Intensive Care Unit Delirium Nursing CE Course for APRNs

Risk Factors

Delirium is a clinical manifestation of stress that impacts the central nervous system (CNS) function in a vulnerable patient. There are numerous potential pathophysiological causes of delirium, with each patient likely experiencing one or more interconnected and complex processes. Risk factors for developing ICU delirium can be categorized into predisposing factors (i.e., present before admission to the hospital) and precipitating factors (i.e., acquired in the hospital related to the environment or treatment in the ICU; Arumugam et al., 2017; Mart et al., 2021; Ramirez Echeverria et al., 2022).

The 2018 clinical practice guidelines of the SCCM identified risk factors that are strongly associated with the development of ICU delirium, including modifiable factors (e.g., benzodiazepine use and blood transfusions) and non-modifiable factors (e.g., older age, dementia, prior history of coma, pre-ICU emergency surgery or trauma, and increasing acute physiology and chronic health evaluation [APACHE] or American Society of Anesthesiologists [ASA] classification of physical health score; Devlin et al., 2018). Predisposing factors are modifiable and non-modifiable patient characteristics that increase the likelihood of developing ICU delirium and can include:

• older age (i.e., over 70)
• preexisting cognitive impairment (i.e., dementia, stroke, or Parkinson's disease)
• multimorbidity (e.g., cardiac disease, hypertension, respiratory disease)
• male gender
• vision and hearing impairment
• frailty
• terminal illness
• alcohol and drug abuse
• current tobacco use (Ali & Cascella, 2022; Francis & Young, 2022; Huang, 2022)

In addition to predisposing risk factors, numerous precipitating factors contribute to the development of ICU delirium. These factors are usually considered reversible but not always. Critical illness constitutes a severe systemic insult, and the consequences of the illness, ICU environment, and various treatment strategies can place patients at high risk for delirium development (Francis & Young, 2022; Huang, 2022; Kotfis et al., 2018). Table 1 outlines common precipitating factors for ICU delirium.

Table 1

Precipitating Factors for ICU Delirium

(Berry, 2022; Francis & Young, 2022; Huang, 2022; Kotfis et al., 2018)

Pathophysiology

The pathogenesis of delirium is multifactorial and not well understood. Given its numerous causes, a single mechanism is unlikely to explain delirium. ICU delirium can be specifically challenging to understand, given the complexity of the underlying illness and management strategies. More likely, the pathogenesis of delirium may be attributed to the interplay of physiological insults and other unique patient characteristics. Several theoretical mechanisms have been proposed, including older age, oxidative stress, neurotransmitter dysregulation, sleep-wake cycle dysfunction, and neuroinflammation with microglial activation (Huang, 2022; Poulsen et al., 2021; Ramirez Echeverria et al., 2022).

Older Age

As adults age, numerous physiological changes cause a decreased physiologic reserve and an increased vulnerability to illness and stress. More specifically, older adults can experience decreased perfusion to the brain, changes in the proportion of stress-regulating neurotransmitters, and increased neuronal aging or loss (Ramirez Echeverria et al., 2022).

Reactive Oxidation Stress

Reactive oxygen and nitrogen species are mediators of cellular damage. Due to its high lipid content and low antioxidant capacity, the CNS is particularly vulnerable to reactive-oxidation stress. A reduction of cerebral oxidative metabolism can lead to an imbalance of neurotransmission. Researchers have found diffuse slowing of electrical activity on electroencephalography (EEG) examination. This reduction in brain metabolism (i.e., cerebral insufficiency) is hypothesized to play a role in delirium and is also prevalent in critical illness and multiple organ dysfunction (Huang, 2022; Ramirez Echeverria et al., 2022).

Neurotransmitter Dysregulation

Research has established an association between decreased acetylcholine and increased dopamine activity. Both neurotransmitter pathways are essential for brain function. Acetylcholine is regulated by dopamine, with excess dopamine reducing acetylcholine production. Acetylcholine production is also depressed due to the medications used to manage critically ill patients, increasing the risk of delirium. In addition, imbalances in the synthesis, release, and degradation of gamma-aminobutyric acid (GABA), glutamate, serotonin, and norepinephrine are hypothesized to play a role in the development of delirium. Neurotransmitter disturbance can alter the functional connectivity of the neurons and can trigger neural cell death (Poulsen et al., 2021; Ramirez Echeverria et al., 2022).

