Transcript to Presentation Handout

A PAINLESS APPROACH TO MANAGING AGITATION
AND DELIRIUM IN THE CRITICALLY ILL
ZACH R. SMITH, PHARM.D., BCPS
CLINICAL PHARMACIST, CRITICAL CARE
HENRY FORD HOSPITAL
The speaker has no actual or potential conflict of interest in relation to this presentation
OBJECTIVES
Pharmacist:
 Describe bedside behavioral assessment tools that can be used to accurately assess for pain, agitation, and
delirium (PAD).
 Compare and contrast the pharmacologic options for the management of PAD.
 Employ a systematic approach to management of PAD.
Technician:
 Recognize bedside behavioral assessment tools used to identify PAD.
 Identify the therapeutic class of a pharmacologic agents used to manage PAD.
 Define the controlled substance classification of medications used to treat PAD.
INTENSIVE CARE UNIT TRIAD
Delirium
Pain
Barr J, et al. Crit Care Med. 2013;41(1):263-306.
Reade MC, et al. N Engl J Med. 2014;370(5):444-54.
Agitation;
unpleasant
awareness
PERSPECTIVE OF PAD IDENTIFICATION IN THE ICU
Pain
assessment
Agitation
assessment
Delirium
assessment
Shapiro BA, et al. Crit Care Med. 1995;23(9):1596-600.
ACCM, et al. 2002;59(2):150-78.
Barr J, et al. Crit Care Med. 2013;41(1):263-306.
1995
2002
2013
None
NRS,
vitals signs
CPOT, BPS
None
SAS,
MAAS
RASS, SAS
CAM-ICU
CAM-ICU,
ICDSC
None
DEFINITIONS
Pain
• Unpleasant sensory and emotional experience associated with actual or
potential tissue damage
Agitation
• Syndrome of excessive motor activity, usually non-purposeful and
associated with internal tension
Delirium
• Disturbance of consciousness and cognition that develops over a short
period of time and fluctuates
Barr J, et al. Crit Care Med. 2013;41(1):263-306.
Crippen D. Crit Care. 1999; 3(3): R35–R46.
Girard TD, et al. Crit Care. 2008;12 Suppl 3:S3.
PATIENT TIMELINE IN THE INTENSIVE CARE UNIT
Manage Underlying Acute Problem:
• Pneumonia
• COPD exacerbation
• Pulmonary
embolism
Management
of pain, agitation and delirium
• Post-operative after major surgery
Day 1 - 5
Day 1
- Endotracheal intubation - Stabilization of patient
& mechanical ventilation (MV)
Tobin MJ. N Engl J Med 1994; 330:1056-1061
McConville JF, et al. N Engl J Med 2012; 367:2233-2239
Ortega R, et al. N Engl J Med 2014;370:e4.
Day 6 - 7
- Extubation from MV
- Monitor 12-24 hours
Day 8 & beyond
- Transfer care to internal
medicine unit
ASSESSMENT OF LIKELIHOOD OF SUCCESSFUL
EXTUBATION FROM THE MECHANICAL VENTILATOR
Spontaneous awakening trial
Spontaneous breathing trial
Kress JP, et al. N Engl J Med. 2000;342(20):1471-7.
Girard TD, et al. Lancet. 2008;371(9607):126-34.
Spontaneous breathing trial
IV sedative/analgesic medications
IV sedative/analgesic medications
Day 1
Spontaneous awakening trial
Day 2
5:00 am
Day 3
5:00 am
PATIENT PERSPECTIVE OF THE ICU AND MECHANICAL
VENTILATION
Commonly cited negative experiences:
 Impaired cognitive function, inability to participate in care
 Problems with sleeping, pain, and anxiety

38.5% remember being in pain

55.2% remember feeling tense or keyed up
One year reflection on a future ICU admission:
 86.5% would receive ICU care and mechanical ventilation (MV) again
 20% indicated significant pain/discomfort from MV would cause them to refuse life-saving intervention
Stein-Parbury J, et al. Am J Crit Care. 2000;9(1):20-7.
Rotondi AJ, et al. Crit Care Med. 2002;30(4):746-52.
Mendelsohn AB, et al. Crit Care Med. 2002;30(7):1439-45.
EPIDEMIOLOGY OF SEDATION USE IN THE UNITES STATES
Intravenous Sedation use in the US 2001-2007
Methods
• Retrospective cohort study of intravenous (IV) infusions in MV patients
• 147 ICUs (n = 109,671)
Results
• 51.5% of MV patients received ≥ 1 IV sedative infusion
• Propofol 82.2%, benzodiazepine 31.1%, dexmedetomidine 4.0%
• Increased from 2001 to 2007 from 39.7% to 66.7%, respectively
• Only 38.2% who received IV sedation received an analgesic infusion
Conclusion
Increasing number of patients are receiving continuous infusions of sedatives
Wunsch H, et al. Crit Care Med. 2009;37(12):3031-9.
