Long-term Cognitive Impairment and Functional Disability Among Survivors of Severe Sepsis

By Theodore J. Iwashyna, E. W. Ely, Dylan M. Smith, Kenneth M. Langa. Journal of the American Medical Association (JAMA), 2010

2,260 citations recorded by the source corpus.

Context Cognitive impairment and functional disability are major determinants of caregiving needs and societal healthcare costs. Although the incidence of severe sepsis is high and rising, especially among older adults, the magnitude of patients’ long-term cognitive and functional limitations after sepsis is unknown. Objective Determine the change in cognitive impairment and physical functioning among patients who survive severe sepsis, controlling for their pre-sepsis functioning. Design Prospective cohort. Setting The Health and Retirement Study (HRS) conducted interviews with a nationally representative cohort of older Americans every 2 years during 1998–2006. There were 9,223 HRS respondents with linked Medicare claims who had a baseline cognitive and functional assessment 1998–2004. Patients 1,520 hospitalizations for severe sepsis occurred in 1,194 patients, as ascertained from Medicare claims linked to the HRS. Of this group, 516 individuals survived 623 episodes of severe sepsis and had at least 1 follow-up survey, and were analyzed here. A comparison group included 5,574 respondents who experienced a non-sepsis general hospitalization in the study period, of whom 4,517 survived to at least 1 follow-up survey for analysis here. Interventions None Main Outcomes Measures Personal interviews with respondents and proxies were used to assess cognitive impairment using the validated modified-TICS and IQCODE questionnaires. Disability was measured by the number of ADLs and IADLs for which patients needed assistance. We used within-person regression to identify the association of sepsis with changes in the trajectory of disability with up to 8 years of post-sepsis follow-up. Results Survivors’ mean age at hospitalization was 76.9 years. The prevalence of moderate/severe cognitive impairment increased 10.6 percentage points among patients who survived severe sepsis, an odds ratio of 3.33, (95% 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 (mean 1.57 new limitations [95% CI: 0.99, 2.15], where no effect would be 0 new limitations) and in those with mild/moderate limitations before sepsis (mean 1.50 new limitations [95% CI: 0.87, 2.12]). In contrast, non-sepsis general hospitalizations were associated with no change in moderate/severe cognitive impairment (OR: 1.15, 95% CI: 0.80, 1.67, differences versus sepsis p=0.012) and much smaller changes in functional limitations (mean 0.48 [95% CI: 0.39, 0.56] and 0.43 [95% CI: 0.23, 0.63] new limitations among those with no and mild/moderate limits before hospitalization, respectively; differences versus sepsis p<0.001 and p=0.001). The declines in cognitive and physical function persisted for up to 8 years of follow-up. Conclusion 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. Identifying modifiable components of hospital and rehabilitation care to prevent these disabilities would be valuable for patients and their families.

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Citations in the corpus

Epidemiology of severe sepsis (2013, background): “For example, elderly survivors of severe sepsis are up to three times as likely to develop persistent cognitive and functional impairments compared with elderly controls not hospitalized for sepsis.(75) Acute infections may worsen pre-existing chronic diseases or new chronic diseases may emerge.”
Enhancing Recovery From Sepsis (2018, unknown): “Overall, one-sixth experience severe persistent physical disability or cognitive impairment, and one-third die during the following year.(6,12) Half of deaths in the year after hospitalization for sepsis are related to complications of sepsis, while half are explained by age or preexisting comorbidi”
Acute skeletal muscle wasting in critical illness. (2013, background): “Period ventilated, median (range), d 10 (2-62) 8.”
Improving long-term outcomes after discharge from intensive care unit: Report from a stakeholders' conference* (2012, background): “The few existing studies with data beyond 2-yr follow-up have been instrumental in demonstrating areas of true long-term morbidities (52), and the potential recurrence of morbidities in survivors followed-up for 5–8 yrs after ICU discharge (16, 53, 54).”
Sepsis: current dogma and new perspectives. (2014, background): “(Kaukonen et al., 2014), annually some 500,000 new cases enter the survivor pool; these survivors are at risk for early death, with 5 year mortality rates as high as 75% (Iwashyna et al., 2010).”
Prognostic Accuracy of the SOFA Score, SIRS Criteria, and qSOFA Score for In-Hospital Mortality Among Adults With Suspected Infection Admitted to the Intensive Care Unit (2017, methodology): “These included (1) mechanically ventilated vs nonventilated patients, (2) using multiple imputation to account for missing data, (3) using a Glasgow Coma Scale score less than 14 vs less than 15 for calculation of qSOFA, (4) having patients with chronic organ dysfunction either excluded or assigned ”
Machine Learning and Decision Support in Critical Care (2016, methodology): “[28] study quality of life among severe sepsis survivors by using an already-established link between the Health Retirement Study and Medicare files for patients admitted to ICUs.”
Long-term complications of critical care (2011, background): “Furthermore, a study of patients 65 yrs old with severe sepsis showed a 4-fold increase in new, post-ICU moderate or severe cognitive impairment lasting up to 8 yrs (113).”
Clinical review: intensive care unit acquired weakness (2015, background): “Several other studies have confirmed such persisting physical limitations [97–101] as well as reduced quality of life following ARDS, sepsis, and mechanical ventilation [97, 98, 102], in addition to impaired return to work [92, 95, 96] and cognitive dysfunction [103].”