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Servizio di Anestesia e Rianimazione Ospedale di Faenza(RA)
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.)
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PONV
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Hill RP, Lubarsky DA, Phillips-Bute B, Fortney JT, Creed MR, Glass PSA, Gan TJ: Cost-effectiveness of prophylactic antiemetic therapy with ondansetron, droperidol, or
placebo. ANESTHESIOLOGY 2000; 92:958-67.
prophylaxis with 1.25 mg intravenous droperidol was the most cost-effective approach
Cost considerations:» acquisition cost of a drug» costs of wasted drug» the need for adjunctive drugs to manage side effects» costs of nursing labor» Nursing labor costs are linearly related to the time an individual nurse spends with
a patient. » However, institutional costs may not increase if a patient spends an additional 15—
30 min in the postanesthesia care unit (PACU), unless overtime costs are incurred.» improved patient satisfaction
The cost-effectiveness of prophylactic antiemetic therapy depends on:» the underlying incidence of PONV » and on the costs and effectiveness of the drugs used for prophylaxis.
Servizio di Anestesia e Rianimazione Ospedale di Faenza(RA)
What drug should be used for PONV prophylaxis in high-risk patients? A more expensive drug may be preferred and reduce total institutional costs if it is more effective or associated with a decreased side-effect profile, a greater patient satisfaction, or an quicker return to work. There is convincing evidence from a systematic review of 54 blinded studies of 7,234 patients that ondansetron is more effective than metoclopramide, but not more effective than 1.25 mg droperidol for PONV prophylaxis in adults. Droperidol has also been shown to be as effective as tropisetron and dolasetron. Antiserotonin drugs are associated with increased headache, whereas central nervous system side effects of dysphoria, restlessness, and drowsiness have been reported with droperidol. However, when the dose of droperidol was limited to 1.25 mg intravenous, the incidence of these central nervous system events did not differ compared with ondansetron. It is also important to note that there were no patient preferences for a specific regimen in the study by Hill et al. In this era of cost containment, the less expensive drug, droperidol, should be used for PONV prophylaxis in the adult patient population until more effective drugs with decreased side effects are developed or the costs of alternative drugs are lowered. Similarly, in the absence of evidence to suggest that any available antiserotonin agent is superior to another in effectiveness or side-effect profile, the least expensive one should be used. In contrast to adults, PONV prophylaxis with droperidol is less effective than ondansetron in children and is associated with increased drowsiness, delayed discharge, and extrapyramidal side effects. The preferential use of ondansetron in this patient population may be justified.
Servizio di Anestesia e Rianimazione Ospedale di Faenza(RA)
Postoperative Nausea and Vomiting:
Prevention and Treatment
Claudio Melloni
Anestesia e Rianimazione
Ospedale degli Infermi di Faenza(RA)
Servizio di Anestesia e Rianimazione Ospedale di Faenza(RA)
The Cost-effective Management of Postoperative Nausea and Vomiting
EDITORIAL VIEW AUTHOR(S): Watcha, Mehernoor F., M.D.
Anesthesiology92:931-3, 2000
Servizio di Anestesia e Rianimazione Ospedale di Faenza(RA)
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
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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» observed on site by a third party. » As a consequence of the effects of both suggestion and increased detection, repeatedly questioning patients about
PONV might result in a higher percentage of patients reporting PONV and receiving antiemetic therapy than would be the case in normal practice. In our study, blinded trial nurses did not communicate PONV findings to PACU nurses caring for patients, and PONV scores in the case report form were unavailable to PACU nurses.
Servizio di Anestesia e Rianimazione Ospedale di Faenza(RA)
Importance of the issue PONV is :
» A limiting factor in the early discharge of ambulatory surgical patients» The leading cause of unanticipated hospital admission
PONV may:» Increase recovery room time» Expand nursing care» Increase total health care costs» Cause high level of patient discomfort---pain,hematoma,wound
dehiscence…» Cause high level of patient dissatisfaction» KO!!!
Servizio di Anestesia e Rianimazione Ospedale di Faenza(RA)
Macario A, Weinger M,Carney S, Kim A.Which clinical anesthesia outcomes are important to
avoid?Anesth.Analg.1999;89:652-8.
02468
101214161820
rank valore relativo
vomito
gagging sul tubo
dolore
nausea
ricordo senza dolore
debolezza residua
brivido
mal di gola
sonnolenza
Dal + indesiderabil
eAl 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.
Servizio di Anestesia e Rianimazione Ospedale di Faenza(RA)
Sintomi accusati dai pazienti a casa dopo interventi eseguiti in regime di day
surgery(da Wu et al.,Anesthesiology 2002).
dolorenauseavomitocefaleasonnolenzagir.di testafatica
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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)
0
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doloretossire sul tubo etvomitonauseadisorientamentomal di golabrividosonnolenzasete
Valori relativi !
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Beauregard L, Pomp A, Choinière M. Severity and impact of pain after day-surgery
Can J Anaesth 1998 / 45 / 304-11
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Servizio di Anestesia e Rianimazione Ospedale di Faenza(RA)
Sintomi accusati dai pazienti a casa dopo interventi eseguiti in regime di day
surgery(da Wu et al.,Anesthesiology 2002).
dolorenauseavomitocefaleasonnolenzagir.di testafatica
Servizio di Anestesia e Rianimazione Ospedale di Faenza(RA)
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)
0
5
10
15
20
25
30
doloretossire sul tubo etvomitonauseadisorientamentomal di golabrividosonnolenzasete
Valori relativi !
Servizio di Anestesia e Rianimazione Ospedale di Faenza(RA)
Beauregard L, Pomp A, Choinière M. Severity and impact of pain after day-surgery
Can J Anaesth 1998 / 45 / 304-11
0102030405060708090
100
%
do
lore
PO
NV
gir
.tes
ta
son
no
len
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ma
l d
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Servizio di Anestesia e Rianimazione Ospedale di Faenza(RA)
Can PONV be predicted?
Risk factor analysis
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Sinclair et al.Can PONV be predicted?Anesthesiology
1999;91:109-18 17,638 consecutive ambulatory surgical patients;>90% ASA I /II 5,812 men and 11,826 women mean (± SD) age of 46.7 ± 21.2 yr. prospectively studied during a 3-yr period ASU of The Toronto Hospital, Western Division telephone interview 24 h after operation was obtained. Preoperative patient characteristics and intraoperative variables were
documented on specifically designed, standardized adverse-outcome check-off forms.
i.v.2—4 mg morphine for pain relief and 25—50 mg dimenhydrinate for nausea or vomiting.
Overall PONV incidence 4.6%:9.1 % at 24 hrs interview.
Servizio di Anestesia e Rianimazione Ospedale di Faenza(RA)
Sinclair et al.Can PONV be predicted?Anesthesiology
1999;91:109-18
Patients with PONV underwent significantly longer procedures (67 ± 57 min vs. 51 ± 44 min; P < 0.0001), and the duration of their stay in the PACU (72 ± 32 min vs. 49 ± 25 min; P < 0.0001) and the ASU (157 ± 84 min vs. 95 ± 53 min; P < 0.0001) was also significantly longer ().
Among patients undergoing general anesthesia, those who experienced PONV during the immediate postoperative period had received significantly higher doses of alfentanil, fentanyl, and midazolam during operation (). The same was true of those who received monitored anesthesia care. Patients experiencing PONV received significantly higher doses of dimenhydrinate in the PACU and ASU (37 ± 19 mg vs. 23 ± 11 mg; P < 0.0001). Among patients who received general anesthesia, those with PONV within 24 h after surgery received significantly higher doses of morphine in the PACU and ASU than did those without PONV (6.3 ± 3.6 mg vs. 5.3 ± 3.5 mg; P = 0.008).
Among patients undergoing general anesthesia, 1,225 (12%) received a nondepolarizing muscle relaxant during operation. Five hundred patients (41%) received a reversal agent (483 received neostigmine, 17 received edrophonium) at the end of the procedure. There was no significant difference in PONV between those who received a reversal agent and those who did not (19.2% vs. 15.7%; P = 0.11).
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Sinclair DR, Chung F,Mezei G.Can PONV be predicted?Anesthesiology 1999;91:109-18
Background: Retrospective studies fail to identify predictors of postoperative nausea and vomiting (PONV). The authors prospectively studied 17,638 consecutive outpatients who had surgery to identify these predictors.
Methods: Data on medical conditions, anesthesia, surgery, and PONV were collected in the 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.
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Frequency of PONV by type of anesthesia and duration of surgery.
Sinclair et al.Can PONV be predicted?Anesthesiology 1999;91:109-18
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PONV prolongs PACU and amb.surg.unit stay Sinclair et al.Can
PONV be predicted?Anesthesiology 1999;91:109-18
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Independent predictors of PONV Sinclair et al.Can PONV be predicted?Anesthesiology
1999;91:109-18
age A 10-yr increase in age was associated with a 13% decrease in the likelihood of PONV. sex Men had one third the risk for PONV compared with women. smoking status Smokers had two thirds the risk for PONV compared with nonsmokers history of previous PONV, had a threefold increase in the likelihood PONV compared with patients with no
previous PONV. type of anesthesia: General anesthesia increased the likelihood of PONV 11 times compared with other types of
anesthesia. duration of anesthesia, direct association between the duration of anesthesia and the risk for PONV. A 30-min
increase in duration predicted a 59% increase in the incidence of PONV type of surgery :
» plastic surgery had a sevenfold increase in the risk for PONV.» orthopedic shoulder surgery, ophthalmologic, or ENT procedures had a four- to sixfold increase.» orthopedic (nonshoulder) and gynecologic (non-D&C) procedures had a threefold increase in
the risk for PONV. Compared with the reference group, which includes general surgery, gynecologic dilation and curettage (D&C), urologic surgery, neurosurgery, and chronic pain blockENT
» dental surgery 14.3%, orthopedic 7.6%,plastic surgery 7.4%.Urologic, gynecologic, neurologic, or general surgery had an incidence of PONV corresponding to the overall average 4%
Servizio di Anestesia e Rianimazione Ospedale di Faenza(RA)
Sinclair et al.Can PONV be predicted?Anesthesiology 1999;91:109-18
In our study, the incidence of PONV was 4.6% in the PACU and ASU and 9.1% at the 24-h interview. A previous study of 143 ambulatory surgical patients found an increase in PONV 48 h after discharge (16.8%) compared with the incidence in the PACU (9.8%). Because medications administered in the ambulatory surgery center undergo metabolism and elimination within 48 h after discharge, the increase in postdischarge PONV suggests a multifactorial cause related to early ambulation and resumption of oral intake.
The frequency of PONV in the PACU and ASU varied according to sex, ASA status, age, type and duration of anesthesia, type of surgery, and type of procedure within the same surgical specialty. The high frequency of PONV in the PACU and ASU (> 15%) among breast augmentation, strabismus repair, laparoscopic sterilization, varicose vein stripping, dental, and orthopedic shoulder procedures may justify the use of prophylactic antiemetics.
