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Dexamethasone or combined with others for postoperative nausea and vomiting in children: A systematic review
Asian Journal of Surgery xxx (xxxx) xxx
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Review Article
Dexamethasone or combined with others for postoperative nausea and vomiting in children: A systematic review Jieting Liu a, b, c, d, e, Huijuan Li c, d, e, Jie Zhang c, Xiashan Dong c, Jianjun Xue c, e, g, Xiue Shi h, Kehu Yang a, c, d, e, f, h, * a
The First Clinical Medical College, Lanzhou University, Lanzhou, 730000, PR China Lanzhou University Second Hospital, Lanzhou, 730000, PR China Evidence-based Social Science Research Center, School of Public Health, Lanzhou University, Lanzhou, 730000, PR China d Evidence-based Medicine Center, School of Basic Medical Sciences, Lanzhou University, Lanzhou, 730000, PR China e Key Laboratory of Evidence Based Medicine and Knowledge Translation of Gansu Province, Lanzhou, 730000, PR China f Institute of Clinical Research and Evidence Based Medicine, Gansu Provincial Hospital, Lanzhou, 730000, PR China g Gansu Provincial Hospital of TCM, Lanzhou, 730000, PR China h Institute for Evidence Based Rehabilitation Medicine of Gansu Province, Lanzhou, 730000, PR China b c
a r t i c l e i n f o
a b s t r a c t
Article history: Received 4 July 2019 Accepted 21 November 2019 Available online xxx
Postoperative nausea and vomiting (PONV) is one of the most common and unpleasant postoperative complications in children. This study aims to evaluate the efficacy and safety of using dexamethasone alone or combined other drugs on the incidence of PONV in children. A systematic search of the literature was conducted from inception until March, 2019. Literature selection and data extraction were conducted by two independent reviewers. Statistical analysis was performed using the software package Review Manager Version 5.3.3. Twenty studies with total 2505 participants were included. The pooled analysis used a random-effect model showed that dexamethasone had significantly greater efficacy in incidence of POV and PON in postoperative 24 h than control. Subgroup analysis indicated the RR of dexamethasone 0.5 mg/kg group was the lowest compared subgroup dexamethasone 0.3 mg/kg and 0.3e0.5 mg/kg. There was no difference for early POV between dexamethasone and placebo groups. Dexamethasone combined with others also could significantly reduce the incidence of POV in postoperative 24 h. Few adverse effects were reported. This study indicates that dexamethasone is effective for preventing incidence of PONV in children. And multimodal approaches have shown more effectively to prevent the incidence of POV. © 2020 Asian Surgical Association and Taiwan Robotic Surgery Association. Publishing services by Elsevier B.V. This is an open access article under the CC BY-NC-ND license (http://creativecommons.org/ licenses/by-nc-nd/4.0/).
Keywords: Dexamethasone Postoperative nausea and vomiting Children
1. Introduction Postoperative nausea and vomiting (PONV) is one of the most common and unpleasant postoperative complications, which is a major concern in surgical patients.1 PONV affects about 20e40% of surgical patients, with certain high-risk patients experiencing rates of up to 80%.2e4 It has a high incidence in children, especially for tonsillectomy and strabismus surgery.5e7 PONV could lead to several adverse consequences, including dehydration, electrolyte
* Corresponding author. The First Clinical Medical College; Evidence-based Medicine Center, School of Basic Medical Sciences; 199 Donggang West Road, Lanzhou University, Lanzhou, Gansu Province, China. E-mail address: [email protected] (K. Yang).
imbalance, sub-conjunctival hemorrhage, the wound dehiscence.8,9 It has also been reported PONV is associated with delayed hospital discharge, unplanned hospital admission, and increased financial costs required for patient care.10,11 Several anti-emetic drugs have been described for the prophylactic control of PONV. Dexamethasone is common practice in surgery, as part of a multimodal pain and antiemetic strategy.12,13 Previous systematic reviews have showed that preoperative dexamethasone treatment reduces PONV in children after strabismus surgery and thyroidectomy.14,15 However, due to limited sample size and low-quality studies design, the conclusions remain to be confirmed further. In the last few years, some new studies that explored the efficacy of dexamethasone for PONV in children have become available.16,17 Besides, there are several studies explored the effect of
https://doi.org/10.1016/j.asjsur.2019.11.012 1015-9584/© 2020 Asian Surgical Association and Taiwan Robotic Surgery Association. Publishing services by Elsevier B.V. This is an open access article under the CC BY-NCND license (http://creativecommons.org/licenses/by-nc-nd/4.0/).
Please cite this article as: Liu J et al., Dexamethasone or combined with others for postoperative nausea and vomiting in children: A systematic review, Asian Journal of Surgery, https://doi.org/10.1016/j.asjsur.2019.11.012
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dexamethasone combined with other drugs for PONV.14,18 Therefore, this systematic review aims to evaluate of the efficacy and safety of the use of dexamethasone or combined other drugs on the incidence of PONV in children.
2. Methods 2.1. Literature search This review follows the guidelines for Preferred Reporting Items for Systematic reviews and Meta-analyses (PRISMA).19e22 Guidance is also sought from the Cochrane handbook as well as some highquality articles from published journals to provide the framework for the statistical analysis.23e25 A systematic search of the literature was conducted from inception until March, 2019 using the PubMed, EMBASE, Web of science, and Cochrane library. No language, publication date or publication status restrictions were used. The search terms were used the following terminology: Dexamethasone, Ceroids, Corticosteroids, Dexamethas*, Pediatrics, Child*, Adolescent, Nausea, Vomiting. In addition, the references of all eligible studies were manually retrieved to ensure the comprehensiveness of the search. The detailed search strategies for PubMed were presented in Table S1 of Supplementary materials.
2.2. Inclusion criteria We included for all randomized controlled trials (RCTs) that studied the efficacy of dexamethasone alone or combined with other drugs compared with a placebo or no treatment for PONV in children. The detailed criteria following “PICOS” principle (P: Participants, I: Intervention, C: Control, O: Outcomes, S: Study designs) were showed in Table 1. And comments, reply, non-systematic review, non-English language articles, conference abstracts, and repeated publication were excluded.
2.4. Risk of bias assessment We assessed the study quality of each included trial according to the recommendations outlined in the Cochrane Handbook for Systematic Reviews of Interventions.26 We took into account the following items: allocation sequence generation, concealment of allocation, blinding of participants and investigators, incomplete outcome data, selective outcome reporting, and other sources of bias. The risk of bias was examined by two reviewers concurrently, and discrepancies were resolved by consensus. 2.5. Statistical analysis Statistical analysis was performed using the software package Review Manager Version 5.3.3 (Nordic Cochrane Centre, The Cochrane Collaboration, Copenhagen, Denmark) and STATA version 12 (Stata Corp LP, College Station, TX, United States). Pooled risk ratio (RR) with 95% confidence interval (CI) was utilized to analyze dichotomous data, while continuous data were analyzed as mean differences (MDs) with 95% CIs. Heterogeneity was evaluated using the chi-square test, for which P < 0.1 was considered statistically significant. The I2 value was used to quantify the impact of heterogeneity on each analysis. Given the level of heterogeneity observed, the random-effects model results are reported within the text and figures. Subgroup analysis was carried out according to different dosage of dexamethasone. Potential publication bias was explored by visual inspection of the funnel plot for asymmetry. 3. Results 3.1. Search results A total of 2313 records were identified by searching the selected databases (Figure S1). After excluding duplicate records and after preliminary screening, 37 full-text records were assessed for eligibility. Finally, 20 studies met the inclusion criteria. The exclusion reason for full texts were listed in Table S2 of Supplementary materials.
2.3. Literature selection and data extraction 3.2. Study characteristics The retrieved records were imported into the EndNote X7 software and the duplicate publications were excluded. Two reviewers (LHJ and DXS) independently read the titles and abstracts of all identified records to exclude those that were clearly not relevant. Then the full texts of the articles retained were reviewed to further determine their suitability. The excluded reasons for full texts were list in Table S2 of Supplementary materials. Differences opinions were resolved by consensus. The data were extracted by two reviewers (LHJ and DXS) independently using a pre-defined form. The following characteristics of the guidelines were collected: the first author, publication year, country, number of included participants, timing of administration, intervention, control, type of surgery, and outcomes and main conclusion. Any discrepancies were resolved by consensus.
