post op n and v anesthesia
TRANSCRIPT
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Prevention and Treatment of Postoperative Nausea and Vomiting
Phillip E. Scuderi, M.D.Department of AnesthesiologyWake Forest University School of MedicineWinston-Salem, NC 27157-1009
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Critical Evaluation of Data
Quality of individual clinical trials Evaluation of data in aggregate Estimation of treatment consequences
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Evidence Based MedicineRating 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. Nonrandomized controlled trial or case report
V. Expert opinion
Strength of Recommendation based on expert opinion
A. Good evidence to support the recommendation
B. Fair evidence to support the recommendation
C. Insufficient evidence to recommend for or against
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Measures of Treatment Consequences
Relative Risk Reduction The 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 and
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
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Measures of Treatment Consequences
Numbers Needed to be Treated
Relative Risk Reduction
0.5 - 0.300.50
= 0.40
Odds Ratio
[0.30 / (1 - 0.30)]
[0.50 / (1 - 0.50)] = 0.43
Absolute Risk Reduction
0.5 - 0.3 = 0.20 1 0.5 - 0.3
= 5
Placebo = 0.50Treatment = 0.30
Rates of Adverse Events
Laupacis et al. NEJM 1988;318:1728-1733
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Chemoreceptor Receptor Zone
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Pharmacologic Group Dopamine (D2) Muscarinic Cholinergic Histamine Serotonin
Anticholinergics Scopolamine + ++++ + –
Antihistamines Cyclizine Dimenhydrinate Diphenhydramine Hydroxyzine Medizine Promethazine
+++++++
++++++++++++++
++++++++++++++++++++++++
––––––
Antiserotonins Dolasetron Granisetron Ondansetron Ramosetron
––––
––––
––––
++++++++++++++++
Benzamides Domperidone Metoclopramide
+++++++
––
––
+++
Butyrophenones Droperidol Haloperidol
++++++++
––
++
+–
Phenothiazines Chlorpromazine Fluphenazine Perphenazine Prochlorperazine
++++++++++++++++
++
+++++
++++++++++
–+++
Steroids Betamethasone Dexamethasone
––
––
––
––
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Currently Available Medications
5HT3 (serotonin) antagonists - ondansetron Butyrophenones - droperidol Benzamides - metoclopramide Antihistamines - promethazine, dimenhydrinate Steroids - dexamethasone Phenothiazines- promethazine, prochlorperazine Anticholinergics – scopolamine
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Evidence Rating for Antiemetics
Strength of Evidence Treatment Consequences*
Prevention Treatment Prevention Treatment
Ondansetron 4 mg I-A I-A 5.5 – 6.5 3.2 – 3.9
*NNT
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Prevention of PONV:Ondansetron Versus Placebo
62
76 77
46
0
20
40
60
80
100
Placebo 1 mg 4 mg 8 mg
Ondansetron Dose
% o
f P
atie
nts
wit
h N
o E
mes
is
McKenzie et al. Anesthesiology 1993;78:21-28
All patients, 0 - 24 hrs
*
† †
* p = 0.010† p < 0.001
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Ondansetron Dose Response:Prevention
Dose of Ondansetron
Early Efficacy (0 - 6 hrs)
Late Efficacy (0 - 48 hrs)
1 mg 9.0 15
4 mg 5.5 6.5
8 mg 6.5 5.0
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
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Evidence Rating for Antiemetics
Strength of Evidence Treatment Consequences*
Prevention Treatment Prevention Treatment
Ondansetron 4 mg I-A I-A 5.5 – 6.5 3.2 – 3.9
Ondansetron 1 mg - I-A - 3.8 – 4.8
*NNT
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Treatment of PONV:Ondansetron Versus Placebo
