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Assessment and Treatment of Pain, Agitation and Delirium in the Mechanically Ventilated ICU Patient - Adult - Inpatient

Assessment and Treatment of Pain, Agitation and Delirium in the Mechanically Ventilated ICU Patient - Adult - Inpatient - Clinical Hub, UW Health Clinical Tool Search, UW Health Clinical Tool Search, Clinical Practice Guidelines, Pain and Sedation


1
Assessment and Treatment of Pain, Agitation,
and Delirium in the Mechanically Ventilated
Intensive Care Unit Patient – Adult - Inpatient
Clinical Practice Guideline
Note: Active Table of Content- Click to follow link
EXECUTIVE SUMMARY ............................................................................................................................ 2
SCOPE ........................................................................................................................................................ 4
METHODOLOGY ....................................................................................................................................... 5
INTRODUCTION......................................................................................................................................... 6
RECOMMENDATIONS .............................................................................................................................. 6
UW HEALTH IMPLEMENTATION........................................................................................................... 16
REFERENCES.......................................................................................................................................... 17
Contact for Changes: Contact for Content:
Name: Philip J Trapskin, PharmD, BCPS Name: Carin Endres, PharmD, BCPS
Phone Number: 263-1328 Phone Number: 265-8160
Email Address: ptrapskin@uwhealth.org Email Address:cendres2@uwhealth.org
Guideline Author(s): Jeffrey Fish, PharmD, BCPS; Ryan Draheim, PharmD;
Coordinating Team Members: Jeffrey Fish, PharmD, BCPS, Carin Endres, PharmD, BCPS,
Review Individuals/Bodies: Jeffrey Wells, MD, Pierre Kory, MD, Jonathon Ketzler, MD, Anne
O’Connor, MD, Josh Medow, MD, MS, Anna Krupp, RN, MS, CCNS, CCRN, Michelle Thoma, PharmD,
BCACP, Ryan Draheim, PharmD, Linda Stevens, DNP, RN-BC, CPHQ, CSPHP, Emily Wilhelmson,
MSN, RN, Peggy Riley MN, MPH, RN
Committee Approvals/Dates:
TLC QI Committee – August 2015
Critical Care Committee – August 2015 (Interim revisions August 2016)
UW Health Pharmacy and Therapeutics Committee (Last Periodic Review: September 2015)
ξ Interim revisions (August 2016, July 2017)
Release Date: October 2016 Next Review Date: September 2018
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2
Executive Summary
Guideline Overview
This guideline describes the use of medications for the treatment of pain, agitation and delirium
in mechanically ventilated adult patients admitted to an intensive care unit.

Key Practice Recommendations
1. Pain
1.1 Assessment
1.1.1 Pain should be assessed in the adult ICU setting using validated pain
assessment tools (pain intensity scale or critical care pain observation tool
[CPOT]) (Class I, Level B)
1.2 Treatment
1.2.1 Non-pharmacologic interventions may be reasonable to help alleviate pain
(Class IIa, Level C)
1.2.2 Intravenous opioids are indicated as first-line therapy to treat non-neuropathic
pain in ICU patients (Class I, Level B)
1.2.3 Use of non-opioid analgesics is reasonable, if appropriate, in order to
decrease opioid requirements, or to reduce opioid-related adverse effects
(Class IIa, Level C)
1.2.4 A goal CPOT of ≤ 2 is recommended for most ICU patients (Class I, Level
B).

2. Agitation
2.1 Assessment
2.1.1 Agitation should be assessed by using the Richmond Agitation Sedation
Scale (RASS) (Class I, Level B)
2.2 Treatment
2.2.1 Analgesia-first sedation is recommended in adult ICU patients who are
mechanically ventilated (Class I, Level B)
2.2.2 Bolus injections are recommended in preference to continuous infusions. The
sedative agent of choice for bolus dosing is midazolam. (Class I, Level C)
2.2.3 Continuous infusion sedation strategies using non-benzodiazepine sedatives
may be reasonable to choose over sedation with benzodiazepines in
mechanically ventilated adult ICU patients. (Class IIa, Level B)
2.2.4 A goal RASS score of -1 to +1is recommended for most ICU patients (Class
I, Level B)

3. Delirium
3.1 Assessment
3.1.1 ICU patients should be routinely assessed for the presence of delirium using
the Confusion Assessment Method for the ICU (CAM-ICU) (Class I, Level A)
3.2 Prophylaxis
3.2.1 Non-pharmacologic therapies should be attempted to reduce the incidence of
delirium (Class I, Level B)
3.3 Treatment
3.3.1 Pharmacologic agents may be considered to reduce the duration of delirium
(Class IIb, Level C)

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3
4. Continuous infusion titration
4.1 Continuous infusion rate adjustments should be performed in accordance with the
Pain, Agitation and Delirium Infusion Titration Practice Protocol – Adult – Inpatient
(Class I, Level B)

5. Analgesic-specific guidelines
5.1 Fentanyl and hydromorphone are the recommended bolus analgesics for most
patients (Class I, Level C)

6. Sedative-specific guidelines
6.1 The Richmond Agitation Sedation Scale (RASS) is recommended as the therapeutic
target for the infusion of sedative agents (Class I, Level B)
6.2 Midazolam is the preferred bolus sedative in most patients not on a continuous
infusion sedative (Class I, Level C)
6.3
7. Spontaneous awakening trial (SAT)
7.1 Daily interruption of analgesic and / or sedative infusions should occur on all patients
when ordered by the provider (Class I, Level B)
7.2 If the patient passes the SAT, the patient will should be transitioned to a
spontaneous breathing trial (SBT) in coordination with respiratory therapy (RT)
(Class I, Level B)

Companion Documents
Spontaneous Awakening Trial (SAT) Practice Protocol – Adult – Inpatient
Pain, Agitation and Delirium Infusion Titration Practice Protocol – Adult – Inpatient
IP – Pain Agitation Delirium – Intermittent Doses – Adult – ICU – Supplemental [4626]
IP – Pain Agitation Delirium – Infusions – Adult – ICU – Supplemental [4631]

Pertinent UWHC Policies & Procedures
UWHC Administrative Policy 8.38: UWHC Adult Sedation Policy

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4
Scope
Clinical Specialty:
This guideline may be used by any prescriber treating an adult patient for pain, agitation,
and/or delirium in the intensive care unit.

Intended Users:
Physicians, Pharmacists, Registered Nurses, and Advanced Practice Providers

Objective(s):
The objective of this guideline is to demonstrate and describe how a nurse will treat pain,
agitation and delirium in critically ill patients based upon patient assessment criteria.
Additionally, this guideline will help to identify patients meeting clinical criteria for conducting a
spontaneous awakening trial (SAT) and spontaneous breathing trial (SBT), and presents the
process for carrying out the SAT.

Target Population:
Mechanically ventilated adult critical care patients

Interventions and Practices Considered:
This guideline contains strategies for the assessment and management of pain, agitation, and
delirium in mechanically ventilated, critically ill adult patients. It outlines medications and
dosing recommendations, and also provides information about spontaneous awakening trials.

Major Outcomes Considered:
The major outcomes considered in this guideline are appropriate treatment of pain, providing
adequate sedation, and to address delirium. Efficacy and safety are measured by tracking the
duration of time on mechanical ventilation, and length of stay in the intensive care unit and in
the hospital, respectively.