Twenty studies5,16e18,27e42 with total 2505 participants were included in this meta-analysis. All of them were randomized controlled trials (RCTs). Of 20 RCTs, the year of published between 1998 and 2019. The sample sizes range from 41 to 349. The studies came from 14 different countries. Fourteen studies28,34,37,41 were from India. Three studies 2931were based in Saudi Arabia. Two studies35,36 were from Turkey, one from Australia,27 Iran,18 America,32 Canada,33 Czech Republic,17 Egypt,5 United Arab Emirates,38 Brazil,39 Lebanon,42 and Japan.16 The dosage of dexamethasone varied, range from 0.05 mg/kg to 1 mg/kg. Surgical procedures included tonsillectomy, adenotonsillectomy, strabismus, middle ear surgery, scoliosis correction surgery, dental surgery, and inguinal hernia, umbilical hernia, cryptorchidism, or phimosis surgery. Nine
Table 1 The inclusion criteria. Category
Inclusion criteria
Population Intervention Comparison Outcome
People <18 years of age, without country restriction Dexamethasone alone or combined with other drugs Placebo or no intervention Primary outcomes included the early incidence of postoperative of vomiting (POV), the incidence POV in postoperative 24 h, and postoperative of nausea (PON) in postoperative 24 h. Secondary outcomes included the need for rescue anti-emetics and adverse effects. Randomized controlled trials (RCTs)
Study design
Please cite this article as: Liu J et al., Dexamethasone or combined with others for postoperative nausea and vomiting in children: A systematic review, Asian Journal of Surgery, https://doi.org/10.1016/j.asjsur.2019.11.012
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studies5,16,17,27,29,32,33,36,42 were two-armed, five28,35,37,39,41 were three-armed and six18,30,31,34,38,40 were four-armed. Eight studies18,28,30,31,37e39,41 compared dexamethasone combined with others with placebo. Three studies34,35,40 compared different dosage of dexamethasone with placebo. The baseline characteristics were balanced among the treatment groups in included studies. Table 2 lists the characteristics of these studies. 3.3. Dexamethasone versus placebo 3.3.1. Incidence of POV after postoperative 24 h Ten studies5,16e18,27,28,31,33,34,40 compared the incidence of POV after postoperative 24 h between the dexamethasone and control group. Of them, two studies34,40 contained three different dosage of dexamethasone groups. The pooled analysis used a random-effect model showed that dexamethasone had significantly greater efficacy in incidence of POV in postoperative 24 h than control (RR [95% CI] ¼ 0.45 [0.37, 0.55], I2 ¼ 26%) (Fig. 1). Subgroup analysis indicated the RR of dexamethasone 0.5 mg/kg group was the lowest compared subgroup dexamethasone 0.3 mg/kg and 0.3e0.5 mg/ kg (Fig. 1). However, the heterogeneity of subgroup of dosage 0.3e0.5 mg/kg dexamethasone existed. 3.3.2. Early incidence of POV Six studies5,18,32,36,39,42 investigated the early incidence of POV (during the postanesthesia care unit, PACU). The meta-analysis of the calculated data failed to show a difference between two groups (RR [95% CI] ¼ 0.69 [0.42, 1.13], I2 ¼ 62%) (Fig. 2). 3.3.3. Incidence of PON after postoperative 24 h Five studies17,28,30,31,41 reported the incidence of PON after postoperative 24 h. The meta-analysis indicated dexamethasone caused a reduction in the incidence of PON after postoperative 24 h (RR [95% CI] ¼ 0.37 [0.19, 0.70], I2 ¼ 47%) (Fig. 3). 3.3.4. Need for rescue antiemetic Six studies5,16,27,29,32,36 reported the need for rescue antiemetic. The combined analysis showed dexamethasone could decrease the use of rescue antiemetic compared with control (RR [95% CI] ¼ 0.56 [0.34, 0.91], I2 ¼ 57%) (Figure S2). 3.4. Dexamethasone with others versus placebo 3.4.1. Incidence of POV after postoperative 24 h Seven studies18,30,31,37e39,41 investigated the efficacy of dexamethasone combined with other drugs for the incidence of POV compared with placebo. Three38,39,41 compared the dexamethasone plus ondansetron with placebo, one18 evaluated the effect of dexamethasone in combination with ketamine, one37 evaluated the effectiveness of a granisetronedexamethasone combination, two30,31 evaluated the efficacy of dexamethasone combination with midazolam. Five studies18,30,37,38,41 reported the POV after postoperative 24 h. The combined results showed that dexamethasone with had a significantly greater efficacy in preventing POV after postoperative 24 h than placebo (RR [95% CI] ¼ 0.09 [0.04, 0.20], I2 ¼ 0%) (Fig. 4). 3.5. Adverse effects Eleven studies reported there were no adverse outcomes attributable to dexamethasone. Two studies5,37 reported there were no differences in the incidence of adverse events between dexamethasone and placebo group. One40 reported dexamethasone was associated with an increased risk of postoperative bleeding. The study28 by Subramaniam et al showed
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dexamethasone group had a higher incidence of facial flushing and headache than placebo. 3.6. Risk of bias in included studies Table S3 in Supplementary materials. show the risk of bias for each study separately. Fifteen of 20 studies5,16,17,27,28,31,33e37,39e41 reported on the randomization process. Ten studies5,16,28,30e34,37,40 had adequate allocation concealment. All of studies stated the blinding process for patients and personnel. Thirteen studies5,16,18,27,28,30,31,33,34,37e40 described the outcome assessor was adequately blinded to avoid detection bias. 3.7. Publication bias Publication bias was examined for POV in postoperative 24 h compared dexamethasone versus placebo. Visual inspection of funnel plot indicated no asymmetry and there was no evidence of potential publication bias (Figure S3). 4. Discussion This study suggests dexamethasone causes a significant reduction in the incidence of POV and PON after postoperative 24 h in children and reduces the use of antiemetic. Subgroup analysis indicates the RR of dexamethasone 0.5 mg/kg group was the lowest compared subgroup of dexamethasone 0.3 mg/kg and 0.3e0.5 mg/kg. However, there is no significant difference for the early PON compared dexamethasone with placebo. Besides, dexamethasone combined with other drugs also could significantly reduce the incidence of POV. Of the 20 studies included in this meta analysis, the doses of dexamethasone were various, range from 0.05 mg/kg to 1.0 mg/kg. And the maximum dose was also different among included studies. Besides, it also differed for the measure outcomes and the definition of POV. Some studies16,30e32,36,40 counted retching as vomiting event, while others29,37,38 recorded the episode of vomiting and retching respectively. These existed discrepancies of clinical methods might increase the heterogeneity of pool analysis and impact