The results of this study indicate that delirium persists and is associated with a high one-year mortality rate. Patients whose delirium persisted were nearly three times more likely to die during the one-year follow-up compared to patients who resolved their delirium, even after adjusting for the confounding effects of age, gender, comorbidity, functional status and dementia. Notably, the contribution of persistent delirium to increased mortality is significant and substantial among individuals with and without dementia.
Compared to the one-year (2004) mortality rates of acute conditions such as heart disease (27%) and influenza/pneumonia (3%), the mortality rate for persistent delirium is substantially higher.42
Furthermore, for survivors, failure to recover function often leads to long-term nursing home placement, 43
decreased quality of life and increased healthcare expenditures since the resolution of delirium in the PAC setting is a prerequisite for functional recovery.44
The vast majority of previous research on the association between delirium and mortality has been done in the hospital setting and the findings are inconsistent. Although most studies reported an association between delirium and mortality in unadjusted analyses, not all associations persisted after adjusting for confounding factors. Dolan et al. 12
, Francis et al. 45
, Inouye et al. 14
, and Pompei et al. 20
reported that delirium was not significantly associated with mortality after adjusting for confounding factors, but many of these studies may have been under-powered for examination of mortality. Kakuma et al. 15
, Kelly et al. 16
, Metitieri et al. 19
, McCusker et al. 17
and Rockwood et al. 21
reported that delirium was associated with an increased risk of death even after adjusting for confounding factors.
Marcantonio et al.22
compared six-month mortality rates for 504 subjects with either delirium (n=188), subsyndromal delirium (n=246) or no delirium (n=70). Subjects with delirium were 5.2 [95%CI 1.8–14.5] times more likely to die compared to subjects without delirium, independent of age, preexisting dementia and medical comorbidity. The current study differs from the Marcantonio et al.22
study in that all subjects were delirious at admission and were followed prospectively, regardless of setting, to see if delirium persisted. In all previous studies, delirium was defined as present or absent at a single time point. Results from our current analyses support and extend previous studies by examining changes in delirium over time at four follow-up time-points.
The focus of this study was to examine the association between persistent delirium and mortality while controlling for factors that could potentially confound this association. Our focus was not to examine the direct association of these confounding factors with delirium or mortality, or the potential role these factors might play in the causal chain between persistent delirium and mortality.
One unique aspect distinguishing this study from previous studies is that it focused on persistent delirium. Traditionally, delirium has been viewed as a transient event. This study adds to the accumulating body of evidence 1–3, 8, 44, 46, 47
that delirium may not be a transient, short-lived phenomenon.
Our results have substantial clinical relevance. Notably, we found an increased risk of mortality with the presence of delirium over time. When delirium resolves, the risk of death diminishes thereafter (). This temporal association provides stronger evidence of an etiologic link between delirium and mortality than previous studies.
Our results suggest that delirium may not merely be a marker for sicker individuals who are going to die of their underlying disease, but rather that delirium may confer its own independent mortality risk.48
The delirious individual is unable to effectively interact with the environment, leading to a vicious cycle of worsening debility and adverse events that may result in death. Resolution of delirium at any time is a worthy clinical goal and efforts should continue throughout the continuum of care.
The strengths of this study deserve comment. First, trained research personnel, using an established and validated diagnostic algorithm (CAM), performed the delirium assessments. Second, our study used repeated time assessments of delirium thus allowing the examination of delirium and its association with mortality over time. Third, our study involved detailed interviews with family and facility caregivers to assess baseline characteristics and important covariates. Fourth, mortality data was obtained from 3 sources: the National Death Index, medical record reviews, and proxy informants and corroborated across the sources. Fifth, although the cohort was initially enrolled in the PAC setting, patients were interviewed at follow-up regardless of residence. Finally, we screened nearly 5000 new PAC admissions with detailed mental status assessments, and the final sample represents the largest cohort of delirious patients ever enrolled in a research study.
This study has several limitations. Our data were collected on patients with delirium admitted to PAC facilities in a single metropolitan region and our findings may not generalize to patients with delirium recruited in other settings or locations. This study did not have information on other potential confounding factors such as drug use (e.g., antipsychotics) or nutritional status. Dementia status was identified in the discharge summary or in a discussion with the family and this could lead to an under-reporting. Also, a small percent of patients without follow-up assessment were excluded and it was not possible to determine if their delirium resolved. Finally, despite the adjustment for confounders, it is possible that failure to resolve delirium is an exceptionally good marker of frailty or comorbidity. Thus, rather than conferring direct mortality risk, delirium may serve as a marker for impaired homeostasis in the elderly and may have prognostic value independent of the usual markers of illness severity.13
In conclusion, delirium is persistent and associated with a nearly three-fold increase in one-year mortality, independent of age, gender, morbidity, functional status and dementia. This association is present independent of dementia status. Future studies should examine the association of persistence of subsyndromal delirium and one year mortality. 22
Future research is needed to develop effective interventions designed to resolve delirium in a timely manner. Before interventions can be targeted at delirious patients, we need to better understand what is different about residents who remain delirious and what factors contribute to their death. Such factors include chronic health conditions, medications and aggressiveness of medical care. These interventions may reduce the high one-year mortality associated with unresolved delirium in the PAC, community and other settings.