Guideline Metrics
Treatment therapies will be periodically reviewed to determine guideline compliance, the
addition of new literature, and cost considerations. Patient Safety Net events (PSNs) related to
pain, agitation and delirium treatment are reviewed throughout the year.
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5
Methodology
Methods Used to Collect/Select the Evidence:
The guidelines are based on the Society of Critical Care Medicine (SCCM) guidelines for the
management of pain, agitation and delirium in adult patients in the ICU1, a review of the
relevant literature since the guidelines were released, discussions with internal experts,
consensus based recommendations and the GRADE rating scale.

Rating Scheme for the Strength of the Evidence and Recommendations:
A modified Grading of Recommendations Assessment, Development, and Evaluation
(GRADE) developed by the American Heart Association and American College of Cardiology
was used to assess the Quality and Strength of Evidence in this Clinical Practice Guideline.2




Methods Used to Formulate the Recommendations:
Recommendations were based on strength of evidence and clinical expert consensus.
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6
Introduction
Patients admitted to the intensive care unit (ICU) often require medications for pain, sedation
and delirium to maintain comfort with mechanical ventilation. Optimizing the use of these
medications, in conjunction with spontaneous awakening trials (SAT) and spontaneous
breathing trials (SBT), has been shown to decrease ICU and hospital length of stay, and
improve patient clinical outcomes.3
Recommendations
1. Pain1
1.1 Assessment4-11
1.1.1 ICU patients commonly experience both procedural and non-procedural pain,
whether at rest or during routine cares. Pain should be assessed in the adult
ICU setting by using validated pain assessment tools (Class I, Level B)
1.1.1.1 In patients who are able to self-report, pain should be assessed by
using a pain intensity scale (e.g. 0-10). (Class I, Level C)
1.1.1.2 In patients who are unable to self-report, presence of pain should be
assessed by using the Critical-Care Pain Observation Tool (CPOT)
(Class 1, Level C)
1.1.1.3 Monitor ongoing effectiveness of the current pain management
modalities. . The reassessment of pain is ongoing. Response to pain
interventions is reassessed in a manner appropriate to the route and
method of pain control (Table 1). Pain reassessment should be
documented per UWHC Clinical Policy 8.76, Pain Management, and prior
to each pain treatment intervention.
1.1.2 Vital signs should not be used alone to assess pain in ICU patients (Class III,
Level C), but may be reasonable as a cue to begin further reassessment of
pain. (Class IIb, Level C).
1.2 Treatment (Tables 1 and 2)
1.2.1 Non-pharmacologic interventions, such as music therapy, relaxation
techniques, repositioning, heat and cold, may be reasonable to help alleviate
pain.1 (Class IIb, Level C)
1.2.2 Intravenous opioids are indicated as first-line therapy to treat non-neuropathic
pain in ICU patients12-29(Class I, Level B)
1.2.2.1 See table 2 for recommended dosing (Class I, Level B).
1.2.2.2 Medications
1.2.2.2.1 Fentanyl
1.2.2.2.2 Hydromorphone
1.2.2.2.3 Morphine
1.2.2.2.3.1 Not recommended in renal dysfunction due to risk for
metabolite accumulation or with hemodynamic instability due to
potential for histamine release and worsening hemodynamics.
(Class III, Level C)
1.2.2.3 Bolus dosing regimens
1.2.2.3.1 Low: may be considered in patients at risk for adverse reactions
due to higher doses (Class IIb, Level C)
1.2.2.3.1.1 Elderly (Age >65)
1.2.2.3.1.2 Patients with renal and / or liver dysfunction
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7
1.2.2.3.2 Standard: reasonable in most patients not at increased risk of
adverse reactions (Class IIa, Level C)
1.2.2.4 Range order dosage choice (Class IIa, Level C)
1.2.2.4.1 Patient should be assessed as to whether they have received
opioids in the past or have an indication for needing a higher
starting dose (ie post-operative or acute trauma)
1.2.2.4.2 If patient is assessed to be opioid naïve or not have an indication to
need a higher starting dose, provide the lowest dose in the range
first
1.2.2.4.3 If patient has received opioids in the past or has an indication for
needing a higher starting dose, give the previous equivalent dose
or a dose higher than the lowest dose in the range, whichever is
higher
1.2.2.4.3.1 If the pain score remains the same / increases or if the
patient self-reports continued pain, continue to increase the
dose within the dosing range until maximum dose in range is
achieved
1.2.2.4.3.2 If pain persists after administration of three increasing opioid
boluses in one hour, initiation of a continuous infusion of the
opioid may be considered
1.2.3 It may be reasonable for a provider to order a continuous opioid infusion and
forgo the initial trial of bolus doses, based on the patient presentation and
clinical judgment (Class IIb, Level C)
1.2.4 Use of non-opioid analgesics is reasonable, if appropriate, in order to
decrease opioid requirements, or to reduce opioid-related adverse effects
(Class IIa, Level C)
1.2.4.1 Gabapentin in addition to IV opioids may be considered for the
treatment of neuropathic pain17,25 (Class IIb, Level C)
1.2.5 Pre-emptive opioids are reasonable to be administered prior to invasive and
potentially painful procedures (e.g. chest tube removal) (Class IIa, Level C)
1.2.6 In patients on continuous infusions at goal pain assessment, an attempt
should be made every shift to decrease the infusion rate by the “Titration
Dose to Achieve Goal” in table 2 (Class I, Level C)

Table 1. Pharmacokinetic Parameters and Common Adverse Effects of Sedatives,
Analgesics, and Antipsychotics1,30,31
Drug Onset Duration T 1/2 Primary Route of Elimination Noteworthy Adverse Effects
Dexmedetomidine 5-10 minutes 2-4 hours 2-3
hours
Hepatic CYP2A6
metabolism to inactive
metabolites, and direct
glucuronidation. Renal
elimination of inactive
metabolites.
Rapid infusion can cause hypertension
and bradycardia.
Continuous infusions may cause
bradycardia or hypotension.
Caution in patients with low volume,
heart rate and blood pressure.
Fentanyl < 1 minute
30-60 minutes;
extended with
prolonged infusions
2-4
hours
Hepatic CYP 3A4
metabolism to inactive
metabolites. 10%
excreted unchanged in
urine.
Chest wall rigidity with high doses.
Prolonged sedation with continuous
infusions and obesity and/or renal
dysfunction.
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8
Drug Onset Duration T 1/2
Primary Route of
Elimination Noteworthy Adverse Effects
Hydromorphone 3-5 minutes
4-5 hours; extended
with prolonged
infusions
2-3
hours
Hepatic glucuronidation
to inactive metabolites.
7% excreted unchanged
in urine.
Rare hypotension.
Midazolam 3-5 minutes
30-90 minutes;
extended with
prolonged infusions
2-6
hours
Hepatic CYP3A4
metabolism to active
metabolites. 50% of
metabolites excreted in
urine.
Prolonged sedation with infusions, drug
accumulation in obese patients or
patients with hepatic and/or renal
insufficiency.
Morphine 5 minutes
4-5 hours; extended
with prolonged
infusions
3-5
hours
Hepatic glucuronidation
to some active
metabolites. Renal
elimination of active
metabolites as well as
small amount of
unchanged drug.

