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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.)


PONV


Hill RP, Lubarsky DA, Phillips-Bute B, Fortney JT, Creed MR, Glass PSA, Gan TJ: Cost-effectiveness of prophylactic antiemetic therapy with ondansetron, droperidol, or

placebo. ANESTHESIOLOGY 2000; 92:958-67.

prophylaxis with 1.25 mg intravenous droperidol was the most cost-effective approach

Cost considerations:» acquisition cost of a drug» costs of wasted drug» the need for adjunctive drugs to manage side effects» costs of nursing labor» Nursing labor costs are linearly related to the time an individual nurse spends with

a patient. » However, institutional costs may not increase if a patient spends an additional 15—

30 min in the postanesthesia care unit (PACU), unless overtime costs are incurred.» improved patient satisfaction

The cost-effectiveness of prophylactic antiemetic therapy depends on:» the underlying incidence of PONV » and on the costs and effectiveness of the drugs used for prophylaxis.


What drug should be used for PONV prophylaxis in high-risk patients? A more expensive drug may be preferred and reduce total institutional costs if it is more effective or associated with a decreased side-effect profile, a greater patient satisfaction, or an quicker return to work. There is convincing evidence from a systematic review of 54 blinded studies of 7,234 patients that ondansetron is more effective than metoclopramide, but not more effective than 1.25 mg droperidol for PONV prophylaxis in adults. Droperidol has also been shown to be as effective as tropisetron and dolasetron. Antiserotonin drugs are associated with increased headache, whereas central nervous system side effects of dysphoria, restlessness, and drowsiness have been reported with droperidol. However, when the dose of droperidol was limited to 1.25 mg intravenous, the incidence of these central nervous system events did not differ compared with ondansetron. It is also important to note that there were no patient preferences for a specific regimen in the study by Hill et al. In this era of cost containment, the less expensive drug, droperidol, should be used for PONV prophylaxis in the adult patient population until more effective drugs with decreased side effects are developed or the costs of alternative drugs are lowered. Similarly, in the absence of evidence to suggest that any available antiserotonin agent is superior to another in effectiveness or side-effect profile, the least expensive one should be used. In contrast to adults, PONV prophylaxis with droperidol is less effective than ondansetron in children and is associated with increased drowsiness, delayed discharge, and extrapyramidal side effects. The preferential use of ondansetron in this patient population may be justified.


Postoperative Nausea and Vomiting:

Prevention and Treatment

Claudio Melloni

Anestesia e Rianimazione

Ospedale degli Infermi di Faenza(RA)


The Cost-effective Management of Postoperative Nausea and Vomiting

EDITORIAL VIEW AUTHOR(S): Watcha, Mehernoor F., M.D.

Anesthesiology92:931-3, 2000


Topics Importance of the issue Risk factors Pharmacologic approaches to management Adjuvants (nonpharmacologic) Efficacy versus outcome Prevention versus treatment Postdischarge nausea and vomiting Multimodal management


Methodological questions(from Visserer et al…)

definitions of PONV:» nausea only, » nausea and vomiting» vomiting only.

This has hampered interstudy comparability. Because we scored nausea, retching, and vomiting independently, our data allowed for alternative end-point definitions. The Venn diagrams in show that PONV is primarily determined by the presence of nausea. When vomiting and retching are combined and taken as one end point, the incidence of PONV is lower, but similar differences between isoflurane and TIVA remain. Accordingly, the results of the various possible PONV end points are comparable, provided that nausea is included.

Diversity in methods of data collection may also account for some of the observed differences. Emetic symptoms can be quantified as:» retrospective self-report» established through explicit questioning» 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.


Importance of the issue PONV is :

» A limiting factor in the early discharge of ambulatory surgical patients» The leading cause of unanticipated hospital admission

PONV may:» Increase recovery room time» Expand nursing care» Increase total health care costs» Cause high level of patient discomfort---pain,hematoma,wound

dehiscence…» Cause high level of patient dissatisfaction» KO!!!


Macario A, Weinger M,Carney S, Kim A.Which clinical anesthesia outcomes are important to

avoid?Anesth.Analg.1999;89:652-8.

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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.


Sintomi accusati dai pazienti a casa dopo interventi eseguiti in regime di day

surgery(da Wu et al.,Anesthesiology 2002).

dolorenauseavomitocefaleasonnolenzagir.di testafatica


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)

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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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Sintomi accusati dai pazienti a casa dopo interventi eseguiti in regime di day

surgery(da Wu et al.,Anesthesiology 2002).

dolorenauseavomitocefaleasonnolenzagir.di testafatica


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)

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Valori relativi !


Beauregard L, Pomp A, Choinière M. Severity and impact of pain after day-surgery

Can J Anaesth 1998 / 45 / 304-11

0102030405060708090

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Can PONV be predicted?

Risk factor analysis


Sinclair et al.Can PONV be predicted?Anesthesiology

1999;91:109-18 17,638 consecutive ambulatory surgical patients;>90% ASA I /II 5,812 men and 11,826 women mean (± SD) age of 46.7 ± 21.2 yr. prospectively studied during a 3-yr period ASU of The Toronto Hospital, Western Division telephone interview 24 h after operation was obtained. Preoperative patient characteristics and intraoperative variables were

documented on specifically designed, standardized adverse-outcome check-off forms.

i.v.2—4 mg morphine for pain relief and 25—50 mg dimenhydrinate for nausea or vomiting.

Overall PONV incidence 4.6%:9.1 % at 24 hrs interview.


Sinclair et al.Can PONV be predicted?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).


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.


Frequency of PONV by type of anesthesia and duration of surgery.

Sinclair et al.Can PONV be predicted?Anesthesiology 1999;91:109-18


PONV prolongs PACU and amb.surg.unit stay Sinclair et al.Can

PONV be predicted?Anesthesiology 1999;91:109-18


Independent predictors of PONV Sinclair et al.Can PONV be predicted?Anesthesiology

1999;91:109-18

age A 10-yr increase in age was associated with a 13% decrease in the likelihood of PONV. sex Men had one third the risk for PONV compared with women. smoking status Smokers had two thirds the risk for PONV compared with nonsmokers history of previous PONV, had a threefold increase in the likelihood PONV compared with patients with no

previous PONV. type of anesthesia: General anesthesia increased the likelihood of PONV 11 times compared with other types of

anesthesia. duration of anesthesia, direct association between the duration of anesthesia and the risk for PONV. A 30-min

increase in duration predicted a 59% increase in the incidence of PONV type of surgery :

» plastic surgery had a sevenfold increase in the risk for PONV.» orthopedic shoulder surgery, ophthalmologic, or ENT procedures had a four- to sixfold increase.» orthopedic (nonshoulder) and gynecologic (non-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%



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.



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.



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.



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.



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.



