Journal of Clinical Anesthesia (2014) xx, xxx–xxx
Dexamethasone for the prevention of postoperative sore throat: a systematic review and meta-analysis☆,☆☆ Xiang Zhao MD (Staff Anesthesiologist) a , Xiuhong Cao MD (Staff Anesthesiologist) b , Quan Li MD, PhD (Professor) a,⁎ a
Department of Anesthesiology, Shanghai East Hospital, Tongji University School of Medicine, Shanghai, China Department of Anesthesiology, Shanghai First Maternity and Infant Hospital, Tongji University School of Medicine, Shanghai, China
Received 25 October 2013; revised 3 June 2014; accepted 9 June 2014
Keywords: Dexamethasone; Postoperative sore throat; POST; Meta-analysis
Abstract Study Objective: To determine the antiemetic efficacy of dexamethasone in the prevention of postoperative sore throat (POST) and postoperative hoarseness (PH). Design: Meta-analysis. Setting: Metropolitan university medical center. Measurements: This systematic review and meta-analysis was conducted and reported in agreement with the PRISMA guideline. We searched online databases of MEDLINE (from 1966 to August 2013), EMBASE (from 1982 to August 2013), Google Scholar, and the Cochrane Database of Systematic Review. Relative ratios (RRs) and 95% confidence interval (CI) were calculated. Results: : Four trials with a total of 480 patients were included for the analysis: 283 received prophylactic dexamethasone and 197 received placebo. Pooled result by random-effects model showed that dexamethasone significantly decreased the incidence of POST at 1 hour (RR = 0.51, 95% CI 0.270.94, P = .03; P for heterogeneity = .0005, I2 = 83%) and at 24 hour postextubation (RR = 0.46, 95% CI 0.26-0.79, P b .05; P for heterogeneity = .01, I2 = 72%). Our analysis indicated that dexamethasone significantly decreased the incidence of PH at 1 hour (RR = 0.22, 95% CI 0.11-0.46, P b .01; P for heterogeneity = .48, I2 = 0%), but did not affect the incidence of PH at 24 hours postextubation (RR = 0.67, 95% CI 0.37-1.20, P N .1; P for heterogeneity = .12, I2 = 59%). Conclusion: Our meta-analysis suggested that intravenous dexamethasone can effectively reduce the incidence of POST both at 1 and at 24 hours postextubation. In addition, the present study showed that prophylactic dexamethasone reduced the incidence of PH at 1 hours but not at 24 hours postextubation. © 2014 Elsevier Inc. All rights reserved.
Declaration of interest: None declared. Funding: This research was funded internally by the Department of Anesthesiology, Shanghai East Hospital, Tongji University School of Medicine. No outside funding was provided by any governmental, other public or private agency, or industrial entity. ⁎ Corresponding author at: Department of Anesthesiology, Shanghai East Hospital, Tongji University School of Medicine, 150 Jimo Rd, Shanghai China. E-mail address: [email protected]
(Q. Li). ☆☆
http://dx.doi.org/10.1016/j.jclinane.2014.06.014 0952-8180/© 2014 Elsevier Inc. All rights reserved.
1. Introduction Postoperative sore throat (POST) is a common occurrence after general anesthesia with endotracheal intubation, with the incidence ranging from 6.6% to 90% [1,2]. Incidence of POST depends on various factors such as female sex, history
2 of smoking or lung diseases, postoperative nausea , the size of the endotracheal tube, the cuff pressure, and the time and manipulations needed to insert the tube . The common methods for the prevention of POST include use of a smaller endotracheal tube to reduce contact area with mucosa [4,5], low intracuff pressure , cuff filled with saline or lidocaine [7,8], and inhalation of steroid. Dexamethasone is a potent corticosteroid with analgesic, anti-inflammatory, and antiemetic effects [10–12]. Recent studies indicated that dexamethasone may be an effective method for the prevention of POST. However, reports from the literature were confusing and inconsistent. Bagchi et al  showed that prophylactic intravenous dexamethasone reduces the incidence of POST at 1 hour postextubation by 30%, with the efficacy being 60%, whereas Ruangsin et al  reported that the intravenous dexamethasone had no significant effect against POST after endotrachea intubation. Therefore, the preventive effect of dexamethasone has not been clearly defined. The aim of this systematic review and meta-analysis was to determine the anti-inflammatory efficacy of dexamethasone in the prevention of POST.
2. Materials and methods 2.1. Systematic search This systematic review and meta-analysis was conducted and reported in agreement with the PRISMA guideline . Online databases of MEDLINE (from1966 to August 2013), EMBASE (from 1982 to August 2013), Google Scholar, and the Cochrane Database of Systematic Review were searched; words and medical subheadings of “dexamethasone” and “sore throat” were used for databases searching. References from relevant articles were reviewed to identify additional studies. Although no language restriction was used, all studies included in this systematic review were published in English. The initial research yielded 55 randomized clinical trials (RCTs).
