Delirium

From Wikipedia, the free encyclopedia Delirium, or acute confusional state, is severe confusion that develops quickly, and often fluctuates in intensity. It is a common[when?] neuropsychiatric syndrome with a core feature of acute onset, meaning it has been present from hours to days, but not months or years. Delirium represents an organically caused decline from a previously-attained level of cognitive functioning. Delirium typically appears suddenly with a readily-identifiable time of onset, such as a time space of a few hours, or overnight. It is typified by fluctuating course, attentional deficits and generalized severe disorganization of behavior. It typically involves other cognitive deficits, changes in arousal (hyperactive, hypoactive, or mixed), perceptual deficits, altered sleep-wake cycle, and psychotic features such as hallucinations and delusions. Delirium 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. It is a corollary of the criteria that a diagnosis of delirium cannot be made without a previous assessment, or knowledge, of the affected person's baseline level of cognitive function. In other words, a mentally disabled or demented person who is operating at their own baseline level of mental ability would be expected to appear delirious without a baseline mental functional status against which to compare. Delirium may be caused by a disease process outside the brain that affects the brain, such as infection (urinary tract infection, pneumonia) or drug effects, particularly anticholinergics or other CNS depressants (benzodiazepines and opioids).[1] Although hallucinations and delusions are sometimes present in delirium, these are not required for the diagnosis, and the symptoms of delirium are clinically distinct from those induced by psychosis or hallucinogens (with the exception of deliriants.) Delirium must by definition be caused by an organic process, i.e., a physically identifiable structural, functional, or chemical problem in the brain (see organic brain syndrome), and thus, fluctuations of mentation due to changes in purely psychiatric processes or diseases, such as sudden psychosis from schizophrenia or bipolar disorder, are (by definition) not termed delirium. Like its components (inability to focus attention, mental confusion and various impairments in awareness and temporal and spatial orientation), delirium is the common symptomatic manifestation of new organic brain dysfunction (for any reason). Delirium requires both a sudden change in mentation, and an organic cause for this. Thus, without careful assessment and history, delirium can easily be confused with a number of psychiatric disorders or long term organic brain syndromes, because many of the signs and symptoms of delirium are conditions also present in dementia, depression, and psychosis.[2] Delirium may newly appear on a background of mental illness, baseline intellectual disability, or dementia, without being due to any of these problems.

Treatment of delirium requires treatment of the underlying organic cause(s). In some cases, temporary or palliative or symptomatic treatments are used to comfort patients or to allow better patient management (for example, a patient who, without understanding, is trying to pull out a ventilation tube that is required for survival). Delirium is probably the single most common acute disorder affecting adults in general hospitals. It affects 10-20% of all hospitalized adults, and 3040% of elderly hospitalized patients and up to 80% of ICUpatients. In ICU patients or in other patients requiring critical care, delirium is not simply an acute brain disorder but in fact is a harbinger of much greater likelihood of death within the 12 months which follow the ICU patient's hospital discharge.[3] Contents [hide]

1 Definition 2 Signs and symptoms o 2.1 Inattention and associated cognitive deficits o 2.2 Higher level thinking processes o 2.3 Circadian disruption o 2.4 Persistent delirium o 2.5 Acquired dementia in ICU survivors 3 Pathophysiology: Animal models 4 Causes o 4.1 Critical illness o 4.2 Heatstroke o 4.3 Substance withdrawal o 4.4 Gross structural brain disorders o 4.5 Neurological disorders o 4.6 Circulatory o 4.7 Metabolic o 4.8 Medication o 4.9 Drugs 5 Differential diagnosis o 5.1 Mental illness 6 Diagnosis o 6.1 Diagnosis in ICU 7 Prognosis 8 Prevention 9 Treatment

10 Epidemiology 11 Society and culture o 11.1 Costs 12 See also 13 References 14 Further reading 15 External links [edit]Definition In common usage, delirium is often used to refer to drowsiness, disorientation, and hallucination. In broader medical terminology, however, a number of other symptoms, including a sudden inability to focus attention, and even (occasionally) sleeplessness and severe agitation and irritability, also define "delirium," and hallucination, drowsiness, and disorientation are not required. There are several medical definitions of delirium (including those in the DSM-IV and ICD-10). However, all include some core features. The core features are:

Disturbance of consciousness (that is, reduced clarity of awareness of the environment, with reduced ability to focus, sustain, or shift attention) Change in cognition (e.g., problem-solving impairment or memory impairment) or a perceptual disturbance Onset of hours to days, and tendency to fluctuate. Behaviour may be either overactive or underactive, sleep is often disturbed. Thinking is slow and muddled but the content is often complex.[4]

Common features also tend to include: Intrusive abnormalities of awareness and affect, such as hallucinations or inappropriate emotional states[clarify]. [edit]Signs and symptoms Delirium is a neuropsychiatric syndrome with a broad range of cognitive and neurobehavioural symptoms that involve cognition, thought, language, sleep-wake cycle, perception, affect, and motor behaviour. This constellation of symptoms along with the cardinal symptom of inattention presenting with an acute onset and fluctuating course are characteristic of delirium. The change in cognition (memory deficit, disorientation, language disturbance) or the development of a perceptual disturbance, must be one that is not better accounted for by a preexisting, established, or evolving dementia. .[5]

