Delirium

DSMV lists five key features that characterize delirium:1. Disturbance in attention (reduced ability to direct, focus, sustain, and shift attention)

and awareness.2. The disturbance develops over a short period of time (usually hours to days),

represents a change from baseline, and tends to fluctuate during the course of theday.

3. An additional disturbance in cognition (memory deficit, disorientation, language,visuospatial ability or perception)

4. The disturbances are not better explained by another preexisting, evolving orestablished neurocognitive disorder, and do not occur in the context of a severelyreduced level of arousal such as coma

5. There is evidence from the history, physical examination, or laboratory findings thatthe disturbance is caused by a medical condition, substance intoxication orwithdrawal, or medication side effect.

Additional features that may accompany delirium and confusion include the following:1. Psychomotor behavioral disturbances such as hypoactivity, hyperactivity with

increased sympathetic activity, and impairment in sleep duration and architecture.2. Variable emotional disturbances, including fear, depression, euphoria, or perplexity

There is no generally accepted consensus regarding the distinction between delirium and confusional

states. "acute confusional state" and "encephalopathy" are often used synonymously with delirium.

Confused patients are unable to think with normal speed, clarity, or coherence.

EPIDEMIOLOGY:

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10- 50%of older surgical patients.

70% of elderly in intensive care units

40%hospice units.

20%postacute care settings

Nursing home

The pathophysiology of delirium:

The biologic basis of delirium is poorly understood in part because it is difficult to study severely ill

patients with conventional electrophysiologic tests, brain imaging, or neurotransmitter assays.

1. Neurobiology of inattention:Arousal and attention may be disrupted by brain lesions involving the ascending reticular

activating system (ARAS) from the midpontine tegmentum rostrally to the anterior cingulate

regions.

Attention is governed by the "nondominant" parietal and frontal lobes. Thus with inattention,

there is typically some disruption of the integrated function of these regions.

electroencephalography (EEG) in acutely ill patients established that delirium was a disturbance

of global cortical function, characterized by slowing of the dominant posterior alpha rhythm and

the appearance of abnormal slow wave activity. The major exception appeared to be that of

delirium accompanying alcohol and sedative drug withdrawal, in which low voltage, fast wave

activity predominated

The results of brainstem auditory evoked potential, somatosensory evoked potentials, and

neuroimaging studies have supported an important role for subcortical (eg, thalamus, basal

ganglia, and pontine reticular formation) as well as cortical structures in the pathogenesis of

delirium

These findings correlate with clinical reports that patients with subcortical strokes and basal

ganglia abnormalities (including Parkinson disease) have a higher susceptibility to delirium.

2. Neurotransmitter and humoral mechanismsa) Acetylcholine depletion: this theory is supported by:

1. precipitating factors of delirium, such as hypoxia, hypoglycemia, and

thiamine deficiency, decrease acetylcholine synthesis in the central

nervous system (CNS)

2. Alzheimer disease, which is characterized by a loss of cholinergic

neurons, increases the risk of delirium due to anticholinergic

medications.

3. serum anticholinergic activity, measured with binding assays

employing purified preparations of brain muscarinic receptors,

correlates with the severity of delirium in postoperative and medical

patients

b) increased dopamine, serotonin, GABA,

c) Proinflammatory cytokines such as tumor necrosis factor alpha

transforming growth factor-b, interleukin-1, and interleukin-10 also may

have a role in the pathogenesis of delirium play prominent roles in the

induction of microvascular dysfunction and microglial activation,

Microvascular dysfunction may result in impaired cerebral blood flow in the

frontal and temporal lobes, Microglial activation seems to impair

neurotransmitter metabolism, particularly that of acetylcholine S-100b may be

elevated in sepsis associated delirium but not in septic patients without

delirium

3. Diminished cerebral oxidative metabolism

4. The limbic-hypothalamic-pituitary-adrenal axis and delirium sustained high

levels of cortisol occurring with acute stress can precipitate and/or sustain delirium

5. Deficiencies in cellular maintenance processes, such as utilization of glucose

and oxygen, cell membrane repair, and axonal transport, are postulated to result

from global insults that lead to delirium.

