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Nausea and Vomiting in Pregnancy – Management Options for Hyperemesis Gravidarum

CLINICAL ACTIONS:

Nausea and vomiting are common in pregnancy, with a recurrence rate of 15%-81% in subsequent pregnancies. The goal is to not only reduce symptoms but prevent persistent vomiting, known as hyperemesis gravidarum. Consider the following management options (based on ACOG guidance):

Nonpharmacologic Treatment

Research limited but the following may be helpful

  • Avoid a full stomach with frequent, small meals every 1–2 hours
    • Minimize spicy or fatty foods
  • Eliminate supplemental iron
    • Substitute folic acid for iron-containing prenatal vitamins
  • Eat
    • Bland or dry foods
    • High-protein snacks and crackers in the morning before getting out of bed
    • Ginger 250 mg 4 times per day
  • Avoid sensory stimuli
    • Odors, heat, humidity, noise, and flickering lights/stimuli that may provoke onset of symptoms
  • Prenatal vitamins for 1 month prior to conception may reduce symptoms
  • Acupressure, acupuncture, or electrical nerve stimulation (acustimulation)
    • P6 or Neiguan point (located three finger breadths below the wrist on the inside of the wrist in between the two tendons)
    • Evidence is inconclusive with conflicting conclusions
    • Consider P6 acupressure with wrist bands

Pharmacologic Treatment

Initial ‘First Line’ Options

  • Vitamin B6 (pyridoxine) or Vitamin B6 plus doxylamine
    • Vitamin B6
      • 10-25 mg orally (alone or in combination with doxylamine 12.5 mg orally) 3 or 4 times per day OR
    • Vitamin B6 10 mg/ doxylamine 10 mg combination
      • 2 tablets orally at bedtime initially, up to 4 tablets per day (1 tablet in the AM, 1 tab in the midafternoon, and 2 tablets at bedtime) OR
    • Vitamin B6 20 mg/ doxylamine 20 mg combination
      • 1 tablet orally at bedtime initially, up to 2 tablets per day (1 tablet in the AM and 1 tablet at bedtime)

If Symptoms Persist Add the Following (presented in alphabetical order)

  • Dimenhydrinate
    • 25-50 mg every 4 to 6 hours, orally as needed (do not exceed 200 mg per day if also on doxylamine) OR
  •  Diphenhydramine
    • 25-50 mg every 4 to 6 hours, orally OR
  • Prochlorperazine
    • 25 mg every 12 hours, rectally OR
  •  Promethazine
    • 12.5-25 mg every 4 to 6 hours, orally or rectally

If Symptoms Persist but No Dehydration Add Any of the Following (presented in alphabetical order)

  • Metoclopramide
    • 5-10 mg every 6 to 8 hours, IM or orally OR
  • Ondansetron
    • 4 mg orally every 8 hours OR
  • Promethazine
    • 12.5-25 mg every 4 to 6 hours, orally, IM or rectally OR 
  • Trimethobenzamide
    • 200 mg every 6 to 8 hours, IM

If Symptoms Persist and the Patient is Dehydrated

  • IV fluid replacement
    • If patient vomiting for > 3 weeks
      • IV thiamine, 100 mg with initial rehydration fluid and 100 mg daily for 2 to 3 days, followed by IV multivitamins are recommended to prevent Wernicke encephalopathy

If Symptoms Persist Even With the Addition of IV Fluids, Add Any of the Following (presented in alphabetical order)

  • Dimenhydrinate IV
    • 50 mg (in 50 mL saline, over 20 min) every 4 to 6 hours OR
  • Metoclopramide IV
    • 5-10 mg every 8 hours OR
  • Ondansetron IV
    • 8 mg, over 15 minutes, every 12 hours OR
  • Promethazine IV
    • 12.5-25 mg every 4 to 6 hours

If Symptoms Still Persist Despite IV Fluids and Above IV Medications, Add the Following (presented in alphabetical order)

