Hyperemesis Gravidarum Author: Dotun A Ogunyemi, MD; Chief Editor: David Chelmow, MD

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Overview Presentation DDx Workup Treatment Medication Follow-up

Updated: Aug 16, 2011

Overview

BackgroundNausea and vomiting in pregnancy is extremely common. Hyperemesisgravidarum (HEG) is the most severe form of nausea and vomiting inpregnancy. A continuous spectrum of the severity of nausea and vomitingranges from the nausea and vomiting that occurs in most pregnancies tothe severe disorder of hyperemesis gravidarum.

Studies estimate that nausea and vomiting occurs in 50-90% ofpregnancies. The nausea and vomiting associated with pregnancy usuallybegins by 9-10 weeks of gestation, peaks at 11-13 weeks, and resolves inmost cases by 12-14 weeks. In 1-10% of pregnancies, symptoms maycontinue beyond 20-22 weeks.[1, 2]

Normal nausea and vomiting may be an evolutionary protectivemechanism—it may protect the pregnant woman and her embryo fromharmful substances in food, such as pathogenic microorganisms in meatproducts and toxins in plants, with the effect being maximal duringembryogenesis (the most vulnerable period of pregnancy). This issupported by studies showing that women who had nausea and vomitingwere less likely to have miscarriages and stillbirth.[3, 4]

Hyperemesis gravidarum is characterized by persistent nausea andvomiting associated with ketosis and weight loss (>5% of prepregnancyweight). Hyperemesis gravidarum may cause volume depletion,electrolytes and acid-base imbalances, nutritional deficiencies, and even

death. Severe hyperemesis requiring hospital admission occurs in 0.3-2%of pregnancies.[5]

PathophysiologyThe physiologic basis of hyperemesis gravidarum is controversial.Hyperemesis gravidarum appears to occur as a complex interaction ofbiological, psychological, and sociocultural factors. The following theorieshave been proposed:

Hormonal changesWomen with hyperemesis gravidarum often have high hCG levels thatcause transient hyperthyroidism. hCG can physiologically stimulate thethyroid gland thyroid-stimulating hormone (TSH) receptor. hCG levels peakin the first trimester. Some women with hyperemesis gravidarum appear tohave clinical hyperthyroidism. However, in a larger portion (50-70%), TSHis transiently suppressed and the free thyroxine (T4) index is elevated (40-73%) with no clinical signs of hyperthyroidism, circulating thyroidantibodies, or enlargement of the thyroid. In transient hyperthyroidism ofhyperemesis gravidarum, thyroid function normalizes by the middle of thesecond trimester without antithyroid treatment. Clinically overthyperthyroidism and thyroid antibodies are usually absent.[4, 6, 7, 5]

A report on a unique family with recurrent gestational hyperthyroidismassociated with hyperemesis gravidarum showed a mutation in theextracellular domain of the TSH receptor that made it responsive to normallevels of hCG. Thus, cases of hyperemesis gravidarum with a normal hCGmay be due to varying hCG isotypes.[8, 9]

A positive correlation between the serum hCG elevation level and free T4levels has been found, and the severity of nausea appears to be related tothe degree of thyroid stimulation. hCG may not be independently involvedin the etiology of hyperemesis gravidarum but may be indirectly involved byits ability to stimulate the thyroid. For these patients, hCG levels werelinked to increased levels of immunoglobulin M, complement, andlymphocytes. Thus, an immune process may be responsible for increasedcirculating hCG or isoforms of hCG with a higher activity for the thyroid.Critics of this theory note that (1) nausea and vomiting are not usualsymptoms of hyperthyroidism, (2) signs of biochemical hyperthyroidism are

not universal in cases of hyperemesis gravidarum, and (3) some studieshave failed to correlate the severity of symptoms with biochemicalabnormalities.[10, 11, 12]

Some studies link high estradiol levels to the severity of nausea andvomiting in patients who are pregnant, while others find no correlationbetween estrogen levels and the severity of nausea and vomiting inpregnant women. Previous intolerance to oral contraceptives is associatedwith nausea and vomiting in pregnancy. Progesterone also peaks in thefirst trimester and decreases smooth muscle activity; however, studieshave failed to show any connection between progesterone levels andsymptoms of nausea and vomiting in pregnant women. Lagiou et al studiedprospectively 209 women with nausea and vomiting who showed thatestradiol levels were positively correlated while prolactin levels wereinversely associated with nausea and vomiting in pregnancy and nocorrelation existed with estriol, progesterone, or sex-hormone bindingglobulin.[13]

