Dexamethasone for Antiemesis in Laparoscopic Gynecologic Surgery

A Systematic Review and Meta-Analysis

Alice Pham,
MD, FRCSC,

and Grace Liu,

MD, FRCSC

OBJECTIVE: To estimate the beneficial and harmful effects of dexamethasone for prevention of postoperative nausea and vomiting in women undergoing laparoscopic gynecologic surgery. DATA SOURCES: We searched the following bibliographic databases: MEDLINE (from 1946 to January 2012), Embase (from 1980 to 2012 week 3), the Cochrane Central Register of Controlled Trials (from inception to January 2012), and ISI Web of Knowledge (from 1950 to January 2012). We also screened trial registries, reference lists of retrieved studies, and other sources of unpublished literature. METHODS OF STUDY SELECTION: Two reviewers screened in duplicate and independently searched results for inclusion. We included randomized controlled trials (RCTs) comparing dexamethasone with a placebo in patients undergoing laparoscopic gynecologic surgery. TABULATION, INTEGRATION, AND RESULTS: Two reviewers completed data extraction and assessed trials for bias in duplicate and independently. We used the Grading of Recommendations Assessment, Development, and Evaluation methodology to assess the quality of evidence across studies at the outcome level. A total of 13 RCTs with 1,695 patients met inclusion criteria. Data were pooled based on the random-effects model. The use of prophylactic dexamethasone significantly decreases the incidence of postoperative nausea (relative risk [RR] 0.56, 95% confidence interval [CI] 0.450.71), postoperative vomiting (RR 0.35, 95% CI 0.250.48), the need for rescue
From the Department of Obstetrics and Gynecology, Sunnybrook Health Sciences Centre, Toronto, Ontario, Canada. The authors thank Elie Akl for instruction, advice, and editorial support in the preparation of this manuscript. Corresponding author: Alice Pham, MD, FRCSC, Department of Obstetrics and Gynecology, Sunnybrook Health Sciences Centre, Suite B627, 2075 Bayview Avenue, Toronto, ON, M4N 3M5, Canada; e-mail: alice.pham@mail.utoronto.ca. Financial Disclosure The authors did not report any potential conflicts of interest. 2012 by The American College of Obstetricians and Gynecologists. Published by Lippincott Williams & Wilkins. ISSN: 0029-7844/12

antiemetics (RR 0.39, 95% CI 0.290.52), and time to meet discharge criteria (mean 28.5 minutes, 95% CI 24.632.4). The estimated number needed to treat to prevent nausea in one patient was eight (95% CI 513), whereas that for vomiting was five (95% CI 46). There was no observed increase in adverse events. The quality of the evidence ranged from very low to moderate. CONCLUSION: This systematic review provides evidence that dexamethasone decreases the incidence of postoperative nausea and vomiting after laparoscopic gynecologic surgery, with no observed increase in side effects.
(Obstet Gynecol 2012;120:145158) DOI: http://10.1097/AOG.0b013e31827590f3

he incidence of postoperative nausea and vomiting is significant after laparoscopic gynecologic surgery, affecting between 50% and 90% of patients.1 This is likely related to the increased intra-abdominal pressure required in laparoscopic surgery, and it is likely related to the fact that female gender confers a two-fold to fourfold increase in risk.1,2 Three other main risk factors for postoperative nausea and vomiting have been identified: history of motion sickness or postoperative nausea and vomiting; nonsmoking status; and use of postoperative opioids.1,3 A variety of antiemetics with different mechanisms of action have been used both in combination and as single agents, including anticholinergics, dopamine receptor antagonists, and antihistamines. Dexamethasone is a corticosteroid known for its antiemetic effects, particularly in chemotherapy-induced nausea. Its mechanism of action, however, remains unclear. A systematic review found that in patients undergoing laparoscopic cholecystectomy, dexamethasone, as compared with placebo, reduced the incidence of nausea (relative risk [RR] 0.59, 95% confidence interval [CI] 0.480.72), vomiting (RR 0.41, 95% CI 0.300.55), and postoperative nausea or vomiting (RR 0.55, 95% CI 0.780.98).4 Postoperative pain also appeared to be reduced (ratio of means 0.87, 95% CI

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0.780.98); however, there was a considerable amount of unexplained heterogeneity (I 2590.4%). The incidence of side effects (headache and dizziness) was found to be similar between the treatment groups. The objective of this systematic review was to estimate the beneficial and harmful effects of dexamethasone compared with no dexamethasone in the gynecologic surgical patient population.