Sleep-Wake Cycle Dysfunction

Disruption of the sleep-wake cycle, including sleep duration and melatonin secretion, leads to widespread dysfunction in other systems. Specifically, melatonin impacts the function of the CNS, impacting glucose regulation, antioxidant defense, core body temperature, and immune system function (Ramirez Echeverria et al., 2022).

Neuroinflammation

Inflammatory markers (i.e., chemokines, tumor necrosis factor-alpha, and cytokines) produced during critical illness can initiate a cascade of events that leads to microvascular compromise, endothelial damage, and thrombin formation. Damage to endothelial cell-to-cell adhesions occurs at the blood-brain barrier, resulting in increased endothelial permeability. This increased permeability promotes CNS inflammation, causing decreased cerebral blood flow, ischemia, and neuronal death (Ali & Cascella, 2022; Ramirez Echeverria et al., 2022).

Neuroendocrine

Increased physiological stress stimulates the release of glucocorticoids, which increases the vulnerability of neurons to damage. Neuronal damage can impact cellular signaling, glial cell behavior, and gene transcription (Ramirez Echeverria et al., 2022).

Clinical Manifestations

Delirium is characterized by a disturbance of consciousness and altered cognition that develops over a short time and tends to fluctuate throughout the day. One of the earliest manifestations of delirium is a change in a patient's level of awareness and the ability to focus, shift, or sustain attention. These changes may be subtle at first, potentially going unnoticed. HCPs will encounter additional challenges when assessing for these changes in critically ill patients, especially those requiring sedation or MV. A patient with an altered level of consciousness may present with drowsiness or lethargy, which can also occur with a critical illness (Francis & Young, 2022).

Cognitive changes with delirium may manifest as memory loss, disorientation, and difficulty with speech and language. Perceptual disturbances may manifest as delusions of harm (i.e., the harm inflicted on them) or believing that objects or shadows in the room represent a person. Hallucinations can be auditory, somatosensory, or visual. HCPs need to determine the patient's baseline cognitive status to assess for changes. Delirium can manifest quickly, usually within hours to days of the physiological insult. Depending on the underlying etiology, delirium can persist for days to months. Clinical manifestations of delirium can wax and wane, typically worsening in the evening and night. In addition, delirium often has a prodromal phase, where patients may report sleep disturbances, anxiety, depression, irritability, hypersensitivity to light or sound, fatigue, and restlessness. As delirium progresses, perceptual disturbances and cognitive impairment become more prominent. Clinical manifestations will also vary depending on the type of delirium: hypoactive delirium presents with lethargy, whereas hyperactive delirium can present with agitation, psychotic features, and poor judgment (Francis & Young, 2022; Huang, 2022).

Evaluation and Diagnosis

Although ICU delirium is frequently encountered, many cases will go undiagnosed because of the complexity of the underlying illness and the ICU management strategies. About 75% of delirium cases will remain undiagnosed without structured detection tools. Early detection and diagnosis are critical for preventing complications and reducing mortality. There are two important aspects to evaluating and diagnosing delirium: recognizing that delirium is present and determining the underlying etiology. Recognizing delirium can be challenging for HCPs since patients can have varying signs and symptoms that can be attributed to an underlying illness and treatment strategies, including medications. Hyperactive delirium is usually easier to detect because the patient displays agitation, aggression, and hyperactive behaviors. ICU delirium more frequently presents as hypoactive delirium, which is much harder to detect because clinical manifestations are less disruptive, making recognition particularly challenging (Francis & Young, 2022; Ramirez Echeverria et al., 2022).

The Diagnostic and Statistical Manual of Mental Disorders 5^th edition Text Revision (DSM-5-TR) criteria are considered the gold standard for diagnosing delirium (APA, 2022). These criteria include the following:

• severe change in mental abilities leading to a lack of focus and situational recognition of their environment
• these symptoms are radically different from the patient's healthy state and occur quickly (hours or days) with a waxing and waning of symptoms over the day
• additional mental alterations are also present, including:
  • confusion regarding where they are or why, the time/day/year
  • inability to understand the spatial relationship between objects
  • speech deficits
  • inability to interpret information
  • forgetfulness
• the changes described above cannot be attributed to another neurological disorder and are not associated with a decreased level of consciousness
• clinical evidence indicates that the changes are due to substance use or cessation of prolonged use, a medical condition, a toxin, or a combination of these (APA, 2022)

