eMedicine Specialties > Emergency Medicine > Obstetrics & Gynecology

Pregnancy, Hyperemesis Gravidarum: Treatment & Medication

Author: Susan Renee Wilcox, MD, Resident, Department of Emergency Medicine, Harvard Medical School
Coauthor(s): Alison Edelman, MD, Assistant Professor, Department of Obstetrics and Gynecology, Oregon Health Sciences University; Judith R Logan, MD, MS, Assistant Professor, Department of Medical Informatics and Clinical Epidemiology, Oregon Health and Science University
Contributor Information and Disclosures

Updated: Dec 10, 2008

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 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.

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. 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

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

10-20 mg PO qd for up to 3 wk or 10 mg IV qd for 3 d

Pediatric

Not established

May decrease levodopa, phenytoin, and phenobarbital serum levels

Pregnancy

A - Fetal risk not revealed in controlled studies in humans

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

100 mg IV/IM qd for up to 2 wk

Pediatric

Not established

Pregnancy

A - Fetal risk not revealed in controlled studies in humans

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

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

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

0.25-1 mg/kg PO/IV/IM/PR 4-6 times/d prn

May have additive effects when used concurrently with other CNS depressants or anticonvulsants; coadministration with epinephrine may cause hypotension

Pregnancy

C - Fetal risk revealed in studies in animals but not established or not studied in humans; may use if benefits outweigh risk to fetus

Precautions

Caution in cardiovascular disease, impaired liver function, seizures, sleep apnea, asthma, and acute-angle glaucoma; may cause drowsiness


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

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

>12 years: Administer as in adults

Coadministration with other CNS depressants or anticonvulsants may cause additive effects; with epinephrine may cause hypotension

Documented hypersensitivity; bone marrow suppression; narrow-angle glaucoma; severe liver or cardiac disease

Pregnancy

C - Fetal risk revealed in studies in animals but not established or not studied in humans; may use if benefits outweigh risk to fetus

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


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

10 mg PO up to qid 30 min before meals and at hs

Pediatric

>12 years: Administer as in adults

Anticholinergics may antagonize effects; opiate analgesics may increase toxicity in CNS

Documented hypersensitivity; pheochromocytoma or GI hemorrhage, obstruction, or perforation; history of seizure disorders

Pregnancy

B - Fetal risk not confirmed in studies in humans but has been shown in some studies in animals

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

50-100 mg PO q4-6h; not to exceed 400 mg/d; not to exceed 200 mg/d if also taking doxylamine

Pediatric

>12 years: Administer as in adults

Caution advised when using with other anticholinergic agents or sedating agents, may have additive effect

Pregnancy

B - Fetal risk not confirmed in studies in humans but has been shown in some studies in animals

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

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

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

Potentiates effect of CNS depressants; alcohol in syrup form may interact with medications that can cause disulfiramlike reactions

Documented hypersensitivity; MAOI use

Pregnancy

C - Fetal risk revealed in studies in animals but not established or not studied in humans; may use if benefits outweigh risk to fetus

Precautions

May exacerbate angle-closure glaucoma, hyperthyroidism, peptic ulcer, and urinary tract obstruction


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

25-50 mg PO q12-24h; not to exceed 100 mg/d

Pediatric

>12 years: Administer as in adults

May increase toxicity of CNS depressants, neuroleptics, and anticholinergics

Pregnancy

B - Fetal risk not confirmed in studies in humans but has been shown in some studies in animals

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

2-4 mg IV q6-8h

Pediatric

>12 years: Administer as in adults

CYP450 inducers (eg, barbiturates, rifampin, carbamazepine, phenytoin) can change half-life and clearance of (dose adjustment usually not required)

Pregnancy

B - Fetal risk not confirmed in studies in humans but has been shown in some studies in animals

Precautions

Medication is for prevention of nausea and vomiting, not for rescue of nausea and vomiting

More on Pregnancy, Hyperemesis Gravidarum

Overview: Pregnancy, Hyperemesis Gravidarum
Differential Diagnoses & Workup: Pregnancy, Hyperemesis Gravidarum
Treatment & Medication: Pregnancy, Hyperemesis Gravidarum
Follow-up: Pregnancy, Hyperemesis Gravidarum
References

References

  1. ACOG (American College of Obstetrics and Gynecology). ACOG (American College of Obstetrics and Gynecology) Practice Bulletin: nausea and vomiting of pregnancy. Obstet Gynecol. Apr 2004;103(4):803-14. [Medline].