Servizio di Anestesia e Rianimazione Ospedale di Faenza(RA)
Sinclair et al.Can PONV be predicted?Anesthesiology 1999;91:109-18
Patients undergoing breast augmentation had a 41.5% incidence of PONV in the immediate postoperative period and 42.9% 24 h after operation. The incidence of PONV in breast surgery has been reported to be 37—59%. Further studies are needed to determine the cause of this apparently high incidence of PONV. Among the patients having orthopedic procedures, those undergoing shoulder surgery experienced the highest frequency of PONV (16.6%), possibly because of the high use of postoperative opioids. Ondansetron (8 mg) has been shown to be more efficacious than metoclopramide (10 mg) in reducing 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.
Servizio di Anestesia e Rianimazione Ospedale di Faenza(RA)
Sinclair et al.Can PONV be predicted?Anesthesiology 1999;91:109-18
Among the intraoperative anesthetic drugs, alfentanil and fentanyl were administered in significantly higher doses in patients with PONV. Although these doses do not demonstrate causality, the amount of narcotics may contribute to the incidence of PONV. Furthermore, patients with PONV stayed longer in the PACU and ASU (23 and 62 min, respectively). Despite a significantly higher dose of dimenhydrinate among these patients, it remains unclear whether this longer stay was due to the treatment of PONV. A decrease in PONV may reduce the duration of postoperative stay and increase the 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.
Servizio di Anestesia e Rianimazione Ospedale di Faenza(RA)
Sinclair et al.Can PONV be predicted?Anesthesiology 1999;91:109-18
In this study, sex, age, smoking, previous PONV, type and duration of anesthesia, and type of surgery were independent predictors of PONV. Men had one third the risk for PONV that women had. Previous reports supported this sex difference and attributed the finding to variations in serum gonadotropin or other hormone levels.
Another predictor of PONV was age. Age decreased the likelihood of PONV by 13% for each 10-yr increase. Pioneer studies described a decreasing incidence among men with increasing age and an insignificant decrease among women until the eighth decade. In contrast, our study showed a gradual decrease in PONV after age 50 yr. Interestingly, Koivuranta et al., using the forward procedure of logistic regression, did not find age to be a predictive factor for nausea, except for patients older than 50 yr who were undergoing joint replacement and spinal surgery, in whom there was an increased risk for postoperative vomiting.
Smoking was also a predictor of PONV. Smoking decreased the likelihood of PONV by 34%. The relation between smoking and PONV was not evident in the literature for many years. A multicenter study of anesthetic outcomes showed a lower risk for PONV in smokers (relative risk = 0.6). Our results are consistent with recent studies that identified smoking as a protective factor against PONV.
Servizio di Anestesia e Rianimazione Ospedale di Faenza(RA)
Sinclair et al.Can PONV be predicted?Anesthesiology 1999;91:109-18
Another predictor of PONV is previous PONV, which increases the likelihood of PONV by three times. A recent study showed previous PONV as the second strongest predictor of PONV, in addition to a twofold increased risk for PONV among these patients. Although an older study reports a 52-fold increased risk for PONV among patients with a history of PONV, its power is reduced by its small sample size.
Anesthetic technique was also a predictor of PONV. Patients receiving general anesthesia were approximately 11 times more likely to experience PONV than were those who received monitored anesthesia care, regional anesthesia, or chronic pain block. PONV can be reduced by supplementing nitrous oxide and oxygen with propofol rather than a volatile gas. Total intravenous anesthesia protects against PONV more than does general anesthesia with volatile agents. Because our results apply to general anesthesia with volatile agents, further study is required to determine the predictive power of general anesthesia with intravenous agents.
The duration of anesthesia was another predictor of PONV, increasing the risk for PONV by 59% for each 30-min increase. This finding could be related to the larger number of potentially emetic drugs administered during longer procedures. Our results are consistent with the previously reported 17.5% incidence of PONV for anesthesia lasting 30—90 min, which increased to 46% for procedures lasting 150—210 min.
The type of surgery was a significant predictor of PONV. Patients undergoing plastic, ophthalmologic, and orthopedic shoulder surgery were at least six times more likely to experience PONV than were patients in the reference group. Compared with the reference group, patients having ENT—dental, nonshoulder orthopedic, and non-D&C gynecologic surgery were two to four times as likely to experience PONV. ENT and dental surgery and orthopedic surgery involve bone injury and damage to the periosteum, resulting in significant postoperative pain. Similarly, recent studies support the high incidence of severe pain after plastic surgery. There is evidence that nausea often accompanies pain in the early postoperative period and that both can be relieved in many cases by using intravenous opiates. Further study of an improved effect of postoperative analgesia on the incidence of PONV in ENT and dental, orthopedic, and plastic surgery outpatients is needed.
A history of motion sickness is associated with an increased incidence of PONV. A large prospective survey of a wide spectrum of procedures concluded that a history of motion sickness was the fourth strongest predictor of PONV. Ultimately, a previous history of motion sickness was not included in our analysis of the predictive factors of PONV.
Servizio di Anestesia e Rianimazione Ospedale di Faenza(RA)
Sinclair et al.Can PONV be predicted?Anesthesiology 1999;91:109-18
A well-designed logistic regression model of factors associated with PONV will help guide patient selection for antiemetic therapy. Palazzo and Evans developed a model to predict PONV. However, their study has several limitations. Because the coefficients of the study were derived from a small sample of patients having orthopedic surgery, the model is not applicable to various types of surgical patients. The model also lacks validation by statistical techniques that evaluate the model's ability to predict PONV correctly. Koivuranta et al. developed a risk score to predict PONV and measured the power of the model by calculating the area under the ROC. Although patient and surgery related factors were addressed in their model, the coefficients were derived from pediatric and adult inpatients. Anesthesia-related factors were not included. Similarly, The predictive model developed by Apfel et al., which was derived from adult inpatients, also lacks anesthesia-related factors. Unlike patient-related factors and many surgery-related factors that cannot be modified in the perioperative period, many anesthesia-related factors, such as anesthetic technique, sometimes can be modified. Anesthesia-related factors must be included in the model to determine the potential effect of a change in anesthetic technique. We present the only model that is derived from ambulatory patients and incorporates anesthesia-related factors. This model is the most comprehensive logistic regression model of patient-, anesthesia-, and surgery-related factors associated with PONV (see appendix 1). This model will be able to predict patients' risk for PONV according to their sex, age, previous PONV, history of motion sickness, duration of anesthesia, anesthetic technique, and type of surgery. We evaluate the model's ability to correctly predict PONV and determine the power of the model by calculating the area under the ROC curve.
Knowledge of these predictors of PONV should increase anesthesiologists' efforts to reduce the incidence of PONV by selecting patients for antiemetic therapy. This may lead to improved cost-effective use of available drugs and resources.
Servizio di Anestesia e Rianimazione Ospedale di Faenza(RA)
Fitting the model to the data, we can obtain the maximum likelihood estimate of the parameters for each variable. Based on the maximum likelihood estimates from the final models, it is possible to calculate an expected risk of occurrence of the specific adverse event for any patient.
where Age = age in years/10; Sex = 1 if male and 0 if female; Smoke = 1 if
smoker and 0 if nonsmoker; PONV History = 1 if previous PONV and 0 if no previous PONV; Duration = duration of surgery in 30-min increments; GA = 1 if general anesthesia and 0 if other type of anesthesia; ENT = 1 if ENT and 0 if other type of surgery; Ophthalm = 1 if ophthalmology and 0 if other type of surgery; Plastic = 1 if plastic surgery and 0 if other type of surgery; GynNonDC = 1 if gynecologic non D&C procedure and 0 if other type of surgery; OrtKnee = 1 if orthopedic procedure involving knee and 0 if other type of surgery; OrtShoulder = 1 if orthopedic procedure involving the shoulder and 0 if other type of surgery; OrtOther = 1 if orthopedic procedure involving neither knee nor shoulder and 0 if other type of surgery.
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Logistic regression da:Sinclair et al.Can PONV be predicted?Anesthesiology 1999;91:109-18
P=1/1+e esponente
con il segno neg. all’esponente la probabilità aumenta perché e elevato ad esp negativo diminuisce sempre + con il risultato che 1+e tende a 1 e dunque P=1/1,ossia 100%
Con il segno positivo all’esponente e aumenta sempre + e allora 1+e aumenta e dunque il denominatorer dell’equazione aumenta e dunque 1/un numero in aumento fa scendere la probabilità perché viene 1/5,cioè 20%,1/10=10%,ecc…..
Esponente=-5,97+(-0,14 *age)+(-1,03*sex)+(-0,42*smoke)+(1,14*PONV history)+(0,46*duration)+(2,36*GA)+(1,48*ENT)+(1,77*ophtalm)+(1,90*plastic)+(1,20 Gynecol non DC)+(1,04 ort knee)+(1,78*ortshoulder)+(0.94 ort
other) where Age = age in years/10; Sex = 1 if male and 0 if female; Smoke = 1 if smoker and 0 if nonsmoker; PONV History
= 1 if previous PONV and 0 if no previous PONV; Duration = duration of surgery in 30-min increments; GA = 1 if general anesthesia and 0 if other type of anesthesia; ENT = 1 if ENT and 0 if other type of surgery; Ophthalm = 1 if ophthalmology and 0 if other type of surgery; Plastic = 1 if plastic surgery and 0 if other type of surgery; GynNonDC = 1 if gynecologic non D&C procedure and 0 if other type of surgery; OrtKnee = 1 if orthopedic procedure involving knee and 0 if other type of surgery; OrtShoulder = 1 if orthopedic procedure involving the shoulder and 0 if other type of surgery; OrtOther = 1 if orthopedic procedure involving neither knee nor shoulder and 0 if other type of surgery.
Servizio di Anestesia e Rianimazione Ospedale di Faenza(RA)
Importance of the work by Sinclair et al…
Fitting the model to the data, we can obtain the maximum likelihood estimate of the parameters for each variable. Based on the maximum likelihood estimates from the final models, it is possible to calculate an expected risk of occurrence of the specific adverse event for any patient.
Servizio di Anestesia e Rianimazione Ospedale di Faenza(RA)
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%.
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Risk Factors
Non-anesthetic factors Anesthetic related factors Postoperative factors
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Risk factors da Samba 2007:1
Patient specific Female gender Non smoking status Hx of ponv/motion sickness
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Risk factors da Samba 2007:2
Anesthetoc risk factors Use on intraop volatile anesth Use on intraop and postop opioids Use of intraop N2O
Servizio di Anestesia e Rianimazione Ospedale di Faenza(RA)
Risk factors da Samba 2007:3
Surgical risk factors Duration of surgery Each 30 min increase in duration of surgery
oncreases the risk by 60%,so thyat a baseline risk of 10% increases to 16% after 30 min
Type of surgery laparoscopy;,laparotomy;breast,strabismus,pl
astic,maxillofacial,gynecological,abdominal,neurologic ,opthalmologic,urologic
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Risk Factors
Age Gender Body habitus Hx motion sickness Hx PONV Anxiety Concomitant disease Operative procedure Duration of surgery
Non-anesthetic Factors
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Risk Factors
Preanesthetic medication Gastric distension Gastric suctioning Anesthetic technique Anesthetic agents
Anesthetic Related Factors
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Risk Factors
Pain Dizziness Ambulation Oral intake Opioids
Postoperative Factors
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Postoperative Nausea and Vomiting:Anesthetic Related Factors
Nitrous oxide
Volatile anesthetics
NMB reversal
Propofol
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Risk FactorsNitrous Oxide and PONV
Omission of Nitrous Oxide during Anesthesia Reduces the Incidence of Postoperative Nausea and Vomiting. A Meta-Analysis
Divatia et al. Anesthesiology 1996;85:1055-1062
Twenty-Four of Twenty-Seven Studies Show a Greater Incidence of Emesis Associated with Nitrous Oxide than with Alternative Anesthetics
Hartung. Anesth Analg 1996;83:114-116
Omitting Nitrous Oxide in General Anaesthesia: Meta-Analysis of Intraoperative Awareness and Postoperative Emesis in Randomized Controlled Trials
Tramer et al. BJA 1996;76:186-193
Servizio di Anestesia e Rianimazione Ospedale di Faenza(RA)
Risk FactorsNitrous Oxide and PONV
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
Omitting nitrous oxide from general anesthesia:
Tramer et al. BJA 1996;76:186-193
Servizio di Anestesia e Rianimazione Ospedale di Faenza(RA)
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 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.
