The prevalence of depression, anxiety, and posttraumatic stress disorder (PTSD) symptoms in intensive care unit (ICU) survivors ranges from 17% to 44%.1-4 Psychiatric comorbidity, the presence of 2 or more psychiatric disorders, is highly prevalent in survivors of acute respiratory distress syndrome and is associated with higher mortality in postsurgical ICU survivors.5-7 While long-term cognitive impairment in patients with ICU delirium has been associated with poor quality of life (QoL),1 the effects of psychiatric comorbidity on QoL among similar patients are not as well understood. In this study, we examined whether psychiatric comorbidity was associated with poorer QoL in survivors of ICU delirium.
We examined subjects who participated in the Pharmacologic Management of Delirium (PMD) clinical trial. This trial examined the efficacy of a pharmacological intervention for patients who developed ICU delirium at a local tertiary-care academic hospital.8 Out of 62 patients who participated in the follow-up of the PMD study, 58 completed QoL interviews and validated psychiatric screens (Patient Health Questionnaire-9 [PHQ-9] for depression, the Generalized Anxiety Disorder-7 [GAD-7] questionnaire for anxiety, and the Post-Traumatic Stress Syndrome [PTSS-10] questionnaire for PTSD) at 3 months after hospital discharge. High psychiatric comorbidity was defined as having significant symptoms for all 3 conditions (depression: PHQ-9 score ≥ 10; anxiety: GAD-7 ≥ 10; and PTSD: PTSS-10 > 35). No psychiatric morbidity was defined as having no significant symptoms for all 3 conditions. Low to moderate (low-moderate) psychiatric morbidity was defined as having symptoms for 1 to 2 conditions.
Participants also completed 2 complementary QoL measures: the EuroQol 5 dimensions questionnaire 3-level (EQ-5D-3L) Index and the EuroQol 5 dimensions Visual Analog Scale (EQ-5D-VAS).9 The EQ-5D-3L Index asks participants to rate themselves as having (1) no problems, (2) some problems, or (3) extreme problems on the following 5 scales: mobility, self-care, usual activities, pain/discomfort, and anxiety/depression. The scores are then indexed against the US population to create a continuous index scale ranging from −0.11 to 1.00. A score of 1 represents perfect health, 0 represents death, and negative values indicate a health state worse than death. The EQ-5D-VAS asks participants to draw a line on a visual scale from an anchor box to the point that represents their health state. The score ranges from 0 being the worst imaginable health state to 100 being the best imaginable health state. Demographic information, clinical characteristics, and prior history of depression, anxiety, and PTSD were obtained through PMD study records and clinical records. The Charlson Comorbidity Index, which measures chronic comorbidities, and Acute Physiology and Chronic Health Evaluation II, which estimates acute severity of illness within 24 hours of ICU admission, were calculated from patients’ available clinical information.
Fisher’s exact tests were used to compare dichotomous outcomes. Analysis of variance (ANOVA) was used to compare continuous outcomes across the 3 psychiatric groups. Analysis of covariance (ANCOVA) was used to determine whether psychiatric comorbidity in survivors of ICU delirium was associated with QoL measures. Models were adjusted for the following covariates: age, gender, Charlson Comorbidity Index, discharged to home, prior history of depression, and prior history of anxiety. To assess the relationship of psychiatric comorbidity with QoL, we chose the 2 continuous QoL measures as the outcome. Because we were interested in the effect of psychiatric burden on QoL, we used ANCOVA with QoL as the dependent variable and psychiatric burden as an independent variable. Pairwise comparisons were then performed when overall differences were significant (P < 0.05). We performed 2 separate sensitivity analyses. The first analysis looked solely at the subgroup of patients from the medical intensive care unit. We also recalculated the EQ-5D-3L index excluding the anxiety/depression item.
Nearly one-third of patients (18/58) had high psychiatric burden. The table looks at the demographic and clinical characteristics of patients with high psychiatric comorbidity versus those of low-moderate psychiatric comorbidity and those with no psychiatric morbidity. Patient groups did not differ significantly in terms of demographics. For clinical characteristics, patients with high psychiatric comorbidity were more likely than patients with low-moderate psychiatric comorbidity to have a prior history of depression (P < 0.05).
Patients with high psychiatric comorbidity were more likely to have a poorer QoL when compared with patients with low-moderate psychiatric comorbidity and to those with no morbidity as measured by a lower EQ-5D-3L Index (no, 0.69 ± 0.25; low-moderate, 0.70 ± 0.19; high, 0.48 ± 0.24; P = 0.006) and EQ-5D-VAS (no, 67.0 ± 20.7; low-moderate, 76.6 ± 20.0; high, 50.8 ± 22.4; P = 0.004). After adjusting for covariates, patients with high psychiatric comorbidity had a poorer QoL compared with those with no morbidity or low-moderate comorbidity on the EQ-5D-3L Index (P = 0.017 for overall differences), whereas patients who had high psychiatric comorbidity had a poorer QoL compared to those with low-moderate comorbidity on the EQ-5D-VAS (P = 0.039 for overall differences; Figure). Subgroup analysis of MICU patients yielded similar results. Patients with high psychiatric burden had significantly poorer QoL as measured by the EQ-5D-3L (unadjusted P = 0.044, adjusted P = 0.003) and the EQ-5D-VAS (unadjusted P = 0.007, adjusted P = 0.021). After excluding the anxiety/depression item from the EQ-5D-3L, we observed similar differences (no, 0.71 ± 0.24; low-moderate, 0.75 ± 0.15; high, 0.58 ± 0.22; unadjusted P = 0.062; adjusted P = 0.040).
