Sedation and Delirium

1 What is delirium?

Delirium is defined by the Diagnostic and Statistical Manual of Mental Disorders (DSM-IV) as:

2 Why is it important to diagnose delirium?

The true prevalence and magnitude of delirium have been poorly documented because a myriad of terms, such as acute confusional state, intensive care unit (ICU) psychosis, acute brain dysfunction, and encephalopathy have been used historically to describe this condition. Although the overall prevalence of delirium in the community is only 1% to 2%, the prevalence increases with age, rising to 14% among those more than 85 years old. It may range from 14% to 24% with incidence rates up to 60% among general hospital populations, especially in older patients and those in nursing homes or post–acute care settings. In critically ill patients in the ICU (medical, surgical, trauma, and burn units) the reported prevalence of delirium is 20% to 80%, depending on the severity of illness, and may be closer to 80% in those who are receiving mechanical ventilation. In spite of this, the condition is often unrecognized by clinicians or the symptoms are incorrectly attributed to dementia or depression or considered an expected, inconsequential complication of critical illness. Numerous national and international surveys have shown a disconnect between the perceived importance of delirium, the accuracy of diagnosis, and the implementation of management and treatment techniques. Given that delirium is the most common organ dysfunction seen in critically ill patients and is associated with worse acute and long-term outcomes, it is important to diagnose and manage the disease by implementation of validated screening protocols.

3 What morbidity and mortality are associated with delirium?

Delirium is a strong predictor of a longer hospital stay, longer times receiving mechanical ventilation, higher costs, and increased risk for death. Additionally, each additional day with delirium increases the risk for dying by 10%. Patients with longer periods of delirium are also associated with more cognitive decline, when evaluated after 1 year, attesting to the importance of detecting and managing delirium early in the course of illness.

4 Describe the clinical features of delirium

The most important feature of delirium is a disturbance of consciousness accompanied by inattention and a change in cognition that cannot be explained by preexisting or evolving dementia. The condition develops over a short period of time, usually hours to days, and tends to fluctuate during the course of the day.

Delirium may be manifested by a reduced clarity of awareness of the environment and ability to focus, sustain, or shift attention. This may be accompanied by memory impairment, disorientation, or language disturbance. Speech or language disturbances may be evident as dysarthria, dysnomia, dysgraphia, or even aphasia. In some cases, speech is rambling and irrelevant, in others pressured and incoherent, with unpredictable switching from subject to subject. Perceptual disturbances may include misinterpretations, illusions, or hallucinations. Delusion is often associated with a disturbance in the sleep-wake cycle. Patients may also exhibit anxiety, fear, depression, irritability, anger, euphoria, and apathy.

5 What are the subtypes of delirium?

Delirium can be classified by psychomotor behavior into the following:

Patients with both features have mixed delirium.

6 Describe risk factors for delirium

Many risk factors for delirium exist, and these can be divided by host, acute illness, and iatrogenic and environmental factors (Table 73-1). Many of these factors are modifiable. Fortunately, several mnemonics can aid clinicians in recalling the list; two common ones are IWATCHDEATH and DELIRIUM (Table 73-2).

^{Table 73-1} Risk Factors for Delirium

^* Modifiable risk factors.

^{Table 73-2} Mnemonics for Risk Factors for Delirium

CHF, Congestive heart failure; CVA, cerebrovascular accident; MI, myocardial infarction.

7 How is delirium diagnosed?

The diagnosis of delirium is primarily clinical and is based on careful bedside observation of key features. It is a two-step process. Level of arousal is first measured, and, if the patient is arousable, delirium evaluation can be performed by instruments such as the Confusion Assessment Method or the Delirium Rating Scale–Revised 98 (DRS-R 98) in hospitalized patients. The DRS-R 98 provides a measure of severity of delirium in addition to the ability to diagnose delirium. In the ICU, delirium can be diagnosed by using a sedation scale to assess arousal followed by either the Confusion Assessment Method for the ICU (CAM-ICU) or the Intensive Care Delirium Screening Checklist (ICDSC); both these instruments are reliable and have been validated in critically ill patients.