SOURCES
We searched the following bibliographic databases: MEDLINE (from 1946 to third week of January 2012), Embase (from 1980 to third week of 2012), the Cochrane Central Register of Controlled Trials (from inception to third week of January 2012), and ISI Web of Knowledge (from 1950 to third week of January 2012) for abstracts. We screened the electronically available conference proceedings from the Society of Obstetricians and Gynecologists of Canada (20062011), the American College of Obstetricians and Gynecologists (20082011), the American Association of Gynecologic Laparoscopists (www.aagl.org; 20082011), the Canadian Anesthesiologists Society (www.cas.ca; 20072011), and the American Society of Anesthesiologists (ASA; www.asahq.org; 2000 2011). We also screened trial registries, reference lists of included studies, and contacted clinical experts. There were no limits on language, date, or form of publication. We used the following search terms to search all databases: laparoscopy; endoscopy; video-assisted surgery; gynecologic surgical procedures; steroids; and dexamethasone and all of its generic and trade names. We used a study filter for randomized controlled trials, from the Cochrane handbook, and limited our search to human studies. See Appendix 1 (available online at http://links.lww.com/AOG/A333) for the full search strategy. We developed a protocol with inclusion criteria and methods of analysis and registered it on PROSPERO: International prospective register of systematic reviews. 5 The registration number is CRD42012002160 and is available online (http://www.crd.york.ac.uk/PROSPERO).

STUDY SELECTION
Two reviewers (A.P. and G.L.) screened in duplicate and independently all titles and abstracts from the search results. If either reviewer identified a study as being potentially eligible, the full-text article was retrieved for review. Both reviewers, in duplicate and independently, performed full-text screening for eligibility. We resolved all disagreements by consensus.

Agreement between the two reviewers was calculated using Cohen weighted kappa statistic (kw). We reviewed published randomized controlled trials in which the intervention was perioperative corticosteroid administration compared with placebo in patients undergoing laparoscopic gynecologic surgery. Quasi-randomized trials, essentially those trials lacking random allocation, were eligible for extraction of data on outcomes not assessed by randomized controlled trials.6 Trials in which laparoscopic procedures were converted to open were included in the review. Studies with a range of doses, route (oral, intravenous, intramuscular, inhalational), and timing of administration (preoperative, intraoperative, or postoperative) were included. Primary outcomes of interest were postoperative nausea, vomiting, or both. Secondary outcomes included adverse events (infection, hyperglycemia, admission to the intensive care unit, reoperation, mortality), need for postoperative rescue antiemetics, degree of postoperative pain (measured on any scale), need for postoperative analgesics, conversion to laparotomy, quality of life (measured on any validated scale), and hospital length of stay. We used a piloted standardized data extraction form and instruction manual to abstract data independently and in duplicate. We resolved disagreements through discussion and consensus and contacted authors if further information was required. Data extracted from each study included relevant information on study identifiers and characteristics of trial participants, including age, body mass index (BMI, calculated as weight (kg)/[height (m)]2), ASA class, history of postoperative nausea and vomiting, and motion sickness; the trials exclusion and inclusion criteria; characteristics of the intervention (including type, dose, route, and timing); type of comparator (no intervention compared with placebo); and type of outcome measure. Both reviewers assessed in duplicate and independently, in an unblinded manner, the methodologic quality using the Cochrane risk of bias tool. The quality indicators included adequacy of sequence generation, allocation concealment, blinding of participants, personnel and outcome assessors, selective outcome reporting, extent of loss to follow-up, stopping early for benefit, and adherence to intention-to-treat analysis. Summary measures for dichotomous data (postoperative nausea or vomiting, rates of adverse events, need for rescue antiemetics and analgesics) were expressed as RRs. Summary measures for continuous data were expressed as mean differences (postoperative pain, length of hospital stay, quality of life). If different scales were used to measure a continuous variable, the standardized mean difference was calculated. The standardized mean difference standardizes the results

