Delirium, Depression and Long-Term cognitive Impairment

Introduction Over the last decade, we are seeing increased survival rates from critical care stays. However, critical care survivors are at increased risk for long-term physical, psychological, and cognitive impairments. While there is substantial work examining how premorbid medical and demographic factors influence adverse long-term outcomes, less is known about how pre-existing psychiatric illnesses such as depression may influence ICU course and post-ICU outcomes. Delirium is a key negative prognostic indicator of poor post-ICU course. and a risk factor for cognitive impairment. Along with changes in cognitive performance, the most frequent psychological sequela found in intensive care unit (ICU) survivors is depression. Depression affects approximately one third of adults in the ICU and increases the risk of mortality in the 2 years after discharge. It is unclear how depression and cognitive performance deficits may interact. In adult and geriatric populations depression is itself a risk factor for cognitive impairment. Cognitive deficits in attention, memory and executive function are seen in depressed patients and ICU survivors who suffered delirium. The purpose of the study is to examine whether premorbid history of depression influences acute and long-term critical care outcomes. We hypothesized that a premorbid history of depression would be associated with a more complicated ICU course, quantified as days of delirium. We also hypothesized that a premorbid depression would be associated with greater levels of cognitive impairment and greater depression severity in the year following ICU stay. Methods Patients admitted to the medical/surgical ICU services were eligible for enrollment in the Brain ICU longitudinal cohort study. We determined a pre-admission history of depression from the health proxy. Patients were assessed for delirium using the Confusion Assessment Method for the ICU (CAM-ICU) and level of consciousness using the Richmond Agitation-Sedation Scale (RASS). Patients were assessed after hospital discharge at 3 and 12 months (+/- 1 month) for depression using the Beck Depression Inventory-II (BDI-II). In all long-term models, we included patients who had any assessment data available at a given time point to have the same number of patients in cognitive outcomes and depressive symptom severity models at a given time point. Missing outcome and covariate data was handled using five imputations (with three burn-in imputations) and predictive mean matching. All continuous covariates were allowed to have a nonlinear relationship with DCFDs using restricted cubic splines with three knots, except for IQCODE which has too little variability to allow splines. Primary models examined the effect of pre-admission history of depression on: a) ICU course, measured as delirium/coma free days; b) post-discharge cognitive performance, measured by the RBANS total score; and c) post-discharge depression symptom severity, measured by the BDI. To examine the effect of depression history on delirium/coma free days we used a proportional odds logistic regression model adjusting for age, gender, Charlson Score, Framingham Stroke Risk Profile, IQCODE, years of education, AHRQ socioeconomic status index, CSHA frailty and APACHE APS at enrollment. To examine the association of a reported pre-admission history of depression with long-term cognition and depression, we used multivariable regression with history of depression as our primary exposure of interest and either RBANS global cognition scores or Beck Depression Inventory II (BDI-II) depression scores as outcomes. We created separate models to examine these outcome measures at 3 and 12 months after hospital discharge. Results A total of 821 were included in the analysis. The median age at enrollment was 61 years and 261 (33%) had a history of depression prior to their critical illness. After adjusting for demographic and other relevant covariates, a pre-admission history of depression, was not associated with days of delirium or coma in the ICU (OR 0.78, 95% CI, 0.59 - 1.03 p= 0.077). We did not observe an effect of pre-admission history of depression on RBANS scores at either 3 months or 12 months compared to those with no prior history of depression (3 months -0.04, 95% CI, -2.70 - 2.62 p=0.97; 12 months 1.5, 95% CI, -1.26 – 4.26 p= 0.28). Patients with a prior history of depression were more likely to have higher BDI scores at 3 months and 12 months (3 months OR 2.15, 95% CI, 1.42 – 3.24 p= 0.001; 12 months OR 1.89, 95% CI, 1.24- 2.87 p=0.003). Conclusions Patients with a history of depression prior to ICU stay exhibit a greater severity of depressive symptoms in the following year.