INTENSIVE CARE

Pain, agitation and Learning objectives

delirium in the intensive After reading this article, you should be able to:

care unit C

C
outline the reasons patients experience pain in ICU
demonstrate methods used to assess pain in ICU
C explain why patients experience agitation in ICU
Christopher McGovern C describe strategies used to optimize sedative drug use
Richard Cowan C define delirium and identify its precipitants
C outline a management strategy for a delirious patient
Richard Appleton
Barbara Miles
further physiological derangement and injury. Analgesic, anxio-
lytic and sedative medications are frequently used to alleviate
any distress from these insults. Non-pharmacological measures
Abstract
combined with these drugs should be used as part of a bespoke,
Pain, agitation and delirium are common during critical illness and are
patient-centred and multi-faceted care package to ensure that
associated with many adverse consequences. A key aim of critical
pain, agitation and delirium are minimized in ICU patients.
care is the facilitation of a calm, comfortable patient who can interact
with their family and staff. Intensive care unit (ICU) patients frequently
have pain from a variety of sources, many of which are not readily Pain
appreciated or actively managed. This article explores the challenges
Pain is defined as an unpleasant sensory and emotional experi-
of assessing pain in the ICU and outlines methods that can be used to
ence associated with actual or potential tissue damage or
better identify and manage pain in this patient group. Agitation in ICU
described in terms of such damage. It is a common problem in
is often multifactorial, with many of its sources under-recognized. We
ICU, with interventional pain being reported in around 50% of
will discuss the potential reasons that ICU patients become agitated,
patients and, perhaps more importantly, pain at rest being re-
methods for measuring agitation and the actions that can be taken
ported in 30e50% of patients.1
to alleviate it. Although the use of sedative and anxiolytic drugs is
There is no clear difference in pain levels between surgical
common in ICU, their use is not without risks. This article will outline
and medical patients. Some studies have demonstrated that
these risks, the variety of drugs available and how to use these
medical patients experience greater pain intensity than surgical,
drugs to a targeted effect. We will also explore delirium, its risk factors,
potentially due to less analgesic use as there is no surgical
precipitants and associated morbidity and mortality. This article will
wound. Patients frequently report pain as a significant part of
discuss how to diagnose delirium and the methods used to prevent
their ICU recollection after ICU discharge.
and manage it.
Pain and the stress response are associated with detrimental
Keywords Agitation; analgesia; delirium; pain; sedation physiological consequences including increased stress hormone
production, vasoconstriction, increased catabolism with
Royal College of Anaesthetists CPD Matrix: 1A02, 1D01, 1D02, 2C05, 3C00
impaired tissue perfusion and wound healing. These conse-
quences can extend beyond short term physiological sequelae to
persisting psychological problems such as chronic pain and post-
traumatic stress disorder (PTSD).
Admission to intensive care follows the primary insult of the
patient’s underlying illness. The secondary insult of the in-
terventions and care required to support them in ICU then fol- Why are ICU patients in pain?
lows. Pain, agitation and delirium often coexist in critically Pain in the ICU population can be divided into procedural pain
unwell patients and can exacerbate each other, contributing to and pain at rest.

Procedural pain: multiple procedures common to the intensive

care environment can be painful, e.g. vascular line or drain
Christopher McGovern MBChB MCEM FRCA FFICM is a Specialist insertion, wound care and patient repositioning. Many such
Trainee Registrar in Anaesthetics and Intensive Care Medicine in the procedures are often carried out without additional analgesia.
West of Scotland, UK. Conflicts of interest: none declared.
Tracheal suctioning, commonly reported as a source of pain and
Richard Cowan MBChB(Hons) MRCP(UK) FRCA FFICM is a Specialist distress by patients, is often performed without additional
Trainee Registrar in Anaesthetics and Intensive Care Medicine in the analgesia.
West of Scotland, UK. Conflicts of interest: none declared.
Richard Appleton MBChB FRCA FFICM is a Consultant in Anaesthetics Pain at rest: rest pain in the trauma or surgical population is
and Critical Care at the Queen Elizabeth University Hospital, easily attributed to wounds, fractures or the site of surgery.
Glasgow, Scotland, UK. Conflicts of interest: none declared. However, other common sources of pain can be related to
Barbara Miles MBChB FRCA FFICM is a Consultant in Anaesthetics and indwelling lines, tubes and catheters, gastrointestinal discomfort
Intensive Care Medicine at the Glasgow Royal Infirmary, Glasgow, (from ileus, spasm or constipation) or musculoskeletal pain from
Scotland, UK. Conflicts of interest: none declared. immobility or pressure areas.

