Benzodiazepines and Delirium in the Young and Old: Truth Be Told or Still Not Sold?*

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Over a century after Thomas Salter’s “Practical Observations on Delirium,” the field of critical care medicine has seen an explosion in delirium research. Viewing delirium through a historical lens is key to understanding incremental steps that have been crucial to advancing our practice in the ICU. Sparked by a call to action for consistent and accurate differentiation of dementia in elderly patients from the “acute confusional state” of delirium (2), the Confusion Assessment Method (CAM) was developed and validated in 1990 to enable detection of delirium by nonpsychiatric clinicians in high-risk settings such as the inpatient wards and emergency department (3). Almost a decade later, the first study to report neuropsychological sequelae of ICU survivors with acute respiratory distress syndrome was published—what we now know as postintensive care syndrome (4). As the negative impact of delirium on outcomes in hospitalized adults became clear (5), the need to characterize and address delirium in the critical care setting was heightened, leading to validation of the CAM-ICU (6) and Intensive Care Delirium Screening Checklist (7). This major turning point for research on ICU delirium provided the crucial foundation for discovery on delirium prevalence, risk factors, therapies, and outcomes in critically ill patients to improve ICU care.
We have learned an extraordinary amount about ICU delirium over the last 2 decades, which is associated with increased duration of mechanical ventilation, length of hospital stay, long-term cognitive impairment, and mortality in adults (8, 9). There is no question that the cause of delirium can be multifactorial and challenging to diagnose in a complex patient within a complex ICU environment. However, a large body of evidence focused on modifiable risk factors has uncovered clear associations between sedative exposure, specifically benzodiazepines, and the development of delirium in medical and surgical ICU patients (10, 11). These findings have ignited an evolving international paradigm shift in traditional approaches to ICU care, known as “ICU liberation,” focused on minimizing sedation to optimize wakefulness and increase mobility in lieu of deep sedation and bed rest (12, 13).
In pediatrics, we have followed with our own pursuit of discovery in ICU delirium, albeit only in the last 5 years (14). A culture of heavy sedation and bed rest has long been the standard of care in pediatric critical care due to concerns of safety, and our efforts to ensure that children do not remember their PICU stay (15). As of 2013, a combination of opioid and benzodiazepine infusions still reigned supreme among pediatric intensivists as the first-line sedation regimen for intubated infants and children, and attention to PICU delirium was not yet apparent (15). In order to recognize the problem, there was a critical need to first develop and validate tools for delirium screening in an extraordinarily heterogeneous population of patients with varying developmental levels. The pediatric CAM-ICU (CAM-ICU) and Cornell Assessment of Pediatric Delirium, two highly sensitive and specific tools for delirium screening in the PICU, have opened the door for rigorous pediatric delirium research in all ages (16, 17). In just the last year, we have learned that the international point prevalence of pediatric delirium is 25%, increasing to 38% for children in the PICU 6 days or longer (18). Risk factors include younger age, mechanical ventilation, benzodiazepines, narcotics, and physical restraint use (18, 19). Most recently, a prospective, longitudinal cohort study demonstrated that PICU delirium was independently associated with mortality (19).
In this issue of Critical Care Medicine, Smith et al (20) report the results of their timely study investigating associations between delirium, short-term outcomes, and modifiable risk factors including benzodiazepine exposure in infants and young children admitted to the PICU.

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