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Monitored Anesthesia Care (MAC) may include varying levels of sedation, analgesia, and anxiolysis. The provider of MAC must be prepared and qualified to convert to general anesthesia when necessary.
Monitored Anesthesia Care (MAC) may include varying levels of sedation, analgesia, and anxiolysis. The provider of MAC must be prepared and qualified to convert to general anesthesia when necessary.
Monitored Anesthesia Care (MAC) may include varying levels of sedation, analgesia, and anxiolysis. The provider of MAC must be prepared and qualified to convert to general anesthesia when necessary.
Associate Professor of Anesthesiology and Neurosurgery New York University Medical Center New York, New York
Dexmedetomidine for Monitored Anesthesia Care (MAC)
We have completed our review of this application, as amended, and it is approved, effective on the date of this letter, for use as recommended in the enclosed agreed-upon labeling text.
Monitored Anesthesia Care: Definition Monitored Anesthesia Care (MAC) may include varying levels of sedation, analgesia, and anxiolysis as necessary. The provider of MAC must be prepared and qualified to convert to general anesthesia when necessary.
Position on Monitored Anesthesia Care, ASA 2005 Continuum of Depth of Sedation Minimal Sedation (Anxiolysis) Moderate Sedation/ Analgesia (Conscious Sedation) Deep Sedation/ Analgesia General Anesthesia Responsiveness Normal Response to verbal Stimulation Purposeful response to verbal or tactile stimulation Purposeful response after repeated or painful stimulation Unarousable, even with painful stimulation Airway Unaffected No intervention required Intervention may be required Intervention often required Spontaneous ventilation Unaffected Adequate May be inadequate Frequently inadequate Cardiovascular function Unaffected Usually maintained Usually maintained May be impaired Practice Guidelines for Sedation and Analgesia by Non-Anesthesiologists, Anesthesiology 2002
Injury and Liability Associated with Monitored Anesthesia Care Bhananker and colleagues assessed the patterns of injury and liability associated with monitored anesthesia care (MAC; n = 121) as compared with general (n = 1519) and regional anesthesia (n = 312) Bhananker S, Anesthesiology 2006 0 10 20 30 40 50 60 Death/Perm Brain Damage Permanent Disabling Temp/Nondisabling MAC General Regional * * * * * P<.025 MAC versus Regional %
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c l a i m s
i n
a n e s t h e s i a
g r o u p
Injury Associated with MAC N=121 %
Respiratory event 24 Cardiovascular event 14 Equipment failure/malfunctioning 21 Related to regional block 2 Inadequate anesthesia/patient movement 11 Medication related 9 Other events 20
Bhananker S, Anesthesiology 2006 Characteristics of an Ideal Sedative Cooperative sedation Minimal depression of ventilation Hemodynamic stability Analgesic effects Wide therapeutic window Minimal risks of side effects Favorable pharmacodynamic/ pharmacokinetic profile Amnesia (?) Study Design: Monitored Anesthesia Care 325 Patients: 260 Dex; 65 Placebo receiving MAC for surgical procedures; 25 US sites 2 Precedex Arms: 0.5 mcg/kg/10 min load or 1.0 mcg/kg/10 min load; 0.6 mcg/kg/hr maintenance titrated 0.2 1.0 mcg/kg/hr. OAA/S Scale: Midazolam rescue for > 4. Primary Endpoint: % of pts not requiring MDZ based on OAA/S. Secondary Endpoints: total MDZ, fentanyl, sedation failures; pt satisfaction; anesthesiologist assessment; PONV Safety: respiratory depression; hemodynamic stability MAC Primary Efficacy Requirement of Rescue Midazolam (MDZ)
Rescue MDZ/ No Rescue MDZ DEX 0.5 mcg/kg N=134
n (%) DEX 1 mcg/kg N=129
n (%) PBO N=63