ANAESTHESIA AND INTENSIVE CARE MEDICINE --:- 1 Ó 2018 Published by Elsevier Ltd.

Please cite this article in press as: McGovern C, et al., Pain, agitation and delirium in the intensive care unit, Anaesthesia and intensive care
medicine (2018), https://doi.org/10.1016/j.mpaic.2018.10.001
 INTENSIVE CARE

Assessing pain withdrawal phenomena. The choice of opioid will depend on

staff familiarity, local practice and patient factors such as renal
Given the subjective nature of pain, the gold standard method
function and underlying pathology.
for pain assessment is using a validated self-reporting measure
Given the drive towards analgesia-based sedative regimes,
such as the numerical rating scale with a visual support (NRS-V).
drugs such as remifentanil have gained favour due to their easy
Unfortunately, given the nature of critical illness, the use of
titratability as an infusion and context insensitive half-life. This
sedative medications and high incidence of delirium, patients are
allows the rapid delivery of potent analgesia during procedures
often unable to use self-reporting tools to allow assessment of
or painful interventions, as well as a reliable and quick reduction
their pain. Hence, the identification of pain relies on surrogate
in plasma levels upon discontinuing the infusion. This rapid
markers such as observations made at the bedside.
offset of remifentanil means that an alternative analgesic plan
Tools such as the Critical Care Pain Observation Tool (CPOT)2
should be considered before stopping an infusion.
have been developed which detect the presence of pain by
assessing and scoring patient-centred features:
Paracetamol: is commonly used as a simple analgesic out with

facial expression
critical care. When used as an adjunct to opioids, it has an opioid
 relaxed expression (0 points), some facial muscle ten-
sparing effect. This finding has been echoed in some small
sion e.g. frowning (1 point) or grimacing (2 points)
studies carried out in critical care, showing improved patient

body movements
pain experience and reduced opioid use. Paracetamol has also
 Absence of movement (0 points), cautious or protective
been investigated for its antipyretic effects in sepsis, and
movements (1 point) or restless and agitated e.g. pulling
although it does not alter outcomes, it does appear to be safe.
tube, thrashing (2 points)
As with any drug in the critically ill, the pharmacokinetics of

muscle tension
paracetamol can be unpredictable and should be used with
 relaxed muscle tone (0 points), resistance to movements
caution in patients with liver impairment or those of low body
(1 point) or rigidity (2 points)
mass. Paracetamol administration is also associated with a

ventilation OR vocalization
modest fall in blood pressure.
 tolerating invasive ventilation (0 points), coughing (1
point) or significant asynchrony (2 points)
Non-steroidal anti-inflammatory drugs: NSAIDs such as
 normal tone and voice (0 points), sighing (1 point),
ibuprofen and diclofenac have a side effect profile that often
crying (2 points).
limits their use within critical care. They are associated with
The maximum score is 8 with a score >2 indicating the
renal impairment, gastrointestinal irritation, bronchoconstriction
presence of pain that should trigger interventions or further
and impaired platelet function.
analgesia. Such scales have been found to be reliable and valid
Some studies have demonstrated a reduction in opioid con-
across the wide variety of patient groups encountered in the ICU.
sumption when adjuvant NSAIDs are used. However, they
Although CPOT does not accurately reflect the severity of pain
should be used with caution in the critically ill and only in
in the same way a self-reported scale does, it is useful in iden-
selected circumstances such as young patients with little or no
tifying the presence of pain and the effectiveness of analgesic
comorbidities.
interventions.
Haemodynamic changes have not been found to be reliable
Regional analgesia: drugs such as lignocaine and bupivicaine
methods of assessing pain in critical care, although any change
are most commonly used to provide regional analgesia via
should prompt an assessment of a patient’s pain.
epidural or peripheral nerve catheters. Other methods of
Managing pain administration include local infiltration, single-shot nerve blocks
Given the high incidence of pain in the ICU population, many or the use of topical patches.
papers and guidelines recommend an analgesia-based sedation, The benefit of epidural analgesia has been demonstrated in
or ‘analgosedation’, approach to managing ICU patients.3 This major abdominal aortic surgery, with improved pain control,
approach prioritizes analgesia over sedation or hypnosis, with reduced myocardial infarction, reduced respiratory failure,
the aim of having a comfortable, lucid and interactive patient. reduced duration of mechanical ventilation and length of ICU
This approach has demonstrated a reduction in the use of hyp- stay.
notic agents, duration of mechanical ventilation and ICU length The use of other regional techniques has also been investi-
of stay. gated, including paravertebral and intercostal blocks for trau-
matic rib fractures. Theoretically, such regional techniques could
Opioids: remain the mainstay of analgesia in critical care due to reduce opioid use, improve respiratory function and reduce res-
their potent analgesic and antitussive effects. These drugs act as piratory complication. However, limited evidence regarding such
agonists with varying affinities for mu, kappa and delta opioid techniques exists to support their routine use.
receptors. Some examples include morphine, fentanyl, alfentanil Intravenous lignocaine infusions have been used as an adju-
and remifentanil. vant analgesic in the perioperative period. However, this method
Each drug has its advantages and disadvantages surrounding has not been investigated in the intensive care population. Given
metabolism, potency, titratability and cost. Side effects common the unpredictable pharmacokinetics and potential for neurolog-
to all opioids include respiratory depression, constipation and ical and cardiovascular toxicity, the safety of such a technique in
ileus, hypotension, pruritis, nausea, delirium, tolerance and ICU would need to be demonstrated.

