Pregnancy, Hyperemesis Gravidarum

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1 Page 1 of 11 (Advertisement) Home Specialties Resource Centers CME PDA Contributor Recruitment Patient Educ February 7, 2006 nmlkji Articles nmlkj Images nmlkj CME Advanced Search Consumer Health Link to this site You are in: emedicine Specialties > Emergency Medicine > Obstetrics And Gynecology, Hyperemesis Gravidarum Last Updated: October 5, 2004 Rate this Article to a Colleague Get CME/CE for article Synonyms and related keywords: nausea and vomiting in pregnancy, pernicious vomiting in pregnancy, uncontrollable vomitin pregnancy, severe nausea and vomiting in pregnancy, morning sickness AUTHOR INFORMATION Section 1 of 10 Author: Alison Edelman, MD, Assistant Professor, Department of Obstetrics and Gynecology, Oregon H Sciences University Coauthor(s): Judith R Logan, MD, MS, Assistant Professor, Department of Medical Informatics and Clin Epidemiology, Oregon Health and Science University Alison Edelman, MD, is a member of the following medical societies: American College of Obstetricians Gynecologists Editor(s): Assaad J Sayah, MD, Assistant Clinical Professor of Emergency Medicine, Tufts University Sc Medicine; Chairman, Department of Emergency Medicine, Caritas Good Samaritan Medical Center; Talavera, PharmD, PhD, Senior Pharmacy Editor, emedicine; Mark Zwanger, MD, MBA, Assistant Pro Department of Emergency Medicine, Thomas Jefferson University; John Halamka, MD, Chief Informatio CareGroup Healthcare System, Assistant Professor of Medicine, Department of Emergency Medicine, B Deaconess Medical Center; Assistant Professor of Medicine, Harvard Medical School; and Robert E O'C MD, MPH, Director of Education and Research, Department of Emergency Medicine, Christiana Care He System; Professor of Emergency Medicine, Thomas Jefferson University Disclosure INTRODUCTION Section 2 of 10 Background: Nausea and vomiting are common in pregnancy. Approximately 70-85% of all gravid wom experience nausea and/or vomiting. Hyperemesis gravidarum is a severe and intractable form of nausea

2 Page 2 of 11 vomiting in pregnancy. It is a diagnosis of exclusion and may result in weight loss; nutritional deficiencies abnormalities in fluids, electrolyte levels, and acid-base balance. The peak incidence is at 8-12 weeks of and symptoms usually resolve by week 16. Interestingly, nausea and vomiting of pregnancy is generally with a lower rate of miscarriage. Pathophysiology: Various organ systems may be involved if hyperemesis gravidarum is severe and unt the response to treatment is poor. Frequency: In the US: Hyperemesis gravidarum occurs in cases per 1000 pregnancies. The prevalence in molar pregnancies and multiple pregnancies. Mortality/Morbidity: Before intravenous fluid therapy, mortality was not uncommon, but now it is rare wi treatment. When hyperemesis gravidarum is treated, no adverse outcomes (eg, prematurity, low birth we Apgar scores, congenital abnormalities) are expected. Age: The incidence is higher in younger women than in older women. CLINICAL Section 3 of 10 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. Physical: Findings at physical examination may include the following: Weight loss Dehydration Causes: Decreased skin turgor Postural changes in BP and pulse The cause of severe nausea and vomiting in pregnancy has not been identified. Extreme nausea and vomiting may be related to elevated levels of estrogens or human chorionic gonadotropin. An association exists with hyperthyroidism, pyridoxine deficiency, and psychological factors.

3 Page 3 of 11 An association between Helicobacter pylori seropositivity and hyperemesis gravidarum may exist. DIFFERENTIALS Section 4 of 10 Appendicitis, Acute Diabetic Ketoacidosis Gastritis and Peptic Ulcer Disease Gastroenteritis Hepatitis Pancreatitis, Preeclampsia Other Problems to be Considered: Pyelonephritis Molar pregnancy Pseudotumor cerebri Acute fatty liver of pregnancy WORKUP Lab Studies:

4 Page 4 of 11 Obtain electrolyte levels. Measure urine gravity and ketones. Perform liver function tests (LFTs) if hepatitis is a concern. Of note, LFTs can be slightly elevated w Perform a complete blood count and urinalysis to rule out other causes, with particular concern for Hyperthyroidism causing nausea and vomiting is rare, a T3 and T4 should be drawn if this is a conc hyperemesis gravidarum.) Obtain serum amylase-to-creatinine ratio if pancreatitis is a concern. Make sure that the patient has had ultrasonographic confirmation of her pregnancy to rule out Mola TREATMENT Emergency Department Care: Replace fluids and administer antiemetics, if required. Lactated Ringer solution is a good choice. Consider the addition of glucose, multivitamins, magnesium, pyridoxine, and/or thiamine. Dextrose solutions may stop fat breakdown. Continue treatment until patient can tolerate oral fluids and until test results show little or no ketone

