Hyperemesis Gravidarum in Emergency Medicine 

Updated: Feb 04, 2021
Author: Feras H Khan, MD; Chief Editor: Jeter (Jay) Pritchard Taylor, III, MD 

Overview

Practice Essentials

Hyperemesis gravidarum is defined as a severe and intractable form of nausea and vomiting in pregnancy. It is a diagnosis of exclusion. Early treatment of nausea and vomiting of pregnancy may prevent progression to hyperemesis gravidarum.

Signs and symptoms

Nausea and vomiting occur in early pregnancy and do not respond to simple measures, such as reassurance and dietary changes. Physical examination findings may include weight loss and dehydration.

See Presentation for more detail.

Diagnosis

Laboratory studies

Laboratory testing may include the following:

  • Obtaining electrolyte, blood urea nitrogen and creatinine, and serum ketone levels
  • Measuring urine gravity and ketones
  • Performing liver function tests if hepatitis is a concern
  • Performing a complete blood count and urinalysis to rule out other causes, with particular concern for pyelonephritis
  • Obtaining serum amylase-to-creatinine ratio and/or lipase level if pancreatitis is a concern

Imaging studies

Ultrasonographic evaluation is recommended to detect molar pregnancy or multiple gestations.

See Workup for more detail.

Treatment

The initial management of hyperemesis gravidarum should be conservative and may include rest, avoidance of sensory triggers, and dietary recommendations. Alternative therapies may include acupressure.

The only drug approved by the US Food and Drug Administration for the treatment of nausea and vomiting in pregnancy is doxylamine/pyridoxine. The following medications have also been used in women with hyperemesis gravidarum:

  • Vitamins, such as pyridoxine
  • Herbal remedies, such as ginger
  • Antiemetics
  • Corticosteroids
  • Antihistamines

See Treatment and Medication for more detail.

Background

Nausea and vomiting are common in pregnancy, occurring in 70-85% of all gravid women.[1, 2]

Hyperemesis gravidarum is a severe and intractable form of nausea and vomiting in pregnancy, affecting 0.8-2.3% of pregnant women.[2, 3] It is a diagnosis of exclusion and may result in weight loss; nutritional deficiencies; and abnormalities in fluids, electrolyte levels, and acid-base balance. The peak incidence is at 8-12 weeks of pregnancy, and symptoms usually resolve by week 20 in all but 10% of patients. Uncomplicated nausea and vomiting of pregnancy is generally associated with a lower rate of miscarriage, but hyperemesis gravidarum may affect the health and well-being of both the pregnant woman and the fetus.

Pathophysiology

The etiology of nausea and vomiting of pregnancy is unknown. Many have postulated that nausea and vomiting are protective in pregnancy to reduce exposures to potentially teratogenic materials. Some theories hold that elevated human chorionic gonadotropin (hCG) or estradiol levels could be causative, due to correlations in numerous studies between levels and symptoms, but this has not been demonstrated conclusively. Psychological theories of the etiology are falling out of favor, and the American College of Obstetrics and Gynecology warns that attributing vomiting to psychological disorders has likely impeded progress in understanding the true etiology of hyperemesis gravidarum.[4]

Etiology

The cause of severe nausea and vomiting in pregnancy has not been identified. Hyperemesis may have a genetic component, as sisters and daughters of women with hyperemesis have a higher incidence.

Hyperemesis is also associated with hyperemesis in prior pregnancy, female gestation, multiple gestation, triploidy, trisomy 21, current or prior molar pregnancy, and hydrops fetalis.

Women with history of motion sickness, migraine headaches, psychiatric illness, pregestational diabetes, being underweight pregestation,[5]  hyperthyroidism, pyridoxine deficiency, and gastrointestinal disorders are also at an increased risk. The use of assisted reproductive technology has been associated with hyperemesis.[6]

Some studies have suggested that Helicobacter pylori infection may play a role in hyperemesis,[7]  but the data are inconclusive.

Cigarette smoking and maternal age older than 30 years appear to be protective.

Epidemiology

United States statistics

Hyperemesis gravidarum occurs in 0.5-2% of pregnancies, with the variation in incidence arising from different diagnostic criteria and ethnic variations.[8] Studies have found an admission rate of 0.8% for hyperemesis gravidarum[9] and an average of 1.3 hospital admissions per hyperemesis patient, with an average hospital stay of 2.6-4 days.

International statistics

In a study conducted in Finland, the incidence of hyperemesis gravidarum was 1.3%.[6]

Race- and age-related demographics

Hyperemesis patients are more likely to be nonwhite.

Patients younger than 30 years are more likely to experience hyperemesis.

