Skousen Sedation2.ppt
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.
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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
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
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
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
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
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.
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.
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
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.
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)
Monitored Anesthesia Care
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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.
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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.
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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, %
**
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.
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*
*
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
Cardiovascular Surgery
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.
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
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
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
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
Neurological Effects
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.
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.
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.
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.
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.
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.
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.
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
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.
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
*
* †
* ‡*
Pediatric Sedation
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.
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†
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)
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.
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.
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.
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
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
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.
Bariatric Surgery
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.
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
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
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
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.
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
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.
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
Postoperative Sedation
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
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.
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
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
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
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
Algorithms
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
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.
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.
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
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.
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.
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.
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
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
Thank You!