术后恶心呕吐的预防和治疗（英文）

Postoperative Nausea and Vomiting: Prevention and Treatment Phillip E. Scuderi, M.D. Department of Anesthesiology Wake Forest University School of Medicine Winston-Salem, NC 27157-1009 Postoperative Nausea and Vomiting: Prevention and Treatment /anesthesia Historical Perspective on PONV Postoperative Nausea and Vomiting: Its Etiology, Treatment, and Prevention Mehernoor F. Watcha and Paul F. White Anesthesiology 1992;77:162-184 Quality of Clinical Trials nAppearance of control treatment nBlinding of randomization process nBlinding of patients and observers, nSample size estimate and power analysis nConfidence intervals nStatistical analyses nWithdrawals nSide effect discussions Greenfield et al. Anesth Analg 2003;96:S88 Quality of Clinical Trials Greenfield et al. Anesth Analg 2003;96:S88 Quality of Clinical Trials nInvestigators nImprove rigor of study protocols nImprove quality of data analysis nPeer Reviewers nProcess of randomization nPower analysis nBlinding Suggestions for Improvement Greenfield et al. Anesth Analg 2003;96:S88 Critical Evaluation of Data nQuality of individual clinical trials nType and adequacy of controls used nBlinding process nSample size, power analysis nAppropriateness of endpoints chosen nConfidence limits particularly for negative studies nStatistical analysis Critical Evaluation of Data nQuality of individual clinical trials nEvaluation of data in aggregate Evidence Based Medicine Rating Scale Level of evidence based on study design I. Large randomized, controlled trial (n100 per group) II. Systematic review III. Small randomized, controlled trial (n8 mg Numbers Needed to be Treated Tramer et al. Anesthesiology 1997;87:1277-1289 II-A Evidence Rating for Antiemetics Strength of EvidenceTreatment Consequences* PreventionTreatmentPreventionTreatment Ondansetron 4 mgI-AI-A5.5 6.53.2 3.9 Ondansetron 1 mg-I-A-3.8 4.8 *NNT Treatment of PONV: Ondansetron Versus Placebo Scuderi et al. Anesthesiology 1993;78:2-5 Hantler et al. Anesthesiology 1992;77:A16 * * * * * * p 0.001 I-A Ondansetron Dose Response: Treatment u All three doses significantly different than placebo u No significant difference in antiemetic efficacy between the three doses of ondansetron Numbers Needed to be Treated Tramer et al. BMJ 1997;314:1088-1092 II-A Evidence Rating for Antiemetics Strength of EvidenceTreatment Consequences* PreventionTreatmentPreventionTreatment Ondansetron 4 mgI-AI-A5.5 6.53.2 3.9 Ondansetron 1 mg-I-A-3.8 4.8 Dolasetron 12.5 mgI-AI-A4.0 5.03.6 4.2 *NNT Prevention of PONV: Dolasetron Versus Placebo *p 0.0003 compared to placebo Graczyk et al. Anesth Analg 1997;84:325-330 * * * * * * * * * I-A Treatment of PONV: Dolasetron Versus Placebo *p 0.001 compared to placebo Kovac et al. Anesth Analg 1997;85:546-552 * * * * * * I-A Evidence Rating for Antiemetics Strength of EvidenceTreatment Consequences* PreventionTreatmentPreventionTreatment Ondansetron 4 mgI-AI-A5.5 6.53.2 3.9 Ondansetron 1 mg-I-A-3.8 4.8 Dolasetron 12.5 mgI-AI-A4.0 5.03.6 4.2 Granisetron 1mgI-AI-A3.1 4.23.1 3.8 *NNT Prevention of PONV: Granisetron Versus Placebo Wilson et al. BJA 1996;76:515-518 * *p 0.001 compared to placebo No Vomiting I-A