Skousen Sedation2.ppt

108

Transcript of Skousen Sedation2.ppt

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Roy N Skousen, DOHillcrest Medical Center, Staff Anesthesiologist

Director Neuro-Surgical and Obstetrical Anesthesia Services

Associate Professor Clinical AnesthesiaOklahoma State University College of Osteopathic Medicine

Tulsa, Oklahoma

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Disclosure The Academy for Continued Healthcare Learning (ACHL) requires that the faculty participating in a CME/CE activity disclose any relevant affiliation or other financial relationship (1) with the manufacturers of any commercial product(s) and/or provider(s) of commercial services discussed in an educational presentation, and (2) with any commercial supporters of the activity. Conflict resolution must occur prior to the CME/CE activity. The ACHL also requires participating faculty to disclose when unapproved/unlabeled uses of a product are discussed in a CME/CE activity.

The faculty member has provided the following disclosure information.

Dr Roy N Skousen, has disclosed the following commercial/financial relationships: Member of Speakers Bureau for Baxter Pharmaceuticals.

The faculty discloses that they will discuss the unapproved/off label use of sedatives and analgesics.

The Academy for Continued Healthcare Learning staff members and others involved with the planning, development, and review of the content for this activity have no relevant affiliations or financial relationships to disclose.

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The content for this activity was developed independently of the commercial supporter. All materials are included with permission. The opinions expressed are those of the faculty and are not to be construed as those of the publisher or grantor.

This educational activity was planned and produced in accordance with the ACCME Essential Areas and Elements, Policies, and Standards for Commercial Support as well as the ACPE Criteria for Quality and Interpretive Guidelines. Recommendations involving clinical medicine in a continuing medical education (CME/CE) activity must be based on evidence that is accepted within the profession of medicine as adequate justification for their indications and contraindications in the care of patients. All scientific research referred to, reported, or used in CME/CE in support or justification of a patient care recommendation must conform to the generally accepted standards of experimental design, data collection, and analysis.

Participants are advised that one or more presentations in this CME/CE activity may contain references to unapproved or unlabeled uses of drugs or devices. Participants should note that the use of these agents outside current approved labeling is considered investigational and are advised to consult current prescribing information for these products.

Disclaimer

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Learning Objectives

Upon completion of this activity, participants will Evaluate methods for the systematic assessment of

patient sedation and analgesia in acute care settings to optimize use of appropriate sedatives and analgesics

Compare safety and efficacy of various sedatives and analgesics to aid in the selection of appropriate agents for procedural, nonsurgical sedation

Analyze current research data to re-evaluate use of sedatives and analgesics in specific patient populations

Assess the safety and efficacy of dexmedetomidine as either the primary sedative or as an anesthetic adjuvant during surgery

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Overview of Current Sedativeand Analgesic Agents

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Characteristics of an Ideal Sedative

Rapid onset of action allows rapid recovery after discontinuation1

Effective at providing adequate sedation with predictable dose response1,2

Easy to administer1,3

Lack of drug accumulation1

Few adverse effects1-3

Minimal adverse interactions with other drugs1-3

Cost-effective3

Predictable dose response2

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. Pharmacother. 2006;26:798-805.4Nelson LE, et al. Anesthesiol. 2003;98:428-436.

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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

2 agonists Clonidine 1986

Dexmedetomidine 1999

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

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Ranges Reported in Healthy Patients* and ICU Patients

Comparison of Pharmacokinetics

3Bhana N, et al. Drugs. 2000;59:263.4Prescribing information for respective drugs.

5Mallikaarjun S, et al. J Clin Pharmacol. 2004;44:179-187.

0.32-0.64 mL/kg/hr2Dexmedetomidine3

1.9-4.36-23Clonidine2

17-316.3-32Propofol1

1.2-4.110-15 Lorazepam1

4.3-6.63.4-11Midazolam1

0.4-0.921-120Diazepam1

8.6-15.06.9-36.0Fentanyl18.6-23.02.0-5.5Morphine1

10-1328-38Haloperidol1

Hepatic/renal insufficiency

Hepatic impairment

Hepatic/renal insufficiency

Hepatic/renal insufficiency

Hepatic insufficiency

Hepatic insufficiency

Hepatic insufficiency

Renal insufficiency

Systemic Clearance

(mL/kg/min)EliminationHalf-life (hr)Agent

Potential for Accumulation4

*Healthy patients: no renal or hepatic disease

3.45-4.5 L/h75Aripiprazole4,5

7.57Olanzapine4 --

7.57Ziprasidone4 Hepatic insufficiency

Hepatic insufficiency

1Wagner BKJ, et al. Clin Pharmacokinet. 1997;33:426-453.2Khan ZP, et al. Anaesthesia. 1999;54:146-165.

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Opioids

Clinical Effects Analgesia1

Sedation1

1Harvey MA. Am J Crit Care. 1996;5:7-16.2Wagner BKJ, 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.

Adverse Effects Respiratory depression1,2

Hypotension1,2

Bradycardia1,2

Constipation1

Tolerance1

Withdrawal symptoms1,2

Dysphoria3,4

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Haloperidol

Clinical Effects

Hypnotic agent with antipsychotic properties1

– For treatment of delirium in critically ill adults1

Does not cause respiratory depression1

1Harvey MA. Am J Crit Care. 1996;5:7-16.2Crippen DW. Crit Care Clin. 1990;6:369-392.

Adverse Effects

Dysphoria2

Adverse CV effects include QT interval prolongation

Extrapyramidal symptoms, neuroleptic malignant syndrome (rare)1

Metabolism altered by drug-drug interactions2

F

O

NCl

OH

Haloperidol

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Benzodiazepines Lorazepam

Clinical Effects Sedation, anxiolysis, and

amnesia1

Commonly used for long-term sedation2

4Neale BW, et al. Ann Pharmacother. 2005;39:1732-1736.

5Wilson KC, et al. Chest. 2005;128:1674-1681.6Mathews A, et al. J Psychopharmacol. 2002;16:345-354.

7Pandharipande P, et al. Anesthesiol. 2006;104:21-26.

Adverse Effects Slower onset of action than

midazolam2,3

Retrograde and anterograde amnesia can exceed desirability6

Delirium7

Severe Adverse Effect Metabolic acidosis

(propylene glycol toxicity)4,5

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.

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BenzodiazepinesMidazolam

Clinical Effects Sedation, anxiolysis,

and amnesia1

Rapid onset of action intravenously1

1Blanchard AR. 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.

Adverse Effects May accumulate in liver

and/or renal failure1

Anterograde amnesia2

Prolonged recovery after long-term use3

Combination with opioids increases hypotensive effects1

Respiratory depression4

Adverse hemodynamicevents in pediatric patients with cardiovascular instability4

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Propofol

Clinical Effects Sedation1

Hypnosis1

Anxiolysis1

Muscle relaxation1

ICP1

Cerebral metabolic rate1

Antiemetic2

Adverse Effects Respiratory depression

(exacerbated by opioids)1

Hypotension1

Decreased myocardial contractility3

Preservative issues4

Potential for infection4

Tolerance5

Serum triglycerides4

Severe Adverse Effect Propofol infusion syndrome6

4Diprivan [package insert]. AstraZeneca Pharmaceuticals; 2004.5Zapantis A, et al. Crit Care Nurs Clin N Am. 2005;17:211-223.

6Riker RR, et al. Pharmacother. 2005;25(5 Pt 2):8S-18S.

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.