8 How can detection of delirium be improved?

The Society of Critical Care Medicine (SCCM) has published guidelines for the use of sedatives and analgesics in the ICU. They recommend routine monitoring of pain, anxiety, and delirium with use of validated tools and documentation of responses to therapy for these conditions. A number of tools have been developed recently and validated for use, in both patients with endotracheal tubes in place and those without endotracheal tubes, and measured against a gold standard, the DSM criteria. These are the following:

Of these, the CAM-ICU and the ICDSC are the most frequently used instruments that have been translated into a number of languages.

These screening instruments differ in the components of delirium they evaluate, the threshold for diagnosing delirium, and their ability to be used in patients with impaired vision and hearing and in those who have endotracheal tubes and are receiving mechanical ventilation. Hence, it is important to consider the patient population when choosing the instrument.

9 What causes delirium?

The pathophysiology of delirium is poorly understood, although a number of hypotheses exist.

10 Which drugs are most likely to be associated with delirium?

Many drugs are considered to be risk factors for the development of delirium.

Marcantonio found that delirium was significantly associated with postoperative exposure to meperidine and benzodiazepines, although not to other commonly prescribed opiates. Long-acting benzodiazepines had a trend toward stronger association with delirium than the short-acting agents, and high-dose exposures had a trend toward stronger association than low-dose exposures. Although targeted pain control has been shown to be associated with improved rates of delirium, overzealous administration of opiates has been associated with worse outcomes. Similarly in the ICU, studies have shown that opioids and benzodiazepines are risk factors for delirium in medical and surgical ICU patients, though trauma and burn patients who have pain appear to be protected from development of delirium with intravenous opiates. The class of benzodiazepines does not seem to change the risk profile, with both lorazepam and midazolam being significant risk factors for delirium.

11 What psychiatric diagnoses may be confused with delirium?

Dementia can be difficult to distinguish from delirium, particularly when information about baseline cognitive functioning is unavailable, and is the most common differential diagnosis. Memory impairment is common to both delirium and dementia, but the person with dementia alone is alert and does not have the disturbance in consciousness that is characteristic of delirium. In delirium, the onset of symptoms is much more rapid and fluctuates during a 24-hour period. Delirium that is characterized by vivid hallucinations, delusions, language disturbances, and agitation must be distinguished from psychotic disorder, schizophrenia, schizophreniform disorder, and mood disorder with psychotic features. Finally, delirium associated with fear, anxiety, and dissociative symptoms such as depersonalization must be distinguished from acute stress disorder. Delirium must also be distinguished from malingering and factitious disorder.

12 How should the work-up of delirium be pursued?

The SCCM recommends routine monitoring of delirium with use of validated tools. A rapid assessment should be performed, including assessment of vital signs and physical examination to rule out life-threatening problems (e.g., hypoxia, self-extubation, pneumothorax, hypotension) or other acutely reversible physiologic causes (e.g., hypoglycemia, metabolic acidosis, stroke, seizure, pain). The IWATCHDEATH and DELIRIUM mnemonics can be particularly helpful for guiding this initial evaluation. See Table 73-2.

13 What studies should be considered in the work-up of delirium?

Routine laboratory tests are important but not the mainstay of diagnosis. These include a complete blood cell count, electrolytes, blood urea nitrogen, creatinine, glucose, calcium, pulse oximetry or arterial blood gas, urinalysis, urine drug screens, liver function tests with serum albumin, cultures, chest radiograph, and electrocardiogram. Cerebrospinal fluid examination should also be considered for cases in which meningitis or encephalitis is suspected. Other tests that need to be considered are VDRL, for the human immunodeficiency virus, B₁₂ and folate, heavy metal screen, antinuclear antibody, ammonia level, thyroid-stimulating hormone, measurement of serum medication levels (e.g., digoxin), and urinary porphyrins. Electroencephalogram changes have been seen in patients with delirium. Other tests that are still experimental include brain imaging and measures of serum anticholinergic activity.

