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 Educational Purpose
This curriculum deck will update readers on recent advances
regarding the use of analgesia and sedation in acute care settings.

Learning Objectives
Upon completion of this activity, participants should be able to
ƒ Describe the rationale for the use of analgesia and sedation in
acute care settings
ƒ Compare the current analgesics and sedatives, and assess their
benefits and limitations
ƒ Review the clinical study evidence supporting the use of current
agents for acute care sedation and analgesia
ƒ Discuss the rationale for pharmacoeconomic analyses of
therapeutic agents in various acute care settings
 Program Overview

ƒ General Anesthesia and Sedation Background

ƒ Comfort Care in the Acute Care Setting
ƒ Overview of Current Sedative and Analgesic Agents
ƒ Dexmedetomidine
ƒ Pharmacoecononmic Data
ƒ Neurological Effects
ƒ Pediatric Applications
ƒ Dexmedetomidine in Bariatric Surgery
ƒ Algorithms
ƒ Summary
 General Analgesia
and
Sedation Background
 Purpose of Analgesia and Sedation
in Acute Care Settings
ƒ Provide adequate pain control1
ƒ Optimize safety for patients and their
caregivers2
ƒ Enhance patient comfort1
ƒ Facilitate mechanical ventilation3
ƒ Reduce anxiety1
ƒ Prevent delirium1
ƒ Induce sleep when required1
ƒ Induce appropriate level of amnesia3

1Ely EW, et al. JAMA. 2003;289:2983-2991.

2Blanchard AR. Postgrad Med. 2002;111:59-74.
3Kress JP, et al. Am J Respir Crit Care Med. 2002;166:1024–1028.
Need for Analgesia and Sedation in Acute Care
Physiological and Neurobehavioral Considerations

• Failure to address pain in acute care patients may lead to

– Agitation and anxiety
– Hypermetabolic states
– Increased endogenous catecholamine activity
– Myocardial ischemia
• Acute care patients may demonstrate periods of
disorientation during which psychotic behavior occurs
• Certain types of sedation can reduce the risk of harm to
the patient or others

Kress JP, et al. Am J Respir Crit Care Med. 2002;166:1024–1028.

 Factors Leading to Agitation
Modifiable Non-Modifiable

Memory Loss1
Mechanical Devices1
Pain
Confusion1
Alarms1
Anxiety
Inconsiderate Providers1 Age/History1
Agitation
Chemical/Physiologic Loss of Control1
Imbalance1
Surgical Stress1
Medications1,2 Delirium
Fear1
Noises1
Lights/Temperature1
Nonchanging Environment
Sleep Deprivation1

1ASHP Therapeutic Guidelines. Best Practices for Heath-System Pharmacy. 2003-2004;486-512.

2McKinley S, et al. Am J Crit Care. 2004;13:146-152.
 Goals of Sedation and Analgesia

ƒ Optimize safety for acute care patients and their

caregivers1,2
ƒ Relieve pain and anxiety1-3
ƒ Attenuate the harmful adrenergic response1,2
ƒ Improve compliance with care1,2
ƒ Facilitate communication with caregivers and
family members1,2
ƒ Avoid or reduce delirium1,2,4

1Blanchard AR. Postgrad Med. 2002;111:59-74.

2Jacobi J, et al. Crit Care Med. 2002;30:119-141.
3Dasta JF, et al. Pharmacotherapy. 2006;26:798-805.
4Ely EW, et al. JAMA. 2004;291:1753-1762.
 Characteristics of an Ideal Sedative

ƒ Rapid onset of action allows rapid recovery after

discontinuation1
ƒ Effective at providing adequate sedation with
predictable dose response1,2
ƒ Easy to administer1,3
ƒ Lack of drug accumulation1
ƒ Few adverse effects1-3
ƒ Minimal adverse interactions with other drugs1-3
ƒ Cost effective3
ƒ Predictable dose response2
ƒ Promotes natural sleep4

1Ostermann ME, et al. JAMA. 2000;283:1451-1459.

2Jacobi et al. Crit Care Med. 2002;30:119-141.
3Dasta JF, et al. Pharmacotherapy. 2006;26:798-805..
4Nelson LE, et al. Anesthesiology. 2003;98:428-436.
 Targeting Patient Comfort

ƒ On-target sedation:
Oversedation ƒ Decreases weaning
period1
ƒ Is not associated with
muscular atrophy1
On- ƒ Decreases LOS and cost2
Target ƒ Provides cardiovascular1
Sedation and intraoperative
hemodynamic stability3
ƒ Improves patient safety1,3
ƒ Facilitates neurological
assessment3
Undersedation
1McGaffiganPA. Crit Care Nursing. 2002;Feb Suppl:29-36.
2Dasta et al. Pharmacotherapy. 2006;26:798-805.
3Arbour R. Am J Crit Care Nursing. 2004;13:66-73.
Importance of Optimizing Levels of Sedation

Undersedation Oversedation
ƒ Anxiety1 ƒ Prolonged weaning3
ƒ Ventilator dysynchrony2 ƒ Respiratory depression4
ƒ Dislodging invasive lines/ ƒ Lack of patient cooperation for
devices1 assessment and therapeutic measures1
ƒ May increase posttraumatic ƒ Inability to communicate with health care
stress syndrome1 providers or family members1
ƒ Increased O2 consumption1 ƒ Delirium2
ƒ Delirium2 ƒ Hypoactivity1
ƒ Hyperactivity1
ƒ Minimal amnesia2

1McGaffigan PA. Crit Care Nursing. 2002;Feb Suppl:29-36.

2ASHP Therapeutic Guidelines. Best Practices for Heath-System Pharmacy. 2003-2004;486-512.
3Carrasco G. Crit Care. 2000;4:217–225.
4Blanchard AR. Postgrad Med. 2002;111:59-74.
 Incidence of Inadequate Sedation

ƒ Continuous sedation carries the risks

15.4% associated with oversedation and may
Undersedated1
increase the duration of mechanical
30.6% ventilation (MV)1,2
On-Target1
ƒ MV patients accrue significantly more
cost during their ICU stay than non-MV
patients 3
54.0% – $31,574 versus $12,931, P<.0013
Oversedated1
ƒ Sedation should be titrated to achieve a
cooperative patient and daily wake-up, a
JCAHO requirement2,3

1Kaplan L, et al. Crit Care. 2000;4(suppl 1):S110.

2Kress et al. N Engl J Med. 2000;342:1471-1477.
3Dasta JF, et al. Crit Care Med. 2005;33:1266-1271.
 Oversedation

On-
Target
Sedation

Undersedation
Costs and Effects of
Undersedation
• Increased staffing needs (nursing and
respiratory care)1
• Patient/family discomfort and
dissatisfaction
• Decreased staff satisfaction
• Need for an appropriate use of paralysis
• Adverse physiologic consequences
• Reflex shift to oversedation
Costs and Effects of
Oversedation
• Inability to adequately examine the patient
• Increased costs of diagnostic imaging and
other tests
• Possible delayed diagnosis of treatable
problems
• Prolonged mechanical ventilation time
• Prolonged stay in acute care settings
• Prolonged hospital stay

1Kress JP, et al. N Engl J Med. 2000;342:1471-1477.

