Postoperative Nausea and Vomiting in Adults

Introduction

• PONV affects around one-third of patients who receive inhalational anesthetics without prophylaxis, though estimates range from as low as 10% to as high as 80%.¹
• PONV can lead to prolonged stays in the postanesthesia care unit (PACU), unanticipated hospital admissions, increased risk of aspiration, and discomfort for the patient.²
• It is estimated that an episode of vomiting prolongs PACU stay by about 25 minutes.³

Risk Factors

• Risk factors for PONV in adults can be categorized as surgical, anesthetic, or patient-related factors^1,2 (Figure 1).
• Patient-related
  • Nonsmoker
  • Female gender
  • History of motion sickness and/or PONV
  • Postoperative opioid use
  • Young age (< 50 years old)
• Anesthesia-related
  • Volatile anesthetics
  • Nitrous oxide
  • Higher doses of perioperative opioids
• Surgery-related
  • Long duration of surgery
  • Type of surgery (abdominal, gynecological, cholecystectomy)

Risk Stratification

• The simplified Apfel score can be used to predict the patient’s risk for PONV. 0,1, 2, 3, and 4 risk factors correspond to PONV risks of approximately 10%, 20%, 40%, 60%, and 80% respectively.²

Prophylaxis

• To reduce the baseline risk of PONV, several strategies may be considered:²
  • Regional anesthesia should be performed or analgesic blocks used as a part of a multimodal pain management plan.
  • If general anesthesia is necessary, using a propofol-based total intravenous anesthetic (TIVA) should be considered and volatile anesthetics should be avoided.
  • Nitrous oxide exposure (less than 1 hour) and opioids should be minimized.
  • Sugammadex reversal should be considered instead of neostigmine.
  • Adequate hydration of patients undergoing same-day surgery should be ensured.
• For patients with one or two risk factors, at least two antiemetic medications are recommended; three to four antiemetic medications may be beneficial if more than two risk factors are present.
• Aprepitant (Neurokinin 1 (NK1) receptor antagonist) has been reported to have high effectiveness, with decreased need for rescue antiemetics and longer duration of PONV relief.⁴ It is more effective at the prevention of postoperative vomiting than nausea.²

Medications to Treat PONV

• Five neurotransmitter receptor sites are important in the vomiting reflex: M1 (muscarinic), D2 (dopamine), H1 (histamine), 5-hydroxytryptamine-3 (5HT₃) (serotonin), and NK1 (substance P).⁵
• The area postrema is an important site for M1, D2, 5HT₃, and NK1 receptors; the vestibular nucleus is associated with H1 receptors; and vagal afferent neurons are associated with 5HT₃ receptors.⁵
• Medications used to prevent and treat PONV interact with many different receptor targets, and often a single agent will interact with more than one receptor:
  • NK1 receptor antagonists (e.g., aprepitant)
    • Targets the nucleus tractus solitaries and area postrema
    • Side effects: aprepitant is a moderate inhibitor of CYP3A4; rolapitant inhibits CYP2D6.⁵
  • 5HT₃ receptor antagonists (e.g., ondansetron, granisetron)
    • Targets the area postrema
    • Side effects: mild headache (most frequent), lightheadedness, dizziness, constipation, QTc prolongation⁵
  • Antihistamines (e.g., hydroxyzine, diphenhydramine, promethazine)
    • Side effects: sedation
  • Corticosteroids (e.g., dexamethasone)
    • Exact mechanism unknown; thought to inhibit prostaglandins peripherally and antagonize serotonin centrally³
    • Side effects: insomnia, increased energy, mood changes⁵
  • Propofol
    • Antiemetic mechanism unknown; thought to be due to direct depressant effect on the chemoreceptor trigger zone and vagal nuclei⁶
  • Dopamine antagonists (e.g., metoclopramide, prochlorperazine)
    • Targets the area postrema
    • Side effects: extrapyramidal effects and dystonia (more seen with the pediatric population)³
  • Anticholinergics (e.g., scopolamine, promethazine)
    • Antagonizes muscarinic receptors of the vestibular apparatus and the nucleus of the tractus solitarus³
    • Side effects: sedation, dry mouth, visual disturbance⁵
  • Phenothiazines (e.g., promethazine, prochlorperazine)
    • Antagonize D2-dopamine receptors in the area postrema of the midbrain; also have M1-muscarinic and H1-histamine blocking effects⁵
    • Side effects: sedation, extrapyramidal effects, hypotension⁵
  • Butyrophenones (e.g., droperidol, haloperidol)
    • Antagonize central dopaminergic receptors³
    • Side effects: sedation, agitation, extrapyramidal effects, hypotension
    • Black box warning: risk of prolonged QTc and torsades de pointes
  • Benzamides (e.g., metoclopramide, domperidone)
    • Antagonize central and peripheral dopaminergic receptors; weak 5HT₃ blockade at higher doses
    • Side effects: anxiety, restlessness, depression, hyperprolactinemia, QT interval prolongation⁵
      • Domperidone is a D2 blocker with selective peripheral activity in the upper GI tract; it does not cross the blood-brain barrier and lacks central nervous system side effects associated with metoclopramide.⁵
    • Black box warning: risk of irreversible tardive dyskinesia with high dosing and long-term use⁵
  • Prokinetics (e.g., metoclopramide)
    • Increases gastrointestinal tract motility, decreases gastric emptying time and gastric volume, increases lower esophageal sphincter tone³
  • Vasopressors (e.g., ephedrine)
    • May prevent nausea associated with hypotension³

Rescue Treatment

• If a patient experiences PONV, the same medications used for prophylaxis may be used as rescue treatment.
• Rescue antiemetics should be of a different mechanism of action than the agents given as prophylaxis.
• Reversible causes for nausea and vomiting should be considered:²
  • Excessive opioids
  • Blood in pharynx
  • Bowel obstruction