Post Operative Nausea & Vomiting: The Role of Antiemetics

1. Post Operative Nausea & Vomiting: The Role of Antiemetics Cedric Dupont-Eisner M.D.

2. Post Operative Nausea & Vomiting (PONV) • 25 - 30% have nausea &/or vomiting during the postoperative period. • Occurs in as many as 70% of high-risk patients1,2 • Nausea and vomiting = post op pain3 1Apfel CC et al. Anesthesiology. 1999;91:693–700. 2Gan TJ et al. Anesthesiology. 1996;85:1036–1042. 3Macario A et al. Anesth Analg. 1999;89:652–658.

3. 5 Most Undesirable Surgical Outcomes Perspective of Pts vs Anesthesiologists 1Macario A et al. Anesth Analg. 1999;89:652–658. 2Macario A et al. Anesth Analg. 1999;88:1085–1091.

4. MECHANISM OF PONV • Peripheral • GI stimulation of CN X • Central • Pathways that affect the CTZ include: • Cerebellum • Afferents from Vestibular System • CN X • CN VIII

5. Chemoreceptor Trigger Zone and Emetic Center Antagonist 5-HT3 RAs Droperidol Promethazine Atropine NK-1 RA Agonist Dopamine (D2) 5-HT3 Muscarinic Histamine Substance P Receptor Site • Nitrogen mustard • Cisplatin • Digoxin glycoside • Opioid, analgesics • Vestibular portion • of 8th nerve • N2O • GI tract distension • Higher centers (vision, taste) • Pharynx Chemoreceptor Trigger Zone (CTZ) Area Postrema Mediastinum Parvicellular Reticular Formation Emetic Center ? Vagus Watcha MF, White PF. Anesthesiology. 1992;77:162–184.

8. Just The Facts • Numerous publications state universal PONV prophylaxis is not cost effective • Pts at  risk for PONV should not receive prophylaxis 2º to antiemetic side effects and increased cost

9.  or < 16 yrs ♀   Prior Hx of PONV Volatile anesthetics Opioids Nitrous Concomitant Dz* Duration of surgery** Procedure type Identify PONV Pts

10. ♀ Previous PONV  Surgery time > 60 min  Factors Risks 0 17% 1 18% 2 42% 3 54% 4 74% 5 87% Risk Factors: Scores Koivuranta, Apfel et al.

11. Identify POV Pediatric Patients • Risks are similar to adults, except: • Twice as frequent as in adults •  w/ age,  after puberty • = • Risk  more consistently w/ certain procedures*

12. Avoid: opioids & hypnotics* Nitrous high-dose reversal agent (neostigmine) dehydration Attempt  [O2]  air entry into stomach Propofol is a protective antiemetic  Baseline PONV Risks

13. Prior to Surgery Dexamethasone Scopolamine Post Operative Ondansetron Dolasetron Granisteron Droperidol Prochlorperazine Promethazine PONV Prophylaxis

14. POV Prophylaxis • Dexamethasone • Ondanestron • Dolasteron • Droperidol • Dimenhydrinate • Perphenazine

15. PONV: Consensus Conference Guidelines for Managing PONV Gan TJ, Meyer T, Apfel CC, Chung F, Davis PJ, Eubanks S, Kovac A, Philip BK, Sessler DI, Temo J, Tramer MR, Watcha M. Anesth Analg. 2003;97:62–71

16. Consensus Guidelines for Managing PONV • All 5-HT3 receptor antagonists are equally effective for both prophylaxis & PONV tx • Preinduction Metoclopramide 10 mg is ineffective for PONV prophylaxis

17. Phenothiazines Chlorpromazine, prochlorperazine, promethazine Butyrophenones Droperidol (haloperidol) Benzamides Metoclopramide Anticholinergics Scopolamine Antihistamines Dimenhydrinate, hydroxyzine 5-HT3 antagonists Dolasetron, granisetron, ondansetron Others Dexamethasone Dronabinol (9THC) Antiemetics—Members by Class • Upcoming class for PONV already approved for CINV • NK1-receptor antagonists