Delirium is a multifactorial disorder. (systemic illness+ predisposing factor+

medication)

Risk factors of delirium:

1. The most commonly identified risk factors are underlying brain diseases such as dementia,

2. 75Age>

3. sensory impairment

4. multiple comorbidities

5. multiple drugs

6. postoperative

7. frailty, Malnourishment, terminal illness

Precipitating factors of delirium:

1. Drugs: medications (eg, opioids, sedative-hypnotics, antipsychotics, lithium, skeletal

muscle relaxers, polypharmacy), Drugs of abuse (eg, ethanol, heroin, hallucinogens,

nonmedicinal use of prescription medications), Withdrawal states (eg, ethanol,

benzodiazepines)

2. Infections Sepsis, Systemic infections; fever-related delirium

3. Metabolic derangements Electrolyte disturbance (elevated or depressed): sodium,

calcium, magnesium, phosphate Endocrine disturbance (depressed or increased):

thyroid, parathyroid, pancreas, pituitary, adrenal, Hypercarbia, Hyperglycemia and

hypoglycemia, Hyperosmolar and hypoosmolar states, Hypoxemia, Nutritional:

Wernicke's encephalopathy, vitamin B12 deficiency, possibly folate and niacin

deficiencies, dehydration

4. Brain disorders CNS infections: encephalitis, meningitis, brain or epidural abscess,

Epileptic seizures, especially nonconvulsive status epilepticus, Head injury,

Hypertensive encephalopathy

5. Systemic organ failure Cardiac failure, Liver failure: acute, chronic Pulmonary

disease, including hypercarbia and hypoxemia,Renal failure: acute, chronic

6. Physical disorders(Burns, Electrocution, Hyperthermia, Hypothermia Trauma: with

systemic inflammatory response syndrome, *head injury, fat embolism)

7. Pain

8. Stool impaction

9. Urine retention

Deliriums:D rugs (particularly narcotics and anticholinergics), withdrawal esp.EtOH and

benzodiazepines,dehydration

E ndocrine (hypo and hyperglycemia,hypercalcemia, hypo, hyperthyroidism)

L ow oxygen hypoxia

I nfections (particularly UTIs and pneumonia)

R etention- urinary

I nflammatory arthritis (eg. gout),neurological (eg. meningitis); I ntoxication

U nderperfused CHF, CVA, Acute MI

M etabolic sodium, potassium,azotemia, liver failure

S tool fecal impaction

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Anticholinergics (Atropine. Benztropine,Diphenhydramine, Scopolamine,

Trihexyphenidyl

Analgesics (Nonsteroidal antiinflammatory agents Opioids (especially meperidine)

Steroids

Antiparkinson (anticholinergic and dopaminergic Amantadine, Bromocriptine,

Levodopa, Pergolide, Pramipexole, Ropinirole)

Muscle relaxants: Baclofen, Cyclobenzaprine

Sedatives (benzodiazepines, barbiturates)

Anticonvulsants

Antihistamines Ranitidine

Antiarrhythmics (digitalis)

Antihypertensives

Antidepressants

Antimicrobials (penicillin, cephalosporins, quinolones)

Sympathomimetics

Polypharmacy itself

Clinical presentation:

The condition typically develops over a short period of time and tends tofluctuate during the course of the day. There is a change from baselineA disturbance of consciousness: is a change in the level of awareness and theability to focus, sustain, or shift attention. This loss of mental clarity is often subtleand may precede more flagrant signs of delirium by one day or more. Distractibility,one of the hallmarks of delirium, is often evident in conversation, Patients will appearobviously drowsy, lethargic, or even semi-comatose in more advanced casesofdelirium. The opposite extreme, hypervigilance, may also occur in cases of alcohol

or sedative drug withdrawal, but such a presentation is less common in olderpersons.Change in cognition: memory loss, disorientation, and difficulty with language andspeech

o Perceptual disturbances: Vague delusions of harm often accompany thesemisperceptions. Hallucinations can be visual, auditory or somatosensory,usually with lack of insight

o A variety of language difficulties can occur. Patients may lose the ability towrite or to speak a second language.

There is often a prodromal phase: Prodromal features include complaints offatigue, sleep disturbance (excessive daytime somnolence or insomnia), depression,anxiety, restlessness, irritability and hypersensitivity to light or sound.subsyndromal deliriumAffective disorder: emotional lability, , irritability, anxiety, dysphoriaOther features: psychomotor agitation, sleep-wake reversals, irritability, anxiety,emotional lability, and hypersensitivity to lights and sounds. These features are notseen in all patients with delirium

Subtypes:

Hyperactive 10-15% characterized by agitation, restlessness, and emotional labilityHypoactive 40-70% decreased responsiveness, withdrawal, and apathyMixed 50% Periods of hyperactivity and lethargy

EVALUATION: often missed

Recognizing the disorder, and uncovering the underlying medical illness that has caused

delirium multiple underlying conditions are often found

History: Collateral information from family, nursing

knowledge of the patient's baseline level of functioning and cognition

a medication list,

medical history

history of mental illness

history of risk factors, precipitating factors

Focused assessment:

vital signs

the state of hydration

skin condition

Potential infectious foci.

