Lolita Grygalytė1, Agnė Timlerytė1, Raimundas Vaitkevičius2
1Lithuanian University of Health Sciences, Medical academy, Faculty of Medicine
2Department of Intensive Care, Lithuanian University of Health Sciences
Abstract
Delirium is an acute illness and is a frequent condition in the intensive care unit (ICU) setting. It is characterized by an altered state of consciousness, impaired perception, cognition and attention, alongside with the patients’ ability to receive, process, store and recall information. Hallucinations, circadian rhythm and emotional dysregulation might also be present. There are three subtypes of delirium – hyperactive, hypoactive and mixed. Elderly patients and those with many underlying diseases are most at risk for developing delirium. Persistent monitoring for ICU delirium should be performed as early detection and treatment could result in better outcome. Delirium is diagnosed clinically, using diagnostic tools such as Richmond Agitation Sedation Scale (RASS), Confusion Assessment Method (CAM)-ICU or Intensive Care Delirium Screening Checklist (ICDSC). The diagnostic criteria for delirium are described in the DSM-5 classification. While treating delirium, it is important to treat any predisposing conditions or diseases. Typical and atypical antipsychotics, although frequently used to treat this syndrome, are not proven to shorten the duration of delirium, mechanical ventilation or lower mortality rates. Dexmedetomidine is recommended for mechanically ventilated patients who cannot be extubated due to agitation.
Keywords: ICU delirium, delirium in the critically ill, delirium risk factors, delirium management, delirium prevention, CAM-ICU, critical care.
Journal of Medical Sciences. Jan 30, 2021 - Volume 9 | Issue 1. Electronic - ISSN: 2345-0592
16
Medical Sciences 2021 Vol. 9 (1), p. 16-22
Delirium in the critically ill: risk factors, diagnosis, management
and prevention
Lolita Grygalytė
1
, Agnė Timlerytė
1
, Raimundas Vaitkevičius
2
1
Lithuanian University of Health Sciences, Medical academy, Faculty of Medicine
2
Department of Intensive Care, Lithuanian University of Health Sciences
Abstract
Delirium is an acute illness and is a frequent condition in the intensive care unit (ICU) setting. It is characterized
by an altered state of consciousness, impaired perception, cognition and attention, alongside with the patients’
ability to receive, process, store and recall information. Hallucinations, circadian rhythm and emotional
dysregulation might also be present. There are three subtypes of delirium – hyperactive, hypoactive and mixed.
Elderly patients and those with many underlying diseases are most at risk for developing delirium. Persistent
monitoring for ICU delirium should be performed as early detection and treatment could result in better outcome.
Delirium is diagnosed clinically, using diagnostic tools such as Richmond Agitation Sedation Scale (RASS),
Confusion Assessment Method (CAM)-ICU or Intensive Care Delirium Screening Checklist (ICDSC). The
diagnostic criteria for delirium are described in the DSM-5 classification. While treating delirium, it is important
to treat any predisposing conditions or diseases. Typical and atypical antipsychotics, although frequently used to
treat this syndrome, are not proven to shorten the duration of delirium, mechanical ventilation or lower mortality
rates. Dexmedetomidine is recommended for mechanically ventilated patients who cannot be extubated due to
agitation.
Keywords: ICU delirium, delirium in the critically ill, delirium risk factors, delirium management, delirium
prevention, CAM-ICU, critical care.
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17
Introduction
Delirium is a quite common condition in the ICU.
American Psychiatric Association Diagnostic and
statistical manual of mental disorders, fifth edition,
defines delirium as an acute disturbance in attention
and awareness with changes in cognition and is not
explained by a pre-existing neurocognitive disorder
and caused by another medical condition [1].
Patients who have a high risk for developing
delirium in the ICU include elderly people and those
with a history of preexisting dementia, hypertension,
alcoholism and a higher APACHE II score [2,3].
ICU delirium could also be associated with long
term consequences such as cognitive impairment,
dementia [3,4]. It has also been linked to higher
mortality rates and longer duration of
hospitalization, resulting in higher health care costs
[5,6]. The identification, prevention and treatment of
delirium is crucial in the intensive care setting as it
can improve outcome, therefore a routine
assessment using a validated screening tool is
necessary [3].
