the meta-analysis (Gupta

A,Wu,CL,Elkassabani,N,Krug,CE,Parker,SD,Fleisher LA.Does the routine
prophylactic use of antieme...
PONV

Servizio di Anestesia e Rianimazione Ospedale di Faenza(RA)
Hill RP, Lubarsky DA, Phillips-Bute B, Fortney JT, Creed MR, Glass PSA,
Gan TJ: Cost-effectiveness of prophylactic antieme...
What drug should be used for PONV prophylaxis in high-risk patients? A more expensive drug
may be preferred and reduce tot...
Postoperative Nausea and Vomiting:
Prevention and Treatment
Claudio Melloni
Anestesia e Rianimazione
Ospedale degli Inferm...
AUTHOR(S): Watcha, Mehernoor F., M.D.
Anesthesiology
92:931-3, 2000

Servizio di Anestesia e Rianimazione Ospedale di Faen...
Topics
Importance of the issue
Risk factors
Pharmacologic approaches to management
Adjuvants (nonpharmacologic)
Efficacy v...
Methodological questions(from Visserer
et al…)
definitions of PONV:
» nausea only,
» nausea and vomiting
» vomiting only.
...
Importance of the issue
PONV is :
» A limiting factor in the early discharge of ambulatory surgical patients
» The leading...
Macario A, Weinger M,Carney S, Kim A.Which clinical
anesthesia outcomes are important to avoid?
Anesth.Analg.1999;89:652-8...
Sintomi accusati dai pazienti a casa dopo interventi
eseguiti in regime di day surgery(da Wu et
al.,Anesthesiology 2002).
...
Quali problemi preferirebbero evitare i pazienti sottoposti a
day surgery?

(da Jenkins, K.; Grady, D.; Wong, J.; Correa, ...
Beauregard L, Pomp A, Choinière M.
Severity and impact of pain after day-surgery Can J Anaesth
1998 / 45 / 304-11

Servizi...
Sintomi accusati dai pazienti a casa dopo interventi
eseguiti in regime di day surgery(da Wu et
al.,Anesthesiology 2002).
...
Quali problemi preferirebbero evitare i pazienti sottoposti a
day surgery?

(da Jenkins, K.; Grady, D.; Wong, J.; Correa, ...
Beauregard L, Pomp A, Choinière M.
Severity and impact of pain after day-surgery Can J Anaesth
1998 / 45 / 304-11

Servizi...
Can PONV be predicted?
Risk factor analysis

Servizio di Anestesia e Rianimazione Ospedale di Faenza(RA)
Sinclair et al.Can PONV be predicted?
Anesthesiology 1999;91:109-18
17,638 consecutive ambulatory surgical patients;>90% A...
Sinclair et al.Can PONV be predicted?
Anesthesiology 1999;91:109-18
Patients with PONV underwent significantly longer proc...
Sinclair DR, Chung F,Mezei G.Can PONV be predicted?
Anesthesiology 1999;91:109-18
Background: Retrospective studies fail t...
Frequency of PONV by type of anesthesia
and duration of surgery. Sinclair et al.Can PONV be predicted?
Anesthesiology 1999...
PONV prolongs PACU and
amb.surg.unit stay Sinclair et al.Can PONV be
predicted?Anesthesiology 1999;91:109-18

Servizio di ...
Independent predictors of PONV
Sinclair et al.Can PONV be predicted?Anesthesiology 1999;91:109-18

age A 10-yr increase in...
Sinclair et al.Can PONV be predicted?Anesthesiology
1999;91:109-18
In our study, the incidence of PONV was 4.6% in the PAC...
Sinclair et al.Can PONV be predicted?Anesthesiology
1999;91:109-18
Patients undergoing breast augmentation had a 41.5% inc...
Sinclair et al.Can PONV be predicted?Anesthesiology
1999;91:109-18
Among the intraoperative anesthetic drugs, alfentanil a...
Sinclair et al.Can PONV be predicted?Anesthesiology
1999;91:109-18
In this study, sex, age, smoking, previous PONV, type a...
Sinclair et al.Can PONV be predicted?Anesthesiology
1999;91:109-18
Another predictor of PONV is previous PONV, which incre...
Sinclair et al.Can PONV be predicted?Anesthesiology
1999;91:109-18
A well-designed logistic regression model of factors as...
Fitting the model to the data, we can obtain the maximum likelihood estimate of
the parameters for each variable. Based on...
Logistic regression da:Sinclair et al.Can PONV be predicted?
Anesthesiology 1999;91:109-18

P=1/1+e esponente
con il segno...
Importance of the work by
Sinclair et al…
Fitting the model to the data, we can obtain
the maximum likelihood estimate of ...
Appendix 1
Logistic regression is used to model the relation between explanatory variables and binary outcome variables. T...
Risk Factors
Non-anesthetic factors
Anesthetic related factors
Postoperative factors

Servizio di Anestesia e Rianimazione...
Risk factors da Samba 2007:1
Patient specific
Female gender
Non smoking status
Hx of ponv/motion sickness

Servizio di Ane...
Risk factors da Samba 2007:2
Anesthetoc risk factors
Use on intraop volatile anesth
Use on intraop and postop opioids
Use ...
Risk factors da Samba 2007:3
Surgical risk factors
Duration of surgery
Each 30 min increase in duration of surgery
oncreas...
Risk Factors
Non-anesthetic Factors
Age
Gender
Body habitus
Hx motion sickness
Hx PONV
Anxiety
Concomitant disease
Operati...
Risk Factors
Anesthetic Related Factors
Preanesthetic medication
Gastric distension
Gastric suctioning
Anesthetic techniqu...
Risk Factors
Postoperative Factors
Pain
Dizziness
Ambulation
Oral intake
Opioids

Servizio di Anestesia e Rianimazione Osp...
Postoperative Nausea and Vomiting:
Anesthetic Related Factors

Nitrous oxide
Volatile anesthetics
NMB reversal
Propofol

S...
Risk Factors

Nitrous Oxide and PONV
Omission of Nitrous Oxide during Anesthesia Reduces
the Incidence of Postoperative Na...
Risk Factors

Nitrous Oxide and PONV
Omitting nitrous oxide from general anesthesia:
Decreases POV significantly only if t...
Controlled Trial of Total Intravenous Anesthesia with Propofol versus
Inhalation Anesthesia with Isoflurane–Nitrous Oxide ...
Visseret al . Randomized Controlled Trial of Total Intravenous
Anesthesia with Propofol versus Inhalation Anesthesia with ...
Visseret al . Randomized Controlled Trial of Total Intravenous
Anesthesia with Propofol versus Inhalation Anesthesia with ...
Visseret al . Randomized Controlled Trial of Total Intravenous
Anesthesia with Propofol versus Inhalation Anesthesia with ...
Anesthesia with Propofol versus Inhalation Anesthesia with Isoflurane–
Nitrous Oxide Postoperative Nausea and Vomiting and...
PONV %
(Visseret al . Randomized Controlled Trial of Total Intravenous Anesthesia with Propofol versus
Inhalation Anesthes...
Rescue antiemetics
(Visseret al . Randomized Controlled Trial of Total Intravenous Anesthesia with Propofol
versus Inhalat...
Cost analysis
Detailed drug acquisition costs at the time of the
study can be found in the Web Enhancement, ).
shows the i...
The cumulative incidence of PONV was significantly lower after TIVA than after isoflurane. Absolute risk
reduction with TI...
IS PONV incidence different
between LMA and ETT?
Joshi GP, Inagaki Y, White PF, TaylorKennedy L, Wat LI, Gevirtz C,
McCran...
Risk Factors
Volatile anesthetics
Risk Factors

OR*

CI

isoflurane

3.41

2.18; 5.37

sevoflurane

2.78

1.79; 4.31

enfl...
Risk Factors

Reversal of Neuromuscular Block
Omitting neostigmine may have a clinically
relevant antiemetic effect when h...
Risk Factors

Propofol and PONV
Analysis by NNT

All Control Event Rates
Early

Late

Nausea
Induction
Maintenance

Vomiti...
Risk Factors
Antiemetic Effects of Propofol
Investigations

Randomized

Double-Blind

Placebo-Controlled

Effective

Chemo...
Risk Factors
Logistic Regression
Palazzo M, Evans R. Logistic regression analysis of fixed patient factors for
postoperati...
Risk Factors
Logistic Regression
Younger age
Nonsmoking history
Female
Hx of motion sickness
Hx of PONV
Increased duration...
Risk Factors
Simplified Scoring System
Female
Nonsmoking history
Hx of motion sickness or PONV
Use of postoperative opioid...
Simplified scoring system from
Apfel for adults
For every risk factor the sum is additive:
Point 0 risk 10%
Point 1 risk 2...
Servizio di Anestesia e Rianimazione Ospedale di Faenza(RA)
Simplified risk score from Apfel et al. to predict the
patients risk for PONVin adults . When 0, 1, 2, 3, or 4 of the depi...
Simplified scoring system from
Eberhardt 39 di Sambafor
children
Surgery> 30 min
Age> 3
Strabismus surgery
Hx of POV or PO...
Simplified risk score from Eberhart et al. (39) to predict the
risk for POV in children. When 0, 1, 2, 3, or 4 of the depi...
Problems............
to separate independent factors vs
dependent factors................
No risk model can actually predi...
PONV
PONV
fattori di rischio

donne
giovani
giovani
età
età
fertile
fertile
gravide
gravide
post
post
partum
partum

Non
s...
Use of prophylactic antiemetics should be
based on valid assessment of the patients risk
for POV or PONV.
In other words.....
Particular medical risk
more liberal prophylaxis is appropriate for patients in
whom vomiting poses a particular medical r...
Strategies to Reduce Baseline Risk
Avoidance of general anesthesia by the use of regional
anesthesia (11,16) (randomized, ...
Trattamento del PONV

Servizio di Anestesia e Rianimazione Ospedale di Faenza(RA)
Management of PONV:

Pharmacological Approaches
Medications
Dose response
Comparative efficacy
Combination therapy
Timing ...
Servizio di Anestesia e Rianimazione Ospedale di Faenza(RA)
Servizio di Anestesia e Rianimazione Ospedale di Faenza(RA)
Figure 3

Servizio di Anestesia e Rianimazione Ospedale di Faenza(RA)
Servizio di Anestesia e Rianimazione Ospedale di Faenza(RA)
Servizio di Anestesia e Rianimazione Ospedale di Faenza(RA)
Antiemetici
Antiemetici
evoluzione del pensiero
metoclopramide
droperidol
ondansetron

preso dalla gastroenterologia
preso...
PONV
PONV
Recettori coinvolti
ondansetron

butirofenoni::droperidol
butirofenoni::droperidol

metoclopramide
metoclopramid...
Currently Available Medications
5HT3 (serotonin) antagonists - ondansetron
Butyrophenones - droperidol
Benzamides - metocl...
5HT3 Antagonists and PONV
(Summer 2002)
5HT3 Antagonist

Clinical Trials

Ondansetron *

275

Dolasetron*

20

Granisetron...
Prevention of PONV:

Ondansetron Versus Placebo
% of Patients with No Emesis

All patients, 0 - 24 hrs
100
80
60

†
76

4 ...
Ondansetron Dose Response:
Prevention

Numbers Needed to be Treated

Dose of
Ondansetron

Early Efficacy
(0 - 6 hrs)

Late...
Treatment of PONV:

% with Complete Response

Ondansetron Versus Placebo
100
80

*
57

60
40

*

60

*

57

*
40

32

*

4...
Ondansetron Dose Response:
Treatment

Numbers Needed to be Treated

Dose of
Ondansetron

Early Efficacy
(0 - 6 hrs)

Late ...
Breakthrough PONV:

Percent Complete Response

Repeat Dosing With Ondansetron
100
* p = 0.074

80

† p = 0.342

60
43
40

...
Prevention of PONV:

Complete Response %

Dolasetron Versus Placebo
100
80

*
* * 56
* 52 **
50

60
40

31

* * **
*
46 * ...
Treatment of PONV:

Dolasetron Versus Placebo
Complete Response %

Placebo

12.5 mg

25 mg

50 mg

100 mg

100
80
*
*
55

...
Prevention of PONV:

Ondansetron Versus Dolasetron
Placebo

Dolasetron 25 mg

Dolasetron 50 mg

Ondansetron 4 mg

% of Pat...
Prevention of PONV:

Ondansetron Versus Dolasetron
Postoperative Vomiting

% without Symptoms

Dolasetron 12.5 mg

Dolaset...
Prevention of PONV:

Ondansetron Versus Dolasetron
Postoperative Nausea

% without Symptoms

Dolasetron 12.5 mg

Dolasetro...
Prevention of PONV:

Ondansetron Versus Droperidol
Complete Response
Placebo

Droperidol 0.625 mg

Droperidol 1.25 mg

Ond...
Prevention of PONV:

Ondansetron Versus Droperidol
No Nausea

% of Patients

100

* p < 0 .05 compared to placebo
† p < 0....
Droperidol Adverse Events
Reports
273 “reports” from 1997-2001
127 serious adverse events
89 total deaths
Droperidol 2.5 m...
Droperidol

FDA Box Warning
No case details provided
Droperidol has been used for over 40 years
Why a problem now?
No evid...
Putting It in Perspective
Circumstance

Annual Fatalities

Transportation
motor vehicle
pedestrian
cyclists
rail
bus
airli...
Prevention of PONV:
Metoclopramide

“In summary, metoclopramide, although used as an
antiemetic for almost 40 years in the...
Prevention of PONV:
Dexamethasone

“In conclusion, in the surgical setting, a single prophylactic
dose of dexamethasone is...
Prevention of PONV:
Dexamethasone

Dose ranging
Major gynecological surgery
Placeb
1.25 mg
o

2.5
mg

5.0 mg 10.0 mg

Pati...
Prevention of PONV:
Scopolamine

Undefined control event rate
Small Studies
Outcome

Large Studies

Trials

NNT

Trials

N...
Prevention of PONV:
Scopolamine

Defined control event rate
Small Studies
Outcome

Large Studies

Trials

NNT

Trials

NNT...
Prevention of PONV:
Scopolamine

Adverse Events

Event
Visual
disturbances

NNH
5.6

Dry mouth

12.5

Dizziness

50.0

Agi...
Prevention of PONV:
Dimenhydrinate

Early (0-6 h)
Outcome

Overall (0-48 h)

Trials

NNT

Trials

NNT

PONV

8

8.3

16

5...
Prevention of PONV:
Combination Therapy

Ondansetron/Dexamethasone
McKenzie R, et al. Comparison of ondansetron with ondan...
Prevention of PONV:
Combination Therapy

Ondansetron/Droperidol
Pueyo FJ, et al. Combination of ondansetron and droperidol...
Prevention of PONV:
Combination Therapy

Which Combination?
5-HT3 + drop
Event

5-HT3 + dex

N

Rate

N

Rate

P-value

OR...
Prevention of PONV:
Combination Therapy
Placebo

Metoclopramide

Dolasetron

Ondansetron

nausea (%)

13

7

3

3

vomitin...
Prevention of PONV:

Timing of Administration
Ondansetron
Sun et al. The effect of timing on ondansetron administration in...
Tang J,Wang B, White PF,Watcha M,Qi J,Wender R.The effect of timing
of ondansetron administration on its efficacy,cost eff...
Tang J,Wang B, White PF,Watcha M,Qi J,Wender R.The effect of timing
of ondansetron administration on its efficacy,cost eff...
Tang J,Wang B, White PF,Watcha M,Qi J,Wender R.The effect of timing
of ondansetron administration on its efficacy,cost eff...
Tang J,Wang B, White PF,Watcha M,Qi J,Wender R.The effect of timing
of ondansetron administration on its efficacy,cost eff...
Incidence of nausea and vomiting in the Pacu in the 4
treatment groups:placebo,ondansetron 2 mg pre and 2 mg post surg

I
...
Incidence of nausea and vomiting in the 24 hrs post surgery
in the 4 treatment groups:placebo,,ondansetron 2 mg pre and 2 ...
Servizio di Anestesia e Rianimazione Ospedale di Faenza(RA)
Timing of Administration:
Dexamethasone
Group 1

Group 2

Group 3

(Preinduction)

(Postextubation)

(Placebo)

nausea (%)...
Management of PONV:

Adjuvants (Nonpharmacologic)

