Skip Navigation LinksHome > January 2014 - Volume 118 - Issue 1 > Consensus Guidelines for the Management of Postoperative Nau...
Anesthesia & Analgesia:
doi: 10.1213/ANE.0000000000000002
Ambulatory Anesthesiology: Special Article

Consensus Guidelines for the Management of Postoperative Nausea and Vomiting

Gan, Tong J. MD, MHS, FRCA*; Diemunsch, Pierre MD, PhD; Habib, Ashraf S. MB, FRCA*; Kovac, Anthony MD; Kranke, Peter MD, PhD, MBA§; Meyer, Tricia A. PharmD, MS, FASHP; Watcha, Mehernoor MD; Chung, Frances MBBS#; Angus, Shane AA-C, MS**; Apfel, Christian C. MD, PhD††; Bergese, Sergio D. MD‡‡; Candiotti, Keith A. MD§§; Chan, Matthew TV MB, BS, FANZCA‖‖; Davis, Peter J. MD¶¶; Hooper, Vallire D. PhD, RN, CPAN, FAAN##; Lagoo-Deenadayalan, Sandhya MD, PhD***; Myles, Paul MD†††; Nezat, Greg CRNA, CDR, USN, PhD§§§; Philip, Beverly K. MD‖‖‖; Tramèr, Martin R. MD, DPhil¶¶¶

Free Access
Supplemental Author Material
Continuing Medical Education
Article Outline
Collapse Box

Author Information

From the *Department of Anesthesiology, Duke University Medical Center, Durham, North Carolina; Service d’Anesthésiologie–Réanimation Chirurgicale, CHU de Hautepierre, and EA 3072, Faculté de Médecine, Strasbourg, France; Department of Anesthesiology, University of Kansas Medical Center, Kansas City, Kansas; §Department of Anesthesiology, University of Wuerzburg, Wuerzburg, Germany; Department of Pharmacy/Anesthesiology, BaylorScott & White Health, Temple, Texas Department of Anesthesiology & Pediatrics, Texas Children’s Hospital, Baylor College of Medicine, Houston, Texas; #Department of Anesthesia, Toronto Western Hospital, University Health Network, University of Toronto, Toronto, Ontario, Canada; **Department of Anesthesiology and Perioperative Medicine, Case Western Reserve University School of Medicine, Washington, District of Columbia; ††Department of Anesthesia and Perioperative Care, UCSF Medical Center at Mt. Zion, San Francisco, California; ‡‡Department of Anesthesiology, Wexner Medical Center, Ohio State University, Columbus, Ohio; §§Department of Anesthesiology, Perioperative Medicine, and Pain Management, University of Miami, Miami, Florida; ‖‖Department of Anaesthesia and Intensive Care, The Chinese University of Hong Kong, Shatin, New Territories, Hong Kong; ¶¶Department of Anesthesia, Children’s Hospital of Pittsburgh of UPMC, Pittsburgh, Pennsylvania; ##System Nursing Education and Research, Mission Health System, Asheville, North Carolina; ***Department of Surgery, Duke University Medical Center, Durham, North Carolina; †††Department of Anaesthesia and Perioperative Medicine, Alfred Hospital; Academic Board of Anaesthesia and Perioperative Medicine, Monash University, Melbourne, Australia; §§§Naval Medical Center Portsmouth, Porstmouth, Virginia; ‖‖‖Department of Anesthesiology, Perioperative and Pain Medicine, Brigham and Women’s Hospital, Harvard Medical School, Boston, Massachusetts; and ¶¶¶Division of Anaesthesiology, Geneva University Hospitals, Geneva, Switzerland.

Accepted for publication September 13, 2013.

Supplemental digital content is available for this article. Direct URL citations appear in the printed text and are provided in the HTML and PDF versions of this article on the journal’s Web site.

Funding: Not funded.

Conflicts of Interest: See Disclosures at the end of the article.

Reprints will not be available from the authors.

Address correspondence to Tong J. Gan, MD, Department of Anesthesiology, Duke University Medical Center, PO Box 3094, Durham, NC 27710. Address e-mail to tjgan@duke.edu.

Collapse Box

Abstract

The present guidelines are the most recent data on postoperative nausea and vomiting (PONV) and an update on the 2 previous sets of guidelines published in 2003 and 2007. These guidelines were compiled by a multidisciplinary international panel of individuals with interest and expertise in PONV under the auspices of the Society for Ambulatory Anesthesia. The panel members critically and systematically evaluated the current medical literature on PONV to provide an evidence-based reference tool for the management of adults and children who are undergoing surgery and are at increased risk for PONV. These guidelines identify patients at risk for PONV in adults and children; recommend approaches for reducing baseline risks for PONV; identify the most effective antiemetic single therapy and combination therapy regimens for PONV prophylaxis, including nonpharmacologic approaches; recommend strategies for treatment of PONV when it occurs; provide an algorithm for the management of individuals at increased risk for PONV as well as steps to ensure PONV prevention and treatment are implemented in the clinical setting.

Back to Top | Article Outline

WHAT OTHER GUIDELINES ARE AVAILABLE ON THIS TOPIC?

Several guidelines on the management of postoperative nausea and vomiting (PONV) have been published.1–7 Among them, 2 were the previous versions of the present guidelines by the same group, published in 2003 and 2007.1,2 One set of guidelines was published by the American Society of Perianesthesia Nurses in 20063 and another published in the Canadian Journal of Obstetrics and Gynaecology in 2008.6 Subsequently, 3 PONV guidelines were published in the French, Spanish, and German language.4,5,7 A recent update on practice guidelines for postoperative care was published by the American Society of Anesthesiologists task force on postoperative care.8

Back to Top | Article Outline

WHY WAS THIS GUIDELINE DEVELOPED?

The goal of the current guidelines is to provide current and comprehensive information to practicing physicians, nurse anesthetists, anesthesiologist assistants, pharmacists, perianesthesia, perioperative and ward nurses as well as other health care providers about strategies to prevent and treat PONV in adults and children undergoing surgery.

Back to Top | Article Outline

HOW DOES THIS GUIDELINE DIFFER FROM EXISTING GUIDELINES?

A systematic literature search yielded several hundred publications on PONV since the 2007 Society for Ambulatory Anesthesia PONV guidelines, and a number of new antiemetics were introduced along with additional new data on PONV risk assessment and management strategies. The present guidelines are the most recent data on PONV and an update on 2 previous sets of guidelines published in 2003 and 2007 by the same group.1,2 The 2 guidelines published in 2006 and 2008 focused primarily on perianesthesia nurses and gynecologists and did not have up-to-date information on the management of PONV.3,6 The other 3 guidelines were published in non-English language.4,5,7 The scope of the postoperative care guidelines published by the American Society of Anesthesiologists were broad, covering patient assessment, monitoring, and overall management of patients after anesthesia, and recommendations on the risk assessment and management of PONV were not adequately addressed.8

Back to Top | Article Outline

WHY DOES THIS GUIDELINE DIFFER FROM EXISTING GUIDELINES?

The present guidelines include new information on PONV risk factors; a risk scoring system for postdischarge nausea and vomiting; recommendations on new antiemetics, for example, neurokinin-1 receptor antagonists; changes in recommendations from previous guidelines based on new published information on efficacy and risk of antiemetics, including new data on QT prolongation; recommendation on a new antiemetic combination strategy and a multimodal prevention approach in adults and children to prevent PONV and implementation of PONV prevention and treatment strategies in the clinical setting.

Postoperative nausea and vomiting (PONV) are common and distressing to patients. The general incidence of vomiting is about 30%, the incidence of nausea is about 50%, and in a subset of high-risk patients, the PONV rate can be as high as 80%.9–11 Unresolved PONV may result in prolonged postanesthesia care unit (PACU) stay and unanticipated hospital admission that result in a significant increase in overall health care costs.12–14 The goal of PONV prophylaxis is therefore to decrease the incidence of PONV and thus patient-related distress and reduce health care costs.12–15

Several guidelines on the management of PONV have been published.1–7 However, they are either in non-English language,4,5,7 targeted for a specific surgical population,6 or have not been updated in recent years.1–3 A recent update by the American Society of Anesthesiologists task force on postoperative care published practice guidelines for postoperative care.8 Because the scope of the guidelines was broad, covering patient assessment, monitoring, and overall management of patients after anesthesia, and recommendations on the risk assessment and management of PONV were not adequately addressed. The present guidelines are the most recent data on PONV and an update on the 2 previous sets of guidelines published in 2003 and 2007.1,2 A systematic literature search yielded several hundred publications on PONV since the 2007 guidelines, and a number of new antiemetics were introduced along with new data on PONV management strategies. This update includes new information on PONV risk factors including a risk scoring system for postdischarge nausea and vomiting (PDNV); recommendations on new antiemetics, for example, neurokinin-1 receptor antagonists; changes in recommendations from previous guidelines based on new published information on efficacy and risk of antiemetics, including new data on QT prolongation; recommendation on a new antiemetic combination strategy and a multimodal prevention approach in adults and children to prevent PONV; implementation of PONV prevention and treatment strategies in the clinical setting and a future research agenda for PONV management. The new information is outlined at the beginning of each guideline. The goal of the current guidelines is to provide current and comprehensive information to practicing physicians, nurse anesthetists, anesthesiologist assistants, pharmacists, perianesthesia, perioperative and ward nurses as well as other health care providers about strategies to prevent and treat PONV in adults and children undergoing surgery.

Back to Top | Article Outline

ESTABLISHMENT OF EXPERT GUIDELINES

The present guidelines were developed under the auspices of the Society for Ambulatory Anesthesia. While the previous 2 sets of guidelines were funded through educational grants, this update received no outside funding. Neither the society nor the experts received any funding from industry for this work. Panel members gathered during a Society for Ambulatory Anesthesia midyear meeting, a day before the commencement of the American Society of Anesthesiologists annual meeting. The primary author convened a multidisciplinary international panel of individuals, some of whom had previously developed the first and second guidelines,1,2 and sought additional experts from other health care disciplines. The panel selections were based on significant expertise in this area of research and representation in professional societies with an interest in the management of PONV. Panel members were asked to review the medical literature on PONV (starting from 2007). Working in groups, the participants researched a specific topic and presented evidence-based data to the group, who discussed the evidence and reached consensus on its inclusion in the guidelines. When full agreement could not be obtained, the majority view was presented, and the lack of full agreement was stated.

Back to Top | Article Outline

METHODS

We followed the guideline development process similar to that published in 2007.2 A systematic review of the literature concerning PONV management in adult and pediatric patients undergoing surgery was conducted according to the protocol recommended by the Cochrane Collaboration.16 We searched the Cochrane Controlled Trials Register, the Cochrane Library, MEDLINE, and EMBASE from January 2007 to October 2011. A reference librarian and a coauthor (FC) familiar with literature search protocol of the Cochrane Collaboration (Marina Englesakis, Toronto, Ontario, Canada) designed and conducted the electronic search strategy with input from members of the consensus panel. The search was divided into 6 areas: algorithms, prophylaxis, treatment effectiveness, nonpharmacological or alternative therapy, risk assessment, and risk reduction. The Medline search on algorithm of PONV protocols yielded 171 titles, prophylaxis 433 titles, treatment effectiveness 567 titles, and nonpharmacological or alternative therapy 320 titles. The search on risk assessment of PONV yielded 564 titles and risk reduction 549 titles. The search strategy and the keywords used are presented in Appendix 1 (see Supplemental Digital Content 1, http://links.lww.com/AA/A688). We hand-searched the reference lists from the already retrieved articles to identify further trials. The search was limited to human trials but not limited by language. The librarian deleted duplicate records. Clinical studies reported by Fujii et al were excluded due to research misconduct.17 The search results were screened by the authors in a stepwise manner to identify the eligible studies. In the first step, we screened the titles, and irrelevant papers were excluded. In the next step, we read the abstract or full text of the papers for inclusion. The number of and reason for excluded studies in this step were recorded. We selected all reviews, trials, or randomized controlled trials (RCTs) on PONV management (Appendix 1, see Supplemental Digital Content 1, http://links.lww.com/AA/A688).

Back to Top | Article Outline
Goals of Guidelines

The panel defined the following goals for the guidelines: (1) Understand who is at risk for PONV in adults and postoperative vomiting (POV) in children; (2) Establish factors that reduce the baseline risks for PONV; (3) Determine the most effective antiemetic single drug and combination therapy regimens for PONV/POV prophylaxis, including pharmacologic and nonpharmacologic approaches; (4) Ascertain the optimal approach to treatment of PONV and PDNV with or without PONV prophylaxis; (5) Determine the optimal dosing and timing of antiemetic prophylaxis; (6) Evaluate the cost-effectiveness of various PONV management strategies; (7) Create an algorithm to identify individuals at increased risk for PONV and suggest effective treatment strategies; and (8) Propose a research agenda for future studies.

Back to Top | Article Outline
Scientific Evidence Grading

A number of grading systems have been proposed to characterize the strength of evidence of the RCTs and observational studies supporting a treatment. The panel decided to use a scientific evidence grading system previously used by the American Society of Anesthesiologists in their practice guidelines for acute pain management in the perioperative setting (Appendix 2).18 Study findings from published scientific literature were aggregated and are reported in summary form by evidence category, as described below. All literature (e.g., RCTs, observational studies, case reports) relevant to each topic was considered when evaluating the findings.

Back to Top | Article Outline
Guideline 1. Identify Patients’ Risk for PONV

New information: Additional studies identify the younger age group (<50 years) as a significant risk factor for PONV (odds ratio, OR; 95% confidence interval [CI]): 1.79 (1.39–2.30) compared with those who are 50 years or older.19 Type of surgery as a risk factor is still debated. New evidence suggests that cholecystectomy: 1.90 (1.36–2.68), gynecological surgery: 1.24 (1.02–1.52), and laparoscopic: 1.37 (1.07–1.77) approach are associated with a higher incidence of PONV when compared with general surgery as a reference group.20 The contribution of intraoperative opioids to PONV is weak, and there is no difference among the different opioids. A recent meta-analysis reaffirmed previously known PONV risk factors but with somewhat different order of importance. Female gender was the strongest patient-specific predictor (OR 2.57, 95% CI, 2.32–2.84), followed by a history of PONV (2.09, 1.90–2.29), nonsmoking status (1.82, 1.68–1.98), history of motion sickness (1.77, 1.55–2.04), and age (0.88 per decade, 0.84–0.92). The use of volatile anesthetics was the strongest anesthesia-related predictor (1.82, 1.56–2.13), followed by the duration of anesthesia (1.46 h−1, 1.30–1.63), postoperative opioid use (1.47, 1.31–1.65), and nitrous oxide (1.45, 1.06–1.98).19,20

PDNV is a major concern for the anesthesia care provider with the growth in ambulatory surgeries. A new validated simplified risk score for adults for PDNV includes the risk factors of female sex, age <50 years, history of PONV, opioid use in PACU, and nausea in PACU.19

A simplified risk score for PONV in adults is shown in Table 1 and Figure 1. A simplified risk score for PDNV in adults is shown in Figure 2. A simplified risk score for POV in children is shown in Figure 3.

Table 1
Table 1
Image Tools
Figure 1
Figure 1
Image Tools
Figure 2
Figure 2
Image Tools
Figure 3
Figure 3
Image Tools
Back to Top | Article Outline
Patient Risk Assessment for PONV

A number of risk factors have been associated with an increased incidence of PONV. However, some of these factors may be only simple associations. For objective risk assessment, it is recommended to focus on those that independently predict PONV after accounting for other confounding factors. We identified those independent risk factors that remain significant in multivariable analyses of large cohort studies (Table 1).

The most likely causes of PONV are volatile anesthetics, nitrous oxide, and postoperative opioids.21,22 The effect of volatile anesthetics on PONV is dose-dependent and particularly prominent in the first 2 to 6 hours after surgery.21 Irrespective of the specific drug given,23,24 postoperative opioids also increase the risk for PONV in a dose-dependent manner,25 and this effect appears to last for as long as opioids are used for pain control in the postoperative period.19 This most likely explains why the incidence of PONV is lower with opioid-free regional anesthesia26 and reduced opioid consumption through the use of non-opioid analgesics,27 perioperative alpha-2 agonists,28 and beta-blockers.29

Despite the triggers mentioned above, many patients do not experience PONV, most likely because the development of PONV also depends on the individual patient’s susceptibility.30 Patient-specific risk factors for PONV in adults include female sex, a history of PONV and/or motion sickness, nonsmoking status, and young age.9–11,19,21,31,32 Type of surgery is strongly believed to be a risk factor for PONV, yet it is difficult to prove that it is an independent risk factor. Certain types of surgery may be associated with a frequent incidence of PONV (e.g., abdominal surgeries), not because of a specific emetogenic pathway, but could be as a result of a long exposure to general anesthesia and higher doses of opioids. More recent studies suggest laparoscopic, gynecological surgery, and cholecystectomy are risk factors that independently increase the risk for PONV.11,21,31,33–35 However, the reference groups used differed widely among studies, which may have led to a bias toward positive results.

Evidence for other commonly believed risk factors is either: (1) Not clinically relevant for the prediction of PONV (e.g., anxiety),36 (2) Uncertain (e.g., menstrual cycle,37 neostigmine,38,39 and perioperative fasting),40 or (3) Disproven (e.g., nasogastric tube, obesity, and supplemental oxygen).41–43

Back to Top | Article Outline
Risk Score

Like all drugs, antiemetics carry some risk for adverse effects, which range in severity from mild headache to possibly more meaningful QTc prolongations that may rarely be associated with cardiac arrest.44 Therefore, a patient’s baseline risk for PONV should be objectively assessed using a validated risk score that is based on independent predictors, so the number and choice of prophylactic antiemetics can be titrated against the patient’s risk.

Even though there is strong evidence for a couple of truly independent risk factors for PONV, none of those risk factors taken alone as a single predictor is clinically sufficient for a risk assessment or to make clinical decisions about the need for prophylactic antiemetics.21 Therefore, a patient’s baseline risk for PONV should be objectively assessed using a validated risk score that is based on these independent predictors. Indeed, use of PONV risk scores has been demonstrated to significantly reduce the institutional rate of PONV.45–47 The 2 most commonly used risk scores for inpatients undergoing balanced inhaled anesthesia are the Koivuranta score and the Apfel score.9,10 The Apfel simplified risk score is based on 4 predictors: female sex, history of PONV and/or motion sickness, nonsmoking status, and use of postoperative opioids (Fig. 1).9 The incidence of PONV with the presence of 0, 1, 2, 3, and 4 risk factors is about 10%, 20%, 40%, 60%, and 80%, respectively.9 The panel considers patients with 0–1, 2 or 3, and more risk factor as “low,” “medium,” and “high” risk categories, respectively.

Given that several antiemetics are now generic and inexpensive, some experts suggest it may be appropriate to give 1 or 2 antiemetics to all patients. However, this strategy puts the low-risk patients at unnecessary risk for rare but well-described side effects. Although risk scores are an objective approach to assessing the patient’s risk for PONV or PDNV, they are not completely predictive, with sensitivity and specificity of between 65% and 70%. In addition, other clinically relevant aspects should also be taken into consideration by the anesthesia care provider, such as whether vomiting would pose a significant medical risk, for example, in patients with wired jaws, increased intracranial pressure, and after gastric or esophageal surgery.

Because ambulatory procedures are typically shorter and less invasive than inpatient procedures, they are associated with a lower risk of PONV in the PACU.19 However, PDNV presents a significant risk to discharged patients who, by definition, no longer have access to fast-onset IV antiemetics or monitored care. A recent study on 2170 U.S. outpatients reported that the incidence of PDNV is 37% in the first 48 hours after discharge and identified 5 independent predictors of PDNV including female sex, age<50 years, history of PONV, opioid use in the PACU, and nausea in the PACU.19 Validation of a simplified PDNV risk score based on these risk factors showed that the incidence of PDNV with 0, 1, 2, 3, 4, or 5 of these risk factors was about 10%, 20%, 30%, 50%, 60%, and 80%, respectively (Fig. 2).19

Back to Top | Article Outline
Assessment for POV in Children

In the 2007 Guidelines,2 we referred to a single center study by Eberhart et al.48 who identified 4 independent predictors of POV in children: duration of surgery >30 minutes; age >3 years; history of POV in patient, parent, or sibling; and strabismus surgery. Based on the presence of 0, 1, 2, 3, and 4 factors, the risk of POV was 9%, 10%, 30%, 55%, and 70%, respectively (Fig. 3). Kranke et al.49 performed an external validation of this score in a different institution in children not undergoing strabismus surgery. They noted the actual incidence of POV when prophylaxis was not used was 3.4%, 11.6%, 28.2%, and 42.3%, respectively in the presence of 0, 1, 2, or 3 factors. These findings support the earlier recommendation of using a simplified score to estimate the child’s risk of POV.

Back to Top | Article Outline
Guideline 2. Reduce Baseline Risk Factors for PONV

New Information: Minimization of neostigmine dosage has been removed from the list of strategies to reduce baseline risk as new evidence did not find this to be helpful, and the evidence is contradictory. In children, subhypnotic doses of propofol infusion in combination with an antiemetic significantly reduce incidence of PONV.50,51

Approaches for decreasing baseline risk factors are presented in Table 2.