The aim of this review was to evaluate the risk
factors, clinical presentation, diagnosis,
management, prevention and prognosis of delirium
in critically ill patients.
Methodology
Data search was conducted in electronic scientific
databases PubMed, ScienceDirect, UpToDate,
Wiley etc. using search words included: ICU
delirium, delirium in the critically ill, delirium risk
factors, delirium outcomes. We reviewed and
examined the most relevant sources on this topic.
Risk factors and pathogenesis
In order to improve our understanding of ICU
delirium, it is necessary to recognize the most
important risk factors. The knowledege of these risk
factors could also be of use to the development of
prevention strategies. 2018 Society of Critical Care
Medicine Pain, Agitation and Delirium guidelines
acknowledge a few risk factors that are significantly
associated with ICU delirium, including preexisting
dementia, history of hypertension, alcoholism and a
higher Acute Physiology and Chronic Health
Evaluation (APACHE) II score [3]. Strong evidence
suggests that age is a risk factor for ICU delirium
[2]. Other important risk factors include mechanical
ventilation, (poly)trauma, delirium previous day,
coma, use of physical restraints [2,7,8]. Some cases
indicate that the use of sedatives such as
benzodiazepines or propofol could be a risk factor
for delirium [7,9] though it is lacking evidence [2].
Environmental factors should also be considered, as
lack of daylight, ICU sound level and interruptions
could increase the risk of delirium [10].
The pathophysiology of delirium is a complex
process and is yet to be understood. There are
several hypotheses described, including a focus on
neuroinflammation, an aberrant stress response,
neurotransmitter imbalances and neuronal network
alterations [10]. The most common changes in
neurotransmitter systems inlcude deficiencies in
acetylcholine and/or melatonin availability, excess
in dopamine, norepinephrine and/or glutamate
release and variable alterations in serotonin,
histamine and/or gamma-amino butyric acid. With
aging the activity acetylcholine, melatonin,
serotonin, histamine and gamma-amino butyric acid
is likely to be decreased. Trauma, surgery and
medical illness are associated with acetylcholine,
melatonin deficiency, excess in dopamine,
norepinephrine and glutamate release. Alcohol,
sleep deprivation and infection can also affect these
neurotransmitters [4]. The treatment and prevention
of delirium is based on targeting these systems.
Oxidative stress and a disturbance of circadian
integrity may also contribute to the pathogenesis of
delirium. It is thought that delirium could not be
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explained based solely on one hypothesis and they
complement each other [10].
Clinical presentation
Delirium is described as a complex neurocognitive
syndrome caused by an organic global brain
dysfunction. The prevalence of this syndrome is
reported to be up to 50% out of all patients in the
ICU [11]. Delirium is a state of disturbed
consciousness and has the onset of hours or days.
The patients‘ perception, cognition and attention are
impaired, alongside with their ability to receive,
process, store and recall information. It is important
to highlight that these symptoms cannot be
attributed to coexisting conditions like dementia,
sedation or coma [12]. The severity of delirium is
fluctuating and disturbances like disorientation,
memory deficit, changes in language or visuospatial
ability may appear over time. Other features that
may be a part of this syndrome are delusions,
dysarthria, dysgraphia, emotional disturbancies
(fear, anxiety, anger, apathy, depression, euphoria),
abnormal psychomotor activity and sleep-wake
cycle disturbancies. The prodromal period is
characterized by frequent awakening or difficulty
falling asleep, irritability, anxiety and restlessness
[11,13]. There are three subtypes of delirium:
hyperactive, hypoactive and mixed. A patient with
hyperactive delirium will suffer from agitation,
anxiety and will make attempts to remove all
external devices (drains, catheters, face masks,
intravenous lines) [12]. This subtype is also
associated with hallucinations and delusions [13].
Hypoactive delirium is diagnosed when a patient is
withdrawn, somnolent and has a reduced
responsiveness to stimuli. This subtype is often
confused with depression or fatigue, however,
patients may also experience hallucinations or
delusions. The mixed subtype is characterized by
fluctuations between hyperactive and hypoactive
states [11,12].
