Delirium and Acute Confusional States - Prevention, Treatment, and Prognosis - UpToDate
Delirium and Acute Confusional States - Prevention, Treatment, and Prognosis - UpToDate
Delirium and Acute Confusional States - Prevention, Treatment, and Prognosis - UpToDate
Todos os tópicos são atualizados à medida que novas evidências se tornam disponíveis e nosso processo de
revisão por pares é concluído.
Revisão da literatura atual até: agosto de 2022. | Este tópico foi atualizado pela última vez: 22 de maio de
2019.
INTRODUÇÃO
Delirium é considerado por alguns como um tipo específico de estado confusional que se
caracteriza por aumento da vigilância junto com hiperatividade psicomotora e autonômica e
se manifesta como agitação, tremores e alucinações. Nesta discussão, no entanto, o termo
"delírio" será usado como sinônimo de "estado confusional agudo" e incluirá estados
caracterizados por sonolência e diminuição da excitação, o chamado "delírio hipoativo".
PREVENÇÃO
Modificando os fatores de risco — Vários fatores foram identificados como causadores ou
contribuintes para o delirium em pacientes em risco.
● Gerenciando a dor – A dor pode ser um fator de risco significativo para o delirium. O
uso de medicamentos não opióides deve ser usado sempre que possível, pois estes são
menos propensos a agravar o delirium. Os médicos devem equilibrar os benefícios do
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uso de opioides para tratar a dor significativa com o potencial de delirium relacionado
aos opioides. Intervenções não farmacológicas são atraentes nesse cenário. Em um
estudo, o bloqueio do compartimento da fáscia ilíaca após a cirurgia do quadril foi
associado a uma incidência reduzida de delirium pós-operatório em pacientes de risco
intermediário, mas não em pacientes de alto risco [ 11 ].
Pacientes com câncer com delirium terminal e dor podem se beneficiar da troca de
opioides de ação mais curta por agentes de ação prolongada, como a metadona [ 17 ].
Os médicos também devem considerar a possibilidade de que a hiperalgesia induzida
por opioides possa causar dor irruptiva e devem considerar o uso de analgesia não
opioide para controle da dor. (Consulte "Prevenção e gerenciamento de efeitos
colaterais em pacientes que recebem opióides para dor crônica", seção sobre
'hiperalgesia induzida por opióides' .)
Medicamentos para prevenir o delirium — As evidências disponíveis não suportam o uso
de medicamentos para prevenir o delirium em ambientes de alto risco, como cuidados
agudos, terapia intensiva, cirurgia cardíaca ou outros cuidados pós-operatórios [ 24-27 ]. Os
investigadores continuam a estudar o potencial benefício dos inibidores da colinesterase,
agentes antipsicóticos e outros:
outro lado, em um estudo maior em 452 pacientes com fratura aguda do quadril, não
houve benefício da administração de melatonina [ 51 ].
GESTÃO
● Metabolic encephalopathy – These include the following, which are discussed in detail
separately. (See "Acute toxic-metabolic encephalopathy in adults".)
Certain acute drug-poisoning syndromes can be rapidly treated with the appropriate
antidote. (See "General approach to drug poisoning in adults".)
While Wernicke encephalopathy is not common, many older hospitalized patients have
biochemical evidence of thiamine deficiency [55]. In addition, chronic alcoholism is often
difficult to detect in this population, and symptoms of persistent alcoholic delirium may be
difficult to distinguish from those of Wernicke encephalopathy [56]. Thiamine
supplementation is inexpensive and virtually risk free; it should be provided to all
hospitalized patients with evidence of nutritional deficiency. (See "Wernicke
encephalopathy".)
It has long been assumed that the outcome of delirium could be improved by earlier
identification of the disorder and comprehensive intervention to treat underlying causes and
prevent subsequent complications such as immobility, aspiration, and skin breakdown.
Unfortunately, there are few controlled studies. One study found that early identification and
comprehensive geriatric consultation for patients with established delirium had little impact
on length of stay, functional outcome, or survival [57]; another found that multicomponent
interventions shortened the duration of delirium but had no impact on mortality or nursing
home use [58]. Stronger evidence supports the use of these interdisciplinary efforts for
prevention of delirium. (See 'Modifying risk factors' above.)
This team approach should also include family or other caregivers who may feel frightened
or exhausted; delirium can be the "last straw" for those who have been caring for the
demented. Caregiver resources must be realistically assessed.
Because delirium may require weeks or months to fully resolve, management often extends
into subacute settings [59,60]. Transfers of care to new settings are periods of particular
vulnerability for older patients, and it is important to effectively communicate information
about mental status to the accepting treatment team [61].
