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{{Delirium}}
{{CMG}}; {{AE}} {{PB}}; [[User:Vishal Khurana|Vishal Khurana]], M.B.B.S., M.D. [mailto:vishdoc24@gmail.com]
{{CMG}}; {{AE}}  {{Sara.Zand}} {{PB}}; [[User:Vishal Khurana|Vishal Khurana]], M.B.B.S., M.D. [mailto:vishdoc24@gmail.com]


==Overview==
==Overview==
Delirium is an acute and relatively sudden (developing over hours to days) decline in attention-focus, perception, and [[cognition]].  It is not synonymous with [[drowsiness]], and may occur without itIt is commonly associated with a disturbance of [[consciousness]] (e.g., reduced clarity of awareness of the environment).  The change in [[cognition]] (memory deficit, disorientation, language disturbance) or the development of a perceptual disturbance, must be one that is not better accounted by a preexisting, established, or evolving [[dementia]].  Usually the rapidly fluctuating time course of delirium is used to help in the latter distinction.
[[Delirium]] is an acute and relatively sudden (developing over hours to days) decline in [[attention-focus]], [[perception]], and [[cognition]]. [[Delirium]] is commonly associated with a disturbance of [[consciousness]] or reduced clarity of awareness about the [[environment]]. The change in [[cognition]] including [[memory deficit]], [[disorientation]], [[language disturbance]] or the development of a [[perceptual]] disturbance may happen with rapid fluctuation course. The concept of [[delirium]] has been evolving over centuries. [[Delirium]] was first identified in the 16th century. In the second half of the 19th century, [[delirium]] was identified by French workers as [[chaotic thinking]] and [[cognitive]] failure, clouding of [[consciousness]], temporospatial [[disorientation]]. The definition of [[confusion]] and [[delirium]] was established by Chaslin and Bonhoeffer as the stereotyped manifestations of acute [[brain]] failure. [[Delirium]] is classified on the basis of etiology, duration, and severity. Hyperactive [[delirium]] is defined as increased [[psychomotor]] activity, which may occur with increased [[mood]] [[lability]], [[agitation]], non cooperative [[attitude]] towards [[medical]] treatment. Hypoactive [[delirium]] is explained by a hypoactive level of [[psychomotor]] activity, which may exist along with increased [[lethargy]] or [[stupor]], [[inattentiveness]] and [[motor]] slowness and is much more common among [[ICU]] admitted [[patients]] with severe disease.The exact [[pathophysiology]] of [[delirium]] is still being investigatedThe roles of [[neurotransmitters]] like [[acetylcholine]] and [[dopamine]] seem to be important. It involves disrupted connectivity between [[cortical]] and [[subcortical]] areas of the [[brain]], especially areas concerned with [[sleep]] and [[awakening]]. The role of increased inflammatory [[cytokines]] has been shown in [[delirious ]] [[patients]]. [[Delirium]] may be caused by severe physical or [[mental illness]], or any process which interferes with the normal metabolism or function of the brain such as [[fever]], [[pain]], [[poison]] ([[toxic]] [[approved drug|drug]] reactions), [[brain]] injury, [[surgery]], [[traumatic]] shock, severe lack of [[food]] or [[water]] or [[sleep]], and even withdrawal symptoms of certain [[drug]] and [[alcohol]] dependent states.  In addition, there is an interaction between acute and chronic [[symptoms]] of [[brain]] dysfunction. [[Delirious]] states are more easily produced in people already suffering from underlying chronic [[brain]] dysfunction. A very common cause of [[delirium ]] in elderly people is a [[urinary tract infection]], which is easily treatable with [[antibiotics]].
[[Delirium]], like [[mental confusion]], is a very general and nonspecific symptom of [[organ]] dysfunction. In addition to many organic causes relating to a structural defect or a [[metabolic]] problem in the [[brain]], there are also some [[psychiatric]] causes, which may also include a component of [[mental]] or [[emotional]] stress, [[mental]] disease.[[Delirium]] is differentiated from other causes [[cognitive]] dysfunction such as [[psychiatric Disorders]], [[dementia]]. Unlike [[dementia]], the course of [[delirium]] is reversible with fluctuation in level of [[consciousness]].The [[prevalence]] of [[delirium]] is approximately 23,000 per 100,000 hospitalized [[patients]] worldwide. Between May 2009 to August 2012, the incidence of [[delirium]] was estimated to be 8700 cases per 100,000 African-Americans in Indianapolis. [[Delirium]] is more commonly observed among [[elderly patients]], especially age> 65 year-old. [[Male]] < 65 year-old are more commonly affected with [[delirium]]. [[Delirium]] is more commonly observed among [[Female]]≥ 85-year-old with [[medical]] [[comorbidities]]. There is no racial predilection for [[delirium]]. [[Young]] [[African-American]] [[patients]]  are less likely to develop [[delirium]] compared with Caucasians of the same [[age]].Common risk factors associated with [[delirium]] include [[older]] age, [[dementia]], [[hypertension]], [[emergency]] [[surgery]] or [[trauma]] before [[ICU]] admission, [[mechanical ventilation]], [[metabolic acidosis]], [[delirium]] on the prior day , [[coma]].The duration of [[delirium]] may vary from hours to months. After remission , [[delirium]] may increase the risk of functional decline, [[cognitive dysfunction]], and [[institutional placement]], and with higher [[mortality]]. [[Delirium]] in the elderly, can cause many complications, which may include [[pneumonia]] and [[decubitus ulcers]], prolonging [[hospital]] stays. [[Delirium]] was associated with longer postoperative recovery periods, longer hospital stays, and long-term disability after [[orthopedic]] surgery. Common complications associated with  [[delirium]] include increased [[mortality]], [[cognitive impairment]], longer durations of [[mechanical ventilation]], longer lengths of stay in the [[ICU]]. Prognosis is dependent on the severity of [[delirium]], and the 1 year [[mortality rate]] of [[patients]] with [[delirium]] is approximately 10%-26%.The DSM V, and ICD-10 have provided diagnostic criteria for [[delirium]]. Definition based on [[DSM-5]] include disturbance in [[attention]] and [[awareness]] (reduced ability to direct, focus, shift [[attention]] and reduced [[orientation]] to [[envinment]]), initiation of disturbance over a short period of [[time]] during several hours or days  with fluctuation  in severity over a day, disturbance in [[cognition]] ([[memory deficit]], [[disorientation]], [[language]], [[visuospatial]] ability, [[perception]], disturbance other than evolving [[neurocognitive]] disorder, disturbance due to [[medical]] [[condition]], [[substance intoxication]], or withdrawal. Other definitions of [[delirium]] include disturbance in [[cognition]],