Servizio di Anestesia e Rianimazione Ospedale di Faenza(RA)
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 isoflurane–nitrous oxide anesthesia (number needed to treat = 6). Both anesthetic techniques were otherwise similar. Anesthesia costs were more than three times greater for propofol TIVA, without economic gains from shorter stay in the postanesthesia care unit.
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Visseret al . Randomized Controlled Trial of Total Intravenous Anesthesia with Propofol versus Inhalation Anesthesia with Isoflurane–Nitrous Oxide Postoperative
Nausea and Vomiting and Economic Analysis.Anesthesiology.95:616-626, 2001
Servizio di Anestesia e Rianimazione Ospedale di Faenza(RA)
Visseret al . Randomized Controlled Trial of Total Intravenous Anesthesia with Propofol versus Inhalation Anesthesia with Isoflurane–Nitrous Oxide Postoperative
Nausea and Vomiting and Economic Analysis.Anesthesiology.95:616-626, 2001
Servizio di Anestesia e Rianimazione Ospedale di Faenza(RA)
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
0
5
10
15
20
25
30
35
40
after anesth. Pacudischarge
24 hr 48 hr 72hr.
inpatients Iso/N2Oinpatients tivaoutpatients iso/N2Ooutpatients tiva
Servizio di Anestesia e Rianimazione Ospedale di Faenza(RA)
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)
0
10
20
30
40
50
60
70
%
inpatients outpatients
tivaisof/N2O
Servizio di Anestesia e Rianimazione Ospedale di Faenza(RA)
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)
0
5
10
15
20
25
30
35
40
%
inpatients outpatients
tivaisof/N2O
Servizio di Anestesia e Rianimazione Ospedale di Faenza(RA)
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 antiemetics comprised less than 2% of total drug costs. No differences in the use of analgesics were observed. The actual costs of all anesthetic drugs in the study groups can be found in the Web Enhancement, ).
Median length of hospitalization was 3 days in both randomization arms (10th–90th percentiles: 1–9 days after isoflurane and 1–10 days after TIVA; difference not significant). Sixty percent of the inpatients and 77% of the outpatients had a paid job. There was no statistically significant difference in the number of days to return to work with both strategies (median, 14 days for inpatients and 10 days for outpatients).
After 14 days, Short Form-36 general health scores showed no differences between patients in the isoflurane and TIVA groups. Therefore, as intended, we conducted a cost identification analysis that focused on overall cost differences given equivalent clinical outcome. The additional cost per surgical session for TIVA when compared with isoflurane was $28.98 for inpatients and $14.87 for outpatients.
If we were to consider the transient reduction of PONV as a clinical end point, then cost-effectiveness analysis would be justifiable (with cost per additional patient free of PONV as the outcome measure). To avoid PONV in the first 24 h after surgery in one inpatient who would have suffered from PONV after isoflurane, six patients would have to receive TIVA (absolute risk reduction, 17; NNT = 6), totaling $174 ($29 ´ 6). Accordingly, to avoid PONV until 24 h in one outpatient, five patients would have to receive TIVA (absolute risk reduction, 20; NNT = 5), amounting to $75.
Economic Implications for the Hospital. In 1998, 15,590 patients underwent surgery in the hospital under study. Approximately 7,770 of these patients were older than 18 yr
and eligible to receive either isoflurane or TIVA. If all patients would have received TIVA, the additional cost of propofol for 1998 would have been $225,218. The additional costs for TIVA are lower when the decreased use of antiemetics after TIVA is taken into account. When either metoclopramide or droperidol are used as primary antiemetic therapy, savings resulting from decreased use of antiemetics would amount to $2,220 after TIVA, equaling 1% of the additional drug acquisition cost for propofol. If ondansetron, a more expensive antiemetic, would have been the first-choice antiemetic therapy, decreased use of antiemetics after TIVA would save $6,324 in the cost of antiemetics.
Servizio di Anestesia e Rianimazione Ospedale di Faenza(RA)
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 unjustified.
Among inpatients, the study anesthetics consisted of induction with either propofol or thiopental, followed by TIVA or isoflurane. All outpatients received propofol for induction. If propofol used for anesthesia induction only were antiemetic, irrespective of the maintenance regimen, the magnitude of the reduction in relative risk among outpatients would have been less than actually occurred among outpatients in the current study. This finding supports results from a metaanalysis by Tramer et al., who showed that propofol for anesthesia induction followed by a nonpropofol maintenance technique did not result in PONV reduction.
The difference in airway management among the inpatients (more laryngeal mask airways in the propofol group) is probably caused by the fact that the ultimate selection of airway management may have been determined or altered after disclosure of the anesthetic allocation (TIVA is recommended in combination with the laryngeal mask airway). A recent study by Joshi et al. showed that PONV was similar for patients with endotracheal tubes and laryngeal mask airways when an identical anesthetic technique was used. Therefore, the difference in airway management in the current study is not likely to be a confounding factor.
Many anesthesiologists add N2O to propofol anesthesia because the additive effect allows for lower infusion rates, which reduces cost. Furthermore, it has been suggested that supplementing TIVA with N2O would reduce the incidence of awareness and recall (equal for both techniques in this study). However, N2O may increase the incidence of PONV. A recent metaanalysis showed a pooled odds ratio for omitting N2O of 0.63 (0.53–0.75, 95% confidence interval). The current trial was not designed to determine to what extent PONV after inhalational anesthesia is caused by N2O or isoflurane. If the treatments had consisted of propofol–N2O versus isoflurane–N2O, the treatment effect of TIVA might have been smaller.
The shorter length of stay at the PACU or DCU after TIVA (approximately 15 min) has also been reported by other investigators. Patients without PONV were discharged from the PACU–DCU sooner after TIVA than after isoflurane. Our protocol required patients to remain in the PACU for at least 1 h. The observed 15-min shorter PACU times will probably not hold for procedures in which a patient can be discharged to the ward after 30 min. Although it would appear that faster recovery times directly decrease costs, it is difficult to convert these shorter PACU and DCU stays into economic gains. The flow through the operating rooms and PACU–DCU is a chained process; Dexter and Tinker stated that “the major determinant of PACU costs is, by far, the distribution of admissions.” Furthermore, a system of flexible staffing would be a necessity. Therefore, in the setting of this study, it is unlikely that the PACU time with TIVA can be used to recover one additional patient or to reduce the number of PACU nurses by one. In a more homogeneous population with respect to type of surgery, and in case of brief standardized procedures, translation of shorter recovery after TIVA into economic gains is more likely. This could probably be best achieved in an office-based anesthesia setting or an ambulatory surgicenter.
At the time of the study, TIVA with propofol was two to three times more expensive than conventional anesthesia with isoflurane and N2O when considering intraoperative costs only. Using the NNT, the costs of preventing PONV in one additional patient by using TIVA instead of isoflurane were $174 in inpatients and $75 in outpatients. A reduction of propofol acquisition cost by 65% would make TIVA equally expensive as isoflurane–N2O in outpatients. For inpatients, a propofol cost reduction of 75% would make the cost of TIVA similar to that of isoflurane–N2O. The patent on the current propofol emulsion (Diprivan, AstraZeneca Nederland, Zoetermeer, The Netherlands) has recently expired in The Netherlands, resulting in a steep decrease of propofol acquisition cost (up to 75% reduction, depending on the formulation [1% vs. 2%] and type of packaging [prefilled syringes or glass vial]). With this unanticipated large cost decrease, several cost considerations have lost relevance (university setting, case mix, drug waste caused by the forced use of prefilled 50-ml syringes when using target controlled infusion pumps).
Because this study was conducted in a single academic institution, external validity (ability to generalize) is an issue. However, the study population comprised a large heterogeneous group of unselected patients and surgical procedures of varying duration, although very brief procedures were underrepresented. In addition, the design of this trial, apart from random assignment of TIVA or isoflurane and strict blinding procedures, did not interfere with current practice patterns. Therefore, our study patients and surgical procedures are comparable to those in other teaching institutions.
In conclusion, we have shown that propofol TIVA results in a reduction of PONV, particularly in the early postoperative period. TIVA increases patient comfort and patient ratings of anesthesia., while slightly reducing PACU and DCU discharge times. However, anesthesia costs were greater, and no clear economic gains were found.
The authors thank Wilco E. van Genderen, M.D. (Anesthesiologist, Medical Center Alkmaar, The Netherlands), and Lucilla E. Overdijk, M.D. (Anesthesiologist, Onze Lieve Vrouwe Gasthuis, Amsterdam, The Netherlands), for constructive input in the design of this study, the team of research nurses for their enthusiasm and dedication, and the anesthesiologists and anesthesiology residents of the Academic Medical Center, University of Amsterdam, for their support and help with patient inclusion. Many thanks also to John Hartung, Ph.D. (State University of New York Health Science Center, Brooklyn, NY), whose careful editing of the manuscript was invaluable.
Servizio di Anestesia e Rianimazione Ospedale di Faenza(RA)
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
Servizio di Anestesia e Rianimazione Ospedale di Faenza(RA)
Risk FactorsVolatile anesthetics
Risk Factors OR* CI
Volatile anesthetics
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
Servizio di Anestesia e Rianimazione Ospedale di Faenza(RA)
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
Servizio di Anestesia e Rianimazione Ospedale di Faenza(RA)
Risk Factors Propofol and PONV
Early Late
Nausea Vomiting Any Nausea Vomiting Any
Induction 9.3* 13.7* 20.9 50.1 14.9 NA
Maintenance 8* 9.2* 6.2* 5.8* 10.1* 10
Early Late
Nausea Vomiting Any Nausea Vomiting Any
Induction 5.0* 7.0* 14 28 10 NA
Maintenance 4.7* 4.9* 4.9* 6.1* 8.3* 7.1
All Control Event Rates
20% - 60% Control Event Rate
Tramer et al. BJA 1997;78:247-255
Analysis by NNT
Servizio di Anestesia e Rianimazione Ospedale di Faenza(RA)
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
Servizio di Anestesia e Rianimazione Ospedale di Faenza(RA)
Risk Factors
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.
Logistic Regression
Servizio di Anestesia e Rianimazione Ospedale di Faenza(RA)
Risk Factors
Younger age Nonsmoking history Female Hx of motion sickness Hx of PONV Increased duration of operation
Logistic Regression
Servizio di Anestesia e Rianimazione Ospedale di Faenza(RA)
Risk Factors
Female Nonsmoking history Hx of motion sickness or PONV Use of postoperative opioids
Simplified Scoring System
Incidence of PONVRisk Factors Incidence
0 10%
1 21%
2 39%
3 61%
4 79% Apfel CC et al. Anesthesiology 1999;91:693-700.
