Adverse side effects of dexamethasone in surgical patients

In the perioperative period, dexamethasone is widely and effectively used for prophylaxis of postoperative nausea and vomiting (PONV), for pain management, and to facilitate early discharge after ambulatory surgery.Long-term treatment with steroids has many side effects, such as adrenal insufficiency, increased infection risk, hyperglycaemia, high blood pressure, osteoporosis, and development of diabetes mellitus. However, whether a single steroid load during surgery has negative effects during the postoperative period has not yet been studied.

To assess the effects of a steroid load of dexamethasone on postoperative systemic or wound infection, delayed wound healing, and blood glucose change in adult surgical patients (with planned subgroup analysis of patients with and without diabetes).

We searched MEDLINE, Embase, the Cochrane Central Register of Controlled Trials (CENTRAL), in the Cochrane Library, and the Web of Science for relevant articles on 29 January 2018. We searched without language or date restriction two clinical trial registries to identify ongoing studies, and we handsearched the reference lists of relevant publications to identify all eligible trials.

We searched for randomized controlled trials comparing an incidental steroid load of dexamethasone versus a control intervention for adult patients undergoing surgery. We required that studies include a follow-up of 30 days for proper assessment of the number of postoperative infections, delayed wound healing, and the glycaemic response.

Two review authors independently screened studies for eligibility, extracted data from relevant studies, and assessed all included studies for bias. We resolved differences by discussion and pooled included studies in a meta-analysis. We calculated Peto odds ratios (ORs) for dichotomous outcomes and mean differences (MDs) for continuous outcomes. Our primary outcomes were postoperative systemic or wound infection, delayed wound healing, and glycaemic response within 24 hours. We created a funnel plot for the primary outcome postoperative (wound or systemic) infection. We used GRADE to assess the quality of evidence for each outcome.

We included in the meta-analysis 38 studies that included adults undergoing a large variety of surgical procedures (i.e. abdominal surgery, cardiac surgery, neurosurgery, and orthopaedic surgery). Age range of participants was 18 to 80 years. There is probably little or no difference in the risk of postoperative (wound or systemic) infection with dexamethasone compared with no treatment, placebo, or active control (ramosetron, ondansetron, or tropisetron) (Peto OR 1.01, 95% confidence interval (CI) 0.80 to 1.27; 4931 participants, 27 studies; I² = 27%; moderate-quality evidence). The effects of dexamethasone on delayed wound healing are unclear because the wide confidence interval includes both meaningful benefit and harm (Peto OR 0.99, 95% CI 0.28 to 3.43; 1072 participants, eight studies; I² = 0%; low-quality evidence). Dexamethasone may produce a mild increase in glucose levels among participants without diabetes during the first 12 hours after surgery (MD 13 mg/dL, 95% CI 6 to 21; 10 studies; 595 participants; I² = 50%; low-quality evidence). We identified two studies reporting on glycaemic response after dexamethasone in participants with diabetes within 24 hours after surgery (MD 32 mg/dL, 95% CI 15 to 49; 74 participants; I² = 0%; very low-quality evidence).

A single dose of dexamethasone probably does not increase the risk for postoperative infection. It is uncertain whether dexamethasone has an effect on delayed wound healing in the general surgical population owing to imprecision in trial results. Participants with increased risk for delayed wound healing (e.g. participants with diabetes, those taking immunosuppressive drugs) were not included in the randomized studies reporting on delayed wound healing included in this meta-analysis; therefore our findings should be extrapolated to the clinical setting with caution. Furthermore, one has to keep in mind that dexamethasone induces a mild increase in glucose. For patients with diabetes, very limited evidence suggests a more pronounced increase in glucose. Whether this influences wound healing in a clinically relevant way remains to be established. Once assessed, the three studies awaiting classification and two that are ongoing may alter the conclusions of this review.