Skip Navigation LinksHome > September 2011 - Volume 115 - Issue 3 > Perioperative Single Dose Systemic Dexamethasone for Postope...
Anesthesiology:
doi: 10.1097/ALN.0b013e31822a24c2
Pain Medicine

Perioperative Single Dose Systemic Dexamethasone for Postoperative Pain: A Meta-analysis of Randomized Controlled Trials

De Oliveira, Gildàsio S. Jr M.D.*; Almeida, Marcela D. M.D.; Benzon, Honorio T. M.D.; McCarthy, Robert J. Pharm.D.§

Free Access
Continued Medical Education
Article Outline
Collapse Box

Author Information

Collapse Box

Abstract

Background: Dexamethasone is frequently administered in the perioperative period to reduce postoperative nausea and vomiting. In contrast, the analgesic effects of dexamethasone are not well defined. The authors performed a meta-analysis to evaluate the dose-dependent analgesic effects of perioperative dexamethasone.
Methods: We followed the PRISMA statement guidelines. A wide search was performed to identify randomized controlled trials that evaluated the effects of a single dose systemic dexamethasone on postoperative pain and opioid consumption. Meta-analysis was performed using a random-effect model. Effects of dexamethasone dose were evaluated by pooling studies into three dosage groups: low (less than 0.1 mg/kg), intermediate (0.11–0.2 mg/kg) and high (≥0.21 mg/kg).
Results: Twenty-four randomized clinical trials with 2,751 subjects were included. The mean (95% CI) combined effects favored dexamethasone over placebo for pain at rest (≤4 h, −0.32 [0.47 to −0.18], 24 h, −0.49 [−0.67 to −0.31]) and with movement (≤ 4 h, −0.64 [−0.86 to −0.41], 24 h, −0.47 [−0.71 to −0.24]). Opioid consumption was decreased to a similar extent with moderate −0.82 (−1.30 to −0.42) and high −0.85 (−1.24 to −0.46) dexamethasone, but not decreased with low-dose dexamethasone −0.18 (−0.39–0.03). No increase in analgesic effectiveness or reduction in opioid use could be demonstrated between the high- and intermediate-dose dexamethasone. Preoperative administration of dexamethasone appears to produce a more consistent analgesic effect compared with intraoperative administration.
Conclusion: Dexamethasone at doses more than 0.1 mg/kg is an effective adjunct in multimodal strategies to reduce postoperative pain and opioid consumption after surgery. The preoperative administration of the drug produces less variation of effects on pain outcomes.
Back to Top | Article Outline

What We Already Know about This Topic

* Dexamethasone is often used to prevent postoperative nausea and vomiting, but its effects on pain are less well studied
Back to Top | Article Outline

What This Article Tells Us That Is New

* In a meta-analysis of approximately 2,500 patients, dexamethasone, >0.1 mg/kg, reduced postoperative pain and opioid consumption
ACUTE postoperative pain is an undesirable outcome that can delay functional recovery for patients undergoing surgical procedures. Multimodal analgesic approaches have been used as an important strategy to mitigate postoperative pain.1 The effectiveness of adjunct agents, including ketamine,2 gabapentin,3 paracetamol, and nonsteroidal antiinflammatory drugs,4 have been examined in systematic reviews that demonstrate their benefits in reducing postoperative pain and/or opioid consumption. These agents became useful multimodal analgesic strategies.5 Dexamethasone is a corticosteroid commonly used perioperatively to reduce postoperative nausea and vomiting6 and may have a beneficial role in postoperative analgesia. However, in a systematic review of dexamethasone after laparoscopic cholecystectomy, the postoperative analgesic effect of dexamethasone, examined as a secondary outcome was found to be inconclusive.7 Therefore, the effect of dexamethasone on postoperative pain as well as the optimal dose to reduce pain has not been clearly defined. Currently, dexamethasone is not recommended as a component of a multimodal drug strategy to decrease postsurgical pain.
The objective of this quantitative systematic review was to assess the efficacy and dose dependency of single-dose perioperative dexamethasone on postsurgical pain outcomes. We also evaluated the dose-dependent side effects of single dose dexamethasone in the perioperative period.
Back to Top | Article Outline