18. Phenothiazines • Chlorpromazine, Prochlorperazine, Promethazine • Antipsychotic agents • Blocks D2 receptors in CTZ and CNX • SIDE EFFECTS: EPS, sedation, dizziness, blurred vision, skin reactions, orthostatic hypotension chlorpromazine • Prochlorperazine-heterocyclic side chain

19. Butyrophenones • Droperidol • α blocker, D2 receptor antagonist (binds to D2 receptor) • Acts at both CTZ and area postrema • SIDE EFFECTS: EPS, sedation, QTc prolongation

20. FDA Advisory For Droperidol • Risk of fatal cardiac arrhythmia • The black box warns: • consider alternative medications in pts at high risk for cardiac arrhythmia • use only low doses when other initially recommended antiemetics fail • use as a 2nd agent when an initial treatment fails.

21. Benzamide • Metoclopramide • Specific dopamine D2 antagonist •  LES tone which enhances gastric motility • Short (1 to 2 hours) duration of action. • SIDE EFFECTS: EPS, restlessness, drowsiness, fatigue, agranulocytosis, methemoglobinemia

22. Anticholinergics • Scopolamine • Inhibit cholinergic and muscarinic CNS receptors. • Crosses the blood-brain barrier. • More effective against motion-induced emesis than against motion-induced nausea. • SIDE EFFECTS: sedation, CNS excitation, dry mouth, urinary retention, blurred vision, confusion, disorientation, hallucinations Night Shade

23. Antihistamines • Dimenhydrinate, Hydroxyzine, Cyclizine • Block acetylcholine in the vestibular apparatus and histamine H1 receptors in the nucleus of the solitary tract. • SIDE EFFECTS: blurred vision, urinary retention, dry mouth, and sedation

24. 5-HT3 Antagonists • (Ondansetron (Zofran®), Granisetron (Kytril®), Tropisetron (Navoban®), and Dolasetron (Anzemet®) • No sedation, extrapyramidal reactions, adverse effects on vital signs or laboratory tests, or drug interactions with other anesthetic medications. • SIDE EFFECTS: Headache, dizziness, constipation

25. PROPOFOL • mechanism unknown

26. Dexamethasone • Synthetic steroid not indicated for treatment of PONV in the United States. • Hypotheses • inhibition of prostaglandin syn. •  tryptophan • release of endorphins • change in csf opening pressure • + psychological effects of steroids ACUTE SIDE EFFECTS: flushing and perineal itching.

27. DRONABINOL Marinol® • 9THC • Unknown mechanism involves inhibition of CTZ • SIDE EFFECTS: dizziness, drowsiness, nausea (not emesis) • Schedule II drug

28. Moderate High Algorithm for PONV Prophylaxis Evaluate risk of PONVin surgical patient Low Consider regionalanesthesia No prophylaxis unless there is medical risk of sequelae from vomiting Not indicated If general anesthesia is used, reduce baseline risk factors when clinically practical & consider using nonpharmacologic therapies Patients at moderate risk Patients at high risk Consider antiemetic prophylaxiswith monotherapy (adults) or combination therapy (children and adults) Initiate combination therapy with 2 or 3 prophylactic agents from different classes Gan TJ et al. Anesth Analg. 2003;97:62–71.

29. 1st Line 5-HT3 antagonists Ondansetron 4-8mg I.V. Dolasetron 12,5mg I.V. Granisetron 0.35mg – 1mg I.V. Tropisetron* Dexamethasone 5-10mg I.V.before induction Droperidol 0.65 –1.25mg I.V. 2nd Line Dimenhydrinate Ephedrine Prochlorperazine Promethazine Scopolamine Nonpharmacologic techniques Acupuncture Hypnosis Antiemetic Therapy for PONV Prophylaxis in Adults  FDA *Currently not FDA-approved for PONV in the US Adapted from Gan TJ et al. Anesth Analg. 2003;97:62–71.

30. PONV Tx in Pts Who Did Not Receive Prophylaxis or Whom Prophylaxis Failed *Low-dose 5-HT3 RA dosing (dolasetron 12.5 mg; granisetron 0.1 mg; ondansetron 1 mg; tropisetron 5 mg) Adapted from Gan TJ et al. Anesth Analg. 2003;97:62–71.

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