The evaluation of delirium should include a thorough history, a comprehensive physical examination, laboratory tests, and possibly imaging. The history and physical examination will determine the necessary tests and imaging due to the multifactorial nature of delirium. The DSM criteria provide a framework for assessing delirium. HCPs should never minimize lethargy or somnolence by assuming that a patient's illness, medications, or management strategies are causing the changes identified within the DSM criteria. Critically ill patients who are sedated or requiring MV may limit an HCP's ability to assess memory, speech, and level of awareness (Francis & Young, 2022; Ramirez Echeverria et al., 2022).

History

A thorough history to assess for delirium is only possible for patients who can respond to voice. A family member or caregiver may be able to provide valuable historical information about the patient's baseline mental status. Many patients with delirium may also have underlying dementia; therefore, knowing the patient's baseline mental status can help determine whether an acute change has occurred. Dementia infrequently causes inattention or fluctuating consciousness. Sundowning (i.e., behavioral deterioration during the evening hours) is common among hospitalized patients with dementia. Sundowning can be difficult to differentiate from delirium; therefore, HCPs should presume that acute changes are delirium until proven otherwise. HCPs should also elicit information from the patient or a family member about the presenting illness or injury, as this is likely a contributing factor to delirium (Huang, 2022; Ramirez Echeverria et al., 2022). Additional information that HCPs should explore when completing a thorough history includes:

• any changes in medications (review current medications to identify any high-risk medications like opioids, anticholinergics, etc.); see Table 1
• any new symptoms (e.g., fever, dysuria, pain, coughing, headache, or changes in eating, bowel, or bladder habits)
• any changes in sleep (e.g., deprivation or change in environment)
• any use of alcohol or illicit drugs
• past medical history
• any recent falls (Berry, 2022; Huang, 2022; Ramirez Echeverria et al., 2022)

Physical Examination

A comprehensive physical examination can be challenging for patients who are confused and uncooperative. When possible, HCPs should perform a physical examination, including respiratory, neurological, cardiac, mental status, abdominal, musculoskeletal, and skin assessments. In cases where a comprehensive physical examination is impossible, HCPs may choose to perform a focused assessment (Francis & Young, 2022; Ramirez Echeverria et al., 2022). The focused assessment should include the following:

• vital signs
• potential foci for infection
• neurologic examination
• skin, head, and neck assessment
• hydration status (Huang, 2022)

HCPs must be able to identify abnormal assessment findings that could facilitate the identification of the underlying etiology. A low oxygen saturation (e.g., below 90%) could suggest a hypoxic etiology. For patients with a fever and tachycardia, HCPs should consider sepsis or delirium tremens (i.e., due to alcohol withdrawal). Neck stiffness could indicate meningitis, whereas hypotension and decreased urine output could indicate CNS hypoperfusion. Focal neurological deficits could indicate a hemorrhage, a stroke, or increased intracranial pressure (ICP). Lacerations, bruises, or swelling are signs of trauma, while needle marks can indicate illicit drug use (Berry, 2022; Huang, 2022).

Neurologic Examination

As discussed previously, a neurologic examination for patients with critical illness in the ICU can be challenging due to illness severity, sedation, MV, or other management strategies. HCPs should perform a detailed neurological examination when possible, starting with attention. Various tests can be used to assess attention, including naming the days of the week forward and backward, immediate repetition of three named objects, or digit span (i.e., repeating seven digits forward and five digits backward). After an initial assessment, HCPs should use standardized diagnostic criteria (e.g., DSM-5-TR) to diagnose delirium. The SCCM guidelines recommend that all critically ill patients should be screened regularly for delirium using a validated tool such as the Confusion Assessment Method (CAM), CAM-ICU, or the Intensive Care Delirium Screening Checklist (ICDSC). Both tools are extensively validated in the literature and can be used for an initial diagnosis or ongoing evaluation. In addition, both tools allow for the assessment of attention, memory, and orientation; can be administered by nonpsychiatric ICU personnel; and can be adapted for patients who cannot speak due to MV. Research has shown that delirium is often unrecognized without validated screening tools in the ICU setting (Ali & Cascella, 2022; Devlin et al., 2018; Ramirez Echeverria et al., 2022).

