Pain, Agitation, and

Delirium (PAD) Care in

the ICU

Hani Sammour, MD, PB

Anesthesia and IC, Shifa hospital
Majority of critically ill patients experience
significant distress, anxiety, and agitation
during their intensive care unit stays.

Numerous factors, including sleep deprivation,

unfamiliar environment, delirium, adverse
medication effect, pain, and extreme anxiety can
contribute to ICU patient distress.
Intensivists often employ various sedative
agents to relieve ICU associated distress and
prevent secondary complications of such
distress.

There are a variety of pharmacologic agents

used for this purpose, including
benzodiazepines, propofol, antipsychotic
agents, and alpha agonists.
Important pathophysiologic mechanisms associate
distress include significant increases in
catecholamines, cortisol, growth hormone,
vasopressin, prolactin, glucagon, fatty acids, and
protein catabolism.

Clinically significant sequelae of this physiologic

dysregulation include fluid and electrolyte
imbalances, altered wound healing , and
disturbances of the sleep wake cycles.
Complexity of PAD
 Pain
An unpleasant sensory and emotional“
experience associated with actual or potential
”.tissue damage
Causes Complications
Chronic pain Stress
Disease Hyper-
Sleep-loss
metabolism
Impaired Impaired
Routine Invasive wound immune
Care Devices healing function
Post-
Feelings of
Immobility traumatic
Helplessnes
stress
s
disorder
 Assessment of
Question: Can painPain
be accurately assessed in the
ICU?
Obstacles:
* Subjective, differs between individuals
* Self-reporting = GOLD standard

Behavioral Pain Scale

(BPS)

Critical Care Pain

Observation Tool (CPOT)
 Options for Pain

IV Opioids • Acute pain

Gabapentin
• Neuropathic pain
Carbamazepine

NSAIDS
Acetaminophen • Non-neuropathic pain
Ketamine
8
 Pain - Summary
 Guideline Statement: “We suggest that pain be
routinely monitored in all adult ICU patients.”

 Guideline Statement: “We recommend that IV

opioids be considered as the first-line drug class
of choice to treat non-neuropathic pain…”

 Guideline Statement: “Analgesia-first sedation

should be used in mechanically ventilated adult
ICU patients…”

9
 Review Question -
1.
1
Among those listed, which medication is the
preferred option for acute pain in the ICU?

A. Ketamine
B. Acetaminophen
C. Morphine
D. Ketorolac
 Agitation
A syndrome of excessive motor activity, usually“
non-purposeful and associated with internal
”.tension
Causes

Pain Hypoxia

Hypoglycemi
Withdrawal
a

Delirium Hypotension
11
 Correctable Causes of
Agitation
*Full bladder
*Uncomfortable bed position
*Inadequate ventilator flow rates
*Mental illness
*Uremia
*Drug side effects
*Disorientation
*Sleep deprivation
*Noise
*Inability to communicate
 Medications Associated With Agitation in ICU Patients
Antibiotics
Acyclovir Amphotericin B
Cephalosporins Ciprofloxacin
Imipenem – cilastatin Ketoconazole
Metronidazole Penicillin
Rifampin Trimethoprim – Sulfamethoxazole
Anticonvulsants
Phenobarbital Phenytoin
Cardiac Drugs
Captopril Clonidine
Digoxin Dopamine
Labetalol Lidocaine
Nifedipine Nitroprusside
Propranolol Quinidine Sulfate
Corticosteroids
Dexamethasone Methylprednisolone
Opiold Analgesics
Codeine Meperidine
Morphine Sulfate
Miscellaneous Drugs
Anticholinergics Benzodiazepines
Hydroxyzine Ketamine
Metoclopramide Nonsteroidal anti – inflammatory
drugs
Drugs for Sedation

Benzodiazepines

Propofol

Dexmedetomidine
 Options for
Sedation
Midazola
m
Propof
ol
Dexmedetomidi
ne
Amnesia X X

Analgesia X
Anticonvulsi
X X
on
Antiemesis X

Anxiolysis X X

Hypnosis X X

Sedation X X X

Bradycardia X

Hypotension X X X
Respiratory 15
X X
Depression
 Agitation -
 Guideline Summary
Statement: “Maintaininglight levels of
sedation in adult ICU patients is associated with
improved clinical outcomes.”
 Guideline Statement: “We recommend either daily
sedation interruption or a light target level of sedation
be routinely used in mechanically ventilated adult ICU
patients.”