Table 2
Table 2
Image Tools
Back to Top | Article Outline

DISCUSSION

Reducing baseline risk factors can significantly decrease the incidence of PONV. Strategies recommended to reduce baseline risk include: (1) The avoidance of general anesthesia by the use of regional anesthesia; (2) Preferential use of propofol infusions; (3) Avoidance of nitrous oxide; (4) Avoidance of volatile anesthetics; (5) Minimization of perioperative opioids; and (6) Adequate hydration (Table 2).2

Use of regional anesthesia was associated with a lower incidence of PONV than general anesthesia in both children and adults.11,52 Sinclair et al.11 found the risk for PONV was 9 times less among patients receiving regional anesthesia than those receiving general anesthesia. When general anesthesia was required, use of propofol for induction and maintenance of anesthesia decreased the incidence of early PONV (occurring within the first 6 hours; number-needed-to-treat [NNT] = 5).53

The IMPACT study evaluated 6 strategies to reduce PONV in 5199 high-risk patients.47 They found that a combination of propofol and air/oxygen (total IV anesthesia [TIVA]) had additive effects, reducing PONV risk by approximately 25%.47 These findings are supported by 2 meta-analyses demonstrating that avoiding nitrous oxide reduced PONV risk54,55 and a randomized, placebo-controlled trial showing that volatile anesthetics were the primary cause of early PONV (0–2 hours after surgery), but that they did not have an impact on delayed PONV (2–24 hours after surgery).21 However, nitrous oxide had little impact when the baseline risk for PONV is low.55

Baseline risk for PONV can also be reduced by minimizing postoperative opioids.9,21,25,54,56–58 To achieve satisfactory analgesia without opioids, alternate modalities of pain management may be used. RCTs and meta-analyses show that perioperative nonsteroidal anti-inflammatory drugs (NSAIDs) and cyclooxygenase-2 inhibitors27,59,60 and less so intraoperative ketamine61 may have a morphine-sparing effect in the postoperative period. The decrease in opioid consumption using opioid analgesic adjuncts has been demonstrated to decrease the incidence of opioid-related nausea and vomiting.62

Reducing the dose or avoiding neostigmine had been shown to reduce the baseline risk for PONV. Meta-analyses demonstrate that high-dose neostigmine (>2.5 mg) was associated with increased PONV and that reducing the dose can decrease PONV risk.39,63 However, more recent data disputed the clinical importance of neostigmine’s effects on PONV.38 Hence, minimization of neostigmine dosage has been removed from the list of strategies to reduce the baseline risk.

Systematic reviews of RCTs show that supplemental oxygen had no effect on nausea or overall vomiting, although it may reduce the risk of early vomiting.64 As a result, supplemental oxygen is not recommended for the prevention of PONV in these guidelines.

A number of recently published studies demonstrate that reducing baseline risk factors is also effective for decreasing the incidence of POV in children. In the pediatric patient population, regional anesthesia is usually performed while the child is receiving general anesthesia to reduce stress associated with inserting needles. A major benefit of a combined general and regional anesthetic technique is the reduction in perioperative opioid requirements and consequently, reduced postoperative emesis. Children randomized to a wrist block during hand surgery had less emesis than those receiving perioperative opioids.65 Similarly, children receiving a peribulbar block or topical lidocaine during strabismus repair had less emesis than a control group.66 In another study, there were fewer incidents of POV when children receive a bupivacaine-induced subtenon block during strabismus surgery compared with a sham block with saline.67 However, in a study of children undergoing cataract surgery, the reduction in emesis rates in those receiving a subtenon block with a lidocaine–bupivacaine mixture did not reach statistical significance, although this group had significantly less pain and drowsiness and required less rescue analgesia compared with those receiving a sham block.68

The benefit of propofol infusions during tonsillectomies in pediatric patients has been studied.50,51 Children receiving intraoperative propofol in subhypnotic doses (bolus of 1 mg/kg followed by an infusion at 20 mcg/kg/min) combined with dexamethasone had less emesis than those receiving dexamethasone alone.50 Similarly, treatment with a combination of subhypnotic propofol and tropisetron provided better prophylaxis against POV than tropisetron alone in this patient population.51

NSAIDs are used in the perioperative period with the aim of reducing opioid requirements, but there are concerns about increased postoperative bleeding with their use. In a systematic review, Cardwell et al.69 concluded that NSAIDs do not increase bleeding after tonsillectomy/adenoidectomy procedures. In 12 trials evaluating the effect of NSAIDS on POV in 928 children, less emesis was noted in the treated groups (OR 0.49, 95% CI, 0.29–0.83).

Adequate hydration is another simple strategy to reduce emesis. Goodarzi et al.70 showed that high dose IV fluids at 30 mL/kg were associated with less emesis than the standard 10 mL/kg therapy during strabismus repair. However, routine gastric decompression and limiting oral intake after surgery were ineffective in reducing emesis in the postoperative period in children.71–73

Back to Top | Article Outline
Guideline 3. Administer PONV Prophylaxis Using 1 to 2 Interventions in Adults at Moderate Risk for PONV

New Information: Clinically approved drugs that are new or with further studies since the last guidelines are: (1) 5HT3 receptor antagonists: ramosetron and palonosetron; (2) NK-1 receptor antagonist: aprepitant, casopitant, and rolapitant; (3) corticosteroid: methylprednisolone; (4) butyrophenone: haloperidol; and (5) antihistamine: meclizine. Concerns have been raised regarding the effects of the first generation 5HT3 receptor antagonists on the QTc interval. Dolasetron is no longer marketed in the United States because of its risk of QTc prolongation and torsade de pointes. However, the use of droperidol in combination with a 5HT3 receptor antagonist, such as ondansetron, did not increase the risk of QT prolongation. Recent studies raised concerns about the effect of dexamethasone on postoperative infection and blood glucose levels 6 to 12 hours postoperatively.

Strategies not evaluated in the 2007 guidelines and found to be not effective for PONV prophylaxis include music therapy, isopropyl alcohol inhalation, intraoperative gastric decompression, the proton pump inhibitor esomeprazole, ginger root, nicotine patch to nonsmokers, cannabinoids (nabilone and tetra-hydrocannabinol), and intraoperative supplemental oxygen. Morindal citrofolin linn (noni fruit) showed effectiveness in reducing early postoperative nausea. A small dose (2 mg) of midazolam when given toward the end of surgery is effective in reducing PONV. Since the publication of the last guideline, a new meta-analysis on P6 stimulation has been published. The timing of acupoint P6 electrical stimulation did not impact PONV with similar reductions in PONV achieved when the stimulation was initiated either before or after anesthesia induction. Neuromuscular stimulation over the median nerve reduced PONV in the early postoperative period, particularly when tetanic stimulation was used. While adequate IV fluid hydration was effective to reduce PONV, the type of fluid (crystalloid versus colloid) did not have an effect on PONV when similar volumes were used in surgeries with minimal fluid shifts.

Prophylactic doses and timing for administration of antiemetics in adults are shown in Table 3. A treatment algorithm is presented in Figure 4.

Table 3
Table 3
Image Tools
Figure 4
Figure 4
Image Tools
Back to Top | Article Outline

DISCUSSION

The recommended pharmacologic antiemetics for PONV prophylaxis in adults include the 5-hydroxytryptamine (5-HT3) receptor antagonists (ondansetron, dolasetron, granisetron, tropisetron, ramosetron, and palonosetron), neurokinin-1 (NK-1) receptor antagonists (aprepitant, casopitant, and rolapitant), corticosteroids (dexamethasone and methylprednisolone), butyrophenones (droperidol and haloperidol), antihistamines (dimenhydrinate and meclizine), and anticholinergics (transdermal scopolamine [TDS]). While PONV prevention is recommended in a subset of patients, current evidence does not support giving prophylactic antiemetics to all patients who undergo surgical procedures. However, with more inexpensive generics becoming available, properly conducted cost-effectiveness (C/E) studies need to be done to support the more universal use of prophylactic antiemetics. Ondansetron 4 mg, droperidol 1.25 mg, and dexamethasone 4 mg were equally effective, and each independently reduced PONV risk by approximately 25%.47 The recommended doses and timing of these drugs are listed in Table 3. Recommendations given are evidence based, and not all the drugs have a Food and Drug Administration (FDA) indication for PONV.

Back to Top | Article Outline
5-HT3 Receptor Antagonists
Ondansetron

Most of the available research on the 5-HT3 receptor antagonists involves ondansetron, which has greater antivomiting than antinausea effects. Ondansetron is the “gold standard” compared with other antiemetics. It has a recommended dose of 4 mg, a NNT of approximately 6 for prevention of vomiting (0–24 hours), and a NNT of approximately 7 for prevention of nausea.74 The effect of the ondansetron 8 mg oral disintegrating table is equivalent to the 4 mg IV dose.75,76 Ondansetron is as effective as other 5-HT3s74 including ramosetron 0.3 mg.77 It is also as effective as dexamethasone47 and haloperidol 1 mg IV,78–80 with no difference in effect on the QTc interval.81 However, it is less effective than aprepitant81 for reducing emesis and palonosetron for the incidence of PONV.82

Back to Top | Article Outline
Dolasetron

Prospective RCTs show a prophylactic dose of 12.5 mg dolasetron effectively prevents PONV.83–85 That prophylactic dose is as effective as ondansetron 4 mg.86,87 Other data show dolasetron is more effective than droperidol in preventing PONV after surgery for prognathism.88 A study by Janicki et al.89 found granisetron is more effective in preventing PONV than dolasetron. These differences may be due to duplication of the CYP2D6 allele causing ultrarapid metabolism of dolasetron. In December 2010, the FDA announced that IV dolasetron should no longer be used for chemotherapy-induced nausea and vomiting in adults and children because of concerns of QT prolongation and torsade de pointes.90 At present, dolasetron is no longer marketed in the United States but may be available in other countries.

Back to Top | Article Outline
Granisetron

Granisetron, 0.35 to 3 mg IV (5–20 mcg/kg), is as effective as other first generation 5HT3 receptor antagonists.91–93 Granisetron, 3 mg IV, is also as effective as dexamethasone 8 mg, and the combination is better than either drug alone.94 Similarly, granisetron 1 mg plus cyclizine 40 mg is more effective than granisetron 1 mg or cyclizine 50 mg alone.95 However, compared with palonosetron 0.075 mg, granisetron 2.5 mg is as effective at 3 hours and 3 to 24 hours but less effective at 24 to 48 hours.96

Back to Top | Article Outline
Tropisetron

Tropisetron 2 mg IV is effective for PONV prophylaxis.97 It is as effective as ondansetron, granisetron,98 and droperidol and more effective than metoclopramide.99 The combination of tropisetron plus dexamethasone is more effective than either drug alone.100 Tropisetron is not approved in the United States.

Back to Top | Article Outline
Ramosetron

Ramosetron is not approved in the United States but available in other parts of the world. It is more effective with IV versus PO dosing (1–24 hours postoperatively).101 Ramosetron 0.3 mg IV is the most effective dose to prevent vomiting and decrease nausea for patients receiving fentanyl patient-controlled analgesia (PCA).102

Back to Top | Article Outline
Palonosetron

Palonosetron is a second generation 5HT3 receptor antagonist with a half-life of 40 hours.103,104 The most effective dose is 0.075 mg IV approved for 24 hours.105,106 Palonosetron 0.075 mg is more effective than granisetron 1 mg96 and ondansetron 4 mg82 in preventing PONV.

Back to Top | Article Outline
Timing of Administration

Ondansetron, dolasetron, granisetron, and tropisetron are most effective in the prophylaxis of PONV when given at the end of surgery,85,107–110 although some data on dolasetron suggest timing may have little effect on efficacy.111 Palonosetron is typically given at the start of surgery.105,106

Back to Top | Article Outline
Adverse Events

The 5-HT3 receptor antagonists have a favorable side effect profile, and while generally considered equally safe, all except palonosetron affect the QTc interval. In June 2012, the U.S. FDA recommended the dose of ondansetron for chemotherapy-induced nausea and vomiting should not exceed 16 mg in a single dose because of risks of QT prolongation. In December 2012, the FDA notified that the 32 mg single IV dose will no longer be marketed.112 However, there was no change in the recommended dose of ondansetron 4 mg to prevent PONV.90 The number-needed-to-harm (NNH) with a single dose of ondansetron is 36 for headache, 31 for elevated liver enzymes, and 23 for constipation.54

Back to Top | Article Outline
Nk-1 Receptor Antagonists
Aprepitant

Aprepitant is an NK-1 receptor antagonist with a 40-hour half-life. In 2 large RCTs, aprepitant (40 and 80 mg per os) was similar to ondansetron in achieving complete response (no vomiting and no use of rescue antiemetic) for 24 hours after surgery. However, aprepitant was significantly more effective than ondansetron for preventing vomiting at 24 and 48 hours after surgery and in reducing nausea severity in the first 48 hours after surgery.81,113 It also has a greater antiemetic effect compared with ondansetron. When used in combination, aprepitant 40 mg per os, plus dexamethasone, is more effective than ondansetron plus dexamethasone in preventing POV in patients undergoing craniotomy.114 A dose-ranging study for gynecologic laparotomy patients found a 80 mg per os dose of aprepitant is the most appropriate dose and is more effective than a 40 mg dose.115 The clinical experience with the use of aprepitant is still limited, and its role in routine prophylaxis is not established.116

Back to Top | Article Outline
Casopitant

A Phase 3 study of casopitant shows the combination of casopitant, 50 to 150 mg per os, plus ondansetron 4 mg, is more effective than ondansetron alone.117,118 Casopitant has not been approved for use.

Back to Top | Article Outline
Rolapitant

Rolapitant has a 180-hour half-life and better PONV prophylaxis than placebo. A clinical trial by Gan et al.119 showed no difference between groups receiving oral rolapitant and ondansetron 4 mg IV at 24 hours, but more patients experienced no emesis with the rolapitant 70 and 200 mg doses at 72 and 120 hours, respectively. Rolapitant has not been approved for use.

Back to Top | Article Outline
Corticosteroids
Dexamethasone

The corticosteroid dexamethasone effectively prevents nausea and vomiting in postoperative patients.120,121 A prophylactic dose of 4 to 5 mg IV for patients at increased risk for PONV is recommended after anesthesia induction rather than at the end of surgery.121 For PONV prophylaxis, the efficacy of dexamethasone 4 mg IV is similar to ondansetron 4 mg IV and droperidol 1.25 mg IV.47 More recent studies increasingly use the higher dose of dexamethasone 8 mg IV rather than the minimum effective dose of 4 to 5 mg.122–126

Preoperative dexamethasone 8 mg enhances the postdischarge quality of recovery in addition to reducing nausea, pain, and fatigue.127 Dexamethasone also has dose-dependent effects on quality of recovery. At 24 hours, patients receiving dexamethasone 0.1 vs 0.05 mg/kg required less opioid and reported less nausea, sore throat, muscle pain, and difficulty falling asleep.128 A meta-analysis evaluating the dose-dependent analgesic effects of perioperative dexamethasone found that doses >0.1 mg/kg are an effective adjunct in multimodal strategies to reduce postoperative pain and opioid consumption.129,130 With these additional benefits of pain relief and better quality of recovery, a prophylactic dose of dexamethasone 0.1 mg/kg or 8 mg in adults may be considered though further confirmation is needed for this larger dose.

Data on safety of perioperative dexamethasone are inconclusive. In most studies, a single dose of perioperative dexamethasone does not appear to increase the risk of wound infection.120,129 However, a recent study reported that intraoperative dexamethasone 4 to 8 mg may confer an increased risk of postoperative infection.131 Weighing the risk-benefit ratio, a recent editorial suggests a single dose of dexamethasone 4 to 8 mg is safe when used for PONV prophylaxis.132 In addition, recent studies showed significant increases in blood glucose that occur 6 to 12 hours postoperatively in normal subjects,133,134 those with impaired glucose tolerance,134 and type 2 diabetic135 and obese134 surgical patients who receive dexamethasone 8 mg. In view of this evidence, use of dexamethasone in labile diabetic patients is relatively contraindicated.

Back to Top | Article Outline
Methylprednisolone

Methylprednisolone 40 mg IV is effective for the prevention of late PONV.136,137 There is no evidence to suggest that the adverse effect of methylprednisolone is any different from dexamethasone.

Back to Top | Article Outline
Butyrophenones
Droperidol

Prophylactic doses of droperidol 0.625 to 1.25 mg IV are effective for the prevention of PONV.138–140 The efficacy of droperidol is similar to ondansetron for PONV prophylaxis, with an NNT of approximately 5 for prevention of nausea and vomiting (0–24 hours).140 Droperidol is most effective when administered at the end of surgery.140 For PONV prevention, droperidol is superior to metoclopramide doses of <20 mg.141 A recent meta-analysis suggests that with prophylactic low-dose droperidol (<1 mg or 15 µg/kg IV) in adults, there is still significant antiemetic efficacy with a low risk of adverse effects.142

Many physicians stopped using droperidol in 2001 due to the FDA “black box” restrictions on its use. However, the droperidol doses used for the management of PONV are extremely low, and it is believed that at these dosing levels, droperidol is unlikely to be associated with significant cardiovascular events. Several studies have documented the equal QTc effects of droperidol versus ondansetron.44,143 In an in vitro electrophysiological drug interaction study, ondansetron did not further increase the QT prolongation caused by droperidol when used in clinically relevant concentrations.144 In a clinical study, droperidol plus ondansetron combination was more effective than either drug alone, and QT prolongation with the combination versus placebo was equivalent to either drug alone.145 Due to the 2001 black box warning, droperidol is not the first choice for PONV prophylaxis in many countries. However, a recent survey suggested that in 19 of 24 European countries, representing an estimated 73,000 anesthesiologists, droperidol is regularly used as an antiemetic.142

Back to Top | Article Outline
Haloperidol

Haloperidol has antiemetic properties when used in low doses and has been investigated as an alternative to droperidol.146,147 At doses much lower than those used to treat psychiatric disorders, 0.5 to 2 mg IM or IV, haloperidol effectively reduced PONV risk with a NNT of between 4 and 6.146 At these doses, sedation does not occur, and cardiac arrhythmias are not reported. Haloperidol carries a risk of QTc prolongation in its label and is not recommended as first-line therapy. Haloperidol 1 mg IM or IV may be regarded as an alternative to droperidol. Of potential interest, haloperidol may be given IM or orally. Its efficacy can be increased when combined with other antiemetics such as dexamethasone or ondansetron. As with droperidol, the combination of haloperidol with the 5-HT3 receptor antagonists does not increase the risk of QT prolongation.148 Only one of 806 patients (0.1%) exposed to haloperidol 4 mg had extrapyramidal symptoms.146

When haloperidol 1 mg was compared with ondansetron 4 mg and placebo, there was no difference in QTc effect among the 3 groups. There was no difference in PONV incidence between haloperidol and ondansetron given before the end of surgery, but both were not significantly better than placebo at 24 hours.78 There was no difference in early antiemetic efficacy between haloperidol 1 mg and ondansetron 4 mg and no difference in the risk of QT prolongation.80 Comparing haloperidol 2 mg IV vs ondansetron 4 mg IV given before the end of surgery, there was no difference in effect on early versus late PONV or QTc prolongation.79 However, Meyer-Massetti et al.149 recently reviewed the literature and all FDA Med Watch reports of haloperidol-associated adverse events and recommended doses of haloperidol <2 mg to reduce the risk of side effects and QT prolongation. Low-dose haloperidol 1 mg vs droperidol 0.625 mg given after induction showed no difference in early or late PONV and no extrapyramidal symptoms with either drug.150 The timing of haloperidol 2 mg IV at induction versus end of surgery administration did not make a difference.151 It should be noted that the use of haloperidol as an antiemetic or the IV route of administration is not an FDA-approved indication.

Back to Top | Article Outline
Antihistamines
Dimenhydrinate

Dimenhydrinate is an antihistamine with antiemetic effects. The recommended dose is 1 mg/kg IV.152–154 Data from placebo-controlled trials suggest that its antiemetic efficacy may be similar to the 5-HT3 receptor antagonists, dexamethasone, and droperidol.154 However, not enough data are available to establish the optimal timing and dose response for dimenhydrinate administration or its side effect profile. Direct comparisons with other antiemetic drugs are lacking.

Back to Top | Article Outline
Meclizine

Meclizine has a longer duration of PONV effect than ondansetron.155 Meclizine 50 mg per os plus ondansetron 4 mg IV is more effective than either ondansetron or meclizine alone.155

Back to Top | Article Outline
Anticholinergic
Transdermal Scopolamine

A systematic review of TDS showed that it is useful as an adjunct to other antiemetic therapies.156 The patch effectively prevented nausea and vomiting postoperatively up to 24 hours with a NNT of 6. It can be applied the evening before surgery or 2 to 4 hours before the start of anesthesia due to its 2- to 4-hour onset of effect.156,157 Adverse events associated with TDS are generally mild, the most common being visual disturbances (NNH = 5.6), dry mouth (NNH = 13), and dizziness (NNH = 50).158 Dry mouth occurs mostly on the first day of use. A higher prevalence of visual disturbances can be observed at 24 to 48 hours.156 TDS is useful for control of nausea in the setting of PCA.159,160 New data show equal effectiveness with single drug therapy using TDS, ondansetron, or droperidol.161

Back to Top | Article Outline
Phenothiazines
Perphenazine

Perphenazine is a phenothiazine derivative that has been used for the prevention of PONV at doses between 2.5 mg to 5 mg IV or IM.162 A recent systematic review from 6 RCTs demonstrated a relative risk reduction (RRR) of 0.5 (95% CI, 0.37–0.67) for PONV with a recommended dose of 5 mg IV, with no increase in sedation and drowsiness when compared with placebo.162

Back to Top | Article Outline
Metoclopramide

Metoclopramide is a weak antiemetic and at a dose of 10 mg is not effective in reducing the incidence of nausea and vomiting.163 In a study with >3000 patients, metoclopramide had an antiemetic effect when given in doses larger than 20 mg. Metoclopramide’s dose-response curve was evaluated in the presence of dexamethasone 8 mg IV administered 30 to 60 minutes before the end of surgery. Metoclopramide in 25 and 50 mg doses had an effect similar to ondansetron 4 mg for early PONV but a smaller effect than ondansetron for late PONV. The NNT for metoclopramide 10, 25, and 50 mg for PONV at 24 hours is 30, 16, and 11, respectively. Dyskinesia or extrapyramidal symptoms were 0.3%, 0.6%, and 0.6%, respectively, and can increase with increasing metoclopramide doses. The NNH for extrapyramidal symptoms with the 25 or 50 mg doses is 140.35

Back to Top | Article Outline
Other Antiemetics
Propofol

Propofol is a sedative-hypnotic widely used for induction and maintenance of general anesthesia and monitored anesthesia care sedation with local or regional anesthesia.164 Numerous studies have demonstrated propofol has antiemetic properties. The median plasma propofol concentration associated with an antiemetic response was 343 ng/mL, which is much lower than the concentration ranges associated with general anesthesia (3–6 mcg/mL) or sedation (1–3 mcg/mL), allowing propofol to have antiemetic properties in the subhypnotic dose range.165

Propofol used as part of TIVA is recommended to reduce baseline risk for PONV. The use of propofol for induction and maintenance of anesthesia decreases the incidence of early PONV (occurring within the first 6 hours), with the NNT = 5.53,166 The combination of propofol and air/oxygen (TIVA) reduces the PONV risk by approximately 25%.47 A systematic review of 58 studies demonstrated that use of propofol versus inhaled anesthesia also reduced the incidence of PDNV.167

The benefit of a small dose propofol infusion (bolus of 1 mg/kg followed by an infusion at 20 mcg/kg/min), either by itself or in combination with other antiemetics, has been shown to reduce PONV.50,51

Propofol, in small doses (20 mg as needed), can be used for rescue therapy for patients in the direct care environment, for example, PACU, and has been found as effective as ondansetron.168,169 However, the antiemetic effect with low doses of propofol is likely brief.