A well-designed logistic regression model of factors associated with PONV will help guide patient selection for antiemetic therapy. Palazzo and Evans developed a model to predict PONV. However, their study has several limitations. Because the coefficients of the study were derived from a small sample of patients having orthopedic surgery, the model is not applicable to various types of surgical patients. The model also lacks validation by statistical techniques that evaluate the model's ability to predict PONV correctly. Koivuranta et al. developed a risk score to predict PONV and measured the power of the model by calculating the area under the ROC. Although patient and surgery related factors were addressed in their model, the coefficients were derived from pediatric and adult inpatients. Anesthesia-related factors were not included. Similarly, The predictive model developed by Apfel et al., which was derived from adult inpatients, also lacks anesthesia-related factors. Unlike patient-related factors and many surgery-related factors that cannot be modified in the perioperative period, many anesthesia-related factors, such as anesthetic technique, sometimes can be modified. Anesthesia-related factors must be included in the model to determine the potential effect of a change in anesthetic technique. We present the only model that is derived from ambulatory patients and incorporates anesthesia-related factors. This model is the most comprehensive logistic regression model of patient-, anesthesia-, and surgery-related factors associated with PONV (see appendix 1). This model will be able to predict patients' risk for PONV according to their sex, age, previous PONV, history of motion sickness, duration of anesthesia, anesthetic technique, and type of surgery. We evaluate the model's ability to correctly predict PONV and determine the power of the model by calculating the area under the ROC curve.

Knowledge of these predictors of PONV should increase anesthesiologists' efforts to reduce the incidence of PONV by selecting patients for antiemetic therapy. This may lead to improved cost-effective use of available drugs and resources.


Fitting the model to the data, we can obtain the maximum likelihood estimate of the parameters for each variable. Based on the maximum likelihood estimates from the final models, it is possible to calculate an expected risk of occurrence of the specific adverse event for any patient.

where Age = age in years/10; Sex = 1 if male and 0 if female; Smoke = 1 if

smoker and 0 if nonsmoker; PONV History = 1 if previous PONV and 0 if no previous PONV; Duration = duration of surgery in 30-min increments; GA = 1 if general anesthesia and 0 if other type of anesthesia; ENT = 1 if ENT and 0 if other type of surgery; Ophthalm = 1 if ophthalmology and 0 if other type of surgery; Plastic = 1 if plastic surgery and 0 if other type of surgery; GynNonDC = 1 if gynecologic non 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.


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.


Importance of the work by Sinclair et al…

Fitting the model to the data, we can obtain the maximum likelihood estimate of the parameters for each variable. Based on the maximum likelihood estimates from the final models, it is possible to calculate an expected risk of occurrence of the specific adverse event for any patient.


Appendix 1 Logistic regression is used to model the relation between explanatory variables and binary outcome variables. The logistic regression

modeling assumes that the probability of an event (i.e., the occurrence of the outcome) is associated with the values of the explanatory variables in the following way:

where where p = probability of the occurrence of the outcome, xi = value of the ith independent variable, and bi events for any patient = parameter

estimates for the ith variable. Fitting the model to the data, we can obtain the maximum likelihood estimate of the parameters for each variable. Based on the maximum

likelihood estimates from the final models, it is possible to calculate an expected risk of occurrence of the specific adverse event for any patient.

Examples The risk for patient 1, a 30-yr-old woman with a history of smoking and previous PONV undergoing a 1-h shoulder (orthopedic) operation

with general anesthesia is 35.2%. The risk for patient 2, a 40-yr-old nonsmoking man with no previous PONV undergoing a 1-h knee arthroscopy (orthopedic) without general

anesthesia is 0.4%. The risk for patient 3, a 70-yr-old smoking man with no previous PONV undergoing a 1-h cataract surgery (ophthalmologic) without general

anesthesia is 0.3%. The risk for patient 4, a 32-yr-old nonsmoking woman with previous PONV undergoing a 30-min laparoscopy (gynecologic) with general

anesthesia is 22.1% The risk for patient 5, a 22-yr-old woman with a history of smoking and previous PONV undergoing a 90-min bilateral breast augmentation

(plastic surgery) with general anesthesia is 52%.


Risk Factors

Non-anesthetic factors Anesthetic related factors Postoperative factors


Risk factors da Samba 2007:1

Patient specific Female gender Non smoking status Hx of ponv/motion sickness



Anesthetoc risk factors Use on intraop volatile anesth Use on intraop and postop opioids Use of intraop N2O



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


Risk Factors

Age Gender Body habitus Hx motion sickness Hx PONV Anxiety Concomitant disease Operative procedure Duration of surgery

Non-anesthetic Factors


Risk Factors

Preanesthetic medication Gastric distension Gastric suctioning Anesthetic technique Anesthetic agents

Anesthetic Related Factors


Risk Factors

Pain Dizziness Ambulation Oral intake Opioids

Postoperative Factors


Postoperative Nausea and Vomiting:Anesthetic Related Factors

Nitrous oxide

Volatile anesthetics

NMB reversal

Propofol


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


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


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.


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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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)

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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)

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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.


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.


IS PONV incidence different between LMA and

ETT?

Joshi GP, Inagaki Y, White PF, Taylor-Kennedy L, Wat LI, Gevirtz C, McCraney JM, McCulloch DA: Use of the laryngeal mask airway as an alternative to the tracheal tube during ambulatory anesthesia. Anesth Analg 85:573–7, 199


Risk 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


Risk Factors Reversal of Neuromuscular Block

Omitting neostigmine may have a clinically relevant antiemetic effect when high doses are used

Omitting NMB antagonism introduces a non-negligent risk of residual paralysis even when short acting NMB agents are used

Tramer MR, Fuchs-Buder T. BJA 1999;82:379-386


Risk Factors Propofol and PONV

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


Risk Factors Antiemetic Effects of Propofol

Investigations Randomized Double-Blind Placebo-Controlled Effective

Chemotherapy Induced Emesis

Scher 1992 no no no yes

Borgeat 1993 no no no yes

Borgeat 1994 no no no yes

PONV

Campbell 1991 yes yes yes no

Borgeat 1992 yes yes yes yes

Ewalenko 1996 yes yes yes yes

Montgomery 1996 yes yes yes no

Scuderi 1996 yes yes yes no

Gan 1997 no no no yes

Gan 1999 yes yes yes yes


Risk Factors

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


Risk Factors

Younger age Nonsmoking history Female Hx of motion sickness Hx of PONV Increased duration of operation

Logistic Regression


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.


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%


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


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%


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%.


