Summary

Introduction

Delirium is an acute, fluctuating change in mental status, with inattention, disorganised thinking, and altered levels of consciousness. [1] It is a potentially life-threatening disorder characterised by high morbidity and mortality.

Adverse sequelae

Mortality for those diagnosed with delirium in hospital is twice that of patients with similar medical conditions without delirium and rises as high as 14% within 1 month of diagnosis. [2] Delirium occurs in 20% to 25% of hospitalisations annually [3] and is the most common hospital-related complication in the US. [4] Despite its frequency, delirium is frequently under-recognised given the fluctuating nature of symptoms and an overall under-appreciation of its significance by healthcare providers. Moreover, delirium has also been associated with elevated risks for functional and cognitive decline, poor rehabilitation potential, institutionalisation, and re-hospitalisation. [1] [5] [6] [7] While delirium is generally considered reversible, studies suggest that delirium symptoms can last for weeks to months following onset. [8] Persistent delirium has been found to be frequent in older hospitalised patients, and associated with adverse outcomes. [9]

Classification

The Diagnostic and Statistical Manual of Mental Disorders IV notes that in order to be diagnosed with delirium, a patient must show all 4 of the following features. [10]

1. A disturbance in consciousness (i.e., reduced clarity of awareness of the environment) is evident, with reduced ability to focus, sustain, or shift attention. This disturbance in consciousness might be subtle, initially presenting solely as lethargy or distractibility, and might be frequently dismissed by clinicians and/or family members as being related to the primary illness.

2. A change in cognition (such as memory deficit, disorientation, language disturbance) or the development of a perceptual disturbance not better accounted for by a pre-existing or evolving dementia.

3. The disturbance develops over a short period (usually hours to days) and tends to fluctuate during the course of the day.

4. There is evidence from the history, physical examination, or laboratory findings that the disturbance is caused by the direct physiological consequences of a general medical condition, substance intoxication, or substance withdrawal.

Three clinical subtypes of delirium have been identified. [11] [12] These include:

1. Hyperactive delirium - a condition where a patient might have heightened arousal, with restlessness, agitation, hallucinations, and inappropriate behaviour

2. Hypoactive delirium - a condition where a patient might display lethargy, reduced motor activity, incoherent speech, and lack of interest

3. Mixed delirium - a combination of hyperactive and hypoactive signs and symptoms.

The term sub-syndromal delirium has also been used to define partially resolved or incomplete forms of delirium.

Epidemiology

The prevalence of delirium in the community is believed to be 1% to 2%, a figure that increases to 14% for patients aged >85 years. [8] Delirium affects up to 30% of all older medical patients. [13] Prevalence ranges from 10% and 40% in older hospitalised patients. [3] Among hospitalised patients, the prevalence of delirium ranges from 14% to 24% in the emergency department, to 15% to 53% for postoperative patients, and 70% to 87% for intensive care patients. [14] [15]

Pathophysiology

• The pathophysiology of delirium remains relatively unclear. In general, neuroimaging studies reveal disruptions in higher cortical functioning in multiple disparate areas of the brain, including the prefrontal cortex, subcortical structures, thalamus, basal ganglia, lingual gyri, and frontal, fusiform, and temporoparietal cortex. [16]

• Electroencephalographic (EEG) studies also show diffuse slowing of cortical activity.

• Theories on the pathogenesis of delirium point to the role of neurotransmitters, inflammation, and chronic stress on the brain. For example, the role of cholinergic deficiency in inducing delirium is strengthened by the clear association of anticholinergic drug use with increased incidence. [17]

• Dopaminergic excess is also believed to contribute, as evident by the protective role of dopamine antagonists, such as antipsychotic medications. Other neurotransmitters have also been implicated including noradrenaline, serotonin, gamma-aminobutyric acid, glutamate, and melatonin.

• Evidence also points to the role of cytokines such as interleukins 1 and 2 and TNF-alpha and interferon in contributing to delirium. [18]

• Finally, chronic hypercortisolism, as induced by chronic stress secondary to illness or trauma, may also contribute to delirium initiation. [19]