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2 AgonistsClonidine

Clinical Effects Antihypertensive1,2

Analgesia1

Anxiolysis1

Sedation1

Shivering1

Potentiate effects of opioids, sedatives, and anesthetics1

Decrease sympathetic activity1

1Kamibayashi T, et al. Anesthesiol. 2000;93:1345-1349. 2Catapres [package insert]. Ridgefield, CT: Boehringer Ingelheim Pharmaceuticals Inc; 2004.

3Nishina K, et al. Anesthesiol. 2002;96:323-329.

Adverse Effects Bradycardia1

Dry mouth1

Hypotension3

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2 AgonistsDexmedetomidine

Clinical Effects Antihypertensive1,2

Sedation1,2

Analgesia1,2

Shivering3

Anxiolysis4

Patient rousability4

Potentiate effects of opioids, sedatives, and anesthetics1,2

Decrease sympathetic activity1,5

4Riker RR, et al. Pharmacother. 2005;25(5 Pt 2):8S-18S.5Venn RA, et al. Brit J Anaesthesia. 2001;87:684-690.

6Shehabi Y, et al. Intensive Care Med. 2004;30:2188-2196.

Adverse Effects Bradycardia6

Hypotension6

Dry mouth2

Vasoconstriction with rapid infusion or at high doses2

Nausea2

1Kamibayashi T, et al. Anesthesiol. 2000;93:1345-1349.2Precedex [package insert]. Lake Forest, IL: Hospira Inc; 2004.3Doufas AG, et al. Stroke. 2003;34:1218-1223.

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Physiology of 2 Receptors

Reprinted with permission from Kamibayashi T, et al. Anesthesiol. 2000;93:1346.

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Effects of Current Sedativeand Analgesic Agents

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Benzo- diazepines

Propofol Opioids 2 Agonists Haloperidol

Sedation X X X X X

Alleviate anxiety1,2 X X

Analgesic properties1-4 X X

Promote arousability during sedation2-4 X

Facilitate ventilation during weaning2-4 X

No respiratory depression1-4 X X

Control delirium1-4 X X

Comparison of Clinical Effects

1Blanchard AR. Postgrad Med. 2002;111:59-74.2Kamibayashi T, et al. Anesthesiol. 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.

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Benzo- diazepines

Propofol Opioids 2 Agonists Haloperidol

Organ protection (ie, neural, cardiac, renal)1,2,6

X X

Control stress response1-3 X

Reduces shivering2,3 X

Cooperative sedation1 dexmedetomidine

Diuretic action4 dexmedetomidine

Mimics natural sleep1,5 dexmedetomidine

Comparison of Clinical Effects

1Aantaa R, et al. Drugs of the Future. 1993;18:49-56.2Kamibayashi T, et al. Anesthesiol. 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-

235.5Huupponen E, et al. Acta Anaesthesiol Scand. 2008;52:289-294.

6Adembri C, et al. CNS Drug Rev. 2007;13:333-351.

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Benzo- diazepines

Propofol Opioids 2 Agonists Haloperidol

Prolonged weaning1 X X X*

Respiratory depression1 X X X

Hypotension1-3 X X X X X

Constipation1 X

Deliriogenic X X X

Tachycardia1 morphine

Bradycardia1 fentanyl X X

Comparison of Adverse Effects

*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.

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Arousability From Sedation

During cognitive and cold pressor testing

Just prior to cognitive and cold pressor testing

Dexmedetomidine Infusion(μg/kg/hr)

0

20

40

60

80

100

Placebo 0.2 0.6

BIS

Hall JE, et al. Anesth Analg. 2000;90:699-705.

Patients were infused with placebo or 1 of 2 doses of dexmedetomidine and monitored with the Bispectral Index System (BIS) before stimulation and immediately after being asked to perform cognitive and cold pressor tests

Patients receiving either infusion of dexmedetomidine could be completely aroused by a mild stimulus

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ModerateLowPlacebo

50

60

70

80

90

100

pre 10 20 30 40 50 60 tests 0.5 1 tests 1.5 2 3 4 tests

Infusion Period (min) Recovery Period (hr)

BIS

Arousability From Sedation

Hall JE, et al. Anesth Analg. 2000;90:699-705.

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Sedative-AnalgesicsRisk for Transitioning to Delirium

Evaluation of delirium in 198 mechanically ventilated patients as a function of sedative and analgesic dose during the previous 24 hours

Lorazepam was an independent risk factor for daily transition to delirium

For every unit dose of lorazepam, a 20% increased risk of delirium was observed

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

Medication

Transitioning to Delirium Odds Ratio (95% CI) P-Value

Lorazepam 1.2 (1.1-1.4) .003

Midazolam 1.7 (0.9-3.2) .09

Fentanyl 1.2 (1.0-1.5) .09

Morphine 1.1 (0.9-1.2) .24

Propofol 1.2 (0.9-1.7) .18

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Risk of Transitioning to Delirium

Pandharipande P, et al. Anesthesiol. 2006:104:21-26.Courtesy of EW Ely, MD, MPH.

Lorazepam Dose, mg

Del

irium

Ris

k

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Serious Complications Associated With Delirium

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)

Response Number (%)

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

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MENDS Trial: Effect on Acute Brain Dysfunction

Pandharipande PP, et al. JAMA. 2007;298:2644-2653.

Double-blind, randomized, controlled trial compared investigational use dexmedetomidine (1.5 μg/kg/hr, maximum) with lorazepam (10 mg/hr, maximum) for up to 120 hours

Measured delirium, coma, and sedation level in 106 adult mechanically ventilated medical and surgical ICU patients

Patients were monitored twice daily for delirium using the Confusion Assessment Method of the ICU (CAM-ICU)

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MENDS Trial: Effect on Acute Brain Dysfunction

Pandharipande PP, et al. JAMA. 2007;298:2644-2653.

Dexmedetomidine resulted in more days alive without delirium or coma (P=.01) and a lower prevalence of coma (P<.001) than lorazepam

Dexmedetomidine resulted in more time spent within sedation goals than lorazepam (P=.04)

The 28-day mortality in the dexmedetomidine group was 17% versus 27% in the lorazepam group (P=.18)

Da

ys

Lorazepam

Dexmedetomidine02

46

810

12

p = 0.011

Delirium/Coma-Free Days Delirium-Free Days

p = 0.086

Dexmedetomidine Lorazepam

p = 0.001

Coma-Free Days

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MENDS Trial: Safety Profile

OutcomeLorazepam

(n=50)Dexmedetomidine

(n=51)P-Value

Lowest SBP 97 (88,102) 96 (88,105) .58

Ever hypotensive (SBP <80) 20% 25% .51

Days on vasoactive meds 0 (0,3) 0 (0,2) .72

Sinus bradycardia (<60/min) 4% 17% .03

Heart rate <40 2% 2% .99

Self-extubations (reintubations) 2 (2) 4 (3) .41

Courtesy of EW Ely, MD, MPH. Pandharipande PP, et al. JAMA. 2007;298:2644-2653.

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MENDS Trial: Safety Profile

No differences between dexmedetomidine and lorazepam treatment groups in– Troponin

– SGPT

– Bilirubin

– ACTH

– Cortisol

– LH

– Prolactin

– Testosterone

Courtesy of EW Ely, MD, MPH. Pandharipande PP, et al. JAMA. 2007;298:2644-2653.

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Factors Affecting ICU Cost

ICU stays account for nearly a third of total inpatient costs1

High ICU costs may be due to mechanical ventilation (MV) and/or delirium1

Sedatives have the potential to prolong MV and may increase healthcare costs2,3

Incorporation of a daily sedation interruption policy into a medical ICU guideline can significantly reduce ICU stays and days of MV4

1Dasta JF, et al. Crit Care Med. 2005;33:1266-1271.2Ostermann ME, et al. JAMA. 2000;283:1451-1459.