ANAESTHESIA AND INTENSIVE CARE MEDICINE --:- 2 Ó 2018 Published by Elsevier Ltd.

Please cite this article in press as: McGovern C, et al., Pain, agitation and delirium in the intensive care unit, Anaesthesia and intensive care
medicine (2018), https://doi.org/10.1016/j.mpaic.2018.10.001
 INTENSIVE CARE

Neuropathic pain medication: multiple drugs exist for use in The ICU environment can exacerbate anxiety by being
acute and chronic neuropathic pain including gabapentin, confined to bed in unfamiliar surroundings with unfamiliar faces.
amitriptyline, carbamazepine and pregabalin. There has been Pain and unpleasant stimuli such as loud noises, monitor alarms
limited study of such drugs in the ICU population out with spe- and bright lights can disturb and fragment sleep, further aggra-
cific indications such as in Guillain-Barre syndrome, where there vating anxiety.
is some improvement in pain scores and opioid consumption. Other stressors may include financial worries, concerns for
There is little evidence surrounding this broad and varied their family or simply the fear associated with critical illness,
class of drugs in critically ill patients. Their safety profile and recovery or death.
effectiveness in ICU is largely unknown.
Managing agitation
Other analgesic drugs: given the overlap of effects, other drugs Managing agitation involves searching for underlying causes or
with analgesic properties including alpha-2 agonists and NDMA exacerbating factors and addressing them, targeting the goal of a
antagonists will be discussed later in this article. calm, lucid, cooperative and interactive patient. Specific efforts
should be made to regularly orientate and reassure patients
Agitation regarding their environment, treatment and progress. Should this
prove insufficient, then the mainstay of treatment is sedative or
Anxiety and agitation are commonly experienced by patients in anxiolytic medication.
intensive care. The incidence of agitation in the ICU population is The use of sedative medications in the management of
reported to be between 50% and 70%, occurring either at the agitation should be targeted towards a specific end-point. Mul-
time of admission or developing several days following tiple papers and guidelines exist with the aim of improving
admission.4 sedative practice in critical care, such as the ‘eCASH’ (early
The reasons for agitation are frequently multifactorial. Drug Comfort using Analgesia, minimal Sedatives and maximal Hu-
and alcohol withdrawal or toxicity, delirium or an underlying mane care) concept,5 detailed in Figure 1.
psychiatric disorder can be causative factors. Underlying central Such guidelines advocate a holistic, patient-centred approach
nervous system pathology, such as brain injury or meningoen- to sedation in combination with targeted analgesia, good sleep
cephalitis, can also cause agitation. hygiene, environmental optimization, early mobilization and

The eCASH concept

Early Comfortable
implementation Cooperative and
Calm • Opioids
• Multimodal opioid
sparing adjuvants

Pain
Anxiety
Humane person/
Agitation
family centred
Delirium
Immobility

• Mobilization
• Sleep promotion Sedatives • Avoid unjustified
• Environmental minimized and deep sedationa
modulation targeted • Sedative titration to
• Family engagement
pre-specified goal

The eCASH concept: early implementation to manage and prevent pain, anxiety, agitation, delirium and immobility and facilitate patient-
centred care.
a
Moderate or deep sedation remains relevant for some situations, including the management of severe respiratory failure with ventilator–
patient dyssynchrony, prevention of awareness in patients receiving neuromuscular blocking agents, status epilepticus, surgical conditions
necessitating strict immobilization and some cases of severe brain injury with intracranial hypertension.

