The PONV Problem
Transcription
The PONV Problem
The PONV Problem JBL PONV PDNV OIE MINV Leslie.John@Mayo.EDU The PONV Problem: Frequent – Predictable – Evaluable – Expensive – Dissatisfying – Avoidable John B. Leslie, MD, MBA Professor Department of Anesthesiology Mayo Clinic College of Medicine Rochester, Minnesota Consultant in Anesthesiology Mayo Clinic Arizona, Scottsdale, AZ Professor of Clinical Anesthesia University of Arizona, Tucson, AZ JBL PONV “Terminology” • • • • • • • • • • • • • • • • • • Air the diced carrots Barf - Boot - Blow - Brack Bark at the moon Blow foam, chunks, or bile Bring it up for a vote Burpin’ solid Call Uncle Earl or Ralph Call Europe Call on great white telephone Call up the beasties Chumming Chunder and Chunks Clean house Core dump Drive the porcelain bus Drive the Buick Emit with a food fountain Empty your bucket • • • • • • • • • • • • • • • • • • Fertilize the carpet Growl at the ground Hurl - Hack - Heave - Huey Liquid laugh or yawn Lunch re-run Laugh at the carpet Make an inventory Make a pavement pizza Private exorcism (AKA LB) Produce the liquid laugh Puke - Spew - Retch - Urp Park the tiger Protein spill Shout at your shoes Sick-up and spew Technicolor yawn Toss your cookies Vomit or Un-eat Have we solved the PONV “little big problem” ? 3 decades of clinical trials Risk Stratification Multiple combination therapies Guidelines & Updated Guidelines “Breakthrough medications” “Break-the-Bank Expenses” JBL Many Patients Experience PONV Beyond the PACU Incidence of PONV/PDNV/OIE • Overall range: 25% to 30% • • High-risk patients: 70% to 80% • 35% to 67% of patients may experience PDNV • PONV may persist for 5 days after surgery • Opioid-induced emesis (OIE): 10% to 60% • No 1 or No 2 adverse outcome following routine outpatient surgery! Gan TJ, et al Guidelines for the Management of PONV; Anesth Anal, Vol 105, December, 2007. Kovac. Drugs. 2000;59:213243; Natof et al. In: Wetchler, ed. Anesthesia for Ambulatory Surgery. 2nd ed. 1991:437-474; Carroll et al. Anesth Analg. 1995;80:903-909; Gan et al. Anesth Analg. 2002;94:1199-2000; Gan. JAMA. 2002;287:1233-1236; Leslie and Bash. Poster presented at: NYSSA 57th Postgraduate Assembly; December 13, 2003; New York, NY; Gan et al. Anesth Analg. 2003;97:6271; Chung et al. Eur J Anaesthesiol. 1999;16:669-677; Hirayama et al. Yakugaku Zasshi. 2001;121:179-185. John B Leslie, MD MBA 100 Initial Experience of PONV Among Affected Patients, % • Outpatient range: 20% to 80%, depending on the patient population Overall: 41% had PONV and … of patients who experienced PONV, nearly 80% initially did so in the PACU and/or within 48 hours after discharge. 78% 80 60 40 36% 20 0 Initial PONV in the PACU (21/58) Initial PONV in the PACU and/or Within 48 Hours After PACU Discharge (45/58) Study Design: Data from a study examining patients’ experiences with PONV following discharge from outpatient surgery centers. Incidence of PONV was measured in the recovery room, by telephone the day after discharge, and by a questionnaire that patients were instructed to complete 5 days after discharge. A total of 143 outpatients (aged ≥18 years) who received general anesthesia and underwent 1 of 4 selected surgeries (laparoscopy, dilation and curettage, arthroscopy, or hernia repair) provided complete data. Some patients who initially experienced PONV within 48 hours after PACU discharge continued to experience PONV for up to 5 days after PACU discharge. Carroll NV et al. Anesth Analg. 