Materials and Methods

This quantitative systematic review was conducted following the guidelines of the PRISMA statement.8
Back to Top | Article Outline
Systematic Search
Published reports of randomized trials evaluating the effects of dexamethasone on surgical postoperative pain were searched using the National Library of Medicine's PubMed database, the Cochrane Database of Systematic Reviews, and Google Scholar inclusive to September 1, 2010. Free text and MeSH terms “dexamethasone,” “pain,” “postoperative,” “preoperative,” “analgesia,” and “opioid” were used individually and in various combinations. No language restriction was used. The search was limited to randomized controlled clinical trials in subjects older than 18 yr. An attempt to identify additional studies not found by the primary search methods was made by reviewing the reference lists from identified studies. No search was performed for unpublished studies. This initial search yielded 211 randomized clinical trials.
Back to Top | Article Outline
Selection of Included Studies
The study's inclusion and exclusion criteria were determined before the systematic search. Two authors (GDO and MDA) independently evaluated the abstract and results of the 211 articles obtained by the initial search. Articles that were clearly not relevant based on our inclusion and exclusion criteria were excluded at this phase. Disagreements on inclusion of the articles were resolved by discussion among the evaluators. If an agreement could not be reached, the dispute was resolved with the help of a third investigator (HTB).
Back to Top | Article Outline
Inclusion and Exclusion Criteria
We included randomized controlled trials of a single perioperative intravenous dexamethasone administration with an inactive (placebo or “no treatment”) control group. Excluded were trials reporting analgesia after emergency medicine, dental, and nonsurgical pain. Trials evaluating more than one dose of perioperative dexamethasone were also excluded to maximize clinical homogeneity. Studies containing a concurrent use of an alternative multimodal analgesia regimen were excluded if a direct comparison of dexamethasone and placebo could not be established. Included studies had to report at least pain scores or opioid consumption on postoperative pain outcomes. No minimum sample size was required for inclusion in the meta-analysis.
Back to Top | Article Outline
Validity Scoring
Two authors (GSD and MDA) independently read the included reports and assessed their methodologic validity using a modified Jadad five-point quality scale.9 The scale evaluates the study for the following: randomization, double-blind evaluation, concealment of study group to evaluator, valid randomization method, and completeness of data at follow-up. Discrepancies in rating of the trials were resolved by discussion among the evaluators. If an agreement could not be reached, the dispute was resolved with the help of a third investigator (HTB). Because only randomized trials were included in the analysis, the minimum possible score of an included trial was 1 and the maximum was 5. Trials were not excluded or weighted in the analysis based on quality assessment scores.
Back to Top | Article Outline
Data Extraction
Two authors (GDO and MDA) independently evaluated the full manuscripts of all included trials and performed data extraction using a data collection form specifically developed for this review.
Discrepancies were resolved by discussion between the two investigators (GDO and MDA). If an agreement could not be reached between the two investigators, the decision was made by a third investigator (HTB). Data extracted from trials included dexamethasone dose and time of administration, sample size, number of subjects in treatment groups, follow-up period, type of surgery, early pain scores (≤4 h) at rest and at movement, late pain scores (24 h) at rest and at movement, cumulative opioid consumption, time to opioid administration (minutes), length of hospital stay (hours), and adverse events. Postoperative opioid consumption was converted to the equivalent dose of intravenous morphine.10 Visual analog scale or numeric rating scale of pain were converted to a 0–10 numeric rating scale.
Data were initially extracted from tables. For data not available in tables, attempts to contact authors were made; if the authors did not respond or did not have current contact information, the data were abstracted from available figures. Dichotomous data on the presence or absence of adverse effects was extracted and converted to incidence while continuous data were recorded using mean and SD. Data presented only as median and range were converted to means and SD using previously described methodology.11 When required, the SD for pain scores was estimated using the most extreme values. The most conservative value was used when the same outcome was reported more than one time for a determined period. Dexamethasone dose was converted to units in mg/kg using the mean weight reported for the dexamethasone groups. When no information about group weight was available, 70 kg was used.
To facilitate a quantitative analysis and to examine dose dependency of the outcomes, comparisons were stratified by dose into three groups: low-dose (≤0.10 mg/kg), intermediate-dose (0.11–0.20 mg/kg), and high-dose (≥0.21 mg/kg) dexamethasone. The dosage ranges were derived from clinical guidelines for postoperative nausea and vomiting that favor low dose compared with intermediated dose dexamethasone for antiemetic prophylaxis.6 The high-dose group represents doses greater than those routinely used for antiemetic prophylaxis.
Back to Top | Article Outline
Definition of Relevant Outcome Data
Primary Outcomes.
Early acute postoperative pain scores (visual analog scale or numeric rating scale) at rest and at movement (0–4 h postoperatively); late acute postoperative pain scores (visual analog scale or numeric rating scale) at rest and at movement (24 h postoperatively); and cumulative opioid consumption (up to 24 h) in the postoperative period.
Back to Top | Article Outline
Secondary Outcomes.
The time to first analgesic administration (minutes); time to hospital discharge (hours); and incidence and severity (visual analog scale or numeric rating scale) scores of chronic pain. In addition, adverse events including postoperative infection (wound, urinary tract, and pneumonia), hyperglycemic events, delayed healing, and pruritus were examined.
Back to Top | Article Outline
Meta-analyses
The standardized mean differences with 95% CI were determined and reported for continuous data. For dichotomous data (adverse effects), the Peto odds ratio (to account for the potential of zero counts in the cells for low-frequency outcomes) and 95% CI are reported. A significant effect compared with placebo required that the 95% CI for continuous data did not include 0 and for dichotomous data, the CI did not include 1.0. We calculated number needed to harm, based on the absolute risk reduction, with 95% CI as an estimate of a harmful effect. We used the lower 95% CI estimate of the number needed to harm to describe the largest increase in adverse events that could be excluded by our analysis. Because of the different surgical procedures, we used a random effect model in an attempt to generalize our findings to studies not included in our meta-analysis.12 Publication bias was evaluated by examining for asymmetric funnel plots using the Egger regression test.13 A one-sided P < 0.05 was considered an indication of an asymmetric funnel plot. A file drawer analysis described by Rosenthal14 was performed in the case of an asymmetric funnel plot. The test estimates the lowest number of additional studies that if they would become available would reduce the combined effect to nonsignificance assuming the average z-value of the combined P values of these missing studies would be 0.14 Sensitivity analysis was also performed to assess the effect of the elimination of a single trial on the outcome of the analysis.
Heterogeneity of the included studies was considered to be present if the I2 statistic was greater than 30%. Further analysis was planned a priori to explore relevant heterogeneity. Subgroup analysis was performed to investigate the effect of time of dexamethasone administration (preoperative vs. intraoperative) on the pain outcomes. A Q statistic was used to compare the effects between subgroups. The proportion of the total variance explained by the covariates (R2) was calculated by dividing random effects pooled estimates of variance (τ squared) within studies by total variance (total τ squared). The value obtained was then subtracted from 1. When values fall outside the range of 0–100%, they were set to the closest value (0% or 100%).
Comparisons between the different doses of dexamethasone and were made using a Z test with Bonferroni correction for multiple comparisons. Analysis was performed using Comprehensive Meta-analysis software version 2 (Biostat, Englewood, NJ).
Back to Top | Article Outline