the result credibility. Several published studies43e46 indicated dexamethasone administration was an effective measure to reduce PONV incidence for laparoscopic cholecystectomy, gynecological surgery and thyroidectomy, and gastrointestinal. Results of these study were in line with our study. A meta-analysis47 investigated the safety and efficacy of dexamethasone combined with other antiemetics versus single antiemetics for the prevention of PONV after laparoscopic cholecystectomy. The results showed that dexamethasone combined with other antiemetics provided better prophylaxis than single antiemetics against PONV. Similarly, our study showed the pooled RR value of dexamethasone combined with others was lower than dexamethasone alone. In this study, few adverse effects about dexamethasone were reported. It remains uncertain for possible side effects of the perioperative use of dexamethasone. One included study showed there was a higher incidence of facial flushing and headache when 1.0 mg/kg dexamethasone was treated.28 Another study by Bellis JR et al48 systematically reviewed the relationship of the use of dexamethasone in pediatric tonsillectomy and the risk of posttonsillectomy haemorrhage in children. Their results showed dexamethasone did not significantly increase risk of posttonsillectomy haemorrhage in children based on current evidence. Besides, one Cochrane systematic review indicated that dexamethasone did not increase the risk of a postoperative wound infection, but may produce a mild increase in glucose levels.49
Please cite this article as: Liu J et al., Dexamethasone or combined with others for postoperative nausea and vomiting in children: A systematic review, Asian Journal of Surgery, https://doi.org/10.1016/j.asjsur.2019.11.012
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Table 2 Characteristics of included studies. Study
Country
ASA Age, yr PS
Wakamiya 201916
Japan
NR
D: 14.6 ± 2.2; C: 14.4 ± 1.7
D: 48; C: 50 scoliosis correction surgery
Vosdoganis Australia 199922 Subramaniam India 200123
ASA I-II ASA I-II
D: 5.0 ± 2.2; C: 5.7 ± 2.2 D: 7.6 ± 3.8; O: 6.9 ± 3.5 C: 7.11 ± 2.91
D: 22; C: 19 tonsillectomy
during induction of anesthesia NR
D: 45; O: 45 strabismus C: 45
after induction iv of anesthesia
Samarkandi Saudi 200424 Arabia 18 Iran Safavi 2012
ASA I-II ASA I-II
D: 7.17 ± 2.95; C: 7.28 ± 0.89 K: 8.7 ± 1.9; D: 8.6 ± 1.7 KþD:7.8 ± 2.2; C:7.9 ± 2.1 ASA GþD:6.6 ± 2.1; I OþD:7.3 ± 2.5; MþD:8.3 ± 3.9; C:6.6 ± 2.1
D: 29; C: 31 tonsillectomy
after induction iv of anesthesia iv before induction of anesthesia
Riad W 200925 Saudi Arabia
Riad W 200726 Saudi Arabia
Pappas 199827 USA Michal 201817 Czech Republic Canada McIntyre 28 2012 29 India Madan R 2005 Karaman 200930
Turkey
Kaan 200631
Turkey
Hisham 201633
Gombar 200732
ASA I-II United Arab ASA Emirates I
India
Elhakim 20035 Egypt de Orange 201234
Christoph 200835
Bhardwaj N 200436
ASA D: 6.0 ± 2.5; M: I 7.2 ± 2.4; MþD:8.3 ± 3.9; C: 6.7 ± 2.9 ASA D: 6.0 ± 2.5 I-II C: 5.8 ± 2.7 ASA D: 4.2 ± 1.32 I-II C: 4.1 ± 1.29 ASA D: 4.64 ± 1.5 I-II C: 4.54 ± 1.6 ASA D 0.25: 8 ± 4; D 0.5: I-II 8 ± 4; D 1.0: 6 ± 4; C: 8 ± 5 NR 5.88 ± 1.5
D: 7.6 ± 5.1 C: 9.3 ± 7.4 D: 6.03 ± 1.9; O: 6.4 ± 1.6; DþO: 6.25 ± 2; C: 6.39 ± 1.7
No. of patients
Surgery/Condition
K: 30; D: 30 tonsillectomy KþD: 30; C: 30
Aouad 200137 Lebanon
saline
NO
iv
D: 0.4 mg/kg saline (maximum of 8 mg) saline D: 1 mg/kg (maximum of 25 mg) O: 0.1 mg/kg (maximum of 4 mg)
NR
D: 25; M: 25 strabismus MþD: 25; C: 25
after induction iv of anesthesia
D: 63 C: 65 D: 35 C: 35 D: 87 C: 91 D 0.25: 42; D 0.5: 42; D 1: 41; C: 41 D 0.2: 50; D 0.7: 50; C: 50 D: 32 C: 30 D: 91; O: 86 DþO: 91; C: 81
after induction of anesthesia after induction of anesthesia after induction of anesthesia after tracheal intubation
G: 30; GþD: ASA G: 10.5 (4e12); I-II GþD: 10 (4e12); C: 30 C: 30 10 (3e12) ASA D: 5.2 ± 2.5 D: 55 I-II C: 5.1 ± 2.7 C: 55 D: 43 ASA D: 4.6 ± 2.5 OþD: 44 I-II OþD: 4.7 ± 2.4 C: 42 C: 5 ± 2.4
ASA D: 5.1 ± 2.2 I-II C: 4.6 ± 2.0
D: 0.15 mg/kg
after induction iv of anesthesia
adenotonsillectomy adenoidectomy dental surgery strabismus
adenotonsillectomy or tonsillectomy
D: 53 C: 53
NR
iv iv iv iv
iv
tonsillectomy
after induction iv of anesthesia iv dental rehabilitation NR under general anesthesia
middle ear surgery
after induction iv of anesthesia
tonsillectomy
after induction iv of anesthesia after induction iv of anesthesia
tonsillectomy
after induction iv of anesthesia
after general anesthesia
Control Adverse effects
iv
GþD: 25; strabismus OþD: 25 MþD: 25; C: 25
inguinal hernia, umbilical hernia, cryptorchidism, or phimosis surgery Switzerland NR D 0.05: 6 (2e13); D D 0.05: 53; tonsillectomy D 0.15: 54; 0.15: 5 (3e12); D 0.5: 6 (2e16); C: 6 D 0.5 : 52; C: 54 (3e11) India ASA O: 6.5 ± 2.8; OþD: O: 39; OþD: strabismus I-II 6.3 ± 3.1 C: 6.4 ± 3.2 31 C: 30 Brazil
Timing of Route of Intervention dose administration administration
iv
after induction iv of anesthesia
D: 0.3 mg/kg
saline
Headache, Facial flushing, Wound problems NO
K: 0.5 mg/kg; D: 0.5 mg/kg KþD: D 0.5 mg/kg þ K 0.5 mg/kg GþD: G 0.01 mg/ kg þ D 0.5 mg/kg OþD: O 0.05 mg/ kg þ D 0.5 mg/kg MþD: M 0.05 mg/ kg þ D 0.5 mg/kg D: 0.5 mg/kg; M: 0.05 mg/kg MþD: M 0.05 mg/ kg þ D 0.5 mg/kg D: 1 mg/kg (maximal of 25 mg) D: 0.15 mg/kg (maximum of 4 mg) D: 0.3 mg/kg (maximum of 8 mg) D: 0.25 mg/kg, 0.5 mg/ kg, 1 mg/kg
saline
NR
saline
NO
saline
NO
saline
NR
saline
NO
saline
NO
saline
NO
D: 0.2 mg/kg, 0.7 mg/ saline kg
NO
D: 0.5 mg/kg (maximum 16 mg) D: 0.2 mg/kg (maximum of 8 mg) O: 0.1 mg/kg (maximum of 4 mg) DþO: D 0.2 mg/kg þ O 0.1 mg/kg G: 0.04 mg/kg; GþD: G 0.04 mg/kg þ D 0.15 mg/kg D: 0.5 mg/kg (maximum of 8 mg) D: 0.15 mg/kg (maximum dose 4 mg); OþD: O 0.1 mg/ kgþD 0.15 mg/kg D: 0.05 mg/kg, 0.15 mg/kg, 0.5 mg/kg
saline
NO
saline
NR
saline
No differences
saline
No differences
saline
NR
saline
postoperative hemorrhage
saline
NO
saline
NO
O:0.15 mg/ kg(maximum dose 4 mg); OþD:O 0.15 mg/kg þ D 0.2 mg/kg D: 0.5 mg/kg (maximum of 8 mg)
Data are presented as mean SD except * mean (range); D: dexamethasone; O: ondansetron; G: granisetron; K: ketamine; M: midazolam; C: control; ASA: American Society of Anesthesiologists; PS: physical status; iv: intravenous; NR: not reported.
Please cite this article as: Liu J et al., Dexamethasone or combined with others for postoperative nausea and vomiting in children: A systematic review, Asian Journal of Surgery, https://doi.org/10.1016/j.asjsur.2019.11.012
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Fig. 1. Forest plot of different dosages for POV after postoperative 24 h compared dexamethasone versus placebo.
Fig. 2. Forrest plot of early incidence of POV compared dexamethasone versus placebo.
Fig. 3. Forest plot of PON after postoperative 24 h compared dexamethasone versus placebo.