 Guideline Statement: “The use of sedation scales,

sedation protocols designed to minimize sedative use,
and the use of nonbenzodiazepine medications are
associated with improved ICU patient outcomes.”
16
 Review Question -
2
2. Deep sedation in the ICU is associated with which
of the following outcomes?

A. Increased ICU length of stay

B. Increased mortality

C. Both A and B

D. None of the above

 Delirium
“Sudden, severe
Acute Change or
confusion and
Fluctuation in
rapid changes in Mental Status
brain function &
that occur with
physical or Inattention
mental illness.”
&
Disorganized Altered Level of
Thinking OR Consciousness

Delirium
18
 Delirium

Complications
Increased
Increased
Increased LOS time on
cost
ventilator
Long term
Agitation cognitive Mortality
deficits
 Significance of ICU Delirium

 Seen in > 50% of ICU patients

 Three times higher risk of death by six months

 Four times greater frequency of medical device

removal

 Five times more ventilator days

 Nine times higher incidence of cognitive impairment
at hospital discharge
 Delirium

Assessed via:
• Confusion Assessment Method (CAM-ICU)
• Intensive Care Delirium Screening Checklist
(ICDSC)
 Delirium – Risk
At Baseline Factors During Stay
(Non-Modifiable) (Modifiable)

Dementia or CNS diseases Pain

Hypertension Benzodiazepines

Metabolic derangement Narcotics

or Alcoholism

Higher severity of illness Immobility

Age Sleep deprivation

Substances (withdrawal as well

Infection
as direct effect)
 Delirium
Treatment
 Correct inciting factor

 No treatment FDA approved

 Guideline Statement: “There is no published

evidence that treatment with haloperidol reduces
the duration of delirium.”
 Guideline Statement: “Atypical antipsychotics
may reduce the duration of delirium.” (Level C)
 Delirium

Prevention
Guideline Statement: “We recommend
performing early mobilization to reduce the
incidence and duration of delirium”

 Guideline Statement: “We provide no

recommendation for a pharmacologic delirium
prevention protocol”
 Guideline Statement: “Benzodiazepine use
may be a risk factor for the development of
delirium”
 Review Question -
3
3. The 2013 PAD guidelines recommend which of the
following agents for prevention of delirium?

A. Haloperidol

B. Lorazepam

C. Ziprasidone

D. None of the above

 PAD Management
* PAD management presents many challenges

* A few specific strategies have demonstrated

success

* Implementation and performance is

inconsistent
 ABCDEF Care Bundle

A Assess, prevent, & manage pain

Both SAT (Spontaneous Awakening Trial)
B and SBT (Spontaneous Breathing Trial)

C Choice of analgesia and sedation

D Delirium: Assess, prevent, manage

E ABCDEF
Early mobility Care
and exercise *
Bundle
F Family engagement and empowerment
Benefits of the ABCDEF Protocol
 The ICU Liberation Bundle
* Decrease the likelihood of hospital death within
seven days by 68%

* Reduce delirium and coma days by 25%-50%

* Reduce physical restraint use by more than 60%
* Cut ICU readmissions in half
* Reduce discharges to nursing home and
rehabilitation facilities by 40%
Spontaneous Awakening Trial
SAT reduced ventilator time by = 2 days
Spontaneous Breathing Trial
SBT reduced weaning time by = 2 days
 Parameters Indicating Readiness to Wean
1. Underlying cause for mechanical ventilation resolved
Improved chest x-ray
Minimal secretions
Normal breath sound

2. Mental readiness (conscious & can protect his A/W)

3. Hemodynamic stability:
Adequate cardiac output
Absence of hypotension
Minimal vasopressor therapy
 Parameters Indicating Readiness to Wean