P-6 acupuncture point stimulation
Supplemental oxygen
Aggressive periop...
P-6 Acupuncture Point
Stimulation
Zarate E, Mingus M, White PF, Chiu JW, Scuderi
PE, et al. The use of transcutaneous acup...
P-6 Acupuncture Point
Stimulation
Control of Nausea

TAES

Sham

Placebo

PACU

25

17

28

45 min

36

51

32

90 min

27...
Supplemental Oxygen
Greif R, Laciny S, Rapf B, et al. Supplemental
oxygen reduces the incidence of
postoperative nausea an...
Supplemental Oxygen
30 % Oxygen

80% Oxygen

P Value

Male/Female

57/62

41/71

0.110

0-6 hr

PONV (%)

15.1

8

0.141

...
Supplemental Oxygen
30 % Oxygen

80% Oxygen

Ondansetron

Patients (female)

80

79

71

0-6 hr

PONV (%)

36

20

27

nau...
Intravenous Fluid Therapy
Incidence of Postop Nausea
20
Low Infusion

High Infusion

Incidence %

15
10
5

*
0
30 min

60 ...
Pain and PONV
Effects

% of Total Patients

Pain relieved, nausea relieved

68.5

Pain reduced, nausea relieved

11.5

Pai...
Efficacy Versus Outcome

Servizio di Anestesia e Rianimazione Ospedale di Faenza(RA)
Surrogate End Points
Are They Meaningful

Appropriate end points
Duration of PACU stay
Incidence of unplanned admissions
P...
Measures of Outcome
Mortality
Morbidity
Patient satisfaction
Cost
Servizio di Anestesia e Rianimazione Ospedale di Faenza(...
Risk of Mortality and Adverse
Outcome in a Tertiary Care
Population
Adverse outcomes

1:125

Death (all causes)

1:500

An...
Complications of PONV
Electrolyte imbalance
Tension on sutures, evisceration
Venous hypertension, bleeding
Aspiration
Dela...
Unanticipated Admissions
Reasons for Admission
Pain
Bleeding
Intractable Vomiting
Perforated Uterus
Extensive Surgery
Urin...
Cost Savings From the
Management of PONV
Analysis of strategies to decrease postanesthesia care
unit costs:
1. Supplies an...
Subject Preference Following Surgery
Preoperative
Levels
Mental Acuity

Preference

awake

drowsy

asleep

5%

Pain

none
...
Patient Preference Following Surgery
Preoperative
Outcome
Vomiting
Gagging
Pain
Nausea
Recall w/o pain
Shivering
Residual ...
Patient Satisfaction With Outpatient Surgery
Postoperative
Considered
Factor
Important

Preoperative
Avoidance of Delays
S...
Efficacy Versus Outcome

If efficacy is an appropriate endpoint when evaluating
analgesics, why not when evaluating antiem...
Prevention Versus Treatment
Question:
Does routine* administration of prophylactic
antiemetics improve outcome when compar...
Frequency of PACU Treatment
by Risk Factors and Group
PACU TREATMENT
REQUIRED BY GROUP

RISK FACTORS
Subgroup

Gender

Pri...
Efficacy of Prophylaxis – Overall
Ondansetron

Placebo

285

290

0, 0, 0

0,0,2

0.54

No Tx Required (%)

204 (71.6)

17...
Efficacy of Prophylaxis - Group E
Ondansetron

Placebo

58

60

0,0,4

0,0,6

0.49

No Tx Required (%)

36 (62)

26 (43)

...
Outcomes - Treatment vs Prophylaxis
Patient Satisfaction, Time to Discharge
Ondansetron

Placebo

P

Total patients

285

...
Prevention Versus Treatment
Answer:
Routine administration of prophylactic antiemetics does reduce
the incidence of emesis...
Multimodal Management of PONV:
Hypothesis

A multi-modal approach to the
management of PONV can result in a
zero incidence...
Multimodal Management of PONV:
Results

Group I

Group II

Group III

Multimodal

Ondansetron

Placebo

Patients

60

42

...
Multimodal Management of PONV:
Simplified Algorithm

I. INDUCTION
II. MAINTENANCE
A. PreO2
A. Propofol 50 mcg/kg/min
B. Pr...
Multimodal Management of
PONV:
Simplified Algorithm

Cost Analysis
COST ($)
Case duration

1 hour

2 hours

3 hours

Drope...
Multimodal Management of PONV:
Conclusions

Elimination of PONV in outpatients is possible with multimodal management
Algo...
PONV
PONV
we know the risk factors
Preventive strategy

non emetogenic drugs...

Antiemetic
Prophylaxis

Selected at risk ...
PONV dopo la dimissione

Servizio di Anestesia e Rianimazione Ospedale di Faenza(RA)
Efficacy of antiemetic medication on postdischarge nausea

(Gupta A,Wu,CL,Elkassabani,N,Krug,CE,Parker,SD,Fleisher LA.Does...
Efficacy of antiemetic medication on posdtdischarge
vomiting (Gupta A,Wu,CL,Elkassabani,N,Krug,CE,Parker,SD,Fleisher LA.Do...
Postdischarge nausea

(Gupta A,Wu,CL,Elkassabani,N,Krug,CE,Parker,SD,Fleisher LA.Does the routine
prophylactic use of anti...
Postdischarge vomiting

(Gupta A,Wu,CL,Elkassabani,N,Krug,CE,Parker,SD,Fleisher LA.Does the routine
prophylactic use of an...
Postdicharge nausea in the ondansetron 4
mg group vs the placebo group
Gyn
Lap
Isof

0,90
0,80
0,70
0,60

%

0,50
0,40
0,3...
Per uno studio nostro su
POnv(io,Lorenz….???
Data
Co-nome
Età/peso/alt
Sex
Asa e patol concomit
Cinetosi
Ponv pregr
Premed...
Postdischarge nausea in the combination
group(>1 drug) vs the placebo group
Gyn
%
0,90

Lap
Isof

0,80
0,70

GYN
D&C
Propo...
Postdischarge vomiting in the combination
group(>1 drug) vs the placebo group
%

0,50
0,45
0,40

Gyn
Lap
Isof

0,35
0,30
0...
Postdicharge vomiting in the ondansetron 4
mg group vs the placebo group
0,50
0,45
0,40
0,35
0,30
0,25
0,20
0,15
0,10
0,05...
Post Discharge Nausea and Vomiting
Incidence
Severity
Contributing factors
Prevention
Treatment

Servizio di Anestesia e R...
Post Discharge Symptoms
Following Ambulatory Surgery
Symptom
Pain
Nausea
Vomiting
Headache
Drowsiness
Dizziness
Fatigue

I...
Strabismus Surgery

Postdischarge Vomiting
Ondansetron

Droperidol

Metoclopramide

Placebo

40

40

40

40

Predischarge ...
Post Discharge:
Time to first emetic episode
6

68%
5

5

4

4

3

3
2

2
1
0

5

3
2

1

2
1

2

1

1

0

0-4

1

0

4-8
...
Postdischarge Vomiting:
Ondansetron versus Placebo
Ondansetron

Placebo

P-value

(n = 70)

(n = 70)

Patients with emesis...
Postdischarge Vomiting:
Ondansetron versus Placebo
ODT

Placebo

P-value

patients

30

30

Predischarge emesis

3%

0%

n...
Final recommendations

Servizio di Anestesia e Rianimazione Ospedale di Faenza(RA)
General Recommendations
Use generic drugs for “routine” prophylaxis
Treat breakthrough symptoms with 5HT3 antagonists
Don’...
Watcha MF, White PF: Postoperative nausea and vomiting:
Prophylaxis versus treatment. Anesth Analg 89:1337-9, 1999
???Anes...
Antiemetic choice
drug effectiveness
side-effect profile---clinical context
patient preference
associated reduction of tot...
Antiemetic choice
Antiemetic choice

Clinical effectiveness

Side effect profile

Clinical context

Servizio di Anestesia ...
Ewalenko P, Janny S, Dejonckheere M,
Andry G, Wyns C: Antiemetic effect of
subhypnotic doses of propofol after
thyroidecto...
Montgomery 1996
• We studied the antiemetic effects of a low dose
infusion of propofol for 24 h after major
gynaecological...
Ding
• To compare the intraoperative conditions and
postoperative recovery of patients following the
use of either propofo...
GAN
• Background: Breast surgery is associated with a
high incidence of postoperative nausea and
vomiting. Propofol and pr...
Servizio di Anestesia e Rianimazione Ospedale di Faenza(RA)
AUTHOR(S): Watcha, Mehernoor F., M.D.
Anesthesiology
92:931-3, 2000

Servizio di Anestesia e Rianimazione Ospedale di Faen...
Biblio PONV recente
Tramèr, M.; Moore, A.; McQuay, H.Propofol anestesia and poostoperastive nausea and vomitino:quantitati...
Poi ci sono 2 file su Acer o Vaio picolo
su Post duischarge nv e una
citazione;trasferire con link……………

Servizio di Anest...
Propofol & PONV
Campbell Anaesth Intens Care

Campbell NN, Thomas AD: Does propofol have an anti-emetic effect? A
19:385-7...
Campbell Anaesth Intens Care
19:385-7, 1991
• In order to investigate the putative anti-emetic
effect of propofol, 53 pati...
Esempi pratici
Appendix 1
Logistic regression is used to model the relation between explanatory variables and binary outco...
Prevenzione del PONV:
Dexamethasone

Dose ranging
Major gynecological surgery
Placeb
1.25 mg
o

2.5
mg

5.0 mg 10.0 mg

Pa...
Prevenzione del PONV:
Scopolamine

Undefined control event rate
Small Studies
Outcome

Large Studies

Trials

NNT

Trials
...
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PONV(postoperative nausea and vomiting) from a lecture presented in 2008.At the end there are some more references,not graphs.

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  • Patients received thiopental for induction, opioid and potent inhalation anesthetic plus nitrous oxide for maintenance. Type of surgical procedure seems to not be an independent risk factor.
  • Randomized, double blind prospective placebo controlled dose ranging. Females 18 - 70 yo outpatients undergoing gyn surgery. Stratified by prior history of PONV. Total of 580 patients enrolled, 544 patients evaluated. Standard anesthetic including barbiturate, opioid, isofulrane or enflurane, NMB agent with reversal and nitrous oxide. Study medication administered immediately before induction.
  • Randomized, prospective, double blind, placebo controlled, dose ranging. Two parallel studies performed. Multicenter with 20 total sites. Over 2500 total patients enrolled, 1000 patients (500 in each study) received study medication. 90 % female. Standard anesthetic included barbiturate, opioid, NMB agent and reversal, nitrous and either isoflurane or enflurane. Complete response defined as no vomiting, no rescue medication.
  • Randomized, double blind placebo controlled multicenter study to evaluate the effect of an additional 4 mg of ondansetron for treatment of breakthrough PONV occurring in PACU in outpatients who received ondansetron 4 mg as prophylaxis. 2199 male and female patients enrolled. 428 patients experienced PONV or requested antiemetics were randomized to receive an addition dose of 4 mg of ondansetron or placebo. Complete response defined as no emesis or no rescue medication.
  • Randomized, double blind, placebo controlled, dose ranging. multicenter (25) trial. 635 females undergoing outpatient laparoscopy. Standard anesthetic including barbiturate, NMB, reversal, opioid, and isoflurance. Study medication was administered 15 before discontinuation of nitrous oxide. Followed for 24 hours. Complete response defined as no vomiting and no rescue antiemetic.
  • Randomized, double blind, placebo controlled, dose ranging study. Multicenter trial at 30 sites. 1557 adults undergoing outpatient surgery were enrolled. Standard anesthetic included barbiturate, opioid, nitrous oxide, isoflurane, NMB if required, reversal of NMB if indicated. The subset of those who experienced PONV (620, 40%) were stratified by gender (106 males, 514 females). Entered into treatment if patient had one or more emetic episodes within two hr postop and or nausea lasting longer than 5 min reported as moderate to severe.
  • Double blind, placebo controlled multicenter trial. Efficacy by complete response (0 emetic episodes, no rescue antiemetics) and total response (complete response plus no nausea. 517 total patients, various surgical procedures. Study medication administered at induction. Standard anesthetic included thiopentone, opioid, nitrous oxide, and potent inhalation agent. In patients monitored for 24 hours.
  • Randomized, double blind, 200 outpatients undergoing otolaryngologic procedures. Recorded number of emetic episodes, maximum nausea score, time to discharge. No difference in efficacy data. No difference in efficacy data including need for rescue antiemetics, nausea, maximum nausea score, multiple episodes of PONV. No difference in outcome data including time to discharge ready or patient satisfaction.
  • Randomized, double blind, 200 outpatients undergoing otolaryngologic procedures. Recorded number of emetic episodes, maximum nausea score, time to discharge. No difference in efficacy data. No difference inefficacy data including need for rescue antiemetics, nausea, maximum nausea score, multiple episodes of PONV. No difference in outcome data including time to discharge ready or patient satisfaction.
  • Combination of two randomized, double blind placebo controlled trials. 2061 adult outpatients at increased risk for PONV enrolled. Study medication administered 20 min before induction of anesthesia. Standard anesthetic regimen included barbiturate induction, nitrous oxide, and either isoflurane or enflurane. Complete response defined as no emesis, no rescue. No difference in patient satisfaction among active groups. All were better than placebo.
  • Combination of two randomized, double blind placebo controlled trials. 2061 adult outpatients at increased risk for PONV enrolled. Study medication administered 20 min before induction of anesthesia. Standard anesthetic regimen included barbiturate induction, nitrous oxide, and either isoflurane or enflurane. Complete response defined as no emesis, no rescue. No difference in patient satisfaction among active groups. All were better than placebo.
  • Meta analysis, 27 studies identified, 2 excluded. 1311 patients analyzed. Combination of droperidol and ondansetron (298) or granisetron (200). Combination of dexamethasone and ondansetron (280), granisetron (467) or tropisetron (66). 20 trials in adults, 5 in children.
  • 110 outpatients for short duration procedures. All received droperidol 0.625 mg and dexamethasone 4 mg. In addition, treatment groups received metoclopramide 10, dolasetron 12.5 mg, or ondansetron 4 mg. All patients induced with propofol, maintained with desflurane and nitrous oxide
  • Randomized, prospective, double blind. Females undergoing abdominal hysterectomy, ages 35-45 yrs. Dexamethasone dose 10 mg IV. 120 total subjects, 40 per group. Propofol induction, vecuronium, isoflurane, fentanyl. NMB reversal glycopyrrolate and neostigmine.
  • Multicenter (4), randomized, double blind, placebo and sham controlled. 250 adult patients undergoing laparoscopic cholecystectomy. Transcutaneous acupoint electrical stimulation (TAES) applied at Nei-Guan P6 acupuncture point. Sham group had inactive device place at the P6 point with no electrical stimulation. Placebo group had inactive device placed on dorsal surface of wrist. Statistically significant improvement in nausea and severity of nausea of active device compared to placebo and sham. No decrease in the incidence of vomiting
  • Single center trial. 231 patients (male and female) undergoing elective colon resection with expected procedure duration &gt;2 hr. Standard anesthetic included thiopental induction, vecuronium, fentanyl, isoflurane, oxygen, and nitrogen. NMB antagonized with glycopyrrolate and neostigmine. Patients randomized to receive 30% oxygen balance nitrogen or 80% oxygen balance nitrogen during surgery and for the first 2 hrs postop. Rescue with ondansetron 4 mg after 30 min of nausea, 2 episodes of vomiting or at patient or physician request. Nausea rated on three point scale – none, mild, severe. Episodes of vomiting were counted and scored on severity by time period – none, mild (1 episode), moderate (2 or 3 episodes), severe (more than 3 episodes). PONV any nausea or vomiting.
  • Single center trial. 240 patients (female undergoing gynecological laparoscopy with expected duration &gt; 1 hr. Patients were randomized to receive 30% oxygen balance nitrogen, 80% oxygen balance nitrogen, or Ondansetron 8 mg after induction with 30% oxygen balance nitrogen. Standard anesthetic included thiopental induction, vecuronium, fentanyl, isoflurane, oxygen, and nitrogen. NMB antagonized with glycopyrrolate and neostigmine. Postoperatively all patients received oxygen at 2 l/min by face mask for 2 hr. Ondansetron 4 mg for rescue for any vomiting or nausea lasting more than 15-20 min.
  • 200 ( m=15, f=185) patients undergoing outpatient surgical procedures (gyn: laparoscopy=6, D&amp;C=172; orthopedic 15; gen surgery 7) randomized to receive 20 ml/kg or 2 ml/kg IV fluid in the perioperative period.
  • Single center study. Randomized, double blind, placebo controlled. 60 female patients undergoing gynecologic laparoscopy. Standard anesthetic including propofol, fentanyl, succinylcholine, cisatracurium, sevoflurane, nitrous oxide, and NMB reversal with neostigmine and glycopyrrolate. Ondansetron 4 mg IV at induction. Patients randomized to receive ondansetron ODT 8mg or placebo immediately before discharge from ambulatory surgery unit and again 12 hours later.
  • Ponv corso itinerante 08