  • Chlorpromazine
    • 25-50 mg every 4 to 6 hours IM or IV or 10-25 mg orally every 4 to 6 hours OR
  • Methylprednisolone
    • 16 mg every 8 hours orally or IV for 3 days
    • Taper over 2 weeks to lowest effective dose
    • Limit duration to 6 weeks

Potential Side Effects of Medications

  • Be especially careful if using multiple medications together
  • Use of a dopamine antagonist (e.g., metoclopramide) and various phenothiazine medications (e.g., promethazine, prochlorperazine, or chlorpromazine) increase the risk of
    • extrapyramidal effects (eg, tardive dyskinesia)
    • neuroleptic malignant syndrome (rare)
      • Life-threatening reaction
      • High fever, confusion, rigid muscles, and symptoms of autonomic nervous system instability
  • Serotonin 5-HT3 inhibitors (e.g., ondansetron) in combination with phenothiazine medications (e.g., chlorpromazine) may increase risk of QT interval prolongation

Hyperemesis Gravidarum

  • Most common indication for admission in early pregnancy
    • Occurs in 0.3-3.0% of pregnancies
  • No single accepted definition
    • Diagnosis of exclusion
  • Following are the most common criteria
    • Persistent vomiting unrelated to other causes
    • Significant, large ketonuria
      • Electrolyte, liver and thyroid function tests may be abnormal
    • 5% weight loss from pre-pregnancy weigh
  • Initiate antiemetic therapy before symptom onset to reduce severity of nausea and vomiting
  • IV hydration should be used for patients who cannot tolerate oral liquids or if clinical signs of dehydration are present
  • Ketosis and vitamin deficiency should be corrected
  • Enteral tube feeding is recommended if patient is unresponsive to medical therapy and their weight cannot be maintained
  • Rule out other causes of intractable vomiting before making a diagnosis of hyperemesis gravidarum

SYNOPSIS:

The etiology of nausea and vomiting of pregnancy is unknown, with 50-80% of women experiencing nausea and 50% experiencing vomiting. Ultrasound may be helpful to identify multiple gestation and molar pregnancy (see Risk Factors below).  Abnormal maternal thyroid tests are sometimes seen and are related to gestational transient thyrotoxicosis and/or hyperemesis gravidarum.  Management includes supportive therapy and not antithyroid medications.

KEY POINTS:

  • Risk factors for hyperemesis gravidarum
    • Increased placental mass
      • Molar gestation or multiple gestation
    • History of motion sickness or family or personal history of hyperemesis gravidarum
    • Female fetuses
  • According to ACOG “A patient’s perception of the severity of her symptoms and her desire for treatment are influential in clinical decision making”
    • A validated scoring system has been published known as the mother risk Pregnancy-Unique Quantification of Emesis and nausea (PUQE) that may be helpful (see ‘Learn More – Primary Sources’, below)
  • Symptoms of nausea and vomiting of pregnancy can occur prior to 9 weeks gestation
  • Fetal Effects
    • Evidence is conflicting as to whether there is a higher incidence of small for gestational age and premature  infants born to mothers with hyperemesis gravidarum
    • No association noted with perinatal or neonatal mortality
    • Mild to moderate vomiting has little effect on pregnancy outcome
    • Lower rates of miscarriage have been documented, likely due to healthy placenta and not protective effect of nausea and vomiting
  • ACOG states

it is appropriate to reassure patients that the presence of nausea and vomiting of pregnancy and even hyperemesis gravidarum most often portends well for pregnancy outcome

Learn more:

ACOG Practice Bulletin 189: Nausea and Vomiting of Pregnancy

Nausea and Vomiting of Pregnancy: Using the 24-hour Pregnancy-Unique Quantification of Emesis (PUQE-24) Scale (2009)

RCOG Guideline 69: The Management of Nausea and Vomiting in Pregnancy and Hyperemesis Gravidarum