Please cite this article as: Liu J et al., Dexamethasone or combined with others for postoperative nausea and vomiting in children: A systematic review, Asian Journal of Surgery, https://doi.org/10.1016/j.asjsur.2019.11.012
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Fig. 4. Forest plot of POV after postoperative 24 h compared dexamethasone with others versus placebo.
Therefore, it is suggested that future more well-design studies are needed to explore the potential side effects of the dexamethasone. The optimal dose of dexamethasone for prevention of PONV in pediatric surgery was still unclear. In our study, three included studies compared different doses of dexamethasone with placebo for PONV. One suggested dexamethasone 0.25 mg/kg was equally effective compared with larger doses (0.5 mg/kg or 1.0 mg/kg) for preventing PONV. However, Karaman et al thought 0.7 mg/kg dosage of dexamethasone was much a preferable choice depending of its effectiveness on decreasing postoperative morbidity rather than 0.2 mg/kg dosage. Another study40 indicated dexamethasone dose-dependently decreased the incidence of PONV. In our study, no difference was observed in the incidence of early vomiting during PACU between dexamethasone group and placebo group. That possible reason might be explained that dexamethasone has a prolonged biological half-life of 36e48 h and it start to work out later.50 Therefore, it is suggested the dexamethasone administration should be started before surgery as possible as early. Moreover, dexamethasone is a cost-effective in preventing PONV compared other antiemetic. It is reported the cost to benefit a child with dexamethasone was approximately 22 times less than that of ondansetron.28 The strengths of this review included the explicit application of eligibility criteria, the reporting of study quality, the standardized data extraction, and the rigorous analytical approach. However, there were several limitations. Firstly, our literature searches of the English databases were extensive, but non-English language articles were not included. Secondly, variability of the clinical methods and non-uniform outcomes measure, including the type of anesthesia technique, type of surgery, co-intervention drugs, time of administration dexamethasone, contributed to the notable heterogeneity. Moreover, the subgroup analysis by different dosage failed to reduce the heterogeneity. 5. Conclusions This systematic review indicates that dexamethasone could reduce the incidence of POV and PON in children. And multimodal approaches have shown more effectively to prevent the incidence of POV. Due to the existed heterogeneity, future high quality researches are needed to explore the effective dosage of dexamethasone and the potential adverse effects. Contributors Huijuan Li performed the search strategy and ran the search process. Jie Zhang and Xiashan Dong selected which studies to include. Xiue Shi and Jianjun Xue extracted related data. Jieting Liu wrote the manuscript. Kehu Yang reviewed the use of English. All authors read, provided feedback and approved the final manuscript.
Provenance and peer review Not commissioned, externally peer reviewed. Declaration of competing interest None. Appendix A. Supplementary data Supplementary data to this article can be found online at https://doi.org/10.1016/j.asjsur.2019.11.012. References 1. Cao X, White PF, Ma H. An update on the management of postoperative nausea and vomiting. J Anesth. 2017;31(4):617e626, 2017/08/01. 2. Dobbeleir M, De Coster J, Coucke W, Politis C. Postoperative nausea and vomiting after oral and maxillofacial surgery: a prospective study. Int J Oral Maxillofac Surg. 2018;47(6):721e725, 2018/06/01/. 3. Obrink E, Jildenstal P, Oddby E, Jakobsson JG. Post-operative nausea and vomiting: update on predicting the probability and ways to minimize its occurrence, with focus on ambulatory surgery. Int J Surg. Mar 2015;15: 100e106. 4. Phillips C, Brookes CD, Rich J, Arbon J, Turvey TA. Postoperative nausea and vomiting following orthognathic surgery. Int J Oral Maxillofac Surg. Jun 2015;44(6):745e751. 5. Elhakim M, Ali NM, Rashed I, Riad MK, Refat M. Dexamethasone reduces postoperative vomiting and pain after pediatric tonsillectomy. Can J Anaesth. Apr 2003;50(4):392e397. 6. Rose JB, Watcha MF. Postoperative nausea and vomiting in paediatric patients. Br J Anaesth. Jul 1999;83(1):104e117. 7. Williams AR, Conroy JM. The anesthetic management of the pediatric strabismus patient. J AAPOS : Off Publ Am Assoc Pediatr Ophthalmol Strabismus. Apr 1998;2(2):113e115. 8. Brettner F, Janitza S, Prull K, et al. Gender-specific differences in low-dose haloperidol response for prevention of postoperative nausea and vomiting: a register-based cohort study. PLoS One. 2016;11(1), e0146746. 9. Gayer S, Tutiven J. Anesthesia for pediatric ocular surgery. Ophthalmol Clin North Am. Jun 2006;19(2):269e278. 10. Patel RI, Hannallah RS. Anesthetic complications following pediatric ambulatory surgery: a 3-yr study. Anesthesiology. Dec 1988;69(6):1009e1012. 11. Benn J, Arnold G, Wei I, Riley C, Aleva F. Using quality indicators in anaesthesia: feeding back data to improve care. Br J Anaesth. Jul 2012;109(1):80e91. 12. Palmer GM, Pirakalathanan P, Skinner AV. A multi-centre multi-national survey of anaesthetists regarding the range of anaesthetic and surgical practices for paediatric scoliosis surgery. Anaesth Intensive Care. Nov 2010;38(6): 1077e1084. 13. Jakobsson J. Preoperative single-dose intravenous dexamethasone during ambulatory surgery: update around the benefit versus risk. Curr Opin Anaesthesiol. Dec 2010;23(6):682e686. 14. Shen YD, Chen CY, Wu CH, Cherng YG, Tam KW. Dexamethasone, ondansetron, and their combination and postoperative nausea and vomiting in children undergoing strabismus surgery: a meta-analysis of randomized controlled trials. Paediatr Anaesth. May 2014;24(5):490e498. 15. 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. Nov 2006;97(5):593e604. 16. Wakamiya R, Seki H, Ideno S, et al. Effects of prophylactic dexamethasone on postoperative nausea and vomiting in scoliosis correction surgery: a doubleblind, randomized, placebo-controlled clinical trial. Sci Rep. Feb 14 2019;9(1): 2119. 17. Frelich M, Divak J, Vodicka V, Masarova M, Jor O, Gal R. Dexamethasone
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reduces the incidence of postoperative nausea and vomiting in children undergoing endoscopic adenoidectomy under general anesthesia without increasing the risk of postoperative hemorrhage. Med Sci Monit : Int Med J Exp Clin Res. Nov 22 2018;24:8430e8438. Safavi M, Honarmand A, Habibabady MR, Baraty S, Aghadavoudi O. Assessing intravenous ketamine and intravenous dexamethasone separately and in combination for early oral intake, vomiting and postoperative pain relief in children following tonsillectomy. Med Arh. 2012;66(2):111e115. Ge L, Tian JH, Li YN, et al. Association between prospective registration and overall reporting and methodological quality of systematic reviews: a metaepidemiological study. J Clin Epidemiol. 2018;93. S0895435617300458. Pieper D, Buechter RB, Li L, Prediger B, Eikermann M. Systematic review found AMSTAR, but not R(evised)-AMSTAR, to have good measurement properties. J Clin Epidemiol. 2015;68(5):574e583. Tian J, Zhang J, Ge L, Yang K, Song F. The methodological and reporting quality of systematic reviews from China and the USA are similar. J Clin Epidemiol. 2017;85. S0895435616308162. Yao L, Sun R, Chen YL, et al. The quality of evidence in Chinese meta-analyses needs to be improved. J Clin Epidemiol. 2016;74:73e79. Huang D, Song XP, Cui Q, Tian J, Wang Q, Yang K. Is there an association between aircraft noise exposure and the incidence of hypertension? A metaanalysis of 16784 participants. Noise Health. 2015;17(75):93e97. Li X, Wei L, Shang W, et al. Trace and evaluation systems for health services quality in rural and remote areas: a systematic review. J Public Health. 