Post Operative Nausea & Vomiting

1. Post Operative Nausea & Vomiting Nicole Weiss MD September 22, 2010

2. Objectives • Importance PONV • Risk Factors • Review of anti-emetics and strategies aimed at reducing PONV • Risk based treatment • Rescue Therapy • Tulane University Pharmacy

3. The Patient • 41 y/o female with a h/o of PONV scheduled for an outpatient laparoscopic cholecystectomy • Motion sickness • Non-smoker

4. PONV: Importance? • High Level of patient concern (second to pain) • -willingness to pay $56-$100 • Major cause of unanticipated hospital admissions • Rare complications: pulmonary aspiration, incisional disruption

5. Physiology • Vomiting Center • Located in the Medulla • Tickling the back of the Throat • Gastric Distension • Vestibular Stimulation (Etoh) • Cerebral Cortex • Chemoreceptor trigger zone • Outside of the BBB communicates with the vomiting center • Blood Borne Drugs or Hormones • Neurotransmitters involved: • Dopamine, 5-HT, Substance P, Ach

6. Apfel. Miller's Anesthesia.

7. Strategies for Minimizing PONV • Identify high risk patients -25-30% incidence of PONV -0.18% intractable PONV • Avoid emetogenic stimuli • Multimodal antiemetic therapy

8. Risk FactorsPatient, Procedure, Anesthesia • History of previous PONV • History of motion sickness • History of migraines • Female gender post puberty • Childhood after infancy and young adulthood • Nonsmoker • The type of surgery: laparoscopic, middle ear, ophthalmologic, craniotomy • Increasing duration of surgery • Dehydration • Pain • Use of volatile anesthetics, opioids, nitrous oxide or neostigmine “Up to 70% incidence of PONV in “high risk” patients (Kim)

9. Apfel’s Simplified Risk (Adults) • 1,2,3 or 4 risk factors-->10, 20,60,80% • Female • H/o of PONV or motion sickness • Non smoking • Postoperative IV opiods Apfel, et al. NEJM. 2004.

10. Drugs associated with PONV • Nitrous oxide • Volatile agents • Etomidate • Neostigmine (high doses) • Excessive opiods

11. Comparison of Agents Apfel, et al. 2002.

12. Protective Anesthesia • Hydration • Regional Anesthesia • TIVA • Utilizing propofol as effective as ondansetron • Dose response relationship for propofol • Oxygen • Acupuncture

13. Antiemetics • Antagonists of 5-HT3 • Antagonists of D2 • Antagonists of H1 • Antagonists of M Receptors • Antagonists of Neurokinin-1 • Corticosteroids

14. Dopaminergic Agents • Haloperidol • Similar efficacy to ondansetron • Not approved for IV use secondary to cardiac arrhythmias • Droperidol • Effective • Short half life-3 hours • Increased sedation • FDA black label

15. Clinically Relevant? • Study comparing ondansetron and droperidol QT prolongation Charbit B, et al. Anesthesiology. 2005.

16. Dopamine Antagonists • Metoclopramide • Prokinetic effects • Studies show 10mg dose no more effective than a placebo • Higher doses (50mg) may be effective • Dyskinetic and extrapyramidal side effects

17. Other Drugs NOT Included in this Talk • Metoclopramide • Ranitidine • Sodium citrate • Omeprazole • GERD and aspiration precautions are different from PONV

18. 5HT-3 Antagonists • Ondansetron, granisetron & dolasetron • Work at the chemoreceptor trigger zone & at vagal afferents in the GI tract • Anti-vomiting better than anti-nausea • All three equal in efficacy, few side effects • Four hour half-life, but genetic of polymorphisms of p450 can lead to ultra short metabolism • Palonosetron (Aloxi) • RCT demonstrated efficacy • Approved for PONV in 2008 • Duration of up to 72 hours

19. Anticholinergics • Scopolamine patch showed to be equally effective to ondansetron • Side effects include: • Dry mouth • Visual disturbances • Dizziness • Agitation

20. Corticosteroids • Dexamethasone • Meta-analysis shows 8-10mg effective • No reports of dexamethasone-related side effects in small doses • Slow onset of action, better efficacy if given in the beginning of a case

21. Antihistamines • Dimenhydrinate (Dramamine) & Diphenhydramine • Anticholinergic Properties • Side effects: • Sedation • Dry Mouth • Blurred vision • Urinary Retention • Prolonged recovery from anesthesia • Vascular necrosis (promethazine)

22. Neurokinin-1 Antagonists (Substance P Receptors) • Work on the final common pathway from the emetic center • Aprepitant (Emend) • Recent studies indicate more effective than ondansetron in preventing emesis, similar efficacy in preventing nausea • Patent expiration 2011-2015 • Casopitant & Rolapitant

