Frailty, delirium and hospital mortality of older adults admitted to intensive care, a mediation analysis: the Delirium (Deli) in ICU study.
Authors: Sanchez David , Brennan Kathleen , Safye Masar El , Shunker Sharon-Ann , Bogdanoski Tony , Hedges Sonja , Hou Yu Chin , Lynch Joan M , Hunt Leanne , Alexandrou Evan , Saxena Manoj , Abel Simon , Lakshmanan Ramanathan , Bhonagiri Deepak , Parr Michael J. , Aneman Anders , Chroinin Danielle Ni , Hillman Kenneth M. , Frost Steven Alfred 
Published: August 2020

Abstract
Background
As the population ages clinical frailty among older adults admitted to intensive care has been proposed as an important determinant of patient outcomes. Among this group of frail patients an acute episode of delirium is also common, and both frailty and delirium increase the risk of mortality. However, the complex relationship between frailty, delirium and mortality has not been extensively explored in the intensive care setting. Therefore, the aim of this study was to explore the relationship between clinical frailty, acute delirium and hospital mortality of older adults admitted to intensive care.
Methods
This study is part of a Delirium in Intensive Care (Deli) study that is being conducted across the South Western Sydney Local Health District, between May 2019 and April 2020. During the initial 6-month baseline period, clinical frailty status on admission to ICU, among adults aged 50-years or more, acute episodes of delirium, and the outcomes of ICU and hospital stay will be described. Mediation analysis was used to assess the relationship between frailty, delirium and risk of hospital death.
Results
During the 6-month baseline period 997 patients, aged 50-years or more, were included in this study. The average age was 71-years (IQR, 63–79), 55% were male (n = 537). Among these patients 39.2% (95% CI 36.1–42.3%, n = 396) had a Clinical Frailty Score (CFS) of 5 or more, and 13.0% (n = 127) had at least one acute episode of delirium. Frail patients were at greater risk of an episode of delirium (17% versus 10%, adjusted Rate Ratio (adjRR) = 1.61, 95% Confidence Interval (CI) 1.14–2.28, p = 0.007), had a longer hospital stay (2.6 days, 95% CI 1–7 days, p = 0.009), and higher risk of hospital mortality (19% versus 7%, adjRR = 2.43, 95% CI 1.68–3.57, p < 0.001), when compared to non-frail patients. Patients who were frail and experienced an acute episode of delirium in the ICU had a 35% rate of hospital mortality, versus 10% among non-frail patients who also experienced delirium in the ICU (p = 0.034, for interaction between frailty, delirium and hospital mortality). The proportion of the effect of frailty and risk of hospital mortality mediated by an acute episode of delirium in the ICU was estimated to 9.4% (95% CI 2–24%).
Conclusion
This study has been able to show that clinical frailty on admission increases the risk of delirium by approximately 60%, and both increase the risk of hospital mortality. One in three frail patients who experienced 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, and, importantly to discuss these issues in an open and empathetic way with the patient and their families.