Delirium and Acute Confusional States - Prevention, Treatment, and Prognosis - UpToDate

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Delirium e estados confusionais agudos: prevenção,

tratamento e prognóstico
Autor: Joseph Francis, Jr, MD, MPH
Editores de seção: Michael J Aminoff, MD, DSc, Kenneth E Schmader, MD
Editor Adjunto: Janet L Wilterdink, MD
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 um estado confusional agudo caracterizado por uma alteração da consciência

com capacidade reduzida de focalizar, sustentar ou desviar a atenção. Isso resulta em um
distúrbio cognitivo ou perceptivo que não é melhor explicado por uma demência
preexistente, estabelecida ou em evolução. O delirium se desenvolve em um curto período
de tempo (geralmente horas a dias) e tende a flutuar ao longo do dia. O delirium geralmente
é causado por uma condição médica, intoxicação por substância ou efeito colateral de
medicamento.
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".
O manejo do delirium é baseado principalmente em consenso de especialistas e estudos

observacionais, e apenas um pequeno número de ensaios clínicos controlados, que são
difíceis de realizar em pacientes com comprometimento cognitivo. A preponderância das
evidências é mais convincente para a prevenção primária do delirium usando abordagens
não farmacológicas e multicomponentes direcionadas amplamente a pacientes de alto risco
[ 1-3 ]. A prevenção e a terapia do delirium são baseadas nos seguintes princípios:
https://www.uptodate.com/contents/delirium-and-acute-confusional-states-prevention-treatment-and-prognosis/print?search=delirium e estados … 1/27

● Evitar fatores conhecidos por causar ou agravar o delirium, como vários

medicamentos, desidratação, imobilização, deficiência sensorial e interrupção do ciclo
sono-vigília
● Identificar e tratar a doença aguda subjacente
● Fornecer cuidados de suporte e restauradores para evitar mais declínio físico e

cognitivo
● Quando apropriado, controlar comportamentos perigosos e severamente

perturbadores usando agentes farmacológicos de baixa dose e ação curta para que as
três primeiras etapas possam ser realizadas
A prevenção, tratamento e prognóstico do delirium serão revistos aqui. A definição,

epidemiologia, patogênese, características clínicas e diagnóstico de delirium são discutidos
separadamente. (Consulte "Diagnóstico de delírio e estados confusionais" .)
PREVENÇÃO
Nenhuma intervenção ou grupo de intervenções previne de forma confiável o delirium; no

entanto, intervenções não farmacológicas multicomponentes que controlam muitos dos
fatores de risco modificáveis parecem reduzir a incidência de delirium [ 3,4 ].
Modificando os fatores de risco — Vários fatores foram identificados como causadores ou
contribuintes para o delirium em pacientes em risco.
Exemplos de intervenções destinadas a mitigar os fatores de risco para delirium incluem:
● Protocolos de orientação – O fornecimento de relógios, calendários, janelas com

vistas externas e reorientação verbal dos pacientes podem atenuar a confusão
resultante da desorientação em ambientes desconhecidos.
● Estimulação cognitiva – Pacientes com comprometimento cognitivo, em particular,

podem se beneficiar de atividades como visitas regulares de familiares e amigos. Ao
mesmo tempo, a superestimulação sensorial deve ser evitada, principalmente à noite.
● Facilitação do sono fisiológico – Procedimentos médicos e de enfermagem, incluindo

a administração de medicamentos, devem ser evitados durante as horas de sono,
quando possível. O ruído noturno deve ser reduzido. Um estudo randomizado
descobriu que o uso de tampões de ouvido à noite estava associado a uma menor
incidência de confusão em pacientes de unidade de terapia intensiva (UTI) [ 5 ].

