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1、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,http:/www.wfubmc.edu/anesthesia pscuderiwfubmc.edu,Hist
2、orical 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,Appearance of control treatment Blinding of randomization process Blinding of patients and observers,
3、Sample size estimate and power analysis Confidence intervals Statistical analyses Withdrawals Side 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,Investigators Improve rigor of study proto
4、cols Improve quality of data analysis Peer Reviewers Process of randomization Power analysis Blinding,Suggestions for Improvement,Greenfield et al. Anesth Analg 2003;96:S88,Critical Evaluation of Data,Quality of individual clinical trials Type and adequacy of controls used Blinding process Sample si
5、ze, power analysis Appropriateness of endpoints chosen Confidence limits particularly for negative studies Statistical analysis,Critical Evaluation of Data,Quality of individual clinical trials Evaluation of data in aggregate,Evidence Based Medicine Rating Scale,Level of evidence based on study desi
6、gn I. Large randomized, controlled trial (n100 per group) II. Systematic review III. Small randomized, controlled trial (n100 per group) IV. Nonrandomized controlled trial or case report V. Expert opinion Strength of Recommendation based on expert opinion A. Good evidence to support the recommendati
7、on B. Fair evidence to support the recommendation C. Insufficient evidence to recommend for or against,Critical Evaluation of Data,Quality of individual clinical trials Evaluation of data in aggregate Estimation of treatment consequences,Measures of Treatment Consequences,Relative Risk Reduction The
8、 reduction of adverse events achieved by a treatment, expressed as a proportion of the control rate Odds Ratio The traditional expression of the relative likelihood of an outcome expressed as P/(1 - P) where P = probability Absolute Risk Reduction The difference in event rates between the control an
9、d treatment groups Numbers Needed to be Treated (NNT) The number of patients who must be treated in order to prevent one adverse event. It is mathematically equivalent to the reciprocal of the absolute risk reduction.,Laupacis et al. NEJM 1988;318:1728-1733,Measures of Treatment Consequences,Laupaci
10、s et al. NEJM 1988;318:1728-1733,Topics,Risk factors Pharmacologic approaches to management Adjuvants (nonpharmacologic) Efficacy versus outcome Prevention versus treatment Postdischarge nausea and vomiting Multimodal management,Topics,Risk factors,Risk Factors,Non-anesthetic factors Anesthetic rela
11、ted factors Postoperative factors,Risk Factors,Age Gender Body habitus Hx motion sickness Hx PONV Anxiety Concomitant disease Operative procedure Duration of surgery,Non-anesthetic Factors,Risk Factors,Preanesthetic medication Gastric distension Gastric suctioning Anesthetic technique Anesthetic age
12、nts,Anesthetic Related Factors,Risk Factors,Pain Dizziness Ambulation Oral intake Opioids,Postoperative Factors,Risk Factors Patient Specific,Palazzo M, Evans R. Logistic regression analysis of fixed patient factors for postoperative sickness: a model for risk assessment. Br J Anaesth 1993;70:135-40
13、.,Koivuranta M, Lr E, Snre L, Alahuhta S. A survey of postoperative nausea and vomiting. Anaesthesia 1997;52:443-49.,Apfel CC, Greim CA, Haubitz I, et al. A risk score to predict the probability of postoperative vomiting in adults. Acta Anaesthesiol Scand 1998;42:495-501.,Logistic Regression,Risk Fa
14、ctors Patient Specific,Younger age Nonsmoking history Female Hx of motion sickness Hx of PONV Increased duration of operation,Logistic Regression,Risk Factors Patient Specific,Female Nonsmoking history Hx of motion sickness or PONV Use of postoperative opioids,Simplified Scoring System,Incidence of
