Pregnancy, Hyperemesis Gravidarum - Treatment and Medication
Treatment
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.
- 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.
- 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.
Medication
The American College of Obstetrics and Gynecology recommends that first-line treatment of nausea and vomiting of pregnancy should start with pyridoxine (vitamin B-6) with or without doxylamine. 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 showed 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 available in the United States 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.
If this is unsuccessful, adding or switching to PO, PR, or IV antiemetics may be required. Typical antiemetics such as promethazine 12.5-25 mg every 4 hours or prochlorperazine 25 mg rectally every 12 hours are 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. Ondansetron has limited safety and efficacy data, but it is increasing in use.
Corticosteroids have a possible benefit in the treatment of hyperemesis gravidarum. 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 48 mg daily for 3 days, either orally or intravenously. Patients who do not respond within 3 days are not likely to respond. For those that 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 avoid before 10 weeks' gestation.
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 on adverse effects on pregnancy outcomes. 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.
Drug Category: Nutritional supplements -- 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). | |
| Adult Dose | 10-20 mg PO qd for up to 3 wk or 10 mg IV qd for 3 d |
|---|---|
| Pediatric Dose | Not established |
| Contraindications | Documented hypersensitivity |
| Interactions | May decrease levodopa, phenytoin, and phenobarbital serum levels |
| Pregnancy | A - Safe in pregnancy |
| Precautions | >200 mg/d may precipitate withdrawal effects when discontinued |
| Thiamine (Vitamin B1, Thiamilate) -- Used in the treatment of thiamine deficiency including Wernicke encephalopathy syndrome. | |
| Adult Dose | 100 mg IV/IM qd for up to 2 wk |
|---|---|
| Pediatric Dose | Not established |
| Contraindications | Documented hypersensitivity |
| Interactions | None reported |
| Pregnancy | A - Safe in pregnancy |
| Precautions | Sensitivity reactions can occur (intradermal test-dose recommended in suspected sensitivity); deaths have resulted from IV use; sudden onset or worsening of Wernicke encephalopathy, following glucose administration, may occur in thiamine-deficient patients; administer before or with dextrose-containing fluids in suspected thiamine deficiency |
Drug Category: Antiemetics -- No drug has been approved by the FDA for the treatment of nausea and vomiting in pregnancy since Benedictine. Any antiemetic must be prescribed with caution.
| 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. | |||||||||||
| Adult Dose | 12.5 mg PO/PR tid and 25 mg hs 25 mg IV/IM, and repeat prn in 2 h; switch to PO as soon as possible Pediatric Dose | 0.25-1 mg/kg PO/IV/IM/PR 4-6 times/d prn | Contraindications | Documented hypersensitivity | Interactions | May have additive effects when used concurrently with other CNS depressants or anticonvulsants; coadministration with epinephrine may cause hypotension | Pregnancy |
C - Safety for use during pregnancy has not been established.
| Precautions | Caution in cardiovascular disease, impaired liver function, seizures, sleep apnea, asthma, and acute-angle glaucoma; may cause drowsiness | |
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| 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. | |||||||||||
| Adult Dose | 5-10 mg PO/IM tid/qid, not to exceed 40 mg/d 2.5-10 mg IV q3-4h prn; not to exceed 10 mg/dose or 40 mg/d 25 mg PR bid Pediatric Dose | >12 years: Administer as in adults | Contraindications | Documented hypersensitivity; bone marrow suppression; narrow-angle glaucoma; severe liver or cardiac disease | Interactions | Coadministration with other CNS depressants or anticonvulsants may cause additive effects; with epinephrine may cause hypotension | Pregnancy |
C - Safety for use during pregnancy has not been established.
| Precautions | Drug-induced Parkinson syndrome or pseudoparkinsonism occurs frequently; akathisia is the most common extrapyramidal reaction in elderly patients; lowers seizure threshold; caution with history of seizures | |
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| 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. | |
| Adult Dose | 10 mg PO up to qid 30 min before meals and at hs |
|---|---|
| Pediatric Dose | >12 years: Administer as in adults |
| Contraindications | Documented hypersensitivity; pheochromocytoma or GI hemorrhage, obstruction, or perforation; history of seizure disorders |
| Interactions | Anticholinergics may antagonize effects; opiate analgesics may increase toxicity in CNS |
| Pregnancy | B - Usually safe but benefits must outweigh the risks. |
| Precautions | Avoid with medications that can cause extrapyramidal reactions; caution in a history of mental illness and Parkinson disease |
| 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. | |
| Adult Dose | 50-100 mg PO q4-6h; not to exceed 400 mg/d; not to exceed 200 mg/d if also taking doxylamine |
|---|---|
| Pediatric Dose | >12 years: Administer as in adults |
| Contraindications | Documented hypersensitivity |
| Interactions | Caution advised when using with other anticholinergic agents or sedating agents, may have additive effect |
| Pregnancy | B - Usually safe but benefits must outweigh the risks. |
| Precautions | Previously linked to increased rate of birth defects, recent case-control study found no evidence of teratogenicity May cause drowsiness, headaches, fatigue, paradoxical CNS stimulation |
| Diphenhydramine (Benadryl) -- Used for the treatment and prophylaxis of vestibular disorders that may cause nausea and vomiting. | |||||||||||
| Adult Dose | 25-50 mg PO q6-8h prn; not to exceed 400 mg/d 10-50 mg IV/IM q6-8h prn; not to exceed 400 mg/d Pediatric Dose | 12.5-25 mg PO tid/qid, 5 mg/kg/d, or 150 mg/m2/d divided tid/qid; not to exceed 300 mg/d | 5 mg/kg/d IV/IM or 150 mg/m2/d divided qid; not to exceed 300 mg/d Contraindications | Documented hypersensitivity; MAOI use | Interactions | Potentiates effect of CNS depressants; alcohol in syrup form may interact with medications that can cause disulfiramlike reactions | Pregnancy | C - Safety for use during pregnancy has not been established.
| Precautions | May exacerbate angle-closure glaucoma, hyperthyroidism, peptic ulcer, and urinary tract obstruction | |
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| 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. | |
| Adult Dose | 25-50 mg PO q12-24h; not to exceed 100 mg/d |
|---|---|
| Pediatric Dose | >12 years: Administer as in adults |
| Contraindications | Documented hypersensitivity |
| Interactions | May increase toxicity of CNS depressants, neuroleptics, and anticholinergics |
| Pregnancy | B - Usually safe but benefits must outweigh the risks. |
| Precautions | Caution in angle-closure glaucoma, prostatic hypertrophy, pyloric or duodenal obstruction, bladder-neck obstruction |
| 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. | |
| Adult Dose | 2-4 mg IV q6-8h |
|---|---|
| Pediatric Dose | >12 years: Administer as in adults |
| Contraindications | Documented hypersensitivity |
| Interactions | CYP450 inducers (eg, barbiturates, rifampin, carbamazepine, phenytoin) can change half-life and clearance of (dose adjustment usually not required) |
| Pregnancy | B - Usually safe but benefits must outweigh the risks. |
| Precautions | Medication is for prevention of nausea and vomiting, not for rescue of nausea and vomiting |
| « Previous Page | Section 3 of 4 |
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Synonyms And Related Keywords
hyperemesis gravidarum, nausea and vomiting in pregnancy, pernicious vomiting in pregnancy, uncontrollable vomiting in pregnancy, severe nausea and vomiting in pregnancy, morning sickness, miscarriage