Results

Fig. 1
Fig. 1
Image Tools
Table 1
Table 1
Image Tools
Of the 211 initially evaluated abstracts, 38 studies initially met the inclusion criteria (fig. 1). Fourteen studies were subsequently excluded: 12 either had no acute pain outcomes, data could not be extracted, or authors could not be reached1526; one trial used multiple doses27; and one trial evaluated oral dexamethasone.28 The characteristics of included studies are listed in table 1. The evaluated trials included data from 2,751 subjects and were published between 1997 and 2010.2952 The median number of patients in the included studies receiving dexamethasone was 40. The median modified Jadad scale score was 4. The trials tested a single dose of dexamethasone given either preoperatively or intraoperatively in a large variety of surgical procedures. All 24 studies reported on opioid consumption and/or pain scores. Six studies reported pain scores for both rest and activity.30,31,38,39,43,45
Back to Top | Article Outline
Early (0–4 h) Pain at Rest
Fig. 2
Fig. 2
Image Tools
Fig. 3
Fig. 3
Image Tools
The overall effect of dexamethasone on early pain at rest compared with placebo favored dexamethasone with a mean difference (95% CI) of −0.32 (−0.46 to −0.18) (fig. 2). The funnel plot did not demonstrate asymmetry, indicating that there was not substantial publication bias (P = 0.43) (fig. 3).
The aggregate effect of the six studies evaluating low-dose dexamethasone on early pain at rest2934 did not achieve statistical significance at −0.33 (−0.70 to 0.04) of dexamethasone compared with placebo (fig. 2). All the studies assessed dexamethasone given intraoperatively. Post hoc sensitivity analysis demonstrated that removal of the study of Thangaswamy et al.30 would change the analysis to result in a significant effect of −0.42 (−0.81 to −0.03) for low-dose dexamethasone compared with placebo.
The effect of the combined 11 studies examining the effect of intermediate-dose dexamethasone on early pain at rest2931,3542 suggests a decrease in early pain of −0.33 (−0.52 to −0.13) compared with placebo. There was no difference in the effect of time of drug administration on early pain and 38% of the total variance in the effect was explained by the time of drug administration. The heterogeneity for studies evaluating the preoperative administration was low (I2 = 0) but it was high for studies examining the intraoperative administration of the drug (I2 = 77).
Five studies evaluated the effect of high-dose dexamethasone on early postoperative pain at rest.31,39,4244 One study44 provided two comparisons that were included in the analysis. There was a beneficial effect of dexamethasone on early pain of −0.29 (−0.57 to −0.02). Dexamethasone was administered intraoperatively in all of these studies. No difference in effectiveness was found among the dexamethasone groups on early pain at rest.
Back to Top | Article Outline
Early (0–4 h) Pain at Movement
Fig. 4
Fig. 4
Image Tools
Fig. 5
Fig. 5
Image Tools
The overall effect of dexamethasone on early pain at movement compared with placebo favored dexamethasone with a mean difference (95% CI) of −0.64 (−0.86 to −0.41) (fig. 4) The funnel demonstrated some asymmetry (P = 0.04) with one of the seven studies outside the 95% CI, indicating some heterogeneity favoring dexamethasone; however, the low number of studies limits the potential for evaluating substantial publication bias (fig. 5).
Two studies evaluated the effect of low-dose dexamethasone on early pain at movement,30,31 showing a reduction when compared with placebo, −0.43(−0.84 to −0.03). Three studies assessed the effect of moderate-dose dexamethasone on early pain at movement,30,31,38 showing a reduction when compared with placebo, −0.65 (−0.96 to −0.35), and two studies evaluating high dose dexamethasone on early pain at movement31,39 also demonstrated a decrease in pain when compared with placebo, −1.09 (−1.77 to −0.42). There was no difference between the effects of different doses of dexamethasone on early pain at movement.
Back to Top | Article Outline
Late (24 h) Pain at Rest
Fig. 6
Fig. 6
Image Tools
Fig. 7
Fig. 7
Image Tools
The overall effect of dexamethasone on late pain at rest compared with placebo favored dexamethasone with a mean difference (95% CI) of −0.49 (−0.67 to −0.31) (fig. 6). The funnel demonstrated moderate asymmetry (P = 0.01) with 5 of the 25 studies outside the 95% CI with 240,41 favoring placebo and 331,35,42 favoring dexamethasone (fig. 7).
The effects of dexamethasone (compared with placebo) on late pain at rest by dosing groups is presented in figure 6. Five studies examined the effects of low-dose dexamethasone on late pain at rest.29,30,31,33,45 One study45 provided two comparisons and both were included in the analysis. A positive effect on late pain at rest of −0.47 (−0.68 to −0.25) was observed. There was no evidence of asymmetry in the funnel plot (P = 0.15).
Twelve studies evaluated the effect of intermediate-dose dexamethasone on late pain at rest.30,31,3538,40,41,4548 One study48 provided two comparisons and both were included in the analysis. There was a decrease in late pain at rest of −0.41 (−0.80 to −0.03) compared with placebo. There was no evidence of asymmetry in the funnel plot (P = 0.09). There was a greater effect when dexamethasone was given preoperatively, −0.77 (−0.95–0.09) compared with intraoperative administration, −0.007 (−0.12–0.11) (P < 0.001).
The six studies examining the effect of high-dose dexamethasone on late pain at rest 31,39,42,43,45,49 demonstrated a decrease in pain of −1.0 (−1.77 to −0.26) compared with placebo. There was no evidence of asymmetry on the funnel plot (P = 0.14). All studies assessed dexamethasone given intraoperatively. There was no difference in the effect on late pain when the high-dose dexamethasone was compared with the moderate- (P = 0.13) or the low-dose (P = 0.14) groups.
Back to Top | Article Outline
Late Pain at Movement
Fig. 8
Fig. 8
Image Tools
Fig. 9
Fig. 9
Image Tools
The overall effect of dexamethasone on late pain at movement compared with placebo favored dexamethasone with a mean difference (95% CI) of −0.47 (−0.71 to −0.24) (fig. 8). The funnel demonstrated asymmetry (P = 0.003) with one study43 favoring dexamethasone outside the 95% CI (fig. 9).
Three studies examined the effect of low-dose dexamethasone.30,31,45 One of the studies45 provided data for two comparisons and both were included in the analysis. Low-dose dexamethasone demonstrated a reduction of −0.39 (−0.66 to −0.12) in late pain at movement. There was no evidence of asymmetry on the funnel plot (P = 0.43).
Four studies examining the effect of moderate-dose dexamethasone30,31,38,45 also showed a reduction in pain of −0.52 (−1.02, −0.03). However, the analysis was limited by asymmetry (P = 0.05). Rosenthal analysis predicted that 14 missing studies would be required to change the analysis. There was no difference in the influence of time of drug administration on the dexamethasone effects (P = 0.45), with 18% of the total accounted variance due to time of administration. There was high heterogeneity in the effect when the drug was administered intraoperatively (I2 = 89) and low heterogeneity when the drug was administered preoperatively (I2 = 0).