TENETS OF PAIN MANAGEMENT IN CRITICALLY ILL
1.
All clinicians are advocates for pain control
2.
Most (if not all) patients will experience pain
3.
Err on the side of presuming pain is present, when input for pain is not available
4.
It is easier to prevent the escalation of pain through early recognition and control
5.
Analgesic agents should be started prior to or concomitantly with sedative agents
Erstad BL, et al. Chest. 2009;135(4):1075-86.
Pasero C, et al. Chest. 2009;135(6):1665-72.
SOURCES OF PAIN
27–77% experience significant pain in ICU
Elements of routine ICU care:
• Turning
• Physical therapy
Tissue Injury:
• Surgery
• Trauma
• Pressure areas
Devabhakthuni S, et al. Ann Pharmacother 2012:530–540
Reade MC, et al. N Engl J Med. 2014;370(5):444-54.
Peitz GJ, et al. Crit Care Med. 2013;41(9 Suppl 1):S46-56.
Affective component:
• “this pain means I’m
more likely to die”
Pain
Vascular access
Endotracheal tube
OUTCOMES ASSOCIATED WITH UNTREATED PAIN IN THE ICU
Acute
Hospitalization
Long Term
Lindenbaum L, et al. Surg Clin North Am. 2012;92(6):1621-36.
Barr J, et al. Crit Care Med. 2013;41(1):263-306.
• ↑ catecholamine, hyperglycemia, catabolism of muscle tissue
• insufficient sleep, suppression of immune cells
• ↑ risk of delirium
• Impaired wound healing
• ↑ risk of posttraumatic stress disorder (PTSD), chronic pain,
and lower health-related quality of life
IDENTIFYING PAIN IN THE CRITICALLY ILL
 Physiologic indicators such as hypertension and tachycardia poorly correlate with pain
 Self-report of pain is the “gold standard” (VAS: 0-10)
 ≥ 4: significant pain
 The Society of Critical Care Medicine (SCCM) recommends using the behavioral pain scale (BPS)
and critical care pain observation tool (CPOT)
 Most valid and reliable behavioral measures of pain in those unable to self-report
 Frequency of pain assessment with VAS, BPS, or CPOT:
 ≥ 4 times per 8 hour shift and as needed
Barr J, et al. Crit Care Med. 2013;41(1):263-306.
IDENTIFYING PAIN IN THE CRITICALLY ILL
 Behavior Pain Scale (BPS):
 3 - 12 scale
Item
Description
Facial
expression
Relaxed
Partially tightened
Fully tightened
Grimacing
1
2
3
4
Upper limb
movements
No movement
Partially bent
Fully bent
Permanently retracted
1
2
3
4
Compliance
with MV
Tolerating movement
Coughing but tolerating MV
Fighting ventilator
Unable to control MV
1
2
3
4
 3 indicates no pain
 Treat pain if score ≥ 5
 Treat within 30 minutes and reassess
Payen JF, et al. Crit Care Med. 2001;29(12):2258-63.
Barr J, et al. Crit Care Med. 2013;41(1):263-306.
Score
IDENTIFYING PAIN IN THE CRITICALLY ILL
 Critical Care Pain Observation Tool
(CPOT):
 0 – 8 scale
 0 indicates no pain
 Treat pain if score ≥ 3
 Validated in patients not on MV
 Treat within 30 minutes and reassess
Gélinas C, et al. Am J Crit Care. 2006;15(4):420-7.
Barr J, et al. Crit Care Med. 2013;41(1):263-306.
Item
Description
Facial
Expression
Relaxed, neutral
Tense
Grimacing
0
1
2
Body
Movements
Absence of movements
Protection
Relentlessness
0
1
2
Muscle
Tension
Relaxed
Tense, rigid
Very tense or rigid
0
1
2
Compliance
Tolerating MV or normal breaths
with MV – or– Coughing with MV or moaning
Vocalization
Fighting MV or crying out
Score
0
1
2
PHARMACOLOGIC MANAGEMENT OF PAIN
Opiates
(Schedule)
Mechanism
of action
Onset
Half-life (t ½)
Intermittent Dosing
Metabolism
(IV)
(Context-sensitive t ½)
(Infusion Dosing)
(Active metabolite)
Fentanyl
(C-II)
mu-receptor
agonist
1-2 min
2-4 hr
(6-12 hr infusion)
0.35-0.5 mcg/kg Q 0.5 hr
(0.7-10 mcg/kg/hr)
N-dealkylation
C3A4/5
(none)
Morphine
(C-II)
mu-receptor
agonist
5-10 min
3-4 hr
2-4 mg IV Q 1-2 hr
(2-30 mg/hr)
Glucuronidation
(6 & 3-glucuronide metabolite)
Hydromorphone mu-receptor
(C-II)
agonist
5-15 min
2-3 hr
0.2-0.6 mg Q 1-2 hr
(0.5-3 mg/hr)
Glucuronidation
(none)
15-60 hr
IV/PO: 5-40 mg Q6-12
hr
(not recommended)
N-demethylation
CYP3A4/5, 2D6, 2B6, 1A2
(N-demethylated derivative)
Methadone
(C-II)
mu-receptor
agonist,
NMDA
antagonist
Barr J, et al. Crit Care Med. 2013;41(1):263-306.
