A pilot study of intravenous ondansetron for hyperemesis gravidarum

Christopher A. Sullivan, BScBiol, MD
Director, Maternal-Foetal Medicine, Department of Obstetrics and Gynaecology, The Stamford Hospital, Connecticut, Assistant Professor, Department of Obstetrics and Gynaecology, New York Medical College, New York, U.S.A.

Ondansetron has been shown to be an effective antiemetic in chemotherapy and anaesthesia literature. It blocks central and peripheral serotonin type 3 receptors, which are thought to be important in the reflex that induces vomiting. Because of this distinct mechanism of action, patients with hyperemesis in pregnancy were thought to be ideal candidates for therapy. Teratogenesis data indicated no birth defects in rabbits and rodents. Furthermore, there were two case reports of patients experiencing immediate cessation of intractable emesis after administration of ondansetron.

We attempted to determine whether the antiemetic ondansetron would be more effective than promethazine in treating hyperemesis gravidarum.1 Patients with hyperemesis gravidarum who required hospital admission were randomized to receive either intravenous ondansetron (n = 15) or intravenous promethazine (n = 15) in a double-blind manner. Patients were demo- graphically matched between the two groups. The patient population was predominantly African American and was socioeconomically disadvantaged.

Severity of disease was determined by electrolyte status, weight loss, ketonuria and prior use of outpatient antiemetics, i.e.:

Exclusion criteria were:

Outcome variables included the degree of nausea, weight gain during treatment, days of hospitalization and number of medication doses.

Patients were randomized to either ondansetron 10 mg or promethazine (Phenergan) 50 mg, both given intravenously. Nurses and investigators were blinded to the therapy. The first dose was mandatory, subsequent doses were given when requested by the patient. Patients were on intravenous hydration, with nothing by mouth, during the first 24 hours. Hydration was continued until they were eating a bland diet.

Weight, ketonuria and side effects were monitored daily. The degree of nausea was measured using a visual analog scale every eight hours. Patients were asked to gauge the nausea from the previous eight hours, and the three scores were averaged for a daily score. Patients were identified as treatment failures if there was no change in their nausea or emesis after 48 hours. These patients were then excluded from further data collection. All patients were prescribed promethazine suppositories at discharge to home.

In this preliminary investigation ondansetron offered no advantage when compared with promethazine in the relief of nausea, weight gain, days of hospitalization (4.5 ± 2.3 vs 4.5 ± 1.5) and total doses of medication per hospitalization (2.1 ± 1.2 vs 1.9 ± 1.3). Eight patients complained of sedation in the promethazine group, none in the ondansetron group. The results of the patients' visual analog scores showed no difference between the two drugs. In both the ondansetron and promethazine patients, a dramatic reduction in nausea occurred from day 1 to day 2. Daily weight gain progressed equally in the two groups. Infant birth weights were similar for the two groups of study patients, and no teratogenicity was noted.

This preliminary trial of ondansetron demonstrated no benefit over promethazine in patients hospitalized for hyperemesis gravidarum. Ondansetron is significantly more expensive per dose than promethazine.

The limitations of this study include the consideration that an improved dosing regimen may have provided a different response, e.g., stratified dosing. Furthermore, a post hoc analysis showed that a cohort of 528 patients would have been needed for a power of 0.8. The initial power analysis indicated

34 patients were required in order to show a 50% difference between the two treatments.

Reference:

  1. Sullivan CA, Johnson CA, Roach H, Martin RW, Stewart DK, Morrison JC. A pilot study of intravenous ondansetron for hyperemesis gravidarum. Am J Obstet Gynecol 1996;174:1565-8.

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