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Three Part Question

In [pregnant women who are vomiting] is [metoclopramide better than promethazine] at [reducing nausea and vomiting]?

Clinical Scenario

A frazzled colleague comes to you one shift. His pregnant wife has been up all night for about a week vomiting. She is constantly nauseated and, although managing to drink and eat, is getting a bit fed up. They've tried promethazine OTC (all the chemist would sell them). You say that metoclopramide has always worked well in your experience and is recommended by the BNF. However, at home later, you wonder if there is any evidence for this.

Search Strategy

Medline 1950 to present. Accessed using the Ovid SP interface at BMA.org 27/10/2008.

{Hyperemesis Gravidarum/th, pc, dt OR (pregnancy and vomiting).mp} AND { Metoclopramide/ad, tu AND Promethazine/ad, tu}
The Cochrane database of systematic reviews. Accessed via Wiley InterScience through Athens 27/10/2008

Search Outcome

The MEDLINE search returned 4 results of which one partially answered the three-part question. This is discussed below.
The relevant Cochrane review was also identified, no studies compared were relevant to the BET. The authors of the Cochrane review comment that they identified a trial registered and relevant but that they were unable to contact the author.

Relevant Paper(s)

Author, date and country	Patient group	Study type (level of evidence)	Outcomes	Key results	Study Weaknesses
Bsat, FA, Hoffman, DE, Seubert DE 2003 USA	174 singleton, first trimester pregnancies	Prospective RCT with three treatment arms, comparing metoclopramide (plus pyridoxine), promethazine and prochlorperazine.	Visual analog score (VAS) of wound measured by two blinded physicians and the patient at 9 and 12 months	No significant difference between the VAS scores in each group. Maximum difference 3.6mm, below minimum clinical important difference of 10-15mm.	The claimed benefit (demonstrated in the paper's discussion) of a non-statistically significant advantage (less episodes of emesis, subjective feeling of being "better") could be due to the metoclopramide, or pyridoxine, or both.
			No statistically signivicant difference found between any of the treatment arms
			Decrease in pain intensity on 100 mm VAS after study drug administration.	Morphine group: 24 (SD 23) mm Placebo group: 20 (SD 18 mm. Mean difference: 4 mm (95% CI 25 to 12 mm)
			Difference between time of arrival in ED and time of surgical decision for disposition of patient	Morphine group: 269 min Placebo group: 307 min Mean difference: 234 min (95% CI 2105 to 40 min)

Comment(s)

Vomiting and nausea in pregnancy is a common reason to presentation to the ED. Many women settle without the need for pharmacotherapeutic intervention. However, for those who have persistent or troublesome symptoms, some form of treatment is warranted. Unfortunately, there is little evidence for any superiority of the two drugs mentioned in the three part question. As mentioned, the beneficial effects (non-specific, p=0.014) of B6-metoclopramide combination could be due to either compound, both individually or synergistically. There are no RCTs comparing one compound against another. The Cochrane review by Jewell and Young mentions a registered RCT that would answer the three part question. Unfortunately they were unable to retrieve this paper. This review also compares multiple therapeutic interventions and conclude that many agents are better than placebo for reducing nausea and vomiting. They conclude that pyridoxine alone, is a suitable first line agent in the dose of 10 - 25 mg TDS. They also conclude that ginger root may be beneficial.

Clinical Bottom Line

Nausea and vomiting in pregnancy is common. No evidence of statistically-significant benefit is seen for any particular agent over another. Treatment with vitamin B6 supplement may be cheaper and better tolerated than more traditional antiemetic agents. Recognition of the sick parturient who is in need of admission and intravenous fluids is paramount.

References

1. Bsat, FA, Hoffman, DE, Seubert DE Comparison of Three Outpatient Regimens in the Management of Nausea and Vomiting in Pregnancy
2. Jewell D, Young G. Interventions for nausea and vomiting in early pregnancy Cochrane collabaration Cochrane Database of Systematic Reviews 2003, Issue 4. Art. No.: CD000145. DOI: 10.1002/14651858.CD0