Transcript Beta-Blocker’s in Anesthesia

β-blocker’s in Anesthesia
Donald M. Voltz, M.D.
Assistant Professor of Anesthesiology
Case Western Reserve University/University
Hospitals of Cleveland
Goals
 To provide everyone with enough information
to begin comfortably using beta-blockers in
the perioperative period.
Objectives
 Physiology of Adrenergic Receptors
 β -adrenergic antagonists
 Clinical Application of β-blockers
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Cardiac Protection
Hemodynamic Control
Decreasing Anesthetic Requirements
 Guidelines for Beta-blocker Usage in the OR
β -adrenergic Receptor
Physiology
β-blocker Receptor Types
 β
1
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Receptors
Predominant receptor on cardiac myocytes
 β 2 Receptors
 Involved in contraction and relaxation of heart failure
 Peripheral vasodilitation and bronchial dilatation
 β 3 Receptors
 Negative inotropy via NO-dependant pathway
 May play a role in deterioration of cardiac function in
heart failure
β – Receptor Biologic Responses
 Chronotropy
 Dromotropy
 Inotropy
 Cellular Growth
 Cellular Death (apoptosis)
β-Receptor Intracellular Signaling
β -Receptor Down-Regulation
 Phosphorylation (down regulation)
 Translocation (sequestration)
 Degredation
β -Receptor Down-Regulation
 Down-regulation begins within a few hours
after an elevation of catecholamines
 Initial phase is the uncoupling of receptor and
signal transduction
 Late phase results in degradation of
receptors
 Down-regulation has been reported to persist
for 1 week after laparotomy, thoracotomy, and
cardiac bypass
β -Receptor Down-Regulation
Cell Death – Necrosis and Apoptosis
 Catecholamines are toxic to cardiac cells
 Tachycardia with Isoproterenol significantly
increased apototic death than ventricular
pacing
 Cardiac cell death is reduced in patients with
subarachnoid bleeding when treated with
atenolol
β -adrenergic Antagonist
Medications
β -adrenergic Antagonists
Generation
Characteristics
Medications
st
1
No ancillary
Properties
propranolol,
timolol, nadolol
nd
2
β1-selective
metoprolol,
atenolol, esmolol,
bisoprolol
rd
3
β1-selective, with
ancillary properties
carvedilol,
bucindolol
β 1/ β 2 selectivity
Medication
Propranolol
Metoprolol
Atenolol
Esmolol
Bisoprolol
Carvedilol
Bucindolol
Celiprolol
Nebivolol
β 1/ β 2 Selectivity
2.1
74
75
70
119
7.2
1.4
300
293
Ancillary Properties of β-blockers
 Membrane-Stabilizing Activity
 Intrinsic Sympathomimetic Activity
 Lipid Solubility
 Antioxidant Activity
 Anti-adhesive Activity
 α1-Antagonistic Activity
Clinical Actions of β -blockers
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Lowering heart rate
Decreasing blood pressure
Decreasing atherosclerotic plaque stiffness
Decreased platelet activation
Anti-arrhythmic effects
Cardiac protection – not HR dependant
Decrease in anesthetic and analgesic
requirements
 Improvement of immune response
Cardiac Effects of β-blockade
Clinical Evidence for β –
blocker Use
Clinical Applications for β -blockade
 Cardiac Protection
 Hemodynamic Control
 Immune Modulation
 Modulation of Coagulation
 Decreased Anesthetic Requirements
Myocardial Protection
 Well studied in vascular patient’s who are at
high risk for perioperative cardiac events
 Evolving evidence supports there use as a
standard of care in at risk patients
 Likely to find increasing role in the future
Effect of Atenolol on Mortality and Cardiovascular Morbidity after
Noncardiac Surgery
Dennis T. Mangano, Ph.D., M.D., Elizabeth L. Layug, M.D., Arthur Wallace, Ph.D., M.D., Ida Tateo,
M.S., for The Multicenter Study of Perioperative Ischemia Research Group
Volume 335:1713-1721
December 5, 1996
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Number 23
Mangano, et al. 1996
 Randomized trial of atenolol vs. saline (n=99,
n=101)
 Patient followed for 2 years
 Mortality decreased in atenolol group
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0% vs 8% at 6 months
3% vs 14% at 1 year
10% vs 21% at 2 years
Wallace, et al. 1998
 200 pts randomized to atenolol or saline
 EKG, Holter monitor, and CPK w/ MB were
followed 24 hr prior and 7 days after surgery
 Atenolol 0,5, or 10 mg or placebo prior to
induction and every 12 hours until po than qd
for 1 week
Wallace, et al. 1998
 Decreased perioperative myocardial ischemia
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17/99 esmolol vs 34/101 placebo (days 0-2)
24/99 esmolol vs 39/101 placebo (days 0-7)
Polderman, et al. 1999
 846 pts with one or more cardiac risk factors; 173
positive dobutamine stress tests
 Bisoprolol in 59; Placebo in 53
 Nonfatal MI
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0% bisoprolol
17% placebo group
 Cardiac Death
 3.4% bisoprolol group
 17% placebo group
What Patients are at Risk
B-blockers & At Risk Patients
 Presence of CAD
 History of Myocardial Infarction
 Typical Angina or Atypical Angina with + Stress Test
 At Risk for CAD (2 or more of the following)
 Age >65 years
 Hypertension
 Active Smoker
 Serum Cholesterol > 240 mg/dl
 Diabetes Mellitus
B-blockers and Cardioprotection
 How well are we doing with at risk patients?