 Guidelines and Standards

ƒ JCAHO Standards
ƒ 2002 SCCM Guidelines
ƒ Anesthesia Patient Safety Foundation
ƒ ASA Guidelines
ƒ Institute of Medicine
 Comfort Care
in the
Acute Care Setting
 Assessing Pain

ƒ Faces Pain Rating Scale1

ƒ Visual Analog Scale (VAS)1
ƒ Pain questionnaire1
– Qualitative aspects1
ƒ Sympathetic response to pain1

1Jacox A, et al. Management of Cancer Pain. AHCPR publication 94-0592. 1994.

 Assessing Sedation

ƒ Ramsay Sedation Scale

ƒ Observer’s Assessment of Alertness/Sedation
Scale (OAA/SS)
ƒ Motor Activity Assessment Scale (MAAS)
ƒ Riker’s Sedation-Agitation Scale (SAS)
ƒ Richmond Agitation-Sedation Scale (RASS)
ƒ Brain function monitoring
 Assessing Anxiety and Delirium
ƒ State-Trait Anxiety Inventory (STAI)1

ƒ Hamilton Rating Scales for Depression and Anxiety2

ƒ The Hospital Anxiety and Depression Scale3

ƒ Linear Analog Anxiety Scale4

ƒ Surrogate markers of stress response5

ƒ The Confusion Assessment Method for the Diagnosis

of Delirium in the ICU (CAM-ICU)6

1Shedletsky R, et al. J Pers. 1974;42:511-527.

2Hamilton M. Br J Soc Clin Psychol. 1967;6:278-296.
3Zigmond, AS, et al. Acta Psychiatr Scand. 1983;67:361-370.
4Sriwatanakul K, et al. Clin Pharmacol Ther. 1983;34:234-239.
5Lewis KS, et al. Am J Hosp Pharm. 1994;51:1539-1554.
6 Ely EW, et al. Crit Care Med. 2001; 29:1370–1379.
 Characteristics of Cooperative Sedation

ƒ In cooperative sedation, patients ƒ Facilitates participation in

easily transition from sleep to therapeutic maneuvers2
wakefulness and task ƒ Allows for patient interaction
performance when aroused1 in care decisions2
ƒ Patients are able to resume rest ƒ May contribute to shorter
when not stimulated1 recovery room convalescence3
ƒ Cooperative sedation is most ƒ Reduces risk of developing
useful during procedures in which drug-induced complications3
communication with the patient
must be maintained1

1Bekker AY, et al. Neurosurgery. 2005;57(1 Suppl 1):1-10.

2Burns AM, et al. Drugs. 1992;43:507-515.
3Sedation. Encyclopedia of Medicine. Ed. Jacqueline L. Longe. Thomson Gale, 2002. eNotes.com. 2006. 6 Mar, 2006

http://health.enotes.com/medicine-encyclopedia/sedation
 Examples of Cooperative Sedation

ƒ Allows for accurate evaluation of the

neuropsychological status of mechanically
ventilated patients1
ƒ Facilitates direct evaluation of cerebral perfusion
during carotid endarterectomy2
ƒ Patients are comfortable and responsive during
cortical mapping2

1Bekker AY, et al. Neurosurgery. 2005; 57(1 Suppl):1-10.

2Ard JL, et al. Surgical Neurology. 2005;63:114-117.
 Negative Outcomes Associated With
Poor Cooperative Sedation
ƒ Pain that is not communicated in acute care
settings can result in1
– Increased stress response
– Guarding of muscles and muscle rigidity around
area of pain, leading to pulmonary dysfunction
– Exhaustion and disorientation
– Poor patient cooperation
ƒ Inability to assess patients can result in
– Increased number of diagnostic tests
– Increased time on ventilator
– Increased LOS
– Increased overall costs
1Jacobi J, et al. Crit Care Med. 2002;30:119-141.
 Institutional Effects of Implementing
Rational Use Guidelines
ƒ Prospective analysis of 156 ICU patients who
required mechanical ventilation and continuous
analgesia, sedation, and/or neuromuscular
blockade1
ƒ One group (n = 84) was tracked after
guidelines were implemented1
ƒ Length of hospital and ICU stay and duration of
mechanical ventilation were all shorter in the
guidelines group1
ƒ Institution of the guidelines led to a decline in
mean drug costs across all drug classes
studied1
1Mascia MF, et al. Crit Care Med. 2000;28:2300-2306.
 Implementation of Clinical Pathways
Clinical Outcome and Cost Burden

ƒ Large-scale implementation project with

comparison to historic controls1
ƒ Outcomes management study including
evidence-based clinical pathways and protocols
for weaning acute care patients1
ƒ Participants included 595 pre-outcomes
management patients and 510 post-outcomes
management patients mechanically ventilated
for >3 consecutive days1

1Burns SM, et al. Crit Care Med. 2003;31:2752-2763.

 Implementation of Clinical Pathways
Clinical Outcome and Cost Burden (Cont’d)

ƒ Significant differences in clinical outcomes were

demonstrated between the 2 groups1
– Decreased ventilator duration by 1 day (P=.0001)1
– ICU stay reduced by 3 days (P=.0008)1
– Hospital length of stay reduced by 2 days (P=.0001)1
– Mortality rate declined from 38% to 31% (P=.02)1
ƒ More than $3 million cost savings were realized
in the OM group1

1Burns SM, et al. Crit Care Med. 2003;31:2752-2763.

Overview of Current Sedative
and
Analgesic Agents
 Overview of Current Sedative
and Analgesic Agents
Drug Class Examples Year FDA Approved

Opioids Morphine Prior to 1938

Fentanyl 1968
Butyrophenones Haloperidol 1967
Benzodiazepines Diazepam 1963
Lorazepam 1963
Midazolam 1985
Sedatives/hypnotics Propofol 1989
α2 Agonists Clonidine 1986
Dexmedetomidine 1999

http://www.fda.gov/cder/ob/default.htm
 Opioids

Clinical Effects Adverse Effects

ƒ Analgesia1 ƒ Respiratory depression1,2
ƒ Sedation1 ƒ Hypotension1,2
ƒ Bradycardia1,2
ƒ Constipation1
ƒ Tolerance1
ƒ Withdrawal symptoms1,2
ƒ Dysphoria3,4
Fentanyl Morphine

1Harvey MA. Am J Crit Care. 1996;5:7-16.