1-3 days
CONTEXT SENSITIVE HALF LIFE
Hughes MA, et al. Anesthesiology. 1992;76(3):334-41.
ADVERSE EFFECTS
Fentanyl
Morphine
Over sedation in obese,
hepatic dysfunction &
IV continuous infusions
Over sedation in with
renal dysfunction
Hydromorphone
Accumulation with
hepatic impairment
Methadone
QTc prolongation,
torsades de pointes
Withdrawal
Unpredictable
pharmacokinetics
Withdrawal
Hypotension more
common than fentanyl
Bradycardia with larger
doses
Devlin JW, et al. Crit Care Med. 2010;38(6 Suppl):S231-43.
Barr J, et al. Crit Care Med. 2013;41(1):263-306.
Withdrawal
Constipation,
postoperative ileus
Unpredictable
pharmacodynamics in
opiate naïve patients
PHARMACOLOGIC MANAGEMENT OF PAIN
Non-opiates - Route
(Schedule)
Onset
Half-life
Dosing
(maximum daily dose)
Metabolism
(Active metabolite)
Adverse Effects
Acetaminophen - PO
(NS)
30 min
2-4 hr
325-1000 mg Q 4-6 hr
(≤ 4 g/day)
Glucuronidation,
sulfonation
Hepatic dysfunction
Ketamine - IV
(C-III)
30 sec
2-3 hr
Loading dose 0.1–0.5 mg/kg,
then 0.05– 0.4 mg/kg/hr
N-demethylation
(Norketamine)
Hallucinations, emergence
reaction
Ketorolac - IV
(NS)
10 min
2-9 hr
30 mg, then 15–30 mg Q 6 hr
(120 mg/day × 5 days)
Hydroxylation,
conjugation, renal
Renal, gastrointestinal
Ibuprofen - PO
(NS)
25 min
2.5 hr
400 mg Q 4 hr
(2.4 g/day )
Oxidation
Renal, gastrointestinal
n/a
5-7 hr
100 mg TID
(3600 mg/day)
Renal
Sedation, confusion,
dizziness, ataxia
4-5 hr
12-65 hr
50–100 mg BID
(1200 mg/day)
Oxidation
Nystagmus, diplopia,
lethargy, SJS, drug interaction
Gabapentin – PO
(NS)
Carbamazepine – PO
(NS)
Barr J, et al. Crit Care Med. 2013;41(1):263-306.
CAVEATS OF PAIN MANAGEMENT IN ICU
 Opioids are first line in the treatment of
non-neuropathic pain
 No head to head trials to establish first line
opioid agent
 Use a neuropathic agent for neuropathic pain
 Patients on a home opioid regimen
should receive an equivalent regimen
 Consider non-opioid agents to reduce
opioid requirements
Barr J, et al. Crit Care Med. 2013;41(1):263-306.
Equi-Analgesic Opioid Dose (mg)
Opioid
IV
PO
Fentanyl
0.1
-
Hydromorphone
1.5
7.5
Morphine
10
30
-
-
Methadone
SOURCES OF AGITATION IN THE ICU
Sleep deprivation
MV dyssynchrony
Physical restraint
Inability to communicate
Withdrawal from chronic
psychoactive medications
Frustration
Agitation;
unpleasant
awareness
Substance abuse or withdrawal
Noise
Pain
Barr J, et al. Crit Care Med. 2013;41(1):263-306.
Reade MC, et al. N Engl J Med. 2014;370(5):444-54.
Lack of homeostasis:
• Eating
• Drinking
Anxiety
(appropriate or pathologic)
NURSING SEDATION PRACTICE IN MV PATIENTS: US
SURVEY 2010
• Survey mailed to members of the American Association of Critical Care Nurses
Statement
(n = 423)
Disagree/Strongly
Disagree (%)
Neutral (%)
Agree/Strongly
Agree (%)
MV is uncomfortable
1.7
8.1
90.2
MV is stressful
1.7
6.4
91.9
Sedation necessary for patient comfort
1.4
9.7
80.8
All MV patients should be sedated
45.7
21.6
32.7
13
9
78
20.3
19.6
60.1
Broad parameters for sedation orders
Clear communication sedation goals
between RN and MD
Guttormson JL, et al. Intensive Crit Care Nurs. 2010;26(1):44-50.
