Evidence-Based Approaches to Managing Nausea and Vomiting in Early Pregnancy

Tekoa L. King, CNM, MPH; Patricia Aikins Murphy, CNM, DrPH

J Midwifery Womens Health. 2009;54(6):430-444.

Clinical Implications

A stepwise and systematic approach to the clinical management of women with NVP using treatments that have been shown to be both safe and efficacious will best help affected women. Using a systematic approach in combination with frequent clinic visits (every 4 days to weekly for women with severe symptoms) can also prevent escalating morbidity and save health care resources. That said, it is important to note that there are no standard treatment algorithms and to remember that many of medications used to treat NVP are not approved by the FDA specifically for this purpose. The clinical management algorithm currently recommended by both ACOG^[92] and the Society of Obstetricians and Gynaecologists of Canada^[110] is based on the work of the Motherisk Team at The Hospital for Sick Children in Toronto, Ontario, Canada. The algorithm presented in Figure 5 is adapted from recommendations from Levichek et al.,^[111] ACOG,^[92] the Society of Obstetricians and Gynaecologists of Canada,^[110] and formatted for use by clinicians in the United States.

(Enlarge Image)

Figure 5.

Protocol for assessing and treating women with nausea and vomiting in pregnancy. Adapted from the American College of Obstetricians and Gynecologists,^[92] Arsenault et al.,^[110] and Levichek et al.^[111]

Most women with a PUQE Index score of ≤6 (mild) are not retching or vomiting frequently and, in general, they are most likely to manage their NVP with lifestyle modifications and nonpharmacologic treatments. Ginger can be considered as a monotherapy or as an adjunct therapy to other treatments. Acupressure and acupuncture may also be of benefit for some women.

When the PUQE Index score is ≥7 or when a woman desires medication to help decrease nausea, start with vitamin B6 25 mg 3 times per day and half of a tablet of doxylamine (Unisom tablets) taken 3 times per day. The safety profile of both of these agents is very good.^[85,112,113] If a woman needs relief from occasional retching and/or vomiting, phenothiazines will reliably stop vomiting episodes, and most professional association guidelines recommend adding phenothiazines first for women who need relief from vomiting.^[92,110,114] Phenothiazines taken orally or used as a rectal suppository can be helpful for breakthrough vomiting, but because they are associated with significant sedation, women may not feel comfortable taking them. Therefore, metoclopramide (Reglan) is recommended if a medication is needed for regular daily use.

Severe nausea or frequent retching/vomiting can quickly result in dehydration. When a woman has signs of dehydration, management is intensified and frequent follow-up needs to be instituted. Treatment of dehydration can involve both IV fluid replacement and antiemetics that suppress vomiting. Metoclopramide can be used intravenously to interrupt an episode of vomiting, and it can be then prescribed orally for use at home after a hospital visit. Weekly visits to record the woman's weight and assess her urine for signs of dehydration are important, because a woman may need frequent changes in her treatment regimen before an effective and individualized treatment plan can be established.

Ondansetron (Zofran) has a unique role in the treatment of NVP. It has a reputation for being the most effective antiemetic in use, but the single study published to date that compared ondansetron to other antiemetics in pregnant women did not find it to be more effective than phenothiazines.^[115] It is being used more frequently, and because it is very expensive, many insurance companies will not approve its use until a woman has failed more conventional therapies. More research needs to be performed to better determine if the perceived effectiveness of ondansetron is real.

When nausea and retching/vomiting results in dehydration despite a trial of an antiemetic that reliably stops vomiting (e.g., metoclopramide, phenothiazines, or ondansetron), medical consultation and referral is necessary. If the NVP is severe enough to entertain a diagnosis of HG, inpatient management may be required. HG is diagnosed after other etiologies of severe nausea and vomiting, such as molar pregnancy or multiple gestation, are ruled out. Regardless of the etiology, treatment for the nausea and vomiting will be instituted. Inpatient admission can involve several therapeutic regimens that include intravenous fluids, antiemetics, vitamin B1 replacement to prevent Wernicke encephalopathy,^[116] corticosteroids, and nasogastric feeding or parenteral nutrition.^[117] Home health services can be extremely helpful in outpatient care after a hospitalization for HG.^[118] Although the management of HG is not the focus of this review, the interested reader can find more detailed information about inpatient management in several recent reviews.^[32,92,117]

1 2 3 4 5 6 7 8 9

Next Section

Cite this: Evidence-Based Approaches to Managing Nausea and Vomiting in Early Pregnancy - Medscape - Oct 30, 2009.

