May 18, 2009 — A protocol including metoclopramide plus diphenhydramine may be helpful for hyperemesis gravidarum (HG), the most severe form of nausea and vomiting during pregnancy, according to the results of a retrospective cohort study reported in the May issue of the European Journal of Obstetrics & Gynecology and Reproductive Biology.
"[HG] is the second most common reason for hospitalisation during pregnancy," write Anaïs Lacasse, BSc, from the University of Montreal in Quebec, Canada, and colleagues. "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."
From 2002 to 2006, 130 pregnant women diagnosed with HG were treated at CHU Sainte-Justine with the new protocol, consisting of intravenous (IV) metoclopramide 1.2 to 1.8 mg/hour plus diphenhydramine 50 mg every 6 hours. Outcomes in these women were compared with those in a historical control group of 99 women with HG who were treated in the same institution between 1998 and 2001 with IV droperidol 0.5 to 1 mg/hour plus diphenhydramine 25 to 50 mg every 6 hours.
Compared with the old protocol including droperidol, the new protocol was associated with greater improvement in vomiting symptoms (36% vs 21%; P = .0397), with fewer adverse events. Both protocols were associated with similar rates of reduction in nausea symptoms, length of hospitalization (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," the study authors write. "The combination metoclopramide and diphenhydramine was associated with a higher improvement of vomiting symptoms, and fewer adverse events."
Limitations of this study include that the baseline HG status at first hospitalization was different between the 2 study groups (but the severity of vomiting symptoms on day 1 of the first hospitalization was not different between groups). Other limitations include a lack of data for hematocrit, liver function, blood urea, or creatinine; and a small sample size, limiting conclusions on the safety of metoclopramide plus diphenhydramine during pregnancy.
"The new HG protocol was not better than the droperidol and diphenhydramine combination when looking at improvement of nausea symptoms, length of hospitalisation, and rehospitalisations for HG," the study authors conclude." However, its use is justified given safety concerns regarding the use of droperidol."
The study authors have disclosed no relevant financial relationships.
Eur J Obstet Gynecol Reprod Biol. 2009:143:43-49.
Clinical Context
HG, the most severe form of nausea and vomiting of pregnancy, is intractable vomiting associated with weight loss of at least 5% of prepregnancy weight, dehydration, ketonuria, and hypokalemia. Second only to preterm labor, HG is a leading cause of hospitalization during pregnancy.
There is no gold standard for HG treatment, but droperidol and diphenhydramine have been used since 1998. Warnings about the cardiovascular toxicity of injectable droperidol, including QT prolongations, serious arrhythmia, and sudden death, were issued by the US Food and Drug Administration in December 2001 and subsequently by Health Canada. A new HG protocol replacing droperidol with metoclopramide has been used since June 2002 but has not previously been evaluated.
Study Highlights
- The goals of this retrospective cohort study were to compare a new HG protocol with an old HG protocol in terms of nausea and vomiting symptoms, length of hospitalization for HG, rate of rehospitalization, and rate of adverse events.
- The new protocol consisted of IV metoclopramide 1.2 to 1.8 mg/hour plus diphenhydramine 50 mg every 6 hours.
- The old protocol consisted of IV droperidol 0.5 to 1 mg/hour plus diphenhydramine 25 to 50 mg every 6 hours.
- From 2002 to 2006, 130 pregnant women diagnosed with HG were treated at CHU Sainte-Justine with the new protocol; their outcomes were compared with those in 99 women with HG treated in the same institution between 1998 and 2001 using the old protocol.
- Compared with the old protocol, the new protocol was associated with greater improvement in vomiting symptoms (36% vs 21%; P = .0397).
- The new protocol group had slightly lower improvement in nausea symptoms (50% vs 58%; P = .0398), but this was not thought to be clinically relevant.
- The new HG protocol was associated with significantly fewer adverse events than the old protocol, with dystonia in 0.88% vs 9.2% of the patients (P = .0065), tachycardia in 3.5% vs 14.3% of the patients (P = .0053), and anxiety/nervousness in 3.5% vs 14.3% of the patients (P = .0053).
- Length of hospitalization was similar for both protocols (3.7 days vs 3.1 days).
- Rate of rehospitalization for HG was similar for both protocols (19.23% vs 24.44%).
- The only predictor of rehospitalization for HG in women treated with the new protocol was race (black women were more likely to be rehospitalized for HG than white women).
- The investigators concluded that the new protocol is a good therapeutic option for HG, with greater improvement in vomiting symptoms and fewer adverse events than the old protocol.
- Limitations of this study include different baseline HG status at first hospitalization in the 2 groups, lack of laboratory data, and small sample size limiting conclusions on the safety of metoclopramide plus diphenhydramine during pregnancy.
Clinical Implications
- For treatment of HG, a new protocol consisting of IV metoclopramide 1.2 to 1.8 mg/hour plus diphenhydramine 50 mg every 6 hours appears to be a good therapeutic option for HG, with greater improvement in vomiting symptoms than achieved with the old protocol consisting of IV droperidol 0.5 to 1 mg/hour plus diphenhydramine 25 to 50 mg every 6 hours.
- The new HG protocol was associated with significantly fewer adverse events than the old protocol, with lower rates of dystonia, tachycardia, and anxiety/nervousness. Length of hospitalization and rate of rehospitalization for HG were similar for both protocols.
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