TOP MYTHS REGARDING SEDATION IN THE ICU
1) All MV ICU patients require sedatives
- Undesirable effects (respiratory depression, ↑ MV, ↑ length of stay (LOS), ↑ ICU delirium)
2) Sedatives help to facilitate sleep in ICU patients
- Propofol and benzodiazepines (BZD) suppress level III & IV sleep patters (REM sleep)
- When used to promote sleep are associated with higher rates of delirium
3) It is easier to care for deeply sedated ICU patients
- Associated with longer MV time, ICU LOS and development of delirium
Peitz GJ, et al. Crit Care Med. 2013;41(9 Suppl 1):S46-56.
GOALS OF AGITATION MANAGEMENT
1.
Develop a structured approach for sedation
2.
Perform patient assessment and optimize the ICU environment
 Restart outpatient medications as appropriate
3.
Regularly perform monitoring and documentation of evaluations
 Establish goals using validated scales
4.
Implement a structured patient-focused management strategy
 Focus first on analgesia, then sedation
 Select sedative based on allergies, organ function, and anticipated duration of therapy
5.
Recognize and take steps to ameliorate analgesic/sedative withdrawal
 Implement a structured strategy to avoid accumulation of medications
Barr J, et al. Crit Care Med. 2013;41(1):263-306.
Sessler CN, et al. Chest. 2008;133(2):552-65.
MONITORING SEDATION IN THE ICU
 The SCCM recommends using the Richmond agitation-sedation scale (RASS) and
Sedation-agitation scale (SAS)
 Most valid and reliable subjective sedation assessments
 Frequency of agitation assessment:
 ≥ 4 times per shift (8 hour) and as needed
Robinson BR, et al. Crit Care Med. 2013;41(9 Suppl 1):S16-29.
Barr J, et al. Crit Care Med. 2013;41(1):263-306.
GOAL LEVEL OF SEDATION IN THE ICU
 Sedatives should be titrated to maintain a light rather than deep level of sedation,
unless clinically contraindicated
 Light sedation: RASS: -2 to 0 or SAS: 4 to 3
 Pharmacologic induced coma (deep sedation) is associated with delirium
Barr J, et al. Crit Care Med. 2013;41(1):263-306.
Kollef MH, et al. Chest. 1998;114(2):541-8.
MONITORING SEDATION IN THE ICU: RASS AND SAS
RASS
Score
Term
Description
+4
Combative
Overtly combative, violent
+3
Very agitated
Removes devices, aggressive
+2
Agitated
Non-purposeful movements
+1
Restless
Anxious, but not vigorous
0
Alert and calm
-1
Drowsy
Sustained awakening by voice
-2
Light sedation
Awakes, eye contact to voice
-3
Moderate sedation
Movement/eyes open to voice
-4
Deep sedation
Movement to physical stimulus
-5
Unable to rouse
No response to voice/physical
stimulus
Ely EW, et al. JAMA. 2003;289(22):2983-91.
Riker RR, et al. Crit Care Med. 1999;27(7):1325-9.
SAS
Score
Term
Description
7
Dangerous
agitation
Pulling at ET tube/catheters, get out of
bed, requires restraints, striking at staff,
thrashing in bed
6
Very agitated
Requiring restraint, frequent verbal
reminding of limits, biting ET tube
5
Agitated
Tries to sit up, calms down in response
to verbal commands
4
Calm and
cooperative
Calm and cooperative, follows
commands
3
Sedated
Awakens to verbal stimuli, follows simple
commands
2
Very sedated
Arouses to physical stimuli, but does not
follow commands
1
Unarousable
No response to noxious stimuli
SELECTION OF SEDATIVE AGENT
 Guidelines suggest using non- BZD sedatives (dexmedetomidine or propofol) over BZD to improve
clinical outcomes in MV patients
 Considerations:
1.
Indication and sedation goal for each patient
2.
Pharmacology of the drug, side effect profile, and patient tolerance
3.
Cost of sedative
4.
Alcohol or BZD withdrawal should be treated with BZD
 A meta-analysis including six trials (n = 1,235) found that non-BZD sedatives compared to BZD were
associated with a shorter ICU LOS (1.62 days; p < 0.05) and duration of MV (1.9 days; p < 0.05)
 No difference in prevalence of delirium or short term mortality
Barr J, et al. Crit Care Med. 2013;41(1):263-306.
