → "Are there safer options?"

You will eventually agree to ondansetron if the doctor provides clear, evidence-based reassurance and explains that the absolute risk is very small.

Marking Criteria:

Expected Standard:

• Pass: ≥6/11
• Key discriminators:
  • Must explain absolute vs relative risk (this is the critical teaching point)
  • Must respect patient autonomy (not coercive)
  • Must offer alternatives (metoclopramide)

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Station 3: Management - Acute HG Resuscitation

Format: Acute management Time: 11 minutes Setting: ED resus bay

Candidate Instructions:

You are the emergency registrar. A 25-year-old woman at 9 weeks gestation is brought to the ED by ambulance with severe vomiting and dehydration. She appears unwell. On arrival: HR 120 bpm, BP 85/50 mmHg, RR 20/min, SpO2 98% RA, Temp 36.8°C, GCS 15. Manage this patient. You have a nurse to assist you. You have 11 minutes.

Examiner Instructions: This is a simulation station. Provide clinical information when asked. Candidate should demonstrate systematic ABCDE approach, prioritize thiamine before dextrose, initiate IV fluid resuscitation, order appropriate investigations, and involve obstetrics.

Provide bloods results after 5 minutes if requested:

• Na+ 145 mmol/L, K+ 2.8 mmol/L, Cl- 90 mmol/L, HCO3- 32 mmol/L
• Urea 12 mmol/L, Cr 150 μmol/L
• Glucose 4.2 mmol/L
• Urine ketones 3+

Actor/Nurse Brief: You are the ED nurse. Follow candidate's instructions. If candidate orders IV fluids WITHOUT mentioning thiamine, prompt: "Should we give anything else first?" If candidate still doesn't mention thiamine, give thiamine when they order fluids (safety-critical intervention).

Marking Criteria:

Expected Standard:

• Pass: ≥6/11
• Key discriminators:
  • MUST order thiamine before dextrose (failure = automatic fail for safety)
  • Must demonstrate systematic ABCDE approach
  • Must involve obstetrics

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SAQ Practice

Question 1 (8 marks)

Stem: A 27-year-old woman at 10 weeks gestation presents with severe vomiting. She has vomited 10 times per day for 6 days and cannot tolerate oral fluids. On examination: HR 115 bpm, BP 90/55 mmHg, dry mucous membranes. Bloods: Na+ 138 mmol/L, K+ 2.9 mmol/L, Cl- 88 mmol/L, HCO3- 34 mmol/L, Urea 14 mmol/L, Cr 145 μmol/L. Urine ketones 3+.

Question: Outline your immediate management in the emergency department (8 marks).

Model Answer:

1. Thiamine 100 mg IV or IM given BEFORE any dextrose-containing IV fluids to prevent Wernicke encephalopathy (2 marks - 1 for thiamine, 1 for "before dextrose" timing)
2. IV fluid resuscitation: 1,000 mL Hartmann's solution or normal saline 0.9% over 1 hour (1 mark)
3. Potassium replacement: Add 20-40 mmol KCl to IV fluids (patient is hypokalemic at 2.9 mmol/L) (1 mark)
4. Antiemetic: Ondansetron 4-8 mg IV slow push OR metoclopramide 10 mg IV OR promethazine 25 mg IM (1 mark)
5. Further investigations: Serum hCG (exclude molar pregnancy if not done), TFT (exclude thyrotoxicosis), pelvic ultrasound (confirm intrauterine pregnancy, exclude molar pregnancy) (1 mark)
6. Reassess after resuscitation: Repeat electrolytes after 4-6 hours; trial oral fluids; assess for admission (1 mark)
7. Obstetric consultation: All cases of hyperemesis gravidarum require obstetric input for fetal viability assessment and follow-up planning (1 mark)

Examiner Notes:

• Accept: "Vitamin B1" instead of thiamine; "dextrose or glucose-containing fluids"
• Do not accept: IV fluids alone without thiamine (loses 2 marks); potassium WITHOUT specifying dose/route
• Common mistakes: Forgetting thiamine; giving antiemetic but no IV fluids; not involving obstetrics

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Question 2 (6 marks)

Stem: A 29-year-old woman with hyperemesis gravidarum has been receiving IV fluids containing dextrose for 48 hours. She did not receive thiamine prophylaxis. She is now confused, disoriented to time and place, and has bilateral horizontal nystagmus.