impairment of [[immediate recall]] and [[recent memory]], [[disorientation]] to [[time]], [[place]], [[person]], disturbance in [[sleep wake]] cycle, [[Psychomotor disturbances]],[[emotional disturbances]] in a period of less than 6 months.[[Delirium]] causes impairment in functions, [[sleep-wake cycle]] and also has a behavioral component. Common [[symptoms]] associated with [[delirium]] include altered [[level of consciousness]], [[inattention]], [[disorientation]], [[hallucination]], [[delusions]], [[agitation]], inappropriate [[speech]], [[sleep]]–[[wake]] disturbances, [[ Symptom]] fluctuation, [[emotional disturbance]]. Subclinical [[delirium]] or prodromal [[delirium]] may precede by 1 to 3 days prior to an overt [[delirium]], which presents as [[restlessness]], [[anxiety]], irritability, [[distractibility]], [[sleep disturbance]] with less severe [[cognitive]] impairment in comparison to [[delirium]].It is important to do a thorough [[physical examination]] to find out the underlying etiology of [[delirium]]. Systemic [[physical examination]] includes testing [[vital signs]] such as [[temperature]], [[pulse rate]], [[blood pressure]], and [[respiration]] and also  evaluation of [[mental]] status. [[Patients]] may seem disoriented with difficulty in  sustaining [[attention]], problem in [[short-term memory]], poor [[insight]] and  impaired [[judgment]].Laboratory findings may differ according to the etiology of [[delirium]]. Following investigations are done in [[delirium]]: [[pulse oximetry]], [[electrolytes]], [[blood glucose]], [[liver]] function tests, [[blood urea nitrogen]], [[creatinine]], [[vitamin B12 ]], [[Folate levels]], measurement therapeutic drug levels, [[urine]] drug screen for substance use, [[blood]] [[alcohol]] level, [[complete blood count]], [[urinalysis]], [[thyroid function testing]], [[erythrocyte sedimentation rate]], [[C-reactive protein]], [[rapid plasma reagin]] screening for [[syphilis]], [[acquired immune deficiency syndrome]]/[[human immunodeficiency virus]] ([[AIDS]]/[[HIV]]) screening.[[Brain CT scan]] is helpful in the diagnosis the underlying cause of [[delirium]]. Findings on [[brain]] [[CT scan]] among [[patients]] admitted with [[delirium]] include: acute or subacute [[infarct]], [[ haemorrhage]], [[abscess]], [[neoplasm]], [[vasculitis]], [[posterior reversible encephalopathy syndrome]],  [[encephalitis]],  acute [[demyelination]], [[ Fat embolism]].[[Brain]] [[MRI]] is valuable tool for diagnosis  the underlying cause of [[delirium]] when the [[brain]] [[CT]] scan findings are not informative. The most common finding on [[brain]] [[MRI]] that was missed by [[brain]] [[CT]] scan was [[ischemia]].[[EEG]] maybe helpful for the diagnosis of [[delirium]].  [[EEG]] findings associated with [[delirium]] include [[periodic discharges]], triphasic waves ,lateralized [[rhythmic]] delta ,low voltage/generalized attenuation, theta or delta generalized slowing.The presence of either theta or delta generalized slowing correlated strongly with [[delirium]] severity regardless of [[arousal]] state (hyper- or hypoactive) and [[comorbidities]].Treatment of [[delirium]] involves two main strategies: first, treatment of the underlying presumed acute cause or causes, secondly, optimizing [[conditions]] of the [[brain]].  This involves ensuring that the [[patient]] with [[delirium]] has adequate [[oxygenation]], [[hydration]], [[nutrition]], and normal levels of [[metabolites]], so that [[drug ]] effects are minimized, [[constipation]] treated, [[pain ]] treated, and so on.  Detection and management of [[mental]] [[stress]] are also very importantTherefore, the traditional concept that the treatment of [[delirium ]] is treating the cause is not adequate. Common [[medications]] which are used for treatment of  [[delirium]]  include [[antipsychotic]] drugs, [[benzodiazepines]], [[cholinestrase inhibitors]], [[selective -a2 receptor agonist]], [[melatonin]] based [[medications]], and  [[ketamine]]. It is important to prevent [[delirium]] as [[delirium]] is itself [[neurotoxic]]. [[Delirium]] is associated with global [[brain]] atrophy and [[white matter]] disruption. Various non pharmacological and pharmacological interventions are found to be effective to prevent [[delirium]]. [[Primary prevention]] sterategies for Post-operative [delirium]] include use of [[haloperidol]], second generation [[antipsychotics]], iliac fascia block, lower levels of intraoperative [[ propofol]] for sedation, continuous intravenous infusion of [[dexmedetomidine]], and use of [[Melatonin]]. [[ketamine]] is not useful for prevention of postoperative [[delirium]]. Preoperative administration of [[gabapentin]] is not effective for prevention of postoperative [[delirium]].[[Secondary prevention]] strategies following [[delirium]] include avoidance of [[anticholinergic]] drugs, attention to [[environmental factors]] (sensory input, [[orientation aids]], reassuring [[human contact]], routine screening for finding high risk [[patients]], early recognition of any change or fluctuation of [[mental]] state or [[behaviour]].