  2. Aikins Murphy P. Alternative therapies for nausea and vomiting of pregnancy. Obstet Gynecol. Jan 1998;91(1):149-55. [Medline].

  3. Bailit JL. Hyperemesis gravidarium: Epidemiologic findings from a large cohort. Am J Obstet Gynecol. Sep 2005;193(3 Pt 1):811-4. [Medline].

  4. Bashiri A, Neumann L, Maymon E. Hyperemesis gravidarum: epidemiologic features, complications and outcome. Eur J Obstet Gynecol Reprod Biol. Dec 1995;63(2):135-8. [Medline].

  5. Boone SA, Shields KM. Treating pregnancy-related nausea and vomiting with ginger. Ann Pharmacother. Oct 2005;39(10):1710-3. [Medline].

  6. [Best Evidence] Borrelli F, Capasso R, Aviello G, et al. Effectiveness and safety of ginger in the treatment of pregnancy-induced nausea and vomiting. Obstet Gynecol. Apr 2005;105(4):849-56. [Medline].

  7. Carmichael SL, Shaw GM. Maternal corticosteroid use and risk of selected congenital anomalies. Am J Med Genet. Sep 17 1999;86(3):242-4. [Medline].

  8. Cedergren M, Brynhildsen J, Josefsson A, et al. Hyperemesis gravidarum that requires hospitalization and the use of antiemetic drugs in relation to maternal body composition. Am J Obstet Gynecol. Apr 2008;198:412.e1-5. [Medline].

  9. Chan NN. Thyroid function in hyperemesis gravidarum. Lancet. Jun 26 1999;353(9171):2243. [Medline].

  10. Child TJ. Management of hyperemesis in pregnant women. Lancet. Jan 23 1999;353(9149):325. [Medline].

  11. Chiossi G, Neri I, Cavazzuti M. Hyperemesis gravidarum complicated by wernicke encephalopathy: background, case report, and review of the literature. Obstet Gynecol Surv. Apr 2006;61(4):255-68. [Medline].

  12. Czeizel AE, Dudas I, Fritz G. The effect of periconceptional multivitamin-mineral supplementation on vertigo, nausea and vomiting in the first trimester of pregnancy. Arch Gynecol Obstet. 1992;251(4):181-5. [Medline].

  13. Czeizel AE, Vargha P. A case-control study of congenital abnormality and dimenhydrinate usage during pregnancy. Arch Gynecol Obstet. Feb 2005;271(2):113-8. [Medline].

  14. Davis M. Nausea and vomiting of pregnancy: an evidence-based review. J Perinat Neonatal Nurs. Oct-Dec 2004;18(4):312-28. [Medline].

  15. Dickson MJ. Management of hyperemesis in pregnant women. Lancet. Jan 23 1999;353(9149):325. [Medline].

  16. Dodds L, Fell DB, Joseph KS, et al. Outcomes of pregnancies complicated by hyperemesis gravidarum. Obstet Gynecol. Feb 2006;107(2 Pt 1):285-92. [Medline].

  17. Fell DB, Dodds L, Joseph KS, et al. Risk factors for hyperemesis gravidarum requiring hospital admission during pregnancy. Obstet Gynecol. Feb 2006;107(2 Pt 1):277-84. [Medline].

  18. Fischer-Rasmussen W, Kjaer SK, Dahl C. Ginger treatment of hyperemesis gravidarum. Eur J Obstet Gynecol Reprod Biol. Jan 4 1991;38(1):19-24. [Medline].

  19. Frigo P, Lang C, Reisenberger K. Hyperemesis gravidarum associated with Helicobacter pylori seropositivity. Obstet Gynecol. Apr 1998;91(4):615-7. [Medline].

  20. Fukada Y, Ohta S, Mizuno K. Rhabdomyolysis secondary to hyperemesis gravidarum. Acta Obstet Gynecol Scand. Jan 1999;78(1):71. [Medline].