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Not Very Well!
Prophylactic beta-blockade to prevent myocardial infarction
perioperatively in high-risk patients who undergoing general surgical
procedures.
Taylor RC, Pagliarello G.
Can J Surg. 2003 Jun;46(3):216-22
 236 pts for laparotomy
 143 pts at risk for CAD
 60.8% did not receive B-blockers pre-op
 33% pts had B-blockers discontinued
The Effect of Heart Rate Control on Myocardial
Ischemia Among High-Risk Patients After Vascular
Surgery
Khether E. Raby, MD, FACC*, Sorin J. Brull, MD , Farris
Timimi, MD, Shamsuddin Akhtar, MD, Stanley Rosenbaum,
MD, Cameron Naimi, BS, and Anthony D. Whittemore, MD
Anesth Analg. 1999 Mar;88(3):477-82
The Effect of Heart Rate Control on Myocardial
Ischemia Among High-Risk Patients After
Vascular Surgery
 Vascular Pts at High Risk for CAD underwent
24 hrs Holter Monitoring
 26 of 150 pts had significant ischemia as
measured by ST-depression – PreOp
 Randomized to Esmolol gtt (n=15) or Placebo
(n=11)
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Titrated to HR 20% below ischemic threshold
 Holter Monitoring for 48 hrs PostOp
The Effect of Heart Rate Control on Myocardial
Ischemia Among High-Risk Patients After
Vascular Surgery
 Ischemia Present Post-Op
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73% in Placebo Group (8 of 11)
33% in Esmolol Group (5 of 15)
 Number of Hours HR < Ischemic Threshold
 9 of 15 pts in Esmolol group <20% and all
without ischemia
 4 of 11 pts in Placebo group <20%. 3 of 4
without ischemia
Anti-Arrhythmic Effects
 High risk pts with CAD under-going
noncardiac surgery have PVC’s or ventricular
tachyarrythmias (50% incidence)
 Cardiac surgery pts are at high risk of
developing atrial fibrillation
 Blunting sympathetic tone decreases
incidence of both atrial and ventricular
tachyarrythmias
 β-blockers counteract epinephrine-induced
hypokalemia
Balanced Anesthesia and
Beta-blockers
Analge s ia
Am ne s ia
Components of Balanced Anesthesia
3/15/2003 - v2
Uncons cious ne s s
He m odynam ic Control
Paralys is
B-blockers and Anesthetic
Reduction
Beneficial Effects from B-Adrenergic Blockade in Elderly
Patients Undergoing Noncardiac Surgery
Michael Zaugg, M.D.; Thomas Tagliente, M.D., Ph.D.; Eliana Lucchinetti, M.S.; Ellis
Jacobs, Ph.D.; Marina Krol, Ph.D.; Carol Bodian, Dr.P.H.; David L. Reich, M.D.; Jeffrey
H. Silverstein, M.D.
ANESTHESIOLOGY 1999;91:1674-1686
Beneficial Effects from B-Adrenergic Blockade in Elderly Patients
Undergoing Noncardiac Surgery
 N=63 patients for noncardiac surgery
 Monitored – Neuropeptide Y, epinephrine,
norepinephrine, cortisol, and ACTH
 Randomly assigned
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Group 1: no atenolol
Group 2: Pre- and Post-operative atenolol
Group 3: Intraoperative Atenolol
Beneficial Effects from B-Adrenergic Blockade in Elderly Patients
Undergoing Noncardiac Surgery
Beneficial Effects from β -Adrenergic Blockade in
Elderly Patients Undergoing Noncardiac Surgery
 Beta-blockade did not change
neuroendocrine stress response
 Lower Narcotic Requirement
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Groups II and III – 27.7% less fentanyl
 Lower Anesthetic Requirements
 Group III – 37.5% less isoflurane (BIS same in
all groups)
 Lower PACU Morphine requirements
 Shorter PACU times
Beta-blockers and Bariatric Surgery
 Randomized Study of Morbidly Obese
Patients Undergoing Gastric Bypass
 Metoprolol vs. Placebo
 Evaluate
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Intraoperative Volatile Requirements
PACU Pain Requirement
PCA Usage
Atenolol May Not Modify
Anesthetic Depth Indicators
in Elderly Patients –
A Second Look at the Data
Zaugg, et. al.
Can J Anesth 2003; 50: 638-42
Atenolol May Not Modify Anesthetic Depth
Indicators in Elderly Patients –
A Second Look at the Data
 Does atenolol result in light anesthesia with
the reduction of volatile agents?
 Are our abilities to adequately judge
anesthetic depth impaired with atenolol?