Delirium can easily be confused with a number of [[psychiatric disorders]] because many of the signs and symptoms are conditions present in [[dementia]], [[clinical depression|depression]], and [[psychosis]].  Delirium is probably the single most common acute disorder affecting adults in general hospitals.
==Historical Perspective==
The concept of [[delirium]] has been evolving over centuries. [[Delirium]] was first identified in the 16th century. In the second half of the 19th century, [[delirium]] was identified by French workers as [[chaotic thinking]] and [[cognitive]] failure, clouding of [[consciousness]], temporospatial [[disorientation]]. The definition of [[confusion]] and [[delirium]] was established by Chaslin and Bonhoeffer as the stereotyped manifestations of acute [[brain]] failure.


Delirium by itself is not a disease, but rather a clinical syndrome (a set of symptoms), which result from an underlying disease or new problem with mentation. Distressing symptoms of delirium are sometimes treated with [[antipsychotic]], preferably those with minimal [[anticholinergic]] activity, such as [[haloperidol]] or [[risperidone]], or else with [[benzodiazepine]], which decrease the anxiety felt by a person who may also be disoriented, and has difficulty completing tasks. However, since these drug treatments do not address the underlying cause of delirium, and may mask changes in delirium which themselves may be helpful in assessing the patient's underlying changes in health, their use is difficultBecause delirium is a mere symptom of another problem that may be very subtle, the wisdom of treatment of the delirious patient with drugs must overcome natural skepticism, and requires a high degree of skill.
==Pathophysiology==
The exact [[pathophysiology]] of [[delirium]] is still being investigated.  The roles of [[neurotransmitters]] like [[acetylcholine]] and [[dopamine]] seem to be important. It involves disrupted connectivity between [[cortical]] and [[subcortical]] areas of the [[brain]], especially areas concerned with [[sleep]] and [[awakening]]. The role of increased inflammatory [[cytokines]] has been shown in [[delirious ]] [[patients]].
==Causes==
[[Delirium]] may be caused by severe physical or [[mental illness]], or any process which interferes with the normal metabolism or function of the brain such as [[fever]], [[pain]], [[poison]] ([[toxic]] [[approved drug|drug]] reactions), [[brain]] injury, [[surgery]], [[traumatic]] shock, severe lack of [[food]] or [[water]] or [[sleep]], and even withdrawal symptoms of certain [[drug]] and [[alcohol]] dependent states.  In addition, there is an interaction between acute and chronic [[symptoms]] of [[brain]] dysfunction. [[Delirious]] states are more easily produced in people already suffering from underlying chronic [[brain]] dysfunction. A very common cause of [[delirium ]] in elderly people is a [[urinary tract infection]], which is easily treatable with [[antibiotics]].
[[Delirium]], like [[mental confusion]], is a very general and nonspecific symptom of [[organ]] dysfunction. In addition to many organic causes relating to a structural defect or a [[metabolic]] problem in the [[brain]], there are also some [[psychiatric]] causes, which may also include a component of [[mental]] or [[emotional]] stress, [[mental]] disease.
==Differentiating [disease name] from other Diseases==
[[Delirium]] is differentiated from other causes [[cognitive]] dysfunction such as [[psychiatric Disorders]], [[dementia]]. Unlike [[dementia]], the course of [[delirium]] is reversible with fluctuation in level of [[consciousness]].
 