2WagnerBKJ, et al. Clin Pharmacokinet. 1997;33:426-453.
3Dean AJ, et al. J Psychiatry Neurosci. 2006;31:38-45.
4Gerra G, et al. Drug Alcohol Depend. 2004;75:37-45.
 Haloperidol

Clinical Effects Adverse Effects

ƒ Hypnotic agent with ƒ Dysphoria2
antipsychotic properties1 ƒ Adverse CV effects include
– For treatment of QT interval prolongation,
delirium in critically ill extrapyramidal symptoms,
adults1 neuroleptic malignant
ƒ Does not cause syndrome (rare)1
respiratory depression1 ƒ Metabolism altered by drug-
drug interactions2

Haloperidol
O OH
F N
CI
1Harvey MA. Am J Crit Care. 1996;5:7-16.
2Crippen DW. Crit Care Clin. 1990;6:369-392.
 Benzodiazepines
Lorazepam
Clinical Effects Adverse Effects
ƒ Sedation, anxiolysis, ƒ Slower onset of action than
and amnesia1 midazolam2,3
ƒ Commonly used for ƒ Metabolic Acidosis (propylene
long-term sedation2 glycol toxicity)4,5
ƒ Retrograde and anterograde
amnesia can exceed
desirability6
ƒ Delirium7

1Lerch C, et al. Br Med Bull. 1999;55:76-95.

2Shafer A. Crit Care Med. 1998;26:947-956.
3Wagner BKJ, et al. Clin Pharmacokinet. 1997;33:426-453.
4Neale BW, et al. Ann Pharmacother. 2005;39:1732-1736.
5Wilson KC, et al. Chest. 2005;128:1674-1681.
6Mathew A, et al. Psychpharmacol. 2002;16:345-354.
7Pandharipande P, et al. Anesthesiology. 2006;104:21-26.
 Benzodiazepines
Midazolam
Clinical Effects Adverse Effects
ƒ Sedation, anxiolysis, ƒ May accumulate in liver and/or renal failure1
and amnesia1 ƒ Anterograde amnesia2
ƒ Rapid onset of action ƒ Prolonged recovery after long-term use3
intravenously1 ƒ Combination with opioids increases
hypotensive effects1
ƒ Respiratory depression4
ƒ Adverse hemodynamic events have been
reported in pediatric patients with
cardiovascular instability4

1BlanchardAR. Postgrad Med. 2002;111:59-74.

2Harvey MA. Am J Crit Care. 1996;5:7-16.
3Shafer A. Crit Care Med. 1998;26:947-956.
4Midazolam [package insert]. Weston, FL: Apotex Corp; 2000.
 Propofol

Clinical Effects Adverse Effects

ƒ Sedation1 ƒ Respiratory depression (exacerbated
ƒ Hypnosis1 by opioids)1
ƒ Anxiolysis1 ƒ Hypotension1
ƒ Muscle relaxation1 ƒ Decreased myocardial contractility3
ƒ ↓ ICP1 ƒ Preservative issues4
ƒ ↓ Cerebral metabolic rate1 ƒ Potential for infection4
ƒ Antiemetic2 ƒ Tolerance5
ƒ Propofol infusion syndrome6
ƒ ↑ Serum triglycerides4

OH

(CH3)2 CH CH (CH3)2
1Harvey MA. Am J Crit Care.1996;5:7-16.
2Apfel CC, et al. Anaesthesist. 2005;54:201-9.
3Lerch C, et al. Br Med Bull. 1999;55:76-95.
4Diprivan [package insert]. AstraZeneca Pharmaceuticals; 2004.
5Zapantis A, et al. Crit Care Nurs Clin N Am. 2005;17:211-223.
6Riker RR, et al. Pharmacotherapy. 2005;25(5 Pt 2):8S-18S.
 α2 Agonists: Clonidine

Clinical Effects Adverse Effects

ƒ Antihypertensive1,2 ƒ Bradycardia1
ƒ Analgesia1 ƒ Dry mouth1
ƒ Anxiolysis1 ƒ Hypotension3
ƒ Sedation1
ƒ ↓ Shivering1 Clonidine
H
Cl
N
N

N
Cl

1Kamibayashi T, et al. Anesthesiology. 2000;93:1345-1349; 2Catapres [package insert]. Ridgefield, CT: Boehringer Ingelheim
Pharmaceuticals Inc; 2004. 3Nishima K, et al. Anesthesiology. 2004;59:323-329.
 α2 Agonists: Dexmedetomidine

Clinical Effects Adverse Effects

ƒ Antihypertensive1,2 ƒ Bradycardia6
ƒ Sedative1,2 ƒ Hypotension6
ƒ Analgesic1,2 ƒ Dry mouth2
ƒ ↓ Shivering3 ƒ Vasoconstriction with
ƒ Anxiolytic effects4 rapid infusion or at
ƒ Patient rousability4 high doses2
ƒ Potentiates effects of opioids, ƒ Nausea2
sedatives, and anesthetics2
ƒ Decreased sympathetic
activity5 Dexmedetomidine
H CH3

1Kamibayashi T, et al. Anesthesiology. 2000;93:1345-1349.

2Precedex [package insert]. Lake Forest, IL: Hospira Inc; 2004.
3Doufas AG, et al. Stroke. 2003;34:1218-1223.
CH3 4Riker RR, et al. Pharmacotherapy. 2005;25(5 Pt 2):8S-18S.
N
5Venn RA, et al. Brit J Anaesthesia. 2001;87:684-690.
CH3
6Shehabi Y, et al. Intensive Care Med. 2004;30:2188-2196.
 Key Components of the
Ascending Arousal System

Saper CB, et al. Nature. 2005;437:1257-1263.

 Key Projections to the
Ascending Arousal System

Saper CB, et al. Nature. 2005;437:1257-1263.

“Switch” Mechanisms of Alertness and Sleep
ORX
a LC
TMN Awake
Raphe
VLPO
eVLPO On

ORX
b
VLPO
eVLPO
Sleep
LC
TMN
Raphe

Off

Saper CB, et al. Nature. 2005;437:1257-1263.

Clinical Characteristics of Dexmedetomidine

ƒ Cooperative sedation1
ƒ Analgesia2,3
ƒ Organ Protection (ie, neural, renal, cardiac)1
ƒ Anxiolysis2,3
ƒ Controls hyperadrenergic response to stress1-3
ƒ Reduces shivering3
ƒ Diuretic action4
ƒ Mimics Natural Sleep1

1AantaaR, et al. Drugs of the Future. 1993;18:49-56.

2KamibayashiT, et al. Anesthesiology. 2000;93:1345-1349.
3Wagner BKJ, et al. Clin Pharmacokinet. 1997;33:426-453.
4Goodman LS, et al. The Pharmacological Basis of Therapeutics. New York, NY: McGraw-Hill;2004:232-235.
Physiology of Dexmedetomidine
α2A, α2C Locus Ceruleus

α2A Brainstem vasomotor center

Anxiolysis

Vagomimetic action

Blocks cardioaccelerator nerve

α2B CNS-based thermoregulatory inhibition

α2B Cerebral vessels and peripheral vasculature

α2A Dorsal horn of the spinal cord

X
α2A Peripheral smooth-muscle cells

α2B

Reprinted with permission from Kamibayashi T, et al.

Anesthesiology. 2000;93:1346.
 Comparison of Clinical Effects
Benzo-
Propofol Opioids Dexmedetomidine Haloperidol
diazepines

Sedation X X X X X

Alleviate anxiety1,2 X X
Analgesic
X X
Properties1-4
Promote
arousability during X
sedation2-4
Facilitate ventilation
during weaning2-4
X

No respiratory
depression1-4
X X

Control delirium1-4 X X

1Blanchard AR. Postgrad Med. 2002;111:59-74.