Four studies evaluated the effect of high-dose dexamethasone on late pain at movement,31,39,43,45 demonstrating a reduction in pain of −3.16 (−4.95 to −1.38). The analysis was potentially affected by asymmetry of the sample (P = 0.01), indicating a publication bias for positive studies. Rosenthal analysis suggested that 104 missing studies would be needed to increase the P value above 0.05. Post hoc sensitivity analysis demonstrated that removal of the Kardash et al.43 study would result in a change in the effect of the high dose dexamethasone group on late pain to −0.84 (−1.12 to −0.56) when compared with placebo. With the Kardash et al.43 study included high-dose dexamethasone showed improvement in late pain at movement compared with the low (P = 0.003) or intermediate (P = 0.004) dose; whereas with the Kardash et al. study removed high-dose dexamethasone showed improvement in late pain at movement compared with the low (P = 0.01) but not intermediate (P = 0.26) dose.
Back to Top | Article Outline
Postoperative Opioid Cconsumption
Fig. 10
Fig. 10
Image Tools
Fig. 11
Fig. 11
Image Tools
The overall effect of dexamethasone on postoperative opioid consumption compared with placebo favored dexamethasone with a mean difference (95% CI) of −0.41 (−0.58 to −0.24) (fig. 10). The funnel plot did not demonstrate asymmetry indicating that there was not substantial publication bias (P = 0.35) (fig. 11).
Four studies evaluated the effect of low-dose dexamethasone on postoperative opioid consumption.30,31,45,50 One study provided data for two comparisons, and both were included in the analysis.45 No difference in opioid consumption compared with placebo was found at −0.17 (−0.38 to 0.03). All of the studies evaluated dexamethasone administered during the intraoperative period.
Nine studies examined the effect of moderate dose dexamethasone on postoperative opioid consumption demonstrating an opioid-sparing effect of −0.82 (−1.22 to −0.42) compared with placebo.30,31,35,36,38,40,41,45,51 Moderate-dose dexamethasone also decreased opioid consumption compared with low dose (P = 0.003). When given in the preoperative period, the mean effect of dexamethasone on opioid consumption was −0.9 (−1.15 to −0.72) compared with −0.48 (−1.04 to −0.07) when given intraoperatively (P = 0.1), suggesting an advantage for preoperative administration. In addition, 46% of the between-studies variation in effect was due to the time of drug administration.
Five studies assessed the effects of high-dose dexamethasone on postoperative opioid consumption.31,39,43,44,45 One study51 provided data for two comparisons, and both were included in the analysis. There was a reduction in postoperative opioid consumption of −0.84 (−1.24 to −0.45) compared with placebo. All studies included in the analysis evaluated dexamethasone administered intraoperatively. High- dose dexamethasone reduced opioid consumption compared with low dose (P = 0.002), but there was no difference in the opioid-sparing effect when comparing moderate-dose and high-dose dexamethasone (P = 0.94).
Back to Top | Article Outline
Chronic Pain (3 Months or Longer)
None of the included studies reported on chronic pain.
Back to Top | Article Outline
Time to First Analgesic Administration (Minutes)
Four studies evaluated the effects of low-dose dexamethasone on time to analgesic administration.30,31,45,50 One study45 provided data for two comparisons, and both were included in the analysis. There was a prolongation of the time to analgesic requirement when the low dexamethasone group was compared with placebo at 0.70 (0.01–1.39). There was no evidence of an asymmetric funnel plot (P = 0.07). The studies demonstrated high heterogeneity (I2 = 89) but the between-studies variability could not be explained by the time of drug administration.
Three studies evaluated the effect of intermediate-dose dexamethasone on time to analgesic requirement,30,31,45 showing no effect on the time to analgesic requirement: 1.09 (−0.2 to 2.41). There was no evidence of asymmetric funnel plots (P = 0.21). The analysis was limited by high heterogeneity that could not be explained by time of administration of dexamethasone (I2 = 92). Only two studies evaluated the effect of high-dose dexamethasone on time to analgesic requirement, showing no delay on the time to analgesic requirement: 0.72 (−0.70 to 2.14).31,45 The analysis was limited by the low number of studies and high heterogeneity (I2 = 92). Both studies evaluated dexamethasone given during the intraoperative period.
Back to Top | Article Outline
Time to Hospital Discharge (Hours)
Five studies examined the effect of low-dose dexamethasone on time to hospital discharge compared with placebo.30,32,34,45,50 One study45 provided data for two comparisons, and both were included in the analysis. The combined data showed a decrease in time to hospital discharge: −0.47 (−0.72 to −0.2). The analysis was limited by the presence of an asymmetric funnel plot (P = 0.04), with Rosenthal analysis suggesting 30 missing studies would be needed to change the results.
Six studies assessed the effect of moderate-dose dexamethasone compared with placebo on time to hospital discharge.30,35,36,40,45,47 There was a reduction in time to discharge, −0.47 (−0.91 to −0.04), and no evidence of an asymmetric funnel plot (P = 0.40). Heterogeneity was high (I2 = 89), with 16% of the total variance attributable to the time of drug administration. Only one study45 that evaluated the effect of high-dose dexamethasone on the time to hospital discharge demonstrated a 5.5-h reduction when compared with placebo (P < 0.001).
Back to Top | Article Outline
Safety Analysis
Among the studies evaluating low dose dexamethasone, two did not comment on adverse side effects.29,32 Three studies reported no difference in adverse side effects,33,45,50 two specifically reported no difference in postoperative wound infection,30,34 and one study specifically reported no cases with delayed wound healing.30 One study reported no difference in changes of blood glucose between the dexamethasone and placebo group.30
Among studies evaluating moderate doses of dexamethasone, two did not report on side effects,37,51 two reported no differences in adverse side effects,41,45 eight specifically reported no cases of postoperative wound infection,30,35,36,40,4648,52 and one reported the same incidence of wound infection in the dexamethasone and placebo groups,38 resulting in a 0.2% (0.05% to 1%) incidence of postoperative infection for both the dexamethasone and placebo groups. These numbers resulted in an overall risk difference (95% CI) of 0% (−1.2% to 1.2%) between the moderate dose dexamethasone group and saline. The lower estimate of the 95% CI of the number needed to harm is 83, therefore indicating that we can exclude one additional case of wound infection in fewer than 83 patients. Two studies reported no difference in change of blood glucose30,36 and four studies specifically reported no differences in wound healing.
Among studies evaluating high-dose dexamethasone, one study did not comment on side effects,49 two reported no cases of serious side effects,39,45 one specifically reported no cases of wound infection or delayed wound healing,43 and one trial reported a single case of wound infection in the placebo group and no case in the dexamethasone groups44These numbers resulted in an overall risk difference (95% CI) of 0.3% (−2.5% to 3.1%). The lower estimate of the number needed to harm is 32, indicating that we can rule out one additional case of wound infection in fewer than 32 patients. Three studies31,43,45 showed no decrease in the odds ratio (95% CI) for pruritus: 0.72 (0.2 to 2.1) compared with placebo.
Back to Top | Article Outline