1995;80:903–909. JBL The PONV Problem PONV Remains a Problem Despite Current Therapies 1. 2. 3. 4. JBL JBL The Real Value of Guidelines? Overall Up to 30% for all surgeries and patient populations.1–3 Outpatient About 40% of patients with PONV treated at outpatient surgery centers.4 Breakthrough More than 30% of patients with PONV were receiving prophylactic antiemetics.3 — No significant differences among ondansetron, dexamethasone, and droperidol Kovac AL. Drugs. 2000;59:213–243. Habib AS, Gan TJ. Can J Anesth. 2004;51:326–341. Apfel CC et al. N Engl J Med. 2004;350:2441–2451. Carroll NV et al. Anesth Analg. 1995;80:903–909. JBL PONV vs PDNV: Under-Recognized Problem JBL PONV vs PDNV: Under-Recognized Problem Prospective Study of 2170 Outpatients in 12 USA Centers C Apfel, S Shi, A Kovac, A Shilling, J Leslie, B Philip, on behalf of the PDNV Study Group: IARS Annual Mtg. 2009 C Apfel, S Shi, A Kovac, A Shilling, J Leslie, B Philip, on behalf of the PDNV Study Group: IARS Annual Mtg. 2009 JBL PONV vs PDNV: Under-Recognized Problem Conclusion: The results of this 12-center multicenter cohort study showed a substantial incidence of PDNV in the US.… Clinical trials that address this patient population with a long acting antiemetic strategy are needed What does failure to prevent PONV actually cost? Patient Risk Patient discomfort Patient dissatisfaction Economic burden C Apfel, S Shi, A Kovac, A Shilling, J Leslie, B Philip, on behalf of the PDNV Study Group: IARS Annual Mtg. 2009 John B Leslie, MD MBA The PONV Problem JBL JBL PONV: #1 Patient Problem Potential Consequences of PONV • • Emesis is the postoperative outcome least preferred by patients Medical Consequences PONV — — — — Can cause electrolyte abnormalities and dehydration Can cause tension on suture lines1,2 Venous hypertension2 Can cause hematomas (increased bleeding) beneath surgical flaps,1 vascular anastomosis, aneurysm clipping, etc — Can place the patient at risk for pulmonary aspiration of vomit if airway reflexes are depressed from lingering effects of anesthetic and analgesic drugs1,2 (esp increased risk with jaw wired closed) 1 Postoperative Outcomes Least Preferred by Patients Rank Practical Consequences of PONV — — Delayed Discharge after out-patient surgery2 Unanticipated hospital admission1 Postoperative Outcomes 1 Vomiting 2 Gagging on endotracheal tube 3 Incisional pain 4 Nausea 5 Recall without pain 6 Residual weakness 7 Shivering 8 Sore throat 9 Somnolence Data from a survey of adult patients (N=101) conducted at Stanford University Medical Center. Patients were eligible if they were scheduled to undergo surgery at the center. Patients were asked to rank-order 10 possible postoperative outcomes from most to least desirable. F-test <0.01. 1. Golembiewski J, et al Am J Health-Sys Pharm; Vol 62 Jun, 2005 2. Watcha MF, White PF. Anesthesiology. 1992;77:162–184. Adapted from Macario A et al. Anesth Analg. 