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


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


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


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


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)


Trattamento del PONV


Management of PONV:Pharmacological Approaches

Medications Dose response Comparative efficacy Combination therapy Timing of administration


Figure 3


AntiemeticiAntiemeticievoluzione del pensieroevoluzione del pensiero

metoclopramidemetoclopramidepreso dalla gastroenterologiapreso dalla gastroenterologia

droperidoldroperidol preso dagli antipsicotici....preso dagli antipsicotici....

ondansetronondansetronla nuova frontiera...la nuova frontiera...

granisetrongranisetron


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


Currently Available Medications

5HT3 (serotonin) antagonists - ondansetron Butyrophenones - droperidol Benzamides - metoclopramide Antihistamines - dimenhydrinate Steroids - dexamethasone Phenothiazines-

promethazine,prochlorperazine Anticholinergics – scopolamine


5HT3 Antagonists and PONV (Summer 2002)

5HT3 Antagonist Clinical Trials

Ondansetron * 275

Dolasetron* 20

Granisetron* 66

Tropisetron 27

Ramosetron 29

Palenosetron 5

* Approved for PONV indication


Prevention of PONV:Ondansetron Versus Placebo

62

76 77

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


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


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


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


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


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

* ***

**** *


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

****

** * *


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

***

*



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



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


Postoperative Nausea

No statistically significant differences among the groups


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

‡


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


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


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)


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


Prevention of PONV:Metoclopramide

“In summary, metoclopramide, although used as an antiemetic for almost 40 years in the prevention of PONV, has no clinically relevant antiemetic effect . . . it is very likely that the doses used in daily clinical practice are too low.”

Henzi I, Walder B, and Tramer, MR. Metoclopramide in the prevention of postoperative nausea and vomiting: a quantitative systematic review of randomized, placebo-controlled studies. BJA 1999;83:761-771


Prevention of PONV:Dexamethasone

“In conclusion, in the surgical setting, a single prophylactic dose of dexamethasone is antiemetic compared with placebo without evidence of clinically relevant toxicity in otherwise healthy patients. Late efficacy (i.e., up to 24 hours) seems to be most pronounced.”

Henzi I, Walder B, and Tramer, MR. Dexamethasone for the prevention of postoperative nausea and vomiting: a quantitative systematic review. Anesth Analg 2000;90:186-194

Eberhart LH. Morin AM. Georgieff M. Dexamethasone for prophylaxis of postoperative nausea and vomiting. A meta-analysis of randomized controlled studies. Anaesthesist. 2000 ;49:713-20


Prevention of PONV:Dexamethasone

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


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






Nausea 2 5.3 5 5.0

PONV 8 2.9 8 6.7

Rescue 4 3.8 3 7.0


Defined control event rate



Event NNH

Visual disturbances

5.6

Dry mouth 12.5

Dizziness 50.0

Agitation 100.1


Adverse Events


Prevention of PONV:Dimenhydrinate

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


PONV 8 8.3 16 5.0

Vomiting 6 7.7 14 4.8

Nausea 2 8.3 7 5.9

Kranke, et al. Acta Anaesth Scand 2002;46:238-244


Prevention of PONV:Combination Therapy

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



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



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


Placebo Metoclopramide Dolasetron Ondansetron

Predischarge

nausea (%) 13 7 3 3

vomiting (%) 0 0 0 0

rescue (%) 0 0 0 0

Postdischarge

nausea (%) 13 10 7 3

vomiting (%) 0 0 0 0

rescue (%) 0 0 0 0


Tang, et al. Anesthesiology 2001; 95:A43


Prevention of PONV:Timing of Administration

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


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.




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).




setting.Anesth.Analg 1998;96:........


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


efficacy,cost effectiveness and cost benefit as a prophylactic antiemetic in the ambulatory setting.Anesth.Analg

1998;96:........

**

*


Incidence of nausea and vomiting in the 24 hrs post surgery in the 4 treatment

groups:placebo,,ondansetron 2 mg pre and 2 mg post surg,ondansetron 4 mg preinduction,ondansetron 4 mg at the end of

surgery.

0

10

20

30

40

50

60

70

80

nausea% vomit% rescueantiemetics

nausea VASmedio(mm)

vomiting>2times

placebosplit dosepreinductionpostsurg


efficacy,cost effectiveness and cost benefit as a prophylactic antiemetic in the ambulatory setting.Anesth.Analg

1998;96:........

*

* *

**


Timing of Administration:Dexamethasone

Group 1(Preinduction)

Group 2(Postextubation)

Group 3(Placebo)

0 – 2 hr

nausea (%) 10 25 33

vomiting (%) 5 20 20

total (%) 15*† 45 53

2 – 24 hr

nausea (%) 15 18 30

vomiting (%) 10 10 25

total (%) 25* 28* 55

Wang et al. Anesth Analg 2000;91;136-139* Compared to Group 3† Compared to Group 2


Management of PONV:Adjuvants (Nonpharmacologic)

P-6 acupuncture point stimulation Supplemental oxygen Aggressive perioperative rehydration Preemptive analgesia


P-6 Acupuncture Point Stimulation

Zarate E, Mingus M, White PF, Chiu JW, Scuderi PE, et al. The use of transcutaneous acupoint electrical stimulation for preventing nausea and vomiting after laparoscopic surgery. Anesth Analg 2001;92:629-35.


P-6 Acupuncture Point Stimulation

TAES Sham 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


* compared to sham

† compared to placebo


Supplemental Oxygen

Greif R, Laciny S, Rapf B, et al. Supplemental oxygen reduces the incidence of postoperative nausea and vomiting. Anesthesiology 1999;91:1246-52.

Goll V, Ozan A, Greif R, et al. Ondansetron is no more effective than supplemental intraoperative oxygen for prevention of postoperative nausea and vomiting. Anesth Analg 2001;92:112-17.


Supplemental Oxygen

30 % Oxygen 80% Oxygen P Value

Male/Female 57/62 41/71 0.110

0-6 hr PONV (%) 15.1 8 0.141

nausea (%) 15.1 8 0.077

vomiting (%) 1.7 0 0.169

6-24 hr PONV (%) 22.2 19.9 0.045

nausea (%) 17.6 8.9 0.066

vomiting (%) 5.9 1.8 0.108

0-24 hr PONV (%) 30.3 17 0.027

nausea (%) 27.7 16 0.034

vomiting (%) 5.9 1.8 0.108

Greif et al. Anesthesiology 1999;91:1246-1252


Supplemental Oxygen

30 % Oxygen 80% Oxygen Ondansetron

Patients (female) 80 79 71

0-6 hr PONV (%) 36 20 27

nausea (%) 35 20 27

vomiting (%) 19 9 14

6-24 hr PONV (%) 13 4 6

nausea (%) 11 4 6

vomiting (%) 9 4 1

0-24 hr PONV (%) 44 22* 30

nausea (%) 41 22* 30

vomiting (%) 26 10* 15

Goll et al. Anesth Analg 2001;92:112-117


Intravenous Fluid Therapy

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


Pain and PONV

Effects % of Total Patients

Pain relieved, nausea relieved 68.5

Pain reduced, nausea relieved 11.5

Pain relieved, nausea persisted 9.5

Pain persisted, nausea persisted 10.5

Andersen et al. Can Anaesth Soc J 23:366-369, 1976


Efficacy Versus Outcome


Surrogate End PointsAre They Meaningful

Appropriate end points Duration of PACU stay Incidence of unplanned admissions Patient satisfaction