Gastrointestinal dysfunctionThe stomach pacemaker causes rhythmic peristaltic contractions of thestomach. Abnormal myoelectric activity may cause a variety of gastricdysrhythmias, including tachygastrias and bradygastrias. Gastricdysrhythmias have been associated with morning sickness. The presenceof dysrhythmias was associated with nausea while normal myoelectricalactivity was present in the absence of nausea. Mechanisms that causegastric dysrhythmias include elevated estrogen or progesterone levels,thyroid disorders, abnormalities in vagal and sympathetic tone, andvasopressin secretion in response to intravascular volume perturbation.Many of these factors are present in early pregnancy. Thesepathophysiologic factors are hypothesized to be more severe or thegastrointestinal tract more sensitive to the neural/humoral changes in thosewho develop hyperemesis gravidarum.[14]

Hepatic dysfunctionLiver disease, usually consisting of mild serum transaminase elevation,occurs in almost 50% of patients with hyperemesis gravidarum. Impairmentof mitochondrial fatty acid oxidation (FAO) has been hypothesized to play a

role in the pathogenesis of maternal liver disease associated withhyperemesis gravidarum. It has been suggested that women heterozygousfor FAO defects develop hyperemesis gravidarum associated with liverdisease while carrying fetuses with FAO defects due to accumulation offatty acids in the placenta and subsequent generation of reactive oxygenspecies. Alternatively, it is possible that starvation leading to peripherallipolysis and increased load of fatty acids in maternal-fetal circulation,combined with reduced capacity of the mitochondria to oxidize fatty acids inmothers heterozygous for FAO defects, can also cause hyperemesisgravidarum and liver injury while carrying nonaffected fetuses.

Lipid alterationsJarnfelt-Samsioe et al found higher levels of triglycerides, total cholesterol,and phospholipids in women with hyperemesis gravidarum compared withmatched, nonvomiting, pregnant and nonpregnant controls. This may berelated to the abnormalities in hepatic function in pregnant women.However, Ustun et al found decreased levels of total cholesterol, LDLcholesterol, apoA and apoB in women with hyperemesis gravidarumcompared with controls.[15, 16]

InfectionHelicobacter pylori is a bacterium found in the stomach that may aggravatenausea and vomiting in pregnancy. Studies have found conflicting evidenceof the role of H pylori in hyperemesis gravidarum. Recent studies in theUnited States have not shown association with hyperemesis gravidarum.However, persistent nausea and vomiting beyond the second trimester maybe due to an active peptic ulcer caused by H pylori infection.[17, 18]

Vestibular and olfactionHyperacuity of the olfactory system may be a contributing factor to nauseaand vomiting during pregnancy. Many pregnant women report the smell ofcooking food, particularly meats, as triggers to nausea. Striking similaritiesbetween hyperemesis gravidarum and motion sickness suggest thatunmasking of subclinical vestibular disorders may account for some casesof hyperemesis gravidarum.[19, 20]

GeneticIn studies examining the familial link of hyperemesis gravidarum, researchsuggests a possible genetic aspect to hyperemesis. A study was performedlooking at 544,087 pregnancies from Norway’s mandatory birth registryfrom 1967-2005. This study demonstrated that daughters born from apregnancy complicated by hyperemesis had a 3% risk of havinghyperemesis in their own pregnancy. Women who were born after anunaffected pregnancy had a risk of 1.1%.[21] In surveys administered tomothers who had pregnancies complicated by hyperemesis, higher rates ofhyperemesis were reported among their relatives. This was particularly soin their sisters.[22]

Overall, the data suggest that a genetic predisposition may play a role inthe development of hyperemesis gravidarium.

Biochemical researchHyperemesis gravidarum is associated with overactivation of sympatheticnerves and enhanced production of tumor necrosis factor (TNF)-alpha.[23] Increased adenosine levels have also been noted; sinceadenosine is an established suppressor of excessive sympathetic nervesactivation and cytokine production, the increase in plasma adenosine inhyperemesis gravidarum may be modulatory.[24] Trophoblast-derivedcytokines have been reported to induce secretion of hCG.