Metabolites accumulate in renal
insufficiency causing additional
prolonged sedation. Histamine release
can result in hypotension.
Propofol <1 minute
10 minutes; extended
with prolonged
infusions
26-32
hours
Hepatic CYP2B6
metabolism and
unknown extrahepatic
mechanisms to inactive
metabolites. Renal
elimination of inactive
metabolites.
Propofol infusion syndrome,
hypotension, hypertriglyceridemia,
metabolic acidosis, elevated creatinine
kinase.

Drug Onset Duration T 1/2
Primary Route of
Elimination Noteworthy Adverse Effects
Haloperidol 30-60 minutes 6 hours 14-18
hours
Hepatic glucuronidation,
and CYP 3A4
metabolism to inactive
metabolites. 15% fecal
elimination.
QTc prolongation, extrapyramidal
symptoms, caution with other
medications that inhibit CYP3A4
metabolism, neuroleptic malignant
syndrome, avoid in Parkinson’s disease.
Quetiapine
(only available orally)
Unknown, reaches
peak concentration
in 2 hours
Unknown,
approximately 12
hours
9-12
hours
Hepatic CYP3A4
metabolism to active and
inactive metabolites.
75% metabolites
excreted in urine. 20%
fecal elimination.
QTc prolongation, extrapyramidal
symptoms, caution with other
medications that inhibit CYP3A4
metabolism, neuroleptic malignant
syndrome.
Olanzapine
(only available orally)
Unknown, reaches
peak concentration
in 6 hours
Unknown 21-54
hours
Hepatic CYP1A2 and
CYP2D6 metabolism to
inactive metabolites.
50% metabolites
excreted in urine, 30%
fecal elimination
QTc prolongation less than quetiapine,
extrapyramidal symptoms, caution with
other medications that inhibit CYP1A2
and CYP2D6 metabolism, neuroleptic
malignant syndrome.




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9
Table 2. Opioid Dose Titration Table1,30,31 (Class I, Level B)

Drug Recommended
Bolus Dosea,b
Recommended
Maintenance
Infusion Rangeb
Recommended
Initial Rate of
Infusionb
Titration Dose
to Achieve
Goalc
Rate of
Maintenance
Infusion
T itration

First Notification
Value
(provider must
be notified when
parameter
reached)

Second
Notification
Value
(MD must be
notified when
parameter
reached, order
needed to
exceed dose)
Fentanyl
Lowd: 12.5-
50mcg q15min
prn
Standard: 25-
100mcg q15min
prn
25-200 mcg/hr 25-50 mcg/hr 25 mcg/hr 15 minutes 100 mcg/hr 200 mcg/hr RR < 10
Hydromorphone
Low: 0.1-0.4mg
q15min prn
Standard: 0.4-
1mg q15min prn
0.2-2 mg/hr 0.2-0.4 mg/hr 0.2 mg/hr 15 minutes 1.5 mg/hr 2 mg/hr
RR < 10
Morphine
Low: 0.5-2mg
q15min prn
Standard: 1-4mg
q15min prn
1-10 mg/hr 1-2 mg/hr 1 mg/hr 30 minutes 6 mg/hr

10 mg/hr
RR < 10

a For bolus dosing recommendations see section 1.2.2.4 and 2.2.2.1
b Opioid tolerant patients and patients assessed to have a higher need (ie post-operative and trauma) may require
higher doses. If unclear as to which dose to initiate, consult with unit pharmacist or provider.
c
May need to hold infusion or titrate slower in hypotensive patients
d
Use Low bolus dose in patients who are considered to be at risk for adverse reactions with higher doses (i.e.
Elderly (Age >65) and/or patients with renal and / or liver dysfunction))

2. Agitation1
2.1 Assessment
2.1.1 Agitation should be assessed by using the Richmond Agitation Sedation
Scale (RASS), which has been shown to be a reliable tool in assessing depth
of sedation32-36(Class I, Level B)
Monitor ongoing effectiveness of the current agitation management
modalities. The reassessment of agitation is ongoing. Response to
interventions is reassessed in a manner appropriate to the route and method
of agitation control (Table 3). Agitation reassessment should be documented
per Inpatient Nursing Documentation Requirements, and prior to each pain or
agitation treatment intervention.
2.1.2 It is reasonable to identify and treat potential underlying causes of agitation
prior to administering medications. These include pain, delirium, hypoxemia,
hypoglycemia, hypotension and / or withdrawal from alcohol or other
medications/substances (Class IIa, Level C)
2.2 Treatment (Tables 1,2, 3)
2.2.1 Analgesia-first sedation is recommended in adult ICU patients who are
mechanically ventilated37-40(Class I, Level B)
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10
2.2.1.1 Opioid boluses and infusions may be titrated to RASS scores of -1
to +1 (unless provider has specified a RASS goal), if being used for
sedation (Class IIa, Level B)
2.2.2 Bolus injections are recommended in preference to continuous infusions. The
agent of choice for sedative bolus injections is midazolam. (Class I, Level C)
2.2.2.1 Bolus dosing regimens
2.2.2.1.1 Low: may be considered in patients at risk for adverse reactions
due to higher doses (Class IIb, Level C)
2.2.2.1.1.1 Elderly (Age >65)
2.2.2.1.1.2 Patients with renal and / or liver dysfunction
2.2.2.1.2 Standard: reasonable in most patients not at increased risk of
adverse reactions (Class IIa, Level C)
2.2.2.2 Range order dosage choice (Class IIa, Level C)
2.2.2.2.1 If the patient’s RASS score is 1 or 2, provide the lowest dose in
range first
2.2.2.2.2 If the patient’s RASS score is 3 or 4, start with a higher dose in the
range first
2.2.2.2.2.1 If the RASS score remains the same / increases, continue to
increase the dose within the dosing range until maximum dose
in range is achieved
2.2.2.2.2.2 If agitation persists after administration of three increasing
boluses in 1 hour, initiation of a continuous infusion of an opioid,
propofol, dexmedetomidine, or midazolam is reasonable
2.2.2.3 For patients requiring frequent neurologic exams, initial use of propofol
or dexmedetomidine infusions may be considered (see 2.2.4) (Class IIb,
Level C)
2.2.2.4 A provider may consider ordering a continuous infusion and forgo the
initial trial of at least three boluses, based on the patient presentation
and clinical judgment (Class IIb, Level C)
2.2.3 Continuous infusion sedation strategies using non-benzodiazepine sedatives
may be reasonable to choose over sedation with benzodiazepines in
mechanically ventilated adult ICU patients41-59 (Class IIa, Level B)
2.2.3.1 Sustained use of continuous infusion benzodiazepine sedatives may be
associated with adverse clinical outcomes (e.g. prolonged dependence
on mechanical ventilation, increased ICU length of stay, and the
development of delirium41,42,46-54
2.2.4 Suggested choice of sedative agent for continuous infusions
2.2.4.1 Propofol: first-line (Class IIa, Level C)
2.2.4.2 Dexmedetomidine: second-line (Class IIa, Level C)
2.2.4.3 Midazolam infusion: third-line (Class IIa, Level C)
2.2.4.3.1 Continuous infusions of midazolam should be reserved for
patients who cannot tolerate propofol, or do not achieve goal
sedation with dexmedetomidine (Class I, Level C)
2.2.5 See table 3 for recommended dosing (Class I, Level B)
2.2.6 A goal RASS score of -1 to +1 is recommended for most ICU patients, unless
a deeper level of sedation is required due to a patient-specific clinical
scenario. Lighter levels of sedation have been shown to decrease ventilator
and ICU length of stay, and improve clinical outcomes3,60-71 (Class I, Level B)
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11
2.2.6.1 In patients at goal RASS score, an attempt should be made every
shift to decrease the infusion rate by the “Titration Dose to Achieve
Goal” in table 2 and 3 (Class I, Level C)
2.2.7 A spontaneous awakening trial should be attempted daily in patients who
meet inclusion criteria3,61,72-74 (Class I, Level B)
2.2.7.1 See section 7. Spontaneous Awakening Trial

