Long-term cognitive impairment and functional disability among survivors of severe sepsis.

Iwashyna, Theodore J.; Ely, E. Wesley; Smith, Dylan M.; Langa, Kenneth M.

doi:10.1001/jama.2010.1553

Cited by 2,582Sepsis Diagnosis and TreatmentIntensive Care Unit Cognitive DisordersDementia and Cognitive Impairment Research

Long-term cognitive impairment and functional disability among survivors of severe sepsis.

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Iwashyna, Theodore J., Ely, E. Wesley, Smith, Dylan M., Langa, Kenneth M.·2010·JAMA

DOI 10.1001/jama.2010.1553PMC PMC3345288

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Abstract

CONTEXT: Cognitive impairment and functional disability are major determinants of caregiving needs and societal health care costs. Although the incidence of severe sepsis is high and increasing, the magnitude of patients' long-term cognitive and functional limitations after sepsis is unknown. OBJECTIVE: To determine the change in cognitive impairment and physical functioning among patients who survive severe sepsis, controlling for their presepsis functioning. DESIGN, SETTING, AND PATIENTS: A prospective cohort involving 1194 patients with 1520 hospitalizations for severe sepsis drawn from the Health and Retirement Study, a nationally representative survey of US residents (1998-2006). A total of 9223 respondents had a baseline cognitive and functional assessment and had linked Medicare claims; 516 survived severe sepsis and 4517 survived a nonsepsis hospitalization to at least 1 follow-up survey and are included in the analysis. MAIN OUTCOME MEASURES: Personal interviews were conducted with respondents or proxies using validated surveys to assess the presence of cognitive impairment and to determine the number of activities of daily living (ADLs) and instrumental ADLs (IADLs) for which patients needed assistance. RESULTS: Survivors' mean age at hospitalization was 76.9 years. The prevalence of moderate to severe cognitive impairment increased 10.6 percentage points among patients who survived severe sepsis, an odds ratio (OR) of 3.34 (95% confidence interval [CI], 1.53-7.25) in multivariable regression. Likewise, a high rate of new functional limitations was seen following sepsis: in those with no limits before sepsis, a mean 1.57 new limitations (95% CI, 0.99-2.15); and for those with mild to moderate limitations before sepsis, a mean of 1.50 new limitations (95% CI, 0.87-2.12). In contrast, nonsepsis general hospitalizations were associated with no change in moderate to severe cognitive impairment (OR, 1.15; 95% CI, 0.80-1.67; P for difference vs sepsis = .01) and with the development of fewer new limitations (mean among those with no limits before hospitalization, 0.48; 95% CI, 0.39-0.57; P for difference vs sepsis <.001 and mean among those with mild to moderate limits, 0.43; 95% CI, 0.23-0.63; P for difference = .001). The declines in cognitive and physical function persisted for at least 8 years. CONCLUSIONS: Severe sepsis in this older population was independently associated with substantial and persistent new cognitive impairment and functional disability among survivors. The magnitude of these new deficits was large, likely resulting in a pivotal downturn in patients' ability to live independently.