2Kamibayashi T, et al Anesthesiology. 2000;95:1345-1349.
3Maze M. et al. Anesthetic Pharmacology: Physiologic Principals and Clinical Practice. Churchill Livingstone; 2004.
4Maze M, et al. Crit Care Clin. 2001;4:881.
 Comparison of Adverse Effects
Benzo-
Propofol Opioids Dexmedetomidine Haloperidol
diazepines
Prolonged
X X X*
weaning1
Respiratory
X X X
depression1
Hypotension1-3 X X X X X

Constipation1 X

Deliriogenic X X X

Tachycardia1 Morphine

Bradycardia1 Fentanyl X X

*
Excluding remifentanil

1Harvey MA. Am J Crit Care. 1996;5:7-16.

2Aantaa R, et al. Drugs of the Future. 1993;18:49-56.
3Maze M. Crit Care Clin. 2001;4:881;
 Sedative-Analgesics
Risk for Transitioning to Delirium

Transitioning to
Delirium Only • Evaluation of 198
Odds Ratio mechanically ventilated
Medication (95% CI) P Value patients to determine the
probability of daily
Lorazepam 1.2 (1.1-1.4) .003 transition to delirium1
– As a function of sedative
Midazolam 1.7 (0.9-3.2) .09 and analgesic dose
administration during the
Fentanyl 1.2 (1.0-1.5) .09 previous 24 hours1
Morphine 1.1 (0.9-1.2) .24 • Lorazepam was an
independent risk factor for
Propofol 1.2 (0.9-1.7) .18 daily transition to delirum1

1Panharipande P, et al. Anesthesiology. 2006;104:21-26.

 Serious Complications Associated
With Delirium

Response Number (%)

Prolonged ventilation 179 (20)
Patient injury 179 (20)
Respiratory complications 176 (19)
Self-extubation 80 (9)
Sepsis/shock 60 (7)
Prolonged LOS 58 (6)
Oversedation 52 (6)
Death 36 (4)

Ely EW, et al. Crit Care Med. 2004;32:106-112.

 Incidence of ICU Delirium

60 • Evaluation of 90
patients undergoing
50 cardiac surgery to
determine the
probability of
Delirium, %

40
development of
postoperative delirium1
30
• Post-operative sedation
with dexmedetomidine
20 may be associated with
a lower incidence of
10 delirium compared with
more conventional
forms of sedation1
0
Dexmedetomidine Propofol Midazolam
Maldonado JR, et al. Anesthesiology. 2003; 99: A465.
 Comparison of Pharmacokinetics
Ranges Reported in Healthy Patients* and ICU Patients
Systemic
Elimination Clearance Potential for
Agent Half-life (hr) (mL/kg/min) Accumulation4

Morphine1 2.0-5.5 8.6-23 Hepatic/renal insufficiency

Fentanyl1 6.9-36.0 8.6-15.0 Hepatic impairment

Diazepam1 21-120 0.4-0.9 Hepatic/renal insufficiency

Midazolam1 3.4-11 4.3-6.6 Hepatic/renal insufficiency

Lorazepam1 10-15 1.2-4.1 Hepatic insufficiency

Propofol1 6.3-32 17-31 –

Clonidine2 6-23 1.9-4.3 Renal insufficiency

Dexmedetomidine3 2 0.32-0.64 mL/hr/kg Hepatic insufficiency

Haloperidol1 28-38 10-13 Hepatic insufficiency

Aripiprazole4,5 75 3.45-4.5 L/h Hepatic insufficiency

Olanzapine4 7 7.5 --
Ziprasidone4 7 7.5 Hepatic insufficiency
*Healthy patients: no renal or hepatic disease.
1Wagner BKJ, et al. Clin Pharmacokinet. 1997;33:426-453;
2Khan ZP, et al. Anaesthesia. 1999;54:146-165; 3Bhana N, et al. Drugs. 2000;59:263;
4Prescribing information for respective drugs; 5Mallikaarjun S, et al. J Clin Pharmacol. 2004;44:179-187.
Dexmedetomidine
 Arousability From Sedation During
Dexmedetomidine Infusion

Just prior to cognitive and cold pressor testing ƒ Patients were infused with
During cognitive and cold pressor testing placebo or 1 of 2 doses of
100 dexmedetomidine and
monitored with the Bispectral
80
Index System (BIS) before
60 stimulation and immediately
B IS

40 after being asked to perform

20
cognitive and cold pressor
tests1
0
Placebo 0.2 0.6 ƒ Patients receiving either
Dexmedetomidine
infusion of dexmedetomidine
Infusion could be completely aroused
(mcg/kg/h) by a mild stimulus1

BIS indicates Bispectral Index System

1Hall JE, et al. Anesth Analg. 2000;90:699-705.
 Comparison of Dexmedetomidine
With Propofol
ƒ 20 adult ICU patients were randomized to
either dexmedetomidine or propofol1
– Dexmedetomidine; 10-minute 2.5 mcg/kg/h
loading dose, 0.2-2.5 mcg/kg/h maintenance dose1
– Propofol; ≤1 mg/kg 10-minute loading dose (if
required), 1-3 mg/kg/h maintenance dose1
ƒ Additional analgesia, if necessary, was
provided by alfentanil1
ƒ Depth of sedation was measured with RSS
and BIS1
ƒ Dexmedetomidine and propofol produced an
equivalent depth of sedation1
1Venn RM, et al. Br J Anaesth. 2001;87:684-690.
 Predictable Effects on
Mean Heart Rate, beats/min
Heart Rate and Arterial Pressure
120
110
Propofol ƒ Significantly lower heart
Dexmedetomidine
100
rates in the
Heart 90
dexmedetomidine group
Rate 80 during intubation
70 (P=.034) but not after
60 sedative discontinuation
50 (P=.15)1
0 1 2 3 4 5 6 7 8 +4 +8 +12 +16 +20 +24 − Predictable 10%
Mean Arterial Pressure, mm Hg

175 decrease with

160 plateau1
145
SBP 130 ƒ No significant differences
115 in systolic and diastolic
100
85
blood pressures (P=.60)1
DBP 70 ƒ Attenuates postoperative
55
40 tachycardia2
0 1 2 3 4 5 6 7 8 +4 +8 +12 +16 +20 +24

Sedative Discontinued
1Venn RM, et al. Br J Anaesth. 2001;87:684-690.
2Venn RM, et al. Br J Anaesth. 2001;86:650-656.
Note: Reductions from baseline shown.
 Postoperative Effects of Dexmedetomidine

100
More Pain

Propofol
40 Dexmedetomidine
VAS Pain

30

20 Improved
Less Pain

10 *† postoperative pain
0 and greater
100 sedation with
More Alert

80
*† dexmedetomidine
compared with
VAS Sedation

60
propofol1
Less Alert

40
0
Pre- Surg 5 20 35 50 65
surg End
Time After Surgery, minutes
*P<.05 difference over time compared with baseline
†
P<.05 difference between groups
1Arain SR, et al. Anesth Analg. 2002;95:461-466.
 Morphine-Sparing Effects in
Inpatient Surgery
12
ƒ 34 patients scheduled Morphine