2.2. Study selection Two reviewers selected eligible RCTs independently. After a primary screening of titles and abstracts, full-text articles of potentially relevant RCTs were retrieved and further evaluation of eligibility. Fifty-one trials were not relevant based on inclusion and exclusion criteria. Disagreements between 2 authors were resolved by discussion with a third author.
X. Zhao et al. endotracheal intubation, and (3) outcome: incidence of POST or postoperative hoarseness (PH). Excluded were trials reporting dexamethasone administration without an active (placebo or “no treatment”) control group or patients with no endotracheal intubation.
2.4. Assessment of study quality Two authors independently read the included RCTs and assessed their methodological validity using a modified Jadad five-point quality scale . The scale evaluates the study for the following items: randomization, double-blind evaluation, concealment of study group to evaluator, valid randomization method, and completeness of data at follow-up. The minimum possible score of an included trial was 1 and the maximum was 5.
2.5. Date extraction Data were abstracted independently by using a standardized data collection form. Data included dexamethasone dose, ample size, number of subjects in treatment groups, type of surgery, and POST and/or PH at 1 and/or 24 hours. The primary outcome of the data was the incidence of POST at 1 and at 24 hours after surgery. The secondary outcomes were the incidence of PH at 1 and at 24 hours.
2.6. Statistical analysis For dichotomous data, relative ratios (RRs) and 95% confidence interval (CI) were calculated. The heterogeneity of the included studies was considered significant, if the P value of χ2 test was less than .10 or I2 greater than 50%, and then a random-effects model was used; otherwise, a fixed-effects model was used. Further analysis was planned a priori to explore relevant heterogeneity. Subgroup analysis was performed comparing a single-does dexamethasone with multiple-dose dexamethasone group in studies. Sensitivity analysis was performed by omitting one study each time and investigating the influence of a single study on the overall pooled estimate. Publication bias was assessed by visually inspecting funnel plots if at least 10 trials of each intervention were included. However, we were not able to create funnel plots because of the trials in our meta-analysis were small. A P value less than .05 was considered statistically significant. All statistical analyses were performed using Review Manager Version 5.1 (RevMan5.1; The Cochrane Collaboration, Oxford, United Kingdom).
3. Results 2.3. Inclusion and exclusion criteria 3.1. Identification and selection of study Randomized controlled trials met the following criteria: (1) intervention: perioperative intravenous dexamethasone, (2) population: patients undergoing general anesthesia after
The comprehensive search yielded a total of 55 records, and 9 studies initially met the inclusion criteria (Fig. 1) [13,14,17–
Dexamethasone for preventing POST 23]. Five studies were subsequently excluded for reasons demonstrated in Fig. 1 [17–21]. Finally, 4 trials with a total of 480 patients were included for the analysis [13,14,22,23].
3.2. Study characteristics and quality All included trials were conducted in Asian and published in English. The included studies were published between 2007 and 2012. The median modified Jadad scale score was 5. Data from 480 patients were analyzed: 283 received prophylactic dexamethasone and 197 received placebo. The characteristics of included studies are listed in Table. The characteristics included the authors, the year of publication, the anesthesia duration, dexamethasone dose of administration, number of subjects in treatment groups, type of surgery, and POST and/or PH at 1 and/or 24 hours; different regimens of dexamethasone were tested, most frequently, 4 mg intravenously (IV)  or 8 mg IV [14,23], and 0.1 mg/kg IV  or 0.2 mg/kg IV [13,22]. Two studies included 2 does dexamethasone [14,22]; the number of subjects in dexamethasone groups was combined. Two studies included the outcome of PH at 1 and 24 hours [13,22]. For the purpose of this analysis, our study had POST as primary outcomes and PH as secondary outcomes.
3.3. Primary outcomes Data on primary outcomes were available in 4 trials [13,14,22,23]. Pooled result by random-effects model showed that dexamethasone significantly decreased the incidence of POST at 1 hour (RR = 0.51, 95% CI 0.27-0.94, P = .03; P for heterogeneity = .0005, I2 = 83%; Fig. 2) and at 24 hours postextubation (RR = 0.46, 95% CI 0.26-0.79, P b .05; P for heterogeneity = .01, I2 = 72%; Fig. 3). Subgroup analysis according to different dexamethasone groups (1-dose dexamethasone group, 2-dose dexamethasone groups) showed that
3 the incidence of POST at 1 hour was effectively reduced in the 1-dose dexamethasone group (RR = 0.37, 95% CI 0.25-0.57, P b .00001; P for heterogeneity = .83, I2 = 0%; Fig. 2), whereas it was not effectively reduced in the 2-dose dexamethasone groups (RR = 0.66, 95% CI 0.24-1.87, P = .44; P for heterogeneity = .0005, I2 = 92%; Fig. 2). Sensitivity analysis suggested that the trial by Ruangsin et al  was the source of heterogeneity. Except in this trial, heterogeneity was in acceptable ranges (RR = 0.22, 95% CI 0.11-0.46, P b .01; P for heterogeneity = .48, I 2 = 0%; Fig. 4). Meanwhile, subgroup analysis was performed at 24 hours of POST; the efficacy (RR = 0.49, 95% CI 0.26-0.91, P = .02, P for heterogeneity = .12, I2 = 59%; RR = 0.40, 95% CI 0.11-1.46, P = .17, P for heterogeneity = .003, I2 = 88%; Fig. 3) was similar to the incidence of POST at 1 hour. Sensitivity analysis was performed by omitting one study each time; the pooled result was still significant (P b .05). Because the trials were small, funnel plots were not presented in our meta-analysis.