Table 3. Sedative Agent Dose Titration Table1,30,31 (Class I, Level B)
Drug Recommended
Bolus Dosea
Recommended
Maintenance
Infusion Range
Recommended
Initial Rate of
Infusiona
Titration
Dose to
Achieve
Goala
Rate of
Maintenance
Infusion
T itration
First
Notification
Value
(provider
must be
notified
when
parameter
reached)

Second
Notification
Value
(MD must be
notified when
parameter
reached, order
needed to
increase dose)
Dexmedetomidine

0.5-1 mcg/kg over at
least 10min if HR
>70, MAP >70 and
RASS >2
0.2-1.5 mcg/kg/hr 0.2-0.4 mcg/kg/hr
0.1-0.2
mcg/kg/hr 5-15 min
1.1
mcg/kg/hr
1.5 mcg/kg/hr

HR < 60 bpm
SBP ≤ 90
mmHg
MAP < 60
mmHg
Propofol 0.3-0.5 mg/kg
10-70 mcg/kg/min
(most ICU
patients)

5-50 mcg/kg/min
(neurosurgery ICU
patients)
10-20
mcg/kg/min
10-20
mcg/kg/min 10 min
50
mcg/kg/min
70 mcg/kg/min

SBP ≤ 90
mmHg
MAP < 60
mmHg
Midazolam
Lowb: 0.5-2mg
q15min prn
Standard: 1-4mg
q15min prn
1-10 mg/hr 1-2 mg/hr 1-2 mg/hr 30 min 4 mg/hr 10 mg/hr
a Patients with RASS scores of 3 or 4, may need the higher dose to achieve their sedation goal
b
Use Low bolus dose in patients who are considered to be at risk for adverse reactions with higher doses (i.e.
Elderly (Age >65) and/or patients with renal and / or liver dysfunction)) If unclear as to which dose to
initiate, consult with unit pharmacist or provider.


3. Delirium1
3.1 Assessment
3.1.1 Delirium has been associated with increased hospital length of stay and
mortality. ICU patients should be routinely assessed for the presence of
delirium75-87 (Class I, Level B)
3.1.2 Delirium should be assessed by using the Confusion Assessment Method for
the ICU (CAM-ICU) tool every shift and as needed with changes in the
patient’s mental status88-92 (Class I, Level A)
3.2 Prophylaxis
3.2.1 Non-pharmacologic therapies such as early mobilization, frequent orientation,
and facilitating sleep-wake cycles should be attempted in order to reduce the
incidence and duration of delirium93,94 (Class I, Level B)
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12
3.2.2 Antipsychotics should not be used for prevention of delirium (Class III, Level
C)
3.2.3 Dexmedetomidine should not be used for the prevention of delirium due to
lack of evidence for benefit (Class III, Level C)
3.3 Treatment (Tables 1 and 4)
3.3.1 Pharmacologic agents may be considered to reduce the duration of delirium
(Class IIb, Level C)
3.3.1.1 Quetiapine or olanzapine: reasonable for hyperactive or hypoactive
delirium (Class IIa, Level C)
3.3.1.2 Haloperidol: reasonable for acute hyperactive delirium requiring
rapid treatment (Class IIa, level C)
3.3.1.3 Caution is reasonable when using these agents in patients on other
medications that prolong the QT interval, Parkinson’s disease
and/or a history of neuroleptic malignant syndrome (Class IIb,
Level C)
3.3.1.4 Patients should be assessed daily for continuing need of
antipsychotics for delirium (Class I, Level C)
3.3.2 If delirium is present, dexmedetomidine is reasonable to choose over
continuous infusion midazolam in order to reduce the duration of
delirium52,95,96 (Class IIa, Level B)

Table 4. Dosing recommendations for agents used for delirium1,30,31 (Class I, Level B)
Drug Recommended Route
Recommended
PRN Dosage
Recommended
Starting
Scheduled
Dosagea
Titration
Dose to
Achieve
Goal
Rate of
Titration
Recommended
Maximum Dose
Haloperidol IV 1.5-5 mg every
1-4 hours prn
1-2 mg every 4
hours
Double
dose
Every
30-60
minutes
40 mg/dose
200 mg/day
Quetiapine Oral 25-50 mg every 8-12 hours prn 25-50 mg BID 25-50 mg Daily
100 mg/dose
300 mg/day
Olanzapine Oral 5 mg every 12-24 hours prn
2.5-5 mg 2
times daily 5 mg Daily
10 mg/day
20 mg/day
a
Use higher dose for patients with severe hyperactive delirium. If unclear as to which dose to initiate, consult with
unit pharmacist or provider.


4. Continuous Infusion Titration1,4,5
4.1.1 4. The continuous infusion(s) should be initiated at the “Recommended
Initial Rate of Infusion” from table 2-3 or at the current rate if the patient is
already on an infusion (Class I, Level B).
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4.1.1.1 A bolus dose prior to initiating the infusion is reasonable per
the “Recommended Bolus Dose” from table 2-3 (Class IIa, Level B
4.1.2 If the patient is currently having or is anticipated to have acute pain and /
or agitation, the nurse should bolus the patient up to three times in a 4
hour period per the “Recommended Bolus Dose” from table 2-3 before
increasing the infusion (Class I, Level C). This is to prevent excessive
escalation of infusions when the patient may only require as needed
administration in order to regain appropriate sedation and / or pain levels.
4.1.3 The rate and frequency of dose titration is dependent upon the patient’s
individual parameters, clinical status, and response to therapy, but should
not occur more frequently than indicated in the “Titration Dose to Achieve
Goal” and the “Rate of Maintenance Infusion Titration “ in Table 2-3
(Class III, Level C).
4.1.4 If the patient is over sedated based on the sedation score goal and not
experiencing moderate to severe pain, then the infusion rate can be
decreased by the “Titration Dose Increment” and “Rate of Dose Titration”
in Table 2-3 if both of the following criteria are met (Class I, Level C):
4.1.4.1 ≤ 3 PRN sedative or analgesic doses have been given within the
last 8 hours (other than bolus doses for painful procedures or
cares)
4.1.4.2 The infusion rate has not changed in the previous 4 hours

5. Analgesic-specific guidelines
5.1 Fentanyl and hydromorphone are the recommended bolus opioids in preference to
alternative agents for most patients (Class I, Level C)
5.1.1 Morphine is an alternative opioid option, however it should not be used for
patients with renal dysfunction (Class IIa, Level C)
5.1.2 See table 2 for recommended dosing of opioids (Class I, Level B)
5.2 Pre-emptive opioids are recommended to be administered prior to invasive and
potentially painful procedures to alleviate pain (Class I, Level C)
5.3 Other behaviors or change in function may represent pain for patients who are
unable to self-report presence of pain. Downward titration of opioids may be
considered in the setting of reduction in behaviors or improvement in function in
conjunction with pain scale scores (Class IIb, Level C).