1999;89:652–658. © 1999. With permission from Lippincott Williams & Wilkins. JBL JBL Cost Components in PONV Episodes What do Surgical Patients Most Want to Avoid? Cost Components for an Episode of Emesis “… avoiding Post-Operative Nausea and Vomiting seems to be a high priority for most Patients”1 (% total median management cost per patient) Hospital admission PACU 10% delay 4% Ranking and Relative Values ($100) of Patient Outcomes* $20 n=62 $18.05 $17.86 $16.96 $13.82 $15 Materials* 0.2% $11.82 $10 $7.99 MD/CRNA 5% Personnel 83% PACU nurses 78% $7.60 $5 $3.04 Antiemetic cost 3% $Vomiting Gagging on ET Tube Pain Recall w/out Pain Nausea Residual Weakness Shivering Sore Throat *Per item of basin, gloves, paper, linen, and gown *Patients were asked to distribute $100 among 10 outcomes, with proportionally more money being allocated to the more undesirable outcomes (eg, patients assigned $18.05 of $100 to avoid vomiting). Hill RP et al. Anesthesiology. 2000;92:958-967. Macario, A, et al Which Clinical Anesthesia Outcomes; Anesth Anal, 1999; 89;652-8 JBL PONV Incurs Higher Cost$ • In a study conducted in 2000, PONV was associated with increased cost* — A single episode of emesis costs an average of $305 — A single episode of nausea costs an average of $82 • PONV is a major factor limiting early discharge of ambulatory surgical patients (1st or 2nd all major studies) • PONV is a leading cause of unanticipated hospital admissions (24% primary reason) • Preventing PONV can be cost-effective * PACU personnel costs are biggest component: NOT PHARMACEUTICALS Hill RP et al. Anesthesiology. 2000;92:958-967 Lau H & Brooks DC. Arch Surg (2001) 136:1150-53. John B Leslie, MD MBA JBL The PONV Problem PONV PDNV OIE MINV JBL “Volatile anaesthetics may be the main cause of early but not delayed postoperative vomiting: a randomized controlled trial of [5x] factorial design.” 750 combinations: Gender, Surgery, Opioids, Maintenance, PONV Prophylaxis 1180 patients 50% pediatric JBL Apfel BJA 2002;88:659 Why do patients develop PONV? JBL JBL JBL JBL PONV Risk Prediction Tool? PONV Risk Factors PONV Risk Factors (cont) • Patient related1-7 • Surgery related1-5 —Duration of surgery —Operative procedure (e.g., gynecologic, laparoscopic, eye, plastic, abdominal) —Female gender —History of PONV and/or motion sickness —Nonsmokers —Younger age —Anxiety —Underlying disease (e.g., GI obstruction, neuromuscular disorders, gastric hypomotility) • Anesthesia related1-3,6-8 —Volatile anesthetics —General anesthesia —Duration of anesthesia —Postoperative opioids —Muscle relaxant antagonists (e.g., neostigmine) 1. Watcha MF, White PF. Anesthesiology. 1992;77:162-184. 2. Kovac AL. Drugs. 2000;59:213-243. 3. Apfel CC, et al. Acta Anaesthesiol Scand. 1998;42:495-501. 4. Apfel CC, et al. Anesthesiology. 1999;91:693-700. 5. Koivuranta M, et al. Anaesthesia. 1997;52:443-449. 6.Apfel CC, Roewer N. Int Anesthesiol Clin. 2003;41:13-32. 7. Apfel CC. Anesthesiology News Special Edition. 2006:71-76. 23 John B Leslie, MD MBA 1. Watcha MF, White PF. Anesthesiology. 1992;77:162-184. 2. Kovac AL. Drugs. 2000;59:213-243. 3. Apfel CC, et al. Br J Anaesth. 2002;88:659-668. 4. Cohen MM, et al. Anesth Analg. 1994;78:7-16. 5. Koivuranta M, et al. Anaesthesia. 1997;52:443-449. 6. Apfel CC, et al. Anaesthesia. 2004;59:10781082. 7. Roberts GW, et al. Anesth Analg. 2005;101:1343-1348. 8. Apfel CC, et al. Anesthesiology. 1999;91:693-700. 