Immunoglobulins C3 and C4 and lymphocyte counts are significantly higherin women with hyperemesis gravidarum. T-helper 1/T-helper 2 balance isdecreased in women with hyperemesis gravidarum, which results inincreased humoral immunity. Increased fetal DNA has been found in thematernal plasma of women with hyperemesis gravidarum, and theincreased DNA is speculated to be derived from trophoblasts that havebeen destroyed by the hyperactive maternal immune system. Thus,hyperemesis gravidarum may be mediated by immunologic aberrations inpregnancy.[25, 26, 27, 28]

Psychological issues

Physiological changes associated with pregnancy interact with eachwoman's psychologic state and cultural values. Psychologic responsesmay interact with and exacerbate the physiology of nausea and vomitingduring pregnancy. Nonetheless, hyperemesis gravidarum is typically thecause of, as opposed to the result of, psychologic stress. In very unusualinstances, cases of hyperemesis gravidarum could represent psychiatricillness, including conversion or somatization disorder ormajor depression.[29, 30, 31]

Epidemiology

FrequencyUnited StatesOf all pregnancies, 0.3-2% are affected by hyperemesis gravidarum(approximately 5 per 1000 pregnancies).

InternationalHyperemesis gravidarum appears to be more common in westernizedindustrialized societies and urban areas than rural areas.

Mortality/MorbidityHyperemesis gravidarum was a significant cause of maternal death before1940. In Great Britain, mortality decreased from 159 deaths per millionbirths from 1931-1940 to 3 deaths per million births from 1951-1960.Charlotte Brontë is thought to have died of hyperemesis gravidarum in1855. In the United States, 7 deaths from hyperemesis gravidarum werereported in the 1930s. Today, although hyperemesis gravidarum is stillassociated with significant morbidity, it is still a rare cause of maternalmortality.

Many hours of productive work are lost because of nausea and vomitingduring pregnancy. Nearly 50% of employed women believe that their workis affected, and up to 25% require time off from work.

Hyperemesis gravidarum is a debilitating illness that can cause severesuffering, which profoundly affects both patients and their families. Inabout half of the women there is an adverse effect on spousal

relationships, and 55% have feelings of depression. In one study of 140women with hyperemesis gravidarum, 27% required multiplehospitalizations. The financial burden of hyperemesis gravidarum on theAmerican health system has been estimated as approximately $130million dollars per year, excluding physician fees.

Women with hyperemesis gravidarum who have a low pregnancy weightgain (< 15.4 lb or 7 kg) have increased risk for delivering neonates of lowbirth weight, delivering neonates who are small for gestational age,preterm delivery, and a 5-minute Apgar score of less than 7.

RaceNo clear racial predominance is noted for hyperemesis gravidarum.

Hyperemesis gravidarum is less common in American Indian and Eskimopopulations.

Hyperemesis gravidarum is less common in African and some Asianpopulations (but not industrialized Japan).

Sex: Hyperemesis gravidarum affects females.

Age: The risk of hyperemesis gravidarum appears to decrease withadvanced maternal age.

Proceed to Clinical Presentation

History The defining symptoms of hyperemesis gravidarum are gastrointestinal in

nature and include nausea and vomiting. Other common symptoms include ptyalism (excessive salivation), fatigue,

weakness, and dizziness. Patients may experience the following:

Sleep disturbance Hyperolfaction Dysgeusia Decreased gustatory discernment Depression Anxiety Irritability

Mood changes Decreased concentration

When obtaining history from the patient, discuss present symptoms. Obtaininformation pertaining to the timing, onset, severity, pattern, and alleviatingand exacerbating factors (eg, relationship to meals, medications, prenatalvitamins, stress, other triggers).

A thorough review of systems for any symptoms that might suggest othergastrointestinal, renal, endocrine, and central nervous system disorders isvital.

Review past medical history, placing emphasis on past medical conditions,surgeries, medications, allergies, adverse drug reactions, family history,social history (including support system), employment, habits, and diet.