Back to Top | Article Outline
Alpha2-Agonists

In a meta-analysis, perioperative systemic alpha2-adrenoceptor agonists (clonidine and dexmedetomidine) showed a significant albeit weak and short-lived antinausea effect.170 This effect may be explained by direct antiemetic properties of alpha2-agonists or its opioid-sparing effect, although the biological basis remains obscure.

Back to Top | Article Outline
Mirtazapine

Mirtazapine is a noradrenergic and specific serotonergic antidepressant.

Prophylactic mirtazapine delays the onset of PONV.171 Mirtazapine 30 mg per os plus dexamethasone 8 mg reduces the incidence of late PONV by >50% compared with dexamethasone 8 mg alone. Less rescue medication is needed with the combination of antiemetics.

Back to Top | Article Outline
Gabapentin

Gabapentin doses of 600 mg per os given 2 hours before surgery effectively decreases PONV.172–174 Given 1 hours before surgery, gabapentin 800 mg per os is as effective as dexamethasone 8 mg IV, and the combination is better than either drug alone.175

Back to Top | Article Outline
Midazolam

Midazolam decreases nausea and vomiting compared with placebo.176,177 Midazolam 2 mg when administered 30 minutes before the end of surgery was as effective against PONV as ondansetron 4 mg.178 While there was no significant difference using midazolam 0.075 mg/kg or dexamethasone 10 mg, their combination provided a more favorable effect than either drug alone.179,180 Midazolam 1 mg/h was as effective as a subhypnotic dose of propofol 1 mg/kg/h when given at the end of surgery.177 For PONV prophylaxis, midazolam was more effective than metoclopramide 10 mg.181,182 Midazolam 2 mg given 30 minutes before end of surgery decreased PONV more effectively than midazolam 35 mcg/kg premedication.183

Back to Top | Article Outline
Combination Antiemetic Therapy

Combination therapy for PONV prophylaxis is preferable to using a single drug alone.47,122,145,155,184–189 Apfel et al.47 demonstrated that the effects of antiemetics acting on different receptors are additive. Adults at moderate risk for PONV should receive combination therapy with drugs from different classes as the efficacy is optimized when a combination of drugs with different mechanisms of action are administered. The 5-HT3 antagonists have better antiemetic than antinausea efficacy but are associated with headache. These drugs can be used in combination with droperidol, which has greater antinausea efficacy and is associated with lower risk of headache.190 The 5-HT3 antagonists can also be effectively combined with dexamethasone.120

Optimal antiemetic dosing with combination therapy needs to be established. Combination therapy regimens using ondansetron with either droperidol or dexamethasone are most widely studied. It has been suggested that when used as combination therapy, dexamethasone doses should not exceed 10 mg IV, droperidol doses should not exceed 1 mg IV, and ondansetron doses in adults should not exceed 4 mg and can be much lower.191

Multiple studies confirm the effectiveness of combination therapy with dexamethasone.179,180,185,186,192–195 In particular, many have evaluated the combination of dexamethasone plus granisetron or ondansetron186,196–198 with one demonstrating that low-dose granisetron, 0.1 mg, combined with dexamethasone 8 mg is as effective as ondansetron 4 mg plus dexamethasone 8 mg.192 Another study evaluating low-dose ondansetron showed similar rates of PONV between dexamethasone 8 mg and ondansetron 0.1 mg/kg and dexamethasone 8 mg and granisetron 40 mcg/kg.199

The combination of haloperidol 2 mg plus dexamethasone 5 mg was more effective than haloperidol or dexamethasone alone,200 and combination therapy with haloperidol 1.5 mg plus dexamethasone 8 mg effectively prevented PONV.126 Moreover, less nausea and vomiting occurred in the dexamethasone combination groups than with ondansetron,184 granisetron,201 or haloperidol200 alone. When dexamethasone 4 mg was used in combination with droperidol 0.625 mg, there was no increase in the incidence of side effects.191 When propofol 0.5 mg/kg was combined with dexamethasone 8 mg, the regimen had twice the effectiveness as propofol alone.122 Similarly, combining TDS with other drugs such as ondansetron187 or dexamethasone202 was better than using a single drug alone.

Combination therapy with ondansetron has also been widely studied. When ondansetron was combined with casopitant117,118 or TDS,187 the combination therapy was more effective than single drug therapy. A study evaluating ondansetron plus haloperidol at 8 hours postoperatively showed that the combination was better than either drug alone.203 The difference is primarily one of antinausea rather than antivomiting efficacy. The combination was also not associated with any increase in adverse events such as dystonia, akathisia, or QT prolongation.

Back to Top | Article Outline
Patient-Controlled Analgesia

Approximately one-third of patients who are treated with opioids for postoperative pain will have nausea and vomiting.204 Droperidol effectively reduced the risk of nausea and vomiting, with a NNT of approximately 3, when given concomitantly with morphine in a PCA device.204,205 Other studies evaluating the effects of various other antiemetics on PCA-related PONV showed a benefit. Ramosetron was more effective than ondansetron in preventing vomiting and reducing nausea in relation to fentanyl-based PCA.102 The combination of metoclopramide 50 mg plus dimenhydramine 60 mg added to PCA decreased the severity of PCA-related PONV.206 TDS plus dexamethasone 8 mg was more effective than ramosetron 0.3 mg plus dexamethasone 8mg in patients receiving epidural PCA.202 Ondansetron, 8 mg, proved more effective than metoclopramide for controlling opioid-induced emesis and nausea in this population.207

Back to Top | Article Outline
Lack or Limited Evidence of Effect

The following strategies are not effective for PONV prophylaxis: music therapy,208,209 isopropyl alcohol inhalation,210 intraoperative gastric decompression,41 the proton pump inhibitor esomeprazole,211,212 and administration of nicotine patch 7 mg to nonsmokers.215 The latter modality may actually increase the incidence and severity of PONV.215,216

There is insufficient evidence regarding the efficacy of hypnosis for PONV prophylaxis.217 Cannabinoids (nabilone, tetra-hydrocannabinol), although promising in the control of chemotherapy-induced sickness, are not effective for PONV.218,219

Two meta-analyses have addressed the impact of intraoperative supplemental oxygen on the incidence of PONV.64,220 There is no convincing evidence that high inspired oxygen fraction reduces PONV.

In 2 RCTs, the phenothiazines, promethazine, 12.5 to 25 mg IV, administered at the induction of surgery, and prochlorperazine, 5–10 mg IV, given at the end of surgery were shown to have some antiemetic efficacy.221,222 Similarly, it is suggested that the phenylethylamine, ephedrine, 0.5 mg/kg IM, has an antiemetic effect when administered at the end of surgery.223,224 However, due to a paucity of data, evidence is not as strong as for the other, well-documented antiemetic drugs; therefore, further research is warranted before these drugs or techniques can be recommended as first-line therapy. It should be noted that there is an FDA black box warning on promethazine hydrochloride injection. Promethazine should neither be administered into an artery nor administered under the skin because of the risk of severe tissue injury, including gangrene. There is also a risk that the drug can leach out from the vein during IV administration and cause serious damage to the surrounding tissue. If IV administration is desired, the drug should be diluted and a properly functioning IV line and a slow rate of administration should be ensured. The preferred route of administration is deep IM injection.225

Back to Top | Article Outline
Nonpharmacologic Prophylaxis

A meta-analysis of 40 articles including 4858 subjects226 concluded that P6 stimulation with 10 different acupuncture modalities reduces nausea, vomiting, and the need for rescue antiemetics compared with sham stimulation (Evidence A1). The efficacy of P6 stimulation is similar to that of prophylactic antiemetics such as ondansetron, droperidol, metoclopramide, cyclizine, and prochlorperazine. In subgroup analysis, there was no difference in effectiveness in adults compared with children or invasive versus noninvasive modalities for P6 stimulation. The timing of transcutaneous acupoint electrical stimulation does not impact PONV, with similar reductions being achieved with stimulation initiated before or after induction of anesthesia.227,228 Neuromuscular stimulation over the median nerve also reduces the incidence of PONV in the early postoperative period, particularly when tetanic stimulation is used.229,230

Back to Top | Article Outline
Other Methods and Alternative Therapies

Adequate IV fluid hydration is an effective strategy for reducing the baseline risk for PONV (Evidence A2).231,232 However, there was no difference in efficacy between crystalloids and colloids when similar volumes were used in surgeries associated with minimal fluid shifts.233,234

Low-dose naloxone, 0.25 mcg/kg/h, reduced nausea and vomiting and decreased the need for rescue medication compared with placebo in adult patients235 and significantly reduced opioid-related side effects including nausea in children and adolescents.236 Lower infusion rates of 0.05, 0.1, and 0.2 mcg/kg/h were also effective in reducing the incidence of nausea and sedation induced by tramadol infusion with the highest rate of 0.2 mcg/kg/h showing efficacy in reducing the incidence of vomiting.237 Another opioid antagonist, nalmefene (no longer available in the United States), reduced opioid-induced nausea, vomiting, and need for rescue medication in patients receiving PCA.238

While earlier meta-analyses did not find ginger to be an effective modality for PONV prophylaxis (Evidence A1),48,239 a more recent meta-analysis concluded that fixed dose of at least 1g per os administered 1 hour before induction of anesthesia is more effective than placebo (Evidence A1).240 A recent study suggested that Morinda Citrifolia Linn (Noni fruit) in a dose of 600 mg might be effective in reducing nausea in the early postoperative period (Evidence A3).241

Back to Top | Article Outline
Cost-Effectiveness

The C/E of therapy is one of the primary considerations in determining whether to use PONV prophylaxis. However, studies assessing C/E of PONV interventions have several drawbacks; they use variable methodologies and are often too small to be reliable, and many are not specifically designed for that purpose. This panel recommends that future C/E studies be conducted according to established guidelines.242–244 Such guidelines address components of the numerator and denominator of a C/E ratio. The numerator should measure resource use, and the denominator should provide a value of health consequences.

Willingness to pay is a recommended measure in cost benefit analyses. Gan et al.245 found that patients are willing to pay approximately $100 to prevent experiencing PONV, and Diez246 found parents are willing to spend approximately $80 to prevent POV in their children. Reducing baseline risk can be a cost-effective strategy. For example, it is more cost-effective to use a propofol/isoflurane regimen, which is associated with the lowest cost per episode of PONV avoided, than either propofol/sevoflurane or sevoflurane/sevoflurane.247 However, generic sevoflurane is now available that will reduce the costs.

C/E assessments for PONV prophylaxis are more difficult and depend on the specific model and assumptions chosen. It is estimated that each episode of emesis delays discharge from the PACU by approximately 20 minutes.248 However, in a retrospective study of patients who underwent ambulatory surgery, Dexter and Tinker249 demonstrated that if PONV could have been eliminated in patients who suffered this complication, the length of PACU stay for all patients would only have been reduced by <5%. Hill et al.14 found that prophylaxis in high-risk patients is more cost-effective than placebo due to increased costs associated with nausea and vomiting. The additional costs associated with PONV in placebo patients are up to 100 times higher compared with prophylaxis with a generic antiemetic, and the cost of treating vomiting is 3 times higher than the cost of treating nausea. Similarly, a study evaluating dolasetron, droperidol, or no prophylaxis in high-risk patients showed that prophylaxis with either of the 2 antiemetics is more cost-effective than no prophylaxis and subsequent rescue therapy.250 However, in a study that did not assess C/E but evaluated factors affecting cost, there was no difference in the time to discharge, rate of unanticipated admission, or time to return to normal activity between the prophylaxis and treatment groups in an ambulatory setting apart from the highest risk group (female patients with a history of motion sickness or PONV who were undergoing highly emetogenic procedures) who reported high patient satisfaction when prophylaxis was given.251 It has been suggested that PONV prophylaxis is cost-effective with the older, less expensive drugs when patients have a 10% or greater risk of emesis.252 These studies were conducted before the availability of generic ondansetron. In another model, treatment of PONV with ondansetron proved more cost-effective than prevention in both a low- (30%) and a high-risk(60%) setting.253 This was due to the high success rate of treating established PONV, even with low doses of ondansetron (1 mg). When using a willingness to pay rate of $100 per case avoided, PONV prophylaxis proved cost-effective in groups with a 40% risk of PONV. Lower drug acquisition costs would generally support PONV prophylaxis in patient groups at a lower risk for PONV. The decision about whether or not to use PONV prophylaxis, or to treat patients with established symptoms, not only depends on the efficacy of the drug but also on the baseline risk for PONV, adverse effects of the antiemetics, and drug acquisition costs, which will vary from 1 setting to another. For instance, anesthesiologists may be more likely to administer prophylaxis with an inexpensive generic antiemetic even if the baseline risk is low and, consequently, many patients must be treated prophylactically for one to benefit.

Back to Top | Article Outline
Guideline 4. Administer Prophylactic Therapy With Combination (≥2) Interventions/Multimodal Therapy in Patients at High Risk for PONV

New Information: New antiemetic combination therapies have been reported. These include midazolam and dexamethasone,177,180 dexamethasone 8 mg IV at induction plus ondansetron 4 mg IV at the end of surgery plus ondansetron 8 mg PO postoperatively254 and haloperidol 2.5 mg plus dexamethasone 5 mg IV after induction.200 Among the NK1 RAs, aprepitant (40 mg) in combination with dexamethasone 10 mg proved superior to ondansetron 4 mg and dexamethasone 10 mg in preventing vomiting in neurosurgical patients up to 48 hours after surgery.114 The combination of casopitan and ondansetron proved more effective than ondansetron alone.117,118 (Additional details of the study are described in the PDNV section.

Recommended combination therapy is shown in Table 4. A treatment algorithm is presented in Figure 4.

Table 4
Table 4
Image Tools
Back to Top | Article Outline

DISCUSSION

Patients who are at high risk for PONV should receive prophylaxis with combination therapy or a multimodal approach that includes 2 or more interventions (Table 4). When considering anesthesia, use regional anesthesia or TIVA with propofol if patients are at high risk for PONV. If general anesthesia is used, reduce baseline risk factors when possible. Nonpharmacologic therapies as adjuncts to pharmacologic therapy should be considered. Antiemetics recommended for prophylaxis in adults and children are shown in Table 3 and Table 5.

Table 5
Table 5
Image Tools

When used in combination, drugs from different classes should be selected to optimize their effects. For PONV prophylaxis, the efficacy of dexamethasone 4 mg IV, ondansetron 4 mg IV, and droperidol 1.25 mg IV appears to be similar.47 Systematic reviews addressing specific therapeutic combinations showed the combination of a 5-HT3 receptor antagonist with either dexamethasone or droperidol was more effective than monotherapy with any of the drugs255,188,189,256 Similarly, droperidol combined with dexamethasone was more effective than either drug alone.47 When the different combinations are compared, no differences are found between 5-HT3 receptor antagonist plus droperidol, 5-HT3 receptor antagonist plus dexamethasone, and droperidol plus dexamethasone.47,257 Combinations involving metoclopramide are not found to reduce PONV to a greater extent than monotherapy.258–260

A multimodal approach to minimize PONV combined nonpharmacologic and pharmacologic prophylaxis as well as interventions that reduced baseline risk.261,262 Habib et al.263 evaluated a multimodal approach to reduce PONV that consisted of preoperative anxiolysis (midazolam), prophylactic antiemetics (droperidol at induction and ondansetron at end of surgery), TIVA with propofol, and local anesthetic infiltration and ketorolac. No nitrous oxide was used. Patients who received multimodal therapy had a 80% complete response rate compared with a 43% to 63% response rate among patients receiving either inhaled drug or TIVA alone.

Back to Top | Article Outline
Guideline 5. Administer Prophylactic Antiemetic Therapy to Children at Increased Risk for POV; As in Adults, Use of Combination Therapy Is Most Effective

New Information: Numerous appropriately powered studies add additional support for the use of combination antiemetics for children at high risk for POV, with a large volume of data to suggest that prophylaxis with a combination of a 5-HT3 antagonist and a steroid should be administered for most pediatric patients at high risk for POV unless there is a contraindication. New data on pharmacokinetics of ondansetron in children <2 years of age are now available. Dolasetron is not promoted in the United States because of the risks of cardiac arrhythmias. Concerns have been raised about the use of steroids in children at risk for tumor lysis syndrome and the use of 5-HT3 antagonists in children with prolonged QT syndrome.

The prophylactic antiemetic doses recommended for children at risk for POV are shown in Table 5.

Recommended combination therapy is shown in Table 4.

Back to Top | Article Outline

DISCUSSION

In children, the POV rate can be twice as high as in adults, which suggests a greater need for POV prophylaxis in this population.264 Children who are at moderate or high risk for POV should receive combination therapy with at least 2 prophylactic drugs from different classes (Table 5).

There are now many studies that confirmed the efficacy of 5 HT3 antagonists as prophylactic antiemetics in the pediatric patient population, including studies of oral disintegrating tablets of ondansetron.265,266 However, in contrast to the data in adult studies, the efficacy of ondansetron in preventing emesis after craniotomy was not established in children, probably because the sample size was too small, even after pooling data from 2 pediatric studies.267,268

The evidence supporting the prophylactic use of ondansetron in reducing POV has been extended to children aged 1 to 24 months.269 Newer data on the pharmacokinetics of ondansetron in children aged 1 to 48 months showed clearance was decreased by 76%, 53%, and 31%, respectively for 1-, 3-, and 6-month-old subjects.270 Simulations show that a dose of 0.1 mg/kg in the infant younger than 6 months produces levels similar to that of 0.15 mg/kg in older children. This is attributed to the immaturity of the cytochrome P450 enzymes, particularly CYP3A4 that increases from 30% at 1 month to adult values by 6 to 12 months, and CYP1A2 that reaches 35% of adult values at 1 year. The authors concluded that children younger than 4 months should be monitored more closely after receiving ondansetron but did not make specific recommendations on the duration or modality of monitoring.270

Back to Top | Article Outline
Ondansetron and Other 5 HT3 Antagonists

There is now good evidence to suggest that 5 HT3 antagonists and dexamethasone are the most effective antiemetics in the prophylaxis of pediatric POV. A study by Bolton et al.271 evaluating 557 children undergoing tonsillectomy/adenoidectomy found ondansetron was more effective than metoclopramide in preventing POV. A systematic review in children undergoing tonsillectomies also found that the 5 HT3 antagonists and dexamethasone were the most effective prophylactic antiemetics with insufficient evidence for the efficacy of dimenhydrinate, droperidol, or perphenazine (Table 1).73 In a more recent quantitative systematic review of children undergoing a variety of surgical procedures, Schnabel et al.162 concluded that perphenazine is an effective antiemetic compared with placebo, but a 5 HT3 antagonist (ondansetron or granisetron) was more effective. In a Bayesian meta-analysis of 6 single drug therapy and 5 combinations of antiemetics in children, Engelman et al.272 note that the most pessimistic expectations are that single drug prophylaxis with the 5 HT3 receptor antagonists or dexamethasone result in a 50% to 60% RRR and that the expected RRR of the combination is 80%. In this study, the risk reduction with droperidol was 40%.

Back to Top | Article Outline
Dexamethasone

The dose-effect relationship of dexamethasone is unclear. Most studies use a dose of 0.5 mg/kg.73 Kim et al.195 found no differences in POV rates or secondary outcomes in children receiving 0.0625, 0.125, 0.25, 0.5, or 1 mg/kg (maximum dose 24 mg) during adeno-tonsillectomy procedures. Thus, they concluded there is no justification for using higher doses than 0.0625 mg/kg. However, another study of the same patient population showed a dose-dependent reduction in POV with the best response in children receiving 0.5 mg/kg.273 Steward et al.274 in an updated Cochrane review of steroids for tonsillectomy patients stated that “the question of appropriate dosing remains unanswered and final recommendations must await randomized dose-control trials.”

There are no new data to base a recommendation on the timing of administration of these drugs. There are no differences in POV in children who receive tropisetron immediately after induction or at the end of surgery during short tonsillectomy procedures.275 There are also no published pediatric data to make recommendations on the use of palonosetron or the NK-1 antagonists in pediatric POV. A RCT without a placebo arm found no differences in the 48-hour rates of POV in children receiving 0.5, 1.0, or 1.5 mg/kg palonosteron.276

Based on this evidence, we would recommend the prophylactic use of a combination of dexamethasone and ondansetron in most pediatric patients at high risk for POV unless there are contraindications. This is similar to the recommendation by the Association of Pediatric Anaesthetists of Great Britain and Ireland.277

Back to Top | Article Outline

SIDE EFFECTS OF DRUGS

Ondansetron

Cardiovascular complications have been reported after ondansetron therapy. An 11-year-old child undergoing a thyroglossal duct cyst excision developed ventricular tachycardia after receiving ondansetron and dimenhydrinate.278 Subsequent studies showed she had an undiagnosed long QT syndrome. There is a report of a death from ventricular tachycardia in a patient receiving ondansetron in the emergency department279 and another report of severe bradycardia during incision and drainage of an abscess.280 The effects of droperidol and ondansetron on myocardial repolarization have been studied when given alone or in combination to healthy children.281 There were clinically insignificant changes with lengthening of the QT intervals by 10 to 17 millisecond and of the Tp-e intervals by 0 to 7 millisecond without any differences between the groups. These data suggest clinicians should be aware of these risks especially in children with prolonged QT syndrome.

