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Meclozine/metoclopramide/ondansetron Lack of efficacy during pregnancy: case report

A 30-year-old pregnant woman exhibited lack of efficacy during treatment with metoclopramide, ondansetron and meclozine for hyperemesis gravidarum [not all dosages and routes stated]. The pregnant woman presented with 2 week history of nausea and 2 day history of frequent vomiting. She could not eat for last 4–5 days. She also had an unintended weight loss of 5kg within the last weeks. She reported slightly decreased consciousness and fatigue. She had no history of ketoacidosis, eating disorder, ketogenic diet or intake of alcohol. She had a significant history of hyperemesis gravidarum in two earlier pregnancies, which was not significant in current pregnancy. Subsequent blood test showed a capillary glucose level of 11.9 mmol/L, arterial pH of 7.30 and bicarbonate concentration 16.7 mmol/L. A urine test showed severe ketonuria (>15.6 mmol/L). A pregnancy test was positive, while an ultrasound showed a singleton pregnancy with intrauterine fetus at 9 gestational weeks. According to the protocol, she started receiving treatment for ketoacidosis including IV insulin 6 IE/hour with potassium chloride infusion 0.3% (500 mL/hour) and sodium chloride 0.9% infusion (250–500 mg/hour). The sodium-chloride infusion was switched to glucose 10% infusion following detection of plasma glucose level of 6.8 mmol/L. Based on the glucose level, the insulin dose was reduced to 0–3 IE/hour. After 3 hours of initiation of the ketoacidosis regimen, her pH normalised to 7.36. At that time bicarbonate was 17.2 mmol/L and ketonuria was negative after 5 hour. Further treatment was simplified to one drip of glucose–insulin–potassium drip, including glucose 10%, insulin-aspart 20IE and potassium 20 mmol. After 36 hours of hospitalisation, nausea and vomiting were persisting, which lead to insufficient oral food and fluid intake. The condition was considered as hyperemesis gravidarum. She was administered with glucose 10% infusion (60 mL/hour) and SC insulin treatment with insulin-aspart as required. Blood glucose level was monitored every 2 hour, which ranged between 6.3 mmol/L and 10.1 mmol/L. After 2 days of hospitalisation, she was initiated with basal bolus insulin treatment with insulin-aspart at meals and insulin-detemir before bedtime. Due to persistent vomiting and nausea, she continued to receive glucose 10% infusion (60 mL/hour). She received antiemetic treatment with metoclopramide, ondansetron and meclizine; however, she continued to exhibit hyperemesis prohibiting oral food and fluid intake. Therefore, she started receiving parenteral nutritional after 10days of initial episode of ketoacidosis, while basal bolus insulin treatment continued. During hospitalisation, urine ketones analysis was performed at intervals. At gestational week 18, as no clinical effect was obtained with approved antiemetics, she started receiving off-label oral prednisolone 50mg daily. Thereafter, she had improvement in her condition, leading to discontinuation of pa