Diagnostic criteria and assessment
As there are no laboratory or radiological tests
available for the diagnosis of delirium, this
syndrome is diagnosed clinically [14]. Ideally,
making the diagnosis consists of a clinical interview,
collateral history and evaluating the patient’s
cognition, which allows to operationalize the DSM-
5 diagnostic criteria [11]. The criteria include: a
disturbance in attention and awareness, a quick
onset and a fluctuating course of illness, an
additional disturbance in cognition. The
disturbances are not better explained by another pre-
existing, established, or evolving neurocognitive
disorder and do not occur in the context of a severely
reduced level of arousal, such as coma. There is
evidence from the history, physical examination, or
laboratory findings that the disturbance is a direct
physiological consequence of another medical
condition, a substance, a toxin, or is due to multiple
etiologies [1]. However, the majority of clinicians
find the DSM-5 classification complicated and time-
consuming. Therefore, several diagnostic tools are
being used in order to allow physicians to diagnose
delirium effectively [14].
The first step in diagnosing delirium is assessing the
level of consciousness. This can be done using the
Richmond Agitation-Sedation Scale (RASS). The
score of this scale ranges from -5 (unarousable, has
no response to voice or physical stimulation, reacts
only to touch) to +4 (aggressive, fights and
endangers the staff). If the level of consciousness is
deeply altered – RASS score being -5 or -4 – it is
recommended to stop monitoring and reassess the
score later. When higher levels of consciousness are
maintained, the second step of diagnostics can be
taken. In this step, the content of consciousness is
evaluated using the Confusion Assessment Method
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(CAM)-ICU scale, which consists of four features:
acute onset of mental status changes or fluctuating
course, inattention, altered level of consciousness
and disorganized thinking. When the first two
features are absent, it is unnecessary to examine the
rest [7]. Another monitoring tool for delirium is the
Intensive Care Delirium Screening Checklist
(ICDSC), which assesses altered level of
consciousness, inattention, disorientation,
psychosis, altered psychomotor activity,
inappropriate speech or mood, sleep disturbances
and symptom fluctuation. Both tools can be
effectively used by nursing staff, if appropriate
training has been provided [15]. Examination for
delirium should be conducted every 8-12 hours or
when the patients’ status changes [12].
Management
The cornerstone in managing delirium is correcting
any homeostasis-impairing diseases and medical
conditions that may be contributing to the
development of delirium. Data on effective
pharmacological treatment of delirium is limited as
there are no large randomised studies [12,15]. The
clinical approach usually consists of typical and
atypical antipsychotics, although the evidence of
their use is conflicting [15]. Haloperidol has been
considered to be the gold standard in treating
delirium and is still widely used by many clinicians.
However, there is no evidence that haloperidol
reduces the duration of delirium in the ICU [3,14].
In the recent years, atypical antipsychotics (such as
quetiapine, risperidone and olanzapine) have been
used for treating patients who are able to take oral
medication [14]. A study on the efficacy of
quetiapine has demonstrated a quicker treatment for
the first episode of delirium, although it had no
effect on the ICU stay and mortality [12]. As there
is evidence that suggests that the routine use of
haloperidol or atypical antipsychotics is not
associated with a shorter duration of delirium,
mechanical ventilation or lower mortality rates, it is
only recommended to administer these drugs to
patients who are experiencing significant anxiety,
hallucinations, delusions or agitation [3]. It is
important to note that the use of antipsychotics is not
recommended in patients who are at risk for
torsades de pointes [13].
Another drug used for treating delirium is a central
receptor alpha-2-adrenoreceptor agonist
dexmedetomidine [12]. This drug is recommended
for mechanically ventilated patients, when
extubation is precluded by agitation [3].
Administering dexmedetomidine is associated with
a shorter ICU stay, faster resolution of delirium
symptoms and fewer over-sedation episodes, the
most common side effect being bradycardia.
Although there is evidence that supports the use of
dexmedetomidine in the treatment of refractory
delirium, further trials are needed to examine its role
as a first line therapy [15]. However, if delirium is
caused by alcohol withdrawal or benzodiazepine
dependence, the usage of benzodiazepines is
recommended [12].
Since the diagnosis of delirium includes an altered
mental state, a patient is considered cured when
CAM-ICU stays negative for 24 hours. Therefore,
even if the result is negative during one shift,
monitoring the patient should be continued up to 24
hours and further pharmacological treatment must
be considered, although the dose might be reduced
[12].