 
==Epidemiology and Demographics==
The [[prevalence]] of [[delirium]] is approximately 23,000 per 100,000 hospitalized [[patients]] worldwide. Between May 2009 to August 2012, the incidence of [[delirium]] was estimated to be 8700 cases per 100,000 African-Americans in Indianapolis. [[Delirium]] is more commonly observed among [[elderly patients]], especially age> 65 year-old. [[Male]] < 65 year-old are more commonly affected with [[delirium]]. [[Delirium]] is more commonly observed among [[Female]]≥ 85-year-old with [[medical]] [[comorbidities]]. There is no racial predilection for [[delirium]]. [[Young]] [[African-American]] [[patients]]  are less likely to develop [[delirium]] compared with Caucasians of the same [[age]].
 
 
==Risk Factors==
Common risk factors associated with [[delirium]] include [[older]] age, [[dementia]], [[hypertension]], [[emergency]] [[surgery]] or [[trauma]] before [[ICU]] admission, [[mechanical ventilation]], [[metabolic acidosis]], [[delirium]] on the prior day , [[coma]].
 
 
==Natural History, Complications and Prognosis==
The duration of [[delirium]] may vary from hours to months. After remission , [[delirium]] may increase the risk of functional decline, [[cognitive dysfunction]], and [[institutional placement]], and with higher [[mortality]]. [[Delirium]] in the elderly, can cause many complications, which may include [[pneumonia]] and [[decubitus ulcers]], prolonging [[hospital]] stays. [[Delirium]] was associated with longer postoperative recovery periods, longer hospital stays, and long-term disability after [[orthopedic]] surgery. Common complications associated with  [[delirium]] include increased [[mortality]], [[cognitive impairment]], longer durations of [[mechanical ventilation]], longer lengths of stay in the [[ICU]]. Prognosis is  dependent on the severity of [[delirium]], and the 1 year [[mortality rate]] of [[patients]] with [[delirium]] is approximately 10%-26%.
 
 
==Diagnosis==
===Diagnostic Criteria===
The DSM V, and ICD-10 have provided diagnostic criteria for [[delirium]]. Definition based on [[DSM-5]] include disturbance in [[attention]] and [[awareness]] (reduced ability to direct, focus, shift [[attention]] and reduced [[orientation]] to [[envinment]]), initiation of disturbance over a short period of [[time]] during several hours or days  with fluctuation  in severity over a day, disturbance in [[cognition]] ([[memory deficit]], [[disorientation]], [[language]], [[visuospatial]] ability, [[perception, disturbance other than evolving [[neurocognitive]] disorder, disturbance due to [[medical]] [[condition]], [[substance intoxication]], or withdrawal. Other definitions of [[delirium]] include disturbance in [[cognition]],
impairment of [[immediate recall]] and [[recent memory]], [[disorientation]] to [[time]], [[place]], [[person]], disturbance in [[sleep wake]] cycle, [[Psychomotor disturbances]],[[emotional disturbances]] in a period of less than 6 months.
 
 
==History and Symptoms==
[[Delirium]] causes impairment in functions, [[sleep-wake cycle]] and also has a behavioral component. Common [[symptoms]] associated with [[delirium]] include altered [[level of consciousness]], [[inattention]], [[disorientation]], [[hallucination]], [[delusions]], [[agitation]], inappropriate [[speech]], [[sleep]]–[[wake]] disturbances, [[ Symptom]] fluctuation, [[emotional disturbance]]. Subclinical [[delirium]] or prodromal [[delirium]] may precede by 1 to 3 days prior to an overt [[delirium]], which presents as [[restlessness]], [[anxiety]], irritability, [[distractibility]], [[sleep disturbance]] with less severe [[cognitive]] impairment in comparison to [[delirium]]
 
 
==Physical Examination==
It is important to do a thorough [[physical examination]] to find out the underlying etiology of [[delirium]]. Systemic [[physical examination]] includes testing [[vital signs]] such as [[temperature]], [[pulse rate]], [[blood pressure]], and [[respiration]] and also  evaluation of [[mental]] status. [[Patients]] may seem disoriented with difficulty in  sustaining [[attention]], problem in [[short-term memory]], poor [[insight]] and impaired [[judgment]].
 