Richmond Agitation-Sedation Scale (RASS)

The diagnosis of delirium for critically ill patients is a 2-step process. Before utilizing a screening tool such as the CAM-ICU, HCPs must thoroughly assess each patient's level of consciousness. To complete this assessment, HCPs should use an established sedation scale such as the Richmond Agitation-Sedation Scale (RASS). The RASS is a 10-point scale, ranging from -5 to 4, that assesses alertness and agitated behavior in critically ill patients; it is most frequently used with mechanically ventilated patients. The RASS can be administered in 30 to 60 seconds, and the scoring is based on HCP observation and patient response to auditory and physical stimulation. Scores from -1 to -5 denote levels of sedation, and scores of +1 to +4 denote levels of agitation (Ali & Cascella, 2022; Sessler et al., 2002). See Table 2 for RASS scores and associated descriptions.

Table 2

Richmond Agitation-Sedation Scale

(Sessler et al., 2002)

To utilize the RASS tool, HCPs should follow these steps (Ali & Cascella, 2022; Sessler et al., 2002):

1. Observe the patient; if the patient is alert and calm, the score is 0.
2. If the patient is not alert, state their name, and direct them to open their eyes and look at the speaker; repeat once if necessary.
   • If the patient has eye opening and eye contact sustained for more than 10 seconds, the score is -1.
   • If the patient has eye opening and eye contact sustained for less than 10 seconds, the score is -2.
   • If the patient has any movement in response to voice, excluding eye contact, then the score is -3.
3. If the patient does not respond to voice, stimulate the patient physically by shaking their shoulder; if there is no response, try rubbing their sternum.
4. If the patient has any movement to physical stimulation, the score is -4. If the patient has no response to voice or physical stimulation, the score is -5.

Any patient who scores -3 to +4 should be further assessed for delirium, utilizing the CAM-ICU. However, further assessment for delirium cannot be performed for patients who score -4 or -5, as this indicates deep sedation or a coma (Ali & Cascella, 2022; Kotfis et al., 2018; Sessler et al., 2002).

Confusion Assessment Method – ICU (CAM-ICU)

The CAM is a tool that HCPs can use to identify when delirium is a probable diagnosis. This tool has been used widely across medical and surgical settings and is reliable and valid, with a sensitivity of 94% to 100% and a specificity of 90% to 95%. In a review of bedside instruments used to detect the presence of delirium, the CAM tool was the most accurate, while the Mini-Mental Status Examination was the least accurate. The CAM-ICU was adapted from the CAM assessment and has been validated, with a sensitivity of 47% to 100% and a specificity of 81% to 100%. The CAM-ICU tool allows HCPs to consider observed behaviors and nonverbal responses to simple questions, as well as auditory and visual-recognition tasks for mechanically ventilated patients. In addition, the CAM-ICU takes 2 to 5 minutes to administer, making it ideal for incorporating into a bedside assessment. Table 3 depicts the CAM-ICU diagnosis tool with the features of delirium and associated assessment. The diagnosis of delirium requires the presence of 1 and 2, plus either 3 or 4 (Francis & Young, 2022; Poulsen et al., 2021; Ramirez Echeverria et al., 2022).

Table 3

CAM-ICU Diagnosis Tool for Delirium

(Francis & Young, 2022; Ramirez Echeverria et al., 2022)

Intensive Care Delirium Screening Checklist

The ICDSC is another delirium screening tool frequently used in the ICU. Researchers have found that the CAM-ICU and the ICDSC have high agreement rates. The ICDSC can be administered in 2 to 5 minutes and has a sensitivity of 64% to 99% and a specificity of 61% to 88%. Like the CAM-ICU, the ICDSC has two steps. HCPs must first assess a patient's level of consciousness based on the 5-point scale, ranging from A (unresponsive) to E (exaggerated response). No further delirium assessment can be performed for patients who score an A or B. Further assessment includes checking information collected during the previous 24 hours for patients who score C to E. The HCP will determine if eight items were present or absent, leading to a score of 0 to 8. A score of 4 to 8 is considered diagnostic of delirium. Table 4 depicts the ICDSC criteria for delirium screening (Ali & Cascella, 2022; Poulsen et al., 2021).

