Management of PONV

1. Management of PONV Dr. Jay A. Avila Staff Anesthesiologist PACU Medical Officer USNH Camp Pendleton

2. Objective • To apply newest evidence-based-medicine to our management of PONV • To increase patient satisfaction • To maximize cost effectiveness • To speed up patient discharge from PACU and SDSU Jay A. Avila LCDR, MC, USNR

3. Current Practice – Pre-operatively • Patient stratification ranges from none or minimal to appropriate • Bicitra and Reglan for all pregnant or GERD patients • Prophylaxis ranges from none or minimal to triple combination • Anesthetic plan modification based on patient stratification ranges from none to appropriate Jay A. Avila LCDR, MC, USNR

4. Current Practice – Pre-operatively • Agents used: • Ondansetron 4 mg IV • Metoclopramide 10 mg IV • Dexamethasone 4-10 mg IV • Vistaril 25 mg IM and IV • Scopolamine Patch Jay A. Avila LCDR, MC, USNR

5. Current Practice - Intraoperatively • Propofol induction • Adequate hydration and avoidance of hypotension • Ondansetron pre-induction, at induction or shortly after • Ondansetron at the end of surgery • Metoclopramide initially and/or at the end • Droperidol 0.625-1.25 mg IV at the end • Dexamethasone 4-10 mg IV initially or at the end • Reversal usage considerations • Propofol before emergence (20 mg IV) • TIVA(Propofol) with or w/o volatile agent with or w/o NO Jay A. Avila LCDR, MC, USNR

6. Current Practice - Postoperatively • Hydration: Crystalloid 1000 cc at 100cc/hr • Rescue medications: • Zofran 4 mg IV initially and/or repeat • Reglan 10 mg IV initially and/or repeat • Phenergan 12.5-25 mg IV Jay A. Avila LCDR, MC, USNR

7. Pathophysiology of Nausea and Vomiting Jay A. Avila LCDR, MC, USNR

8. Pathways in CTZ/Emetic Center Stimulation Antagonist Anticholinergics Antidopaminergics 5-HT3 Antihistamine Agonist Muscarinic/Cholinergic Dopamine (D2) 5-HT3 Histamine Receptor Site m CTZ Area Postrema Jay A. Avila LCDR, MC, USNR Adapted from Watcha MF et al. Anesthesiology. 1992;77:162-184.

9. Agonists and Antagonists Associated with Nausea and Vomiting Jay A. Avila LCDR, MC, USNR

10. Jay A. Avila LCDR, MC, USNR

11. Jay A. Avila LCDR, MC, USNR

12. Socio-economic Aspects of PONV • Common complication of surgery • Limiting factor in early discharge • Leading cause of unanticipated hospital admission • Increased recovery room time, increased nursing care and potential hospital admission: All increase Total Health Costs Jay A. Avila LCDR, MC, USNR

13. Socio-economic Aspects of PONV • High Levels of Patient disconfort and dissatisfaction • PONV may be of greater concern than post-op pain • Patients willing to spend up to $ 100 out of pocket for effective antiemetic Jay A. Avila LCDR, MC, USNR

14. Socio-economic Aspects of PONV • 25-30% of surgical patients experience nausea and/or vomiting post-operatively • Intractable PONV about 0.18% • High risk patients may have 70-80% incidence of PONV • Emphasis shift from in-patient to out-patient surgery has increased interest in prevention and treatment of PONV Jay A. Avila LCDR, MC, USNR

15. Socio-economic Aspects of PONV • Optimal approach to PONV remains unclear: • Treat all high risk patients? • Ideal rescue therapy • Published evidence suggests universal PONV prophylaxis in not cost-effective • AIMS (Anesthesia Information Management Systems) have been created to stratify and predict and prevent PONV • Guidelines for prevention of PONV have been published Jay A. Avila LCDR, MC, USNR

16. Socio-economic Aspects of PONV • Guidelines previously published have been based on data taken from systematic reviews of randomized trials • Evidence from single studies or logistic regression data (identifying risks factors for PONV) had not been included either Jay A. Avila LCDR, MC, USNR

17. Consensus Guidelines for Managing PONV • Multidisciplinary expert panel reviewed available literature up to 02/2002 • Recommendations based on best available evidence regarding prevention and rescue therapy of PONV Jay A. Avila LCDR, MC, USNR

18. Goals of Guidelines • Identify primary risks factors for PONV in adults and children • Reduce baseline risks • Identify optimal approach to PONV prevention and therapy in various patient populations • Determine optimal choice and timing of anti-emetic administration • Identify most effective mono-therapy and combination therapy regimes Jay A. Avila LCDR, MC, USNR

19. Strength of Evidence • Panel analyzed and evaluated pertinent medical literature using widely used Evidence Rating Scales • In the absence of published data, recommedations were based on expert opinion Jay A. Avila LCDR, MC, USNR

