This study provides new evidence for the importance of the number of days of ICU delirium as a risk factor for mortality. Previous ICU studies have found an association with the presence of delirium and mortality (6
) but not between number of days of delirium in ICU and mortality. The results of this study have important implications for the older hospitalized populations. Delirium should be considered as a significant, serious problem and treated as a possible contributor to mortality risk.
Delirium or brain dysfunction has often been thought of as a consequence of critical illness that would resolve when the acute illness resolved. Evidence is mounting that delirium itself is a strong predictor of increased length of mechanical ventilation, longer ICU stays, increased cost, prolonged neuropsychological dysfunction, and mortality (5
). Our results support those shown by Ely and colleagues that ICU delirium in mechanically ventilated patients is associated with 6-month mortality (6
). Lin and colleagues demonstrated increased hospital mortality in 106 mechanically ventilated patients with delirium, but there was no difference in the mean duration of ICU delirium between survivors and nonsurvivors (11
). In a small cohort of mechanically ventilated patients, days of delirium were associated with persistent cognitive impairment at 3 months (34
). Our work supports the findings of Ely (6
) and is novel in that it demonstrates that the duration of ICU delirium is associated with mortality up to 1 year after ICU admission even after adjusting for important potential confounders. The HR of 1.10 can be interpreted as saying that “each day of delirium in the ICU increases the hazard of mortality by 10%.” The cumulative effect of multiple days is multiplicative rather than additive.
Although delirium is a syndrome and there are likely multiple etiologic mechanisms that may lead to the clinical diagnosis, there is little knowledge concerning the pathogenesis of delirium in the ICU. We cannot point to a specific pathogenic process responsible for the association between delirium and increased mortality, but the pathogenic mechanisms need to be elucidated for the field to move forward.
Other factors significantly associated with 1-year mortality in our multivariable model, such as age, severity of illness, comorbidities, and impairment in IADLs, are consistent with other research on older hospitalized patients.
Although there are several studies that examine algorithms or medications for treating delirium in older hospitalized patients, these interventions have not been examined in an ICU setting (35
). Although prevention of delirium is an ideal approach and an area of ongoing investigation, many older patients present to the ICU with delirium. In one study, 72% of the patients had delirium on their first ICU day (30
). Although prevention of delirium within the ICU may be difficult, it may be possible to reduce delirium duration or severity. Schweickert and colleagues recently demonstrated a reduction in ICU delirium days with a protocol of early mobilization and occupational therapy (38
Although treatment of the underlying critical illness is the first step in resolving delirium, there are ICU-related factors that can be addressed. One possibility that may be important in reducing delirium duration is a reexamination of the way we provide anxiety and pain control in the ICU setting. Several studies have documented the risk of delirium occurrence with the use of psychoactive medications in the ICU (3
). Recently the receipt of benzodiazepines or opioids has been associated with increased delirium duration in a cohort of older ICU patients (30
). A recent randomized controlled trial demonstrated that patients who received dexmedetomidine versus midazolam for sedation had less delirium (40
The impact of reducing delirium duration on outcomes needs to be investigated further. Though current Critical Care and Psychiatric society guidelines recommend using antipsychotics to treat delirium, there are limited data to support these recommendations (41
). Although antipsychotics, such as haloperidol, are often given to treat delirium, especially agitated delirium, there are no randomized controlled trials of delirium treatment in critical illness, and there are no FDA-approved medications for delirium treatment. If the number of days of ICU delirium is increasing mortality up to 1 year after ICU admission, prevention and treatment strategies need to be developed.
ICU admissions are an expensive component of healthcare, accounting for 1% of the US gross domestic product annually (45
). In a study by Milbrandt, after controlling for potentially confounding variables, mechanically ventilated patients with one episode of delirium had a 40% increase in ICU and total hospital costs compared with patients with no delirium (8
). In this study, the presence of delirium and severity, as measured by number of days of delirium, were independently associated with increased ICU and hospital costs. In addition to a possible mortality reduction, reducing cost is an important reason to investigate strategies aimed at reducing delirium duration.
A major strength of this study is the accurate delirium detection using validated methods that included CAM-ICU and chart review for delirium. A second strength is the very high participation rate and the small amount of missing data. There are several limitations in this study. First, this was a single-site study, and although the study cohort reflected a broad range of diagnoses, other types of critically ill patients should be investigated for mortality risk from chronic delirium, including patients in surgical ICUs. Second, there are limitations associated with the definition of duration of ICU delirium. The count of the number of days of ICU delirium might have been attenuated by deaths in the ICU or by discharge from the ICU. However, we investigated the possible impact of these limitations with sensitivity analyses and bootstrapping techniques, and these supplementary findings were consistent with our reported multivariable model results.
As we begin to confront a rapidly aging society, adequate high-quality disease management and care is needed. Given that a larger number of days of ICU delirium are associated with higher mortality, increased efforts to prevent, detect, and treat delirium are needed. Without appropriate preventive and management strategies for delirium, the burgeoning older population will face an increased burden of delirium and even higher mortality.