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to a uniform scale before the data can be pooled.6 When medians, ranges, or both were reported, these were converted to means and standard deviations, or both, to pool the results for the meta-analysis.7 Statistical analyses were conducted using the program Review Manager 5.1 software.8 We tested for heterogeneity using the statistical tests x2 and I 2. The I 2 statistic measures the percentage of the variability in effect estimates that is attributable to heterogeneity rather than sampling error.6 Results were combined in a meta-analysis using the random-effects model because it provided a more conservative effect estimate. For continuous variables, the inverse variance method was used, which essentially calculates a point estimate by weighting each study by the inverse variance of its treatment effect estimate.6 The MantelHaenszel method was used to pool dichotomous variables. Different doses of dexamethasone were combined into a single treatment arm to allow for pair-wise comparison with control.6 We used the Grading of Recommendations Assessment, Development, and Evaluation approach to assess

the quality of evidence by outcome across studies.9 The approach takes into consideration the following factors: type of study design; indirectness; imprecision; inconsistency; and publication bias. We evaluated the possibility of publication bias by constructing Begg and Egger inverted funnel plots, which show asymmetry in the presence of evident publication bias.10 Subgroup analyses, specified a priori, were performed for outcomes if significant heterogeneity was found to determine whether an interaction was present. Subgroup analyses were planned for age, ASA classification, BMI, comorbidities (specifically, history of motion sickness or postoperative nausea and vomiting), dose, timing of administration, cointerventions, definition of nausea, vomiting, pain, and duration of surgery. Sensitivity analyses were prespecified. Studies with the highest risk of bias were excluded and analysis was repeated to determine whether heterogeneity could be reduced. In addition, sensitivity analysis also was performed to estimate the effect on outcome from excluding studies that did not report mean, standard deviation, or both.

Records identied through database searching n=621

Records identied through other sources n=3

Records after duplicates removed N=410

Records screened n=410 Records excluded n=385 Full-text articles assessed for eligibility n=25

Studies included in qualitative synthesis n=13

Excluded studies: n=12 Comparator not placebo, or no intervention: 8 Published only in abstract format: 3 Author under investigation for alleged research misconduct: 1 RCT not included; did not report postoperative nausea or vomiting events in dexamethasone group n=1

Fig. 1. Flow of included studies. RCT, randomized controlled trial.

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Studies included in quantitative synthesis n=12

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RESULTS
The search strategy identified a total of 624 citations. After removing duplicates, 410 citations remained. Title and abstract screening excluded 384 of these citations because they did not meet inclusion criteria. Of the 26 trials that remained, we were not able to obtain the full text for one of these.11 The full-text screening of the remaining 25 citations identified 14 eligible studies, but one trial was excluded because the author is currently undergoing investigation for alleged research misconduct12,13 (Fig. 1). The agreement between the two reviewers was complete (Cohen kw51) for full-text screening. Characteristics of included studies are provided in Table 1 in Appendix 2 (available online at http://links.lww.com/AOG/A334). All 13 studies were randomized controlled trials. Eleven were published in English and two included English translations from Portuguese. The studies involved a total of 1,695 patients undergoing laparoscopic gynecologic surgery. All studies used dexamethasone as a prophylactic antiemetic, administered in a single dose. Doses (415 mg) and timing (preoperatively 2 hours before surgery to administration at the end of surgery) varied between studies. All studies used a placebo control. All 13 studies measured the incidence of postoperative nausea or vomiting.1426 One study assessed postoperative nausea or vomiting but did not report the number of events in the dexamethasone group.16 Six studies14,15,19,20,24,26 reported on side effects, one of which24 examined blood sugar elevations as well as wound infection and delayed wound healing. Postoperative pain scores, as measured by a visual analog scale or numeric rating scale, were reported in eight studies.15,17,1922,24,26 Quality of life was reported in one study.17 Need for postoperative rescue antiemetics was reported in three studies.19,21,26 Need for postoperative analgesia was reported in six studies.15,17,20,22,24,26 Three studies reported on conversion to laparotomy.15,17,20 Total hospital length of stay was not reported in any study; however, time to meet discharge criteria was reported in three studies.17,22,24 Studies varied regarding their risk of bias. Their methodologic quality is described in Table 1 in Appendix 2 (http://links.lww.com/AOG/A334). Sequence generation, the method used to generate the random allocation sequence, was adequate in eight studies.14,15,17,19,20,22,24,25 Allocation concealment was unclear in three studies.18,21,23 Two studies16,18 did not report blinding in any of the five groups that could potentially introduce bias (patients, health care providers, data collectors, outcome assessors, data ana-