Prevention of PONV: Granisetron Versus Placebo Wilson et al. BJA 1996;76:515-518 * * *p 0.001 compared to placebo No Nausea I-A Prevention of PONV: Granisetron Versus Placebo Wilson et al. BJA 1996;76:515-518 * * *p 0.001 compared to placebo Total Control I-A Treatment of PONV: Granisetron Versus Placebo Taylor et al. JCA. 1997:9;658-663 * * * *p 0.001 compared to placebo No Vomiting I-A Treatment of PONV: Granisetron Versus Placebo Taylor et al. JCA. 1997:9;658-663 * * *p 0.005 compared to placebo No Nausea I-A Evidence Rating for Antiemetics Strength of EvidenceTreatment Consequences* PreventionTreatmentPreventionTreatment Ondansetron 4 mgI-AI-A5.5 6.53.2 3.9 Ondansetron 1 mg-I-A-3.8 4.8 Dolasetron 12.5 mgI-AI-A4.0 5.03.6 4.2 Granisetron 1 mgI-AI-A3.1 4.23.1 3.8 DroperidolI-A-4.3 5.0? *NNT Prevention of PONV: Ondansetron Versus Droperidol Fortney et al. Anesth Analg 1998;86:731-738 Complete Response * * * * * * * p 0 .05 compared to placebo p 0.05 compared to ondansetron 4 mg p ,0.05 compared to droperidol 0.625 mg I-A Prevention of PONV: Ondansetron Versus Droperidol Fortney et al. Anesth Analg 1998;86:731-738 No Nausea * p 0 .05 compared to placebo p 0.05 compared to droperidol 0.625 mg and ondansetron 4 mg I-A Evidence Rating for Antiemetics Strength of EvidenceTreatment Consequences* PreventionTreatmentPreventionTreatment Ondansetron 4 mgI-AI-A5.5 6.53.2 3.9 Ondansetron 1 mg-I-A-3.8 4.8 Dolasetron 12.5 mgI-AI-A4.0 5.03.6 4.2 Granisetron 1 mgI-AI-A3.1 4.23.1 3.8 DroperidolI-A-4.3 5.0? DexamethasoneII-A-4.3 7.1- *NNT Prevention of PONV: Dexamethasone n“In conclusion, in the surgical setting, a single prophylactic dose of dexamethasone is antiemetic compared with placebo without evidence of clinically relevant toxicity in otherwise healthy patients. Late efficacy (i.e., Up to 24 hours) seems to be most pronounced.” Henzi I, Walder B, and Tramer, MR. Dexamethasone for the prevention of postoperative nausea and vomiting: a quantitative systematic review. Anesth Analg 2000;90:186-194 Eberhart LH. Morin AM. Georgieff M. Dexamethasone for prophylaxis of postoperative nausea and vomiting. A meta-analysis of randomized controlled studies. Anaesthesist. 2000 ;49:713-20 II-A Evidence Rating for Antiemetics Strength of EvidenceTreatment Consequences* PreventionTreatmentPreventionTreatment Ondansetron 4 mgI-AI-A5.5 6.53.2 3.9 Ondansetron 1 mg-I-A-3.8 4.8 Dolasetron 12.5 mgI-AI-A4.0 5.03.6 4.2 Granisetron 1 mgI-AI-A3.1 4.23.1 3.8 DroperidolI-A-4.3 5.0? DexamethasoneII-A-4.3 7.1- DimenhydrinateII-AV-B4.8 8.0? *NNT Prevention of PONV: Dimenhydrinate Early (0-6 h)Overall (0-48 h) OutcomeTrialsNNTTrialsNNT PONV88.3165.0 Vomiting67.7144.8 Nausea28.375.9 Kranke, et al. Acta Anaesth Scand 2002;46:238-244 II-A Evidence Rating for Antiemetics Strength of EvidenceTreatment Consequences* PreventionTreatmentPreventionTreatment Ondansetron 4 mgI-AI-A5.5 6.53.2 3.9 Ondansetron 1 mg-I-A-3.8 4.8 Dolasetron 12.5 mgI-AI-A4.0 5.03.6 4.2 Granisetron 1 mgI-AI-A3.1 4.23.1 3.8 DroperidolI-A-4.3 5.0? DexamethasoneII-A-4.3 7.1- DimenhydrinateII-AV-B4.8 8.0? PromethazineIII-BV-B? *NNT Prevention of PONV: Promethazine Khalil et al. JCA 1999;11:596-600 * *p 0.05 compared to placebo