Figure 1

ANAESTHESIA AND INTENSIVE CARE MEDICINE --:- 3 Ó 2018 Published by Elsevier Ltd.

Please cite this article in press as: McGovern C, et al., Pain, agitation and delirium in the intensive care unit, Anaesthesia and intensive care
medicine (2018), https://doi.org/10.1016/j.mpaic.2018.10.001
 INTENSIVE CARE

family engagement in patient care. Holistic, non- certain pathologies, at least initially, are likely to be excluded
pharmacological measures include reducing night time light from sedation breaks and a pragmatic approach should be taken
and noise, using earplugs and eye masks to promote sleep and to weigh the risks and benefits of such a technique in these
restricting medical interventions to daylight hours. Sedative groups (e.g patients with raised intracranial pressure, unstable
drugs should be continually reassessed and used at their lowest spinal fractures, multiple complex injuries or airway pathology).
effective dose.
Sedation protocols: algorithms or protocols can be used to titrate
Measuring agitation and sedation sedative drugs to a specified target using a validated sedation
Several tools are available for monitoring the levels of sedation at scale. Medical or nursing staff continuously adjust sedative
the bedside. These can be used to track fluctuations over time medications based on the frequent assessment of a patient’s
and guide interventions to help achieve an optimal level of depth of sedation or the presence of agitation.
sedation. The ideal tool for measuring sedation should be easy to There is evidence supporting the use of such an approach and
use, easy to interpret and have good inter-user reliability. this method is recommended by multiple review articles and
One of the most common tools used is the Richmond guidelines.
AgitationeSedation Scale (RASS),6 which categorizes patients Currently, no evidence exists to definitively say which seda-
from the most deeply sedated 5 (unable to rouse) to the most tion practice is superior to the other.7 What is more important is
agitated þ4 (combative), with zero representing an alert and the evolving culture behind sedation, with a shift away from a
calm patient. RASS and other scales have been validated in ICU norm of deep sedation to targeting a comfortable, lucid and
and their use is recommended in the Pain Agitation and Delirium interactive patient.
(PAD) Guidelines.3
Beyond clinical bedside measures of sedation, other more Other indications for sedative drugs
objective measures of sedation depth include evoked potentials, Sedative medications can be used for specific purposes beyond
oesophageal pressure monitors, heart rate variability monitors anxiolysis and improving patient comfort.
and electroencephalograms. Although these are classically used
as depth of anaesthesia monitors, they may also be useful ad- Sleep: it is well recognized that critical illness and intensive care
juncts in the ICU. admission can result in fragmented sleep and a disruption of
Processed electroencephalograms such as the Bispectral Index circadian rhythm. Poor sleep is associated with adverse sequelae
(BIS) monitor may add diagnostic value when looking for cerebral such as delirium, impaired immunity and increased stress hor-
hypoxia, seizure activity, changes in cerebral oxygen consumption mone production. Multiple studies have been carried out looking
and cerebral perfusion. Some studies have demonstrated good at the impact of several drugs to promote sleep and maintain a
correlation between BIS levels and RASS scores. They should, physiological sleepewake cycle. There is insufficient evidence to
however, be used with caution due to potential interference from support the routine use of these medications at present.
electromyogram (EMG) signals, the pathophysiological changes of
critical illness, changes in core temperature and multiple drugs End-of-life care: providing effective palliative care is an impor-
including catecholamines and ketamine. tant role for intensive care staff. Sedative medications are
The use of such monitors is not universal practice but they commonly used to provide comfort and relieve distress or anxi-
may be useful in select patient groups, such as those requiring ety in the dying patient.
deep sedation during neuromuscular blockade or anaesthesia for Cultural and geographical variations exist regarding the legal
painful procedures at the bedside (e.g. percutaneous and ethical issues surrounding end of life care practice. The
tracheostomy). overarching principle should be that sedative drugs are used to
provide comfort and symptom relief to patients in their final days
Titrating sedatives
and hours.
When using sedative medications to provide anxiolysis or com-
fort, strategies should be in place to ensure the lowest effective
dose is used. Two broad methods exist as interventions to Anaesthesia: many sedative drugs such as propofol can be
minimize and optimize sedative use in the ICU. titrated to higher doses to achieve anaesthesia. This may be
desirable for patients undergoing surgical procedures or when
Sedation breaks: a daily sedation interruption, or ‘sedation muscle relaxant infusions are being used.
break’, involves temporary discontinuation of sedative infusions
to assess the patient’s underlying neurological condition and Reducing cerebral metabolic rate: some sedative medications
ongoing need for further sedation. This approach has been act to reduce cerebral oxygen consumption, making them useful
combined with spontaneous breathing trials and physiotherapy adjuncts in the treatment of traumatic brain injury or in the
sessions to wean patients from mechanical ventilation and has- prevention of secondary brain injury following cardiac arrest.
ten recovery. Studies of this approach show that it reduces
duration of mechanical ventilation, length of ICU stay and need Seizure treatment: benzodiazepines remain the first line treat-
for CT brain imaging. ment for the management of seizure activity. Other sedatives
Some caution must be exercised when using this approach as such as propofol and ketamine have anti-seizure activity and
some studies have demonstrated an increased risk of self extu- barbiturates such as thiopental can be used in the management of
bation (but not an increased rate of re-intubation). Patients with refractory status epilepticus.