    1. 1. the meta-analysis (Gupta A,Wu,CL,Elkassabani,N,Krug,CE,Parker,SD,Fleisher LA.Does the routine prophylactic use of antiemetics affect the incidence of postischarge nausea and vomuint following ambulatory surgery?.Anesthesiology 2003;99:488-95.) Servizio di Anestesia e Rianimazione Ospedale di Faenza(RA)
    2. 2. PONV Servizio di Anestesia e Rianimazione Ospedale di Faenza(RA)
    3. 3. Hill RP, Lubarsky DA, Phillips-Bute B, Fortney JT, Creed MR, Glass PSA, Gan TJ: Cost-effectiveness of prophylactic antiemetic therapy with ondansetron, droperidol, or placebo. ANESTHESIOLOGY 2000; 92:958-67. prophylaxis with 1.25 mg intravenous droperidol was the most cost-effective approach Cost considerations: » » » » » acquisition cost of a drug costs of wasted drug the need for adjunctive drugs to manage side effects costs of nursing labor Nursing labor costs are linearly related to the time an individual nurse spends with a patient. » However, institutional costs may not increase if a patient spends an additional 15— 30 min in the postanesthesia care unit (PACU), unless overtime costs are incurred. » improved patient satisfaction The cost-effectiveness of prophylactic antiemetic therapy depends on: » the underlying incidence of PONV » and on the costs and effectiveness of the drugs used for prophylaxis. Servizio di Anestesia e Rianimazione Ospedale di Faenza(RA)
    4. 4. What drug should be used for PONV prophylaxis in high-risk patients? A more expensive drug may be preferred and reduce total institutional costs if it is more effective or associated with a decreased side-effect profile, a greater patient satisfaction, or an quicker return to work. There is convincing evidence from a systematic review of 54 blinded studies of 7,234 patients that ondansetron is more effective than metoclopramide, but not more effective than 1.25 mg droperidol for PONV prophylaxis in adults. Droperidol has also been shown to be as effective as tropisetron and dolasetron. Antiserotonin drugs are associated with increased headache, whereas central nervous system side effects of dysphoria, restlessness, and drowsiness have been reported with droperidol. However, when the dose of droperidol was limited to 1.25 mg intravenous, the incidence of these central nervous system events did not differ compared with ondansetron. It is also important to note that there were no patient preferences for a specific regimen in the study by Hill et al. In this era of cost containment, the less expensive drug, droperidol, should be used for PONV prophylaxis in the adult patient population until more effective drugs with decreased side effects are developed or the costs of alternative drugs are lowered. Similarly, in the absence of evidence to suggest that any available antiserotonin agent is superior to another in effectiveness or side-effect profile, the least expensive one should be used. In contrast to adults, PONV prophylaxis with droperidol is less effective than ondansetron in children and is associated with increased drowsiness, delayed discharge, and extrapyramidal side effects. The preferential use of ondansetron in this patient population may be justified. Servizio di Anestesia e Rianimazione Ospedale di Faenza(RA)
    5. 5. Postoperative Nausea and Vomiting: Prevention and Treatment Claudio Melloni Anestesia e Rianimazione Ospedale degli Infermi di Faenza(RA) Servizio di Anestesia e Rianimazione Ospedale di Faenza(RA)
    6. 6. AUTHOR(S): Watcha, Mehernoor F., M.D. Anesthesiology 92:931-3, 2000 Servizio di Anestesia e Rianimazione Ospedale di Faenza(RA)
    7. 7. Topics Importance of the issue Risk factors Pharmacologic approaches to management Adjuvants (nonpharmacologic) Efficacy versus outcome Prevention versus treatment Postdischarge nausea and vomiting Multimodal management Servizio di Anestesia e Rianimazione Ospedale di Faenza(RA)
    8. 8. Methodological questions(from Visserer et al…) definitions of PONV: » nausea only, » nausea and vomiting » vomiting only. This has hampered interstudy comparability. Because we scored nausea, retching, and vomiting independently, our data allowed for alternative end-point definitions. The Venn diagrams in show that PONV is primarily determined by the presence of nausea. When vomiting and retching are combined and taken as one end point, the incidence of PONV is lower, but similar differences between isoflurane and TIVA remain. Accordingly, the results of the various possible PONV end points are comparable, provided that nausea is included. Diversity in methods of data collection may also account for some of the observed differences. Emetic symptoms can be quantified as: » retrospective self-report Ospedale di Faenza(RA) Servizio di Anestesia e Rianimazione
    9. 9. Importance of the issue PONV is : » A limiting factor in the early discharge of ambulatory surgical patients » The leading cause of unanticipated hospital admission PONV may: » » » » Increase recovery room time Expand nursing care Increase total health care costs Cause high level of patient discomfort---pain,hematoma,wound dehiscence… » Cause high level of patient dissatisfaction » KO!!! Servizio di Anestesia e Rianimazione Ospedale di Faenza(RA)
    10. 10. Macario A, Weinger M,Carney S, Kim A.Which clinical anesthesia outcomes are important to avoid? Anesth.Analg.1999;89:652-8. 20 18 16 14 12 10 8 6 4 2 0 distribute $100 among the 10 outcomes , proportionally more money being allocated to the more undesirable outcomes. The dollar allocations were used to determine the relative value of each outcome. vomito gagging sul tubo dolore nausea ricordo senza dolore debolezza residua brivido mal di gola sonnolenza Dal + indesiderabile Al meno indesiderabile rank valore relativo Servizio di Anestesia e Rianimazione Ospedale di Faenza(RA)
    11. 11. Sintomi accusati dai pazienti a casa dopo interventi eseguiti in regime di day surgery(da Wu et al.,Anesthesiology 2002). dolore nausea vomito cefalea sonnolenza gir.di testa fatica Servizio di Anestesia e Rianimazione Ospedale di Faenza(RA)
    12. 12. Quali problemi preferirebbero evitare i pazienti sottoposti a day surgery? (da Jenkins, K.; Grady, D.; Wong, J.; Correa, R.; Armanious, S.; Chung, F.*Post-operative recovery: day surgery patients' preferences Br. J. Anaesth. 2001; 86:272-274) 30 Valori relativi ! 25 dolore tossire sul tubo et vomito nausea disorientamento mal di gola brivido sonnolenza sete 20 15 10 5 0 Servizio di Anestesia e Rianimazione Ospedale di Faenza(RA)
    13. 13. Beauregard L, Pomp A, Choinière M. Severity and impact of pain after day-surgery Can J Anaesth 1998 / 45 / 304-11 Servizio di Anestesia e Rianimazione Ospedale di Faenza(RA) fatica raucedine mal di gola cefalea sonnolenza gir.testa PONV I g. II g VII g dolore 100 90 80 70 60 % 50 40 30 20 10 0
    14. 14. Sintomi accusati dai pazienti a casa dopo interventi eseguiti in regime di day surgery(da Wu et al.,Anesthesiology 2002). dolore nausea vomito cefalea sonnolenza gir.di testa fatica Servizio di Anestesia e Rianimazione Ospedale di Faenza(RA)
    15. 15. Quali problemi preferirebbero evitare i pazienti sottoposti a day surgery? (da Jenkins, K.; Grady, D.; Wong, J.; Correa, R.; Armanious, S.; Chung, F.*Post-operative recovery: day surgery patients' preferences Br. J. Anaesth. 2001; 86:272-274) 30 Valori relativi ! 25 dolore tossire sul tubo et vomito nausea disorientamento mal di gola brivido sonnolenza sete 20 15 10 5 0 Servizio di Anestesia e Rianimazione Ospedale di Faenza(RA)
    16. 16. Beauregard L, Pomp A, Choinière M. Severity and impact of pain after day-surgery Can J Anaesth 1998 / 45 / 304-11 Servizio di Anestesia e Rianimazione Ospedale di Faenza(RA) fatica raucedine mal di gola cefalea sonnolenza gir.testa PONV I g. II g VII g dolore 100 90 80 70 60 % 50 40 30 20 10 0
    17. 17. Can PONV be predicted? Risk factor analysis Servizio di Anestesia e Rianimazione Ospedale di Faenza(RA)
    18. 18. Sinclair et al.Can PONV be predicted? Anesthesiology 1999;91:109-18 17,638 consecutive ambulatory surgical patients;>90% ASA I /II 5,812 men and 11,826 women mean (± SD) age of 46.7 ± 21.2 yr. prospectively studied during a 3-yr period ASU of The Toronto Hospital, Western Division telephone interview 24 h after operation was obtained. Preoperative patient characteristics and intraoperative variables were documented on specifically designed, standardized adverse-outcome check-off forms. i.v.2—4 mg morphine for pain relief and 25—50 mg dimenhydrinate for nausea or vomiting. Overall PONV incidence 4.6%:9.1 % at 24 hrs interview. Servizio di Anestesia e Rianimazione Ospedale di Faenza(RA)
    19. 19. Sinclair et al.Can PONV be predicted? Anesthesiology 1999;91:109-18 Patients with PONV underwent significantly longer procedures (67 ± 57 min vs. 51 ± 44 min; P < 0.0001), and the duration of their stay in the PACU (72 ± 32 min vs. 49 ± 25 min; P < 0.0001) and the ASU (157 ± 84 min vs. 95 ± 53 min; P < 0.0001) was also significantly longer (). Among patients undergoing general anesthesia, those who experienced PONV during the immediate postoperative period had received significantly higher doses of alfentanil, fentanyl, and midazolam during operation (). The same was true of those who received monitored anesthesia care. Patients experiencing PONV received significantly higher doses of dimenhydrinate in the PACU and ASU (37 ± 19 mg vs. 23 ± 11 mg; P < 0.0001). Among patients who received general anesthesia, those with PONV within 24 h after surgery received significantly higher doses of morphine in the PACU and ASU than did those without PONV (6.3 ± 3.6 mg vs. 5.3 ± 3.5 mg; P = 0.008). Among patients undergoing general anesthesia, 1,225 (12%) received a nondepolarizing muscle relaxant during operation. Five hundred patients (41%) received a reversal agent (483 received neostigmine, 17 received edrophonium) at the end of the procedure. There was no significant difference in PONV between those who received a reversal agent and those who did not (19.2% vs. 15.7%; P = 0.11). Servizio di Anestesia e Rianimazione Ospedale di Faenza(RA)
    20. 20. Sinclair DR, Chung F,Mezei G.Can PONV be predicted? Anesthesiology 1999;91:109-18 Background: Retrospective studies fail to identify predictors of postoperative nausea and vomiting (PONV). The authors prospectively studied 17,638 consecutive outpatients who had surgery to identify these predictors. Methods: Data on medical conditions, anesthesia, surgery, and PONV were collected in the postanesthesia care unit, in the ambulatory surgical unit, and in telephone interviews conducted 24 h after surgery. Multiple logistic regression with backward stepwise elimination was used to develop a predictive model. An independent set of patients was used to validate the model. Results: Age (younger or older), sex (female or male), smoking status (nonsmokers or smokers), previous PONV, type of anesthesia (general or other), duration of anesthesia (longer or shorter), and type of surgery (plastic, orthopedic shoulder, or other) were independent predictors of PONV. A 10-yr increase in age decreased the likelihood of PONV by 13%. The risk for men was one third that for women. A 30-min increase in the duration of anesthesia increased the likelihood of PONV by 59%. General anesthesia increased the likelihood of PONV 11 times compared with other types of anesthesia. Patients with plastic and orthopedic shoulder surgery had a sixfold increase in the risk for PONV. The model predicted PONV accurately and yielded an area under the receiver operating characteristic curve of 0.785 ± 0.011 using an independent validation set. Conclusions: A validated mathematical model is provided to calculate the risk of PONV in outpatients having surgery. Knowing the factors that predict PONV will help anesthesiologists determine which patients will need antiemetic therapy. Servizio di Anestesia e Rianimazione Ospedale di Faenza(RA)
    21. 21. Frequency of PONV by type of anesthesia and duration of surgery. Sinclair et al.Can PONV be predicted? Anesthesiology 1999;91:109-18 Servizio di Anestesia e Rianimazione Ospedale di Faenza(RA)
    22. 22. PONV prolongs PACU and amb.surg.unit stay Sinclair et al.Can PONV be predicted?Anesthesiology 1999;91:109-18 Servizio di Anestesia e Rianimazione Ospedale di Faenza(RA)
    23. 23. Independent predictors of PONV Sinclair et al.Can PONV be predicted?Anesthesiology 1999;91:109-18 age A 10-yr increase in age was associated with a 13% decrease in the likelihood of PONV. sex Men had one third the risk for PONV compared with women. smoking status Smokers had two thirds the risk for PONV compared with nonsmokers history of previous PONV, had a threefold increase in the likelihood PONV compared with patients with no previous PONV. type of anesthesia: General anesthesia increased the likelihood of PONV 11 times compared with other types of anesthesia. duration of anesthesia, direct association between the duration of anesthesia and the risk for PONV. A 30-min increase in duration predicted a 59% increase in the incidence of PONV type of surgery : » plastic surgery had a sevenfold increase in the risk for PONV. » orthopedic shoulder surgery, ophthalmologic, or ENT procedures had a four- to sixfold increase. » orthopedic (nonshoulder) and gynecologic (non-D&C) procedures had a threefold increase in the risk for PONV. Compared with the reference group, which includes general surgery, gynecologic dilation and curettage (D&C), urologic surgery, neurosurgery, and chronic pain blockENT » dental surgery 14.3%, orthopedic 7.6%,plastic surgery 7.4%.Urologic, gynecologic, neurologic, or general surgery had an incidence of PONV corresponding to the overall average 4% Servizio di Anestesia e Rianimazione Ospedale di Faenza(RA)
    24. 24. Sinclair et al.Can PONV be predicted?Anesthesiology 1999;91:109-18 In our study, the incidence of PONV was 4.6% in the PACU and ASU and 9.1% at the 24-h interview. A previous study of 143 ambulatory surgical patients found an increase in PONV 48 h after discharge (16.8%) compared with the incidence in the PACU (9.8%). Because medications administered in the ambulatory surgery center undergo metabolism and elimination within 48 h after discharge, the increase in postdischarge PONV suggests a multifactorial cause related to early ambulation and resumption of oral intake. The frequency of PONV in the PACU and ASU varied according to sex, ASA status, age, type and duration of anesthesia, type of surgery, and type of procedure within the same surgical specialty. The high frequency of PONV in the PACU and ASU (> 15%) among breast augmentation, strabismus repair, laparoscopic sterilization, varicose vein stripping, dental, and orthopedic shoulder procedures may justify the use of prophylactic antiemetics. Servizio di Anestesia e Rianimazione Ospedale di Faenza(RA)
