Ponv corso itinerante 2008.

Studies addressing PostDischarge nausea & vomiting in
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)

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.

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.

Postoperative Nausea and Vomiting:
Prevention and Treatment
Claudio Melloni
Anestesia e Rianimazione
Ospedale degli Infermi di Faenza(RA)

AUTHOR(S): Watcha, Mehernoor F., M.D.
Anesthesiology
92:931-3, 2000

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

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
» established through explicit questioning

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!!!

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
Dal +
indesiderabile
Al meno
indesiderabile
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.
rank valore relativo
vomito
gagging sul tubo
dolore
nausea
ricordo senza dolore
debolezza residua
brivido
mal di gola
sonnolenza

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

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
25
20
15
10
5
0
dolore
tossire sul tubo et
vomito
nausea
disorientamento
mal di gola
brivido
sonnolenza
sete
Valori relativi !

Beauregard L, Pomp A, Choinière M.
Severity and impact of pain after day-surgery Can J Anaesth
1998 / 45 / 304-11
100
90
80
70
60
50
40
30
20
10
0
%
dolore
PONV
gir.testa
sonnolenza
cefalea
mal di gola
raucedine
fatica
I g.
II g
VII g

Can PONV be predicted?
Risk factor analysis

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.

Sinclair et al.Can PONV be predicted?
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).

Sinclair DR, Chung F,Mezei G.Can PONV be predicted?
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 post-anesthesia
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.

Frequency of PONV by type of anesthesia
and duration of surgery. Sinclair et al.Can PONV be predicted?

PONV prolongs PACU and
amb.surg.unit stay Sinclair et al.Can PONV be
predicted?Anesthesiology 1999;91:109-18

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-DC) procedures had a threefold increase in
the risk for PONV. Compared with the reference group, which includes general surgery,
gynecologic dilation and curettage (DC), 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%

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.

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 opioid-induced
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.

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 cost-effectiveness
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.

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.

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-DC 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.

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 PONV by selecting patients for antiemetic therapy. This may lead to improved
cost-effective use of available drugs and resources.

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 DC 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.

Logistic regression da:Sinclair et al.Can PONV be predicted?
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
and Servizio 0 if other type of surgery; GynNonDC = 1 if gynecologic non DC procedure and 0 if other type of
surgery; OrtKnee di Anestesia = 1 if orthopedic e Rianimazione procedure involving Ospedale knee and 0 if di other Faenza(type of RA)
surgery; OrtShoulder = 1
if orthopedic procedure involving the shoulder and 0 if other type of surgery; OrtOther = 1 if orthopedic

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.


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%.

Risk Factors
Non-anesthetic factors
Anesthetic related factors
Postoperative factors

Risk Factors
Non-anesthetic Factors
Age
Gender
Body habitus
Hx motion sickness
Hx PONV
Anxiety
Concomitant disease
Operative procedure
Duration of surgery

Risk Factors
Anesthetic Related Factors
Preanesthetic medication
Gastric distension
Gastric suctioning
Anesthetic technique
Anesthetic agents

Risk Factors
Postoperative Factors
Pain
Dizziness
Ambulation
Oral intake
Opioids

Postoperative Nausea and Vomiting:
Anesthetic Related Factors
Nitrous oxide
Volatile anesthetics
NMB reversal
Propofol

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

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

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
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.

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
with Servizio isoflurane–di Anestesia nitrous e Rianimazione oxide anesthesia Ospedale di Faenza((number RA)
needed to

40
35
30
25
20
15
10
5
0
after anesth. Pacu
discharge
24 hr 48 hr 72hr.
inpatients Iso/N2O
inpatients tiva
outpatients iso/N2O
outpatients tiva

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
30
20
10
0
%
inpatients outpatients
tiva
isof/N2O

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
20
15
10
5
0
%
inpatients outpatients
tiva
isof/N2O

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
isoflurane group (36% vs. 18%). The total costs of

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. 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
same extent for all patient groups. Therefore, the practice of reserving TIVA for high-risk patients only seems

IS PONV incidence different
between LMA and ETT?
Joshi GP, Inagaki Y, White PF, Taylor-
Kennedy 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

Risk Factors
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
Apfel et al. BJA 2002;88:659-668
* Compared to propofol

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 non-negligent
risk of residual paralysis even
when short acting NMB agents are used
Tramer MR, Fuchs-Buder T. BJA 1999;82:379-386

Risk Factors
Propofol and PONV
All Control Event Rates
Early Late
Nausea Vomiting Any Nausea Vomiting Any
Analysis by NNT
Induction 9.3* 13.7* 20.9 50.1 14.9 NA
Maintenance 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

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
PONV
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

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;70:135-
40.
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.

Risk Factors
Logistic Regression
Younger age
Nonsmoking history
Female
Hx of motion sickness
Hx of PONV
Increased duration of operation

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% Apfel CC et al. Anesthesiology 1999;91:693-700.

PPOONNVV
ffaattttoorrii ddii rriisscchhiioo
ddoonnnnee
ggiioovvaannii
età
fertile
ggrraavviiddee
post
partum
iinntteerrvveennttii
muscoli
extraoculari
orecchio
medio
pelvi
femm.in
laparoscopia
deambulazione
precoce
bbaammbbiinnii
soggetti
a
cinetosi
pregresso
PONV
ffaarrmmaaccii
ooppppiiooiiddii
anestetici
inalatori
Neurosurg N2O
Breast surg
Laparotomy
Plastic surg.
Non
smokers

Trattamento del PONV

Management of PONV:
Pharmacological Approaches
Medications
Dose response
Comparative efficacy
Combination therapy
Timing of administration

AAnnttiieemmeettiiccii
eevvoolluuzziioonnee ddeell ppeennssiieerroo
mmeettoocclloopprraammiiddee pprreessoo ddaallllaa ggaassttrrooeenntteerroollooggiiaa
ddrrooppeerriiddooll pprreessoo ddaaggllii aannttiippssiiccoottiiccii........
oonnddaannsseettrroonn llaa nnuuoovvaa ffrroonnttiieerraa......
ggrraanniisseettrroonn

PPOONNVV
RReecceettttoorrii ccooiinnvvoollttii
bbuuttiirrooffeennoonnii::::ddrrooppeerriiddooll
ffeennoottiiaazziinnee
CCRRTTZZ
55HHtt33
DD22
mmeettoocclloopprraammiiddee
AAcchh HH11
oonnddaannsseettrroonn
ggrraanniisseettrroonn
ttrrooppiisseettrroonn
aannttisisttaammininicici:i:::imimeeddrrininaattoo,,ididrroossssizizininaa,,cciciclilzizininaa
ssccooppoollaammiinnaa
sstteerrooiiddii
Combination
therapy

Currently Available Medications
5HT3 (serotonin) antagonists - ondansetron
Butyrophenones - droperidol
Benzamides - metoclopramide
Antihistamines - dimenhydrinate
Steroids - dexamethasone
Phenothiazines-promethazine,
prochlorperazine
Anticholinergics – scopolamine

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

Prevention of PONV:
Ondansetron Versus Placebo
*
62
† †
76 77
All patients, 0 - 24 hrs
46
100
80
60
40
20
0
Placebo 1 mg 4 mg 8 mg
Ondansetron Dose
% of Patients with No Emesis
McKenzie et al. Anesthesiology 1993;78:21-28
* p = 0.010
† p 0.001

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

Treatment of PONV:
Ondansetron Versus Placebo
% with Complete Response Placebo 1 mg 4 mg 8 mg
32
20
* * *
57
* * *
40
60
45 44
57
100
80
60
40
20
0
0 - 2 hr 2 - 24 hr
Scuderi et al. Anesthesiology 1993;78:2-5
Hantler et al. Anesthesiology 1992;77:A16
* p 0.001

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
Tramer et al. BMJ 1997;314:1088-1092

Breakthrough PONV:
Repeat Dosing With Ondansetron
Response
* p = 0.074
† p = 0.342
Complete 43
* 34 32
†
Percent 28
0 - 2 hours 0 - 24 hours 100
80
60
40
20
0
Placebo Ondansetron 4 mg
Kovac et al. J. Clin Anesth 1999;11:453-459