6. Sedative-specific guidelines
6.1 The Richmond Agitation Sedation Scale (RASS) is recommended as the
therapeutic scale for the use of sedative agents 32-36 (Class I, Level B)
6.2 Propofol should not be used in non-mechanically ventilated patients (Class III,
Level C)
6.3 The following laboratory markers should be monitored every 2-3 days in order to
assess for propofol side effects: triglycerides, creatinine kinase, and lactate (Class
I, Level C)
6.4 Midazolam is the preferred bolus sedative in most patients not on a continuous
infusion sedative (Class I, Level C)

7. Spontaneous Awakening Trial (SAT)1,3,60,97
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7.1 Daily interruption of analgesic and / or opioid infusions should occur on all patients
if patient passes safety screen, perform spontaneous awakening trial (Class I,
Level B)
7.2 Registered Nurses should determine if it is safe to perform a spontaneous
awakening trial using the following SAT safety screening questions97 (Class I,
Level B)
7.2.1 Is patient receiving a sedative infusion for active seizures?
7.2.2 Is patient receiving a sedative infusion for alcohol withdrawal?
7.2.3 Is patient receiving a sedative infusion in attempt to control intracranial
pressure?
7.2.4 Is patient receiving paralytic agent?
7.2.5 Is the patient’s RASS > 2?
7.2.6 Is there documentation of myocardial ischemia in the past 24 hours?
7.2.7 Is the patient undergoing induced hypothermia post-cardiac arrest?
7.2.8 Is the patient undergoing withdrawal of life support?
7.2.9 Was the patient a difficult intubation?
7.3 If YES to one or more of 7.2.1-7.2.9, do not proceed to SAT and re-evaluate in 24
hours97 (Class I, Level B)
7.4 If NO to all of 7.2.1-7.2.9, continue with SAT. It is recommended to coordinate the
daily spontaneous awakening trial with the spontaneous breathing trial97 (Class I,
Level B)
7.5 To perform the SAT, the nurse should turn off both the sedative and opioid infusions
(Class I, Level B)
7.5.1 If the patient experiences acute pain during the SAT, bolus doses from the
opioid infusion per the “Recommended Bolus Dose” in table 2 are
reasonable (Class IIa, Level B)
7.6 The SAT will be terminated if the patient meets any of the following termination
criteria97 (Class I, Level B)
7.6.1 RASS score >2 for 5 minutes or longer
7.6.2 Pulse oximetry reading < 88% for 5 minutes or longer
7.6.3 Respiration rate > 35 breaths/minute for 5 minutes or longer
7.6.4 New cardiac arrhythmia
7.6.5 Intracranial pressure > 20 mmHg
7.6.6 Two or more of the following symptoms of respiratory distress: heart rate
increase of > 20 beats/minute, heart rate < 55 beats/minute, use of
accessory muscles, abdominal paradox, diaphoresis or dyspnea
7.7 If the SAT is terminated, the sedative and / or opioid infusion(s) should be restarted
at half the previous rate and will be re-titrated to goal pain assessment and sedation
score per the Pain, Agitation, and Delirium Continuous Infusion Titration Practice
Protocol – Adult – Inpatient3,60,97 (Class I, Level B)
7.8 If the patient passes the SAT, the patient should be transitioned to a spontaneous
breathing trial (SBT) in coordination with respiratory therapy (RT)60,97 (Class I, Level
B)
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7.8.1 If infusions remain off for > 24 hours, the pharmacist should change the
infusions back to “as needed” in HealthLink per (Class I, Level C)
7.9 If the patient fails the SBT or is not deemed to be appropriate for extubation for other
reasons, then the nurse should manage infusion(s) based upon the following
criteria3,60 (Class I, Level B)
7.9.1 If at goal pain assessment and / or sedation score: continue with infusion(s)
off. (Class I, Level B)
7.9.1.1 If infusions remain off for > 24 hours, the pharmacist should change the
infusions back to “as needed” in HealthLink.(Class I, Level C)
7.9.2 If not at goal pain assessment and / or sedation score: Use up to 3 boluses of
the opioid and sedative from the infusions per table 2 and 3 to maintain goals.
If unable to maintain at goals with boluses, restart the infusion(s) at half the
previous rate and titrate to goal pain assessment and sedation score per the
“Pain, Agitation, and Delirium Continuous Infusion Titration Practice Protocol
– Adult – Inpatient” (Class I, Level B)
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UW Health Implementation
Potential Benefits1:
1. Pain assessment and treatment are associated with a reduction in ICU length of stay and
duration of mechanical ventilation.
2. Maintaining lighter levels of sedation are associated with shorter duration of mechanical
ventilation and a shorter length of ICU length of stay.
3. Decreasing use and amount of benzodiazepines may be associated with a decreased incidence
of delirium.
4. Protocolizing management of pain, agitation, and delirium in mechanically ventilated patients
lessens complications associated with inadequate or inappropriate therapy.
5. Standardizing titration of analgesic and sedative infusions will lead to more consistent patient
care.
6. Conducting spontaneous awakening trials is associated with decreased length of mechanical
ventilation, ICU length of stay, post-traumatic stress disorder, and mortality.
7. Potential higher medication costs will be offset by earlier extubation and decreased ICU length
of stay.

Potential Harms1:
1. Potential of complications (i.e., increased self-extubations, increased line removal) from lighter
levels of sedation and spontaneous awakening trials.
2. If more dexmedetomidine is used, a higher cost of medications.

Implementation Plan
1. Guideline will be housed on U-Connect
2. Release of the guideline will be advertised in the Clinical Knowledge Management Corner within
the Best Practice newsletter

Implementation Tools
1. Implementation Tools, Education Plan and Compliance:
1.1. To ensure that the CPG is implemented effectively, nurses will receive unit-based training
of the CPG. Training will include an overview of the CPG and completion of assessments
using the approved assessment tools.
2. Health Link Integration:
2.1. Two order sets have been developed in alignment with this CPG to facilitate and ensure
that the CPG is followed accordingly. In addition, the assessment tools have been built
into flowsheets with Health Link to simplify nursing documentation and to provide effective
reports that will be used to monitor outcomes.
3. Evaluating use and utility of CPG:
3.1. To monitor usage of the CPG, usage of the order sets will be monitored. In addition, two
reports will be created to monitor pain, delirium, and sedation scores. One of these reports
will be run daily so that the clinical nurse specialist can monitor completion of patient
assessments per the CPG. Another report will be run monthly to track sedation goals.
Other reports including sedation costs, sedation usage, and length of stay reports will be
utilized to trend and monitor quality outcomes after implementation of the CPG.

