Given the important role that inflammation may play in the development of postoperative delirium and cognitive dysfunction after cardiopulmonary bypass, researchers have long been on the hunt for an agent to stop this destructive process and aid recovery in affected patients.
Yet, according to an analysis of the SIRS (Steroids In caRdiac Surgery) trial, that agent is not methylprednisolone. The study concluded that high doses of the steroid neither reduce delirium nor improve the quality of recovery in high-risk cardiac surgical patients.
“We know that high-dose steroids offer no benefit in cardiac surgery, whether it’s mortality or morbidity, delirium or postoperative cognitive dysfunction,” said Colin F. Royse, MD, professor of anesthesiology at the University of Melbourne, in Australia. “What we do not know is whether the quality of recovery—that is, recovery from the patient’s perspective—is different with steroids.”
Focus on Quality of Recovery
Given this question, the researchers conducted a substudy in the randomized double-blind SIRS trial, which involved 550 adult patients in three hospitals—one each in the United States, Canada and Australia. As part of the study, patients were randomly assigned to receive either placebo or 250 mg of methylprednisolone at induction and 250 mg of methylprednisolone before cardiopulmonary bypass.
Each participant completed the Postoperative Quality of Recovery Scale before surgery and on days 1, 2, 3, 30 and 180 days after surgery. Patients also completed the Confusion Assessment Method scale for delirium on days 1, 2 and 3. Recovery was defined as a return to, or improvement in, preoperative values.
As Dr. Royse reported at the Major Trials session of the 2016 American Society of Anesthesiologists annual meeting, 482 patients were available for analysis of recovery and 498 for analysis of delirium. It was found that although the quality of recovery improved over time, there were no statistically significant differences between groups in overall quality of recovery or any of the individual recovery domains (P>0.05 for all).
Postoperative delirium occurred in 8% of patients receiving methylprednisolone and 10% of controls (P=0.357), with no significant differences in delirium subdomains between groups.
The researchers, whose findings also appear in Anesthesiology (2017;126:223-233), also examined the effects of methylprednisolone on patients with low baseline levels of cognition. “This made us sit up and really think about these cardiac surgery patients: Nearly 49% were considered to have low baseline cognition,” Dr. Royse explained. “So we’re dealing with a particularly fragile population.”
Nevertheless, the analysis revealed that there were no significant differences favoring methylprednisolone in any domain.
Despite these findings, delirium did come into play, perhaps even more so than the researchers suspected. “If a patient had delirium, it was serious,” Dr. Royse said. Indeed, recovery was significantly worse in patients with postoperative delirium in the cognitive (P=0.004) and physiologic (P<0.001) domains.
“What’s fascinating is that in the early days, it’s difficult to see that difference,” he added. “But the further you go, the worse it is. It may well be that if you suffer delirium, the effect on recovery may be even longer than six months and we might find further deviation.”
Overall, the trial confirmed that there is no evidence that high-dose methylprednisolone improves quality of recovery or reduces delirium. “As such, we cannot support its use in these patients,” Dr. Royse said. “Recovery is slow and often incomplete, even six months after cardiac surgery.
“Of course, we can put a positive spin on the story as well,” he added. “Recovery does improve over time. And it’s especially encouraging in those patients who we considered cognitively frail—they actually recovered just as well as those with normal cognition in the other functional domains.”
As M. Alparslan Turan, MD, noted, the delirium rates uncovered in the SIRS trial differ from those published in other research. “I’m very happy about your results, because I was having difficulty finding delirious patients after cardiac surgery in one of my studies,” said Dr. Turan, who is the vice-chair of the Department of Outcomes Research at the Cleveland Clinic, in Ohio. “Why do you think the incidence of delirium is 8% to 10% in your study—which is very similar to my findings—but very different from the published rate in other studies?”
“It’s difficult to say,” Dr. Royse replied . “There is a lot of subjective assessment with respect to how individual clinicians define delirium. Even if you use the CAM-ICU, there’s some subjectivity. And in fact, if you look at some of the less serious forms of delirium, you’d get a much higher incidence.”