Frailty, delirium and hospital mortality of older adults admitted to intensive care: the Delirium (Deli) in ICU study

The population is ageing worldwide; the 841 million people older than 60 years in 2013 is estimated to more than double to 2 billion by 2050 [23]. This increase in life expectancy has been influential in changing the characteristics of older patients admitted to the intensive care unit (ICU) and has highlighted frailty as an important emerging clinical problem [1, 2, 4‐6]. Among older patients admitted to the ICU, an acute episode of delirium is also common, and has been suggested as a sign of brain frailty [10, 13, 16, 21], and is associated with a longer intensive care and hospital stay [8, 17], and increased risk of mortality. The complex relationship between frailty, delirium and risk of mortality has not been extensively explored in the ICU setting. Therefore, the aim of this study was to explore the relationship between clinical frailty on admission, an episode of delirium and hospital mortality of older adults admitted to the ICU.

This study of the relationship between clinical frailty, delirium and hospital mortality is part of a larger, nurse-led interventional study, to reduce the burden of delirium in the adult ICU setting, which has been described previously [15]. In brief, the Delirium in ICU (Deli) Study is a randomised stepped-wedge intervention trial, including the four adult intensive care units across the South Western Sydney Local Health District (SWSLHD). The intervention is a nurse-led non-pharmacological bundle of care, to reduce the incidence of delirium among adults admitted to the ICU. The data for this specific study of the relationship between frailty, delirium and hospital mortality is based on the baseline period (pre-intervention phase) of the larger Deli Study. This sub-study was planned prior to the commencement of data collection on 1 May 2019.

The total numbers of admissions to the four adult ICUs during the baseline period, and the number of patients included in the study aged 50 years or more, once inclusion and exclusion criteria were applied are presented in Fig. 1. Due to the stepped-wedge nature of the overall 12-month Deli Study, each ICU individually crossed over from baseline to interventions after the initial 3-month baseline period; the four ICUs contributed 3 to 6 months of data for analysis. Based on clinical frailty status on admission to ICU, the characteristics and outcomes of the 997 patients included in this study are presented in Table 1. For example, 39.2% (95% CI 36.1–42.3%, n = 396) had a Clinical Frailty Score (CFS) of 5 or more on admission to ICU; frail patients were older (77 versus 67 years, p < 0.001), were more likely female (50% versus 42%, p = 0.021) and had a higher rate of multiple admissions to ICU during the study period (6% versus 4%, p = 0.017). Delirium was more common among the frail (17% versus 10%, p = 0.002) compared to the non-frail; length of stay in the ICU and hospital were longer, 3 versus 2 days for ICU stay (p < 0.001) and 11 versus 9 days for hospital stay (p < 0.001), respectively. And frail patients had higher rates of ICU and hospital mortality, 10% versus 3% for ICU death (p < 0.001) and 19% versus 7% for hospital death (p < 0.001). Based on the age group, frailty status, rates of delirium, ICU and hospital length of stay, and mortality are presented in Table 2. Older patients had higher rates of frailty, delirium and mortality and stayed in the ICU and hospital longer (all p values for trend < 0.01).

Based on the frailty status, risks of delirium and hospital mortality are presented in Table 3. Frail patients were at greater risk of an episode of delirium (17% versus 10%, adjusted rate ratio (_adjRR) = 1.71, 95% confidence interval (CI) 1.20–2.43, p = 0.003), and a higher risk of hospital mortality (19% versus 7%, _adjRR = 2.54, 95% CI 1.72–3.75, p < 0.001), when compared to non-frail patients. Frail patients, not being recognised to experience an episode of delirium during and ICU stay, had a 15.5% rates of hospital mortality, compared to a rate of 6.6% among non-frail patients without delirium (_adjRR = 2.24, 95% CI 1.37 to 3.67, p = 0.001). Patients who were frail on admission to ICU and experienced an acute episode of delirium in the ICU had a 35.9% rate of hospital mortality, versus 9.9% among non-frail admissions who also experienced delirium in the ICU (_adjRR = 4.16, 95% CI 1.50 to 11.52, p = 0.004).