4. Adequate oxygenation & ventilation:

Adequate resp. muscle strength
PaO2 >60 mmHg with FiO2 < 0.5
PCO2 <50 mmHg
RR<30 /min
Spontaneous TV > 5ml /kg
Minute ventilation < 10 L/min
PEEP < 8 cm H2O
Pressure support < 8 cm H2O
Parameters Indicating Readiness to Wean

5. Absence of factors that impair weaning

Infection
Anemia
Hypokalemia
Sleep deprivation
Pain
Abdominal distention
Sedation in ICU
 Goals of Sedation in ICU

* Patient comfort
* Control of pain
* Anxiolysis and amnesia
* Blunting adverse autonomic and hemodynamic responses
* Facilitate nursing management
* Facilitate mechanical ventilation
* Avoid self-extubation
* Reduce oxygen consumption
* Treatment or Diagnostic procedures
 Characteristics of an ideal
sedation agents for the ICU

*Lack of respiratory depression

*Analgesia, especially for surgical patients
*Rapid onset, titratable, with a short elimination half-
time

*Sedation with ease of orientation and arousability

*Anxiolytic
*Hemodynamic stability
 The Challenges of ICU
Sedation

*Assessment of sedation
*Altered pharmacology
*Tolerance
*Delayed emergence
*Withdrawal
*Drug interaction
 Sedation

Causes for Agitation Sedatives

Incidence of Inadequate Sedation
 Complications of Under/Over Sedation
Undersedation Sedatives

Causes for Agitation

Agitation & anxiety
Pain and discomfort
Catheter displacement
Inadequate ventilation
Hypertension
Tachycardia
Arrhythmias
Myocardial ischemia
Wound disruption
Patient injury
Patient recall (PTSD)
AGITATED PATIENT
 Complications of Under/Over Sedation

Causes for Agitation

Oversedation

Prolonged sedation
Delayed emergence
Sedatives
Respiratory depression
Hypotension
Bradycardia
Increased protein breakdown
Muscle atrophy
Pressure injury
Loss of patient-staff interaction
Increased LOS
Increased risk of complications
(VAP & VTE)
DEEPLY SEDATED
Strategies for Patient Comfort

* Set treatment goal

* Quantitate sedation and pain
* Choose the right medication
* Use combined infusion
* Reevaluate need
* Treat withdrawal
Daily Goal is Arousable, Comfortable
Sedation

Sedation needs to be protocolized and titrated to

goal:
• Lighten sedation to appropriate wakefulness daily.

Effect of this strategy on outcomes:

• One- to seven-day reduction in length of sedation and
mechanical ventilation needs
• 50% reduction in tracheostomies
• Three-fold reduction in the need for diagnostic evaluation of CNS
 Protocols and Assessment
Tools
Titration of sedatives and analgesics guided by
assessment tools:
• Validated Sedation assessment tools:
• Ramsay Sedation Scale [RSS].
• Sedation-Agitation Scale [SAS].
• Richmond Sedation-Agitation Scale [RSAS], etc.)
No evidence that one is preferred over another
• None validated in ICU Pain assessment tools:
• Numeric Rating Scale [NRS],
• Visual Analogue Scale [VAS], etc.)
Sedation Scales
Very useful, very
underused
 What Sedation Scales Do

* Provide a semiquantitative “score”

* Standardize treatment endpoints
* Facilitate sedation studies
* Help to avoid oversedation
What Sedation Scales Don’t
Do

*Assess anxiety
*Assess pain
*Assess sedation in paralyzed patients
*Predict outcome
Sedation Scoring
Scales
Sedation should be targeted to a Ramsay score of

2 to 3.

Many levels of sedation and no levels of agitation

 SAS (Sedation – Agitation Scale)
The SAS is scored from 1 (unarousable ) to 7 (dangerous agitation)
Level Behaviors

7 Dangerous agitation pulls at endotracheal tube, tries to remove

catheter climbs over bed rail , strikes at staff, thrashes side - to –
side.
6 Very agitated . Does not calm , despite frequent verbal
reminders; requires verbal reminding of limits, physical
restraints; bites endotracheal tube.