Servizio di Anestesia e Rianimazione Ospedale di Faenza(RA)
Simplified scoring system from Apfel for adults
For every risk factor the sum is additive: Point 0 risk 10% Point 1 risk 20% Point 2 risk 40% Point 3 risk 60% Point 4 risk 80%
Servizio di Anestesia e Rianimazione Ospedale di Faenza(RA)
Servizio di Anestesia e Rianimazione Ospedale di Faenza(RA)
Simplified risk score from Apfel et al. to predict thepatients risk for PONVin adults . When 0, 1, 2, 3, or 4 of the
depicted independent predictors are present, the corresponding riskfor PONV is approximately 10%, 20%, 40%,
60%, or 80%.
Figure 1
Servizio di Anestesia e Rianimazione Ospedale di Faenza(RA)
Simplified scoring system from Eberhardt 39 di
Sambafor children
Surgery> 30 min Age> 3 Strabismus surgery Hx of POV or POnv in relatives Sum 0......4 Risk 10%,10%,30%,55%,70%
Servizio di Anestesia e Rianimazione Ospedale di Faenza(RA)
Simplified risk score from Eberhart et al. (39) to predict therisk for POV in children. When 0, 1, 2, 3, or 4 of the depictedindependent predictors are present, the corresponding riskfor PONV is approximately 10%, 10%, 30%, 55%, or 70%.
Servizio di Anestesia e Rianimazione Ospedale di Faenza(RA)
Problems............
to separate independent factors vs dependent factors................
No risk model can actually predict the likelihood of an individual having PONV;risk models only allow clinicians to etimate the risk of PONV among patients groups
Servizio di Anestesia e Rianimazione Ospedale di Faenza(RA)
PONVPONVfattori di rischiofattori di rischio
donnedonne
giovanigiovani
etàfertile
etàfertile
gravidegravide
postpartum
postpartum
interventiinterventi
muscoliextraoculari
muscoliextraoculari
orecchiomedio
orecchiomedio
pelvifemm.inlaparoscopia
pelvifemm.inlaparoscopia
deambulazioneprecoce
deambulazioneprecoce
bambinibambini
soggettia
cinetosi
soggettia
cinetosipregresso
PONVpregresso
PONV farmacifarmaci
oppioidioppioidi
anesteticiinalatori
anesteticiinalatori
N2ONeurosurgBreast surgLaparotomyPlastic surg.
Non smoker
s
Servizio di Anestesia e Rianimazione Ospedale di Faenza(RA)
Use of prophylactic antiemetics should be based on valid assessment of the patients risk for POV or PONV.
In other words....antiemetic prophylaxis shouild be used only when the patient individual risk is sufficiently high.
Estimate:baseline risk * baseline risk reduction resulting from prophylaxisUse of prophylactic antiemetics should be based on
This approach produces a clinically meaningful decrease in the risk of PONV
Servizio di Anestesia e Rianimazione Ospedale di Faenza(RA)
Particular medical risk
more liberal prophylaxis is appropriate for patients in whom vomiting poses a particular medical risk:
wired jaws increased intracranial pressure gastric or esophageal surgery when the anesthesia care provider determines the need or the patient has a strong preference to avoid PONV
Servizio di Anestesia e Rianimazione Ospedale di Faenza(RA)
Strategies to Reduce Baseline Risk
Avoidance of general anesthesia by the use of regional anesthesia (11,16) (randomized, controlled trial, RCT)
Use of propofol for induction and maintenance of Anesthesia(4,14,41,42) (RCT/systematic review, SR)
Avoidance of nitrous oxide (3,4,43,44) (RCT/SR) Avoidance of volatile anesthetics (15,28) (RCT) Minimization of intraoperative (SR) and postoperative opioids (3,13,15,17,18,20,28,43) (RCT/SR) Minimization of neostigmine (19,45) (SR) Adequate hydration (46) (RCT)
Servizio di Anestesia e Rianimazione Ospedale di Faenza(RA)
Trattamento del PONV
Servizio di Anestesia e Rianimazione Ospedale di Faenza(RA)
Management of PONV:Pharmacological Approaches
Medications Dose response Comparative efficacy Combination therapy Timing of administration
Servizio di Anestesia e Rianimazione Ospedale di Faenza(RA)
Servizio di Anestesia e Rianimazione Ospedale di Faenza(RA)
Servizio di Anestesia e Rianimazione Ospedale di Faenza(RA)
Figure 3
Servizio di Anestesia e Rianimazione Ospedale di Faenza(RA)
Servizio di Anestesia e Rianimazione Ospedale di Faenza(RA)
Servizio di Anestesia e Rianimazione Ospedale di Faenza(RA)
AntiemeticiAntiemeticievoluzione del pensieroevoluzione del pensiero
metoclopramidemetoclopramidepreso dalla gastroenterologiapreso dalla gastroenterologia
droperidoldroperidol preso dagli antipsicotici....preso dagli antipsicotici....
ondansetronondansetronla nuova frontiera...la nuova frontiera...
granisetrongranisetron
Servizio di Anestesia e Rianimazione Ospedale di Faenza(RA)
PONVPONVRecettori coinvoltiRecettori coinvolti
CRTZCRTZ
5Ht35Ht3
H1H1AchAch
D2D2
ondansetronondansetron
granisetrongranisetron
tropisetrontropisetron
antistaminici::imedrinato,idrossizina,ciclizinaantistaminici::imedrinato,idrossizina,ciclizina
butirofenoni::droperidolbutirofenoni::droperidol
fenotiazinefenotiazine
scopolaminascopolamina
metoclopramidemetoclopramide
steroidisteroidi
Combinationtherapy
Combinationtherapy
Servizio di Anestesia e Rianimazione Ospedale di Faenza(RA)
Currently Available Medications
5HT3 (serotonin) antagonists - ondansetron Butyrophenones - droperidol Benzamides - metoclopramide Antihistamines - dimenhydrinate Steroids - dexamethasone Phenothiazines-
promethazine,prochlorperazine Anticholinergics – scopolamine
Servizio di Anestesia e Rianimazione Ospedale di Faenza(RA)
5HT3 Antagonists and PONV (Summer 2002)
5HT3 Antagonist Clinical Trials
Ondansetron * 275
Dolasetron* 20
Granisetron* 66
Tropisetron 27
Ramosetron 29
Palenosetron 5
* Approved for PONV indication
Servizio di Anestesia e Rianimazione Ospedale di Faenza(RA)
Prevention of PONV:Ondansetron Versus Placebo
62
76 77
46
0
20
40
60
80
100
Placebo 1 mg 4 mg 8 mg
Ondansetron Dose
% o
f P
ati
ents
wit
h N
o E
mes
is
McKenzie et al. Anesthesiology 1993;78:21-28
All patients, 0 - 24 hrs
*
† †
* p = 0.010† p < 0.001
Servizio di Anestesia e Rianimazione Ospedale di Faenza(RA)
Ondansetron Dose Response:Prevention
Dose ofOndansetron
Early Efficacy(0 - 6 hrs)
Late Efficacy(0 - 48 hrs)
1 mg 9.0 15
4 mg 5.5 6.5
8 mg 6.5 5.0 Only 4 mg and 8 mg were significantly different than placebo No further improvement with doses >8 mg
Numbers Needed to be Treated
Tramer et al. Anesthesiology 1997;87:1277-1289
Servizio di Anestesia e Rianimazione Ospedale di Faenza(RA)
Treatment of PONV:Ondansetron Versus Placebo
32
20
57
40
60
45 44
57
0
20
40
60
80
100
0 - 2 hr 2 - 24 hr
% w
ith
Com
ple
te R
esp
on
se
Placebo 1 mg 4 mg 8 mg
Scuderi et al. Anesthesiology 1993;78:2-5Hantler et al. Anesthesiology 1992;77:A16
** *
* **
* p < 0.001
Servizio di Anestesia e Rianimazione Ospedale di Faenza(RA)
Ondansetron Dose Response:Treatment
Dose ofOndansetron
Early Efficacy(0 - 6 hrs)
Late Efficacy(0 - 24 hrs)
1 mg 3.8 4.8
4 mg 3.2 3.9
8 mg 3.1 4.1
All three doses significantly different than placebo No significant difference in antiemetic efficacy
between the three doses of ondansetron
Numbers Needed to be Treated
Tramer et al. BMJ 1997;314:1088-1092
Servizio di Anestesia e Rianimazione Ospedale di Faenza(RA)
Breakthrough PONV:Repeat Dosing With Ondansetron
43
323428
0
20
40
60
80
100
0 - 2 hours 0 - 24 hours
Per
cen
t C
om
ple
te R
esp
on
se
Placebo Ondansetron 4 mg
Kovac et al. J. Clin Anesth 1999;11:453-459
* †
* p = 0.074
† p = 0.342
Servizio di Anestesia e Rianimazione Ospedale di Faenza(RA)
Prevention of PONV:Dolasetron Versus Placebo
31 28 33
50 465252
39
5543
56 57
0
20
40
60
80
100
All Patients Previous PONV No PONV
Co
mp
lete
Res
po
nse
%
Placebo 12.5 mg 25 mg 50 mg
* ***
* *
*p < 0.0003 compared to placebo
* **
Graczyk et al. Anesth Analg 1997;84:325-330
* ***
**** *
Servizio di Anestesia e Rianimazione Ospedale di Faenza(RA)
Treatment of PONV:Dolasetron Versus Placebo
27
11
55
35
50
28
51
2929
48
0
20
40
60
80
100
0 - 2 hrs 0 - 24 hrs
Co
mp
lete
Res
po
nse
%
Placebo 12.5 mg 25 mg 50 mg 100 mg
* * **
* * * *
*p < 0.001 compared to placebo
Kovac et al. Anesth Analg 1997;85:546-552
****
** * *
Servizio di Anestesia e Rianimazione Ospedale di Faenza(RA)
Prevention of PONV:Ondansetron Versus Dolasetron
49
36
5143
7160
5464
0
20
40
60
80
100
Complete Response Total Response
% of
Pati
ents
Placebo Dolasetron 25 mg Dolasetron 50 mg Ondansetron 4 mg
Korttila K et al. Acta Anaesthesiol Scand 1997;41:914-922
**†
* p < 0.05 versus placebo and dolasetron 25 mg † p < 0.05 versus placebo only
***
*
Servizio di Anestesia e Rianimazione Ospedale di Faenza(RA)
Prevention of PONV:Ondansetron Versus Dolasetron
9294
96 9696 9698
100
80
100
In-hospital Postdischarge
% w
itho
ut S
ympt
oms
Dolasetron 12.5 mg Dolasetron 25 mg Ondansetron 4 mg Ondansetron 8 mg
Zarate E, et al. Anesth Analg 2000;90:1352-1358
Postoperative Vomiting
No statistically significant differences among the groups
Servizio di Anestesia e Rianimazione Ospedale di Faenza(RA)
Prevention of PONV:Ondansetron Versus Dolasetron
7382
76 767787 86
70
0
20
40
60
80
100
In-hospital Postdischarge
% w
itho
ut S
ympt
oms
Dolasetron 12.5 mg Dolasetron 25 mg Ondansetron 4 mg Ondansetron 8 mg
Zarate E, et al. Anesth Analg 2000;90:1352-1358
Postoperative Nausea
No statistically significant differences among the groups
Servizio di Anestesia e Rianimazione Ospedale di Faenza(RA)
Prevention of PONV:Ondansetron Versus Droperidol
4636
63
48
6956 53
62
0
20
40
60
80
100
0 - 2 hr 0 - 24 hr
% o
f P
atie
nts
Placebo Droperidol 0.625 mg Droperidol 1.25 mg Ondansetron 4 mg
Fortney et al. Anesth Analg 1998;86:731-738
Complete Response
*** *
**
†
* p < 0 .05 compared to placebo† p < 0.05 compared to ondansetron 4 mg‡ p ,<0.05 compared to droperidol 0.625 mg
‡
Servizio di Anestesia e Rianimazione Ospedale di Faenza(RA)
Prevention of PONV:Ondansetron Versus Droperidol
2329
4329
0
20
40
60
80
100
0 - 24 hr
% o
f P
atie
nts
Placebo Droperidol 0.625 mg Droperidol 1.25 mg Ondansetron 4 mg
Fortney et al. Anesth Analg 1998;86:731-738
No Nausea
†
* p < 0 .05 compared to placebo† p < 0.05 compared to droperidol 0.625 mg
and ondansetron 4 mg
Servizio di Anestesia e Rianimazione Ospedale di Faenza(RA)
Droperidol Adverse Events Reports
273 “reports” from 1997-2001 127 serious adverse events 89 total deaths Droperidol 2.5 mg or less
» 6 deaths» 5 Torsades or VT (1 fatality)
Norton et al. Anesthesiology 2002:A-1196
Servizio di Anestesia e Rianimazione Ospedale di Faenza(RA)
DroperidolFDA Box Warning
No case details provided Droperidol has been used for over 40 years Why a problem now? No evidence of adverse events in published trials No published case reports An association does not prove cause and effect If prolonged QTc is an issue then 5HT3 antagonists should also
carry the same warning At least 3 cases of VT associated with 5HT3 administration No “denominator” provided (or available)
Servizio di Anestesia e Rianimazione Ospedale di Faenza(RA)
Putting It in Perspective
Circumstance Annual FatalitiesTransportation 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
Servizio di Anestesia e Rianimazione Ospedale di Faenza(RA)
Prevention of PONV:Metoclopramide
“In summary, metoclopramide, although used as an antiemetic for almost 40 years in the prevention of PONV, has no clinically relevant antiemetic effect . . . it is very likely that the doses used in daily clinical practice are too low.”
