NEUROVISION: Covert Stroke Common After Noncardiac Surgery

Deborah Brauser

February 21, 2019

HONOLULU — The occurrence of a covert stroke after elective noncardiac surgery is common for older patients — and may lead to increased risk for cognitive decline, new research suggests.

Results from the prospective NEUROVISION trial, which included more than 1100 patients from nine countries, were presented here at the International Stroke Conference (ISC) 2019.

Perioperative acute stroke occurred in one in every 14 participants. Delirium within 3 days after surgery occurred in 10% of the patients who experienced a covert stroke vs 5% of those who did not.

In addition, 42% vs 29% of the groups, respectively, showed cognitive decline on the Montreal Cognitive Assessment (MoCA) 1 year later. The covert stroke group also had an adjusted odds ratio (OR) of 1.98 for increased risk for cognitive decline compared with those who did not experience a stroke.

"When we see covert strokes, we see that they are these small areas of acute infarction," lead author Marko Mrkobrada, MD, general internist and associate professor at the University of Western Ontario, Canada, told Medscape Medical News.

"One concern we had at the beginning of this study was whether it was truly possible that such a small infarct would have a cognitive effect at 1 year; but we saw that not only does it have an effect on cognition, it had an effect in the immediate perioperative setting," Mrkobrada said. "These small acute strokes doubled the risk of delirium, which is a very profound alteration in cognitive function."

Dr Marko Mrkobrada

"Misclassified Manifestations"

Worldwide, 200 million adults undergo major noncardiac surgery annually," the investigators write. "Only 0.5% of patients suffer a clinically overt perioperative stroke, but the prevalence and impact of covert strokes in [these] patients is unknown."

Mrkobrada noted that covert strokes are brain infarcts that are not recognized acutely because of "unappreciated, subtle, or misclassified manifestations — yet they're detected on brain imaging." He added that this type of stroke is more common than overt stroke.

For NEUROVISION, the investigators enrolled and analyzed 1114 patients at least 65 years of age (mean age, 73 years; 56.5% men) from 12 centers in nine countries. All participants underwent elective noncardiac surgery with an anticipated hospital stay of at least two nights.

Clinical variables and neurocognitive function were assessed presurgery (baseline) and again 1-year postsurgery.

Cognitive decline was defined as a decrease of at least two points on the MoCA from baseline to the 1-year follow-up, and was the primary outcome. The mean MoCA score at baseline was 25.

Between postoperative days 2 and 9, the patients were scheduled for a brain MRI. Two neuroradiologists assessed each scan for acute brain infarcts on the diffusion-weighted imaging (DWI) sequence, as well as for chronic infarction, hemorrhage, and white matter lesions on other sequences.

Key secondary outcomes included incidence of perioperative covert stroke, as well as delirium within the first 3 days after surgery.

Possible "Embolic Etiology"

Among the study participants, 78 experienced an acute covert stroke (7%; 95% confidence interval [CI], 5.6 – 8.7%).

"And 13% of patients with covert stroke had multiple acute ischemic lesions, raising the possibility of embolic etiology," Mrkobrada said during his presentation.

Among the 461 patients who underwent orthopedic surgery, 5.6% experienced a covert stroke. In addition, a covert stroke was seen in:

  • 9.2% of the 262 patients undergoing urology or gynecology surgery

  • 6.6% of the 259 patients undergoing general surgery

  • 10% of the 40 patients undergoing vascular surgery

  • 13.8% of the 32 patients undergoing thoracic surgery

  • 6.5% of the 31 patients undergoing spinal surgery

  • 3.1% of the 29 patients undergoing "low-risk" surgery

The hazard ratio (HR) for postoperative delirium was 2.24 for patients who had a covert stroke vs those who did not have a covert stroke (95% CI, 1.06 – 4.73; P = .029).

The between-group difference was also significant for incidence of cognitive decline, as shown by scores on the MoCA (42% vs 29.4%; P = .028).

After adjusting for a number of baseline variables, including history of stroke and surgery type, the OR was 1.98 for increased risk for cognitive decline for those who had had a covert stroke vs those who did not (95% CI, 1.22 – 3.20; P = .005).

"This was highly statistically significant," Mrkobrada told meeting attendees. "This also represents an absolute risk increase of 12.6%."