    25. 25. Sinclair et al.Can PONV be predicted?Anesthesiology 1999;91:109-18 Patients undergoing breast augmentation had a 41.5% incidence of PONV in the immediate postoperative period and 42.9% 24 h after operation. The incidence of PONV in breast surgery has been reported to be 37—59%. Further studies are needed to determine the cause of this apparently high incidence of PONV. Among the patients having orthopedic procedures, those undergoing shoulder surgery experienced the highest frequency of PONV (16.6%), possibly because of the high use of postoperative opioids. Ondansetron (8 mg) has been shown to be more efficacious than metoclopramide (10 mg) in reducing opioidinduced PONV. Alternative pain treatment such as suprascapular nerve blocks and ketorolac may be helpful in reducing the use of postoperative opioids, thereby reducing the likelihood of PONV. Among the patients having ophthalmologic procedures, those undergoing strabismus surgery had a high incidence of PONV (22%). This may be caused by an oculocardiac reflex vagal response triggered by eye-muscle manipulation. Servizio di Anestesia e Rianimazione Ospedale di Faenza(RA)
    26. 26. Sinclair et al.Can PONV be predicted?Anesthesiology 1999;91:109-18 Among the intraoperative anesthetic drugs, alfentanil and fentanyl were administered in significantly higher doses in patients with PONV. Although these doses do not demonstrate causality, the amount of narcotics may contribute to the incidence of PONV. Furthermore, patients with PONV stayed longer in the PACU and ASU (23 and 62 min, respectively). Despite a significantly higher dose of dimenhydrinate among these patients, it remains unclear whether this longer stay was due to the treatment of PONV. A decrease in PONV may reduce the duration of postoperative stay and increase the costeffectiveness of the ASU. As an alternative or adjunct to opioids in the ambulatory surgery setting, nonsteroidal antiinflammatory drugs should be considered for patients or surgical groups at high risk for PONV. Servizio di Anestesia e Rianimazione Ospedale di Faenza(RA)
    27. 27. Sinclair et al.Can PONV be predicted?Anesthesiology 1999;91:109-18 In this study, sex, age, smoking, previous PONV, type and duration of anesthesia, and type of surgery were independent predictors of PONV. Men had one third the risk for PONV that women had. Previous reports supported this sex difference and attributed the finding to variations in serum gonadotropin or other hormone levels. Another predictor of PONV was age. Age decreased the likelihood of PONV by 13% for each 10-yr increase. Pioneer studies described a decreasing incidence among men with increasing age and an insignificant decrease among women until the eighth decade. In contrast, our study showed a gradual decrease in PONV after age 50 yr. Interestingly, Koivuranta et al., using the forward procedure of logistic regression, did not find age to be a predictive factor for nausea, except for patients older than 50 yr who were undergoing joint replacement and spinal surgery, in whom there was an increased risk for postoperative vomiting. Smoking was also a predictor of PONV. Smoking decreased the likelihood of PONV by 34%. The relation between smoking and PONV was not evident in the literature for many years. A multicenter study of anesthetic outcomes showed a lower risk for PONV in smokers (relative risk = 0.6). Our results are consistent with recent studies that identified smoking as a protective factor against PONV. Servizio di Anestesia e Rianimazione Ospedale di Faenza(RA)
    28. 28. Sinclair et al.Can PONV be predicted?Anesthesiology 1999;91:109-18 Another predictor of PONV is previous PONV, which increases the likelihood of PONV by three times. A recent study showed previous PONV as the second strongest predictor of PONV, in addition to a twofold increased risk for PONV among these patients. Although an older study reports a 52-fold increased risk for PONV among patients with a history of PONV, its power is reduced by its small sample size. Anesthetic technique was also a predictor of PONV. Patients receiving general anesthesia were approximately 11 times more likely to experience PONV than were those who received monitored anesthesia care, regional anesthesia, or chronic pain block. PONV can be reduced by supplementing nitrous oxide and oxygen with propofol rather than a volatile gas. Total intravenous anesthesia protects against PONV more than does general anesthesia with volatile agents. Because our results apply to general anesthesia with volatile agents, further study is required to determine the predictive power of general anesthesia with intravenous agents. The duration of anesthesia was another predictor of PONV, increasing the risk for PONV by 59% for each 30-min increase. This finding could be related to the larger number of potentially emetic drugs administered during longer procedures. Our results are consistent with the previously reported 17.5% incidence of PONV for anesthesia lasting 30—90 min, which increased to 46% for procedures lasting 150—210 min. The type of surgery was a significant predictor of PONV. Patients undergoing plastic, ophthalmologic, and orthopedic shoulder surgery were at least six times more likely to experience PONV than were patients in the reference group. Compared with the reference group, patients having ENT—dental, nonshoulder orthopedic, and non-D&C gynecologic surgery were two to four times as likely to experience PONV. ENT and dental surgery and orthopedic surgery involve bone injury and damage to the periosteum, resulting in significant postoperative pain. Similarly, recent studies support the high incidence of severe pain after plastic surgery. There is evidence that nausea often accompanies pain in the early postoperative period and that both can be relieved in many cases by using intravenous opiates. Further study of an improved effect of postoperative analgesia on the incidence of PONV in ENT and dental, orthopedic, and plastic surgery outpatients is needed. A history of motion sickness is associated with an increased incidence of PONV. A large prospective survey of a wide spectrum of procedures concluded that a history of motion sickness was the fourth strongest predictor of PONV. Ultimately, a previous history of motion sickness was not included in our analysis of the predictive factors of PONV. Servizio di Anestesia e Rianimazione Ospedale di Faenza(RA)
    29. 29. Sinclair et al.Can PONV be predicted?Anesthesiology 1999;91:109-18 A well-designed logistic regression model of factors associated with PONV will help guide patient selection for antiemetic therapy. Palazzo and Evans developed a model to predict PONV. However, their study has several limitations. Because the coefficients of the study were derived from a small sample of patients having orthopedic surgery, the model is not applicable to various types of surgical patients. The model also lacks validation by statistical techniques that evaluate the model's ability to predict PONV correctly. Koivuranta et al. developed a risk score to predict PONV and measured the power of the model by calculating the area under the ROC. Although patient and surgery related factors were addressed in their model, the coefficients were derived from pediatric and adult inpatients. Anesthesia-related factors were not included. Similarly, The predictive model developed by Apfel et al., which was derived from adult inpatients, also lacks anesthesia-related factors. Unlike patient-related factors and many surgery-related factors that cannot be modified in the perioperative period, many anesthesia-related factors, such as anesthetic technique, sometimes can be modified. Anesthesia-related factors must be included in the model to determine the potential effect of a change in anesthetic technique. We present the only model that is derived from ambulatory patients and incorporates anesthesia-related factors. This model is the most comprehensive logistic regression model of patient-, anesthesia-, and surgery-related factors associated with PONV (see appendix 1). This model will be able to predict patients' risk for PONV according to their sex, age, previous PONV, history of motion sickness, duration of anesthesia, anesthetic technique, and type of surgery. We evaluate the model's ability to correctly predict PONV and determine the power of the model by calculating the area under the ROC curve. Knowledge of these predictors of PONV should increase anesthesiologists' efforts to reduce the incidence of PONVRianimazione Ospedale di Faenza(RA) Servizio di Anestesia e by selecting patients for antiemetic therapy. This may lead to improved cost-effective use of available drugs and resources.
    30. 30. Fitting the model to the data, we can obtain the maximum likelihood estimate of the parameters for each variable. Based on the maximum likelihood estimates from the final models, it is possible to calculate an expected risk of occurrence of the specific adverse event for any patient. where Age = age in years/10; Sex = 1 if male and 0 if female; Smoke = 1 if smoker and 0 if nonsmoker; PONV History = 1 if previous PONV and 0 if no previous PONV; Duration = duration of surgery in 30-min increments; GA = 1 if general anesthesia and 0 if other type of anesthesia; ENT = 1 if ENT and 0 if other type of surgery; Ophthalm = 1 if ophthalmology and 0 if other type of surgery; Plastic = 1 if plastic surgery and 0 if other type of surgery; GynNonDC = 1 if gynecologic non D&C procedure and 0 if other type of surgery; OrtKnee = 1 if orthopedic procedure involving knee and 0 if other type of surgery; OrtShoulder = 1 if orthopedic procedure involving the shoulder and 0 if other type of surgery; OrtOther = 1 if orthopedic procedure involving neither knee nor shoulder and 0 if other type of surgery. Servizio di Anestesia e Rianimazione Ospedale di Faenza(RA)
    31. 31. Logistic regression da:Sinclair et al.Can PONV be predicted? Anesthesiology 1999;91:109-18 P=1/1+e esponente con il segno neg. all’esponente la probabilità aumenta perché e elevato ad esp negativo diminuisce sempre + con il risultato che 1+e tende a 1 e dunque P=1/1,ossia 100% Con il segno positivo all’esponente e aumenta sempre + e allora 1+e aumenta e dunque il denominatorer dell’equazione aumenta e dunque 1/un numero in aumento fa scendere la probabilità perché viene 1/5,cioè 20%,1/10=10%,ecc….. Esponente=-5,97+(-0,14 *age)+(-1,03*sex)+ (-0,42*smoke)+(1,14*PONV history)+ (0,46*duration)+(2,36*GA)+(1,48*ENT)+ (1,77*ophtalm)+(1,90*plastic)+(1,20 Gynecol non DC)+(1,04 ort knee)+(1,78*ortshoulder) +(0.94 ort other) where Age = age in years/10; Sex = 1 if male and 0 if female; Smoke = 1 if smoker and 0 if nonsmoker; PONV History = 1 if previous PONV and 0 if no previous PONV; Duration = duration of surgery in 30-min increments; GA = 1 if general anesthesia and 0 if other type of anesthesia; ENT = 1 if ENT and 0 if other type of surgery; Ophthalm = 1 if ophthalmology and 0 if other type of surgery; Plastic = 1 if plastic surgery Servizio type of surgery; GynNonDC = 1 if gynecologic non D&C procedure and 0 if other type of and 0 if other di Anestesia e Rianimazione Ospedale di Faenza(RA)
    32. 32. Importance of the work by Sinclair et al… Fitting the model to the data, we can obtain the maximum likelihood estimate of the parameters for each variable. Based on the maximum likelihood estimates from the final models, it is possible to calculate an expected risk of occurrence of the specific adverse event for any patient. Servizio di Anestesia e Rianimazione Ospedale di Faenza(RA)
    33. 33. Appendix 1 Logistic regression is used to model the relation between explanatory variables and binary outcome variables. The logistic regression modeling assumes that the probability of an event (i.e., the occurrence of the outcome) is associated with the values of the explanatory variables in the following way: where where p = probability of the occurrence of the outcome, xi = value of the ith independent variable, and bi events for any patient = parameter estimates for the ith variable. Fitting the model to the data, we can obtain the maximum likelihood estimate of the parameters for each variable. Based on the maximum likelihood estimates from the final models, it is possible to calculate an expected risk of occurrence of the specific adverse event for any patient. Examples The risk for patient 1, a 30-yr-old woman with a history of smoking and previous PONV undergoing a 1-h shoulder (orthopedic) operation with general anesthesia is 35.2%. The risk for patient 2, a 40-yr-old nonsmoking man with no previous PONV undergoing a 1-h knee arthroscopy (orthopedic) without general anesthesia is 0.4%. The risk for patient 3, a 70-yr-old smoking man with no previous PONV undergoing a 1-h cataract surgery (ophthalmologic) without general anesthesia is 0.3%. The risk for patient 4, a 32-yr-old nonsmoking woman with previous PONV undergoing a 30-min laparoscopy (gynecologic) with general anesthesia is 22.1% The risk for patient 5, a 22-yr-old woman with a history of smoking and previous PONV undergoing a 90-min bilateral breast augmentation (plastic surgery) with general anesthesia is 52%. Servizio di Anestesia e Rianimazione Ospedale di Faenza(RA)
    34. 34. Risk Factors Non-anesthetic factors Anesthetic related factors Postoperative factors Servizio di Anestesia e Rianimazione Ospedale di Faenza(RA)
    35. 35. Risk factors da Samba 2007:1 Patient specific Female gender Non smoking status Hx of ponv/motion sickness Servizio di Anestesia e Rianimazione Ospedale di Faenza(RA)
    36. 36. Risk factors da Samba 2007:2 Anesthetoc risk factors Use on intraop volatile anesth Use on intraop and postop opioids Use of intraop N2O Servizio di Anestesia e Rianimazione Ospedale di Faenza(RA)
    37. 37. Risk factors da Samba 2007:3 Surgical risk factors Duration of surgery Each 30 min increase in duration of surgery oncreases the risk by 60%,so thyat a baseline risk of 10% increases to 16% after 30 min Type of surgery laparoscopy;,laparotomy;breast,strabismus,pl astic,maxillofacial,gynecological,abdominal,ne urologic ,opthalmologic,urologic Servizio di Anestesia e Rianimazione Ospedale di Faenza(RA)
    38. 38. Risk Factors Non-anesthetic Factors Age Gender Body habitus Hx motion sickness Hx PONV Anxiety Concomitant disease Operative procedure Duration of surgery Servizio di Anestesia e Rianimazione Ospedale di Faenza(RA)
    39. 39. Risk Factors Anesthetic Related Factors Preanesthetic medication Gastric distension Gastric suctioning Anesthetic technique Anesthetic agents Servizio di Anestesia e Rianimazione Ospedale di Faenza(RA)
    40. 40. Risk Factors Postoperative Factors Pain Dizziness Ambulation Oral intake Opioids Servizio di Anestesia e Rianimazione Ospedale di Faenza(RA)
    41. 41. Postoperative Nausea and Vomiting: Anesthetic Related Factors Nitrous oxide Volatile anesthetics NMB reversal Propofol Servizio di Anestesia e Rianimazione Ospedale di Faenza(RA)
    42. 42. Risk Factors Nitrous Oxide and PONV Omission of Nitrous Oxide during Anesthesia Reduces the Incidence of Postoperative Nausea and Vomiting. A Meta-Analysis Divatia et al. Anesthesiology 1996;85:1055-1062 Twenty-Four of Twenty-Seven Studies Show a Greater Incidence of Emesis Associated with Nitrous Oxide than with Alternative Anesthetics Hartung. Anesth Analg 1996;83:114-116 Omitting Nitrous Oxide in General Anaesthesia: Meta-Analysis of Intraoperative Awareness and Postoperative Emesis in Randomized Controlled Trials Tramer et al. BJA 1996;76:186-193 Servizio di Anestesia e Rianimazione Ospedale di Faenza(RA)