5 Agitated , Anxious or mildly agitated , attempts to sit up, calms

down to verbal instructions.
4 Calm and cooperative. Calm , awakens easily, follow commands

3 Sedated. Difficult to arouse, awakens to verbal stimuli or gentle

shaking but drifts off again, follows simple commands

2 Very sedated. Arouses to physical stimuli but does not

communicate or follow commands, may move spontaneously

1 Unarousable. Minimal or no response to noxious stimuli, does not

communicate or follow commands.
 Choose the Right Drug

Sedation Analgesia

Amnesia Hypnosis Anxiolysis

 Sedation Options:
Benzodiazepines (Midazolam and
Lorazepam)
Pharmacokinetics/dynamics
• Lorazepam: onset 5 - 10 minutes, half-life 10 hours,
• Midazolam: onset 1 - 2 minutes, half-life 3 hours, active metabolite
• Accumulates in renal disease
Benefits
• Anxiolytic
• Amnestic
• Sedating
Risks
• Delirium
• NO analgesia
• Excessive sedation: especially after long-term sustained use
• Respiratory failure (especially with concurrent opiate use)
• Withdrawal
 Benzodiazepines

Peaks Duration Onset

5-30 min >20 hr 2-5 min Diazepam

5-10 min 30-120 min 2-3 min Midazolam
30 min 10-20 hr 5-20 min Lorazepam
 Sedation Options: Propofol
Pharmacokinetics/dynamics: onset 1 - 2 minutes,
terminal half-life 6 hours, duration 10 minutes, hepatic
metabolism
Benefits
• Rapid onset and offset and easily titrated
• Hypnotic and antiemetic
• Can be used for intractable seizures and elevated intracranial
pressure
Risks
• Not reliably amnestic, especially at low doses
• NO analgesia!
• Hypotension
• Hypertriglyceridemia; lipid source (1.1 kcal/ml)
• Respiratory depression
• Propofol Infusion Syndrome
- Cardiac failure, rhabdomyolysis, severe metabolic acidosis, and renal
failure
- Caution should be exercised at doses > 5mg/kg for more than 48 hours
- Particularly problematic when used simultaneously in patient receiving
catecholamines and/or steroids
 Propofol

Onset Peaks Duration

Propofol 30-60 2-5 min short

sec
 Propofol Dosing

* Antiemetic: 0.2-0.3 mg/kg/hr

* Anxiolytic: 0.25-1 mg/kg/hr

* Sedative, hypnotic: 20-50 g/kg/min

(Common practice 1-4 mg/kg/hr)

* Anesthetic: > 6 mg/kg/hr

 Opiate and Benzodiazepine
Withdrawal
Frequency related to dose and duration
• 32% if receiving high doses for longer than a week
Onset depends on the half-lives of the parent drug and its
active metabolites
Clinical signs and symptoms are common among agents
• CNS activation: seizures, hallucinations,
• GI disturbances: nausea, vomiting, diarrhea
• Sympathetic hyperactivity: tachycardia, hypertension, tachypnea,
sweating, fever
No prospectively evaluated weaning protocols available
• 10 - 20% daily decrease in dose
• 20 - 40% initial decrease in dose with additional daily reductions of
10 - 20%
 Treat Withdrawal

*Acute management
*Resume sedation
*Beta-blockade, dexmedetomidine
*Prolonged management
*Methadone 5-10 mg Tab bid
*Clonidine 0.1-0.2 mg Tab q8h
*Lorazepam 1-2 mg IV q8h
Sedation Options: Dexmedetomidine
Alpha-2-adrenergic agonist like clonidine
Has been shown to decrease the need for other sedation
in postoperative ICU patients
Potentially useful while decreasing other sedatives to
prevent withdrawal
Benefits
• Does not cause respiratory depression
• Short-acting
• Produces sympatholysis which may be advantageous in certain patients
Risks
• No amnesia
• Bradycardia and hypotension can be excessive
 Indications

* Intensive Care Unit Sedation

* Sedation of initially intubated and mechanically ventilated,

postsurgical patients during treatment in an intensive care
setting by continuous intravenous infusion.
* It has been continuously infused in mechanically ventilated
patients prior to extubation, during extubation, and post-
extubation. It is not necessary to discontinue the drug prior
to extubation.