3MacLaren R, et al. Pharmacother. 2005;25:1319-1328.4Wittbrodt ET. Pharmacother. 2005;25(5 Pt 2):3S-7S.

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MENDS Trial: Cost of Care$

Outcome Lorazepam Dexmedetomidine P-Value

Pharmacy 20.6 (10,42) 27.4 (16,46) .15

Respiratory 2.9 (2,6) 3.5 (2,7) .35

ICU cost 59.5 (36,83) 61.4 (37,108) .32

$ – Costs represented in thousands, US dollars (Median, IQR)

Courtesy of EW Ely, MD, MPH. Pandharipande PP, et al. JAMA. 2007;298:2644-2653.

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34 Pandharipande PP, et al. Anesthesiol. 2008;109:A418.

Compared dexmedetomidine sedation (n=19) with lorazepam sedation (n=20) in septic patients from the MENDS trial

Patients treated for up to 5 days, titrated to target Richmond Agitation-Sedation Scale (RASS)

Measured delirium, coma, and sedation level

Patients were monitored daily for delirium using the Confusion Assessment Method of the ICU (CAM-ICU)

MENDS Trial: Outcomes in Septic ICU Patients

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Outcome Lorazepam Dexmedetomidine P-Value

Delirium/coma-free days 1.5 (1, 5) 8 (4, 10) .002

Delirium-free days 7.4 (4, 8.2) 10 (7.5, 10) .01

Any delirium 70% 79% .52

MV-free days 2 (0, 8.5) 9.5 (0, 11.6) .04

Mortality 50% 21% .06

MENDS Trial: Outcomes in Septic ICU Patients

Pandharipande PP, et al. Anesthesiol. 2008;109:A418.

Safety Lorazepam Dexmedetomidine P-Value

Bradycardia 5% 11% .58

Any hypotension 25% 32% .51

Number of pressors 1.2 (1, 1.8) 1 (1, 1.4) .72

Pressor increase on study drug 35% 32% .03

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SEDCOM Trial:Long-Term Sedation in ICU Patients

Riker RR, et al. JAMA. 2009;301:489-499.

Double-blind, randomized, multicenter trial comparing long-term (>24 hr) dexmedetomidine (dex, n=244) with midazolam (mz, n=122)

Sedatives (dex 0.2-1.4 μg/kg/hr or mz 0.02-0.1 mg/kg/hr) titrated for light sedation, administered up to 30 days

Percentage of time within sedation target range was the primary end point

Sedation assessed with Richmond Agitation-Sedation Scale (RASS)

Delirium assessed with Confusion Assessment Method of the ICU (CAM-ICU)

Additional measures included duration of ventilation, length of stay in the ICU, nursing assessments, and adverse events

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OutcomeMidazolam

(n=122)Dexmedetomidine

(n=244)P-

Value

Time in target sedation range, % 75.1 77.3 .18

Patients completing daily arousal test 103 (84.3%) 225 (92%) .09

Patients requiring sedation interruption 112 (91.8%) 222 (91%) .85

Duration of sedation, days 4.1 3.5 .01

Time to extubation, days 5.6 3.7 .01

ICU length of stay, days 7.6 5.9 .24

Delirium prevalence 93 (76.6%) 132 (54%) .001

Delirium-free days 1.7 2.5 .002

Patients receiving open-label midazolam 60 (49%) 153 (63%) .02

Midazolam dose, mg/kg 0.11 0.09 .65

Patients receiving fentanyl 97 (79.5%) 180 (73.8%) .25

Fentanyl dose, μg/kg 9.6 6.4 .27

SEDCOM Trial:Efficacy Outcomes

Riker RR, et al. JAMA. 2009;301:489-499.

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0

20

40

60

80

100

Baseline 1 2 3 4 5 6

Pa

tien

ts W

ith D

elir

ium

, %

Midazolam

Dexmedetomidine

dexmedetomidine versus midazolam, P<.001

SEDCOM Trial:Prevalence of Delirium

Sample Size 118 229 109 206 92 175 77 134 57 92 42 60 44 34

Riker RR, et al. JAMA. 2009;301:489-499.

Treatment Day

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SEDCOM Trial:Safety Outcomes

Riker RR, et al. JAMA. 2009;301:489-499.

OutcomeMidazolam

(n=122)Dexmedetomidine

(n=244)P-

Value

Bradycardia 23 (18.9%) 103 (42.2%) .001

Bradycardia requiring intervention 1 (0.8%) 12 (4.9%) .07

Tachycardia 54 (44.3%) 62 (25.4%) .001

Tachycardia requiring intervention 12 (9.8%) 24 (9.8%) .99

Hypotension 68 (55.7%) 137 (56.1%) .99

Hypotension requiring intervention 33 (27%) 69 (28.3%) .90

Hypertension 54 (44.3%) 106 (43.4%) .91

Hypertension requiring intervention 36 (29.5) 46 (18.9) .02

Hyperglycemia 52 (42.6%) 138 (56.6%) .02

Infections 24 (19.7%) 25 (10.2%) .02

30-day mortality 31 (25.4%) 55 (22.5%) .60

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SEDCOM Trial:Summary

High doses of dex were safely administered for up to 30 days

No differences were observed in time at sedation target between mz and dex

Time to extubation and sedation duration were significantly lower in the dex group

Patients receiving dex experienced significantly less delirium

Bradycardia was the most notable adverse effect observed in the dex group

Riker RR, et al. JAMA. 2009;301:489-499.

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Extubation in the ICU

Arpino PA, et al. J Clin Pharm Ther. 2008;33:25-30.Siobal MS, et al. Resp Care. 2006;51:492-496.

Sedation used to decrease agitation in patients requiring mechanical ventilation

Sedative doses are reduced for spontaneous breathing trials and to facilitate extubation but can lead to agitation that requires resumption of sedation

Dexmedetomidine administered to facilitate extubation in mechanically ventilated patients who failed previous weaning attempts

Use of dexmedetomidine was associated with reductions in concomitant sedative and analgesic administration and led to successful extubation in many of the patients studied

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Awake Fiberoptic Intubation

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Sedative Properties for Awake Fiberoptic Intubation

Decrease discomfort in patients with difficult airways

Maintain airway with spontaneous ventilations to avoid respiratory depression and pulmonary aspiration

Provide adequate anxiolysis

Patient should be cooperative or rousable and not resist intubation

Carollo DS, et al. Curr Opin Anaesthesiol. 2008;21:457-461.Bergese SD, et al. J Clin Anesthesia. 2007;19:141-144.

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Case Reports of Awake Fiberoptic Intubation

Dexmedetomidine investigated as the sole sedative for awake fiberoptic intubation

Examined hemodynamic, oxygenation, and sedative effects

Abdelmalak B, et al. J Clin Anesthesia. 2007;19:370-373.

PatientReduction in MAP, %

Reduction in Heart Rate, %

Time to Ramsay Score of 4 (min)

Time to Intubation (min)

1 35 32 22 2.0

2 27 17 16 0.5

3 48 20 15 2.0

4 38 25 19 1.5

5 18 26 14 2.0

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Sedation for Awake Fiberoptic Intubation

Multicenter Phase III trial to evaluate the safety and efficacy of dexmedetomidine for sedation during elective awake fiberoptic intubation (AFOI)

Patients received dex 1.0 μg/kg and 0.7 μg/kg/hr (n=55), or placebo (n=50)

The primary end point was the percentage of patients receiving rescue midazolam to maintain appropriate sedation level

Sedation measured according to the Ramsay Sedation Scale (RSS)

Bergese SD, et al. Anesthesiol. 2008;109:A186.