14 How is delirium treated?

Once delirium is noted, an underlying cause should be ruled out before attempting pharmacologic intervention. Once life-threatening causes are ruled out, focus should be on the following:

To improve patient outcome, an evidence-based organizational approach referred to as the ABCDE bundle (Awakening and Breathing trials, Choice of appropriate sedation, Delirium monitoring, and Early mobility and exercise) is presented.

15 Describe the pharmacologic management of delirium

Patients who manifest delirium should be treated with a traditional antipsychotic medication (haloperidol) per the SCCM guidelines. Newer atypical antipsychotic agents (e.g., risperidone, ziprasidone, quetiapine, or olanzapine) also may prove helpful for the treatment of delirium. Although the Modifying the Incidence of Delirium (MIND) study showed no difference in the duration of delirium between haloperidol, ziprasidone, or placebo when used for prophylaxis and treatment, a smaller study done by Devlin et al. showed that quetiapine was more effective than placebo in resolution of delirium when supplementing ongoing haloperidol therapy. Data from the MENDS study and the SEDCOM trial support the view that dexmedetomidine can decrease the duration and prevalence of delirium when compared with lorazepam or midazolam. Benzodiazepines remain the drugs of choice for the treatment of delirium tremens (and other withdrawal syndromes) and seizures (Table 73-3).

^{Table 73-3} Pharmacologic Treatment of Delirium in Hospitalized Patients

IM, Intramuscular; PO, orally.

*Note: See text for more rapid effects with IV/IM dosing.

16 Describe the use of haloperidol in delirium

The SCCM guidelines recommend haloperidol as the drug of choice. It is a butyrophenone typical antipsychotic. It does not suppress the respiratory drive and works as a dopamine receptor antagonist by blocking the D₂ receptor, treating the positive symptoms (hallucinations and unstructured thought patterns).

Adverse effects include hypotension, acute dystonias, extrapyramidal effects, laryngeal spasm, malignant hyperthermia, glucose and lipid dysregulation, and anticholinergic effects. Perhaps the most immediately life-threatening adverse effect of antipsychotics is torsades de pointes, and these agents should not be given to patients with prolonged QT intervals unless thought to be absolutely necessary.

17 How is haloperidol dosed in delirium?

A recommended starting dose is 2 to 5 mg (IV or IM) every 6 to 12 hours; the maximum effective doses are usually around 20 mg/day.

18 How are second-generation antipsychotic agents used in delirium?

Newer atypical antipsychotic agents (e.g., risperidone, ziprasidone, quetiapine, and olanzapine) may also prove helpful for delirium. The advantage over haloperidol is theoretic and may be related to its effect not only on dopamine but also on other neurotransmitters such as serotonin, acetylcholine, and norepinephrine. Studies need to be repeated with larger patient populations before any concrete recommendations can be made regarding the efficacy of typical or atypical antipsychotics in delirium.

Key Points Delirium

1. Delirium is a disturbance of consciousness with inattention, accompanied by a change in cognition or perceptual disturbances that develop over a short period of time and fluctuate over days.

2. Delirium is associated with significant morbidity and mortality.

3. Diagnosis of delirium is a two-step process. Level of arousal is first measured, and, if the patient is arousable, delirium evaluation is performed with use of validated instruments.

4. Pharmacologic treatment should be used only after giving adequate attention to correction of modifiable contributing factors.

5. Pharmacologic treatments:

Haloperidol is considered to be the first-line drug and should be started at a low dose.

Atypical antipsychotics have also been used when risk for adverse events such as QTc prolongation or extrapyramidal side effects is estimated to be high. These drugs include olanzapine, risperidone, quetiapine, and ziprasidone.

Benzodiazepines should be reserved for use only in delirium associated with alcohol withdrawal.