● Mobilização precoce e uso minimizado de contenção física para pacientes com

mobilidade limitada – Um estudo em pacientes criticamente enfermos em ventilação
mecânica constatou que a instituição precoce de fisioterapia e terapia ocupacional,
juntamente com a consequente interrupção do uso de sedativos, estava associada a
um menor número de dias de internação com delírio [ 6 ].
● Aparelhos visuais e auditivos para pacientes com essas deficiências
● Evitar e/ou monitorar o uso de medicamentos problemáticos – Os medicamentos

são frequentemente implicados na precipitação do delirium, particularmente naqueles
que já estão em risco ( tabela 1 ).
Os benzodiazepínicos, em particular, são frequentemente implicados. Em uma revisão

sistemática, os autores concluíram que os benzodiazepínicos devem ser evitados em
pacientes de alto risco, enquanto se deve ter cautela na prescrição de opioides,
diidropiridinas e anti-histamínicos [ 7 ].
Em um grande estudo de controle randomizado por clusters baseado em casas de

repouso, a implementação de um sistema informatizado para identificar o uso de
medicamentos problemáticos e desencadear uma revisão de medicamentos foi
associada a uma menor incidência de delirium (HR = 0,42) [ 8 ].
● Evitar e tratar complicações médicas – Sabe-se que várias condições médicas

causam ou agravam o delirium; estes devem ser geridos agressivamente e evitados
sempre que possível.
Alguns estudos se concentraram especificamente na reposição precoce de volume para

pacientes com delirium. Enquanto um pequeno estudo falhou em mostrar um
benefício para o manejo da hidratação na incidência de delirium em um ambiente de
cuidados de longo prazo, o pequeno número de pacientes (98) e o curto período de
tempo de intervenção (quatro semanas) limitaram a capacidade deste estudo de
demonstrar eficácia [ 9 ].
Hipoxemia e infecções são outras complicações comuns em ambientes e pacientes de

alto risco. Estes podem contribuir para o delirium e devem ser monitorados ativamente
e tratados quando identificados. Um programa de intervenção administrado por uma
equipe de consultores geriátricos que enfatizou evitar complicações médicas alcançou
uma redução de um terço na incidência de delirium entre 126 pacientes idosos
submetidos à cirurgia de quadril [ 10 ].
● 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
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 ].
Estudos em pacientes submetidos à cirurgia sugerem que o tratamento preventivo da

dor pode reduzir a incidência de delirium. Em um estudo com 58 pacientes idosos, a
administração de cetamina (administrada em dose única durante a indução da
anestesia para cirurgia cardíaca) foi associada a uma menor taxa de delírio pós-
operatório (3 versus 31%) [ 12 ]. No entanto, fazer recomendações generalizadas de
tais estudos é difícil devido ao pequeno tamanho da amostra, uso inconsistente de
intervenções não farmacológicas e falta de informações sobre os resultados a longo
prazo [ 13 ]. A cetamina não parece ser mais útil na prevenção do delírio pós-
operatório, conforme discutido na seção seguinte.
Certas classes de opióides são provavelmente melhor evitadas em pacientes mais

velhos e outras propensas ao delírio. A meperidina , em particular, demonstrou em
vários estudos prospectivos aumentar o risco de delirium [ 14-16 ].
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' .)
O uso de protocolos de enfermagem para melhor gerenciar a dor demonstrou reduzir

a gravidade e a duração, mas não a incidência, do delirium [ 18 ].
Em um estudo, uma intervenção multicomponente usou protocolos padronizados para

rastrear e controlar seis fatores de risco para delirium em 852 pacientes hospitalizados com
70 anos ou mais: déficit cognitivo, privação de sono, imobilidade, deficiência visual,
deficiência auditiva e desidratação [ 19]. Intervenções como as listadas acima foram
direcionadas aos fatores de risco identificados. Esse programa resultou em uma redução
significativa no número de episódios de delirium em comparação com os cuidados habituais
(62 versus 90) e no número total de dias com delirium (105 versus 161); não houve efeito
sobre a gravidade do delirium ou a taxa de recorrência. Desde então, os pesquisadores
relataram que os hospitais comunitários foram capazes de implementar este programa com
sucesso quando houve comprometimento de recursos pela liderança do hospital e
adaptação adequada dos protocolos às necessidades locais [ 20 ]. Estudos randomizados
subsequentes confirmaram que tais intervenções multicomponentes podem reduzir a

incidência de delirium e/ou complicações relacionadas [ 3,21-23 ].
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:
● Os inibidores da colinesterase ( p . No entanto, os ensaios clínicos não demonstraram

redução na prevalência ou incidência de delirium, e os efeitos colaterais foram maiores
em pacientes que receberam esses medicamentos [ 29-33 ].
● Agentes antipsicóticos, administrados profilaticamente e em baixas doses, foram