Obtaining a thorough gynecologic history of symptoms, such as vaginalbleeding or spotting, past pregnancies, past use of oral contraceptives, andresponse to oral contraceptives used, is important.

Physical The physical examination is usually unremarkable in patients with

hyperemesis gravidarum. The physical examination findings may be more helpful if the patient has

unusual complaints suggestive of other disorders (eg, bleeding, abdominalpain).

Pay attention to the vital signs, including standing and lying blood pressureand pulse, volume status (eg, mucous membrane condition, skin turgor,neck veins, mental status), general appearance (eg, nutrition, weight),thyroid examination findings, abdominal examination findings, cardiacexamination findings, and neurologic examination findings.

CausesIn a review of 1,301 cases of hyperemesis gravidarum from Canada, Fell etal showed that medical complications of hyperthyroid disorders, psychiatricillness, previous molar disease, gastrointestinal disorders, pregestationaldiabetes, and asthma were significantly independent risk factors forhyperemesis gravidarum, whereas maternal smoking and maternal ageolder than 30 years decreased the risk. Pregnancies with female fetusesand multiple fetuses were also at increased risk.[32, 33]

In some studies, women from low to middle socioeconomic class, womenwith lower levels of education, women with previous pregnancies with

nausea and vomiting, women in their first pregnancy, and women withprevious intolerance to oral contraceptives more commonly experiencenausea and vomiting during pregnancy. Nausea and vomiting duringpregnancy is also more common with multiple-gestation pregnancies.

Other factors that have been proposed include ethnicity, occupationalstatus, fetal anomalies, increased body weight, nausea and vomiting in aprior pregnancy, history of infertility, interpregnancy interval, corpus luteumin right ovary, and prior intolerance to oral contraceptives.

Risk factors for hyperemesis gravidarum may include the following:o Previous pregnancies with hyperemesis gravidarumo Greater body weighto Multiple gestationso Trophoblastic diseaseo Nulliparity

Cigarette smoking is associated with a decreased risk for hyperemesisgravidarum.

Proceed to Differential Diagnoses

Differential Diagnoses Appendicitis Biliary Disease Diabetic Ketoacidosis Esophagitis Fatty Liver Gastroenteritis Gastroesophageal Reflux Disease Hepatitis Hyperparathyroidism Hyperthyroidism Irritable Bowel Syndrome Nephrolithiasis Pancreatitis, Acute Paralytic Ileus/Bowel Obstruction Peptic Ulcer Disease Porphyria, Acute Intermittent Preeclampsia

Proceed to Workup

Laboratory StudiesInitial lab studies for hyperemesis gravidarum should include the following:

Urinalysis for ketones and specific gravity: A sign of starvation, ketonesmay be harmful to fetal development. High specific gravity occurs withvolume depletion.

Serum electrolytes and ketones: Assess electrolyte status to evaluate forlow potassium or sodium, identify hyperchloremic metabolic alkalosis oracidosis, and evaluate renal function and volume status.

Liver enzymes and bilirubin: Elevated transaminase levels may occur inas many as 50% of patients with hyperemesis gravidarum. Mildtransaminitis often resolves once the nausea has resolved. Significantlyelevated liver enzymes, however, may be a sign of another underlyingliver condition, such as hepatitis (viral, ischemic, autoimmune), or someother etiology of liver injury.[34]

Amylase/lipase: Amylase level is elevated in approximately 10% ofpatients with hyperemesis gravidarum. Lipase, when combined withamylase, can increase the specificity in diagnosing pancreatitis as anetiology.

TSH, free thyroxine: Hyperemesis gravidarum is often associated with atransient hyperthyroidism and suppressed TSH levels in 50-60% of cases.However, an elevated free thyroxine may suggest that overthyperthyroidism is present, thus necessitating further workup andtreatment.[35]

Urine culture: This may be indicated because urinary tract infection iscommon in pregnancy and can be associated with nausea and vomiting.

Calcium level: Consider measuring Ca++ levels. Some rare cases havebeen reported of hypercalcemia being associated with hyperemesisgravidarum, resulting from hyperparathyroidism.