Back to Top | Article Outline
Steroids

Tumor lysis syndrome has been reported in children with leukemia who received intraoperative dexamethasone.282,283 One patient with an undiagnosed acute lymphoblastic leukemia developed hyperkalemia and a fatal cardiac arrest during a tonsillectomy procedure.282 A study of steroids in children undergoing tonsillectomies was terminated early because of increased bleeding in patients receiving dexamethasone.273 There has been considerable discussion about this unexpected finding as it was a secondary outcome and was not adjusted for other risk factors.284 The statistical significance of increased bleeding was lost when primary hemorrhage cases, which are largely related to surgical technique, were excluded. Other studies including a meta-analysis and retrospective reviews have failed to show increased postoperative bleeding between patients receiving dexamethasone and controls in both meta-analyses and retrospective reviews.285–287 Although the incidence of bleeding may not increase, there was an increased incidence of operative reintervention for bleeding episodes in a systematic review of children receiving steroids during adenotonsillectomy.288 In the updated Cochrane review, Steward et al.274 stated “any suggestion that single-dose dexamethasone increases bleeding risk needs to be substantiated with further studies.” The most recent clinical practice guidelines from the American Academy of Otolaryngology-Head and Neck Surgery continue to make a strong recommendation for the use of a single dose of dexamethasone in children undergoing tonsillectomy.289 This guideline was based on a preponderance of benefit over harm, including benefits from decreased throat pain, POV, and earlier resumption of oral intake.289

Back to Top | Article Outline
Nonpharmacologic Therapy

Two meta-analyses showed acupuncture and acustimulation were effective in reducing POV in children.290,291 Pooled data from 12 studies showed all modalities reduce vomiting (risk reduction 0.69, 95% CI, 0.59–0.8). There were no differences between acustimulation and medications in reducing POV. However, therapeutic suggestion through earphones during anesthesia for tonsillectomy/adenoidectomy was ineffective.292

Back to Top | Article Outline
Guideline 6. Provide Antiemetic Treatment to Patients With PONV who did not Receive Prophylaxis or in whom Prophylaxis Failed

A treatment algorithm for adults is presented in Figure 4.

New information: Additional studies on the use of isopropyl alcohol for the treatment of established PONV are discussed. Further data suggest the futility of repeat antiemetic when administered within 6 hours of the previous antiemetic administration.

Back to Top | Article Outline

DISCUSSION

When nausea and vomiting occur postoperatively, treatment should be administered with an antiemetic from a pharmacologic class that is different from the prophylactic drug initially given, or if no prophylaxis was given, the recommended treatment is a low-dose 5-HT3 antagonist.190,293 The 5-HT3 antagonists are the only drugs that have been adequately studied for the treatment of existing PONV.190,294 The doses of 5-HT3 antagonists used for treatment are smaller than those used for prophylaxis: ondansetron 1.0 mg; granisetron 0.1 mg; and tropisetron 0.5 mg (NNT = 4–5).54,190 All the 5-HT3 antagonists, except palonosetron (that has not been studied for PONV treatment), are equally antiemetic for the treatment of established PONV.190

Alternative treatments for established PONV include dexamethasone, 2 to 4 mg IV, droperidol, 0.625 mg IV, or promethazine 6.25 to 12.5 mg IV.293,295,297 Propofol, 20 mg as needed, can be considered for rescue therapy in patients still in the PACU and is as effective as ondansetron.165,169,298 However, the antiemetic effect with low doses of propofol is probably brief.165,298

Although isopropyl alcohol inhalation is not effective for the prophylaxis of PONV,210 aromatherapy with isopropyl alcohol was effective in achieving a quicker reduction in nausea severity compared with promethazine or ondansetron when used for the treatment of PONV (Evidence A2).299–301 However, since studies investigating its use had limitations, it is not clear whether it is an effective modality for the complete control of PONV. Better-designed studies investigating the use of isopropyl alcohol for the treatment of PONV are needed.

Repeating the medication given for PONV prophylaxis within the first 6 hours after the initial dose conferred no additional benefit.302 During the first 4 postoperative hours, patients who failed PONV prophylaxis with ondansetron 4 mg did not respond either to a second administration of ondansetron 4 mg or to crossover with granisetron 0.1 or 1 mg.302,303 If >6 hours has elapsed, it may be possible to achieve some effect with a second dose of a 5-HT3 antagonist or butyrophenone (droperidol or haloperidol), but this has not been demonstrated in clinical trials and should only be attempted if triple therapy has been used for prophylaxis and if no alternatives are available for rescue that have not been used for prophylaxis. Readministration of longer-acting drugs, for example, dexamethasone, TDS, aprepitant, and palonosetron is not recommended.

The attempt at rescue should be initiated when the patient complains of PONV and, at the same time, an evaluation should be performed to exclude an inciting medication or mechanical factor for nausea and/or vomiting. Contributing factors might include an opioid PCA, blood draining down the throat, or an abdominal obstruction. There is no large-scale study to base recommendations on the use of rescue antiemetics in children who have failed prophylactic antiemetics.

Back to Top | Article Outline
Postdischarge Nausea and Vomiting

As many as one-third to one-half of patients who undergo ambulatory surgery experience PDNV.304 Such patients often do not have access to treatment for their PDNV. A systematic review of all studies assessing PDNV after outpatient surgery found that, on discharge, 17% of patients experience nausea (range, 0%–55%) and 8% have vomiting (range, 0%–16%).305

Since ambulatory surgery constitutes about 60% of all surgical procedures in the United States, many studies are focusing on how to prevent PDNV.83,84,103 As these studies show, PDNV is still a significant problem. New research in this area is centered on mixing IV and per os doses of different drugs, administered at various time points, to evaluate the effects on reducing PDNV. The results show that mixing IV and per os antiemetics at various perioperative times decreases PDNV. For instance, 1 study found that dexamethasone 8 mg IV at induction plus ondansetron 4 mg IV at the end of surgery plus ondansetron 8 mg per os postoperatively had a greater effect on decreasing PDNV than ondansetron 4 mg IV alone at the end of surgery.254

Other studies evaluated different combinations for PDNV. The combination of haloperidol 2.5 mg plus dexamethasone 5 mg IV after induction was more effective than droperidol 1.25 mg, haloperidol 2 mg, or dexamethasone 5 mg alone, all of which were more effective than placebo.200 Aprepitant 40 mg, 120 mg, and ondansetron 4 mg decreased PONV to a similar extent during the 0- to 24-hour postoperative period; however, 24 to 48 hours postoperatively, aprepitant 40 mg and 120 mg had an equal effect, which was more effective than ondansetron 4 mg.113 In other PDNV trials, the combination of casopitant plus ondansetron was more effective than ondansetron alone,118 and ondansetron 4mg IV was equivalent to granisetron 1 mg per os.92

Administration of prophylactic antiemetics may be warranted in patients at high risk for PDNV; however, many of the available antiemetics have a short half-life and may not be suitable for this purpose. A meta-analysis assessing prophylactic therapy for PDNV after ambulatory surgery found a NNT of approximately 5 with combination therapy versus a NNT of approximately 12 to 13 for ondansetron 4 mg or dexamethasone 4 to 10 mg alone.304 Droperidol was ineffective at preventing PDNV at a dose <1 mg, and there was insufficient evidence to evaluate droperidol >1 mg. A systematic review of 58 articles demonstrated that use of propofol versus inhaled anesthetics also reduced the incidence of PDNV (P < 0.05).167 Small RCTs have demonstrated efficacy in preventing PDNV with orally disintegrating ondansetron tablets, acupoint stimulation of P6, and transdermal scopolamine.157,306,307

Back to Top | Article Outline
Guideline 7. Ensure PONV Prevention and Treatment Is Implemented in the Clinical Setting

New information: This section is new to emphasize the importance of implementing PONV prevention and treatment strategies in the clinical setting.

Measures must be put in place to determine whether suggested algorithms for the management of PONV are actually implemented as standard operating procedure in clinical settings and that these practices lead to improvement of PONV management.

Back to Top | Article Outline
Clinical PONV Protocols and Algorithms to Implement PONV Policies

Recommendations for the administration of antiemetic interventions traditionally support the application of a “valid assessment of the patient`s risk for POV or PONV.”2 Furthermore, when developing a management strategy for each individual patient, the choice should be based on patient preference, cost-efficiency, level of PONV risk, and patient’s preexisting condition (e.g., avoid QT prolonging antiemetics in patients with prolonged QT syndrome and TDS in closed angle glaucoma patients).2 Such recommendations are based on the goal that antiemetics and other interventions reduce the baseline risk for PONV in “high-risk patients,” that is, patients who actually need antiemetic prevention. This would save costs and prevent pharmacological exposure among patients who will not vomit anyway. Assuming that each antiemetic intervention is associated with a defined RRR that has been determined by clinical trials and meta-analyses, this RRR translates into an absolute risk reduction (ARR) that depends mainly on the control event rate (CER) in a given patient population. If the CER is high (e.g., 60%), then an antiemetic with a RRR of 30% reduces the incidence in that population to 42% (ARR = 18). This means that approximately 6 patients (1/0.18) need to be treated with antiemetics for one to stay completely free from PONV. If, using the same antiemetic with similar efficacy, the CER is 10%, the ARR would equal 3%, and approximately 33 patients (33 = 1/0.03) need to be treated for one to benefit from the administration of antiemetics in that population (= NNT).308

The validity of these assumptions in a clinical scenario rests on: (1) The ability to correctly classify the PONV risk; (2) The acquisition costs of antiemetics; (3) The potential of antiemetics to cause adverse effects as well as; (4) The clinical applicability and compliance with guidelines depending on their structure (e.g., general multimodal prevention versus various risk-adapted approaches or a combination of these approaches).

Back to Top | Article Outline
Classifying PONV Risk With Risk Model

Clinical risk models have made substantial contributions to eliminate presumed risk factors, so more reasonable risk assessment is now feasible for patients.9,10,48 However, it is important to note “that no risk model can accurately predict the likelihood of an individual having PONV,” rather they allow us “to estimate the risk for PONV among patient groups.”2,309 Furthermore, problems may arise in the prospective determination of what constitutes “opioid therapy,” “motion sickness,” “smoking status” or even “PONV history” (e.g., patient developed PONV after one of previous 3 anesthetics). However, for patient populations, it has been shown in observational trials that:

1. (a) the allocation of patients to risk groups was successful,45 and (b) a risk-adapted PONV protocol effectively reduced the institutional PONV incidence.46 (B2)

Back to Top | Article Outline

THE ACQUISITION COSTS OF ANTIEMETICS

These costs of some of the antiemetics have decreased dramatically during recent years as generic versions have become available and also vary to a large extent from country to country and among different institutions. Published analyses suggest that “PONV prophylaxis is cost-effective with the older, less expensive drugs when patients have a 10% or more risk of emesis.”252 Lower drug acquisition costs may even “support PONV prophylaxis in patient groups at a lower risk for PONV.”2 Newer substances that entered the pharmaceutical market are associated with significant costs, but older molecules should not per se constitute a relevant obstacle to a liberal administration of antiemetics.

Back to Top | Article Outline
Potential for Adverse Effects

The safety of antiemetics is well established considering the huge amount of clinical data available and their summary in valid meta-analyses.310 Limited adverse effects have been associated with the use of minimum effective doses of most recommended antiemetics.

Back to Top | Article Outline
Clinical Applicability and Compliance With Guideline

A risk-adapted PONV protocol effectively reduced institutional PONV incidence.46 (B2). However, it has to be considered that the results of such a protocol were obtained in a clinical study that had good compliance with proposed algorithms, in contrast to clinical implementation in the routine busy setting.

Back to Top | Article Outline
Clinical Effectiveness of PONV Protocols

As observed with other settings and pharmacological preventive measures, effectiveness may be different from efficacy evaluations. The latter may be partly due to poor compliance with existing protocols. This seems to be true in the setting of PONV, where irrespective of tremendous amounts of research findings observational studies investigating whether PONV prevention based on existing clinical guidelines (even if present in the intranet or in the format of a booklet) are poorly implemented (B2). This phenomenon was detected for adults311 and pediatric patients.312 Therefore, some studies suggest the introduction of electronic reminders to improve compliance with standard operating procedures.313,314

The argument that poor education is the root cause for the reluctance to administer appropriate antiemetic prophylaxis seems to be invalid, since the problem persists even after intense educational activities.315 In 1 study, even after training and continuous provider feedback, only 47% and 37% of moderate (2 risk factors present) or high-risk patients (3 risk factors present) received the scheduled prophylactic treatment using a very simple algorithm that suggested administering 1 antiemetic per risk factor found in the preoperative assessment.315 Instead, almost all patients received single antiemetic prophylaxis that was the de facto standard at the site where the study took place.315

Arguing that treating PONV only after symptoms occur is as effective and as appropriate for patients as prevention, disregards the findings of a recent trial showing that PONV symptoms, and nausea in particular, are frequently missed in a busy clinical scenario. This observational study shows only 42% and 29% of PONV episodes were actually detected by the regular staff in the PACU and on the ward, respectively.316

Back to Top | Article Outline
Guideline 8. Use General Multimodal Prevention to Facilitate Implementation of PONV Policies

New information: This is a new section to recommend a multimodal prevention approach to facilitate implementation of PONV (Tables 6 and 7).

Table 6
Table 6
Image Tools
Table 7
Table 7
Image Tools

In view of the poor guideline compliance with risk-adapted approaches and no general preventive measures, multimodal prevention strategy (adjusted with additional measures in high-risk patients) may be an option to facilitate clinical implementation. This is especially true for high-risk patients in which the latter procedure may overcome the hurdle to provide multimodal prevention (Tables 6 and 7).

In 1 study, despite intense educational strategies that resulted in fewer institutional PONV incidences, it was surprising to note that no significant difference in the rate of administration of antiemetic prophylaxis was observed between the overall ‘‘before’’ and ‘‘after’’ patient populations (31.4% vs 36.8%).317 The only difference was in the rate of administration of antiemetic prophylaxis in the high-risk group (with an Apfel simplified score >2), which reached statistical significance (36.4% to 52.8%). This underscores the observed extremely low compliance with institutional PONV policies. In another report, it was stated that only 37% of medium and high-risk patients received the specified prophylaxis, leading to suboptimal PONV prevention in moderate and high-risk patients.318

As a result, fast-track protocols often incorporate multimodal preventive PONV strategies.319,320 General multimodal strategies may well be a starting point to facilitate clinical implementation of better PONV protection of patients.321 Such approaches may prove more effective than strictly risk-based approaches that rely on no prevention in low-risk patients. The goal, therefore, is for antiemetic multimodal prevention to become an integral part of anesthesia.322

Back to Top | Article Outline
Research Agenda for PONV

PONV has been extensively studied, and there is an excellent evidence base to guide clinical practice. Perhaps, the biggest problem is that many anesthesia care providers fail to translate this knowledge into changes in practice.315,323 One of the obstacles to widespread adoption of previous guidelines may be the lack of conviction regarding the clinical importance of PONV and/or unresolved aspects of the risk-benefit of PONV prophylaxis or treatment. One way the latter issue might be clarified is to obtain accurate data regarding the incidence of PONV and the clinical and psychological implications of suffering from nausea and vomiting. The incidence of adverse effects of antiemetics, such as headache, prolonged QT interval, hyperglycemia, and sepsis will better assist clinicians in the management decision-making process. Risk-benefit can be summarized by calculating the likelihood of harm, expressed as the NNT divided by the NNH.324 Such a statistic would only be valid however when both benefit and harm are comparable in their intensity and duration.

There are too many unhelpful PONV studies, many of which address questions that are already known, such as efficacy of many of the established antiemetics, or include too few patients when analyzing risk factors for PONV. We strongly advise against such redundant research.

Back to Top | Article Outline

CONCLUSIONS

These guidelines provide a comprehensive, evidence-based reference tool for the management of patients undergoing surgical procedures who may be at risk for PONV. Not all surgical patients will benefit from antiemetic prophylaxis, thus identification of patients who are at increased risk using available risk scores leads to the most effective use of therapy and the greatest cost-efficacy. Although antiemetic prophylaxis cannot eliminate the risk for PONV, it can significantly reduce the incidence. When developing a management strategy for each individual patient, the choice should be based on patient preference, C/E, and level of PONV risk.

Among the interventions considered, a reduction in baseline risk factors and use of nonpharmacologic therapy are least likely to cause adverse events. PONV prophylaxis should be considered for patients at moderate to high risk for PONV. Depending on the level of risk, prophylaxis should be initiated with monotherapy or combination therapy using interventions that reduce baseline risk, nonpharmacologic approaches, and antiemetics. Antiemetic combinations are recommended for patients at moderate and high risk for PONV. All prophylaxis in children at moderate or high risk for POV should include combination therapy using a 5-HT3 antagonist and a second drug. Because the effects of interventions from different drug classes are additive, combining interventions has an additive effect in risk reduction.

When rescue therapy is required, the antiemetic should be chosen from a different therapeutic class than the drugs used for prophylaxis, and potentially one with a different mode of administration. If PONV occurs within 6 hours postoperatively, patients should not receive a repeat dose of the prophylactic antiemetic. An emetic episode more than 6 hours postoperatively can be treated with any of the drugs used for prophylaxis except dexamethasone, TDS, aprepitant, and palonosetron.

There are significant challenges in implementing an institution-wide, comprehensive PONV prevention protocol based on a detailed risk-adapted approach. A more practical risk assessment using a more liberal preventive strategy may be a better alternative in a busy clinical environment such that it becomes an integral part of anesthesia.

Back to Top | Article Outline

APPENDIX 2

Category A: Supportive Literature

Randomized controlled trials report statistically significant (P < 0.01) differences between clinical interventions for a specified clinical outcome.

Level 1: The literature contains multiple randomized controlled trials, and aggregated findings are supported by meta-analysis.

Level 2: The literature contains multiple randomized controlled trials, but the number of studies is insufficient to conduct a viable meta-analysis for the purpose of these guidelines.

Level 3: The literature contains a single randomized controlled trial.

Back to Top | Article Outline
Category B: Suggestive Literature

Information from observational studies permits inference of beneficial or harmful relationships among clinical interventions and clinical outcomes.

Level 1: The literature contains observational comparisons (e.g., cohort, case-control research designs) of clinical interventions or conditions and indicates statistically significant differences between clinical interventions for a specified clinical outcome.

Level 2: The literature contains noncomparative observational studies with associative (e.g., relative risk, correlation) or descriptive statistics.

Level 3: The literature contains case reports.

Back to Top | Article Outline
Category C: Equivocal Literature

The literature cannot determine whether there are beneficial or harmful relationships among clinical interventions and clinical outcomes.

Level 1: Meta-analysis did not find significant differences (P > 0.01) among groups or conditions.

Level 2: The number of studies is insufficient to conduct meta-analysis, and (1) randomized controlled trials have not found significant differences among groups or conditions, or (2) randomized controlled trials report inconsistent findings.

Level 3: Observational studies report inconsistent findings or do not permit inference of beneficial or harmful relationships.

Back to Top | Article Outline
Category D: Insufficient Evidence from Literature

The lack of scientific evidence in the literature is described by the following terms.

Inadequate: The available literature cannot be used to assess relationships among clinical interventions and clinical outcomes. The literature either does not meet the criteria for content as defined in the “Focus” of the Guidelines or does not permit a clear interpretation of findings due to methodological concerns (e.g., confounding in study design or implementation).

Silent: No identified studies address the specified relationships among interventions and outcomes.

Back to Top | Article Outline

APPENDIX 3

This set of guidelines have been officially endorsed by the following societies:

American Academy of Anesthesiologist Assistants

American Association of Nurse Anesthetists

American Society of Anesthesiologists

American Society of Health Systems Pharmacists

American Society of PeriAnesthesia Nurses

Australian and New Zealand College of Anaesthetists

Chinese Society of Anesthesiology

CongresoLationoamericano de Sociedades de Anestesia

European Society of Anaesthesiology

Hong Kong College of Anaesthesiologists

Malaysian Society of Anaesthesiologists

Singapore Society of Anaesthesiologists

South African Society of Anaesthesiologists

Back to Top | Article Outline

RECUSE NOTE

Dr. Peter J. Davis is the Section Editor for Pediatric Anesthesiology for the Journal. This manuscript was handled by Dr. Steven L. Shafer, Editor-in-Chief, and Dr. Davis was not involved in any way with the editorial process or decision.

Back to Top | Article Outline

DISCLOSURES

Name: Tong J Gan, MD.

Contribution: This author helped write the manuscript.

Attestation: Tong J Gan has approved the final manuscript.

Conflicts of Interest: Tong J Gan has received research grants or honorarium from Acacia, Pacira. Baxter, Cubist, Fresenius, Hospira and Merck.

Name: Pierre Diemunsch, MD, PhD.

Contribution: This author helped write the manuscript and helped lead the subgroups.

Attestation: Pierre Diemunsch has approved the final manuscript.

Conflicts of Interest: Pierre Diemunsch has given paid lectures and received consultant fees and research grants from Merck, Glaxo, Astra Zeneca, and Prostrakan.

Name: Ashraf S. Habib, MB, FRCA.

Contribution: This author helped write the manuscript and helped lead the subgroups.

Attestation: Ashraf Habib has approved the final manuscript.

Conflicts of Interest: The author has no conflicts of interest to declare.

Name: Anthony Kovac, MD.

Contribution: This author helped write the manuscript and helped lead the subgroups.

Attestation: Anthony Kovac has approved the final manuscript.

Conflicts of Interest: Anthony Kovac has received honoraria from Baxter, Helsinn, and Merck.

Name: Peter Kranke, MD, PhD, MBA.