20. Evidence Rating Scale Level of Evidence based on Study design • I Large, randomized, controlled trial, n ≥ 100 per group • II Systematic review • III Small randomized, controlled trial, n ≤ 100 per group • IV Non-randomized, controlled trial or case report • V Expert opinion Strength of recommendation based on expert opinion • A Good evidence to support recommendation • B Fair evidence • C Insufficient evidence to recommend for or against Jay A. Avila LCDR, MC, USNR

21. Consensus Guidelines • The following factors were considered: • PONV risk level • Potential morbidity associated with PONV: • Suture dehiscence • Esophageal rupture • Hematoma formation • Aspiration pneumonitis • Potential adverse events • QT prolongation, fatal arrhythmias • Efficacy of antiemetics • Cost of therapy • Increased health care costs associated with PONV Jay A. Avila LCDR, MC, USNR

22. Consensus Guidelines • Not all patients should receive prophylaxis • Low risk patients unlikely to benefit • Unnecessary risk from potential side effects • Prophylaxis should be reserved for moderate to high risk patients Jay A. Avila LCDR, MC, USNR

23. Guideline # 1 • Identify adults at high risk for PONV Jay A. Avila LCDR, MC, USNR

24. Adults at High Risk for PONV • Apfel et al. identified four primary risk factors in patients receiving balanced anesthesia: • Female gender IA • Non-smoking status IVA • Prior history of PONV/Motion sickness IVA • Use of opioids: Intra-op/Post-op IIA/IVA Jay A. Avila LCDR, MC, USNR

25. Incidence of PONVApfel et al. • No factors 10% • One factor 20% • Two factors 40% • Three factors 60% • Four factors 80% Jay A. Avila LCDR, MC, USNR

26. Type of Surgery and PONV • Sinclair et al. study of 18,000 ambulatory patients suggests PONV risk > 15% • Breast augmentation IVB • Dental surgery IVB • Orthopedic shoulder procedures IVB • Gynecologic laparoscopy IVB • Varicose vein stripping IVB • Strabismus repair IVB Jay A. Avila LCDR, MC, USNR

27. Duration of Surgery and PONV • Each 30-minute increase in surgery time increases PONV incidence by 60%, thus, • A baseline risk of 10% is increased to 16% after 30 minutes • IVA evidence Jay A. Avila LCDR, MC, USNR

28. Guideline # 2 • Identify Children at high risk for POV Jay A. Avila LCDR, MC, USNR

29. Children at High Risk for PONV • Only POV studied • Leading post-operative complaint from parents • Leading cause of re-admission • POV increases as age increases • Rare < 2 yrs • ≥ 40% if > 3 yrs (2x as frequent as adults) • Incidence tapers at puberty • No sex difference before puberty • Risk increases more specifically with certain surgeries: T&A, strabismus, hernias, orchiopexy, penile procedures Jay A. Avila LCDR, MC, USNR

30. Guideline # 3 • Reduce baseline risk factors for PONV Jay A. Avila LCDR, MC, USNR

31. Baseline Risk Factor Reduction • Scuderi et al. tested a multimodal approach to reducing PONV in a randomized controlled clinical trial of women undergoing outpatient laparoscopy • Multimodal: • Pre-operative anxiolysis • Aggressive hydration • Oxygen • Droperidol + Dexamethasone at induction • Ondansetron at the end • TIVA with propofol + remifentanil • Ketorolac • No nitrous oxide or muscle relaxation Jay A. Avila LCDR, MC, USNR

32. Baseline Risk Factor Reduction • Patients who received multimodal therapy had 98% complete response rate • Antiemetic monotherapy: 76% • Saline placebo: 59% • Level of satisfaction was the same between multimodal and monotherapy respondents Jay A. Avila LCDR, MC, USNR

33. Baseline Risk Factor Reduction • Regional anesthesia IIIA • Induction/maintenance with Propofol IA • Intra-op supplemental O2 IIIB • Aggressive hydration IIIA • Avoidance of Nitrous Oxide IIA • Avoidance of volatile anesthetics IA • Minimization of intra-op/post-op opioids IIA/IVA • Minimization of neostigmine IIA Jay A. Avila LCDR, MC, USNR

34. Guideline # 4 • Antiemetic therapy for PONV prophylaxis in adults Jay A. Avila LCDR, MC, USNR

35. Antiemetic Therapy for Adults • Serotonin receptor antagonists • Steroids • Butyrophenones • Phenothiazines • Anticholenergics • Benzamides • Antihistamines • Others Jay A. Avila LCDR, MC, USNR

36. Antiemetic Therapy for Adults • Serotonin receptor antagonists • No profile difference between them • FDA approved ondansetron at 4 mg IV prior to induction • Leeser and Scuderi in ‘91 and ‘93 respectively determined optimal dose at 4 mg at start of anesthesia • Sun et al. : For ENT surgery is more effective at end of surgery • Tang et al. and Graczyk et al. For gynecologic outpatient surgery more effective at the end of surgery Jay A. Avila LCDR, MC, USNR

37. Antiemetic Therapy for Adults • Serotonin receptor antagonists • Ondansetron more effective as antiemetic than antinausea (NNT 7 vs 6) • NTH 36 for HA • NTH 31 for increased liver enzymes • NTH 23 for constipation • MOA specific and selective 5-HT3 antagonism Jay A. Avila LCDR, MC, USNR