lysts). Selective reporting bias was difficult to assess because no study was included in a trial registry or had published protocols. None of the studies clearly stated an intention-to-treat analysis and five studies followed a per-protocol analysis,15,17,19,20,25 thereby exposing them to further potential bias. All studies had more than 95% follow-up and none was stopped early for benefit. We analyzed postoperative nausea and vomiting as two separate outcomes and not as a composite to avoid the risk of double-counting. Nine trials14,15,1719,21,23,25,26 reported postoperative nausea. The pooled estimate showed a statistically significant reduction in nausea in patients treated with dexamethasone compared with placebo (RR 0.56, 95% CI 0.45 0.71; I 250%) (Fig. 2). The estimated number needed to treat to prevent nausea in one patient was eight (95% CI 513). The quality of evidence was moderate. Ten trials14,15,1721,23,25,26 reported postoperative vomiting. The pooled analysis showed a statistically significant decrease in vomiting in patients receiving dexamethasone compared with placebo (RR 0.35, 95% CI 0.250.48; I 250%) (Fig. 3). The estimated number needed to treat to prevent vomiting in one patient was five (95% CI 46). The quality of evidence was low. Subgroup analysis did not rule out a clinically significant reduction in the incidence of postoperative vomiting with increasing doses of dexamethasone (P5.68) (Fig. 4), or with administration of dexamethasone at the time of induction of anesthesia (P5.10). Five trials15,19,21,25,26 reported on the need for a rescue antiemetic, either ondansetron or metoclopramide, administered intravenously. The pooled analysis showed a significant reduction in the need for a rescue antiemetic postoperatively (RR 0.39, 95% CI 0.29 0.52; I 250%). The quality of evidence was moderate. Four trials15,17,22,26 reported on the need for a rescue analgesic. The pooled analysis did not exclude a clinically significant reduction in the need for a postoperative rescue analgesic (RR 0.92, 95% CI 0.741.14). There was a high degree of heterogeneity (I 2555%; P5.08) that could not be explained by any of the planned subgroup analyses. The quality of evidence was low. Three trials21,22,26 measured postoperative pain scores, using either a visual analog scale or a numeric rating scale. The pooled effect estimate suggested a decrease in the pain score of 1.03 (standardized mean difference; 95% CI 0.012.07), but we did not exclude an absence of effect. The quality of evidence was very low. There was a high degree of heterogeneity (I 2593%; P,.001) that could not be explained by any of the planned subgroup analyses. Subgroup

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Fig. 2. Pooled analysis of nausea across studies.

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analysis based on exclusion of patients with BMI higher than 3035 was statistically significant with the test for subgroup differences (x259.30; df51; P5.002). Studies that excluded patients with BMIs higher than 3035 had a decrease in pain score of 0.51 (95% CI 0.411.42); those studies that had no BMI exclusion criteria had a greater decrease in pain score of 2.13 (95% CI 1.632.62). Two trials17,20 reported on conversion to laparotomy. The pooled estimate did not exclude an increase in the rates of conversion (RR 0.69, 95% CI 0.05 10.27). There was a high degree of heterogeneity (I 2566%; P5.09) that could not be explored by subgroup analysis or sensitivity analysis because of the limited number of studies with this outcome. No trials reported total length of hospital stay. However, time to meet discharge criteria was reported in three trials,17,22,24 and the pooled analysis showed that patients treated with dexamethasone decreased time to