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46 *P<.001 compared with placebo

2.85

1.07

0

1

2

3

4

Placebo Dex

Mid

azol

am, m

g

*

86.0

47.3

0

25

50

75

100

Placebo Dex

Mid

azol

am T

reat

men

t, %

*

Sedation for Awake Fiberoptic Intubation

Safety of dex for AFOI assessed through adverse events, lab tests, and vital signs

Hemodynamic stability was determined as a function of the time systolic blood pressure and heart rate were outside the normal range

Incidence of respiratory depression was similar between groups

Hypotension was the most common adverse event in the dex group; hypertension and tachycardia were the most common adverse events in the placebo group

Hemodynamic stability was similar between groups

Bergese SD, et al. Anesthesiol. 2008;109:A186.

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Comparing Agents for Awake Fiberoptic Intubation

Remifentanil (Rem) and dexmedetomidine (Dex) as local anesthetic adjuncts for awake fiberoptic intubation (AFOI)

30 patients with difficult airways were randomly assigned to receive either Rem (0.75 μg/kg; 0.075 μg/kg/min) or Dex (0.4 μg/kg; 0.7 μg/kg/hr) for AFOI

Data included heart rate, blood pressure, respiratory rate, bispectral index (BIS) level, SpO2, and Ramsay Sedation Scale (RSS) score

Hagberg CA, et al. Anesthesiol. 2008;109:A14.

Results Significantly more patients in the Rem group were intubated on the

first attempt (P=.02)

Dex patients had significantly greater oxygen saturation (P=.03)

Patients receiving Dex had a significantly lower RSS score (P=.008), but took longer to reach an RSS level of 3 (P<.05)

The Dex group had a significantly lower mean BIS (P=.018)

Page 48: Skousen Sedation2.ppt

Monitored Anesthesia Care

Page 49: Skousen Sedation2.ppt

49

Monitored Anesthesia Care (MAC)

Specific anesthetic protocol that includes careful monitoring and support of vital functions

Ensures adequate spontaneous ventilation; airway management is minimal and noninvasive

In general, MAC can be characterized by

– A sedated patient who can breathe spontaneously and is responsive to being called by name

– A sedation score ≥3 as assessed with the Observer’s Assessment of Alertness/Sedation Scale (OAA/S) or a bispectral index (BIS) <60

– Oxygen administration and airway control with partial or no mechanical ventilation

Piccioni F, et al. Minerva Anestesiol. 2008;74:393-408.

Page 50: Skousen Sedation2.ppt

50

Sedation During MAC

Multicenter Phase III trial to evaluate the safety and efficacy of dexmedetomidine for sedation of nonintubated patients under MAC

326 patients undergoing various elective procedures and/or surgeries under MAC received dex 1.0 μg/kg (n=129), dex 0.5 μg/kg (n=134), or placebo (n=63)

Sedation level measured according to Observer’s Assessment of Alertness/Sedation Scale (OAA/S)

Satisfaction was measured with the Iowa Satisfaction With Anesthesia Scale (ISAS) and anxiety was assessed before, during, and after drug administration

Candiotti K, et al. Anesthesiol. 2008;109:A1202.

Page 51: Skousen Sedation2.ppt

51

Midazolam UseFentanyl Use

Sedation During MAC

Candiotti K, et al. Anesthesiol. 2008;109:A1202.*P<.001 compared with placebo

4.1

1.40.9

0

1

2

3

4

5

Placebo Dex 0.5 Dex 1.0

Mid

azol

am, m

g

**

144.4

84.8 83.6

0

50

100

150

200

Placebo Dex 0.5 Dex 1.0

Fen

tany

l, μg

**

88.9

59.0

42.6

0

25

50

75

100

Placebo Dex 0.5 Dex 1.0

Fen

tany

l Tre

atm

ent,

%

**

96.8

59.7

45.7

0

25

50

75

100

Placebo Dex 0.5 Dex 1.0

Mid

azol

am T

reat

men

t, %

**

Page 52: Skousen Sedation2.ppt

52

Sedation During MAC

Dex maintained sedation level without additional midazolam significantly better than placebo

Significantly fewer patients on dex required postoperative analgesic treatment (P=.025)

ISAS scores were significantly higher in patients from both dex groups (P<.001)

Anxiety scores were significantly lower in patients in the dex 1.0 μg/kg group (P=.007)

Respiratory depression was significantly greater in the placebo group

The data indicate that dex is safe and effective in patients undergoing various procedures during MAC

Candiotti K, et al. Anesthesiol. 2008;109:A1202.

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53

MAC in Vascular Surgery

Study examining safety and efficacy of dexmedetomidine as the primary sedative for vascular procedures under MAC

55 patients receiving vascular stents or fistula placement under MAC received dex 1.0 μg/kg (n=21), dex 0.5 μg/kg (n=24), or placebo (n=10)

Sedation level measured according to Observer’s Assessment of Alertness/Sedation Scale (OAA/S)

Dex was effective for sedation during vascular procedures under MAC

No serious adverse hemodynamic or respiratory events occurred

Huncke TK, et al. Anesthesiol. 2008;109:A449.*P<.001 versus placebo

4.2

0.9 1.0

0

1

2

3

4

5

Placebo Dex 0.5 Dex 1.0

Mid

azo

lam

Do

se, m

g

**

220.0

65.544.0

0

50

100

150

200

250

Placebo Dex 0.5 Dex 1.0

Fe

nta

nyl

Do

se, μ

g*

*

Page 54: Skousen Sedation2.ppt

54

MAC for Cardiac Catheterization

Mester R, et al. Amer J Ther. 2008;15:24-30.

Retrospective analysis of ketamine–dexmedetomidine combination sedation for cardiac catheterization in children (N=16) under MAC

Sedation initiated with 2 mg/kg ketamine and 1 μg/kg dexmedetomidine, maintained by 2 μg/kg/hr dexmedetomidine

Heart rate, blood pressure, and oxygen saturation recorded; sedation efficacy determined by need for additional ketamine

Both the low heart rate and the high heart rate after ketamine–dexmedetomidine bolus administration significantly differed from baseline heart rate (91±20 versus 103±21 beats/min, P<.001; 110±25 versus 103±21 beats/min, P<.01)

No changes occurred in blood pressure or respiration rate; 3 patients required additional ketamine

The ketamine–dexmedetomidine combination was concluded to be safe and effective for cardiac catheterization under MAC

Page 55: Skousen Sedation2.ppt

Cardiovascular Surgery

Page 56: Skousen Sedation2.ppt

56

Sedative Propertiesfor Cardiovascular Surgery

Lack of respiratory depression

Cooperative sedation aids in assessing neurophysiological function during vascular procedures such as endarterectomy

Hemodynamic stabilization is desirable during cardiovascular surgery

Attenuates hypertension and tachycardia

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

Page 57: Skousen Sedation2.ppt

57

Effects of Dexmedetomidine and Propofol on Heart Rate

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

Mean heart rates were similar between groups throughout the study period

-10

-5

0

5

10

15

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

Mea

n H

ear

t R

ate

Cha

nge,

bea

ts/m

in

Time, hoursMinutes

PropofolDexmedetomidine

Postoperative CABG Sedation

Page 58: Skousen Sedation2.ppt

58 Afanador C, et al. Anesthesiol. 2008;109:A1643.

Anesthesia Coadjuvant in Heart Surgery

Retrospective cohort study of patients undergoing elective heart surgery

103 patients received dexmedetomidine, 97 patients did not

Data collected from records included demographic characteristics, premedication, surgical procedure, total doses of all intraoperative sedatives and anesthetics, extubation rate, sedation rate in ICU, ICU morphine, time in ICU

Page 59: Skousen Sedation2.ppt

59

271234

0

100

200

300

400

No Dex Dex

Thi

open

tal,

mg *

3.73.3

0

1

2

3

4

5

No Dex Dex

Mid

azol

am, m

g

Total Midazolam Dose

Total Thiopental Dose

P=.019

849

221

0

250

500

750

1000

No Dex Dex

Fen

tany

l, μg

*

314

197

0

100

200

300

400

No Dex Dex

Tim

e to

Ext

ubat

ion,

min

*

Anesthesia Coadjuvant in Heart Surgery

Afanador C, et al. Anesthesiol. 2008;109:A1643.