Physical restraints should be used only as a last resort, if at all, as they frequently increase
agitation and create additional problems, such as loss of mobility, pressure ulcers,
aspiration, and prolonged delirium. In one study, restraint use among patients in a medical
inpatient unit was associated with a threefold increased odds of persistent delirium at time
of hospital discharge [65]. Alternatives to restraint use, such as constant observation
(preferably by someone familiar to the patient such as a family member), may be more
effective.
may be used in closely monitored settings (intensive care unit [ICU]) where the goals and
sedation needs are different (see "Sedative-analgesic medications in critically ill adults:
Properties, dose regimens, and adverse effects", section on 'Antipsychotics'). Haloperidol can
be administered orally, intramuscularly (IM), or intravenously. The onset of action may be as
soon as 5 to 20 minutes after intravenous administration or longer with the IM or oral route.
An immediate response is not expected. Intravenous haloperidol has been associated with
clinically significant QT prolongation requiring additional precautions with its use. (See
"Acquired long QT syndrome: Definitions, pathophysiology, and causes".)
We recommend only short-term use of antipsychotic agents, as these agents have been
associated with a higher risk of mortality and possibly stroke when used in patients with
dementia [66]. (See "Management of neuropsychiatric symptoms of dementia".)
Data supporting the use of antipsychotic agents for managing delirium are limited
[25,67,68]. In one of the largest randomized trials, 1183 patients with delirium in the
intensive care unit were treated with twice-daily haloperidol, ziprasidone, or placebo; doses
were adjusted based on resolution of symptoms or the development of side effects [69].
Outcomes (median days alive without delirium or coma) were similar between patient
groups. Limitations of this study include that both hypoactive and hyperactive delirium was
included, and that the primary endpoint was duration of delirium rather than control of
agitation, which is the usual indication for these agents. In addition, all patients were treated
with a multicomponent nonpharmacologic intervention, which may have contributed to the
overall lower rate of delirium and the ability to detect differences related to medical
treatment. Other smaller trials have suggested that these agents may reduce the severity of
delirium episodes [34,70,71], but overall, the evidence supporting the use of pharmacologic
agents is inconclusive [27].
Because of the longer clinical experience with haloperidol, it remains the standard therapy in
this setting [72]. The newer atypical antipsychotic agents, quetiapine, risperidone,
ziprasidone, and olanzapine, have fewer side effects in other clinical settings, and in small
studies they appear to have similar efficacy to haloperidol [73-75]. A meta-analysis of three
small studies that compared haloperidol with risperidone and olanzapine found that the
three agents were similarly effective in treating delirium [76]. A small clinical trial compared
escalating doses of quetiapine with placebo as add-on treatment to as-needed haloperidol in
36 patients in the ICU with delirium [77]. Quetiapine was associated with a shorter duration
of delirium, reduced agitation, and higher rates of discharge to home after hospitalization.
By contrast, a randomized trial comparing haloperidol, ziprasidone, and placebo in ICU
patients found that active treatment did not improve outcomes when measured by number
of days alive without altered mental status or the incidence of adverse events [68].
Extrapyramidal side effects are higher in patients treated with high-dose haloperidol (>4.5
mg per day), but were similar among patients treated with low-dose haloperidol, olanzapine,
and risperidone in one study [76,78]; in general, haloperidol should be avoided in favor of
atypical antipsychotics in patients with parkinsonism. Sedation and hypotension can also
occur as a side effect of these medications [77]. (See "Prognosis and treatment of dementia
with Lewy bodies" and "Management of nonmotor symptoms in Parkinson disease".)
Benzodiazepines (eg, lorazepam 0.5 to 1 mg) have a more rapid onset of action (five minutes
after parenteral administration) than the antipsychotics, but they can worsen confusion and
sedation [70]. In a prospective study of ICU patients, lorazepam was an independent risk
factor for incident delirium, increasing the risk by approximately 20 percent [80]. A
systematic review of benzodiazepine use in delirium found two studies comparing
benzodiazepine versus antipsychotic agents; one study found no advantage, the other found
decreased effectiveness of benzodiazepines compared with antipsychotics [81]. In two
randomized trials of sedative treatment in mechanically ventilated ICU patients, the
benzodiazepine midazolam was associated with significantly more delirium compared with
dexmedetomidine treatment (77 versus 54 percent) [82], while similar outcomes were
observed with lorazepam and dexmedetomidine [83].
A randomized clinical trial compared rivastigmine with placebo in 104 hospitalized intensive
care patients with delirium who were also prescribed haloperidol. The trial was stopped
early because of higher mortality in the rivastigmine group (22 versus 8 percent) [84].