5 Page 5 of 11 MEDICATION Early treatment of nausea and vomiting of pregnancy may prevent progression to hyperemesis gravidaru of a multivitamin at the time of conception. The American College of Obstetrics and Gynecology recomm nausea and vomiting of pregnancy should start with pyridoxine (vitamin B-6) with or without doxylamine. switching to PO, PR, or IV antiemetics may be required. Steroids are sometimes used to treat refractory hyperemesis gravidarum. The treatment is a steroid burs used in acute asthma attacks. Several recent studies, however, have confirmed a weak association (1 pe oral clefts and methylprednisolone use in the first trimester. In addition to the medications mentioned below, ginger is a common remedy for nausea and vomiting in randomized, double-blind, crossover trial of ginger in pregnancy have been reported. Symptoms were re clinical or experimental data about adverse effects of ginger in pregnancy exist. The FDA does not regula Practitioners of traditional Chinese medicine believe that stimulation of acupuncture point P6 can relieve used as an alternative or complement to Western medications. The data about acupressure for nausea, Band is an easy over-the-counter product that stimulates the P6 site. Drug Category: Antiemetics -- No drug has been approved by the FDA for the treatment of nausea an Benedictine. Any antiemetic must be prescribed with caution. Promethazine (Phenergan) -- Antidopaminergic agent effective in

6 Page 6 of 11 postsynaptic mesolimbic dopaminergic receptors in brain and red brainstem reticular system. Not to be administered SC or intra lesions may develop mg PO/PR tid and 25 mg at hs 25 mg IV/IM, and repeat prn in 2 h; switch to PO as soon as poss mg/kg PO/IV/IM/PR 4-6 times/d prn May have additive effects when used concurrently with other CN anticonvulsants; coadministration with epinephrine may cause hy C - Safety for use during pregnancy has not been established. Caution in cardiovascular disease, impaired liver function, seizur and acute-angle glaucoma; may cause drowsiness Prochlorperazine (Compazine) -- Antidopaminergic drug that ma vomiting by blocking postsynaptic mesolimbic dopamine recepto effects and by depressing the reticular activating system mg PO/IM tid/qid, not to exceed 40 mg/d mg IV q3-4h prn; not to exceed 10 mg/dose or 40 mg/d 25 mg PR bid >12 years: Administer as in adults ; bone marrow suppression, narrow severe liver or cardiac disease Coadministration with other CNS depressants or anticonvulsants effects; with epinephrine may cause hypotension C - Safety for use during pregnancy has not been established. Drug-induced Parkinson syndrome or pseudoparkinsonism occur the most common extrapyramidal reaction in elderly patients; low caution with history of seizures Meclizine (Antivert, Antrizine, Meni-D, Dramamine, Marezine) the middle-ear labyrinth and blocks conduction in middle pathways. These effects are associated with relief of nausea and mg PO q12-24h; not to exceed 100 mg/d >12 years: Administer as in adults May increase toxicity of CNS depressants, neuroleptics, and anti B - Usually safe but benefits must outweigh the risks. Caution in angle-closure glaucoma, prostatic hypertrophy, pyloric bladder-neck obstruction Ondansetron (Zofran) -- Selective 5-HT3-receptor antagonist tha peripherally and centrally, used in the prevention of nausea and in the liver with the P-450 mechanism. 2-4 mg IV q6-8h