Total Fentanyl Dose

Extubation in ICU

P<.0001

P=.002

Page 60: Skousen Sedation2.ppt

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

Immediate Extubation FollowingCardiac Surgery

Horswell et al conducted a study of immediate extubation after off-pump coronary artery bypass graft (OPCAB) in 514 patients

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

All patients were successfully extubated immediately after dressing application

The investigators concluded that immediate extubation of OPCAB patients is feasible and probably safe

Page 61: Skousen Sedation2.ppt

Neurological Effects

Page 62: Skousen Sedation2.ppt

62

Sedative Propertiesfor Neurosurgery

Intraoperative hemodynamic stability

Lack of respiratory depression

Patients easily transition from sleep to wakefulness and task performance when aroused and then back to sleep when not stimulated

Does not increase intracranial pressure

Allows for consistent and reliable somatosensory evoked potential amplitudes or latencies

Bekker A, Sturaitis MK. Neurosurgery. 2005;57:1-10.Rozet I. Curr Opin Anesthesiol. 2008;21:537-543.

Page 63: Skousen Sedation2.ppt

63

Hemodynamics During Craniotomy

Double-blind, placebo-controlled study in patients undergoing intracranial surgery

Comparison of patients receiving either sevoflurane-opioid-placebo anesthesia (n=28) or sevoflurane-opioid-dexmedetomidine anesthesia (n=28)

Data collected– Hemodynamic variables – systolic blood pressure (SBP)

and heart rate (HR)

– Administration of sevoflurane, opioids, and/or antihypertensive agents intraoperatively

– Time spent in PACU and administration of opioids and/or antihypertensive agents postoperatively

Bekker A, et al. Anesth Analg. 2008;107:1340-1347.

Page 64: Skousen Sedation2.ppt

64

Hemodynamics During Craniotomy

Placebo (n=28) Dexmedetomidine (n=28)

AUCSBP (mmHg×min/hr) Median (IQR) Median (IQR)

>130 mmHg 35 (10-101) 9 (1-49)*

<90 mmHg 27 (8-58) 48 (10-96)

AUCHR (beats×min/hr)

>90 bpm 12 (0-59) 8 (0-26)

<50 bpm 0 (0-2) 0 (0-4)

Intraoperative Average Mean (SD) Mean (SD)

SBP (mmHg) 106.5 (9.9) 102.2 (9.4)

HR (bpm) 74.6 (13.0) 67.9 (1.7)*AUC = Area Under the Curve; SBP = Systolic Blood Pressure; HR = Heart Rate; bpm = Beats per Minute; IQR = Interquartile Range (25th – 75th percentile)

*P<.05 compared with placebo

Bekker A, et al. Anesth Analg. 2008;107:1340-1347.

Page 65: Skousen Sedation2.ppt

65

Hemodynamics During Craniotomy

Placebo (n=28) Dexmedetomidine (n=28)

Intraoperative Drugs

Sevoflurane, mean (%ET) 1.16 (0.38) 1.00 (0.37)

Fentanyl, μg/kg 2.6 (1.9) 1.9 (1.0)

Remifentanil, μg/kg 27 (13) 19 (11)*

Any BP med, n (%) 24 (86%) 12 (43%)†

Postoperative Measures

PACU duration (min) 130 (27) 91 (17)‡

Times SBP >130 mmHg 2.5 (2.0) 1.25 (1.55)*

Any analgesic, n (%) 18 (64%) 15 (54%)

Any BP med, n (%) 14 (50%) 10 (36%)

ET = End-tidal; PACU = Postanesthesia Care Unit; SBP = Systolic Blood Pressure Values given are mean (SD) unless otherwise indicated

*P<.05 compared with placebo †P=.0008 compared with placebo ‡P<.0001 compared with placebo Bekker A, et al. Anesth Analg. 2008;107:1340-1347.

Page 66: Skousen Sedation2.ppt

66

Examples of Cooperative SedationNeurological Examples

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

Intraoperative neurophysiological testing1 – Can verify that surgical target has been localized1

– Is used to assess the production of an intended functional change1

Carotid endarterectomy performed in awake patients allows evaluation of cerebral perfusion by continuous examination of neurologic function2

1Bekker AY, et al. Neurosurgery. 2005;57:1-10.2Bekker AY, et al. J Neurosurg Anesthesiol. 2004;16:126-135.

Page 67: Skousen Sedation2.ppt

67

Cerebral Blood FlowClinical Data

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

No detrimental effect on local brain tissue oxygenation in patients undergoing cerebral vascular surgery1

Under normotensive conditions in the setting of compromised cerebral circulation, dexmedetomidine has no apparent adverse effects1

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.

Page 68: Skousen Sedation2.ppt

68

Prielipp and colleagues analyzed data from 9 supine volunteers to assess the potential for dexmedetomidine-induced decreases in regional and global CBF

Patients were infused with a 1.0 μg/kg IV loading dose of dexmedetomidine, followed by an infusion of either

– 0.2 μg/kg/hr (low dose)

– 0.6 μg/kg/hr (high dose)

Cerebral Blood FlowDecreased Cerebral Metabolic Rate

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

Page 69: Skousen Sedation2.ppt

69

Cerebral Blood Flow Decreased Cerebral Metabolic Rate

Both low and high doses– Reduced global CBF by

one third– Decreased mean

systemic BP, HR, and CO 15% to 20%

– Increased PaCO2 no more than 5 mmHg

CBF decreased from baseline throughout dexmedetomidine infusion and for at least 30 minutes thereafterNote: Color intensity correlates with CBF

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

Baseline Low Infusion High Infusion 30 min post- termination

Page 70: Skousen Sedation2.ppt

70

Cerebral Blood Flow and Cerebral Metabolic Rate

Investigation of the effect of dexmedetomidine on cerebral blood flow and cerebral metabolic rate in humans– 6 healthy volunteers (males, 33 to 57 years) – Data collected included middle cerebral artery blood flow

velocity and blood gas levels– Cerebral metabolic rate equivalent determined

mathematically

2 within-subjects dexmedetomidine treatment conditions

– 0.6 ng/ml and 1.2 ng/ml plasma dexmedetomidine concentrations

Drummond JC, et al. Anesthesiol. 2008;108:225-232.

Page 71: Skousen Sedation2.ppt

71

Cerebral Blood Flow and Cerebral Metabolic Rate

Dexmedetomidine produces a dose-dependent reduction in both cerebral blood flow velocity (CBFV) and cerebral metabolic rate equivalent (CMRe)

Drummond JC, et al. Anesthesiol. 2008;108:225-232.

*P<.05 versus pre-sedation (PreSed)†P<.05 versus 0.6 ng/ml dex‡P<.05 versus 1.2 ng/ml dex

20

30

40

50

PreSed 0.6 Dex 1.2 Dex Recovery

CB

FV

(cm

/se

c)

0.0

1.0

2.0

3.0

PreSed 0.6 Dex 1.2 Dex Recovery

CM

Re

*

* †

* ‡*

Page 72: Skousen Sedation2.ppt

Pediatric Sedation

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73

Sedative Properties in Pediatrics

“Ideal” pediatric sedation should Reduce anxiety in both children and parents

Obtain cooperation of the child

Sufficiently immobilize the child to perform the procedure

Induce awareness and amnesia

Reduce discomfort and pain

Keep the child safe

Tobias JD, et al. Pediatr Crit Care Med. 2007;8:115-131.