2017;26(2):1e9. Pan B, Ge L, Xun YQ, et al. Exercise training modalities in patients with type 2 diabetes mellitus: a systematic review and network meta-analysis. Int J Behav Nutr Phys Act. 2018;15(1):72. Higgins JPT, Altman DG, Gøtzsche PC, et al. The Cochrane Collaboration's tool for assessing risk of bias in randomised trials. BMJ. 2011;343:d5928. Vosdoganis F, Baines DB. The effect of single dose intravenous dexamethasone in tonsillectomy in children. Anaesth Intensive Care. Oct 1999;27(5):489e492. Subramaniam B, Madan R, Sadhasivam S, et al. Dexamethasone is a costeffective alternative to ondansetron in preventing PONV after paediatric strabismus repair. Br J Anaesth. Jan 2001;86(1):84e89. Samarkandi AH, Shaikh MA, Ahmad RA, Alammar AY. Use of dexamethasone to reduce postoperative vomiting and pain after pediatric tonsillectomy procedures. Saudi Med J. Nov 2004;25(11):1636e1639. Riad W, Marouf H. Combination therapy in the prevention of PONV after strabismus surgery in children: granisetron, ondansetron, midazolam with dexamethasone. Middle East J Anesthesiol. Oct 2009;20(3):431e436. Riad W, Altaf R, Abdulla A, Oudan H. Effect of midazolam, dexamethasone and their combination on the prevention of nausea and vomiting following strabismus repair in children. Eur J Anaesthesiol. Aug 2007;24(8):697e701. Pappas AL, Sukhani R, Hotaling AJ, et al. The effect of preoperative dexamethasone on the immediate and delayed postoperative morbidity in children undergoing adenotonsillectomy. Anesth Analg. Jul 1998;87(1):57e61. McIntyre RE, Hardcastle C, Eng RL, et al. Effect of dexamethasone on postoperative morbidity after dental rehabilitation in children. Can J Anaesth. Jan 2012;59(1):34e40. Madan R, Bhatia A, Chakithandy S, et al. Prophylactic dexamethasone for postoperative nausea and vomiting in pediatric strabismus surgery: a dose ranging and safety evaluation study. Anesth Analg. Jun 2005;100(6): 1622e1626. Karaman M, Ilhan AE, Dereci G, Tek A. Determination of optimum dosage of
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intraoperative single dose dexamethasone in pediatric tonsillectomy and adenotonsillectomy. Int J Pediatr Otorhinolaryngol. Nov 2009;73(11): 1513e1515. Kaan MN, Odabasi O, Gezer E, Daldal A. The effect of preoperative dexamethasone on early oral intake, vomiting and pain after tonsillectomy. Int J Pediatr Otorhinolaryngol. Jan 2006;70(1):73e79. Gombar S, Kaur J, Kumar Gombar K, Dass A, Singh A. Superior anti-emetic efficacy of granisetron-dexamethasone combination in children undergoing middle ear surgery. Acta Anaesthesiol Scand. May 2007;51(5):621e624. El Batawi HY, Shorrab AA. Intra operative use of anti emetic drugs for children undergoing full dental rehabilitation under general anesthesia. A double blind randomized clinical trial. J Clin Pediatr Dent. 2016;40(3):235e240. de Orange FA, Marques J, Flores M, Borges PS. Dexamethasone versus ondansetron in combination with dexamethasone for the prophylaxis of postoperative vomiting in pediatric outpatients: a double-blind, randomized, placebo-controlled clinical trial. Paediatr Anaesth. Sep 2012;22(9):890e896. Czarnetzki C, Elia N, Lysakowski C, et al. Dexamethasone and risk of nausea and vomiting and postoperative bleeding after tonsillectomy in children: a randomized trial. Jama. Dec 10 2008;300(22):2621e2630. Bhardwaj N, Bala I, Kaur C, Chari P. Comparison of ondansetron with ondansetron plus dexamethasone for antiemetic prophylaxis in children undergoing strabismus surgery. J Pediatr Ophthalmol Strabismus. Mar-Apr 2004;41(2): 100e104. Aouad MT, Siddik SS, Rizk LB, Zaytoun GM, Baraka AS. The effect of dexamethasone on postoperative vomiting after tonsillectomy. Anesth Analg. Mar 2001;92(3):636e640. Tarantino I, Warschkow R, Beutner U, et al. Efficacy of a single preoperative dexamethasone dose to prevent nausea and vomiting after thyroidectomy (the tPONV study): a randomized, double-blind, placebo-controlled clinical trial. Ann Surg. Dec 2015;262(6):934e940. Wang B, He KH, Jiang MB, Liu C, Min S. Effect of prophylactic dexamethasone on nausea and vomiting after laparoscopic gynecological operation: metaanalysis. Middle East J Anesthesiol. Oct 2011;21(3):397e402. 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. Nov 2008;248(5):751e762. Dexamethasone versus standard treatment for postoperative nausea and vomiting in gastrointestinal surgery: randomised controlled trial (DREAMS Trial). Bmj. Apr 18 2017;357:j1455. Awad K, Ahmed H, Abushouk AI, et al. Dexamethasone combined with other antiemetics versus single antiemetics for prevention of postoperative nausea and vomiting after laparoscopic cholecystectomy: an updated systematic review and meta-analysis. Int J Surg. Dec 2016;36(Pt A):152e163. Bellis JR, Pirmohamed M, Nunn AJ, et al. Dexamethasone and haemorrhage risk in paediatric tonsillectomy: a systematic review and meta-analysis. Br J Anaesth. Jul 2014;113(1):23e42. Polderman JA, Farhang-Razi V, Van Dieren S, et al. Adverse side effects of dexamethasone in surgical patients. Cochrane Database Syst Rev. Aug 28 2018;8:Cd011940. Haynes R. Adrenocorticotropic hormone: adrenocortical steroids and their synthetic analogs-inhibitors of the synthesis and actions of adrenocortical hormones. In: Goodman Gilman A, Gilman LS, Rall TW, Murad F, eds. The Pharmacological Basis of Therapeutics. 8th ed. New York: Pergamon Press; 1990: 1447e1448.
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Review Article
Dexamethasone or combined with others for postoperative nausea and vomiting in children: A systematic review Jieting Liu a, b, c, d, e, Huijuan Li c, d, e, Jie Zhang c, Xiashan Dong c, Jianjun Xue c, e, g, Xiue Shi h, Kehu Yang a, c, d, e, f, h, * a
The First Clinical Medical College, Lanzhou University, Lanzhou, 730000, PR China Lanzhou University Second Hospital, Lanzhou, 730000, PR China Evidence-based Social Science Research Center, School of Public Health, Lanzhou University, Lanzhou, 730000, PR China d Evidence-based Medicine Center, School of Basic Medical Sciences, Lanzhou University, Lanzhou, 730000, PR China e Key Laboratory of Evidence Based Medicine and Knowledge Translation of Gansu Province, Lanzhou, 730000, PR China f Institute of Clinical Research and Evidence Based Medicine, Gansu Provincial Hospital, Lanzhou, 730000, PR China g Gansu Provincial Hospital of TCM, Lanzhou, 730000, PR China h Institute for Evidence Based Rehabilitation Medicine of Gansu Province, Lanzhou, 730000, PR China b c
a r t i c l e i n f o
a b s t r a c t
Article history: Received 4 July 2019 Accepted 21 November 2019 Available online xxx
Postoperative nausea and vomiting (PONV) is one of the most common and unpleasant postoperative complications in children. This study aims to evaluate the efficacy and safety of using dexamethasone alone or combined other drugs on the incidence of PONV in children. A systematic search of the literature was conducted from inception until March, 2019. Literature selection and data extraction were conducted by two independent reviewers. Statistical analysis was performed using the software package Review Manager Version 5.3.3. Twenty studies with total 2505 participants were included. The pooled analysis used a random-effect model showed that dexamethasone had significantly greater efficacy in incidence of POV and PON in postoperative 24 h than control. Subgroup analysis indicated the RR of dexamethasone 0.5 mg/kg group was the lowest compared subgroup dexamethasone 0.3 mg/kg and 0.3e0.5 mg/kg. There was no difference for early POV between dexamethasone and placebo groups. Dexamethasone combined with others also could significantly reduce the incidence of POV in postoperative 24 h. Few adverse effects were reported. This study indicates that dexamethasone is effective for preventing incidence of PONV in children. And multimodal approaches have shown more effectively to prevent the incidence of POV. © 2020 Asian Surgical Association and Taiwan Robotic Surgery Association. Publishing services by Elsevier B.V. This is an open access article under the CC BY-NC-ND license (http://creativecommons.org/ licenses/by-nc-nd/4.0/).
