Delirium

Adam B. King

Christopher G. Hughes

INTRODUCTION

Delirium is a clinical syndrome characterized by fluctuations in mental status caused by acute cerebral dysfunction. Patients may present with inattention, disorganized thinking, disorientation, and/or altered levels of consciousness. Other symptoms associated with delirium include sleep disturbances, abnormal psychomotor activity, hallucinations, and emotional disturbances such as fear, depression, or anxiety. Patients may experience symptomatology that is hyperactive or hypoactive or fluctuate between both (mixed delirium). Although hyperactive delirium is more dramatic, hypoactive delirium is more common and much more underdiagnosed.

Development of delirium while in the intensive care unit (ICU) has been associated with increased cost, ICU length of stay, hospital length of stay, and long-term cognitive dysfunction. This risk is independent of preexisting comorbid conditions, severity of concurrent illness, and age. Additionally, duration of delirium has been shown to increase the relative risk of death by 10% per day of delirium.

Delirium is common among hospitalized patients. Upon admission, approximately 11% to 25% of elderly patients are delirious, and an additional 30% or so will go on to develop delirium. Delirium is even more frequent among critically ill patients; it is estimated that up to 80% of patients in the ICU experience an episode of delirium. Given the implications of an episode of delirium on patient outcomes, prevention and treatment is of utmost importance.

MANAGEMENT STRATEGY

Rule out life-threatening causes of mental status change such as hypoxia, hypercarbia, drug ingestion/withdrawal, or seizures.
Perform focused history and physical exam including assessment of arousal level and delirium with tools such as the confusion assessment method (CAM) or confusion assessment method for the intensive care unit (CAM-ICU).
Focus on appropriate and early removal of catheters/restraints, promote sleep, perform early mobilization, provide glasses and hearing aids, and eliminate unnecessary alarms and auditory stimuli (e.g., television).
Establish a calm, reassuring environment, and promote human contact, especially with loved ones.
Ensure patient and staff safety. Pharmacologic management may be required in patients whose agitation puts them at risk for harming themselves or others.

CAUSES OF DELIRIUM

The underlying mechanism of delirium or acute brain dysfunction has many proposed mechanisms. Systemic inflammation, cholinergic deficiency, and disturbances in other neurotransmitters such as serotonin and norepinephrine have been implicated in the development of delirium.

Risk factors for delirium can be characterized into patient factors, current illness factors, and iatrogenic causes, as outlined in Table 10.1. Baseline patient factors that have been associated with development of delirium include preexisting dementia, history of hypertension, alcoholism, and a high severity of illness upon admission. Additionally, age has been shown to be an independent risk factor for development of delirium outside of the ICU; however, within the ICU, there is discordance about it as a risk factor.

Clinicians are able to modify several risk factors for delirium by improving sleep hygiene and sedative regimens and avoiding medications that might trigger delirium. For instance, lorazepam administration is an independent risk factor for development of delirium in ICU patients undergoing mechanical ventilation. In addition, midazolam administration has been associated with worse delirium outcomes in mixed ICU patients.

Analgesic regimens, specifically opiates, do not have a clearly defined relationship with development of delirium. In fact, inadequate pain control is a risk factor for development of delirium. In a prospective study that enrolled patients with hip fractures without preexisting delirium, patients who received less than 10 mg of morphine equivalents per day were at increased risk of development of delirium. However, other studies have associated morphine and meperidine administration with the development of delirium. It appears that adequate pain control might be beneficial in protection against delirium, but use of opiates for sedation might place patients at risk for development of delirium.

NEUROANATOMY

Neuroanatomic changes that include brain atrophy and white matter changes have been witnessed in patients with delirium. White matter changes continue to persist even after hospital discharge and may be the cause of long-term cognitive impairment in these patients. In addition, patients have dysregulation of acetylcholine, dopamine, and γ-aminobutyric acid.

TABLE 10.1 Clinical Risk Factors for Delirium

Patient Factors	Acute Illness	Iatrogenic Causes
Baseline cognitive impairment	Electrolyte disturbances	Sedative medications
Age	Hypoxemia	Sleep disturbances
Baseline comorbidity	Global severity of disease	Anticholinergic medications
Frailty	Sepsis	Analgesic medications

FOCUSED HISTORY

Evaluation of the patient with suspected delirium should start with a history and physical exam. Causes of delirium such as drug ingestion, alcohol or drug withdrawal, metabolic derangements, and infection should be sought. Because features of delirium such as confusion or inattention may be present, history may be difficult to obtain from the patient. Assistance from staff or family members may be necessary. In addition, baseline functional status of the patient should be obtained, as this can help differentiate between dementia and delirium.