32
20
57
40
60
45 44
57
0
20
40
60
80
100
0 - 2 hr 2 - 24 hr
% w
ith
Com
plet
e R
espo
nse
Placebo 1 mg 4 mg 8 mg
Scuderi et al. Anesthesiology 1993;78:2-5Hantler et al. Anesthesiology 1992;77:A16
** *
* **
* p < 0.001
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Ondansetron Dose Response:Treatment
Dose of Ondansetron
Early Efficacy (0 - 6 hrs)
Late Efficacy (0 - 24 hrs)
1 mg 3.8 4.8
4 mg 3.2 3.9
8 mg 3.1 4.1
All three doses significantly different than placebo 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
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Evidence Rating for Antiemetics
Strength of Evidence Treatment Consequences*
Prevention Treatment Prevention Treatment
Ondansetron 4 mg I-A I-A 5.5 – 6.5 3.2 – 3.9
Ondansetron 1 mg - I-A - 3.8 – 4.8
Dolasetron 12.5 mg I-A I-A 4.0 – 5.0 3.6 – 4.2
*NNT
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Prevention of PONV:Dolasetron Versus Placebo
31 28 33
50 465252
39
5543
56 57
0
20
40
60
80
100
All Patients Previous PONV No PONV
Com
ple
te R
esp
onse
%
Placebo 12.5 mg 25 mg 50 mg
*p < 0.0003 compared to placeboGraczyk et al. Anesth Analg 1997;84:325-330
***
****
* *
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Treatment of PONV:Dolasetron Versus Placebo
27
11
55
35
50
28
51
2929
48
0
20
40
60
80
100
0 - 2 hrs 0 - 24 hrs
Com
ple
te R
esp
onse
%
Placebo 12.5 mg 25 mg 50 mg 100 mg
*p < 0.001 compared to placeboKovac et al. Anesth Analg 1997;85:546-552
****
** * *
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Evidence Rating for Antiemetics
Strength of Evidence Treatment Consequences*
Prevention Treatment Prevention Treatment
Ondansetron 4 mg I-A I-A 5.5 – 6.5 3.2 – 3.9
Ondansetron 1 mg - I-A - 3.8 – 4.8
Dolasetron 12.5 mg I-A I-A 4.0 – 5.0 3.6 – 4.2
Granisetron 1mg I-A I-A 3.1 – 4.2 3.1 – 3.8
*NNT
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Prevention of PONV:Granisetron Versus Placebo
49.658.3
78.4 76.6
33.844.7
63.4 61.7
0102030405060708090
100
Placebo 0.1 mg 1.0 mg 3.0mg
% P
atie
nts
0-6 hr 0-24 hr
Wilson et al. BJA 1996;76:515-518
* *
*p < 0.001 compared to placebo
No Vomiting
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Prevention of PONV:Granisetron Versus Placebo
34.6 38.6
63.457
21.828
5042.2
0102030405060708090
100
Placebo 0.1 mg 1.0 mg 3.0mg
% P
atie
nts
0-6 hr 0-24 hr
Wilson et al. BJA 1996;76:515-518
* *
*p < 0.001 compared to placebo
No Nausea
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Prevention of PONV:Granisetron Versus Placebo
31.637.1
63.454.7
1826.5
49.342.2
0102030405060708090
100
Placebo 0.1 mg 1.0 mg 3.0mg
% P
atie
nts
0-6 hr 0-24 hr
Wilson et al. BJA 1996;76:515-518
* *
*p < 0.001 compared to placebo
Total Control
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Treatment of PONV:Granisetron Versus Placebo
26.3
53.157.9 60
19.6
38.345.9 48.8
0102030405060708090
100
Placebo 0.1 mg 1.0 mg 3.0mg
% P
atie
nts
0-6 hr 0-24 hr
Taylor et al. JCA. 1997:9;658-663
* * *
*p < 0.001 compared to placebo
No Vomiting
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Treatment of PONV:Granisetron Versus Placebo
16.6
39.8 40.6 42.4
12.8
26.6 30.136.8
0102030405060708090
100
Placebo 0.1 mg 1.0 mg 3.0mg
% P
atie
nts
0-6 hr 0-24 hr
Taylor et al. JCA. 1997:9;658-663
* * *
*p < 0.005 compared to placebo
No Nausea
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Evidence Rating for Antiemetics
Strength of Evidence Treatment Consequences*
Prevention Treatment Prevention Treatment
Ondansetron 4 mg I-A I-A 5.5 – 6.5 3.2 – 3.9
Ondansetron 1 mg - I-A - 3.8 – 4.8
Dolasetron 12.5 mg I-A I-A 4.0 – 5.0 3.6 – 4.2
Granisetron 1 mg I-A I-A 3.1 – 4.2 3.1 – 3.8
Droperidol I-A - 4.3 – 5.0 ?
