Approach Considerations
If the patient is being treated on an outpatient bases, monitor her regularly, paying attention to symptoms and to the state of mind of the patient and family. Monitor weight and urinary ketones at each visit.
Some patients note improvement of nausea and vomiting with decreased activity and increased rest. Other patients suggest that fresh outdoor air may improve symptoms.
Inpatient care of hyperemesis gravidarum may be necessary if outpatient treatment fails or if severe fluid and/or electrolyte imbalance and nutritional compromise exist (see Treatment).
In some refractory severe cases of hyperemesis gravidarum, if maternal survival is threatened, or if hyperemesis gravidarum is causing severe physical and psychological burden, termination of the pregnancy should be considered. [5]
Medical Care
Initial management may include reassurance, dietary recommendations, and support. Alternative therapies may include acupressure and hypnosis. [4, 46]
Note the following:
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Studies have not shown a clear benefit of acupressure in patients with hyperemesis gravidarum. However, a randomized study by Rosen et al using pressure or electrical stimulation at the P6 (or Neguian) point on the inside of the wrist showed some efficacy in reducing nausea and vomiting and promoting weight gain in women with hyperemesis gravidarum. [47]
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More controversy surrounds the benefit of hypnosis, but it has been studied in some cases of hyperemesis gravidarum and has been shown to be beneficial.
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Psychological counseling may be considered. [4]
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Outpatient or home intravenous (IV) hydration should be considered. If medications and outpatient hydration fail or if severe electrolyte disturbances persist, inpatient admission for IV hydration may be necessary.
Pharmacologic therapy
If pharmacologic therapy is necessary, treatment may be initiated by giving vitamin B-6 10-25 mg 3-4 times daily; doxylamine 12.5 mg 3-4 times daily can be used in addition. Ginger capsules 250 mg 4 times daily can be added at this point if the patient is still vomiting; this has been shown to be effective in randomized trials. [48, 49]
A study by Liu et al found that the use of probiotic supplements during pregnancy reduced the number of episodes of vomiting by 33% and the duration of nausea by 16%. [50]
Metoclopramide 5-10 mg orally every 8 hours may be used next. Promethazine 12.5 mg orally or rectally q4h or dimenhydrinate 50-100 mg orally q4-6h may be added as well. Ondansetron 4-8 mg orally or IV q8h can be used for further refractory cases. Methylprednisolone 16 mg orally or IV q8h for 3 days, tapered to the lowest effective dose, can be used if persistent vomiting occurs despite the above therapy. Steroids seem to increase risk for oral clefts in first 10 weeks of gestation. [1, 51]
The only FDA-approved drug for treating nausea and vomiting in pregnancy is doxylamine-pyridoxine (Diclegis). [52, 53] Originally sold between 1956 and 1983 under a different brand name, 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 of the new formulation of doxylamine-pyridoxine was based on a study of pregnant women between 7 and 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 the trial participants. [54]
Doxylamine-pyridoxine’s approval did not include hyperemesis gravidarum, but a study by Koren and Maltepe showed that 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%). [55]
Metoclopramide is widely used for nausea and vomiting during pregnancy, but information regarding human teratogenicity has been lacking. Matok et al found no increased risk for major congenital malformations, low birth weight, preterm delivery, Apgar scores, or perinatal death between infants of mothers who took metoclopramide within the first trimester compared with infants’ mothers who did not take metoclopramide. The retrospective cohort study included a total of 81,703 infants who were born to women registered in a single health system with computerized maternal and infant hospital records. Of these, 3458 (4.2%) had first trimester exposure to metoclopramide. [56]
Since confirmation of adherence was unavailable, a secondary analysis was performed on infants of mothers who refilled their prescription for metoclopramide at least once (n=758), and no increased risk was found in this subpopulation exposed to metoclopramide compared with infants not exposed. Additionally, the results of the study were unchanged when therapeutic abortions of exposed and unexposed fetuses were included in the analysis.
The study provides clinicians reassurance that metoclopramide does not cause congenital malformations; although, dopamine antagonists can cause maternal extrapyramidal symptoms (ie, acute dystonic reactions, tardive dyskinesia).
If hypokalemia is severe or symptomatic, potassium should be replaced parenterally. Before administering IV potassium, renal function should be evaluated. Potassium is usually added to intravenous fluid to achieve a concentration of 40 mEq/L (and not >80 mEq/L). An infusion rate of 10 mEq of potassium per hour should be safe as long as urine output is adequate.
When administrating intravenous hydration to a patient who has severe volume depletion in an effort to prevent the development of Wernicke encephalopathy, avoid intravenous glucose until intravenous thiamine has been administered.
If persistent dehydration, electrolyte loss, and/or weight loss occur despite above therapy, nutrition supplementation by either the parenteral or enteral route is indicated. The standard method has been via total parenteral nutrition (TPN). However, documented risks of bacteremia, sepsis, and thrombosis have been associated with the PICC lines required for TPN supplementation. Nasogastric tube placement and subsequent enteral feeding has been shown in small series and reports to be a valid alternative, with less complication risks, similar efficacy, and similar outcomes in regard to neonatal outcome when compared with TPN. [57]
Consultations
Patients with hyperemesis gravidarum 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 supportive or focal psychotherapy or psychiatric medications may be indicated. Behavioral therapy may be beneficial early in the course of hyperemesis gravidarum.
When certain disorders are considered the cause of nausea and vomiting (see Differentials), referral to a gastroenterologist or surgeon may be necessary.
Diet
Initial suggestions for dietary modification in patients with nausea and vomiting associated with pregnancy include the following:
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Eat when hungry, regardless of normal meal times.
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Eat frequent small meals.
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Avoid fatty and spicy foods and emetogenic foods or smells. Increase intake of bland or dry foods.
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Eliminate pills with iron.
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High protein snacks are helpful.
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Crackers in the morning may be helpful.
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Increase intake of carbonated beverages.
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Other suggested foods include herbal teas containing peppermint or ginger, other ginger-containing beverages, broth, crackers, unbuttered toast, gelatin, or frozen desserts.
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Preconception use of prenatal vitamins may decrease nausea and vomiting associated with pregnancy.