ANAESTHESIA AND INTENSIVE CARE MEDICINE --:- 4 Ó 2018 Published by Elsevier Ltd.

Please cite this article in press as: McGovern C, et al., Pain, agitation and delirium in the intensive care unit, Anaesthesia and intensive care
medicine (2018), https://doi.org/10.1016/j.mpaic.2018.10.001
 INTENSIVE CARE

Drug withdrawal and toxicity: benzodiazepines are commonly various inhibitory neurotransmitters. It is claimed its effects
used in the management of toxicity from illicit drug use or more closely resemble physiological sleep and allow for a more
alcohol withdrawal. Of note, patients taking long term benzodi- comfortable, lucid and interactive patient.
azepines, whether prescribed or recreational, should be managed Multiple studies looking at the potential of dexmedetomidine
cautiously as sudden discontinuation may result in withdrawal have been carried out. The MIDEX and PRODEX studies
symptoms or seizures. demonstrated dexmedetomidine to be non-inferior to both pro-
pofol and midazolam. The DahLIA trial found an increase in
Risks of sedation ventilator free hours and shorter duration of delirium when
Mounting evidence demonstrates that deep sedation, even in the dexmedetomidine was added to standard sedation therapy in
earliest stages of admission to ICU, is associated with prolonged patients with hyperactive delirium. The DESIRE trial found no
periods of mechanical ventilation, prolonged ICU stay and an difference in mortality or ventilator free days in patients with
increased risk of death.8 sepsis or pancreatitis managed with dexmedetomidine versus
Other risks of over-sedation include critical illness neuropathy propofol or midazolam.
and myopathy, cardiovascular and respiratory depression, Clonidine is less alpha-2 receptor specific than dexmedeto-
increased rates of delirium, immune suppression, ileus and long- midine and has been less extensively studied as a sedative in
term sequelae such as cognitive decline and post-traumatic stress ICU. A recent systematic review found that it may play a role as
disorder. an adjuvant sedative medication with narcotic sparing proper-
Besides the risks of too much sedation, too little sedation may ties. However, its use is associated with hypotension.
also be associated with harm. This may include physical injury to
the patient or loss of medical devices such as the endotracheal Benzodiazepines: there are various drugs in this class including
tube. Concerns have also been raised over increased levels of midazolam, lorazepam and diazepam, each varying in their po-
awareness during a patient’s stay, resulting in distress and lasting tency, duration of action and pharmacokinetic properties. They
psychological harm. Several studies have demonstrated that are generally inexpensive with minimal cardiovascular effects
increased awareness does not result in psychological harm. but are respiratory depressants with risks of accumulation in
liver and renal impairment.
What drugs to use Once a mainstay of sedative practice in ICU, the use of ben-
Multiple sedative agents exist. Sedative use is usually combined zodiazepines has declined in recent years due to evidence of an
with analgesics, namely opioids. Consideration should be given increased risk of delirium with their use. They remain first line
to each drug’s pharmacokinetic and pharmacodynamic proper- drugs for treating seizures, alcohol withdrawal and recreational
ties, especially in the context of critical illness and possible he- drug toxicity.
patic or renal impairment. Drugs given as infusions can
accumulate and the adverse side effects of many drugs can be Ketamine: is an N-methyl D-aspartate (NMDA) receptor agonist.
more pronounced in critically ill patients. It has analgesic and sedative properties though also produces
The choice of sedative agent will often depend on local policy, sympathetic stimulation with the associated effects of broncho-
physician preference, cost and familiarity. A wide variety exists: dilation, increased cerebral blood flow and intracranial pressure.
Due to the potential for distressing hallucinations and night-
Propofol: (2,6-diisopropylphenol) acts at GABA receptors and is mares, it is usually given with an additional sedative agent and
easily titratable when used as an infusion. Studies comparing reserved as an adjunct for managing life threatening asthma or
propofol to benzodiazepines have found improved outcomes patients with complex pain problems.
such as reduced time on a ventilator, reduced time in ICU and
improved survival. Thiopental: is a barbiturate that is rarely used as a maintenance
It has the disadvantages of cardiorespiratory depression and sedative agent due to its long context sensitive half-life and