Median duration of delirium was also longer in the rivastigmine group (5 versus 3 days, p =
0.06). Cholinesterase inhibitors are also not helpful in the prevention of delirium. (See
'Prevention' above.)
Managing pain — In the appropriate setting (postoperative, post-trauma), the role of pain
as a contributor to delirium and agitation should be considered, and analgesia provided. As
discussed above, therapies to reduce pain should be administered with some caution as they
also have the potential to contribute to delirium. (See 'Modifying risk factors' above.)
In one randomized study of 53 patients after cardiac surgery, those who received morphine
(5 mg IM) had more rapid improvement of agitation and were less likely to require additional
sedatives than those who were administered haloperidol (5 mg IM) [85]. Other outcomes
were not assessed.
One study suggested that patients with hypoactive delirium have a similar response to
treatment with haloperidol as those who were agitated [86]. Other case reports and one
uncontrolled case series have suggested that treatment with the stimulant drug
methylphenidate may be associated with improved alertness and cognition [87-89].
However, in the absence of stronger evidence, psychostimulants such methylphenidate or
modafinil cannot be recommended for treating hypoactive delirium because of the potential
risk of precipitating agitation or worsening psychotic symptoms [90].
Hyperactive as well as hypoactive presentations of terminal delirium are both common; the
former may require management with antipsychotic medication, usually haloperidol, as
described above [94,95]. In the setting of severe preterminal patient distress, palliative
sedation using short-acting, titratable benzodiazepines such as midazolam has been
suggested as a potential alternative [96]. However, routine use of such agents in end-of-life
delirium is not warranted. A multicenter, double-blind, randomized trial of risperidone,
haloperidol, and placebo among patients receiving palliative care in hospice or hospital
settings found patients in the placebo arm had fewer distressing delirium symptoms and
better overall survival [97]. (See 'Antipsychotic medications' above.)
In one small case series, methadone appeared to be effective in the treatment of both
refractory pain and terminal delirium when antipsychotic medication was not [17].
Midazolam sedation has also been described as a therapeutic option in this setting [98,99].
(See "Overview of managing common non-pain symptoms in palliative care", section on
'Palliative sedation'.)
Relying upon implied consent or substituted judgment in cases of delirium introduces other
difficulties since clinicians and proxies do not always make the same decisions as patients.
Every effort should be made to determine what the patient's own treatment preferences are,
and to not assume that decision-making capacity is "all or none." In some cases, for
example, psychopharmacologic treatment of delirium may restore sufficient mental capacity
to allow a discussion of treatment preferences [102]. In addition, since delirium typically
fluctuates in severity, there may also be periods of lucidity in which a discussion of treatment
preferences may take place.
OUTCOMES
Delirium has an enormous impact upon the health of older persons. Patients with delirium
experience prolonged hospitalizations, functional and cognitive decline, higher mortality,
and higher risk for institutionalization, even after adjusting for baseline differences in age,
comorbid illness, or dementia [103-110].
Studies have also found a relationship between the duration of delirium and mortality
[116,117]. In one study, protracted delirium (ie, persistent symptoms of confusion at six
months) was associated with increased one-year mortality compared with those whose
symptoms had resolved more quickly, regardless of whether or not patients also had
underlying dementia [115].
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One long-term follow-up study found that after two years, only one-third of patients who
had experienced delirium still lived independently in the community [119]. Another
prospective study of 225 patients after heart surgery found that those who experienced
delirium were more likely to have a persistent drop in Mini-Mental State Examination (MMSE)
scores over baseline at six months compared with those who did not suffer delirium (40
versus 24 percent); at 12 months the differences were not quite statistically significant (31
versus 20 percent, p = 0.055) [120]. In a study of 821 patients admitted to medical or surgical
intensive care, the duration of delirium was associated with worse cognitive function at 3
and 12 months. While only 6 percent had cognitive impairment at baseline, at 12 months, 34
percent had deficits that were similar to patients with moderate traumatic brain injury [121].
Other studies have found that patients with delirium are more likely to have long-term
cognitive problems than hospitalized patients who did not suffer from delirium [122]. Thus,
although delirium is considered potentially reversible, impairments may be prolonged and
perhaps permanent, particularly in frail, older patients.
Episodes of delirium during hospitalization adversely affect the course of the disease in
patients with Alzheimer disease (AD). Of 263 participants in the Massachusetts Alzheimer's
Disease Research Center patient registry who experienced hospitalization, 56 percent
developed delirium during hospitalization. Although the AD patients with and without
delirium had similar rates of cognitive decline prior to hospitalization, after hospitalization,
deterioration proceeded at twice the rate in the year after hospitalization compared with
patients who did not develop delirium. The higher rate of cognitive decline was evident for
up to five years after the hospital stay [123,124]. Patients with AD who experienced delirium
also had an increased risk of death and institutionalization [109].
