Miami Beach, Fla.—Steroids do not appear to prevent cognitive decline after cardiac surgery, Dutch researchers have found.

Experts said the results, although perhaps disappointing, should not come as much surprise given that although researchers have devoted substantial energy on why some patients experience cognitive decline following coronary artery bypass graft (CABG) surgery, a definitive answer to the question remains elusive.

The latest study was a secondary analysis of the DECS (Dexamethasone for Cardiac Surgery) trial (see Anesthesiology News, July 2012, page 1). Diederik van Dijk, MD, PhD, a cardiac anesthesiologist and intensivist at University Medical Center Utrecht, in The Netherlands, who headed the work, and his colleagues had theorized that a postoperative inflammatory response might be the culprit. So they randomized 291 patients to determine whether prophylactic administration of 1 mg/kg of dexamethasone could blunt cognitive loss compared with placebo.

The answer was no.

“[The] risk for cognitive decline at one month was not lower in the dexamethasone group but it was higher, 14% versus 7% in the placebo group. However, the difference between the groups was not statistically significant, which is the story of my life,” said Dr. van Dijk, who presented the findings at a session of the 2013 annual meeting of the Society of Cardiovascular Anesthesiologists (SCA).

Significant Insignificance

It might indeed seem that way for Dr. van Dijk, who was a co-author of the primary trial, “Intraoperative High-Dose Dexamethasone for Cardiac Surgery: A Randomized Controlled Trial,” which yielded a nonsignificant finding (JAMA 2012;308:1761-1767). That study found that although the 30-day adverse event rate favored dexamethasone over placebo, he said, “the difference was not statistically significant, so it’s a negative trial.”

In the cognitive substudy, the difference in cognitive decline approached significance when Dr. van Dijk’s team controlled for two demographic differences between the groups. Despite the random assignment of 145 patients to steroid treatment and another 146 to placebo, mean age in the treatment group was almost two years younger (63.8 vs. 65.5 years); 17 participants also had diabetes compared with 30 participants in the placebo group. “So one could argue patients in the placebo group were at higher risk for postoperative cognitive decline at one month follow-up,” Dr. van Dijk said.

The mean standardized cognitive test performance was lower in the dexamethasone group, –0.38 versus –0.13 for placebo, not a statistically significant difference, Dr. van Dijk said. All participants underwent a battery of neuropsychological cognitive testing at baseline, one month after cardiac surgery and 12 months after the procedure. Tests included the Corsi Blocks Task, Grooved Pegboard Task, Trail Making Test, Digit Span Task and the Rey Auditory Verbal Learning Task.

The 12-month findings are “more reassuring because most patients have recovered and there is a low risk for cognitive decline in both groups that is not different anymore between the two groups,” said Dr. van Dijk, whose study was supported by a mid-career grant from the SCA.

“This is an interesting trial, for which the primary outcomes were first presented at the 2012 Society of Cardiovascular Anesthesiologists annual meeting,” said session moderator Hilary P. Grocott, MD, professor of anesthesiology at the University of Manitoba in Winnipeg, Canada. “This important secondary analysis of cognitive outcome is further interesting as it sheds additional doubt on any significant benefit to steroids on even the softer outcomes such as postoperative cognition. It seems that any way we look at it, steroids appear to have no significant beneficial neurologic effect.”

The failure of steroids to alleviate the problem is far from an anomaly. Why some patients experience cognitive decline following CABG surgery has been a mystery for decades.

“The heyday of postoperative cognitive dysfunction research was about 10 to 12 years ago, with publications in major journals, showing a high incidence of cognitive decline in the first year and in first five-year follow-up studies,” Dr. van Dijk said.

However, results of research in the past decade taught clinical investigators two things, he observed. “We may have overestimated the incidence of the problem. Studies in volunteers show there is considerable variation in cognitive test performance. When you choose the wrong cutoff level for what is normal, you can end up with a high level of false-positive cases.

“The other thing we’ve learned is avoiding cardiopulmonary bypass doesn’t really help,” Dr. van Dijk added (JAMA 2007;297:701-708; N Engl J Med 2013;368:1179-1188). “This has been a great disappointment to many of us because it’s so natural to assume that cardiopulmonary bypass is responsible.”

Further research is needed. “We need alternate explanations for how cardiac surgery can cause postoperative cognitive decline,” Dr. van Dijk said.