This prospective analysis of 160 acute lung injury survivors demonstrates that depressive symptoms at 6 months after ALI are both common and potentially associated with features of critical illness and intensive care. In this research, representing the largest published study of long-term psychiatric morbidity in ALI survivors to date, the factors most consistently associated with depressive symptoms included admission to a surgical (versus medical or trauma) ICU, maximum organ dysfunction score, and higher mean daily benzodiazepine dose in the ICU.
The 26% prevalence of a positive depression screening test at 6 months after ALI in this study is similar to the 28% prevalence observed earlier in our cohort at 3 month follow-up (22
) and the 25% – 32% rates reported in other populations of mechanically ventilated patients at 6 to 12 months after discharge (23
). This prevalence is substantially higher than the 8% prevalence of a positive depression screening test (using HAD depression sub-scale score ≥8) in a general adult population (26
) and further confirms the high burden of psychiatric morbidity in ALI survivors.
Among the 12 characteristics we examined in the ICU, three (admission to surgical ICU, maximum organ dysfunction, and benzodiazepine dose) were significantly associated with depressive symptoms, when measured as both a continuous score and as a binary outcome (positive screening test). However, given the relatively small body of literature in this field, we caution that these associations are exploratory in nature. Regarding ICU type, specifically, we caution that only 14% of our cohort was admitted to a surgical ICU, thus limiting our ability to compare surgical versus medical ICUs. Furthermore, in order to avoid overlooking associations of potential clinical importance, we did not adjust for multiple comparisons; hence, statistical chance may play a role in our findings.
Using a subset of the present cohort (n = 104, 65% of the present sample), we previously investigated the association of ICU hypoglycemia with depressive symptoms at 3 months post-ALI. This variable had a significant association, as did two patient baseline factors (pre-admission anxiety/depression and morbid obesity) and, to a lesser extent, one other ICU-related factor (higher daily benzodiazepine dose) (22
). These associations with depressive symptoms at 3 months were all re-confirmed using the full cohort analyzed in this study (data not shown). Of these four factors, only benzodiazepine dose remained significantly associated with depressive symptoms at 6 months post-ALI. In addition, two new ICU-related factors – admission to a surgical ICU and maximum ICU organ dysfunction score – were also significantly associated with depressive symptoms at 6 months. These differences in findings at 3 versus 6 months suggest that post-ALI depressive symptoms may follow a dynamic course; notably, only 61% of patients with a positive depression screening test at 6 months had a positive screen at 3 months. These differences may also reflect statistical chance; alternatively, surgical issues or severity of illness during intensive care may result in lasting physical morbidity that influences psychopathology more in the medium term than shortly after hospital discharge.
Prior studies have suggested that post-ICU depression is associated with pre-ICU functional status (8
) and duration of ICU stay or sedative administration (27
). In univariable analyses, we found similar associations of all three variables with mean HAD score. However, the effects of these variables were markedly attenuated in our multivariable models, which adjusted for other covariates not included in the original studies (adjusted p = 0.59 for duration of benzodiazepines; other variables in ). Though we did find a significant association between depressive symptoms and mean benzodiazepine dose, this relationship may not be causal; rather, it may reflect that patient distress in the ICU (prompting more sedation) identifies individuals who are more likely to be distressed in general (28
). Our study also differs in methodology from prior studies. Weinert et al (8
) evaluated patients with acute respiratory failure rather than ALI and combined results from 2- and 6-month follow-up into a single analysis. Nelson et al (27
) used a retrospective questionnaire format administered to 24 patients at 6 – 41 months after ALI and evaluated the duration of any sedative use, evaluating both benzodiazepines and narcotics together. These differences in study design may provide additional explanation for the differences noted when comparing our results with these prior studies.
This research has a number of potential limitations. First, we measured depressive symptoms at follow-up with the seven-item HAD depression subscale. Although this screening instrument has been validated in medically ill patients and has been used in >700 studies (17
), including numerous studies of ICU survivors (29
), a positive screening test does not represent a clinical diagnosis of depression. In addition, the HAD instrument does not include measures of physical symptoms, guilt, worthlessness or suicidality, and while its sensitivity for clinical depression is high (17
), it may miss depressed patients in whom anhedonia is not prominent. Future studies using clinical interviews of ICU survivors would be useful in this regard. Second, we limited our study to depressive symptoms and cannot comment on associations with other potentially important psychiatric outcomes, such as post-traumatic stress (6
). Third, we did not collect detailed data on prior psychiatric history or post-ALI psychiatric treatment (e.g., psychotherapy and antidepressants), which might reduce the burden of depressive symptoms in patients who would otherwise meet clinical criteria for depression (8
). Fourth, 18% of hospital survivors died within six months of ALI, and an additional 13% declined participation in this longitudinal study. Although losses to follow-up in this study were less than in prior longitudinal cohorts of ARDS survivors (3
), our results may not generalize to all ALI survivors.