FOCUSED EXAM

Physical exam should look for possible sources of infection (e.g., pneumonia or urinary tract infection) as the cause of the patient’s acute change in mental status. In addition, physical exam findings suggestive of drug exposure may be useful. For example, anticholinergic exposure would reveal increased temperature, flushed dry skin, tachycardia, and pupillary dilation on exam. Focal neurologic findings that could point to seizure activity or stroke should also be sought.

The development of validated instruments now allows for assessment of patient’s level of arousal and content of consciousness even when a patient is mechanically ventilated. The Richmond Agitation-Sedation Scale (RASS) (Table 10.2) and the Riker Sedation-Agitation Scale (SAS) are commonly used tools that can be used to assess level of arousal. Assessment for delirium cannot occur if the patient is deemed unresponsive by the sedation scales (RASS −4 to −5 or SAS of 1 to 2). If the patient is responsive to verbal stimuli, then delirium can be assessed using tools such as the CAM, the CAM-ICU, or the Intensive Care Delirium Screening Checklist (ICDSC). Further information about these tools used for diagnosis of delirium can be found in the “Diagnosis” section.

Delirium is a syndrome of brain dysfunction and rarely presents as a single clinical entity. Pure hyperactive delirium is less common despite being the foremost perception of delirium to most clinicians. Patients with hyperactive delirium display prominent agitated motor behaviors such as pulling at lines/catheters and physically or verbally assaulting staff. In contrast, most patients are either hypoactive or have a mixed subtype. Hypoactive delirium is characterized by slow patient movements, decreased speed of cognition, and decreased alertness. It might be associated with worse outcomes; however, patients are often overlooked because they are not displaying disruptive behavior.

TABLE 10.2 Richmond Agitation-Sedation Scale Richmond Agitation-Sedation Scale

Score	Term	Description
+4	Combative	Overly combative, violent, immediate danger to staff
+3	Very agitated	Pulls or removes tube(s) or catheter(s); aggressive
+2	Agitated	Frequent or nonpurposeful movements, fights ventilator
+1	Restless	Anxious but movements not aggressive/vigorous
0	Alert and calm
−1	Drowsy	Not fully alert but has sustained awakening (eye opening/eye contact) to voice >10 s
−2	Light sedation	Briefly awakens with eye contact to voice (<10 s)
−3	Moderate sedation	Movement or eye opening to voice (but no eye contact)
−4	Deep sedation	No response to voice but movement or eye opening to physical stimulation
−5	Unarousable	No response to voice or physical stimulation

DIAGNOSIS

In addition to a history and physical exam, other causes of changes in mental status should be sought. An electrolyte panel, blood count, and liver and thyroid function tests should be obtained. Additionally, infectious causes should be ruled out with appropriate testing such as chest radiograph, urinalysis, and culture data. Hypoxemia and hypercarbia should also be excluded as causes of confusion, which may require arterial blood gas analysis.

After a thorough history and physical exam, the next step is determining the patient’s level of arousal through the use of a sedation scale such as the RASS, as described in the physical exam section. If the patient is determined to be unresponsive, RASS −4 or −5, then they are in a coma and cannot be assessed for delirium. There are several validated tools through which delirium diagnosis and screening can be performed.

TOOLS FOR SCREENING AND DIAGNOSIS

Diagnosis of delirium relies on determination from the history and physical that the condition is an acute change in the patients’ status. In patients who are not mechanically ventilated, the CAM (Table 10.3) can be used for diagnosis. The CAM assesses the patient for the key features of delirium such as an acute onset, fluctuating course, and inattention. It then assesses the patient for other symptomatology of delirium such as disorganized thinking or altered level of consciousness.

In critically ill or mechanically ventilated patients, the CAM-ICU (Table 10.4) and ICDSC (Table 10.5) have been validated. The CAM-ICU assesses the same four features as the CAM in an abbreviated manner more applicable to patients with critical illness: acute change or fluctuation in mental status, inattention, disorganized thinking, and an altered level of consciousness. The ICDSC uses eight diagnostic features; the diagnosis of delirium requires four or more features to be present.

DIAGNOSIS OF DELIRIUM AFTER STROKE

The incidence of poststroke delirium varies from 10% to 48%. Diagnosis of delirium in this patient population requires the ability to differentiate
delirium from mental status changes from the underlying disease process. The CAM-ICU has been validated in stroke patients by comparing it to the Diagnostic and Statistical Manual of Mental Disorders, 4th edition (DSM-IV), criteria for delirium. The CAM-ICU proved to be 76% sensitive and 98% specific for the diagnosis of delirium after stroke. The positive predictive value was 91%.

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