  21. Golberg D, Szilagyi A, Graves L. Hyperemesis gravidarum and Helicobacter pylori infection: a systematic review. Obstet Gynecol. Sept 2007;110:695-703. [Medline].

  22. Goodwin TM. Hyperemesis Gravidarum. Obstet Gynecol Clin N Am. Sept 2008;35:401-417. [Medline].

  23. Hod M, Orvieto R, Kaplan B. Hyperemesis gravidarum. A review. J Reprod Med. Aug 1994;39(8):605-12. [Medline].

  24. Holmgren C, Aagaard-Tillery KM, Silver RM, Porter TF, Varner M. Hyperemesis in pregnancy: an evaluation of treatment strategies with maternal and neonatal outcomes. Am J Obstet Gynecol. Jan 2008;198:56.e1-4. [Medline].

  25. Hoo JJ. Acupressure for hyperemesis gravidarum. Am J Obstet Gynecol. Jun 1997;176(6):1395-7. [Medline].

  26. Jacoby EB, Porter KB. Helicobacter pylori infection and persistent hyperemesis gravidarum. Am J Perinatol. 1999;16:85-8. [Medline].

  27. Jewell D, Young G. Interventions for nausea and vomiting in early pregnancy. Cochrane Database Syst Rev. 2003;CD000145. [Medline].

  28. Kocak I, Akcan Y, Ustun C, et al. Helicobacter pylori seropositivity in patients with hyperemesis gravidarum. Int J Gynaecol Obstet. Sep 1999;66(3):251-4. [Medline].

  29. Kousen M. Treatment of nausea and vomiting in pregnancy. Am Fam Physician. Nov 15 1993;48(7):1279-84. [Medline].

  30. Lee RH, Pan VL, Wing DA. The prevalence of Helicobacter pylori in the Hispanic population affected by hyperemesis gravidarum. Am J Obstet Gynecol. Sep 2005;193(3 Pt 2):1024-7. [Medline].

  31. Meighan M, Wood AF. The impact of hyperemesis gravidarum on maternal role assumption. J Obstet Gynecol Neonatal Nurs. Mar-Apr 2005;34(2):172-9. [Medline].

  32. Nageotte MP, Briggs GG, Towers CV. Droperidol and diphenhydramine in the management of hyperemesis gravidarum. Am J Obstet Gynecol. Jun 1996;174(6):1801-5; discussion 1805-6. [Medline].

  33. Nelson-Piercy C. Treatment of nausea and vomiting in pregnancy. When should it be treated and what can be safely taken?. Drug Saf. Aug 1998;19(2):155-64. [Medline].

  34. Newman V, Fullerton JT, Anderson PO. Clinical advances in the management of severe nausea and vomiting during pregnancy. J Obstet Gynecol Neonatal Nurs. Nov-Dec 1993;22(6):483-90. [Medline].

  35. Park-Wyllie L, Mazzotta P, Pastuszak A, et al. Birth defects after maternal exposure to corticosteroids: prospective cohort study and meta-analysis of epidemiological studies. Teratology. Dec 2000;62(6):385-92. [Medline].

  36. Petik D, Puho E, Czeizel AE. Evaluation of maternal infusion therapy during pregnancy for fetal development. Int J Med Sci. Oct 2005;2(4):137-42. [Medline].

  37. Quinlan JD, Hill DA. Nausea and vomiting of pregnancy. Am Fam Physician. Jul 2003;68 (1):121-8. [Medline].

  38. Robinson JN, Banerjee R, Thiet MP. Coagulopathy secondary to vitamin K deficiency in hyperemesis gravidarum. Obstet Gynecol. Oct 1998;92(4 Pt 2):673-5. [Medline].

  39. Rodriguez-Pinilla E, Martinez-Frias ML. Corticosteroids during pregnancy and oral clefts: a case-control study. Teratology. Jul 1998;58(1):2-5. [Medline].

  40. Russo-Stieglitz KE, Levine AB, Wagner BA. Pregnancy outcome in patients requiring parenteral nutrition. J Matern Fetal Med. Jul-Aug 1999;8(4):164-7. [Medline].