Delirium occurs as a stage of consciousness in the continuum between normal awakeness/alertness and coma. During the 20th century, delirium was described as a clouding of consciousness but this rather nebulous concept has been replaced by a better understanding of the components of phenomenology that culminate in severely impaired higher order brain functions. Specifically, a disproportionate disturbance of attentional processes, including environmental awareness difficulties, along with impaired higher level thinking reflected in irrelevant, unfocused or illogical thought processes and impaired abstraction and comprehension (i.e., executive cognition and semantic language function) typifies the delirious state. Sleep-wake cycle fragmentation belies a circadian disturbance that may contribute to the abnormal level of consciousness and alterations in motor behaviour. Accumulating evidence indicates three core domains of delirium phenomenology: Cognition, composed of inattention and other cognitive deficits; Higher Level Thinking Processes including impaired executive function, semantic expression and comprehension; and Circadian Rhythm including altered motor activity and fragmented sleep-wake cycle.[6]Phenomenology studies suggest that core symptoms occur with greater frequency while other less consistent associated symptoms may reflect the biochemical influence of particular aetiologies or genetic, neuronal or physiological vulnerabilities.[6] [edit]Inattention and associated cognitive deficits Inattention is the cardinal and required symptom to diagnose delirium and is noticeable on interview by distractibility and inability to shift and / or sustain attention. More formal testing can include the months of the year backwards, serial sevens or digit span tests. Disorientation (another symptom of confusion, and usually a more severe one) describes the loss of awareness of the surroundings, environment and context in which the person exists. It may also appear with delirium, but it is not required, as noted. Disorientation may occur in time (not knowing what time of day, day of week, month, season or year it is), place (not knowing where one is) or person (not knowing who one is). Memory impairment occurs and is linked to inattention. Reduction in formation of new longterm memory (which by definition survives withdrawal of attention), is common in delirium, because initial formation of (new) long-term memories generally requires an even higher degree of attention than do short-term memory tasks. Since older memories are retained without need of concentration, previously formed long-term memories (i.e., those formed before the period of delirium) are usually preserved in all but the most severe cases of delirium. [edit]Higher level thinking processes Delirious patients have diminished comprehension as evidenced by reduced grasp of their surroundings and difficulties in connecting with their immediate environment, executive dysfunction affecting abstraction, initiation/perseveration, switching mental sets, working memory, temporal sequencing and organization, insight and judgment. Though none of these cognitive deficits is specific to delirium, the array and pattern is highly suggestive.

Language disturbances in delirium include dysnomia, paraphasias, impaired comprehension, dysgraphia, and word-finding difficulties. Incoherent or illogical / rambling conversation is reported commonly. Disorganised thinking includes tangentiality, circumstantiality and a proneness to loose associations between elements of thought which results in speech that often makes limited sense with multiple apparent irrelevancies. This aspect of delirium is common but often difficult for non-experts to assess reliably. [edit]Circadian disruption Disruption of sleep-wake cycle is almost invariably present in delirium and often predates the appearance of a full-blown episode. Minor disturbances with insomnia or excessive daytime somnolence may be hard to distinguish from other medically ill patients without delirium, but delirium typically involves more substantial alterations with sleep fragmentation or even complete sleep-wake cycle reversal that reflect disturbed circadian rhythm regulation. The relationship of circadian disturbances to the characteristic fluctuating severity of delirium symptoms over a 24 hour period or to motor disturbance is unknown. Motor activity alterations are very common in delirium. They have been used to define clinical subtypes (hypoactive, hyperactive, mixed) though studies are inconsistent as to the prevalence of these subtypes.[7] Cognitive impairments and EEG slowing are comparable in hyperactive and hypoactive patients though other symptoms may vary. Psychotic symptoms occur in both although the prevailing stereotype suggests that they only occur in hyperactive cases. Hypoactive cases are prone to non detection or misdiagnosis as depression. A range of studies suggest that motor subtypes differ regarding underlying pathophysiology, treatment needs, and prognosis for function and mortality though inconsistent subtype definitions and poorer detection of hypoactives impacts interpretation of these findings.[8] Psychotic symptoms occur in up to 50% of patients with delirium. While the common nonmedical view of a delirious patient is one who is hallucinating, most people who are medically delirious do not have either hallucinations or delusions. Thought content abnormalities include suspiciousness, overvalued ideation and frank delusions. Delusions are typically poorly-formed and less stereotyped than in schizophrenia or Alzheimers disease. They usually relate to persecutory themes of impending danger or threat in the immediate environment (e.g. being poisoned by nurses). Misperceptions include depersonalisation, delusional misidentifications, illusions and hallucinations. Hallucinations and illusions are frequently visual though can be tactile and auditory. Abnormalities of affect which may attend the state of delirium may include many distortions to perceived or communicated emotional states. Emotional states may also fluctuate, so that a delirious person may rapidly change between, for example, terror, sadness and jocularity.[9] [edit]Persistent delirium It was thought for many years that all delirium was a transient state of brain dysfunction that fluctuated on an hourly basis. Interestingly, Barrough noted in 1583 that if delirium resolves, it