Prevention of PONV:
Dolasetron Versus Placebo
* * *
* *
56 57
* *
50 52 46 *
52
39
43
31 28 33
55
100
80
60
40
20
0
All Patients Previous PONV No PONV
Complete Response %
Placebo 12.5 mg 25 mg 50 mg
*p 0.0003 compared to placebo
*
Graczyk et al. Anesth Analg 1997;84:325-330
* * *
*
* *
* *

Treatment of PONV:
Dolasetron Versus Placebo
27
Placebo 12.5 mg 25 mg 50 mg 100 mg
11
*
* 55
* * *
* *
* * *
35
50
* * *
28
51
29 29
48
100
80
60
40
20
0
0 - 2 hrs 0 - 24 hrs
Complete Response %
*p 0.001 compared to placebo
Kovac et al. Anesth Analg 1997;85:546-552

Prevention of PONV:
Ondansetron Versus Dolasetron
Placebo Dolasetron 25 mg Dolasetron 50 mg Ondansetron 4 mg
* * †
*
Patients
49
51
43
of 36
% Complete Response Total Response 71
*
60
100
80
60
40
20
* p 0.05 versus placebo and dolasetron 25 mg
† p 0.05 versus placebo only
54
64
0
Korttila K et al. Acta Anaesthesiol Scand 1997;41:914-922

Prevention of PONV:
Dolasetron 12.5 mg Dolasetron 25 mg Ondansetron 4 mg Ondansetron 8 mg
92
96 96 96 96
94
100
98
100
80
In-hospital Postdischarge
% without Symptoms
Zarate E, et al. Anesth Analg 2000;90:1352-1358
Postoperative Vomiting
No statistically significant differences
among the groups

Prevention of PONV:
Postoperative Nausea
Dolasetron 12.5 mg Dolasetron 25 mg Ondansetron 4 mg Ondansetron 8 mg
73
76 77 82 76
87 86
70
100
80
60
40
20
0
In-hospital Postdischarge
% without Symptoms
No statistically significant differences
among the groups

Prevention of PONV:
Ondansetron Versus Droperidol
Complete Response
Placebo Droperidol 0.625 mg Droperidol 1.25 mg Ondansetron 4 mg
46
* * * *
36
63
*
48
†
69
*
‡
56 53
62
100
80
60
40
20
0
0 - 2 hr 0 - 24 hr
% of Patients
Fortney et al. Anesth Analg 1998;86:731-738
* p 0 .05 compared to placebo
† p 0.05 compared to ondansetron 4 mg
‡ p ,0.05 compared to droperidol 0.625 mg

Prevention of PONV:
Ondansetron Versus Droperidol
No Nausea
* p 0 .05 compared to placebo
† p 0.05 compared to droperidol 0.625 mg
and ondansetron 4 mg
Patients
*
of 23 29
% 0 - 24 hr *
†
43
*
29
100
80
60
40
20
0
Placebo Droperidol 0.625 mg Droperidol 1.25 mg Ondansetron 4 mg
Fortney et al. Anesth Analg 1998;86:731-738

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

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)

Putting It in Perspective
Circumstance Annual Fatalities
Transportation
motor vehicle 37,409
pedestrian 4,739
cyclists 690
rail 518
bus 299
airline 92
Animal Related
dog bite 20
auto-deer collisions 130
Other
lightning 90
boating 734

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

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

Prevention of PONV:
Dexamethasone
Major gynecological surgery
Placeb
o 1.25 mg 2.5
mg 5.0 mg 10.0 mg
Dose ranging
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

Prevention of PONV:
Scopolamine
Small Studies Large Studies
Undefined control event rate
Outcome 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

Prevention of PONV:
Scopolamine
Defined control event rate
Nausea 2 5.3 5 5.0
PONV 8 2.9 8 6.7
Rescue 4 3.8 3 7.0

Prevention of PONV:
Scopolamine
Adverse Events
Event NNH
Visual
disturbances 5.6
Dry mouth 12.5
Dizziness 50.0
Agitation 100.1

Prevention of PONV:
Dimenhydrinate
Early (0-6 h) Overall (0-48 h)
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

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

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-ht3-
receptor antagonists, alone or in combination, for prophylaxis of
postoperative nausea and vomiting. A meta-analysis of randomized
controlled trials. Acta Anaesthesiologica Scandinavica. 2000;44:1252-7

Prevention of PONV:
Combination Therapy
Which Combination?
Event
5-HT3 + drop 5-HT3 + dex
N Rate N Rate P-value OR
Early
Nausea 138 17% 260 11% 0.12 1.6
Vomiting 318 1% 419 1% 1.00 1.0
Late
Nausea 358 27% 623 21%* 0.02 1.4
Vomiting 443 9% 813 9% 1.00 0.9
Ashraf et al. Anesthesiology 2001; 95:A-41

Prevention of PONV:
Combination Therapy
Placebo Metoclopramide Dolasetron Ondansetron
Predischarge
nausea (%) 13 7 3 3
vomiting (%) 0 0 0 0
rescue (%) 0 0 0 0
Postdischarge
nausea (%) 13 10 7 3
vomiting (%) 0 0 0 0
rescue (%) 0 0 0 0
Tang, et al. Anesthesiology 2001; 95:A43

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;93:906-
911
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

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 cost-benefits,
and the effect on the patient's quality of life after discharge have not been established. In this placebo-controlled,
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.

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).

IIncidence of nausea and vomiting in the Pacu 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
40
30
20
10
0
*
*
*
nausea% vomit% rescue
antiemetics
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
nausea VAS
at 2 h(mm)
placebo
split dose
preinduction
end of surgery
antiemetic in the ambulatory setting.Anesth.Analg 1998;96:........

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
40
30
20
10
0
nausea% vomit% rescue
antiemetics
nausea VAS
medio(mm)
vomiting2
times
placebo
split dose
preinduction
postsurg
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:........
*
* *
* *

Timing of Administration:
Dexamethasone
Group 1
(Preinduction)
Group 2
(Postextubation)
Group 3
(Placebo)
0 – 2 hr
nausea (%) 10 25 33
vomiting (%) 5 20 20
total (%) 15*† 45 53
2 – 24 hr
nausea (%) 15 18 30
vomiting (%) 10 10 25
total (%) 25* 28* 55
Wang et al. Anesth Analg 2000;91;136-139
* Compared to Group 3
† Compared to Group 2

Management of PONV:
Adjuvants (Nonpharmacologic)
P-6 acupuncture point stimulation
Supplemental oxygen
Aggressive perioperative rehydration
Preemptive analgesia

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.

P-6 Acupuncture Point
Stimulation
TAES Sham Placebo
Control of Nausea
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

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.

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
6-24 hr PONV (%) 22.2 19.9 0.045
nausea (%) 17.6 8.9 0.066
vomiting (%) 5.9 1.8 0.108
0-24 hr PONV (%) 30.3 17 0.027
nausea (%) 27.7 16 0.034
vomiting (%) 5.9 1.8 0.108
Greif et al. Anesthesiology 1999;91:1246-1252

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
6-24 hr PONV (%) 13 4 6
nausea (%) 11 4 6
vomiting (%) 9 4 1
0-24 hr PONV (%) 44 22* 30
nausea (%) 41 22* 30
vomiting (%) 26 10* 15
Goll et al. Anesth Analg 2001;92:112-117

Intravenous Fluid Therapy
Incidence of Postop Nausea
20
15
10
5
0
Low Infusion High Infusion
30 min 60 min DIS Day 1
Time
Incidence %
*
Yogendran S, et al. Anesth Analg 1995;80:682-686
High Infusion = 20 ml/kg
Low Infusion = 2 ml/kg

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

Efficacy Versus Outcome

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

Measures of Outcome
Mortality
Morbidity
Patient satisfaction
Cost

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)

Complications of PONV
Electrolyte imbalance
Tension on sutures, evisceration
Venous hypertension, bleeding
Aspiration
Delayed discharge (outpatients)
Dehydration
Unanticipated admission

Unanticipated Admissions
Reasons for Admission Number Percent
Pain 18 19
Bleeding 18 19
Intractable Vomiting 17 18
Perforated Uterus 7 7
Extensive Surgery 6 6
Urinary Retention 5 5
Additional Surgery 4 4
Gold et al. JAMA 1989;262:3008-3010
Overall Admission Rate = 0.01
PONV Admission Rate = 0.002

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 PACU
staffing
Dexter et al. Anesthesiology 1995;82:94-101