the risk of the rare but potentially fatal propofol infusion syn- problems with life threatening effects on plasma potassium levels
drome (PRIS). PRIS is likely due to mitochondrial dysfunction when given as an infusion. It remains a therapeutic option for
and its presentation is very variable. Features may include liver refractory raised intracranial pressure and status epilepticus.
impairment, metabolic acidosis, rhabdomyolysis and hyper-
triglyceridaemia. The dose should not exceed 4 mg/kg/hr, Antipsychotic agents: there are a number of agents in this class
although cases of PRIS have been reported at lower doses. including haloperidol, quetiapine and olanzapine. Haloperidol
has been studied the most. It is used both as a sedative agent and
Alpha-2 agonists: dexmedetomidine and clonidine are alpha-2 as a specific treatment for delirium and agitation. There is evi-
agonists with both sedative and analgesic effects. Their main dence that sedation with a regime of haloperidol and propofol
side effects include hypotension and bradycardia. Due to their reduces sedative use when compared to midazolam and propo-
minimal respiratory depression and their potential to reduce or fol. Although there is limited evidence that haloperidol reduces
even treat delirium, there has been increased interest in their use the rate or duration of delirium, it remains a suitable option for
over recent years. treating acute agitation.
Dexmedetomidine is a highly selective alpha-2 receptor Antipsychotic agents are associated with extrapyramidal side
agonist and acts independently of the GABA-mediated activity effects and cardiac conduction abnormalities, namely QT pro-
unlike many other sedatives. Its main action occurs at the pons, longation. QT prolongation is recognized to be common in crit-
inhibiting noradrenaline release and causing the release of ically ill patients and can lead to life-threatening arrhythmias.

ANAESTHESIA AND INTENSIVE CARE MEDICINE --:- 5 Ó 2018 Published by Elsevier Ltd.

Please cite this article in press as: McGovern C, et al., Pain, agitation and delirium in the intensive care unit, Anaesthesia and intensive care
medicine (2018), https://doi.org/10.1016/j.mpaic.2018.10.001
 INTENSIVE CARE

Volatile agents: although common place in the theatre setting, agitated, restless and sometimes combative. Hypoactive delirium
inhalational agents such as sevoflurane and desflurane are rarely can be harder to recognize with predominantly features of leth-
used in the ICU. Equipment such as the AnaConDaÔ allow the argy and inattention. Patients with mixed delirium fluctuate be-
addition of volatile agent to an ICU ventilator circuit. Small tween hypoactive and hyperactive states.
studies have demonstrated this approach as feasible and the re- The exact pathophysiology of delirium is poorly understood,
sults of larger studies are awaited. with an imbalance of central neurotransmitters including dopa-
mine and acetylcholine being postulated as the underlying cause.
Delirium
Risk factors for delirium
Delirium is a common syndrome associated with illness. It pre- Patient factors such as increasing age, chronic drug or alcohol
sents as an acute change in mental status with inattention and use, hearing or visual impairment, existing cognitive dysfunction
cognitive dysfunction. The severity of delirium tends to fluctuate and malnutrition predispose to delirium.
through the day, often being worse at night. Within the hospital setting, modifiable precipitating factors
Delirium is very common in ICU patients: varying incidences are also present. These include the use of various drugs com-
are reported. Large reviews suggest that around one third of all mon to the ICU, e.g. steroids, sedatives, anticholinergics and
ICU patients suffer from delirium.9 This proportion rises in opioids. Other risk factors for delirium include illness severity,
ventilated patients where an incidence of up to 80% has been sleep disturbance, electrolyte abnormalities and general
found. The presence of delirium is an independent risk factor for anaesthesia.
an increased length of stay in ICU and hospital, persisting
cognitive impairment after ICU and increased mortality. Each Diagnosing delirium
additional day a patient spends with delirium increases their risk Hyperactive delirium is usually easy to recognize, but hypoactive
of these adverse events. forms of delirium are associated with the same morbidity and
Delirium can be classified into hyperactive, hypoactive and mortality. In order to detect such delirium we can use validated
mixed phenotypes. Patients with hyperactive delirium are screening tools.