Contribution: This author helped write the manuscript and helped lead the subgroups.

Attestation: Peter Kranke has approved the final manuscript.

Conflicts of Interest: Peter Kranke was involved in the conduct of clinical trials and acted as clinical advisor for Acacia Pharma, Ltd., Cambridge, UK. Consulted for Fresenius Kabi, Deutschland GmbH, Bad Homburg, Germany, and for ProStrakan Pharma, GmbH, Dusseldorf, Germany.

Name: Tricia A. Meyer, PharmD, MS, FASHP.

Contribution: This author helped write the manuscript and helped lead the subgroups.

Attestation: Tricia A. Meyer has approved the final manuscript.

Conflicts of Interest: Tricia A. Meyer has received research support from Merck.

Name: Mehernoor Watcha, MD.

Contribution: This author helped write the manuscript and helped lead the subgroups.

Attestation: Mehernoor Watcha has approved the final manuscript.

Conflicts of Interest: The author has no conflicts of interest to declare.

Name: Frances Chung, MBBS.

Contribution: This author helped write the manuscript and coordinated the literature search process.

Attestation: Frances Chung has approved the final manuscript.

Conflicts of Interest: The author has no conflicts of interest to declare.

Name: Shane Angus, AA-C, MS.

Contribution: This author helped write the manuscript.

Attestation: Shane Angus has approved the final manuscript.

Conflicts of Interest: The author has no conflicts of interest to declare.

Name: Christian C. Apfel, MD, PhD.

Contribution: This author helped write the manuscript.

Attestation: Christian C. Apfel has approved the final manuscript.

Conflicts of Interest: The author has no conflicts of interest to declare.

Name: Sergio D. Bergese, MD.

Contribution: This author helped write the manuscript.

Attestation: Sergio D. Bergese has approved the final manuscript.

Conflicts of Interest: Sergio D. Bergese is a consultant with Baxter.

Name: Keith A. Candiotti, MD.

Contribution: This author helped write the manuscript.

Attestation: Keith A. Candiotti has approved the final manuscript.

Conflicts of Interest: Keith A. Candiotti has received research grant support from Merck and Helsinn.

Name: Matthew TV Chan, MB, BS, FANZCA.

Contribution: This author helped write the manuscript.

Attestation: Matthew TV Chan has approved the final manuscript.

Conflicts of Interest: The author has no conflicts of interest to declare.

Name: Peter J. Davis, MD.

Contribution: This author helped write the manuscript.

Attestation: Peter J. Davis has approved the final manuscript.

Conflicts of Interest: Peter J. Davis received research grant support from Janssen, Hospira, and Cumberland.

Name: Vallire D. Hooper, PhD, RN, CPAN, FAAN.

Contribution: This author helped write the manuscript.

Attestation: Vallire D. Hooper has approved the final manuscript.

Conflicts of Interest: The author has no conflicts of interest to declare.

Name: Sandhya Lagoo-Deenadayalan, MD, PhD.

Contribution: This author helped write the manuscript.

Attestation: Sandhya Lagoo-Deenadayalan has approved the final manuscript.

Conflicts of Interest: The author has no conflicts of interest to declare.

Name: Paul Myles, MD.

Contribution: This author helped write the manuscript.

Attestation: Paul Myles has approved the final manuscript.

Conflicts of Interest: The author has no conflicts of interest to declare.

Name: Greg Nezat, CRNA, PhD.

Contribution: This author helped write the manuscript.

Attestation: Greg Nezat has approved the final manuscript.

Conflicts of Interest: The author has no conflicts of interest to declare.

Name: Beverly K. Philip, MD.

Contribution: This author helped write the manuscript.

Attestation: Beverly K. Philip has approved the final manuscript.

Conflicts of Interest: Beverly K. Philip has financial relationship with Cumberland and Merck.

Name: Martin R. Tramèr, MD, DPhil.

Contribution: This author helped write the manuscript.

Attestation: Martin R. Tramèr has approved the final manuscript.

Conflicts of Interest: The author has no conflicts of interest to declare.

Back to Top | Article Outline

ACKNOWLEDGMENTS

The authors would like to thank Marina Englesakis, BA (Hons), MLIS, Information Specialist, Health Sciences Library, University Health Network, Toronto, Ontario, Canada, and Frances Chung, MBBS, Professor, Department of Anesthesia, University Health Network, University of Toronto, for their assistance and coordination with the literature search.

Back to Top | Article Outline

REFERENCES

1. Gan TJ, Meyer T, Apfel CC, Chung F, Davis PJ, Eubanks S, Kovac A, Philip BK, Sessler DI, Temo J, Tramèr MR, Watcha MDepartment of Anesthesiology, Duke University Medical Center. . Consensus guidelines for managing postoperative nausea and vomiting. Anesth Analg. 2003;97:62–71

2. Gan TJ, Meyer TA, Apfel CC, Chung F, Davis PJ, Habib AS, Hooper VD, Kovac AL, Kranke P, Myles P, Philip BK, Samsa G, Sessler DI, Temo J, Tramèr MR, Vander Kolk C, Watcha MSociety for Ambulatory Anesthesia. . Society for Ambulatory Anesthesia guidelines for the management of postoperative nausea and vomiting. Anesth Analg. 2007;105:1615–28

3. . ASPAN’S evidence-based clinical practice guideline for the prevention and/or management of PONV/PDNV. J Perianesth Nurs. 2006;21:230–50

4. Diemunsch PSociété française d’anesthésie et de réanimation. . [Conference of experts–short text. Management of postoperative nausea and vomiting. French Society of Anesthesia and Resuscitation]. Ann Fr Anesth Reanim. 2008;27:866–78

5. Gómez-Arnau JI, Aguilar JL, Bovaira P, Bustos F, De Andrés J, de la Pinta JC, García-Fernández J, López-Alvarez S, López-Olaondo L, Neira F, Planas A, Pueyo J, Vila P, Torres LMGrupo de Trabajo de NVPO de la Sociedad Española de Anestesiología y Reanimación. . [Postoperative nausea and vomiting and opioid-induced nausea and vomiting: guidelines for prevention and treatment]. Rev Esp Anestesiol Reanim. 2010;57:508–24

6. McCracken G, Houston P, Lefebvre GSociety of Obstetricians and Gynecologists of Canada. . Guideline for the management of postoperative nausea and vomiting. J Obstet Gynaecol Can. 2008;30:600–7, 608–16

7. Rüsch D, Becke K, Eberhart LH, Franck M, Hönig A, Morin AM, Opel S, Piper S, Treiber H, Ullrich L, Wallenborn J, Kranke P. [Postoperative nausea and vomiting (PONV)-recommendations for risk assessment, prophylaxis and therapy-results of an expert panel meeting]. Anasthesiol Intensivmed Notfallmed Schmerzther. 2011;46:158–70

8. Apfelbaum JL, Silverstein JH, Chung FF, Connis RT, Fillmore RB, Hunt SE, Nickinovich DG, Schreiner MS, Silverstein JH, Apfelbaum JL, Barlow JC, Chung FF, Connis RT, Fillmore RB, Hunt SE, Joas TA, Nickinovich DG, Schreiner MSAmerican Society of Anesthesiologists Task Force on Postanesthetic Care. . Practice guidelines for postanesthetic care: an updated report by the American Society of Anesthesiologists Task Force on Postanesthetic Care. Anesthesiology. 2013;118:291–307

9. Apfel CC, Läärä E, Koivuranta M, Greim CA, Roewer N. A simplified risk score for predicting postoperative nausea and vomiting: conclusions from cross-validations between two centers. Anesthesiology. 1999;91:693–700

10. Koivuranta M, Läärä E, Snåre L, Alahuhta S. A survey of postoperative nausea and vomiting. Anaesthesia. 1997;52:443–9

11. Sinclair DR, Chung F, Mezei G. Can postoperative nausea and vomiting be predicted? Anesthesiology. 1999;91:109–18

12. Fortier J, Chung F, Su J. Unanticipated admission after ambulatory surgery–a prospective study. Can J Anaesth. 1998;45:612–9

13. Gold BS, Kitz DS, Lecky JH, Neuhaus JM. Unanticipated admission to the hospital following ambulatory surgery. JAMA. 1989;262:3008–10

14. Hill RP, Lubarsky DA, Phillips-Bute B, Fortney JT, Creed MR, Glass PS, Gan TJ. Cost-effectiveness of prophylactic antiemetic therapy with ondansetron, droperidol, or placebo. Anesthesiology. 2000;92:958–67

15. Tramèr MR. Strategies for postoperative nausea and vomiting. Best Pract Res Clin Anaesthesiol. 2004;18:693–701

16. Higgins JPT, Green SThe Cochrane Collaboration. Cochrane Handbook for Systematic Reviews of Interventions Version 5.0.0 [updated February 2008]. 2008 Available at: http://www.cochrane-handbook.org. Accessed May 18, 2013

17. Habib AS, Gan TJ. Scientific fraud: impact of Fujii’s data on our current knowledge and practice for the management of postoperative nausea and vomiting. Anesth Analg. 2013;116:520–2

18. . Practice guidelines for acute pain management in the perioperative setting: an updated report by the American Society of Anesthesiologists Task Force on Acute Pain Management. Anesthesiology. 2012;116:248–73

19. Apfel CC, Philip BK, Cakmakkaya OS, Shilling A, Shi YY, Leslie JB, Allard M, Turan A, Windle P, Odom-Forren J, Hooper VD, Radke OC, Ruiz J, Kovac A. Who is at risk for postdischarge nausea and vomiting after ambulatory surgery? Anesthesiology. 2012;117:475–86

20. Apfel CC, Heidrich FM, Jukar-Rao S, Jalota L, Hornuss C, Whelan RP, Zhang K, Cakmakkaya OS. Evidence-based analysis of risk factors for postoperative nausea and vomiting. Br J Anaesth. 2012;109:742–53

21. Apfel CC, Kranke P, Katz MH, Goepfert C, Papenfuss T, Rauch S, Heineck R, Greim CA, Roewer N. Volatile anaesthetics may be the main cause of early but not delayed postoperative vomiting: a randomized controlled trial of factorial design. Br J Anaesth. 2002;88:659–68

22. Myles PS, Leslie K, Chan MT, Forbes A, Paech MJ, Peyton P, Silbert BS, Pascoe EENIGMA Trial Group. . Avoidance of nitrous oxide for patients undergoing major surgery: a randomized controlled trial. Anesthesiology. 2007;107:221–31

23. Breitfeld C, Peters J, Vockel T, Lorenz C, Eikermann M. Emetic effects of morphine and piritramide. Br J Anaesth. 2003;91:218–23

24. Hong D, Flood P, Diaz G. The side effects of morphine and hydromorphone patient-controlled analgesia. Anesth Analg. 2008;107:1384–9

25. Roberts GW, Bekker TB, Carlsen HH, Moffatt CH, Slattery PJ, McClure AF. Postoperative nausea and vomiting are strongly influenced by postoperative opioid use in a dose-related manner. Anesth Analg. 2005;101:1343–8

26. Liu SS, Strodtbeck WM, Richman JM, Wu CL. A comparison of regional versus general anesthesia for ambulatory anesthesia: a meta-analysis of randomized controlled trials. Anesth Analg. 2005;101:1634–42

27. Marret E, Kurdi O, Zufferey P, Bonnet F. Effects of nonsteroidal antiinflammatory drugs on patient-controlled analgesia morphine side effects: meta-analysis of randomized controlled trials. Anesthesiology. 2005;102:1249–60

28. Gurbet A, Basagan-Mogol E, Turker G, Ugun F, Kaya FN, Ozcan B. Intraoperative infusion of dexmedetomidine reduces perioperative analgesic requirements. Can J Anaesth. 2006;53:646–52

29. Collard V, Mistraletti G, Taqi A, Asenjo JF, Feldman LS, Fried GM, Carli F. Intraoperative esmolol infusion in the absence of opioids spares postoperative fentanyl in patients undergoing ambulatory laparoscopic cholecystectomy. Anesth Analg. 2007;105:1255–62

30. Janicki PK, Vealey R, Liu J, Escajeda J, Postula M, Welker K. Genome-wide Association study using pooled DNA to identify candidate markers mediating susceptibility to postoperative nausea and vomiting. Anesthesiology. 2011;115:54–64

31. Apfel CC, Kranke P, Eberhart LH. Comparison of surgical site and patient’s history with a simplified risk score for the prediction of postoperative nausea and vomiting. Anaesthesia. 2004;59:1078–82

32. Leslie K, Myles PS, Chan MT, Paech MJ, Peyton P, Forbes A, McKenzie DENIGMA Trial Group. . Risk factors for severe postoperative nausea and vomiting in a randomized trial of nitrous oxide-based vs nitrous oxide-free anaesthesia. Br J Anaesth. 2008;101:498–505

33. Cohen MM, Duncan PG, DeBoer DP, Tweed WA. The postoperative interview: assessing risk factors for nausea and vomiting. Anesth Analg. 1994;78:7–16

34. Stadler M, Bardiau F, Seidel L, Albert A, Boogaerts JG. Difference in risk factors for postoperative nausea and vomiting. Anesthesiology. 2003;98:46–52

35. Wallenborn J, Gelbrich G, Bulst D, Behrends K, Wallenborn H, Rohrbach A, Krause U, Kühnast T, Wiegel M, Olthoff D. Prevention of postoperative nausea and vomiting by metoclopramide combined with dexamethasone: randomised double blind multicentre trial. BMJ. 2006;333:324

36. Van den Bosch JE, Moons KG, Bonsel GJ, Kalkman CJ. Does measurement of preoperative anxiety have added value for predicting postoperative nausea and vomiting? Anesth Analg. 2005;100:1525–32

37. Eberhart LH, Morin AM, Georgieff M. [The menstruation cycle in the postoperative phase. Its effect of the incidence of nausea and vomiting]. Anaesthesist. 2000;49:532–5

38. Cheng CR, Sessler DI, Apfel CC. Does neostigmine administration produce a clinically important increase in postoperative nausea and vomiting? Anesth Analg. 2005;101:1349–55

39. Tramèr MR, Fuchs-Buder T. Omitting antagonism of neuromuscular block: effect on postoperative nausea and vomiting and risk of residual paralysis. A systematic review. Br J Anaesth. 1999;82:379–86

40. Gan TJ. Risk factors for postoperative nausea and vomiting. Anesth Analg. 2006;102:1884–98

41. Kerger KH, Mascha E, Steinbrecher B, Frietsch T, Radke OC, Stoecklein K, Frenkel C, Fritz G, Danner K, Turan A, Apfel CCIMPACT Investigators. . Routine use of nasogastric tubes does not reduce postoperative nausea and vomiting. Anesth Analg. 2009;109:768–73

42. Orhan-Sungur M, Kranke P, Sessler D, Apfel CC. Does supplemental oxygen reduce postoperative nausea and vomiting? A meta-analysis of randomized controlled trials. Anesth Analg. 2008;106:1733–8

43. Kranke P, Apefel CC, Papenfuss T, Rauch S, Löbmann U, Rübsam B, Greim CA, Roewer N. An increased body mass index is no risk factor for postoperative nausea and vomiting. A systematic review and results of original data. Acta Anaesthesiol Scand. 2001;45:160–6

44. Charbit B, Albaladejo P, Funck-Brentano C, Legrand M, Samain E, Marty J. Prolongation of QTc interval after postoperative nausea and vomiting treatment by droperidol or ondansetron. Anesthesiology. 2005;102:1094–100

45. Pierre S, Benais H, Pouymayou J. Apfel’s simplified score may favourably predict the risk of postoperative nausea and vomiting. Can J Anaesth. 2002;49:237–42

46. Pierre S, Corno G, Benais H, Apfel CC. A risk score-dependent antiemetic approach effectively reduces postoperative nausea and vomiting–a continuous quality improvement initiative. Can J Anaesth. 2004;51:320–5

47. Apfel CC, Korttila K, Abdalla M, Kerger H, Turan A, Vedder I, Zernak C, Danner K, Jokela R, Pocock SJ, Trenkler S, Kredel M, Biedler A, Sessler DI, Roewer NIMPACT Investigators. . A factorial trial of six interventions for the prevention of postoperative nausea and vomiting. N Engl J Med. 2004;350:2441–51

48. Eberhart LH, Geldner G, Kranke P, Morin AM, Schäuffelen A, Treiber H, Wulf H. The development and validation of a risk score to predict the probability of postoperative vomiting in pediatric patients. Anesth Analg. 2004;99:1630–7

49. Kranke P, Eberhart LH, Toker H, Roewer N, Wulf H, Kiefer P. A prospective evaluation of the POVOC score for the prediction of postoperative vomiting in children. Anesth Analg. 2007;105:1592–7

50. Erdem AF, Yoruk O, Alici HA, Cesur M, Atalay C, Altas E, Kursad H, Yuksek MS. Subhypnotic propofol infusion plus dexamethasone is more effective than dexamethasone alone for the prevention of vomiting in children after tonsillectomy. Paediatr Anaesth. 2008;18:878–83

51. Erdem AF, Yoruk O, Silbir F, Alici HA, Cesur M, Dogan N, Aktan B, Sutbeyaz Y. Tropisetron plus subhypnotic propofol infusion is more effective than tropisetron alone for the prevention of vomiting in children after tonsillectomy. Anaesth Intensive Care. 2009;37:54–9

52. Rowley MP, Brown TC. Postoperative vomiting in children. Anaesth Intensive Care. 1982;10:309–13

53. 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 with vomiting and economic analysis. Anesthesiology. 2001;95:616–26

54. Tramèr M, Moore A, McQuay H. Meta-analytic comparison of prophylactic antiemetic efficacy for postoperative nausea and vomiting: propofol anaesthesia vs omitting nitrous oxide vs total i.v. anaesthesia with propofol. Br J Anaesth. 1997;78:256–9

55. Tramèr M, Moore A, McQuay H. Omitting nitrous oxide in general anaesthesia: meta-analysis of intraoperative awareness and postoperative emesis in randomized controlled trials. Br J Anaesth. 1996;76:186–93

56. Møiniche S, Rømsing J, Dahl JB, Tramèr MR. Nonsteroidal antiinflammatory drugs and the risk of operative site bleeding after tonsillectomy: a quantitative systematic review. Anesth Analg. 2003;96:68–77

57. Polati E, Verlato G, Finco G, Mosaner W, Grosso S, Gottin L, Pinaroli AM, Ischia S. Ondansetron versus metoclopramide in the treatment of postoperative nausea and vomiting. Anesth Analg. 1997;85:395–9

58. Sukhani R, Vazquez J, Pappas AL, Frey K, Aasen M, Slogoff S. Recovery after propofol with and without intraoperative fentanyl in patients undergoing ambulatory gynecologic laparoscopy. Anesth Analg. 1996;83:975–81

59. Elia N, Lysakowski C, Tramèr MR. Does multimodal analgesia with acetaminophen, nonsteroidal antiinflammatory drugs, or selective cyclooxygenase-2 inhibitors and patient-controlled analgesia morphine offer advantages over morphine alone? Meta-analyses of randomized trials. Anesthesiology. 2005;103:1296–304

60. Gan TJ, Joshi GP, Zhao SZ, Hanna DB, Cheung RY, Chen C. Presurgical intravenous parecoxib sodium and follow-up oral valdecoxib for pain management after laparoscopic cholecystectomy surgery reduces opioid requirements and opioid-related adverse effects. Acta Anaesthesiol Scand. 2004;48:1194–207

61. Elia N, Tramèr MR. Ketamine and postoperative pain–a quantitative systematic review of randomised trials. Pain. 2005;113:61–70

62. Chan KS, Chen WH, Gan TJ, Hsieh R, Chen C, Lakshminarayanan M, Revicki DA. Development and validation of a composite score based on clinically meaningful events for the opioid-related symptom distress scale. Qual Life Res. 2009;18:1331–40

63. Ho KM, Ismail H, Lee KC, Branch R. Use of intrathecal neostigmine as an adjunct to other spinal medications in perioperative and peripartum analgesia: a meta-analysis. Anaesth Intensive Care. 2005;33:41–53

64. Orhan-Sungur M, Kranke P, Sessler D, Apfel CC. Does supplemental oxygen reduce postoperative nausea and vomiting? A meta-analysis of randomized controlled trials. Anesth Analg. 2008;106:1733–8

65. De Windt AC, Asehnoune K, Roquilly A, Guillaud C, Le Roux C, Pinaud M, Lejus C. An opioid-free anaesthetic using nerve blocks enhances rapid recovery after minor hand surgery in children. Eur J Anaesthesiol. 2010;27:521–5

66. Gupta N, Kumar R, Kumar S, Sehgal R, Sharma KR. A prospective randomised double blind study to evaluate the effect of peribulbar block or topical application of local anaesthesia combined with general anaesthesia on intra-operative and postoperative complications during paediatric strabismus surgery. Anaesthesia. 2007;62:1110–3

67. Steib A, Karcenty A, Calache E, Franckhauser J, Dupeyron JP, Speeg-Schatz C. Effects of subtenon anesthesia combined with general anesthesia on perioperative analgesic requirements in pediatric strabismus surgery. Reg Anesth Pain Med. 2005;30:478–83

68. Ghai B, Ram J, Makkar JK, Wig J, Kaushik S. Subtenon block compared to intravenous fentanyl for perioperative analgesia in pediatric cataract surgery. Anesth Analg. 2009;108:1132–8

69. Cardwell ME, Siviter G, Smith AF. Nonsteroidal anti-inflammatory drugs and perioperative bleeding in paediatric tonsillectomy. Cochrane Database Syst Rev. 2013;7:CD003591

70. Goodarzi M, Matar MM, Shafa M, Townsend JE, Gonzalez I. A prospective randomized blinded study of the effect of intravenous fluid therapy on postoperative nausea and vomiting in children undergoing strabismus surgery. Paediatr Anaesth. 2006;16:49–53

71. Chukudebelu O, Leonard DS, Healy A, McCoy D, Charles D, Hone S, Rafferty M. The effect of gastric decompression on postoperative nausea and emesis in pediatric, tonsillectomy patients. Int J Pediatr Otorhinolaryngol. 2010;74:674–6