Subject Preference Following Surgery
Levels Preference
Preoperative
Mental Acuity awake drowsy asleep 5%
Pain none mild moderate 18%
Emetic Sxs none nausea vomiting 40%
Muscle Aches no yes 11%
Dysphoria no yes 16%
Cost none $15 $35 $50 10%
Orkin FK. Anesth Analg 1992;74:S225

Patient Preference Following Surgery
Relative Value
Ranking (%)
(out of 100) First Second Third
Preoperative
Outcome
Mean
Rank
Vomiting 2.55 18.5 24 31 23
Gagging 2.95 18.6 22 20 24
Pain 3.46 16.8 22 16 16
Nausea 4.05 12.5 6 18 14
Recall w/o pain 4.87 13.8 20 6 4
Shivering 5.39 7.3 1 6 7
Residual weakness 5.43 7.2 5 4 11
Sore Throat 8.04 3.2 0 0 0
Somnolence 8.18 2.9 0 0 0
Normal 10.00 0.2 0 0 0
Macario et al. Anesth Analg, 1999;89:652-658

Patient Satisfaction With Outpatient Surgery
Factor
Considered
Factor
Important
Ranking in
Top 5 (%)
Rank Order
of top 5
Postoperative
Preoperative
Avoidance of Delays 86 45 5
Starting IV smoothly 95 53 4
Intraoperative
Friendliness of OR Staff 97 67 1
Postoperative
Management of Postop pain 96 62 3
Surgeon’s PACU visit 96 63 2
Treatment of PONV 90 31
Tarazi and Philip. Am J Anesthesiology 1998;25:154-157

Efficacy Versus Outcome
If efficacy is an appropriate endpoint when evaluating
analgesics, why not when evaluating antiemetics?

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

Frequency of PACU Treatment
by Risk Factors and Group
RISK FACTORS
PACU TREATMENT
REQUIRED BY GROUP
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%
1 Emetogenic procedures - laparoscopy, strabismus surgery, middle ear surgery, herniography,
tonsillectomy, adenoidectomy, uvulopalatopharyngoplasty
Scuderi et al. Anesthesiology. 1999;90:360-371

Efficacy of Prophylaxis – Overall
Ondansetron Placebo p-value
Total 285 290
Nausea Score PACU Entry
median, 75th, 90th 0, 0, 0 0,0,2 0.54
No Tx Required (%) 204 (71.6) 179 (61.7) 0.01
Treatment Required
Nausea (%) 64 (22.5) 70 (24.1) 0.63
Vomiting (%) 17 (6.0) 41 (14.1) 0.001
Total (%) 81 (28) 111 (38) 0.01
Nausea Score @ TX
median, 75th, 90th
nausea score 0 (%)
5,8,10
(100)
6,9,10
(96.4) 0.14

Efficacy of Prophylaxis - Group E
Ondansetron
Placebo p-value
Total
58
60
Nausea Score PACU Entry
median, 75th, 90th
0,0,4
0,0,6
0.49
No Tx Required (%)
36 (62) 26 (43) 0.045
Treatment Required
Nausea (%) 17 (29) 21 (35)
Vomiting (%) 5 (9) 13 (22)
Total (%)
22 (38) 34 (57) 0.045

Outcomes - Treatment vs Prophylaxis
Patient Satisfaction, Time to Discharge
Ondansetron Placebo P NNT
Total patients 285 290 --
All Patients - placebo Tx excluded 245 235 --
Satisfaction PONV: yes/no (%) 97% 93% 0.04 25
Satisfaction Overall: (11 pt scale)* 7,9,10 7,9,10 0.76
Time to discharge (95% CI) min 87(82,92) 92(86,98) 0.23
Group E patients - placebo Tx excluded 47 42 --
Satisfaction PONV: yes/no (%) 47 (100) 37 (90) 0.04 10
Satisfaction Overall: (11 pt scale)* 7,9,10 8,9,10 0.73
Time to discharge (95% CI) min 99(85,114) 117(98,139) 0.13
* 10th, 25th, median

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

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

Results
Group I Group II Group III P values
Multimodal Ondansetron Placebo
Patients 60 42 37
Hx Risk Factors (%) 48 64 65 0.17*†
Tx required (%) 2 24 41 0.0001*†
Vomiting before discharge (%) 0 7 22 0.67* 0.003†
Vomiting after discharge (%) 12 21 32 0.27* 0.02†
Satisfaction with PONV (%) 100 100 92 0.05†‡
Satisfaction score 10 (%) 5 6 37 1.00* 0.0013‡
Time to discharge ready (mean) 128 162 192 0.0015*; 0.0001†
*Group I vs II; † Group I vs III; Group II vs III‡ Scuderi at al. Anesth Analg 2000;91:408-414

Simplified Algorithm
I. INDUCTION
A. PreO2
B. Propofol 2 - 4 mg/kg
C. Opioid prn
D. Neuromuscular blockade prn
C. Droperidol 10 mcg/kg
D. Decadron 4 - 8 mg
II. MAINTENANCE
A. Propofol 50 mcg/kg/min
B. Potent inhalation agent/remif
C.Generous hydration
D Nitrous oxide prn
E. NMB reversal prn
III. EMERGENCE
A. Ondansetron 1 mg IV
B. Suction oropharynx
C. Extubate when awake
Early aggressive
postop pain therapy

Multimodal Management of
PONV:
Simplified Algorithm
COST ($)
Cost Analysis
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

Conclusions
Elimination of PONV in outpatients is possible with multi-modal
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

PPOONNVV
wwee kknnooww tthhee rriisskk ffaaccttoorrss
PPrreevveennttiivvee ssttrraatteeggyy nnoonn eemmeettooggeenniicc ddrruuggss......
Antiemetic
Prophylaxis
SSeelleecctteedd aatt rriisskk ggrroouuppss
IImmmmeeddiiaattee ttrreeaattmmeenntt in case of
occurrence.....

PONV dopo la dimissione

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.)

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.)

Postdischarge nausea
100
80
60
40
20
0
Relative Risk (%) of antiemetic medication on
postdischarge nausea
placebo
ondans 1 mg
ondans 4 mg
ondans 8 mg
drop 1 mg
drop1 mg
dexameth
betametas
combination

Postdischarge vomiting
100
80
60
40
20
0
Relative Risk % of antiemetic medication on
Postdischarge vomiting
placebo
ondans 1 mg
ondans 4 mg
ondans 8 mg
drop 1 mg
drop1 mg
dexameth
betametas
combination

Postdicharge nausea in the ondansetron 4
mg group vs the placebo group
0,90
0,80
0,70
0,60
0,50
0,40
0,30
0,20
0,10
0,00
Ma lins
Tan g
Ahmed
Tan g
Wi lson
Mc Ken zie
Sun
Cholwi l l
Wu
Wag le y
treatm
control
%
Gyn
Lap
Isofl
Gyn
Lap
Desf
Gyn
Lap
Isof
VLC
Isof
Gyn
Lap
DEsf
Gyn
Lap
Iso
Enf
ORL
Desf
Gyn
Lap
Isof
Gyn
Lap
Isof
Maxill
Midaz
Fent
metex

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

Postdischarge nausea in the combination
group(1 drug) vs the placebo group
0,90
0,80
0,70
0,60
0,50
0,40
0,30
0,20
0,10
0,00
Ahmed Tzeng Wu
treatment
control
%
Gyn
Lap
Isof
GYN
DC
Propof
Gyn
Lap
Isof

Postdischarge vomiting in the combination
group(1 drug) 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
Ahmed Tzeng Scuderi
treatment
control
% Gyn
Lap
GYN Sevo
DC
Propof
Gyn
Lap
Isof

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
Ahmed
Tang
Malins
Tang
McKenzie
Pexton
Scuderi
Cholwill
Sun
Wagley
Scuderi
treatment
control
Gin
Lap
sevo
Gyn
Lap
Isof

Post Discharge Nausea and Vomiting
Incidence
Severity
Contributing factors
Prevention
Treatment

Post Discharge Symptoms
Following Ambulatory Surgery
Symptom Incidence (%)
Pain 45
Nausea 17
Vomiting 8
Headache 17
Drowsiness 42
Dizziness 18
Fatigue 21
Wu CL, et al. Anesthesiology 2002;96:994-1003