38. Antiemetic Therapy for Adults • Dexamethasone • Henzi et al. found that 8-10 mg IV effectively prevents nausea and vomiting with NNT of 4 • Liu and Wang found 2.5-5 mg just as effective • Most effective when used before induction • Dreaded side effects common with long term administration (increased wound infection, adrenal suppression, etc.)have not been noted after a single bolus dose Jay A. Avila LCDR, MC, USNR

39. Antiemetic Therapy for Adults • Dexamethasone • MOA unknown • Prostaglandin antagonism • Release of endorphins • Anti-inflammatory and membrane stabilizing effect Jay A. Avila LCDR, MC, USNR

40. Antiemetic Therapy for Adults • Droperidol (Butyrophenones) • Efficacy equivalent to ondansetron’s • NNT 5 • Most effective when given at the end of surgery • Black Box Warning • ..may cause death or life-threatening events associated with QT prolongation and torsades de pointes • Based on 10 reported cases after over 30 years of use • Dolasetron and ondansetron in combo with metoclopramide have also been involved in QT prolongation • McCormick (2002) and Scuderi (2003) currently performing studies to define effect of droperidol on QTc interval Jay A. Avila LCDR, MC, USNR

41. Antiemetic Therapy for Adults • Droperidol • MOA strong D2 antagonism acting at the CTZ and area postrema • Effective dose 0.625-1.25 mg IV IA Jay A. Avila LCDR, MC, USNR

42. Antiemetic Therapy for Adults • Phenothiazines • Act as sedatives and counter effect of opioids at CTZ (Howat, 1960; Dundee et al. 1965,; Wood 1979) • Limited use in ambulatory setting due to sedation effects • In 1999 Khalil et al. found promethazine effective for middle ear surgery antiemesis when used along or in combo with ondansetron Jay A. Avila LCDR, MC, USNR

43. Antiemetic Therapy for Adults • Phenothiazines • MOA direct blocking of D2 receptors in CTZ • Extrapyramidal effects possible • “Neuroleptic malignant syndrome” is rare but possible • promethazine 12.5-25 mg IV and prochlorperazine 5-10 mg IV at the end of surgery effective Jay A. Avila LCDR, MC, USNR

44. Antiemetic Therapy for Adults • Anticholinergics • Atropine, glycopyrrolate and scopolamine have all been tested as antiemetics. • Cerebral cortex and ponds rich with cholinergic and muscarinic receptors • Dundee et al. found atropine and scopolamine better than glycopyrrolate to counter action of opioids Jay A. Avila LCDR, MC, USNR

45. Antiemetic Therapy for Adults • Scopolamine transdermally was found to prevent PONV effectively (Kranke et al. meta-analysis 2002) however, incidence of side effects was “inexcusably high” • Side effects visual disturbances, sedation, dry mouth, dizziness and memory dysfunction are common Jay A. Avila LCDR, MC, USNR

46. Antiemetic Therapy for Adults • Benzamides • Metoclopramide most “effective” in this class • MOA • Specific D2 antagonism in CTZ • High dose antagonizes 5-HT3 • Cholinergic action in stomach increases LES tone and decreases transit time increasing peristaltic motility • Opioid induced PONV treated as gastric stasis is reversed • Extrapyramidal side effects, cardiac dysrhythmias, dysphoria Jay A. Avila LCDR, MC, USNR

47. Antiemetic Therapy for Adults • Should metoclopramide be used? • Metoclopramide has been used for over 40 years • Wilson et al. studied 230 patients (2001) found metoclopramide 10 mg IV as effective as ondansetron 4 mg for prophylaxis of PONV after lap chole • Quaynor et al. (2002) found same equivalence with 20 mg metoclopramide and 8 mg ondansetron during same same surgical procedure Jay A. Avila LCDR, MC, USNR

48. Antiemetic Therapy for Adults • Should metoclopramide be used? • Henzi et al. in 1999 did systematic review of 66 studies and 3260 patients: No evidence of dose-responsiveness with oral, intranasal or IV in either adults or children • Panel of experts convened in march 2003: • “Although most members agreed that it could not be recommended as an antiemetic, agreement was not unanimous” Jay A. Avila LCDR, MC, USNR

49. Antiemetic Therapy for Adults • Should metoclopramide be used? • Continued use at 10 mg is clearly inadequate • Chemotherapy induced nausea and vomiting is treated with 2 mg/Kg- This regimen is better than placebo with only minor side effects • Cholinergic action may justify its use in conjunction with opioids Jay A. Avila LCDR, MC, USNR

50. Antiemetic Therapy for Adults • Antihistamines • MOA: Block Acetyl-ch in vestibular apparatus and H1 in nucleus of solitary tract • Act mainly in vomiting center and vestibular pathways • Kranke et al. 2002 – meta-analysis showed dimenhydranate prevented PONV in early phase with NNT 8 • Significant side effects limits outpatient use Jay A. Avila LCDR, MC, USNR