 
==Laboratory Findings==
Laboratory findings may differ according to the etiology of [[delirium]]. Following investigations are done in [[delirium]]: [[pulse oximetry]], [[electrolytes]], [[blood glucose]], [[liver]] function tests, [[blood urea nitrogen]], [[creatinine]], [[vitamin B12 ]], [[Folate levels]], measurement therapeutic drug levels, [[urine]] drug screen for substance use, [[blood]] [[alcohol]] level, [[complete blood count]], [[urinalysis]], [[thyroid function testing]], [[erythrocyte sedimentation rate]], [[C-reactive protein]], [[rapid plasma reagin]] screening for [[syphilis]], [[acquired immune deficiency syndrome]]/[[human immunodeficiency virus]] ([[AIDS]]/[[HIV]]) screening.
 
 
==CT scan==
[[Brain CT scan]] is helpful in the diagnosis the underlying cause of [[delirium]]. Findings on [[brain]] [[CT scan]] among [[patients]] admitted with [[delirium]] include: acute or subacute [[infarct]], [[ haemorrhage]], [[abscess]], [[neoplasm]], [[vasculitis]], [[posterior reversible encephalopathy syndrome]],  [[encephalitis]],  acute [[demyelination]], [[ Fat embolism]].
 
 
==MRI==
[[Brain]] [[MRI]] is valuable tool for diagnosis  the underlying cause of [[delirium]] when the [[brain]] [[CT]] scan findings are not informative. The most common finding on [[brain]] [[MRI]] that was missed by  [[brain]] [[CT]] scan was [[ischemia]].
 
 
 
==Other Diagnostic Studies==
[[EEG]] maybe helpful for the diagnosis of [[delirium]].  [[EEG]] findings associated with [[delirium]] include [[periodic discharges]], triphasic waves ,lateralized [[rhythmic]] delta ,low voltage/generalized attenuation, theta or delta generalized slowing.The presence of either theta or delta generalized slowing correlated strongly with [[delirium]] severity regardless of [[arousal]] state (hyper- or hypoactive) and [[comorbidities]].
 
 
 
==Treatment==
===Medical Therapy===
Treatment of [[delirium]] involves two main strategies: first, treatment of the underlying presumed acute cause or causes, secondly, optimizing [[conditions]] of the [[brain]]This involves ensuring that the [[patient]] with [[delirium]] has adequate [[oxygenation]], [[hydration]], [[nutrition]], and normal levels of [[metabolites]], so that [[drug ]] effects are minimized, [[constipation]] treated, [[pain ]] treated, and so on.  Detection and management of [[mental]] [[stress]] are also very important.  Therefore, the traditional concept that the treatment of [[delirium ]] is treating the cause is not adequate. Common [[medications]] is used for [[delirium]] treatment include [[antipsychotic]] drugs, [[benzodiazepines]], [[cholinestrase inhibitors]], [[selective -a2 receptor agonist]], [[melatonin]] based [[medications]], [[ketamine]].
 
 
==Prevention==
===Primary prevention===
It is important to prevent [[delirium]] as [[delirium]] is itself [[neurotoxic]]. [[Delirium]] is associated with global [[brain]] atrophy and [[white matter]] disruption.  Various non pharmacological and pharmacological interventions are found to be effective to prevent [[delirium]]. [[Primary prevention]] sterategy for Post-operative [[delirium]] may  include use of [[haloperidol]], second generation [[antipsychotics]], iliac fascia block, lower levels of intraoperative [[ propofol]]  for sedation, continuous intravenous infusion of [[dexmedetomidine]],and use of [[Melatonin]]. [[ketamine]] is not useful in preventing postoperative [[delirium]]. Preoperative administration of [[gabapentin]] is not effective for prevention of postoperative [[delirium]].
 
===Secondary prevention===
[[Secondary prevention]] strategies following [[delirium]] include avoid [[anticholinergic]] drugs, attend to [[environmental factors]] (sensory input, [[orientation aids], reassuring [[human contact]], routine screening for finding high risk [[patients]], early recognition of any change or fluctuation of [[mental]] state or [[behaviour]].


==References==
{{Reflist|2}}


[[Category:Neurology]]
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Latest revision as of 13:35, 29 April 2021

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Editor-In-Chief: C. Michael Gibson, M.S., M.D. [1]; Associate Editor(s)-in-Chief: Sara Zand, M.D.[2] Pratik Bahekar, MBBS [3]; Vishal Khurana, M.B.B.S., M.D. [4]

