Hyperemesis Gravidarum in Emergency Medicine Medication
- Author: Susan Renee Wilcox, MD; Chief Editor: Jeter (Jay) Pritchard Taylor, III, MD more...
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 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.
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%).
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. 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.[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.
Pyridoxine deficiency may have an etiologic role. Severe nutritional deficiencies may lead to thiamine deficiency and result in Wernicke encephalopathy.
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).
Used in the treatment of thiamine deficiency including Wernicke encephalopathy syndrome.
Useful in the treatment of symptomatic nausea and vomiting.
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.
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.
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.
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.
Used as an antimotion sickness agent, dimenhydrinate has been demonstrated to be effective in reducing hyperemesis and is an acceptable second-line agent.
Used for the treatment and prophylaxis of vestibular disorders that may cause nausea and vomiting.
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.
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.
Bottomley C, Bourne T. Management strategies for hyperemesis. Best Pract Res Clin Obstet Gynaecol. 2009 Aug. 23(4):549-64. [Medline].
Maltepe C. Surviving morning sickness successfully: from patient's perception to rational management. J Popul Ther Clin Pharmacol. 2014. 21(3):e555-64. [Medline].
Vandraas KF, Vikanes AV, Stoer NC, et al. Hyperemesis gravidarum and risk of cancer in offspring, a Scandinavian registry-based nested case-control study. BMC Cancer. 2015 May 13. 15:398. [Medline].
Summers A. Emergency management of hyperemesis gravidarum. Emerg Nurse. 2012 Jul. 20(4):24-8. [Medline].
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].
Golberg D, Szilagyi A, Graves L. Hyperemesis gravidarum and Helicobacter pylori infection: a systematic review. Obstet Gynecol. Sept 2007. 110:695-703. [Medline].
Goodwin TM. Hyperemesis Gravidarum. Obstet Gynecol Clin N Am. Sept 2008. 35:401-417. [Medline].
Fell DB, Dodds L, Joseph KS, et al. Risk factors for hyperemesis gravidarum requiring hospital admission during pregnancy. Obstet Gynecol. 2006 Feb. 107(2 Pt 1):277-84. [Medline].
Dodds L, Fell DB, Joseph KS, et al. Outcomes of pregnancies complicated by hyperemesis gravidarum. Obstet Gynecol. 2006 Feb. 107(2 Pt 1):285-92. [Medline].
American College of Obstetricians and Gynecologists. Practice bulletin no. 153: nausea and vomiting of pregnancy. Obstet Gynecol. 2015 Sep. 126 (3):e12-24. [Medline].
Murphy A, McCarthy FP, McElroy B, et al. Day care versus inpatient management of nausea and vomiting of pregnancy: cost utility analysis of a randomised controlled trial. Eur J Obstet Gynecol Reprod Biol. 2015 Dec 12. 197:78-82. [Medline].
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].
[Guideline] ACOG (American College of Obstetrics and Gynecology). ACOG (American College of Obstetrics and Gynecology) Practice Bulletin: nausea and vomiting of pregnancy. Obstet Gynecol. 2004 Apr. 103(4):803-14. [Medline]. [Full Text].
Koren G, Clark S, Hankins GD, et al. Effectiveness of delayed-release doxylamine and pyridoxine for nausea and vomiting of pregnancy: a randomized placebo controlled trial. Am J Obstet Gynecol. 2010 Dec. 203(6):571.e1-7. [Medline].
Koren G, Maltepe C. Preemptive Diclectin therapy for the management of nausea and vomiting of pregnancy and hyperemesis gravidarum (abstract). ClinicalTrials.gov. Available at http://clinicaltrials.gov/show/NCT00293644. Accessed: April 10, 2013.
Poon SL. Towards evidence-based emergency medicine: Best BETs from the Manchester Royal Infirmary. BET 2: Steroid therapy in the treatment of intractable hyperemesis gravidarum. Emerg Med J. 2011 Oct. 28(10):898-900. [Medline].