Prognosis

One study has demonstrated that adverse fetal outcomes are mostly limited to poor maternal weight gain.[10]  Women who gained less than 7 kg in pregnancy were more likely to have fetal complications, but those with hyperemesis and greater than 7 kg weight gain had no increased risk. This research indicates that treating hyperemesis gravidarum such that the patient is able to gain weight portends a better prognosis.

Mortality/morbidity

With mild-to-moderate vomiting, the patient and the fetus are unlikely to experience any increased morbidity or mortality. Before the advent of intravenous hydration, hyperemesis was a major cause of maternal death. Currently, mortality is exceedingly rare, but maternal morbidities may include Wernicke encephalopathy from vitamin B-1 deficiency, Mallory-Weiss tears, esophageal rupture, pneumothorax, and acute tubular necrosis. Hyperemesis is the second leading cause of hospitalization in pregnancy, second only to preterm labor. Additionally, many women experience significant psychosocial morbidity, occasionally interfering with assumption of the maternal role and rarely leading to termination of the pregnancy.

Complications

Complications of vomiting rarely occur; however, Mallory-Weiss tears and esophageal perforations have been reported.

Women with hyperemesis and poor weight gain have lower average birth weights and are more likely to have a small for gestational age infant and may be at higher risk for preterm birth.

In severe cases, without thiamine supplementation, Wernicke encephalopathy may occur (ie, diplopia, nystagmus, disorientation, confusion, coma).

If treatment is unsuccessful, complications of prolonged dehydration and starvation may occur.

 

Presentation

History

Nausea and vomiting occur in early pregnancy and are nonresponsive to simple measures, such as reassurance and dietary changes.

Fever and abdominal pain are not characteristic of hyperemesis gravidarum.

If vomiting begins after 9 weeks' gestation, other causes should be investigated.

Physical Examination

Findings at physical examination may include the following:

  • Weight loss

  • Dehydration: Decreased skin turgor; postural changes in blood pressure (BP) and pulse

Abdominal tenderness, fever, and goiter likely indicate another process.

 

DDx

Diagnostic Considerations

No drugs are approved by the FDA for the treatment of nausea and vomiting in pregnancy, and the expected benefits of treatment should outweigh the risks.

Other conditions to be considered in patients with suspected hyperemesis gravidarum include the following:

  • Pyelonephritis

  • Molar pregnancy

  • Pseudotumor cerebri

  • Acute fatty liver of pregnancy

Differential Diagnoses

 

Workup

Approach Considerations

Laboratory studies

Laboratory testing may include the following:

  • Obtaining electrolyte, BUN and creatinine, and serum ketone levels.

  • Measuring urine gravity and ketones.

  • Performing liver function tests (LFTs) if hepatitis is a concern. Of note, LFTs can be slightly elevated with hyperemesis gravidarum.

  • Performing a complete blood count and urinalysis to rule out other causes, with particular concern for pyelonephritis.

  • Obtaining serum amylase-to-creatinine ratio and/or lipase level if pancreatitis is a concern.

Note the following:

  • Hyperthyroidism causing nausea and vomiting is rare; a T3 and T4 level should be drawn if this is a concern. (Thyroid-stimulating hormone [TSH] can be suppressed in hyperemesis gravidarum.)

  • Serum hCG levels are not clinically useful in a patient with a known intrauterine pregnancy (IUP) and hyperemesis.

Imaging studies

The patient should have an ultrasonographic evaluation of her pregnancy to look for molar pregnancy or multiple gestations.

 

Treatment

Approach Considerations

The American College of Obstetricians and Gynecologists updated guidelines on the treatment of nausea/vomiting in pregnancy and recommend the following[11] :

  • The combination of doxylamine and vitamin B6 should be considered first-line pharmacotherapy.
  • Treating nausea and vomiting early in pregnancy, before it progresses, can help control symptoms and prevent more serious complications, including hospitalization.
  • Nausea or vomiting almost always presents before 9 weeks of gestation. When nausea or vomiting begins for the first time after 9 weeks, other conditions should be considered.
  • Taking prenatal vitamins for 3 months before conception may reduce the incidence and severity of nausea and vomiting in pregnancy.
  • In patients with hyperemesis gravidarum who also have suppressed thyroid-stimulating hormone levels, treatment of hyperthyroidism should not begin without evidence (such as goiter, thyroid autoantibodies, or both) of thyroid disease.
  • Treatment with ginger has shown benefit in reducing nausea and can be considered a nonpharmacologic option.
  • Treatment of severe nausea and vomiting of pregnancy or hyperemesis gravidarum with methylprednisolone may be effective in refractory cases; however, the risk profile of methylprednisolone suggests it should be used as a last resort.