Hematocrit: This may be elevated because of volume contraction. Hepatitis panel: If clinically indicated, hepatitis A, B, or C may be confused

with hyperemesis gravidarum.[5]

Imaging Studies Obstetric ultrasonography is usually warranted in patients with HEG to

evaluate for multiple gestations or trophoblastic disease.

Additional imaging studies generally are not needed unless the clinicalpresentation is atypical (eg, nausea and/or vomiting beginning after 9-10wk of gestation, nausea and/or vomiting persisting after 20-22 wk, acutesevere exacerbation) or another disorder is suggested based on history orphysical examination findings.

If indicated clinically, performing upper abdominal ultrasonography toevaluate the pancreas and/or biliary tree appears to be a low-risk study.

In rare cases, abdominal CT scan or even MRI may be indicated ifappendicitis is under consideration as a cause of nausea and vomiting inpregnancy.

ProceduresIn patients with abdominal pain or upper gastrointestinal bleeding, uppergastrointestinal endoscopy appears to be safe in pregnancy, althoughcareful monitoring is suggested.

Proceed to Treatment & Management

Medical CareInitial management should be conservative and may include reassurance,dietary recommendations, and support. Alternative therapies may includeacupressure and hypnosis.[36]

Studies have not shown a clear benefit of acupressure in patients withhyperemesis gravidarum. However, a randomized study by Rosen et alusing pressure or electrical stimulation at the P6 (or Neguian) point on theinside of the wrist showed some efficacy in reducing nausea and vomitingand promoting weight gain in women with hyperemesis gravidarum.[37]

More controversy surrounds the benefit of hypnosis, but it has beenstudied in some cases of hyperemesis gravidarum and has been shownto be beneficial.

Psychological counseling may be considered.[36]

Outpatient or home intravenous hydration should be considered. Ifmedications and outpatient hydration fail or if severe electrolytedisturbances persist, inpatient admission for intravenous hydration maybe necessary.

Pharmacologic therapyIf pharmacologic therapy is necessary, treatment may be initiated usingvitamin B-6, 10-25 mg daily, 3-4 times daily; doxylamine, 12.5 mg, 3-4times daily can be used in addition. The herb, ginger capsules 250 mg 4times daily, can be added at this point if patient is still vomiting since it hasbeen shown to be effective in randomized trials.[38] Metoclopramide, 5-10mg taken orally q8h may be used next. Promethazine, 12.5 mg orally orrectally q4h, or dimenhydrinate 50-100 mg orally q4-6h, may be added aswell. Ondansetron 4-8 mg orally or IV q8h can be used for further refractorycases. Methylprednisolone, 16 mg orally or IV q8h for 3 days, with a taperto lowest effective dose, can be used if persistent vomiting occurs despitethe above therapy. Steroids seem to increase risk for oral clefts in first 10weeks of gestation.[39, 5]

Metoclopramide is widely used for nausea and vomiting during pregnancy,but information regarding human teratogenicity has been lacking. Matok etal found no increased risk for major congenital malformations, low birthweight, preterm delivery, Apgar scores, or perinatal death between infantsof mothers who took metoclopramide within the first trimester comparedwith infants’ mothers who did not take metoclopramide. The retrospectivecohort study included a total of 81,703 infants who were born to womenregistered in a single health system with computerized maternal and infanthospital records. Of these, 3458 (4.2%) had first trimester exposure tometoclopramide.[40]

Since confirmation of adherence was unavailable, a secondary analysiswas performed on infants of mothers who refilled their prescription formetoclopramide at least once (n=758), and no increased risk was found inthis subpopulation exposed to metoclopramide compared with infants notexposed. Additionally, the results of the study were unchanged whentherapeutic abortions of exposed and unexposed fetuses were included inthe analysis.

The study provides clinicians reassurance that metoclopramide does notcause congenital malformations; although, dopamine antagonists cancause maternal extrapyramidal symptoms (ie, acute dystonic reactions,tardive dyskinesia).

If hypokalemia is severe or symptomatic, potassium should be replacedparenterally. Before administering intravenous potassium, renal functionshould be evaluated. Potassium is usually added to intravenous fluid to

achieve a concentration of 40 mEq/L (and not >80 mEq/L). An infusion rateof 10 mEq of potassium per hour should be safe as long as urine output isadequate.