Atenolol May Not Modify Anesthetic Depth
Indicators in Elderly Patients –
A Second Look at the Data
 45 patients from the prior study we used (post
hoc)
 Collected HR, MAP, SBP, and BIS output
 Subgroups were analyzed
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Group I n=12
Group II n=16
Group III n=17
Atenolol May Not Modify Anesthetic Depth
Indicators in Elderly Patients –
A Second Look at the Data
 Group III received 39.5% less isoflurane than
Group I
 Group II and III received 21% less fentanyl
than Group I
 All Groups had similar intraoperative BIS
levels (53-54)
 Atenolol reduces anesthetic requirements but
not modify depth of anesthesia indicators
β-Blockers and Memory
 Lipophilic β-blockers can cross the blood-
brain barrier
 Propranolol has been shown to blunt storage
of emotionally charged events
 Some thoughts that perioperative β-blockade
may be useful to blunt recall
Esmolol Promotes
Electroencephalographic Burst
Suppression During
Propofol/Alfentanil Anesthesia
Jay W. Johansen
Anesth Analg 2001; 93:1526-31
Esmolol Promotes Electroencephalographic Burst
Suppression During Propofol/Alfentanil Anesthesia
 N=20 patients
 Alfentanil Groups (50 or 150 ng/ml)
 Saline vs Esmolol infusion
 Monitored BIS output and Suppression Ratio
Esmolol Promotes Electroencephalographic Burst
Suppression During Propofol/Alfentanil Anesthesia
 BIS Output
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Esmolol – 40% reduction (37→22)
Saline – no change
 Suppression Ratio
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Esmolol – 13.4 fold increase (5 → 67)
Saline – no change
Efficacy of esmolol versus
alfentanil as a supplement to
propofol-nitrous oxide
anesthesia
Smith, J. Van Hemelrijck, and P. White
Anesth Analg 2003;97:1633-1638
Efficacy of esmolol versus alfentanil as a supplement
to propofol-nitrous oxide anesthesia
 N=97 patients for arthroscopy
 Compared esmolol to alfentanil
Efficacy of esmolol versus alfentanil as a supplement
to propofol-nitrous oxide anesthesia
 Esmolol decreased time to eye opening (7.2
vs 9.8 min)
 Esmolol reported more pain in PACU
 Esmolol required more opiods in PACU
Esmolol Potentiates
Reduction in Minimal
Alveolar Isoflurane
Concentration
Jay W. Johansen, et al.
Anesth Analg 1998; 87:671-6
Esmolol Potentiates Reduction in Minimal Alveolar
Isoflurane Concentration
 N=100; divided into 5 groups
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Isoflurane alone
Isoflurane with large dose esmolol (250
mcg/kg/min)
Isoflurane with Alfentanil
Isoflurane, Alfentanil, small dose esmolol (50
mcg/kg/min)
Isoflurane, Alfentanil, large dose esmolol (250
mcg/kg/min)
Esmolol Potentiates Reduction in Minimal Alveolar
Isoflurane Concentration
 MAC levels after steady state
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Isoflurane – 1.28%
Iso + large dose Esmolol – 1.23%
Iso + Alfentanil – 0.96%*
Iso + Alfentanil + small dose Esmolol – 0.96%
Iso + Alfentanil _ large dose Esmolol –
0.74%**
Perioperative Immune Modulation
 Stress response decreases immune function
 Natural killer cells have decreased cytotoxic
activity in the perioperative period
 Nadolol has been shown to blunt a
hypothermic decrease in natural killer cell
cytotoxic activity
Contraindications of
β -blockers
β-blocker Adverse Reactions
 Very well tolerated in the perioperative period
 May see hypotension in severely volume
contracted patients
 Patients with severe heart failure may acutely
have problems. Titrate slowly.
 Avoid in symptomatic bradycardia
 Caution in patients with advanced conduction
impairments
β-blocker Adverse Reactions
 Bradycardia – is it symptomatic???
 Bronchospasm in COPD/Asthma patients –
no evidence to suggest problem in these
patients with selective agents
 Heart Failure – use carefully in patients with
low EF, however, has been shown to improve
function with ACEI in end-stage CHF
Management of
Complications Related to βBlockade
Treatment of Symptomatic
Bradycardia from β-blockers
 Use of Vagolytic Medications
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Glycopyrolate
Atropine
 Glucagon 2.5 mcg/kg iv
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Pronounced chronotropic effect
Treatment of Hypotension from
β-blockers
 β-agonists are not useful in treating cardiac
decompensation
 Phosphodiesterase III inhibitors (milrinone) retain full
hemodynamic effects without excessive tachycardia
 Combination of glucagon and milrinone restores
cardiac output but often increases heart rate
significantly
 Combination of β-blockers with PDE3I’s may allow for
perioperative β-blockade in severe heart failure
Guidelines for Using
β -blockers in the OR
Summary for At Risk Patients
 Preemptive Bradycardia
 Think about heart rate as separate from blood
pressure
 Be aggressive with heart rate control
 Incorporate into preoperative and
postoperative care.
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Involve Primary Care Physician
Involve Vascular Surgeon and Nursing
The End