Definition

The diagnosis of delirium is primarily clinical and is based on careful observation of key features. The gold standard criteria for its diagnosis, as described in the Diagnostic and Statistical Manual of Mental Disorders (DSM), continue to evolve.¹^–³ Delirium manifests with the following: a reduced ability to focus, sustain, or shift attention; a change in cognition or development of perceptual disturbance that is not better accounted for by preexisting established or evolving dementia; a disturbance that develops over a short period of time and tends to fluctuate over the course of the day; and evidence that the disturbance is caused by the direct physiologic consequences of a general medical condition.³

Subtypes of delirium may be classified by psychomotor symptoms: hyperactive-hyperalert, hypoactive-hypoalert, or mixed.⁴ In hyperactive delirium, a patient may have heightened arousal, with restlessness, agitation, hallucinations, or inappropriate behavior. In hypoactive delirium, a patient may be lethargic, with reduced motor activity, incoherent speech, or lack of interest. Mixed delirium is a combination of hyperactive and hypoactive signs of delirium.

Epidemiology

Many hospitalized older patients become delirious, and hospital mortality rates among patients with delirium range from 25% to 33%.^5,⁶ In a systematic review of prospective studies of patients with hip fracture, the incidence of postoperative delirium ranged from 4% to 53.5%.⁷ Investigators disagree on whether hyperactive or hypoactive delirium is more common among patients with hip fracture.^8,⁹

In addition to death, delirium has been associated with longer length of hospital stay, increased hospital-acquired complications, persistent cognitive deficits, poor functional recovery, and increased rates of discharge to long-term care.^6,¹⁰^–¹³ The total additional 1-year health care cost estimates attributable to delirium range from $16,303 to $64,421 (US dollars in 2005) per patient.¹⁴

Pathophysiology

The pathogenesis of delirium remains uncertain because of the heterogeneity of the delirium syndrome. The three most popular theories are neurotransmission, inflammation, and chronic stress.

Central cholinergic deficiency is the leading hypothesized neurotransmitter mechanism. A patient’s drug-related anticholinergic exposure results in more severe symptoms of delirium.¹⁵ Dopaminergic excess, norepinephrine excess, melatonin deficiency, and derangements in serotonin have also been implicated because of their interactions with acetylcholine.¹⁶^–¹⁸

Under the inflammation hypothesis, delirium is believed to be a central nervous system response to systemic inflammation during a state of blood-brain barrier compromise.¹⁹ Thus, cytokines may also contribute to delirium. In particular, interleukin-1 (IL-1), IL-2, IL-6, and tumor necrosis factor-alpha (TNF-alpha) are of interest.²⁰^–²²

Chronic stress activates the sympathetic nervous system and the hypothalamic-pituitary-adrenocortical axis. This process, in turn, results in higher cytokine levels and chronic hypercortisolism.²³ Elderly patients with postoperative confusion have increased cortisol concentrations.²¹

Diagnosis

Although the gold standard criteria for the diagnosis of delirium are found in the Diagnostic and Statistical Manual of Mental Disorders (DSM), a simpler bedside instrument may be used to increase the likelihood of making a correct diagnosis. The most widely used instrument is the Confusion Assessment Method (CAM). The tool was validated against the reference standard ratings of geropsychiatrists based on the DSM Third Revised Edition and was designed to allow nonpsychiatric clinicians to diagnose delirium quickly and accurately after brief formal cognitive testing. The CAM can be administered in 5 minutes.²⁴

The CAM includes an instrument and a diagnostic algorithm for identification of delirium. The instrument assesses the presence, severity, and fluctuation of nine features of delirium: acute onset, inattention, disorganized thinking, altered level of consciousness, disorientation, memory impairment, perceptual disturbances, psychomotor agitation or retardation, and altered sleep-wake cycle. The CAM diagnostic algorithm is based on four central features of delirium: (1) acute onset and fluctuating course, (2) inattention, (3) disorganized thinking, and (4) altered level of consciousness. A diagnosis of delirium according to the CAM requires the presence of features 1, 2, and either 3 or 4²⁴ (Table 16-1).