Cumulative Morphine
10 Dexmedetomidine
for inpatient surgery1 8

Used, mg
ƒ Randomized to either 6
P<.01
dexmedetomidine or 4

morphine1 2
0
ƒ Agents were started 30 0 10 20 30 40 50 60 70

minutes before the end Minutes in PACU

of surgery1 12.5 P<.01

ƒ Dexmedetomidine Average Total Morphine 10

Used, mg
reduced the early 7.5

postoperative need for 5

morphine by 66%1 2.5

0
Morphine Dexmedetomidine
1Arain SR, et al. Anesth Analg. 2004;98:153-158.
Reduction of Postoperative Requirement for
Epidural Opioids With Dexmedetomidine
ƒ Prospective, randomized, double-blind study with 28
patients scheduled for thoracotomy for wedge
resection, lobectomy, or pneumonectomy1
ƒ Bupivacaine was administered in an acute care
setting through a thoracic epidural, and patients were
randomized to receive either IV placebo or IV
dexmedetomidine (20-minute, 0.5 mcg/kg loading
dose plus infusion of 0.4 mcg/kg/h)1
ƒ Supplemental analgesia (fentanyl), vital signs, and
blood gasses were monitored1

1Wahlander S, et al. J Cardiothorac Vasc Anesth. 2005;19:630-635.

 Reduction of Postoperative Requirement for
Opioids With Dexmedetomidine
Requirement for Supplemental Epidural (ED) Fentanyl
ƒ The requirement for
supplemental ED
80 fentanyl analgesia was
Total Fentanyl Used, mcg

significantly greater in
70 66.1 P=.039
the placebo group1
60
ƒ Dexmedetomidine is a
50 potentially effective
40 analgesic adjunct to
thoracic ED bupivacaine
30 infusion and may
20 decrease the
requirement for opioids
10 5.3
and potential for
0 respiratory depression1
Placebo Dexmedetomidine

1Wahlander S, et al. J Cardiothorac Vasc Anesth. 2005;19:630-635.

 Injury and Liability Associated With Monitored
Anesthesia Care
ƒ Bhananker and colleagues
MAC General Regional
assessed the patterns of injury
60 * and liability associated with
monitored anesthesia care (MAC;
n = 121) compared with general
Claims in Anesthesia Group, %

50 (n = 1519) and regional

* * anesthesia (n = 312)
40 ƒ The proportion of claims for death
and permanent brain damage
30 was reduced in regional
* anesthesia compared with MAC
20 ƒ In contrast, the severity of injury
was similar between MAC claims
10 and those associated with
general anesthesia
0
Death/Perm Brain Permanent Disabling Temp/Nondisabling
Damage

* P<.025 MAC versus Regional

Bhananker S, et al. Anesthesiology. 2006;104:228-34.

Injury and Liability Associated With Monitored
Anesthesia Care (Cont’d)

ƒ Respiratory depression due to sedative, hypnotic,

and/or analgesic overdose was responsible for 21% of
MAC-related claims
– 24% occurred during endoscopic procedures
– Nearly 75% received a combination of two or more drugs
• Either a benzodiazepine and an opioid or propofol plus others
ƒ Death or brain damage resulted in most of the claims
related to oversedation
ƒ Resolution of legal claims associated with oversedation
cost an average of $254,000 per patient

Bhananker S, et al. Anesthesiology. 2006;104:228-34.

Pharmacoeconomic Data
 Factors Affecting ICU Cost

ƒ ICU stays account for nearly a third of total inpatient costs1

ƒ High ICU costs may be due to mechanical ventilation (MV)
and/or delirium1,2
ƒ Sedatives have the potential to prolong MV and may
increase healthcare costs3,4
ƒ Incorporation of a daily sedation interruption policy into a
medical ICU guideline can significantly reduce ICU stays
and days of MV5

1Dasta JF, et al. Crit Care Med. 2005;33:1266-1271.

2 MilbrantEB, et al. Crit Care Med. 2004;32:955-962.
3Ostermann ME, et al. JAMA. 2000;283:1451-1459.
4MacLaren R, et al. Pharmacotherapy. 2005;25:1319-1328.
5Wittbrodt ET. Pharmacotherapy. 2005;25(5 Pt 2):3S-7S.
 Limitations of Pharmacoeconomic
Studies on Sedation

ƒ Small sample sizes1

ƒ Results not applicable to other clinical sites1
ƒ Too few have been conducted to date1
ƒ Most do not evaluate total cost1,2

1Ostermann ME, et al. JAMA. 2000;283:1451-1459.

2MacLaren R, et al. Pharmacotherapy. 2005;25:1319-1328.
 Pharmacoeconomic Analysis
Outcomes Analysis in Cardiac Surgery
ƒ 12-month retrospective administrative claims
database analysis (2003-2004)1
ƒ Nationally representative sample of 250 medical and
surgical hospitals1
ƒ Comparison of patients receiving either midazolam
plus propofol (M+P, n = 9996) or dexmedetomidine
plus M+P (D+M+P, n = 356)1
– Patients who were admitted to the hospital for either a
cardiovascular valve or vessel procedure1
– Patient demographics and outcomes were obtained from the
hospital billing claim form, UB-921
ƒ Admissions with lengths of stay more than 100 days
were excluded from all analyses

1Dasta JF, et al. Pharmacotherapy. 2006;26:798-805.

 Pharmacoeconomic Analysis
Baseline Characteristics
M+P D+M+P
Characteristic n = 9996 n = 356 P-Value
Age, y (mean [SD]) 65.6 (12.0) 61.0 (11.1) <.0001
Male 67.6% 78.9% <.0001
Patient Charlson Comorbidity Index <.05
0 34.4% 40.2%
1 56.7% 53.7%
2 7.6% 4.5%
3 1.0% 1.6%
4 0.3% 0%
Mechanical Ventilation/Intubation
Patients 78.1% 98.0% <.0001
Duration, days 5.46 4.82 <.01

1Dasta JF, et al. Pharmacotherapy. 2006;26:798-805.

