Transcript Monitored Anesthesia Care with Dexmedetomidine: A

Monitored Anesthesia Care
with Dexmedetomidine: A
Prospective, Randomized,
Double-Blind, Multicenter Trial
Dr. Keith Candiotti
Department of Anesthesiology
University of Miami
This study was funded by Hospira Inc.
MAC Investigators
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Martin W. Allard
Alex Y. Bekker
Sergio D. Bergese
Keith A. Candiotti
Eric L. Diamond
Dennis D. Doblar
Thomas J. Ebert
Marc Feldmam
Robert B. Fisher
Tong J. Gan
Steven Gayer
Ira J. Gottlieb
Craig T. Hartrick
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Gary R. Haynes
Fima Lenkovsky
Terri Monk
Paul A. Moore
Thomas N. Pajewski
Beverly K. Philip
Michael A.E. Ramsay
Ruben Ricardo
Bernhard Riedel
Charles R. Roberson
Fred E. Shapiro
Jeffrey H. Silverstein
Tracey L. Stierer.
• A 2006 review of closed claims in the ASA
Closed Claims Database reveals that
oversedation leading to respiratory depression
played a major role in patient injuries during
MAC.
• MAC claims were fewer than GA overall
• Claims for death or permanent brain damage
were 40%, similar to GA1
1Bhananker SM et al. Anesthesiology 2006;104:228-34.
• Most commonly used drugs are midazolam,
propofol and fentanyl.
• All 3 of these drugs is known to cause
respiratory depression-especially in
combination.
1Bhananker
SM et al. Anesthesiology 2006;104:228-34.
• DEX is a centrally acting alpha-2 receptor
antagonist that does not produce significant
respiratory depression.1-3
• Dex has an analgesic-sparing effect, reducing
opioid requirements both during and after
surgery.3
• The agent also possess a sympatholytic effect
that can mitigate tachycardia and HTN.3
1 Ebert TJ et al. Anesthesiology 2000;93:382-94. 2 Venn RM et al. Crit Care 2000;4:302-8.
3 Arain SR et al. AA 2002;95:461-6
• DEX is currently approved for use in initially
intubated patients in an intensive care setting.
• This trial was designed to evaluate the safety
and efficacy of DEX in non-intubated patients in
a large multicenter trial (26 sites) using it as the
primary sedative agent.
• FDA trial designed to compare against a placebo
group using midazolam and fentanyl for rescue.
Study Design
• Randomized 2:2:1
• LOAD
– DEX 0.5 mcg/kg load
– DEX 1 mcg/kg load
– Saline Placebo
• MAINTENANCE
– Both DEX groups 0.6 mcg/kg/hr (titrated)
– Placebo had saline infusion
DEX 130
DEX 130
PBO 65
Load
DEX 0.5
mg/kg
10 min
DEX 1
mcg/kg
10 min
PBO
10 min
Maintenance
0.6
mcg/kg/hr
titrate
0.6
mcg/kg/hr
titrate
PBO
Infusion
Midazolam/Fentanyl Rescue
• Observer’s Assessment of
Alertness/Sedation Scale used (OAA/S)
• 5=responds to name spoken in normal tone
• 4=responds only after mild prodding or shaking
• 3=responds only after name loudly and/or
repeatedly
• 2=lethargic response to name spoken in normal
tone
• 1=does not respond to mild prodding or shaking
• Study drug started at least 15 min prior to block
or local anesthetic
• Midazolam 0.5 mg doses given for OAA/S>4
• Fentanyl was given for pain
• Primary endpoint
– % patients not requiring midazolam for rescue based
on an OAA/S of ≤ 4.
• Secondary endpoint
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Total rescue midazolam and/or fentanyl
Time to rescue
Patients who converted to alternative therapy
Readiness for D/C
Hemodynamic stability
Patient and Anesthesiologist Satisfaction
• Safety endpoints
– Cardiac and pulmonary etc.
• 326 in intent-to-treat
• Randomization was good
• Fewer patients in both DEX groups
required midazolam and used less (p<
0.001)
• Both DEX groups required less fentanyl
(p< 0.01)
Mean
1.4 mg
Mean
0.9 mg
Mean
4.1 mg
Groups vs. PBO (p< 0.001)
• Anesthesiologists indicated that DEX was
easier to control than PBO + midazolam
(p<0.009)
• PBO required more fentanyl in PACU than
DEX 1 mcg load group (p≤0.068)
• Patient satisfaction was higher with DEX
(p<0.009)
• Most common AE with DEX were protocol
defined bradycardia and hypotension
which were predominately mild to
moderate in severity and did not require
intervention.
• Mean decrease in SBP (p≤0.043) and
DBP (p<0.001) was greater in DEX than
PBO group.
• HR decrease in both DEX groups was
significant from baseline and vs. PBO
group (p<0.001)
• Incidence of significant respiratory
depression (RR < 8 or O2 Sat% < 90%)
was lower in DEX treated patients
(p=0.018)
• Coadministration of midazolam or fentanyl
with DEX was not associated with an
increase in hypotension, bradycardia or
respiratory depression.
• In PBO group midazolam and fentanyl
were associated with a respective 13.1
and 16.1% rate absolute respiratory
depression or need for intervention.
• DEX is an effective baseline sedative for
patients undergoing MAC for a variety of
procedures.
• Less opioids are required and less
respiratory depression is seen with DEX.
• FDA decision based on this trial:
“This supplemental new drug application
provides for the use of Precedex Injection
for sedation of nonintubated patients prior
to and/or during surgical and other
procedures”.