*NNT
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Prevention of PONV:Ondansetron Versus Droperidol
4636
63
48
6956 53
62
0
20
40
60
80
100
0 - 2 hr 0 - 24 hr
% o
f P
atie
nts
Placebo Droperidol 0.625 mg Droperidol 1.25 mg Ondansetron 4 mg
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
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Prevention of PONV:Ondansetron Versus Droperidol
2329
4329
0
20
40
60
80
100
0 - 24 hr
% o
f Pa
tient
s
Placebo Droperidol 0.625 mg Droperidol 1.25 mg Ondansetron 4 mg
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
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Droperidol FDA Box Warning
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Droperidol Adverse Events Reports
273 “reports” from 1997-2001 127 serious adverse events 89 total deaths Droperidol 1.25 mg or less
10 cases 5 VT/VF 2 deaths
Habib et al. Anesth Analg 2003;96:1377-1379
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Droperidol and QTc Prolongation
Effect of Low-dose Droperidol on the QT Interval during and after General AnesthesiaWhite et al. Anesthesiology 2005; 102:1101-1105
Prolongation of QTc Interval after Postoperative Nausea and Vomiting Treatment by Droperidol or OndansetronCharbit et al. Anesthesiology 2005; 102:1094-1100
You (Still) Can’t Disprove the Existence of DragonsScuderi. Anesthesiology 2005; 102:1081-1082
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Droperidol:The FDA Box Warning
Droperidol has been used for over 40 years Why a problem now? No evidence of adverse events in published trials No published case reports An association does not prove cause and effect If prolonged QTc is an issue then 5HT3 antagonists
should also carry the same warning At least 3 cases of VT associated with 5HT3
administration No “denominator” provided (or available)
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BOGUS!
Droperidol FDA Box Warning
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Evidence Rating for Antiemetics
Strength of Evidence Treatment Consequences*
Prevention Treatment Prevention Treatment
Ondansetron 4 mg I-A I-A 5.5 – 6.5 3.2 – 3.9
Ondansetron 1 mg - I-A - 3.8 – 4.8
Dolasetron 12.5 mg I-A I-A 4.0 – 5.0 3.6 – 4.2
Granisetron 1 mg I-A I-A 3.1 – 4.2 3.1 – 3.8
Droperidol I-A - 4.3 – 5.0 ?
Dexamethasone II-A - 4.3 – 7.1 -
*NNT
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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.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
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Evidence Rating for Antiemetics
Strength of Evidence Treatment Consequences*
Prevention Treatment Prevention Treatment
Ondansetron 4 mg I-A I-A 5.5 – 6.5 3.2 – 3.9
Ondansetron 1 mg - I-A - 3.8 – 4.8
Dolasetron 12.5 mg I-A I-A 4.0 – 5.0 3.6 – 4.2
Granisetron 1 mg I-A I-A 3.1 – 4.2 3.1 – 3.8
Droperidol I-A - 4.3 – 5.0 ?
Dexamethasone II-A - 4.3 – 7.1 -
Dimenhydrinate II-A V-B 4.8 – 8.0 ?
*NNT
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Prevention of PONV:Dimenhydrinate
Early (0-6 h) Overall (0-48 h)
Outcome Trials NNT Trials NNT
PONV 8 8.3 16 5.0
Vomiting 6 7.7 14 4.8
Nausea 2 8.3 7 5.9
Kranke, et al. Acta Anaesth Scand 2002;46:238-244
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Evidence Rating for Antiemetics
Strength of Evidence Treatment Consequences*
Prevention Treatment Prevention Treatment
Ondansetron 4 mg I-A I-A 5.5 – 6.5 3.2 – 3.9
Ondansetron 1 mg - I-A - 3.8 – 4.8
Dolasetron 12.5 mg I-A I-A 4.0 – 5.0 3.6 – 4.2
Granisetron 1 mg I-A I-A 3.1 – 4.2 3.1 – 3.8
Droperidol I-A - 4.3 – 5.0 ?
Dexamethasone II-A - 4.3 – 7.1 -
Dimenhydrinate II-A V-B 4.8 – 8.0 ?
*NNT
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Evidence Rating for Antiemetics
Strength of Evidence Treatment Consequences*
Prevention Treatment Prevention Treatment
Ondansetron 4 mg I-A I-A 5.5 – 6.5 3.2 – 3.9
Ondansetron 1 mg - I-A - 3.8 – 4.8
Dolasetron 12.5 mg I-A I-A 4.0 – 5.0 3.6 – 4.2
Granisetron 1 mg I-A I-A 3.1 – 4.2 3.1 – 3.8
Droperidol I-A - 4.3 – 5.0 ?
