Postoperative nausea and vomiting is one of the most important causes of patients’ discomfort [
Among the drugs that are being used for PONV prophylaxis, 5HT3 antagonists, such as ondansetron, granisetron, palonosetron, and ramosetron, and dexamethasone are the two most commonly used nowadays. However, no drug has been found to provide complete PONV prophylaxis. A number of studies have compared ondansetron with dexamethasone for PONV prophylaxis after laparoscopic surgeries. These studies are not unanimous in reporting their results and there is no consensus on which drug is better in PONV prophylaxis. However, in most of the studies, the number of patients that received study drug is relatively small in number ranging from 20 to 100 and that may be one of the reasons why statistical significance could not be found. Hence, we planned this meta-analysis of randomized control trials where ondansetron has been compared with dexamethasone for PONV prophylaxis in patients undergoing laparoscopic surgeries.
A protocol of this meta-analysis has not been registered. We followed PRISMA-P 2015 [
Randomized controlled trails published in English language comparing dexamethasone with ondansetron for PONV prophylaxis in patients undergoing laparoscopic surgeries under general anaesthesia were eligible to be included in this meta-analysis. Retrospective studies, prospective observational studies, case series, and reports were not included in this meta-analysis. Multiple arm trials, where dexamethasone and ondansetron have been included in two arms, have also been included in this meta-analysis.
Full text of the RCTs included in this meta-analysis was downloaded from the electronic sources. We did not contact authors for unpublished data. We did not also search for unpublished or ongoing trials.
Two authors (Souvik Maitra and Anirban Som) independently searched PubMed and CENTRAL (the Cochrane Collaboration’s Register of Clinical Trials) for eligible controlled trials using the following search words: “dexamethasone laparoscopy,” “ondansetron laparoscopy,” “ondansetron dexamethasone laparoscopy,” “ondansetron PONV laparoscopy,” and “dexamethasone PONV laparoscopy” until January 10, 2015. The details of search strategy in PubMed have been mentioned in supplementary digital content. References from the primary search result were also manually searched for potentially eligible trials.
We included published prospective randomized controlled trial where dexamethasone has been compared with ondansetron for PONV prophylaxis in patients undergoing laparoscopic surgeries. Two independent authors (Souvik Maitra and Anirban Som) selected the eligible trials. Any disagreement between two authors was solved by discussing with a third author (Dalim K. Baidya).
Two authors independently (Dalim K. Baidya, Sulagna Bhattacharjee) extracted all data from the eligible trials. The following data were collected from each of the studies: name of the first author, year of publication, total number patients studied, type of surgery, anaesthesia details (induction agent, use of TIVA, use of nitrous oxide, and use of opioid analgesic in postoperative period), dose and time of administration of study drug, postoperative outcome (when and how assessed), use of rescue antiemetics if any, and any reported complications. Initially, all data were tabulated in Microsoft Excel
The quality of eligible trials was assessed using the “risk of bias” tool within Review Manager, version 5.2.3 software (Review Manager [RevMan] Version 5.2. Copenhagen: The Nordic Cochrane Centre, The Cochrane Collaboration, 2012) by two authors working independently (Souvik Maitra and Sulagna Bhattacharjee). Random sequence generation, allocation concealment, blinding, incomplete data, and selective reporting were assessed; based on the method of the trials, each was graded “yes,” “no,” or “unclear,” which reflected a high risk of bias, low risk of bias, and uncertain bias, respectively.
The primary outcome of the meta-analysis was incidence of PONV in first 24 h of surgery. The secondary outcomes were incidence of PONV in first 4–6 h after surgery, incidence of nausea at first 4–6 h and 24 h after surgery, use of antiemetics, and complications.
Statistical analysis was performed by Review Manager, version 5.2.3 software (Review Manager [RevMan] Version 5.2. Copenhagen: The Nordic Cochrane Centre, The Cochrane Collaboration, 2012).