may be followed by a "loss of memory and reasoning power." Recent long-term studies bear this out, showing that many patients end up meeting criteria for delirium for an alarmingly long time.[10] For example, in ICU cohorts, it is common to find that 10% of patients still have delirium at the time of hospital discharge.[11] [edit]Acquired dementia in ICU survivors Dementia is supposed to be an entity that continues to decline, such as Alzheimers disease. Another way of looking at dementia, however, is not strictly based on the decline component but on the degree of memory and executive function problems. It is now known, for example, that between 50% and 70% of ICU patients have tremendous problems with ongoing brain dysfunction that looks a lot like the degree of problems experienced by Alzheimers or TBI (traumatic brain injury) patients and which leaves too many ICU survivors disabled and unable to go back to work and unable to serve effectively as the matriarchs and patriarchs of their families.[12] This is a distressing personal and public health problem that is getting an increasing amount of scrutiny in ongoing investigations. The implications of such an acquired dementialike illness (note: the term here is being used in a circumstance in which not all patients continue to decline as some have persistent yet stable brain dysfunction and others with newly acquired brain problems can recover fully) are profound at the private level, dismantling the persons life in very practical ways such as inability to find a car in a parking lot or even complete shopping lists or job-related tasks done previously for years. The societal relevance is also huge when one considers work-force issues related to the inability of a young wage earner being unable to work because of either being a newly disabled ICU survivor him/herself or because he/she now has to care for their family member who is now suffering this dementialike illness following ICU care. [edit]Pathophysiology: Animal models The pathophysiology of delirium is not well understood and a lack of animal models that are relevant to the syndrome has left many key questions in delirium pathophysiology unanswered. Earliest rodent models of delirium used an antagonist of the muscarinic acetylcholine receptors, atropine, to induce cognitive and EEG changes similar to delirium. Similar anticholinergic drugs such as biperiden and scopolamine have also produced delirium-like effects. These models, along with clinical studies of drugs with anticholinergic activity have contributed to a hypocholinergic theory of delirium.[13] Profound systemic inflammation occurring during bacteraemia/sepsis is also known to cause delirium (often termed septic encephalopathy). Modeling this in mice also causes robust brain dysfunction and probably a delirium-like state, although these animals are typically too sick to assess cognitively and measures such as EEG and magnetic resonance imaging/spectroscopy are necessary to demonstrate dysfunction. Animal models that interrogate interactions between prior degenerative pathology and superimposed systemic inflammation have been developed more recently and these demonstrate

that even mild systemic inflammation, a frequent trigger for clinical delirium, induces acute and transient attentional/working memory deficits, but only in animals with prior pathology. Prior dementia or age-associated cognitive impairment is the primary predisposing factor for clinical delirium and prior pathology as defined by these new animal models may consist of synaptic loss, network disconnectivity, and primed microglia (brain macrophages that are primed by the primary pathology to produce exaggerated responses to subsequent inflammatory insults). While it is difficult to state with confidence whether delirium is occurring in a non-verbal animal, comparisons with human DSM-IV criteria remain useful. According to DSM-IV, demonstration of acute onset impairments in attention and some other cognitive domain, that cannot be better explained by existing dementia and that are triggered by physiological disturbances resulting from some general medical condition should be present in order to reach a diagnosis of delirium. Recent animal models fulfill these criteria reasonably well.[14] Whether the deficit is one of attention or short-term memory is difficult to dissect, but it is undeniably distinct from long-term memory, consistent with observations in patients with delirium. There is an urgent need to understand more about the mechanisms of dysfunction underpinning delirium and data arising from these and other animal models must form part of the discussion on delirium pathophysiology. [edit]Causes Delirium is a very general and nonspecific symptom of brain dysfunction. Delirium may be caused by physical illness, which can be mild, or any process which interferes with the normal metabolism or function of the brain. For example, electric shock, fever, pain, poisons (including toxic drug reactions), brain injury, hypoxia, anoxia, surgery, traumatic shock, lack of food or water or sleep, and even withdrawal symptoms of certain drug and alcohol dependent states, are all known to cause delirium. In addition, there is an interaction between acute and chronic symptoms of brain dysfunction; delirious states are more easily produced in people already suffering with underlying chronic brain dysfunction.[15] [edit]Critical illness The most common behavioral manifestation of acute brain dysfunction is delirium, which occurs in up to 60% to 80% of mechanically ventilated medical and surgical ICU patients and 50% to 70% of non-ventilated medical ICU patients.[15] During the ICU stay, acute delirium is associated with complications of mechanical ventilation including nosocomial pneumonia, self-extubation, and reintubation.[3] ICU delirium predicts a 3- to 11-fold increased risk of death at 6 months even after controlling for relevant covariates such as severity of illness.[3] Of late, delirium has been recognized by some as a sixth vital sign, and it is recommended that delirium assessment be a part of routine ICU management.[16] The elderly may be at particular risk for this spectrum of delirium and dementia.[17] A firm understanding of the pathophysiologic mechanisms of delirium remains elusive despite improved diagnosis and potential treatments.