Dexamethasone II-A - 4.3 – 7.1 -
Dimenhydrinate II-A - 4.8 – 8.0 ?
Metoclopramide - IV-B - ?
*NNT
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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 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
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Evidence Rating for Antiemetics
Strength of Evidence Treatment Consequences*
Prevention Treatment Prevention Treatment
Ondansetron 4 mg I-A I-A 5.5 – 6.5 3.2 – 3.9
Ondansetron 1 mg - I-A - 3.8 – 4.8
Dolasetron 12.5 mg I-A I-A 4.0 – 5.0 3.6 – 4.2
Granisetron 1 mg I-A I-A 3.1 – 4.2 3.1 – 3.8
Droperidol I-A - 4.3 – 5.0 ?
Dexamethasone II-A - 4.3 – 7.1 -
Dimenhydrinate II-A - 4.8 – 8.0 ?
Metoclopramide - V-B - ?
Scopolamine patch II-B - 5.0 – 7.0 ?
*NNT
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Prevention of PONV:Scopolamine
Small Studies Large Studies
Outcome Trials NNT Trials NNT
Vomiting 6 3.3 5 5.9
Nausea 2 5.3 5 5.0
PONV 8 2.9 8 6.7
Rescue 4 3.8 3 7.0
Kranke, et al. Anesth Analg 2002;95:133-143
Defined control event rate
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Prevention of PONV:Scopolamine
Event NNH
Visual disturbances 5.6
Dry mouth 12.5
Dizziness 50.0
Agitation 100.1
Kranke, et al. Anesth Analg 2002;95:133-143
Adverse Events
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Evidence Rating for Antiemetics
Strength of Evidence Treatment Consequences*
Prevention Treatment Prevention Treatment
Ondansetron 4 mg I-A I-A 5.5 – 6.5 3.2 – 3.9
Ondansetron 1 mg - I-A - 3.8 – 4.8
Dolasetron 12.5 mg I-A I-A 4.0 – 5.0 3.6 – 4.2
Granisetron 1 mg I-A I-A 3.1 – 4.2 3.1 – 3.8
Droperidol I-A - 4.3 – 5.0 ?
Dexamethasone II-A - 4.3 – 7.1 -
Dimenhydrinate II-A - 4.8 – 8.0 ?
Metoclopramide - IV-B - ?
Scopolamine patch II-B - 5.0 – 7.0 ?
*NNT
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Ondansetron and DolasetronPerception versus Reality
Browning BA, Fort CA, Kemp KD, Shimata MF, Strube MD: Ondansetron versus dolasetron: a comparison study in the prevention of postoperative nausea and vomiting in patients undergoing gynecological procedures. AANA.J. 2004; 72: 129-32
Karamanlioglu B, Turan A, Memis D, Sut N: Comparison of oral dolasetron and ondansetron in the prophylaxis of postoperative nausea and vomiting in children. Eur.J.Anaesthesiol. 2003; 20: 831-5
Olutoye O, Jantzen EC, Alexis R, Rajchert D, Schreiner MS, Watcha MF: A comparison of the costs and efficacy of ondansetron and dolasetron in the prophylaxis of postoperative vomiting in pediatric patients undergoing ambulatory surgery. Anesth.Analg. 2003; 97: 390-6
Walker JB: Efficacy of single-dose intravenous dolasetron versus ondansetron in the prevention of postoperative nausea and vomiting. Clin.Ther. 2001; 23: 932-8
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Ondansetron and DolasetronPerception versus Reality
Paech MJ, Rucklidge MW, Banks SL, Gurrin LC, Orlikowski CE, Pavy TJ: The efficacy and cost-effectiveness of prophylactic 5-hydroxytryptamine3 receptor antagonists: tropisetron, ondansetron and dolasetron. Anaesth.Intensive Care 2003; 31: 11-7
Sukhani R, Pappas AL, Lurie J, Hotaling AJ, Park A, Fluder E: Ondansetron and dolasetron provide equivalent postoperative vomiting control after ambulatory tonsillectomy in dexamethasone-pretreated children. Anesth.Analg. 2002; 95: 1230-5
Zarate E, Watcha MF, White PF, Klein KW, Sa RM, Stewart DG: A comparison of the costs and efficacy of ondansetron versus dolasetron for antiemetic prophylaxis. Anesth.Analg. 2000; 90: 1352-8
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Prevention of PONV:Combination Therapy
McKenzie R, et al. Comparison of ondansetron 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. 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
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Prevention of PONV:Combination Therapy
Pueyo FJ, et al. Combination of ondansetron and droperidol 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 the 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 trials. Acta Anaesthesiologica scandinavica. 2000;44:1252-7
Ondansetron/Droperidol
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Prevention of PONV:Combination Therapy
Which Combination?