  41. Safari HR, Alsulyman OM, Gherman RB. Experience with oral methylprednisolone in the treatment of refractory hyperemesis gravidarum. Am J Obstet Gynecol. May 1998;178(5):1054-8. [Medline].

  42. Safari HR, Fassett MJ, Souter IC. The efficacy of methylprednisolone in the treatment of hyperemesis gravidarum: a randomized, double-blind, controlled study. Am J Obstet Gynecol. Oct 1998;179(4):921-4. [Medline].

  43. Sahakian V, Rouse D, Sipes S, et al. Vitamin B6 is effective therapy for nausea and vomiting of pregnancy: a randomized, double-blind placebo-controlled study. Obstet Gynecol. Jul 1991;78(1):33-6. [Medline].

  44. Selitsky T, Chandra P, Schiavello HJ. Wernicke's encephalopathy with hyperemesis and ketoacidosis. Obstet Gynecol. Feb 2006;107(2 Pt 2):486-90. [Medline].

  45. Serrano P, Velloso A, Garcia-Luna PP. Enteral nutrition by percutaneous endoscopic gastrojejunostomy in severe hyperemesis gravidarum: a report of two cases. Clin Nutr. Jun 1998;17(3):135-9. [Medline].

  46. Sullivan CA, Johnson CA, Roach H. A pilot study of intravenous ondansetron for hyperemesis gravidarum. Am J Obstet Gynecol. May 1996;174(5):1565-8. [Medline].

  47. Verberg MF, Gillott DJ, Al-Fardan N. Hyperemesis gravidarum, a literature review. Hum Reprod Update. Sep-Oct 2005;11(5):527-39:[Medline].

Further Reading

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

Contributor Information and Disclosures

Author

Susan Renee Wilcox, MD, Resident, Department of Emergency Medicine, Harvard Medical School
Susan Renee Wilcox, MD is a member of the following medical societies: Phi Beta Kappa
Disclosure: Nothing to disclose.

Coauthor(s)

Alison Edelman, MD, Assistant Professor, Department of Obstetrics and Gynecology, Oregon Health Sciences University
Alison Edelman, MD is a member of the following medical societies: American College of Obstetricians and Gynecologists
Disclosure: Organon Honoraria Speaking and teaching

Judith R Logan, MD, MS, Assistant Professor, Department of Medical Informatics and Clinical Epidemiology, Oregon Health and Science University
Judith R Logan, MD, MS is a member of the following medical societies: American Medical Informatics Association
Disclosure: Nothing to disclose.

Medical Editor

Assaad J Sayah, MD, Chief, Department of Emergency Medicine, Cambridge Health Alliance
Assaad J Sayah, MD is a member of the following medical societies: National Association of EMS Physicians
Disclosure: Nothing to disclose.

Pharmacy Editor

Francisco Talavera, PharmD, PhD, Senior Pharmacy Editor, eMedicine
Disclosure: Nothing to disclose.

Managing Editor

Mark Zwanger, MD, MBA, Assistant Professor, Department of Emergency Medicine, Thomas Jefferson University
Mark Zwanger, MD, MBA is a member of the following medical societies: American Academy of Emergency Medicine, American College of Emergency Physicians, and American Medical Association
Disclosure: Nothing to disclose.

CME Editor

John D Halamka, MD, MS, Associate Professor of Medicine, Harvard Medical School, Beth Israel Deaconess Medical Center; Chief Information Officer, CareGroup Healthcare System and Harvard Medical School; Attending Physician, Division of Emergency Medicine, Beth Israel Deaconess Medical Center
John D Halamka, MD, MS is a member of the following medical societies: American College of Emergency Physicians, American Medical Informatics Association, Phi Beta Kappa, and Society for Academic Emergency Medicine
Disclosure: Nothing to disclose.

Chief Editor

Pamela L Dyne, MD, Professor of Clinical Medicine/Emergency Medicine, David Geffen School of Medicine at UCLA; Attending Physician, Department of Emergency Medicine, Olive View-UCLA Medical Center
Pamela L Dyne, MD is a member of the following medical societies: American Academy of Emergency Medicine, American College of Emergency Physicians, and Society for Academic Emergency Medicine
Disclosure: Nothing to disclose.

 
 
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