Strabismus Surgery
Postdischarge Vomiting
Ondansetron Droperidol Metoclopramide Placebo
Patients 40 40 40 40
Predischarge emesis 2 (5%)* 2 (5%)* 13 (33%) 10 (25%)
Postdischarge emesis 10 (25%) 10 (25%) 8 (20%) 10 (25%)
*Significantly different from metoclopramide (p=0.003) and placebo (p=0.025)
Scuderi PE, et al. JCA 1997;9:551-558

Post Discharge:
Time to first emetic episode
5
2
68%
1 1 1
0 0
3
6
5
4
3
2
1
0
2
3
2
0
2
1
0
5
1
0
4
1 1 1
2
0-4 4-8 8-12 12-16 16-20 20-24
Time (hrs)
0
Droperidol Metoclopramide Ondansetron Placebo
Scuderi PE, et al. JCA 1997;9:551-558

Postdischarge Vomiting:
Ondansetron versus Placebo
Ondansetron Placebo P-value
(n = 70) (n = 70)
Predischarge
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
Postdischarge
Patients with emesis 6 (8.6%) 9 (12.9%) 0.59
Relative risk (95% CI) 0.667 (0.46; 5.70)
Time to first emesis
Median hr (range) 17 (1, 20) 5 (1, 16) 0.05
Mean±SEM 13.8 ± 3.0 5.9 ± 1.7
Scuderi PE, et al. Anesthesiology 2000;93:A37

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
Gan TJ, et al. Anesth Analg 2002;94:1199-1200
* p0.05

Final recommendations

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

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%)
High risk
(30-60%)
Prophylaxis
Drop 1,25 mg
+ steroid+-
metoclopr
Extremely high risk
(60%)
No Prophylaxis
Rescue only:
Ond 1 mg
Dolas 12,5
Prophylaxis
Drop 1,25 mg
Rescue
ONd 1 mg
Dolas 12,5
Rescuew
OND 1 mg
Dola 12,5
Prophylaxis
Drop 1,25+
Steroid+
Ond 8 mg or
Dola 12,5
Rescue:
Metoclopr
Phenotiaz
Addit 5HT3
Or other antiemetic

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.

Antiemetic choice
Antiemetic choice
Clinical effectiveness Side effect profile Patient acceptance Cost
Clinical context

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,
• prospective, randomi1z9ed9,6 c o,ntrolled 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
opioids given during and after operation, and total
amount of the study drug infused after operation.

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.
There were no side effects from the

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
intubation and atracurium 10 to 20 mg i.v. to
provide adequate relaxation during the

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
oxide—oxygen, and fentanyl. Group PIP received
propofol, isoflurane, nitrous oxide—oxygen, and

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;91:1408-
14.
(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.

Poi ci sono 2 file su Acer o Vaio picolo
su Post duischarge nv e una
citazione;trasferire con link……………

Propofol PONV
Campbell Anaesth Intens Care
Campbell NN, Thomas AD: Does propofol have an anti-emetic effect? A prospective study of the anti-emetic effect of propofol following laparoscopy. Anaesth Intens Care 19:385-7, 1991
reported that a subanesthetic dose of propofol administered at the end of surgery had no antiemetic anesthetic
19:385-7, 1991
effect in patients undergoing laparoscopy using an isoflurane-based
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 , 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 enflurane versus propofol. J Clin Anesth 5:447-50, 1993
suggested that a low dose of propofol was effective in preventing PONV after either an isoflurane- or an enflurane-based anesthetic.
• 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.
Gan TJ, Ginsberg B, Grant AP, Glass PSA: Double-blind, randomized comparison of ondansetron and intraoperative propofol to prevent postoperative nausea and vomiting. ANESTHESIOLOGY 85:1036-42, 1996 reported that use of
propofol as an induction agent and at the end of surgery during isoflurane-based anesthesia failed to prevent PONV in patients undergoing breast surgery compared
with using propofol both for induction and maintenance of anesthesia.
Scuderi PE, D'Angelo R, Harris L, Mims GR III, Weeks DB, James RL: Small-dose propofol by continuous infusion does not prevent postoperative vomiting in females undergoing outpatient laparoscopy. Anesth Analg 84:71-5, 1997
reported that a low-dose infusion of propofol similarly failed to show any beneficial effect in reducing PONV when used as the sole prophylactic medication in female
patients undergoing outpatient laparoscopy using an isoflurane-based anesthetic technique.
In the current study, propofol had significant antiemetic activity when administered at the end of surgery with sevoflurane anesthesia but not when it was
administered in conjunction with desflurane anesthesia. To detect an effect of propofol after desflurane in this patient population, a much larger group would be
necessary. The failure of propofol to more effectively protect against PONV after desflurane anesthesia is consistent with the findings of Van Hemelrijck et al. when
propofol was administered for induction followed by desflurane for maintenance of anesthesia. Of interest, a previous study involving the use of sevoflurane and
propofol showed that the use of propofol to induce anesthesia was effective in reducing PONV after sevoflurane anesthesia in outpatients undergoing laparoscopic
surgery. However, although the small dose of propofol (0.5 mg/kg) administered at the end of surgery prolonged the times to awakening and orientation, the time to
discharge from the postanesthesia care unit was not delayed. More importantly, the times to home-readiness for discharge were decreased for patients receiving a
subhypnotic dose of propofol after a sevoflurane-based anesthetic.

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.

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%.

Prevenzione del PONV:
Dexamethasone
Major gynecological surgery
Placeb
o 1.25 mg 2.5
mg 5.0 mg 10.0 mg
Dose ranging
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

Scopolamine
Undefined control event rate
Nausea 7 3.4 6 5.9
PONV 11 2.5 9 7.1
Rescue 4 3.8 6 20.0

Scopolamine
Defined control event rate
Nausea 2 5.3 5 5.0
PONV 8 2.9 8 6.7
Rescue 4 3.8 3 7.0

Scopolamine
Adverse Events
Event NNH
Visual
disturbances 5.6
Dry mouth 12.5
Dizziness 50.0
Agitation 100.1

Dimenhydrinate
Early (0-6 h) Overall (0-48 h)
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

Visser K, Hassink EA, Bonsel GJ,Moen J,Kalkman CJ. Randomized
Controlled Trial of Total Intravenous Anesthesia with Propofol versus
Inhalation Anesthesia with Isoflurane–Nitrous Oxide Postoperative
Nausea andVomiting and Economic Analysis.Anesthesiology.95:616-626,
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
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.

Vissern et al . Randomized Controlled Trial of Total Intravenous
40
35
30
25
20
15
10
5
0
after anesth. Pacu
discharge
2,010 unselected surgical patients
Unversity of Amsterdam Hospital
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.
24 hr 48 hr 72hr.
inpatients Iso/N2O
inpatients tiva
outpatients iso/N2O
outpatients tiva

Analisi dei costi
40
35
30
25
20
15
10
5
0
$
inpts outpta
TPS/Isof
Propof tiva
2 h
1 h

Antiemetic choice
Clinical effectiveness Side effect profile Patient acceptance Clinical contexttt
Earlier Patient