Fisher. Anesthesiology 1994;81:795-796


Measures of Outcome

Mortality

Morbidity

Patient satisfaction

Cost


Risk of Mortality and Adverse Outcome in a Tertiary Care

Population

Adverse outcomes 1:125

Death (all causes) 1:500

Anesthesia provider error causing adverseoutcome

1:1,500

Risk of death (anesthesia cause only) 1:250,000

Patient Safety in Anesthesia Practice. Morel and Eichorn (ed)


Complications of PONV

Electrolyte imbalance

Tension on sutures, evisceration

Venous hypertension, bleeding

Aspiration

Delayed discharge (outpatients)

Dehydration

Unanticipated admission


Unanticipated Admissions

Reasons for Admission Number Percent

Pain 18 19

Bleeding 18 19

Intractable Vomiting 17 18

Perforated Uterus 7 7

Extensive Surgery 6 6

Urinary Retention 5 5

Additional Surgery 4 4

Gold et al. JAMA 1989;262:3008-3010

Overall Admission Rate = 0.01

PONV Admission Rate = 0.002


Cost Savings From the Management of PONV

Analysis of strategies to decrease postanesthesia care unit costs:

1. Supplies and medications account for 2% of PACU charges

2. Personnel account for almost all PACU charges

3. PACU staffing is determined by peak PACU patient load

4. Peak PACU patient load is determined by OR scheduling

5. Elimination of PONV would decrease PACU stay by less than 4.8% which would not be sufficient to decrease the level of PACU staffing

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


Subject Preference Following Surgery

Levels Preference

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


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


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


Efficacy Versus Outcome

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


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


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


Efficacy of Prophylaxis – Overall

Ondansetron Placebo p-value

Total 285 290

Nausea Score PACU Entry median, 75th, 90th 0, 0, 0 0,0,2 0.54

No Tx Required (%) 204 (71.6) 179 (61.7) 0.01

Treatment Required Nausea (%) 64 (22.5) 70 (24.1) 0.63 Vomiting (%) 17 (6.0) 41 (14.1) 0.001 Total (%) 81 (28) 111 (38) 0.01

Nausea Score @ TX median, 75th, 90th

nausea score >0 (%)5,8,10(100)

6,9,10(96.4) 0.14



Efficacy of Prophylaxis - Group E

Ondansetron

Placebo p-value

Total

58

60

Nausea Score PACU Entry median, 75th, 90th

0,0,4

0,0,6

0.49

No Tx Required (%)

36 (62) 26 (43) 0.045

Treatment Required Nausea (%) 17 (29) 21 (35) Vomiting (%) 5 (9) 13 (22) Total (%)

22 (38) 34 (57) 0.045



Outcomes - Treatment vs Prophylaxis Patient Satisfaction, Time to Discharge

Ondansetron Placebo P NNT

Total patients 285 290 --

All Patients - placebo Tx excluded 245 235 --

Satisfaction PONV: yes/no (%) 97% 93% 0.04 25

Satisfaction Overall: (11 pt scale)* 7,9,10 7,9,10 0.76

Time to discharge (95% CI) min 87(82,92) 92(86,98) 0.23

Group E patients - placebo Tx excluded 47 42 --

Satisfaction PONV: yes/no (%) 47 (100) 37 (90) 0.04 10



* 10th, 25th, medianScuderi et al. Anesthesiology. 1999;90:360-371



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:


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


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


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



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


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


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.....


PONV dopo la dimissione


Efficacy of antiemetic medication on postdischarge nausea (Gupta

A,Wu,CL,Elkassabani,N,Krug,CE,Parker,SD,Fleisher LA.Does the routine prophylactic use of antiemetics affect the incidence of postischarge nausea

and vomuint following ambulatory surgery?.Anesthesiology 2003;99:488-95.)


Efficacy of antiemetic medication on posdtdischarge vomiting (Gupta

A,Wu,CL,Elkassabani,N,Krug,CE,Parker,SD,Fleisher LA.Does the routine prophylactic use of antiemetics affect the incidence of postischarge nausea



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


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


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


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


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


Per uno studio nostro su POnv(io,Lorenz….???

Data Co-nome Età/peso/alt Sex Asa e patol concomit Cinetosi Ponv pregr Premed

Sede Iniz interv Fine interv Propofol Fent Remifent N2O Vapore:quale….. Tipo interv Protesi resp LMA Guedel IOT Resp spont/ass/IPPV FiO2 Flebotot Risv;immediato/velcoe/lento

Analg postop;ketorolac tramadol mep altro Efficacia analg postop Sintodian si no/quando/quanto Zofran Si NO quando quanto Nausea postop 123 Vomito postop123 Rescue treatm Nausea I g 123 Analg I g Efficacia analg I g Vomito I g 123 Rescue treatm I g


Postdischarge nausea in the combination group(>1 drug) vs the

placebo group

0,00

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


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


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


Post Discharge Nausea and Vomiting

Incidence Severity Contributing factors Prevention Treatment


Post Discharge Symptoms Following Ambulatory

Surgery

Symptom Incidence (%)

Pain 45

Nausea 17

Vomiting 8

Headache 17

Drowsiness 42

Dizziness 18

Fatigue 21

Wu CL, et al. Anesthesiology 2002;96:994-1003


Strabismus 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


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


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


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


Final recommendations


General Recommendations

Use generic drugs for “routine” prophylaxis Treat breakthrough symptoms with 5HT3 antagonists

Don’t repeat dose with 5HT3 antagonists Treat with different classes of antiemetics For high risk patients use combination prophylaxis Consider propofol infusion as part of anesthetic Prevent and control pain Consider post-discharge therapy


Watcha MF, White PF: Postoperative nausea and vomiting: Prophylaxis versus treatment. Anesth

Analg 89:1337-9, 1999???Anesthesiology 92;931-3:2000

Estimated risk of PONV

Low risk(<10%)Mila to moderate

(10-30%)High risk(30-60%)

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


Antiemetic choice drug effectiveness side-effect profile---clinical context patient preference associated reduction of total costs

» Nursing» Hospital stay» Earlier discharge » Earlier return to work...» Patient satisfaction.


Antiemetic choice

Antiemetic choice

Clinical effectiveness Side effect profile Patient acceptance Cost

Clinical context


Ewalenko P, Janny S, Dejonckheere M,Andry G, Wyns C: Antiemetic effect of

subhypnotic doses of propofol 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.


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


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.


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.


The Cost-effective Management of Postoperative Nausea and Vomiting

EDITORIAL VIEW AUTHOR(S): Watcha, Mehernoor F., M.D.

Anesthesiology92:931-3, 2000


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.


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


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.


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.


Esempi pratici Appendix 1 Logistic regression is used to model the relation between explanatory variables and binary outcome variables. The logistic regression

modeling assumes that the probability of an event (i.e., the occurrence of the outcome) is associated with the values of the explanatory variables in the following way:

where where p = probability of the occurrence of the outcome, xi = value of the ith independent variable, and bi events for any patient = parameter

estimates for the ith variable. Fitting the model to the data, we can obtain the maximum likelihood estimate of the parameters for each variable. Based on the maximum

likelihood estimates from the final models, it is possible to calculate an expected risk of occurrence of the specific adverse event for any patient.