Keywords: Dexamethasone Postoperative nausea and vomiting Children
1. Introduction Postoperative nausea and vomiting (PONV) is one of the most common and unpleasant postoperative complications, which is a major concern in surgical patients.1 PONV affects about 20e40% of surgical patients, with certain high-risk patients experiencing rates of up to 80%.2e4 It has a high incidence in children, especially for tonsillectomy and strabismus surgery.5e7 PONV could lead to several adverse consequences, including dehydration, electrolyte
* Corresponding author. The First Clinical Medical College; Evidence-based Medicine Center, School of Basic Medical Sciences; 199 Donggang West Road, Lanzhou University, Lanzhou, Gansu Province, China. E-mail address: [email protected] (K. Yang).
imbalance, sub-conjunctival hemorrhage, the wound dehiscence.8,9 It has also been reported PONV is associated with delayed hospital discharge, unplanned hospital admission, and increased financial costs required for patient care.10,11 Several anti-emetic drugs have been described for the prophylactic control of PONV. Dexamethasone is common practice in surgery, as part of a multimodal pain and antiemetic strategy.12,13 Previous systematic reviews have showed that preoperative dexamethasone treatment reduces PONV in children after strabismus surgery and thyroidectomy.14,15 However, due to limited sample size and low-quality studies design, the conclusions remain to be confirmed further. In the last few years, some new studies that explored the efficacy of dexamethasone for PONV in children have become available.16,17 Besides, there are several studies explored the effect of
https://doi.org/10.1016/j.asjsur.2019.11.012 1015-9584/© 2020 Asian Surgical Association and Taiwan Robotic Surgery Association. Publishing services by Elsevier B.V. This is an open access article under the CC BY-NCND license (http://creativecommons.org/licenses/by-nc-nd/4.0/).
Please cite this article as: Liu J et al., Dexamethasone or combined with others for postoperative nausea and vomiting in children: A systematic review, Asian Journal of Surgery, https://doi.org/10.1016/j.asjsur.2019.11.012
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J. Liu et al. / Asian Journal of Surgery xxx (xxxx) xxx
dexamethasone combined with other drugs for PONV.14,18 Therefore, this systematic review aims to evaluate of the efficacy and safety of the use of dexamethasone or combined other drugs on the incidence of PONV in children.
2. Methods 2.1. Literature search This review follows the guidelines for Preferred Reporting Items for Systematic reviews and Meta-analyses (PRISMA).19e22 Guidance is also sought from the Cochrane handbook as well as some highquality articles from published journals to provide the framework for the statistical analysis.23e25 A systematic search of the literature was conducted from inception until March, 2019 using the PubMed, EMBASE, Web of science, and Cochrane library. No language, publication date or publication status restrictions were used. The search terms were used the following terminology: Dexamethasone, Ceroids, Corticosteroids, Dexamethas*, Pediatrics, Child*, Adolescent, Nausea, Vomiting. In addition, the references of all eligible studies were manually retrieved to ensure the comprehensiveness of the search. The detailed search strategies for PubMed were presented in Table S1 of Supplementary materials.
2.2. Inclusion criteria We included for all randomized controlled trials (RCTs) that studied the efficacy of dexamethasone alone or combined with other drugs compared with a placebo or no treatment for PONV in children. The detailed criteria following “PICOS” principle (P: Participants, I: Intervention, C: Control, O: Outcomes, S: Study designs) were showed in Table 1. And comments, reply, non-systematic review, non-English language articles, conference abstracts, and repeated publication were excluded.
2.4. Risk of bias assessment We assessed the study quality of each included trial according to the recommendations outlined in the Cochrane Handbook for Systematic Reviews of Interventions.26 We took into account the following items: allocation sequence generation, concealment of allocation, blinding of participants and investigators, incomplete outcome data, selective outcome reporting, and other sources of bias. The risk of bias was examined by two reviewers concurrently, and discrepancies were resolved by consensus. 2.5. Statistical analysis Statistical analysis was performed using the software package Review Manager Version 5.3.3 (Nordic Cochrane Centre, The Cochrane Collaboration, Copenhagen, Denmark) and STATA version 12 (Stata Corp LP, College Station, TX, United States). Pooled risk ratio (RR) with 95% confidence interval (CI) was utilized to analyze dichotomous data, while continuous data were analyzed as mean differences (MDs) with 95% CIs. Heterogeneity was evaluated using the chi-square test, for which P < 0.1 was considered statistically significant. The I2 value was used to quantify the impact of heterogeneity on each analysis. Given the level of heterogeneity observed, the random-effects model results are reported within the text and figures. Subgroup analysis was carried out according to different dosage of dexamethasone. Potential publication bias was explored by visual inspection of the funnel plot for asymmetry. 3. Results 3.1. Search results A total of 2313 records were identified by searching the selected databases (Figure S1). After excluding duplicate records and after preliminary screening, 37 full-text records were assessed for eligibility. Finally, 20 studies met the inclusion criteria. The exclusion reason for full texts were listed in Table S2 of Supplementary materials.
2.3. Literature selection and data extraction 3.2. Study characteristics The retrieved records were imported into the EndNote X7 software and the duplicate publications were excluded. Two reviewers (LHJ and DXS) independently read the titles and abstracts of all identified records to exclude those that were clearly not relevant. Then the full texts of the articles retained were reviewed to further determine their suitability. The excluded reasons for full texts were list in Table S2 of Supplementary materials. Differences opinions were resolved by consensus. The data were extracted by two reviewers (LHJ and DXS) independently using a pre-defined form. The following characteristics of the guidelines were collected: the first author, publication year, country, number of included participants, timing of administration, intervention, control, type of surgery, and outcomes and main conclusion. Any discrepancies were resolved by consensus.