estudados no ambiente pós-operatório e de cuidados intensivos e foram associados a
benefícios inconsistentes e, na melhor das hipóteses, modestos na incidência,
gravidade e duração do delirium [ 34-40 ]. Em um desses estudos, o tratamento foi
associado ao aumento da gravidade e maior duração do delirium [ 39 ]. Uma revisão
sistemática de 2013 e uma meta-análise de seis estudos concluíram que esse
tratamento reduziu a incidência de delirium, mas não a gravidade ou a duração; nem a
incidência de eventos adversos associados foi reduzida [ 37 ]. Nesta análise, os
antipsicóticos de segunda geração pareceram ser mais benéficos em comparação com
o haloperidol .
● A administração de dexmedetomidina foi estudada no tratamento e prevenção de

delirium no pós-operatório e em cuidados intensivos, com resultados mistos. Em um
estudo randomizado, a dexmedetomidina em baixa dose (0,1 mcg/kg por hora,
administrada nas primeiras 32 horas de pós-operatório) foi associada a uma menor
incidência de delirium pós-operatório (9 versus 23 por cento; OR 0,35, IC 95% 0,22-0,54)
. Alguns, mas não todos, os estudos encontraram resultados semelhantes [ 41-43 ]. Os
efeitos adversos da dexmedetomidina incluem bradicardia dose-dependente e
hipotensão [ 44-46 ].
● A gabapentina , em estudo piloto, reduziu a incidência de delírio pós-operatório, talvez

pela redução da dor e administração de opióides [ 47 ].
● A melatonina mostrou eficácia inconsistente na prevenção do delirium. Em dois

pequenos ensaios em pacientes idosos internados (67.145 pacientes) com doença
médica, os agonistas da melatonina, ramelteon e melatonina, pareciam estar
associados a uma menor incidência de delírio [ 48,49 ]. A administração pré-operatória
de melatonina foi encontrada para reduzir a incidência de delírio pós-operatório em
um estudo randomizado de 222 pacientes submetidos à cirurgia de quadril [ 50 ]. Por

outro lado, em um estudo maior em 452 pacientes com fratura aguda do quadril, não
houve benefício da administração de melatonina [ 51 ].
● Analgésicos para controlar a dor podem reduzir a incidência ou gravidade do delirium,

conforme discutido na seção acima. No entanto, eles não devem ser usados de forma
não seletiva. Embora o uso profilático de cetamina para prevenir a dor tenha sido
associado à redução da incidência de delirium pós-operatório, conforme discutido na
seção acima, um estudo randomizado incluindo um amplo grupo de pacientes
submetidos a uma variedade de cirurgias não encontrou diferença na incidência de
delirium entre os grupos de cetamina e placebo. 52 ]. Experiências negativas como
alucinações e pesadelos foram maiores em pacientes que receberam cetamina.
GESTÃO
Os princípios subjacentes à gestão do delirium estão resumidos no algoritmo (

algoritmo 1 ). O algoritmo inclui dois caminhos que são seguidos simultaneamente: um
para gerenciar o distúrbio de comportamento e outro para encontrar e tratar o distúrbio
médico subjacente. Uma advertência importante é que os sintomas do delirium podem ter
uma duração prolongada, estendendo-se por muitas semanas no período pós-agudo após a
correção das causas subjacentes e dos fatores de risco.
Tratamento de condições subjacentes — Praticamente qualquer condição médica pode

precipitar delirium em um paciente suscetível; múltiplas condições subjacentes são
frequentemente encontradas [ 53 ]. Quando a doença aguda subjacente responsável pelo
delirium é identificada, a terapia específica é direcionada para a condição médica. (Consulte
"Encefalopatia tóxico-metabólica aguda em adultos", seção sobre 'Etiologias específicas' .)
As condições observadas mais comumente em estudos prospectivos de delirium incluem:
● Metabolic encephalopathy – These include the following, which are discussed in detail
separately. (See "Acute toxic-metabolic encephalopathy in adults".)
• Fluid and electrolyte disturbances (dehydration, hyponatremia/hypernatremia,

hypo/hypercalcemia)
• Infections (sepsis, urinary tract, respiratory tract, skin and soft-tissue)
• Organ failure (uremia, liver failure, hypoxemia/hypercarbia)
• Hypoglycemia
● Drug toxicity – Drug toxicity causes or contributes to approximately 30 percent of all