[edit]Heatstroke When the body temperature rises beyond a critical temperature, into the range of 105F (40,6C) to 108F (42,2C) the person is likely to develop heatstroke. Only sometimes symptoms include delirium, but eventually result in the loss of consciousness if the body temperature is not decreased.[clarification needed] [edit]Substance withdrawal Drug withdrawal is a common cause of delirium. The most notable are alcohol withdrawal and benzodiazepine withdrawal but other drug withdrawals both from licit and illicit drugs can sometimes cause delirium. [edit]Gross structural brain disorders Head trauma (i.e., concussion, traumatic bleeding, penetrating injury, etc.) Gross structural damage from brain disease (stroke, spontaneous bleeding, tumor, etc.) [edit]Neurological disorders Various neurological disorders Lack of sleep [edit]Circulatory Intracranial hypertension [edit]Metabolic Hypoxia Hypoglycemia Electrolyte imbalance (dehydration, water intoxication) [edit]Medication Medications including psychotropic medications, opiates and benzodiazepines, as well as the interaction of certain prescription drugs.[1][18] [edit]Drugs Intoxication by various drugs, alcohol, or anesthetics Sudden withdrawal of chronic drug use in a person with certain types of drug addiction (e.g. alcohol, see delirium tremens, and many other sedating drugs) Poisons (including carbon monoxide and metabolic blockade) [edit]Differential diagnosis [edit]Mental illness

Some mental illnesses, such as mania, or some types of acute psychosis, may cause a rapidly fluctuating impairment of cognitive function and ability to focus. However, they are not technically causes of delirium, since any fluctuating cognitive symptoms that occur as a result of these mental disorders are considered by definition to be due to the mental disorder itself, and to be a part of it. Thus, physical disorders can be said to produce delirium as a mental side-effect or symptom, although primary mental disorders which produce the symptom cannot be put into this category once identified. However, such symptoms may be impossible to distinguish clinically from delirium resulting from physical disorders, if a diagnosis of an underlying mental disorder is yet to be made.[citation needed] [edit]Diagnosis Differential points from other processes and syndromes that cause cognitive dysfunction:

Delirium may be distinguished from psychosis, in which consciousness and cognition may not be impaired (however, there may be overlap, as some acute psychosis, especially with mania, is capable of producing delirium-like states). Delirium is distinguished from dementia (chronic organic brain syndrome) which describes an "acquired" (non-congenital) and usually irreversible cognitive and psychosocial decline in function. Dementia usually results from an identifiable degenerative brain disease (for example Alzheimer disease or Huntington's disease). Dementia is usually not associated with a change in level of consciousness, and a diagnosis of dementia requires a chronic impairment. Delirium is distinguished from depression. Delirium is distinguished by time-course from the confusion and lack of attention which result from long term learning disorders and varieties of congenital brain dysfunction. Delirium has also been referred to as 'acute confusional state' or 'acute brain syndrome'. The key word in both of these descriptions is "acute" (meaning: of recent onset), since delirium may share many of the clinical (i.e., symptomatic) features of dementia, developmental disability, or attention-deficit hyperactivity disorder, with the important exceptionof symptom duration. Delirium is not the same as confusion, although the two syndromes may overlap and be present at the same time. However, a confused patient may not be delirious (an example would be a stable, demented person who is disoriented to time and place), and a delirious person may not be confused (for example, a person in severe pain may not be able to focus attention because of the pain, and thus be by definition delirious, but may be completely oriented and not at all confused).

Delirium represents an organically caused decline from a previously-attained level of cognitive functioning. It is a corollary of these differential criteria that a diagnosis of deliriumcannot be made without a previous assessment, or knowledge, of the affected person's baseline level of cognitive function. In other words, a mentally disabled or demented person who is operating

at their own baseline level of mental ability might appear to be delirious without a baseline functional status against which to compare. [edit]Diagnosis in ICU In the ICU, international guidelines recommend that every patient gets checked for delirium every day (usually twice or more a day) using a validated clinical tool.[19] The two most widely used are the Confusion Assessment Method for the ICU (CAM-ICU)[20] and the Intensive Care Delirium Screening Checklist (ICDSC).[21] There are translations of these tools in over 20 languages and they are used globally in many thousands of ICUs, and instructional videos and a myriad of implementation tips are available.[22] It is not as important which tool is used as that the patient gets monitored. Without using one of these tools, 75% of ICU delirium is missed by the practicing team, which leaves the patient without any likely active interventions to help reduce the duration of his/her delirium.[23] The most salient component of the definition of delirium that nurses and other healthcare professionals use at the bedside is whether or not the patient can pay attention and follow simple commands (see videos and literature[22]). The advent of daily monitoring for delirium had led to important changes in the culture of ICUs and rounds in that the entire team can now discuss the brain and how it is doing in terms of being on (not delirious) or off (delirious) and then focus on the several most likely causes of delirium in any specific patient. Thus, it is not the monitoring itself that changes the patients clinical course, but rather it is this combination of monitoring and then relaying the information on rounds in the ICU that makes such a huge difference in awareness of this form of organ dysfunction and then enables a difference to be made in clinical outcomes. [edit]Prognosis There is substantial evidence that delirium results in long-term poor outcomes in older persons admitted to hospital.[24] This systematic review only included studies that looked for an independent effect of delirium (i.e., after accounting for other associations with poor outcomes, for example co-morbidity or illness severity). In older persons admitted to hospital, individuals experiencing delirium are twice as likely to die than those who do not (meta-analysis of 12 studies).[24] In the only prospective study conducted in the general population, older persons reporting delirium also showed higher mortality (60% increase).[25] Institutionalisation was also twice as likely after an admission with delirium (meta-analysis of 7 studies).[24] In a community-based population examining individuals after an episode of severe infection (though not specifically delirium), these persons acquired more functional limitations (i.e. required more assistance with their care needs) than those not experiencing infection.[26] After an episode of delirium in the general population, functional dependence increased threefold.[25]