Gozal D, et al. Curr Opin Anesthesiol. 2008;21:494-498.

Page 74: Skousen Sedation2.ppt

74

Use of Sedatives During MRI

Large-scale investigation of safety and efficacy of dexmedetomidine as the sole sedative for pediatric MRI

Comparison of 3 sedation protocols

– Protocol 1 = 2.0 μg/kg dex bolus; 1.0 μg/kg/hr dex infusion (n=416)

– Protocol 2 = 3.0 μg/kg dex bolus; 1.5 μg/kg/hr dex infusion (n=164)

– Protocol 3 = 3.0 μg/kg dex bolus; 2.0 μg/kg/hr dex infusion (n=167)

No unexpected adverse effects occurred; bradycardia was observed in 16% of children

*P<.001; protocol 1 versus protocols 2 and 3†P<.001; protocol 3 versus protocols 1 and 2

Mason KP, et al. Pediatr Anesth. 2008;18:403-411.

Characteristic Protocol 1 Protocol 2 Protocol 3 P-Value

Time to sedation (min) 13.4±6.1 11.8±4.1 11.8±4.4 .001*

Sedation duration (min) 49.8±16.9 47.6±16.4 58.6±22.8 .001†

Time to recovery (min) 35.2±29.4 32.1±20.0 24.8±19.5 .001†

Page 75: Skousen Sedation2.ppt

75

0

10

20

30P

atie

nts,

%

Use of Sedatives During MRI

*P<.01 compared with protocol 1†P<.001 compared with protocol 1 Mason KP, et al. Pediatr Anesth. 2008;18:403-

411.

RescuePentobarbital

Rescue DexPre-MRI

Rescue Dex During MRI

*

Protocol 1 (2 μg/kg, 1 μg/kg/hr)

Protocol 2 (3 μg/kg, 1.5 μg/kg/hr)

Protocol 3 (3 μg/kg, 2 μg/kg/hr)

Page 76: Skousen Sedation2.ppt

76

MRI Sedative Comparisons

80 children aged 1-7 years randomly assigned to either dexmedetomidine or midazolam

– 10-minute loading doses: 1 μg/kg dexmedetomidine, 0.2 mg/kg midazolam

– Infusions: 0.5 μg/kg/hr dexmedetomidine, 6 μg/kg/hr midazolam

The quality of MRI was significantly better (P<.001) and the rate of adequate sedation was significantly higher (P<.001) with dexmedetomidine

0

10

20

30

40

1 2 3

Nu

mb

er

of

Pa

tien

ts

MidazolamDexmedetomidine

1 = no motion2 = minor movement3 = major movement

necessitating another scan

Quality of MRI

*P<.001 compared with midazolam

*

*

Koroglu A, et al. Br J Anaesth. 2005;94:821-824.

Page 77: Skousen Sedation2.ppt

77

Sedation in Pediatric Acute Care Patients

20 pediatric ICU patients randomized to either midazolam (starting dose 0.1 mg/kg/hr) or dexmedetomidine (starting dose 0.25 or 0.5 μg/kg/hr)

Morphine used intermittently, as needed

0.25 μg/kg/hr dexmedetomidine was equivalent to 0.22 mg/kg/hr midazolam

0.5 μg/kg/hr dexmedetomidine provided more effective sedation than 0.22 mg/kg/hr midazolam – Less morphine use

– Decrease in the number of Ramsay scores of 1 (fewer patients oversedated) [Not shown]

0

0.1

0.2

0.3

0.4

0.5

0.6

0.7

0.8

Midazolam 0.25 0.5T

ota

l Mo

rph

ine

Use

d, m

g/k

g/2

4 h

Dexmedetomidine (μg/kg/hr)

*

*P=.01 compared with midazolam

Reduced Need for Morphine

Tobias JD, et al. South Med J. 2004;97:451-455.

Page 78: Skousen Sedation2.ppt

78

Preanesthetic Sedation in Children

Children randomized to receive preanesthesia sedation with midazolam (0.5 mg/kg; n=22), clonidine (4.0 μg/kg; n=18), or dexmedetomidine (1.0 μg/kg; n=20)

Measurements included postoperative pain and anxiety, sedation, adverse effects, and hemodynamics

No differences were observed between groups for adverse effects or for postoperative anxiety

Schmidt AP, et al. Pediatr Anesth. 2007;17:667-674.

Page 79: Skousen Sedation2.ppt

79

0

20

40

60

80

100

120

Me

an

He

art

Ra

te, b

pm

Preanesthetic Sedation in ChildrenHemodynamic Effects

0

15

30

45

60

75

90

Me

an

Art

eri

al P

ress

ure

, mm

Hg

*P<.001 compared with clonidine and dexmedetomidine

Schmidt AP, et al. Pediatr Anesth. 2007;17:667-674.

BeforeInduction

AfterInduction

DuringSurgery

Midazolam Clonidine Dexmedetomidine

BeforeInduction

AfterInduction

DuringSurgery

* **P<.001

P=.019 P=.031

Page 80: Skousen Sedation2.ppt

80

0

20

40

60

80

100

Pa

tien

ts, %

Preanesthetic Sedation in ChildrenPostoperative Pain

0

20

40

60

80

100

Pa

tien

ts, %

Schmidt AP, et al. Pediatr Anesth. 2007;17:667-674.

None Mild Moderate

Midazolam Clonidine Dexmedetomidine

None–Mild Moderate–SevereSevere

P=.05, midazolam compared with clonidine and dexmedetomidine

Verbal Pain Scale Ratings Visual Analog Pain Scale Ratings

P=.0021, midazolam compared with clonidine and dexmedetomidine

Page 81: Skousen Sedation2.ppt

81

69 pediatric patients undergoing tonsillectomy and adenoidectomy

In addition to sevoflurane anesthesia, patients received dexmedetomidine (Dex, n=35) or fentanyl (Fen, n=34)

Heart rate and systolic blood pressure were significantly lower in Dex group during the intraoperative period and in the PACU

Significantly fewer patients in the Dex group received rescue Fen

No difference in Objective Pain Score measures between groups

12.4

6.38

0

5

10

15

Fen DexA

gita

tion

Du

ratio

n, m

in

*

*P<.03 compared withfentanyl

Emergence Agitation

Patel A, et al. Anesthesiol. 2008;109:A604.

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Bariatric Surgery

Page 83: Skousen Sedation2.ppt

83

Intraoperative Sedation in Bariatric Surgery

Rising incidence of morbid obesity is increasing the need for bariatric surgery1,2

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

Perioperative administration of dexmedetomidine has been shown to be cardioprotective and neuroprotective while providing a hemodynamically stable course and reducing the need for opioids and inhalational agents3

1Hofer RE, et al. Can J Anaesth. 2005;52:176-180.2Feld JM, et al. J Clin Anesthesia. 2006;18:24-28.

3Ramsay MA. Semin Anesth. 2006;25:51-56.

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84

Bariatric Surgery Sedation Comparison

*P<.05 compared with fentanylFeld JM, et al. J Clin Anesthesia. 2006;18:24-28.