 Pharmacoeconomic Analysis
Reduced Mean Total Treatment Charges

120
P<.05 ƒ 12-month retrospective
$106K administrative claims
Treatment Charges, $Thousands

100 database analysis1

$89K
ƒ Comparison of patients
80 receiving either
midazolam plus propofol
60 (M+P) or
dexmedetomidine plus
M+P (D+M+P)1
40
ƒ The D+M+P cohort
20
showed significant
reductions in per patient
total charges1
0

M+P D+M+P

M+P, n = 9996
D+M+P, n = 356
1Dasta JF, et al. Pharmacotherapy. 2006;26:798-805.
 Pharmacoeconomic Analysis
Departmental Treatment Charges
ICU/CCU Operating Room
20 20
$17.7K P<.0001 $17.3K P<.0001
Charges, $Thousands

Charges, $Thousands
18 18
16 16
14 14 $12.8K
12 12
10 10
8 8
6
4 $2.8K
6
4 Reductions in
2
0
2
0 ICU and OR
M+P D+M+P M+P D+M+P charges offset
Pharmacy Anesthesia
increases in
18 P<.0001 $16.7K 4 P<.0001 other areas
$3.4K
Charges, $Thousands

Charges, $Thousands

16
14 $12.7K 3
12
$2.5K
10
2
8
6
4 1
2
0 0

M+P D+M+P M+P D+M+P

M+P, n = 9996
D+M+P, n = 356
1Dasta JF, et al. Pharmacotherapy. 2006;26:798-805.
 Pharmacoeconomic Analysis
Reduced Hospitalization and Mortality

Mean Length of Stay Mean Days in ICU/CCU Mortality Rate

P<.0001 P<.0001 P=.0142
10 9.4 6 4
8.8 5.3
9
5
8 3.0%
3

Mortality Rate, %
7
4
Mean Days

Mean Days
6
5 3 2
4
2
3 1.4 1.0%
1
2
1
1
0 0 0
M+P D+M+P M+P D+M+P M+P D+M+P

M+P, n = 9996
D+M+P, n = 356
1Dasta JF, et al. Pharmacotherapy. 2006;26:798-805.
 Pharmacoeconomic Analysis
Reduced Charges, Hospitalization, and Mortality in
Patients With Cardiac Vessel Procedures
Mean Total Charges Mean Length of Stay Mortality Rate
P<.05 P<.01 P=.1074
120 10 3
8.9
9 2.5%
100 $97K 8.1 2.5
8
Charges, $Thousands

Mortality Rate, %
$80K 7
80 2
Mean Days

6
60 5 1.5
4 1.0%
40 1
3
2
20 0.5
1
0 0 0
M+P D+M+P M+P D+M+P M+P D+M+P

M+P, n = 7577 1Dasta JF, et al. Pharmacotherapy. 2006;26:798-805.

D+M+P, n = 293
 Pharmacoeconomic Analysis
Study Limitations

ƒ Dosage
ƒ Duration of therapies
ƒ Influence of practice patterns/institutional
variability unknown
ƒ Lack of randomization of patients to treatment
introduced risk of selection or channeling bias
ƒ Assigning causality based on results not
possible1

1Dasta JF, et al. Pharmacotherapy. 2006;26:798-805.

 Pharmacoeconomic Analysis
Study Conclusions
ƒ Dexmedetomidine was added to standard sedative
regimens (midazolam + propofol) under actual
practice conditions1
ƒ Largest study measuring the pharmacoeconomic
and clinical outcomes of any sedation agent in this
population
ƒ Potential demonstrable clinical and economic
benefits of including dexmedetomidine in sedation
regimens1
– Addition of dexmedetomidine to the standard of care was
associated with significant reductions in total LOS, stay in
ICU/CCU, and mortality1
– Significantly lower total treatment charges1
1Dasta JF, et al. Pharmacotherapy. 2006;26:798-805.
 Properties of Dexmedetomidine
in Cardiovascular Surgery

ƒ Lack of respiratory depression

ƒ Cooperative sedation aids in assessing
neurophysiological function during
vascular procedures such as
endarterectomy
ƒ Hemodynamic stabilization is desirable
during cardiovascular surgery
ƒ Attenuates hypertension and tachycardia

Aantaa R, et al. Eur J Anaesthesiol. 2006;23:361-372.

 Postoperative CABG Sedation
Dexmedetomidine Versus Propofol

Effects of Dexmedetomidine and Propofol on Heart Rate

15 Mean heart rates were

similar between groups
Mean Heart Rate Change, beats/min

10
throughout the study
period1

5
Propofol
Dexmedetomidine
0

-5

-10
10 20 30 1 2 3 4 5 6 7 8 9 10 11 12 13 14 15 16 17 18 19 20 21 22 23 24
Minutes
Time, hours

1Herr DL, et al. J Cardiothorac Vasc Anesth. 2003;17:576-584.

 Immediate Extubation Following
Cardiac Surgery
ƒ Horswell et al conducted a study of immediate
extubation after off-pump coronary artery bypass graft
(OPCAB) in 514 patients
ƒ Following surgery, each patient received 2 or more of
the following: epidural anesthesia, IV morphine on
demand, IV ketorolac on schedule, and/or continuous IV
dexmedetomidine
ƒ All patients were successfully extubated immediately
after dressing application
ƒ The investigators concluded that immediate extubation
of OPCAB patients is feasible and probably safe1

1Horswell JL, et al. J Cardiothorac Vasc Anesth. 2005;19:282-287.

 Use of Perioperative Dexmedetomidine
in Vascular Surgery
Dexmedetomidine Placebo ƒ Significant between
nmol/mL mg/gm creatinine group changes from
10
9 Norepinephrine *
1100
1000 Normetanephrine #
baseline for plasma
8
#
*
#
*
900
#
*
*
epinephrine (P<.05) and
7 800
norepinephrine (P<.001)
6 700 #

5 600
*
ƒ Plasma norepinephrine
4
3
500
400
concentrations were 2 to
2 300 3 times lower in the
1
baseline preop intub extub PAC U PACU+60
200
baseline intraop POD1 AM POD1 PM POD2 AM POD2 PM
dexmedetomidine group
nmol/mL mg/gm creatinine at both tracheal
5 350
extubation and at 60 min
Epinephrine Metanephrine
4 #
*
300 after arrival to PACU
3
* *
250 ƒ Plasma epinephrine
2 200
concentrations were
lower in the
1 150
dexmedetomidine group
0
baseline preop intub extub PACU PACU+60
100
baseline intraop POD1 AM POD1 PM POD2 AM POD2 PM
only during tracheal
extubation
# Significantly different (P<.05) from dexmedetomidine group.
* Significantly different (P<.05) from baseline.
1Talke P, et al. Anesth Analg. 2000;90:834-839.
Neurological Effects
 Properties of Dexmedetomidine
in Neurosurgery

ƒ Intraoperative hemodynamic stability1

ƒ Lack of respiratory depression1
ƒ Patients easily transition from sleep to
wakefulness and task performance when
aroused, and then back to sleep when not
stimulated1
ƒ Does not increase intracranial pressure1
ƒ Allows for consistent and reliable
somatosensory evoked potential amplitudes
or latencies1
1Bekker A, Sturaitis MK. Neurosurgery. 2005;57:1-10.
 Examples of Cooperative Sedation
Neurological Examples
ƒ Intracranial surgical procedures often require patient
cooperation for functional assessment1
– The procedure is frequently limited by the location/spatial extent
of the lesion and its relationship to functioning tissue1
– Surgeons balance the benefits of an aggressive resection with
anticipated neurological dysfunction1
ƒ Intraoperative neurophysiological testing1
– Can verify that surgical target has been localized1
– Is used to assess the production of an intended functional
change1
ƒ Carotid endarterectomy performed in awake patients
allows evaluation of cerebral perfusion by continuous
examination of neurologic function2

1Bekker AY, et al. Neurosurgery. 2005; 57(1 Suppl):1-10.

