Delirium may be a troubling consequence of high-risk cardiac surgery in elderly patients, but that can be avoided with the administration of intraoperative dexmedetomidine, according to a team of Toronto researchers. This benefit, they added, does not come with the burden of negative hemodynamic changes.
“Delirium affects as many as one in five elderly patients having cardiac surgery,” said Natalie Silverton, MD, a fellow in anesthesia at the University of Toronto and Toronto General Hospital, Ontario, Canada. “Delirium is distressing to our patients and their families. But in addition to that, it’s associated with long-term cognitive impairment, increased morbidity and mortality, increased hospital costs, and lengths of stay in the ICU and hospital.”
The α2-receptor antagonist dexmedetomidine possesses both sedative and analgesic properties, but lacks clinically significant anticholinergic effects and respiratory depression, which makes it an ideal agent for this patient population. “Although dexmedetomidine may be assoc iated with a decreased risk of delirium, most prospective, randomized studies of the agent involve medical ICU patients, not postsurgical patients.”
To help get a better grasp of dexmedetomidine’s real-world effect on the elderly undergoing cardiac surgery, Dr. Silverton and her colleagues enrolled 183 patients into the trial. Patients were either at least 60 years old and undergoing elective complex cardiac surgery or older than 70 years and undergoing either isolated coronary revascularization or single valve repair/replacement. Patients with a history of psychiatric disease, delirium or severe dementia, or who were undergoing emergency procedures, were excluded.
Patients underwent routine anesthetic and surgical care. Upon arrival to the ICU, the participants received either a dexmedetomidine bolus of 0.4 mg/kg followed by an infusion of 0.2 to 0.7 mg/kg per hour, or a propofol infusion of 25 to 50 mg/kg per minute. The dexmedetomidine infusion was continued for a maximum of 24 hours, or until the patient left the ICU. “And because there were no concerns with respiratory depression, they were able to continue with the dexmedetomidine in the ICU, even after extubation,” she noted. Propofol was discontinued on extubation.
A Significant Reduction
Delirium was assessed with the Confusion Assessment Method (CAM) for the ICU before surgery and every 12 hours thereafter, or as needed according to the patient’s condition during the first five postoperative days. Patients were determined to be either CAM positive (delirium present) or CAM negative (delirium absent).
As Dr. Silverton reported at the 2015 annual meeting of the Canadian Anesthesiologists’ Society (abstract 86224), 16 of the 91 patients receiving dexmedetomidine had postoperative delirium (17.5%; 95% CI, 9.7%-25.3%). By comparison, 29 of the 92 patients receiving propofol experienced delirium (31.5%; 95% CI, 22.0%-41.0%; P=0.028).
“This was not only statistically significant, but also clinically significant in that it’s a relative risk reduction of 55% and an absolute risk reduction of 14%,” Dr. Silverton explained.
The median duration of delirium was two days in the dexmedetomidine patients (range, 1-4 days), compared with three days (range, 1-5 days) for the propofol patients (P=0.04). “As opposed to some of the other studies of dexmedetomidine, we had no difference in extubation time, no difference in ICU or hospital lengths of stay,” she added. “Primarily, I think that’s because we had some patients who were intubated for very short periods of time, whereas in some of the medical ICU studies patients were intubated for days or weeks. That’s where you see the real difference.”
Of interest, the researchers also found no difference in hemodynamic changes between groups. “There was no difference in inotrope or vasopressor requirements between the two groups,” Dr. Silverton said. There was also no difference in permanent pacemaker placement or mortality between groups.
These results are promising in that they give clinicians the opportunity to see real clinical differences, she added. “According to these data, we needed to treat only eight elderly cardiac surgery patients with dexmedetomidine for 24 hours to prevent one case of delirium.”
According to Dr. Silverton, there’s room for a more significant effect on patients with dexmedetomidine, given some fine-tuning of the drug’s administration schedule. “At our institution we run propofol through the case, and then they go to the ICU on propofol,” she said. “By comparison, the dexmedetomidine group had their propofol stopped at the end of surgery, received 24 hours of dexmedetomidine in the ICU and, for those requiring continued sedation past 24 hours, went back to propofol. So they got a lot of propofol and a little bit of dexmedetomidine … and we still saw a big effect.
“So my thought is that if these patients could have dexmedetomidine run intraoperatively instead of propofol, they might see a more profound effect. There is certainly a lot more work to be done with dexmedetomidine.”