Boone SA, Shields KM. Treating pregnancy-related nausea and vomiting with ginger. Ann Pharmacother. 2005 Oct. 39(10):1710-3. [Medline].
Borrelli F, Capasso R, Aviello G, et al. Effectiveness and safety of ginger in the treatment of pregnancy-induced nausea and vomiting. Obstet Gynecol. 2005 Apr. 105(4):849-56. [Medline].
Aikins Murphy P. Alternative therapies for nausea and vomiting of pregnancy. Obstet Gynecol. 1998 Jan. 91(1):149-55. [Medline].
Bailit JL. Hyperemesis gravidarium: Epidemiologic findings from a large cohort. Am J Obstet Gynecol. 2005 Sep. 193(3 Pt 1):811-4. [Medline].
Bashiri A, Neumann L, Maymon E. Hyperemesis gravidarum: epidemiologic features, complications and outcome. Eur J Obstet Gynecol Reprod Biol. 1995 Dec. 63(2):135-8. [Medline].
Carmichael SL, Shaw GM. Maternal corticosteroid use and risk of selected congenital anomalies. Am J Med Genet. 1999 Sep 17. 86(3):242-4. [Medline].
Chan NN. Thyroid function in hyperemesis gravidarum. Lancet. 1999 Jun 26. 353(9171):2243. [Medline].
Child TJ. Management of hyperemesis in pregnant women. Lancet. 1999 Jan 23. 353(9149):325. [Medline].
Chiossi G, Neri I, Cavazzuti M. Hyperemesis gravidarum complicated by Wernicke encephalopathy: background, case report, and review of the literature. Obstet Gynecol Surv. 2006 Apr. 61(4):255-68. [Medline].
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].
Czeizel AE, Vargha P. A case-control study of congenital abnormality and dimenhydrinate usage during pregnancy. Arch Gynecol Obstet. 2005 Feb. 271(2):113-8. [Medline].
Davis M. Nausea and vomiting of pregnancy: an evidence-based review. J Perinat Neonatal Nurs. 2004 Oct-Dec. 18(4):312-28. [Medline].
Dickson MJ. Management of hyperemesis in pregnant women. Lancet. 1999 Jan 23. 353(9149):325. [Medline].
Einarson A, Maltepe C, Navioz Y, Kennedy D, Tan MP, Koren G. The safety of ondansetron for nausea and vomiting of pregnancy: a prospective comparative study. BJOG. 2004 Sep. 111(9):940-3. [Medline].
Fischer-Rasmussen W, Kjaer SK, Dahl C. Ginger treatment of hyperemesis gravidarum. Eur J Obstet Gynecol Reprod Biol. 1991 Jan 4. 38(1):19-24. [Medline].
Frigo P, Lang C, Reisenberger K. Hyperemesis gravidarum associated with Helicobacter pylori seropositivity. Obstet Gynecol. 1998 Apr. 91(4):615-7. [Medline].
Fukada Y, Ohta S, Mizuno K. Rhabdomyolysis secondary to hyperemesis gravidarum. Acta Obstet Gynecol Scand. 1999 Jan. 78(1):71. [Medline].
Hod M, Orvieto R, Kaplan B. Hyperemesis gravidarum. A review. J Reprod Med. 1994 Aug. 39(8):605-12. [Medline].
Hoo JJ. Acupressure for hyperemesis gravidarum. Am J Obstet Gynecol. 1997 Jun. 176(6):1395-7. [Medline].
Jacoby EB, Porter KB. Helicobacter pylori infection and persistent hyperemesis gravidarum. Am J Perinatol. 1999. 16:85-8. [Medline].
Jewell D, Young G. Interventions for nausea and vomiting in early pregnancy. Cochrane Database Syst Rev. 2003. CD000145. [Medline].
Kocak I, Akcan Y, Ustun C, et al. Helicobacter pylori seropositivity in patients with hyperemesis gravidarum. Int J Gynaecol Obstet. 1999 Sep. 66(3):251-4. [Medline].