If the values were reported as median and an interquartile range or total range of values, the median itself was used to estimate mean for samples >25. The standard deviation was estimated from the median and the low and high end of the range for samples smaller than 15, as range/4 for samples from 15 to 70, and as range/6 for samples more than 70. If only an interquartile range was available, standard deviation was estimated as interquartile range/1.35 [
We calculated the following: (1) the odds ratio (OR) for each dichotomous outcome at individual study level; (2) the pooled OR using the Mantel-Haenszel method; (3) mean difference for each continuous outcome at individual study level; and (4) pooled mean difference using inverse variance method. All statistical variables were calculated with 95% confidence interval (95% CI). The
Initial database searching revealed 476 articles and after removing duplicate articles 126 unique articles were found. Finally eligible articles were searched from title and abstract. Eight randomized control trials fulfilled our eligibility criteria and seven of them have been included in this systematic review and meta-analysis [
Characteristics of individual studies.
Study | Participants | Intervention | Duration of surgery | Intraabdominal pressure | Control | Rescue antiemetic | Complications | Outcome | Source of bias |
---|---|---|---|---|---|---|---|---|---|
Alghanem et al. 2010 [ |
ASA 1 and ASA 2 patients aged 18–70 years scheduled for elective laparoscopic cholecystectomy |
|
44.5 |
10 to 16 mmHg |
|
Metoclopramide 10 mg rescue dose, in patients with intractable nausea or lasting for at least 15 min, or at patients request anytime, or with vomiting | No significant complications | Episodes of PONV, nausea and vomiting at |
|
|
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D’souza et al. 2011 [ |
Women aged 20–60 years with ASA grade I/II scheduled for gynecologic laparoscopic surgery |
|
Actual value not reported, no difference in surgical time | 10 to 14 mmHg |
|
Nausea/vomiting assessed with 4-point scale, retching considered as vomiting, rescue dose 10 mg metoclopramide intravenous | Not reported | Episodes of nausea and vomiting at 0–3 hours, |
Use of nitrous oxide, no mention about intraoperative opioid use |
|
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Erhan et al. 2008 [ |
80 ASA I or ASA II patients (61 women and 19 men), aged 21–75 years |
|
72.0 |
12 mmHg |
|
PONV recorded by nursing staff, both nausea and vomiting assessed, rescue antiemetic 10 mg metoclopramide intravenous | No significant side-effects | Incidence of nausea and vomiting was recorded |
|
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Gautam et al. 2008 [ |
150 ASA I-II patients, aged between 23 and 65 years, undergoing |
|
79.77 |
Below 15 mmHg |
|
PONV assessed by 3-point scale, 10 mg metoclopramide intravenous given when if 2 score points were reached or on patients demand | No side-effects reported | Incidence of nausea and vomiting till 24 h after surgery | |
|
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Mendes et al. 2009 [ |
77 patients |
|
122.5 |
Not mentioned |
|
Blinded anesthesiologist, administered 50 mg in presence of nausea or vomiting | No side effects reported | Incidence of nausea vomiting up to 24 h after surgery | Use of intraoperative morphine |
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Gupta et al. 2006 [ |
100 adult patients undergoing laparoscopic cholecystectomy |
|
20–60 (48) min dexa group versus 20–55 (46) min in ondansetron group | 12 mmHg |
|
Ondansetron 4 mg intravenously irrespective of the group if patients develop nausea or vomiting, administered by house staff | No postoperative complication reported | Incidence of nausea vomiting up to 48 h after surgery | |
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Yuksek et al. 2003 [ |
ASA PS I or II patients, aged |
|
50.3 (14–98) min in dexa group versus 62.1 (23–90) min in ondansetron group | 12–18 min |
|
Nausea vomiting assessed by 3-point ordinal scale, rescue 10 mg metoclopramide intravenous by blinded investigator | No complication was reported | Incidence of PONV |
PRISMA flow diagram to show study selection procedure.
Risk of biases in the individual studies.
We have separately analyzed incidence of nausea at 4–6 postoperative hours and again within 24 hours. Incidence of postoperative nausea is significantly lower at 4–6 h when dexamethasone was used instead of ondansetron (
Forest plot showing odds ratio of incidence of (a) postoperative nausea at 4–6 h and (b) at 24 h at individual study level and pooled analysis level.