No Vomiting III-B Prevention of PONV: Promethazine Khalil et al. JCA 1999;11:596-600 * *p 0.05 compared to placebo No Nausea * III-B Prevention of PONV: Promethazine Khalil et al. JCA 1999;11:596-600 * *p 0.05 compared to placebo Total Response * III-B Evidence Rating for Antiemetics Strength of EvidenceTreatment Consequences* PreventionTreatmentPreventionTreatment Ondansetron 4 mgI-AI-A5.5 6.53.2 3.9 Ondansetron 1 mg-I-A-3.8 4.8 Dolasetron 12.5 mgI-AI-A4.0 5.03.6 4.2 Granisetron 1 mgI-AI-A3.1 4.23.1 3.8 DroperidolI-A-4.3 5.0? DexamethasoneII-A-4.3 7.1- DimenhydrinateII-AV-B4.8 8.0? PromethazineIII-BV-B? Metoclopramide-V-B? *NNT Prevention of PONV: Metoclopramide n“In summary, metoclopramide, although used as an antiemetic for almost 40 years in the prevention of PONV, has no clinically relevant antiemetic effect . . . it is very likely that the doses used in daily clinical practice are too low.” Henzi I, Walder B, and Tramer, MR. Metoclopramide in the prevention of postoperative nausea and vomiting: a quantitative systematic review of randomized, placebo-controlled studies. BJA 1999;83:761-771 II-A Evidence Rating for Antiemetics Strength of EvidenceTreatment Consequences* PreventionTreatmentPreventionTreatment Ondansetron 4 mgI-AI-A5.5 6.53.2 3.9 Ondansetron 1 mg-I-A-3.8 4.8 Dolasetron 12.5 mgI-AI-A4.0 5.03.6 4.2 Granisetron 1 mgI-AI-A3.1 4.23.1 3.8 DroperidolI-A-4.3 5.0? DexamethasoneII-A-4.3 7.1- DimenhydrinateII-AV-B4.8 8.0? PromethazineIII-BV-B? Metoclopramide-V-B-? Scopolamine patchII-B-5.0 7.0? *NNT Prevention of PONV: Scopolamine Small StudiesLarge Studies OutcomeTrialsNNTTrialsNNT Vomiting 63.355.9 Nausea25.355.0 PONV82.986.7 Rescue43.837.0 Kranke, et al. Anesth Analg 2002;95:133-143 Defined control event rateII-A Prevention of PONV: Scopolamine EventNNH Visual disturbances5.6 Dry mouth12.5 Dizziness50.0 Agitation100.1 Kranke, et al. Anesth Analg 2002;95:133-143 Adverse Events II-A Evidence Rating for Antiemetics Strength of EvidenceTreatment Consequences* PreventionTreatmentPreventionTreatment Ondansetron 4 mgI-AI-A5.5 6.53.2 3.9 Ondansetron 1 mg-I-A-3.8 4.8 Dolasetron 12.5 mgI-AI-A4.0 5.03.6 4.2 Granisetron 1 mgI-AI-A3.1 4.23.1 3.8 DroperidolI-A-4.3 5.0? DexamethasoneII-A-4.3 7.1- DimenhydrinateII-AV-B4.8 8.0? PromethazineIII-BV-B? Metoclopramide-V-B-? Scopolamine patchII-B-5.0 7.0? *NNT Prevention of PONV: Combination Therapy nMcKenzie R, et al. Comparison of ondansetron with ondansetron plus dexamethasone in the prevention of postoperative nausea and vomiting. Anesth Analg 1994;79:961-964 nLopez-Olaondo L, et al. Combination of ondansetron and dexamethasone in the prophylaxis of postoperative nausea and vomiting. BJA 1996;76:835 -840 nEberhart LH. Morin AM. Georgieff M. Dexamethasone for prophylaxis of postoperative nausea and vomiting. A meta-analysis of randomized controlled studies. Anaesthetist. 2000 ;49:713-20 (meta analysis) Ondansetron/Dexamethasone III-A Prevention of PONV: Combination Therapy nPueyo FJ, et al. Combination of ondansetron and droperidol in the prophylaxis of postoperative nausea and vomiting. Anesth Analg 1996;83:117-122 nMcKenzie R, et al. Droperidol/ondansetron combination controls nausea and vomiting after tubal banding. Anesth Analg 1996;83:1218-1222 nKlockgether-Radke A, et al. Ondansetron, droperidol and their combination for the prevention of post-operative vomiting in children. Eur J Anesthesiology. 