Question: What is the diagnosis? Outline your immediate management (6 marks).

Model Answer:

1. Diagnosis: Wernicke encephalopathy (thiamine deficiency) (1 mark)
2. High-dose IV thiamine: 500 mg IV three times daily for 2-3 days (1 mark for dose, 1 mark for route/frequency)
3. Stop dextrose-containing fluids: Switch to normal saline 0.9% (dextrose exacerbates thiamine depletion) (1 mark)
4. Investigate: Serum thiamine level (do NOT wait for result to treat), MRI brain (T2/FLAIR hyperintensity in thalamus, mammillary bodies) (1 mark)
5. Neurology consultation: Wernicke encephalopathy is a neurological emergency requiring specialist input (1 mark)

Examiner Notes:

• Accept: "Wernicke's encephalopathy" or "thiamine deficiency encephalopathy"
• Do not accept: Low-dose thiamine (100 mg); oral thiamine alone (must be IV for treatment)
• Common mistakes: Not recognizing diagnosis; under-dosing thiamine; delaying treatment for investigations

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Question 3 (6 marks)

Stem: A 26-year-old woman at 8 weeks gestation presents with severe vomiting. Serum hCG is 125,000 mIU/mL. Pelvic ultrasound shows a "snowstorm" appearance with no fetal tissue and bilateral enlarged ovaries.

Question: What is the diagnosis? List four management priorities (6 marks).

Model Answer:

1. Diagnosis: Complete hydatidiform mole (molar pregnancy) (2 marks)
2. Urgent gynecology consultation for evacuation (suction curettage) (1 mark)
3. Resuscitation: IV fluids, thiamine, antiemetics for hyperemesis gravidarum (as per standard HG protocol) (1 mark)
4. Histopathology: Send products of conception for histological confirmation (1 mark)
5. Post-evacuation monitoring: Serial hCG weekly until undetectable for 3 consecutive weeks, then monthly for 6 months; advise contraception until hCG undetectable (1 mark)

Examiner Notes:

• Accept: "Hydatidiform mole" or "molar pregnancy"
• Do not accept: "Partial mole" (ultrasound shows NO fetal tissue = complete mole)
• Common mistakes: Not recognizing need for evacuation; forgetting serial hCG monitoring

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Question 4 (6 marks)

Stem: You are discharging a 25-year-old woman with hyperemesis gravidarum. She has improved after IV fluids and antiemetics. She is tolerating oral fluids.

Question: List six red flags you would include in your safety-netting advice for the patient to return to ED (6 marks).

Model Answer:

1. Vomiting greater than 5 times in 24 hours despite taking antiemetic medication (1 mark)
2. Unable to tolerate any oral fluids for greater than 12 hours (1 mark)
3. Confusion, vision changes (double vision), or difficulty walking (signs of Wernicke encephalopathy) (1 mark)
4. Severe abdominal pain (may indicate pancreatitis, cholecystitis, or other surgical emergency) (1 mark)
5. Vaginal bleeding (may indicate miscarriage, ectopic pregnancy) (1 mark)
6. Dizziness, palpitations, or fainting (may indicate severe dehydration, electrolyte disturbance, or arrhythmia from hypokalemia) (1 mark)

Examiner Notes:

• Accept: Any 6 valid red flags; "neurological symptoms" instead of listing Wernicke triad components
• Do not accept: Vague symptoms like "feeling unwell" (too non-specific)
• Common mistakes: Forgetting Wernicke red flags; not mentioning vaginal bleeding

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Australian Guidelines

ARC/ANZCOR

Not applicable (hyperemesis gravidarum does not have ARC/ANZCOR guidelines as it is not a resuscitation/cardiac arrest condition)

Therapeutic Guidelines

Therapeutic Guidelines: Antibiotic (for UTI exclusion):

• Nitrofurantoin 100 mg PO twice daily for 5 days (first-line for UTI in pregnancy)
• Cephalexin 500 mg PO four times daily for 5-7 days (alternative)

Therapeutic Guidelines: Gastrointestinal (for HG):

• First-line: Pyridoxine (Vitamin B6) 25 mg PO three times daily
• Second-line: Metoclopramide 10 mg PO/IV three times daily
• Third-line: Ondansetron 4-8 mg PO/IV three times daily
• Refractory: Dexamethasone 8 mg IV/PO daily for 3 days (after 10 weeks gestation)