Jin FL, Chung F. Postoperative pain—a challenge
for anaesthetists in ambulatory surgery. Can J
Anaesth 1998; 45:293-6.
In this issue, Beauregard and colleagues report on a study they conducted in a large teaching hospital on 89 ambulatory surgical patients to assess the intensity, duration,
and impact of pain during their hospital stay and on the first, second and seventh postoperative days. More than 40% of the patients reported moderate to severe pain
during their hospitalisation. Our study on 10,008 consecutive patients undergoing ambulatory surgery showed that severe pain was suffered by 5.3% of patients in the
Postanaesthesia Care Unit and 1.3% of patients in the Ambulatory Surgery Unit. These results indicated that there was still a high incidence of severe pain after routine
postoperative pain treatment during the hospital stay. In another study, a 24-hr telephone interview with the parents of 84 paediatric patients who underwent tonsillectomy
indicated that pain control was inadequate in 25% of the patients. Beauregard and colleagues extended their investigation to the seventh postoperative day and found that
the pain decreased with time but was still considerable. Postoperative pain affected the patients' return to normal functioning. These results indicated that routine
management of post-discharge pain could not eliminate the pain completely. Effective postoperative pain control for patients with severe pain is needed, and take-home
analgesia protocols need to be developed.
Some factors can predict the occurrence of postoperative pain. More men than women experience intense postoperative pain. The patients with a higher body mass
index had a high incidence of severe pain postoperatively, because the dose of opioid (fentanyl or alfentanil) administered during the surgical procedure was inadequate.
The anaesthetist should pay more attention to increasing the dose of opioid properly during surgical procedures. In addition, lengthy surgical procedures and certain types
of operations (orthopaedic, urological, general, plastic, neurosurgical, and ENT/dental) are predictors of severe pain.
Successful postoperative pain control also depends on the knowledge and demands of the patient. A questionnaire for evaluating the general public's perception of
postoperative pain revealed that almost 50% of patients were prepared to suffer pain rather than to complain. They knew little about postoperative pain and were confident
in the ability of doctors and nurses to treat it. High satisfaction with a relatively high pain level was also found in Beauregard's study. Postoperative pain can have a
deteriorative effect on the recovery of the patient from surgery, whereas multimodal balanced analgesia can accelerate postoperative rehabilitation and reduce hospital stay.
Therefore, patient education is required for optimal pain management after ambulatory surgery. Patients should be given a full explanation of the need to minimise or
reduce postoperative pain, and they should be informed of the various methods available to treat it. They should be assured that any pain that does occur will be properly
and promptly treated.
The continued training of doctors, nurses, and medical students in the prevention and proper management of postoperative pain is necessary. Beauregard and
colleagues found that many instructions given to patients did not clearly indicate the intake frequency, dose adjustment, and control of side effects of analgesics. In the
study of Rose et al., pain management practices were successfully changed after anaesthetists were educated and patients were made more aware of pain as an important
problem. Another study showed that an audit of opioid prescribing considerably improved the prescribing of opioids, especially the frequency with which they were
prescribed.
An ideal postoperative analgesic protocol would be practical, effective, safe, have minimal side effects, and be cost-effective. Sustained-release morphine, synthetic
opioid agonist-antagonist analgesics (butorphanol), nonsteroidal anti-inflammatory drugs (NSAID), patient-controlled analgesia, local anaesthetic techniques (neuroaxial,
intraarticular nerve block), and non-pharmacological techniques (transcutaneous acupoint electrical stimulation) have broadened the choices for the management of
postoperative pain. For reduction of opioid-related postoperative nausea and vomiting, the use of opioids and nonopioids combined with local anaesthetic techniques has
been increasing. A randomised double-blind study of suprascapular nerve block for pain relief in arthroscopic shoulder surgery showed a 40% reduction in analgesic
consumption and a reduction in pain at rest and on abduction. Another randomised double-blind study on preoperative multimodal analgesia for ambulatory patients who
underwent laparoscopic cholecystectomy used a combination of preoperative meperidine and ketorolac by intramuscular bolus injection and local anaesthetic infiltration into
the incision during laparoscopic cholecystectomy. The results showed that the concomitant use of local anaesthetic, NSAID, and opioid drugs was very effective in
diminishing postoperative pain and reducing the stay in the ambulatory care unit. These new modalities demonstrate good effects on pain control and reduce the adverse
outcomes related to surgery. The results encourage us to continue studies in this field.
Some new analgesic techniques are still controversial, and their clinical efficacy remains to be proved. The safety of some anaesthetic techniques should be further
verified. For example, Bean-Lijewski reported two life-threatening cases of upper airway obstruction that resulted from glossopharyngeal nerve block for pain relief after
paediatric tonsillectomy. New techniques must be evaluated with respect to cost, quality of recovery, duration of recovery, and postoperative adverse outcome.
In conclusion, severe postoperative pain in ambulatory surgical patients in the hospital and at home should not be underestimated. It is a challenge for anaesthetists to
develop new analgesic techniques that are both safe and cost-effective, facilitate early ambulation, and do not increase the incidence of postoperative adverse outcomes.

Postoperative pain in ambulatory
surger. Anesth Analg 1997;
85:808-16.
Our study on 10,008 consecutive patients
undergoing ambulatory surgery showed that
severe pain was suffered by 5.3% of patients
in the Postanaesthesia Care Unit and 1.3% of
patients in the Ambulatory Surgery Unit.
These results indicated that there was still a
high incidence of severe pain after routine
postoperative pain treatment during the
hospital stay.

Rocchi A,Chung F,Forte L.. Canadian survey of
postsurgical pain and pain medications
experiences.Can.J.Anesth.2002;49:1053-1056
.
To assess the postoperative pain and pain medication experiences of Canadians.
Methods: Three hundred and five general population subjects from across Canada who had surgery in the
previous three years were retrospectively questioned regarding pain experiences in the surgical facility and
at home, pain medication efficacy and pain medication satisfaction.
Results: While in the surgical facility, pain was experienced by 68% of patients who expected overnight
admission (“inpatients”) and 49% of patients who expected same-day discharge (“outpatients”). Overall,
47% of inpatients and 15% of outpatients reported that their highest experience of pain was severe or
extreme; 25% of inpatients and 9% of outpatients reported that their average pain was severe or extreme. In
the two weeks post-discharge, 79% and 74% respectively of inpatients and outpatients experienced pain.
Severe or extreme pain occurred at home in 25% of inpatients and 28% of outpatients; average pain was
severe or extreme for 9% of inpatients and 12% of outpatients.
Complete or a lot of pain relief was experienced by 54% to 72% patients who received pain medication;
higher rates of pain medication satisfaction were reported than rates of pain relief from pain medication.
Conclusion: Severe or extreme pain was experienced by many surgical patients. Improvements could be
made to patients' postsurgical pain experience in Canada, both in the surgical facility and subsequent to
discharge.
ABSTRACT:

Sutters KA, Miaskowski C. Inadequate pain management and associated morbidity in children at home after tonsillectomy. J Ped Nurs 1997; 12:178-85.
3: Chung F. Recovery pattern and home-readiness after ambulatory surgery. Anesth Analg 1995; 80:896-902.
4: Fortier J, Chung F, Su J. Predictive factors of unanticipated admission in ambulatory surgery: a prospective stud. Anesthesiology 1996; 85:A27.
5: 7: Scott NB, Hodson M. Public perceptions of postoperative pain and its relief. Anaesthesia 1997; 52:438-42.
8: Moote CA. The prevention of postoperative pain. Can J Anaesth 1994; 41:527-33.
9: Smith AF. The prevention of postoperative pain: shouldn't it begin at medical school? (Letter) Can J Anaesth 1995; 42:256-7.
10: Rose DK, Cohen MM, Yee DA. Changing the practice of pain management. Anesth Analg 1997; 84:764-72.
11: Humphries CA, Counsell DJ, Pediani RC, Close SL. Audit of opioid prescribing: the effect of hospital guidelines. Anaesthesia 1997; 52:745-9.
12: Joshi GP. Postoperative pain management. In: White PF (Ed.). Ambulatory Anesthesia Surgery, 1st ed. London: W.B. Saunders Company Ltd, 1997: 477-86.
13: Gourlay GK, Cherry DA, Onley MM, et al. Pharmacokinetics and pharmacodynamics of twenty-four-hourly Kapanol compared to twelve-hourly MS Contin in the
treatment of severe cancer pain. Pain 1997; 69:295-302.
14: Cannon CR. Transnasal butorphanol: pain relief in the head and neck patient. Otolaryngol Head Neck Surg 1997; 116:197-200.
15: Wasylak TJ, Abbott FV, English MJM, Jeans ME. Reduction of postoperative morbidity following patient-controlled morphine. Can J Anaesth 1990; 37:726-31.
16: Striebel HW, Oelmann T, Spies C, Rieger A, Schwagmeier R. Patient-controlled intranasal analgesia: a method for noninvasive postoperative pain management. Anesth
Analg 1996; 83:548-51.
17: Fuller JG, McMorland GH, Douglas MJ, Palmer L. Epidural morphine for analgesia after Caesarean section: a report of 4880 patients. Can J Anaesth 1990; 37:636-40.
18: Reuben SS, Connelly NR. Postoperative analgesia for out-patient arthroscopic knee surgery with intraarticular bupivacaine and ketorolac. Anesth Analg 1995; 80:1154-
7.
19: Bourke DL, Furman WR. Improved postoperative analgesia with morphine added to axillary block solution. J Clin Anesth 1993; 5:114-7.
20: Ritchie ED, Tong D, Chung F, Norris AM, Miniaci A, Vairavanathan SD. Suprascapular nerve block for postoperative pain relief in arthroscopic shoulder surgery: a new
modality. Anesth Analg 1997; 84:1306-12.
21: Bean-Lijewski JD. Glossopharyngeal nerve block for pain relief after pediatric tonsillectomy: retrospective analysis and two cases of life-threatening upper airway
obstruction from an interrupted trial. Anesth Analg 1997; 84:1232-8.
22: Wang B, Tang J, White PF, et al. Effect of the intensity of transcutaneous acupoint electrical stimulation on the post-operative analgesic requirement. Anesth Analg
1997; 85:406-13.
23: Marquardt HM, Razis PA. Prepacked take-home analgesia for day case surgery. Br J Nurs 1996; 5:1114-8.
24: Michaloliakou C, Chung F, Sharma S. Preoperative multimodal analgesia facilitates recovery after ambulatory laparoscopic cholecystectomy. Anesth Analg 1996; 82:44-
51.
25: Badner NH, Bourne RB, Rorabeck CH, Doyle JA. Addition of morphine to intra-articular bupivacaine does not improve analgesia following knee joint replacement. Reg
Anesth 1997; 22:347-50.
26: Pande AC, Pyke RE, Greiner M, Wideman GL, Benjamin R, Pierce MW. Analgesic efficacy of enadoline versus placebo or morphine in postsurgical pain. Clin
Neuropharmacol 1996; 19:451-6.
27: Looi-Lyons LC, Chung FF, Chan VW, McQuestion M. Respiratory depression: an adverse outcome during patient controlled analgesia therapy. J Clin Anesth 1996;
8:151-6.