The association between delirium and dementia is complex. The systematic review estimated a 13-fold increase in dementia after delirium (meta-analysis of 2 studies).[24] However, it is difficult to be certain that this is accurate because the population admitted to hospital includes persons with undiagnosed dementia (i.e. the dementia was present before the delirium, rather than caused by it). In prospective studies, people hospitalised from any cause appear to be at greater risk of dementia[27] and faster trajectories of cognitive decline,[27][28] but these studies did not specifically look at delirium. In the only population-based prospective study of delirium, older persons had an eight-fold increase in dementia and faster cognitive decline.[25] The same association is also evident in persons already diagnosed with Alzheimers dementia.[29] [edit]Prevention Episodes of delirium can be prevented by identifying hospitalized people at risk of the condition: those over 65, those with a known cognitive impairment, those with hip fracture, those with severe illness.[30] Close observation for the early signs is recommended in those people. Systematically addressing the common contributing factors (such as constipation, dehydration and polypharmacy), as well as providing adequate lighting, signage and ways to tell the time, may prevent delirium.[30][31] It is thought that 3040% of all cases of delirium could be prevented, and that high rates of delirium reflect negatively on the quality of care.[31] [edit]Treatment Treatment of delirium involves two main strategies: first, treatment of the underlying presumed acute cause or causes; secondly, optimising conditions for the brain. This involves ensuring that the patient with delirium has adequate oxygenation, hydration, nutrition, and normal levels of metabolites, that drug effects are minimised, constipation treated, pain treated, and so on. Detection and management of mental stress is also very important. Therefore, the traditional concept that the treatment of delirium is 'treat the cause' is not adequate; patients with delirium actually require a highly detailed and expert analysis of all the factors which might be disrupting brain function. Non-pharmacological treatments are the first measure in delirium, unless there is severe agitation that places the person at risk of harming oneself or others. Avoiding unnecessary movement, involving family members, having recognizable faces at the bedside, having means of orientation available (such as a clock and a calendar) may be sufficient in stabilizing the situation.[30][31] If this is insufficient, verbal and non-verbal de-escalation techniques may be required to offer reassurances and calm the person experiencing delirium.[30] Only if this fails, or if de-escalation techniques are inappropriate, is pharmacological treatment indicated.[30][31] The T-A-DA method (tolerate, anticipate, don't agitate)[32] is an effective management technique for people with delirium. All unnecessary attachments are removed (IVs, catheters, NG tubes) which allows for greater mobility.[32] Patient behavior is tolerated even if it is not

considered normal as long as it does not put the patient or other people in danger.[32]This technique requires that patients have close supervision to ensure that they remain safe.[32] Patient behavior is anticipated so care givers can plan required care. Patients are treated to reduce agitation.[32] Reducing agitation may mean that patients are not reoriented if reorientation causes agitation.[32] Physical restraints are often used as a last resort with patients in a severe delirium. Restraint use should be avoided as it can increase agitation and risk of injury.[33] In order to avoid the use of restraints some patients may require constant supervision. The pharmacological treatment for delirium depends on its cause. Antipsychotics, particularly haloperidol, are the most commonly used drugs for delirium and the most studied.[30][31] Evidence is weaker for the atypical antipsychotics, such as risperidone, olanzapine and quetiapine.[31][34] British professional guidelines by the National Institute for Health and Clinical Excellence advise haloperidol or olanzapine.[30] Benzodiazepines themselves can cause delirium or worsen it,[31] and lack a reliable evidence base.[35] However, if delirium is due to alcohol withdrawal or benzodiazepine withdrawal or if antipsychotics are contraindicated (e.g. in Parkinson's disease or neuroleptic malignant syndrome), then benzodiazepines are recommended.[31] Similarly, people with dementia with Lewy bodies may have significant side-effects to antipsychotics, and should either be treated with a small dose or not at all.[30] The antidepressant trazodone is occasionally used in the treatment of delirium, but it carries a risk of oversedation, and its use has not been well studied.[31] [edit]Epidemiology The highest prevalence of delirium (often 50% to 75% of patients) is generally seen in critically ill patients in the intensive care unit or ICU (which used to be referred to by the misnomers "ICU psychosis" or "ICU syndrome", terms largely abandoned for the more widely accepted and scientifically supported term ICU Delirium.[22] Since the advent of validated and easy-toimplement delirium instruments for ICU patients such as the Confusion Assessment Method for the ICU (CAM-ICU)[20] and the Intensive Care Delirium Screening Checkllist (IC-DSC).,[21] of the hundreds of thousands of ICU patients who develop delirium in ICUs every year, it has been recognized that most of them belong to the hypoactive variety, which is easily missed and invisible to the managing teams unless actively monitored using such instruments. The causes of delirium in such patients depend on the underlying illnesses, new problems like sepsis and low oxygen levels, and the sedative and pain medicines that are nearly universally given to all ICU patients. Outside the ICU, on hospital wards and in nursing homes, the problem of delirium is also a very important medical problem, especially for older patients. The most recent area of the hospital in which delirium is just beginning to be monitored routinely in many centers is the Emergency Department.

