Reader Question: What is the most appropriate way to prescribe ondansetron for ordinary or post op nausea? 

 Response:

Postoperative nausea and vomiting (PONV) occurs in 30% of surgical patients and is a major concern for patients as they contemplate surgery^[1]. Risk factors for development of PONV include female gender, history of motion sickness or PONV, type and duration of surgery and use of postoperative opioids. Development of PONV can increase discomfort, dissatisfaction, length of stay and overall health care costs for patients.^[1]

Ondansetron is indicated in the United States for the prevention of postoperative nausea and vomiting (PONV) in adults and children.^[2] Suggested oral dosing for adults is a single 16 mg dose one hour before anesthesia with no recommendations for the pediatric population. Injectable ondansetron may be given as a 4 mg dose infused over 2 -5 minutes for patients older than one month and a 1 mg/kg dose for newborns to infants one month old.^[3]

Ondansetron is a selective 5-HT3-receptor antagonist that blocks serotonin peripherally on vagal nerve terminals and centrally in the chemoreceptor trigger zone. The onset of action is about 30 minutes with metabolism occurring in the liver. Bioavailability is around 56% to 71% via the oral route. Ondansetron’s half-life is 3 to 6 hours at the maximum dose in chemotherapy patients of 32 mg daily.^[2]

One study looked at PONV after cardiac surgery where 4 mg of ondansetron IV was given at the end of surgery and 12 mg was added to the patients’ PCA pump which had a pre-set volume for all patients.^[4] Ondansetron significantly reduced PONV when compared to placebo in these patients.^[4] Another study looked at ondansetron 4 mg IV given to shoulder surgery patients 30 minutes before the end of their surgery.^[5] This study also showed a significant reduction in PONV when compared to placebo.^[5]

According to consensus guidelines for managing PONV, IV ondansetron is most effective when given at the end of surgery and shows more of an anti-vomiting effect than anti-nausea.^[1,6]  The number needed to treat (NNT) for IV ondansetron 4 mg is approximately 7 for the prevention of nausea, indicating 7 patients would need to be treated with ondansetron 4mg IV to prevent one patient’s nausea^[6]. The NNT to prevent one case of postoperative vomiting is 6.^[1] The 8 mg dose has a NNT of 6 for the prevention of nausea and a NNT of 5 for the prevention of vomiting.^[1] The guidelines suggest that if PONV occurs within 6 hours after surgery, patients should not receive a repeat dose of ondansetron if it was used prophylatically.^[1] For episodes occurring more than 6 hours after surgery, patients can be treated with a repeat dose of IV ondansetron 4-8 mg.^[1]

Ondansetron has a favorable side effect profile^[1,6] The number needed to harm (NNH) with a single dose of ondansetron is 36 for headache indicating one case of headache for each 36 patients treated with ondansetron. The NNH is 31 for increased liver enzymes and 23 for constipation.^[1] According to the International Anesthesia Research Society guidelines on PONV, if prophylaxis of ondansetron fails <6 hours after surgery, a different class of antiemetic should be given, however a dose of ondansetron can be repeated if it has been >6 hours after the end of surgery.^[1] If the repeat dose fails to adequately control nausea and vomiting, another antiemetic may be chosen to alleviate further nausea and vomiting.^[1]

Literature pertaining to treatment of general nausea and vomiting with ondansetron is limited. Ondansetron is not specifically indicated for general nausea and vomiting. Several studies have shown some utility of ondansetron when used in a pediatric population to treat vomiting in acute gastroenteritis. The mechanism of action of ondansetron suggests it would have a possible role in treating general nausea and vomiting as it acts on the chemoreceptor trigger zone that controls vomiting.^[1]. One of the primary sites of action of the chemoreceptor trigger zone is mediated by the 5-HT receptor. Ondansetron may play a role in inhibiting the chemoreceptor trigger zone, which may help to control general N/V in patients.^[4]

References:

1.       Tong, J. Gan, Tricia Meyer, Christian Apfel, et al. "Society for Ambulatory Anesthesia Guidelines for the Management of Postoperative Nausea and Vomiting." International Anesthesia Research Society. 105.6 (2007): 1615-28. Web. 15 Nov. 2011.

2.       Zofran Tablets Prescribing Information. GlaxoSmithKline, Research Triangle Park, NC 27709. September, 2011.

3.       Zofran Injection for Intravenous Use Prescribing Information. GlaxoSmithKline, Research Triangle Park, NC 27709. September, 2011.

4.       Choi, DK, JH Chin, EH Lee, et al. "Prophylactic control of post-operative nausea and vomiting using ondansetron and ramosetron after cardiac surgery."International Journal of Anaesthesiology and Intensive Care, Pain and Emergency Medicine. 54. (2010): 962-969. Print.

5.       Chen, YF, WN Yeh, KH Lee, et al. "Intravenous Ondansetron as Antiemetic Prophylaxis for Postoperative Nausea and Vomiting after Shoulder Arthroscopy." Journal of Chang Gung Medicine. 34. (2011): 205-12. Print.

6.       Wilhelm, Sheila M., Michelle L. Dehoorne-Smith, and Pramodini B. Kale-Pradhan. "Prevention of Postoperative Nausea and Vomiting." Annals of Pharmacotherapy. 41.1 (2007): 68-78. < http://www.theannals.com.lecomlrc.lecom.edu/content/41/1/68.full.pdf+html?sid=21c3ff81-a493-4848-a966-032fcf197b4b >. Accessed March 18, 2011.

7.       Hornby, PJ. "Central neurocircuitry associated with emesis." American Journal of Medicine. 111.Supplement 8A (2001): 106S-112S. Print.

8.       Cheng, A. Emergency Department Use of Oral Ondansetron for acute gastroenteritis-related vomiting in infants and children. Paediatr Child Health. 2011 March; 16(3): 177–179.