Examples The risk for patient 1, a 30-yr-old woman with a history of smoking and previous PONV undergoing a 1-h shoulder (orthopedic) operation

with general anesthesia is 35.2%. The risk for patient 2, a 40-yr-old nonsmoking man with no previous PONV undergoing a 1-h knee arthroscopy (orthopedic) without general

anesthesia is 0.4%. The risk for patient 3, a 70-yr-old smoking man with no previous PONV undergoing a 1-h cataract surgery (ophthalmologic) without general

anesthesia is 0.3%. The risk for patient 4, a 32-yr-old nonsmoking woman with previous PONV undergoing a 30-min laparoscopy (gynecologic) with general

anesthesia is 22.1% The risk for patient 5, a 22-yr-old woman with a history of smoking and previous PONV undergoing a 90-min bilateral breast augmentation

(plastic surgery) with general anesthesia is 52%.


Prevenzione del PONV:Dexamethasone

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


Prevenzione del PONV:Scopolamine




Nausea 7 3.4 6 5.9

PONV 11 2.5 9 7.1

Rescue 4 3.8 6 20.0


Undefined control event rate






Nausea 2 5.3 5 5.0

PONV 8 2.9 8 6.7

Rescue 4 3.8 3 7.0


Defined control event rate



Event NNH

Visual disturbances

5.6

Dry mouth 12.5

Dizziness 50.0

Agitation 100.1


Adverse Events


Prevenzione del PONV:Dimenhydrinate

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


PONV 8 8.3 16 5.0

Vomiting 6 7.7 14 4.8

Nausea 2 8.3 7 5.9

Kranke, et al. Acta Anaesth Scand 2002;46:238-244


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.




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.


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.


Analisi dei costi

0

5

10

15

20

25

30

35

40

$

inpts outpta

TPS/IsofPropof tiva

2 h

1 h


Efficacy of Prophylaxis – Overall

Ondansetron Placebo p-value

Total 285 290

Nausea Score PACU Entry median, 75th, 90th 0, 0, 0 0,0,2 0.54

No Tx Required (%) 204 (71.6) 179 (61.7) 0.01

Treatment Required Nausea (%) 64 (22.5) 70 (24.1) 0.63 Vomiting (%) 17 (6.0) 41 (14.1) 0.001 Total (%) 81 (28) 111 (38) 0.01

Nausea Score @ TX median, 75th, 90th

nausea score >0 (%)5,8,10(100)

6,9,10(96.4) 0.14



Efficacy of Prophylaxis - Group E

Ondansetron

Placebo p-value

Total

58

60

Nausea Score PACU Entry median, 75th, 90th

0,0,4

0,0,6

0.49

No Tx Required (%)

36 (62) 26 (43) 0.045

Treatment Required Nausea (%) 17 (29) 21 (35) Vomiting (%) 5 (9) 13 (22) Total (%)

22 (38) 34 (57) 0.045



Outcomes - Treatment vs Prophylaxis Patient Satisfaction, Time to Discharge

Ondansetron Placebo P NNT

Total patients 285 290 --

All Patients - placebo Tx excluded 245 235 --

Satisfaction PONV: yes/no (%) 97% 93% 0.04 25



Group E patients - placebo Tx excluded 47 42 --

Satisfaction PONV: yes/no (%) 47 (100) 37 (90) 0.04 10



* 10th, 25th, medianScuderi et al. Anesthesiology. 1999;90:360-371



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:



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


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


Antiemetic choice

Clinical effectiveness Side effect profile Patient acceptance Cost

Clinical contexttt

NursingHospital stay

Earlier discharge Earlier return to work...

Patient satisfaction


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.


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.


Rocchi A,Chung F,Forte L.. Canadian survey of postsurgical pain and pain

medications experiences.Can.J.Anesth.2002;49:1053-

1056

. To assess the postoperative pain and pain medication experiences of Canadians. Methods: Three hundred and five general population subjects from across Canada who had surgery in the

previous three years were retrospectively questioned regarding pain experiences in the surgical facility and at home, pain medication efficacy and pain medication satisfaction.

Results: While in the surgical facility, pain was experienced by 68% of patients who expected overnight admission (“inpatients”) and 49% of patients who expected same-day discharge (“outpatients”). Overall, 47% of inpatients and 15% of outpatients reported that their highest experience of pain was severe or extreme; 25% of inpatients and 9% of outpatients reported that their average pain was severe or extreme. In the two weeks post-discharge, 79% and 74% respectively of inpatients and outpatients experienced pain. Severe or extreme pain occurred at home in 25% of inpatients and 28% of outpatients; average pain was severe or extreme for 9% of inpatients and 12% of outpatients.

Complete or a lot of pain relief was experienced by 54% to 72% patients who received pain medication; higher rates of pain medication satisfaction were reported than rates of pain relief from pain medication.

Conclusion: Severe or extreme pain was experienced by many surgical patients. Improvements could be made to patients' postsurgical pain experience in Canada, both in the surgical facility and subsequent to discharge.

ABSTRACT:


Sutters KA, Miaskowski C. Inadequate pain management and associated morbidity in children at home after tonsillectomy. J Ped Nurs 1997; 12:178-85. 3: Chung F. Recovery pattern and home-readiness after ambulatory surgery. Anesth Analg 1995; 80:896-902. 4: Fortier J, Chung F, Su J. Predictive factors of unanticipated admission in ambulatory surgery: a prospective stud. Anesthesiology 1996; 85:A27. 5: 7: Scott NB, Hodson M. Public perceptions of postoperative pain and its relief. Anaesthesia 1997; 52:438-42. 8: Moote CA. The prevention of postoperative pain. Can J Anaesth 1994; 41:527-33. 9: Smith AF. The prevention of postoperative pain: shouldn't it begin at medical school? (Letter) Can J Anaesth 1995; 42:256-7. 10: Rose DK, Cohen MM, Yee DA. Changing the practice of pain management. Anesth Analg 1997; 84:764-72. 11: Humphries CA, Counsell DJ, Pediani RC, Close SL. Audit of opioid prescribing: the effect of hospital guidelines. Anaesthesia 1997; 52:745-9. 12: Joshi GP. Postoperative pain management. In: White PF (Ed.). Ambulatory Anesthesia & Surgery, 1st ed. London: W.B. Saunders Company Ltd, 1997: 477-86. 13: Gourlay GK, Cherry DA, Onley MM, et al. Pharmacokinetics and pharmacodynamics of twenty-four-hourly Kapanol compared to twelve-hourly MS Contin in the

treatment of severe cancer pain. Pain 1997; 69:295-302. 14: Cannon CR. Transnasal butorphanol: pain relief in the head and neck patient. Otolaryngol Head Neck Surg 1997; 116:197-200. 15: Wasylak TJ, Abbott FV, English MJM, Jeans ME. Reduction of postoperative morbidity following patient-controlled morphine. Can J Anaesth 1990; 37:726-31. 16: Striebel HW, Oelmann T, Spies C, Rieger A, Schwagmeier R. Patient-controlled intranasal analgesia: a method for noninvasive postoperative pain management. Anesth