23. Combinations versus single drugs • Multiple RCT compare a combination of antiemetics versus a single agent • Improved outcomes with combinations of anti-emetics (except for studies with metoclopramide)

24. IMPACT International Multicenter Protocol to Assess Antiemetic Combinations, 2004 • Large multicenter RCT • 5,199 high risk patients • Six Variables: 2x2x2x2x2x2 (64 groups) • Ondansetron • Dexamethasone • Droperidol • Air (versus NO) • Propofol (versus inhaled agents), • Remifentanil (versus fentanyl) • Primary Outcome- PONV in 1st 24 hours • Relative risk of combined antiemetics equal to multiplying the relative risk of each single agent together Apfel, C, et al. IMPACT. Anaesthetist. 2005.

25. Algorithms for the prevention of PONV • Risk adapted algorithms can reduce PONV in select patient populations • None have proved to be universally applicable

26. Guidelines for Antiemetic Therapy • Patient Factors • Female • H/o of PONV or motion sickness • Non-smoker • Use of opiods • Surgical Factors • Laparoscopy • Laparotomy • Craniotomy • Strabismus • ENT 2-4 Factors 1. Droperidol +5HT-3 Antag 2. Decadron+5HT-3 Antag. 3. Droperidol+Decadron >4 Factors Combination of antiemetics + TIVA with propofol 1-2 Factors 5HT-3 Antag. Decadron Scopolamine Droperidol Evidence Based Anesthesia

27. Rescue Therapy • Lack of data • Mechanical Factors: • Secretions, gastric distension, opiates • Choose a different drug class in the first six hours • 5HT-3 Antagonists • Non-sedating • Better anti-vomiting than anti nausea • Not dose responsive • Not indicated if failed ondansetron prophylaxis • Droperiol • Dexamethasone

28. Tulane Pharmacy Costs • Wholesale Price • Markup 5x wholesale price • Submitted to Insurance Company • Government Reimbursement for Operative Antiemetic Drugs • Facility Surgery Fee

29. Ondansetron $0.78 per dose • Droperidol $4.08 • Dimenhydrinate$0.04 Courtesy of Bob Self, Tulane Pharmacy Director

30. What does this mean? • High risk patients ALWAYS warrant aggressive prophylaxis • Ondansetron • 50 patients a day, 260 days a year…costs Tulane: $57,000 per year • Puts patients at risk for side effects • Only 0.18% patients experience severe PONV requiring hospitalization…almost all can be identified by risk factors

31. References • Costanzo, Linda. Physiology. 4th Ed. Lippincott Williams & Wilkins: Philadelphia, 2007. • Gan TJ. Risk factors for postoperative nausea and vomiting. Anesth Analog 2006;102:1884-98. • Gan, T.J. Effective Management of PONV and Pain in Ambulatory Settings. • Glidden, Randall. NMS Clinical Manuals. Lippincott Williams & Wilkins: Philadelphia, 2003. • Habib, Ashraf. What Is the Best Strategy to Prevent Postoperative Nausea and Vomiting? Evidence-Based Practice of Anesthesiology. 2nd edition. Sunders Elsevier. 269-275. • Kranke P. Algorithms for the prevention of postoperative nausea and vomiting: an efficacy and efficiency simulation. European Journal of Anaesthesiology 2007, 24,10:856-867. • Kim, Eun Jin. Combination of Antiemetics for the Prevention of Postoperative Nausea and Vomiting in High Risk Patients. J Korean Med Sci 2007; 22:878-82. • Apfel, CC. A Factorial Trial Six Interventions for the prevention of postoperative nausea and vomiting. Anaesthesist. 54 (3). Mar 2005. 201-9. • Apfel CC., Kranke P, Katz MH, et al: Volatile Anesthetics may be the main cause of early, but not delayed postoperative vomiting: A randomized controlled trial of factorial design. Br J of Anesthesia. 88: 659-668, 2002. • Apfel, CC, Korttila K, Abdallah M, et al.: A factorial Trial of Six interventions for postoperative nausea and vomiting. New England Journal of Medicine. 2004; 350, 2441-2451. • Miller, R, et al. Miller’s Anesthesia. 7th ed. Churchill Livingstone: 2009. • Kovac A. A randomized, double-blind controlled trial of three different doses of palonosetron versus placebo in preventing postoperative nausea and vomiting over a 72-hour period. Anesthesiology Analogue. 107 (2): 439-44. • Charbit B, et al.. AnesthesioDroperidol and ondansetron-induced QT interval prologation: a clinical drug interaction studylogy. Aug 2008; 109 (2): 206-12.