creation date: 2025-07-23 18:59
tags: Pathologies
Delirium
Background
Definitions
Delirium is a syndrome that develops typically in the elderly characterized by alteration of attention, consciousness, and cognition that develops over a short period and fluctuates throughout the day.
Delirium is caused by an underlying medical condition and is not better explained by another preexisting, evolving, or established neurocognitive disorder.
Etiology
The spectrum of conditions and causes of delirium are varied and extensive. Discussed here are the more common etiologies.
The most common cause of delirium are medication side effects.
- American Geriatrics Society Beers Criteria exhaustively lists medications with potential for harmful side effects in older adults
- BADMAPS: Benzos Anticholinergics Dopaminergics Metoclopramide Antipsychotics PPIs Sulfonylureas
- Prescription medications (eg. opioids, sedatives, antipsychotics, lithium, muscle relaxants, polypharmacy)
- Nonprescription medications (eg. antihistamines)
- Drugs of abuse (eg. ethanol, heroin, hallucinogens)
- Withdrawal states (eg. ethanol, benzodiazepines)
- Medication side effects (eg. serotonin syndrome)
Infection can also caused delirium. This can be due to sepsis or systemic/fever-related. It should be noted that asymptomatic bacteriuria is common in older patients and can lead to the underlying cause being prematurely attributed to a UTI. (Aside: overtreatment of asymptomatic bacteriuria may exacerbate delirium)
Metabolic abnormalities include:
- Electrolyte disturbances (eg. sodium, calcium, magnesium, phosphate)
- Endocrine disturbances (eg. thyroid, parathyroid, pancreas, pituitary, adrenal)
- Hypercapnia
- Hyperglycemia and hypoglycemia
- Hyperosmolar and hypoosmolar states
- Hypoxemia
- Inborn errors of metabolism
- Nutritional (eg. Wernicke encephalopathy, vit. B12 deficiency)
Brain disorders and systemic organ failure:
- CNS infections
- Epileptic seizures, especially nonconvulsive status epilepticus
- Head injury
- Hypertensive encephalopathy
- Psychiatric disorders
- Cardiac failure
- Hematologic abnormalities
- Liver failure
- Pulmonary disease
- Renal failure
Poisons and toxins (eg. atypical alcohols, carbon monoxide, plant-derived) and physical disorders (eg. burns, electrocution, hypo-/hyperthermia, trauma) can also manifest as delirium.
In highly vulnerable patients, even smaller disturbances such as constipation, dehydration, or urinary retention can precipitate delirium.
Pathogenesis
Delirium is a manifestation of stress on the function of the central nervous system. The pathophysiology of delirium is generally accepted to be multifactorial, involving precipitant factors or insults to a vulnerable patient with predisposing factors, both of which are discussed below.
A number of processes have been hypothesized to contribute to the pathophysiology:
Increased age
Age-related changes diminishes physiological reserves, increasing vulnerability to physical stress and illness. Changes include:
- Decreased brain blood perfusion
- Increased neuron loss
- Change to proportion of stress-regulating neurotransmitters
Neuroinflammation
Peripheral inflammatory insults causes cell-cell adhesions at blood brain barrier resulting in central nervous system inflammation.
Reactive oxidation species
ROS and RNS mediate cellular damage including central nervous system, which is particularly susceptible.
Circadian rhythm dysregulation
Disruption to sleep duration and melatonin secretion leads to central nervous system function disruption including sleep-wake cycles, glucose regulation, core body temperature, antioxidant defences, and immune responses.
Neurotransmitter imbalance
Delirium is associated with decreased acetylcholine and increased dopamine activity.
Neuroendocrine
Glucocorticoid release due to physiological stress increases risk of neuron damage.
Clinical Presentation
Signs & Symptoms
Delirium manifests with several key features.
Disturbance of consciousness
- One of the earliest manifestations
- Change in awareness
- Change in ability to focus, sustain, or shift attention (distractibility)
- Often subtle, possibly reported as “isn’t acting quite right” from family
Altered cognition
- Memory loss, disorientation, and difficulty with language and speech
- Mental status testing may document degree of impairment as well as patient’s attentiveness while answering questions
- Baseline should be ascertained from family/friends
- Illusions (false misinterpretation of stimulus)/hallucinations (perception without stimulus); hallucination typically visual
Temporal course
Acute nature differs from dementia:
- Develops over hours to days
- Persists for days to months
Unstable features: - Symptoms are more severe in the evening and at night
- Features may fluctuate throughout the day
Prodromal phase: - May occur, especially with older patients
- Complaints of fatigue, sleep disturbances, depression, anxiety, restlessness, irritability, hypersensitivity to light/sound
- Blends into quiet/hypoactive delirium or erupts to agitated confusional state
Other features
In older patients, the only manifestation of acute illness may be delirium. Delirium should be treated with prompt medical attention.