This study among adults, aged 50 years or more, admitted to the ICU has been able to show that clinical frailty on admission increases the risk of delirium, resulted in a longer ICU and hospital stay, and increases the risk of in-hospital mortality. Importantly, our study suggests that a proportion of the effect of frailty on the increased risk of hospital mortality is modified by delirium, and one in three frail patients who experienced an acute episode of delirium in the ICU did not survive to hospital discharge (Fig. 2). These results suggest the importance of recognising clinical frailty in the ICU setting, not just to improve the prediction of outcomes from critical illness, but to identify patients at the greatest risk of adverse events such as delirium; to institute measures to reduce risk; and hopefully improve outcomes. The presence of frailty on admission to the ICU may also be considered as a marker of someone nearing the end of their life. This prognostic information together with inherent uncertainty should be shared with the patient and their families in an honest and empathetic way.

The prevalence of clinical frailty among adults admitted to the ICU has been previously described [2, 5, 9] and, along with the results of our study, showed longer lengths of stay and increased risk of mortality. However, our study may be one of the first to specifically explore the relationship between frailty, delirium and risk of death. The prevalence of frailty among adults aged 50 years or more was reported to be 32.8% (95% CI 28.3–37.5%), in Alberta, Canada [2], from six hospitals, and is similar to our rate of 39.2% (95% CI 36.1–42.3%). Frailty among the very elderly (aged 80+ years) admitted to the ICU has also been extensively explored, in terms of ICU and hospital outcomes [5, 9, 11], and the increased prevalence in this very elderly group has highlighted frailty as an important predictor of short-term mortality. Importantly, this study has described the moderating effect of delirium in the relationship between frailty and increased risk of hospital mortality, in that frail patients who experience an episode of delirium in the ICU are at the greatest risk hospital death.

The results of our study need to be considered in the context of some potential weaknesses and strengths. Firstly, the classification of frailty in the clinical setting, especially among critically ill patients, is difficult—however, the work by Rockwood et al. in developing the Clinical Frailty Score (CFS) has made this task easier. For instance, the CFS used in this study has demonstrated a similar concordance to the more detailed cumulative deficit method in predicting 28-day mortality, among study participants in the Canadian Health and Ageing Cohort [19]. And given the impracticality of using a comprehensive geriatric assessment in the ICU setting to identify frailty, the risk of our study participants being misclassified is a potential weakness.

Another obvious problem is the identification of delirium in the ICU setting is often subject to some error. However, the majority of this error is related to false negatives (sensitivity of 0.81) when the CAM and CAM-ICU had been compared to a more exhaustive assessment of delirium using the Diagnostic and Statistical Manual of Mental Disorders (DSM IV) [22]. Importantly, false-positive rates have been estimated to be low (1%) when also compared to DSM IV [22]. The consequences of this would be that delirium rates may be underestimated, and using the method suggested by Kelsey et al. [14] (using the above estimates of sensitivity and specificity of 0.81 and 0.99, respectively), the overall observed rate of 12.5% would increase to approximately 14.6%. Also, our inclusion and exclusion criteria may account for our lower rates of delirium, which was based on our larger (12 months) interventional study and may limit the generalisability of our results to all patients admitted to the ICU. A strength of this study is that it has been conducted across a number of adult ICUs and that both frailty and delirium statuses were purposely collected as part of our larger study.

The implications of our finding are twofold: (1) frailty in the ICU setting is common and needs to be routinely identified as part of the characteristics of patients admitted to the ICU and (2) frail patients in the ICU are at greater risk of adverse events, such as delirium, and have worse hospital and long-term outcomes. Further work in this area needs to identify modifiable risk factors to reduce the risk of adverse events, such as delirium, among this vulnerable group of patients cared for in the ICU, and explore more extensive outcomes of those who are frail and survive an ICU and hospital stay, for instance, functional outcomes (both at discharge and at 6- and 12-month follow-up), quality of life and longer-term mortality in the months following discharge from hospital.

This study among adults, aged 50 years or more, admitted to the ICU has been able to show that clinical frailty on admission increases the risk of delirium by 60%. The effect of frailty on the increased risk of hospital mortality is moderated by delirium, and one in three frail patients who experience an acute episode of delirium during their stay in the ICU did not survive to hospital discharge. These results suggest the importance of recognising clinical frailty in the ICU setting, not just to improve the prediction of outcomes from critical illness, but to identify patients at the greatest risk of adverse events such as delirium, and institute measures to reduce risk, improve health outcomes where possible and share prognostic information in a genuine way with the patient and their carer.