Delirium at admission was significantly associated with poor hospital outcomes in overall (combined three-site) analyses at discharge and 3-month follow-up, including new nursing home placement, death or new nursing home placement, and decline in ADLs. The contribution of delirium to these poor outcomes remained statistically significant even after controlling for age, gender, dementia, APACHE II score, ADL score, and IADL score in all of these analyses. The relationship of delirium at admission to death alone (35 events at discharge and 98 at 3-month follow-up) and to length of hospital stay were not statistically significant. The relatively small number of in-hospital deaths in the combined sample, with a limited power of 32% to detect a significant association, precluded drawing any definitive conclusions about the effect of delirium on hospital mortality. By 3-month follow-up, the number of deaths in the combined sample increased, yielding a statistically significant association of delirium and mortality in the crude analysis. However, after multivariate adjustment, the effect was diminished (adjusted OR 1.6; 95% CI 0.8, 3.2) and no longer achieved statistical significance. Future studies with increased sample sizes are needed to further examine the relationship of delirium to hospital and longer-term mortality.
The advantages of the current study include its multisite nature, which allowed us to maximize the number of our relatively infrequent study outcomes. This is one of the largest prospective studies of delirium to date. In addition, the replication of findings across sites with diverse study populations provides substantial evidence of the robustness of the overall conclusions. Finally, the standardized, prospective nature of the data collection enhanced the uniformity and validity of our measurements of delirium, control variables, and study outcomes.
Our findings of the long-term effect of delirium on poor outcomes corroborate recent studies on the long persistence and duration of delirium symptoms.7, 11, 41
These studies indicate that delirium and its effects may be much more enduring than previously believed, and that persistent partial forms of the syndrome are quite common—contributing further to the long-term deleterious effects of delirium.
Several important caveats and limitations of this study should be highlighted. First, the three study populations examined were disparate in many baseline characteristics (). Thus, homogeneity needed to be carefully assessed before combining site-specific results. Before pooling any data for combined analyses, we verified that the Breslow-Day test for homogeneity resulted in p≥ .10. The fact that the trends were similar across all sites, despite the diverse nature of the populations, supports the external validity of the findings.
Second, incident delirium (developing during hospitalization) was not examined as an additional prognostic variable because it was not assessed at all sites. In this study, only prevalent delirium (present at hospital admission) was examined, and those with incident delirium were classified as not delirious at admission. Because patients with incident delirium are more likely to behave like patients who had prevalent delirium rather than patients who never developed delirium, a potential misclassification bias was present, which most likely reduced the overall power of the study and diminished the magnitude of the associations found. The inclusion of incident delirium would most likely have increased the predictive power of our models. However, the fact that associations with the outcomes of interest were still found, despite the potential bias against them, supports the robustness of the findings.
Third, only one of many available measures of illness severity or comorbidity was included in these analyses. The APACHE II score was selected by the core group of investigators involved in the HOPE project,20
because of its well-accepted and widely used nature, its inclusion of both acute and chronic disease components, and the availability of comparative data from other samples of acutely ill elderly patients. Individual diagnoses were not examined as predictors of mortality because previous studies in older populations have shown that functional measures are stronger predictors of hospital outcomes than medical diagnoses or diagnosis-related groups.42, 43
The inclusion of functional and cognitive measures in our models provided additional control for important prognostic variables, which have been widely recognized to reflect the overall “burden of illness” and to exert substantial prognostic impact on outcomes of hospitalization.26, 42–44
Taken together, the APACHE II, functional, and cognitive measures provide a potent and plausible indicator of illness severity and comorbidity for older hospitalized patients.
Fourth, the large amount of missing data for our functional decline outcome may have limited our ability to draw definitive conclusions about the effect of delirium. In many cases, these missing interviews were unavoidable owing to unanticipated discharges, refusals of patients to be interviewed when discharge was imminent, and lack of availability of sufficient interview staff. In particular, the Chicago site had a large amount of missing data, and the group with missing data were considerably more likely to have poor prognostic predictors. Thus, it was not surprising that the delirious group did not have significantly more functional decline, because much of the data were missing from this group. However, the missing data from Yale and Cleveland were not related to our prognostic predictors and were equally distributed between delirious and nondelirious groups. Thus, the findings from these two sites should still be valid.35
Our findings suggest that delirium itself is an important prognostic determinant of hospital outcomes, rather than merely a marker of poor prognostic characteristics. Even after controlling for age, gender, dementia, APACHE II score, and functional measures (ADL and IADL scores), delirium emerged as an important independent predictor of new nursing home placement, death or new nursing home placement (combined outcome), and functional decline. Although the exact mechanisms by which delirium leads to these poor hospital outcomes need further investigation, the effect is plausible because delirium has been hypothesized to contribute to aspiration pneumonia; daytime somnolence with immobilization, pressure ulcers, and pulmonary emboli; use of psychoactive medications to control agitation and insomnia (with their attendant complications); injury; and related problems.45–48
Thus, delirium serves as an important prognostic variable for hospitalized older patients, and should potentially be considered in case-mix adjustment or risk stratification systems in hospitalized older populations. At a minimum, delirium should be included as a control variable in studies examining hospital outcomes in acutely ill older persons. Furthermore, we hope that the results of this study motivate clinicians to more closely monitor high-risk patients, avoid use of psychoactive medications in these patients, and aggressively monitor mental status for incipient delirium.