7 Page 7 of 11 >12 years: Administer as in adults CYP450 inducers (eg, barbiturates, rifampin, carbamazepine, ph life and clearance of (dose adjustment usually not required) B - Usually safe but benefits must outweigh the risks. Medication is for the prevention of nausea and vomiting, not for r vomiting Diphenhydramine (Benadryl) -- Used for the treatment and proph disorders that may cause nausea and vomiting mg PO q6-8h prn; not to exceed 400 mg/d mg IV/IM q6-8h prn; not to exceed 400 mg/d mg PO tid/qid, 5 mg/kg/d, or 150 mg/m 2 /d divided tid/qid 5 mg/kg/d IV/IM or 150 mg/m 2 /d divided qid; not to exceed 300 m ; MAOI use Potentiates effect of CNS depressants; alcohol in syrup form ma medications that can cause disulfiramlike reactions C - Safety for use during pregnancy has not been established. May exacerbate angle-closure glaucoma, hyperthyroidism, peptic obstruction Droperidol (Inapsine) -- Neuroleptic agent that may reduce emes stimulation of the chemoreceptor trigger zone mg IV/IM q3-4h prn >12 years: Administer as in adults May increase toxicity of CNS depressants C - Safety for use during pregnancy has not been established. Hypovolemic patients may experience hypotension; may decreas pressure; tardive dyskinesia (40%); possible high rate of extrapy elderly patients; life-threatening arrhythmias may occur May cause QT prolongation (delayed recharging of heart betwee following injection of doses at or below recommended levels; pro potentially fatal heart arrhythmia known as torsades de pointes (T undergo a 12-lead ECG prior to administration of drug to determi prolonged (ie, QTc >440 msec for males or 450 msec for females prolonged, droperidol should not be administered; for patients in droperidol treatment is felt to outweigh risks of potentially serious monitoring should be performed prior to treatment and continued completing treatment to monitor for arrhythmias Metoclopramide (Reglan) -- Works as an antiemetic by blocking chemoreceptor trigger zone of the CNS. Usually reserved for use to control symptoms. Stimulates intestinal motility and is metabol

8 Page 8 of mg PO up to qid 30 min before meals and at hs >12 years: Administer as in adults ; pheochromocytoma or GI hemorrh perforation; history of seizure disorders Anticholinergics may antagonize effects; opiate analgesics may i B - Usually safe but benefits must outweigh the risks. Avoid with medications that can cause extrapyramidal reactions; mental illness and Parkinson disease Drug Category: Nutritional supplements -- Pyridoxine deficiency may have an etiologic role. Severe to thiamine deficiency and result in Wernicke encephalopathy. Pyridoxine (Vitamin B6, Hexa-Betalin) -- Some use pyridoxine wi ingredients in Benedictine, an antiemetic no longer available in th in Europe). In the US, doxylamine can be found in the over Unisom (effective dose is half tablet) mg PO qd for up to 3 wk or 10 mg IV qd for 3 d Not established May decrease levodopa, phenytoin, and phenobarbital serum lev A - Safe in pregnancy >200 mg/d may precipitate withdrawal effects when discontinued Thiamine (Vitamin B 1, Thiamilate) -- Used in the treatment of thia Wernicke encephalopathy syndrome. 100 mg daily IV/IM for up to 2 wk Not established None reported A - Safe in pregnancy Sensitivity reactions can occur (intradermal test-dose recommen sensitivity); deaths have resulted from IV use; sudden onset or w encephalopathy, following glucose administration, may occur in t patients; administer before or with dextrose-containing fluids in s deficiency FOLLOW-UP Further Inpatient Care: Admit patients with any of the following: Severe dehydration and inability to tolerate oral fluids

9 Page 9 of 11 Severe electrolyte abnormality Acidosis Infection Malnutrition Weight loss Patients who continue to lose weight may require enteral feeding or parenteral nutrition. Further Outpatient Care: Reassurance Frequent small meals with high-carbohydrate or high-protein content (Avoid offensive odors, fatty fo supplements.) Psychological intervention (Consider counseling or hypnotherapy.) In/Out Patient Meds: As an outpatient, trial of pyridoxine (vitamin B-6) with/without doxylamine Oral or parenteral antiemetics if the patient's condition is unresponsive to fluids, dietary restrictions, Complications: Complications of vomiting rarely occur; however, Mallory-Weiss tears and esophageal perforations In severe cases, without thiamine supplementation, Wernicke encephalopathy may occur (ie, diplop confusion, coma). If treatment is unsuccessful, complications of prolonged dehydration and starvation may occur. Prognosis: Generally, the condition is self limited. Patient Education: For excellent patient education resources, visit emedicine's and Reproduction Center education articles and, Vomiting. MISCELLANEOUS