Psychiatric comorbidities in ICU survivors are common and pose a significant clinical issue. Patients with multiple psychiatric comorbidities can be more complicated to identify from a diagnostic standpoint and often require more prolonged, intensive mental health treatment when compared with patients with a single psychiatric disorder.10,11 Our study showed that high psychiatric comorbidity in survivors of ICU delirium is associated with a decreased QoL compared with those with no psychiatric comorbidity or with low-moderate psychiatric comorbidity. This finding is consistent with previous studies in the general population that patients with multiple psychiatric comorbidities are associated with a poorer QoL compared with patients with a single psychiatric comorbidity.10,11
There is a pressing need to better characterize psychiatric comorbidities in ICU survivors because our current evidence suggests that the prevalence of psychiatric comorbidities of ICU survivors is substantially higher than that of the general population. We found that nearly one-third of survivors of ICU delirium had comorbid depression, anxiety, and PTSD symptoms at 3 months. This is consistent with the few other studies of ICU survivors, which showed a prevalence of psychiatric comorbidity of 25% to 33%.5,12 These rates are substantially higher than the prevalence in the general population of 6%.13
The high rate of psychiatric comorbidities may render it difficult to effectively treat the mental health symptoms in ICU survivors.14 Treating multiple psychiatric comorbidities may also be especially challenging in survivors of ICU delirium because they have a high prevalence of cognitive impairment. Mental health treatments for patients with psychiatric disorders and comorbid cognitive impairment are limited. Better characterization of psychiatric comorbidity in ICU survivors, particularly those with ICU delirium, is vital to the development of more effective, bundled treatments for this population with multiple comorbidities.
Standardized screenings of ICU survivors at a high risk for psychiatric disorders, such as survivors of ICU delirium, may help to identify patients with comorbid psychiatric disorder symptoms and have them referred to appropriate treatment earlier with the hope of improving their QoL sooner. Although opportunities to deliver integrated outpatient collaborative mental health and medical care for a subspecialty population are limited, one potential model of care would be to utilize a collaborative-care model in an ICU survivor clinic.15
Strengths of our study include the examination of psychiatric comorbidities in survivors of ICU delirium, who often have a poor QoL. A deeper understanding of psychiatric comorbidity and its relationship with QoL is needed to better understand how to deliver more effective treatments for these survivors. Limitations include the small sample size, a one-time measurement of psychiatric comorbidities at the 3-month follow-up based on screenings tools, and a lack of objective measures of physical functioning to determine the effects of psychiatric comorbidities on physical functioning. There may also have been differences in how patients with no psychiatric comorbidity responded to the EQ-5D-VAS as a result of premorbid differences (eg, they were healthier prior to their ICU stay and perceived their survivor status more negatively). This may explain why we did not see a statistically significant difference between no psychiatric comorbidity and high psychiatric comorbidity groups on the EQ-5D-VAS. Nevertheless, we did see a difference between the low-moderate psychiatric comorbidity group on EQ-5D-VAS and differences between the no comorbidity and low-moderate comorbidity groups versus the high comorbidity group on the EQ-5D-3L. Finally, data about psychiatric history and QoL prior to ICU hospitalization were limited. Therefore, truly determining incidence versus prevalence of post-ICU comorbidities and whether psychiatric symptoms and its effects on QoL were due to ICU hospitalization or to premorbid psychiatric symptoms is difficult.
Our study demonstrated that in survivors of ICU delirium, higher comorbidity of psychiatric symptoms was associated with poorer QoL. Future studies will need to confirm these findings. We will also need to identify potentially reversible risk factors for psychiatric comorbidity and poorer QoL and develop treatments to effectively target the mental health symptoms of survivors of ICU delirium.
Grant support: The PMD trial is funded through the National Institutes of Health grant R01AG054205-02. SW is supported by NIA 2P30AG010133. AP is supported by CMS 1 L1 CMS331444-02-00, Indiana CTSI, and NIA R01AG054205-02. SG is supported by NIA 2P30AG010133, NIA 5R01AG045350, and NIA R01AG054205-02. SK is supported by NHBLI 5T32HL091816-07. MB is supported by NIA R01 AG040220-05, AHRQ P30 HS024384-02, CMS 1 L1 CMS331444-02-00, NIA R01 AG030618-05A1 and NIA R01AG054205-02. BK is supported by NIA K23-AG043476 and NHLBI R01HL131730. The funding agency had no role in the development of the study design, collection, analysis, interpretation of data, manuscript development, or the decision to submit the manuscript for publication. Conflicts of interest include MB, SG, and AP being funded by NIA R01AG054205-02 for the PMD study.