Event
5-HT3 + drop 5-HT3 + dex
N Rate N Rate P-value OR
Early
Nausea 138 17% 260 11% 0.12 1.6
Vomiting 318 1% 419 1% 1.00 1.0
Late
Nausea 358 27% 623 21%* 0.02 1.4
Vomiting 443 9% 813 9% 1.00 0.9Ashraf et al. Anesthesiology 2001; 95:A-41
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Prevention of PONV:Timing of Administration
Sun et al. The effect of timing on ondansetron administration in 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 administration on its efficacy as a prophylactic antiemetic for postoperative nausea and vomiting. Anesth Analg 2000;91;136-139
Ondansetron
Dexamethasone
Dolasetron
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Breakthrough PONV:Repeat Dosing With Ondansetron
43
323428
0
20
40
60
80
100
0 - 2 hours 0 - 24 hours
Per
cen
t C
omp
lete
Res
pon
se
Placebo Ondansetron 4 mg
Kovac et al. J. Clin Anesth 1999;11:453-459
* †
* p = 0.074
† p = 0.342
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Propofol and PONV
Early Late
Nausea Vomiting Any Nausea Vomiting Any
Induction 9.3* 13.7* 20.9 50.1 14.9 NA
Maintenance 8* 9.2* 6.2* 5.8* 10.1* 10
Early Late
Nausea Vomiting Any Nausea Vomiting Any
Induction 5.0* 7.0* 14 28 10 NA
Maintenance 4.7* 4.9* 4.9* 6.1* 8.3* 7.1
All Control Event Rates
20% - 60% Control Event Rate
*Analysis by NNT
Tramer et al. BJA 1997;78:247-255
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Propofol and PONV
Determination of Plasma Concentrations of Propofol Associated with 50% Reduction in Postoperative Nausea
Gan TJ, Glass PSA, Howell ST, Canada AT, et al.Anesthesiology 1997;87:779-784
CACI devise targeted plasma concentrations of 100, 200, 400, and 800 ng/ml
Median plasma concentration associated with antiemetic response - 343 ng/ml
17 mcg/kg/min propofol yields 400 - 540 ng/ml plasma concentration
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Propofol “PCA”
Propofol Patient Controlled Antiemesis is a Safe and Effective Method for Treatment of Postoperative Nausea and Vomiting
Gan TJ, El-Molem H, Ray J, Glass PSA, Anesthesiology 1999; 90:1564-1570
Three medications per delivery: propofol 20mg, propofol 40 mg, or placeboLockout interval 5 min, no maximum dose limitNausea scores were 34% and 40% less than placeboPlacebo group had an 8 and 5 fold increase in risk of emesis and a 5 fold increase in incidence of rescueNo differences in sedationPatients in treatment groups were more satisfied than those in placebo group
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Intravenous Fluid Therapy
0
5
10
15
20
Inci
denc
e %
30 min 60 min DIS Day 1
Time
High Infusion Low Infusion
*
Yogendran S, et al. Anesth Analg 1995;80:682-686
High Infusion = 20 ml/kg
Low Infusion = 2 ml/kg
Incidence on Postop NauseaIII-A
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Intravenous Fluid Therapy
10 ml/kg
n = 71
30 ml/kg
n = 70 P value
Cumulative 48 h
vomiting 25.7 8.6 0.01
nausea, severe 27.1 5.7 0.001
nausea, total 37.1 37.1 0.86
antiemetic use 22.9 11.9 0.146
Manger et al. BJA 2004;93:381-385
All values in percent
III-A
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Intravenous Fluid Therapy
