Sepsis triples the odds that older patients will develop enduring cognitive and functional impairment, even if they had been healthy before the infection, according to a report in the Oct. 27 issue JAMA.
The sepsis survivors’ cognitive and functional declines are of such a magnitude that significant increases in caregiver time and nursing home admission are required and rates of depression and death rise precipitously. “These data argue that the burden of sepsis survivorship is a substantial, underrecognized public health problem with major implications for patients, families, and the health care system,” Dr. Theodore J. Iwashyna of the University of Michigan, Ann Arbor, and his associates wrote in their report (JAMA 2010;304:1787-94).
Hundreds of thousands of patients are hospitalized with sepsis every year in the United States, and “it has been suspected that many are discharged with a new – but poorly defined – constellation of cognitive and functional impairments.” But the long-term impact of severe sepsis has not been studied systematically until now.
The findings “suggest that nearly 20,000 new cases per year of moderate to severe cognitive impairment in the elderly might be attributable to sepsis. Thus, an episode of severe sepsis, even when survived, might represent a sentinel event in the lives of patients and their families, resulting in new and often persistent disability, in some cases even resembling dementia,” Dr. Iwashyna and his associates noted.
The level of impairment in these sepsis survivors “has been associated with an additional 40 hours per week of informal care provided by families, analogous to an additional full-time job,” they added.
Dr. Iwashyna and his colleagues examined the issue using data from an ongoing nationally representative cohort study of more than 27,000 Americans aged 50 years and older at baseline, which enabled them to assess the cognition and physical functioning of 516 survivors of severe sepsis for up to 8 years preceding and 8 years following 623 hospitalizations for the condition. For comparison, they performed a similar analysis of 5,574 patients in the cohort with hospitalizations that were not for either sepsis or critical care. The definition of severe sepsis required evidence of both an infection and new-onset organ dysfunction during a single hospitalization.
Sepsis nearly tripled the rate of moderate to severe cognitive impairment. Only 6% of study subjects were impaired before the episode of sepsis, compared with 17% afterward.
Moreover, the incidence of cognitive impairment was nearly identical between patients who had been cognitively healthy before their infections and those who had already been showing signs of mild cognitive impairment when they developed sepsis, indicating that cognitively normal adults are just as susceptible to the sepsis-associated damage as others.
Sepsis survivors also showed additional physical impairments – a “substantial worsening in their trajectory” – that were even greater in previously healthy people than in those who had shown mild declines in physical functioning before they developed sepsis.
“Not only was sepsis associated with an acute increase in the number of functional limitations, but sepsis also heralded a more rapid rate of developing further limitations thereafter,” the investigators noted.
They replicated these results in several further analyses of the data. For example, postsepsis impairments were consistent, regardless of whether patients had required mechanical ventilation or not and regardless of whether they were older or younger than 65 years when hospitalized.
These declines were much greater than were those noted in the comparison group of older patients hospitalized for reasons other than sepsis.
As an observational study, this report could establish only an association, not causality. But there are several pathways by which sepsis and its treatment could plausibly lead to cognitive and physical decline. Sepsis could cause a direct inflammatory and hypoperfusion-mediated degradation of neurons and muscle fibers, which can be exacerbated by prolonged immobility. Hypotension and hypoperfusion can also contribute directly to brain injury, the investigators said.
This study was supported by several institutes of the National Institutes of Health, the Society of Critical Care Medicine, the Michigan Institute for Clinical and Health Research, the U.S. Department of Veterans Affairs, and the Tennessee Valley Geriatric Research, Education, and Clinical Center.
The investigators had no disclosures to report.