    43. 43. Risk Factors Nitrous Oxide and PONV Omitting nitrous oxide from general anesthesia: Decreases POV significantly only if the baseline risk is high Does not affect nausea or complete control of emesis Increases the incidence of intraoperative awareness Tramer et al. BJA 1996;76:186-193 Servizio di Anestesia e Rianimazione Ospedale di Faenza(RA)
    44. 44. Controlled Trial of Total Intravenous Anesthesia with Propofol versus Inhalation Anesthesia with Isoflurane–Nitrous Oxide Postoperative Nausea and Vomiting and Economic Analysis.Anesthesiology.95:616626, 2001 incidence of PONV after TIVA with propofol versus inhalational anesthesia with isoflurane–nitrous oxide randomized trial 2,010 unselected surgical patients Unversity of Amsterdam Hospital Elective inpatients 1,447 + outpatients 563 randomly assigned to inhalational anesthesia with isoflurane–nitrous oxide or TIVA with propofol–air. Cumulative incidence of PONV recorded for 72 h by blinded observers. Cost data of anesthetics, antiemetics, disposables, and equipment were collected. Cost differences caused by duration of postanesthesia care unit stay and hospitalization were analyzed. Servizio di Anestesia e Rianimazione Ospedale di Faenza(RA)
    45. 45. Visseret al . Randomized Controlled Trial of Total Intravenous Anesthesia with Propofol versus Inhalation Anesthesia with Isoflurane– Nitrous Oxide Postoperative Nausea and Vomiting and Economic Analysis.Anesthesiology.95:616-626, 2001 TIVA reduced the absolute risk of postoperative nausea and vomiting up to 72 h by 15% among inpatients (from 61% to 46%, P < 0.001) and by 18% among outpatients (from 46% to 28%, P < 0.001). This effect was most pronounced in the early postoperative period. The cost of anesthesia was more than three times greater for propofol TIVA. Median duration of stay in the postanesthesia care unit was 135 min after isoflurane versus 115 min after TIVA for inpatients (P < 0.001) and 160 min after isoflurane versus 150 min after TIVA for outpatients (P = 0.039). Duration of hospitalization was equal in both arms. Conclusion: Propofol TIVA results in a clinically relevant reduction of postoperative nausea and vomiting compared Servizio di Anestesia e Rianimazione Ospedale di Faenza(RA)
    46. 46. Visseret al . Randomized Controlled Trial of Total Intravenous Anesthesia with Propofol versus Inhalation Anesthesia with Isoflurane– Nitrous Oxide Postoperative Nausea and Vomiting and Economic Analysis.Anesthesiology.95:616-626, 2001 Servizio di Anestesia e Rianimazione Ospedale di Faenza(RA)
    47. 47. Visseret al . Randomized Controlled Trial of Total Intravenous Anesthesia with Propofol versus Inhalation Anesthesia with Isoflurane– Nitrous Oxide Postoperative Nausea and Vomiting and Economic Analysis.Anesthesiology.95:616-626, 2001 Servizio di Anestesia e Rianimazione Ospedale di Faenza(RA)
    48. 48. Anesthesia with Propofol versus Inhalation Anesthesia with Isoflurane– Nitrous Oxide Postoperative Nausea and Vomiting and Economic Analysis.Anesthesiology.95:616-626, 2001 40 35 30 25 inpatients Iso/N2O inpatients tiva outpatients iso/N2O outpatients tiva 20 15 10 5 0 after anesth. Pacu discharge 24 hr 48 hr Servizio di Anestesia e Rianimazione Ospedale di Faenza(RA) 72hr.
    49. 49. PONV % (Visseret al . Randomized Controlled Trial of Total Intravenous Anesthesia with Propofol versus Inhalation Anesthesia with Isoflurane–Nitrous Oxide Postoperative Nausea and Vomiting and Economic Analysis.Anesthesiology.95:616-626, 2001) 70 60 50 % 40 tiva isof/N2O 30 20 10 0 inpatients Servizio di Anestesia e Rianimazione Ospedale di Faenza(RA) outpatients
    50. 50. Rescue antiemetics (Visseret al . Randomized Controlled Trial of Total Intravenous Anesthesia with Propofol versus Inhalation Anesthesia with Isoflurane–Nitrous Oxide Postoperative Nausea and Vomiting and Economic Analysis.Anesthesiology.95:616-626, 2001) 40 35 30 25 tiva isof/N2O % 20 15 10 5 0 inpatients Servizio di Anestesia e Rianimazione Ospedale di Faenza(RA) outpatients
    51. 51. Cost analysis Detailed drug acquisition costs at the time of the study can be found in the Web Enhancement, ). shows the intraoperative volumes of anesthetics. For inpatients (median duration of anesthesia = 2 h) median costs (10th–90th percentile) of induction with thiopental and maintenance with isoflurane were $10.84 (5.67–22.64) versus $39.53 (19.89– 75.74) for propofol TIVA. In outpatients (median duration of anesthesia = 1 h), these amounts for induction with propofol and maintenance with isoflurane were $13.10 (8.51–20.18) versus $28.31 (19.89–47.69) for propofol TIVA. Use of antiemetics was twice as high in the Servizio di Anestesia e Rianimazione Ospedale di Faenza(RA)
    52. 52. The cumulative incidence of PONV was significantly lower after TIVA than after isoflurane. Absolute risk reduction with TIVA was between 15 and 20% (NNT = 7–5) depending on duration of follow-up. Moreover, from the patients’ perspective, TIVA was superior. The PONV reduction in the current study is in agreement with results from two recent metaanalyses that pooled data from several smaller studies comparing propofol with inhalational agents. Tramer et al. and Sneyd et al. found an NNT with propofol TIVA of 6 and 7, respectively, to prevent one early PONV incident (< 6 h). Our follow-up period was long compared with other PONV studies. The effect of the anesthetic technique was most prominent in the first 24 h after surgery (early PONV), whereas beyond that point the incidence of PONV increased equally in both groups. This suggests that anesthetic-induced PONV is most important in the first 24 h after surgery, whereas PONV resulting from the surgical procedure and postoperative analgesics dominates thereafter. Power analysis was based on PONV incidences from the literature available at the time of study design. The higher-than-expected PONV incidence increased the power of the study to detect a difference in PONV between TIVA and isoflurane. Moreover, the large sample size strengthens the results of subgroup analyses and the inference regarding the lack of difference in the incidence of complications between the TIVA and isoflurane groups. As expected, type of surgery was a major determinant of PONV frequency in both groups, and it modified the effect of the anesthetic technique on PONV. Patients undergoing superficial surgical procedures benefited most from TIVA (absolute risk reduction = 18%; NNT = 6). An unexpected finding was that, in the patients undergoing abdominal procedures, TIVA was unable to suppress the occurrence of PONV, although the number of intraabdominal procedures was relatively low. We cannot exclude that TIVA may suppress early PONV for intraabdominal procedures. For laparoscopic procedures, we were unable to detect a protective effect from TIVA. This finding has not been previously reported and refutes results from previous studies. Demographic characteristics also affected the probability of PONV, with female gender and younger age predisposing toward higher incidence in both groups. One hypothesis at the outset of the study was that the results might reveal subgroups of patients who would benefit more from TIVA. e Rianimazione Ospedale di Faenza(RA) Servizio di Anestesia This would allow identification of subgroups for whom TIVA could be especially advantageous. However, except for abdominal and laparoscopic procedures, TIVA proved beneficial to the
    53. 53. IS PONV incidence different between LMA and ETT? Joshi GP, Inagaki Y, White PF, TaylorKennedy L, Wat LI, Gevirtz C, McCraney JM, McCulloch DA: Use of the laryngeal mask airway as an alternative to the tracheal tube during ambulatory anesthesia. Anesth Analg 85:573–7, 199 Servizio di Anestesia e Rianimazione Ospedale di Faenza(RA)
    54. 54. Risk Factors Volatile anesthetics Risk Factors OR* CI isoflurane 3.41 2.18; 5.37 sevoflurane 2.78 1.79; 4.31 enflurane 3.11 1.98; 4.88 Volatile anesthetics * Compared to propofol Apfel et al. BJA 2002;88:659-668 Servizio di Anestesia e Rianimazione Ospedale di Faenza(RA)
    55. 55. Risk Factors Reversal of Neuromuscular Block Omitting neostigmine may have a clinically relevant antiemetic effect when high doses are used Omitting NMB antagonism introduces a nonnegligent risk of residual paralysis even when short acting NMB agents are used Tramer MR, Fuchs-Buder T. BJA 1999;82:379-386 Servizio di Anestesia e Rianimazione Ospedale di Faenza(RA)
    56. 56. Risk Factors Propofol and PONV Analysis by NNT All Control Event Rates Early Late Nausea Induction Maintenance Vomiting Any Nausea Vomiting Any 9.3* 13.7* 20.9 50.1 14.9 NA 8* 9.2* 6.2* 5.8* 10.1* 10 20% - 60% Control Event Rate 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 Tramer et al. BJA 1997;78:247-255 Servizio di Anestesia e Rianimazione Ospedale di Faenza(RA)
    57. 57. Risk Factors Antiemetic Effects of Propofol Investigations Randomized Double-Blind Placebo-Controlled Effective Chemotherapy Induced Emesis Scher 1992 no no no yes Borgeat 1993 no no no yes Borgeat 1994 no no no yes Campbell 1991 yes yes yes no Borgeat 1992 yes yes yes yes Ewalenko 1996 yes yes yes yes Montgomery 1996 yes yes yes no Scuderi 1996 yes yes yes no Gan 1997 no no no yes Gan 1999 yes yes yes yes PONV Servizio di Anestesia e Rianimazione Ospedale di Faenza(RA)
    58. 58. Risk Factors Logistic Regression Palazzo M, Evans R. Logistic regression analysis of fixed patient factors for postoperative sickness: a model for risk assessment. Br J Anaesth 1993;70:13540. Koivuranta M, Läärä E, Snåre 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. Servizio di Anestesia e Rianimazione Ospedale di Faenza(RA)
    59. 59. Risk Factors Logistic Regression Younger age Nonsmoking history Female Hx of motion sickness Hx of PONV Increased duration of operation Servizio di Anestesia e Rianimazione Ospedale di Faenza(RA)
    60. 60. Risk Factors Simplified Scoring System Female Nonsmoking history Hx of motion sickness or PONV Use of postoperative opioids Incidence of PONV Risk Factors Incidence 0 10% 1 21% 2 39% 3 61% 4 79% Servizio di Anestesia e Rianimazione Ospedale di Faenza(RA) Apfel CC et al. Anesthesiology 1999;91:693-700.
    61. 61. Simplified scoring system from Apfel for adults For every risk factor the sum is additive: Point 0 risk 10% Point 1 risk 20% Point 2 risk 40% Point 3 risk 60% Point 4 risk 80% Servizio di Anestesia e Rianimazione Ospedale di Faenza(RA)
    62. 62. Servizio di Anestesia e Rianimazione Ospedale di Faenza(RA)
    63. 63. Simplified risk score from Apfel et al. to predict the patients risk for PONVin adults . When 0, 1, 2, 3, or 4 of the depicted independent predictors are present, the corresponding riskfor PONV is approximately 10%, 20%, 40%, 60%, or 80%. Figure 1 Servizio di Anestesia e Rianimazione Ospedale di Faenza(RA)
    64. 64. Simplified scoring system from Eberhardt 39 di Sambafor children Surgery> 30 min Age> 3 Strabismus surgery Hx of POV or POnv in relatives Sum 0......4 Risk 10%,10%,30%,55%,70% Servizio di Anestesia e Rianimazione Ospedale di Faenza(RA)
    65. 65. Simplified risk score from Eberhart et al. (39) to predict the risk for POV in children. When 0, 1, 2, 3, or 4 of the depicted independent predictors are present, the corresponding risk for PONV is approximately 10%, 10%, 30%, 55%, or 70%. Servizio di Anestesia e Rianimazione Ospedale di Faenza(RA)
    66. 66. Problems............ to separate independent factors vs dependent factors................ No risk model can actually predict the likelihood of an individual having PONV;risk models only allow clinicians to etimate the risk of PONV among patients groups Servizio di Anestesia e Rianimazione Ospedale di Faenza(RA)
    67. 67. PONV PONV fattori di rischio donne giovani giovani età età fertile fertile gravide gravide post post partum partum Non smokers interventi bambini muscoli muscoli extraoculari extraoculari deambulazione deambulazione precoce precoce pregresso PONV farmaci oppioidi oppioidi anestetici anestetici inalatori inalatori orecchio orecchio medio medio pelvi pelvi femm.in femm.in laparoscopia laparoscopia soggetti a cinetosi Neurosurg Breast surg Laparotomy Plastic surg. Servizio di Anestesia e Rianimazione Ospedale di Faenza(RA) N2O
    68. 68. Use of prophylactic antiemetics should be based on valid assessment of the patients risk for POV or PONV. In other words....antiemetic prophylaxis shouild be used only when the patient individual risk is sufficiently high. Estimate:baseline risk * baseline risk reduction resulting from prophylaxisUse of prophylactic antiemetics should be based on This approach produces a clinically meaningful decrease in the risk of PONV Servizio di Anestesia e Rianimazione Ospedale di Faenza(RA)
    69. 69. Particular medical risk more liberal prophylaxis is appropriate for patients in whom vomiting poses a particular medical risk: wired jaws increased intracranial pressure gastric or esophageal surgery when the anesthesia care provider determines the need or the patient has a strong preference to avoid PONV Servizio di Anestesia e Rianimazione Ospedale di Faenza(RA)
    70. 70. Strategies to Reduce Baseline Risk Avoidance of general anesthesia by the use of regional anesthesia (11,16) (randomized, controlled trial, RCT) Use of propofol for induction and maintenance of Anesthesia(4,14,41,42) (RCT/systematic review, SR) Avoidance of nitrous oxide (3,4,43,44) (RCT/SR) Avoidance of volatile anesthetics (15,28) (RCT) Minimization of intraoperative (SR) and postoperative opioids (3,13,15,17,18,20,28,43) (RCT/SR) Minimization of neostigmine (19,45) (SR) Adequate hydration (46) (RCT) Servizio di Anestesia e Rianimazione Ospedale di Faenza(RA)
    71. 71. Trattamento del PONV Servizio di Anestesia e Rianimazione Ospedale di Faenza(RA)
    72. 72. Management of PONV: Pharmacological Approaches Medications Dose response Comparative efficacy Combination therapy Timing of administration Servizio di Anestesia e Rianimazione Ospedale di Faenza(RA)
    73. 73. Servizio di Anestesia e Rianimazione Ospedale di Faenza(RA)
    74. 74. Servizio di Anestesia e Rianimazione Ospedale di Faenza(RA)
    75. 75. Figure 3 Servizio di Anestesia e Rianimazione Ospedale di Faenza(RA)
    76. 76. Servizio di Anestesia e Rianimazione Ospedale di Faenza(RA)
    77. 77. Servizio di Anestesia e Rianimazione Ospedale di Faenza(RA)
    78. 78. Antiemetici Antiemetici evoluzione del pensiero metoclopramide droperidol ondansetron preso dalla gastroenterologia preso dalla gastroenterologia preso dagli antipsicotici.... preso dagli antipsicotici.... la nuova frontiera... granisetron Servizio di Anestesia e Rianimazione Ospedale di Faenza(RA)
    79. 79. PONV PONV Recettori coinvolti ondansetron butirofenoni::droperidol butirofenoni::droperidol metoclopramide metoclopramide granisetron fenotiazine fenotiazine D2 5Ht3 steroidi tropisetron CRTZ Combination Combination therapy therapy Ach scopolamina scopolamina Servizio di Anestesia e Rianimazione Ospedale di Faenza(RA) H1 antistaminici::imedrinato,idrossizina,ciclizina antistaminici::imedrinato,idrossizina,ciclizina