Postoperative pain in ambulatory
surgery. Anesth Analg 1997;
85:808-16.

The continued training of doctors, nurses, and medical students in the prevention and proper management of
postoperative pain is necessary. Moote CA. The prevention of postoperative pain. Can J Anaesth 1994; 41:527-33.
9: Smith AF. The prevention of postoperative pain: shouldn't it begin at medical school? (Letter) Can J Anaesth
1995; 42:256-7.
Beauregard and colleagues found that many instructions given to patients did not clearly indicate the intake
frequency, dose adjustment, and control of side effects of analgesics. In the study of Rose et al., Rose DK, Cohen
MM, Yee DA. Changing the practice of pain management. Anesth Analg 1997; 84:764-72.
pain management practices were successfully changed after anaesthetists were educated and patients were made
more aware of pain as an important problem. Another study Humphries CA, Counsell DJ, Pediani RC, Close SL.
Audit of opioid prescribing: the effect of hospital guidelines. Anaesthesia 1997; 52:745-9.
MEDLINEÒ RECORD:
AB - The effects of prescribing guidelines for analgesia were assessed by auditing prescriptions for opioids before
and after the introduction of hospital prescribing guidelines. Opioid prescriptions were collected by the pharmacy
department over a 2-week period in November 1994 and repeated in November 1995. Following the initial audit,
analgesic prescribing guidelines were introduced. A statistically significant increase was achieved in the number of
prescriptions that were correct for both dose and frequency according to both the British National Formulary
recommendations (40-61%; p 0.001) and our Acute Pain Service guidelines (16-26%; p 0.05). There was a
statistically significant decrease in the number of prescriptions that were inadequate for both dose and frequency
according to both the British National Formulary recommendations (18-3%; p 0.001) and our Acute Pain Service
guidelines (36-17%; p = 0.001). The use of accessible prescribing guidelines promotes demonstrable
improvements in opioid prescribing.
showed that an audit of opioid prescribing considerably improved the prescribing of opioids, especially the
frequency with which they were prescribed.

An ideal postoperative analgesic protocol would be practical, effective, safe, have minimal
side effects, and be cost-effective. Sustained-release morphine, synthetic opioid agonist-antagonist
analgesics (butorphanol), nonsteroidal anti-inflammatory drugs (NSAID), patient-controlled
analgesia, local anaesthetic techniques (neuroaxial, intraarticular nerve block),
and non-pharmacological techniques (transcutaneous acupoint electrical stimulation) have
broadened the choices for the management of postoperative pain. For reduction of opioid-related
postoperative nausea and vomiting, the use of opioids and nonopioids combined with
local anaesthetic techniques has been increasing. A randomised double-blind study of
suprascapular nerve block for pain relief in arthroscopic shoulder surgery showed a 40%
reduction in analgesic consumption and a reduction in pain at rest and on abduction.
Another randomised double-blind study on preoperative multimodal analgesia for ambulatory
patients who underwent laparoscopic cholecystectomy used a combination of preoperative
meperidine and ketorolac by intramuscular bolus injection and local anaesthetic infiltration
into the incision during laparoscopic cholecystectomy. The results showed that the
concomitant use of local anaesthetic, NSAID, and opioid drugs was very effective in
diminishing postoperative pain and reducing the stay in the ambulatory care unit. These new
modalities demonstrate good effects on pain control and reduce the adverse outcomes
related to surgery. The results encourage us to continue studies in this field.

Wasylak TJ, Abbott FV, English MJM,
Jeans ME. Reduction of postoperative
morbidity following patient-controlled
morphine. Can J Anaesth 1990; 37:726-
31.
16:

Reuben SS, Connelly NR. Postoperative
analgesia for out-patient arthroscopic
knee surgery with intraarticular
bupivacaine and ketorolac. Anesth
Analg 1995; 80:1154-7.

Bourke DL, Furman WR. Improved postoperative
analgesia with morphine added to axillary block
solution. J Clin Anesth 1993; 5:114-7.
20: Ritchie ED, Tong D, Chung F, Norris AM, Miniaci
A, Vairavanathan SD. Suprascapular nerve block for
postoperative pain relief in arthroscopic shoulder
surgery: a new modality. Anesth Analg 1997;
84:1306-12.
21: Bean-Lijewski JD. Glossopharyngeal nerve block
for pain relief after pediatric tonsillectomy:
retrospective analysis and two cases of life-threatening
upper airway obstruction from an
interrupted trial. Anesth Analg 1997; 84:1232-8.

Wang B, Tang J, White PF, et al. Effect
of the intensity of transcutaneous
acupoint electrical stimulation on the
post-operative analgesic requirement.
Anesth Analg 1997; 85:406-13.

Marquardt HM, Razis PA. Prepacked take-home analgesia for
day case surgery. Br J Nurs 1996; 5:1114-8.
Another randomised double-blind study on preoperative
multimodal analgesia for ambulatory patients who underwent
laparoscopic cholecystectomy used a combination of
preoperative meperidine and ketorolac by intramuscular bolus
injection and local anaesthetic infiltration into the incision during
laparoscopic cholecystectomy. The results showed that the
concomitant use of local anaesthetic, NSAID, and opioid drugs
was very effective in diminishing postoperative pain and reducing
the stay in the ambulatory care unit.
» 24: Michaloliakou C, Chung F, Sharma S. Preoperative multimodal
analgesia facilitates recovery after ambulatory laparoscopic
cholecystectomy. Anesth Analg 1996; 82:44-51.