24 The PONV Problem JBL PONV Risk Factors (cont) JBL Comparison of predictive models for PONV • Most predictive1-3 Apfel Koivuranta Palazzo Sinclair —Female gender —Nonsmokers —History of PONV/motion sickness —Postoperative opioid analgesics • Multiple (≥3) risk factors2 —60%–80% of patients may experience PONV 1. Kovac AL. Drugs. 2000;59:213-243. 2. Apfel CC, et al. Anesthesiology. 1999;91:693-700. 3. Apfel CC. Anesthesiology News Special Edition. 2006:71-76. “A risk score to predict the probability of postoperative vomiting in adults.” 25 Apfel et al. Br J Anaesth 2002;88:234-40 JBL JBL SAMBA Algorithm Factors for PONV 1137 ENT patients split into an evaluation set (533) and a validation set (584) • POV Risk (probability) = Adult Risk Factors 1 1 + e-z Children Risk Factors Surgery > 30 min Patient Related • Where: Z = (no=0, yes=1) + 1.28*(female gender) - 0.029*(age) - 0.74*(smoking) + 0.63*(history motion sickness or PONV) + 0.26*(duration) - 0.92 Environmental History of PONV or Motion Sickness Postop Opioids Age > 3 years Female Gender Emetogenic surgery (type & duration) Strabismus surgery Non-Smoker History of POV or relative with PONV Gan et al. Anesth Analg. 2007;105:1615-28. Apfel et al. Acta Anaesthesiol Scand 1998;42:495-501 JBL Simplified Risk Score to Predict PONV in Adults1 PONV PDNV OIE MINV JBL When either 1, 2, 3 or 4 of the independent PONV predictors are present, the corresponding risk for PONV increases Risk Factors Points 100 Female Gender 1 80 Non-Smoker 1 60 History of PONV** 1 40 Percent Risk for PONV 80 60 40 20 Postoperative Opioids 1 20 Sum = 0, 1, 2, 3, 4 0 ** or motion sickness? 10 0 Risk Factor 1 Risk Factor 2 Risk 3 Risk 4 Risk Factors Factors Factors For example (YELLOW BOX), if a patient is a “female” “non-smoker” she has 2 risk factors and there is a 40% chance of her experiencing PONV 1. Gan TJ, et al Guidelines for the Management of PONV; Anesth Anal, Vol 105, December, 2007 John B Leslie, MD MBA Where are we in the development and implementation of “best practices” PONV guidelines? The PONV Problem JBL JBL Strategies to Reduce Baseline PONV Risk PONV Patient-At-Risk “Game Plan” • Avoidance of general anesthesia by the use of regional anesthesia (RCT) • Use of propofol for induction and maintenance of anesthesia (RCT/SR) • Avoidance of nitrous oxide (RCT/SR) • Avoidance of volatile anesthetics (RCT) • Minimization of intraoperative and postoperative opioids (RCT/SR) • Minimization of neostigmine (SR) • Adequate hydration (RCT) Gan et al. Anesth Analg. 2007;105:1615-28. JBL Guidelines for Antiemetic Prophylaxis for PONV Receptor Site Affinity Drug ASA 20021 ASPAN 20062 • Prophylaxis with: —5-HT3 RA —Droperidol —Dexamethasone —Metoclopramide —5-HT3 RA + dexamethsone • If required, rescue with 5-HT3 RA FDA Approved SAMBA 20073 • Prophylaxis with 1 or more: —5-HT3 RA —Droperidol —Dexamethasone —H1 receptor blocker —Transdermal scopolamine patch Prochlorperazine • Assess patient risk • Reduce baseline risk factors • Prophylaxis with 1-2 interventions for patients at moderate risk: —5-HT RA 33 JBL PONV Treatment Team 9 Receptor Site Affinity Serotonin Dopamine Histamine Muscarinic + ++++ ++ ++ ++++ + + Haloperidol 3 • Give adequate IV hydration —Droperidol, haloperidol • Use total IV anesthesia —Dexamethasone —H1 receptor blocker • If patient fails in PACU, then —Transdermal scopolamine administer another category of patch agent —Promethazine, • If required, rescue with prochlorperazine, perphenazine promethazine, prochlorperazine, —Ephedrine or metoclopramide • High-risk multimodal approach • If patient fails, then administer another category of agent ASA=American Society of Anesthesiologists; ASPAN=American Society of PeriAnesthesia Nurses; SAMBA=Society for Ambulatory Anesthesia. 