Koren G, Maltepe C. Pre-emptive therapy for severe nausea and vomiting of pregnancy and hyperemesis gravidarum. J Obstet Gynaecol. 2004 Aug. 24(5):530-3. [Medline].
Kousen M. Treatment of nausea and vomiting in pregnancy. Am Fam Physician. 1993 Nov 15. 48(7):1279-84. [Medline].
Lee RH, Pan VL, Wing DA. The prevalence of Helicobacter pylori in the Hispanic population affected by hyperemesis gravidarum. Am J Obstet Gynecol. 2005 Sep. 193(3 Pt 2):1024-7. [Medline].
Meighan M, Wood AF. The impact of hyperemesis gravidarum on maternal role assumption. J Obstet Gynecol Neonatal Nurs. 2005 Mar-Apr. 34(2):172-9. [Medline].
Nageotte MP, Briggs GG, Towers CV. Droperidol and diphenhydramine in the management of hyperemesis gravidarum. Am J Obstet Gynecol. 1996 Jun. 174(6):1801-5; discussion 1805-6. [Medline].
Nelson-Piercy C. Treatment of nausea and vomiting in pregnancy. When should it be treated and what can be safely taken?. Drug Saf. 1998 Aug. 19(2):155-64. [Medline].
Newman V, Fullerton JT, Anderson PO. Clinical advances in the management of severe nausea and vomiting during pregnancy. J Obstet Gynecol Neonatal Nurs. 1993 Nov-Dec. 22(6):483-90. [Medline].
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. 2000 Dec. 62(6):385-92. [Medline].
Petik D, Puho E, Czeizel AE. Evaluation of maternal infusion therapy during pregnancy for fetal development. Int J Med Sci. 2005 Oct. 2(4):137-42. [Medline].
Quinlan JD, Hill DA. Nausea and vomiting of pregnancy. Am Fam Physician. 2003 Jul. 68 (1):121-8. [Medline].
Robinson JN, Banerjee R, Thiet MP. Coagulopathy secondary to vitamin K deficiency in hyperemesis gravidarum. Obstet Gynecol. 1998 Oct. 92(4 Pt 2):673-5. [Medline].
Rodriguez-Pinilla E, Martinez-Frias ML. Corticosteroids during pregnancy and oral clefts: a case-control study. Teratology. 1998 Jul. 58(1):2-5. [Medline].
Russo-Stieglitz KE, Levine AB, Wagner BA. Pregnancy outcome in patients requiring parenteral nutrition. J Matern Fetal Med. 1999 Jul-Aug. 8(4):164-7. [Medline].
Safari HR, Alsulyman OM, Gherman RB. Experience with oral methylprednisolone in the treatment of refractory hyperemesis gravidarum. Am J Obstet Gynecol. 1998 May. 178(5):1054-8. [Medline].
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. 1998 Oct. 179(4):921-4. [Medline].
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. 1991 Jul. 78(1):33-6. [Medline].
Selitsky T, Chandra P, Schiavello HJ. Wernicke's encephalopathy with hyperemesis and ketoacidosis. Obstet Gynecol. 2006 Feb. 107(2 Pt 2):486-90. [Medline].
Serrano P, Velloso A, Garcia-Luna PP. Enteral nutrition by percutaneous endoscopic gastrojejunostomy in severe hyperemesis gravidarum: a report of two cases. Clin Nutr. 1998 Jun. 17(3):135-9. [Medline].
Sullivan CA, Johnson CA, Roach H. A pilot study of intravenous ondansetron for hyperemesis gravidarum. Am J Obstet Gynecol. 1996 May. 174(5):1565-8. [Medline].
Verberg MF, Gillott DJ, Al-Fardan N. Hyperemesis gravidarum, a literature review. Hum Reprod Update. 2005 Sep-Oct. 11(5):527-39:[Medline].
Matthews A, Haas DM, O'Mathuna DP, Dowswell T. Interventions for nausea and vomiting in early pregnancy. Cochrane Database Syst Rev. 2015 Sep 8. 9:CD007575. [Medline].