Table 4

The Intensive Care Delirium Screening Checklist

(Ali & Cascella, 2022; Girard et al., 2008)

Diagnostic Testing

Additional diagnostic testing may be needed based on the patient's history and physical examination findings to facilitate the diagnosis of the underlying etiology. Laboratory testing may be indicated; a complete blood count (CBC), complete metabolic profile (CMP), urinalysis, and urine culture are usually appropriate for all patients with delirium. Additional laboratory testing should be done if these initial tests do not uncover a specific etiology or suspicion warrants specific testing. Some additional tests might include serum drug levels (e.g., lithium, digoxin, quinidine), urine and serum toxicology screening, arterial blood gas (ABG), thyroid-stimulating hormone (TSH), vitamin B12, erythrocyte sedimentation rate (ESR), antinuclear antibody (ANA), liver function tests, and blood cultures (Francis & Young, 2022; Huang, 2022; Ramirez Echeverria et al., 2022).

Neuroimaging with head computed tomography (CT) should be done on certain patients based on their history and physical examination and if initial testing has not revealed the cause of delirium. Neuroimaging may not be necessary for patients with no obvious signs of trauma or new focal neurological signs who are arousable, can follow commands, and/or have a treatable condition that has been identified. However, a head CT should be performed if a patient does not improve with treatment as expected. For some patients, magnetic resonance imaging (MRI) may be considered since it is more sensitive than a CT scan for detecting an acute stroke or specific brain lesions (Francis & Young, 2022; Huang, 2022; Ramirez Echeverria et al., 2022).

Other diagnostic tests may include chest radiography, an electrocardiogram (ECG), and a bladder scan. A lumbar puncture may be warranted for patients with signs and symptoms of infection where the source is unknown. A cerebrospinal fluid (CSF) evaluation can help identify bacterial meningitis or encephalitis. For patients with a fever, HCPs should have a low threshold to perform a lumbar puncture. Finally, electroencephalography (EEG) should be considered for patients with altered levels of consciousness to monitor for seizure activity (i.e., subclinical or nonconvulsive) or confirm the metabolic or infectious encephalopathies that have characteristic EEG patterns (Francis & Young, 2022; Huang, 2022; Ramirez Echeverria et al., 2022).

Prognosis

The prognosis for patients with ICU delirium can vary based on the underlying etiology, the timing of diagnosis and intervention, and patient comorbidities. Recovery may be slower for older patients, those with severe disease, and those who are mechanically ventilated. ICU delirium can lead to a longer duration of MV, prolonged hospitalization, high morbidity and mortality rates, cognitive and functional decline, and an increased risk of long-term care placement. Mortality rates for patients with delirium are estimated to be 14% at 1 month and 22% at 6 months compared to patients without delirium. In addition, patients who develop delirium while admitted to the hospital have a 35% to 40% mortality rate within 1 year. Patients with ICU delirium are also more likely to experience aspiration pneumonia, pressure ulcers, decreased mobility, falls, malnutrition, and fluid and electrolyte imbalances (Francis, 2019; Huang, 2022; Ramirez Echeverria et al., 2022).

Critically ill patients with delirium are at risk for prolonged mechanical ventilation (PMV). The Centers for Medicare and Medicaid Services (CMS) define PMV as more than 21 days of MV for at least 6 hours per day. An estimated 300,000 patients require MV each year in the US. Of these patients, between 4% and 13% require PMV, which equates to 7,250 to 11,400 patients needing PMV at any time. PMV is associated with increased length of stay (LOS), healthcare costs, ventilator-associated events (VAEs), morbidity, and mortality (King Han, 2022).

Post-Intensive-Care Syndrome (PICS)

ICU delirium is also associated with long-term cognitive, mental, and physical impairments that are termed post-intensive-care syndrome (PICS). PICS refers to a group of problems patients can experience after surviving critical illnesses and MV (American Thoracic Society, 2020). PICS is characterized by prolonged impairment in cognition, mental health, and physical functioning that can persist for years following ICU admission (Lacomis, 2021). As many as 50% of patients who survive critical illness experience at least one PICS-associated complication, negatively impacting 5-year morbidity and mortality (American Thoracic Society, 2020). The physical impairments of PICS arise from patients who experienced ICU-acquired weakness (ICUAW; i.e., neuromuscular weakness secondary to critical illness, prolonged bed rest, and immobility), with long-term sequelae that can include persistent generalized weakness, poor mobility, falls, joint contractures, and an inability to perform ADLs. PICS can affect anyone who survives critical illness, even those who were healthy before their illness. People with existing chronic medical conditions such as lung disease or muscle disorders are at a higher risk of developing PICS. In addition, people with psychiatric illness or cognitive impairment (e.g., dementia) are more likely to experience more severe symptoms after discharge. Patients receiving MV are at higher risk for developing PICS related to muscle weakness and the likelihood of having severe infections, acute respiratory distress syndrome (ARDS), hypoxia, ICU delirium, and hypotension (American Thoracic Society, 2020; Lacomis, 2021).

