SEATTLE – Low protein C levels appear to be associated with the cognitive impairment many patients have after a stay in the intensive care unit, according to a study of 46 patients conducted 3 months after they left the hospital.
“We believe low protein C levels in critically ill patients predict long-term cognitive impairment,” said Dr. E. Wesley Ely, of the department of medicine at Vanderbilt University, Nashville.
“The reason we think it is relevant is that there are different lines of intervention we could use for our elderly patients who do develop sepsis,” he said at the annual meeting of the American Geriatrics Society.
Protein C is a vitamin K-dependent plasma protein that, when activated by thrombin, inhibits the clotting cascade, and therefore is able to turn off coagulopathies like those seen in sepsis patients and others in the ICU.
The study found that 23 patients with long-term cognitive impairment, of 46 patients who had been mechanically ventilated in an ICU, had a mean protein C activity 28% lower than those patients who did not have cognitive impairment after their stay.
The patients came from a larger study of patients on mechanical ventilation during an ICU stay, during which the patients had plasma drawn. Dr. Timothy D. Girard, this study's primary investigator, went to great lengths to find and perform cognitive tests on as many of those patients as possible 3 months later, even going so far as to track them down to trailer-home parks hundreds of miles away, Dr. Ely said.
The initial study enrolled 113 patients, of whom 77 survived to discharge. Another 11 patients died before 3 months. Of the remaining 66 patients, half of whom had had sepsis, 46 were given a battery of tests.
“It's about as high a follow-up as you are going to be able to get in a study like this,” he said.
The battery of neuropsychological tests administered to the patients took about an hour and a half to complete, and measured nine domains of cognitive function.
And the criteria for cognitive impairment used by the investigators was fairly stringent, to exclude deficits not clearly caused by the ICU experience, Dr. Ely said. The amount of impairment allowed in the study would have been readily apparent in the patients before their stay.
The investigation also involved assessing levels of D-dimer, plasminogen activator inhibitor-1, and von Willebrand factor, none of which differed between the two groups.
The difference in protein C was such that a decrease of 1 natural log equated to a 6-point drop in the neuropsychological score. And, a 6-point drop is “a big deal,” Dr. Ely said.
“With a 6-point drop, you are taking yourself down by nearly a standard deviation. This is a situation where people can have trouble finding their car in a parking lot or balancing a checkbook.”
The most striking and common deficits seen the study were in executive function and memory.
Previous cohort studies done at Vanderbilt have suggested that cognitive impairment following an ICU stay is quite common, occurring in between 50% and 66% of all elderly patients, Dr. Ely noted.