Discussion

Several important findings emerged from our meta-analysis. First, intermediate-dose dexamethasone (0.11–0.2 mg/kg) had opioid-sparing effects. It also reduced early and late pain both at rest and at movement. Heterogeneity was partially explained by the time of drug administration (preoperative vs. intraoperative). High-dose dexamethasone (more than 0.2 mg/kg) had opioid-sparing effects and also decreased pain scores. We were unable to detect a difference in opioid use for the low-dose dexamethasone (less than 0.1 mg/kg) when given intraoperatively despite a reduction in late pain at rest and at movement. There is evidence that a single perioperative systemic dexamethasone dose can be used as part of a multimodal pain strategy to reduce postoperative pain.
Our findings have important clinical implications because lower dose dexamethasone is commonly given intraoperatively at the time of anesthesia induction to reduce postoperative nausea and vomiting.6 By giving intermediate doses of dexamethasone (0.11–0.2 mg/kg), beneficial effects on postoperative pain and a reduction in opioid consumption in addition to decreased nausea and vomiting can be achieved.7 The decreased variability in analgesic effectiveness when moderate-dose dexamethasone was administered preoperatively favors preoperative rather than intraoperative administration of the drug. This finding is consistent with the time to peak effect of dexamethasone (45 min to 1 h). A potential limitation to the preoperative administration of dexamethasone is that it can frequently (50–70%) produce extreme perineal pain when given rapidly in low volumes.53 This effect can be avoided if the dexamethasone dose is diluted in 50 ml saline solution and infused over 10 min.54
In a comparison, the high-dose dexamethasone group reduced late pain at movement compared with the intermediate dose, but did not show a significant advantage in opioid-sparing effects, early pain at rest and at movement, and late pain at rest. Dexamethasone was administered intraoperatively for all of the studies evaluating the high-dose group, which limited our ability to investigate the influence of the time of drug administration on the outcome measures. In regard to early pain at rest, the three dexamethasone groups had similar point estimate reductions, but we were unable to demonstrate a statistically significant effect for the low dose group.
Our review provided evidence that a single dose of perioperative dexamethasone did not increase dose-limiting complications such as wound infection nor does it appear to delay wound healing. This conclusion is strongest for the moderate doses of dexamethasone because there are greater numbers of patients studied at this dosing level. Our study corroborates the safety assessment regarding postoperative wound infection and healing in a systematic review evaluating a single dose of a different corticosteroid (methylprednisolone).55 Because we included several procedures and not only contaminated surgeries, our findings cannot be generalized to patients at high risk of developing postoperative wound infection. Blood glucose alterations were specifically mentioned in only two studies, limiting any safety assessment on this important side effect.
Time to hospital discharge, an important outcome due to its economic implications and affected by the presence of postoperative pain,56 showed a similar positive effect in both low-dose and intermediate-dose groups. The analysis, however, was limited by the presence of publication bias in the low dexamethasone group, and by high heterogeneity in the moderate-dose group. It is conceivable that further reduction in postoperative pain could affect discharge time, although we were unable to demonstrate this in our current analysis.
Our meta-analysis had several limitations. In an attempt to generalize our findings to different surgical procedures, we included different types of surgeries that may have affected the heterogeneity in some of our analyses. Varying methods of postoperative pain management across the studies were another potential source of heterogeneity. We could not demonstrate a decrease in opioid-related side effects such as pruritus because of the low number of studies by dosing group reporting on these side effects. We also did not examine the effect of dexamethasone on postoperative nausea and vomiting. We believe that this analysis would be biased by a large number of studies that evaluated postoperative nausea and vomiting but not postoperative pain and that were, therefore, excluded from our analysis.
Our quantitative review raises important questions that need to be addressed in future studies. First, the effect of low and high dose dexamethasone given preoperatively on postoperative pain needs further investigation. Second, side effects such as wound infection and healing with high-dose dexamethasone, especially in open surgical procedures, need additional evaluation. Third, because acute pain can contribute to the development of chronic pain,57 studies assessing the effects of dexamethasone on chronic postoperative pain are also warranted. The data originated in the current study should be confirmed by large dose-ranging randomized clinical trials.
In summary, low-dose dexamethasone when given intraoperatively does not have opioid sparing effects after surgery. High-dose dexamethasone (more than 0.2 mg/kg) when given intraoperatively has opioid-sparing effects and decreased postoperative pain; however, it does not seem to be advantageous when compared with intermediate (0.11 to 0.2 mg/kg) doses. Intermediate dose dexamethasone (0.11 to 0.2 mg/kg) is a safe and effective multimodal pain strategy after surgical procedures. The preoperative administration of the drug provides a greater effect on postoperative pain.
Back to Top | Article Outline

References

1. White PF: The changing role of non-opioid analgesic techniques in the management of postoperative pain. Anesth Analg 2005; 101:S5–22

2. Bell RF, Dahl JB, Moore RA, Kalso E: Perioperative ketamine for acute postoperative pain. Cochrane Database Syst Rev 2006 ;(1):CD004603

3. Ho KY, Gan TJ, Habib AS: Gabapentin and postoperative pain: A systematic review of randomized controlled trials. Pain 2006; 126:91–101

4. Ong CK, Seymour RA, Lirk P, Merry AF: Combining paracetamol (acetaminophen) with nonsteroidal antiinflammatory drugs: A qualitative systematic review of analgesic efficacy for acute postoperative pain. Anesth Analg 2010; 110:1170–9

5. White PF: Multimodal analgesia: Its role in preventing postoperative pain. Curr Opin Investig Drugs 2008; 9:76–82

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

7. 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; 248:751–62

8. Liberati A, Altman DG, Tetzlaff J, Mulrow C, Gøtzsche PC, Ioannidis JP, Clarke M, Devereaux PJ, Kleijnen J, Moher D: The PRISMA statement for reporting systematic reviews and meta-analyses of studies that evaluate health care interventions: Explanation and elaboration. J Clin Epidemiol 2009; 62:e1–34