cases of delirium ( table 1) [54]. Clinicians must be aware that delirium can occur
even with "therapeutic" levels of such agents as digoxin or lithium, particularly in at-risk
patients.
Certain acute drug-poisoning syndromes can be rapidly treated with the appropriate
antidote. (See "General approach to drug poisoning in adults".)
● Withdrawal from alcohol and sedatives – The treatment of alcohol withdrawal is

discussed separately. (See "Management of moderate and severe alcohol withdrawal
syndromes", section on 'Management'.)
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".)
Supportive medical care — The delirious patient is at risk for complications of immobility

and confusion, leading to a high prevalence of irreversible functional decline.
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.)
Nonetheless, an interdisciplinary approach to delirium should focus upon maintaining

adequate hydration and nutrition, enhancing mobility and range of motion, treating pain
and discomfort, preventing skin breakdown, ameliorating incontinence (seen in over half of
delirious patients), and minimizing the risk of aspiration pneumonitis.
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].

Managing agitation — Managing disruptive behavior, particularly agitation and combative

behavior, is a challenging aspect of delirium therapy. This hyperactive delirium is less
common in older patients and, when it occurs, alternates with periods of hypoactive
delirium, which may be less obvious to the clinical staff [62]. Periods of disruptive and
hyperactive behavior place the patient at risk for falls, wandering off, or inadvertently
removing intravenous lines and feeding tubes.
When delirium is manifest by agitation, symptom control is occasionally necessary to

prevent harm or to allow evaluation and treatment. While nonpharmacologic interventions
should be the mainstay of treatment, a cautious trial of psychotropic medication may be
warranted in these circumstances. Unfortunately, there are limited data to guide treatment
as the available studies have significant methodologic limitations [25,26]. It has also been
observed that use of psychotropic medication to manage delirium appears to correlate more
strongly with caregiver distress than with the actual severity of delirium symptoms [63].
Nonpharmacologic interventions — Mild confusion and agitation may respond to

interpersonal and environmental manipulations. The hospital environment, characterized by
high ambient noise, poor lighting, lack of windows, frequent room changes, and restraint
use, often contributes to worsening confusion. Special units that address these concerns
have improved the functional outcomes of hospitalization in such frail patients [64].
Frequent reassurance, touch, and verbal orientation can lessen disruptive behaviors; family
members or other familiar persons are preferred, but professional sitters can also be used
to effect. Delusions and hallucinations should be neither endorsed nor challenged. Other
specific interventions are discussed above. (See 'Modifying risk factors' 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. 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.
Antipsychotic medications — When indicated, antipsychotic agents are generally used to

treat severe agitation in the patient with delirium, because these symptoms are associated
with self-harm and effective alternatives are not available. No medication is currently
approved by the US Food and Drug Administration (FDA) for the management of delirium, so
the use of these agents for such an indication is off-label.
Based on limited evidence, we suggest low-dose haloperidol (0.5 to 1 mg) be used as

needed to control moderate to severe agitation or psychotic symptoms, up to a maximum
dose of 5 mg per day. Continuous or prophylactic dosing is not recommended. Higher doses
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 — Benzodiazepines have a limited role in the treatment of delirium; they

are primarily indicated in cases of sedative drug and alcohol withdrawal or when
antipsychotic drugs are contraindicated. Surveys of practicing clinicians suggest that
benzodiazepines are overprescribed for patients with delirium [79]. (See "Sedative-analgesic
medications in critically ill adults: Selection, initiation, maintenance, and withdrawal".)
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].
Cholinesterase inhibitors — Cholinesterase inhibitors do not have a role in the treatment

or symptom management of delirium.
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.)
Other sedative agents — Other sedative agents (eg, dexmedetomidine, propofol, as well

as benzodiazepines and antipsychotics) are often used in the critical care setting to manage
anxiety and pain, as well as delirium, and are believed at times to contribute to delirium as
well as to manage agitation. The selection and management of these agents are discussed
separately. (See "Sedative-analgesic medications in critically ill adults: Selection, initiation,
maintenance, and withdrawal" and "Sedative-analgesic medications in critically ill adults:
Properties, dose regimens, and adverse effects".)
https://www.uptodate.com/contents/delirium-and-acute-confusional-states-prevention-treatment-and-prognosis/print?search=delirium e estados… 10/27
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.
Hypoactive delirium — In general, symptomatic treatment is not used for hypoactive

delirium.
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].
Terminal delirium — Delirium is common in palliative care settings and causes significant

distress to family members [91]. Underlying causes are often multifactorial, but up to 50
percent of episodes are reversible, particularly when the underlying cause is either
dehydration or medication related [92,93].
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'.)