15、PONV,Apfel CC et al. Anesthesiology 1999;91:693-700.,Risk Factors Anesthetic Related,Apfel et al. BJA 2002;88:659-668,* Compared to propofol,Volatile Anesthetics,Risk Factors Anesthetic Related,Nitrous Oxide and PONV,Risk Factors Anesthetic Related,Decreases POV significantly only if the baseline ri
16、sk is high Does not affect nausea or complete control of emesis Increases the incidence of intraoperative awareness,Omitting nitrous oxide from general anesthesia:,Tramer et al. BJA 1996;76:186-193,Nitrous Oxide and PONV,Risk Factors Surgical Risk Factors,Duration of Surgery,Type of Surgery,Apfel et
17、 al. BJA 2002;88:659-668 Sinclair et al. Anesthesiology 1999; 91:109-118,Sinclair et al. Anesthesiology 1999; 91:109-118 Apfel et al. BJA 2002;88:659-668 Fabling et al. Anesth Analg 2000;91:358-361 Gan et al. Anesthesiology 1996;85:1036-1042,Evidence Based Medicine Risk Factors for PONV in Adults,Pa
18、tient-specific factors Female gender (I-A) Nonsmoking status (IV-A) History of PONV/motion sickness (IV-A) Anesthetic risk factors Use of volatile anesthetics (I-A) Nitrous oxide (II-A) Intraoperative opioids (II-A) Postoperative opioids (IV-A) Surgical risk factors Duration of surgery (IV-A) Type o
19、f surgery (IV-B),Gan et al. et al. Anesth Analg 2003; 97:62-71,Topics,Risk factors Pharmacologic approaches to management,Currently Available Medications,5HT3 (serotonin) antagonists - ondansetron Butyrophenones - droperidol Benzamides - metoclopramide Antihistamines - promethazine, dimenhydrinate S
20、teroids - dexamethasone Phenothiazines- promethazine, prochlorperazine Anticholinergics scopolamine,Evidence Rating for Antiemetics,*NNT,Prevention of PONV: Ondansetron Versus Placebo,McKenzie et al. Anesthesiology 1993;78:21-28,All patients, 0 - 24 hrs,*,* p = 0.010 p 0.001,I-A,Ondansetron Dose Res
21、ponse: Prevention,Only 4 mg and 8 mg were significantly different than placebo No further improvement with doses 8 mg,Numbers Needed to be Treated,Tramer et al. Anesthesiology 1997;87:1277-1289,II-A,Evidence Rating for Antiemetics,*NNT,Treatment of PONV: Ondansetron Versus Placebo,Scuderi et al. Ane
22、sthesiology 1993;78:2-5 Hantler et al. Anesthesiology 1992;77:A16,*,*,*,*,*,*,* p 0.001,I-A,Ondansetron Dose Response: Treatment,All three doses significantly different than placebo No significant difference in antiemetic efficacy between the three doses of ondansetron,Numbers Needed to be Treated,T
23、ramer et al. BMJ 1997;314:1088-1092,II-A,Evidence Rating for Antiemetics,*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
24、et al. Anesth Analg 1997;85:546-552,*,*,*,*,*,*,*,*,I-A,Evidence Rating for Antiemetics,*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-
25、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
26、 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,*NNT,Prevention of PONV: Ondansetron Versus Droperidol,Fortney et al. Anesth Analg 1998;86:731-738,Complete Response,*,*,*,*,
27、*,*,* 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 ondansetr
28、on 4 mg,I-A,Evidence Rating for Antiemetics,*NNT,Prevention of PONV: Dexamethasone,“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
29、.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 postoperati
30、ve nausea and vomiting. A meta-analysis of randomized controlled studies. Anaesthesist. 2000 ;49:713-20,II-A,Evidence Rating for Antiemetics,*NNT,Prevention of PONV: Dimenhydrinate,Kranke, et al. Acta Anaesth Scand 2002;46:238-244,II-A,Evidence Rating for Antiemetics,*NNT,Prevention of PONV: Prometh
31、azine,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,
32、Total Response,*,III-B,Evidence Rating for Antiemetics,*NNT,Prevention of PONV: Metoclopramide,“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