0

1

2

3

4

5

6

7

1 2 3

De

sflu

ran

e C

on

cen

tra

tion

(%

)

FentanylDexmedetomidine

Surgery Time (hr)

* * *

• Feld and colleagues evaluated whether dexmedetomidine infusion could replace fentanyl in open gastric bypass surgery

• Patients receiving dexmedetomidine required less desflurane at all assessed time points during surgery

• During surgery, blood pressure and heart rate were significantly decreased with dexmedetomidine compared with fentanyl

• Dexmedetomidine was associated with significantly lower postoperative pain, morphine use, and time to extubation

Page 85: Skousen Sedation2.ppt

85

Fentanyl Dexmedetomidine

Surgery duration (min) 229 ± 30 234 ± 28

End of surgery to extubation (min) 14.2 ± 6.6 9.4 ± 2.7*

PACU pain score (0-10, 1 hr) 7.0 (5.25-8.75) 3.5 (0-5.0)*

PACU pain score (0-10, 2 hr) 6.0 (5.0-7.0) 2.0 (0-5.0)*

PACU morphine (mg, 2 hr) 14.6 ± 5.9 6.1 ± 3.5*

PACU mean blood pressure (mmHg, 1 hr) 89 ± 12 77 ± 9*

PACU heart rate per minute (1 hr) 94 ± 13 75 ± 5*

Bariatric Surgery Sedation Comparison

Feld JM, et al. J Clin Anesthesia. 2006;18:24-28.

*P<.05 compared with fentanyl

Page 86: Skousen Sedation2.ppt

86

Bariatric Surgery Sedation Comparison

Feld JM, et al. J Clin Anesthesia. 2006;18:24-28.

120

100

80

60

40

120

100

80

60

40

FentanylDexmedetomidine

Time (min)0 60 120 180

He

art

Ra

te,

BP

M (

min

-1)

Me

an

Blo

od

Pre

ssu

re (

mm

Hg

)

FentanylDexmedetomidine

Page 87: Skousen Sedation2.ppt

87

Prospective, randomized, double-blind, placebo-controlled trial to evaluate the safety and efficacy of dexmedetomidine on recovery after laparoscopic bariatric surgery

Patients received placebo (n=20), 0.2 μg/kg/hr dex (n=19), 0.4 μg/kg/hr dex (n=19), or 0.8 μg/kg/hr dex (n=19)

Data included perioperative hemodynamic variables, postoperative pain scores, rescue analgesics and antiemetics, and duration of stay

Recovery Outcome Variables in Bariatric Surgery

Tufanogullari B, et al. Anesth Analg. 2008;106:1741-1748.

Page 88: Skousen Sedation2.ppt

88

Control (n=20)

Dex 0.2 (n=19)

Dex 0.4 (n=19)

Dex 0.8 (n=19)

Extubation time (min) 7±3 5±3 6±4 9±6

Time in PACU (min) 104±33 81±31* 82±24* 87±24*

Pain score in PACU 5±3 5±3 5±3 4±3

PACU fentanyl (μg) 187±99 113±85* 108±67* 120±78*

PACU nausea/vomiting [n (%)]

13(65)/3(15) 5(25)/1(5)* 6(30)/0(0)* 9(45)/2(11)

Antiemetics administered [n (%)]

14 (70) 6 (30)* 6 (30)* 2 (10)*

Satisfaction with pain management

89±17 86±20 87±16 86±11

Recovery Outcome Variables in Bariatric Surgery

Tufanogullari B, et al. Anesth Analg. 2008;106:1741-1748.

*P<.05 compared with control group

Page 89: Skousen Sedation2.ppt

89

Evaluated the effect of dexmedetomidine on narcotic requirements and duration of stay following bariatric surgery

Patients received placebo or dexmedetomidine for either gastric bypass (n=19 placebo, n=23 dex) or gastric band surgery (n=18 placebo, n=11 dex)

Data included narcotic and antiemetic requirements, pain scores, duration of stay, and vital signs

Narcotic Use and Duration of Stay Following Bariatric Surgery

Dholakia C, et al. J Gastrointest Surg. 2007;11:1556-1559.

Page 90: Skousen Sedation2.ppt

90

Placebo (n=19) Dex (n=23) P-Value

Morphine equiv (total mg) 130 66 .04

Morphine equiv/day (mg) 67 47 .53

Duration of stay (days) 1.9 1.4 .02

Discharge criteria met PO day 1 26% 61% .02

Antiemetic doses 2.7 3.0 .83

PACU pain score 2.7 3.5 .37

Narcotic Use and Duration of Stay Following Bariatric Surgery

Dholakia C, et al. J Gastrointest Surg. 2007;11:1556-1559.

Gas

tric

Byp

ass

Placebo (n=18) Dex (n=11) P-Value

Morphine equiv (total mg) 33 19 .06

Morphine equiv/day (mg) 33 18 .03

Duration of stay (days) 1.0 1.1 .20

Discharge criteria met PO day 1 100% 91% .38

Antiemetic doses 2.2 1.5 .04

PACU pain score 3.6 4.1 .91

Gas

tric

Ban

d

Page 91: Skousen Sedation2.ppt

Postoperative Sedation

Page 92: Skousen Sedation2.ppt

92

Morphine-Sparing Effects in Inpatient Surgery

34 patients scheduled for inpatient surgery

Randomized to either dexmedetomidine or morphine

Agents were started 30 minutes before the end of surgery

Dexmedetomidine reduced the early postoperative need for morphine by 66%

0

3

6

9

12

0 10 20 30 40 50 60 70

Minutes in PACU

Cu

mu

lativ

e M

orp

hin

e

Use

d, m

g

MorphineDexmedetomidine

P<.01

Arain SR, et al. Anesth Analg. 2004;98:153-158.

0

3

6

9

12

Morphine Dexmedetomidine

Ave

rag

e T

ota

l Mo

rph

ine

U

sed

, mg

P<.01

Page 93: Skousen Sedation2.ppt

93

Reduction of Postoperative Requirement for Epidural Opioids

Prospective, randomized, double-blind study with 28 patients scheduled for thoracotomy for wedge resection, lobectomy, or pneumonectomy

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 μg/kg loading dose plus infusion of 0.4 μg/kg/hr)

Supplemental analgesia (fentanyl), vital signs, and blood gasses were monitored

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

Page 94: Skousen Sedation2.ppt

94

Reduction of Postoperative Requirement for Epidural Opioids

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

Requirement for Supplemental Epidural (ED) Fentanyl

66.1

5.3

0

10

20

30

40

50

60

70

80

Placebo Dexmedetomidine

Tot

al F

enta

nyl U

sed,

μg

P=.039

The requirement for supplemental ED fentanyl analgesia was significantly greater in the placebo group

Dexmedetomidine is a potentially effective analgesic adjunct to thoracic ED bupivacaine infusion and may decrease the requirement for opioids and potential for respiratory depression

Page 95: Skousen Sedation2.ppt

95

Reduction in Postoperative Analgesic Use

Investigation of perioperative dexmedetomidine on postoperative pain status

20 patients were randomly assigned to control (n=10) or dex (n=10) groups

Patients in the dex group received 1.0 μg/kg over 10 min, then 1.0 μg/kg/hr

Patient controlled epidural anesthesia (PCEA) was measured

Pain scores assessed with the visual analog scale; no difference observed between groups

No serious adverse hemodynamic events occurred

Ohtani N, et al. Anesthesiol. 2008;109:A552.*P<.05 versus control group

*

0

5

10

15

20

25

Control Dex 1.0

PC

EA

Us

e,

ml

*

0

5

10

15

20

Control Dex 1.0

Tim

e t

o F

irs

t P

CE

A,

hrs

Page 96: Skousen Sedation2.ppt

96

*P<.05 difference over time compared with baseline†P<.05 difference between groups

Arain SR, et al. Anesth Analg. 2002;95:461-466.