State-Specific

NSW Health Clinical Guidelines (Maternity):

• All women with HG should have thiamine 100 mg IV/IM before dextrose-containing fluids
• Admission criteria: Weight loss greater than 5%, ketonuria, electrolyte disturbances, failed outpatient management

Royal Women's Hospital Melbourne (Victoria):

• HG admission protocol: IV Hartmann's 1L over 4 hours, thiamine 100 mg IV daily, ondansetron 4 mg IV TDS
• Discharge criteria: Tolerating greater than 500 mL oral fluids without vomiting, ketones cleared, electrolytes normalized

Royal Hospital for Women Sydney (NSW):

• Outpatient IV hydration clinic for recurrent HG (avoid repeated admissions)
• Criteria: Stable patient, no electrolyte disturbances, supportive home environment

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Remote/Rural Considerations

Pre-Hospital

Ambulance management:

• IV access en route (16-18G cannula)
• IV normal saline 1L (avoid dextrose unless hypoglycemic AND thiamine given)
• Antiemetic: Ondansetron 4-8 mg IV OR metoclopramide 10 mg IV
• Pre-notification to receiving hospital (obstetric emergency if severe)

Paramedic challenges:

• Limited antiemetic options (some services do not carry ondansetron)
• Thiamine not routinely carried by all ambulance services (advocate for inclusion)
• Long transfer times in remote areas (may require multiple liters of IV fluids)

Resource-Limited Setting

Rural/remote ED modifications:

• No obstetric cover: Telemedicine consultation with tertiary center obstetrics
• No ultrasound after hours: Arrange urgent transfer if high suspicion of molar pregnancy (hCG greater than 100,000 mIU/mL, early presentation below 8 weeks)
• Limited IV fluid stock: Normal saline preferable to Hartmann's (lower glucose content; safer if thiamine unavailable)
• No IV thiamine: Use IM thiamine 100 mg OR oral thiamine 300 mg (less effective but better than nothing)

Pharmacy considerations:

• Stock thiamine 100 mg ampoules (essential for HG management)
• Ondansetron availability (PBS-listed for chemotherapy-induced nausea; off-label in pregnancy but widely accepted)
• Metoclopramide (widely available, safe alternative)

Retrieval

Criteria for retrieval to tertiary center:

• Wernicke encephalopathy: Confusion, ophthalmoplegia, ataxia (requires neurology input)
• Severe electrolyte disturbances: K+ below 2.5 mmol/L, Na+ below 125 mmol/L (risk of arrhythmia, seizures)
• Acute kidney injury requiring dialysis: Cr greater than 300 μmol/L with oliguria (rare)
• Suspected molar pregnancy: Requires evacuation by experienced gynecologist
• Refractory HG: Failed treatment at rural center; requires specialist input (TPN consideration)

Royal Flying Doctor Service (RFDS) considerations:

• Flight physiology: Nausea/vomiting may worsen at altitude; pre-medicate with ondansetron 8 mg IV + promethazine 25 mg IM
• Weight-based patient: Ensure accurate weight for drug dosing (use stretcher weight if bed scales unavailable)
• Limited monitoring: Portable monitors only; stabilize before transfer
• Communication: Direct line to receiving hospital obstetric team

RFDS contact numbers:

• NSW/ACT: 1800 625 800
• QLD: 1300 268 800
• SA/NT: 1300 737 287
• WA: 1300 737 343
• VIC: 1300 737 343

Telemedicine

When to use:

• Rural ED seeking advice on HG management
• Uncertain about admission vs discharge
• Interpreting pelvic ultrasound findings (molar pregnancy vs normal)
• Management of refractory HG

Platforms:

• NSW Telestroke (can be repurposed for obstetric emergencies): 1800 555 677
• QLD Virtual ED: Access via local health service
• VIC NURSE-ON-CALL: 1300 60 60 24 (for patient advice; not clinician-to-clinician)

Information to provide:

• Gestational age, LMP, pregnancy confirmation
• Vomiting severity (frequency, duration, oral tolerance)
• Vital signs, hydration status
• Bloods (UEC, hCG if done)
• Ultrasound findings (if performed)
• Treatment given so far