9. Jadad AR, Moore RA, Carroll D, Jenkinson C, Reynolds DJ, Gavaghan DJ, McQuay HJ: Assessing the quality of reports of randomized clinical trials: Is blinding necessary? Control Clin Trials 1996; 17:1–12

10. Macintyre PE, Ready LB: Pharmacology of opioids, Acute Pain Management: A Practical Guide. 2nd edition. Philadelphia, WB Saunders, 2001, pp 15–49

11. 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

12. DerSimonian R, Laird N: Meta-analysis in clinical trials. Control Clin Trials 1986; 7:177–88

13. Egger M, Davey Smith G, Schneider M, Minder C: Bias in meta-analysis detected by a simple, graphical test. BMJ 1997; 315:629–34

14. Rosenthal R: The file drawer problem and tolerance for null results. Psychol Bull 1979; 86: 638–41

15. McKenzie R, Tantisira B, Karambelkar DJ, Riley TJ, Abdelhady H: Comparison of ondansetron with ondansetron plus dexamethasone in the prevention of postoperative nausea and vomiting. Anesth Analg 1994; 79:961–4

16. Liu YH, Li MJ, Wang PC, Ho ST, Chang CF, Ho CM, Wang JJ: Use of dexamethasone on the prophylaxis of nausea and vomiting after tympanomastoid surgery. Laryngoscope 2001; 111:1271–4

17. Fujii Y, Nakayama M: Reduction of postoperative nausea and vomiting and analgesic requirement with dexamethasone in women undergoing general anesthesia for mastectomy. Breast J 2007; 13:564–7

18. Fujii Y, Nakayama M: Dexamethasone for reduction of nausea, vomiting and analgesic use after gynecological laparoscopic surgery. Int J Gynaecol Obstet 2008; 100:27–30

19. Fujii Y, Itakura M: Reduction of postoperative nausea, vomiting, and analgesic requirement with dexamethasone for patients undergoing laparoscopic cholecystectomy. Surg Endosc 2010; 24:692–6

20. Fujii Y, Nakayama M: Dexamethasone for the reduction of postoperative nausea and vomiting and analgesic requirements after middle ear surgery in adult Japanese patients. Methods Find Exp Clin Pharmacol 2009; 31:337–40

21. Fujii Y, Nakayama M: Efficacy of dexamethasone for reducing postoperative nausea and vomiting and analgesic requirements after thyroidectomy. Otolaryngol Head Neck Surg 2007; 136:274–7

22. Zargar-Shoshtari K, Sammour T, Kahokehr A, Connolly AB, Hill AG: Randomized clinical trial of the effect of glucocorticoids on peritoneal inflammation and postoperative recovery after colectomy. Br J Surg 2009; 96:1253–61

23. López-Olaondo L, Carrascosa F, Pueyo FJ, Monedero P, Busto N, Sáez A: Combination of ondansetron and dexamethasone in the prophylaxis of postoperative nausea and vomiting. Br J Anaesth 1996; 76:835–40

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

25. Movafegh A, Soroush AR, Navi A, Sadeghi M, Esfehani F, Akbarian-Tefaghi N: The effect of intravenous administration of dexamethasone on postoperative pain, nausea, and vomiting after intrathecal injection of meperidine. Anesth Analg 2007; 104:987–9

26. Bergeron SG, Kardash KJ, Huk OL, Zukor DJ, Antoniou J: Perioperative dexamethasone does not affect functional outcome in total hip arthroplasty. Clin Orthop Relat Res 2009; 467:1463–7

27. Lachance M, Lacroix Y, Audet N, Savard P, Thuot F: The use of dexamethasone to reduce pain after tonsillectomy in adults: A double-blind prospective randomized trial. Laryngoscope 2008; 118:232–6

28. Mattila K, Kontinen VK, Kalso E, Hynynen MJ: Dexamethasone decreases oxycodone consumption following osteotomy of the first metatarsal bone: A randomized controlled trial in day surgery. Acta Anaesthesiol Scand 2010; 54:268–76

29. Al-Qudah M, Rashdan Y: Role of dexamethasone in reducing pain after endoscopic sinus surgery in adults: A double-blind prospective randomized trial. Ann Otol Rhinol Laryngol 2010; 119:266–9

30. Thangaswamy CR, Rewari V, Trikha A, Dehran M, Chandralekha: Dexamethasone before total laparoscopic hysterectomy: A randomized controlled dose-response study. J Anesth 2010; 24:24–30

31. Jokela RM, Ahonen JV, Tallgren MK, Marjakangas PC, Korttila KT: The effective analgesic dose of dexamethasone after laparoscopic hysterectomy. Anesth Analg 2009; 109:607–15

32. Wu JI, Lu SF, Chia YY, Yang LC, Fong WP, Tan PH: Sevoflurane with or without antiemetic prophylaxis of dexamethasone in spontaneously breathing patients undergoing outpatient anorectal surgery. J Clin Anesth 2009; 21:469–73

33. Wang JJ, Ho ST, Uen YH, Lin MT, Chen KT, Huang JC, Tzeng JI: Small-dose dexamethasone reduces nausea and vomiting after laparoscopic cholecystectomy: A comparison of tropisetron with saline. Anesth Analg 2002; 95:229–32

34. Coloma M, Duffy LL, White PF, Kendall Tongier W, Huber PJ Jr: Dexamethasone facilitates discharge after outpatient anorectal surgery. Anesth Analg 2001; 92:85–8

35. Sánchez-Rodríguez PE, Fuentes-Orozco C, González-Ojeda A: Effect of dexamethasone on postoperative symptoms in patients undergoing elective laparoscopic cholecystectomy: Randomized clinical trial. World J Surg 2010; 34:895–900

36. Worni M, Schudel HH, Seifert E, Inglin R, Hagemann M, Vorburger SA, Candinas D: Randomized controlled trial on single dose steroid before thyroidectomy for benign disease to improve postoperative nausea, pain, and vocal function. Ann Surg 2008; 248:1060–6

