Perioperative Dexamethasone

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. 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). 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. 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.

Prophylactic corticosteroids are often administered during cardiac surgery to attenuate the inflammatory response to cardiopulmonary bypass and surgical trauma; however, evidence that routine corticosteroid use can prevent major adverse events is lacking. To quantify the effect of intraoperative high-dose dexamethasone on the incidence of major adverse events in patients undergoing cardiac surgery. A multicenter, randomized, double-blind, placebo-controlled trial of 4494 patients aged 18 years or older undergoing cardiac surgery with cardiopulmonary bypass at 8 cardiac surgical centers in The Netherlands enrolled between April 13, 2006, and November 23, 2011. Patients were randomly assigned to receive a single intraoperative dose of 1 mg/kg dexamethasone (n = 2239) or placebo (n = 2255). A composite of death, myocardial infarction, stroke, renal failure, or respiratory failure, within 30 days of randomization. Of the 4494 patients who underwent randomization, 4482 (99.7%) could be evaluated for the primary outcome. A total of 157 patients (7.0%) in the dexamethasone group and 191 patients (8.5%) in the placebo group reached the primary study end point (relative risk, 0.83; 95% CI, 0.67-1.01; absolute risk reduction, -1.5%; 95% CI, -3.0% to 0.1%; P = .07). Dexamethasone was associated with reductions in postoperative infection, duration of postoperative mechanical ventilation, and lengths of intensive care unit and hospital stays. In contrast, dexamethasone was associated with higher postoperative glucose levels. In our trial of adults undergoing cardiac surgery, the use of intraoperative dexamethasone did not reduce the 30-day incidence of major adverse events compared with placebo. clinicaltrials.gov Identifier: NCT00293592.

Dexamethasone is widely used in cancer patients despite the concern that perioperative glucocorticoids may potentially cause immunosuppression. However, studies on the influence of dexamethasone on cancer recurrence after curative surgery have produced conflicting results. The goal of our study was to compare postoperative recurrence-free survival and overall survival between patients with breast cancer who received perioperative dexamethasone and those who did not. The medical records of 2729 patients who underwent breast cancer surgery between November 2005 and December 2010 were reviewed. These patients were followed up until December 2015. The patients were categorised according whether they received a single dose of intravenous dexamethasone perioperatively or not. Cox regression analyses were conducted to evaluate any associations between dexamethasone usage with postoperative recurrence and mortality. Additionally, we performed a sensitivity test with propensity score matching to adjust for selection bias. Among the 2628 patients, 236 (8.5%) received perioperative dexamethasone. No increasing risk for recurrence (hazard ratio [HR], 1.442; 95% confidence interval [CI], 0.969-2.145; P = 0.071) or mortality (HR, 1.256; 95% CI, 0.770-2.047; P = 0.361) after breast cancer surgery were identified in patients who received dexamethasone. Similarly, propensity score matching did not show significant associations in postoperative recurrence (HR, 1.389; 95% CI, 0.904-2.132; P = 0.133) or mortality (HR, 1.506; 95% CI, 0.886-2.561; P = 0.130) in patients who received dexamethasone. We found that a perioperative single dose of dexamethasone is not associated with increased recurrence or mortality after curative surgery in breast cancer patients.

Dexamethasone has an established role in decreasing postoperative nausea and vomiting (PONV); however, the optimal dexamethasone dose for reducing PONV when it is used as a single or combination prophylactic strategy has not been clearly defined. In this study, we evaluated the use of 4 mg to 5 mg and 8 mg to 10 mg IV doses of dexamethasone to prevent PONV when used as a single drug or as part of a combination preventive therapy. A wide search was performed to identify randomized clinical trials that evaluated systemic dexamethasone as a prophylactic drug to reduce postoperative nausea and/or vomiting. The effects of dexamethasone dose were evaluated by pooling studies into 2 groups: 4 mg to 5 mg and 8 mg to 10 mg. The first group represents the suggested dexamethasone dose to prevent PONV by the Society for Ambulatory Anesthesia (SAMBA) guidelines, and the second group represents twice the dose range recommended by the guidelines. The SAMBA guidelines were developed in response to studies, which have been performed to examine different dosages of dexamethasone. Sixty randomized clinical trials with 6696 subjects were included. The 4-mg to 5-mg dose dexamethasone group experienced reduced 24-hour PONV compared with control, odds ratio (OR, 0.31; 95% confidence interval [CI], 0.23-0.41), and number needed to treat (NNT, 3.7; 95% CI, 3.0-4.7). When used together with a second antiemetic, the 4-mg to 5-mg dexamethasone group also experienced reduced 24-hour PONV compared with control (OR, 0.50; 95% CI, 0.35-0.72; NNT, 6.6; 95% CI, 4.3-12.8). The 8-mg to 10-mg dose dexamethasone group experienced decreased 24-hour PONV compared with control (OR, 0.26; 95% CI, 0.20-0.32; NNT, 3.8; 95% CI, 3.0-4.3). Asymmetric funnel plots were observed in the 8-mg to 10-mg dose analysis, suggesting the possibility of publication bias. When used together with a second antiemetic, the 8-mg to 10-mg dose group also experienced reduced incidence of 24-hour PONV (OR, 0.35; 95% CI, 0.22-0.53; NNT, 6.2; 95% CI, 4.5-10). In studies that provided a direct comparison between groups, there was no clinical advantage of the 8-mg to 10-mg dexamethasone dose compared with the 4-mg to 5-mg dose on the incidence of postoperative nausea and/or vomiting. Our results showed that a 4-mg to 5-mg dose of dexamethasone seems to have similar clinical effects in the reduction of PONV as the 8-mg to 10-mg dose when dexamethasone was used as a single drug or as a combination therapy. These findings support the current recommendation of the SAMBA guidelines for PONV, which favors the 4-mg to 5-mg dose regimen of systemic dexamethasone.

