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

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.

Figure 1. Patient Cohorts

Note that this is a hospitalization-level analysis. As such, in the severe sepsis cohort, a single respondent might contribute a hospitalization to the Survivor cohort in one hospitalization, but be Lost to Follow-up after a future hospitalization. Thus the categorization of hospitalizations as included vs. excluded are mutually exclusive, but the categorizations of respondents (*) are not. The comparison hospitalizations were all first hospitalizations.

Figure 2. Cognitive Impairment among Survivors of Severe Sepsis at Each Survey Time Point

The (unadjusted) percentage of surviving patients suffering from cognitive impairment at each time point is shown, on the white background before sepsis and on the grey background after sepsis. 95% confidence intervals for the proportions are shown. Interpretive Example: These data demonstrate that in comparison to relatively stable rates before severe sepsis, the prevalence of moderate/severe cognitive impairment among eventual survivors increased from 6.1% (95% CI: 4.2%, 8.0%) before severe sepsis to 16.7% (95% CI: 13.8%, 19.7%) at the first survey after severe sepsis (p<0.001 by χ²). (See also Table 2.)

Figure 3. Functional Trajectories by Baseline Functioning

The mean number (unadjusted) of functional limitations of surviving cohort members is shown; surveys before sepsis are on the white background and interviews after sepsis are on the gray background. 95% confidence intervals for the means are shown. Interpretive Example: In the groups which had no limitations or mild/moderate limitations prior to sepsis, their trajectory had been stable before sepsis but they developed approximately 2 new limitations after severe sepsis. In contrast, patients with severe limitations at baseline, who had been steadily acquiring limitations over years prior to severe sepsis, had a modest increase from a baseline of 6.99 to 7.98 at their first survey post-sepsis. (See also Table 3.)

Figure 4. Change in Individual ADLs and IADLs

The proportion of patients with difficulty in each of the activities of daily living and instrumental activities of daily living is shown. The last survey before hospitalization is compared to the first survey after severe sepsis. Patients are grouped by functional status as in Figure 3. Interpretive Example: No single ADL or IADL accounted for the worsened functional status among survivors of severe sepsis. Instead, there was a wide range of new difficulties across the array of activities.