When administrating intravenous hydration to a patient who has severevolume depletion in an effort to prevent the development of Wernickeencephalopathy, avoid intravenous glucose until intravenous thiamine hasbeen administered.

If persistent dehydration, electrolyte loss, and/or weight loss occur despiteabove therapy, nutrition supplementation by either the parenteral or enteralroute is indicated. The standard method has been via total parenteralnutrition (TPN). However, documented risks of bacteremia, sepsis, andthrombosis have been associated with the PICC lines required for TPNsupplementation. Nasogastric tube placement and subsequent enteralfeeding has been shown in small series and reports to be a validalternative, with less complication risks, similar efficacy, and similaroutcomes in regard to neonatal outcome when compared with TPN.[41]

Surgical CareIn some refractory severe cases of hyperemesis gravidarum, if maternalsurvival is threatened, or if hyperemesis gravidarum is causing severephysical and psychological burden, termination of the pregnancy should beconsidered.[42]

Consultations Patients with HEG should be under the care of an obstetrician who is

familiar with this disorder. Consultation with a psychiatrist or psychologist may be warranted because

psychological assessment may be needed. In some cases, even supportiveor focal psychotherapy or psychiatric medications may be indicated.Behavioral therapy may be beneficial early in the course of HEG.

When certain disorders are considered the cause of nausea and vomiting(see Differentials), referral to a gastroenterologist or surgeon may benecessary.

DietInitial suggestions for dietary modification in patients with nausea andvomiting associated with pregnancy include the following:

Eat when hungry, regardless of normal meal times.

Eat frequent small meals. Avoid fatty and spicy foods and emetogenic foods or smells. Increase

intake of bland or dry foods. Eliminate pills with iron. High protein snacks are helpful. Crackers in the morning may be helpful. Increase intake of carbonated beverages. Other suggested foods include herbal teas containing peppermint or

ginger, other ginger-containing beverages, broth, crackers, unbutteredtoast, gelatin, or frozen desserts.

Preconception use of prenatal vitamins may decrease nausea andvomiting associated with pregnancy.

ActivitySome patients note improvement of nausea and vomiting with decreasedactivity and increased rest. Other patients suggest that fresh outdoor airmay improve symptoms.

Proceed to Medication

Medication SummaryAntihistamines, antiemetics of the phenothiazine class, and promotilityagents (eg, metoclopramide) have been used in the treatment of nauseaand vomiting during pregnancy.

Vitamin B-6 (pyridoxine) has also been studied in the treatment of nauseaand vomiting during pregnancy and reduced nausea and vomiting whencompared with placebo.

Ondansetron (Zofran), a serotonin-receptor antagonist, showed no benefitover the antiemetic promethazine (Phenergan), at much greater cost. Itmay be reserved for refractory cases. A meta-analysis of 6 randomized,double-blind trials showed that ginger was an effective treatment for HEG.

Steroids may be used in patient's refractory to standard therapy.Promethazine (Phenergan) was compared with methylprednisolone in arandomized, double-blind, controlled trial. Methylprednisolone appeared todecrease the rate of readmission for hyperemesis gravidarum; however,

the patients randomized to promethazine had a significantly longer durationof symptoms prior to treatment.

However, concerns exists about association between oral clefts andmethylprednisolone use in the first trimester; thus, it should be used withcaution before 10 weeks of gestation.

VitaminsClass SummaryEssential for normal DNA synthesis and play a role in various metabolicprocesses.

View full drug informationPyridoxine (Nestrex)Marketed in combination formulations with doxylamine (Benedectin,

Dilectin).Benedectin was taken off the market in the United States in the 1980sbecause of liability issues, but it is available in Canada. Doxylamine isprobably not teratogenic and can be used in combination with pyridoxine ata dose of 10-12.5 mg PO qd/bid.

Herbal medicationsClass SummaryNot approved by the US Food and Drug Administration but are remediesbelieved to improve symptoms.

View full drug informationGingerA randomized, double-blind, crossover trial of a ginger extract was shown

to be more beneficial for reducing symptoms than placebo.

AntiemeticsClass SummaryUseful in the treatment of symptomatic nausea.