A systematic review of delirium in general medical inpatients showed that estimates of delirium prevalence on admission ranged from 10 to 31%.[36] [edit]Society and culture Delirium is one of the oldest forms of mental disorder known in medical history.[37] Sims (1995, p. 31) points out a "superb detailed and lengthy description" of delirium in The Stroller's Tale from Charles Dickens' The Pickwick Papers.[38][39] [edit]Costs In the USA, the cost of a patient admission with delirium is estimated at between $16k and $64k, suggesting the national burden of delirium may range from $38 bn to $150 bn per year (2008 estimate).[40] In the UK, the cost is estimated as 13k per admission.[41] [edit]See also

Deliriant Organic brain syndrome

Background Delirium or acute confusional state is a transient global disorder of cognition. The condition is a medical emergency associated with increased morbidity and mortality rates. Early diagnosis and resolution of symptoms are correlated with the most favorable outcomes. Therefore, it must be treated as a medical emergency. Delirium is not a disease but a syndrome with multiple causes that result in a similar constellation of symptoms. Delirium is defined as a transient, usually reversible, cause of cerebral dysfunction and manifests clinically with a wide range of neuropsychiatric abnormalities. The clinical hallmarks are decreased attention span and a waxing and waning type of confusion. Delirium often is unrecognized or misdiagnosed and commonly is mistaken fordementia, depression, mania, an acute schizophrenic reaction, or part of old age (patients who are elderly are expected to become confused in the hospital). The word delirium is derived from the Latin term meaning "off the track." This syndrome was reported during Hippocrates' time, and, in 1813, Sutton described delirium tremens. Later, Wernicke described the encephalopathy that bears his name. Case study A 78-year-old female was brought to the Emergency Department by her daughter for vomiting, new onset urinary incontinence, confusion, and incoherent speech for the past 2 days. The patient

was disoriented and could see people climbing trees outside the window. She had difficulty sustaining attention, and her level of consciousness waxed and waned. She had been talking about her deceased husband. Patient was also trying to pull out her intravenous access line. Past history included diabetes mellitus, hyperlipidemia, osteoarthritis, and stroke. The patient's family physician had recently prescribed Tylenol with codeine for the patient's severe knee pain 5 days earlier. On examination, the patient was drowsy and falling asleep while practitioners were talking to her. Patient was not cooperative with the physical examination and with a formal mental status examination. Limited examination of the abdomen indicated that it was flat and soft with normal bowel sounds. The patient moves all 4 limbs and plantar is bilateral flexor. Laboratory test results revealed elevated BUN and creatinine levels, and the urine analysis was positive for urinary tract infection. CT scan of the head showed cortical atrophy. Pathophysiology Based on the state of arousal, 3 types of delirium are described. Hyperactive delirium is observed in patients in a state of alcohol withdrawal or intoxication with phencyclidine (PCP), amphetamine, and lysergic acid diethylamide (LSD). Hypoactive delirium is observed in patients in states of hepatic encephalopathy and hypercapnia. In mixed delirium, individuals display daytime sedation with nocturnal agitation and behavioral problems. The mechanism of delirium still is not fully understood. Delirium results from a wide variety of structural or physiological insults. The neuropathogenesis of delirium has been studied in patients with hepatic encephalopathy and alcohol withdrawal. Research in these areas still is limited. The main hypothesis is reversible impairment of cerebral oxidative metabolism and multiple neurotransmitter abnormalities. The following observations support the hypothesis of multiple neurotransmitter abnormalities. Acetylcholine Data from animal and clinical studies support the hypothesis that acetylcholine is one of the critical neurotransmitters in the pathogenesis of delirium.[1] A small prospective study among patients who have undergone elective hip replacement surgery showed reduced preoperative plasma cholinesterase activity in as many as one quarter of patients. In addition, reduced preoperative cholinesterase levels were significantly correlated with postoperative delirium.[2] Clinically, good reasons support this hypothesis. Anticholinergic medications are a well-known cause of acute confusional states, and patients with impaired cholinergic transmission, such those with Alzheimer disease, are particularly susceptible. In patients with postoperative delirium, serum anticholinergic activity is increased. Dopamine

In the brain, a reciprocal relationship exists between cholinergic and dopaminergic activities. In delirium, an excess of dopaminergic activity occurs. Symptomatic relief occurs with antipsychotic medications such as haloperidol and other neuroleptic dopamine blockers. Other neurotransmitters Serotonin: Human and animal studies have found that serotonin is increased in patients with hepatic encephalopathy and septic delirium. Hallucinogens such as LSD act as agonists at the site of serotonin receptors. Serotoninergic agents also can cause delirium. Gamma-aminobutyric acid (GABA): In patients with hepatic encephalopathy, increased inhibitory GABA levels also are observed. An increase in ammonia levels occurs in patients with hepatic encephalopathy, which causes an increase in the amino acids glutamate and glutamine, which are precursors to GABA. Decreases in CNS GABA levels are observed in patients with delirium resulting from benzodiazepine and alcohol withdrawal. Cortisol and beta-endorphins: Delirium has been associated with the disruption of cortisol and beta-endorphin circadian rhythms. This mechanism has been suggested as a possible explanation for delirium caused by exogenous glucocorticoids. Disturbed melatonin disturbance has been associated with sleep disturbances in delirium.[3] Inflammatory mechanism Recent studies have suggested a role for cytokines, such as interleukin-1 and interleukin-6, in the pathogenesis of delirium. Following a wide range of infectious, inflammatory, and toxic insults, endogenous pyrogen, such as interleukin-1, is released from the cells. Head trauma and ischemia, which frequently are associated with delirium, are characterized by brain responses that are mediated by interleukin-1 and interleukin-6.[4, 5] Stress reaction mechanism Studies indicate psychosocial stress and sleep deprivation facilitate the onset of delirium. Structural mechanism The specific neuronal pathways that cause delirium are unknown. Imaging studies of metabolic (eg, hepatic encephalopathy) and structural (eg, traumatic brain injury, stroke) factors support the hypothesis that certain anatomical pathways may play a more important role than others. The reticular formation and its connections are the main sites of arousal and attention. The dorsal tegmental pathway projecting from the mesencephalic reticular formation to the tectum and the thalamus is involved in delirium. Disrupted blood-brain barrier can allow neurotoxic agents and inflammatory cytokines to enter the brain and may cause delirium. Contrast-enhanced MRI can be used to assess the blood-brain barrier.[6, 7]