Disclaimer
CPGs are described to assist clinicians by providing a framework for the evaluation and
treatment of patients. This Clinical Practice Guideline outlines the preferred approach for most
patients. It is not intended to replace a clinician’s judgment or to establish a protocol for all
patients. It is understood that some patients will not fit the clinical condition contemplated by a
guideline and that a guideline will rarely establish the only appropriate approach to a problem
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17
References
1. Barr J, Fraser GL, Puntillo K, et al. Clinical practice guidelines for the management of pain,
agitation, and delirium in adult patients in the intensive care unit. Crit Care Med.
2013;41(1):263-306.
2. Jacobs AK, Kushner FG, Ettinger SM, et al. ACCF/AHA clinical practice guideline
methodology summit report: a report of the American College of Cardiology
Foundation/American Heart Association Task Force on Practice Guidelines. J Am Coll Cardiol.
2013;61(2):213-265.
3. Girard TD, Kress JP, Fuchs BD, et al. Efficacy and safety of a paired sedation and ventilator
weaning protocol for mechanically ventilated patients in intensive care (Awakening and
Breathing Controlled trial): a randomised controlled trial. Lancet. 2008;371(9607):126-134.
4. Payen JF, Bosson JL, Chanques G, Mantz J, Labarere J. Pain assessment is associated with
decreased duration of mechanical ventilation in the intensive care unit: a post Hoc analysis of the
DOLOREA study. Anesthesiology. 2009;111(6):1308-1316.
5. Chanques G, Sebbane M, Barbotte E, Viel E, Eledjam JJ, Jaber S. A prospective study of pain at
rest: incidence and characteristics of an unrecognized symptom in surgical and trauma versus
medical intensive care unit patients. Anesthesiology. Vol 107. United States2007:858-860.
6. Payen JF, Chanques G, Mantz J, et al. Current practices in sedation and analgesia for
mechanically ventilated critically ill patients: a prospective multicenter patient-based study.
Anesthesiology. 2007;106(4):687-695; quiz 891-682.
7. Gelinas C. Management of pain in cardiac surgery ICU patients: have we improved over time?
Intensive Crit Care Nurs. 2007;23(5):298-303.
8. Stanik-Hutt JA, Soeken KL, Belcher AE, Fontaine DK, Gift AG. Pain experiences of
traumatically injured patients in a critical care setting. Am J Crit Care. 2001;10(4):252-259.
9. Puntillo KA, White C, Morris AB, et al. Patients' perceptions and responses to procedural pain:
results from Thunder Project II. Am J Crit Care. 2001;10(4):238-251.
10. Siffleet J, Young J, Nikoletti S, Shaw T. Patients' self-report of procedural pain in the intensive
care unit. J Clin Nurs. 2007;16(11):2142-2148.
11. Puntillo KA, Wild LR, Morris AB, Stanik-Hutt J, Thompson CL, White C. Practices and
predictors of analgesic interventions for adults undergoing painful procedures. Am J Crit Care.
2002;11(5):415-429; quiz 430-411.
12. Memis D, Inal MT, Kavalci G, Sezer A, Sut N. Intravenous paracetamol reduced the use of
opioids, extubation time, and opioid-related adverse effects after major surgery in intensive care
unit. J Crit Care. 2010;25(3):458-462.
13. Rapanos T, Murphy P, Szalai JP, Burlacoff L, Lam-McCulloch J, Kay J. Rectal indomethacin
reduces postoperative pain and morphine use after cardiac surgery. Can J Anaesth.
1999;46(8):725-730.
14. Hynninen MS, Cheng DC, Hossain I, et al. Non-steroidal anti-inflammatory drugs in treatment
of postoperative pain after cardiac surgery. Can J Anaesth. 2000;47(12):1182-1187.
15. Machata AM, Illievich UM, Gustorff B, Gonano C, Fassler K, Spiss CK. Remifentanil for
tracheal tube tolerance: a case control study. Anaesthesia. 2007;62(8):796-801.
16. But AK, Erdil F, Yucel A, Gedik E, Durmus M, Ersoy MO. The effects of single-dose tramadol
on post-operative pain and morphine requirements after coronary artery bypass surgery. Acta
Anaesthesiol Scand. 2007;51(5):601-606.
17. Pandey CK, Raza M, Tripathi M, Navkar DV, Kumar A, Singh UK. The comparative evaluation
of gabapentin and carbamazepine for pain management in Guillain-Barre syndrome patients in
the intensive care unit. Anesth Analg. 2005;101(1):220-225, table of contents.
Copyright © 2017 Univ ersity of Wisconsin Hospitals and Clinics Authority
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18
18. Krishnan K, Elliot SC, Berridge JC, Mallick A. Remifentanil patient-controlled analgesia
following cardiac surgery. Acta Anaesthesiol Scand. 2005;49(6):876-879.
19. Dahaba AA, Grabner T, Rehak PH, List WF, Metzler H. Remifentanil versus morphine analgesia
and sedation for mechanically ventilated critically ill patients: a randomized double blind study.
Anesthesiology. 2004;101(3):640-646.
20. Karabinis A, Mandragos K, Stergiopoulos S, et al. Safety and efficacy of analgesia-based
sedation with remifentanil versus standard hypnotic-based regimens in intensive care unit
patients with brain injuries: a randomised, controlled trial [ISRCTN50308308]. Crit Care.
2004;8(4):R268-280.
21. Chinachoti T, Kessler P, Kirkham A, Werawatganon T. Remifentanil vs morphine for patients in
intensive care unit who need short-term mechanical ventilation. J Med Assoc Thai. 2002;85
Suppl 3:S848-857.
22. Soltesz S, Biedler A, Silomon M, Schopflin I, Molter GP. Recovery after remifentanil and
sufentanil for analgesia and sedation of mechanically ventilated patients after trauma or major
surgery. Br J Anaesth. 2001;86(6):763-768.
23. Breen D, Wilmer A, Bodenham A, et al. Offset of pharmacodynamic effects and safety of
remifentanil in intensive care unit patients with various degrees of renal impairment. Crit Care.
2004;8(1):R21-30.
24. Guillou N, Tanguy M, Seguin P, Branger B, Campion JP, Malledant Y. The effects of small-dose
ketamine on morphine consumption in surgical intensive care unit patients after major abdominal
surgery. Anesth Analg. 2003;97(3):843-847.
25. Pandey CK, Bose N, Garg G, et al. Gabapentin for the treatment of pain in guillain-barre
syndrome: a double-blinded, placebo-controlled, crossover study. Anesth Analg.
2002;95(6):1719-1723, table of contents.
26. Frakes MA, Lord WR, Kociszewski C, Wedel SK. Efficacy of fentanyl analgesia for trauma in
critical care transport. Am J Emerg Med. 2006;24(3):286-289.
27. Carrer S, Bocchi A, Candini M, Donega L, Tartari S. Short term analgesia based sedation in the
Intensive Care Unit: morphine vs remifentanil + morphine. Minerva Anestesiol. 2007;73(6):327-
332.
28. Maddali MM, Kurian E, Fahr J. Extubation time, hemodynamic stability, and postoperative pain
control in patients undergoing coronary artery bypass surgery: an evaluation of fentanyl,
remifentanil, and nonsteroidal antiinflammatory drugs with propofol for perioperative and
postoperative management. J Clin Anesth. 2006;18(8):605-610.
29. Guggenberger H, Schroeder TH, Vonthein R, Dieterich HJ, Shernan SK, Eltzschig HK.
Remifentanil or sufentanil for coronary surgery: comparison of postoperative respiratory