10 Page 10 of 11 Medical/Legal Pitfalls: No drugs are approved by the FDA for the treatment of nausea and vomiting in pregnancy, and the should outweigh the risks. BIBLIOGRAPHY ACOG Practice Bulletin: Nausea and Vomiting of, number 52, April Aikins Murphy P: Alternative therapies for nausea and vomiting of pregnancy. Obstet Gynecol 1998 Bashiri A, Neumann L, Maymon E: Hyperemesis gravidarum: epidemiologic features, complications Gynecol Reprod Biol 1995 Dec; 63(2): 135-8[Medline]. Carmichael SL, Shaw GM: Maternal corticosteroid use and risk of selected congenital anomalies. A (3): 242-4[Medline]. Chan NN: Thyroid function in hyperemesis gravidarum. Lancet 1999 Jun 26; 353(9171): 2243 Child TJ: Management of hyperemesis in pregnant women. Lancet 1999 Jan 23; 353(9149): 325 Czeizel AE, Dudas I, Fritz G, et al: The effect of periconceptional multivitamin-mineral supplementa vomiting in the first trimester of pregnancy. Arch Gynecol Obstet 1992; 251(4): 181-5[Medline] Dickson MJ: Management of hyperemesis in pregnant women. Lancet 1999 Jan 23; 353(9149): 32 Fischer-Rasmussen W, Kjaer SK, Dahl C: Ginger treatment of hyperemesis gravidarum. Eur J Obs Jan 4; 38(1): 19-24[Medline]. Frigo P, Lang C, Reisenberger K: Hyperemesis gravidarum associated with Helicobacter pylori sero Apr; 91(4): 615-7[Medline]. Fukada Y, Ohta S, Mizuno K: Rhabdomyolysis secondary to hyperemesis gravidarum. Acta Obstet 71[Medline]. Hod M, Orvieto R, Kaplan B: Hyperemesis gravidarum. A review. J Reprod Med 1994 Aug; 39(8): 6 Hoo JJ: Acupressure for hyperemesis gravidarum. Am J Obstet Gynecol 1997 Jun; 176(6): 1395 Jacoby EB, Porter KB: Helicobacter pylori infection and persistent hyperemesis gravidarum. Am J P Jewell D, Young G: Interventions for nausea and vomiting in early pregnancy (Cochrane Review). T Chichester, UK: John Wiley and Sons, Ltd. Kocak I, Akcan Y, Ustan C: Helicobacter pylori serpositivity in patients with hyperemesis gravidarum 66: 251-4[Medline]. Kousen M: Treatment of nausea and vomiting in pregnancy. Am Fam Physician 1993 Nov 15; 48(7 Nageotte MP, Briggs GG, Towers CV: Droperidol and diphenhydramine in the management of hype Obstet Gynecol 1996 Jun; 174(6): ; discussion [Medline]. Nelson-Piercy C: Treatment of nausea and vomiting in pregnancy. When should it be treated and w Saf 1998 Aug; 19(2): [Medline]. Newman V, Fullerton JT, Anderson PO: Clinical advances in the management of severe nausea an Obstet Gynecol Neonatal Nurs 1993 Nov-Dec; 22(6): [Medline]. Park-Wyllie L, Mazzotta P, Pastuszak A, et al: Birth defects after maternal exposure to corticostero meta-analysis of epidemiological studies. Teratology 2000 Dec; 62(6): [Medline]. Robinson JN, Banerjee R, Thiet MP: Coagulopathy secondary to vitamin K deficiency in hyperemes 1998 Oct; 92(4 Pt 2): 673-5[Medline]. RodrÃguez-Pinilla E, MartÃnez-FrÃas ML: Corticosteroids during pregnancy and oral clefts: a case Jul; 58(1): 2-5[Medline]. Russo-Stieglitz KE, Levine AB, Wagner BA: outcome in patients requiring parenteral nu Jul-Aug; 8(4): 164-7[Medline]. Safari HR, Fassett MJ, Souter IC: The efficacy of methylprednisolone in the treatment of hypereme double-blind, controlled study. Am J Obstet Gynecol 1998 Oct; 179(4): 921-4[Medline].

11 Page 11 of 11 Safari HR, Alsulyman OM, Gherman RB: Experience with oral methylprednisolone in the treatment gravidarum. Am J Obstet Gynecol 1998 May; 178(5): [Medline]. Sahakian V, Rouse D, Sipes S, et al: Vitamin B6 is effective therapy for nausea and vomiting of pre blind placebo-controlled study. Obstet Gynecol 1991 Jul; 78(1): 33-6[Medline]. Serrano P, Velloso A, Garcia-Luna PP: Enteral nutrition by percutaneous endoscopic gastrojejunos 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 grav 1996 May; 174(5): [Medline]. Medicine is a constantly changing science and not all therapies are clearly established. New research changes drug and treatment therapies daily. The authors, edito efforts to provide information that is up-to-date and accurate and is generally accepted within medical standards at the time of publication. However, as medical scien always possible, the authors, editors, and publisher or any other party involved with the publication of this article do not warrant the information in this article is accura omissions or errors in the article or for the results of using this information. The reader should confirm the information in this article from other sources prior to use. In contraindications should be confirmed in the package insert. FULL DISCLAIMER NOTE:, Hyperemesis Gravidarum excerpt Copyright 2005, emedicine.com, Inc. About Us Privacy Terms of Use Contact Us Advertise Institutional Subscribers We subscribe to the HONcode principles of the Health On the Net Foundation emedicine.com, All Rights Reser