Fraser GL, et al. Crit Care Med. 2013;41(9 Suppl 1):S30-8.
SEDATIVE AGENTS
Agent
(Class)
Mechanism
of action
Onset
(IV)
Elimination t ½
(context sensitive ½)
Intermittent dose
(Infusion dose)
Metabolism
Active
metabolite
2–4 mg Q 2 hr PRN
(0.01–0.05 mg/kg/hr)
Hepatic
Yes
Midazolam
(C-V)
GABA
agonist
2–5 min
Lorazepam
(C-V)
GABA
agonist
15–20 min
8–15 hr
0.02–0.04 mg/kg Q 4
hr PRN
Hepatic
No
Propofol
(NS)
GABA
agonist
1–2 min
3–12 hr
(50 ± 18.6 hr)
(5–80 μg/kg/min)
Hepatic
No
α2 agonist
5–10 min
1.8–3.1 hr
(0.2–1.5 μg/kg/hr)
Hepatic
No
Dexmedetomidine
(NS)
Barr J, et al. Crit Care Med. 2013;41(1):263-306.
3–11 hr
ADVERSE EFFECTS OF SEDATIVES
Midazolam
Lorazepam
Propofol
Dexmedetomidine
Respiratory depression,
hypotension
Respiratory depression,
hypotension
Respiratory depression,
hypotension, bradycardia
Bradycardia, hypotension
Accumulation with ESLD,
obesity, prolonged infusions
Propylene glycol-related
acidosis
Delirium?
Delirium?
Withdrawal
Withdrawal
Riker RR, et al. Pharmacotherapy. 2005;25(5 Pt 2):8S-18S.
Devlin JW, et al. Crit Care Med. 2010;38(6 Suppl):S231-43.
Accumulation
hypertriglyceridemia,
pancreatitis, propofol infusion
syndrome
Excipient allergies (egg, soy,
sulfite)
Withdrawal
Accumulation with ESLD
Withdrawal
WITHDRAWAL SYNDROMES FROM SEDATIVES AND
ANALGESICS
 Described following opioid, benzodiazepine and dexmedetomidine infusions

Etiology: development of physiologic dependence, and abrupt discontinuation

Prevalence: 5–33%

Risk factors: high doses, long duration of administration (≥5 days)

Peak symptoms: 6 hours after discontinuation (variable)

Symptoms: central nervous system stimulation, gastrointestinal disturbance, and sympathetic nervous system activation
 Treatment/prevention:

Sedative/analgesics should be weaned over several days in order to reduce the risk of drug withdrawal


Initial dose reductions of 5% to 40% followed by subsequent reductions of 10% once or twice daily
Initiation of enteral medication (clonidine, methadone, benzodiazepine)
Devlin JW, et al. Crit Care Med. 2010;38(6 Suppl):S231-43.
Barr J, et al. Crit Care Med. 2013;41(1):263-306.
Awissi DK, et al. Crit Care Med. 2013;41(9 Suppl 1):S57-68.
PHARMACOECONOMIC ANALYSIS OF SEDATIVES
Dexmedetomidine vs. BZD
(Data pulled from trial)
(n = 366)
Dexmedetomidine vs. Propofol
(Post-op CABG patients)
(n = 84)
Non-BZD vs BZD
(Cost effectiveness Markov
Model - 2012 cost data)
Dasta JF, et al. Crit Care Med. 2010;38(2):497-503.
Thoma BN, et al. Pharmacoeconomics. 2014;32(2):149-57.
Bioc JJ, et al. J Crit Care. 2014;29(5):753-7.
• Dexmedetomidine associated with a median cost savings of $9,679
• Driver of cost reduction is reduced ICU stay and MV duration
• Dexmedetomidine associated with cost savings of $2,613 per patient
• Total MV duration was ≤ 6 hours in 57.1 % vs 16.7 % in the dexmedetomidine
and propofol, respectively
• Drug costs are higher with Non-BZD vs BZD ($1327 vs $65)
• Total ICU costs lower in Non-BZD vs BZD ($35,380 vs $45,394)
SOURCES OF DELIRIUM IN THE ICU
Sedatives
Substance abuse or withdrawal
Withdrawal from chronic
psychoactive medications
Medical comorbidity
Observable and occult
metabolic abnormalities
Neurologic diagnosis
(e.g., head injury)
Delirium
Preexisting mental impairment
Sleep deprivation
Advanced age
Pain
Noise
Severity of illness
Reported incidence of ICU delirium (16-89%)
Zaal IJ, et al. Drugs. 2012.30;72:1457-71.
Barr J, et al. Crit Care Med. 2013;41(1):263-306.
Reade MC, et al. N Engl J Med. 2014;370(5):444-54.