Emergency Department Care

Early treatment of nausea and vomiting of pregnancy may prevent progression to hyperemesis gravidarum. First-line treatment often involves rest and avoidance of sensory stimuli that may act as triggers. Frequent small meals with avoidance of spicy or fatty foods and increasing high-protein snacks are recommended. 

Perform the following:

  • Replace fluids and administer antiemetics, if required. Normal saline or Lactated Ringer solution is recommended.

  • Consider the addition of glucose, multivitamins, magnesium, pyridoxine, and/or thiamine. For any patient in whom vitamin deficiency is a concern, thiamine 100 mg should be given before initiating dextrose-containing fluids.

  • Note: Dextrose solutions may stop fat breakdown.

  • Continue treatment until the patient can tolerate oral fluids and until test results show little or no ketones in the urine.

Hospitalization

In a cost-utility analysis of day care over inpatient management of nausea and vomiting in pregnancy, European investigators found day care management was 70% more cost effective as well as more effective than inpatient care.[12]  However, admit pregnant patients with any of the following:

  • Persistently abnormal vital signs

  • Severe dehydration and inability to tolerate oral fluids

  • Severe electrolyte abnormality

  • Acidosis

  • Infection

  • Malnutrition

Parenteral antiemetics may be administered if the patient's condition is unresponsive to fluids, dietary restrictions, and oral medications.

Weight loss

Patients who continue to lose weight may require supplemental nutrition. Several care reports demonstrate that enteral tube feedings may be well tolerated and are a reasonable first attempt in admitted patients. Rarely, some women require total parenteral nutrition. Peripherally inserted central catheter (PICC) lines have been shown to have a high complication rate in these patients and should not be considered a routine therapy.[13]

Consultations

Obstetrical consultation is indicated if the patient appears to require admission to the hospital secondary to refractory symptoms unresponsive to ED management.

Outpatient care

Patients should ingest frequent small meals with high-carbohydrate or high-protein content. (Avoid offensive odors, fatty foods, spicy foods, iron supplements.)

Some patients may require outpatient maintenance with pyridoxine  (vitamin B-6) with/without doxylamine or ondansetron or other antiemetic may be considered.

Consider the use of Sea Bands, which apply pressure to the acupressure P6 point.

For women infected with H pylori, case reports have suggested improvement in symptoms with eradication of the infection.

Reassure patients. Some women may find benefit in counseling.

For patient education resources, see Pregnancy Center, as well as Pregnancy and Morning Sickness (Vomiting During Pregnancy).

 

Medication

Medication Summary

The American College of Obstetrics and Gynecology recommends that first-line treatment of nausea and vomiting of pregnancy should start with pyridoxine (vitamin B6) with or without doxylamine.[11]  Pyridoxine has been found to be effective in significantly reducing severe vomiting but is less effective with milder vomiting. Pyridoxine in combination with doxylamine 10 mg, the active ingredient in many over-the-counter sleep agents, has been shown in randomized, placebo-controlled trials to have a 70% reduction in nausea and vomiting. The combination of pyridoxine 10 mg and doxylamine 10 mg was originally available in the United States from 1956 until 1983 as Bendectin, when it was voluntarily removed from the market by the manufacturer due to litigation. Multiple studies have shown no increased risk of birth defects with the pyridoxine-doxylamine combination.

The only FDA-approved drug for treating nausea and vomiting in pregnancy is doxylamine/pyridoxine (Diclegis). Originally sold between 1956 and 1983 with the brand name Bendectin, it was pulled from the market because of safety concerns, which have since been disproved. The new dosage form approved in April 2013 is a delayed-release tablet, that when taken at bedtime, is at its peak serum concentrations in the morning when nausea and vomiting may be worse. Approval was based on a study of pregnant women between 7-14 weeks gestation who were suffering from nausea and vomiting. Compared with placebo, doxylamine/pyridoxine significantly improved both the Pregnancy-Unique Quantification of Emesis and Nausea (PUQE) scores and quality of life of trial participants.[14]

Doxylamine/pyridoxine’s approval did not include hyperemesis gravidarum, but a study by Koren and Maltepe showed the drug may work best when administered before the onset of symptoms. A greater reduction in the recurrence of hyperemesis gravidarum was observed in those who used the doxylamine/pyridoxine combination preemptively compared to those who took the drug at symptom onset (43% vs 17%).[15]

Ondansetron (Zofran), while pregnancy Class B, has become the most common parenteral and oral antiemetic used in US emergency departments due to its efficacy, and it has become the first choice in hyperemesis in the last several years—especially since it became available in a generic form. The Orally Dissolving Tablet (ODT) formulation, while not yet available in generic form, is very helpful in patients who are having a hard time tolerating oral forms. It is a serotonin antagonist and is dose responsive. Starting dosage is 4 mg, either IV or PO, and that dose may be repeated every 15-30 minutes until symptoms improve. Other typical antiemetics such as promethazine 12.5-25 mg IV or PO every 4 hours or prochlorperazine 25 mg rectally every 12 hours are also acceptable second-line agents.