2Bekker AY, et al. J Neurosurg Anesthesiol. 2004;16:126-135.
Dexmedetomidine and Cerebral Blood Flow
Clinical Data
ƒ Reduced cerebral blood flow (CBF) has also been
demonstrated in human studies1
– Reduced CBF may be advantageous for situations such as
traumatic brain injury or large brain tumors1
ƒ No detrimental effect on local brain tissue oxygenation in
patients undergoing cerebral vascular surgery1
ƒ Under normotensive conditions in the setting of
compromised cerebral circulation, dexmedetomidine has
no apparent adverse effects1
ƒ It has been shown that dexmedetomidine is suitable for
preoperative sedation of patients with subarachnoid
hemorrhage (SAH)2

1Bekker A, Sturaitis MK. Neurosurgery. 2005;57:1-10.

2Sato K, et al. Masui. 2006;55:51-54.
Dexmedetomidine and Cerebral Blood Flow
Decreased Cerebral Metabolic Rate

ƒ Prielipp and colleagues analyzed data from nine

supine volunteers to assess the potential for
dexmedetomidine induced decreases in regional
and global CBF
ƒ Patients were infused with a 1 mcg/kg IV loading
dose of dexmedetomidine, followed by an
infusions of either
– 0.2 mcg/kg/h (Low Dose)
– 0.6 mcg/kg/h (High Dose)

Prielipp RC, et al. Anesth Analg.2002;95:1052-1059.

 Dexmedetomidine and Cerebral Blood Flow
Decreased Cerebral Metabolic Rate

Baseline Low Infusion High Infusion 30 min post- ƒ Both low and high doses
termination – Reduced global CBF by
one third
– Decreased mean
systemic BP, HR, and
CO 15% to 20%
– Increased PaCO2 no
more than 5 mm Hg
ƒ CBF decreased from
baseline throughout
dexmedetomidine infusion
and for at least 30 minutes
thereafter
Note: Color intensity correlates with CBF

Prielipp RC, et al. Anesth Analg.2002;95:1052-1059.

 Dexmedetomidine and Cerebral Blood Flow
Cerebral Perfusion in Severe Head Injury

ƒ Prospective study on the effect of dexmedetomidine

in patients with severe head injury
– 12 ICU patients (aged 15 to 64 years)
– Glasgow Coma Scale <8
– Intracranial pressure <20 mm Hg
– O2 saturation monitoring of blood from jugular bulb
ƒ 3 hours of progressive IV dexmedetomidine
perfusion (0.2, 0.4, 0.7 mcg/kg/h)
– All other sedative-analgesic medications previously
withdrawn

Grille P, et al. Neurocirugia. 2005;16:411-8.

 Dexmedetomidine and Cerebral Blood Flow
Cerebral Perfusion in Severe Head Injury (Cont’d)
90 30
ƒ No significant

Intracranial
Pressure
85
Jugular O2

20
80
10 changes from
75
70
0 baseline in the
following
140
65
120

MAP
60
40
100
domains
Cerebral O2

80
35
30 20
– Intracranial
pressure
Perfusion
Cerebral
25
100
20
15
80 – Mean arterial
10
0 30 60 90 120 150 180
60
0 30 60 90 120 150 180
pressure
Time (min) Time (min) – Cerebral
120
profusion
– Jugular bulb
Pressure During Sedation

110
oxygenation
#
Change in Intracranial

# # # # # * * 10
100
*
– Cerebral
Heart Rate

90 5

80 oxygen
70
0 extraction/
60
supply
-5
50
0 30 60 90 120 150 180 0 30 60 90 120 150 180
– Heart rate
Time (min) Time (min)
# P<.05
* P<.001 1Grille P, et al. Neurocirugia. 2005;16:411-8.
Pediatric Applications
 Use of Dexmedetomidine in MRI

ƒ 80 children aged 1-7 years1 Quality of MRI

ƒ Randomly assigned to either
dexmedetomidine or midazolam1 40 Midazolam
– 10-minute loading doses: Dexmedetomidine
1 mcg/kg dexmedetomidine, *
0.2 mg/kg midazolam1 30

Number of Patients
1 = no motion
– Infusions: 0.5 mcg/kg/h 2 = minor movement
dexmedetomidine, 3 = major movement
6 mcg/kg/h midazolam1 20 necessitating another scan

ƒ The quality of MRI was

significantly better (P<.001) and
the rate of adequate sedation was 10
significantly higher (P<.001) with
*
dexmedetomidine1
0
1 2 3
*P<.001 compared with midazolam
1Koroglu A, et al. Br J Anaesth. 2005;94:821-824.
 Dexmedetomidine Superior to Midazolam
in Pediatric Acute Care Patients
• 20 pediatric ICU patients randomized to Reduced Need for Morphine
either dexmedetomidine (starting dose
0.25 or 0.5 mcg/kg/h) or midazolam 0.8
(starting dose 0.1 mg/kg/h)1 *P=.01 compared with midazolam

Total Morphine Used, mg/kg/24 h

0.7
• Morphine was used intermittently as
needed1 0.6
• 0.25 mcg/kg/h dexmedetomidine was
0.5
equivalent to 0.22 mg/kg/h midazolam1
• 0.5 mcg/kg/h dexmedetomidine provided 0.4
more effective sedation than 0.22
0.3 *
mg/kg/h midazolam1
– Less morphine use1 0.2
– Decrease in the number of Ramsay
0.1
scores of 1 (fewer patients oversedated)
[Data not shown]1 0
Midazolam 0.25 0.5 mcg/kg/h
Dexmedetomidine
1Tobias JD, et al. South Med J. 2004;97:451-455.
Propofol Black Box Warnings for Pediatric Use

ƒ Not recommended for

– Induction of anesthesia in patients aged <3 years1
– Maintenance of anesthesia in patients aged <2
months1
ƒ Pediatric use
– Not indicated for ICU sedation or for MAC
sedation for surgical, nonsurgical, or diagnostic
procedures1
– Co-administration of fentanyl and propofol may
result in serious bradycardia1

1Propofol [package insert]. Bedford, OH: Bedford Laboratories; 2005.