37. McKean S, Kochilas X, Kelleher R, Dockery M: Use of intravenous steroids at induction of anaesthesia for adult tonsillectomy to reduce post-operative nausea and vomiting and pain: A double-blind randomized controlled trial. Clin Otolaryngol 2006; 31:36–40

38. Bisgaard T, Klarskov B, Kehlet H, Rosenberg J: Preoperative dexamethasone improves surgical outcome after laparoscopic cholecystectomy: A randomized double-blind placebo-controlled trial. Ann Surg 2003; 238:651–60

39. Hval K, Thagaard KS, Sem TK, Schlichting E, Ellen S, Raeder J, Johan R: The prolonged postoperative analgesic effect when dexamethasone is added to a nonsteroidal antiinflammatory drug (rofecoxib) before breast surgery. Anesth Analg 2007; 105:481–6

40. Bianchin A, De Luca A, Caminiti A: Postoperative vomiting reduction after laparoscopic cholecystectomy with single dose of dexamethasone. Minerva Anestesiol 2007; 73:343–6

41. Chen MS, Hong CL, Chung HS, Tan PP, Tsai CC, Su HH, Wong CH: Dexamethasone effectively reduces postoperative nausea and vomiting in a general surgical adult patient population. Chang Gung Med J 2006; 29:175–81

42. McKenzie R, Riley TJ, Tantisira B, Hamilton DL: Effect of propofol for induction and ondansetron with or without dexamethasone for the prevention of nausea and vomiting after major gynecologic surgery. J Clin Anesth 1997; 9:15–20

43. Kardash KJ, Sarrazin F, Tessler MJ, Velly AM: Single-dose dexamethasone reduces dynamic pain after total hip arthroplasty. Anesth Analg 2008; 106:1253–7

44. Aminmansour B, Khalili HA, Ahmadi J, Nourian M: Effect of high-dose intravenous dexamethasone on postlumbar discectomy pain. Spine 2006; 31:2415–7

45. Elhakim M, Nafie M, Mahmoud K, Atef A: Dexamethasone 8 mg in combination with ondansetron 4 mg appears to be the optimal dose for the prevention of nausea and vomiting after laparoscopic cholecystectomy. Can J Anaesth 2002; 49:922–6

46. Fukami Y, Terasaki M, Okamoto Y, Sakaguchi K, Murata T, Ohkubo M, Nishimae K: Efficacy of preoperative dexamethasone in patients with laparoscopic cholecystectomy: A prospective randomized double-blind study. J Hepatobiliary Pancreat Surg 2009; 16:367–71

47. Feo CV, Sortini D, Ragazzi R, De Palma M, Liboni A: Randomized clinical trial of the effect of preoperative dexamethasone on nausea and vomiting after laparoscopic cholecystectomy. Br J Surg 2006; 93:295–9

48. Lee Y, Lai HY, Lin PC, Huang SJ, Lin YS: Dexamethasone prevents postoperative nausea and vomiting more effectively in women with motion sickness. Can J Anaesth 2003; 50:232–7

49. Carr MM, Williams JG, Carmichael L, Nasser JG: Effect of steroids on posttonsillectomy pain in adults. Arch Otolaryngol Head Neck Surg 1999; 125:1361–4

50. Coloma M, White PF, Markowitz SD, Whitten CW, Macaluso AR, Berrisford SB, Thornton KC: Dexamethasone in combination with dolasetron for prophylaxis in the ambulatory setting: Effect on outcome after laparoscopic cholecystectomy. ANESTHESIOLOGY 2002; 96:1346–50

51. Wang JJ, Ho ST, Liu YH, Lee SC, Liu YC, Liao YC, Ho CM: Dexamethasone reduces nausea and vomiting after laparoscopic cholecystectomy. Br J Anaesth 1999; 83:772–5

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

53. Neff SP, Stapelberg F, Warmington A: Excruciating perineal pain after intravenous dexamethasone. Anaesth Intensive Care 2002; 30:370–1

54. Bell A: Preventing perineal burning from i.v. dexamethasone. Oncol Nurs Forum 1988; 15:199

55. Sauerland S, Nagelschmidt M, Mallmann P, Neugebauer EA: Risks and benefits of preoperative high dose methylprednisolone in surgical patients: A systematic review. Drug Saf 2000; 23:449–61

56. Elvir-Lazo OL, White PF: Postoperative pain management after ambulatory surgery: Role of multimodal analgesia. Anesthesiol Clin 2010; 28:217–24

57. Gärtner R, Jensen MB, Nielsen J, Ewertz M, Kroman N, Kehlet H: Prevalence of and factors associated with persistent pain following breast cancer surgery. JAMA 2009; 302:1985–92

Cited By:

This article has been cited 22 time(s).