Visuoperceptual deficits in delirium such as hallucinations and delusions are not due to the underlying cognitive impairment.[8] Visual hallucinations during alcohol-withdrawal delirium are seen in subjects with polymorphisms of genes coding for dopamine transporter and catechol-Omethyltransferase (COMT).

INTRODUCTION A delirium is a condition that arises within a short period of time (hours to days), in which there is a fluctuating disturbance in consciousness and the patient is often confused. There is also restlessness, or with a quiet delirium, there is apathy and loss of initiative. Hallucinations and/or delusions are common. Per definition, there is an underlying medical disorder. The word delirium comes from the Greek lros' = raving, nonsense; and from the Latin word delirare' or delira decedere' = to go over the line, go off the rails. Delirium is classified under the organic psychosyndromes. Characteristic of these syndromes is that medical disorders lead to relatively clear and consistent psychiatric disease states. A well known example is raving of children with high fever. A delirium usually lasts several days to weeks, depending on the underlying cause and the extent to which it can be influenced. While delirium is, in principle, a temporary disorder, full recovery does not always take place with cognitively vulnerable patients. Delirium is an expression of a serious organic problem. A delirium can be an extremely frightening experience, possibly comparable to persistent nightmares. However, patients will not always be able to recount this, because there may be amnesia for the event or because the patient dies. In many cases, patients do remember the delirium as a very stressful period. In doing so, there is no difference in perception between a hyperactive and quiet delirium. It is also a very stressful experience for those in the patient's environment. Experiencing a death bed that is frightening or includes a delirium may leave an unerasable impression on family, which in turn can be determinant in the image formed of their own illness and deathbed. A delirium can also be disturbing for the treating physician. Certainly when the clinical picture is not immediately recognised and the restlessness is attributed to pain, increasing the pain medication (especially opioids) seems an obvious choice. However, this may in fact worsen the delirium. The occurrence of a delirium is an unfavourable prognostic symptom. The chance of patients dying who are >65 years of age and have been admitted to hospital with a delirium is 2-3x higher than that of patients without delirium. The median survival for patients with an advanced stage of cancer who develop a delirium is 21-24 days. The Anglo-Saxon term terminal restlessness signifies a restless delirium in the terminal phase. This delirium is often accompanied by stimulation of the central nervous system, as can be seen from multifocal myoclonus and the patient's restlessness. The result is partly coordinated and

partly uncoordinated movements, such as tremors, pulling on the sheets and tossing and turning, through to convulsions, sometimes accompanied by groaning or shouting. In some cases delirium cannot be adequately treated. Especially in the terminal phase, causal treatment may no longer be feasible and symptomatic treatment may fall short, in which case the delirium heralds approaching death. Palliative sedation may then be necessary in order to enable the patient to have as much of a dignified death as possible. The worst scenario is called the destructive triangle: 1. A dying patient suddenly becomes confused, restless (sometimes even aggressive) and anxious. Good contact is no longer possible. 2. The family members, who were already emotionally exhausted from the illness, get an enormous shock and lose their balance. 3. Strong pressure is exerted on the physician. He/she must rapidly find a solution. At such a moment, this may mean palliative sedation is applied too fast. Case After an illness process with difficult-to-treat pain and much anxiety, the last phase appeared to proceed smoothly. Strongly emaciated, she was in bed at home. The biggest problem was the heat. By keeping the doors and windows shut where possible during the day and opening everything up at night, it was possible to keep the atmosphere tolerable in the home. She had stopped eating quite some time ago and had barely drunk anything for a few days. She had no pain, thanks to high dose morphine suppositories. She dozed most of the day. When the general practitioner visited her during the day, he found her sleeping peacefully. She could be woken up, but the general practitioner did not make much effort to do so. After all, everything had been said. In addition, a coherent conversation was no longer possible. He preferred to speak with her husband. He said that she was restless at night and did not always recognise him then. She imagined she was in hospital and invariably talked about small white pills; she was convinced she was being poisoned by the wrong pills. Although she had not swallowed any medication for weeks, she continued to express this fear. He was unable to reassure her otherwise. He therefore wondered if his wife would pass away as peacefully as their general practitioner kept predicting. The general practitioner again reassured him that he did not need to worry about this point. After all, she had no pain because of the morphine suppositories. Signs of dehydration were already clearly visible. Death was close and would be mild. How different the situation would turn out to be. Early in the night, she became extremely anxious and restless within a short period of time. She almost climbed over the side rails of the bed, her eyes were wide open without seeing her husband, let along recognising him. Sometimes she talked gibberish, at other times she shouted and shrieked so loud that all the windows had to be closed in consideration of the neighbours. The general practitioner was summoned with haste. He had no idea what to do with this situation. In order to do something, he administered a rectal diazepam, without any effect. He was called again a few hours later. He again administered diazepam, again without any result.