Dexmedetomidine
in
Bariatric Surgery
 Intraoperative Use of
Dexmedetomidine in Bariatric Surgery

ƒ Rising incidence of morbid obesity is increasing the need for

bariatric surgery1,2
ƒ Respiratory comorbidities in morbid obesity may profoundly
impact anesthetic management1,2
– Opioid use may lead to severe respiratory depression1,2
– Ideal analgesics should be free of significant/long-lasting respiratory
effects1,2
ƒ In one center, over 2000 bariatric procedures have been
performed safely using the perioperative administration of
dexmedetomidine, which was shown to be cardioprotective
and neuroprotective while providing a hemodynamically
stable course and reducing the need for opioids and
inhalational agents3 1HoferRE, et al. Can J Anaesth. 2005;52:176-180.
2FeldJM, et al. J Clin Anesthesia. 2006;18:24-28.
3Ramsay MA. Semin Anesth.2006;25:51-56.
Dexmedetomidine Attenuates Blood Pressure
in Bariatric Surgery
120
Mean Blood Pressure (mm Hg)

Fentanyl
Dexmedetomidine
ƒ Feld and colleagues
100 evaluated whether
dexmedetomidine infusion
80 could replace fentanyl in open
gastric bypass surgery1
60
ƒ During surgery, blood
40
pressure and heart rate were
120 significantly decreased with
dexmedetomidine compared
Heart Rate, BPM (min -1)

100 with fentanyl1

ƒ Dexmedetomidine was
80
associated with significantly
lower postoperative pain and
60
morphine use1
40
0 60 120 180
Time (min)
1Feld JM, et al. J Clin Anesthesia. 2006;18:24-28.
Algorithms
 Dexmedetomidine Sedation Algorithm
Initial assessment of patient’s sedation level
Is the patient comfortable, cooperative, and communicative? SAS ≤4 ?
N
N
Is the patient agitated or in pain? SAS >4?
Y
If the patient is somnolent
or unresponsive with SAS Initiate Dexmedetomidine
<3, assess for CNS event, • Begin infusion: 0.2 mcg/kg/hr
metabolic process, and (If SAS<6 and hemodynamics are normal or depressed)
drugs. If dexmedetomidine • If hyperdynamic and SAS >6: Bolus, 1.0 mcg/kg over
infusion is ongoing, 10-20 minutes
decrease by 0.1 mcg/kg/hr
with ongoing assessment Ongoing assessment of patient’s sedation level
of sedation. • SAS >4
• Patient is agitated or in pain? Y

N
Dexmedetomidine infusion rate <0.7 mcg/kg/hr
N Y
Y

Assess pain and implement Increase

supplemental opioid protocol as dexmedetomidine infusion
needed rate <0.1 mcg/kg/hr

Implement supplemental agitation Y

protocol (dexmedetomidine <2.0
mcg/kg/hr) if patient demonstrates
agitation on assessment (SAS > 4)
Peruzzi/NMH/NUMS Protocol. March, 2001.
 Transitioning Long-Term Sedation
to Dexmedetomidine
Titrate propofol every hour with orders not to increase

Administer dexmedetomidine If extreme agitation occurs, add

infusion, benzodiazepine (synergistic
0.4 mcg/kg/hr with dexmedetomidine)

Titrate dexmedetomidine If patient is agitated on waking,

according to HR and BP administer more benzodiazepine
with allowed increases of (requirement is less with
0.2 mcg/kg/hr dexmedetomidine on board)

Increase dose of
dexmedetomidine in PM
to optimize natural sleep
and circadian rhythm

Courtesy of Daniel L. Herr, MD.

 Abdominal Aortic Aneurysm

Administer supplemental O2 via nasal cannulae

ƒ Patients undergoing endovascular
Administer dexmedetomidine loading dose repair of abdominal aortic
1 mcg/kg via infusion pump aneurysms with general (n = 217;
22 used for direct comparison)
Initiate maintenance dexmedetomidine infusion
(0.3 to 0.7 mcg/kg/h) versus dexmedetomidine (n = 14)
sedation
Administer 0.5% bupivacaine
ƒ Dexmedetomidine sedation
Access femoral arteries via 2 small surgical resulted in
incisions in both groins
– Reduced time for surgery
Cannulate arteries and insert grafts – Reduced time for anesthesia
– Reduced opioid requirement
Awaken patient and request holding of breath to
induce apnea. Patient must remain still.

Complete procedure and bring patient to lighter

sedation level prior to OR discharge

Brown BJ, et al. Proc (Bayl Univ Med Cent). 2006;19:213-215.

 Neurosurgery Anesthesia Protocol
Induce as usual; when stable, start dexmedetomidine at 0.7 mcg/kg/h

After 15 mins reduce inhalant anesthetic to half MAC

Opioid use
Routine dose of fentanyl at induction of anesthesia

N
Hemodynamics indicative of
Use supplemental opioid
adequate analgesia?
Y

Five minutes prior to end of procedure,

reduce dexmedetomidine to 0.2 mcg/kg/h

Awaken patient and extubate

Titrate dexmedetomidine after extubation to patient comfort

(usually 0.2 – 0.5 mcg/kg/h)
Courtesy of M. Ramsay, MD.
 Perioperative Bariatric Surgery Algorithm
Preoperative Protocol
Assess cardiac functioning
Indications of cardiomegaly, cardiac failure, CAD, or pulmonary
HTN?
Y N
Optimize cardiac
Assess airway/
state
respiratory system

Obstruction of airway
by adipose tissue?
Y N

Awake fiberoptic Obstructive sleep apnea?

intubation O2 Desaturation Risk?
↓ Lung Volumes
Functional residual capacity
Administer Dexmedetomidine (<0.7 Expiratory reserve
mcg/kg/h) plus topical anesthetic Forced vital capacity
Y
N
Correct head positioning
Use “back up” position at induction Proceed to
of anesthesia and subsequent Intraoperative
recovery Procedure
Courtesy of M. Ramsay, MD.
 Perioperative Bariatric Surgery Algorithm
Intraoperative Protocol
Brief Procedure

Y N

Laproscopic gastric bypass or Roux-en Y gastric bypass

gastric banding
Dexmedetomidine solution
400 mcg/100 mL of 0.9% sodium chloride at
Administer Dexmedetomidine 4 mcg/mL
Loading Dose
0.5 to 0.75 mcg/kg and monitor Initiate dexmedetomidine infusion
for transient hypertension (0.4 to 0.7 mcg/kg/h)
1 hour before completion of surgery

Reduce infusion at end of surgery

(approximately 5 min prior to completion)

Allow patient to gradually awaken

Proceed to Postoperative Procedure

Courtesy of M. Ramsay, MD.

Perioperative Bariatric Surgery Algorithm
Postoperative Protocol

Continue infusion in the recovery room

during and after intubation

Titrate to
No postoperative
0.7 mcg/kg/h for
opioids needed
pain control

Discontinue dexmedetomidine at
discharge from recovery unit

Courtesy of M. Ramsay, MD.

 Overall Summary

ƒ Patient care and safety, as well as physiological

and neurobehavioral considerations, reinforce the
need for sedation in acute care settings
ƒ Attenuating reactions to pain and stress while
optimizing patient communication are important
acute care goals
ƒ Inappropriate sedation and analgesic therapy in
acute care settings leads to poor clinical and
economic outcomes
ƒ Guidelines, standards, clinical pathways, and
algorithms clarify the manner in which sedatives
should be used in acute care settings
– Institutions should have multidisciplinary agreements to
use scale assessment and documentation
 Overall Summary (Cont’d)

ƒ Ongoing developments influence changes in

guidelines and standards
– It is anticipated that JCAHO will add new sedation criteria
– Currently under revision, new SCCM guidelines are
expected in 2007
ƒ Implementation of rational use guidelines in acute
care sedation can result in improved LOS and
reduced costs for medications
ƒ The addition of dexmedetomidine to the current
standard of care is associated with improved
clinical outcomes and reduced total hospital costs