1997;14:362-367 nEberhart LH. Morin AM. Bothner U. Georgieff M. Droperidol and 5HT3- receptor antagonists, alone or in combination, for prophylaxis of postoperative nausea and vomiting. A meta-analysis of randomized controlled trials. Acta Anaesthesiologica scandinavica. 2000;44:1252-7 Ondansetron/Droperidol III-A Prevention of PONV: Combination Therapy Which Combination? Event 5-HT3 + drop5-HT3 + dex NRateNRateP-valueOR Early Nausea 13817%26011%0.121.6 Vomiting 3181%4191%1.001.0 Late Nausea 35827%62321%*0.021.4 Vomiting 4439%8139%1.000.9 Ashraf et al. Anesthesiology 2001; 95:A-41 Prevention of PONV: Timing of Administration nSun et al. The effect of timing on ondansetron administration in outpatients undergoing otolaryngologic surgery. Anesth Analg 1997;84:331-336 nChen et al. The effect of timing of dolasetron administration on its efficacy as a prophylactic antiemetic in the ambulatory setting. Anesth Analg 2001;93:906-911 nWang et al. The effect of timing of dexamethasone administration on its efficacy as a prophylactic antiemetic for postoperative nausea and vomiting. Anesth Analg 2000;91;136- 139 Ondansetron III-A Dexamethasone III-A Dolasetron III-A Breakthrough PONV: Repeat Dosing With Ondansetron Kovac et al. J. Clin Anesth 1999;11:453-459 * * p = 0.074 p = 0.342 I-A Topics nRisk factors nPharmacologic approaches to management nAdjuvants (nonpharmacologic) Management of PONV: Adjuvants (Nonpharmacologic) nP-6 acupuncture point stimulation III-A nSupplemental oxygen III-C nAggressive perioperative rehydration III-A nPreemptive analgesia IV-A Topics nRisk factors nPharmacologic approaches to management nAdjuvants (nonpharmacologic) nEfficacy versus outcome Efficacy Versus Outcome If efficacy alone is an appropriate endpoint when evaluating analgesics, why isnt efficacy a valid endpoint when evaluating antiemetics? Topics nRisk factors nPharmacologic approaches to management nAdjuvants (nonpharmacologic) nEfficacy versus outcome nPrevention versus treatment Prevention versus Treatment Frequency of PACU Treatment by Risk Factors and Group Scuderi et al. Anesthesiology. 1999;90:360-371 Prevention Versus Treatment Routine administration of prophylactic antiemetics does reduce the incidence of emesis both before and after discharge; however, it did not improve any of the measures of outcome following outpatient surgery except in patients at the highest risk for symptoms. Scuderi et al. Anesthesiology. 1999;90:360-371 IA, IIIA Topics nRisk factors nPharmacologic approaches to management nAdjuvants (nonpharmacologic) nEfficacy versus outcome nPrevention versus treatment nPostdischarge nausea and vomiting Post Discharge Symptoms Following Ambulatory Surgery SymptomIncidence (%) Pain45 Nausea17 Vomiting8 Headache17 Drowsiness42 Dizziness18 Fatigue21 Wu CL, et al. Anesthesiology 2002;96:994-1003 Postdischarge Vomiting: Ondansetron Versus Placebo ODTPlaceboP-value Patients3030 Predischarge emesis3%0%n.s Predischarge nausea40%37%n.s Postd