72. Radke OC, Biedler A, Kolodzie K, Cakmakkaya OS, Silomon M, Apfel CC. The effect of postoperative fasting on vomiting in children and their assessment of pain. Paediatr Anaesth. 2009;19:494–9

73. Bolton CM, Myles PS, Nolan T, Sterne JA. Prophylaxis of postoperative vomiting in children undergoing tonsillectomy: a systematic review and meta-analysis. Br J Anaesth. 2006;97:593–604

74. Tramèr MR, Reynolds DJ, Moore RA, McQuay HJ. Efficacy, dose-response, and safety of ondansetron in prevention of postoperative nausea and vomiting: a quantitative systematic review of randomized placebo-controlled trials. Anesthesiology. 1997;87:1277–89

75. Grover VK, Mathew PJ, Hegde H. Efficacy of orally disintegrating ondansetron in preventing postoperative nausea and vomiting after laparoscopic cholecystectomy: a randomised, double-blind placebo controlled study. Anaesthesia. 2009;64:595–600

76. Hartsell T, Long D, Kirsch JR. The efficacy of postoperative ondansetron (Zofran) orally disintegrating tablets for preventing nausea and vomiting after acoustic neuroma surgery. Anesth Analg. 2005;101:1492–6

77. Ryu J, So YM, Hwang J, Do SH. Ramosetron versus ondansetron for the prevention of postoperative nausea and vomiting after laparoscopic cholecystectomy. Surg Endosc. 2010;24:812–7

78. Aouad MT, Siddik-Sayyid SM, Taha SK, Azar MS, Nasr VG, Hakki MA, Zoorob DG, Baraka AS. Haloperidol vs. ondansetron for the prevention of postoperative nausea and vomiting following gynaecological surgery. Eur J Anaesthesiol. 2007;24:171–8

79. Lee Y, Wang PK, Lai HY, Yang YL, Chu CC, Wang JJ. Haloperidol is as effective as ondansetron for preventing postoperative nausea and vomiting. Can J Anaesth. 2007;54:349–54

80. Rosow CE, Haspel KL, Smith SE, Grecu L, Bittner EA. Haloperidol versus ondansetron for prophylaxis of postoperative nausea and vomiting. Anesth Analg. 2008;106:1407–9

81. Diemunsch P, Gan TJ, Philip BK, Girao MJ, Eberhart L, Irwin MG, Pueyo J, Chelly JE, Carides AD, Reiss T, Evans JK, Lawson FCAprepitant-PONV Protocol 091 International Study Group. . Single-dose aprepitant vs ondansetron for the prevention of postoperative nausea and vomiting: a randomized, double-blind phase III trial in patients undergoing open abdominal surgery. Br J Anaesth. 2007;99:202–11

82. Park SK, Cho EJ. A randomized, double-blind trial of palonosetron compared with ondansetron in preventing postoperative nausea and vomiting after gynaecological laparoscopic surgery. J Int Med Res. 2011;39:399–407

83. Golembiewski J, Tokumaru S. Pharmacological prophylaxis and management of adult postoperative/postdischarge nausea and vomiting. J Perianesth Nurs. 2006;21:385–97

84. Le TP, Gan TJ. Update on the management of postoperative nausea and vomiting and postdischarge nausea and vomiting in ambulatory surgery. Anesthesiol Clin. 2010;28:225–49

85. Graczyk SG, McKenzie R, Kallar S, Hickok CB, Melson T, Morrill B, Hahne WF, Brown RA. Intravenous dolasetron for the prevention of postoperative nausea and vomiting after outpatient laparoscopic gynecologic surgery. Anesth Analg. 1997;84:325–30

86. Iatrou CA, Dragoumanis CK, Vogiatzaki TD, Vretzakis GI, Simopoulos CE, Dimitriou VK. Prophylactic intravenous ondansetron and dolasetron in intrathecal morphine-induced pruritus: a randomized, double-blinded, placebo-controlled study. Anesth Analg. 2005;101:1516–20

87. Birmingham SD, Mecklenburg BW, Lujan E, Dacanay RG, Boyle PK, Green R. Dolasetron versus ondansetron as single-agent prophylaxis for patients at increased risk for postoperative nausea and vomiting: a prospective, double-blind, randomized trial. Mil Med. 2006;171:913–6

88. Piper SN, Röhm K, Boldt J, Kranke P, Maleck W, Seifert R, Suttner S. Postoperative nausea and vomiting after surgery for prognathism: not only a question of patients’ comfort. A placebo-controlled comparison of dolasetron and droperidol. J Craniomaxillofac Surg. 2008;36:173–9

89. Janicki PK, Schuler HG, Jarzembowski TM, Rossi M 2nd. Prevention of postoperative nausea and vomiting with granisetron and dolasetron in relation to CYP2D6 genotype. Anesth Analg. 2006;102:1127–33

90. U.S. Department of Health and Human Services. Ondansetron (Zofran) IV: Drug Safety Communication-QT prolongation 2012 [June 18, 2012]. Available at: http://www.fda.gov/Safety/MedWatch/SafetyInformation/SafetyAlertsforHumanMedicalProducts/ucm237341.htm?utm_campaign=Google2&utm_source=fdaSearch&utm_medium=website&utm_term=dolasetron&utm_content=2

91. Bhatia N, Katyal S, Grewal A, Kaul TK. Antiemetic prophylaxis with granisetron, ondansetron and metoclopramide in ambulatory gynaecological laparoscopic surgery: a comparison. J Anaesthesiol Clin Pharmacol. 2008;24:303–6

92. White PF, Tang J, Hamza MA, Ogunnaike B, Lo M, Wender RH, Naruse R, Sloninsky A, Kariger R, Cunneen S, Khalili T. The use of oral granisetron versus intravenous ondansetron for antiemetic prophylaxis in patients undergoing laparoscopic surgery: the effect on emetic symptoms and quality of recovery. Anesth Analg. 2006;102:1387–93

93. Erhan Y, Erhan E, Aydede H, Yumus O, Yentur A. Ondansetron, granisetron, and dexamethasone compared for the prevention of postoperative nausea and vomiting in patients undergoing laparoscopic cholecystectomy: a randomized placebo-controlled study. Surg Endosc. 2008;22:1487–92

94. Sodhi K, Mohindra BK, Sodhi GS, Kumar M. A comparative study of granisetron, dexamethasone, and granisetron plus dexamethasone as prophylactic antiemetic therapy in female patients undergoing breast surgery. J Anaesthesiol Clin Pharmacol. 2007;23:373–8

95. Johns RA, Hanousek J, Montgomery JE. A comparison of cyclizine and granisetron alone and in combination for the prevention of postoperative nausea and vomiting. Anaesthesia. 2006;61:1053–7

96. Bhattacharjee DP, Dawn S, Nayak S, Roy PR, Acharya A, Dey R. A comparative study between palonosetron and granisetron to prevent postoperative nausea and vomiting after laparoscopic cholecystectomy. J Anaesthesiol Clin Pharmacol. 2010;26:480–3

97. Kranke P, Eberhart LH, Apfel CC, Broscheit J, Geldner G, Roewer N. [Tropisetron for prevention of postoperative nausea and vomiting: a quantitative systematic review]. Anaesthesist. 2002;51:805–14

98. Contreras-Domínguez V, Carbonell-Bellolio P. Prophylactic antiemetic therapy for acute abdominal surgery. A comparative study of droperidol, metoclopramide, tropisetron, granisetron and dexamethasone. Rev Bras Anestesiol. 2008;58:35–44

99. Ekinci O, Malat I, Işitmangil G, Aydin N. A randomized comparison of droperidol, metoclopramide, tropisetron, and ondansetron for the prevention of postoperative nausea and vomiting. Gynecol Obstet Invest. 2011;71:59–65

100. Eberhart LH, Büning EK, Folz B, Maybauer DM, Kästner M, Kalder M, Koch T, Kranke P, Wulf H. Anti-emetic prophylaxis with oral tropisetron and/or dexamethasone. Eur J Clin Invest. 2006;36:580–7

101. Lee HJ, Kwon JY, Shin SW, Kim CH, Baek SH, Baik SW, Kim HK, Kim KH. Preoperatively administered ramosetron oral disintegrating tablets for preventing nausea and vomiting associated with patient-controlled analgesia in breast cancer patients. Eur J Anaesthesiol. 2008;25:756–62

102. Choi YS, Shim JK, Yoon do H, Jeon DH, Lee JY, Kwak YL. Effect of ramosetron on patient-controlled analgesia related nausea and vomiting after spine surgery in highly susceptible patients: comparison with ondansetron. Spine (Phila Pa 1976). 2008;33:E602–6

103. George E, Hornuss C, Apfel CC. Neurokinin-1 and novel serotonin antagonists for postoperative and postdischarge nausea and vomiting. Curr Opin Anaesthesiol. 2010;23:714–21

104. Bajwa SS, Bajwa SK, Kaur J, Sharma V, Singh A, Singh A, Goraya S, Parmar S, Singh K. Palonosetron: A novel approach to control postoperative nausea and vomiting in day care surgery. Saudi J Anaesth. 2011;5:19–24

105. Kovac AL, Eberhart L, Kotarski J, Clerici G, Apfel CPalonosetron 04-07 Study Group. . A randomized, double-blind study to evaluate the efficacy and safety of three different doses of palonosetron versus placebo in preventing postoperative nausea and vomiting over a 72-hour period. Anesth Analg. 2008;107:439–44

106. Candiotti KA, Kovac AL, Melson TI, Clerici G, Joo Gan TPalonosetron 04-06 Study Group. . A randomized, double-blind study to evaluate the efficacy and safety of three different doses of palonosetron versus placebo for preventing postoperative nausea and vomiting. Anesth Analg. 2008;107:445–51

107. Sun R, Klein KW, White PF. The effect of timing of ondansetron administration in outpatients undergoing otolaryngologic surgery. Anesth Analg. 1997;84:331–6

108. Wilson AJ, Diemunsch P, Lindeque BG, Scheinin H, Helbo-Hansen HS, Kroeks MV, Kong KL. Single-dose i.v. granisetron in the prevention of postoperative nausea and vomiting. Br J Anaesth. 1996;76:515–8

109. Mikawa K, Takao Y, Nishina K, Shiga M, Maekawa N, Obara H. Optimal dose of granisetron for prophylaxis against postoperative emesis after gynecological surgery. Anesth Analg. 1997;85:652–6

110. D’Angelo R, Philip B, Gan TJ, Kovac A, Hantler C, Doblar D, Melson T, Minkowitz H, Dalby P, Coop A. A randomized, double-blind, close-ranging, pilot study of intravenous granisetron in the prevention of postoperative nausea and vomiting in patients abdominal hysterectomy. Eur J Anaesthesiol. 2005;22:774–9

111. Chen X, Tang J, White PF, Wender RH, Quon R, Sloninsky A, Naruse R, Kariger R, Webb T, Norel E. The effect of timing of dolasetron administration on its efficacy as a prophylactic antiemetic in the ambulatory setting. Anesth Analg. 2001;93:906–11

112. U.S. Food and Drug Administration. Ondansetron (Zofran) 32 mg, Single Intravenous (IV) Dose: Updated Safety Communication–Product Removal due to Potential For Serious Cardiac Risks 2012 [12/14/2012]. Available at: http://www.fda.gov/drugs/drugsafety/ucm271913.htm. Accessed November 18, 2013

113. Gan TJ, Apfel CC, Kovac A, Philip BK, Singla N, Minkowitz H, Habib AS, Knighton J, Carides AD, Zhang H, Horgan KJ, Evans JK, Lawson FCAprepitant-PONV Study Group. . A randomized, double-blind comparison of the NK1 antagonist, aprepitant, versus ondansetron for the prevention of postoperative nausea and vomiting. Anesth Analg. 2007;104:1082–9 tables of contents

114. Habib AS, Keifer JC, Borel CO, White WD, Gan TJ. A comparison of the combination of aprepitant and dexamethasone versus the combination of ondansetron and dexamethasone for the prevention of postoperative nausea and vomiting in patients undergoing craniotomy. Anesth Analg. 2011;112:813–8

115. Gin T, Lai L, Tang Y, Cheng B, Chan M. Aprepitant for preventing postoperative nausea and vomiting: a dose finding study. Eur J Anaesthesiol. 2009;26:128

116. Scuderi PE, White PF. Novel therapies for postoperative nausea and vomiting: statistically significant versus clinically meaningful outcomes. Anesth Analg. 2011;112:750–2

117. Altorjay A, Melson T, Chinachoit T, Kett A, Aqua K, Levin J, Blackburn LM, Lane S, Pergolizzi JV Jr. Casopitant and ondansetron for postoperative nausea and vomiting prevention in women at high risk for emesis: a phase 3 study. Arch Surg. 2011;146:201–6

118. Singla NK, Singla SK, Chung F, Kutsogiannis DJ, Blackburn L, Lane SR, Levin J, Johnson B, Pergolizzi JV Jr. Phase II study to evaluate the safety and efficacy of the oral neurokinin-1 receptor antagonist casopitant (GW679769) administered with ondansetron for the prevention of postoperative and postdischarge nausea and vomiting in high-risk patients. Anesthesiology. 2010;113:74–82

119. Gan TJ, Gu J, Singla N, Chung F, Pearman MH, Bergese SD, Habib AS, Candiotti KA, Mo Y, Huyck S, Creed MR, Cantillon MRolapitant Investigation Group. . Rolapitant for the prevention of postoperative nausea and vomiting: a prospective, double-blinded, placebo-controlled randomized trial. Anesth Analg. 2011;112:804–12

120. Henzi I, Walder B, Tramèr MR. Dexamethasone for the prevention of postoperative nausea and vomiting: a quantitative systematic review. Anesth Analg. 2000;90:186–94

121. Wang JJ, Ho ST, Lee SC, Liu YC, Ho CM. The use of dexamethasone for preventing postoperative nausea and vomiting in females undergoing thyroidectomy: a dose-ranging study. Anesth Analg. 2000;91:1404–7

122. Arslan M, Cicek R, Kalender HT, Yilmaz H. Preventing postoperative nausea and vomiting after laparoscopic cholecystectomy: a prospective, randomized, double-blind study. Curr Ther Res Clin Exp. 2011;72:1–12

123. Arslan M, Demir ME. Prevention of postoperative nausea and vomiting with a small dose of propofol combined with dexamethasone 4 mg or dexamethasone 8 mg in patients undergoing middle ear surgery: a prospective, randomized, double-blind study. Bratisl Lek Listy. 2011;112:332–6

124. Feroci F, Rettori M, Borrelli A, Lenzi E, Ottaviano A, Scatizzi M. Dexamethasone prophylaxis before thyroidectomy to reduce postoperative nausea, pain, and vocal dysfunction: a randomized clinical controlled trial. Head Neck. 2011;33:840–6

125. Bilgin TE, Birbicer H, Ozer Z, Doruk N, Tok E, Oral U. A comparative study of the antiemetic efficacy of dexamethasone, ondansetron, and metoclopramide in patients undergoing gynecological surgery. Med Sci Monit. 2010;16:CR336–41

126. Chaparro LE, Gallo T, Gonzalez NJ, Rivera MF, Peng PW. Effectiveness of combined haloperidol and dexamethasone versus dexamethasone only for postoperative nausea and vomiting in high-risk day surgery patients: a randomized blinded trial. Eur J Anaesthesiol. 2010;27:192–5

127. Murphy GS, Szokol JW, Greenberg SB, Avram MJ, Vender JS, Nisman M, Vaughn J. Preoperative dexamethasone enhances quality of recovery after laparoscopic cholecystectomy: effect on in-hospital and postdischarge recovery outcomes. Anesthesiology. 2011;114:882–90

128. De Oliveira GS Jr, Ahmad S, Fitzgerald PC, Marcus RJ, Altman CS, Panjwani AS, McCarthy RJ. Dose ranging study on the effect of preoperative dexamethasone on postoperative quality of recovery and opioid consumption after ambulatory gynaecological surgery. Br J Anaesth. 2011;107:362–71

129. De Oliveira GS Jr, Almeida MD, Benzon HT, McCarthy RJ. Perioperative single dose systemic dexamethasone for postoperative pain: a meta-analysis of randomized controlled trials. Anesthesiology. 2011;115:575–88

130. Waldron NH, Jones CA, Gan TJ, Allen TK, Habib AS. Impact of perioperative dexamethasone on postoperative analgesia and side-effects: systematic review and meta-analysis. Br J Anaesth. 2013;110:191–200

131. Percival VG, Riddell J, Corcoran TB. Single dose dexamethasone for postoperative nausea and vomiting–a matched case-control study of postoperative infection risk. Anaesth Intensive Care. 2010;38:661–6

132. Ali Khan S, McDonagh DL, Gan TJ. Wound complications with dexamethasone for postoperative nausea and vomiting prophylaxis: a moot point? Anesth Analg. 2013;116:966–8

133. Eberhart LH, Graf J, Morin AM, Stief T, Kalder M, Lattermann R, Schricker T. Randomised controlled trial of the effect of oral premedication with dexamethasone on hyperglycaemic response to abdominal hysterectomy. Eur J Anaesthesiol. 2011;28:195–201

134. Nazar CE, Lacassie HJ, López RA, Muñoz HR. Dexamethasone for postoperative nausea and vomiting prophylaxis: effect on glycaemia in obese patients with impaired glucose tolerance. Eur J Anaesthesiol. 2009;26:318–21

135. Hans P, Vanthuyne A, Dewandre PY, Brichant JF, Bonhomme V. Blood glucose concentration profile after 10 mg dexamethasone in non-diabetic and type 2 diabetic patients undergoing abdominal surgery. Br J Anaesth. 2006;97:164–70

136. Miyagawa Y, Ejiri M, Kuzuya T, Osada T, Ishiguro N, Yamada K. Methylprednisolone reduces postoperative nausea in total knee and hip arthroplasty. J Clin Pharm Ther. 2010;35:679–84

137. Weren M, Demeere JL. Methylprednisolone vs. dexamethasone in the prevention of postoperative nausea and vomiting: a prospective, randomised, double-blind, placebo-controlled trial. Acta Anaesthesiol Belg. 2008;59:1–5

138. Domino KB, Anderson EA, Polissar NL, Posner KL. Comparative efficacy and safety of ondansetron, droperidol, and metoclopramide for preventing postoperative nausea and vomiting: a meta-analysis. Anesth Analg. 1999;88:1370–9

139. Fortney JT, Gan TJ, Graczyk S, Wetchler B, Melson T, Khalil S, McKenzie R, Parrillo S, Glass PS, Moote C, Wermeling D, Parasuraman TV, Duncan B, Creed MR. A comparison of the efficacy, safety, and patient satisfaction of ondansetron versus droperidol as antiemetics for elective outpatient surgical procedures. S3A-409 and S3A-410 Study Groups. Anesth Analg. 1998;86:731–8

140. Henzi I, Sonderegger J, Tramèr MR. Efficacy, dose-response, and adverse effects of droperidol for prevention of postoperative nausea and vomiting. Can J Anaesth. 2000;47:537–51

141. Merker M, Kranke P, Morin AM, Rüsch D, Eberhart LH. [Prophylaxis of nausea and vomiting in the postoperative phase: relative effectiveness of droperidol and metoclopramide]. Anaesthesist. 2011;60:432–40, 442–5

142. Schaub I, Lysakowski C, Elia N, Tramèr MR. Low-dose droperidol (≤1 mg or ≤15 μg·kg-1) for the prevention of postoperative nausea and vomiting in adults: quantitative systematic review of randomised controlled trials. Eur J Anaesthesiol. 2012;29:286–94

143. White PF, Song D, Abrao J, Klein KW, Navarette B. Effect of low-dose droperidol on the QT interval during and after general anesthesia: a placebo-controlled study. Anesthesiology. 2005;102:1101–5

144. Weissenburger J, Funck-Brentano C, Jaillon P, Charbit B. Droperidol and ondansetron in vitro electrophysiological drug interaction study. Fundam Clin Pharmacol. 2009;23:719–26

145. Chan MT, Choi KC, Gin T, Chui PT, Short TG, Yuen PM, Poon AH, Apfel CC, Gan TJ. The additive interactions between ondansetron and droperidol for preventing postoperative nausea and vomiting. Anesth Analg. 2006;103:1155–62

146. Büttner M, Walder B, von Elm E, Tramèr MR. Is low-dose haloperidol a useful antiemetic?: a meta-analysis of published and unpublished randomized trials. Anesthesiology. 2004;101:1454–63

147. Smith JC 2nd, Wright EL. Haloperidol: an alternative butyrophenone for nausea and vomiting prophylaxis in anesthesia. AANA J. 2005;73:273–5

148. Feng PH, Chu KS, Lu IC, Shieh JP, Tzeng JI, Ho ST, Wang JJ, Chu CC. Haloperidol plus ondansetron prevents postoperative nausea and vomiting in patients undergoing laparoscopic cholecystectomy. Acta Anaesthesiol Taiwan. 2009;47:3–9

149. Meyer-Massetti C, Cheng CM, Sharpe BA, Meier CR, Guglielmo BJ. The FDA extended warning for intravenous haloperidol and torsades de pointes: how should institutions respond? J Hosp Med. 2010;5:E8–16

150. Wang TF, Liu YH, Chu CC, Shieh JP, Tzeng JI, Wang JJ. Low-dose haloperidol prevents post-operative nausea and vomiting after ambulatory laparoscopic surgery. Acta Anaesthesiol Scand. 2008;52:280–4

151. Yang YL, Lai HY, Wang JJ, Wang PK, Chen TY, Chu CC, Lee Y. The timing of haloperidol administration does not affect its prophylactic antiemetic efficacy. Can J Anaesth. 2008;55:270–5

152. Eberhart LH, Seeling W, Bopp TI, Morin AM, Georgieff M. Dimenhydrinate for prevention of post-operative nausea and vomiting in female in-patients. Eur J Anaesthesiol. 1999;16:284–9