When it became light outside, she was exhausted and no longer shouted. She died two hours later. This patient displayed the clinical picture of terminal restlessness. The clear preliminary signs of the delirium were not recognised. During the day everything appeared calm, but a night the patient was confused, suspicious and she had delusions. This was accompanied by disorientation: she did not know where she was and she no longer recognised her husband. The signs were not recognised and so the general practitioner also did not look for possible treatable causes of this delirium, such as a morphine level that was too high as a result of dehydration. After all, while she had not had pain for weeks, the dose of morphine had not been reduced. However, the dehydration posed a risk of intoxication. The right medication had also not been prescribed. The benzodiazepine used, diazepam, simply worsened the delirium. As a result, a terrible situation was able to develop in the middle of the night (a palliative emergency).

PATHOPHYSIOLOGY AND AETIOLOGY A delirium is a manifestation of an acute diffuse cerebral dysregulation, usually determined in a multifactorial manner. There is an imbalance in neurotransmitters, especially a shortage of acetylcholine and a (relative) excess of dopamine. It is for this reason that medication with an anticholinergic (side) effect may trigger a delirium and forms the basis for the use of dopamine antagonists in the drug-based treatment of a delirium. There is always an underlying medical disorder or it is an effect of a drug or substance taken. Even in the palliative phase one or more of these underlying disorders may be treatable, and it is therefore appropriate to actively search for it. In the aetiology, a distinction is made between predisposing factors and precipitating or triggering factors. If there are clear predisposing factors, a minor predisposing factor will already be sufficient to induce a delirium. For example, a urinary tract infection can sometimes be enough to trigger a delirium with an old and fragile brain. On the other hand, very strong precipitating factors are needed to derail a young and healthy brain. The following characteristics are predisposing factors for a delirium:

age 70 years pre-existing cognitive disorders, such as dementia or CVA visual and hearing disorders disorders in the activities of daily living (ADL) use of alcohol and opioids

The following characteristics are precipitating factors for the occurrence of a delirium:

brain tumours and metastases, carcinomatous meningitis fever pneumonia, urinary tract infection hypoxia anaemia electrolytic disorders (especially hyponatraemia, hypernatraemia, hypercalcaemia) hypoglycaemia, hyperglycaemia thyroid function disorders liver failure, renal failure dehydration low serum albumin recent surgery medications withdrawal of medications, nicotine or alcohol urinary retention constipation a change in abode

The following medications may cause a delirium:

opioids: at the start of treatment or on increasing the dose, as well as with chronic use of the same dose during deterioration of the patient associated with weight loss, low serum albumin and/or dehydration all medications with a sedative effect or side effect benzodiazepines or withdrawal of these medications. A relative overdose of these medications may easily occur with liver and/or renal failure corticosteroids may cause psychiatric disturbances, including a delirium. These disturbances especially occur with high doses and usually during the first two weeks of corticosteroid therapy. The latter is not a fixed rule, the disturbances may always occur, at any dose, at any moment and also when gradually reducing corticosteroids. It makes it difficult that corticosteroids are indicated for increased intracranial pressure, as is seen with cerebral metastases. If a delirium subsequently develops, it is sometimes unclear if the cause lies with the cerebral metastasis or the corticosteroid. anticholinergics and drugs with an anticholinergic side effect (e.g. tricyclic antidepressants, some eye drops, phenothiazines, antihistamines, spasmolytics, anti-emetics and antiarrhythmics) antiparkinsonian medications chemotherapeutic agents such as ifosfamide, asparaginase, chlorambucil, cytarabine, vincristine and vinblastine some antibiotics, such as ciprofloxacin, isoniazid and voriconazole other drugs: digoxin and ketamine

In most cases, there are multiple (on average three) precipitating factors. In a third of cases only one precipitating factor is involved. The most common precipitating factors are (in decreasing order of prevalence):

opioids metabolic abnormalities infections recent surgery brain tumours or metastases

MANAGEMENT AND TREATMENT

Adequate treatment of delirium is of great importance for the patient and their family. In the case of a reversible delirium, there appears to be amnesia for the event with some of the patients. However, in many cases (also with quiet deliriums), the occurrence of a delirium leads to lasting memories that are very unpleasant for the patient. It is also very unpleasant for patients who have no recollection of the event, to know that they may have acted very odd. A delirium can also be a very traumatic experience for the patient's family. It is therefore decided in most cases to treat the cause of the delirium, either nonpharmacologically or with medication if required. However, treatment may be foregone in some cases. This applies especially in the dying phase. Many dying patients meet the DSM-IV-TR criteria for a delirium, but only a (small) proportion of these need treatment, for example for motor restlessness or anxiety. It is further of importance to judge and discuss (where possible with the patient and otherwise with his/her legal guardian) in a timely manner what possible protective measures need to be taken to avoid harm. A patient is generally at an increased risk of falling incidents and increased chance of damage to intravenous infusion lines and/or catheters and tubes etc. The medical and nursing care professionals need to be aware of the regulatory frameworks within which protective measures may be applied. For this purpose, institutions should have developed protocols that ensure alignment and outline task division, and include the evaluation of interventions performed.