View full drug information

Prochlorperazine (Compazine)May relieve nausea and vomiting by blocking postsynaptic mesolimbic

dopamine receptors through anticholinergic effects and depressing reticularactivating system. In a placebo-controlled study, 69% of patients givenprochlorperazine reported significant symptom relief, compared to 40% ofpatients in the placebo group.View full drug information

Promethazine (Phenergan)For symptomatic treatment of nausea in vestibular dysfunction.Antidopaminergic agent effective in treating emesis. Blocks postsynapticmesolimbic dopaminergic receptors in brain and reduces stimuli tobrainstem reticular system.

View full drug informationChlorpromazine (Thorazine, Ormazine)Mechanisms responsible for relieving nausea and vomiting include

blocking postsynaptic mesolimbic dopamine receptors, anticholinergiceffects, and depression of RAS. Blocks alpha-adrenergic receptors anddepresses release of hypophyseal and hypothalamic hormones.View full drug information

Trimethobenzamide: (Tebamide, Tigan)Acts centrally to inhibit the medullary chemoreceptor trigger zone.

View full drug information

Metoclopramide (Reglan)Blocks dopamine receptors and (when given in higher doses) also blocksserotonin receptors in chemoreceptor trigger zone of the CNS; enhancesthe response to acetylcholine of tissue in upper GI tract causing enhancedmotility and accelerated gastric emptying without stimulating gastric, biliary,or pancreatic secretions; increases lower esophageal sphincter tone.View full drug information

Ondansetron: (Zofran)Selective 5-HT3-receptor antagonist, blocking serotonin, both peripherallyon vagal nerve terminals and centrally in the chemoreceptor trigger zone.

CorticosteroidsClass SummaryThese agents have profound and varied metabolic effects.

View full drug informationMethylprednisolone (Medrol, Solu-Medrol)May improve symptoms of nausea and vomiting.

AntihistaminesClass SummaryStudied in nausea and vomiting during pregnancy and in small numbers ofpatients with HEG, providing relief in 82% of patients. Appears to be asefficacious as pyridoxine in another study.

View full drug informationMeclizine (Antivert)Decreases excitability of middle ear labyrinth and blocks conduction inmiddle ear vestibular-cerebellar pathways. These effects are associatedwith relief of nausea and vomiting.View full drug information

Diphenhydramine (Benadryl)Competes with histamine for H1-receptor sites on effector cells in thegastrointestinal tract, blood vessels, and respiratory tract; anticholinergicand sedative effects are also seen

Proceed to Follow-up

Further Inpatient CareInpatient care of hyperemesis gravidarum may be necessary if outpatienttreatment fails or if severe fluid and/or electrolyte imbalance and nutritionalcompromise exist (see Treatment).

Further Outpatient CareMonitor patients regularly, paying attention to symptoms and to the state ofmind of the patient and family. Monitor weight and urinary ketones at eachvisit.

Inpatient & Outpatient MedicationsSee Treatment.

Complications Case reports describe the following maternal complications of hyperemesis

gravidarum: Esophageal rupture or perforation Pneumothorax and pneumomediastinum Wernicke encephalopathy or blindness Hepatic disease Seizures, coma, or death

Others complications include renal failure, pancreatitis, deep venousthrombosis, pulmonary embolism, central pontine myelinolysis,rhabdomyolysis, vitamin K deficiency and coagulopathy, and splenicavulsion.

Complications associated with central hyperalimentation include sepsis,fungemia, tamponade, local infection, venous thrombosis, fatty infiltration ofthe placenta, and transaminitis.

PrognosisHyperemesis gravidarum is self-limited and, in most cases, improves by theend of the first trimester. However, symptoms may persist through 20-22weeks of gestation and, in some cases, until delivery.

Patient Education Early patient education about the signs and symptoms of pregnancy may

be beneficial. One study found an association between nausea andvomiting and insufficient knowledge about pregnancy, stress, doubtsregarding the pregnancy, and poor communication with the doctor andspouse.

Early interventions may include reassurance and dietary counseling,including directing the patient to eat small meals, to avoid high-fat or spicyfoods, to follow hunger cues, and to increase the intake of drycarbohydrates and carbonated beverages.

For excellent patient education resources, visiteMedicineHealth's Pregnancy Center. Also, see eMedicineHealth's patienteducation articles Pregnancy andPregnancy, Vomiting.

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