Hyperemesis Gravidarum

Aka: Hyperemesis Gravidarum, Antiemetic in Pregnancy

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II. Definitions

  1. Hyperemesis Gravidarum
    1. Severe, intractable Vomiting in Pregnancy

III. Epidemiology

  1. Incidence: 1-2 per 200 pregnancies (up to 3% in some series)

IV. Pathophysiology

  1. See Morning Sickness

V. History: Diagnosis

  1. Intractable Vomiting with systemic effects
    1. Ketonuria (Acetonuria)
    2. Weight loss (typically 5% of pre-pregnant weight)
    3. Dehydration
    4. Electrolyte disturbance
  2. Occurs in first trimester
  3. Peak Incidence at 10-12 weeks
  4. Often worse in morning
  5. Quantify Vomiting
  6. Establish inability to tolerate oral fluids
  7. Urinary symptoms
    1. Decreased Urine Output
    2. Dysuria
    3. Flank Pain

VI. Signs

  1. Weight loss, or no weight gain
  2. Tachycardia
  3. Dry mucus membranes
  4. Poor Skin Turgor
  5. Fever
  6. Uterine Size
  7. External Fetal heart tone monitoring

VII. Precautions

  1. Hyperemesis before 4 weeks or after 12 weeks gestation may suggest other cause
    1. Consider differential diagnosis as below

VIII. Differential Diagnosis

  1. Gastrointestinal causes
    1. Peptic Ulcer Disease
    2. Cholecystitis
    3. Pancreatitis
    4. Bowel Obstruction
    5. Volvulus
    6. Appendicitis
  2. Genitourinary causes
    1. Pyelonephritis
    2. Nephrolithiasis
    3. Ovarian Torsion
  3. Endocrine causes
    1. Diabetes Mellitus
    2. Hyperthyroidism
  4. Neurologic causes
    1. Migraine Headache
    2. Pseudotumor Cerebri
    3. Vertigo
  5. Miscellaneous conditions
    1. Pneumonia
  6. Pregnancy-Related causes
    1. Acute Fatty Liver of Pregnancy
    2. Pregnancy Induced Hypertension
    3. Molar Pregnancy
    4. Multiple Gestation
    5. Down Syndrome (affecting fetus)
    6. Hydrops fetalis

IX. Labs

  1. Basic Chemistry Panel (basic metabolic panel)
  2. Liver Function Test (or as part of comprehensive metabolic panel)
    1. Aminotransferases (AST, ALT) may exceed 200 IU/L
    2. Serum Bilirubin and Alkaline Phosphatase may be increased up to twice normal
  3. Complete Blood Count
  4. Urinalysis
    1. Evaluate for Urinary Tract Infection
    2. Ketonuria (or Ketonemia) was previously used as a marker for hyperemesis severity
      1. Urine Ketones do NOT correlate with hyperemesis severity
      2. (2014) Am J Obstet Gynecol 211(2): 150 +PMID:24530975 [PubMed]
  5. Urine Culture
  6. Quantitative bhCG
  7. Thyroid Function Test: Free T4 and Thyroid Stimulating Hormone (TSH)
    1. Previously recommended routinely
    2. As of 2015, only recommended for hyperemesis with Hyperthyroidism symptoms, signs

X. Imaging

  1. Ultrasound Pelvis
    1. Previously used to evaluate for Molar Pregnancy or Multiple Gestation
    2. However, ACOG does not recommend routine Ultrasound solely for hyperemesis (unless otherwise indicated)
  2. Ultrasound Right Upper Quadrant
    1. Gallbladder and Pancreas

XI. Management: Non-prescription management

  1. See Morning Sickness for non-pharmacologic measures
  2. Dietitian Consultation
  3. See Morning Sickness
  4. Over the counter agents: Vitamins
    1. Pyridoxine (Vitamin B6)
      1. Dose: 25 mg orally every 6-8 hours
      2. Often used in combination with other agents below (e.g. Doxylamine)
  5. Over-the-counter agents: Antihistamines
    1. Diphenhydramine (Benadryl)
      1. Dose: 25-50 mg IM/IV/PO q4-6 hours
      2. Maximum: 400 mg in 24 hours
    2. Meclizine (Antivert)
      1. Oral: 25-50 mg PO q6 hours
      2. Consider using concurrently with Phenergan
    3. Dimenhydrinate (Dramamine)
      1. Dose: 50-100 mg every 4-6 hours
      2. Maximum: 300 mg in 24 hours
    4. Doxylamine (Unisom, Diclectin)
      1. Dose: 10 mg up to three times daily
  6. Combination
    1. Doxylamine 10 mg and Pyrodoxine 10 mg (Diclegis, previously Bendectin and Diclectin in Canada)
      1. Dose: Start with 2 tabs in PM and may advance to 1 in AM, 1 at Noon and 2 in PM
      2. Originally pulled from market due to safety concerns that were unsubstantiated
      3. Diclegis is very expensive ($570/month) until generic in 2019
        1. However, generic Doxylamine and Pyridoxine are inexpensive at $20/month
      4. Bonjesta (extended release Doxylamine 20 mg and Pyridoxine 20 mg)
        1. Released in 2018, very expensive and no significant added benefit aside from frequency
      5. (2013) Presc Lett 20(6): 32-3
      6. (2018) Presc Lett 25(5): 29