153. Kothari SN, Boyd WC, Bottcher ML, Lambert PJ. Antiemetic efficacy of prophylactic dimenhydrinate (Dramamine) vs ondansetron (Zofran): a randomized, prospective trial inpatients undergoing laparoscopic cholecystectomy. Surg Endosc. 2000;14:926–9

154. Kranke P, Morin AM, Roewer N, Eberhart LH. Dimenhydrinate for prophylaxis of postoperative nausea and vomiting: a meta-analysis of randomized controlled trials. Acta Anaesthesiol Scand. 2002;46:238–44

155. Forrester CM, Benfield DA Jr, Matern CE, Kelly JA, Pellegrini JE. Meclizine in combination with ondansetron for prevention of postoperative nausea and vomiting in a high-risk population. AANA J. 2007;75:27–33

156. Apfel CC, Zhang K, George E, Shi S, Jalota L, Hornuss C, Fero KE, Heidrich F, Pergolizzi JV, Cakmakkaya OS, Kranke P. Transdermal scopolamine for the prevention of postoperative nausea and vomiting: a systematic review and meta-analysis. Clin Ther. 2010;32:1987–2002

157. Bailey PL, Streisand JB, Pace NL, Bubbers SJ, East KA, Mulder S, Stanley TH. Transdermal scopolamine reduces nausea and vomiting after outpatient laparoscopy. Anesthesiology. 1990;72:977–80

158. Kranke P, Morin AM, Roewer N, Wulf H, Eberhart LH. The efficacy and safety of transdermal scopolamine for the prevention of postoperative nausea and vomiting: a quantitative systematic review. Anesth Analg. 2002;95:133–43

159. Semple P, Madej TH, Wheatley RG, Jackson IJ, Stevens J. Transdermal hyoscine with patient-controlled analgesia. Anaesthesia. 1992;47:399–401

160. Harris SN, Sevarino FB, Sinatra RS, Preble L, O’Connor TZ, Silverman DG. Nausea prophylaxis using transdermal scopolamine in the setting of patient-controlled analgesia. Obstet Gynecol. 1991;78:673–7

161. White PF, Tang J, Song D, Coleman JE, Wender RH, Ogunnaike B, Sloninsky A, Kapu R, Shah M, Webb T. Transdermal scopolamine: an alternative to ondansetron and droperidol for the prevention of postoperative and postdischarge emetic symptoms. Anesth Analg. 2007;104:92–6

162. Schnabel A, Eberhart LH, Muellenbach R, Morin AM, Roewer N, Kranke P. Efficacy of perphenazine to prevent postoperative nausea and vomiting: a quantitative systematic review. Eur J Anaesthesiol. 2010;27:1044–51

163. Henzi I, Walder B, Tramèr MR. Metoclopramide in the prevention of postoperative nausea and vomiting: a quantitative systematic review of randomized, placebo-controlled studies. Br J Anaesth. 1999;83:761–71

164. Soppitt AJ, Glass PS, Howell S, Weatherwax K, Gan TJ. The use of propofol for its antiemetic effect: a survey of clinical practice in the United States. J Clin Anesth. 2000;12:265–9

165. Gan TJ, Glass PS, Howell ST, Canada AT, Grant AP, Ginsberg B. Determination of plasma concentrations of propofol associated with 50% reduction in postoperative nausea. Anesthesiology. 1997;87:779–84

166. Tramèr M, Moore A, McQuay H. Propofol anaesthesia and postoperative nausea and vomiting: quantitative systematic review of randomized controlled studies. Br J Anaesth. 1997;78:247–55

167. Gupta A, Stierer T, Zuckerman R, Sakima N, Parker SD, Fleisher LA. Comparison of recovery profile after ambulatory anesthesia with propofol, isoflurane, sevoflurane and desflurane: a systematic review. Anesth Analg. 2004;98:632–41

168. Gan TJ, Ginsberg B, Glass PS, Fortney J, Jhaveri R, Perno R. Opioid-sparing effects of a low-dose infusion of naloxone in patient-administered morphine sulfate. Anesthesiology. 1997;87:1075–81

169. Unlugenc H, Guler T, Gunes Y, Isik G. Comparative study of the antiemetic efficacy of ondansetron, propofol and midazolam in the early postoperative period. Eur J Anaesthesiol. 2004;21:60–5

170. Blaudszun G, Lysakowski C, Elia N, Tramèr MR. Effect of perioperative systemic α2 agonists on postoperative morphine consumption and pain intensity: systematic review and meta-analysis of randomized controlled trials. Anesthesiology. 2012;116:1312–22

171. Chen CC, Lin CS, Ko YP, Hung YC, Lao HC, Hsu YW. Premedication with mirtazapine reduces preoperative anxiety and postoperative nausea and vomiting. Anesth Analg. 2008;106:109–13

172. Bashir F, Mohammad Bhat K, Qazi S, Hashia AM. A randomized, double blind, placebo controlled study evaluating preventive role of gabapentin for PONV in patients undergoing laparascopic cholecystectomy. JK Science. 2009;11:190–3

173. Khademi S, Ghaffarpasand F, Heiran HR, Asefi A. Effects of preoperative gabapentin on postoperative nausea and vomiting after open cholecystectomy: a prospective randomized double-blind placebo-controlled study. Med Princ Pract. 2010;19:57–60

174. Pandey CK, Priye S, Ambesh SP, Singh S, Singh U, Singh PK. Prophylactic gabapentin for prevention of postoperative nausea and vomiting in patients undergoing laparoscopic cholecystectomy: a randomized, double-blind, placebo-controlled study. J Postgrad Med. 2006;52:97–100

175. Koç S, Memis D, Sut N. The preoperative use of gabapentin, dexamethasone, and their combination in varicocele surgery: a randomized controlled trial. Anesth Analg. 2007;105:1137–42

176. Jung JS, Park JS, Kim SO, Lim DG, Park SS, Kwak KH, Cho JD, Jeon YH. Prophylactic antiemetic effect of midazolam after middle ear surgery. Otolaryngol Head Neck Surg. 2007;137:753–6

177. Tarhan O, Canbay O, Celebi N, Uzun S, Sahin A, Coşkun F, Aypar U. Subhypnotic doses of midazolam prevent nausea and vomiting during spinal anesthesia for cesarean section. Minerva Anestesiol. 2007;73:629–33

178. Lee Y, Wang JJ, Yang YL, Chen A, Lai HY. Midazolam vs ondansetron for preventing postoperative nausea and vomiting: a randomised controlled trial. Anaesthesia. 2007;62:18–22

179. Makhdoom NK, Farid MF. Prophylactic antiemetic effects of midazolam, dexamethasone, and its combination after middle ear surgery. Saudi Med J. 2009;30:504–8

180. Yeo J, Jung J, Ryu T, Jeon YH, Kim S, Baek W. Antiemetic efficacy of dexamethasone combined with midazolam after middle ear surgery. Otolaryngol Head Neck Surg. 2009;141:684–8

181. Shahriari A, Khooshideh M, Heidari MH. Prevention of nausea and vomiting in caesarean section under spinal anaesthesia with midazolam or metoclopramide? J Pak Med Assoc. 2009;59:756–9

182. Bedin A, Pinho Mde S, Zanotelli CT, Caldart AS, Turazzi JC, de Castro RA. Dexamethasone compared to metoclopramide in the prophylaxis of emesis in children undergoing ambulatory surgical procedures. Rev Bras Anestesiol. 2005;55:387–96

183. Safavi MR, Honarmand A. Low dose intravenous midazolam for prevention of PONV, in lower abdominal surgery–preoperative vs intraoperative administration. Middle East J Anesthesiol. 2009;20:75–81

184. Alghanem SM, Massad IM, Rashed EM, Abu-Ali HM, Daradkeh SS. Optimization of anesthesia antiemetic measures versus combination therapy using dexamethasone or ondansetron for the prevention of postoperative nausea and vomiting. Surg Endosc. 2010;24:353–8

185. Banihashem N, Hassannasab B, Naziri F, Rahimifar AR, Hosseini V, Shirkhani Z. Comparison of the prophylactic effect of ondansetron and dexamethasone on postoperative nausea and vomiting after intrathecal meperidine in women scheduled for elective cesarean section. JBUMS. 2011;13:30–3

186. Bano F, Zafar S, Aftab S, Haider S. Dexamethasone plus ondansetron for prevention of postoperative nausea and vomiting in patients undergoing laparoscopic cholecystectomy: a comparison with dexamethasone alone. J Coll Physicians Surg Pak. 2008;18:265–9

187. Gan TJ, Sinha AC, Kovac AL, Jones RK, Cohen SA, Battikha JP, Deutsch JS, Pergolizzi JV Jr, Glass PSTDS Study Group. . A randomized, double-blind, multicenter trial comparing transdermal scopolamine plus ondansetron to ondansetron alone for the prevention of postoperative nausea and vomiting in the outpatient setting. Anesth Analg. 2009;108:1498–504

188. 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 randomised controlled trials. Acta Anaesthesiol Scand. 2000;44:1252–7

189. Habib AS, El-Moalem HE, Gan TJ. The efficacy of the 5-HT3 receptor antagonists combined with droperidol for PONV prophylaxis is similar to their combination with dexamethasone. A meta-analysis of randomized controlled trials. Can J Anaesth. 2004;51:311–9

190. Kazemi-Kjellberg F, Henzi I, Tramèr MR. Treatment of established postoperative nausea and vomiting: a quantitative systemic review. BMC Anesthesiol. 2001;1:2 Available at: http://www.biomedcentral.com/1471-2253/1/2. Accessed May 18, 2013

191. Tramèr MR. A rational approach to the control of postoperative nausea and vomiting: evidence from systematic reviews. Part I. Efficacy and harm of antiemetic interventions, and methodological issues. Acta Anaesthesiol Scand. 2001;45:4–13

192. Gan TJ, Coop A, Philip BK. A randomized, double-blind study of granisetron plus dexamethasone versus ondansetron plus dexamethasone to prevent postoperative nausea and vomiting in patients undergoing abdominal hysterectomy. Anesth Analg. 2005;101:1323–9

193. Leksowski K, Peryga P, Szyca R. Ondansetron, metoclopramid, dexamethason, and their combinations compared for the prevention of postoperative nausea and vomiting in patients undergoing laparoscopic cholecystectomy: a prospective randomized study. Surg Endosc. 2006;20:878–82

194. Antonetti M, Kirton O, Bui P, Ademi A, Staff I, Hudson-Civetta JA, Lilly R. The effects of preoperative rofecoxib, metoclopramide, dexamethasone, and ondansetron on postoperative pain and nausea in patients undergoing elective laparoscopic cholecystectomy. Surg Endosc. 2007;21:1855–61

195. Kim MS, Coté CJ, Cristoloveanu C, Roth AG, Vornov P, Jennings MA, Maddalozzo JP, Sullivan C. There is no dose-escalation response to dexamethasone (0.0625-1.0 mg/kg) in pediatric tonsillectomy or adenotonsillectomy patients for preventing vomiting, reducing pain, shortening time to first liquid intake, or the incidence of voice change. Anesth Analg. 2007;104:1052–8 tables of contents

196. Gautam B, Shrestha BR, Lama P, Rai S. Antiemetic prophylaxis against postoperative nausea and vomiting with ondansetron-dexamethasone combination compared to ondansetron or dexamethasone alone for patients undergoing laparoscopic cholecystectomy. Kathmandu Univ Med J (KUMJ). 2008;6:319–28

197. Paech MJ, Rucklidge MW, Lain J, Dodd PH, Bennett EJ, Doherty DA. Ondansetron and dexamethasone dose combinations for prophylaxis against postoperative nausea and vomiting. Anesth Analg. 2007;104:808–14

198. Sriraman R, Indu S, Chari P. Is granisetron-dexamethasone combination better than ondansetron-dexamethasone in the prevention of postoperative nausea and vomiting in outpatient gynaecological laparoscopy? J Anaesthesiol Clin Pharmacol. 2007;23:365–72

199. Dabbous AS, Jabbour-Khoury SI, Nasr VG, Moussa AA, Zbeidy RA, Khouzam NE, El-Khatib MF, Baraka AS. Dexamethasone with either granisetron or ondansetron for postoperative nausea and vomiting in laparoscopic surgery. Middle East J Anesthesiol. 2010;20:565–70

200. Chu CC, Shieh JP, Tzeng JI, Chen JY, Lee Y, Ho ST, Wang JJ. The prophylactic effect of haloperidol plus dexamethasone on postoperative nausea and vomiting in patients undergoing laparoscopically assisted vaginal hysterectomy. Anesth Analg. 2008;106:1402–6

201. Deban Singh L, Nando Singh Y, Ratan Singh N, Pradipkumar Singh L, Hemjit Singh T, Moirangthem GS. A comparison between granisetron and granisetron with dexamethasone for prevention of postoperative nausea and vomiting for laparoscopic cholecystectomy. JMS. 2009;23:51–4

202. Lee HK, Lee JH, Chon SS, Ahn EK, Kim JH, Jang YH. The effect of transdermal scopolamine plus intravenous dexamethasone for the prevention of postoperative nausea and vomiting in patients with epidural PCA after major orthopedic surgery. Korean J Anesthesiol. 2010;58:50–5

203. Grecu L, Bittner EA, Kher J, Smith SE, Rosow CE. Haloperidol plus ondansetron versus ondansetron alone for prophylaxis of postoperative nausea and vomiting. Anesth Analg. 2008;106:1410–3

204. Culebras X, Corpataux JB, Gaggero G, Tramèr MR. The antiemetic efficacy of droperidol added to morphine patient-controlled analgesia: a randomized, controlled, multicenter dose-finding study. Anesth Analg. 2003;97:816–21

205. Tramèr MR, Walder B. Efficacy and adverse effects of prophylactic antiemetics during patient-controlled analgesia therapy: a quantitative systematic review. Anesth Analg. 1999;88:1354–61

206. Chung SD, Lu CW, Chiu B, Liao CH, Yu HJ. Urethro-subcutaneous fistula and bilateral abscesses of the thighs. Int J Infect Dis. 2009;13:e523–4

207. Chung F, Lane R, Spraggs C, McQuade B, Jacka M, Luttropp HH, Alahuta S, Rocherieux S, Roy M, Duvaldestin P, Curtis P. Ondansetron is more effective than metoclopramide for the treatment of opioid-induced emesis in post-surgical adult patients. Ondansetron OIE Post-Surgical Study Group. Eur J Anaesthesiol. 1999;16:669–77

208. Madson AT, Silverman MJ. The effect of music therapy on relaxation, anxiety, pain perception, and nausea in adult solid organ transplant patients. J Music Ther. 2010;47:220–32

209. Reza N, Ali SM, Saeed K, Abul-Qasim A, Reza TH. The impact of music on postoperative pain and anxiety following cesarean section. Middle East J Anesthesiol. 2007;19:573–86

210. Teran L, Hawkins JK. The effectiveness of inhalation isopropyl alcohol vs. granisetron for the prevention of postoperative nausea and vomiting. AANA J. 2007;75:417–22

211. Weilbach C, Kähler K, Thissen U, Rahe-Meyer N, Piepenbrock S. Esomeprazole for the prevention of postoperative nausea and vomiting. A randomized, placebo-controlled trial. Eur J Anaesthesiol. 2006;23:338–40

212. Raeder J, Dahl V, Bjoernestad E, Edlund G, Modin S, Naucler E, Bergheim R, Kilhamn J. Does esomeprazole prevent post-operative nausea and vomiting? Acta Anaesthesiol Scand. 2007;51:217–25

213. Ernst E, Pittler MH. Efficacy of ginger for nausea and vomiting: a systematic review of randomized clinical trials. Br J Anaesth. 2000;84:367–71

214. Morin AM, Betz O, Kranke P, Geldner G, Wulf H, Eberhart LH. [Is ginger a relevant antiemetic for postoperative nausea and vomiting?]. Anasthesiol Intensivmed Notfallmed Schmerzther. 2004;39:281–5

215. Czarnetzki C, Schiffer E, Lysakowski C, Haller G, Bertrand D, Tramèr MR. Transcutaneous nicotine does not prevent postoperative nausea and vomiting: a randomized controlled trial. Br J Clin Pharmacol. 2011;71:383–90

216. Habib AS, White WD, El Gasim MA, Saleh G, Polascik TJ, Moul JW, Gan TJ. Transdermal nicotine for analgesia after radical retropubic prostatectomy. Anesth Analg. 2008;107:999–1004

217. Montgomery GH, Bovbjerg DH, Schnur JB, David D, Goldfarb A, Weltz CR, Schechter C, Graff-Zivin J, Tatrow K, Price DD, Silverstein JH. A randomized clinical trial of a brief hypnosis intervention to control side effects in breast surgery patients. J Natl Cancer Inst. 2007;99:1304–12

218. Tramèr MR, Carroll D, Campbell FA, Reynolds DJ, Moore RA, McQuay HJ. Cannabinoids for control of chemotherapy induced nausea and vomiting: quantitative systematic review. BMJ. 2001;323:16–21

219. Lewis IH, Campbell DN, Barrowcliffe MP. Effect of nabilone on nausea and vomiting after total abdominal hysterectomy. Br J Anaesth. 1994;73:244–6

220. Rincón DA, Valero JF. [Supplemental oxygen for the prevention of postoperative nausea and vomiting: a meta-analysis of randomized clinical trials]. Rev Esp Anestesiol Reanim. 2008;55:101–9

221. Chen JJ, Frame DG, White TJ. Efficacy of ondansetron and prochlorperazine for the prevention of postoperative nausea and vomiting after total hip replacement or total knee replacement procedures: a randomized, double-blind, comparative trial. Arch Intern Med. 1998;158:2124–8

222. Khalil S, Philbrook L, Rabb M, Wells L, Aves T, Villanueva G, Amhan M, Chuang AZ, Lemak NA. Ondansetron/promethazine combination or promethazine alone reduces nausea and vomiting after middle ear surgery. J Clin Anesth. 1999;11:596–600

223. Rothenberg DM, Parnass SM, Litwack K, McCarthy RJ, Newman LM. Efficacy of ephedrine in the prevention of postoperative nausea and vomiting. Anesth Analg. 1991;72:58–61

224. Hagemann E, Halvorsen A, Holgersen O, Tveit T, Raeder JC. Intramuscular ephedrine reduces emesis during the first three hours after abdominal hysterectomy. Acta Anaesthesiol Scand. 2000;44:107–11

225. FDA Requires Boxed Warning for Promethazine Hydrochloride Injection 2009. Available at: http://www.fda.gov/NewsEvents/Newsroom/PressAnnouncements/ucm182498.htm. Accessed May 18, 2013

226. Lee AP. Microfluidic cellular and molecular detection for Lab-on-a-Chip applications. Conf Proc IEEE Eng Med Biol Soc. 2009;2009:4147–9

227. Frey UH, Funk M, Löhlein C, Peters J. Effect of P6 acustimulation on post-operative nausea and vomiting in patients undergoing a laparoscopic cholecystectomy. Acta Anaesthesiol Scand. 2009;53:1341–7

228. Frey UH, Scharmann P, Löhlein C, Peters J. P6 acustimulation effectively decreases postoperative nausea and vomiting in high-risk patients. Br J Anaesth. 2009;102:620–5

229. Arnberger M, Stadelmann K, Alischer P, Ponert R, Melber A, Greif R. Monitoring of neuromuscular blockade at the P6 acupuncture point reduces the incidence of postoperative nausea and vomiting. Anesthesiology. 2007;107:903–8

230. Kim YH, Kim KS, Lee HJ, Shim JC, Yoon SW. The efficacy of several neuromuscular monitoring modes at the P6 acupuncture point in preventing postoperative nausea and vomiting. Anesth Analg. 2011;112:819–23

231. Maharaj CH, Kallam SR, Malik A, Hassett P, Grady D, Laffey JG. Preoperative intravenous fluid therapy decreases postoperative nausea and pain in high risk patients. Anesth Analg. 2005;100:675–82

232. Magner JJ, McCaul C, Carton E, Gardiner J, Buggy D. Effect of intraoperative intravenous crystalloid infusion on postoperative nausea and vomiting after gynaecological laparoscopy: comparison of 30 and 10 ml kg(-1). Br J Anaesth. 2004;93:381–5

233. Haentjens LL, Ghoundiwal D, Touhiri K, Renard M, Engelman E, Anaf V, Simon P, Barvais L, Ickx BE. Does infusion of colloid influence the occurrence of postoperative nausea and vomiting after elective surgery in women? Anesth Analg. 2009;108:1788–93

234. Chaudhary S, Sethi AK, Motiani P, Adatia C. Pre-operative intravenous fluid therapy with crystalloids or colloids on post-operative nausea & vomiting. Indian J Med Res. 2008;127:577–81

235. Gan TJ, Ginsberg B, Glass PS, Fortney J, Jhaveri R, Perno R. Opioid-sparing effects of a low-dose infusion of naloxone in patient-administered morphine sulfate. Anesthesiology. 1997;87:1075–81

236. Maxwell LG, Kaufmann SC, Bitzer S, Jackson EV Jr, McGready J, Kost-Byerly S, Kozlowski L, Rothman SK, Yaster M. The effects of a small-dose naloxone infusion on opioid-induced side effects and analgesia in children and adolescents treated with intravenous patient-controlled analgesia: a double-blind, prospective, randomized, controlled study. Anesth Analg. 2005;100:953–8

237. Jia DL, Ni C, Xu T, Zhang LP, Guo XY. A small-dose naloxone infusion alleviates nausea and sedation without impacting analgesia via intravenous tramadol. Chin Med J (Engl). 2010;123:1695–8

238. Joshi GP, Duffy L, Chehade J, Wesevich J, Gajraj N, Johnson ER. Effects of prophylactic nalmefene on the incidence of morphine-related side effects in patients receiving intravenous patient-controlled analgesia. Anesthesiology. 1999;90:1007–11

239. Betz O, Kranke P, Geldner G, Wulf H, Eberhart LH. [Is ginger a clinically relevant antiemetic? A systematic review of randomized controlled trials]. Forsch Komplementarmed Klass Naturheilkd. 2005;12:14–23