Links to society and government-sponsored guidelines from selected countries and regions
around the world are provided separately. (See "Society guideline links: Delirium and
confusional states in older adults".)
UpToDate offers two types of patient education materials, "The Basics" and "Beyond the
Basics." The Basics patient education pieces are written in plain language, at the 5th to 6th
grade reading level, and they answer the four or five key questions a patient might have
about a given condition. These articles are best for patients who want a general overview
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and who prefer short, easy-to-read materials. Beyond the Basics patient education pieces are
longer, more sophisticated, and more detailed. These articles are written at the 10th to 12th
grade reading level and are best for patients who want in-depth information and are
comfortable with some medical jargon.
Here are the patient education articles that are relevant to this topic. We encourage you to
print or e-mail these topics to your patients. (You can also locate patient education articles
on a variety of subjects by searching on "patient info" and the keyword(s) of interest.)
● Beyond the Basics topic (see "Patient education: Delirium (Beyond the Basics)")
● Effective measures to prevent delirium include avoiding, where possible, those factors
known to cause or aggravate delirium; orientation protocols; environmental
modification and nonpharmacologic sleep aids; early mobilization and minimizing use
of physical restraints; and visual and hearing aids. (See 'Prevention' above.)
● When the underlying acute illness responsible for delirium is identified, specific therapy
is directed toward that condition as the most effective means of reversing the delirium.
(See 'Treatment of underlying conditions' above.)
● Physical restraints should be used only as a last resort, if at all, as they frequently
increase agitation and create additional problems, such as loss of mobility, pressure
ulcers, aspiration, and prolonged delirium. (See 'Nonpharmacologic interventions'
above.)
● Frequent reassurance, touch, and verbal orientation from familiar persons can lessen
disruptive behaviors. (See 'Nonpharmacologic interventions' above.)
using low-dose haloperidol (0.5 to 1 mg orally [PO] or intramuscularly [IM]) (Grade 2C).
Other antipsychotic agents (quetiapine, risperidone, ziprasidone, olanzapine) are
reasonable alternatives. (See 'Antipsychotic medications' above.)
• Clinicians should recognize when the caregiver's distress, rather than reduction of
the severity or duration of delirium, is often a motivating factor in the decision to
prescribe psychotropic medication.
● Delirium may require weeks or months to fully resolve. Episodes of delirium may
adversely affect the course of the disease in patients with Alzheimer disease (AD).
Delirium appears to be associated with increased short- and long-term mortality. (See
'Outcomes' above.)
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Topic 4823 Version 16.0
GRAPHICS
Analgésicos Corticosteroids
Bromocriptine
Antibióticos e antivirais
Levodopa
Aciclovir
Pergolide
Aminoglicosídeos
Pramipexole
Anfotericina B
Ropinirole
Antimaláricos
Gastrointestinal agents
Cefalosporinas
Antiemetics
Cicloserina
Antispasmodics
Fluoroquinolonas
Histamine 2 receptor blockers
Isoniazida
Loperamide
Interferon
Herbal preparations
Linezolida
Atropa belladonna extract
Macrolídeos
Henbane
Metronidazol Mandrake
Ácido nalidíxico Jimson weed
Penicilinas St. John's wort
Rifampina Valerian
Sulfonamidas Hypoglycemics
Atropina Barbiturates
Benztropina Benzodiazepines
Escopolamina Baclofen
Trihexyphenidyl Cyclobenzaprine
Carbamazepine Disulfiram
Phenytoin Interleukin 2
Valproate Lithium
Vigabatrin Phenothiazines
Antidepressants
Mirtazapine
Tricyclic antidepressants
Beta blockers
Clonidine
Digoxin
Diuretics
Methyldopa
Contributor Disclosures
Joseph Francis, Jr, MD, MPH No relevant financial relationship(s) with ineligible companies to
disclose. Michael J Aminoff, MD, DSc Consultant/Advisory Boards: Brain Neurotherapy Bio [Parkinson
disease].
All of the relevant financial relationships listed have been mitigated. Kenneth E Schmader,
MD No relevant financial relationship(s) with ineligible companies to disclose. Janet L Wilterdink,
MD No relevant financial relationship(s) with ineligible companies to disclose.
As divulgações dos contribuidores são analisadas quanto a conflitos de interesse pelo grupo editorial.
Quando encontrados, eles são abordados por meio de um processo de revisão em vários níveis e por
meio de requisitos para referências a serem fornecidas para apoiar o conteúdo. O conteúdo
referenciado apropriadamente é exigido de todos os autores e deve estar em conformidade com os
padrões de evidência do UpToDate.