meet discharge criteria by 28.5 minutes (95% CI 24.6 32.4; I 250%). The quality of evidence was moderate. Only one study assessed quality of life17 using the Quality of Recovery 40 questionnaire, a validated tool to evaluate patients after anesthesia and surgery in the domains of physical comfort, emotional state, physical independence, psychological support, and pain. Scores ranged from 40 to 200, with higher scores representing higher quality of recovery. The mean score of patients treated with dexamethasone was 15.5 points higher than that of placebo patients (95% CI 13.118.0). One study24 reported on hyperglycemia and wound infection, and there were zero events. Of the remaining five studies14,15,19,20,26 that reported on other side effects, two14,15 stated that there was no difference among the treatment groups. One study19 found no side effects related to the use of dexamethasone. Two studies20,26 presented numerical data and found no increase in the incidence of adverse effects.

Fig. 3. Pooled analysis of vomiting across studies.

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Fig. 4. Comparison of postoperative vomiting with subgroup analysis of dose of dexamethasone.

Pham. Dexamethasone for Antiemesis in Gynecologic Surgery. Obstet Gynecol 2012.

The quality of evidence for all outcomes ranged from very low to moderate. A summary of findings table based on the Grading of Recommendations Assessment, Development, and Evaluation methodology can be found in Table 2 in Appendix 2 (http://links.lww.com/AOG/A334). The funnel plot for postoperative vomiting suggests positive publication bias (Appendix 3 [available online at http:// links.lww.com/AOG/A335], which illustrates the inverted funnel plot for trials comparing the effect of dexamethasone and placebo on postoperative vomiting), whereas for other outcomes there were too few

studies to allow for appropriate interpretation of publication bias. Subgroup analyses specified a priori were performed. There was no difference from the results of pooled estimates. There were not enough trials with significant cointerventions or that defined nausea, vomiting, or pain to perform a subgroup analysis. Mean age across the trials was similar in the treatment groups and, hence, a subgroup analysis was not performed. Sensitivity analyses were prespecified. There were four studies18,21,23,26 that did not report or that had unclear randomization sequence generation, three18,21,23

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of which had unclear allocation concealment or did not report allocation concealment. Two studies16,18 did not report on blinding. When those studies that did not report or that had unclear sequence generation were excluded, there was no difference in results from overall pooled estimates across all outcomes. For postoperative pain score, when the studies that did not report mean, standard deviation, or both (requiring the use of estimation formulas to estimate the mean and variance from the median and range) were excluded, only one study remained, thereby precluding the pooling of results. The results of the remaining study, however, were consistent with the overall results. For the outcome of time to meet discharge criteria, there was no difference in the results. This systematic review identified 13 randomized controlled trials that evaluated the beneficial and harmful effects of dexamethasone, as compared with placebo, in patients undergoing laparoscopic gynecologic surgery. Dexamethasone showed a substantial beneficial effect in reducing the incidence of both postoperative nausea and vomiting. In addition, it decreased the time to meet discharge criteria by 29 minutes and significantly decreased the need for a rescue antiemetic. Subgroup analysis did not rule out a clinically significant reduction in postoperative vomiting in patients treated with higher doses of dexamethasone (8 mg) compared with lower doses (45 mg). Those studies that reported on side effects either had no events or found no increase in the incidence of adverse events among all treatment groups. These side effects were observed in the first 24 hours postoperatively and also may have been attributable to a multitude of factors, such as the general anesthetic agents. In terms of postoperative pain scores and the need for rescue analgesia, the data are less certain. This systematic review failed to demonstrate whether dexamethasone had the potential to reduce the severity of postoperative pain, or whether it had any opioidsparing effect. Dexamethasone patients had better quality of recovery, as measured by the Quality of Recover 40 questionnaire, in all five domains of physical comfort, emotional state, physical independence, psychological support, and pain, scoring almost 16 points higher than the placebo group. Although no minimum clinically important difference could be found in the literature, it has been stated that a 10-point difference in the Quality of Recovery 40 questionnaire score is typical of that seen in patients with and without a major postoperative complication, or when comparing minor and major surgical procedures.27 This review has several limitations, most of which are related to the methodologic quality of the included