Table 16-2 Predicting Postoperative Delirium: A Medical Risk Stratification Model *

One point is assigned, on admission, for each of the four risk factors present:

1. Vision impairment (binocular near vision worse than 20/70 after correction)

2. Severe illness (APACHE score >16)

3. Cognitive impairment (Mini-Mental State Examination at admission <24/30)

4. Dehydration (blood urea nitrogen/creatinine ration ≥ 18)

Incidence of Delirium among Hip Surgery Patients^†

Low risk (0 points): 3.8%

Intermediate risk (1-2 points): 11.1%

High risk (3–4 points): 37.1%

APACHE II, Acute Physiological and Chronic Health Evaluation II.

* Data from Inouye SK, Viscoli CM, Horwitz RI, et al. A predictive model for delirium in hospitalized elderly medical patients based on admission characteristics. Ann Intern Med 1993;119:474-81.

† Data from Kalisvaart KJ, Vreeswijk R, de Jonghe JF, et al. Risk factors and prediction of postoperative delirium in elderly hip-surgery patients: implementation and validation of a medical risk factor model. J Am Geriatr Soc 2006;54(5):817–22.

The CAM has been validated in multiple settings and various languages. It has good performance characteristics with a combined sensitivity rate of 94% (95% confidence interval [CI], 91% to 97%), a combined specificity rate of 89% (95% CI, 85% to 94%), and moderate to high interrater reliability (kappa, 0.7 to 1.0).²⁵

Risk Factors

The cause of delirium is typically multifactorial. In the surgical patient, the development of delirium can be linked to predisposing and precipitating factors at the preoperative, intraoperative, and postoperative stages.

Preexisting Patient Factors

Individual risk factors for postoperative delirium include cognitive impairment, older age, functional impairment, sensory impairment, depression, preoperative psychotropic drug use, psychopathologic symptoms, and institutional residence.²⁶ Prolonged waiting time for surgical repair of hip facture may increase the risk of postoperative delirium.²⁷

A predictive medical risk factor model for delirium was developed in a landmark study.²⁸ Under this model, predefined risk factors for delirium are assessed on admission. One point is assigned each of the four risk factors present: cognitive impairment measured using the Mini-Mental State Examination (score <24 indicating cognitive impairment), visual impairment defined as binocular near vision worse than 20/70 after correction using a standardized Snellen test, severe illness measured using the Acute Physiological and Chronic Health Evaluation II (APACHE II) score (scores >16 indicating severe illness), and dehydration (blood urea nitrogen to creatinine ratio ≥18). In this model, low, intermediate, and high risk for delirium are defined as the presence of no risk factors, one or two risk factors, or three or four risk factors, respectively. This medical risk stratification model was later validated in a prospective cohort study of hip surgery patients aged 70 and older whose incidence of delirium was 3.8% in the low-risk group, 11.1% in the intermediate-risk group, and 37.1% in the high-risk group²⁹ (Table 16-2).

Table 16-1 Confusion Assessment Method Diagnostic Algorithm

Feature 1: Acute Onset and Fluctuating Course

This feature is usually obtained from a family member or nurse and is shown by positive responses to the following questions: Is there evidence of an acute change in mental status from the patient’s baseline? Did the (abnormal) behavior fluctuate during the day, that is, tend to come and go, or increase and decrease in severity?

Feature 2: Inattention

This feature is shown by a positive response to the following question: Did the patient have difficulty focusing attention, for example, being easily distractible, or having difficulty keeping track of what was being said?

Feature 3: Disorganized Thinking

This feature is shown by a positive response to the following question: Was the patient’s thinking disorganized or incoherent, such as rambling or irrelevant conversation, unclear or illogical flow of ideas, or unpredictable switching from subject to subject?

Feature 4: Altered Level of Consciousness

This feature is shown by any answer other than “alert” to the following question: Overall, how would you rate this patient’s level of consciousness? (alert [normal]), vigilant [hyperalert], lethargic [drowsy, easily aroused], stupor [difficult to arouse], or coma [unarousable])

The diagnosis of delirium by the CAM requires the presence of features 1 and 2 and either 3 or 4.

Adapted from Inouye SK, Van Dyck CH, Alessi CA, et al. Clarifying confusion: the confusion assessment method. A new method for detection of delirium. Ann Intern Med 1990;113(12):941–8.

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