Physical impairment in PICS affects 25% to 80% of adult ICU survivors, with the highest prevalence among those with sepsis. An estimated 80% of adult ICU survivors will develop symptoms consistent with the cognitive dysfunction component of PICS. Although some of these symptoms may improve over time, many patients have persistent effects for years after discharge, particularly patients with ARDS or sepsis. In addition, as many as 50% of ICU survivors have been diagnosed with post-traumatic stress disorder (PTSD), impacting their mental health for years. Among ICU survivors, risk factors for cognitive impairment include preexisting cognitive deficits, frequent or prolonged periods of hyperglycemia or hypoglycemia, and delirium. There is strong evidence that patients with new-onset or prolonged delirium while in the ICU are at greater risk for long-term cognitive dysfunction. Depression, anxiety, and PTSD are major mental health conditions that occur with ICU delirium and PICS (Poulsen et al., 2021; Smith & Rahman, 2022).

Prevention and Management Strategies

The principles underlying the management of ICU delirium focus on two pathways that should be followed simultaneously: one to identify and treat the underlying medical disorder and the other to manage the behavioral disturbance. Numerous precipitating factors can cause delirium, see Table 1. When the illness or illnesses are identified, treatment strategies should be employed that are specific to those illnesses (Francis, 2019; Reznik & Slooter, 2019).

General Supportive Measures

Critically ill patients with ICU delirium are at risk for complications such as PMV, immobility, and irreversible functional decline. HCPs should implement general support measures to maintain adequate nutrition and hydration, enhance mobility, prevent skin breakdown, ameliorate incontinence, treat pain, minimize sensory deficits (e.g., vision and hearing), and minimize the risk of aspiration. It is also important for these patients to maintain a proper sleep/wake cycle. Their environment should be calm and quiet, with minimal sleep disruptions when possible. An interdisciplinary approach should also include family members and caregivers, allowing them frequent visitation. During daytime hours, HCPs should ensure that windows are open, clocks and calendars are updated, and television or radio programs are utilized to help connect the patient to their routine. Frequent reorientation by HCPs and family members can also effectively manage delirium symptoms (Berry, 2022; Francis, 2019; Huang, 2022).

Nonpharmacologic Multicomponent Interventions 

The SCCM clinical practice guidelines (2018) recommend using a multicomponent, nonpharmacologic intervention focused on reducing the risk factors for ICU delirium, optimizing sleep, and improving cognition and mobility in critically ill patients. The ABCDEF bundle is an example of a protocolized, multicomponent intervention that is frequently used for mechanically ventilated patients in the ICU. Recent research has suggested that when the ABCDEF bundle is used along with the CAM-ICU screening tool, bundle compliance is significantly associated with reduced mortality and more delirium-free ICU days (Devlin et al., 2018).

The ABCDEF bundle of care is an evidence-based approach to preventing complications associated with critical illness and MV (Smith & Rahman, 2021). Traditionally, ICU staff have frequently implemented sedation and restraints to facilitate necessary treatments. However, these iatrogenic aspects of care can threaten patient dignity and result in physical, cognitive, and psychological harm. The ICU Liberation Collaborative is a real-world quality-improvement (QI) initiative designed to engage healthcare facilities in the strategic implementation of an ABCDEF bundle utilizing team-based care. Although the ICU Liberation Collaboration has a specific bundle to guide implementation, it is not designed to be a static, rigidly applied protocol. Instead, the bundle can be adapted to institutional preferences and needs. The concepts were designed to assist all ICU programs (e.g., small and large, community and academic, public and governmental) with varying patient populations. The ICU Liberation Collaboration QI initiative has been implemented in 76 ICUs across the US (Wesley Ely, 2018). The key components of the ABCDEF bundle consist of the following (Mart et al., 2021; Wesley Ely, 2018):