Prevention
ICU delirium is associated with increased mortality,
prolonged hospitalisation and mechanical
ventilation, higher healthcare expenses, worse long-
term outcomes [10,12], therefore, prevention of this
disease is important and certain measures should be
taken. Prevention strategies involve both
nonpharmacologic and pharmacologic approaches.
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First of all, critically ill patients should be regularly
evaluated for delirium using a valid tool, for
example, the CAM-ICU scale as it is essential for a
prompt initiation of treatment and could therefore
result in better outcomes [3]. Secondly, risk factors
should be identified and modified, if possible. This
includes removing physical restraints at the earliest
possible moment, correcting any electrolyte
abnormalities, improving sleep hygiene [10]. Sleep
hygiene could be improved by minimizing sleep
disruptions, providing ear plugs to patients,
promoting normal circadian rhythms [15]. Patients
in the ICU should have access to natural daylight
and family visits [4]. Early mobilization of adult
ICU patients has been also demonstrated to reduce
ICU delirium [10,15].
Benzodiazepines are often linked to delirium in the
ICU, therefore minimizing the use of these agents
should be considered. Dexmedetomidine expresses
sedative and analgesic effects and could be an
acceptable alternative for benzodiazepines [10].
Pharmacologic prevention is often discussed in
literature but the data surrounding it is insufficient.
The use of antipsychotic agents for delirium
prevention is a target for many clinical trials and
some get positive results, one example is a study of
van den Boogaard et al., where it is suggested that
prophylaxis with low dose haloperidol in ICU
patients with a high risk for delirium could have
beneficial effects [16]. However, the overall data
supporting this statement is inadequate and the 2018
Society of Critical Care Medicine Pain, Agitation
and Delirium guidelines do not suggest using
haloperidol or any atypical antipsychotic agent for
delirium prevention [3]. Apart from antipsychotics,
many other agents are considered for delirium
prophylaxis, such as dexmedetomidine,
antiglutamatergic and calcium channel blocking
agents (e.g. gabapentin, carbamazepine), ketamine,
melatonin, statins, acetylcholinesterase inhibitors
[4] but the 2018 Society of Critical Care Medicine
Pain, Agitation and Delirium guidelines established
that the evidence is insufficient and do not
recommend using either of these agents to prevent
delirium in all critically ill adults [3]. More detailed
and extensive clinical trials must be performed in
order to establish the validity of pharmacologic
prevention.
Outcomes
ICU delirium is often associated with higher
mortality rates as well as an increased length of ICU
and hospital stay, longer duration of mechanical
ventilation [5,6]. Intubated patients that developed
delirium also have a reduced chance of successful
extubation and are more likely to develop
respiratory and neurologic complications [4,6,8].
Some studies have found that the severity of ICU
delirium is positively associated with cognitive
impairment at the time of hospital discharge and in
most cases the cognitive function is regained by the
sixth month after discharge but there are cases that
report poor long-term cognitive functioning.
Patients who had developed delirium in the ICU
were also at a higher risk of dementia [4,17]. Some
cases report that ICU delirium could be the cause of
posttraumatic stess disorder (PTSD) [4]. The 2018
Society of Critical Care Medicine Pain, Agitation
and Delirium guidelines point out that delirium in
critically ill adults is strongly associated with
cognitive impairment at 3 and 12 months after ICU
discharge and longer hospital stay and there is no
strong evidence for it to be associated with PTSD or
post-ICU distress, ICU length of stay, depression,
functionality or mortality [3]. Despite that we must
recognize ICU delirium as a serious condition that
should be predicted and treated effectively to reduce
the risks of any negative outcomes.
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Conclusion
ICU delirium is a common condition that could
result in negative outcomes. It is essential to learn
about this condition, its risk factors and clinical
presentation and therefore be able to apply
prophylaxis and promptly initiate treatment. Early
mobilization, proper sleep hygiene and the removal
of physical restraints as early as possible are
important nonpharmacologic prevention measures.
Pharmacologic prevention is not recommended for
all adult ICU patients, however some studies show
low-dose haloperidol could be effective in high-risk
patients. Dexmedetomidine should be considered as
an alternative for benzodiazepines as they could be
considered a risk factor for ICU delirium.
Dexmedetomidine instead of benzodiazepines
should also be used in already delirious patients.
Antipsychotic agents are useful in treating
hallucinations and agitation, but show no significant
reduction in the duration of delirium.
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