Patients over 65 years of age who have severe sepsis have a significantly high risk of long-term cognitive and physical functioning problems, say researchers from University of Michigan Medical School, Ann Arbor in the medical journal JAMA (Journal of the American Medical Association). According to the Centers for Disease Control and Prevention about 750,000 people each year have severe sepsis in America. A significant number of them die.

Sepsis, also known as blood stream infection is when bacteria, other infections or organisms or their toxins get into the bloodstream and sometimes reach organs and tissues in the body. Sepsis is a systemic (whole body) response to an infection, which can lead to organ dysfunction, loss of limbs and death. Sepsis can be triggered by a viral, bacterial, fungal or parasitic infection. It may occur after an accident (trauma), surgery, burns, or such illnesses as pneumonia or cancer.

The authors wrote:

Although severe sepsis is the most common non-cardiac cause of critical illness, the long-term impact of severe sepsis on cognitive and physical functioning is unknown.

Theodore J. Iwashyna, M.D., Ph.D. and team set out to determine whether having severe sepsis raised the risk of long-term cognitive and physical function impairment among patients who survived. Their study involved 1,194 individuals with 1,520 hospitalizations for severe sepsis. They gathered data from the Health and Retirement Study, 1998-2006, which is has nationally representative data on US residents.

Their study also included 9,223 respondents who were assessed for cognitive and physical functioning when the study began. 516 survived a severe sepsis episode while 4,517 were in hospital and survived a non-sepsis event. They were followed up at least once.

As well as assessing their cognitive function, so were their ADLS (activities of daily living) and IADLs (instrumental activities of daily living) for which they needed assistance.

Survivors were hospitalized at an average age of 76.9 years.

They found that the risk of acquiring moderate to severe cognitive impairment was 3.3 times higher among patients who had survived severe sepsis, compared to others who had been hospitalized for non-sepsis episodes.

Among patients with no, mild or moderate pre-existing functional limitations, 1.5 new functional limitations were added for each episode of sepsis.

Those who had been hospitalized for non-sepsis episodes were found to have no increased risk of developing moderate to severe cognitive impairment.

The authors wrote:

Cognitive and functional declines of the magnitude seen after severe sepsis are associated with significant increases in caregiver time, nursing home admission, depression, and mortality. 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.

The authors believe that severe sepsis among the elderly in America adds 20,000 new annual cases of moderate to severe cognitive impairment.

The researchers wrote:

Thus, an episode of severe sepsis, even when survived, may 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.

Future research to identify mechanisms leading from sepsis to cognitive impairment and functional disability - and interventions to prevent or slow these accelerated declines - is especially important now given the aging of the population.

Accompanying Editorial: The Lingering Consequences of Sepsis - A Hidden Public Health Disaster?

Derek C. Angus, M.D., M.P.H., a contributing JAMA editor, and also from the University of Pittsburgh School of Medicine, wrote:

First, the information in this study can help physicians when assessing care options and discussing outcomes with patients and families. Even if clinicians do not know why patients who develop sepsis experience a decline in function, it is clear that many patients do.

Second, the development of pre-clinical models could help establish a better understanding of causality, potential mechanisms, and therapeutic targets. Current models of sepsis only crudely mimic sepsis in the modern ICU and rarely afford an assessment of long-term outcomes among survivors.

Third, a number of relatively simple strategies used in other areas of medicine to promote physical rehabilitation and minimize the effects of neurocognitive dysfunction might be adaptable to the ICU and post-ICU setting and ought to be evaluated in clinical trials.

Fourth, the traditional end point of day 28 all-cause mortality used in the evaluation of any therapy for sepsis should be replaced by longer-term survival data and functional outcomes. Assessing detailed physical and cognitive function is challenging and costly in the multicenter trial environment. However, the larger cost may be from failure to measure these outcomes and miss important benefits or harms of therapies on the lingering consequences of sepsis.

"Long-term Cognitive Impairment and Functional Disability Among Survivors of Severe Sepsis"
Theodore J. Iwashyna, MD, PhD; E. Wesley Ely, MD, MPH; Dylan M. Smith, PhD; Kenneth M. Langa, MD, PhD
JAMA. 2010;304(16):1787-1794. doi:10.1001/jama.2010.1553

Written by Christian Nordqvist