Overview

Delirium is an acute and relatively sudden (developing over hours to days) decline in attention-focus, perception, and cognition. Delirium is commonly associated with a disturbance of consciousness or reduced clarity of awareness about the environment. The change in cognition including memory deficit, disorientation, language disturbance or the development of a perceptual disturbance may happen with rapid fluctuation course. The concept of delirium has been evolving over centuries. Delirium was first identified in the 16th century. In the second half of the 19th century, delirium was identified by French workers as chaotic thinking and cognitive failure, clouding of consciousness, temporospatial disorientation. The definition of confusion and delirium was established by Chaslin and Bonhoeffer as the stereotyped manifestations of acute brain failure. Delirium is classified on the basis of etiology, duration, and severity. Hyperactive delirium is defined as increased psychomotor activity, which may occur with increased mood lability, agitation, non cooperative attitude towards medical treatment. Hypoactive delirium is explained by a hypoactive level of psychomotor activity, which may exist along with increased lethargy or stupor, inattentiveness and motor slowness and is much more common among ICU admitted patients with severe disease.The exact pathophysiology of delirium is still being investigated. The roles of neurotransmitters like acetylcholine and dopamine seem to be important. It involves disrupted connectivity between cortical and subcortical areas of the brain, especially areas concerned with sleep and awakening. The role of increased inflammatory cytokines has been shown in delirious patients. Delirium may be caused by severe physical or mental illness, or any process which interferes with the normal metabolism or function of the brain such as fever, pain, poison (toxic drug reactions), brain injury, surgery, traumatic shock, severe lack of food or water or sleep, and even withdrawal symptoms of certain drug and alcohol dependent states. In addition, there is an interaction between acute and chronic symptoms of brain dysfunction. Delirious states are more easily produced in people already suffering from underlying chronic brain dysfunction. A very common cause of delirium in elderly people is a urinary tract infection, which is easily treatable with antibiotics. Delirium, like mental confusion, is a very general and nonspecific symptom of organ dysfunction. In addition to many organic causes relating to a structural defect or a metabolic problem in the brain, there are also some psychiatric causes, which may also include a component of mental or emotional stress, mental disease.Delirium is differentiated from other causes cognitive dysfunction such as psychiatric Disorders, dementia. Unlike dementia, the course of delirium is reversible with fluctuation in level of consciousness.The prevalence of delirium is approximately 23,000 per 100,000 hospitalized patients worldwide. Between May 2009 to August 2012, the incidence of delirium was estimated to be 8700 cases per 100,000 African-Americans in Indianapolis. Delirium is more commonly observed among elderly patients, especially age> 65 year-old. Male < 65 year-old are more commonly affected with delirium. Delirium is more commonly observed among Female≥ 85-year-old with medical comorbidities. There is no racial predilection for delirium. Young African-American patients are less likely to develop delirium compared with Caucasians of the same age.Common risk factors associated with delirium include older age, dementia, hypertension, emergency surgery or trauma before ICU admission, mechanical ventilation, metabolic acidosis, delirium on the prior day , coma.The duration of delirium may vary from hours to months. After remission , delirium may increase the risk of functional decline, cognitive dysfunction, and institutional placement, and with higher mortality. Delirium in the elderly, can cause many complications, which may include pneumonia and decubitus ulcers, prolonging hospital stays. Delirium was associated with longer postoperative recovery periods, longer hospital stays, and long-term disability after orthopedic surgery. Common complications associated with delirium include increased mortality, cognitive impairment, longer durations of mechanical ventilation, longer lengths of stay in the ICU. Prognosis is dependent on the severity of delirium, and the 1 year mortality rate of patients with delirium is approximately 10%-26%.The DSM V, and ICD-10 have provided diagnostic criteria for delirium. Definition based on DSM-5 include disturbance in attention and awareness (reduced ability to direct, focus, shift attention and reduced orientation to envinment), initiation of disturbance over a short period of time during several hours or days with fluctuation in severity over a day, disturbance in cognition (memory deficit, disorientation, language, visuospatial ability, perception, disturbance other than evolving neurocognitive disorder, disturbance due to medical condition, substance intoxication, or withdrawal. Other definitions of delirium include disturbance in cognition, impairment of immediate recall and recent memory, disorientation to time, place, person, disturbance in sleep wake cycle, Psychomotor disturbances,emotional disturbances in a period of less than 6 months.Delirium causes impairment in functions, sleep-wake cycle and also has a behavioral component. Common symptoms associated with delirium include altered level of consciousness, inattention, disorientation, hallucination, delusions, agitation, inappropriate speech, sleepwake disturbances, Symptom fluctuation, emotional disturbance. Subclinical delirium or prodromal delirium may precede by 1 to 3 days prior to an overt delirium, which presents as restlessness, anxiety, irritability, distractibility, sleep disturbance with less severe cognitive impairment in comparison to delirium.It is important to do a thorough physical examination to find out the underlying etiology of delirium. Systemic physical examination includes testing vital signs such as temperature, pulse rate, blood pressure, and respiration and also evaluation of mental status. Patients may seem disoriented with difficulty in sustaining attention, problem in short-term memory, poor insight and impaired judgment.Laboratory findings may differ according to the etiology of delirium. Following investigations are done in delirium: pulse oximetry, electrolytes, blood glucose, liver function tests, blood urea nitrogen, creatinine, vitamin B12 , Folate levels, measurement therapeutic drug levels, urine drug screen for substance use, blood alcohol level, complete blood count, urinalysis, thyroid function testing, erythrocyte sedimentation rate, C-reactive protein, rapid plasma reagin screening for syphilis, acquired immune deficiency syndrome/human immunodeficiency virus (AIDS/HIV) screening.Brain CT scan is helpful in the diagnosis the underlying cause of delirium. Findings on brain CT scan among patients admitted with delirium include: acute or subacute infarct, haemorrhage, abscess, neoplasm, vasculitis, posterior reversible encephalopathy syndrome, encephalitis, acute demyelination, Fat embolism.Brain MRI is valuable tool for diagnosis the underlying cause of delirium when the brain CT scan findings are not informative. The most common finding on brain MRI that was missed by brain CT scan was ischemia.EEG maybe helpful for the diagnosis of delirium. EEG findings associated with delirium include periodic discharges, triphasic waves ,lateralized rhythmic delta ,low voltage/generalized attenuation, theta or delta generalized slowing.The presence of either theta or delta generalized slowing correlated strongly with delirium severity regardless of arousal state (hyper- or hypoactive) and comorbidities.Treatment of delirium involves two main strategies: first, treatment of the underlying presumed acute cause or causes, secondly, optimizing conditions of the brain. This involves ensuring that the patient with delirium has adequate oxygenation, hydration, nutrition, and normal levels of metabolites, so that drug effects are minimized, constipation treated, pain treated, and so on. Detection and management of mental stress are also very important. Therefore, the traditional concept that the treatment of delirium is treating the cause is not adequate. Common medications which are used for treatment of delirium include antipsychotic drugs, benzodiazepines, cholinestrase inhibitors, selective -a2 receptor agonist, melatonin based medications, and ketamine. It is important to prevent delirium as delirium is itself neurotoxic. Delirium is associated with global brain atrophy and white matter disruption. Various non pharmacological and pharmacological interventions are found to be effective to prevent delirium. Primary prevention sterategies for Post-operative [delirium]] include use of haloperidol, second generation antipsychotics, iliac fascia block, lower levels of intraoperative propofol for sedation, continuous intravenous infusion of dexmedetomidine, and use of Melatonin. ketamine is not useful for prevention of postoperative delirium. Preoperative administration of gabapentin is not effective for prevention of postoperative delirium.Secondary prevention strategies following delirium include avoidance of anticholinergic drugs, attention to environmental factors (sensory input, orientation aids, reassuring human contact, routine screening for finding high risk patients, early recognition of any change or fluctuation of mental state or behaviour.

