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Eur J Obstet Gynecol Reprod Biol. 2009 Mar;143(1):43-9. doi: 10.1016/j.ejogrb.2008.11.007. Epub 2009 Jan 8.

Metoclopramide and diphenhydramine in the treatment of hyperemesis gravidarum: effectiveness and predictors of rehospitalisation.

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  • 1Faculty of Pharmacy, University of Montreal, Montreal, Quebec, Canada.



Hyperemesis gravidarum (HG) is the second most common reason for hospitalisation during pregnancy. Since 2002, a new HG treatment protocol consisting of metoclopramide plus diphenhydramine was put in place at CHU Sainte-Justine, affiliated to University of Montreal, Quebec, Canada. The objectives of this study were to evaluate the effectiveness of this new HG protocol regarding length of hospitalisation for HG, rate of rehospitalisation, evolution of nausea and vomiting symptoms, and rate of adverse events.


A retrospective cohort study was conducted from 2002 to 2006 on the population of pregnant women diagnosed with HG, and treated at CHU Sainte-Justine with the new protocol consisting of intravenous metoclopramide 1.2-1.8 mg/h plus diphenhydramine 50 mg every 6 h. These women were compared to a historical control group consisting of women diagnosed with HG, and treated in the same institution with intravenous droperidol 0.5-1 mg/h plus diphenhydramine 25-50 mg every 6h between 1998 and 2001.


During the study period, a total of 130 pregnant women were exposed to the new HG protocol versus 99 that were exposed to the droperidol and diphenhydramine combination between 1998 and 2001. Our study showed that the new HG protocol was associated with a greater improvement of vomiting symptoms (36% vs. 21%; p=0.0397), and with fewer adverse events. The new HG protocol was equivalent to the droperidol and diphenhydramine combination to reduce nausea symptoms, length of hospitalisation (3.7 days vs. 3.1 days), and rate of rehospitalisation for HG (19.23% vs. 24.44%).


The new protocol consisting of the combination of metoclopramide and diphenhydramine appears to be a good option in the management of hyperemesis gravidarum.

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