Local Anesthetic Techniques
Peripheral nerve blocks and wound infiltration with local anesthetics are commonly used adjuvants to both monitored anesthesia care (MAC) and general anesthetic
techniques because they can provide intra- and postoperative analgesia (). As a result, these techniques can decrease the anesthetic and analgesic requirements during surgery
and reduce the need for opioid analgesics in the postoperative period. More effective pain relief in the early postoperative period from the residual sensory block provided by local
anesthesia can facilitate the recovery process, enabling earlier ambulation and discharge home (i.e., fast-tracking). The use of local anesthetic techniques also decreases the
incidence of postoperative nausea and vomiting and thereby decreases the incidence of prolonged recovery stays and unanticipated hospital admissions related to intractable
emetic symptoms.
Although additional clinical studies are needed to identify the most cost-effective anesthetic techniques for ambulatory surgery, it would seem that peripheral nerve blocks with
sedation (i.e., MAC techniques) offer significant advantages over central neuraxis blockade and general anesthesia in the ambulatory setting . In outpatients undergoing
saphenous vein-stripping surgery, use of a femoral/genitofemoral nerve block significantly improved patient satisfaction with the anesthetic experience . Blockade of the
ilioinguinal and iliohypogastric nerves can significantly decrease the anesthetic and analgesic requirements in both children and adults undergoing inguinal herniorrhaphy,
providing 6–8 h of postoperative analgesia . Similarly, subcutaneous ring block of the penis provides effective perioperative analgesia for circumcision procedures . Local
anesthetic infiltration of the mesosalpinx significantly decreases the pain and cramping after laparoscopic tubal ligation procedures . Pain after arthroscopic shoulder surgery was
decreased significantly by a simple suprascapular nerve block , and pain after knee surgery was minimized with a femoral nerve block . However, more complete perioperative
analgesia for shoulder and knee surgery requires the use of an interscalene brachial plexus block and combined femoral, obturator, lateral femoral cutaneous, and sciatic nerve
blocks, respectively. Although additional preparation time may be required when these major peripheral nerve blocks are performed before surgery, these block techniques can
offer advantages in the postoperative period compared with general or spinal anesthesia .
It has been suggested that performing neural blockade with local anesthetics before the surgical incision may prevent the nociceptive input from altering the excitability of the
central nervous system (e.g., preemptively blocking the N-methyl-D-aspartate-induced “wind up” phenomena and release of inflammatory mediators) . The concept of preemptive
analgesia (or treating postoperative pain by preventing the establishment of central sensitization) seems very logical ; however, its clinical relevance has been questioned. Only
one well controlled study has demonstrated any benefits of pre- versus postincisional local anesthetic administration in the ambulatory setting . A recent qualitative and
quantitative review by Møiniche et al. suggested that evidence is still lacking that the timing of single-dose or continuous postoperative pain treatment is important in the
management of postsurgical pain. These investigators concluded that there is no convincing evidence that preemptive treatment with centrally or peripherally administered local
anesthetics, NSAIDs, opioid analgesics, or ketamine offers any advantage with respect to postoperative pain relief compared with a similar postsurgical analgesic regimen.
Nevertheless, preincisional administration offers advantages over infiltration at the end of surgery with respect to intraoperative analgesia.
Preincisional infiltration with local anesthetics in combination with general anesthesia is clearly superior to general (or spinal) anesthesia alone in relieving postoperative pain .
In fact, preincisional infiltration of the tonsillar bed with bupivacaine decreased both constant pain and pain on swallowing for up to 5 days after tonsillectomy procedures in
children . Preincisional ilioinguinal hypogastric nerve block not only improves intraoperative pain control during inguinal hernia repair, but also reduces the need for oral opioid-containing
analgesics after discharge . Although preincisional infiltration of the operative site with local anesthetics remains a popular technique for reducing the perioperative
opioid analgesic requirement, other more simplified local anesthetic delivery systems (e.g., topical applications) have also been described in the anesthesia literature . Topical
analgesia with lidocaine aerosol was found to be highly effective in decreasing pain, as well as the opioid analgesic requirement, after inguinal herniorrhaphy in adults , and
instillation of 0.25% bupivacaine before surgical closure provided comparable postoperative pain relief to an ilioinguinal/iliohypogastric nerve block in children undergoing hernia
repair . Furthermore, the simple application of topical lidocaine jelly or ointment is as effective as peripheral nerve blocks or parenteral opioids in providing pain relief after
outpatient circumcision .
Intracavitary instillation of local anesthetics is another simple, yet effective, technique for providing pain relief during the early postoperative period after laparoscopic and
arthroscopic procedures. Intraperitoneal administration of local anesthetics during laparoscopy was found to be an efficient method of reducing the intensity of postoperative
scapular pain . However, when bupivacaine was injected at the preperitoneal fascial plane during extraperitoneal laparoscopic hernia repair, it did not reduce postoperative pain .
Local anesthetics can also be injected into joint spaces to provide analgesia during and after arthroscopic surgery . In a placebo-controlled study, intraarticular instillation of 30
mL of 0.5% bupivacaine reduced the opioid requirements and facilitated early mobilization and discharge after knee arthroscopy . A follow-up study involving a combination of
intraarticular bupivacaine and systemic ketorolac (60 mg IV or IM) further decreased pain in the early postoperative recovery period. A wide variety of adjuvants has also been
injected into the intraarticular space to decrease postarthroscopic pain, including morphine, ketorolac, triamcinolone, and clonidine . Small-dose intraarticular morphine 1–3 mg,
in combination with bupivacaine, seems to provide the longest lasting and most cost-effective analgesia after knee arthroscopy . Although administering the intraarticular
morphine before knee surgery was reported to provide a longer duration of analgesia and greater opioid-sparing effects than when it was given at the end of surgery , the clinical
advantages of preemptive analgesia remain controversial .
Local anesthetic supplementation clearly decreases the severity of incisional pain in the early postoperative period. However, outpatients may still experience significant pain
after they have been discharged home because of difficulty in anticipating the degree of pain when the local anesthetic effect wears off. Continuous or intermittent perfusion of
the surgical wound with local anesthetic solutions is an old-fashioned but highly effective technique for extending incisional pain relief into the postdischarge period. Recently, this
technique has been modified to allow for patient-controlled local anesthetic administration after discharge home . However, some investigators have failed to find significant
differences in pain scores or opioid analgesic requirements when the local anesthetic was instilled or injected at the incision site . The response to local analgesia appears to be
influenced by the location, concentration, and volume of the injected local anesthetic solution. For example, Yndgaard et al. demonstrated that subfascially administered
lidocaine was significantly more effective in reducing pain compared with subcutaneous injection after inguinal herniotomy. Finally, combining local anesthetic techniques with
other analgesic modalities as part of multimodal (or “balanced”) analgesic therapy can improve pain control throughout the perioperative period . The concept of balanced
analgesia consists of administering several different analgesic drugs to alter the pathophysiologic processes involved in nociception, thereby producing more effective

NSAIDs

NSAIDs have long been used for treating nonsurgical pain syndromes because of their well known antiinflammatory, antipyretic, and analgesic properties. However, with the
introduction of parenteral preparations of NSAIDs (e.g., ketorolac and diclofenac), these drugs have become more popular in the management of pain associated with ambulatory
surgery. NSAIDs block the synthesis of prostaglandins by inhibiting the enzyme cyclooxygenase (COX), thereby reducing the production of mediators of the acute inflammatory
response. By decreasing the inflammatory response to surgical trauma, NSAIDs have been alleged to reduce peripheral nociception. However, more recent studies also suggest
that the central response to painful stimuli may be modulated by NSAID-induced inhibition of prostaglandin synthesis in the spinal cord .
Early reports suggested that NSAIDs possessed analgesic properties comparable to those of opioid analgesics without opioid-related side effects . When ketorolac was
administered as an adjuvant to propofol/nitrous oxide anesthesia, its use was associated with improved postoperative analgesia and patient comfort, which compared favorably to
fentanyl . Moreover, ketorolac was associated with a decreased incidence of postoperative nausea and vomiting, and patients tolerated oral fluids and were judged fit for
discharge earlier than those receiving opioid compounds. Other investigators have also reported that ketorolac provided similar postoperative pain relief to that of fentanyl but
was associated with less nausea and somnolence and an earlier return of bowel function after ambulatory surgery . Furthermore, it was recently reported that the administration
of ketorolac (30 mg) at the incision site to supplement local anesthesia resulted in significantly less postoperative pain, a better quality of recovery, and earlier discharge
compared with local anesthesia alone . However, when ketorolac was substituted for or combined with fentanyl during outpatient gynecologic and laparoscopic surgical
procedures, the beneficial effects of the NSAID were more variable .
Use of shock-wave lithotripsy to evaluate the effect of NSAIDs on visceral pain, diclofenac produced only a marginal opioid-sparing effect . Furthermore, when diclofenac (1
mg/kg IV) was administered before outpatient arthroscopic surgery, it was found to be associated with similar visual analog pain scores to fentanyl (1 mg/kg IV) . After
gynecologic laparoscopy surgery , diclofenac decreased pain and analgesic requirements for 24 h postoperatively but had little effect on the recovery profile. Similarly, the
administration of ketorolac during the perioperative period in outpatients undergoing laparoscopic cholecystectomy procedures decreased postoperative opioid requirements, but
this contributed to only a marginal improvement in ventilatory function at 4 hr after the operation.
When diclofenac was administered preoperatively to pediatric patients, both the incidence of restlessness and crying and the postoperative opioid requirements were lower in
the diclofenac-treated (versus acetaminophen-treated) patients . Oral ketorolac (1 mg/kg) compared favorably to small-dose acetaminophen (10 mg/kg) for bilateral myringotomy
procedures in children, with the ketorolac-treated patients recording lower pain scores and requiring less analgesic medication in the early postoperative period . In children
undergoing inguinal hernia repair , ketorolac (1 mg/kg IV) compared favorably to caudal bupivacaine 0.2% with respect to pain control and postoperative side effects. In fact, the
ketorolac-treated patients had an improved recovery profile, including less vomiting, shorter times to voiding and ambulation, and earlier discharge home. Furthermore, the
intraoperative administration of ketorolac as an adjuvant to general anesthesia in pediatric patients provided postoperative analgesia comparable to morphine . As expected, the
ketorolac-treated patients experienced less postoperative nausea and vomiting. When ketorolac or morphine are administered for pain control in pediatric patients, ketorolac-induced
analgesia develops more slowly but is longer lasting compared with morphine .
Oral or rectal administration of NSAIDs can also be highly effective in the prophylactic management of pain after ambulatory surgery. For example, when oral naproxen was
administered before laparoscopic surgery, postoperative pain scores, opioid requirements, and time to discharge were significantly reduced . Furthermore, premedication with
oral ibuprofen (800 mg) was associated with superior postoperative analgesia and less nausea compared with fentanyl (75 mg IV) . However, the more important role for oral
NSAIDs is in the postdischarge period. In a recent outpatient study involving the use of a multimodal analgesic technique consisting of alfentanil, lidocaine, ketorolac, and
paracetamol , oral ibuprofen (800 mg every 8 h) was equianalgesic to paracetamol 800 mg plus codeine 60 mg (every 8 h) when administered during the first 72 h after
discharge, and it resulted in better global patient satisfaction and less constipation than the opioid-containing oral analgesic. To achieve the optimal benefit of using NSAIDs in
the perioperative period, these compounds should be continued as prophylactic analgesics for preventive pain management in the postdischarge period .