Ethical considerations — The treatment of patients with delirium is complicated by the

critical nature of their illness and their impaired capacity to make decisions. The doctrine of
"implied consent" allows the emergency treatment of patients with delirium in order to
stabilize a life-threatening process [100]. However, it is important to document the
assessment of cognitive abilities and decision-making capacity. Current practice leaves
considerable room for improvement. As an example, in a prospective study of 173 medical
and surgical procedures performed in patients with delirium at a university hospital,
investigators found no documented assessments of competency or decision-making
capacity, with cognitive assessments documented in only 4 percent of cases [101]. No
informed consent was documented in 19 percent of procedures, and surrogates were used
in only 20 percent.
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].
Mortality — Mortality associated with delirium is high. A report of pooled results from

several studies estimated the one- and six-month mortality to be 14 and 22 percent,
respectively, approximately twice that of patients without delirium [111]. These findings
were likely due in part to the presence of concomitant dementia and severe physical illness
(eg, sepsis). However, prospective observational studies that adjusted for dementia and
other potential confounding factors still found that delirium was an independent marker for
mortality at 6 or 12 months after hospitalization [103,112-115].
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].
Persistent cognitive dysfunction — Signs of delirium may persist for 12 months or longer,

particularly in those with underlying dementia [118].
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].
SOCIETY GUIDELINE LINKS
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".)
INFORMATION FOR PATIENTS
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
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.)
● Basics topic (see "Patient education: Delirium (confusion) (The Basics)")
● Beyond the Basics topic (see "Patient education: Delirium (Beyond the Basics)")
SUMMARY AND RECOMMENDATIONS
Delirium is an acute confusional state characterized by an alteration of consciousness with

reduced ability to focus, sustain, or shift attention.
● 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.)
● Prophylactic medications (cholinesterase inhibitors, ketamine, antipsychotic agents)

have not been conclusively demonstrated to prevent delirium. (See 'Prevention' above.)
● Thiamine supplementation should be considered in all patients with delirium. (See

'Treatment of underlying conditions' 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.)
● A cautious trial of psychotropic medication should be reserved for as-needed treatment

of severe agitation or psychosis with the potential for harm. In this setting, we suggest

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.)
• Haloperidol is associated with a low frequency of sedation and hypotension.
• Haloperidol should be avoided in patients with underlying parkinsonism, for whom

atypical antipsychotics (eg, quetiapine) are preferred.
• Short-term use of antipsychotic agents is advised.
• 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.
● Benzodiazepines should be avoided in patients with or at risk for delirium, except in

cases of sedative drug and alcohol withdrawal or when antipsychotic medications are
contraindicated. (See 'Benzodiazepines' above.)
● Cholinesterase inhibitors are not effective in preventing or treating the symptoms of