XII. Management: Prescription Antiemetics (Take 1/2 hour prior to meals)

  1. See other general management and OTC Medication options above
  2. First-line agents
    1. Consider adding Pyridoxine (Vitamin B6) with or without Doxylamine as listed above
    2. Metoclopramide (Reglan)
      1. Dose: 10 mg orally four times daily or 1-2 mg IV
      2. Risk of Dystonic Reaction (as high as 20%) and Tardive Dyskinesia (rare)
  3. Second-line agents
    1. Prochlorperazine (Compazine)
      1. Parenteral and oral: 5-10 mg IM/IV/PO q4-6 hours
      2. Suppository: 25 mg PR q6-8 hours
    2. Promethazine (Phenergan)
      1. Risk of neonatal respiratory depression near term or during labor
      2. Dose: 12.5-25 mg PO/PR q4-6 hours
      3. Maximum: 100 mg in 24 hours
    3. Vistaril
      1. Dose: 25-50 mg IM/PO q4-6 hours
  4. Refractory hyperemesis management
    1. Ondansetron ODT (Zofran ODT)
      1. Dose: 4 mg orally up to every 6 hours
      2. Commonly used in U.S. for hyperemesis
      3. Although had appeared safe in pregnancy, longterm data were lacking (compared with other agents)
        1. Ondansetron may be associated with 2 fold risk of Congenital Heart Defects and Cleft Palate
        2. ACOG recognizes the inconsistent findings and notes low risk to the fetus
        3. (2014) Presc Lett 21(1): 5
        4. Koren (2012) Can Fam Physician 58(10):1092-3 [PubMed]
    2. Corticosteroid regimen
      1. Methylprednisolone 16 mg PO tid, taper over 2 weeks
      2. Risk of Cleft Palate with first trimester use
        1. Safari (1998) Am J Obstet Gynecol 179:921-4 [PubMed]

XIII. Management: Agents to avoid (mixed or absent safety data)

  1. Avoid Droperidol
  2. Avoid Phosphorated Carbohydrates (Emetrol)
    1. No evidence of benefit and as much Glucose as 2 cans of regular soda
  3. Avoid Scopolamine in first trimester (risk of limb and trunk abnormalities)

XIV. Management: Emergency Department protocol

  1. Initial Fluid Replacement
    1. Approach
      1. Dextrose containing solutions may be preferred (but conssider Thiamine replacement at the same time)
        1. Tan (2013) Obstet Gynecol 12(2 Pt 1): 291-8 +PMID:23232754 [PubMed]
    2. First: Isotonic Saline (NS or LR or D5LR) 1-2 liter bolus
    3. Next: D5LR with 20 KCl at 150 cc/h
  2. Thiamine indications (prevention of Wernicke Encephalopathy)
    1. Transitioning to dextrose solutions
    2. Vomiting >3 weeks or IV fluid >3 days
  3. Inpatient
    1. Follow daily weights
    2. Follow Input and Output

XV. Resources

  1. Gardner in U.S. Pharmacist
    1. http://legacy.uspharmacist.com/oldformat.asp?url=newlook/files/Feat/ACF2F23.cfm&pub_id=8&article_id=54

XVI. Complications

  1. Vomiting-induced GI Trauma (e.g. Mallory Weiss Tear)
  2. Electrolyte abnormalities (e.g. Hypokalemia, Hyponatremia)
  3. Thiamine deficiency (Wernicke Encephalopathy)
  4. Acute Kidney Injury
  5. Severe weight loss in pregnancy

XVII. References

  1. Delaney in Herbert (2018) EM:Rap 18(1): 12-4
  2. Mayo and Welsh (2021) Crit Dec Emerg Med 33(5): 12
  3. (2015) Obstet Gynecol 126(3): 687-8 +PMID: 26287781 [PubMed]
  4. Broussard (1998) Gastroenterol Clin North Am 27(1):123 [PubMed]
  5. Eliakim (2000) Am J Perinatol 17(4):207-18 [PubMed]
  6. Herrell (2014) Am Fam Physician 89(12): 965-70 [PubMed]
  7. Kuscu (2002) Postgrad Med 78(916):76-9 [PubMed]
  8. Quinlan (2003) Am Fam Physician 68(1):121-8 [PubMed]

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