Agitation;
unpleasant
awareness
DELIRIUM
 Diagnostic and Statistical Manual of Mental Disorders-5 (DSM-5) Definition:
1.
Disturbance in attention and orientation to the environment
2.
Disturbance develops over a short period of time
3.
Represents an acute change from baseline
4.
Disturbances in 1 and 3 must not occur in the context of a severely reduced level of arousal (coma)
ICU PRACTITIONER VIEW OF DELIRIUM
Questionnaire
2004
(n = 912)
2009
(n = 1384)
Delirium is a significant or very serious problem
92%
--
Delirium is underdiagnosed
78%
86%
Delirium is routinely screened
40%
59%
An assessment tool is used for identification of delirium
16%
33%
Pharmacologic agent used for treatment
Haloperidol
Lorazepam/benzodiazepines
Atypical antipsychotics
66%
12%
< 5%
86%
35%
40%
Ely EW, et al. Crit Care Med. 2004;32:106-12.
Patel RP, et al. Crit Care Med. 2009;37:825-32.
IMPACT ON ICU PATIENT OUTCOMES
Impact of delirium:
1. ↑ mortality
2. ↑ duration of mechanical ventilation
3. ↑ hospital length of stay (LOS)
4. ↑ cognitive problems
Impact of duration of delirium:
1. ↑ mortality
2. ↑ duration of mechanical ventilation
3. ↑ hospital LOS
4. ↑ cognitive problems
Ely EW, et al. JAMA. 2004;291:1753-62
van den Boogaard M, et al. Crit Care Med. 2012;40:112-8.
Shehabi Y, et al. Crit Care Med. 2010;38:2311-8.
Delirium in the ICU and 6-Month
Survival
IDENTIFICATION OF DELIRIUM IN THE ICU
 Six delirium assessment instruments validated in an ICU population with DSM IV criteria assessed by
psychiatrist
 Evidence based-guidelines recommend:
 Confusion Assessment Method for the Intensive Care Unit (CAM-ICU)
 Intensive Care Delirium Screening Checklist (ICDSC)
Devlin JW, et al. Intensive Care Med. 2007;33:929-40.
Barr J, et al. Crit Care Med. 2013;41:263-306.
Neto AS, et al. Crit Care Med. 2012;40:1946-51.
CAM-ICU SCALE
 Scale is either negative (not delirious)
or positive (delirium present)
 Done every 8-12 hours
 Snapshot of mental status at time of
assessment
 Patients must have features 1 & 2 with
either feature 3 or 4 to score positive
Ely EW, et al. JAMA. 2001;286(21):2703-10.
Devlin JW, et al. Intensive Care Med. 2007;33:929-40.
ICDSC SCALE
Checklist Items
(One point for each positive item)
1) Altered level of consciousness
2) Inattention
3) Disorientation
4) Hallucination, delusion or psychosis
5) Psychomotor agitation
6) Inappropriate speech or mood
7) Sleep/wake cycle disturbance
8) Symptom fluctuation
Ely EW, et al. JAMA. 2001;286(21):2703-10.
Devlin JW, et al. Intensive Care Med. 2007;33:929-40.
 Scale 0 to 8
 Score ≥ 4 identifies delirium
 Done every 8-12 hours
 Assessment of mental status over 8 to 12 hours
SUBTYPES OF DELIRIUM
Positive delirium assessment
Hyperactive Delirium
Mixed Delirium
Hypoactive Delirium
Mixed:
• Prevalence: 6-54.9%
Hyperactive characteristics:
• Agitation (RASS +1 to + 4)
• Associated with hallucinations/delusions
• Prevalence: 1-1.6%
Peterson JF, et al. J Am Geriatr Soc. 2006;54:479-84.
Pandharipande P, et al. Intensive Care Med. 2007;33:1726-31.
Hypoactive characteristics:
• Apathetic, calm or lethargic (RASS -3 to 0)
• Associated with confusion and sedation
• Prevalence: 43.5-64%
RISK FACTORS ASSOCIATED WITH DELIRIUM: SYSTEMATIC REVIEW
Variable
(n = 33 studies included)
High Quality +
Association
Positive
Association
Negative
Association
No
Association
Level of Evidence
Increasing age
9
3
0
3
Strong
Metabolic acidosis
2
1
0
0
Strong
Dementia
2
1
0
0
Strong
Hypertension
2
0
0
0
Strong
APACHE II
5
2
0
2
Strong
Delirium on previous day
2
0
0
0
Strong
Emergency surgery
3
0
0
0
Strong
Coma during ICU
5
0
0
1
Strong
Alcohol use
1
2
0
3
Inconclusive
Benzodiazepines
7
0
1
4
Inconclusive
1
0
0
Strong
Associated with reduced delirium occurrence
Dexmedetomidine
Zaal IJ, et al. Crit Care Med. 2015;43(1):40-7.
