Dexamethasone and Surgical-Site Infection.

BACKGROUND: The glucocorticoid dexamethasone prevents nausea and vomiting after surgery, but there is concern that it may increase the risk of surgical-site infection. METHODS: 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. RESULTS: 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. CONCLUSIONS: 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.).

Dexamethasone and clinically significant postoperative nausea and vomiting: a prespecified substudy of the randomised perioperative administration of dexamethasone and infection (PADDI) trial.

BACKGROUND: Clinically significant postoperative nausea and vomiting (PONV) is a patient-reported outcome which reflects patient experience. Although dexamethasone prevents PONV, it is unknown what impact it has on this experience. METHODS: In this prespecified embedded superiority substudy of the randomised Perioperative Administration of Dexamethasone and Infection (PADDI) trial, patients undergoing non-urgent noncardiac surgery received dexamethasone 8 mg or placebo intravenously after induction of anaesthesia, and completed a validated PONV questionnaire. The primary outcome was the incidence of clinically significant PONV on day 1 or day 2 postoperatively. Secondary outcomes included the incidence of clinically significant PONV and severe PONV on days 1 and 2 considered separately. RESULTS: A total of 1466 participants were included, with 733 patients allocated to the dexamethasone arm and 733 to matched placebo. The primary outcome occurred in 52 patients (7.1%) in the dexamethasone arm and 66 (9%) patients in the placebo arm (relative risk [RR]=0.79; 95% confidence interval [CI], 0.56-1.11; P=0.18). Severe PONV occurred on day 2 in 27 patients (3.9%) in the dexamethasone arm and 47 patients (6.7%) in the placebo arm (RR=0.58; 95% CI, 0.37-0.92; P=0.02; number needed-to-treat (NNT)=36.7; 95% CI, 20-202). In the entire cohort of 8880 PADDI patients, lower nausea scores, less frequent administration of antiemetics, and fewer vomiting events were recorded by patients in the dexamethasone arm up to day 2 after surgery. CONCLUSIONS: Administration of dexamethasone 8 mg i.v. did not influence clinically significant PONV. Dexamethasone administration did, however, decrease the incidence and severity of PONV, and was associated with less frequent administration of antiemetic agents. CLINICAL TRIAL REGISTRATION: ACTRN12614001226695.

The perioperative administration of dexamethasone and infection (PADDI) trial protocol: rationale and design of a pragmatic multicentre non-inferiority study.

INTRODUCTION: The intraoperative administration of dexamethasone for prophylaxis against postoperative nausea and vomiting is a common and recommended practice. The safety of the administration of this immunosuppressive agent at a time of significant immunological disruption has not been rigorously evaluated in terms of infective complications. METHODS/ANALYSIS: This is a pragmatic, multicentre, randomised, controlled, non-inferiority trial. A total of 8880 patients undergoing elective major surgery will be enrolled. Participants will be randomly allocated to receive either dexamethasone 8 mg or placebo intravenously following the induction of anaesthesia in a 1:1 ratio, stratified by centre and diabetes status. Patient enrolment into the trial is ongoing. The primary outcome is surgical site infection at 30 days following surgery, defined according to the Centre for Disease Control criteria. ETHICS/DISSEMINATION: The PADDI trial has been approved by the ethics committees of over 45 participating sites in Australia, New Zealand, Hong Kong, South Africa and the Netherlands. The trial has been endorsed by the Australia and New Zealand College of Anaesthetists Clinical Trials Network and the Australian Society for Infectious Diseases Clinical Research Network. Participant recruitment began in March 2016 and is expected to be complete in mid-2019. Publication of the results of the PADDI trial is anticipated to occur in early 2020. TRIAL REGISTRATION NUMBER: ACTRN12614001226695.