delirium, and often create undesirable side effects. (See 'Cholinesterase inhibitors'
above.)
● 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.)
Use of UpToDate is subject to the Terms of Use.
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109. Fong TG, Jones RN, Marcantonio ER, et al. Adverse outcomes after hospitalization and
delirium in persons with Alzheimer disease. Ann Intern Med 2012; 156:848.
110. Steinmetz J, Siersma V, Kessing LV, et al. Is postoperative cognitive dysfunction a risk
factor for dementia? A cohort follow-up study. Br J Anaesth 2013; 110 Suppl 1:i92.
111. Cole MG, Primeau FJ. Prognosis of delirium in elderly hospital patients. CMAJ 1993;
149:41.
112. Ely EW, Shintani A, Truman B, et al. Delirium as a predictor of mortality in mechanically
ventilated patients in the intensive care unit. JAMA 2004; 291:1753.
113. McCusker J, Cole M, Abrahamowicz M, et al. Delirium predicts 12-month mortality. Arch
Intern Med 2002; 162:457.
114. Leslie DL, Zhang Y, Holford TR, et al. Premature death associated with delirium at 1-year
follow-up. Arch Intern Med 2005; 165:1657.
115. Kiely DK, Marcantonio ER, Inouye SK, et al. Persistent delirium predicts greater
mortality. J Am Geriatr Soc 2009; 57:55.
116. Pisani MA, Kong SY, Kasl SV, et al. Days of delirium are associated with 1-year mortality
in an older intensive care unit population. Am J Respir Crit Care Med 2009; 180:1092.
117. Shehabi Y, Riker RR, Bokesch PM, et al. Delirium duration and mortality in lightly
sedated, mechanically ventilated intensive care patients. Crit Care Med 2010; 38:2311.
118. McCusker J, Cole M, Dendukuri N, et al. The course of delirium in older medical
inpatients: a prospective study. J Gen Intern Med 2003; 18:696.
119. Francis J, Kapoor WN. Prognosis after hospital discharge of older medical patients with
delirium. J Am Geriatr Soc 1992; 40:601.
120. Saczynski JS, Marcantonio ER, Quach L, et al. Cognitive trajectories after postoperative
delirium. N Engl J Med 2012; 367:30.
121. Pandharipande PP, Girard TD, Jackson JC, et al. Long-term cognitive impairment after
critical illness. N Engl J Med 2013; 369:1306.
122. van den Boogaard M, Schoonhoven L, Evers AW, et al. Delirium in critically ill patients:
impact on long-term health-related quality of life and cognitive functioning. Crit Care
Med 2012; 40:112.
123. Fong TG, Jones RN, Shi P, et al. Delirium accelerates cognitive decline in Alzheimer
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124. Gross AL, Jones RN, Habtemariam DA, et al. Delirium and Long-term Cognitive
Trajectory Among Persons With Dementia. Arch Intern Med 2012; 172:1324.
Topic 4823 Version 16.0

GRAPHICS
Drogas que se acredita causar ou prolongar delirium ou estados

confusionais*
Analgésicos Corticosteroids
AINEs Dopamine agonists
Opióides (especialmente meperidina) Amantadine
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
Anticolinérgicos Hypnotics and sedatives
Atropina Barbiturates
Benztropina Benzodiazepines
Difenidramina Muscle relaxants
Escopolamina Baclofen
Trihexyphenidyl Cyclobenzaprine
Antiseizure medications Other CNS-active agents
Carbamazepine Disulfiram

Levetiracetam Cholinesterase inhibitors (eg, donepezil)
Phenytoin Interleukin 2
Valproate Lithium
Vigabatrin Phenothiazines
Antidepressants
Mirtazapine
Selective serotonin reuptake inhibitors
Tricyclic antidepressants
Cardiovascular and hypertension

drugs
Antiarrhythmics
Beta blockers
Clonidine
Digoxin
Diuretics
Methyldopa
AINEs: antiinflamatórios não esteroidais; SNC: sistema nervoso central.
* Não exaustivo, todos os medicamentos devem ser considerados.
Gráfico 70449 Versão 9.0

Avaliação e manejo do paciente com delirium
hemograma completo: hemograma completo; BUN: nitrogênio ureico no sangue; ECG:

eletrocardiograma; TC: tomografia computadorizada; EEG: eletroencefalograma; RM:
ressonância magnética.
Gráfico 59337 Versão 3.0

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.
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21/09/2022 12:02 Delirium and acute confusional states: Prevention, treatment, and prognosis - UpToDate

Reimpressão oficial do UpToDate ®

Delirium e estados confusionais agudos: prevenção,

Delirium é um estado confusional agudo caracterizado por uma alteração da consciência

O manejo do delirium é baseado principalmente em consenso de especialistas e estudos

https://www.uptodate.com/contents/delirium-and-acute-confusional-states-prevention-treatment-and-prognosis/print?search=delirium e estados … 1/27

● Evitar fatores conhecidos por causar ou agravar o delirium, como vários

● Identificar e tratar a doença aguda subjacente

● Fornecer cuidados de suporte e restauradores para evitar mais declínio físico e

● Quando apropriado, controlar comportamentos perigosos e severamente

A prevenção, tratamento e prognóstico do delirium serão revistos aqui. A definição,

Nenhuma intervenção ou grupo de intervenções previne de forma confiável o delirium; no