impairment. Eur J Anaesthesiol. 2006;23(10):832-840.
30. Micromedex 1.0 (Healthcare Series), (electronic version). Thomson Reuters (Healthcare),
Greenwood Village, Colorodo, USA; accessed July 2012.
31. Lexi-Comp Online, Lexi-Drugs Online, Hudson, Ohio: Lexi-Comp, Inc.; 2012; accessed July
2012.
32. Chanques G, Jaber S, Barbotte E, et al. Impact of systematic evaluation of pain and agitation in
an intensive care unit. Crit Care Med. 2006;34(6):1691-1699.
33. Ely EW, Truman B, Shintani A, et al. Monitoring sedation status over time in ICU patients:
reliability and validity of the Richmond Agitation-Sedation Scale (RASS). JAMA.
2003;289(22):2983-2991.
34. Masica AL, Girard TD, Wilkinson GR, et al. Clinical sedation scores as indicators of sedative
and analgesic drug exposure in intensive care unit patients. Am J Geriatr Pharmacother.
2007;5(3):218-231.
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35. Pun BT, Gordon SM, Peterson JF, et al. Large-scale implementation of sedation and delirium
monitoring in the intensive care unit: a report from two medical centers. Crit Care Med.
2005;33(6):1199-1205.
36. Sessler CN, Gosnell MS, Grap MJ, et al. The Richmond Agitation-Sedation Scale: validity and
reliability in adult intensive care unit patients. Am J Respir Crit Care Med. 2002;166(10):1338-
1344.
37. Breen D, Karabinis A, Malbrain M, et al. Decreased duration of mechanical ventilation when
comparing analgesia-based sedation using remifentanil with standard hypnotic-based sedation
for up to 10 days in intensive care unit patients: a randomised trial [ISRCTN47583497]. Crit
Care. 2005;9(3):R200-210.
38. Park G, Lane M, Rogers S, Bassett P. A comparison of hypnotic and analgesic based sedation in
a general intensive care unit. Br J Anaesth. 2007;98(1):76-82.
39. Rozendaal FW, Spronk PE, Snellen FF, et al. Remifentanil-propofol analgo-sedation shortens
duration of ventilation and length of ICU stay compared to a conventional regimen: a centre
randomised, cross-over, open-label study in the Netherlands. Intensive Care Med.
2009;35(2):291-298.
40. Strom T, Martinussen T, Toft P. A protocol of no sedation for critically ill patients receiving
mechanical ventilation: a randomised trial. Lancet. 2010;375(9713):475-480.
41. Jones C, Backman C, Capuzzo M, Flaatten H, Rylander C, Griffiths RD. Precipitants of post-
traumatic stress disorder following intensive care: a hypothesis generating study of diversity in
care. Intensive Care Med. 2007;33(6):978-985.
42. Carson SS, Kress JP, Rodgers JE, et al. A randomized trial of intermittent lorazepam versus
propofol with daily interruption in mechanically ventilated patients. Crit Care Med.
2006;34(5):1326-1332.
43. Weinbroum AA, Halpern P, Rudick V, Sorkine P, Freedman M, Geller E. Midazolam versus
propofol for long-term sedation in the ICU: a randomized prospective comparison. Intensive
Care Med. 1997;23(12):1258-1263.
44. Pandharipande PP, Pun BT, Herr DL, et al. Effect of sedation with dexmedetomidine vs
lorazepam on acute brain dysfunction in mechanically ventilated patients: the MENDS
randomized controlled trial. JAMA. 2007;298(22):2644-2653.
45. Ruokonen E, Parviainen I, Jakob SM, et al. Dexmedetomidine versus propofol/midazolam for
long-term sedation during mechanical ventilation. Intensive Care Med. 2009;35(2):282-290.
46. Maldonado JR, Wysong A, van der Starre PJ, Block T, Miller C, Reitz BA. Dexmedetomidine
and the reduction of postoperative delirium after cardiac surgery. Psychosomatics.
2009;50(3):206-217.
47. Samuelson KA, Lundberg D, Fridlund B. Light vs. heavy sedation during mechanical ventilation
after oesophagectomy--a pilot experimental study focusing on memory. Acta Anaesthesiol
Scand. 2008;52(8):1116-1123.
48. Pandharipande P, Cotton BA, Shintani A, et al. Prevalence and risk factors for development of
delirium in surgical and trauma intensive care unit patients. J Trauma. 2008;65(1):34-41.
49. Pandharipande P, Ely EW. Sedative and analgesic medications: risk factors for delirium and
sleep disturbances in the critically ill. Crit Care Clin. 2006;22(2):313-327, vii.
50. Arroliga AC, Thompson BT, Ancukiewicz M, et al. Use of sedatives, opioids, and
neuromuscular blocking agents in patients with acute lung injury and acute respiratory distress
syndrome. Crit Care Med. 2008;36(4):1083-1088.
51. Ho KM, Ng JY. The use of propofol for medium and long-term sedation in critically ill adult
patients: a meta-analysis. Intensive Care Med. 2008;34(11):1969-1979.
Copyright © 2017 Univ ersity of Wisconsin Hospitals and Clinics Authority
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20
52. Riker RR, Shehabi Y, Bokesch PM, et al. Dexmedetomidine vs midazolam for sedation of
critically ill patients: a randomized trial. JAMA. 2009;301(5):489-499.
53. Fong JJ, Kanji S, Dasta JF, Garpestad E, Devlin JW. Propofol associated with a shorter duration
of mechanical ventilation than scheduled intermittent lorazepam: a database analysis using
Project IMPACT. Ann Pharmacother. 2007;41(12):1986-1991.
54. Esmaoglu A, Ulgey A, Akin A, Boyaci A. Comparison between dexmedetomidine and
midazolam for sedation of eclampsia patients in the intensive care unit. J Crit Care.
2009;24(4):551-555.
55. Anis AH, Wang XH, Leon H, Hall R. Economic evaluation of propofol for sedation of patients
admitted to intensive care units. Anesthesiology. 2002;96(1):196-201.
56. Hall RI, Sandham D, Cardinal P, et al. Propofol vs midazolam for ICU sedation : a Canadian
multicenter randomized trial. Chest. 2001;119(4):1151-1159.
57. Huey-Ling L, Chun-Che S, Jen-Jen T, Shau-Ting L, Hsing IC. Comparison of the effect of
protocol-directed sedation with propofol vs. midazolam by nurses in intensive care: efficacy,
haemodynamic stability and patient satisfaction. J Clin Nurs. 2008;17(11):1510-1517.
58. Searle NR, Cote S, Taillefer J, et al. Propofol or midazolam for sedation and early extubation
following cardiac surgery. Can J Anaesth. 1997;44(6):629-635.
59. Jakob SM, Ruokonen E, Grounds RM, et al. Dexmedetomidine vs midazolam or propofol for
sedation during prolonged mechanical ventilation: two randomized controlled trials. JAMA.
2012;307(11):1151-1160.
60. Brook AD, Ahrens TS, Schaiff R, et al. Effect of a nursing-implemented sedation protocol on the
duration of mechanical ventilation. Crit Care Med. 1999;27(12):2609-2615.
61. Kress JP, Pohlman AS, O'Connor MF, Hall JB. Daily interruption of sedative infusions in
critically ill patients undergoing mechanical ventilation. N Engl J Med. 2000;342(20):1471-1477.
62. Treggiari MM, Romand JA, Yanez ND, et al. Randomized trial of light versus deep sedation on
mental health after critical illness. Crit Care Med. 2009;37(9):2527-2534.
63. Kollef MH, Levy NT, Ahrens TS, Schaiff R, Prentice D, Sherman G. The use of continuous i.v.
sedation is associated with prolongation of mechanical ventilation. Chest. 1998;114(2):541-548.