3
ALL BZD ADMINISTRATION ASSOCIATED WITH DELIRIUM?
 Large cohort study in single mixed-ICU (n = 1,112)
 Patient’s included if in ICU > 24 hours
 Optimal sedation/delirium practices (light sedation, delirium screening)
 Outcomes:
1. If BZD administration is an independent risk factor for delirium the next day
 Controlled for 16 additional risk factors for delirium
2. Rates of delirium with continuous IV versus intermittent IV BZD
 Results:
 4% (per 5 mg of midazolam) increased risk of delirium the following day with BZD administration (p < 0.001)
 Continuous infusion of BZD associated with delirium (OR 1.04, p < 0.004)
 Intermittent BZD: not associated with delirium (OR 0.97, p = 0.44)
Zaal IJ, et al. Intensive Care Med. 2015 Sep. [Epub ahead of print]
GUIDELINE RECOMMENDATIONS: TREATMENT
 Antipsychotics should not be used prophylactically to prevent delirium
 No data supporting the use of haloperidol to reduce the duration of delirium
 Avoid antipsychotics in patients at risk for torsades de pointes (TdP)
 Atypical antipsychotics may reduce the duration of delirium
 A pilot study (n = 36) of quetiapine demonstrated a 3.5 day reduction in delirium
 No difference in ICU LOS, MV days or mortality
 Delirious patients that require continuous IV sedation can receive dexmedetomidine rather than BZD to
reduce the duration of delirium
 Significant daily reduction (~20%) in delirium
Barr J, et al. Crit Care Med. 2013;41:263-306.
SYSTEMATIC ANALYSIS OF INTERVENTIONS TO TREAT ICU
DELIRIUM
 Analysis of 17 trials (n = 2,849) that evaluated pharmacologic and non-pharmacologic
interventions aimed at reducing delirium
 Intervention groups associated with 0.64 less days of delirium (p = 0.01)
 Mortality was not reduced (p = 0.19)
 Pharmacologic intervention:
 Decreased duration of delirium 0.71 days (p = 0.87)
 Antipsychotics: 0.82 days (p = NS)
 α-2 agonist: 0.59 days (p = NS)
Al-Qadheeb NS, et al. Crit Care Med. 2014;42(6):1442-54.
APPROACH TO MANAGEMENT OF DELIRIUM:
WHAT IS A CLINICIAN TO DO?
Screening for Delirium
Mainly Hyperactive delirium
Treat with antipsychotic and with nonpharmacologic measures
- Self harm (pulling invasive lines, etc.)
- Danger to health care team
Positive assessment
Assess need for
sedative to achieve
a light level of
sedation
Reassess PAD regimen
regularly (every 4 hours)
Reade MC, et al. N Engl J Med. 2014;370(5):444-54.
Negative assessment
Mainly Hypoactive delirium
Treat with non-pharmacologic
measures
- Environmental (quiet room, re-orientation)
- Non-pharmacologic (Physical therapy)
- Removal of deliriogenic medications
NON-PHARMACOLOGIC MANAGEMENT
Removal of unnecessary deliriogenic medications:
• Continuous infusion BZD, corticosteroids, anticholinergics
Bruno JJ, et al. Crit Care Nurs Clin North Am. 2010;22:161-78.
PHARMACOTHERAPY OF HYPERACTIVE DELIRIUM
Drug
(Class)
Haloperidol
(NS)
Antipsychotic
Class
Typical
Route
Dosing for ICU Delirium
PO, IV,
IM
2–10 mg IV Q 20–30 min then
25% of loading dose Q 6 hrs
Duration studied
(days)
Adverse effects
variable
QT prolongation, TdP,
lowers seizure threshold
Olanzapine
(NS)
Atypical
PO
5 mg PO Daily
5
QT prolongation, TdP,
neuroleptic malignant
syndrome (NMS)
Quetiapine
(NS)
Atypical
PO
50 mg PO Q 12 Hrs
10
Agranulocytosis, QT
prolongation, TdP, NMS
Atypical
PO
0.5 mg PO Q 12 Hrs
7
QT prolongation, TdP, NMS
Atypical
PO
40 mg PO Q 6 Hrs
14
QT prolongation, TdP, NMS
Risperidone
(NS)
Ziprasidone
(NS)
Consider discontinuation of antipsychotic at the resolution of delirium
Agents should be discontinued before leaving the ICU
Al-Qadheeb NS, et al. Crit Care Med. 2014;42(6):1442-54.