Analg 1996; 83:548-51. 17: Fuller JG, McMorland GH, Douglas MJ, Palmer L. Epidural morphine for analgesia after Caesarean section: a report of 4880 patients. Can J Anaesth 1990; 37:636-40. 18: Reuben SS, Connelly NR. Postoperative analgesia for out-patient arthroscopic knee surgery with intraarticular bupivacaine and ketorolac. Anesth Analg 1995; 80:1154-

7. 19: Bourke DL, Furman WR. Improved postoperative analgesia with morphine added to axillary block solution. J Clin Anesth 1993; 5:114-7. 20: Ritchie ED, Tong D, Chung F, Norris AM, Miniaci A, Vairavanathan SD. Suprascapular nerve block for postoperative pain relief in arthroscopic shoulder surgery: a new

modality. Anesth Analg 1997; 84:1306-12. 21: Bean-Lijewski JD. Glossopharyngeal nerve block for pain relief after pediatric tonsillectomy: retrospective analysis and two cases of life-threatening upper airway

obstruction from an interrupted trial. Anesth Analg 1997; 84:1232-8. 22: Wang B, Tang J, White PF, et al. Effect of the intensity of transcutaneous acupoint electrical stimulation on the post-operative analgesic requirement. Anesth Analg

1997; 85:406-13. 23: Marquardt HM, Razis PA. Prepacked take-home analgesia for day case surgery. Br J Nurs 1996; 5:1114-8. 24: Michaloliakou C, Chung F, Sharma S. Preoperative multimodal analgesia facilitates recovery after ambulatory laparoscopic cholecystectomy. Anesth Analg 1996; 82:44-

51. 25: Badner NH, Bourne RB, Rorabeck CH, Doyle JA. Addition of morphine to intra-articular bupivacaine does not improve analgesia following knee joint replacement. Reg

Anesth 1997; 22:347-50. 26: Pande AC, Pyke RE, Greiner M, Wideman GL, Benjamin R, Pierce MW. Analgesic efficacy of enadoline versus placebo or morphine in postsurgical pain. Clin

Neuropharmacol 1996; 19:451-6. 27: Looi-Lyons LC, Chung FF, Chan VW, McQuestion M. Respiratory depression: an adverse outcome during patient controlled analgesia therapy. J Clin Anesth 1996;

8:151-6.


Chung F, Ritchie E, Su J. Postoperative pain in

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


The continued training of doctors, nurses, and medical students in the prevention and proper management of postoperative pain is necessary. Moote CA. The prevention of postoperative pain. Can J Anaesth 1994; 41:527-33.

9: Smith AF. The prevention of postoperative pain: shouldn't it begin at medical school? (Letter) Can J Anaesth 1995; 42:256-7.

Beauregard and colleagues found that many instructions given to patients did not clearly indicate the intake frequency, dose adjustment, and control of side effects of analgesics. In the study of Rose et al., Rose DK, Cohen MM, Yee DA. Changing the practice of pain management. Anesth Analg 1997; 84:764-72.

pain management practices were successfully changed after anaesthetists were educated and patients were made more aware of pain as an important problem. Another study Humphries CA, Counsell DJ, Pediani RC, Close SL. Audit of opioid prescribing: the effect of hospital guidelines. Anaesthesia 1997; 52:745-9.

MEDLINEÒ RECORD:

AB - The effects of prescribing guidelines for analgesia were assessed by auditing prescriptions for opioids before and after the introduction of hospital prescribing guidelines. Opioid prescriptions were collected by the pharmacy department over a 2-week period in November 1994 and repeated in November 1995. Following the initial audit, analgesic prescribing guidelines were introduced. A statistically significant increase was achieved in the number of prescriptions that were correct for both dose and frequency according to both the British National Formulary recommendations (40-61%; p < 0.001) and our Acute Pain Service guidelines (16-26%; p < 0.05). There was a statistically significant decrease in the number of prescriptions that were inadequate for both dose and frequency according to both the British National Formulary recommendations (18-3%; p < 0.001) and our Acute Pain Service guidelines (36-17%; p = 0.001). The use of accessible prescribing guidelines promotes demonstrable improvements in opioid prescribing.

showed that an audit of opioid prescribing considerably improved the prescribing of opioids, especially the frequency with which they were prescribed.


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


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

16:


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


Bourke DL, Furman WR. Improved postoperative analgesia with morphine added to axillary block solution. J Clin Anesth 1993; 5:114-7.

20: Ritchie ED, Tong D, Chung F, Norris AM, Miniaci A, Vairavanathan SD. Suprascapular nerve block for postoperative pain relief in arthroscopic shoulder surgery: a new modality. Anesth Analg 1997; 84:1306-12.

21: Bean-Lijewski JD. Glossopharyngeal nerve block for pain relief after pediatric tonsillectomy: retrospective analysis and two cases of life-threatening upper airway obstruction from an interrupted trial. Anesth Analg 1997; 84:1232-8.


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


Marquardt HM, Razis PA. Prepacked take-home analgesia for day case surgery. Br J Nurs 1996; 5:1114-8.

Another randomised double-blind study on preoperative multimodal analgesia for ambulatory patients who underwent laparoscopic cholecystectomy used a combination of preoperative meperidine and ketorolac by intramuscular bolus injection and local anaesthetic infiltration into the incision during laparoscopic cholecystectomy. The results showed that the concomitant use of local anaesthetic, NSAID, and opioid drugs was very effective in diminishing postoperative pain and reducing the stay in the ambulatory care unit. » 24: Michaloliakou C, Chung F, Sharma S. Preoperative multimodal

analgesia facilitates recovery after ambulatory laparoscopic cholecystectomy. Anesth Analg 1996; 82:44-51.


Local Anesthetic Techniques Peripheral nerve blocks and wound infiltration with local anesthetics are commonly used adjuvants to both monitored anesthesia care (MAC) and general anesthetic techniques because they can provide

intra- and postoperative analgesia (). As a result, these techniques can decrease the anesthetic and analgesic requirements during surgery and reduce the need for opioid analgesics in the postoperative period. More effective pain relief in the early postoperative period from the residual sensory block provided by local anesthesia can facilitate the recovery process, enabling earlier ambulation and discharge home (i.e., fast-tracking). The use of local anesthetic techniques also decreases the incidence of postoperative nausea and vomiting and thereby decreases the incidence of prolonged recovery stays and unanticipated hospital admissions related to intractable emetic symptoms.

