Paper of the Week: Dexamethasone and Surgical-Site Infection

Tomás B. Corcoran, M.D., Paul S. Myles, D.Sc., Andrew B. Forbes, Ph.D., Allen C. Cheng, Ph.D., Leon A. Bach, Ph.D., Edmond O’Loughlin, M.Clin.Res., Kate Leslie, M.D., Matthew T.V. Chan, Ph.D., David Story, M.D., Timothy G. Short, M.D., Catherine Martin, Ph.D., Pauline Coutts, P.Grad.Dip.N., et al., for the PADDI Investigators, the Australian and New Zealand College of Anaesthetists Clinical Trials Network, and the Australasian Society for Infectious Diseases Clinical Research Network

New England Journal of Medicine 2021; 384:1731-1741
DOI: 10.1056/NEJMoa2028982

Summary by Emanuele Chisari and Marco Di Spagna

Postoperative vomiting and nausea are common problems encountered in perioperative care, occurring in 30% of patients undergoing surgery.¹ To combat this problem, dexamethasone is commonly administered as a prophylaxis and/or treatment in more than 50% of patients undergoing surgery with general anesthesia.^1,2,3 Due to its effects on immune function, there is concern that administration of dexamethasone preoperatively can increase the risk of postoperative infection, especially in vulnerable populations such as patients with diabetes and/or other comorbidities.^6-8

To assess the effects of dexamethasone on risk of surgical site infection, Corcoran et al. conducted a multicenter, randomized, placebo-controlled, triple-blind, noninferiority trial involving a total of 8,725 participants (4,372 in the dexamethasone group and 4,353 in the placebo group), of which 13.2% (576 in the dexamethasone group and 572 in the placebo group) had diabetes mellitus. Patients were administered 8 mg of intravenous dexamethasone or matching placebo after induction of general anesthesia and before surgical site incision. Inclusion criteria included patients undergoing nonurgent, noncardiac, surgery of at least 2 hours duration, surgical site incision length >5cm, and a postoperative overnight hospital stay. The primary outcome was surgical site infection within 30 days after surgery, determined by the CDC definitions. Secondary outcomes included superficial, deep, and organ-space infections within 30 days after surgery.

The authors found that surgical site infection occurred in 8.1% of patients (354 of 4,350) assigned to the dexamethasone group and in 9.1% of patients (394 of 4,328) assigned to the placebo group of the 8,678 patients included in the primary analysis, indicating a risk difference adjusted for diabetes status of −0.9 percentage points (95.6% confidence interval [CI], −2.1 to 0.3; P<0.001 for noninferiority). Secondary analysis results for superficial, deep, and organ-space surgical-site infections showed similar results to those of the primary analysis. Postoperative vomiting and nausea 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) while hyperglycemic events in patients without diabetes occurred in 22 of 3787 (0.6%) in the dexamethasone group and in 6 of 3,776 (0.2%) in the placebo group.

Overall, the authors concluded that dexamethasone was noninferior to placebo regarding the incidence of surgical site infection within 30 days of surgery. The authors recognized that they did not collect data on perioperative factors that might influence the risk of surgical-site infection, such as subtypes of gastrointestinal surgery, types of preoperative bowel and skin preparation, or wound treatment and details of perioperative antibiotic use. The increase in the incidence of new-onset chronic postoperative pain was a finding that has not been identified in previous studies.⁹ Future studies can further assess these outcomes.

References:

1. Gan TJ, Diemunsch P, Habib AS, et al. Consensus guidelines for the management of postoperative nausea and vomiting. Anesth Analg 2014; 118: 85-113.
2. De Oliveira GS Jr, Castro-Alves LJ, Ahmad S, Kendall MC, McCarthy RJ. Dexamethasone to prevent postoperative nausea and vomiting: an updated meta-analysis of randomized controlled trials. Anesth Analg 2013; 116: 58-74.
3. Corcoran TB, Edwards T. A survey of antiemetic dexamethasone administrationfrequency of use and perceptions of benefits and risks. Anaesth Intensive Care 2015; 43: 167-74.
4. Sapolsky RM, Romero LM, Munck AU. How do glucocorticoids influence stress responses? Integrating permissive, suppressive, stimulatory, and preparative actions. Endocr Rev 2000; 21: 55-89.
5. Bain CR, Draxler DF, Taylor R, et al. The early in-vivo effects of a single antiemetic dose of dexamethasone on innate immune cell gene expression and activation in healthy volunteers. Anaesthesia 2018; 73: 955-66.
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8. Ali Khan S, McDonagh DL, Gan TJ. Wound complications with dexamethasone for postoperative nausea and vomiting prophylaxis: a moot point? Anesth Analg 2013; 116: 966-8.
9. De Oliveira GS Jr, Bialek JM, Turan A, McCarthy RJ, Sessler DI. Perioperative dexamethasone and the development of chronic postmastectomy pain: a singlecenter observational cohort study. Reg Anesth Pain Med 2015; 40: 539-44.