Henzi I, Walder B, and Tramer, MR. Metoclopramide in the prevention of postoperative nausea and vomiting: a quantitative systematic review of randomized, placebo-controlled studies. BJA 1999;83:761-771
Servizio di Anestesia e Rianimazione Ospedale di Faenza(RA)
Prevention of PONV:Dexamethasone
“In conclusion, in the surgical setting, a single prophylactic dose of dexamethasone is antiemetic compared with placebo without evidence of clinically relevant toxicity in otherwise healthy patients. Late efficacy (i.e., up to 24 hours) seems to be most pronounced.”
Henzi I, Walder B, and Tramer, MR. Dexamethasone for the prevention of postoperative nausea and vomiting: a quantitative systematic review. Anesth Analg 2000;90:186-194
Eberhart LH. Morin AM. Georgieff M. Dexamethasone for prophylaxis of postoperative nausea and vomiting. A meta-analysis of randomized controlled studies. Anaesthesist. 2000 ;49:713-20
Servizio di Anestesia e Rianimazione Ospedale di Faenza(RA)
Prevention of PONV:Dexamethasone
Placebo
1.25 mg2.5 mg
5.0 mg 10.0 mg
Patients 30 30 30 30 30
Vomiting 19 15 8* 6* 6*
Rescue required 5 0 0 0 0
* P <0.05 compared with placebo and 1.25 mg
Dose ranging
Major gynecological surgery
Liu K, et al. Anesth Analg 1999;89:1316-1318
Servizio di Anestesia e Rianimazione Ospedale di Faenza(RA)
Prevention of PONV:Scopolamine
Small Studies Large Studies
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
Undefined control event rate
Servizio di Anestesia e Rianimazione Ospedale di Faenza(RA)
Prevention of PONV:Scopolamine
Small Studies Large Studies
Outcome Trials NNT Trials NNT
Vomiting 6 3.3 5 5.9
Nausea 2 5.3 5 5.0
PONV 8 2.9 8 6.7
Rescue 4 3.8 3 7.0
Kranke, et al. Anesth Analg 2002;95:133-143
Defined control event rate
Servizio di Anestesia e Rianimazione Ospedale di Faenza(RA)
Prevention of PONV:Scopolamine
Event NNH
Visual disturbances
5.6
Dry mouth 12.5
Dizziness 50.0
Agitation 100.1
Kranke, et al. Anesth Analg 2002;95:133-143
Adverse Events
Servizio di Anestesia e Rianimazione Ospedale di Faenza(RA)
Prevention of PONV:Dimenhydrinate
Early (0-6 h) Overall (0-48 h)
Outcome Trials NNT Trials NNT
PONV 8 8.3 16 5.0
Vomiting 6 7.7 14 4.8
Nausea 2 8.3 7 5.9
Kranke, et al. Acta Anaesth Scand 2002;46:238-244
Servizio di Anestesia e Rianimazione Ospedale di Faenza(RA)
Prevention of PONV:Combination Therapy
McKenzie R, et al. Comparison of ondansetron with ondansetron plus dexamethasone in the prevention of postoperative nausea and vomiting. Anesth Analg 1994;79:961-964
Lopez-Olaondo L, et al. Combination of ondansetron and dexamethasone in the prophylaxis of postoperative nausea and vomiting. BJA 1996;76:835-840
Eberhart LH. Morin AM. Georgieff M. Dexamethasone for prophylaxis of postoperative nausea and vomiting. A meta-analysis of randomized controlled studies. Anaesthesist. 2000 ;49:713-20
Ondansetron/Dexamethasone
Servizio di Anestesia e Rianimazione Ospedale di Faenza(RA)
Prevention of PONV:Combination Therapy
Pueyo FJ, et al. Combination of ondansetron and droperidol in the prophylaxis of postoperative nausea and vomiting. Anesth Analg 1996;83:117-122
McKenzie R, et al. Droperidol/ondansetron combination controls nausea and vomiting after tubal banding. Anesth Analg 1996;83:1218-1222
Klockgether-Radke A, et al. Ondansetron, droperidol and their combination for the prevention of post-operative vomiting in children. Eur J Anesthesiology. 1997;14:362-367
Eberhart LH. Morin AM. Bothner U. Georgieff M. Droperidol and 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
Ondansetron/Droperidol
Servizio di Anestesia e Rianimazione Ospedale di Faenza(RA)
Prevention of PONV:Combination Therapy
Which Combination?
Event
5-HT3 + drop 5-HT3 + dex
N Rate N Rate P-value OR
Early
Nausea 138 17% 260 11% 0.12 1.6
Vomiting 318 1% 419 1% 1.00 1.0
Late
Nausea 358 27% 623 21%* 0.02 1.4
Vomiting 443 9% 813 9% 1.00 0.9Ashraf et al. Anesthesiology 2001; 95:A-41
Servizio di Anestesia e Rianimazione Ospedale di Faenza(RA)
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
Prevention of PONV:Combination Therapy
Tang, et al. Anesthesiology 2001; 95:A43
Servizio di Anestesia e Rianimazione Ospedale di Faenza(RA)
Prevention of PONV:Timing of Administration
Sun et al. The effect of timing on ondansetron administration in outpatients undergoing otolaryngologic surgery. Anesth Analg 1997;84:331-336
Chen et al. The effect of timing of dolasetron administration on its efficacy as a prophylactic antiemetic in the ambulatory setting. Anesth Analg 2001;93:906-911
Wang et al. The effect of timing of dexamethasone administration on its efficacy as a prophylactic antiemetic for postoperative nausea and vomiting. Anesth Analg 2000;91;136-139
Ondansetron
Dexamethasone
Dolasetron
Servizio di Anestesia e Rianimazione Ospedale di Faenza(RA)
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.
Servizio di Anestesia e Rianimazione Ospedale di Faenza(RA)
Tang J,Wang B, White PF,Watcha M,Qi J,Wender R.The effect of timing of ondansetron administration on its
efficacy,cost effectiveness and cost benefit as a prophylactic antiemetic in the ambulatory
setting.Anesth.Analg 1998;96:........
Anesthesia was induced with fentanyl 1.0–1.5 mg/kg IV, followed by propofol 1.5–2.0 mg/kg IV, and tracheal intubation was facilitated with either succinylcholine 1 mg/kg IV or vecuronium 0.1 mg/kg IV. Anesthesia was maintained with desflurane 3%–6% in combination with nitrous oxide (N2O) 60%
oxygen; fentanyl 0.5–1.0 mg/kg IV and vecuronium 1–2 mg IV were administered as needed. If necessary, neuromuscular blockade was antagonized with neostigmine 0.05 mg/kg IV and glycopyrrolate 0.01 mg/kg IV. After tracheal extubation, the patients were transported to the postanesthesia care unit (PACU).
Servizio di Anestesia e Rianimazione Ospedale di Faenza(RA)
Tang J,Wang B, White PF,Watcha M,Qi J,Wender R.The effect of timing of ondansetron administration on its
efficacy,cost effectiveness and cost benefit as a prophylactic antiemetic in the ambulatory
setting.Anesth.Analg 1998;96:........
Servizio di Anestesia e Rianimazione Ospedale di Faenza(RA)
Tang J,Wang B, White PF,Watcha M,Qi J,Wender R.The effect of timing of ondansetron administration on its
efficacy,cost effectiveness and cost benefit as a prophylactic antiemetic in the ambulatory
setting.Anesth.Analg 1998;96:........
Servizio di Anestesia e Rianimazione Ospedale di Faenza(RA)
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.
0
10
20
30
40
50
60
70
80
nausea% vomit% rescueantiemetics
nausea VASat 2 h(mm)
placebo
split dose
preinduction
end of surgery
Tang J,Wang B, White PF,Watcha M,Qi J,Wender R.The effect of timing of ondansetron administration on its
efficacy,cost effectiveness and cost benefit as a prophylactic antiemetic in the ambulatory setting.Anesth.Analg
1998;96:........
**
*
Servizio di Anestesia e Rianimazione Ospedale di Faenza(RA)
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.
0
10
20
30
40
50
60
70
80
nausea% vomit% rescueantiemetics
nausea VASmedio(mm)
vomiting>2times
placebosplit dosepreinductionpostsurg
Tang J,Wang B, White PF,Watcha M,Qi J,Wender R.The effect of timing of ondansetron administration on its
efficacy,cost effectiveness and cost benefit as a prophylactic antiemetic in the ambulatory setting.Anesth.Analg
1998;96:........