studies. For the outcomes of need for rescue analgesic and postoperative pain score, and conversion to laparotomy, the analysis is limited by unexplained moderate to substantial heterogeneity. In addition, for postoperative vomiting, there was a suggestion of positive publication bias from the funnel plot. Our efforts to contact authors of unpublished trials and non-English publications were unsuccessful. Intention-to-treat analysis was either unclear or not performed in any of the studies. This systematic review also includes patients receiving dexamethasone in various doses, at various times, and undergoing a variety of laparoscopic gynecologic procedures, all of different surgical duration. It also includes patients of all ages. However, this does confer greater generalizability to the findings of this review. Strengths of this review include the comprehensive search strategy as well as the rigorous methodology and systematic application of eligibility criteria. A thorough assessment of study quality and risk of bias was performed, in addition to the use of standardized data extraction forms. A priori hypotheses to explain heterogeneity were generated and tested. Although there was the possibility of publication bias for postoperative vomiting, there was a relatively small number of studies involved overall.

CONCLUSION
In clinical practice, it is clear that prophylactic dexamethasone decreases the incidence of postoperative nausea and vomiting after laparoscopic gynecologic surgery, relative to placebo. Given this current evidence, surgeons should consider routinely using prophylactic dexamethasone in this patient population, in the absence of any contraindications. This review did not examine the evidence for the efficacy of dexamethasone compared with those of other commonly used antiemetics for postoperative nausea and vomiting in this surgical population. Future research should be directed at determining whether dexamethasone is effective in reducing postoperative pain. Given that opioids contribute to postoperative nausea and vomiting, it also would be of clinical benefit if dexamethasone were shown to decrease the need for postoperative opioid use. Larger, high-quality, randomized controlled trials powered to detect a difference in this outcome also would strengthen the evidence for using this corticosteroid in an ambulatory surgical setting. Another important outcome to study would be whether dexamethasone use in postmenopausal compared with premenopausal women leads to different overall effects for postoperative nausea and vomiting. The optimal dose and timing of administration also

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remain unclear. Finally, more studies examining overall quality of recovery are warranted. REFERENCES
1. McCracken G, Houston P, Lefebvre G. SOGC Clinical Practice Guideline. Guideline for the management of postoperative nausea and vomiting. J Obstet Gynaecol Can 2008;30:6007, 60816. 2. Raphael JH, Norton AC. Antiemetic efficacy of prophylactic ondansetron in laparoscopic surgery: randomized, double-blind comparison with metoclopramide. Br J Anaesth 1993;71:8458. 3. Wolfgang K, Gassmayr S. Pre-operative anxiety, stress and premedication. Baillires Clin Anesth 1998;12:25364. 4. Karanicolas PJ, Smith SE, Kanbur B, Davies E, Guyatt GH. The impact of prophylactic dexamethasone on nausea and vomiting after laparoscopic cholecystectomy: a systematic review and meta-analysis. Ann Surg 2008;248:75162. 5. PROSPERO: International prospective register of systematic reviews. 2012. Available at: www.crd.york.ac.uk/PROSPERO/. Retrieved March 16, 2012. 6. Higgins JPT, Green S, editors. Cochrane handbook for systematic reviews of interventions. Version 5.1.0. The Cochrane Collaboration; 2011. Available at: www.cochrane-handbook.org. Retrieved February 17, 2012. 7. Hozo SP, Djulbegovic B, Hozo I. Estimating the mean and variance from the median, range, and the size of a sample. BMC Med Res Methodol 2005;5:13. 8. Review Manager (RevMan) [computer program]. Version 5.1. Copenhagen (Denmark): The Nordic Cochrane Centre, The Cochrane Collaboration; 2011. 9. Schnemann H, Brozek J, Oxman A, editors. GRADE handbook for grading quality of evidence and strength of recommendation. Version 3.2. The GRADE Working Group; 2009. Available at: http://www.cc-ims.net/gradepro. Retrieved March 9, 2012. 10. Egger M, Davey Smith G, Schneider M, Minder C. Bias in meta-analysis detected by a simple, graphical test. BMJ 1997; 315:62934. 11. Laiq N, Khan MN, Qureshi FA, Khan S, Jan AS. Dexamethasone as antiemetic during gynaecological laparoscopic surgery. J Coll Physicians Surg Pak 2005;15:77881. 12. Fujii Y, Nakayama M. Dexamethasone for reduction of nausea, vomiting and analgesic use after gynecologic laparoscopic surgery. Int J Gynaecol Obstet 2008;100:2730. 13. Scott JR. Expression of concern. Available at: http://journals. lww.com/greenjournal/Documents/ExpressionOfConcern.pdf. Retrieved September 20, 2012. 14. Biswas BN, Rudra A, Mandal SK. Comparison of ondansetron, dexamethasone, ondansetron plus dexamethasone and placebo in the prevention of nausea and vomiting after laparoscopic tubal ligation. J Indian Med Assoc 2003;101:638, 640, 642.