The Confusion Assessment Method for ICU (CAM-ICU)

1. Acute change or fluctuating course of mental status:

NO CAM-ICU negative
• Is there an acute change from mental status baseline? OR
NO DELERIUM

YES
2. Inattention:
• ‘Squeeze my hand when I say the letter ‘A’’
0–2 CAM-ICU negative
Read the following sequence of letters:
Errors NO DELERIUM
S A V E A H A A R T or C A S A B L A N C A or A B A D B A D A A Y
ERRORS: No squeeze with ‘A’ & Squeeze on letter other than ‘A’
• If unable to complete Letters Pictures
> 2 Errors

3. Altered level of consciousness RASS other CAM-ICU positive

Current RASS level than zero DELERIUM Present
RASS = zero

4. Disorganized thinking:
> 1 Error

3. Does one pound weigh more than two?

4. Can you use a hammer to pound a nail?
0–1
Command: Error CAM-ICU negative
‘Now do the same thing with the other hand’ (Do
NO DELERIUM
not demonstrate)
OR

Figure 2

ANAESTHESIA AND INTENSIVE CARE MEDICINE --:- 6 Ó 2018 Published by Elsevier Ltd.

Please cite this article in press as: McGovern C, et al., Pain, agitation and delirium in the intensive care unit, Anaesthesia and intensive care
medicine (2018), https://doi.org/10.1016/j.mpaic.2018.10.001
 INTENSIVE CARE

The most commonly used include the Confusion Assessment Small studies of dexmedetomidine as a sedative infusion have
Method for ICU (CAM-ICU) (Figure 2) and the Intensive Care shown an association with reduced levels and length of delirium.
Delirium Screening Checklist (ICDSC), both of which have been However, the comparator control groups received benzodiaze-
recommended by the American Society of Critical Care Medicine pines which have been shown to be an independent risk factor
(SCCM). Both of these tools use sedation scales such as RASS and for developing delirium. The results of larger robust studies of
SAS to detect altered levels of consciousness as well as tests of dexmedetomidine, such as the SPICE III trial, are currently
inattention, disorientation and cognition. The ICDSC also in- awaited to evaluate the effect of dexmedetomidine sedation on
corporates questions that look for features of psychosis, hallu- the incidence of delirium.
cinations, psychomotor disturbance, sleep cycle disruption and Other specific therapies aimed at neurotransmitter targets
symptom fluctuation. such as acetylcholine have been studied using the anticholines-
terase drug rivastigmine. This study was abandoned early as
Managing delirium preliminary results suggested that rivastigmine therapy was futile
The management of delirium involves treating the underlying and potentially harmful. Statins have also been investigated due
precipitating acute illness, minimizing modifiable risk factors to their anti-inflammatory effects, but studies so far have shown
and using non-pharmacological and pharmacological treatments. no benefit. A
Given the wide variety of precipitants, various mnemonics exist
as an aide-memoire such as THINK (Table 1).
Non-pharmacological interventions to both prevent and REFERENCES
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the ABCDEF bundle.10 This includes interventions to address A prospective study of pain at rest: incidence and characteristics
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ANAESTHESIA AND INTENSIVE CARE MEDICINE --:- 7 Ó 2018 Published by Elsevier Ltd.

Please cite this article in press as: McGovern C, et al., Pain, agitation and delirium in the intensive care unit, Anaesthesia and intensive care
medicine (2018), https://doi.org/10.1016/j.mpaic.2018.10.001