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References

Guidelines

1. American College of Obstetricians and Gynecologists. ACOG Practice Bulletin No. 189: Nausea and Vomiting of Pregnancy. Obstet Gynecol. 2018;131(1):e15-e30. PMID: 29266076
2. Royal Australian and New Zealand College of Obstetricians and Gynaecologists. Management of Nausea and Vomiting in Early Pregnancy (C-Obs 58). 2016. Available from: https://ranzcog.edu.au

Key Evidence - Epidemiology

3. Fejzo MS, Trovik J, Grooten IJ, et al. Nausea and vomiting of pregnancy and hyperemesis gravidarum. Nat Rev Dis Primers. 2019;5(1):62. PMID: 31515516
4. Fiaschi L, Nelson-Piercy C, Tata LJ. Hospital admission for hyperemesis gravidarum: a nationwide study of occurrence, reoccurrence and risk factors among 8.2 million pregnancies. Hum Reprod. 2016;31(8):1675-1684. PMID: 27251204
5. Veenendaal MV, van Abeelen AF, Painter RC, et al. Consequences of hyperemesis gravidarum for offspring: a systematic review and meta-analysis. BJOG. 2011;118(11):1302-1313. PMID: 21749625

Key Evidence - Pathophysiology

6. Fejzo MS, Fasching PA, Schneider MO, et al. Analysis of GDF15 and IGFBP7 in hyperemesis gravidarum support causality. Geburtshilfe Frauenheilkd. 2019;79(4):382-388. PMID: 31086371
7. Goodwin TM, Montoro M, Mestman JH, et al. The role of chorionic gonadotropin in transient hyperthyroidism of hyperemesis gravidarum. J Clin Endocrinol Metab. 1992;75(5):1333-1337. PMID: 1430095
8. Golberg D, Szilagyi A, Graves L. Hyperemesis gravidarum and Helicobacter pylori infection: a systematic review. Obstet Gynecol. 2007;110(3):695-703. PMID: 17766619

Key Evidence - Wernicke Encephalopathy

9. Chiossi G, Neri I, Cavazzuti M, et al. Hyperemesis gravidarum complicated by Wernicke encephalopathy: background, case report, and review of the literature. Obstet Gynecol Surv. 2006;61(4):255-268. PMID: 16551377
10. Oudman E, Wijnia JW, Oey MJ, et al. Wernicke's encephalopathy in hyperemesis gravidarum: a systematic review. Eur J Obstet Gynecol Reprod Biol. 2019;236:84-93. PMID: 30903900
11. Royal College of Obstetricians and Gynaecologists. The Management of Nausea and Vomiting of Pregnancy and Hyperemesis Gravidarum (Green-top Guideline No. 69). 2016. Available from: https://www.rcog.org.uk

Key Evidence - Antiemetic Safety

12. Huybrechts KF, Hernández-Díaz S, Straub L, et al. Association of maternal first-trimester ondansetron use with cardiac malformations and oral clefts in offspring. JAMA. 2018;320(23):2429-2437. PMID: 30562323
13. Kaplan YC, Richardson JL, Keskin-Arslan E, et al. Use of ondansetron during pregnancy and the risk of major congenital malformations: a systematic review and meta-analysis. Reprod Toxicol. 2019;86:1-13. PMID: 29445548
14. Pasternak B, Svanström H, Mølgaard-Nielsen D, et al. Metoclopramide in pregnancy and risk of major congenital malformations and fetal death. JAMA. 2013;310(15):1601-1611. PMID: 23681490
15. Matok I, Gorodischer R, Koren G, et al. The safety of metoclopramide use in the first trimester of pregnancy. N Engl J Med. 2009;360(24):2528-2535. PMID: 19494218
16. Dorsett AC, Sciscione AC. Ondansetron use in pregnancy: critical appraisal and updated clinical recommendations. Am J Obstet Gynecol MFM. 2021;3(5):100402. PMID: 34103117

Key Evidence - Management

17. Tan PC, Khine PP, Vallikkannu N, et al. Promethazine compared with metoclopramide for hyperemesis gravidarum: a randomized controlled trial. Obstet Gynecol. 2010;115(5):975-981. PMID: 20410772
18. Seto A, Einarson T, Koren G. Pregnancy outcome following first trimester exposure to antihistamines: meta-analysis. Am J Perinatol. 1997;14(3):119-124. PMID: 9259917
19. Matok I, Clark S, Caritis SN, et al. Studying the antiemetic effect of vitamin B6 for morning sickness: pyridoxine and pyridoxal are prodrugs. J Clin Pharmacol. 2014;54(12):1429-1433. PMID: 24965576