Neurologic examination

Assessment tools

1. The Confusion Assessment Method (CAM) a screening tool. The diagnosis

1 2 3 4of delirium requires the presence of features AND plus either OR .1. Acute onset and fluctuating course

2. Inattention

3. Disorganized thinking

4. Altered level of consciousness

2. Serial sevens and spelling a word such asother simple tests of attention, Digit span, Vigilance "A" test

3. Assess disorganized thinking:(

a) Will a stone float on water? (Or: Will a leaf float on water?)b) Are there fish in the sea? (Or: Are there elephants in the sea?)c) Does one pound weigh more than two pounds? (Or: Do two pounds weigh more than

one?)d) Can you use a hammer to pound a nail? (Or: Can you use a hammer to cut wood?)e)

one more finger

4. The CAM ICU instrument, the Intensive Care Delirium Checklist forScreening (ICDSC)both developed for ICU settings

Investigations:

1. Serum electrolytes, creatinine, glucose, calcium, complete blood count, andurinalysis and urine culture, Blood gas determination,

2. ECG and chest Xray3. Drug levels should be ordered where appropriate. Toxic screen of blood and urine4. In the absence of an obvious cause for delirium, further testing including

neuroimaging, lumbar puncture, and EEG is indicated, also needed if neurologicalsigns elicited, also if patient does adequately to treatment.

5. Further testing, such as liver function tests, should be based upon the history andclinical examination. A report of slow cognitive decline over several months, forexample, will increase the importance of evaluating thyroid function and vitamin B12levels.

DIFFERENTIAL DIAGNOSIS

Depression: is associated with dysphoria, and there is less fluctuation than in delirium.

Mood disorders manifest persistent rather than labile mood with more gradual onset

Mania: no disorientation and good cognitive abilities, less distractability

Psychotic illness: schizophrenia, the delusions are usually highly systematized, the history

is longer, and the sensorium is otherwise clear. Onset usually before age of 40. Clouded

consciousness or decreased level of alertness and disorientation more indelirium.

Dementia: cognitive change in Alzheimer disease is typically insidious, progressive, without

much fluctuation, and occurs over a much longer time (months to years). Attention is

relatively intact, as are remote memories in the earlier stages.

baseline level of cognitive function is critical to be able to distinguish delirium from

dementia. Delirium superimposed on dementia is common

Dementia with Lewy bodies (DLB) is similar to Alzheimer disease but can be more easily

confused with delirium, because fluctuations and visual hallucinations are common and

prominent

Nonconvulsive status epilepticus: requires an EEG for detection and continuous EEG formanagement. Often patients show no classic ictal features, but the following features shouldsuggest the possibility of seizures: prominent bilateral facial twitching, unexplainednystagmoid eye movements during obtunded periods, spontaneous hippus, prolonged"postictal state," automatisms (lip smacking, chewing, or swallowing movements), and acuteaphasia or neglect without a structural lesion.it should also be considered in the absence ofthese findings when the etiology of a confusional state remains obscure, Coma patientsfrequently required greater than 24 hours of monitoring to detect the firstelectrographic seizure

Inattention is easily mistaken for fatigue, uncooperativeness, dysphoria, ordisinterest.

Complications of delirium

2ry to life-threatening conditionMalnutritionAspiration pneumoniaPressure ulcersWeakness, decreased mobility, decreased functionFallsIncreased length of stay in hospitalPersistant cognitive dysfunction Signs of delirium may persist for 12 months orlonger, particularly in those with underlying dementiaIncreased risk of future dementia

Hospital Environment Predisposes To Delirium:

a) Many new faces: 10-20 staff may see patient in one day, leading to disorientationb) Decreased cognitive stimuli: urinary catheters and restraints confine patients to bed,

with attendant risksc) Loss of sleep due to noise or intrusionsd) Drugse) Physical Restraints Risky for several reasons Independently associated with

development of delirium, Reduce external stimuli may exacerbate delirium, Mayexacerbate hyperactive behavior

perioperative Risk Factors for Delirium

1. General anesthesia more than regional, muscle relaxants, and the analgesicmeperidine, which is often used for postoperative shivering.