There is great variability in the constellation of features that are present. Delirium is typically grouped into 3 main manifestations:
- Hyperactive delirium, characterized by increased agitation and sympathetic activity
- Hypoactive delirium, characterized by increased somnolence and decreased arousal and is easily mistaken for fatigue or depression
- Mixed presentation, which involves fluctuation between hyper- and hypoactive delirium
History & Physical Exam
A thorough history may not be possible due to the altered cognition. History elicited from family or friends may be more useful.
Important information to elicit promptly include:
- Chronology of onset and symptoms
- Clues that points to underlying etiology (eg. recent febrile illness, history of organ failure, medication list)
As a comprehensive physical exam is often difficult with an uncooperative patient, a focused assessment should be made:
- Vital signs
- State of hydration
- Skin condition
- Potential infectious foci
General appearance may point towards certain underlying conditions. Focal neurologic findings may also be evident but a comprehensive neurologic examination is likely not possible.
Risk factors
Common predisposing factors are:
- Older age (>70 years)
- Dementia (may or may not be clinically diagnosed)
- Functional disabilities
- Male sex
- Poor vision and hearing
- Mild cognitive impairment
- Alcohol use disorder and laboratory abnormalities
Diagnosis
Criteria
The Confusion Assessment Method (CAM) can be used to determine if delirium is the most probable diagnosis.
Diagnosis requires features 1 and 2 plus either 3 or 4:
- Acute onset and fluctuating course (usually obtained by family or nurse)
- Inattention (easily distractible or difficulty keeping track of what was said)
- Disorganized thinking (eg. rambling or irrelevant conversation)
- Altered level of consciousness (anything other than normal/alert)
Work-up
The goal of the delirium work-up is to identify the etiology. Targeted testing is appropriate and should be guided by suspicion or lack thereof.
Laboratory tests:
- Serum electrolytes, creatinine, glucose, calcium, CBC
- Urinalysis and urine culture
- Drug levels
- Toxic screen of blood and urine
- Blood gas determination
- Liver function tests
Neuroimaging with CT head is not routine but is indicated if there are findings on neurologic examination, suspicion of trauma, if no obvious cause is found with initial evaluation, or if the patient is not responding to initial treatment.
Lumbar puncture is necessary when no cause is found with prior workup. This is because cerebrospinal fluid analysis may be the only way to diagnose bacterial or aseptic meningitis and encephalitis. A low threshold should be used for febrile patients with delirium, even when alternative explanations are present or suspected.
Electroencephalography (EEG) are useful to exclude seizures (especially nonconvulsive ones which may not have ictal or post-ictal features) and confirm certain metabolic or infectious encephalopathies.
Differential
The most common diagnoses that present similarly are depression and dementia. However, the key features of acute onset, fluctuating course, altered consciousness, and cognitive decline should differentiate delirium.
Other diagnoses include:
- Sundowning
- Lobar or focal neurologic syndromes
- Nonconvulsive status epilepticus
- Primary psychiatric illnesses
Red Flags / Complications
Delirium has a large impact on health especially older patients. Patients experience:
- Prolonged hospitalizations
- Functional and cognitive decline
- Higher mortality (2x that of patients without delirium)
- Higher risk for institutionalization
Management
Prevention
No intervention reliably prevents delirium. However, modifying risk factors may reduce the incidence of delirium:
- Orientation protocols (eg. provision of clocks, calendars, views of outside)
- Cognitive stimulation (eg. regular visits from friends and family)
- Facilitation of physiologic sleep (eg. avoid administering medications during sleeping hours)
- Mobilization and minimized use of physical restraints
- Visual and hearing aid if needed
- Avoiding use of problematic medications
- Treatment of medical complications and pain
Treatment of underlying conditions
As mentioned previously, virtually any medical condition can precipitate delirium. The mainstay management of delirium is to treat the underlying condition.
Supportive care
Beyond identification and intervention for the underlying causes, supportive care should be done to prevent complications of immobility and confusion. This includes:
- Maintaining adequate hydration and nutrition
- Enhancing mobility and range of motion
- Treating pain and discomfort
- Preventing skin breakdown
- Ameliorating incontinence
- Minimize the risk of aspiration pneumonitis
- Assessment of caregiver resources
Managing agitation
While hyperactive delirium is less common with older patients, manifestations of agitation may need to be controlled to prevent harm and/or to allow evaluation and treatment.
If non-pharmacological interventions such as interpersonal and environmental manipulations are adequate, such interventions should be prioritized. Physical restraints should be used as last resorts and is associated with exacerbation of delirium.
Antipsychotic medications can be used to treat severe agitation - although with limited evidence and off-label.
- Haloperidol 0.5-1 mg prn up to maximum total daily dose of 5 mg (note: risk of QT prolongation)