3.4. Secondary outcomes Two trials reported on the incidence of PH 24 hours after surgery [13,22]. Our analysis indicated that dexamethasone significantly decreased the incidence of PH at 1 hour (RR = 0.22, 95% CI 0.11-0.46, P b .01; P for heterogeneity = .48, I2 = 0%; Fig. 5), but did not affect the incidence of PH at 24 hours postextubation (RR = 0.67, 95% CI 0.37-1.20, P N .1; P for heterogeneity = .12, I2 = 59%; Fig. 6).
4. Discussion 4.1. Explanation of results This is the first meta-analysis of studies of prophylactic dexamethasone on POST after general anesthesia. Intravenous
55 potentially relevant trials
46 trials excluded by screening of titles or abstracts 9 trials full-text relative article
5 trials excluded after article review 3 the control group included dexamethasone 2 data could not be extracted or authors could not be reached
4 trials included in the meta–analysis
Flowchart outlining retrieved, excluded, and evaluated randomized controlled trials.
X. Zhao et al. Table
Summary of studies included in analysis
Authors, year of publication
Anesthesia Treatment duration dexamethason dose
Modified Jadad Total number POST at 1 POST at 24 Postoperative Postoperative score (1-5) of treatment/ h treatment/ h treatment/ hoarseness at hoarseness at control control control 1 h treatment/ 24 h treatment/ control control
Mohan Chandra Mandal, 2012  Jin-Hee Kim, 2008  Thomas and Beevi, 2007  Ruangsin et al, 2012 
45 min 3h b6 h
48 vs 48
9 vs 23
14 vs 21
1 vs 2
14 vs 15
0.1 or 0.2 mg/kg 5
110 vs 56
23 vs 30
8 vs 20
8 vs 20
25 vs 25
55 vs 55
11 vs 31
11 vs 31
4 or 8 mg
70 vs 35
38 vs 17
25 vs 17
POST = postoperative sore throat; NR = none reported.
dexamethasone may effectively reduce the incidence of POST both at 1 hour and at 24 hours postextubation. In addition, prophylactic dexamethasone reduced the incidence of PH at 1 hour, but not at 24 hours postextubation. Postoperative sore throat is one of the most common complaints of patients after endotracheal extubation; many methods to reduce the incidence of POST have been proposed. The study conducted by Borazan et al  showed that oral magnesium lozenges administered 30 minutes before surgery reduced the incidence of POST, especially at 2 and 4 hours after surgery, In another study, Canbay et al  compared the effectiveness of ketamine gargle with placebo in preventing POST after tracheal intubation and found that ketamine gargle significantly reduced the incidence and severity of POST. Our findings have potential clinical implications because lower-dose dexamethasone is commonly given at the time of anesthesia induction to reduce postoperative nausea and vomiting . Given dexamethasone's beneficial effects on POST, Waldron et al  found that perioperative single-dose dexamethasone was associated with small but
statistically significant reductions in postoperative pain, postoperative opioid consumption, need for rescue analgesia, and postanesthesia care unit stays.
4.2. Limitations of the study Several potential limitations of this study should be considered. First, the geographic regions only covered Asia. Therefore, our results limited generalizability to the regions. Second, the effect of low- and high-dose dexamethasone needs further investigation. The data originated in the current study should be confirmed by large dose-ranging RCTs.
4.3. Conclusion In conclusion, intravenous dexamethasone may effectively reduce the incidence of POST both at 1 hour and at 24 hours postextubation. In addition, the present study showed that prophylactic dexamethasone reduced the incidence of PH at 1 hour, but not at 24 hours postextubation.
Forest plot of POST at1 hour after surgery.
Dexamethasone for preventing POST
Forest plot of POST at 24 hours after surgery.
Forest plot of POST at1 hour after surgery, excluding the trial by Ruangsin et al .
Forest plot of PH at1 hour after surgery.
Author contributions Xiang Zhao: study design, literature search, data extraction, data analysis, writing the first draft of the paper, revising the article, and final approval. Xiuhong
Cao: study design, literature search, data extraction, data analysis, writing the first draft of the manuscript, and final approval. Quan Li: study design, data analysis, writing the first draft of the manuscript, revising the article, and final approval.
X. Zhao et al.
Forest plot of PH at 24 hours after surgery.
Acknowledgment The authors thank colleagues for providing additional data not listed in the article.
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