Cognitive Impairment Following ICU Hospitalization

Recent research has demonstrated the presence of cognitive impairment in many patients following Intensive Care Unit (ICU) long-term care. Although estimates differ, it appears that at least 1 in 3 survivors of critical illness will experience long-term cognitive impairment of a severity consistent with mild to moderate dementia. Among specific populations, such as patients with Acute Respiratory Distress Syndrome (ARDS), the prevalence of cognitive dysfunction is even greater and may be as high as 80%.

The acquired cognitive deficits reported by ICU survivors vary in nature and include difficulties in areas of attention/concentration, executive functioning (planning/organizing), memory (short-term, verbal, and visual), processing speed, and visuo-spatial construction. Deficits in these areas can have significant “real world” consequences such as problems returning to work, balancing a checkbook, finding a parked car, or even following a simple recipe. Future research is needed to more fully determine the causes, but investigators believe that cognitive impairment in ICU survivors may be related to a host of factors such as delirium, hypoxemia, advanced age, low education, inflammatory and coagulopathic derangements incurred during disease such as severe sepsis or the toxic effects of large amounts of sedative and analgesic medications on the brain.

Rates of mental health diseases such as depression and post-traumatic stress disorder (PTSD) are also disturbingly high in patients following critical illness. Clinically significant depression may occur in as many as 30% of ICU survivors, while between 15 and 40% of these patients experience symptoms of PTSD. The existence of such psychiatric syndromes, particularly when combined with cognitive impairment, typically results in a diminished quality of life.

The association between delirium and cognitive decline: a review of the empirical literature.

Jackson JC, Gordon SM, Hart RP, Hopkins RO, Ely EW.
Division of Allergy/Pulmonary/Critical Care Medicine, Center for Health Services Research, Vanderbilt University School of Medicine, Nashville, Tennessee 37232-8300, USA.

Delirium is a common neurobehavioral syndrome that occurs across health care settings which is associated with adverse outcomes, including death. There are limited data on long-term cognitive outcomes following delirium. This report reviews the literature regarding relationships between delirium and cognitive impairment. Psych Info and Medline searches and investigation of secondary references for all English language articles on delirium and subsequent cognitive impairment were carried out. Nine papers met inclusion criteria and documented cognitive impairment in patients following delirium. Four papers reported greater cognitive impairment among patients with delirium than matched controls. Four papers reported higher incidence of dementia in patients with a history of delirium. One study found 1 of 3 survivors of critical illness with delirium developed cognitive impairment. The evidence suggests a relationship between delirium and cognitive impairment, although significant questions remain regarding the nature of this association. Additional research on delirium-related effects on long-term cognitive outcome is needed.

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Research issues in the evaluation of cognitive impairment in intensive care unit survivors.

Jackson JC, Gordon SM, Ely EW, Burger C, Hopkins RO.
Division of Allergy, Pulmonary and Critical Care Medicine, T-1218 Medical Center North, Vanderbilt University School of Medicine, Nashville, TN 37232, USA. james.c.jackson@vanderbilt.edu

Neuropsychological assessment has been utilized extensively in the research of cognitive outcomes associated with medical illnesses, such as HIV, and post-surgical procedures, such as coronary artery bypass graft. However, few investigations of intensive care unit (ICU) survivors have examined cognitive function as a clinical outcome. Significant clinical questions exist regarding the impact of critical illness on long-term cognitive function. Many of these questions can be systematically evaluated through the use of standardized neuropsychological assessment instruments within the context of well designed, prospective research trials. This review will provide information for clinical researchers interested in the study of neuropsychological outcomes in intensive care unit survivors ( a comparison article in this issue will address clinical issues related to cognitive functioning).

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Clinical identification of cognitive impairment in ICU survivors: insights for intensivists.

Gordon SM, Jackson JC, Ely EW, Burger C, Hopkins RO.
Center for Health Services Research, Vanderbilt University, 6100 Medical Center East, Nashville, TN 37232, USA.

BACKGROUND: A growing body of research has demonstrated the presence of ongoing cognitive impairment in large numbers of ICU survivors. OBJECTIVE: This review offers a practical framework for practicing intensivists and those following patients after their ICU stay for the identification of cognitive impairment in ICU survivors. CONCLUSIONS: Early detection of cognitive impairment in critically ill patients is an important and achievable goal, but overt cognitive impairment remains unrecognized in most cases. However, it can be identified by objective (test scores) or subjective evidence (clinical judgment, patient observation, family interaction).

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ICU Delirium and Mortality

Despite similar baseline characteristics in a cohort of 275 mechanically ventilated patients, delirium was an independent predictor of higher 6-month mortality and longer stay even after adjusting for relevant covariates including coma and sedative/analgesic medications. See the Figures below and the comment from the multivariable analysis.