    80. 80. Currently Available Medications 5HT3 (serotonin) antagonists - ondansetron Butyrophenones - droperidol Benzamides - metoclopramide Antihistamines - dimenhydrinate Steroids - dexamethasone Phenothiazinespromethazine,prochlorperazine Anticholinergics – scopolamine Servizio di Anestesia e Rianimazione Ospedale di Faenza(RA)
    81. 81. 5HT3 Antagonists and PONV (Summer 2002) 5HT3 Antagonist Clinical Trials Ondansetron * 275 Dolasetron* 20 Granisetron* 66 Tropisetron 27 Ramosetron 29 Palenosetron 5 * Approved for PONV indication Servizio di Anestesia e Rianimazione Ospedale di Faenza(RA)
    82. 82. Prevention of PONV: Ondansetron Versus Placebo % of Patients with No Emesis All patients, 0 - 24 hrs 100 80 60 † 76 4 mg * 62 † 77 8 mg 46 40 20 0 Placebo * p = 0.010 † p < 0.001 1 mg Ondansetron Dose McKenzie et al. Anesthesiology 1993;78:21-28 Servizio di Anestesia e Rianimazione Ospedale di Faenza(RA)
    83. 83. Ondansetron Dose Response: Prevention Numbers Needed to be Treated 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 Tramer et al. Anesthesiology 1997;87:1277-1289 Servizio di Anestesia e Rianimazione Ospedale di Faenza(RA)
    84. 84. Treatment of PONV: % with Complete Response Ondansetron Versus Placebo 100 80 * 57 60 40 * 60 * 57 * 40 32 * 45 * 44 20 20 0 0 - 2 hr * p < 0.001 Placebo 2 - 24 hr 1 mg Servizio di Anestesia e Rianimazione Ospedale di Faenza(RA) 4 mg 8 mg Scuderi et al. Anesthesiology 1993;78:2-5 Hantler et al. Anesthesiology 1992;77:A16
    85. 85. Ondansetron Dose Response: Treatment Numbers Needed to be Treated 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 Servizio di Anestesia e Rianimazione Ospedale di Faenza(RA) Tramer et al. BMJ 1997;314:1088-1092
    86. 86. Breakthrough PONV: Percent Complete Response Repeat Dosing With Ondansetron 100 * p = 0.074 80 † p = 0.342 60 43 40 * 34 32 † 28 20 0 0 - 2 hours Placebo 0 - 24 hours Ondansetron 4 mg Kovac et al. J. Clin Anesth 1999;11:453-459 Servizio di Anestesia e Rianimazione Ospedale di Faenza(RA)
    87. 87. Prevention of PONV: Complete Response % Dolasetron Versus Placebo 100 80 * * * 56 * 52 ** 50 60 40 31 * * ** * 46 * 43 28 39 * * * 55 57 * * * 52 33 20 0 All Patients Placebo Previous PONV 12.5 mg *p < 0.0003 compared to placebo Servizio di Anestesia e Rianimazione Ospedale di Faenza(RA) 25 mg No PONV 50 mg Graczyk et al. Anesth Analg 1997;84:325-330
    88. 88. Treatment of PONV: Dolasetron Versus Placebo Complete Response % Placebo 12.5 mg 25 mg 50 mg 100 mg 100 80 * * 55 60 40 * * 50 * * 48 * * 51 * * 35 27 20 * * 28 * * 29 ** 29 11 0 0 - 2 hrs 0 - 24 hrs *p < 0.001 compared to placebo Servizio di Anestesia e Rianimazione Ospedale di Faenza(RA) Kovac et al. Anesth Analg 1997;85:546-552
    89. 89. Prevention of PONV: Ondansetron Versus Dolasetron Placebo Dolasetron 25 mg Dolasetron 50 mg Ondansetron 4 mg % of Patients 100 * 80 60 71 49 * * * 60 64 51 36 40 † 54 43 20 0 Complete Response Total Response * p < 0.05 versus placebo and dolasetron 25 mg † p < 0.05 versus placebo only Korttila K et al. Acta Anaesthesiol Scand 1997;41:914-922 Servizio di Anestesia e Rianimazione Ospedale di Faenza(RA)
    90. 90. Prevention of PONV: Ondansetron Versus Dolasetron Postoperative Vomiting % without Symptoms Dolasetron 12.5 mg Dolasetron 25 mg Ondansetron 4 mg Ondansetron 8 mg 100 100 96 96 94 92 96 96 98 80 In-hospital No statistically significant differences among the groups Postdischarge Zarate E, et al. Anesth Analg 2000;90:1352-1358 Servizio di Anestesia e Rianimazione Ospedale di Faenza(RA)
    91. 91. Prevention of PONV: Ondansetron Versus Dolasetron Postoperative Nausea % without Symptoms Dolasetron 12.5 mg Dolasetron 25 mg 100 80 73 76 77 Ondansetron 4 mg 82 70 Ondansetron 8 mg 87 76 86 60 40 20 0 In-hospital No statistically significant differences among the groups Postdischarge Zarate E, et al. Anesth Analg 2000;90:1352-1358 Servizio di Anestesia e Rianimazione Ospedale di Faenza(RA)
    92. 92. Prevention of PONV: Ondansetron Versus Droperidol Complete Response Placebo Droperidol 0.625 mg Droperidol 1.25 mg Ondansetron 4 mg % of Patients 100 80 60 * 63 *† 69 * 62 46 * 48 *‡ * 56 53 36 40 20 0 0 - 2 hr * p < 0 .05 compared to placebo † p < 0.05 compared to ondansetron 4 mg ‡ p ,<0.05 compared to droperidol 0.625 mg Servizio di Anestesia e Rianimazione Ospedale di Faenza(RA) 0 - 24 hr Fortney et al. Anesth Analg 1998;86:731-738
    93. 93. Prevention of PONV: Ondansetron Versus Droperidol No Nausea % of Patients 100 * p < 0 .05 compared to placebo † p < 0.05 compared to droperidol 0.625 mg and ondansetron 4 mg 80 60 40 ∗† 43 ∗ 23 29 ∗ 29 20 0 0 - 24 hr Placebo Droperidol 0.625 mg Droperidol 1.25 mg Ondansetron 4 mg Fortney et al. Anesth Analg 1998;86:731-738 Servizio di Anestesia e Rianimazione Ospedale di Faenza(RA)
    94. 94. Droperidol Adverse Events Reports 273 “reports” from 1997-2001 127 serious adverse events 89 total deaths Droperidol 2.5 mg or less » 6 deaths » 5 Torsades or VT (1 fatality) Norton et al. Anesthesiology 2002:A-1196 Servizio di Anestesia e Rianimazione Ospedale di Faenza(RA)
    95. 95. Droperidol FDA Box Warning No case details provided 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) Servizio di Anestesia e Rianimazione Ospedale di Faenza(RA)
    96. 96. Putting It in Perspective Circumstance Annual Fatalities Transportation motor vehicle pedestrian cyclists rail bus airline 37,409 4,739 690 518 299 92 Animal Related dog bite auto-deer collisions 20 130 Other lightning boating Servizio di Anestesia e Rianimazione Ospedale di Faenza(RA) 90 734
    97. 97. 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 Servizio di Anestesia e Rianimazione Ospedale di Faenza(RA)
    98. 98. 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 Servizio di Anestesia e Rianimazione Ospedale di Faenza(RA)
    99. 99. Prevention of PONV: Dexamethasone Dose ranging Major gynecological surgery Placeb 1.25 mg o 2.5 mg 5.0 mg 10.0 mg Patients 30 30 30 30 30 Vomiting 19 15 8* 6* 6* Rescue required 5 0 0 0 0 * P <0.05 compared with placebo and 1.25 mg Liu K, et al. Anesth Analg 1999;89:1316-1318 Servizio di Anestesia e Rianimazione Ospedale di Faenza(RA)
    100. 100. Prevention of PONV: Scopolamine Undefined control event rate Small Studies Outcome Large Studies Trials NNT Trials NNT Vomiting 7 3.6 8 8.3 Nausea 7 3.4 6 5.9 PONV 11 2.5 9 7.1 Rescue 4 3.8 6 20.0 Kranke, et al. Anesth Analg 2002;95:133-143 Servizio di Anestesia e Rianimazione Ospedale di Faenza(RA)
    101. 101. Prevention of PONV: Scopolamine Defined control event rate Small Studies Outcome Large Studies 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 Servizio di Anestesia e Rianimazione Ospedale di Faenza(RA)
    102. 102. Prevention of PONV: Scopolamine Adverse Events Event Visual disturbances NNH 5.6 Dry mouth 12.5 Dizziness 50.0 Agitation 100.1 Kranke, et al. Anesth Analg 2002;95:133-143 Servizio di Anestesia e Rianimazione Ospedale di Faenza(RA)
    103. 103. Prevention of PONV: Dimenhydrinate Early (0-6 h) Outcome Overall (0-48 h) 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 Servizio di Anestesia e Rianimazione Ospedale di Faenza(RA)
    104. 104. Prevention of PONV: Combination Therapy Ondansetron/Dexamethasone 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. Anaesthesist. 2000 ;49:713-20 Servizio di Anestesia e Rianimazione Ospedale di Faenza(RA)
    105. 105. Prevention of PONV: Combination Therapy Ondansetron/Droperidol 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 5-ht3receptor 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 Servizio di Anestesia e Rianimazione Ospedale di Faenza(RA)
    106. 106. Prevention of PONV: Combination Therapy Which Combination? 5-HT3 + drop Event 5-HT3 + dex N Rate N Rate P-value OR Nausea 138 17% 260 11% 0.12 1.6 Vomiting 318 1% 419 1% 1.00 1.0 Nausea 358 27% 623 21%* 0.02 1.4 Vomiting 443 9% 813 9% 1.00 0.9 Early Late Ashraf et al. Anesthesiology 2001; 95:A-41 Servizio di Anestesia e Rianimazione Ospedale di Faenza(RA)
    107. 107. Prevention of PONV: Combination Therapy Placebo Metoclopramide Dolasetron Ondansetron nausea (%) 13 7 3 3 vomiting (%) 0 0 0 0 rescue (%) 0 0 0 0 nausea (%) 13 10 7 3 vomiting (%) 0 0 0 0 rescue (%) 0 0 0 0 Predischarge Postdischarge Servizio di Anestesia e Rianimazione Ospedale di Faenza(RA) Tang, et al. Anesthesiology 2001; 95:A43
    108. 108. Prevention of PONV: Timing of Administration Ondansetron Sun et al. The effect of timing on ondansetron administration in outpatients undergoing otolaryngologic surgery. Anesth Analg 1997;84:331-336 Dolasetron Chen et al. The effect of timing of dolasetron administration on its efficacy as a prophylactic antiemetic in the ambulatory setting. Anesth Analg 2001;93:906911 Dexamethasone 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 Servizio di Anestesia e Rianimazione Ospedale di Faenza(RA)
    109. 109. Tang J,Wang B, White PF,Watcha M,Qi J,Wender R.The effect of timing of ondansetron administration on its efficacy,cost effectiveness and cost benefit as a prophylactic antiemetic in the ambulatory setting.Anesth.Analg 1998;96:........ *ABSTRACT: Although ondansetron (4 mg IV) is effective in the prevention and treatment of postoperative nausea and vomiting (PONV) after ambulatory surgery, the optimal timing of its administration, the cost-effectiveness, the costbenefits, and the effect on the patient's quality of life after discharge have not been established. In this placebocontrolled, double-blind study, 164 healthy women undergoing outpatient gynecological laparoscopic procedures with a standardized anesthetic were randomized to receive placebo (Group A), ondansetron 2 mg at the start of and 2 mg after surgery (Group B), ondansetron 4 mg before induction (Group C), or ondansetron 4 mg after surgery (Group D). The effects of these regimens on the incidence, severity, and costs associated with PONV and discharge characteristics were determined, along with the patient's willingness to pay for antiemetics. Compared with ondansetron given before induction of anesthesia, the administration of ondansetron after surgery was associated with lower nausea scores, earlier intake of normal food, decreased incidence of frequent emesis (more than two episodes), and increased times until 25% of patients failed prophylactic antiemetic therapy (i.e., had an emetic episode or received rescue antiemetics for severe nausea) during the first 24 h postoperatively. This prophylactic regimen was also associated with the highest patient satisfaction and lowest cost-effectiveness ratios. Compared with the placebo group, ondansetron administered after surgery significantly reduced the incidence of PONV in the postanesthesia care unit and during the 24-h follow-up period and facilitated the recovery process by reducing the time to oral intake, ambulation, discharge readiness, resuming regular fluid intake and a normal diet. When ondansetron was given as a “split dose,” its prophylactic antiemetic efficacy was not significantly different from that of the placebo group. In conclusion, the prophylactic administration of ondansetron after surgery, rather than before induction, may be associated with increased patient benefits. Implications: Ondansetron 4 mg IV administered immediately before the end of surgery was the most efficacious in preventing postoperative nausea and vomiting, facilitating both early and late recovery, and improving patient satisfaction after outpatient laparoscopy. Servizio di Anestesia e Rianimazione Ospedale di Faenza(RA)
    110. 110. Tang J,Wang B, White PF,Watcha M,Qi J,Wender R.The effect of timing of ondansetron administration on its efficacy,cost effectiveness and cost benefit as a prophylactic antiemetic in the ambulatory setting.Anesth.Analg 1998;96:........ Anesthesia was induced with fentanyl 1.0–1.5 mg/kg IV, followed by propofol 1.5–2.0 mg/kg IV, and tracheal intubation was facilitated with either succinylcholine 1 mg/kg IV or vecuronium 0.1 mg/kg IV. Anesthesia was maintained with desflurane 3%– 6% in combination with nitrous oxide (N2O) 60% oxygen; fentanyl 0.5–1.0 mg/kg IV and vecuronium 1– 2 mg IV were administered as needed. If necessary, neuromuscular blockade was antagonized with neostigmine 0.05 mg/kg IV and glycopyrrolate 0.01 mg/kg IV. After tracheal extubation, the patients were transported to the postanesthesia care unit (PACU). Servizio di Anestesia e Rianimazione Ospedale di Faenza(RA)
    111. 111. Tang J,Wang B, White PF,Watcha M,Qi J,Wender R.The effect of timing of ondansetron administration on its efficacy,cost effectiveness and cost benefit as a prophylactic antiemetic in the ambulatory setting.Anesth.Analg 1998;96:........ Servizio di Anestesia e Rianimazione Ospedale di Faenza(RA)
    112. 112. Tang J,Wang B, White PF,Watcha M,Qi J,Wender R.The effect of timing of ondansetron administration on its efficacy,cost effectiveness and cost benefit as a prophylactic antiemetic in the ambulatory setting.Anesth.Analg 1998;96:........ Servizio di Anestesia e Rianimazione Ospedale di Faenza(RA)
    113. 113. Incidence of nausea and vomiting in the Pacu in the 4 treatment groups:placebo,ondansetron 2 mg pre and 2 mg post surg I ,ondansetron 4 mg preinduction, ondansetron 4 mg at the end of surgery. 80 70 60 50 40 * placebo split dose preinduction end of surgery * 30 * 20 10 0 nausea% vomit% Tang J,Wang B, White PF,Watcha M,Qi J,Wender R .The effect of timing of ondansetron administration on its efficacy ,cost effectiveness and cost benefit as a prophylactic antiemetic in the ambulatory setting.Anesth.Analg 1998;96:........ rescue nausea VAS antiemetics at 2 h(mm) Servizio di Anestesia e Rianimazione Ospedale di Faenza(RA)
    114. 114. Incidence of nausea and vomiting in the 24 hrs post surgery in the 4 treatment groups:placebo,,ondansetron 2 mg pre and 2 mg post surg ,ondansetron 4 mg preinduction,ondansetron 4 mg at the end of surgery. 80 70 60 50 * placebo split dose preinduction postsurg 40 30 * 20 * 10 0 * nausea% vomit% * rescue nausea VAS vomiting>2 antiemetics medio(mm) times Tang J,Wang B, White PF,Watcha M,Qi J,Wender R Servizio di Anestesia e Rianimazione Ospedale di Faenza(RA) .The effect of timing of ondansetron administration on its efficacy ,cost effectiveness and cost benefit as a prophylactic antiemetic in the ambulatory setting.Anesth.Analg 1998;96:........
    115. 115. Servizio di Anestesia e Rianimazione Ospedale di Faenza(RA)
    116. 116. Timing of Administration: Dexamethasone Group 1 Group 2 Group 3 (Preinduction) (Postextubation) (Placebo) nausea (%) 10 25 33 vomiting (%) 5 20 20 15*† 45 53 nausea (%) 15 18 30 vomiting (%) 10 10 25 total (%) 25* 28* 55 0 – 2 hr total (%) 2 – 24 hr * Compared to Group 3 † Compared to Group 2 Wang et al. Anesth Analg 2000;91;136-139 Servizio di Anestesia e Rianimazione Ospedale di Faenza(RA)
    117. 117. Management of PONV: Adjuvants (Nonpharmacologic) P-6 acupuncture point stimulation Supplemental oxygen Aggressive perioperative rehydration Preemptive analgesia Servizio di Anestesia e Rianimazione Ospedale di Faenza(RA)
    118. 118. 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. Servizio di Anestesia e Rianimazione Ospedale di Faenza(RA)