He added that seven secondary and sensitivity multivariable regression analyses related to cognitive decline "all demonstrated significant and consistent results with the primary analysis." There was also a significant adjusted mean difference between the groups on score change from baseline to 1 year on the Digital Symbol Substitution Test (-2.6; P = .025).

The patients with covert stroke also showed more impairment at 1 year on the trail-making test-B compared with the nonstroke group (change from baseline, 13.4 vs -3.4 seconds to complete the test.) Although this was not deemed statistically significant (P = .06), "it was a clearly clinically significant deterioration in cognitive outcome," Mrkobrada said.

Finally, patients with a covert stroke were significantly more likely to have an overt stroke or TIA by the 1-year follow-up (HR, 4.13; 95% CI, 1.14 – 14.99; P = .019).

Routine Screens Needed?

During the post-presentation question-and-answer session, an attendee asked whether it would be appropriate to start screening for covert stroke as part of routine practice; and if one is identified, "are there any interventions that can help avoid some of the outcomes you described?"

"I think the one thing that could potentially change management is the fact that we found a 2.2 increased risk for delirium after surgery," said Mrkobrada.

"If someone gets delirious or confused or even has aphasia after surgery, it's ascribed to post-op medication or those types of things," he noted. "In terms of change in management, I'd say that if a patient is delirious, it may be reasonable to look for a covert stroke. It certainly would be reasonable to do a much more thorough neurological exam compared to what's currently being done by general practice."

However, Mrkobrada noted that MRIs are expensive. "This is not a screening tool. So we're looking to develop a biobank for biomarkers for acute stroke."

As for possible interventions, he said that information is currently unknown. "But we're putting in grants for the NEUROVISION-2 study. And I think it has to look into things that we can actually change."

Asked later by Medscape Medical News whether clinicians should warn about risk for covert stroke with their older patients considering elective surgery, Mrkobrada said, "that's hard to answer. Elective surgery can have a profound effect on people's quality of life.

"I think the risk of stroke has to be discussed with patients, there's no question. At the same time, surgery itself provides such a huge benefit to patients that I think there shouldn't be a blanket statement of 'you should not have surgery,' " he said.

"The overwhelming point of NEUROVISION is that covert stroke is common, as is cognitive decline; but I don't think we have the answers to what causes all cognitive decline after surgery," Mrkobrada said.

Study Design Concerns

Asked to comment by Medscape Medical News, Bruce Ovbiagele, MD, professor of neurology and associate dean at the University of California, San Francisco, called the findings "compelling" yet mentioned several issues with the study's design.

Dr Bruce Ovbiagele

"There is an aspect of the study that is not as clear to me. They seem to have conducted an MRI after surgery but there wasn't one done before surgery or at 1 year," said Ovbiagele, who was not involved with the research.

"This is important because if you have a patient who is prone to having silent infarcts and who undergoes surgery, when you scan the person afterwards and see one infarct, that could be due to the surgery or it could be due to their own natural propensity for having more infarcts," he said.

In addition, "when you measure their cognitive function at 1 year, it's hard to see whether that's due to the surgery versus due to the evolution of that person's propensity for having more infarcts," Ovbiagele noted. "If they had an MRI before the surgery and one after the surgery, then you would be able to say, 'this was what was going here' and 'this is definitely new.' Then, at 1 year, you could tell that cognitive dysfunction correlates with an increased burden. I think it's harder to say that [that correlates] without the extra MRIs."

He also pointed out a limitation with the use of the DWI and FLAIR MRI sequences. "Those things can be positive for 10 to 14 days. So if somebody had a stroke a week ago and then this person has one 2 days from now, both times [the scans] will 'light up,' " he said.

"The question of cognitive function after noncardiac procedures is an important one to study," but these limitations should be addressed, said Ovbiagele.

"The story here makes sense: that if somebody has a noncardiac-related covert event, presumably that person 1 year later would have some kind of cognitive diminution. But I can't make that kind of leap at this point based on how the study was designed," he concluded.

The study was funded by the Canadian Institutes of Health Research. Mrkobrada and Ovbiagele have disclosed no relevant financial relationships.

International Stroke Conference (ISC) 2019. Abstract LB18.
Presented February 7, 2019.

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