Table 1. Doses of Antiemetics Used to Treat Nausea and Vomiting in Pregnancy
Drug Name (Trade Name)	Dose	Major SEs (Recommendations)	FDA Pregnancy Category
Antihistamines (H₁ antagonists)
Diphenhydramine (Benadryl)	50–100 mg q 4–6 h PO/IM/IV	May cause drowsiness (can be used to offset anxiety caused by metoclopramide or phenothiazines)	B
Dimenhydrinate (Dramamine)	50–100 mg q 4–6 h PO/PR^a; 50 mg (in 50 mL of saline over 20 min) q 4–6 h IV	May cause drowsiness (can be used to offset anxiety caused by metoclopramide or phenothiazines)	B
Doxylamine (Unisom)	12.5 mg twice a day PO or 12.5 mg in morning and 25 mg at night PO		A
Phenothiazines (central D₂ antagonists)
Prochlorperazine (Compazine)	5–10 mg q 4–6 h PO/IM/IV; 25 mg rectal suppository bid; maximum dose is 40 mg/day	Sedation, anticholinergic effects, mouth, EPS, hypotension if given IV too quickly	C
Promethazine (Phenergan)	12.5–25 mg q 4–6 h PO/IM/IV/PR	Sedation, anticholinergic effects, mouth, EPS, hypotension if given IV too quickly	C
Benzamides (central and peripheral D₂ antagonists)
Metoclopramide (Reglan)	5–10 mg PO q 8 h PO/IM; 1–2 mg/kg IV; continuous SQ dose regimens available^b	EPS, agitation, anxiety, acute dystonic reactions (give 50 mg diphenhydramine before dose to prevent EPS)	B
Serotonin antagonists
Ondansetron (Zofran)	4–8 mg PO 3–4 times per day 4–8 mg over 15 min IV q 12 h; may be given 1 mg/h continuously for 24 h	Headache	B
Butyrophenones
Droperidol^c (Inapsine)	0.625–2.5 mg IV over 15 min then 1.25 mg or 2.5 mg IM as needed; can be given IV continuously at 1–1.25 mg/h	EPS, prolonged QT syndrome (give 50 mg diphenhydramine before dose to prevent EPS; reserve for persons who have failed other regimens)	C

bid = Two times daily; EPS = extrapyramidal effects; FDA = US Food and Drug Administration; IM = intramuscular; IV = intravenous; PO = per os (orally); PR = per rectum (rectally); SE = side effect; SQ = subcutaneous.
^aMaximum dose is 200 mg/day if taken concomitantly with doxylamine, 400 mg/day if taken as a single agent.
^bContinuous dose regimens can be found in Buttino Jr et al.^[89]
^cTo be used only after medical consultation and if other medications have failed to resolve symptoms, secondary to risk for prolonged QT syndrome.

Table 2. US Food and Drug Administration Ratings for Drug Use in Pregnancy ^a
Category	Interpretation
A	Adequate, well controlled studies in pregnant women have not shown an increased risk of fetal abnormalities to the fetus in any trimester of pregnancy.
B	Animal studies have revealed no evidence of harm to the fetus, however, there are no adequate and well controlled studies in pregnant women. OR Animal studies have shown an adverse effect, but adequate and well controlled studies in pregnant women have failed to demonstrate a risk to the fetus in any trimester.
C	Animal studies have shown an adverse effect and there are no adequate and well controlled studies in pregnant women. ORNo animal studies have been conducted and there are no adequate and well controlled studies in pregnant women.
D	Adequate well controlled or observational studies in pregnant women have demonstrated a risk to the fetus. However, the benefits of therapy may outweigh the potential risk. For example, the drug may be acceptable if needed in a life-threatening situation or serious disease for which safer drugs cannot be used or are ineffective.
X	Adequate well controlled or observational studies in animals or pregnant women have demonstrated positive evidence of fetal abnormalities or risks. The use of the product is contraindicated in women who are or may become pregnant.

Source: US Food and Drug Administration (21 CFR §201.57).^[72]
^aNote that the US Food and Drug Administration has proposed changes to prescription drug labeling for use in pregnancy and lactation. (See www.fda.gov/Drugs/DevelopmentApprovalProcess/DevelopmentResources/Labeling/ucm093311.htm for additional information.)

Comments

Commenting is limited to medical professionals. To comment please Log-in.

Comments on Medscape are moderated and should be professional in tone and on topic. You must declare any conflicts of interest related to your comments and responses. Please see our Commenting Guide for further information. We reserve the right to remove posts at our sole discretion.