Drug Critieria & Outcomes

Covering PONV from "A to Z"

By Andrew East, PharmD Candidate, Auburn University

Postoperative nausea and vomiting (PONV) is an ever-present matter in the hospital setting that can occur in up to 30% of surgical patients and in up to 70-80% of high-risk individuals. The burden upon the health care system can be measured in cost, length of stay, nursing time, and overall patient well-being. With this in mind, prevention of PONV is important to the health and welfare of patients.

Nausea and vomiting pathway

The nausea and vomiting pathway involves a complex series of neurotransmitters and receptors leading to physiologic changes. Nausea and vomiting are stimulated by areas in both the brain (chemoreceptor trigger zone [CTZ], the vestibular system, and cerebral cortex) and GI tract (the visceral afferent nerves), and different receptor systems are involved with these specific areas. The CTZ is stimulated by serotonin (5-HT3), dopamine (D2), and neurokinin receptors (NK1); the cerebral cortex is stimulated by sensory input; the vestibular system by histamine (H1) and muscarinic receptors; and the visceral nerves by serotonin (5-HT3), dopamine (D2), and neurokinin (NK1). These different receptors are the sites of action for the drugs used to treat and prevent PONV.

Risk factors

To effectively treat PONV, patients must be assessed for risk factors associated with the patient or the surgery itself that can contribute to nausea and vomiting. Certain surgical factors including the type of anesthetic used and type of surgery (abdominal, gynecological, orthopedic, ear, nose, and throat procedures) place patients at a higher risk of PONV. General anesthesia, volatile agents, and inhalation agents also increase a patient's risk. Patient factors include female gender, history of motion sickness or PONV, and use of opioids in the postoperative period. Smoking is considered a protective factor in PONV. Patients with one or fewer risk factors have a 10-20% incidence of PONV, and 80% of patients with two or more risk factors have an incidence of PONV.

Reduction of risk factors is the first step to help prevent PONV.1 Using regional anesthesia instead of general anesthesia, and using intravenous agents such as propofol instead of nitrous oxide and volatile inhaled anesthetics reduce risk factors. The use of NSAIDs instead of opioids, minimizing the use of neostigmine, appropriate hydration, and providing 80% oxygen postoperatively can also lower the chance of PONV.

Prevention and treatment

Non-pharmacological methods can also be used to combat PONV. Acupressure (the use of a wristband to apply pressure to the P6 point on the inner wrist), acupuncture, electroacupuncture, or nerve stimulation can help reduce nausea and vomiting, and acupoint stimulation combined with ondansetron has been shown to act more effectively than ondansetron alone. The use of ginger and aromatherapy showed no benefit in the prevention of PONV.

There are currently eight classes of drugs that are used to prevent PONV:

  • phenothiazines
  • anticholinergics
  • antihistamines
  • butyrophenones
  • substituted benzamide
  • corticosteroids
  • serotonin antagonists
  • neurokinin 1 antagonist

These treatments offer at best a success rate between 40% and 50%, which is only seen in high-risk individuals.

Adverse effects

The older phenothiazines, anticholinergics, and antihistamines are highly associated with sedation, dry mouth, lethargy, and other adverse effects. Extra-pyramidal symptoms, sedation, and tachycardia are known adverse effects of the butyrophenone and substituted benzamide classes. The corticosteroids can cause hyperglycemia, gastrointestinal distress, insomnia, and facial flushing. The newer drug classes of serotonin antagonists (i.e., dolasetron and ondansetron) and the neurokinin 1 antagonist (aprepitant) are usually only linked to the adverse effects of headache, fatigue, and hiccups, and with their increased effectiveness this has made them the new workhorses for the prevention and treatment of PONV.

Clinical trial

A recent trial compared 125 mg aprepitant PO, 40 mg aprepitant PO, and ondansetron 4 mg IV to determine the proportion of patients with complete response 24 hours after surgery.2 The aprepitant 40 mg PO and ondansetron 4mg IV are FDA-approved doses to prevent PONV; the aprepitant 125 mg PO is an unapproved dose for this indication. Complete response was defined as no vomiting and no use of rescue therapy. The study showed no statistically significant difference between the three groups with respect to complete response. No significant difference was seen in the incidences of serious clinical adverse events. Both aprepitant groups delayed the time to first vomiting and had larger proportions of patients that experienced no vomiting.

Cost

Cost-effectiveness is another key issue when talking about the prevention of PONV; this includes both direct and indirect costs. Direct costs include drug acquisition, nursing time, and delayed release from post-anesthesia care unit. Indirect costs can be measured in delayed discharge, hospital readmission, and loss of patient income. It has been shown that high-risk patients that do not receive prophylaxis may incur overall costs 100 times greater than if an antiemetic is used. The easiest and most cost-effective method to reduce PONV is to take steps to eliminate surgical and patient risk factors. The AWP listed price for aprepitant 40 mg is $35.88 and for ondansetron 4 mg vial is $0.76.

Summary

Evidence-based literature supports the use of ondansetron for the prevention of PONV. Ondansetron was recently approved as a generic product, which has significantly reduced its acquisition cost. Although the other therapies are effective at preventing PONV, with its safety and efficacy equal to the more expensive aprepitant and greater than that of the older drug classes, ondansetron should be used preferentially in the prevention of PONV.

References

  1. Wilhelm SM, Dehoorne-Smith ML, Kale-Prabham PB. Prevention of postoperative nausea and vomiting. Ann Pharmacother 2007; 41:68-78. Epub 2007 Jan 2.
  2. Gan TJ, Apfel CC, Kovac A, et al. A randomized, double-blind comparison of the NK1 antagonist, aprepitant, versus ondansetron for the prevention of postoperative nausea and vomiting. Anesth Analg 2007; 104:1082-1089.