COX-2 Inhibitors
In an effort to minimize the potential for operative-site bleeding complications, as well as gastrointestinal
and renal damage, associated with the classical NSAIDs, the more specific COX-2 inhibitors are
being increasingly used as non-opioid adjuvants for minimizing pain during the perioperative period
(). Early studies evaluated the use of celecoxib and rofecoxib for preventative analgesia when
administered for oral premedication . Rofecoxib (50 mg orally [PO]) seems to produce more effective
and sustained analgesia compared with celecoxib (200 mg PO) after surgery . Preliminary data
suggest that celecoxib (200 mg PO) is equivalent to acetaminophen (2 g PO) when administered
before outpatient otorhinolaryngology surgery . However, rofecoxib (50 mg PO) produced significantly
more effective analgesia than acetaminophen (2 g PO), and the pain relief was more sustained in the
postdischarge period . Premedication with rofecoxib also facilitated the recovery process by reducing
postoperative pain and improving the quality of recovery from the patient’s perspective.
More recently, a parenterally active COX-2 inhibitor, parecoxib (20–40 mg IV), has been
investigated as an alternative to ketorolac and diclofenac . Parecoxib is a prodrug with an active
metabolite (valdecoxib) and is similar both pharmacokinetically and pharmacodynamically to
celecoxib. Both preoperative and postoperative administration of this investigational COX-2 drug
seems to exert significant opioid-sparing effects, and these preliminary studies suggest that it can
improve the quality of recovery and patient satisfaction with postoperative pain management.
However, further comparative clinical studies are needed to define the optimal role of COX-2
inhibitors in ambulatory surgery.

Acetaminophen (Paracetamol)
Of the nonopioid analgesics, acetaminophen is potentially one of the most useful, yet it
is vastly underused in the ambulatory setting. When administered in an appropriate oral
or rectal dose, acetaminophen can be a very useful adjuvant during the perioperative
period and compares favorably to the NSAIDs in children . Although Watcha et al.
reported minimal analgesic-sparing effects after a 10 mg/kg dose of acetaminophen,
Rusy et al. found that a larger dose (35 mg/kg per rectum) was as effective as ketorolac
1 mg/kg IV in reducing pain after tonsillectomy procedures and was associated with less
postoperative bleeding than the NSAID. More recently, Korpela et al. demonstrated that
the opioid-sparing effect of acetaminophen was strictly dose related. The optimal dosing
regimen for acetaminophen in children consists of a preoperative initial loading dose of
40 mg/kg followed by a maintenance dose of 20 mg/kg every 6–8 h during the early
postoperative period .
An IV formulation of acetaminophen, known as propacetamol, has been administered
to adults as an alternative to ketorolac in the perioperative period . Propacetamol is a
prodrug that is rapidly and completely hydrolyzed by nonspecific plasma esterases to
form acetaminophen (also known as paracetamol). Although the future role of this non-opioid
parenteral analgesic during the perioperative period is yet to be determined, rectal
acetaminophen (1.3 g) has been successfully used as an adjuvant to NSAIDs and local
anesthetics in adult outpatients as part of a multimodal fast-tracking protocol

Ketamine
Ketamine is a unique anesthetic with analgesic-like properties which has been
used for both the induction and maintenance of anesthesia and as an analgesic
adjuvant during MAC . As a result of its well known side-effect profile (), ketamine
fell into disfavor in the anesthesia community in the early 1980s. However, the
use of so-called small-dose ketamine (0.1–0.2 mg/kg IV) techniques seems to be
associated with a much less frequent incidence of adverse events and with
greater patient and physician acceptance . Recent studies have described the
use of ketamine in combination with propofol for MAC and IV anesthesia . The
administration of ketamine 4–18 mg · kg-1 · min-1 in combination with propofol
30–90 mg · kg-1 · min-1 can obviate the respiratory depression produced by
propofol/opioid combinations while producing positive mood effects after surgery,
and it may even provide for an earlier recovery of cognitive function . In addition,
a single bolus dose of ketamine 0.1–0.15 mg/kg during surgery has been
reported to produce significant opioid-sparing effects after painful ambulatory
surgery procedures . However, the clinical significance of ketamine’s preemptive
analgesic effects remains controversial .

Nonpharmacologic Techniques
Nonpharmacologic “electroanalgesic” techniques (e.g., transcutaneous electrical nerve
stimulation [TENS], acupuncture-like TENS, and percutaneous neuromodulation therapy)
can also be used as adjuvants in the treatment of both acute and chronic pain in the
ambulatory setting . Given the inherent side effects produced by both opioid and non-opioid
analgesics (), it is possible that nonpharmacologic approaches will assume a more
prominent role in the management of pain after ambulatory surgery in the future.
Most studies suggest that TENS produces a 15%–30% decrease in the postoperative
opioid requirement . In addition to reporting that TENS reduces pain and the need for oral
analgesics, Jensen et al. reported a more rapid recovery of joint mobility after outpatient
arthroscopic surgery. In reviewing the medical literature, Carroll et al. found conflicting
results regarding the effect of TENS on the requirement for opioid analgesic medication and
the quality of postoperative pain relief. Several studies suggest that the location, intensity,
and frequency of electrical stimulation are all important factors influencing the efficacy of
TENS (and acupuncture-like TENS) therapies . Moreover, the clinical efficacy of
electroanalgesic techniques remains controversial because of the potential sources of bias
and difficulty in quantifying the inherent placebo effect of the therapy. Other
nonpharmacologic approaches that have also been evaluated as potentially useful analgesic
adjuvants in the perioperative period include cryoanalgesia, ultrasound, laser, and even
hypnosis . However, additional well controlled clinical studies are needed to establish the
benefits of these nonpharmacologic modalities on patient outcome after ambulatory surgery.

management of pain after
ambulatory surgery. Anesth
AnaIg 2002;94:577-85

preventing pain after ambulatory
otolaryngologic surgery .Anesth
Analg 2003 ;96:987-94

Efficacia e soddisfazione della terapia del dolore postop.
Rocchi A,Chung F,Forte L.. Canadian survey of postsurgical pain and pain medications
experiences.Can.J.Anesth.2002;49:1053-1056

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