Although additional clinical studies are needed to identify the most cost-effective anesthetic techniques for ambulatory surgery, it would seem that peripheral nerve blocks with sedation (i.e., MAC techniques) offer significant advantages over central neuraxis blockade and general anesthesia in the ambulatory setting . In outpatients undergoing saphenous vein-stripping surgery, use of a femoral/genitofemoral nerve block significantly improved patient satisfaction with the anesthetic experience . Blockade of the ilioinguinal and iliohypogastric nerves can significantly decrease the anesthetic and analgesic requirements in both children and adults undergoing inguinal herniorrhaphy, providing 6–8 h of postoperative analgesia . Similarly, subcutaneous ring block of the penis provides effective perioperative analgesia for circumcision procedures . Local anesthetic infiltration of the mesosalpinx significantly decreases the pain and cramping after laparoscopic tubal ligation procedures . Pain after arthroscopic shoulder surgery was decreased significantly by a simple suprascapular nerve block , and pain after knee surgery was minimized with a femoral nerve block . However, more complete perioperative analgesia for shoulder and knee surgery requires the use of an interscalene brachial plexus block and combined femoral, obturator, lateral femoral cutaneous, and sciatic nerve blocks, respectively. Although additional preparation time may be required when these major peripheral nerve blocks are performed before surgery, these block techniques can offer advantages in the postoperative period compared with general or spinal anesthesia .

It has been suggested that performing neural blockade with local anesthetics before the surgical incision may prevent the nociceptive input from altering the excitability of the central nervous system (e.g., preemptively blocking the N-methyl-D-aspartate-induced “wind up” phenomena and release of inflammatory mediators) . The concept of preemptive analgesia (or treating postoperative pain by preventing the establishment of central sensitization) seems very logical ; however, its clinical relevance has been questioned. Only one well controlled study has demonstrated any benefits of pre- versus postincisional local anesthetic administration in the ambulatory setting . A recent qualitative and quantitative review by Møiniche et al. suggested that evidence is still lacking that the timing of single-dose or continuous postoperative pain treatment is important in the management of postsurgical pain. These investigators concluded that there is no convincing evidence that preemptive treatment with centrally or peripherally administered local anesthetics, NSAIDs, opioid analgesics, or ketamine offers any advantage with respect to postoperative pain relief compared with a similar postsurgical analgesic regimen. Nevertheless, preincisional administration offers advantages over infiltration at the end of surgery with respect to intraoperative analgesia.

Preincisional infiltration with local anesthetics in combination with general anesthesia is clearly superior to general (or spinal) anesthesia alone in relieving postoperative pain . In fact, preincisional infiltration of the tonsillar bed with bupivacaine decreased both constant pain and pain on swallowing for up to 5 days after tonsillectomy procedures in children . Preincisional ilioinguinal hypogastric nerve block not only improves intraoperative pain control during inguinal hernia repair, but also reduces the need for oral opioid-containing analgesics after discharge . Although preincisional infiltration of the operative site with local anesthetics remains a popular technique for reducing the perioperative opioid analgesic requirement, other more simplified local anesthetic delivery systems (e.g., topical applications) have also been described in the anesthesia literature . Topical analgesia with lidocaine aerosol was found to be highly effective in decreasing pain, as well as the opioid analgesic requirement, after inguinal herniorrhaphy in adults , and instillation of 0.25% bupivacaine before surgical closure provided comparable postoperative pain relief to an ilioinguinal/iliohypogastric nerve block in children undergoing hernia repair . Furthermore, the simple application of topical lidocaine jelly or ointment is as effective as peripheral nerve blocks or parenteral opioids in providing pain relief after outpatient circumcision .

Intracavitary instillation of local anesthetics is another simple, yet effective, technique for providing pain relief during the early postoperative period after laparoscopic and arthroscopic procedures. Intraperitoneal administration of local anesthetics during laparoscopy was found to be an efficient method of reducing the intensity of postoperative scapular pain . However, when bupivacaine was injected at the preperitoneal fascial plane during extraperitoneal laparoscopic hernia repair, it did not reduce postoperative pain . Local anesthetics can also be injected into joint spaces to provide analgesia during and after arthroscopic surgery . In a placebo-controlled study, intraarticular instillation of 30 mL of 0.5% bupivacaine reduced the opioid requirements and facilitated early mobilization and discharge after knee arthroscopy . A follow-up study involving a combination of intraarticular bupivacaine and systemic ketorolac (60 mg IV or IM) further decreased pain in the early postoperative recovery period. A wide variety of adjuvants has also been injected into the intraarticular space to decrease postarthroscopic pain, including morphine, ketorolac, triamcinolone, and clonidine . Small-dose intraarticular morphine 1–3 mg, in combination with bupivacaine, seems to provide the longest lasting and most cost-effective analgesia after knee arthroscopy . Although administering the intraarticular morphine before knee surgery was reported to provide a longer duration of analgesia and greater opioid-sparing effects than when it was given at the end of surgery , the clinical advantages of preemptive analgesia remain controversial .

Local anesthetic supplementation clearly decreases the severity of incisional pain in the early postoperative period. However, outpatients may still experience significant pain after they have been discharged home because of difficulty in anticipating the degree of pain when the local anesthetic effect wears off. Continuous or intermittent perfusion of the surgical wound with local anesthetic solutions is an old-fashioned but highly effective technique for extending incisional pain relief into the postdischarge period. Recently, this technique has been modified to allow for patient-controlled local anesthetic administration after discharge home . However, some investigators have failed to find significant differences in pain scores or opioid analgesic requirements when the local anesthetic was instilled or injected at the incision site . The response to local analgesia appears to be influenced by the location, concentration, and volume of the injected local anesthetic solution. For example, Yndgaard et al. demonstrated that subfascially administered lidocaine was significantly more effective in reducing pain compared with subcutaneous injection after inguinal herniotomy. Finally, combining local anesthetic techniques with other analgesic modalities as part of multimodal (or “balanced”) analgesic therapy can improve pain control throughout the perioperative period . The concept of balanced analgesia consists of administering several different analgesic drugs to alter the pathophysiologic processes involved in nociception, thereby producing more effective 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.


NSAIDs NSAIDs have long been used for treating nonsurgical pain syndromes because of their well known antiinflammatory, antipyretic, and analgesic properties. However, with the

introduction of parenteral preparations of NSAIDs (e.g., ketorolac and diclofenac), these drugs have become more popular in the management of pain associated with ambulatory surgery. NSAIDs block the synthesis of prostaglandins by inhibiting the enzyme cyclooxygenase (COX), thereby reducing the production of mediators of the acute inflammatory response. By decreasing the inflammatory response to surgical trauma, NSAIDs have been alleged to reduce peripheral nociception. However, more recent studies also suggest that the central response to painful stimuli may be modulated by NSAID-induced inhibition of prostaglandin synthesis in the spinal cord .