Annales Francaises D Anesthesie Et De Reanimation
Effect of a single intramuscular dose of dexamethasone on pain after circumcision. A randomized controlled study
Aissaoui, Y; Chkoura, K; Zaini, R; Moujahid, M; Mergad, O; Boughalem, M
Annales Francaises D Anesthesie Et De Reanimation, 32(2): 98-103.
10.1016/j.annfar.2012.12.007
CrossRef
Obesity Surgery
The Combination of Haloperidol, Dexamethasone, and Ondansetron for Prevention of Postoperative Nausea and Vomiting in Laparoscopic Sleeve Gastrectomy: a Randomized Double-Blind Trial
Benevides, ML; Oliveira, SSD; de Aguilar-Nascimento, JE
Obesity Surgery, 23(9): 1389-1396.
10.1007/s11695-013-0923-1
CrossRef
European Spine Journal
A comprehensive multimodal pain treatment reduces opioid consumption after multilevel spine surgery
Mathiesen, O; Dahl, B; Thomsen, BA; Kitter, B; Sonne, N; Dahl, JB; Kehlet, H
European Spine Journal, 22(9): 2089-2096.
10.1007/s00586-013-2826-1
CrossRef
Archives of Gynecology and Obstetrics
Ultrasound-guided Transversus abdominal plane block with multimodal analgesia for pain management after total abdominal hysterectomy
Gasanova, I; Grant, E; Way, M; Rosero, EB; Joshi, GP
Archives of Gynecology and Obstetrics, 288(1): 105-111.
10.1007/s00404-012-2698-3
CrossRef
Journal of Reconstructive Microsurgery
Perioperative Interventions to Reduce Chronic Postsurgical Pain
Carroll, I; Hah, J; Mackey, S; Ottestad, E; Kong, JT; Lahidji, S; Tawfik, V; Younger, J; Curtin, C
Journal of Reconstructive Microsurgery, 29(4): 213-222.
10.1055/s-0032-1329921
CrossRef
International Journal of Surgery
Ramosetron vs. ramosetron plus dexamethasone for the prevention of postoperative nausea and vomiting (PONV) after laparoscopic cholecystectomy: Prospective, randomized, and double-blind study
Ryu, JH; Chang, JE; Kim, HR; Hwang, JW; Oh, AY; Do, SH
International Journal of Surgery, 11(2): 183-187.
10.1016/j.ijsu.2012.12.018
CrossRef
Canadian Journal of Anesthesia-Journal Canadien D Anesthesie
Safety of perioperative dexamethasone administration in children: time for reflection?
Yee, K; Cox, RG
Canadian Journal of Anesthesia-Journal Canadien D Anesthesie, 60(9): 833-839.
10.1007/s12630-013-9980-0
CrossRef
British Journal of Anaesthesia
I.V. and perineural dexamethasone are equivalent in increasing the analgesic duration of a single-shot interscalene block with ropivacaine for shoulder surgery: a prospective, randomized, placebo-controlled study
Desmet, M; Braems, H; Reynvoet, M; Plasschaert, S; Van Cauwelaert, J; Pottel, H; Carlier, S; Missant, C; Van de Velde, M
British Journal of Anaesthesia, 111(3): 445-452.
10.1093/bja/aet109
CrossRef
Hernia
Female gender is a risk factor for pain, discomfort, and fatigue after laparoscopic groin hernia repair
Tolver, MA; Strandfelt, P; Rosenberg, J; Bisgaard, T
Hernia, 17(3): 321-327.
10.1007/s10029-012-0956-8
CrossRef
Pharmacology
Dexamethasone Effect on Postoperative Pain and Tramadol Requirement after Thyroidectomy
Barros, A; Vale, CP; Oliveira, FC; Ventura, C; Assuncao, JP; Ribeiro, CAF; Pereira, FC
Pharmacology, 91(): 153-157.
10.1159/000346612
CrossRef
Journal of Anesthesia
Effects of ramosetron and dexamethasone on postoperative nausea, vomiting, pain, and shivering in female patients undergoing thyroid surgery
Song, YK; Lee, C
Journal of Anesthesia, 27(1): 29-34.
10.1007/s00540-012-1473-8
CrossRef
British Journal of Anaesthesia
Impact of perioperative dexamethasone on postoperative analgesia and side-effects: systematic review and meta-analysis
Waldron, NH; Jones, CA; Gan, TJ; Allen, TK; Habib, AS
British Journal of Anaesthesia, 110(2): 191-200.
10.1093/bja/aes431
CrossRef
Acta Anaesthesiologica Scandinavica
Perioperative glucocorticoids in hip and knee surgery - benefit vs. harm? A review of randomized clinical trials
Lunn, TH; Kehlet, H
Acta Anaesthesiologica Scandinavica, 57(7): 823-834.
10.1111/aas.12115
CrossRef
British Journal of Anaesthesia
Effect of high-dose preoperative methylprednisolone on recovery after total hip arthroplasty: a randomized, double-blind, placebo-controlled trial
Lunn, TH; Andersen, LO; Kristensen, BB; Husted, H; Gaarn-Larsen, L; Bandholm, T; Ladelund, S; Kehlet, H
British Journal of Anaesthesia, 110(1): 66-73.
10.1093/bja/aes345
CrossRef
Clinical Orthopaedics and Related Research
Preemptive Low-dose Dexamethasone Reduces Postoperative Emesis and Pain After TKA: A Randomized Controlled Study
Koh, IJ; Chang, CB; Lee, JH; Jeon, YT; Kim, TK
Clinical Orthopaedics and Related Research, 471(9): 3010-3020.
10.1007/s11999-013-3032-5
CrossRef
Journal of Anesthesia
Adding pregabalin to a multimodal analgesic regimen does not reduce pain scores following cosmetic surgery: a randomized trial
Chaparro, LE; Clarke, H; Valdes, PA; Mira, M; Duque, L; Mitsakakis, N
Journal of Anesthesia, 26(6): 829-835.
10.1007/s00540-012-1447-x
CrossRef
British Journal of Surgery
Contemporary perioperative care strategies
Adamina, M; Gie, O; Demartines, N; Ris, F
British Journal of Surgery, 100(1): 38-54.
10.1002/bjs.8990
CrossRef
Anaesthesia
Routine use of dexamethasone for postoperative nausea and vomiting: the case for
Kakodkar, PS
Anaesthesia, 68(9): 889-891.
10.1111/anae.12308
CrossRef
Anaesthesia
Routine use of dexamethasone for postoperative nausea and vomiting: the case against
Bartlett, R; Hartle, AJ
Anaesthesia, 68(9): 892-896.
10.1111/anae.12309
CrossRef
Colorectal Disease
Evidence-based postoperative pain management after laparoscopic colorectal surgery
Joshi, GP; Bonnet, F; Kehlet, H
Colorectal Disease, 15(2): 146-155.
10.1111/j.1463-1318.2012.03062.x
CrossRef
Anaesthesia and Intensive Care
Duration of cortisol suppression following a single dose of dexamethasone in healthy volunteers: a randomised double-blind placebo-controlled trial
Elston, MS; Conaglen, HM; Hughes, C; Tamatea, JAU; Meyer-Rochow, GY; Conaglen, JV
Anaesthesia and Intensive Care, 41(5): 596-601.

Anesthesiology
Steroids to Ameliorate Postoperative Pain
Turan, A; Sessler, DI
Anesthesiology, 115(3): 457-459.
10.1097/ALN.0b013e31822a2871
PDF (349) | CrossRef
Back to Top | Article Outline

© 2011 American Society of Anesthesiologists, Inc.

Publication of an advertisement in Anesthesiology Online does not constitute endorsement by the American Society of Anesthesiologists, Inc. or Lippincott Williams & Wilkins, Inc. of the product or service being advertised.
Login

Article Tools

Images

CME Test

Share