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Key information from hospitalization is often missing on hospital discharge documentation.
“Key information from hospitalization is often missing on hospital discharge documentation (615-618).”
From Surviving Sepsis Campaign: International Guidelines for Management of Sepsis and Septic Shock 2021. (2021) · cites this paper as [617]
The Methods (Data Source) describe information abstracted from Medicare claims, and the Discussion addresses limitations of the sepsis study. Neither discusses whether key hospitalization information is missing from discharge documentation. Searches for missing information and discharge summaries found no relevant passage; page numbers were not available in our copy. (LLM, conf=0.76)
Experimental — accuracy not yet measured
Early administration of enteral nutrition in patients with sepsis and septic shock has potential physiologic advantages related to maintenance of gut integrity, prevention of intestinal permeability, dampening of the inflammatory response, and modulation of metabolic responses that may reduce insulin resistance.
“The early administration of enteral nutrition in patients with sepsis and septic shock has potential physiologic advantages related to the maintenance of gut integrity and prevention of intestinal permeability, dampening of the inflammatory response, and modulation of metabolic responses that may reduce insulin resistance (529,530).”
From Surviving Sepsis Campaign: International Guidelines for Management of Sepsis and Septic Shock 2021. (2021) · cites this paper as [529]
The Discussion (page unavailable) discusses inflammation and possible causes of long-term cognitive and physical decline after sepsis, not enteral nutrition. Searches for early enteral nutrition, gut integrity, intestinal permeability, and insulin resistance found no passage in our copy addressing the claimed physiologic advantages. (LLM, conf=0.78)
Experimental — accuracy not yet measured
Many sepsis survivors experience short and/or long-term sequelae such as cognitive and/or physical disability, with ongoing recovery persisting for months to years.
“Many sepsis survivors experience short and/or long-term sequela such as cognitive and/or physical disability, with ongoing recovery persisting for months to years [620].”
From Surviving sepsis campaign: international guidelines for management of sepsis and septic shock 2021 (2021) · cites this paper as [620]
Sepsis is associated with newly acquired cognitive impairment and functional disability amongst survivors.
“Sepsis is associated with newly acquired cognitive impairment and functional disability amongst survivors [620].”
From Surviving sepsis campaign: international guidelines for management of sepsis and septic shock 2021 (2021) · cites this paper as [620]
Inflammatory challenges are associated with risk for development of dementia-related symptoms, with increased pro-inflammatory cytokine levels.
“Some studies have reported inflammatory challenges as an associated risk factor for the development of dementia-related symptoms, as they show increased pro-inflammatory cytokines levels [147, 148].”
From Brain-Derived Neurotrophic Factor in Brain Disorders: Focus on Neuroinflammation (2019) · cites this paper as [147]

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Self-citation
Evaluation of Cognitive and Functional Status Among Survivors of Sepsis in a Tertiary Care Hospital in South India (CAFDASS)
Ninan, G. A. (2020)

Authors: Iwashyna, T. J., Ely, E. W., Smith, D. M., & Langa, K. M.
Affiliations: University of Michigan (US)
Vanderbilt University (US)
Stony Brook University Hospital (US)
ORCID: Iwashyna, Theodore J.
Ely, E. Wesley
Smith, Dylan M.
Langa, Kenneth M.
Venue: JAMA
Publisher: American Medical Association (AMA)
Published: 2010-10-27
Volume: 304
Issue: 16
Pages: 1787
ISSN: 0002-9955 (ISSN-L)
0098-7484
DOI: 10.1001/jama.2010.1553
PMC: PMC3345288
OpenAlex: W2098572294
Cited by: 2,582
References: 56
Citations by year: 2026: 162 · 2025: 172 · 2024: 205 · 2023: 190 · 2022: 212 · 2021: 260 · 2020: 223 · 2019: 200 · 2018: 163 · 2017: 151 · 2016: 140 · 2015: 159 · 2014: 116 · 2013: 110 · 2012: 71
FWCI: 52.52
Type: journal article
Language: en
Open access: green
www.ncbi.nlm.nih.gov
Locations: JAMA (publishedVersion)
PubMed (publishedVersion)
Europe PMC (PubMed Central) (acceptedVersion)
PubMed Central (acceptedVersion)
Funders: U.S. Department of Veterans Affairs (U01 AG09740)
National Institutes of Health
Michigan Institute for Clinical and Health Research (UL 1RR024986)
Geriatric Research Education and Clinical Center
National Institute on Aging (U01 AG 09740, R01AG030155, K23AG001023, AG027472, R01AG027472, U01AG009740, R01AG027010)
National Heart, Lung, and Blood Institute (K08HL091249)
National Institute of Diabetes and Digestive and Kidney Diseases (P60DK020572, P60 DK 20572)
National Center for Research Resources (UL1RR024986)
NIH Clinical Center
Topics: Health Sciences › Medicine › Epidemiology › Sepsis Diagnosis and Treatment
Health Sciences › Medicine › Critical Care and Intensive Care Medicine › Intensive Care Unit Cognitive Disorders
Health Sciences › Medicine › Psychiatry and Mental health › Dementia and Cognitive Impairment Research
Keywords: severe sepsis, cognitive impairment, functional disability, activities of daily living, instrumental activities of daily living, long-term outcomes, older adults, hospitalization, Health and Retirement Study, Medicare claims data, health care costs
MeSH terms: Activities of Daily Living, Aged, Aged, 80 and over, Cognition Disorders, Female, Persons with Disabilities, Disabled Persons, Health Status, Hospitalization, Humans, Male, Prospective Studies, Severity of Illness Index, United States, Case-Control Studies, Survivors, Sepsis

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Long-term cognitive impairment and functional disability among survivors of severe sepsis.

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