15. Chu CC, Shieh JP, Tzeng JI, Chen JY, Lee Y, Ho ST, et al. The prophylactic effect of haloperidol plus dexamethasone on postoperative nausea and vomiting in patients undergoing laparoscopically assisted vaginal hysterectomy. Anesth Analg 2008; 106:14026. 16. De Abreu MP, Vieira JL, da Silva IF, Miziara LEPG, Fofano R. Efficacy of ondansetron, metoclopramide, droperidol and dexamethasone in preventing post-gynecologic videolaparoscopy nausea and vomiting in outpatient setting: comparative study. Rev Bras Anestesiol 2006;56:815. 17. De Oliveira GS, Ahmad S, Fitzgerald PC, Marcus RJ, Altman CS, Panjwani AS, et al. 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;107:36271. 18. Ganem EM, Fukushima FB, da Silva DSM, Nakamura G, Castiglia YMM, Vianna PTG. Efficacy of propofol and propofol plus dexamethasone in controlling postoperative nausea and vomiting of gynecologic laparoscopy. Rev Bras Anestesiol 2002;52:394401. 19. Huang J, Shieh J, Tang C, Tzeng J, Koung-Shing C, Wang J. Low-dose dexamethasone effectively prevents postoperative nausea and vomiting after ambulatory laparoscopic surgery. Can J Anesth 2001;48:9737. 20. Jokela RM, Ahonen JV, Tallgren MK, Marjakangas PC, Korttila KT. The effective analgesic dose of dexamethasone after laparoscopic hysterectomy. Anesth Analg 2009;109:60715. 21. Lee Y, Lai H, Lin PC, Huang SJ, Lin YS. Dexamethasone prevents postoperative nausea and vomiting more effectively in women with motion sickness. Can J Anaesth 2003;50:2327. 22. Mohammadi SS. Effects of dexamethasone on early postoperative pain, nausea and vomiting and recovery time after ambulatory laparoscopic surgery. J Med Sci 2007;7:12025. 23. Rimaitis K, Svitojute A, Macas A. The influence of dexamethasone and ketolgan on postoperative nausea and vomiting and estimation of risk factors in women undergoing gynecologic laparoscopic surgeries. Medicina (Kaunas) 2010;46:2617. 24. Thangaswamy CR, Rewari V, Trikha A, Dehran M, Chandralekha. Dexamethasone before total laparoscopic hysterectomy: a randomized controlled dose-response study. J Anesth 2010;24:2430. 25. Wang JJ, Ho ST, Liu HS, Ho CM. Prophylactic antiemetic effect of dexamethasone in women undergoing ambulatory laparoscopic surgery. Br J Anaesth 2000;84:45962. 26. Yuksek MS, Alici HA, Erdem AF, Cesur M. Comparison of prophylactic antiemetic effects of ondansetron and dexamethasone in women undergoing day-case gynaecological laparoscopic surgery. J Int Med Res 2003;31:4818. 27. Myles PS, Weitkamp B, Jones K, Melick J, Hensen S. Validity and reliability of a postoperative quality of recovery score: the QoR-40. Br J Anaesth 2000;84:115.

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