2. Pain, environmental unfamiliarity including disrupted sleep cycles and use of aurinary catheter.

3. Vascular and cardiac surgeries are associated with a high incidence of delirium,possibly because cerebral complications of atherosclerosis may also reduce brainreserve

4. Surgery is characterized by a marked inflammatory response, and inflammation hasbeen implicated both in the pathogenesis of delirium,

5. Hypoperfusion during perioperative period, a reduced blood hemoglobin

TREATMENT APPROACHES TO DELIRIUM

1. Priorities of patient safety insurance

2. Treating the Causes

3. Non pharmacological interventions

4. pharmacological interventions

5. THE BEST MANAGEMENT IS PREVENTION

1. Priorities of patient safety insurance

Rule out life-threatening illness.Stop all suspected medications.Monitor vital signsSafe controlled environmentProtection from physical harm but Avoid physical restraintLow beds, guard rails and careful supervisionMaintaining fluid and electrolyte balance , Adequate nutritionPrevent aspiration , decubitus ulcers2. Treating the predisposing medical condition

Aggressively seek and treat the reversible causes of delirium and to mitigate othernonreversible causesElimination of infectious or inflammatory sources, addressing orthopedic injuries, andremoval of offending medications are also essential.Correcting the most common metabolic and infectious factors, such as serum BUN,creatinine, sodium, and calcium and treatment of urinary tract infections andpneumonia.Manage pain

3. Non pharmacological interventions:

Predictable, orienting environment :easy-to-read calendars and clocksPresence of family members can be helpful , frequent interaction , Frequent verbalorientationlimiting rotation of personnel caring for the patient, minimizing room changes,Support for confusion or hallucinations , encouraged to express fears anddiscomfortsAdequate lighting and reasonable noise level limiting distractions (loud conversation,beepers, overhead speakers, televisions, crowded areas),

Devices available - eye glasses and hearing aids, Avoid sensory deprivation andoverloadSupport normal sleep pattern providing rest and quiet at night time,4. Pharmacological interventions:

General principles:

Psychotropic medications should be reserved for patients in distress due to agitationor psychotic symptomsIn the absence of psychotic symptoms causing stress, treatment of hypoactivedelirium with psychotropic medications is not recommendedPsychotropic medications are not indicated for wanderingAim for monotherapy at the lowest dose, Offer orally first,Taper as soon as possibleReview regime every 48hWill not improve cognition Can reduce behavioural disturbanceAvoid benzodiazepines they are primarily indicated in cases of sedative drug and

alcohol withdrawal or when neuroleptic drugs are contraindicated.

Cholinesterase inhibitors do not have a role in the treatment or symptom

management of delirium

Antipsychotic haloperidol - 0.5 to 1 mg po twice daily - 0.5- 1 mg IM (repeat in 30-60

min if needed

a. - assess for akathisia and extrapyramidal effects

b. - avoid in older persons with parkinsonism

c. in ICU, monitor for QT interval prolongation, torsade de pointes, neuroleptic

malignant syndrome, withdrawal dyskinesias

Atypical antipsychotic

a. Risperidone 0.5 mg twice daily

b. Olanzapine 2.5 to 5 mg once daily

c. Quetiapine 5mg once daily

Benzodiazepine better avoid 0.5 to 1mg (add every 4h as needed)

Antidepressant Trazadone 25 to 150mg at bedtime better avoid

5. THE BEST MANAGEMENT IS PREVENTION

The reorienting environment: Hearing aids, Spectacles, Orientation aidsclocks,calendars, windows with outside views, LightingEncourage food and fluid intakeEncourage early mobilityMaintain sleep patternInvolve relatives and carersAvoid: Constipation, Catheters, Restraint, Sedation, psychoactive drugs, Bed orWard moves, Arguing with the patientThe available evidence does not support the use of medications to prevent deliriumin the acute care or intensive care or postoperative care settings,however,Preoperative Prophylactic low-dose haloperidol, olanzapine, or risperidone maybe effective in decreasing both the severity and duration of delirium episodes,

though they do not prevent development of delirium itself. Gabapentin, in pilotstudy, reduced the incidence of postoperative delirium, perhaps by reducingpain and opioid administration, Melatonin shows promise in the prevention ofdelirium. The melatonin agonist, ramelteonAvoid unnecessary polypharmacy