Early reports suggested that NSAIDs possessed analgesic properties comparable to those of opioid analgesics without opioid-related side effects . When ketorolac was administered as an adjuvant to propofol/nitrous oxide anesthesia, its use was associated with improved postoperative analgesia and patient comfort, which compared favorably to fentanyl . Moreover, ketorolac was associated with a decreased incidence of postoperative nausea and vomiting, and patients tolerated oral fluids and were judged fit for discharge earlier than those receiving opioid compounds. Other investigators have also reported that ketorolac provided similar postoperative pain relief to that of fentanyl but was associated with less nausea and somnolence and an earlier return of bowel function after ambulatory surgery . Furthermore, it was recently reported that the administration of ketorolac (30 mg) at the incision site to supplement local anesthesia resulted in significantly less postoperative pain, a better quality of recovery, and earlier discharge compared with local anesthesia alone . However, when ketorolac was substituted for or combined with fentanyl during outpatient gynecologic and laparoscopic surgical procedures, the beneficial effects of the NSAID were more variable .

Use of shock-wave lithotripsy to evaluate the effect of NSAIDs on visceral pain, diclofenac produced only a marginal opioid-sparing effect . Furthermore, when diclofenac (1 mg/kg IV) was administered before outpatient arthroscopic surgery, it was found to be associated with similar visual analog pain scores to fentanyl (1 mg/kg IV) . After gynecologic laparoscopy surgery , diclofenac decreased pain and analgesic requirements for 24 h postoperatively but had little effect on the recovery profile. Similarly, the administration of ketorolac during the perioperative period in outpatients undergoing laparoscopic cholecystectomy procedures decreased postoperative opioid requirements, but this contributed to only a marginal improvement in ventilatory function at 4 hr after the operation.

When diclofenac was administered preoperatively to pediatric patients, both the incidence of restlessness and crying and the postoperative opioid requirements were lower in the diclofenac-treated (versus acetaminophen-treated) patients . Oral ketorolac (1 mg/kg) compared favorably to small-dose acetaminophen (10 mg/kg) for bilateral myringotomy procedures in children, with the ketorolac-treated patients recording lower pain scores and requiring less analgesic medication in the early postoperative period . In children undergoing inguinal hernia repair , ketorolac (1 mg/kg IV) compared favorably to caudal bupivacaine 0.2% with respect to pain control and postoperative side effects. In fact, the ketorolac-treated patients had an improved recovery profile, including less vomiting, shorter times to voiding and ambulation, and earlier discharge home. Furthermore, the intraoperative administration of ketorolac as an adjuvant to general anesthesia in pediatric patients provided postoperative analgesia comparable to morphine . As expected, the ketorolac-treated patients experienced less postoperative nausea and vomiting. When ketorolac or morphine are administered for pain control in pediatric patients, ketorolac-induced analgesia develops more slowly but is longer lasting compared with morphine .

Oral or rectal administration of NSAIDs can also be highly effective in the prophylactic management of pain after ambulatory surgery. For example, when oral naproxen was administered before laparoscopic surgery, postoperative pain scores, opioid requirements, and time to discharge were significantly reduced . Furthermore, premedication with oral ibuprofen (800 mg) was associated with superior postoperative analgesia and less nausea compared with fentanyl (75 mg IV) . However, the more important role for oral NSAIDs is in the postdischarge period. In a recent outpatient study involving the use of a multimodal analgesic technique consisting of alfentanil, lidocaine, ketorolac, and paracetamol , oral ibuprofen (800 mg every 8 h) was equianalgesic to paracetamol 800 mg plus codeine 60 mg (every 8 h) when administered during the first 72 h after discharge, and it resulted in better global patient satisfaction and less constipation than the opioid-containing oral analgesic. To achieve the optimal benefit of using NSAIDs in the perioperative period, these compounds should be continued as prophylactic analgesics for preventive pain management in the postdischarge period .


COX-2 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.


Acetaminophen (Paracetamol) Of the nonopioid analgesics, acetaminophen is potentially one of the most useful, yet it

is vastly underused in the ambulatory setting. When administered in an appropriate oral or rectal dose, acetaminophen can be a very useful adjuvant during the perioperative period and compares favorably to the NSAIDs in children . Although Watcha et al. reported minimal analgesic-sparing effects after a 10 mg/kg dose of acetaminophen, Rusy et al. found that a larger dose (35 mg/kg per rectum) was as effective as ketorolac 1 mg/kg IV in reducing pain after tonsillectomy procedures and was associated with less postoperative bleeding than the NSAID. More recently, Korpela et al. demonstrated that the opioid-sparing effect of acetaminophen was strictly dose related. The optimal dosing regimen for acetaminophen in children consists of a preoperative initial loading dose of 40 mg/kg followed by a maintenance dose of 20 mg/kg every 6–8 h during the early postoperative period .

An IV formulation of acetaminophen, known as propacetamol, has been administered to adults as an alternative to ketorolac in the perioperative period . Propacetamol is a prodrug that is rapidly and completely hydrolyzed by nonspecific plasma esterases to form acetaminophen (also known as paracetamol). Although the future role of this non-opioid parenteral analgesic during the perioperative period is yet to be determined, rectal acetaminophen (1.3 g) has been successfully used as an adjuvant to NSAIDs and local anesthetics in adult outpatients as part of a multimodal fast-tracking protocol


Ketamine Ketamine is a unique anesthetic with analgesic-like properties which has been

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


Nonpharmacologic Techniques Nonpharmacologic “electroanalgesic” techniques (e.g., transcutaneous electrical nerve

stimulation [TENS], acupuncture-like TENS, and percutaneous neuromodulation therapy) can also be used as adjuvants in the treatment of both acute and chronic pain in the ambulatory setting . Given the inherent side effects produced by both opioid and non-opioid analgesics (), it is possible that nonpharmacologic approaches will assume a more prominent role in the management of pain after ambulatory surgery in the future.

Most studies suggest that TENS produces a 15%–30% decrease in the postoperative opioid requirement . In addition to reporting that TENS reduces pain and the need for oral analgesics, Jensen et al. reported a more rapid recovery of joint mobility after outpatient arthroscopic surgery. In reviewing the medical literature, Carroll et al. found conflicting results regarding the effect of TENS on the requirement for opioid analgesic medication and the quality of postoperative pain relief. Several studies suggest that the location, intensity, and frequency of electrical stimulation are all important factors influencing the efficacy of TENS (and acupuncture-like TENS) therapies . Moreover, the clinical efficacy of electroanalgesic techniques remains controversial because of the potential sources of bias and difficulty in quantifying the inherent placebo effect of the therapy. Other nonpharmacologic approaches that have also been evaluated as potentially useful analgesic adjuvants in the perioperative period include cryoanalgesia, ultrasound, laser, and even hypnosis . However, additional well controlled clinical studies are needed to establish the benefits of these nonpharmacologic modalities on patient outcome after ambulatory surgery.


White PF .The role of non-opioid analgesic techniques in the management of pain after ambulatory surgery.

Anesth AnaIg 2002;94:577-85


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


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


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

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