Critical Care Commentary

Delirium in the ICU: Best sedation practices lead to the best outcomes


Delirium is a frequent form of organ failure among the critically ill, impacting up to 80% of mechanically ventilated patients (Ely EW et al. JAMA. 2004;291[14]:1753-62). Its cardinal manifestations include disturbances in attention and cognition that occur acutely (e.g., hours to days) that are not better explained by another disease process (such as a toxidrome or dementia) (American Psychiatric Association, Diagnostic and Statistical Manual of Mental Disorders. 5th ed., 2013). Duration of delirium in the intensive care unit (ICU) is independently associated with poor outcomes, such as mortality and hospital length of stay, even when accounting for comorbidities, coma duration, sedative use, and severity of illness. Delirium during critical illness is an important bellwether for a patient’s clinical status, often serving as a harbinger for severe or worsening disease.

Dr. Matthew F. Mart, Vanderbilt University, Nashville, Tenn.

Dr. Matthew F. Mart

Over the last two decades, the critical care community has come to understand the importance of recognizing delirium, which is often underdiagnosed, as well as delirium prevention. In the ICU, several factors coalesce to form the perfect environment for the development of delirium. Patients often have preexisting comorbidities that predispose to delirium, such as preexisting cognitive impairment, and the severity of critical illness increases the risk of delirium further. There are also bedside factors, however, that are important for the intensivist to address, many of which are modifiable. These include routinely screening for delirium and assessing level of consciousness, implementing early mobility and rehabilitation, targeting light sedation, and avoiding deliriogenic medications such as benzodiazepines. These evidence-based care practices form the foundation of the 2018 Clinical Practice Guidelines for the Prevention and Management of Pain, Agitation/Sedation, Delirium, Immobility, and Sleep Disruption in Adult Patients in the ICU (i.e., PADIS guidelines), which aim to reduce delirium and iatrogenesis from critical care (Devlin JW et al. Crit Care Med. 2018;46[9]:e825-e873). The severe acute respiratory syndrome–coronavirus 2 (SARS-CoV-2) pathogen that has caused the coronavirus disease 2019 (COVID-19) pandemic, however, has brought unprecedented challenges to critical care. One unfortunate side effect has been increased use of deep sedation and, thus, a greater incidence of delirium (Pun BT et al. Lancet Respir Med. 2021;9[3]:239-50). While the impact of the pandemic is unprecedented, thoughtful and careful sedation use remains vital to providing optimal care for the critically ill patient.

The link between sedation and delirium

The advent of modern mechanical ventilation brought critical care medicine into a period of rapid growth. Practices derived from the operating room, such as deep sedation and paralysis, became commonplace. Yet, starting in the late 1990s and early 2000s, evidence started growing regarding the impact of delirium and the unique aspects of the ICU that made it so prevalent. Delirium is strongly linked to inpatient mortality in mechanically ventilated adults, and it is best understood as an additional form of organ failure, much like other organ failures commonly recognized and treated by intensivists, such as respiratory or renal failure. Certain medications and sedation practices are associated with the development and duration of delirium. Benzodiazepines, a common sedative medication, are strongly linked to the development of delirium. In a study comparing commonly used sedative and analgesic agents, the use of lorazepam was associated with a greater risk of delirium the following day among critically ill, mechanically ventilated patients (Pandhariphande PP et al. Anesthesiology. 2006;104[1]:21-6). Given how commonly benzodiazepines are used and delirium develops in the ICU, this association has striking implications for clinical care and outcomes such as mortality. It is also significant, given that benzodiazepine use has increased during the pandemic, potentially creating significant downstream consequences. Benzodiazepines should be actively avoided when at all possible, given their propensity to lead to delirium, in accordance with the most recent guidelines.


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