1. ASA Task Force on Postanesthetic Care. Anesthesiology. 2002;96:742-752. 2. ASPAN PONV/PDNV Strategic Work Team. J Perianesth Nurs. 2006;21:230-250. 3. Gan TJ, et al. Anesth Analg. 2007;105:1615-1628. Droperidol 9 + ++++ Metoclopramide 9 ++ +++ Scopolamine 9 Dimenhydrinate Hydroxyzine 9 Promethazine 9 Aprepitant 9 Dolasetrron 9 ++++ Granisetron 9 ++++ Ondansetron 9 ++++ Palonosetron 9 ++++ Dexamethasone + ++++ ++ + ++++ ++++ ++ ++ ++++ ++ 1. Watcha MF, White PF. Anesthesiology. 1992;77:162-184. 2. Scuderi PE. Int Anesthesiol Clin. 2003;41:41-66. 3. Prommer E. J Pain Palliat Care Pharmacother. 2005;19:31-39. SAMBA Treatment Algorithm Options for PONV Surgeons Anesthesiologists & Nurse Anesthetists John B Leslie, MD MBA + + + Antagonism of prostaglandins and release of endorphins Peri-Anesthesia Nurse Gan TJ, et al Guidelines for the Management of PONV; Anesth Analgesia, Vol 105, December, 2007 Neurokinin ++++ The Consensus Guidelines for the management of PONV was written by a multi-disciplinary panel that included such clinicians as … Pharmacist JBL PONV Antiemetics Gan et al. Anesth Analg. 2007;105:1615-28. 34 JBL The PONV Problem SAMBA Treatment Algorithm Options for PONV JBL Gan et al. Anesth Analg. 2007;105:1615-28. SAMBA Treatment Algorithm Options for PONV JBL Gan et al. Anesth Analg. 2007;105:1615-28. JBL JBL Increasing the Number of Antiemetics Reduces the Incidence of PONV (n=5161 patients at high risk for PONV) Selecting “Best Shot” PONV/PDNV Drugs? 60 52% chance of PONV % Incidence of PONV 95% Confidence Interval 52 50 37% chance of PONV 37 40 28% chance of PONV 22% chance of PONV 28 30 22 20 10 0 No Antiemetic 1 Antiemetic 2 Antiemetics 3 Antiemetics 0 Antiemetics 1 Antiemetic 2 Antiemetics 3 Antiemetics IV Ondansetron IV Dexamethasone IV Droperidol IV Ond + IV Dex IV Ond + IV Dro IV Dro + IV Dex Adapted from Apfel et al. N Engl J Med. 2004;350:2241-2251. JBL Estimated Incidence of PONV as a function of Baseline Risk Assumption: Each Intervention Reduces risk by 26%1 n=5161 patients at risk for PONV 80% baseline risk 4 Risk Factors The baseline risk levels 0f 10%, 20%, 40%, 60% and 80% reflect the presence of 0,1,2,3 and 4 risk factors respectively, according to a simplified score 80 70 Despite multiple combinations with current drugs, we fail…yes, we fail! Estimated PONV incidence as a function of baseline risk, assuming each intervention reduces relative risk by 26% 60% baseline risk 3 Risk Factors Number of interventions Percenatage 60 50 Baseline risk (no intervention) 40% baseline risk 2 Risk Factors 40 30 20 10 20% baseline risk 1 Risk Factor 10% baseline risk 0 Risk Factors 0 Baseline Risk with No Intervention One Intervention Two Interventions Three Interventions Four Interventions 1 2 3 10% 7% 5% 4% 3% 20% 15% 11% 8% 6% 40% 29% 22% 16% 12% 60% 44% 33% 24% 18% 80% 59% 44% 32% 24% 26% reduction in relative