*
* *
**
Servizio di Anestesia e Rianimazione Ospedale di Faenza(RA)
Servizio di Anestesia e Rianimazione Ospedale di Faenza(RA)
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
Servizio di Anestesia e Rianimazione Ospedale di Faenza(RA)
Management of PONV:Adjuvants (Nonpharmacologic)
P-6 acupuncture point stimulation Supplemental oxygen Aggressive perioperative rehydration Preemptive analgesia
Servizio di Anestesia e Rianimazione Ospedale di Faenza(RA)
P-6 Acupuncture Point Stimulation
Zarate E, Mingus M, White PF, Chiu JW, Scuderi PE, et al. The use of transcutaneous acupoint electrical stimulation for preventing nausea and vomiting after laparoscopic surgery. Anesth Analg 2001;92:629-35.
Servizio di Anestesia e Rianimazione Ospedale di Faenza(RA)
P-6 Acupuncture Point Stimulation
TAES Sham PlaceboPACU 25 17 28
45 min 36 51 32
90 min 27* 51 33
120 min 27 40 41
4 hr 26* 52 35
6 hr 22*† 47 43
9 hr 18*† 42 47
Control of Nausea
Zarate E, et al. Anesth Analg 2001;92:629-35
* compared to sham
† compared to placebo
Servizio di Anestesia e Rianimazione Ospedale di Faenza(RA)
Supplemental Oxygen
Greif R, Laciny S, Rapf B, et al. Supplemental oxygen reduces the incidence of postoperative nausea and vomiting. Anesthesiology 1999;91:1246-52.
Goll V, Ozan A, Greif R, et al. Ondansetron is no more effective than supplemental intraoperative oxygen for prevention of postoperative nausea and vomiting. Anesth Analg 2001;92:112-17.
Servizio di Anestesia e Rianimazione Ospedale di Faenza(RA)
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
Servizio di Anestesia e Rianimazione Ospedale di Faenza(RA)
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
Servizio di Anestesia e Rianimazione Ospedale di Faenza(RA)
Intravenous Fluid Therapy
0
5
10
15
20
30 min 60 min DIS Day 1Time
Inci
den
ce %
Low Infusion High Infusion
*
Yogendran S, et al. Anesth Analg 1995;80:682-686High Infusion = 20 ml/kg
Low Infusion = 2 ml/kg
Incidence of Postop Nausea
Servizio di Anestesia e Rianimazione Ospedale di Faenza(RA)
Pain and PONV
Effects % of Total Patients
Pain relieved, nausea relieved 68.5
Pain reduced, nausea relieved 11.5
Pain relieved, nausea persisted 9.5
Pain persisted, nausea persisted 10.5
Andersen et al. Can Anaesth Soc J 23:366-369, 1976
Servizio di Anestesia e Rianimazione Ospedale di Faenza(RA)
Efficacy Versus Outcome
Servizio di Anestesia e Rianimazione Ospedale di Faenza(RA)
Surrogate End PointsAre They Meaningful
Appropriate end points Duration of PACU stay Incidence of unplanned admissions Patient satisfaction
Fisher. Anesthesiology 1994;81:795-796
Servizio di Anestesia e Rianimazione Ospedale di Faenza(RA)
Measures of Outcome
Mortality
Morbidity
Patient satisfaction
Cost
Servizio di Anestesia e Rianimazione Ospedale di Faenza(RA)
Risk of Mortality and Adverse Outcome in a Tertiary Care
Population
Adverse outcomes 1:125
Death (all causes) 1:500
Anesthesia provider error causing adverseoutcome
1:1,500
Risk of death (anesthesia cause only) 1:250,000
Patient Safety in Anesthesia Practice. Morel and Eichorn (ed)
Servizio di Anestesia e Rianimazione Ospedale di Faenza(RA)
Complications of PONV
Electrolyte imbalance
Tension on sutures, evisceration
Venous hypertension, bleeding
Aspiration
Delayed discharge (outpatients)
Dehydration
Unanticipated admission
Servizio di Anestesia e Rianimazione Ospedale di Faenza(RA)
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
Servizio di Anestesia e Rianimazione Ospedale di Faenza(RA)
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
Servizio di Anestesia e Rianimazione Ospedale di Faenza(RA)
Subject Preference Following Surgery
Levels Preference
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
Preoperative
Servizio di Anestesia e Rianimazione Ospedale di Faenza(RA)
Patient Preference Following Surgery
Ranking (%)Outcome
MeanRank
Relative Value(out of 100) First Second Third
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
Preoperative
Servizio di Anestesia e Rianimazione Ospedale di Faenza(RA)
Patient Satisfaction With Outpatient Surgery
FactorConsidered
FactorImportant
Ranking inTop 5 (%)
Rank Orderof top 5
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
Postoperative
Servizio di Anestesia e Rianimazione Ospedale di Faenza(RA)
Efficacy Versus Outcome
If efficacy is an appropriate endpoint when evaluating analgesics, why not when evaluating antiemetics?
Servizio di Anestesia e Rianimazione Ospedale di Faenza(RA)
Prevention Versus Treatment
Does routine* administration of prophylactic antiemetics improve outcome when compared to rapid symptomatic treatment of postoperative nausea and/or vomiting?
Question:
*Routine: habitual or mechanical (i.e., mindless) performance of an established procedure
Servizio di Anestesia e Rianimazione Ospedale di Faenza(RA)
Frequency of PACU Treatment by Risk Factors and Group
RISK FACTORS PACU TREATMENT
REQUIRED BY GROUP
Subgroup GenderPrior
HistoryEmetogenicProcedure1 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
Servizio di Anestesia e Rianimazione Ospedale di Faenza(RA)
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
Scuderi et al. Anesthesiology. 1999;90:360-371
Servizio di Anestesia e Rianimazione Ospedale di Faenza(RA)
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
Scuderi et al. Anesthesiology. 1999;90:360-371
Servizio di Anestesia e Rianimazione Ospedale di Faenza(RA)
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, medianScuderi et al. Anesthesiology. 1999;90:360-371
Servizio di Anestesia e Rianimazione Ospedale di Faenza(RA)
Prevention Versus Treatment
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
Answer:
Servizio di Anestesia e Rianimazione Ospedale di Faenza(RA)
Multimodal Management of PONV:
Hypothesis
A multi-modal approach to the management of PONV can result in a zero incidence of vomiting (and perhaps nausea) in the immediate postoperative period (i.e., PACU)
Scuderi at al. Anesth Analg 2000;91:408-414
Servizio di Anestesia e Rianimazione Ospedale di Faenza(RA)
Multimodal Management of PONV: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
Servizio di Anestesia e Rianimazione Ospedale di Faenza(RA)
Multimodal Management of PONV:Simplified Algorithm
I. INDUCTION
A. PreO2
B. Propofol 2 - 4 mg/kgC. Opioid prnD. Neuromuscular blockade prnC. Droperidol 10 mcg/kgD. Decadron 4 - 8 mg
II. MAINTENANCEA. Propofol 50 mcg/kg/minB. Potent inhalation agent/remif
C.Generous hydration D Nitrous oxide prnE. NMB reversal prn
III. EMERGENCE A. Ondansetron 1 mg IVB. Suction oropharynxC. Extubate when awake
Early & aggressive postop pain
therapy
Servizio di Anestesia e Rianimazione Ospedale di Faenza(RA)
Multimodal Management of PONV:
Simplified Algorithm
COST ($)
Case duration 1 hour 2 hours 3 hours
Droperidol (10 mcg/kg) $2.10 $2.10 $2.10
Dexamethasone (8 mg) $1.30 $1.30 $1.30
Ondansetron (1 mg) $4.00 $4.00 $4.00
Propofol (50 mcg/kg/min) $7.50 $15.00 $22.50
Total Cost $14.90 $22.40 $29.90
Cost Analysis
Servizio di Anestesia e Rianimazione Ospedale di Faenza(RA)
Multimodal Management of PONV: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
Servizio di Anestesia e Rianimazione Ospedale di Faenza(RA)
PONVPONVwe know the risk factorswe know the risk factors
Preventive strategyPreventive strategy non emetogenic drugs...non emetogenic drugs...
AntiemeticProphylaxisAntiemetic
ProphylaxisSelected at risk groupsSelected at risk groups
Immediate treatmentImmediate treatment in case ofoccurrence.....in case ofoccurrence.....
Servizio di Anestesia e Rianimazione Ospedale di Faenza(RA)
PONV dopo la dimissione
Servizio di Anestesia e Rianimazione Ospedale di Faenza(RA)
Efficacy of antiemetic medication on postdischarge nausea (Gupta
A,Wu,CL,Elkassabani,N,Krug,CE,Parker,SD,Fleisher LA.Does 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)
Efficacy of antiemetic medication on posdtdischarge vomiting (Gupta
A,Wu,CL,Elkassabani,N,Krug,CE,Parker,SD,Fleisher LA.Does the routine prophylactic use of antiemetics affect the incidence of postischarge nausea
and vomuint following ambulatory surgery?.Anesthesiology 2003;99:488-95.)
Servizio di Anestesia e Rianimazione Ospedale di Faenza(RA)
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.)
0
20
40
60
80
100
placebo
Relative Risk (%) of antiemetic medication on postdischarge nausea
ondans 1 mgondans 4 mgondans 8 mgdrop <1 mgdrop>1 mgdexamethbetametascombination
Servizio di Anestesia e Rianimazione Ospedale di Faenza(RA)
Postdischarge vomiting(Gupta A,Wu,CL,Elkassabani,N,Krug,CE,Parker,SD,Fleisher LA.Does the routine prophylactic use of antiemetics affect the incidence of postischarge nausea
and vomuint following ambulatory surgery?.Anesthesiology 2003;99:488-95.)
0
20
40
60
80
100
placebo
Relative Risk % of antiemetic medication on Postdischarge vomiting
ondans 1 mgondans 4 mgondans 8 mgdrop <1 mgdrop>1 mgdexamethbetametascombination
Servizio di Anestesia e Rianimazione Ospedale di Faenza(RA)
Postdicharge nausea in the ondansetron 4 mg group vs the
placebo group
0,00
0,10
0,20
0,30
0,40
0,50
0,60
0,70
0,80
0,90
treatm
control
%GynLapIsofl
GynLapDes
f
Gyn
LapIsof
VLCIsof
GynLapDEsf
GynLapIsoEnf
ORLDesf
GynLapIsof
GynLapIsof
MaxillMidazFent
metex
Servizio di Anestesia e Rianimazione Ospedale di Faenza(RA)
Per uno studio nostro su POnv(io,Lorenz….???