n (%) Did Not Require Rescue MDZ 54 (40.3) 70 (54.3) 2 (3.2) Required Rescue MDZ 80 (59.7) 59 (45.7) 61 (96.8) p-value <0.001 <0.001
MAC Secondary Efficacy Anesthesiologist Assessment
MAC Subject Assessment - Higher Scores are Better 0 0.5 1 1.5 2 2.5 3 1
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s a t i s f i e d
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a n e s t h e s i a 9
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s u r g e r y 1 0
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S c o r e DEX 0.5 mcg/kg DEX 1 mcg/kg PBO * * * * * * * * * * * * * *p <0.05
Overview of Awake Fiberoptic Intubation Trial Double-blind, randomized, placebo-controlled 100 patients: 50 Precedex; 50 Placebo; 18 US sites Precedex: 1.0 mcg/kg/10 min; 0.7 mcg/kg/hr maint Rescue is Midazolam(0.5 mg doses) based on Ramsay Sedation Scale of 1. Primary Endpoint: % of patients requiring Midazolam Secondary Endpoints: Total MDZ dose; other rescue meds; patient satisfaction; anesthesiologist assessment Safety Endpoints: hemodynamic stability; respiratory depression
AWAKE Primary Efficacy Requirement of Rescue Midazolam (MDZ)
Rescue MDZ/No Rescue MDZ DEX (N=55)
n (%) PBO (N=50)
n (%) p-value Required Rescue MDZ 26 (47.3%) 43 (86.0%) <0.001 Did Not Require Rescue MDZ 29 (52.7%)* 7 (14.0%)
Characteristics of Cooperative Sedation In cooperative sedation, patients easily transition from sleep to wakefulness and task performance when aroused Patients are able to resume rest when not stimulated Cooperative sedation is most useful during procedures in which communication with the patient must be maintained
Facilitates participation in therapeutic maneuvers Allows for patient interaction in care decisions May contribute to shorter recovery room convalescence Reduces risk of developing drug-induced complications
The brain is not a sausage, its more like a well tuned musical instrument Rudolfo Llinas Endogenous sleep
Loss of response to external stimuli
Sedative component of anesthesia Arousability From Sedation During Dexmedetomidine Infusion BIS indicates Bispectral Index System During cognitive and cold pressor testing Just prior to cognitive and cold pressor testing Dexmedetomidine Infusion (mcg/kg/h) 0 20 40 60 80 100 Placebo 0.2 0.6 B I S Hall JE, Anesth Analg 2000 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 1
Avoid oversedation Reduce anxiety Maintain communication Minimize respiratory depression
Dexmedetomidine in Carotid Endarterectomy Intraoperative Assessment of Sedation Level by the Blinded Observer Bekker A , J Neurosurg Anesth 2004 The Safety of Dexmedetomidine as Primary Sedative for Awake CEA Total number of patients N=151 General Anesthesia N=10 Regional/Dex N=123 Regional/No Dex N=18 No Shunt N=0 Shunt N=10 No Shunt N=111 Shunt N=12 No Shunt N=12 Shunt N=6 Elective N=10 Obligatory N=0 Elective N=7
Obligatory N=5
Obligatory N=2
Elective N=4 Bekker A, Anesth Analg 2006 Clinical Experience with Dexmedetomidine for DBS Implantation Dex (0.3-0.6 mcg/kg/hr) did not impair intensity of movement disorder or interfere with MER in PD patients
Titration of Dex provided satisfactory sedation for DBS implantation
Dex provided HD stability and decreased the use of antihypertensives 1
Propofol induced dyskinesia was controlled with DEX during DBS placement 2
1 Rozet I, Anesth Analg 2006. 2 Deogaonkar A , Anesthesiology 2006. Dexmedetomidine and Respiratory Depression Minimal effects on ventilation is well documented in human volunteers 1
Lack of respiratory depression was demonstrated in ICU patients 2
1 Belleville JP, Anesthesiology, 1992; Ebert TJ, Anesthesiology, 2000. 2 Venn RM, Crit Care , 2000; Martin E, J Intensive Care Med 2004. Hospira MAC Trial: Respiratory Depression Definition of Respiratory Depression:
Respiratory rate < 8 bpm or oxygen saturation < 90%
Dex 0.5 Dex 1.0 Pcb
5 (3.7%) 3 (2.3%) 8 (12.7%) P<0.018
Both Dex groups: neither respiratory depression nor intervention Plb group: respiratory depression or a need for intervention 13.1% and 16.1% respectively Dexmedetomidine and Hemodynamic Stability Arain SR, Anesth Analg 2002 Bekker A, J Neurosurg Anesth 2004
50 70 90 110 130 150 Baseline Infusion Period PACU B l o o d
P r e s s u r e
( m m H g ) SBP Placebo SBP DEX 1.0 mcg/kg SBP DEX 0.5 mcg/kg DBP Placebo DBP DEX 1.0 mcg/kg DBP DEX 0.5 mcg/kg 50 60 70 80 H e a r t
R a t e
( b p m ) HR Placebo HR DEX 1.0 mcg/kg HR DEX 0.5 mcg/kg 50 70 90 110 130 150 Baseline Infusion Period PACU B l o o d
P r e s s u r e
( m m H g ) SBP Placebo SBP DEX 1.0 mcg/kg SBP DEX 0.5 mcg/kg DBP Placebo DBP DEX 1.0 mcg/kg DBP DEX 0.5 mcg/kg 50 60 70 80 H e a r t
R a t e
( b p m ) HR Placebo HR DEX 1.0 mcg/kg HR DEX 0.5 mcg/kg MAC Trial: Mean Changes in Systolic and Diastolic Blood Pressure and Heart Rate
*P<.05 difference over time compared with baseline
P<.05 difference between groups
0 10 20 30 40 100 V A S
P a i n
0 40 60 80 100 V A S
S e d a t i o n
Propofol Dexmedetomidine 5 20 35 50 65 Surg End Pre- surg Time After Surgery, minutes *
*
Arain SR, Anesth Analg, 2002 Improved postoperative pain and greater sedation with dexmedetomidine compared with propofol Postoperative Effects of Dexmedetomidine L e s s
A l e r t
M o r e
A l e r t
L e s s
P a i n
M o r e
P a i n
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 2.5 5 7.5 10 12.5 Morphine Dexmedetomidine A v e r a g e
T o t a l
M o r p h i n e
U s e d ,
m g P<.01 0 2 4 6 8 10 12 0 10 20 30 40 50 60 70 Minutes in PACU C u m u l a t i v e
M o r p h i n e
U s e d ,
m g Morphine Dexmedetomidine P<.01 Arain SR, Anesth Analg 2004
MAC Trial: Fentanyl Use
Time Period DEX 0.5 mcg/kg N=134 n (%) p value DEX 1 mcg/kg N=129 n (%) p value PBO N=63 n (%) Infusion Period Required Fentanyl 79 (59.0) <0.001 55 (42.6) <0.001 56(88.9) PACU Period Required Fentanyl 5 (3.7) 0.104 5 (3.9) 0.105 6 (9.5) Overall Required Fentanyl 81 (60.4) <0.001 56 (43.4) <0.001 56(88.9) Pharmacokinetics of IV agents Dex Propofol Fentanyl Alfenta Vdcc, l
16 16 30 10 Vdss, l 200 350 330 30 Cl, l/min 0.6 1.8 0.8 0.3 T 1/2a , min 6 4 6 4 T 1/2b , hr 2 1.5 2.5 1 Dexmedetomodine Was Tried as a Primary Sedative for: Sedation in CT and MRI imaging studies Mason K, Ped Anesth 2008 Koroglu A, Anesth Analg 2006 Outpatient third molar surgery Ustin Y, J Oral Maxilfac Surg 2006 Cheung C, Anaesthesia 2007 Cataract surgery Alhashemi J, Br J Anaest 2006 Cardiac catheterization Tosun Z, J Card Vasc Anesth 2006 Mester R, Am J Therap 2008
Use of Dexmedetomidine in MRI 80 children aged 1-7 years Randomly assigned to either dexmedetomidine or midazolam 10-minute loading doses: 1 mcg/kg dexmedetomidine, 0.2 mg/kg midazolam Infusions: 0.5 mcg/kg/h dexmedetomidine, 6 mcg/kg/h midazolam 1
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 N u m b e r
o f
P a t i e n t s Midazolam Dexmedetomidine 1 = no motion 2 = minor movement 3 = major movement necessitating another scan Quality of MRI *P<.001 compared with midazolam * * Koroglu A, Br J Anaesth 2005 Dexmedetomidine for GI Procedures Jalowiecki P, Anesthesiology 2005 Use of Dex was associated with bradycardia, hypotension, vertigo, nausea/vomiting, prolonged recovery
Muller R, Gastroint Endosc 2008 Clinical efficacy of Dex alone is less than propofol during ERCP
Demiraran Y, Can J Gastroenter 2007 Dex may be a good alternative to midazolam for upper endoscopy Dexmedetomidine: Safety Propofol
TI = 3.5
Harrison N, Anesthetic Pharmacology, 2004 Dexmedetomidine:
Jorden V, Ann Pharmacoth, 2004 Pt 1 - 60 times the prescribed dose Pt 2 - 10 times the prescribed dose Pt 3 - 60 times the prescribed dose