    119. 119. P-6 Acupuncture Point Stimulation Control of Nausea TAES Sham Placebo PACU 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 * compared to sham † compared to placebo Zarate E, et al. Anesth Analg 2001;92:629-35 Servizio di Anestesia e Rianimazione Ospedale di Faenza(RA)
    120. 120. Supplemental Oxygen Greif R, Laciny S, Rapf B, et al. Supplemental oxygen reduces the incidence of postoperative nausea and vomiting. Anesthesiology 1999;91:1246-52. Goll V, Ozan A, Greif R, et al. Ondansetron is no more effective than supplemental intraoperative oxygen for prevention of postoperative nausea and vomiting. Anesth Analg 2001;92:112-17. Servizio di Anestesia e Rianimazione Ospedale di Faenza(RA)
    121. 121. Supplemental Oxygen 30 % Oxygen 80% Oxygen P Value Male/Female 57/62 41/71 0.110 0-6 hr PONV (%) 15.1 8 0.141 nausea (%) 15.1 8 0.077 vomiting (%) 1.7 0 0.169 PONV (%) 22.2 19.9 0.045 nausea (%) 17.6 8.9 0.066 vomiting (%) 5.9 1.8 0.108 PONV (%) 30.3 17 0.027 nausea (%) 27.7 16 0.034 vomiting (%) 5.9 1.8 0.108 6-24 hr 0-24 hr Greif et al. Anesthesiology 1999;91:1246-1252 Servizio di Anestesia e Rianimazione Ospedale di Faenza(RA)
    122. 122. Supplemental Oxygen 30 % Oxygen 80% Oxygen Ondansetron Patients (female) 80 79 71 0-6 hr PONV (%) 36 20 27 nausea (%) 35 20 27 vomiting (%) 19 9 14 PONV (%) 13 4 6 nausea (%) 11 4 6 vomiting (%) 9 4 1 PONV (%) 44 22* 30 nausea (%) 41 22* 30 vomiting (%) 26 10* 15 6-24 hr 0-24 hr Goll et al. Anesth Analg 2001;92:112-117 Servizio di Anestesia e Rianimazione Ospedale di Faenza(RA)
    123. 123. Intravenous Fluid Therapy Incidence of Postop Nausea 20 Low Infusion High Infusion Incidence % 15 10 5 * 0 30 min 60 min High Infusion = 20 ml/kg Low Infusion = 2 ml/kg Time DIS Day 1 Yogendran S, et al. Anesth Analg 1995;80:682-686 Servizio di Anestesia e Rianimazione Ospedale di Faenza(RA)
    124. 124. Pain and PONV Effects % of Total Patients Pain relieved, nausea relieved 68.5 Pain reduced, nausea relieved 11.5 Pain relieved, nausea persisted 9.5 Pain persisted, nausea persisted 10.5 Andersen et al. Can Anaesth Soc J 23:366-369, 1976 Servizio di Anestesia e Rianimazione Ospedale di Faenza(RA)
    125. 125. Efficacy Versus Outcome Servizio di Anestesia e Rianimazione Ospedale di Faenza(RA)
    126. 126. Surrogate End Points Are They Meaningful Appropriate end points Duration of PACU stay Incidence of unplanned admissions Patient satisfaction Fisher. Anesthesiology 1994;81:795-796 Servizio di Anestesia e Rianimazione Ospedale di Faenza(RA)
    127. 127. Measures of Outcome Mortality Morbidity Patient satisfaction Cost Servizio di Anestesia e Rianimazione Ospedale di Faenza(RA)
    128. 128. Risk of Mortality and Adverse Outcome in a Tertiary Care Population Adverse outcomes 1:125 Death (all causes) 1:500 Anesthesia provider error causing adverse outcome 1:1,500 Risk of death (anesthesia cause only) 1:250,000 Patient Safety in Anesthesia Practice. Morel and Eichorn (ed) Servizio di Anestesia e Rianimazione Ospedale di Faenza(RA)
    129. 129. Complications of PONV Electrolyte imbalance Tension on sutures, evisceration Venous hypertension, bleeding Aspiration Delayed discharge (outpatients) Dehydration Unanticipated admission Servizio di Anestesia e Rianimazione Ospedale di Faenza(RA)
    130. 130. Unanticipated Admissions Reasons for Admission Pain Bleeding Intractable Vomiting Perforated Uterus Extensive Surgery Urinary Retention Additional Surgery Number Percent 18 18 17 7 6 5 4 19 19 18 7 6 5 4 Overall Admission Rate = 0.01 PONV Admission Rate = 0.002 Servizio di Anestesia e Rianimazione Ospedale di Faenza(RA) Gold et al. JAMA 1989;262:3008-3010
    131. 131. Cost Savings From the Management of PONV Analysis of strategies to decrease postanesthesia care unit costs: 1. Supplies and medications account for 2% of PACU charges 2. Personnel account for almost all PACU charges 3. PACU staffing is determined by peak PACU patient load 4. Peak PACU patient load is determined by OR scheduling 5. Elimination of PONV would decrease PACU stay by less than 4.8% which would not be sufficient to decrease the level of staffing Dexter et al. Anesthesiology 1995;82:94-101 Servizio di Anestesia e Rianimazione Ospedale di Faenza(RA) PACU
    132. 132. Subject Preference Following Surgery Preoperative Levels Mental Acuity Preference awake drowsy asleep 5% Pain none mild moderate 18% Emetic Sxs none nausea vomiting 40% Muscle Aches no yes 11% Dysphoria no yes 16% none $15 Cost $35 $50 Orkin FK. Anesth Analg 1992;74:S225 Servizio di Anestesia e Rianimazione Ospedale di Faenza(RA) 10%
    133. 133. Patient Preference Following Surgery Preoperative Outcome Vomiting Gagging Pain Nausea Recall w/o pain Shivering Residual weakness Sore Throat Somnolence Normal Mean Rank 2.55 2.95 3.46 4.05 4.87 5.39 5.43 8.04 8.18 10.00 Relative Value (out of 100) Ranking (%) First Second Third 18.5 18.6 16.8 12.5 13.8 7.3 7.2 3.2 2.9 0.2 24 22 22 6 20 1 5 0 0 0 31 20 16 18 6 6 4 0 0 0 23 24 16 14 4 7 11 0 0 0 Macario et al. Anesth Analg, 1999;89:652-658 Servizio di Anestesia e Rianimazione Ospedale di Faenza(RA)
    134. 134. Patient Satisfaction With Outpatient Surgery Postoperative Considered Factor Important Preoperative Avoidance of Delays Starting IV smoothly Intraoperative Friendliness of OR Staff Postoperative Management of Postop pain Surgeon’s PACU visit Treatment of PONV Ranking in Top 5 (%) Rank Order of top 5 86 95 Factor 45 53 5 4 97 67 1 96 96 90 62 63 31 3 2 Tarazi and Philip. Am J Anesthesiology 1998;25:154-157 Servizio di Anestesia e Rianimazione Ospedale di Faenza(RA)
    135. 135. Efficacy Versus Outcome If efficacy is an appropriate endpoint when evaluating analgesics, why not when evaluating antiemetics? Servizio di Anestesia e Rianimazione Ospedale di Faenza(RA)
    136. 136. Prevention Versus Treatment Question: Does routine* administration of prophylactic antiemetics improve outcome when compared to rapid symptomatic treatment of postoperative nausea and/or vomiting? *Routine: habitual or mechanical (i.e., mindless) performance of an established procedure Servizio di Anestesia e Rianimazione Ospedale di Faenza(RA)
    137. 137. Frequency of PACU Treatment by Risk Factors and Group PACU TREATMENT REQUIRED BY GROUP RISK FACTORS Subgroup Gender Prior History Emetogenic Procedure1 Ondansetron Placebo A Male Yes Yes 0% 50% B Male Yes No 25% 38% C Male No Yes 7% 25% D Male No No 16% 16% E Female Yes Yes 38% 57% F Female Yes No 45% 53% G Female No Yes 29% 31% H Female No No 14% 17% Emetogenic procedures - laparoscopy, strabismus surgery, middle ear surgery, herniography, tonsillectomy, adenoidectomy, uvulopalatopharyngoplasty 1 Servizio di Anestesia e Rianimazione Ospedale di Faenza(RA) Scuderi et al. Anesthesiology. 1999;90:360-371
    138. 138. Efficacy of Prophylaxis – Overall Ondansetron Placebo 285 290 0, 0, 0 0,0,2 0.54 No Tx Required (%) 204 (71.6) 179 (61.7) 0.01 Treatment Required Nausea (%) Vomiting (%) Total (%) 64 (22.5) 17 (6.0) 81 (28) 70 (24.1) 41 (14.1) 111 (38) 0.63 0.001 0.01 5,8,10 (100) 6,9,10 (96.4) 0.14 Total Nausea Score PACU Entry median, 75th, 90th Nausea Score @ TX median, 75th, 90th nausea score >0 (%) Servizio di Anestesia e Rianimazione Ospedale di Faenza(RA) p-value Scuderi et al. Anesthesiology. 1999;90:360-371
    139. 139. Efficacy of Prophylaxis - Group E Ondansetron Placebo 58 60 0,0,4 0,0,6 0.49 No Tx Required (%) 36 (62) 26 (43) 0.045 Treatment Required Nausea (%) Vomiting (%) Total (%) 17 (29) 5 (9) 22 (38) 21 (35) 13 (22) 34 (57) 0.045 Total Nausea Score PACU Entry median, 75th, 90th p-value Scuderi et al. Anesthesiology. 1999;90:360-371 Servizio di Anestesia e Rianimazione Ospedale di Faenza(RA)
    140. 140. Outcomes - Treatment vs Prophylaxis Patient Satisfaction, Time to Discharge Ondansetron Placebo P Total patients 285 290 -- All Patients - placebo Tx excluded 245 235 -- Satisfaction PONV: yes/no (%) 97% 93% 0.04 7,9,10 7,9,10 0.76 87(82,92) 92(86,98) 0.23 47 42 -- 47 (100) 37 (90) 0.04 7,9,10 8,9,10 0.73 99(85,114) 117(98,139) 0.13 Satisfaction Overall: (11 pt scale)* Time to discharge (95% CI) min Group E patients - placebo Tx excluded Satisfaction PONV: yes/no (%) Satisfaction Overall: (11 pt scale)* Time to discharge (95% CI) min * 10th, 25th, median NNT 25 10 Scuderi et al. Anesthesiology. 1999;90:360-371 Servizio di Anestesia e Rianimazione Ospedale di Faenza(RA)
    141. 141. Prevention Versus Treatment Answer: Routine administration of prophylactic antiemetics does reduce the incidence of emesis both before and after discharge; however, it does not improve “objective” measures of outcome following outpatient surgery except in patients at the highest risk for symptoms Servizio di Anestesia e Rianimazione Ospedale di Faenza(RA)
    142. 142. Multimodal Management of PONV: Hypothesis 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) Scuderi at al. Anesth Analg 2000;91:408-414 Servizio di Anestesia e Rianimazione Ospedale di Faenza(RA)
    143. 143. Multimodal Management of PONV: Results Group I Group II Group III 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‡ Servizio di Anestesia e Rianimazione Ospedale di Faenza(RA) P values Scuderi at al. Anesth Analg 2000;91:408-414
    144. 144. Multimodal Management of PONV: Simplified Algorithm I. INDUCTION II. MAINTENANCE A. PreO2 A. Propofol 50 mcg/kg/min B. Propofol 2 - 4 mg/kg B. Potent inhalation agent/remif C. Opioid prn D. Neuromuscular blockade prn C.Generous hydration D Nitrous oxide prn C. Droperidol 10 mcg/kg Early E. NMB reversal prn D. Decadron 4 - 8 mg & aggress postop pain the III. EMERGENCE A. Ondansetron 1 mg IV B. Suction oropharynx C. Extubate when awake Servizio di Anestesia e Rianimazione Ospedale di Faenza(RA)
    145. 145. Multimodal Management of PONV: Simplified Algorithm Cost Analysis 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 Servizio di Anestesia e Rianimazione Ospedale di Faenza(RA)
    146. 146. Multimodal Management of PONV: Conclusions Elimination of PONV in outpatients is possible with multimodal management Algorithm may be institution and/or procedure specific Identification of the optimal management algorithm may require several iterations Elimination of PONV may not improve objective measures of outcome Servizio di Anestesia e Rianimazione Ospedale di Faenza(RA)
    147. 147. PONV PONV we know the risk factors Preventive strategy non emetogenic drugs... Antiemetic Prophylaxis Selected at risk groups Immediate treatment Servizio di Anestesia e Rianimazione Ospedale di Faenza(RA) in case of occurrence.....
    148. 148. PONV dopo la dimissione Servizio di Anestesia e Rianimazione Ospedale di Faenza(RA)
    149. 149. Efficacy of antiemetic medication on postdischarge nausea (Gupta A,Wu,CL,Elkassabani,N,Krug,CE,Parker,SD,Fleisher LA.Does the routine prophylactic use of antiemetics affect the incidence of postischarge nausea and vomuint following ambulatory surgery?.Anesthesiology 2003;99:488-95.) Servizio di Anestesia e Rianimazione Ospedale di Faenza(RA)
    150. 150. Efficacy of antiemetic medication on posdtdischarge vomiting (Gupta A,Wu,CL,Elkassabani,N,Krug,CE,Parker,SD,Fleisher LA.Does the routine prophylactic use of antiemetics affect the incidence of postischarge nausea and vomuint following ambulatory surgery?.Anesthesiology 2003;99:488-95.) Servizio di Anestesia e Rianimazione Ospedale di Faenza(RA)
    151. 151. Postdischarge nausea (Gupta A,Wu,CL,Elkassabani,N,Krug,CE,Parker,SD,Fleisher LA.Does the routine prophylactic use of antiemetics affect the incidence of postischarge nausea and vomuint following ambulatory surgery?.Anesthesiology 2003;99:488-95.) Relative Risk (%) of antiemetic medication on postdischarge nausea 100 80 60 40 20 0 placebo Servizio di Anestesia e Rianimazione Ospedale di Faenza(RA) ondans 1 mg ondans 4 mg ondans 8 mg drop <1 mg drop>1 mg dexameth betametas combination
    152. 152. Postdischarge vomiting (Gupta A,Wu,CL,Elkassabani,N,Krug,CE,Parker,SD,Fleisher LA.Does the routine prophylactic use of antiemetics affect the incidence of postischarge nausea and vomuint following ambulatory surgery?.Anesthesiology 2003;99:488-95.) Relative Risk % of antiemetic medication on Postdischarge vomiting 100 80 60 40 20 0 placebo Servizio di Anestesia e Rianimazione Ospedale di Faenza(RA) ondans 1 mg ondans 4 mg ondans 8 mg drop <1 mg drop>1 mg dexameth betametas combination
    153. 153. Postdicharge nausea in the ondansetron 4 mg group vs the placebo group Gyn Lap Isof 0,90 0,80 0,70 0,60 % 0,50 0,40 0,30 0,20 0,10 0,00 Gyn Lap Desf Gyn Lap Isofl Gyn Lap Iso Enf Gyn Lap DEsf Maxill Gyn Midaz Gyn ORL Lap Lap Fent Desf Isof Isof metex VLC Isof treatm control W a le y l zi il n n lw g o e o d s e g K n u h u W C S c n s m il a M T W h n g li n a a A T M e Servizio di Anestesia e Rianimazione Ospedale di Faenza(RA)
    154. 154. Per uno studio nostro su POnv(io,Lorenz….??? Data Co-nome Età/peso/alt Sex Asa e patol concomit Cinetosi Ponv pregr Premed Sede Iniz interv Fine interv Propofol Fent Remifent N2O Vapore:quale….. Tipo interv Protesi resp LMA Guedel IOT Resp spont/ass/IPPV FiO2 Flebotot Risv;immediato/velcoe/lento Analg postop;ketorolac tramadol mep altro Efficacia analg postop Sintodian si no/quando/quanto Zofran Si NO quando quanto Nausea postop 123 Vomito postop123 Rescue treatm Nausea I g 123 Analg I g Efficacia analg I g Vomito I g 123 Rescue treatm I g Servizio di Anestesia e Rianimazione Ospedale di Faenza(RA)
    155. 155. Postdischarge nausea in the combination group(>1 drug) vs the placebo group Gyn % 0,90 Lap Isof 0,80 0,70 GYN D&C Propof 0,60 0,50 0,40 0,30 Gyn Lap Isof 0,20 0,10 0,00 Ahmed Tzeng Servizio di Anestesia e Rianimazione Ospedale di Faenza(RA) Wu treatment control
    156. 156. Postdischarge vomiting in the combination group(>1 drug) vs the placebo group % 0,50 0,45 0,40 Gyn Lap Isof 0,35 0,30 0,25 GYN D&C Propof Gyn Lap Sevo treatment control 0,20 0,15 0,10 0,05 0,00 Ahmed Tzeng Servizio di Anestesia e Rianimazione Ospedale di Faenza(RA) Scuderi
    157. 157. Postdicharge vomiting in the ondansetron 4 mg group vs the placebo group 0,50 0,45 0,40 0,35 0,30 0,25 0,20 0,15 0,10 0,05 0,00 Gin Lap sevo Gyn Lap Isof treatment control y le ag W ed n Su i er ud Sc l l wi ol Ch ri e ud Sc on xt Pe zie en cK M ng Ta s in al M ng Ta m Ah Servizio di Anestesia e Rianimazione Ospedale di Faenza(RA)
    158. 158. Post Discharge Nausea and Vomiting Incidence Severity Contributing factors Prevention Treatment Servizio di Anestesia e Rianimazione Ospedale di Faenza(RA)
    159. 159. Post Discharge Symptoms Following Ambulatory Surgery Symptom Pain Nausea Vomiting Headache Drowsiness Dizziness Fatigue Incidence (%) 45 17 8 17 42 18 21 Wu CL, et al. Anesthesiology 2002;96:994-1003 Servizio di Anestesia e Rianimazione Ospedale di Faenza(RA)
    160. 160. Strabismus Surgery Postdischarge Vomiting Ondansetron Droperidol Metoclopramide Placebo 40 40 40 40 Predischarge emesis 2 (5%)* 2 (5%)* 13 (33%) 10 (25%) Postdischarge emesis 10 (25%) 10 (25%) 8 (20%) 10 (25%) Patients *Significantly different from metoclopramide (p=0.003) and placebo (p=0.025) Servizio di Anestesia e Rianimazione Ospedale di Faenza(RA) Scuderi PE, et al. JCA 1997;9:551-558
