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

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

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

XVI. Complications

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Related Studies

Ontology: Hyperemesis Gravidarum (C0020450)

Definition (NCI) Severe, intractable vomiting during pregnancy (usually the first trimester) accompanied by dehydration, weight loss, and electrolyte imbalances.
Definition (MSH) Intractable VOMITING that develops in early PREGNANCY and persists. This can lead to DEHYDRATION and WEIGHT LOSS.
Concepts Sign or Symptom (T184)
MSH D006939
ICD9 643
ICD10 O21
SnomedCT 14094001, 156113005, 267308007
Dutch excessief zwangerschapsbraken, overmatig braken tijdens zwangerschap, gravidarum; hyperemesis, hyperemesis; gravidarum, hyperemesis gravidarum, Overvloedig zwangerschapsbraken, Braken, zwangerschaps-, Hyperemesis gravidarum, Zwangerschapsbraken
French Vomissements excessifs pendant la grossese, Vomissements excessifs au cours de la grossesse, Vomissements incoercibles de la grossesse, Hyperémèse gravidique, Vomissement incoercible de la grossesse
German exzessives Erbrechen waehrend der Schwangerschaft, Uebermaessiges Erbrechen waehrend der Schwangerschaft, Hyperemesis gravidarum, Schwangerschaftserbrechen
Italian Vomito incontrollabile in gravidanza, Vomito eccessivo in gravidanza, Iperemesi gravidica
Portuguese Vómitos em excesso na gravidez, Vómitos excessivos na gravidez, Hiperêmese Gravídica, Hiperêmese das Grávidas, Vômitos Excessivos na Gravidez, Hiperémese gravídica, Vômito Pernicioso na Gravidez
Spanish Vómitos excesivos en el embarazo, Exceso de vómitos en el embarazo, vómito excesivo durante el embarazo, Hiperémesis Gravídica, hiperemesis durante el embarazo, hiperemesis gravídica (trastorno), hiperemesis gravídica, vómito excesivo durante el embarazo (trastorno), vómito intenso Y/O persistente que comienza durante el embarazo, Hiperemesis gravídica, Hiperemesis Gravídica, Vómito Pernicioso del Embarazo
Japanese 強度の妊娠嘔吐, キョウドノニンシンオウト, ニンシンオソ, ニンシンツワリ, 悪阻, 重症妊娠悪阻, 悪阻-重症, おそ, 妊娠悪阻
Swedish Graviditetskräkningar
English Excessive vomiting in pregnancy, Hyperemesis gravidarum, hyperemesis gravidarum (diagnosis), hyperemesis gravidarum, Excess vomiting in pregnancy, Hyperemesis, Hyperemesis Gravidarum [Disease/Finding], excessive vomiting in pregnancy, excessive vomiting pregnancy, hyperemesis of pregnancy, gravidarum hyperemesis, hyperemesis pregnancy, hyperemesis in pregnancy, pregnancy hyperemesis, Gravidarum -hyperemesis, Pregnancy Pernicious Vomiting, Pernicious Vomiting of Pregnancy, Hyperemesis arising during pregnancy, Excessive pregnancy vomiting, Hyperemesis of pregnancy, Excessive vomiting in pregnancy (disorder), Persistent AND/OR vicious vomiting arising during pregnancy, gravidarum; hyperemesis, hyperemesis; gravidarum, Persistent or vicious vomiting arising during pregnancy, Hyperemesis Gravidarum
Czech hyperemesis gravidarum, Nadměrné zvracení v těhotenství, Hyperemesis gravidarum, nadměrné zvracení v těhotenství
Finnish Voimakas raskausoksentelu
Korean 임신중 과다 구토
Polish Wymioty ciężarnych niepowściągliwe
Hungarian Terhességi vészes hányás, Túlzott hányás a terhességben, Túlzott mértékő hányás a terhességben
Norwegian Hyperemesis gravidarum, Vedvarende kvalme og oppkast i svangerskapet