Historical Perspective

The concept of delirium has been evolving over centuries. Delirium was first identified in the 16th century. In the second half of the 19th century, delirium was identified by French workers as chaotic thinking and cognitive failure, clouding of consciousness, temporospatial disorientation. The definition of confusion and delirium was established by Chaslin and Bonhoeffer as the stereotyped manifestations of acute brain failure.

Pathophysiology

The exact pathophysiology of delirium is still being investigated. The roles of neurotransmitters like acetylcholine and dopamine seem to be important. It involves disrupted connectivity between cortical and subcortical areas of the brain, especially areas concerned with sleep and awakening. The role of increased inflammatory cytokines has been shown in delirious patients.

Causes

Delirium may be caused by severe physical or mental illness, or any process which interferes with the normal metabolism or function of the brain such as fever, pain, poison (toxic drug reactions), brain injury, surgery, traumatic shock, severe lack of food or water or sleep, and even withdrawal symptoms of certain drug and alcohol dependent states. In addition, there is an interaction between acute and chronic symptoms of brain dysfunction. Delirious states are more easily produced in people already suffering from underlying chronic brain dysfunction. A very common cause of delirium in elderly people is a urinary tract infection, which is easily treatable with antibiotics. Delirium, like mental confusion, is a very general and nonspecific symptom of organ dysfunction. In addition to many organic causes relating to a structural defect or a metabolic problem in the brain, there are also some psychiatric causes, which may also include a component of mental or emotional stress, mental disease.

Differentiating [disease name] from other Diseases

Delirium is differentiated from other causes cognitive dysfunction such as psychiatric Disorders, dementia. Unlike dementia, the course of delirium is reversible with fluctuation in level of consciousness.


Epidemiology and Demographics

The prevalence of delirium is approximately 23,000 per 100,000 hospitalized patients worldwide. Between May 2009 to August 2012, the incidence of delirium was estimated to be 8700 cases per 100,000 African-Americans in Indianapolis. Delirium is more commonly observed among elderly patients, especially age> 65 year-old. Male < 65 year-old are more commonly affected with delirium. Delirium is more commonly observed among Female≥ 85-year-old with medical comorbidities. There is no racial predilection for delirium. Young African-American patients are less likely to develop delirium compared with Caucasians of the same age.


Risk Factors

Common risk factors associated with delirium include older age, dementia, hypertension, emergency surgery or trauma before ICU admission, mechanical ventilation, metabolic acidosis, delirium on the prior day , coma.