The glucocorticoid dexamethasone prevents nausea and vomiting after surgery, but there is concern that it may increase the risk of surgical-site infection. In this pragmatic, international, noninferiority trial, we randomly assigned 8880 adult patients who were undergoing nonurgent, noncardiac surgery of at least 2 hours' duration, with a skin incision length longer than 5 cm and a postoperative overnight hospital stay, to receive 8 mg of intravenous dexamethasone or matching placebo while under anesthesia. Randomization was stratified according to diabetes status and trial center. The primary outcome was surgical-site infection within 30 days after surgery. The prespecified noninferiority margin was 2.0 percentage points. A total of 8725 participants were included in the modified intention-to-treat population (4372 in the dexamethasone group and 4353 in the placebo group), of whom 13.2% (576 in the dexamethasone group and 572 in the placebo group) had diabetes mellitus. Of the 8678 patients included in the primary analysis, surgical-site infection occurred in 8.1% (354 of 4350 patients) assigned to dexamethasone and in 9.1% (394 of 4328) assigned to placebo (risk difference adjusted for diabetes status, -0.9 percentage points; 95.6% confidence interval [CI], -2.1 to 0.3; P<0.001 for noninferiority). The results for superficial, deep, and organ-space surgical-site infections and in patients with diabetes were similar to those of the primary analysis. Postoperative nausea and vomiting in the first 24 hours after surgery occurred in 42.2% of patients in the dexamethasone group and in 53.9% in the placebo group (risk ratio, 0.78; 95% CI, 0.75 to 0.82). Hyperglycemic events in patients without diabetes occurred in 22 of 3787 (0.6%) in the dexamethasone group and in 6 of 3776 (0.2%) in the placebo group. Dexamethasone was noninferior to placebo with respect to the incidence of surgical-site infection within 30 days after nonurgent, noncardiac surgery. (Funded by the Australian National Health and Medical Research Council and others; PADDI Australian New Zealand Clinical Trials Registry number, ACTRN12614001226695.).

We examined the effects of dexamethasone on postoperative mortality, recurrence-free survival, and side effects in patients undergoing oncologic operations. Dexamethasone prevents nausea and vomiting after anesthesia and may affect cancer proliferation. A total of 30,561 adult patients undergoing solid cancer resection between 2005 and 2020 were included. Multivariable logistic regression was applied to investigate the effect of dexamethasone on 1-year mortality and recurrence-free survival. Effect modification by the cancer's potential for immunogenicity, defined as a recommendation for checkpoint inhibitor therapy based on the National Comprehensive Cancer Network guidelines, was investigated through interaction term analysis. Key safety endpoints were dexamethasone-associated risk of hyperglycemia >180&#xa0;mg/dL within 24 hours and surgical site infections within 30 days after surgery. Dexamethasone was administered to 38.2% (11,666/30,561) of patients (6.5&#xb1;2.3&#xa0;mg). Overall, 3.2% (n=980/30,561) died and 15.4% (n=4718/30,561) experienced cancer recurrence within 1 year of the operation. Dexamethasone was associated with a -0.6% (95% confidence interval: -1.1, -0.2, P =0.007) 1-year mortality risk reduction [adjusted odds ratio (OR adj ): 0.79 (0.67, 0.94), P =0.009; hazard ratio=0.82 (0.69, 0.96), P =0.016] and higher odds of recurrence-free survival [OR adj : 1.28 (1.18, 1.39), P <0.001]. This effect was only present in patients with solid cancers who were defined as not to respond to checkpoint inhibitor therapy [OR adj : 0.70 (0.57, 0.87), P =0.001 vs OR adj : 1.13 (0.85, 1.50), P =0.40]. A high (>0.09&#xa0;mg/kg) dose of dexamethasone increased the risk of postoperative hyperglycemia [OR adj : 1.55 (1.32, 1.82), P <0.001], but not for surgical site infections [OR adj : 0.84 (0.42, 1.71), P =0.63]. Dexamethasone is associated with decreased 1-year mortality and cancer recurrence in patients undergoing surgical resection of cancers that are not candidates for immune modulators. Dexamethasone increased the risk of postoperative hyperglycemia, however, no increase in surgical site infections was identified.