* Conscious Sedation

* Sedation of non-intubated patients prior to and/or during

surgical and other procedures by continuous intravenous
infusion.
 Dosage

Intensive Care Unit Sedation

* Initiation- Loading infusion of up to 1 mcg/kg over 10 to 20 minutes.

* Maintenance- Adults generally require a maintenance infusion of 0.2-
0.7 mcg/kg/hr.

Conscious Sedation

* Clinically effective onset of sedation 10 to 15 minutes after start of

infusion

* Initiation- Loading infusion of 1 mcg/kg over 10 minutes. For patients

over 65 years of age or those undergoing less invasive procedures, a
loading infusion of 0.5 mcg/kg over 10 minutes may be suitable

* Maintenance- Generally initiated at 0.6 mcg /kg/hr and titrated from

0.2 to 1 mcg/kg/hr
 Case Scenario: 1

22-year-old male with isolated closed head injury who

was intubated for GCS of 7
He received 5 mg of morphine, 40 mg of etomidate,
and 100 mg of succinylcholine for his intubation.
He is covered in blood spurting from an arterial
catheter that was just removed, and he appears to be
reaching for his endotracheal tube.
What sedative would you use and why?
What are the particular advantages in this situation?
How could you avoid the disadvantages of this drug?
 Case Scenario:1 - Answer

Propofol will rapidly calm a patient who is displaying

dangerous behavior without need for paralysis.
Titratable and can be weaned quickly to allow for
neurologic exam
Can treat seizures and elevated ICP which may be
present in a head trauma with GCS of eight or less
Minimizing dose and duration will avoid side effects.
 Case Scenario: 2
62-year-old, 65-kg woman with ARDS from aspiration
pneumonia
Her ventilator settings are VC 400, RR 18, PEEP 8, and FIO2
100%. She is dyssynchronous with the ventilator and her
plateau pressure is 37 mm Hg.
She is on propofol at 3 mg/kg/hr, which has been ongoing
since admit four days ago.
She is also on norepinephrine 0.1 mcg/kg/min and she was
just started on steroids.
What do you want to do next?
Do you want to continue the propofol?
Why or why not?
What two iatrogenic problems is she likely at risk for?
 Case Scenario: 2 - Answer

This patient needs optimization of her sedatives, and

potentially chemical paralysis to avoid complications of
ventilator dyssynchrony and high airway pressures.

If you continue to use propofol, higher doses are required

and the patient is already on norepinephrine. In addition,
if paralysis is used, you do not have reliable amnesia.
 Summary
ICU sedation is aimed at keeping the patient
comfortable but easily arousable.

Deep sedation with or without muscle relaxants is

rarely indicated and is associated with a higher
incidence of delirium and death.

Analgo–sedation (analgesia first, and adding

sedation) is administered to relieve pain, anxiety and
discomfort and to facilitate treatment and nursing.
 ICU Agitation/Discomfort

Prevalence
• 50% incidence in those with length of stay > 24 hours

Primary causes: unrelieved pain, delirium, anxiety,

sleep deprivation, etc.

Immediate sequelae:
• Patient-ventilator dyssynchrony
• Increased oxygen consumption
• Self (and health care provider) injury
• Family anxiety

Long-term sequelae: chronic anxiety disorders and

post-traumatic stress disorder (PTSD)
Patient Focused Sedation: Key Points

Non-pharmacological measures

* Minimize:
* Blood draws, X-rays
* Blood pressure measurements, Blood glucose measurements
* Dimming lights at night (sleep-wake cycle)
Selection of Sedatives

* Benzodiazepines- Diazepam, Lorazepam, Midazolam

* Propofol
* Dexmedetomidine
* Haloperidol, other neuroleptics
THANK YOU