Severe Sepsis Associated With Development of Cognitive, Functional Disability Among Older Patients

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Older adults who survived severe sepsis were more likely to develop substantial cognitive impairment and functional disability, according to a study in the Oct. 27 issue of JAMA.

Hundreds of thousands of patients endure severe sepsis each year in the United States, according to background information in the article. 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, the authors write.

Theodore J. Iwashyna, MD, PhD, of the University of Michigan Medical School, Ann Arbor, and colleagues examined whether an episode of severe sepsis increased the odds of subsequent worsened cognitive impairment and functional disability among survivors. The study involved 1,194 patients with 1,520 hospitalizations for severe sepsis from the Health and Retirement Study, a nationally representative survey of U.S. residents (1998-2006). A total of 9,223 respondents had a cognitive and functional assessment at the beginning of the study and also had linked Medicare claims; 516 survived severe sepsis and 4,517 survived a non-sepsis hospitalization to at least one follow-up survey and were included in the analysis. The presence of cognitive impairment was assessed, as was the number of activities of daily living (ADLs) and instrumental ADLs (IADLs) for which patients needed assistance. The average age of survivors at hospitalization was 76.9 years.


The researchers found that the prevalence of moderate to severe cognitive impairment increased 10.6 percentage points among patients who survived severe sepsis, and their odds of acquiring moderate to severe cognitive impairment were 3.3 times higher. Also, a high rate of new functional limitations was seen following sepsis, with an additional average increase of 1.5 new functional limitations per person among those with no or mild to moderate pre-existing functional limitations.

Non-sepsis general hospitalizations were associated with no change in moderate to severe cognitive impairment and with the development of fewer new limitations.

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, under-recognized public health problem with major implications for patients, families, and the health care system.

The authors add that given published dementia and sepsis incidence rates for those ages 65 years or older in the United Slates, their results suggest that nearly 20,000 new cases per year of moderate to severe cognitive impairment in the elderly may be attributable to sepsis. 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 disabilityand interventions to prevent or slow these accelerated declinesis especially important now given the aging of the population.

Derek C. Angus, MD, MPH, of the University of Pittsburgh School of Medicine, and contributing editor to JAMA, writes in an accompanying editorial, The Lingering Consequences of Sepsis: A Hidden Public Health Disaster? that there are several important implications of this study.

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.

References: JAMA. 2010;304[16]:1787-1794; and JAMA. 2010;304[16]:1833-1834.