240. Chaiyakunapruk N, Kitikannakorn N, Nathisuwan S, Leeprakobboon K, Leelasettagool C. The efficacy of ginger for the prevention of postoperative nausea and vomiting: a meta-analysis. Am J Obstet Gynecol. 2006;194:95–9

241. Prapaitrakool S, Itharat A. Morinda citrifolia Linn. for prevention of postoperative nausea and vomiting. J Med Assoc Thai. 2010;93(Suppl 7):S204–9

242. Drummond MF, Jefferson TO. Guidelines for authors and peer reviewers of economic submissions to the BMJ. The BMJ Economic Evaluation Working Party. BMJ. 1996;313:275–83

243. Weinstein MC, Siegel JE, Gold MR, Kamlet MS, Russell LB. Recommendations of the Panel on Cost-effectiveness in Health and Medicine. JAMA. 1996;276:1253–8

244. Siegel JE, Weinstein MC, Russell LB, Gold MR. Recommendations for reporting cost-effectiveness analyses. Panel on Cost-Effectiveness in Health and Medicine. JAMA. 1996;276:1339–41

245. Gan TJ, Ing RJ, de L Dear G, Wright D, El-Moalem HE, Lubarsky DA. How much are patients willing to pay to avoid intraoperative awareness? J Clin Anesth. 2003;15:108–12

246. Diez L. Assessing the willingness of parents to pay for reducing postoperative emesis in children. Pharmacoeconomics. 1998;13:589–95

247. Elliott RA, Payne K, Moore JK, Davies LM, Harper NJ, St Leger AS, Moore EW, Thoms GM, Pollard BJ, McHugh GA, Bennett J, Lawrence G, Kerr J. Which anaesthetic agents are cost-effective in day surgery? Literature review, national survey of practice and randomised controlled trial. Health Technol Assess. 2002;6:1–264

248. Carroll NV, Miederhoff PA, Cox FM, Hirsch JD. Costs incurred by outpatient surgical centers in managing postoperative nausea and vomiting. J Clin Anesth. 1994;6:364–9

249. Dexter F, Tinker JH. Analysis of strategies to decrease postanesthesia care unit costs. Anesthesiology. 1995;82:94–101

250. Frighetto L, Loewen PS, Dolman J, Marra CA. Cost-effectiveness of prophylactic dolasetron or droperidol vs rescue therapy in the prevention of PONV in ambulatory gynecologic surgery. Can J Anaesth. 1999;46:536–43

251. Scuderi PE, James RL, Harris L, Mims GR 3rd. Antiemetic prophylaxis does not improve outcomes after outpatient surgery when compared to symptomatic treatment. Anesthesiology. 1999;90:360–71

252. Watcha MF, Smith I. Cost-effectiveness analysis of antiemetic therapy for ambulatory surgery. J Clin Anesth. 1994;6:370–7

253. Tramèr MR, Phillips C, Reynolds DJ, McQuay HJ, Moore RA. Cost-effectiveness of ondansetron for postoperative nausea and vomiting. Anaesthesia. 1999;54:226–34

254. Pan PH, Lee SC, Harris LC. Antiemetic prophylaxis for postdischarge nausea and vomiting and impact on functional quality of living during recovery in patients with high emetic risks: a prospective, randomized, double-blind comparison of two prophylactic antiemetic regimens. Anesth Analg. 2008;107:429–38

255. Henzi I, Walder B, Tramèr MR. Dexamethasone for the prevention of postoperative nausea and vomiting: a quantitative systematic review. Anesth Analg. 2000;90:186–94

256. Eberhart LH, Högel J, Seeling W, Staack AM, Geldner G, Georgieff M. Evaluation of three risk scores to predict postoperative nausea and vomiting. Acta Anaesthesiol Scand. 2000;44:480–8

257. Habib AS, El-Moalem HE, Gan TJ. The efficacy of the 5-HT3 receptor antagonists combined with droperidol for PONV prophylaxis is similar to their combination with dexamethasone. A meta-analysis of randomized controlled trials. Can J Anaesth. 2004;51:311–9

258. Habib AS, Gan TJ. Combination therapy for postoperative nausea and vomiting-a more effective prophylaxis? Ambul Surg. 2001;9:59–71

259. Eberhart LH, Seeling W, Ulrich B, Morin AM, Georgieff M. Dimenhydrinate and metoclopramide alone or in combination for prophylaxis of PONV. Can J Anaesth. 2000;47:780–5

260. Maddali MM, Mathew J, Fahr J, Zarroug AW. Postoperative nausea and vomiting in diagnostic gynaecological laparoscopic procedures: comparison of the efficacy of the combination of dexamethasone and metoclopramide with that of dexamethasone and ondansetron. J Postgrad Med. 2003;49:302–6

261. Scuderi PE, James RL, Harris L, Mims GR 3rd. Multimodal antiemetic management prevents early postoperative vomiting after outpatient laparoscopy. Anesth Analg. 2000;91:1408–14

262. Gan TJ. Postoperative nausea and vomiting–can it be eliminated? JAMA. 2002;287:1233–6

263. Habib AS, White WD, Eubanks S, Pappas TN, Gan TJ. A randomized comparison of a multimodal management strategy versus combination antiemetics for the prevention of postoperative nausea and vomiting. Anesth Analg. 2004;99:77–81

264. Lerman J. Surgical and patient factors involved in postoperative nausea and vomiting. Br J Anaesth. 1992;69:24S–32S

265. Cohen IT, Joffe D, Hummer K, Soluri A. Ondansetron oral disintegrating tablets: acceptability and efficacy in children undergoing adenotonsillectomy. Anesth Analg. 2005;101:59–63

266. Davis PJ, Fertal KM, Boretsky KR, Fedel GM, Ingram MD, Woelfel SK, Hoffmann PC, Gurnaney H, Young MC. The effects of oral ondansetron disintegrating tablets for prevention of at-home emesis in pediatric patients after ear-nose-throat surgery. Anesth Analg. 2008;106:1117–21

267. Neufeld SM, Newburn-Cook CV. The efficacy of 5-HT3 receptor antagonists for the prevention of postoperative vomiting following craniotomy: two studies in children and young adults. Can J Neurosci Nurs. 2009;31:30–4

268. Subramaniam K, Pandia MP, Dash M, Dash HH, Bithal PK, Bhatia A, Subramaniam B. Scheduled prophylactic ondansetron administration did not improve its antiemetic efficacy after intracranial tumour resection surgery in children. Eur J Anaesthesiol. 2007;24:615–9

269. Khalil SN, Roth AG, Cohen IT, Simhi E, Ansermino JM, Bolos ME, Coté CJ, Hannallah RS, Davis PJ, Brooks PB, Russo MW, Anschuetz GC, Blackburn LM. A double-blind comparison of intravenous ondansetron and placebo for preventing postoperative emesis in 1- to 24-month-old pediatric patients after surgery under general anesthesia. Anesth Analg. 2005;101:356–61

270. Mondick JT, Johnson BM, Haberer LJ, Sale ME, Adamson PC, Coté CJ, Croop JM, Russo MW, Barrett JS, Hoke JF. Population pharmacokinetics of intravenous ondansetron in oncology and surgical patients aged 1-48 months. Eur J Clin Pharmacol. 2010;66:77–86

271. Bolton CM, Myles PS, Carlin JB, Nolan T. Randomized, double-blind study comparing the efficacy of moderate-dose metoclopramide and ondansetron for the prophylactic control of postoperative vomiting in children after tonsillectomy. Br J Anaesth. 2007;99:699–703

272. Engelman E, Salengros JC, Barvais L. How much does pharmacologic prophylaxis reduce postoperative vomiting in children? Calculation of prophylaxis effectiveness and expected incidence of vomiting under treatment using Bayesian meta-analysis. Anesthesiology. 2008;109:1023–35

273. Czarnetzki C, Elia N, Lysakowski C, Dumont L, Landis BN, Giger R, Dulguerov P, Desmeules J, Tramèr MR. Dexamethasone and risk of nausea and vomiting and postoperative bleeding after tonsillectomy in children: a randomized trial. JAMA. 2008;300:2621–30

274. Steward DL, Grisel J, Meinzen-Derr J. Steroids for improving recovery following tonsillectomy in children. Cochrane Database Syst Rev. 2011:CD003997

275. Gross D, Reuss S, Dillier CM, Gerber AC, Weiss M. Early vs late intraoperative administration of tropisetron for the prevention of nausea and vomiting in children undergoing tonsillectomy and/or adenoidectomy. Paediatr Anaesth. 2006;16:444–50

276. Bicer C, Aksu R, Ulgey A, Madenoglu H, Dogan H, Yildiz K, Boyaci A. Different doses of palonosetron for the prevention of postoperative nausea and vomiting in children undergoing strabismus surgery. Drugs R D. 2011;11:29–36


278. McKechnie K, Froese A. Ventricular tachycardia after ondansetron administration in a child with undiagnosed long QT syndrome. Can J Anaesth. 2010;57:453–7

279. Chandrakala R, Vijayashankara CN, Kumar KK, Sarala N. Ondansetron induced fatal ventricular tachycardia. Indian J Pharmacol. 2008;40:186–7

280. Afonso N, Dang A, Namshikar V, Kamat S, Rataboli PV. Intravenous ondansetron causing severe bradycardia: two cases. Ann Card Anaesth. 2009;12:172–3

281. Mehta D, Sanatani S, Whyte SD. The effects of droperidol and ondansetron on dispersion of myocardial repolarization in children. Paediatr Anaesth. 2010;20:905–12

282. McDonnell C, Barlow R, Campisi P, Grant R, Malkin D. Fatal peri-operative acute tumour lysis syndrome precipitated by dexamethasone. Anaesthesia. 2008;63:652–5

283. Osthaus WA, Linderkamp C, Bünte C, Jüttner B, Sümpelmann R. Tumor lysis associated with dexamethasone use in a child with leukemia. Paediatr Anaesth. 2008;18:268–70

284. Gunter JB, Willging JP, Myer CM 3rd. Dexamethasone and postoperative bleeding after tonsillectomy in children. JAMA. 2009;301:1764–5; author reply 1765–6

285. Brigger MT, Cunningham MJ, Hartnick CJ. Dexamethasone administration and postoperative bleeding risk in children undergoing tonsillectomy. Arch Otolaryngol Head Neck Surg. 2010;136:766–72

286. Geva A, Brigger MT. Dexamethasone and tonsillectomy bleeding: a meta-analysis. Otolaryngol Head Neck Surg. 2011;144:838–43

287. Shakeel M, Trinidade A, Al-Adhami A, Karamchandani D, Engelhardt T, Ah-See KW, Kubba H. Intraoperative dexamethasone and the risk of secondary posttonsillectomy hemorrhage. J Otolaryngol Head Neck Surg. 2010;39:732–6

288. Plante J, Turgeon AF, Zarychanski R, Lauzier F, Vigneault L, Moore L, Boutin A, Fergusson DA. Effect of systemic steroids on post-tonsillectomy bleeding and reinterventions: systematic review and meta-analysis of randomised controlled trials. BMJ. 2012;345:e5389

289. Baugh RF, Archer SM, Mitchell RB, Rosenfeld RM, Amin R, Burns JJ, Darrow DH, Giordano T, Litman RS, Li KK, Mannix ME, Schwartz RH, Setzen G, Wald ER, Wall E, Sandberg G, Patel MMAmerican Academy of Otolaryngology-Head and Neck Surgery Foundation. . Clinical practice guideline: tonsillectomy in children. Otolaryngol Head Neck Surg. 2011;144:S1–30

290. Dune LS, Shiao SY. Metaanalysis of acustimulation effects on postoperative nausea and vomiting in children. Explore (NY). 2006;2:314–20

291. Jindal V, Ge A, Mansky PJ. Safety and efficacy of acupuncture in children: a review of the evidence. J Pediatr Hematol Oncol. 2008;30:431–42

292. Fortier MA, Weinberg M, Vitulano LA, Chorney JM, Martin SR, Kain ZN. Effects of therapeutic suggestion in children undergoing general anesthesia: a randomized controlled trial. Paediatr Anaesth. 2010;20:90–9

293. Habib AS, Gan TJ. The effectiveness of rescue antiemetics after failure of prophylaxis with ondansetron or droperidol: a preliminary report. J Clin Anesth. 2005;17:62–5

294. Meyer TA, Roberson CR, Rajab MH, Davis J, McLeskey CH. Dolasetron versus ondansetron for the treatment of postoperative nausea and vomiting. Anesth Analg. 2005;100:373–7

295. Chia YY, Lo Y, Liu K, Tan PH, Chung NC, Ko NH. The effect of promethazine on postoperative pain: a comparison of preoperative, postoperative, and placebo administration in patients following total abdominal hysterectomy. Acta Anaesthesiol Scand. 2004;48:625–30

296. Deleted in proof.

297. Habib AS, Reuveni J, Taguchi A, White WD, Gan TJ. A comparison of ondansetron with promethazine for treating postoperative nausea and vomiting in patients who received prophylaxis with ondansetron: a retrospective database analysis. Anesth Analg. 2007;104:548–51

298. Gan TJ, El-Molem H, Ray J, Glass PS. Patient-controlled antiemesis: a randomized, double-blind comparison of two doses of propofol versus placebo. Anesthesiology. 1999;90:1564–70

299. Pellegrini J, DeLoge J, Bennett J, Kelly J. Comparison of inhalation of isopropyl alcohol vs promethazine in the treatment of postoperative nausea and vomiting (PONV) in patients identified as at high risk for developing PONV. AANA J. 2009;77:293–9

300. Cotton JW, Rowell LR, Hood RR, Pellegrini JE. A comparative analysis of isopropyl alcohol and ondansetron in the treatment of postoperative nausea and vomiting from the hospital setting to the home. AANA J. 2007;75:21–6

301. Winston AW, Rinehart RS, Riley GP, Vacchiano CA, Pellegrini JE. Comparison of inhaled isopropyl alcohol and intravenous ondansetron for treatment of postoperative nausea. AANA J. 2003;71:127–32

302. Kovac AL, O’Connor TA, Pearman MH, Kekoler LJ, Edmondson D, Baughman VL, Angel JJ, Campbell C, Jense HG, Mingus M, Shahvari MB, Creed MR. Efficacy of repeat intravenous dosing of ondansetron in controlling postoperative nausea and vomiting: a randomized, double-blind, placebo-controlled multicenter trial. J Clin Anesth. 1999;11:453–9

303. Candiotti KA, Nhuch F, Kamat A, Deepika K, Arheart KL, Birnbach DJ, Lubarsky DA. Granisetron versus ondansetron treatment for breakthrough postoperative nausea and vomiting after prophylactic ondansetron failure: a pilot study. Anesth Analg. 2007;104:1370–3

304. Gupta A, Wu CL, Elkassabany N, Krug CE, Parker SD, Fleisher LA. Does the routine prophylactic use of antiemetics affect the incidence of postdischarge nausea and vomiting following ambulatory surgery?: a systematic review of randomized controlled trials. Anesthesiology. 2003;99:488–95

305. Wu CL, Berenholtz SM, Pronovost PJ, Fleisher LA. Systematic review and analysis of postdischarge symptoms after outpatient surgery. Anesthesiology. 2002;96:994–1003

306. al-Sadi M, Newman B, Julious SA. Acupuncture in the prevention of postoperative nausea and vomiting. Anaesthesia. 1997;52:658–61

307. Gan TJ, Franiak R, Reeves J. Ondansetron orally disintegrating tablet versus placebo for the prevention of postdischarge nausea and vomiting after ambulatory surgery. Anesth Analg. 2002;94:1199–200

308. Kranke P, Eberhart LH, Gan TJ, Roewer N, Tramèr MR. Algorithms for the prevention of postoperative nausea and vomiting: an efficacy and efficiency simulation. Eur J Anaesthesiol. 2007;24:856–67

309. van den Bosch JE, Kalkman CJ, Vergouwe Y, Van Klei WA, Bonsel GJ, Grobbee DE, Moons KG. Assessing the applicability of scoring systems for predicting postoperative nausea and vomiting. Anaesthesia. 2005;60:323–31

310. Carlisle JB, Stevenson CA. Drugs for preventing postoperative nausea and vomiting. Cochrane Database Syst Rev. 2006;19:CD004125

311. Franck M, Radtke FM, Baumeyer A, Kranke P, Wernecke KD, Spies CD. [Adherence to treatment guidelines for postoperative nausea and vomiting. How well does knowledge transfer result in improved clinical care?]. Anaesthesist. 2010;59:524–8

312. Klotz C, Philippi-Höhne C. [Prophylaxis of postoperative nausea and vomiting in pediatric anesthesia: recommendations and implementation in clinical routine]. Anaesthesist. 2010;59:477–8

313. Kooij FO, Klok T, Hollmann MW, Kal JE. Automated reminders increase adherence to guidelines for administration of prophylaxis for postoperative nausea and vomiting. Eur J Anaesthesiol. 2010;27:187–91

314. Kooij FO, Klok T, Hollmann MW, Kal JE. Decision support increases guideline adherence for prescribing postoperative nausea and vomiting prophylaxis. Anesth Analg. 2008;106:893–8

315. Frenzel JC, Kee SS, Ensor JE, Riedel BJ, Ruiz JR. Ongoing provision of individual clinician performance data improves practice behavior. Anesth Analg. 2010;111:515–9

316. Franck M, Radtke FM, Apfel CC, Kuhly R, Baumeyer A, Brandt C, Wernecke KD, Spies CD. Documentation of post-operative nausea and vomiting in routine clinical practice. J Int Med Res. 2010;38:1034–41

317. Sigaut S, Merckx P, Peuch C, Necib S, Pingeon F, Mantz J. Does an educational strategy based on systematic preoperative assessment of simplified Apfel’s score decrease postoperative nausea and vomiting? Ann Fr Anesth Reanim. 2010;29:765–9

318. Kumar A, Brampton W, Watson S, Reid VL, Neilly D. Postoperative nausea and vomiting: simple risk scoring does work. Eur J Anaesthesiol. 2012;29:57–9; author reply 59–60

319. Jensen K, Kehlet H, Lund CM. Post-operative recovery profile after laparoscopic cholecystectomy: a prospective, observational study of a multimodal anaesthetic regime. Acta Anaesthesiol Scand. 2007;51:464–71

320. Bergland A, Gislason H, Raeder J. Fast-track surgery for bariatric laparoscopic gastric bypass with focus on anaesthesia and peri-operative care. Experience with 500 cases. Acta Anaesthesiol Scand. 2008;52:1394–9

321. Scuderi PE. PRO: anatomical classification of surgical procedures improves our understanding of the mechanisms of postoperative nausea and vomiting. Anesth Analg. 2010;110:410–1

322. Kranke P, Eberhart LH. Possibilities and limitations in the pharmacological management of postoperative nausea and vomiting. Eur J Anaesthesiol. 2011;28:758–65

323. Curran JA, Grimshaw JM, Hayden JA, Campbell B. Knowledge translation research: the science of moving research into policy and practice. J Contin Educ Health Prof. 2011;31:174–80

324. Akobeng AK. Communicating the benefits and harms of treatments. Arch Dis Child. 2008;93:710–3

325. Apfel CC, Meyer A, Orhan-Sungur M, Jalota L, Whelan RP, Jukar-Rao S. Supplemental intravenous crystalloids for the prevention of postoperative nausea and vomiting: quantitative review. Br J Anaesth. 2012;108:893–902

326. Wang JJ, Ho ST, Tzeng JI, Tang CS. The effect of timing of dexamethasone administration on its efficacy as a prophylactic antiemetic for postoperative nausea and vomiting. Anesth Analg. 2000;91:136–9

327. 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

328. Splinter WM. Prevention of vomiting after strabismus surgery in children: dexamethasone alone versus dexamethasone plus low-dose ondansetron. Paediatr Anaesth. 2001;11:591–5

329. Splinter WM, Rhine EJ. Low-dose ondansetron with dexamethasone more effectively decreases vomiting after strabismus surgery in children than does high-dose ondansetron. Anesthesiology. 1998;88:72–5

330. Shende D, Bharti N, Kathirvel S, Madan R. Combination of droperidol and ondansetron reduces PONV after pediatric strabismus surgery more than single drug therapy. Acta Anaesthesiol Scand. 2001;45:756–60

331. Holt R, Rask P, Coulthard KP, Sinclair M, Roberts G, Van Der Walt J, MacKenzie V, Rasmussen M. Tropisetron plus dexamethasone is more effective than tropisetron alone for the prevention of postoperative nausea and vomiting in children undergoing tonsillectomy. Paediatr Anaesth. 2000;10:181–8

332. Madan R, Bhatia A, Chakithandy S, Subramaniam R, Rammohan G, Deshpande S, Singh M, Kaul HL. Prophylactic dexamethasone for postoperative nausea and vomiting in pediatric strabismus surgery: a dose ranging and safety evaluation study. Anesth Analg. 2005;100:1622–6

333. Olutoye O, Jantzen EC, Alexis R, Rajchert D, Schreiner MS, Watcha MF. A comparison of the costs and efficacy of ondansetron and dolasetron in the prophylaxis of postoperative vomiting in pediatric patients undergoing ambulatory surgery. Anesth Analg. 2003;97:390–6

334. Cieslak GD, Watcha MF, Phillips MB, Pennant JH. The dose-response relation and cost-effectiveness of granisetron for the prophylaxis of pediatric postoperative emesis. Anesthesiology. 1996;85:1076–85

335. Khalil SN, Roth AG, Cohen IT, Simhi E, Ansermino JM, Bolos ME, Coté CJ, Hannallah RS, Davis PJ, Brooks PB, Russo MW, Anschuetz GC, Blackburn LM. A double-blind comparison of intravenous ondansetron and placebo for preventing postoperative emesis in 1- to 24-month-old pediatric patients after surgery under general anesthesia. Anesth Analg. 2005;101:356–61

Supplemental Digital Content

Back to Top | Article Outline

© 2014 International Anesthesia Research Society

Login

Become a Society Member