Preoperative Intravenous Fluid Therapy Decreases Postoperative Nausea and Pain in High Risk PatientsMaharaj et al. Anesth Analg 2005; 100:675-682
Frequency of all, moderate, and severe nausea decreased
Overall incidence of PONV decreased
NNT to prevent an occurrence of nausea or vomiting was 3.45
III-A
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NK-1 Antagonists:Prevention
Ondansetron (n=52)
CP122,721 (n=52)
Combination (n=53)
Emesis (24 hr) (%) 18 6 2*
Rescue antiemetics (%) 60 47 44
Median emesis free time 75% of pts. (min)
82 75 362*
Nausea 8 hr (%) 24 hr (%)
76 98
80 96
80 98
Satisfaction with nausea management (%)
81 75 80
Gesztesi Z, Scuderi PE, D’Angelo R, et al. Anesthesiology 2000;93:931-937
III-A
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NK-1 Antagonists:Treatment
2821
5 5
77
50
31 31
0
20
40
60
80
100
2 hr 6 hr 24 hr 72 hr
Time After Treatment
% o
f Pa
tien
ts
Placebo GR205171
Complete Control of Emesis
Diemunsch et al. Anesth Analg 1998;86:S436
21 16
0 0
55
2010 10
0
20
40
60
80
100
2 hr 6 hr 24 hr 72 hr
Time After Treatment
% o
f Pa
tien
ts
Placebo GR205171
Complete Control of Nausea
III-A
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Prevention of PONV:Clonidine
Effects of clonidine on postoperative nausea and vomiting in breast cancer surgery
Oddby-Muhrbeck, Eksborg, Bergendahl, Muhrbeck, et al. Anesthesiology 2002; 96:1109-1111
The efficacy of oral clonidine premedication in the prevention of postoperative vomiting in children following strabismus surgery
Handa, Fujii. Paediatr Anaesth 2001; 11:71-74
Oral clonidine premedication reduces vomiting in children after strabismus surgery. Can J Anaesth 1995; 42: 977––81
Mikawa, Nishina, Maekawa, Asano, Obara. Can J Anaesth 1995; 42: 977-981
III-A
Clonidine 1 mg IV = $55.34
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Prevention of PONV:Clonidine
Effects of clonidine on postoperative nausea and vomiting in breast cancer surgery
Oddby-Muhrbeck, Eksborg, Bergendahl, Muhrbeck, et al. Anesthesiology 2002; 96:1109-1111
The efficacy of oral clonidine premedication in the prevention of postoperative vomiting in children following strabismus surgery
Handa, Fujii. Paediatr Anaesth 2001; 11:71-74
Oral clonidine premedication reduces vomiting in children after strabismus surgery. Can J Anaesth 1995; 42: 977–81
Mikawa, Nishina, Maekawa, Asano, Obara. Can J Anaesth 1995; 42: 977-981
III-A
Clonidine 1 mg IV = $55.34 Clonidine 0.3 mg PO = $0.12
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Prevention of PONV:Haloperidol
Is Low-dose Haloperidol a Useful Antiemetic?Buttner et al. Anesthesiology 2004; 101:1454-1463
Haloperidol 0.5 – 4.0 mg
compared to placebo 0 – 24 hr:
relative benefit: 1.26 – 1.51
NNT: 3.20 – 5.10
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P-6 Acupuncture Point Stimulation
Zarate E, Mingus M, White PF, Chiu JW, Scuderi PE, et al. The use of transcutaneous acupoint electrical stimulation for preventing nausea and vomiting after laparoscopic surgery. Anesth Analg 2001;92:629-35.