Total PONV was also analyzed at 4–6 postoperative hours and 24 postoperative hours. Incidence of PONV was similar 4–6 hours (
Forest plot showing incidence of (a) PONV at 4–6 h and (b) at 24 h at individual study level and pooled analysis.
We have assessed rescue antiemetic use in the first 24 h after surgery. Use of rescue antiemetic is similar between two groups (
None of the studies reported any significant complications attributed to either dexamethasone or ondansetron. Alghanem et al. [
Principal finding of our meta-analysis is that dexamethasone is associated with a less postoperative nausea in first 4–6 hours after laparoscopic surgeries. Postoperative vomiting and nausea at 24 hours are similar with either drug. Need for rescue antiemetic is similar with both drugs. Most important strength of our analysis is that we have not found any significant amount of heterogeneity in any analysis.
Postoperative nausea and vomiting is a common compilation after laparoscopic surgeries and may be even more distressing than postoperative pain. PONV may even delay discharge of the patients [
Individual RCTs have found that dexamethasone and ondansetron are equally effective in PONV prophylaxis after laparoscopic surgeries. However, small sample size was the most important limitation of the RCTs that justifies importance of a meta-analysis. Interestingly we have found that dexamethasone decreases incidence of early PONV after laparoscopic surgeries and none of the previous studies has reported similar findings. Alghanem et al. [
These findings have not been reflected in our analysis because we believe that PONV after laparoscopic surgeries is caused by many factors such as abdominal insufflation; those may not be fully controlled by any single prophylactic drug.
Use of single dose dexamethasone is free from significant side effects including delayed wound healing [
Though we have not found any significant heterogeneity, different studies used different dose regimen of dexamethasone and ondansetron. However, dose ranges used in those studies are already known to be clinically effective. As PONV is multifactorial and hence anaesthetic technique may also affect incidence of PONV, possibility of biases remains there also. Numbers of included studies in this meta-analysis are small; hence, a metaregression considering TIVA, nitrous oxide, and postoperative opioid as covariate was not feasible. Surgical factors are also responsible for PONV and as included studies recruited patients from laparoscopic cholecystectomy and gynecologic laparoscopy, possibility of biases remains here also. In all studies, ondansetron is used before induction of anaesthesia; however, ondansetron is more effective when used near the end of surgery [
Dexamethasone is superior to ondansetron in preventing postoperative nausea after 4–6 h of laparoscopic surgeries. Both the drugs are of equal efficacy in preventing postoperative vomiting up to 24 h after surgery. However, results should be interpreted with caution due to clinical heterogeneity in the included studies.
(“dexamethasone” [MeSH Terms] OR “dexamethasone” [All Fields]) AND (“laparoscopy” [MeSH Terms] OR “laparoscopy” [All Fields]), (“ondansetron” [MeSH Terms] OR “ondansetron” [All Fields]) AND (“laparoscopy” [MeSH Terms] OR “laparoscopy” [All Fields]), (“ondansetron” [MeSH Terms] OR “ondansetron” [All Fields]) AND (“dexamethasone” [MeSH Terms] OR “dexamethasone” [All Fields]) AND (“laparoscopy” [MeSH Terms] OR “laparoscopy” [All Fields]), (“ondansetron” [MeSH Terms] OR “ondansetron” [All Fields]) AND (“postoperative nausea and vomiting” [MeSH Terms] OR (“postoperative” [All Fields] AND “nausea” [All Fields] AND “vomiting” [All Fields]) OR “postoperative nausea and vomiting” [All Fields] OR “ponv” [All Fields]) AND (“laparoscopy” [MeSH Terms] OR “laparoscopy” [All Fields]), (“dexamethasone” [MeSH Terms] OR “dexamethasone” [All Fields]) AND (“postoperative nausea and vomiting” [MeSH Terms] OR (“postoperative” [All Fields] AND “nausea” [All Fields] AND “vomiting” [All Fields]) OR “postoperative nausea and vomiting” [All Fields] OR “ponv” [All Fields]) AND (“laparoscopy” [MeSH Terms] OR “laparoscopy” [All Fields]).
The authors declare that they have no competing interests.