Causes of Delirium
Delirium is caused by a multifactorial combination of predisposing vulnerability factors and precipitating factors, with medications, metabolic disturbances, and infections being the most common triggers. 1
Definition and Characteristics
Delirium is a manifestation of acute brain dysfunction defined as:
- A disturbance in attention and awareness that develops over a short period of time 1
- Fluctuating symptoms throughout the day, often worsening in the evening 1
- Accompanied by a change in cognition that cannot be explained by an established neurocognitive disorder 1
- Directly caused by a physiologic consequence of a medical condition, substance use, medication, or multiple etiologies 1
Predisposing Risk Factors (Vulnerability)
These factors increase baseline vulnerability to developing delirium:
- Advanced age - significantly increases susceptibility 1, 2
- Pre-existing cognitive impairment or dementia - major risk factor 1, 3
- Visual or hearing impairment - impairs sensory input and orientation 1
- Comorbid medical conditions including:
- Poor functional status - reduces physiological reserve 1
- History of alcohol or drug abuse - alters baseline neurological function 1
Precipitating Factors (Triggers)
These factors directly trigger delirium episodes:
Medications
- Psychoactive medications - particularly benzodiazepines 1
- Opioids - especially at higher doses 1
- Corticosteroids - dose-dependent risk 2, 3
- Anticholinergic medications - block neurotransmitter function 4
- Polypharmacy - increases risk through drug interactions 4
Physiological Disturbances
- Infections - especially urinary tract infections and pneumonia 1
- Metabolic abnormalities:
- Hypoxemia - reduces oxygen to brain tissue 5
- Dehydration - alters cerebral perfusion 1
- Organ failure - accumulates toxins affecting brain function 1
Neurological Causes
- Direct brain injury - trauma, stroke, hemorrhage 1
- Seizures - including non-convulsive status epilepticus 1
- Intracranial processes - tumors, metastases, elevated pressure 1
- Meningitis/encephalitis - direct infection of neural tissue 1
Hospital-Related Factors
- Sleep disruption - alters circadian rhythm 1
- Immobilization - particularly with restraints or catheters 1
- Mechanical ventilation - increases risk by 60-80% 1
- Sensory overload or deprivation - disorienting environment 6
- Pain - especially if poorly controlled 5
Cancer-Specific Factors
- Direct tumor effects - brain or leptomeningeal metastases 1
- Paraneoplastic syndromes - including anti-neuronal antibodies 1
- Cancer treatments - chemotherapy and radiotherapy 1
- Specific agents: methotrexate, cisplatin, ifosfamide, cytarabine 1
Pathophysiological Mechanisms
Multiple neurobiological processes likely contribute to delirium pathogenesis:
- Neuroinflammation - systemic inflammation affecting brain function 7
- Neurotransmitter imbalance - particularly acetylcholine deficiency and dopamine excess 7
- Brain vascular dysfunction - altered cerebral perfusion 7
- Impaired neuronal network connectivity - disrupting normal brain communication 7
- Altered brain metabolism - changes in energy utilization 7
Clinical Pitfalls to Avoid
- Missing hypoactive delirium - often underdiagnosed despite being more common than hyperactive delirium 1, 2
- Attributing symptoms to dementia - delirium is superimposed and represents acute change 1
- Overlooking medication causes - particularly in patients on multiple medications 4
- Focusing on a single cause - most cases (69%) have multiple contributing factors 1
- Delayed recognition - increases mortality risk and prolongs hospital stay 1, 8
Assessment Approach
Delirium will frequently go unrecognized without systematic screening using validated tools:
- Confusion Assessment Method (CAM) - widely used in general settings 1
- CAM-ICU or ICDSC - recommended for critical care settings 1
- Richmond Agitation Sedation Scale - helps quantify severity 1
Early detection and addressing underlying causes are essential for reducing morbidity and mortality associated with delirium 8.