• Assess, prevent, and manage pain: Pain is a common occurrence in ICUs that can often go unrecognized and undertreated. Untreated pain is a risk factor for the development of delirium in ICU patients. HCPs must actively assess and manage pain to prevent complications. The preferred first-line medications are IV opioids. Alternative medications (e.g., NSAIDs and gabapentin [Neurontin]) and non-pharmacologic interventions should also be considered to reduce the number of opioid doses required. Adequate pain management reduces delirium and facilitates the performance of other components of the ABCDEF bundle (e.g., early mobilization [EM] and breathing trials).
• Spontaneous awakening trials (SAT) and spontaneous breathing trials (SBT): Coordinated and protocolized SATs and SBTs are foundational to liberation from MV. SATs involve the cessation of sedatives and narcotics for patients receiving MV. Daily interruption of sedation can decrease ventilator days, ventilator-acquired pneumonia (VAP) rates, mortality, and other complications such as ICUAW and PICS. The routine use of SBTs facilitates ventilator weaning and liberation. Using protocolized SBTs has reduced ventilator days, length of stay, mortality, and other complications. HCPs must complete a safety screen before initiating SATs or SBTs.
• Choice of analgesia and sedation: HCPs should use goal-directed sedation and analgesia to reduce each patient's overall drug burden and achieve light sedation. Routine assessments of pain and sedation levels should be done using validated measures. RAAS and the Riker Sedation-Agitation Scale (RAS) are recommended. The goal of sedation and analgesia for critically ill patients should be a calm, alert state allowing for patient interaction.
• Delirium assessment, prevention, and management: Delirium is a pervasive form of brain failure in critically ill patients characterized by waxing and waning confusion. Patients can experience hypoactive or hyperactive delirium. It is associated with increased mortality and long-term complications (e.g., PICS). HCPs play a critical role in identifying delirium, and screening should occur daily in the ICU. Two of the most common and validated instruments for detecting delirium are the ICDSC and the CAM-ICU. Promoting sleep, reducing noise, and providing EM can help minimize the development of delirium.
• Early mobility and exercise: EM is an essential component of the ABCDEF bundle that is often underutilized. Due to certain patients' severity of illness, the safety of EM and physical activity are often a concern for HCPs. Prolonged immobilization results in muscle wasting and weakness, PMV, poor functional status, ICUAW, and PICS. The safety and effectiveness of EM will be discussed in detail below.
• Family engagement and empowerment: Patients with critical illness and those requiring MV often cannot communicate with the care team and their families. Patient-centered care respects individual patient preferences, values, and informed clinical decision-making. Empowering family members to engage in shared decision-making and facilitating open communication improve patient outcomes. Critical illness can lead to significant psychological problems for patients and family members. HCPs who actively engage with patients and family members can prevent serious complications, including delirium, ICUAW, and PICS.

Managing Agitation

Managing agitation and disruptive behaviors can be challenging for HCPs and place patients at risk for falls or inadvertently pulling out catheters or IV lines. Most patients in the ICU will experience hypoactive delirium, but occasionally patients may experience hyperactive delirium with associated agitation. The SCCM guidelines recommend starting with nonpharmacologic interventions to manage agitation. The supportive measures discussed above can be helpful, specifically focusing on the hospital environment. In addition, frequent touch, reorientation, and reassurance can lessen agitation or disruptive behaviors. Physical restraints should be minimized because they can increase agitation and lead to complications such as pressure ulcers, aspiration, and prolonged delirium (Devlin et al., 2018; Francis, 2019).

Pharmacological Considerations

Pharmacological interventions for preventing and treating delirium have been studied more frequently over the last few decades. The SCCM guidelines do not recommend the use of pharmacologic interventions (e.g., haloperidol [Haldol], dexmedetomidine [Precedex], or ketamine [Ketalar]) to prevent delirium in critically ill patients. Although some studies show a decreased incidence of delirium among critically ill patients when these medications are used preventatively, there was no associated decrease in duration of MV, length of ICU stay, or mortality. Although some of these medications may help treat symptoms of agitation, they have not been shown to decrease the duration of delirium and may shift the patient into a hypoactive delirium state (Devlin et al., 2018; Reznik & Slooter, 2019).