Twenty studies5,16e18,27e42 with total 2505 participants were included in this meta-analysis. All of them were randomized controlled trials (RCTs). Of 20 RCTs, the year of published between 1998 and 2019. The sample sizes range from 41 to 349. The studies came from 14 different countries. Fourteen studies28,34,37,41 were from India. Three studies 2931were based in Saudi Arabia. Two studies35,36 were from Turkey, one from Australia,27 Iran,18 America,32 Canada,33 Czech Republic,17 Egypt,5 United Arab Emirates,38 Brazil,39 Lebanon,42 and Japan.16 The dosage of dexamethasone varied, range from 0.05 mg/kg to 1 mg/kg. Surgical procedures included tonsillectomy, adenotonsillectomy, strabismus, middle ear surgery, scoliosis correction surgery, dental surgery, and inguinal hernia, umbilical hernia, cryptorchidism, or phimosis surgery. Nine
Table 1 The inclusion criteria. Category
Inclusion criteria
Population Intervention Comparison Outcome
People <18 years of age, without country restriction Dexamethasone alone or combined with other drugs Placebo or no intervention Primary outcomes included the early incidence of postoperative of vomiting (POV), the incidence POV in postoperative 24 h, and postoperative of nausea (PON) in postoperative 24 h. Secondary outcomes included the need for rescue anti-emetics and adverse effects. Randomized controlled trials (RCTs)
Study design
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studies5,16,17,27,29,32,33,36,42 were two-armed, five28,35,37,39,41 were three-armed and six18,30,31,34,38,40 were four-armed. Eight studies18,28,30,31,37e39,41 compared dexamethasone combined with others with placebo. Three studies34,35,40 compared different dosage of dexamethasone with placebo. The baseline characteristics were balanced among the treatment groups in included studies. Table 2 lists the characteristics of these studies. 3.3. Dexamethasone versus placebo 3.3.1. Incidence of POV after postoperative 24 h Ten studies5,16e18,27,28,31,33,34,40 compared the incidence of POV after postoperative 24 h between the dexamethasone and control group. Of them, two studies34,40 contained three different dosage of dexamethasone groups. The pooled analysis used a random-effect model showed that dexamethasone had significantly greater efficacy in incidence of POV in postoperative 24 h than control (RR [95% CI] ¼ 0.45 [0.37, 0.55], I2 ¼ 26%) (Fig. 1). Subgroup analysis indicated the RR of dexamethasone 0.5 mg/kg group was the lowest compared subgroup dexamethasone 0.3 mg/kg and 0.3e0.5 mg/ kg (Fig. 1). However, the heterogeneity of subgroup of dosage 0.3e0.5 mg/kg dexamethasone existed. 3.3.2. Early incidence of POV Six studies5,18,32,36,39,42 investigated the early incidence of POV (during the postanesthesia care unit, PACU). The meta-analysis of the calculated data failed to show a difference between two groups (RR [95% CI] ¼ 0.69 [0.42, 1.13], I2 ¼ 62%) (Fig. 2). 3.3.3. Incidence of PON after postoperative 24 h Five studies17,28,30,31,41 reported the incidence of PON after postoperative 24 h. The meta-analysis indicated dexamethasone caused a reduction in the incidence of PON after postoperative 24 h (RR [95% CI] ¼ 0.37 [0.19, 0.70], I2 ¼ 47%) (Fig. 3). 3.3.4. Need for rescue antiemetic Six studies5,16,27,29,32,36 reported the need for rescue antiemetic. The combined analysis showed dexamethasone could decrease the use of rescue antiemetic compared with control (RR [95% CI] ¼ 0.56 [0.34, 0.91], I2 ¼ 57%) (Figure S2). 3.4. Dexamethasone with others versus placebo 3.4.1. Incidence of POV after postoperative 24 h Seven studies18,30,31,37e39,41 investigated the efficacy of dexamethasone combined with other drugs for the incidence of POV compared with placebo. Three38,39,41 compared the dexamethasone plus ondansetron with placebo, one18 evaluated the effect of dexamethasone in combination with ketamine, one37 evaluated the effectiveness of a granisetronedexamethasone combination, two30,31 evaluated the efficacy of dexamethasone combination with midazolam. Five studies18,30,37,38,41 reported the POV after postoperative 24 h. The combined results showed that dexamethasone with had a significantly greater efficacy in preventing POV after postoperative 24 h than placebo (RR [95% CI] ¼ 0.09 [0.04, 0.20], I2 ¼ 0%) (Fig. 4). 3.5. Adverse effects Eleven studies reported there were no adverse outcomes attributable to dexamethasone. Two studies5,37 reported there were no differences in the incidence of adverse events between dexamethasone and placebo group. One40 reported dexamethasone was associated with an increased risk of postoperative bleeding. The study28 by Subramaniam et al showed
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dexamethasone group had a higher incidence of facial flushing and headache than placebo. 3.6. Risk of bias in included studies Table S3 in Supplementary materials. show the risk of bias for each study separately. Fifteen of 20 studies5,16,17,27,28,31,33e37,39e41 reported on the randomization process. Ten studies5,16,28,30e34,37,40 had adequate allocation concealment. All of studies stated the blinding process for patients and personnel. Thirteen studies5,16,18,27,28,30,31,33,34,37e40 described the outcome assessor was adequately blinded to avoid detection bias. 3.7. Publication bias Publication bias was examined for POV in postoperative 24 h compared dexamethasone versus placebo. Visual inspection of funnel plot indicated no asymmetry and there was no evidence of potential publication bias (Figure S3). 4. Discussion This study suggests dexamethasone causes a significant reduction in the incidence of POV and PON after postoperative 24 h in children and reduces the use of antiemetic. Subgroup analysis indicates the RR of dexamethasone 0.5 mg/kg group was the lowest compared subgroup of dexamethasone 0.3 mg/kg and 0.3e0.5 mg/kg. However, there is no significant difference for the early PON compared dexamethasone with placebo. Besides, dexamethasone combined with other drugs also could significantly reduce the incidence of POV. Of the 20 studies included in this meta analysis, the doses of dexamethasone were various, range from 0.05 mg/kg to 1.0 mg/kg. And the maximum dose was also different among included studies. Besides, it also differed for the measure outcomes and the definition of POV. Some studies16,30e32,36,40 counted retching as vomiting event, while others29,37,38 recorded the episode of vomiting and retching respectively. These existed discrepancies of clinical methods might increase the heterogeneity of pool analysis and impact the result credibility. Several published studies43e46 indicated dexamethasone administration was an effective measure to reduce PONV incidence for laparoscopic cholecystectomy, gynecological surgery and thyroidectomy, and gastrointestinal. Results of these study were in line with our study. A meta-analysis47 investigated the safety and efficacy of dexamethasone combined with other antiemetics versus single antiemetics for the prevention of PONV after laparoscopic cholecystectomy. The results showed that dexamethasone combined with other antiemetics provided better prophylaxis than single antiemetics against PONV. Similarly, our study showed the pooled RR value of dexamethasone combined with others was lower than dexamethasone alone. In this study, few adverse effects about dexamethasone were reported. It remains uncertain for possible side effects of the perioperative use of dexamethasone. One included study showed there was a higher incidence of facial flushing and headache when 1.0 mg/kg dexamethasone was treated.28 Another study by Bellis JR et al48 systematically reviewed the relationship of the use of dexamethasone in pediatric tonsillectomy and the risk of posttonsillectomy haemorrhage in children. Their results showed dexamethasone did not significantly increase risk of posttonsillectomy haemorrhage in children based on current evidence. Besides, one Cochrane systematic review indicated that dexamethasone did not increase the risk of a postoperative wound infection, but may produce a mild increase in glucose levels.49
Please cite this article as: Liu J et al., Dexamethasone or combined with others for postoperative nausea and vomiting in children: A systematic review, Asian Journal of Surgery, https://doi.org/10.1016/j.asjsur.2019.11.012
