Dexamethasone Shows No Cardiovascular Advantage

The use of high-dose dexamethasone as a prophylactic for patients undergoing cardiac surgery did not lower the 30-day incidence of major cardiovascular events compared with placebo, however, it may reduce occurrence of respiratory failure and infections, according to results of the DECS (Dexamethasone for Cardiac Surgery) trial reported in the Journal of the American Medical Association [2012;308(17):1761-1767].

Despite advancements in surgical techniques, anesthesia management, and postoperative care, cardiac surgery is still associated with a significant risk of major adverse events. To quantify the effect of a single intravenous dose of dexamethasone on the occurrence of major adverse events, researchers conducted the multicenter, randomized, double-blind, placebo-controlled DECS trial of 4494 patients ≥18 years of age who underwent cardiopulmonary bypass at 8 cardiac surgical centers in the Netherlands between April 13, 2006, and November 23, 2011. Patients were randomly assigned to receive a single intravenous dose of 1 mg/kg dexamethasone (n=2339) or placebo (n=2255). The primary end point was composite of death, myocardial infarction (MI), stroke, renal failure, or respiratory failure within 30 days.

Overall, 7% of patients in the dexamethasone group and 8.5% of those in the placebo group reached the primary end point (relative risk [RR], 0.83; 95% confidence interval [CI], 0.67-1.01; absolute risk reduction, −1.5%; 95% CI, −3.0% to 0.1%; P=.07). In an exploratory analysis of individual end-point components, the results were similar for the dexamethasone and placebo groups for the rate of death (1.4% vs 1.5%, respectively; RR, 0.92; 95% CI, 0.57-1.49), MI (1.6% vs 1.7%, respectively; RR 0.90; 95% CI, 0.57-1.42), stroke (1.3% vs 1.4%, respectively; RR, 0.91; 95% CI, 0.55-1.50), and renal failure (1.3% vs 1.8%, respectively; RR, 0.70; 95% CI, 0.44-1.14). Respiratory failure was significantly reduced in the dexamethasone group compared with the placebo group (3.0% vs 4.3%, respectively; RR, 0.69; 95% CI, 0.51-0.94; P=0.02).

The risk of developing a postoperative infection was lower in the dexamethasone group than in the placebo group (9.5% vs 14.8%, respectively; RR, 0.64; 95% CI, 0.54-0.75; P<.001), an effect that was primarily related to a decreased incidence of pneumonia in the dexamethasone group. Furthermore, dexamethasone versus placebo was associated with reductions in duration of postoperative mechanical ventilation (11 hours vs 14.3 hours, respectively; P<.001), length of intensive care unit stay (34.2 hours vs 43.6 hours, respectively; P<.001), and time to discharge from the hospital (11.3 days vs 11.7 days, respectively; P=.009). In contrast, dexamethasone was associated with higher mean serum blood glucose levels compared with placebo (195 mg/dL vs 177 mg/dL, respectively; P<.001).

In a preplanned subgroup analysis, the researchers found an age-dependent effect of dexamethasone on the primary end point. In patients <65 years of age, dexamethasone was associated with lower risk of the primary end point (RR, 0.65; 95% CI, 0.44-0.96; P=.03) compared with patients ≥80 years of age (RR, 1.69; 95% CI, 0.92-3.10; P=.09).

The study was limited because European centers use high-dose dexamethasone during cardiac surgery, but when the surgery is performed in the United States, methylprednisolone is preferred. The effect of high-dose methylprednisolone for cardiac surgery is being studied in the ongoing SIRS (Steroids In Cardiac Surgery) trial.