    161. 161. Post Discharge: Time to first emetic episode 6 68% 5 5 4 4 3 3 2 2 1 0 5 3 2 1 2 1 2 1 1 0 0-4 1 0 4-8 8-12 0 0 1 2 1 1 0 12-16 0 16-20 20-24 Time (hrs) Droperidol Metoclopramide Servizio di Anestesia e Rianimazione Ospedale di Faenza(RA) Ondansetron Placebo Scuderi PE, et al. JCA 1997;9:551-558
    162. 162. Postdischarge Vomiting: Ondansetron versus Placebo Ondansetron Placebo P-value (n = 70) (n = 70) Patients with emesis 6 (8.6 %) 4 (5.7%) 0.75 Patients rescued 7 (10%) 6 (8.6%) 1.00 Emesis (post rescue) 1 (1.4%) 1 (1.4%) 1.00 6 (8.6%) 9 (12.9%) 0.59 0.05 Predischarge Postdischarge Patients with emesis Relative risk (95% CI) 0.667 (0.46; 5.70) Time to first emesis Median hr (range) 17 (1, 20) 5 (1, 16) Mean±SEM 13.8 ± 3.0 5.9 ± 1.7 Servizio di Anestesia e Rianimazione Ospedale di Faenza(RA) Scuderi PE, et al. Anesthesiology 2000;93:A37
    163. 163. Postdischarge Vomiting: Ondansetron versus Placebo ODT Placebo P-value patients 30 30 Predischarge emesis 3% 0% n.s Predischarge nausea 40% 37% n.s Postdischarge emesis 3%* 23% 0.02 Postdischarge nausea 30% 50% 0.11 * p<0.05 Servizio di Anestesia e Rianimazione Ospedale di Faenza(RA) Gan TJ, et al. Anesth Analg 2002;94:1199-1200
    164. 164. Final recommendations Servizio di Anestesia e Rianimazione Ospedale di Faenza(RA)
    165. 165. General Recommendations Use generic drugs for “routine” prophylaxis Treat breakthrough symptoms with 5HT3 antagonists Don’t repeat dose with 5HT3 antagonists Treat with different classes of antiemetics For high risk patients use combination prophylaxis Consider propofol infusion as part of anesthetic Prevent and control pain Consider post-discharge therapy Servizio di Anestesia e Rianimazione Ospedale di Faenza(RA)
    166. 166. Watcha MF, White PF: Postoperative nausea and vomiting: Prophylaxis versus treatment. Anesth Analg 89:1337-9, 1999 ???Anesthesiology 92;931-3:2000 Estimated risk of PONV Low risk(<10%) Mila to moderate (10-30%) Rescue only: Ond 1 mg Dolas 12,5 Rescue ONd 1 mg Dolas 12,5 Servizio di Anestesia e Rianimazione Ospedale di Faenza(RA) Extremely high risk (>60%) Prophylaxis Drop 1,25+ Steroid+ Ond 8 mg or Dola 12,5 Prophylaxis Drop 1,25 mg + steroid+metoclopr Prophylaxis Drop 1,25 mg No Prophylaxis High risk (30-60%) Rescuew OND 1 mg Dola 12,5 Rescue: Metoclopr Phenotiaz Addit 5HT3 Or other antiemet
    167. 167. Antiemetic choice drug effectiveness side-effect profile---clinical context patient preference associated reduction of total costs » Nursing » Hospital stay » Earlier discharge » Earlier return to work... » Patient satisfaction. Servizio di Anestesia e Rianimazione Ospedale di Faenza(RA)
    168. 168. Antiemetic choice Antiemetic choice Clinical effectiveness Side effect profile Clinical context Servizio di Anestesia e Rianimazione Ospedale di Faenza(RA) Patient acceptance Cost
    169. 169. Ewalenko P, Janny S, Dejonckheere M, Andry G, Wyns C: Antiemetic effect of subhypnotic doses of propofol after thyroidectomy. Br J Anaesth 77:463-7, 1996 , • prospective, randomized, controlled trial, we have compared the antiemetic efficacy of subhypnotic doses of propofol, with Intralipid as placebo, after thyroidectomy. We studied 64 patients of both sexes, aged 22-71 yr, ASA I or II, undergoing thyroidectomy. After premedication with a benzodiazepine, balanced anaesthesia was produced with isoflurane and nitrous oxide in oxygen, and supplementary analgesia with fentanyl i.v. as required. Postoperative analgesia was provided with non-opioids, and piritramide 0.25 mg kg-1 i.m. on demand. Patients were allocated randomly and blindly to receive a 20-h infusion of either propofol or 10% Intralipid 0.1 ml kg-1 h-1. Sedation scores, respiratory and cardiovascular variables, and incidence of PONV were assessed every 4 h for 24 h. Pulse oximetry and ECG were monitored continuously. Both groups were comparable in characteristics, surgical and anaesthesia procedures, amount of Servizio di Anestesia e Rianimazione Ospedale di Faenza(RA) opioids given during and after operation, and total
    170. 170. Montgomery 1996 • We studied the antiemetic effects of a low dose infusion of propofol for 24 h after major gynaecological surgery in a double-blind, randomised, controlled trial. Fifty women of ASA physical status 1 or 2 undergoing major gynaecological surgery received an infusion of 1% propofol or intralipid at 0.1 ml.kg-1.h-1 for 24 h after surgery. Pain was managed using morphine delivered by a patient-controlled analgesia pump. The degree of postoperative nausea and vomiting was assessed by the nurses using a four-point ordinal scale, by the patients using a visual analogue scale and by the amount of rescue antiemetic given by the nurses. There were no differences between the two groups in any of the measures of postoperative nausea and vomiting during the first 48 h after surgery. Postoperative nausea and vomiting in the control group was less on the second day compared with the first postoperative day, but not in the propofol group. Servizio di Anestesia e Rianimazione Ospedale di Faenza(RA) There were no side effects from the
    171. 171. Ding • To compare the intraoperative conditions and postoperative recovery of patients following the use of either propofol-nitrous oxide (N2O) or enflurane-N2O for maintenance of outpatient anesthesia. DESIGN: Randomized, single-blind study. SETTING: University hospital outpatient surgery center. PATIENTS: 61 ASA physical status I and II, healthy female outpatients undergoing laparoscopic surgery. INTERVENTIONS: Patients were randomly assigned to one of three anesthetic regimens. Group 1 (control) received thiopental sodium 4 mg/kg intravenously (i.v.), followed by 0.5% to 1.5% enflurane and 67% N2O in oxygen (O2). Group 2 received propofol 2 mg/kg i.v., followed by 0.5% to 1.5% enflurane and 67% N2O in O2. Group 3 received propofol 2 mg/kg i.v., followed by propofol 50 to 160 micrograms/kg/min i.v. and 67% N2O in O2. All patients received succinylcholine 1 mg/kg i.v. to facilitate tracheal Servizio di Anestesia e Rianimazione Ospedale di Faenza(RA) intubation and atracurium 10 to 20 mg i.v. to
    172. 172. GAN • Background: Breast surgery is associated with a high incidence of postoperative nausea and vomiting. Propofol and prophylactic administration of ondansetron are associated with a lower incidence of postoperative nausea and vomiting. To date no comparison of these two drugs has been reported. A randomized study was done to compare the efficacy of ondansetron and intraoperative propofol given in various regimens. • Methods: Study participants included 89 women classified as American Society of Anesthesiologists physical status 1 or 2 who were scheduled for major breast surgery. Patients were randomly assigned to one of four groups. Group O received 4 mg ondansetron in 10 ml 0.9% saline and groups PI, PIP, and PP received 10 ml 0.9% saline before anesthesia induction. Group O received thiopental, isoflurane, nitrous oxide—oxygen, and fentanyl for anesthesia. Group PI received propofol, isoflurane, nitrous Servizio di Anestesia e Rianimazione Ospedale di Faenza(RA) oxide—oxygen, and fentanyl. Group PIP received
    173. 173. Servizio di Anestesia e Rianimazione Ospedale di Faenza(RA)
    174. 174. AUTHOR(S): Watcha, Mehernoor F., M.D. Anesthesiology 92:931-3, 2000 Servizio di Anestesia e Rianimazione Ospedale di Faenza(RA)
    175. 175. Biblio PONV recente Tramèr, M.; Moore, A.; McQuay, H.Propofol anestesia and poostoperastive nausea and vomitino:quantitative systematic review of randomized controlled studies.BRIT.JOURNAL OF ANAESTHESIA 78,1997 (9) Doze,V.A.,Shafer,A.,White,P.F.Nausea and vomiting after outpatient anesthesia:effectiveness of droperidol alone and in combination with metoclopramide.Anesth.Analg., 1987,66,S41. (10)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. BRIT.JOURNAL OF ANAESTHESIA 1999;83:761-771. (11).Tramer M, ,Moore A Mc Quay H Omitting nitrous oxide in general anaesthesia: meta-analysis of intraoperativi awareness and postoperative emesis in randomized controlled trials. Br J Anaesth 1996;76: 869. (12)Tramer MR, Fuchs-Buder T. Omitting antagonism of neuromuscular block:effect on ponv and risk of residual paralysis.A systematic review.BRIT.JOURNAL OF ANAESTHESIA 1999;82:379-386. 13) Tramer MR, Moore RA, Reynolds DJM, McQuay HJ: A quantitative systematic review of ondansetron in treatment of established postoperative nausea and vomiting. BMJ 314:1088-92, 1997 (14). Tramer MR, Reynolds D .. Efficacy, dose-response, and safety of ondansetron in prevention of posto nausea and vomiting. A quantitative systematic review of randomized placebo-controlled trials. Anesthesiology 1997;87:1277-89. (15)Kovac A,Scuderi P,Boerner TF,Chelly JE,Goldberg ME, Hantler CB,Hahne W,Brown RA.On Behalf of the Dolasetron Mesylate PONV Treatment Study Group Treatment of ponv with single intravenous doses of dolasetron mesylate: a multicenter trial. Anesth Analg 1997;85:546-552 (16)Zarate E. Watcha M,White PF,Klein KW, Rego MSa,Stewart DG.A comparino of the costs and efficacy of ondansetron versus dolasetron for antiemetic prophylaxis. Anesth Analg 2000;90,1352-8. ((17)Fortney JT, Gan TJ, Graczyk S, et al. A comparison of the efficacy and patient satisfaction of ondansetron versus droperidol as antiemetics for elective outpatient surgical procedures. Anesth Analg 1998; 86:731-8. (18)Loewen PS,Marra CA,Zed P 5Ht3 receptor antagonists versus traditional agents for the prophylaxis of ponv.Can Anaesth. J 2000;47;1008-18. (19). 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. (20)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. (21)Norton et al ,Anesthesiology 2002;A:1196. (22)Zarate E,Mingus M,White PF.The use of transcutaneous acupoint electrical stimulation for preventing nausea and vomiting after laparoscopic surgery.Anesth.Analg 2001;92:629-35. (23)Goll V,Agka O.,Greif R.O Ondansetron is no more effective than intraoperative oxygen for prevention of ponv .Anesth.Analg. 2001;92:112-17. (24)Yogendran ,S,Asokumar B,Cheng DCH,Chung FA. A prospective randomized double blinded study of the efffect of intravenous fkuid therapy on adverse outcomes on outpatint surgery.ANESTH.ANALG 1995;80:682-6. (25)Scuderi PE,James RL,Harris l,Milne IIIGR.Multimodal antiemetic management prevents early ponv after outpatient laparoscopy. Anesth Analg 2000;91:140814. (26)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. Servizio di Anestesia e Rianimazione Ospedale di Faenza(RA)
    176. 176. Poi ci sono 2 file su Acer o Vaio picolo su Post duischarge nv e una citazione;trasferire con link…………… Servizio di Anestesia e Rianimazione Ospedale di Faenza(RA)
    177. 177. Propofol & PONV Campbell Anaesth Intens Care Campbell NN, Thomas AD: Does propofol have an anti-emetic effect? A 19:385-7, 1991 prospective study of the anti-emetic effect of propofol following laparoscopy. Anaesth Intens Care 19:385-7, 1991 • In order to investigate the putative anti-emetic effect of propofol, 53 patients undergoing gynaecological laparoscopy were given a standard anaesthetic including induction with thiopentone. At the end of surgery, the patients received either a sub-anaesthetic does of propofol or an equivalent volume of normal saline. There was no difference in the incidence of nausea and vomiting between the propofol and control group. It is concluded that low-dose propofol does not have Jannyanti-emetic effect. an S, Dejonckheere M, Andry G, Wyns reported that a subanesthetic dose of propofol administered at the end of surgery had no antiemetic effect in patients undergoing laparoscopy using an isoflurane-based anesthetic Ewalenko P, C: Antiemetic effect of subhypnotic doses of propofol after thyroidectomy. Br J Anaesth 77:463-7, 1996 , Montgomery JE, Sutherland CJ, Kestin IG, Sneyd JR: Infusions of subhypnotic doses of propofol for the prevention of postoperative nausea and vomiting. Anaesthesia 51:554-7, 1996 , Ding Y, Fredman B, White PF: Recovery following outpatient anesthesia: Use of suggested that a low dose of propofol was effective in enflurane versus propofol. J Clin Anesth 5:447-50, 1993 Servizio di Anestesia e Rianimazione Ospedale di Faenza(RA)
    178. 178. Campbell Anaesth Intens Care 19:385-7, 1991 • In order to investigate the putative anti-emetic effect of propofol, 53 patients undergoing gynaecological laparoscopy were given a standard anaesthetic including induction with thiopentone. At the end of surgery, the patients received either a sub-anaesthetic does of propofol or an equivalent volume of normal saline. There was no difference in the incidence of nausea and vomiting between the propofol and control group. It is concluded that low-dose propofol does not have an anti-emetic effect. Servizio di Anestesia e Rianimazione Ospedale di Faenza(RA)
    179. 179. Esempi pratici Appendix 1 Logistic regression is used to model the relation between explanatory variables and binary outcome variables. The logistic regression modeling assumes that the probability of an event (i.e., the occurrence of the outcome) is associated with the values of the explanatory variables in the following way: where where p = probability of the occurrence of the outcome, xi = value of the ith independent variable, and bi events for any patient = parameter estimates for the ith variable. Fitting the model to the data, we can obtain the maximum likelihood estimate of the parameters for each variable. Based on the maximum likelihood estimates from the final models, it is possible to calculate an expected risk of occurrence of the specific adverse event for any patient. Examples The risk for patient 1, a 30-yr-old woman with a history of smoking and previous PONV undergoing a 1-h shoulder (orthopedic) operation with general anesthesia is 35.2%. The risk for patient 2, a 40-yr-old nonsmoking man with no previous PONV undergoing a 1-h knee arthroscopy (orthopedic) without general anesthesia is 0.4%. The risk for patient 3, a 70-yr-old smoking man with no previous PONV undergoing a 1-h cataract surgery (ophthalmologic) without general anesthesia is 0.3%. The risk for patient 4, a 32-yr-old nonsmoking woman with previous PONV undergoing a 30-min laparoscopy (gynecologic) with general anesthesia is 22.1% The risk for patient 5, a 22-yr-old woman with a history of smoking and previous PONV undergoing a 90-min bilateral breast augmentation (plastic surgery) with general anesthesia is 52%. Servizio di Anestesia e Rianimazione Ospedale di Faenza(RA)
    180. 180. Prevenzione del PONV: Dexamethasone Dose ranging Major gynecological surgery Placeb 1.25 mg o 2.5 mg 5.0 mg 10.0 mg Patients 30 30 30 30 30 Vomiting 19 15 8* 6* 6* Rescue required 5 0 0 0 0 * P <0.05 compared with placebo and 1.25 mg Liu K, et al. Anesth Analg 1999;89:1316-1318 Servizio di Anestesia e Rianimazione Ospedale di Faenza(RA)
    181. 181. Prevenzione del PONV: Scopolamine Undefined control event rate Small Studies Outcome Large Studies Trials NNT Trials NNT Vomiting 7 3.6 8 8.3 Nausea 7 3.4 6 5.9 PONV 11 2.5 9 7.1 Rescue 4 3.8 6 20.0 Kranke, et al. Anesth Analg 2002;95:133-143 Servizio di Anestesia e Rianimazione Ospedale di Faenza(RA)

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