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Table 2 Characteristics of included studies. Study
Country
ASA Age, yr PS
Wakamiya 201916
Japan
NR
D: 14.6 ± 2.2; C: 14.4 ± 1.7
D: 48; C: 50 scoliosis correction surgery
Vosdoganis Australia 199922 Subramaniam India 200123
ASA I-II ASA I-II
D: 5.0 ± 2.2; C: 5.7 ± 2.2 D: 7.6 ± 3.8; O: 6.9 ± 3.5 C: 7.11 ± 2.91
D: 22; C: 19 tonsillectomy
during induction of anesthesia NR
D: 45; O: 45 strabismus C: 45
after induction iv of anesthesia
Samarkandi Saudi 200424 Arabia 18 Iran Safavi 2012
ASA I-II ASA I-II
D: 7.17 ± 2.95; C: 7.28 ± 0.89 K: 8.7 ± 1.9; D: 8.6 ± 1.7 KþD:7.8 ± 2.2; C:7.9 ± 2.1 ASA GþD:6.6 ± 2.1; I OþD:7.3 ± 2.5; MþD:8.3 ± 3.9; C:6.6 ± 2.1
D: 29; C: 31 tonsillectomy
after induction iv of anesthesia iv before induction of anesthesia
Riad W 200925 Saudi Arabia
Riad W 200726 Saudi Arabia
Pappas 199827 USA Michal 201817 Czech Republic Canada McIntyre 28 2012 29 India Madan R 2005 Karaman 200930
Turkey
Kaan 200631
Turkey
Hisham 201633
Gombar 200732
ASA I-II United Arab ASA Emirates I
India
Elhakim 20035 Egypt de Orange 201234
Christoph 200835
Bhardwaj N 200436
ASA D: 6.0 ± 2.5; M: I 7.2 ± 2.4; MþD:8.3 ± 3.9; C: 6.7 ± 2.9 ASA D: 6.0 ± 2.5 I-II C: 5.8 ± 2.7 ASA D: 4.2 ± 1.32 I-II C: 4.1 ± 1.29 ASA D: 4.64 ± 1.5 I-II C: 4.54 ± 1.6 ASA D 0.25: 8 ± 4; D 0.5: I-II 8 ± 4; D 1.0: 6 ± 4; C: 8 ± 5 NR 5.88 ± 1.5
D: 7.6 ± 5.1 C: 9.3 ± 7.4 D: 6.03 ± 1.9; O: 6.4 ± 1.6; DþO: 6.25 ± 2; C: 6.39 ± 1.7
No. of patients
Surgery/Condition
K: 30; D: 30 tonsillectomy KþD: 30; C: 30
Aouad 200137 Lebanon
saline
NO
iv
D: 0.4 mg/kg saline (maximum of 8 mg) saline D: 1 mg/kg (maximum of 25 mg) O: 0.1 mg/kg (maximum of 4 mg)
NR
D: 25; M: 25 strabismus MþD: 25; C: 25
after induction iv of anesthesia
D: 63 C: 65 D: 35 C: 35 D: 87 C: 91 D 0.25: 42; D 0.5: 42; D 1: 41; C: 41 D 0.2: 50; D 0.7: 50; C: 50 D: 32 C: 30 D: 91; O: 86 DþO: 91; C: 81
after induction of anesthesia after induction of anesthesia after induction of anesthesia after tracheal intubation
G: 30; GþD: ASA G: 10.5 (4e12); I-II GþD: 10 (4e12); C: 30 C: 30 10 (3e12) ASA D: 5.2 ± 2.5 D: 55 I-II C: 5.1 ± 2.7 C: 55 D: 43 ASA D: 4.6 ± 2.5 OþD: 44 I-II OþD: 4.7 ± 2.4 C: 42 C: 5 ± 2.4
ASA D: 5.1 ± 2.2 I-II C: 4.6 ± 2.0
D: 0.15 mg/kg
after induction iv of anesthesia
adenotonsillectomy adenoidectomy dental surgery strabismus
adenotonsillectomy or tonsillectomy
D: 53 C: 53
NR
iv iv iv iv
iv
tonsillectomy
after induction iv of anesthesia iv dental rehabilitation NR under general anesthesia
middle ear surgery
after induction iv of anesthesia
tonsillectomy
after induction iv of anesthesia after induction iv of anesthesia
tonsillectomy
after induction iv of anesthesia
after general anesthesia
Control Adverse effects
iv
GþD: 25; strabismus OþD: 25 MþD: 25; C: 25
inguinal hernia, umbilical hernia, cryptorchidism, or phimosis surgery Switzerland NR D 0.05: 6 (2e13); D D 0.05: 53; tonsillectomy D 0.15: 54; 0.15: 5 (3e12); D 0.5: 6 (2e16); C: 6 D 0.5 : 52; C: 54 (3e11) India ASA O: 6.5 ± 2.8; OþD: O: 39; OþD: strabismus I-II 6.3 ± 3.1 C: 6.4 ± 3.2 31 C: 30 Brazil
Timing of Route of Intervention dose administration administration
iv
after induction iv of anesthesia
D: 0.3 mg/kg
saline
Headache, Facial flushing, Wound problems NO
K: 0.5 mg/kg; D: 0.5 mg/kg KþD: D 0.5 mg/kg þ K 0.5 mg/kg GþD: G 0.01 mg/ kg þ D 0.5 mg/kg OþD: O 0.05 mg/ kg þ D 0.5 mg/kg MþD: M 0.05 mg/ kg þ D 0.5 mg/kg D: 0.5 mg/kg; M: 0.05 mg/kg MþD: M 0.05 mg/ kg þ D 0.5 mg/kg D: 1 mg/kg (maximal of 25 mg) D: 0.15 mg/kg (maximum of 4 mg) D: 0.3 mg/kg (maximum of 8 mg) D: 0.25 mg/kg, 0.5 mg/ kg, 1 mg/kg
saline
NR
saline
NO
saline
NO
saline
NR
saline
NO
saline
NO
saline
NO
D: 0.2 mg/kg, 0.7 mg/ saline kg
NO
D: 0.5 mg/kg (maximum 16 mg) D: 0.2 mg/kg (maximum of 8 mg) O: 0.1 mg/kg (maximum of 4 mg) DþO: D 0.2 mg/kg þ O 0.1 mg/kg G: 0.04 mg/kg; GþD: G 0.04 mg/kg þ D 0.15 mg/kg D: 0.5 mg/kg (maximum of 8 mg) D: 0.15 mg/kg (maximum dose 4 mg); OþD: O 0.1 mg/ kgþD 0.15 mg/kg D: 0.05 mg/kg, 0.15 mg/kg, 0.5 mg/kg
saline
NO
saline
NR
saline
No differences
saline
No differences
saline
NR
saline
postoperative hemorrhage
saline
NO
saline
NO
O:0.15 mg/ kg(maximum dose 4 mg); OþD:O 0.15 mg/kg þ D 0.2 mg/kg D: 0.5 mg/kg (maximum of 8 mg)
Data are presented as mean SD except * mean (range); D: dexamethasone; O: ondansetron; G: granisetron; K: ketamine; M: midazolam; C: control; ASA: American Society of Anesthesiologists; PS: physical status; iv: intravenous; NR: not reported.
Please cite this article as: Liu J et al., Dexamethasone or combined with others for postoperative nausea and vomiting in children: A systematic review, Asian Journal of Surgery, https://doi.org/10.1016/j.asjsur.2019.11.012
J. Liu et al. / Asian Journal of Surgery xxx (xxxx) xxx
Fig. 1. Forest plot of different dosages for POV after postoperative 24 h compared dexamethasone versus placebo.
Fig. 2. Forrest plot of early incidence of POV compared dexamethasone versus placebo.
Fig. 3. Forest plot of PON after postoperative 24 h compared dexamethasone versus placebo.
Please cite this article as: Liu J et al., Dexamethasone or combined with others for postoperative nausea and vomiting in children: A systematic review, Asian Journal of Surgery, https://doi.org/10.1016/j.asjsur.2019.11.012
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Fig. 4. Forest plot of POV after postoperative 24 h compared dexamethasone with others versus placebo.
Therefore, it is suggested that future more well-design studies are needed to explore the potential side effects of the dexamethasone. The optimal dose of dexamethasone for prevention of PONV in pediatric surgery was still unclear. In our study, three included studies compared different doses of dexamethasone with placebo for PONV. One suggested dexamethasone 0.25 mg/kg was equally effective compared with larger doses (0.5 mg/kg or 1.0 mg/kg) for preventing PONV. However, Karaman et al thought 0.7 mg/kg dosage of dexamethasone was much a preferable choice depending of its effectiveness on decreasing postoperative morbidity rather than 0.2 mg/kg dosage. Another study40 indicated dexamethasone dose-dependently decreased the incidence of PONV. In our study, no difference was observed in the incidence of early vomiting during PACU between dexamethasone group and placebo group. That possible reason might be explained that dexamethasone has a prolonged biological half-life of 36e48 h and it start to work out later.50 Therefore, it is suggested the dexamethasone administration should be started before surgery as possible as early. Moreover, dexamethasone is a cost-effective in preventing PONV compared other antiemetic. It is reported the cost to benefit a child with dexamethasone was approximately 22 times less than that of ondansetron.28 The strengths of this review included the explicit application of eligibility criteria, the reporting of study quality, the standardized data extraction, and the rigorous analytical approach. However, there were several limitations. Firstly, our literature searches of the English databases were extensive, but non-English language articles were not included. Secondly, variability of the clinical methods and non-uniform outcomes measure, including the type of anesthesia technique, type of surgery, co-intervention drugs, time of administration dexamethasone, contributed to the notable heterogeneity. Moreover, the subgroup analysis by different dosage failed to reduce the heterogeneity. 5. Conclusions This systematic review indicates that dexamethasone could reduce the incidence of POV and PON in children. And multimodal approaches have shown more effectively to prevent the incidence of POV. Due to the existed heterogeneity, future high quality researches are needed to explore the effective dosage of dexamethasone and the potential adverse effects. Contributors Huijuan Li performed the search strategy and ran the search process. Jie Zhang and Xiashan Dong selected which studies to include. Xiue Shi and Jianjun Xue extracted related data. Jieting Liu wrote the manuscript. Kehu Yang reviewed the use of English. All authors read, provided feedback and approved the final manuscript.
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Please cite this article as: Liu J et al., Dexamethasone or combined with others for postoperative nausea and vomiting in children: A systematic review, Asian Journal of Surgery, https://doi.org/10.1016/j.asjsur.2019.11.012