Data Co-nome Età/peso/alt Sex Asa e patol concomit Cinetosi Ponv pregr Premed
Sede Iniz interv Fine interv Propofol Fent Remifent N2O Vapore:quale….. Tipo interv Protesi resp LMA Guedel IOT Resp spont/ass/IPPV FiO2 Flebotot Risv;immediato/velcoe/lento
Analg postop;ketorolac tramadol mep altro Efficacia analg postop Sintodian si no/quando/quanto Zofran Si NO quando quanto Nausea postop 123 Vomito postop123 Rescue treatm Nausea I g 123 Analg I g Efficacia analg I g Vomito I g 123 Rescue treatm I g
Servizio di Anestesia e Rianimazione Ospedale di Faenza(RA)
Postdischarge nausea in the combination group(>1 drug) vs the
placebo group
0,00
0,10
0,20
0,30
0,40
0,50
0,60
0,70
0,80
0,90
Ahmed Tzeng Wu
treatment
control
%
GynLapIsof
GYND&C
Propof
GynLapIsof
Servizio di Anestesia e Rianimazione Ospedale di Faenza(RA)
Postdischarge vomiting in the combination group(>1 drug) vs the
placebo group
0,00
0,05
0,10
0,15
0,20
0,25
0,30
0,35
0,40
0,45
0,50
Ahmed Tzeng Scuderi
treatment
control
% GynLap
SevoGYND&C
Propof
GynLapIsof
Servizio di Anestesia e Rianimazione Ospedale di Faenza(RA)
Postdicharge vomiting in the ondansetron 4 mg group vs the
placebo group
0,000,050,100,150,200,250,300,350,400,450,50
treatment
control
GinLapsevo
GynLapIsof
Servizio di Anestesia e Rianimazione Ospedale di Faenza(RA)
Post Discharge Nausea and Vomiting
Incidence Severity Contributing factors Prevention Treatment
Servizio di Anestesia e Rianimazione Ospedale di Faenza(RA)
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
Servizio di Anestesia e Rianimazione Ospedale di Faenza(RA)
Strabismus SurgeryPostdischarge 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
Servizio di Anestesia e Rianimazione Ospedale di Faenza(RA)
Post Discharge:Time to first emetic episode
5
2
0 0
3
0
2
3
2
0
2
1
0
5
1
0
1 11
4
1 1 1
2
0-4 4-8 8-12 12-16 16-20 20-24
Time (hrs)
0
1
2
3
4
5
6
Droperidol Metoclopramide Ondansetron Placebo
68%
Scuderi PE, et al. JCA 1997;9:551-558
Servizio di Anestesia e Rianimazione Ospedale di Faenza(RA)
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
MeanSEM 13.8 3.0 5.9 1.7
Scuderi PE, et al. Anesthesiology 2000;93:A37
Servizio di Anestesia e Rianimazione Ospedale di Faenza(RA)
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* p<0.05
Servizio di Anestesia e Rianimazione Ospedale di Faenza(RA)
Final recommendations
Servizio di Anestesia e Rianimazione Ospedale di Faenza(RA)
General Recommendations
Use generic drugs for “routine” prophylaxis Treat breakthrough symptoms with 5HT3 antagonists
Don’t repeat dose with 5HT3 antagonists Treat with different classes of antiemetics For high risk patients use combination prophylaxis Consider propofol infusion as part of anesthetic Prevent and control pain Consider post-discharge therapy
Servizio di Anestesia e Rianimazione Ospedale di Faenza(RA)
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%)
ProphylaxisDrop 1,25 mg+ steroid+-metoclopr
Extremely high risk(>60%)
No Prophylaxis
Rescue only:Ond 1 mgDolas 12,5
ProphylaxisDrop 1,25 mg
Rescue ONd 1 mgDolas 12,5
RescuewOND 1 mgDola 12,5
ProphylaxisDrop 1,25+
Steroid+Ond 8 mg or
Dola 12,5
Rescue:MetocloprPhenotiazAddit 5HT3
Or other antiemetic
Servizio di Anestesia e Rianimazione Ospedale di Faenza(RA)
Antiemetic choice drug effectiveness side-effect profile---clinical context patient preference associated reduction of total costs
» Nursing» Hospital stay» Earlier discharge » Earlier return to work...» Patient satisfaction.
Servizio di Anestesia e Rianimazione Ospedale di Faenza(RA)
Antiemetic choice
Antiemetic choice
Clinical effectiveness Side effect profile Patient acceptance Cost
Clinical context
Servizio di Anestesia e Rianimazione Ospedale di Faenza(RA)
Ewalenko P, Janny S, Dejonckheere M,Andry G, Wyns C: Antiemetic effect of
subhypnotic doses of propofol afterthyroidectomy. Br J Anaesth 77:463-7,
1996 ,• prospective, randomized, controlled trial, we havecompared the antiemetic efficacy of subhypnoticdoses of propofol, with Intralipid as placebo, afterthyroidectomy. We studied 64 patients of bothsexes, aged 22-71 yr, ASA I or II, undergoingthyroidectomy. After premedication with abenzodiazepine, balanced anaesthesia wasproduced with isoflurane and nitrous oxide inoxygen, and supplementary analgesia withfentanyl i.v. as required. Postoperative analgesiawas provided with non-opioids, and piritramide0.25 mg kg-1 i.m. on demand. Patients wereallocated randomly and blindly to receive a 20-hinfusion of either propofol or 10% Intralipid 0.1ml kg-1 h-1. Sedation scores, respiratory andcardiovascular variables, and incidence of PONVwere assessed every 4 h for 24 h. Pulse oximetryand ECG were monitored continuously. Bothgroups were comparable in characteristics,surgical and anaesthesia procedures, amount ofopioids given during and after operation, and totalamount of the study drug infused after operation.Occurrence of PONV was similar before the start(propofol 41%, Intralipid 50%) and aftercompletion (propofol 0.64%, Intralipid 1.6%) ofinfusion and decreased with time in both groupsduring the infusion. However, symptoms werereduced to nil with propofol but persisted andwere more severe with Intralipid during infusion(P£0.01). The overall incidence of PONV duringinfusion was 10% (three of 32 patients) in thepropofol group and 65% (21 of 32 patients) in theIntralipid group. Cardiovascular and respiratoryvariables, and SpO2 were unaltered, and sedationdecreased similarly with time in both groups. Weconclude that propofol, given at subhypnoticdoses, effectively reduced the incidence of PONVwithout untoward sedative or cardiovasculareffects.
Servizio di Anestesia e Rianimazione Ospedale di Faenza(RA)
Montgomery 1996
• We studied the antiemetic effects of a low doseinfusion of propofol for 24 h after majorgynaecological surgery in a double-blind,randomised, controlled trial. Fifty women of ASAphysical status 1 or 2 undergoing majorgynaecological surgery received an infusion of 1%propofol or intralipid at 0.1 ml.kg-1.h-1 for 24 hafter surgery. Pain was managed using morphinedelivered by a patient-controlled analgesia pump.The degree of postoperative nausea and vomitingwas assessed by the nurses using a four-pointordinal scale, by the patients using a visualanalogue scale and by the amount of rescueantiemetic given by the nurses. There were nodifferences between the two groups in any of themeasures of postoperative nausea and vomitingduring the first 48 h after surgery. Postoperativenausea and vomiting in the control group was lesson the second day compared with the firstpostoperative day, but not in the propofol group.There were no side effects from the
Servizio di Anestesia e Rianimazione Ospedale di Faenza(RA)
Ding
• To compare the intraoperative conditions andpostoperative recovery of patients following theuse of either propofol-nitrous oxide (N2O) orenflurane-N2O for maintenance of outpatientanesthesia. DESIGN: Randomized, single-blindstudy. SETTING: University hospital outpatientsurgery center. PATIENTS: 61 ASA physicalstatus I and II, healthy female outpatientsundergoing laparoscopic surgery.INTERVENTIONS: Patients were randomlyassigned to one of three anesthetic regimens.Group 1 (control) received thiopental sodium 4mg/kg intravenously (i.v.), followed by 0.5% to1.5% enflurane and 67% N2O in oxygen (O2).Group 2 received propofol 2 mg/kg i.v., followedby 0.5% to 1.5% enflurane and 67% N2O in O2.Group 3 received propofol 2 mg/kg i.v., followedby propofol 50 to 160 micrograms/kg/min i.v. and67% N2O in O2. All patients receivedsuccinylcholine 1 mg/kg i.v. to facilitate trachealintubation and atracurium 10 to 20 mg i.v. toprovide adequate relaxation during themaintenance period. MEASUREMENTS ANDMAIN RESULTS: Recovery from anesthesia wasassessed by a research nurse who was unaware ofthe anesthetic technique used. The mean +/- SDtime to eye opening was significantly longer in thethiopental-enflurane-N2O group (Group 1) than inthe propofol-propofol-N2O group (Group 3) (6.1+/- 2.5 minutes vs. 3.5 +/- 2.8 minutes,respectively). In addition, the mean time torespond to verbal commands was significantlyshorter in the propofol induction groups comparedwith the thiopental induction group. However, theuse of enflurane versus propofol for maintenanceof anesthesia did not significantly prolong the timefrom arrival in the recovery room to sitting,tolerating oral fluids, walking, or being judged "fitfor discharge." There were no differences amongthe three groups with respect to postoperative painor analgesic requirements. Finally, patients whoreceived enflurane for maintenance of anesthesiahad a significantly higher frequency of nausea andvomiting than the propofol maintenance group.CONCLUSION: Induction of anesthesia withpropofol is associated with a more rapidemergence from anesthesia than induction withthiopental. Maintenance of anesthesia withenflurane did not prolong recovery compared withmaintenance with propofol, but enflurane wasassociated with increased frequency ofpostoperative nausea and vomiting.
Servizio di Anestesia e Rianimazione Ospedale di Faenza(RA)
GAN
• Background: Breast surgery is associated with ahigh incidence of postoperative nausea andvomiting. Propofol and prophylacticadministration of ondansetron are associated witha lower incidence of postoperative nausea andvomiting. To date no comparison of these twodrugs has been reported. A randomized study wasdone to compare the efficacy of ondansetron andintraoperative propofol given in various regimens.
• Methods: Study participants included 89women classified as American Society ofAnesthesiologists physical status 1 or 2 who werescheduled for major breast surgery. Patients wererandomly assigned to one of four groups. Group Oreceived 4 mg ondansetron in 10 ml 0.9% salineand groups PI, PIP, and PP received 10 ml 0.9%saline before anesthesia induction. Group Oreceived thiopental, isoflurane, nitrousoxide—oxygen, and fentanyl for anesthesia.Group PI received propofol, isoflurane, nitrousoxide—oxygen, and fentanyl. Group PIP receivedpropofol, isoflurane, nitrous oxide—oxygen, andfentanyl. Thirty minutes before expected skinclosure, isoflurane was discontinued and 50 to 150mg × kg-1 × min-1 propofol was givenintravenously to maintain anesthesia. Group PPreceived propofol for induction and maintenanceof anesthesia, nitrous oxide—oxygen, andfentanyl. Postoperative pain relief was providedwith morphine administered by a patient-controlled analgesia pump. The incidence ofnausea and vomiting, requests for rescueantiemetic and sedation, pain scores, andhemodynamic data were recorded for 24 h.
• Results: Within 6 h of surgery, groups O and PPhad a lower incidence of nausea compared withgroups PI and PIP (P < 0.05). Fewer patients ingroup PP (19%) vomited during the 24-h periodcompared with groups O (48%), PI (64%), andPIP (52%) (P < 0.05). The incidence of antiemeticuse was also less in group PP (P < 0.05). Patientsin group PP had lower sedation scores at 30 minand at 1 h (P < 0.05). There were no differencesamong the groups in pain scores, blood pressure,heart rate, respiratory rate, and incidence ofpruritus.
• Conclusions: Propofol administered to induceand maintain anesthesia is more effective thanondansetron (with thiopental—isofluraneanesthesia) in preventing postoperative vomitingand is associated with fewer requests for rescueantiemetic and sedation in the early phase ofrecovery. It is equally effective in preventingpostoperative nausea as ondansetron in the first 6h after operation. Propofol used only as aninduction agent or for induction and at the end ofsurgery were not as protective againstpostoperative nausea and vomiting.