risk of PONV for each additional antiemetic used Adapted from Apfel et al. N Engl J Med. 2004;350:2241-2251. John B Leslie, MD MBA 4 Apfel CC, Korttila K, Abdalla M, et al. A factorial trial of six interventions for the prevention of postoperative nausea and vomiting. N Engl J Med 2004;350:2441-51. JBL The PONV Problem Selecting the Ideal Antiemetic? Pathway? The Numbers are In. We Are Failing ;-( JBL Current & Future Antiemetic Therapy for PONV Prophylaxis in Adults JBL • Serotonin (5-HT3) antagonists • Diphenhydramine (Benadryl®) — Ondansetron (Zofran®) • Nonpharmacologic — Dolasetron (Anzemet®) techniques* — Granisetron (Kytril®) — Tropisetron (Navoban®)* — Palonosetron (Aloxi®) • Dexamethasone (Decadron®)* • Droperidol (Inapsine®)† — Haloperidol (Haldol®)* • • • • — — — — Acupuncture* (Acupressure)* Hypnosis* Aromatherapy* Music therapy* • Dimenhydrinate (Dramamine®) • Neurokinin-1 Antagonists Scopolamine (Transderm Scop®) — Aprepitant (Emend®) — Casopitant (Rezonic)* 5-20-09 Promethazine (Phenergan®) Prochlorperazine (Compazine®) • Cannabinoid — Nabilone (Cesamet®)* Ephedrine* — Dronabinol (Marinol®)* *Currently not FDA-approved for PONV in the United States; †Note package insert black box warning. Modified from Gan et al. Anesth Analg. 2003;97:62-71. JBL PONV Summary and Conclusions • Understanding of emetic pathways continues to evolve — 30% overall incidence 2 — PONV incidence increases with each additional risk factor, thus underscoring need for assessment and preventative intervention 3 • Risk assessment helps identify patients who would benefit from prophylactic antiemetics • Effective PONV prevention strategy incorporates risk assessment that reflects its multifactorial etiology 2 — Peripheral versus central emetogenic triggers 1,2 — Peripheral versus central neurotransmitter/receptor pathways 3.4 • Involvement of different emetic neurotransmitter pathways may impact treatment strategies — Source of emetic stimuli impacts effectiveness of pharmacologic antiemetic intervention 5 — Multiple receptor approach probably logical and effective • Ideal combination unproven: Consider 5-HT3 + steroid + droperidol/haloperidol + SCOP + “special needs” + techniques 2 — New pharmacology 5HT3 antagonist palonosetron — First substance P/NK1 antagonist now available for prevention of troublesome PONV and PDNV: Aprepitant 40 mg — Patient-related characteristics — Surgery-related characteristics — Anesthesia-related characteristics 1. Kovac. Drugs. 2000;59:213-243. 2. Nelson TP. J PeriAnesthesia Nursing 2002;17:178-189. 3. Saito R., et al. J Pharmacol Sci 2003;91:87-94. 4. Hornby PJ. Amer J Med 2001;111:106S-112S. 5. Diemunsch P., Grelot L. Drugs 2000;60:533-546 1. Macario A., et al. Anesth Analg 1999;89:652-658. 2. Kovac. Drugs. 2000;59:213-243. 3. Apfel CC et al. Anesthesiology 1999;91:693-700 JBL SCOAP PONV Challenge Risk stratification can and should be done. Prevention measures should be implemented. Outcome benefits should be producible and measurable. Benefits should include patient satisfaction and reduced costs. The PONV initiative should be widely applicable. John B Leslie, MD MBA JBL (cont) • PONV: Ranked as most undesirable consequence of surgery 1 • Global risk assessment includes evaluation of: PONV Summary and Conclusions JBL Questions? 48