Improved postoperative pain and greater sedation with dexmedetomidine compared with propofol

Postoperative Comparison of Sedatives

0

40

60

80

100

VA

S S

ed

atio

n

5 20 35 50 65SurgEnd

Pre-surg Time After Surgery, minutes

* †

Le

ss A

lert

M

ore

Ale

rt

0

10

20

30

40

100

VA

S P

ain

PropofolDexmedetomidine

* †

Le

ss P

ain

M

ore

Pa

in

Page 97: Skousen Sedation2.ppt

97

Postoperative Pain Score Meta-Analysis

Weighted Mean Difference (95% CI)

–1.78 (–2.53, –1.04)

0

N = 310Study or Subgroup

Favors control

–5 5

–0.42 (–0.98, 0.14)

–1.25 (–1.73, –0.77)

–1.13 (–1.85, –0.40)*

Kida K, et al. Anesthesiol. 2008;109:A1625.

Ozkose 2006

Gurbet 2006

Bakhamees 2007

Subtotal

Favors experimental

–2.03 (–2.80, –1.25)

–0.49 (–1.12, 0.14)

–0.77 (–1.30, –0.25)

–1.06 (–1.88, –0.24)†

Arain 2002

Ustun 2006

Cheung 2007

Subtotal

General anesthesia

Local anesthesia

–1.08 (–1.57, –0.60)‡Total

*P=.002 Dex versus control †P=.01 Dex versus control ‡P<.0001 Dex versus control

Page 98: Skousen Sedation2.ppt

Algorithms

Page 99: Skousen Sedation2.ppt

99

Sedation

Peruzzi/NMH/NUMS Protocol. March, 2001.

Is the patient agitated or in pain? SAS >4?

Initial assessment of patient’s sedation level

Is the patient comfortable, cooperative, and communicative? SAS <4 ?

Initiate Dexmedetomidine• Begin infusion: 0.2 μg/kg/hr

(If SAS<6 and hemodynamics are normal or depressed)• If hyperdynamic and SAS >6: bolus, 1.0 μg/kg over

10-20 minutes

Ongoing assessment of patient’s sedation level• SAS >4 • Patient is agitated or in pain?

Dexmedetomidine infusion rate <0.7 μg/kg/hr

Increase dexmedetomidine infusion rate <0.1 μg/kg/hr

Assess pain and implement supplemental opioid protocol as needed

Implement supplemental agitation protocol (dexmedetomidine <2.0 μg/kg/hr) if patient demonstrates agitation on assessment (SAS >4)

N

N

Y

YIf the patient is somnolent or unresponsive with SAS <3, assess for CNS event, metabolic process, and drugs. If dexmedetomidine infusion is ongoing, decrease by 0.1 μg/kg/hr with ongoing assessment of sedation.

N

N

YY

Y

Page 100: Skousen Sedation2.ppt

100

Long-Term Sedation

Titrate propofol every hour with orders not to increase

Administer dexmedetomidine infusion,

0.4 μg/kg/hr

If extreme agitation occurs, add benzodiazepine (synergistic with

dexmedetomidine)

Titrate dexmedetomidine according to HR and BP

with allowed increases of

0.2 μg/kg/hr

If patient is agitated on waking, administer more benzodiazepine

(requirement is less with dexmedetomidine on board)

Increase dose of dexmedetomidine in PM to optimize natural sleep

and circadian rhythm

Courtesy of Daniel L. Herr, MD.

Page 101: Skousen Sedation2.ppt

101

Abdominal Aortic Aneurysm

Patients undergoing endovascular repair of abdominal aortic aneurysms with general (n = 217; 22 used for direct comparison) versus dexmedetomidine (n = 14) sedation

Dexmedetomidine sedation resulted in

– Reduced time for surgery

– Reduced time for anesthesia

– Reduced opioid requirement

Administer supplemental O2 via nasal cannulae

Initiate maintenance dexmedetomidine infusion (0.3 to 0.7 μg/kg/hr)

Cannulate arteries and insert grafts

Administer dexmedetomidine loading dose 1 μg/kg via infusion pump

Administer 0.5% bupivacaine

Access femoral arteries via 2 small surgical incisions in both groins

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.

Page 102: Skousen Sedation2.ppt

102

Neurosurgery Anesthesia Protocol

Courtesy of M. Ramsay, MD.

Use supplemental opioid

Induce as usual; when stable, start dexmedetomidine at 0.7 μg/kg/hr

After 15 mins reduce inhalant anesthetic to half MAC

Opioid use Routine dose of fentanyl at induction of anesthesia

Hemodynamics indicative of adequate analgesia?

Five minutes prior to end of procedure, reduce dexmedetomidine to 0.2 μg/kg/hr

Awaken patient and extubate

Titrate dexmedetomidine after extubation to patient comfort(usually 0.2-0.5 μg/kg/hr)

N

Y

Page 103: Skousen Sedation2.ppt

103

Perioperative Bariatric Surgery AlgorithmPreoperative Protocol

Assess cardiac functioning Indications of cardiomegaly, cardiac failure, CAD, or pulmonary

HTN?

Optimize cardiac state

Assess airway/ respiratory system

Y N

Obstruction of airway by adipose tissue?

Awake fiberoptic intubation

Obstructive sleep apnea?O2 desaturation risk?

↓ lung volumesFunctional residual

capacityExpiratory reserve

Forced vital capacity

N

Administer dexmedetomidine (<0.7 μg/kg/hr) plus topical

anesthetic

Correct head positioningUse “back up” position at

induction of anesthesia and subsequent recovery

Y

Y

N

Proceed to intraoperative

procedure

Courtesy of M. Ramsay, MD.

Page 104: Skousen Sedation2.ppt

104

Perioperative Bariatric Surgery AlgorithmIntraoperative Protocol

Brief Procedure

Laproscopic gastric bypass or gastric banding

Roux-en Y gastric bypass

Y N

Dexmedetomidine solution400 μg/100 mL of 0.9% sodium chloride at

4 μg/mL

Initiate dexmedetomidine infusion (0.4 to 0.7 μg/kg/hr)

1 hour before completion of surgery

Reduce infusion at end of surgery (approximately 5 min prior to completion)

Administer dexmedetomidine loading dose

0.5 to 0.75 μg/kg and monitor for transient hypertension

Proceed to postoperative procedure

Allow patient to gradually awaken

Courtesy of M. Ramsay, MD.

Page 105: Skousen Sedation2.ppt

105

Perioperative Bariatric Surgery AlgorithmPostoperative Protocol

Continue infusion in the recovery room during and after intubation

Titrate to 0.7 μg/kg/hr for

pain control

Discontinue dexmedetomidine at discharge from recovery unit

No postoperative opioids needed

Courtesy of M. Ramsay, MD.

Page 106: Skousen Sedation2.ppt

106

Overall Summary

Patient care and safety, as well as physiological and neurobehavioral considerations, reinforce the need for sedation in acute care settings

Attenuating reactions to pain and stress while optimizing patient communication are important acute care goals

Inappropriate sedation and analgesic therapy in acute care settings leads to poor clinical outcomes

Guidelines, standards, and algorithms clarify the manner in which sedatives should be used in acute care settings

Page 107: Skousen Sedation2.ppt

107

Overall Summary (Cont’d)

Dexmedetomidine is currently approved for short-term (<24 hr) sedation in mechanically ventilated adults in the ICU

The safety and efficacy of dexmedetomidine has been demonstrated in various procedures and populations including awake fiberoptic intubation, monitored anesthesia care, long-term sedation, pediatric sedation, and awake craniotomy

The addition of dexmedetomidine to the current standard of care is associated with improved clinical outcomes

Page 108: Skousen Sedation2.ppt

Thank You!