Key Evidence - Dexamethasone

20. Carlin A, Alfirevic Z. Physiological changes of pregnancy and monitoring. Best Pract Res Clin Obstet Gynaecol. 2008;22(5):801-823. PMID: 18760680
21. Bondok RS, El Sharnouby NM, Eid HE, et al. Pulsed steroid therapy is an effective treatment for intractable hyperemesis gravidarum. Crit Care Med. 2006;34(11):2781-2783. PMID: 16943732
22. Matthews A, Haas DM, O'Mathúna DP, et al. Interventions for nausea and vomiting in early pregnancy. Cochrane Database Syst Rev. 2015;2015(9):CD007575. PMID: 26348534
23. Guttuso T Jr, Robinson LK, Amankwah KS. Gabapentin use in hyperemesis gravidarum: a pilot study. Early Hum Dev. 2010;86(1):65-66. PMID: 20117892

Key Evidence - Fluid Resuscitation

24. Koren G, Maltepe C. Pre-emptive therapy for severe nausea and vomiting of pregnancy and hyperemesis gravidarum. J Obstet Gynaecol. 2004;24(5):530-533. PMID: 15369935
25. Czeizel AE, Puhó E. Association between severe nausea and vomiting in pregnancy and lower rate of preterm births. Paediatr Perinat Epidemiol. 2004;18(4):253-259. PMID: 15255878

Key Evidence - Molar Pregnancy

26. Seckl MJ, Sebire NJ, Berkowitz RS. Gestational trophoblastic disease. Lancet. 2010;376(9742):717-729. PMID: 20673583
27. Lurain JR. Gestational trophoblastic disease I: epidemiology, pathology, clinical presentation and diagnosis of gestational trophoblastic disease, and management of hydatidiform mole. Am J Obstet Gynecol. 2010;203(6):531-539. PMID: 20728069
28. Berkowitz RS, Goldstein DP. Current advances in the management of gestational trophoblastic disease. Gynecol Oncol. 2013;128(1):3-5. PMID: 23200911

Key Evidence - Thyrotoxicosis

29. Goodwin TM, Hershman JM. Hyperthyroidism due to inappropriate production of human chorionic gonadotropin. Clin Obstet Gynecol. 1997;40(1):32-44. PMID: 9103947
30. Tan JY, Loh KC, Yeo GS, et al. Transient hyperthyroidism of hyperemesis gravidarum. BJOG. 2002;109(6):683-688. PMID: 12118648

Key Evidence - Outcomes

31. Dodds L, Fell DB, Joseph KS, et al. Outcomes of pregnancies complicated by hyperemesis gravidarum. Obstet Gynecol. 2006;107(2 Pt 1):285-292. PMID: 16449113
32. Fell DB, Dodds L, Joseph KS, et al. Risk factors for hyperemesis gravidarum requiring hospital admission during pregnancy. Obstet Gynecol. 2006;107(2 Pt 1):277-284. PMID: 16449112

Australian/NZ Context

33. Australian Institute of Health and Welfare. Australia's Mothers and Babies 2020. Perinatal statistics series no. 37. Cat. no. PER 101. Canberra: AIHW; 2022.
34. Sullivan EA, Hall B, King JF. Maternal deaths in Australia 2003-2005. Maternal deaths series no. 3. Cat. no. PER 42. Sydney: AIHW; 2008.
35. Perinatal and Maternal Mortality Review Committee. Twelfth Annual Report of the Perinatal and Maternal Mortality Review Committee: Reporting mortality 2016. Wellington: Health Quality & Safety Commission; 2018.

Indigenous Health

36. Kildea S, Kruske S, Barclay L, et al. 'Closing the Gap': how maternity services can contribute to reducing poor maternal infant health outcomes for Aboriginal and Torres Strait Islander women. Rural Remote Health. 2010;10(3):1383. PMID: 20658893
37. Panaretto KS, Lee HM, Mitchell MR, et al. Impact of a collaborative shared antenatal care program for urban Indigenous women: a prospective cohort study. Med J Aust. 2005;182(10):514-519. PMID: 15896179
38. Stevenson TN, McArthur C, Chilton M, et al. Prematurity among First Nations in British Columbia, Canada. BMC Pregnancy Childbirth. 2017;17(1):124. PMID: 28431538