Antipsychotic Medications

Antipsychotic medications that function as dopamine receptor antagonists have been a focus of recent studies to prevent and treat delirium. Since excess dopamine may play a role in delirium, these medications have been used clinically. However, no evidence has been found that antipsychotic medications prevent or shorten the duration of delirium in the ICU. The SCCM guidelines suggest that antipsychotics should be reserved for short-term use for patients with agitation that is not responsive to other nonpharmacologic treatment strategies. HCPs should use the lowest effective dose and stop the medication as soon as clinically indicated. Common antipsychotics used for agitation in critically ill patients with delirium include haloperidol (Haldol), quetiapine (Seroquel), and olanzapine (Zyprexa). Haloperidol (Haldol) has been most frequently used because of its availability via intramuscular and IV routes and faster onset of action (i.e., within minutes). It can be administered at 2 mg to 10 mg every 6 hours. However, haloperidol (Haldol) has a high risk of extrapyramidal side effects and a prolonged QT interval at high doses; 2 mg can be safely administered. Quetiapine (Seroquel) and olanzapine (Zyprexa) may have similar efficacy and fewer side effects compared to haloperidol (Haldol) in treating agitated delirium but have been studied less extensively. Quetiapine (Seroquel) can be administered orally in 50 mg tablets, with a maximum daily dose of 400 mg. Olanzapine (Zyprexa) can be administered intramuscularly at 5 mg to 10 mg, with a maximum daily dose of 30 mg (Ali & Cascella, 2022; Devlin et al., 2018; Reznik & Slooter, 2019).

Cholinesterase Inhibitors

Acetylcholine has been linked to the development of delirium, with decreased cholinergic activity causing cognitive dysfunction. Cholinesterase inhibitors are commonly used for patients with dementia, and researchers have conducted a few studies to evaluate the effect of these medications as a potential treatment for delirium. In a randomized, placebo-controlled study of rivastigmine (Exelon) used as an adjunct to haloperidol (Haldol), the rivastigmine (Exelon) group had longer-lasting delirium and increased mortality. Based on these results, the SCCM guidelines do not recommend using cholinesterase inhibitors to treat delirium (Devlin et al., 2018; Reznik & Slooter, 2019).

Sedation Strategies

Preventing delirium in critically ill patients can be challenging, specifically when the patients require MV. Patients receiving MV will require sedating medications, which can increase the risk of delirium. Utilizing the ABCDEF protocol, HCPs should focus on a goal of light sedation, with ventilator liberation as soon as possible. Deep sedation increases the risk of delirium, delayed extubation, and increased mortality. The SCCM guidelines recommend light sedation with daily SATs as part of item B in the ABCDEF protocol. SATs have been found to decrease ventilator dependence and ICU length of stay. HCPs should also be cautious of the type of sedation medications given to critically ill patients. Benzodiazepines, particularly midazolam (Versed) and lorazepam (Ativan), have been associated with an increased risk of delirium. The SCCM guidelines do not recommend benzodiazepines for sedation in critically ill patients except for cases of alcohol or benzodiazepine withdrawal (Devlin et al., 2018; Reznik & Slooter, 2019).

Dexmedetomidine (Precedex) is a centrally acting alpha-2-adrenergic receptor agonist with anxiolytic, sedative, and analgesic-sparing properties. It is recommended for sedation and analgesia because of its ability to maintain light sedation with a lower risk of cognitive effects. Recent research studies comparing benzodiazepines to dexmedetomidine (Precedex) found that sedation with dexmedetomidine (Precedex) reduced the prevalence and length of delirium and the time to extubation. Another recent study found that dexmedetomidine (Precedex) may reduce the incidence of ICU delirium when administered prophylactically; however, more research needs to be done. The SCCM guidelines currently do not recommend pharmacological therapy to prevent delirium. Dexmedetomidine (Precedex) is also effective for treating delirium-associated acute agitation. Recent studies have shown that dexmedetomidine (Precedex) reduced ventilator days, delirium duration, and time to extubation. In addition to favorable outcomes, dexmedetomidine (Precedex) has minimal effects on a patient's respiratory drive but can cause bradycardia. Propofol (Diprivan) is a short-acting general anesthetic that can also be used for sedation in critically ill patients. The SCCM guidelines recommend propofol (Diprivan) or dexmedetomidine (Precedex) over benzodiazepines for sedation in mechanically ventilated, critically ill patients (Devlin et al., 2018; Reznik & Slooter, 2019).

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