64. Kress JP, Gehlbach B, Lacy M, Pliskin N, Pohlman AS, Hall JB. The long-term psychological
effects of daily sedative interruption on critically ill patients. Am J Respir Crit Care Med.
2003;168(12):1457-1461.
65. Kress JP, Vinayak AG, Levitt J, et al. Daily sedative interruption in mechanically ventilated
patients at risk for coronary artery disease. Crit Care Med. 2007;35(2):365-371.
66. Hall RI, MacLaren C, Smith MS, et al. Light versus heavy sedation after cardiac surgery:
myocardial ischemia and the stress response. Maritime Heart Centre and Dalhousie University.
Anesth Analg. 1997;85(5):971-978.
67. Mangano DT, Siliciano D, Hollenberg M, et al. Postoperative myocardial ischemia. Therapeutic
trials using intensive analgesia following surgery. The Study of Perioperative Ischemia (SPI)
Research Group. Anesthesiology. 1992;76(3):342-353.
68. Plunkett JJ, Reeves JD, Ngo L, et al. Urine and plasma catecholamine and cortisol concentrations
after myocardial revascularization. Modulation by continuous sedation. Multicenter Study of
Perioperative Ischemia (McSPI) Research Group, and the Ischemia Research and Education
Foundation (IREF). Anesthesiology. 1997;86(4):785-796.
69. Terao Y, Miura K, Saito M, Sekino M, Fukusaki M, Sumikawa K. Quantitative analysis of the
relationship between sedation and resting energy expenditure in postoperative patients. Crit Care
Med. 2003;31(3):830-833.
70. Samuelson KA, Lundberg D, Fridlund B. Stressful experiences in relation to depth of sedation in
mechanically ventilated patients. Nurs Crit Care. 2007;12(2):93-104.
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71. Samuelson K, Lundberg D, Fridlund B. Memory in relation to depth of sedation in adult
mechanically ventilated intensive care patients. Intensive Care Med. 2006;32(5):660-667.
72. Mehta S, Burry L, Martinez-Motta JC, et al. A randomized trial of daily awakening in critically
ill patients managed with a sedation protocol: a pilot trial. Crit Care Med. 2008;36(7):2092-
2099.
73. Anifantaki S, Prinianakis G, Vitsaksaki E, et al. Daily interruption of sedative infusions in an
adult medical-surgical intensive care unit: randomized controlled trial. J Adv Nurs.
2009;65(5):1054-1060.
74. de Wit M, Gennings C, Jenvey WI, Epstein SK. Randomized trial comparing daily interruption
of sedation and nursing-implemented sedation algorithm in medical intensive care unit patients.
Crit Care. 2008;12(3):R70.
75. Ouimet S, Kavanagh BP, Gottfried SB, Skrobik Y. Incidence, risk factors and consequences of
ICU delirium. Intensive Care Med. 2007;33(1):66-73.
76. Ouimet S, Riker R, Bergeron N, Cossette M, Kavanagh B, Skrobik Y. Subsyndromal delirium in
the ICU: evidence for a disease spectrum. Intensive Care Med. 2007;33(6):1007-1013.
77. Pisani MA, Kong SY, Kasl SV, Murphy TE, Araujo KL, Van Ness PH. Days of delirium are
associated with 1-year mortality in an older intensive care unit population. Am J Respir Crit Care
Med. 2009;180(11):1092-1097.
78. Ely EW, Gautam S, Margolin R, et al. The impact of delirium in the intensive care unit on
hospital length of stay. Intensive Care Med. 2001;27(12):1892-1900.
79. Ely EW, Shintani A, Truman B, et al. Delirium as a predictor of mortality in mechanically
ventilated patients in the intensive care unit. JAMA. 2004;291(14):1753-1762.
80. Lin SM, Liu CY, Wang CH, et al. The impact of delirium on the survival of mechanically
ventilated patients. Crit Care Med. 2004;32(11):2254-2259.
81. Micek ST, Anand NJ, Laible BR, Shannon WD, Kollef MH. Delirium as detected by the CAM-
ICU predicts restraint use among mechanically ventilated medical patients. Crit Care Med.
2005;33(6):1260-1265.
82. Thomason JW, Shintani A, Peterson JF, Pun BT, Jackson JC, Ely EW. Intensive care unit
delirium is an independent predictor of longer hospital stay: a prospective analysis of 261 non-
ventilated patients. Crit Care. 2005;9(4):R375-381.
83. Norkiene I, Ringaitiene D, Misiuriene I, et al. Incidence and precipitating factors of delirium
after coronary artery bypass grafting. Scand Cardiovasc J. 2007;41(3):180-185.
84. Lin SM, Huang CD, Liu CY, et al. Risk factors for the development of early-onset delirium and
the subsequent clinical outcome in mechanically ventilated patients. J Crit Care.
2008;23(3):372-379.
85. Lat I, McMillian W, Taylor S, et al. The impact of delirium on clinical outcomes in mechanically
ventilated surgical and trauma patients. Crit Care Med. 2009;37(6):1898-1905.
86. Han JH, Shintani A, Eden S, et al. Delirium in the emergency department: an independent
predictor of death within 6 months. Ann Emerg Med. 2010;56(3):244-252.e241.
87. Spronk PE, Riekerk B, Hofhuis J, Rommes JH. Occurrence of delirium is severely
underestimated in the ICU during daily care. Intensive Care Med. 2009;35(7):1276-1280.
88. Ely EW, Inouye SK, Bernard GR, et al. Delirium in mechanically ventilated patients: validity
and reliability of the confusion assessment method for the intensive care unit (CAM-ICU).
JAMA. 2001;286(21):2703-2710.
89. Guenther U, Popp J, Koecher L, et al. Validity and reliability of the CAM-ICU Flowsheet to
diagnose delirium in surgical ICU patients. J Crit Care. 2010;25(1):144-151.
90. van Eijk MM, van Marum RJ, Klijn IA, de Wit N, Kesecioglu J, Slooter AJ. Comparison of
delirium assessment tools in a mixed intensive care unit. Crit Care Med. 2009;37(6):1881-1885.
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91. Ely EW, Margolin R, Francis J, et al. Evaluation of delirium in critically ill patients: validation
of the Confusion Assessment Method for the Intensive Care Unit (CAM-ICU). Crit Care Med.
2001;29(7):1370-1379.
92. Soja SL, Pandharipande PP, Fleming SB, et al. Implementation, reliability testing, and
compliance monitoring of the Confusion Assessment Method for the Intensive Care Unit in
trauma patients. Intensive Care Med. 2008;34(7):1263-1268.
93. Schweickert WD, Pohlman MC, Pohlman AS, et al. Early physical and occupational therapy in
mechanically ventilated, critically ill patients: a randomised controlled trial. Lancet.
2009;373(9678):1874-1882.
94. Needham DM, Korupolu R, Zanni JM, et al. Early physical medicine and rehabilitation for
patients with acute respiratory failure: a quality improvement project. Arch Phys Med Rehabil.
2010;91(4):536-542.
95. Girard TD, Pandharipande PP, Carson SS, et al. Feasibility, efficacy, and safety of antipsychotics
for intensive care unit delirium: the MIND randomized, placebo-controlled trial. Crit Care Med.
2010;38(2):428-437.
96. Pandharipande P, Girard T, Sanders R, Thompson J, Maze M, Ely E. Comparison of sedation
with dexmedetomidine versus lorazepam in septic ICU patients. Critical Care 2008, 12(Suppl
2):P275.
97. Balas MC, Vasilevskis EE, Burke WJ, et al. Critical care nurses' role in implementing the
"ABCDE bundle" into practice. Crit Care Nurse. 2012;32(2):35-38, 40-37; quiz 48.

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07/2017CCKM@uwhealth.org