Servizio di Anestesia e Rianimazione Ospedale di Faenza(RA)
Servizio di Anestesia e Rianimazione Ospedale di Faenza(RA)
The Cost-effective Management of Postoperative Nausea and Vomiting
EDITORIAL VIEW AUTHOR(S): Watcha, Mehernoor F., M.D.
Anesthesiology92:931-3, 2000
Servizio di Anestesia e Rianimazione Ospedale di Faenza(RA)
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 a\dverse
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.
Servizio di Anestesia e Rianimazione Ospedale di Faenza(RA)
Poi ci sono 2 file su Acer o Vaio picolo su Post duischarge nv e una citazione;trasferire con link……………
Servizio di Anestesia e Rianimazione Ospedale di Faenza(RA)
Propofol & PONV 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 effect in patients undergoing laparoscopy using an isoflurane-based anesthetic
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.
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 Care19:385-7, 1991
• In order to investigate the putative anti-emeticeffect of propofol, 53 patients undergoinggynaecological laparoscopy were given a standardanaesthetic including induction with thiopentone.At the end of surgery, the patients received eithera sub-anaesthetic does of propofol or anequivalent volume of normal saline. There was nodifference in the incidence of nausea and vomitingbetween the propofol and control group. It isconcluded that low-dose propofol does not havean anti-emetic effect.
Servizio di Anestesia e Rianimazione Ospedale di Faenza(RA)
Campbell Anaesth Intens Care19:385-7, 1991
• In order to investigate the putative anti-emeticeffect of propofol, 53 patients undergoinggynaecological laparoscopy were given a standardanaesthetic including induction with thiopentone.At the end of surgery, the patients received eithera sub-anaesthetic does of propofol or anequivalent volume of normal saline. There was nodifference in the incidence of nausea and vomitingbetween the propofol and control group. It isconcluded that low-dose propofol does not havean anti-emetic effect.
Servizio di Anestesia e Rianimazione Ospedale di Faenza(RA)
Esempi pratici Appendix 1 Logistic regression is used to model the relation between explanatory variables and binary outcome variables. The logistic regression
modeling assumes that the probability of an event (i.e., the occurrence of the outcome) is associated with the values of the explanatory variables in the following way:
where where p = probability of the occurrence of the outcome, xi = value of the ith independent variable, and bi events for any patient = parameter
estimates for the ith variable. Fitting the model to the data, we can obtain the maximum likelihood estimate of the parameters for each variable. Based on the maximum
likelihood estimates from the final models, it is possible to calculate an expected risk of occurrence of the specific adverse event for any patient.
Examples The risk for patient 1, a 30-yr-old woman with a history of smoking and previous PONV undergoing a 1-h shoulder (orthopedic) operation
with general anesthesia is 35.2%. The risk for patient 2, a 40-yr-old nonsmoking man with no previous PONV undergoing a 1-h knee arthroscopy (orthopedic) without general
anesthesia is 0.4%. The risk for patient 3, a 70-yr-old smoking man with no previous PONV undergoing a 1-h cataract surgery (ophthalmologic) without general
anesthesia is 0.3%. The risk for patient 4, a 32-yr-old nonsmoking woman with previous PONV undergoing a 30-min laparoscopy (gynecologic) with general
anesthesia is 22.1% The risk for patient 5, a 22-yr-old woman with a history of smoking and previous PONV undergoing a 90-min bilateral breast augmentation
(plastic surgery) with general anesthesia is 52%.
Servizio di Anestesia e Rianimazione Ospedale di Faenza(RA)
Prevenzione del PONV:Dexamethasone
Placebo
1.25 mg2.5 mg
5.0 mg 10.0 mg
Patients 30 30 30 30 30
Vomiting 19 15 8* 6* 6*
Rescue required 5 0 0 0 0* P <0.05 compared with placebo and 1.25 mg
Dose ranging
Major gynecological surgery
Liu K, et al. Anesth Analg 1999;89:1316-1318
Servizio di Anestesia e Rianimazione Ospedale di Faenza(RA)
Prevenzione del PONV:Scopolamine
Small Studies Large Studies
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
Undefined control event rate
Servizio di Anestesia e Rianimazione Ospedale di Faenza(RA)
Prevenzione del PONV:Scopolamine
Small Studies Large Studies
Outcome Trials NNT Trials NNT
Vomiting 6 3.3 5 5.9
Nausea 2 5.3 5 5.0
PONV 8 2.9 8 6.7
Rescue 4 3.8 3 7.0
Kranke, et al. Anesth Analg 2002;95:133-143
Defined control event rate
Servizio di Anestesia e Rianimazione Ospedale di Faenza(RA)
Prevenzione del PONV:Scopolamine
Event NNH
Visual disturbances
5.6
Dry mouth 12.5
Dizziness 50.0
Agitation 100.1
Kranke, et al. Anesth Analg 2002;95:133-143
Adverse Events
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Prevenzione del PONV:Dimenhydrinate
Early (0-6 h) Overall (0-48 h)
Outcome Trials NNT Trials NNT
PONV 8 8.3 16 5.0
Vomiting 6 7.7 14 4.8
Nausea 2 8.3 7 5.9
Kranke, et al. Acta Anaesth Scand 2002;46:238-244
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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 Elective inpatients 1,447 + outpatients 563 randomly assigned to inhalational anesthesia with isoflurane–nitrous
oxide or TIVA with propofol–air. Cumulative incidence of PONV recorded for 72 h by blinded observers. Cost data of anesthetics, antiemetics, disposables, and equipment were
collected. Cost differences caused by duration of postanesthesia care unit stay and hospitalization were analyzed.
Servizio di Anestesia e Rianimazione Ospedale di Faenza(RA)
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 isoflurane–nitrous oxide anesthesia (number needed to treat = 6). Both anesthetic techniques were otherwise similar. Anesthesia costs were more than three times greater for propofol TIVA, without economic gains from shorter stay in the postanesthesia care unit.
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Vissern et 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
0
5
10
15
20
25
30
35
40
after anesth. Pacudischarge
24 hr 48 hr 72hr.
inpatients Iso/N2O
inpatients tiva
outpatients iso/N2O
outpatients tiva
2,010 unselected surgical patients Unversity of Amsterdam HospitalElective inpatients 1,447 + outpatients 563randomly assigned to inhalational anesthesia
with isoflurane–nitrous oxide or TIVA with propofol–air. Cumulative incidence of PONV recorded
for 72 h by blinded observers.
Servizio di Anestesia e Rianimazione Ospedale di Faenza(RA)
Analisi dei costi
0
5
10
15
20
25
30
35
40
$
inpts outpta
TPS/IsofPropof tiva
2 h
1 h
Servizio di Anestesia e Rianimazione Ospedale di Faenza(RA)
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
Scuderi et al. Anesthesiology. 1999;90:360-371
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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
Scuderi et al. Anesthesiology. 1999;90:360-371
Servizio di Anestesia e Rianimazione Ospedale di Faenza(RA)
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, medianScuderi et al. Anesthesiology. 1999;90:360-371
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Prevention Versus Treatment
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
Answer:
Servizio di Anestesia e Rianimazione Ospedale di Faenza(RA)
Multimodal Management of PONV:
Hypothesis
A multi-modal approach to the management of PONV can result in a zero incidence of vomiting (and perhaps nausea) in the immediate postoperative period (i.e., PACU)
Scuderi at al. Anesth Analg 2000;91:408-414
Servizio di Anestesia e Rianimazione Ospedale di Faenza(RA)
Multimodal Management of PONV: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
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Antiemetic choice
Clinical effectiveness Side effect profile Patient acceptance Cost
Clinical contexttt
NursingHospital stay
Earlier discharge Earlier return to work...
Patient satisfaction
Servizio di Anestesia e Rianimazione Ospedale di Faenza(RA)
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.
Servizio di Anestesia e Rianimazione Ospedale di Faenza(RA)
Chung F, Ritchie E, Su J. 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.
Servizio di Anestesia e Rianimazione Ospedale di Faenza(RA)
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:
Servizio di Anestesia e Rianimazione Ospedale di Faenza(RA)
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.
Servizio di Anestesia e Rianimazione Ospedale di Faenza(RA)
Chung F, Ritchie E, Su J. Postoperative pain in
ambulatory surgery. Anesth Analg 1997; 85:808-16.
Servizio di Anestesia e Rianimazione Ospedale di Faenza(RA)
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.
Servizio di Anestesia e Rianimazione Ospedale di Faenza(RA)
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.
Servizio di Anestesia e Rianimazione Ospedale di Faenza(RA)
Wasylak TJ, Abbott FV, English MJM, Jeans ME. Reduction of postoperative morbidity following patient-controlled morphine. Can J Anaesth 1990; 37:726-31.
16:
Servizio di Anestesia e Rianimazione Ospedale di Faenza(RA)
Reuben SS, Connelly NR. Postoperative analgesia for out-patient arthroscopic knee surgery with intraarticular bupivacaine and ketorolac. Anesth Analg 1995; 80:1154-7.
Servizio di Anestesia e Rianimazione Ospedale di Faenza(RA)
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.
Servizio di Anestesia e Rianimazione Ospedale di Faenza(RA)
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.
Servizio di Anestesia e Rianimazione Ospedale di Faenza(RA)
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.
Servizio di Anestesia e Rianimazione Ospedale di Faenza(RA)
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 perioperative analgesia with fewer side effects .
In summary, local anesthetic wound infiltration and peripheral nerve block techniques are simple, safe, and effective approaches to providing perioperative analgesia in the ambulatory setting. Use of major neural blockade techniques involving the upper (e.g., interscalene brachial plexus block) and lower (e.g., femoral nerve block) extremities can facilitate an earlier discharge after major shoulder and knee reconstructive procedures, respectively . The availability of newer local anesthetic drugs that are alleged to be associated with less toxicity and greater selectivity with respect to sensory and motor blockade (e.g., ropivacaine and levobupivacaine) may further enhance the benefits of local anesthetic supplementation after ambulatory surgery. The addition of adjuvants (e.g., clonidine) can prolong the postoperative analgesia produced by peripheral nerve blocks . Recent studies by Klein et al. suggest that improved pain control could also be achieved after major shoulder and knee procedures by using a disposable, nonelectronic catheter system for continuously infusing local anesthetic solutions. However, additional studies are needed to document the alleged advantages of these newer local anesthetic drugs and techniques. Future studies are also needed to determine the optimal local anesthetic concentrations and infusion rates with the new catheter systems.
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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 .
Servizio di Anestesia e Rianimazione Ospedale di Faenza(RA)
COX-2 InhibitorsIn 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.
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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
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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 .
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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.
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White PF .The role of non-opioid analgesic techniques in the management of pain after ambulatory surgery.
Anesth AnaIg 2002;94:577-85
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Servizio di Anestesia e Rianimazione Ospedale di Faenza(RA)
Servizio di Anestesia e Rianimazione Ospedale di Faenza(RA)
15)Watcha MF et al Cost and effectiveness of rofecoxib,
celecoxib and acctaminophen for preventing pain after
ambulatory otolaryngologic surgery .Anesth Analg
2003 ;96:987-94
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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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Farmacologia degli 5HT3 receptor antagonists
drug onset Terminal HL
Ondansetron:Zofran
30_60 min 3-4 h
tropisetron:Navoban
7-30 h
Granisetron:Kytril 9 h
Dolasetron: 8 h