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P-6 Stimulation:Control of Nausea
TAES Sham PlaceboPACU 25 17 28
45 min 36 51 32
90 min 27* 51 33
120 min 27 40 41
4 hr 26* 52 35
6 hr 22*† 47 43
9 hr 18*† 42 47
Zarate E, et al. Anesth Analg 2001;92:629-35* compared to sham
† compared to placebo
III-A
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P-6 Acupuncture Point Stimulation
TEAS
n = 26
Ondansetron
n = 25
Placebo
n = 24 P value
Nausea 2 h 19 40 79 <0.0001
Emesis
2 h 12 8 25 0.22
24 h 19 32 46 0.12
Complete Response
2 h 77 64 42 0.01
24 h 73 52 38 0.006
Rescue Antiemetic 19 28 54 0.04
Gan et al. Anesth Analg 2004;99:1070-1075All values in percent
III-A
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Multimodal Management of PONV:Hypothesis
Scuderi at al. Anesth Analg 2000;91:408-414
A multi-modal approach to the management of PONV can result in a zero incidence of vomiting (and perhaps nausea) in the immediate postoperative period (i.e., PACU)
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Multimodal Management of PONV:Algorithm for Management
I. PREOPERATIVE
A. Anxiolysis - 10-30 mcg/kg midazolam
B. Fluid - 10 ml/kg minimum
II. INDUCTION
A. PreO2
B. Droperidol 10 mcg/kg
C. Decadron 8 mg
D. Propofol - 2 mg/kg + 200 mcg/kg/min
E. Remifentanil - 1 mcg/kg + 1 mcg/kg/min
F. Intubate 90-120 seconds
G. Gastric decompression
Scuderi at al. Anesth Analg 2000;91:408-414
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Multimodal Management of PONV: Algorithm for Management
III. MAINTENANCE A. Propofol
200 mcg/kg/min x 5 min, then150 mcg/kg/min x 5 min, then100 mcg/kg/min x 5 min, then75 mcg/kg/min until10 minutes prior to end of surgery, then D/C
B. Remifentanil1 mcg/kg/min until intubated, then0.5 mcg/kg/min until trocar, then0.25 mcg/ kg/min titrated to effect or BISD/C 2-3 minutes prior to end of surgery
C. Ketorolac30 mg IV after induction
D. Ondansetron1 mg at end of surgery
E. Fentanyl25 mcg IV 10 minutes prior to end of surgery
Scuderi at al. Anesth Analg 2000;91:408-414
IV. PACU
A. PONV rescue - Dramamine 25 mg
B. Pain rescue - Fentanyl 25 mcg prn
C. Fluids - 25 ml/kg total for OSC stay
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Multimodal Management:Results
Group I Group II Group III P values
Multimodal Ondansetron Placebo
Patients 60 42 37
Hx Risk Factors (%) 48 64 65 0.17*†
Tx required (%) 2 24 41 <0.0001*†
Vomiting before discharge (%) 0 7 22 0.67* 0.003†
Vomiting after discharge (%) 12 21 32 0.27* 0.02†
Satisfaction with PONV (%) 100 100 92 0.05†‡
Satisfaction score <10 (%)5 6 37
1.00* 0.0013‡
Time to discharge ready (mean)128 162 192
0.0015*; 0.0001†
*Group I vs II; † Group I vs III; Group II vs III‡Scuderi at al. Anesth Analg 2000;91:408-414
III-A
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Multimodal Management of PONV:Simplified Algorithm
I. INDUCTION
A. PreO2
B. Propofol 2 - 4 mg/kg
C. Opioid prn
D. NMB prn
C. Droperidol 10 mcg/kg
D. Decadron 4 - 8 mg
II. MAINTENANCE
A. Propofol 50 mcg/kg/min
B. Potent inhalation agent
C. Nitrous oxide prn
E. NMB reversal prn
III. EMERGENCE
A. Ondansetron 1 mg IV
B. Suction oropharynx
C. Extubate when awake
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Multimodal Management of PONV:Simplified Algorithm
COST ($)
Case duration 1 hour 2 hours 3 hours
Droperidol (10 mcg/kg) $2.10 $2.10 $2.10
Dexamethasone (8 mg) $1.30 $1.30 $1.30
Ondansetron (1 mg) $4.00 $4.00 $4.00
Propofol (50 mcg/kg/min)
$7.50 $15.00 $22.50
Total Cost $14.90 $22.40 $29.90
Cost Analysis
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PONV Risk Reduction
Intervention % Relative Risk Reduction
Ondansetron 4mg 26.0
Dexamethasone 4mg 26.4
Droperidol 1.25mg 24.5
Propofol vs volatile 18.9
Nitrogen vs Nitrous 12.1
Apfel, et al. NEJM 2004; 350:2441-2451
I-A
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General Recommendations
Use generic drugs for “routine” prophylaxis Treat breakthrough symptoms with 5HT3 antagonists
Don’t repeat dose with 5HT3 antagonists for failure Treat/prevent with different classes of antiemetics For “high risk” patients use combination prophylaxis and
consider “alternative” therapy Consider propofol infusion as part of anesthetic Hydrate aggressively The best chance for “complete response” is a
multimodal approach