Reference: Ely, E.W., Shintani, A., Truman, B., Speroff, T., Gordon, S.M., Harrell, F.E., Inouye, S.K., Bernard, G.R., Dittus, R.S. Delirium as a predictor of mortality in mechanically ventilated patients in the intensive care unit. JAMA. 291(14): 1753-1762, 2004. (see link on References page)

Figure Legend. Delirium versus Six-month Survival. These Kaplan-Meier plots show the relationship between delirium and 6-month survival. (a) Never vs. Ever Delirium (according to whether or not the patient ever developed delirium in the ICU) (b) Clinical Severity (subdividing the never and ever delirium groups in order to better understand the phenomenology of delirium). The never delirium group, composed of those who were always normal and those who were coma-normal (e.g., deeply sedated and then normal when drugs stopped) had higher survival than the ever delirium group, which was composed of those with delirium only and delirium-coma.

NOTE: After using Cox proportional hazard regression models with time-dependent covariates (multivariable analysis) to adjust for covariates, delirium was independently associated with higher 6-month mortality [adjusted hazard ratio (HR) =3.2 (1.4-7.7), P=0.008], and longer hospital stay [adjusted HR=2.0 (1.4-3.0), P<0.001]. ICU Delirium was also independently associated a longer post-ICU (ward) stay (adjusted P=0.009), fewer days alive and free of mechanical ventilation (adjusted P=0.03), and a higher incidence of cognitive impairment at hospital discharge (adjusted P=0.002).

ICU Delirium and Hospital Length of stay

In this patient cohort, the majority of patients developed delirium in the ICU, and delirium was the strongest independent determinant of length of stay in the hospital. Further study and monitoring in the ICU of this complication and modifiable risk factors for its development are warranted. (see table below)

Reference: Ely EW, Gautam S, Margolin R, Francis J, May L, Speroff T et al. The impact of delirium in the Intensive care unit on hospital length of stay. Intensive Care Med 2001; 27:1892-1900. (see link on References page)

Multiple Linear Regression Model
Predictors of Lengths of Stay in ICU and Hospital*

Using multivariate analysis, delirium was the strongest predictor of length of stay in the hospital (P=0.006) even after adjusting for severity of illness, age, gender, race, and days of benzodiazepine and narcotic drug administration.

* Dependent variables were log transformed prior to analysis, but estimates have been back transformed into original scale for presentation. Beta coefficients can be interpreted as average stay in days (intercept) or expected difference in stay between patients with and without the listed condition; 95% C.I. = 95% confidence intervals; APACHE II = denotes Acute Physiology and Chronic Health Evaluation II score [21]; Drug Days = number of days that a patient received psychoactive medications designated in Methods

** Delirium with onset in the ICU (i.e., “ICU-onset” delirium), duration measured in days. The adjusted r2 for delirium in relation to the ICU stay was 0.37, and for the hospital stay the adjusted r2 was 0.55.

ICU Delirium and Cost

Higher severity and duration of delirium were associated with incrementally greater costs (all p<0.001). Using multivariable analysis to adjust for age, comorbidity, severity of illness, degree of organ dysfunction, nosocomial infection, hospital mortality, and other potential confounders, delirium was associated with 39% higher ICU (95% CI, 12% to 72%) and 31% higher hospital (95% CI, 1% to 70%) costs. Therefore, we conclude that delirium is a common clinical event in mechanically ventilated medical ICU patients and is associated with significantly higher ICU and hospital costs. Future efforts to prevent or treat ICU delirium have the potential to improve patient outcomes and reduce costs of care. (see figures below)

REFERENCE: Milbrandt, E.B., Deppen, S., Harrison, P.L., Shintani, A.K., Speroff, T., Stiles, R.A., Truman, B., Bernard, G.R., Dittus, R.S., Ely, E.W. Costs Associated with Delirium in Mechanically Ventilated Patients. Crit. Care Med. 32 (4):955-962, 2004. (see link on References page)

Median ICU and Hospital Cost Per Patient

This histogram shows cost according to clinical categorization of “ever delirium” vs. “never delirium.” Delirium was significantly associated with increased ICU and hospital cost.

Median ICU and Hospital Cost Per Patient

This histogram shows cost according to cumulative delirium severity indices. Increasing delirium severity was significantly associated with incrementally greater ICU and hospital cost.

ICU Delirium and Dementia Interaction

In this ICU cohort, delirium was a frequent complication in the 185 ICU patients 65 years and older who were studied, and we found that delirium often persisted beyond the ICU stay. Delirium in older ICU persons was a dynamic and complex process as shown in the manuscript. Dementia was an important predisposing risk factor for the development of delirium in this population during and after the ICU stay (see the Figure below).

Reference: McNicoll L, Pisani MA, Zhang Y, Ely EW, Siegel MD, Inouye SK. Delirium in the intensive care unit: occurrence and clinical course in older patients. J Am Geriatr Soc 2003; 51:591-598. (see link on References page)

* Indicates statistical significance at p<0.05 for comparison of groups with and without dementia. NOTE: Patients with dementia were 40% more likely to be delirious (RR 1.4, 95% CI 1.1, 1.7), even after controlling for comorbidity, baseline functional status, severity of illness, and invasive procedures.