APPROACH TO PAD IN MV ADULT ICU PATIENTS
Specific indication for sedation
Indication for deeper sedation
No
Yes
No indication for sedation
Ex: Severe respiratory failure with
neuromuscular blockade
Assess pain and treat with opioid
(CPOT, BPS)
No
Target sedative to deep
sedation (RASS, SAS)
Regularly assess the need
for this level of sedation
Yes
Pain Controlled
Yes
Pharmacologic or
non-pharmacologic intervention
Delirium symptoms controlled
Reade MC, et al. N Engl J Med. 2014;370(5):444-54.
No
Assess for delirium
(CAM-ICU, ICDSC)
Delirious
Yes
No delirium
Assess need for sedative medication
to target light sedation
(RASS, SAS)
SUMMARY
 Validated behavioral scores should be used to identify PAD in critically ill
 Pain should be identified and treated first
 Selection of sedative (if needed) should take into consideration depth of sedation needed, adverse effects and
cost
 Analgesics and sedatives should be titrated to target the lowest effective dose of to prevent accumulation,
adverse effects and withdrawal symptoms
 Managing ICU delirium begins with optimizing the patient environment and removing risk factors for delirium
QUESTION 1
CJ is a 55 year old female admitted to the medical ICU for treatment of pneumonia and respiratory failure requiring
intubation. CJ remains MV on day 4 and is unable to verbally communicate. On rounds the medical resident states they
would like to start a fentanyl infusion because the patient is likely to be in pain because they are diaphoretic, tachycardic
and hypertensive. What would be the most valid and reliable approach to assessing if CJ is truly experiencing pain?
A.
Visual analogue scale (VAS) score
B.
Respiratory rate
C.
Behavioral pain scale (BPS) score
D.
Richmond agitation sedation score (RASS) score
QUESTION 2
RL is a 65 year old male admitted to the ICU with septic shock. He required MV secondary to respiratory failure. His
APACHE II score is 35 and past medical history is pertinent for dementia and hypertension. Given the patients baseline
risk factors for developing ICU delirium, the team asks for your recommendation for a sedative that will treat agitation
but have the lowest association for developing ICU delirium. The patient is currently receiving continuous fentanyl IV at
25 mcg/hr. RL has the following PAD scores: CPOT: 1, RASS: +3, ICDSC: 2.
A.
Midazolam IV 2 mg/hr continuous infusion, target RASS: -2 to 0
B.
Lorazepam IV 1 mg/hr continuous infusion, target RASS: -2 to 0
C.
Diazepam 10 mg per tube Q 12 hours, target RASS: -2 to 0
D.
Dexmedetomidine IV 0.2 mcg/kg/hr continuous infusion, target RASS: -2 to 0
QUESTION 3
Which of the following sedative products is a centrally acting, alpha-2 adrenoceptor agonist?
A.
Dexmedetomidine
B.
Propofol
C.
Midazolam
D.
Lorazepam
QUESTION 4
JR is a 45 year old male who presented to the emergency room after sustaining a GSW to the abdomen requiring
emergent exploratory laparotomy. He is post-op day 2 and currently mechanically ventilated. While staffing in the critical
care satellite pharmacy you receive a phone call from JR’s nurse. The nurse states the patient looks extremely
uncomfortable and wants to know how to best intervene. JR’s pain, agitation and delirium medications at this time include
propofol IV continuous infusion at 50 mcg/kg/min. His CPOT is 8, RASS: + 2, and CAM-ICU: negative. His vital signs are
within normal limits. Which of the following interventions below would be the best approach to managing this patient?
A.
Increase propofol dose until a RASS of -2 to 0 is achieved.
B.
Start fentanyl 50 mcg IV push every 30 minutes PRN CPOT ≥ 3.
C.
Initiate quetiapine 50 mg per tube every 12 hours
D.
Discontinue propofol and initiate dexmedetomidine with a goal RASS of -2 to 0.
QUESTION 5
Which of the following sedative agents is classified as a controlled substance under the federal Controlled Substances Act
(CSA):
A.
Dexmedetomidine
B.
Propofol
C.
Midazolam
D.
Etomidate
QUESTION 6
On post-operative day 7 JR remains mechanically ventilated. His PAD regimen currently includes propofol IV continuous
infusion at 10 mcg/kg/min and fentanyl 50 mcg IV push every 30 minutes PRN CPOT ≥ 3. Over the past 24 hours he has
become increasingly agitated and is biting at his endotracheal tube. Despite the medical team optimizing JRs nonpharmacologic therapies, his PAD scores are as follows: CPOT: 2, RASS: + 3, CAM-ICU: Positive. JR’s QTc is currently
within normal limits. Which agent may reduce the duration of delirium in JR based on the findings from a single small
prospective, randomized, double-blind, placebo-controlled study?
A.
Haloperidol
B.
Quetiapine
C.
Olanzapine
D.
Ziprasidone
QUESTIONS?