Natural History, Complications and Prognosis

The duration of delirium may vary from hours to months. After remission , delirium may increase the risk of functional decline, cognitive dysfunction, and institutional placement, and with higher mortality. Delirium in the elderly, can cause many complications, which may include pneumonia and decubitus ulcers, prolonging hospital stays. Delirium was associated with longer postoperative recovery periods, longer hospital stays, and long-term disability after orthopedic surgery. Common complications associated with delirium include increased mortality, cognitive impairment, longer durations of mechanical ventilation, longer lengths of stay in the ICU. Prognosis is dependent on the severity of delirium, and the 1 year mortality rate of patients with delirium is approximately 10%-26%.


Diagnosis

Diagnostic Criteria

The DSM V, and ICD-10 have provided diagnostic criteria for delirium. Definition based on DSM-5 include disturbance in attention and awareness (reduced ability to direct, focus, shift attention and reduced orientation to envinment), initiation of disturbance over a short period of time during several hours or days with fluctuation in severity over a day, disturbance in cognition (memory deficit, disorientation, language, visuospatial ability, [[perception, disturbance other than evolving neurocognitive disorder, disturbance due to medical condition, substance intoxication, or withdrawal. Other definitions of delirium include disturbance in cognition, impairment of immediate recall and recent memory, disorientation to time, place, person, disturbance in sleep wake cycle, Psychomotor disturbances,emotional disturbances in a period of less than 6 months.


History and Symptoms

Delirium causes impairment in functions, sleep-wake cycle and also has a behavioral component. Common symptoms associated with delirium include altered level of consciousness, inattention, disorientation, hallucination, delusions, agitation, inappropriate speech, sleepwake disturbances, Symptom fluctuation, emotional disturbance. Subclinical delirium or prodromal delirium may precede by 1 to 3 days prior to an overt delirium, which presents as restlessness, anxiety, irritability, distractibility, sleep disturbance with less severe cognitive impairment in comparison to delirium


Physical Examination

It is important to do a thorough physical examination to find out the underlying etiology of delirium. Systemic physical examination includes testing vital signs such as temperature, pulse rate, blood pressure, and respiration and also evaluation of mental status. Patients may seem disoriented with difficulty in sustaining attention, problem in short-term memory, poor insight and impaired judgment.


Laboratory Findings

Laboratory findings may differ according to the etiology of delirium. Following investigations are done in delirium: pulse oximetry, electrolytes, blood glucose, liver function tests, blood urea nitrogen, creatinine, vitamin B12 , Folate levels, measurement therapeutic drug levels, urine drug screen for substance use, blood alcohol level, complete blood count, urinalysis, thyroid function testing, erythrocyte sedimentation rate, C-reactive protein, rapid plasma reagin screening for syphilis, acquired immune deficiency syndrome/human immunodeficiency virus (AIDS/HIV) screening.


CT scan

Brain CT scan is helpful in the diagnosis the underlying cause of delirium. Findings on brain CT scan among patients admitted with delirium include: acute or subacute infarct, haemorrhage, abscess, neoplasm, vasculitis, posterior reversible encephalopathy syndrome, encephalitis, acute demyelination, Fat embolism.


MRI

Brain MRI is valuable tool for diagnosis the underlying cause of delirium when the brain CT scan findings are not informative. The most common finding on brain MRI that was missed by brain CT scan was ischemia.


Other Diagnostic Studies

EEG maybe helpful for the diagnosis of delirium. EEG findings associated with delirium include periodic discharges, triphasic waves ,lateralized rhythmic delta ,low voltage/generalized attenuation, theta or delta generalized slowing.The presence of either theta or delta generalized slowing correlated strongly with delirium severity regardless of arousal state (hyper- or hypoactive) and comorbidities.


Treatment

Medical Therapy

Treatment of delirium involves two main strategies: first, treatment of the underlying presumed acute cause or causes, secondly, optimizing conditions of the brain. This involves ensuring that the patient with delirium has adequate oxygenation, hydration, nutrition, and normal levels of metabolites, so that drug effects are minimized, constipation treated, pain treated, and so on. Detection and management of mental stress are also very important. Therefore, the traditional concept that the treatment of delirium is treating the cause is not adequate. Common medications is used for delirium treatment include antipsychotic drugs, benzodiazepines, cholinestrase inhibitors, selective -a2 receptor agonist, melatonin based medications, ketamine.


Prevention

Primary prevention

It is important to prevent delirium as delirium is itself neurotoxic. Delirium is associated with global brain atrophy and white matter disruption. Various non pharmacological and pharmacological interventions are found to be effective to prevent delirium. Primary prevention sterategy for Post-operative delirium may include use of haloperidol, second generation antipsychotics, iliac fascia block, lower levels of intraoperative propofol for sedation, continuous intravenous infusion of dexmedetomidine,and use of Melatonin. ketamine is not useful in preventing postoperative delirium. Preoperative administration of gabapentin is not effective for prevention of postoperative delirium.

Secondary prevention

Secondary prevention strategies following delirium include avoid anticholinergic drugs, attend to environmental factors (sensory input, [[orientation aids], reassuring human contact, routine screening for finding high risk patients, early recognition of any change or fluctuation of mental state or behaviour.

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