1st February 2024

Background

Delirium is derived from the Latin word ‘de lira’, meaning ‘out of the furrow’.

Delirium is a serious neuropsychiatric syndrome called an acute confusional state or acute brain failure common among medically unwell individuals. It is often misdiagnosed as a psychiatric illness, which can delay the diagnosis and management of the patient. The delay is mainly in offering the right medical intervention. It is a medical emergency.

Delirium is characterised by global impairments in attention and cognition. It is a common and serious condition that can be identified and treated well before it worsens.

Types

1. Hypoactive Delirium
2. Hyperactive Delirium
3. Mixed type of Delirium

DSM 5 Criteria- All the criteria to be met:

1. Disturbance in attention and awareness (reduced ability to direct, focus, sustain and shift attention)
2. The disturbance  develops acutely and fluctuates in severity
3. At least one additional disturbance in cognition (deficits in memory, orientation, language and communication, executive function, visuospatial-visuoperceptual, 
4. Disturbances cannot be explained by pre-existing dementia
5. Disturbances do not occur in the context of a severely reduced level of arousal or coma
6. Evidence of an underlying organic cause or causes (evidence from history, examination or investigations)

Epidemiology

Literature search goes back to the first century. This condition was defined as a state of altered consciousness, behavioural anomalies and fever. Subsequently, it encompassed intoxication and other conditions too.

In the 19th century, delirium was finally defined as a stereotypic manifestation of acute cerebral disturbance and referred to toxic and infective causes. After the 1950s, distinctive cerebral insufficiency or acute brain failure was identified.

• It is the commonest psychiatric presentation of a medical illness observed in admitted patients.
• It is the commonest psychiatric manifestation in medical and surgical patients
• 10-30% of the individuals in the general ward can manifest with delirium at some point of admission.
• The incidence can be as high as 80% among critically ill patients.
• In older individuals, the incidence can be as high as 30-60%
• The incidence in the community is comparatively lower, around 1-2%
• Rates are higher in post-surgical (hip surgery), ICU and palliative care patients. Evidence suggests that this can be of the order of 70-80%.
• Pre-existing dementia increases the risk of delirium by 5 fold
• Almost half of the cases are preventable

Risk factors

• Age is by far the commonest risk factor
• Serious medical conditions- malignancy, burns, dialysis
• Endocrinological abnormalities- hypo or hyperthyroidism and parathyroidism, Cushing’s and Addison’s syndrome
• Environmental changes and emotional distress
• Infections and inflammatory conditions, UTI, constipation
• Major surgery- Usually 2nd/3rd post-op day. Surgeries such as cardiotomy, hip surgery and transplantation have been noted to be risk factors
• Metabolic causes- Hypoglycaemia, hypo or hyperkalaemia, hypo or hypernatremia, acidosis and alkalosis, anaemia, hypoalbuminemia
• Medications- sedatives, hypnotics, steroids, polypharmacy, painkillers, anticholinergics, narcotics
• Nutritional- Anaemia, vitamin deficiencies
• Pain
• Pre-existing CNS lesions- Parkinson’s, stroke, dementia
• Sleep deprivation
• Substance abuse
• Systemic infections- Sepsis, peritonitis, etc.
• Shock
• Sensory deprivation
• Traumatic causes
• In 30% of cases, there is no known cause

Pathophysiology

The aforementioned risk factors contribute to the exposure of the brain to hyperdopaminergic and hypocholinergic states and, therefore, lead to impaired functioning of the brain. 

Multiple pathogeneses have been hypothesised:

1. The permeability of the blood-brain barrier is increased in infections and inflammatory conditions
2. Reduced cerebral perfusion is an added factor in association with CNS conditions
3. Disruption of RAS- Reticular activating system
4. Hyperdopaminergic state due to excess dopamine release in reaction to oxidative stress
5. Hypomelatonin state and hyper norepinephrine can result in sleep-wake disturbances impacting circadian rhythm
6. Excess GABA activity and or reduced activity can be seen causing delirium
7. Cerebral metabolic inadequacy due to impaired glucose metabolism
8. Tissue destruction, infection and inflammation can cause excess cytokines
9. The functional connection between the dorsal anterior cingulate cortex and the suprachiasmatic nucleus is augmented here, while that with the posterior cingulate cortex, parahippocampal gyrus, cerebellum and thalamus is lessened. Likewise, functional connectivity between the dorsolateral prefrontal cortex and posterior cingulate cortex is amplified, while the connectivity is reduced with subcortical regions of the brain.