33、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,*NNT,Prevention of PONV: Scop
34、olamine,Kranke, et al. Anesth Analg 2002;95:133-143,Defined control event rate,II-A,Prevention of PONV: Scopolamine,Kranke, et al. Anesth Analg 2002;95:133-143,Adverse Events,II-A,Evidence Rating for Antiemetics,*NNT,Prevention of PONV: Combination Therapy,McKenzie R, et al. Comparison of ondansetro
35、n with ondansetron plus dexamethasone in the prevention of postoperative nausea and vomiting. Anesth Analg 1994;79:961-964 Lopez-Olaondo L, et al. Combination of ondansetron and dexamethasone in the prophylaxis of postoperative nausea and vomiting. BJA 1996;76:835-840 Eberhart LH. Morin AM. Georgief
36、f 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,Pueyo FJ, et al. Combination of ondansetron and droperidol
37、in the prophylaxis of postoperative nausea and vomiting. Anesth Analg 1996;83:117-122 McKenzie R, et al. Droperidol/ondansetron combination controls nausea and vomiting after tubal banding. Anesth Analg 1996;83:1218-1222 Klockgether-Radke A, et al. Ondansetron, droperidol and their combination for t
38、he prevention of post-operative vomiting in children. Eur J Anesthesiology. 1997;14:362-367 Eberhart 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
39、 trials. Acta Anaesthesiologica scandinavica. 2000;44:1252-7,Ondansetron/Droperidol III-A,Prevention of PONV: Combination Therapy,Which Combination?,Ashraf et al. Anesthesiology 2001; 95:A-41,Prevention of PONV: Timing of Administration,Sun et al. The effect of timing on ondansetron administration i
40、n outpatients undergoing otolaryngologic surgery. Anesth Analg 1997;84:331-336 Chen 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 Wang et al. The effect of timing of dexamethasone administ
41、ration 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,Top
42、ics,Risk factors Pharmacologic approaches to management Adjuvants (nonpharmacologic),Management of PONV: Adjuvants (Nonpharmacologic),P-6 acupuncture point stimulation III-A Supplemental oxygen III-C Aggressive perioperative rehydration III-A Preemptive analgesia IV-A,Topics,Risk factors Pharmacolog
43、ic approaches to management Adjuvants (nonpharmacologic) Efficacy 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,Risk factors Pharmacologic approaches to management
44、 Adjuvants (nonpharmacologic) Efficacy versus outcome Prevention 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 reduc
45、e 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,Risk factors Pharmacologic approaches
46、 to management Adjuvants (nonpharmacologic) Efficacy versus outcome Prevention versus treatment Postdischarge nausea and vomiting,Post Discharge Symptoms Following Ambulatory Surgery,Wu CL, et al. Anesthesiology 2002;96:994-1003,Postdischarge Vomiting: Ondansetron Versus Placebo,Gan TJ, et al. Anest
47、h Analg 2002;94:1199-1200,* p0.05,III-A,Topics,Risk factors Pharmacologic approaches to management Adjuvants (nonpharmacologic) Efficacy versus outcome Prevention versus treatment Postdischarge nausea and vomiting Multimodal management,Multimodal Management: Results,*Group I vs II; Group I vs III; G
48、roup II vs III,Scuderi at al. Anesth Analg 2000;91:408-414,III-A,Topics,Risk factors Pharmacologic approaches to management Adjuvants (nonpharmacologic) Efficacy versus outcome Prevention versus treatment Postdischarge nausea and vomiting Multimodal management,General Recommendations,Use generic dru
49、gs for “routine” prophylaxis Treat breakthrough symptoms with 5HT3 antagonists Dont repeat dose with 5HT3 antagonists for failure Treat with different classes of antiemetics For high risk patients use combination prophylaxis Consider propofol infusion as part of anesthetic Prevent and control pain, hydrate aggressively Consider post-discharge therapy,