Anticholinergics are supported by some data attesting to their safety, but they are not as well studied. Meclizine and dimenhydrinate have both been shown to be more effective than placebo in controlling nausea and vomiting of pregnancy. Metoclopramide, a promotility agent, has been demonstrated to be more effective than placebo in the treatment of hyperemesis gravidarum, and it has not been shown to be associated with increased incidence of congenital malformations.

Corticosteroids have a possible benefit in the treatment of hyperemesis gravidarum.[16] Steroids have been considered a last resort in patients who will require enteral or parenteral nutrition due to weight loss. The most common regimen is methylprednisolone 16 mg, orally or intravenously, every 8 hours for 3 days. Patients who do not respond within 3 days are not likely to respond. For those who do respond, the course may be tapered over 2 weeks. Some recent studies have demonstrated an association between oral clefts and methylprednisolone use in the first trimester. The current recommendation is that corticosteroids be used with caution and avoided before 10 weeks' gestation.[11]

In addition to the medications mentioned below, ginger is a common remedy for nausea and vomiting in pregnancy. Ginger capsules of 250 mg taken 4 times a day have been demonstrated to be effective against nausea and vomiting of pregnancy as well as hyperemesis when compared with placebo, without evidence of significant side effects or adverse effects on pregnancy outcomes.[17, 18] However, no clinical or experimental data about adverse effects of ginger in pregnancy exist. The Food and Drug Administration (FDA) does not regulate ginger products.

Practitioners of traditional Chinese medicine believe that stimulation of acupuncture point P6 can relieve nausea. Acupressure can be used as an alternative or complement to Western medications. However, the data about acupressure for nausea are equivocal. Sea Band is an easy over-the-counter product that stimulates the P6 site.

Nutritional supplements

Class Summary

Pyridoxine deficiency may have an etiologic role. Severe nutritional deficiencies may lead to thiamine deficiency and result in Wernicke encephalopathy.

Pyridoxine (Vitamin B6, Hexa-Betalin)

Some use pyridoxine with doxylamine (active ingredients in Benedictine, an antiemetic no longer available in the United States but still widely used in Europe). In the United States, doxylamine can be found in the over-the-counter medication Unisom (effective dose is half tablet).

Thiamine (Vitamin B1, Thiamilate)

Used in the treatment of thiamine deficiency including Wernicke encephalopathy syndrome.

Antiemetics

Class Summary

Useful in the treatment of symptomatic nausea and vomiting.

Doxylamine/pyridoxine (Diclegis)

Mechanism of action for efficacy to treat morning sickness is unknown. It contains doxylamine, an ethanolamine antihistamine derivative, and pyridoxine, a vitamin B6 analog. It is the only FDA-approved medication for treatment of nausea and vomiting of pregnancy who have not adequately responded to dietary and lifestyle changes.

Promethazine (Phenergan)

Antidopaminergic agent effective in treating emesis. Blocks postsynaptic mesolimbic dopaminergic receptors in brain and reduces stimuli to the brainstem reticular system. Not to be administered SC or intra-arterially, because necrotic lesions may develop.

Prochlorperazine (Compazine)

Antidopaminergic drug that may relieve nausea and vomiting by blocking postsynaptic mesolimbic dopamine receptors with its anticholinergic effects and by depressing the reticular activating system.

Metoclopramide (Reglan)

Works as an antiemetic by blocking dopamine receptors in chemoreceptor trigger zone of the CNS. Usually reserved for use when other therapies fail to control symptoms. Stimulates intestinal motility and is metabolized in the kidneys.

Dimenhydrinate (Dramamine)

Used as an antimotion sickness agent, dimenhydrinate has been demonstrated to be effective in reducing hyperemesis and is an acceptable second-line agent.

Diphenhydramine (Benadryl)

Used for the treatment and prophylaxis of vestibular disorders that may cause nausea and vomiting.

Meclizine (Antivert, Antrizine, Meni-D, Dramamine, Marezine)

Decreases excitability of the middle-ear labyrinth and blocks conduction in middle-ear vestibular-cerebellar pathways. These effects are associated with relief of nausea and vomiting.

Ondansetron (Zofran)

Selective 5-HT3-receptor antagonist that blocks serotonin both peripherally and centrally, used in the prevention of nausea and vomiting. It is metabolized in the liver with P-450 mechanism.