Exemplos de intervenções destinadas a mitigar os fatores de risco para delirium incluem:

● Protocolos de orientação – O fornecimento de relógios, calendários, janelas com

● Estimulação cognitiva – Pacientes com comprometimento cognitivo, em particular,

● Facilitação do sono fisiológico – Procedimentos médicos e de enfermagem, incluindo

https://www.uptodate.com/contents/delirium-and-acute-confusional-states-prevention-treatment-and-prognosis/print?search=delirium e estados … 2/27

● Mobilização precoce e uso minimizado de contenção física para pacientes com

● Aparelhos visuais e auditivos para pacientes com essas deficiências

● Evitar e/ou monitorar o uso de medicamentos problemáticos – Os medicamentos

Os benzodiazepínicos, em particular, são frequentemente implicados. Em uma revisão

Em um grande estudo de controle randomizado por clusters baseado em casas de

● Evitar e tratar complicações médicas – Sabe-se que várias condições médicas

Alguns estudos se concentraram especificamente na reposição precoce de volume para

Hipoxemia e infecções são outras complicações comuns em ambientes e pacientes de

Estudos em pacientes submetidos à cirurgia sugerem que o tratamento preventivo da

Certas classes de opióides são provavelmente melhor evitadas em pacientes mais

O uso de protocolos de enfermagem para melhor gerenciar a dor demonstrou reduzir

Em um estudo, uma intervenção multicomponente usou protocolos padronizados para

subsequentes confirmaram que tais intervenções multicomponentes podem reduzir a

● Os inibidores da colinesterase ( p . No entanto, os ensaios clínicos não demonstraram

● Agentes antipsicóticos, administrados profilaticamente e em baixas doses, foram

● A administração de dexmedetomidina foi estudada no tratamento e prevenção de

● A gabapentina , em estudo piloto, reduziu a incidência de delírio pós-operatório, talvez

● A melatonina mostrou eficácia inconsistente na prevenção do delirium. Em dois

https://www.uptodate.com/contents/delirium-and-acute-confusional-states-prevention-treatment-and-prognosis/print?search=delirium e estados … 5/27

● Analgésicos para controlar a dor podem reduzir a incidência ou gravidade do delirium,

Os princípios subjacentes à gestão do delirium estão resumidos no algoritmo (

Tratamento de condições subjacentes — Praticamente qualquer condição médica pode

As condições observadas mais comumente em estudos prospectivos de delirium incluem:

• Fluid and electrolyte disturbances (dehydration, hyponatremia/hypernatremia,

● Drug toxicity – Drug toxicity causes or contributes to approximately 30 percent of all

● Withdrawal from alcohol and sedatives – The treatment of alcohol withdrawal is

Supportive medical care — The delirious patient is at risk for complications of immobility

Nonetheless, an interdisciplinary approach to delirium should focus upon maintaining

https://www.uptodate.com/contents/delirium-and-acute-confusional-states-prevention-treatment-and-prognosis/print?search=delirium e estados … 7/27

Managing agitation — Managing disruptive behavior, particularly agitation and combative

When delirium is manifest by agitation, symptom control is occasionally necessary to

Nonpharmacologic interventions — Mild confusion and agitation may respond to

Antipsychotic medications — When indicated, antipsychotic agents are generally used to

Based on limited evidence, we suggest low-dose haloperidol (0.5 to 1 mg) be used as

https://www.uptodate.com/contents/delirium-and-acute-confusional-states-prevention-treatment-and-prognosis/print?search=delirium e estados … 9/27

Benzodiazepines — Benzodiazepines have a limited role in the treatment of delirium; they

Cholinesterase inhibitors — Cholinesterase inhibitors do not have a role in the treatment

Other sedative agents — Other sedative agents (eg, dexmedetomidine, propofol, as well

Hypoactive delirium — In general, symptomatic treatment is not used for hypoactive

Terminal delirium — Delirium is common in palliative care settings and causes significant

https://www.uptodate.com/contents/delirium-and-acute-confusional-states-prevention-treatment-and-prognosis/print?search=delirium e estados… 11/27

Ethical considerations — The treatment of patients with delirium is complicated by the

Mortality — Mortality associated with delirium is high. A report of pooled results from

Persistent cognitive dysfunction — Signs of delirium may persist for 12 months or longer,

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