BETA-BLOCKERS IN
CARDIAC SURGERY
PRO
CONTRO
Giovanni Landoni
Stefano Turi
Luigi Tritapepe
Ospedale San Raffaele, Milano
Policlinico Umberto I, Roma
XX SMART MILANO 6 MAGGIO 2009
BETA-BLOCKERS IN CCH
BETA-BLOCKERS IN CARDIAC
SURGERY
BETA-BLOCKERS IN CARDIAC
SURGERY
“.For
patients with elevated biomarkers after CABG, it
is it is particularly important that attention be given to
optimal medical therapy, including the use of betablockers, angiotensin converting enzyme (ACE)
inhibitors, antiplatelet agents, and statins in eligible
individuals”.
ATRIAL FIBRILLATION
• Atrial fibrillation occurs in 30% patients
undergoing CABG (peak on the secondthird post-operative day)
• Increase in the length of stay
• Increase the charges by as much as
10000$
• Increase in post-operative stroke
• Class I Preoperative or early
postoperative administration of betablockers in patients without
contraindications should be used as
the standard therapy to reduce the
incidence and/or clinical sequelae of
atrial fibrillation after CABG. (Level of
Evidence: B)
• Currently, preoperative or early
postoperative administration of betablockers is considered standard therapy to
prevent atrial fibrillation after CABG except
in patients with active bronchospasm or
marked resting bradycardia.
• Withdrawal of beta-blockers in the
perioperative period doubles the incidence
of postoperative atrial fibrillation after
CABG.
BETA-BLOCKERS IN CARDIAC
SURGERY
• First drug choice in treatment of post
CABG FA
• Reduction of hospital length of stay and
cost
BETA-BLOCKERS IN CARDIAC
SURGERY
• Could be useful to use beta-blockers for
the first time in selected patients in the
peri-operative period?
• How and When should we admnister , just
before cardiac surgery, beta-blockers in
patients already taking these drugs?
• What about non.cardiac surgery?
Timing of B blocker administration
•
•
•
•
•
•
•
•
•
•
•
•
•
2 weeks before
1 week before and 30 days after (POLDERMANS)
4 days before
1 day before
2 hours before, than for 5 days
2 hours before (3 studies)
30 minutes before, than for 72 h
Just before surgery (7 studies)
Just before, than for 5-11 days (3 studies)
Before extubation
Post surgery for 48 h
Post surgery for 7 days (MANGANO)
1 h after surgery till hospital discharge
B blocker administration
• 7
Esmolol
• 6
• 4
• 3
Metoprolol
Atenolol
Labetalol
•
•
•
•
Oxprenolol
Timolol
Propranolol
Bisoprolol
1
1
1
1
500-300 ug/kg/min or 1.5-3 mg/kg ev
or 100-200 mg ev
2 or 4 mg ev or 50-100-200 mg os
5 mg ev or 50 mg os (MANGANO)
5 or 10 mg ev or 0.25-1 mg/kg ev
or 100 mg os
20 mg os
10 mg os
10 mg os
5 mg os (POLDERMANS)
Stabilizzazione della
placca
Possibile effetto diretto
su PTL
(infiammazione)
Diminuisce lo
stress
emodinamico
Diminuisce lo stress
di parete sistolico, la
contrattilità e la
frequenza cardiaca
Migliora
domanda/apporto
di O2
Aumenta la durata della
diastole, migliora la
distribuzione del flusso
EFFETTI
BENEFICI
DEI
BETABLOCCANTI
Effetto antiaritmico
Diminuiscono le aritmie
ventricolari, aumenta la soglia
della fibrillazione ventricolare
TERAPIA FARMACOLOGICA
BETA-BLOCCANTI
Controllo
Ipertensione/
tachicardia
Induzione di
ipotensione
TERAPEUTICO
Controllo
emodinamico
Trattamento
aritmie
UTILIZZO
PERIOPERATORIO
DEI BETABLOCCANTI
Trattamento
Ischemia
miocardica
PROFILATTICO
Diminuzione
di morbidità/
mortalità
cardiaca
perioperatoria
In this large North American observational analysis,
preoperative beta-blocker therapy was associated with a
small but consistent survival benefit for patients undergoing
CABG, except among patients with a left ventricular
ejection fraction of less than 30%. This analysis further
suggests that preoperative beta-blocker therapy may be a
useful process measure for CABG quality improvement
assessment.
• 629.877 patients
• 497 hospitals
• 1996-1999
• unadjusted 30-day mortality, 2.8% vs 3.4%;
odds ratio [OR], 0.80; 95% confidence interval
[CI], 0.78-0.82
• Preoperative -blocker use remained associated
with slightly lower mortality after adjusting for
patient risk and center effects using both risk
adjustment (OR, 0.94; 95% CI, 0.91-0.97) and
treatment propensity matching (OR, 0.97; 95%
CI, 0.93-1.00)
• Among patients with a left ventricular
ejection fraction of less than 30%,
however, preoperative -blocker therapy
was associated with a trend toward a
higher mortality rate (OR, 1.13; 95% CI,
0.96-1.33; P=.23).
• The absence of preoperative -blocker
therapy (odds ratio 3.94; 95%
confidence interval, 1.123-13.833; p
0.03) and of an epidural catheter (odds
ratio 3.91; 95% confidence interval,
1.068-14.619; p 0.04) were the only
preoperative and intraoperative
variables independently associated
with a prolonged intensive care unit
stay
• 92 patients
• 1 hospital
• 2008
• 73y
• 60% EF
• CABG
ESMOLOL
Pharmacological properties
•
•
•
•
Ultra short-acting beta-blocker
Half-life 8 minutes
Time to peak effect 6-10 minutes
Wash-out time 20 minutes after stopping
infusion
• Clerance: ester hydrolysis by erytrhrocitary
estherase
• Administration: endovenous,loading dose
followed by continous infusion
CLINICAL USE
•
•
•
•
Hypertension
Myocardial infarction
Myocardial ischaemia
Treatment of arrhytmias
• The first beta-blocker choice in emergency and
in critical patients
SIDE EFFECTS
• Hypotension
• Bradycardia
• Low output cardiac syndrome
• Obstructive pulmonary disease
CARDIAC SURGERY
• Reduction of haemodynamic response to
laringoscopy, intubation, extubation
• Treatment- prevention of arrhytmias postCPB (atrial fibrillation,atrial flutter)
• Alternative to traditional cardioplegic
solutions
META-ANALYSIS
•
•
•
•
23 studies
979 patients
All mono-center studies
Analysis with Review Manager 4.2
• We tried to contact all the corresponding
authors to know if they had new data
ISCHAEMIA
Ischemia
15/122
(12%)
36/140
(27%)
0.009
INOTROPIC DRUGS
Inotropi
29/153
(18%)
48/146
(32%)
0.002
• Rapid injection of an esmolol bolus can quickly
resolve the systolic anterior motion and left
ventricular outflow tract obstruction if it is the
result of haemodynamic factors, alleviating
hyperdynamic left ventricular conditions and
their contribution to dynamic left ventricular
outflow tract obstruction and helping to identify
the few patients who require immediate
additional surgical intervention.
Esmolol to treat systolic anterior motion (SAM)
of the mitral valve causing left ventricular
outflow tract obstruction (LVOT) after mitral
valve repair.
• Systolic anterior motion (SAM) of the mitral valve
causing left ventricular outflow tract obstruction (LVOT)
is common after mitral valve repair but only rarely
necessitates immediate additional surgical intervention.
• The degree of systolic anterior motion extends along a
continuous spectrum from minor chordal-only systolic
anterior motion to its most severe form with permanent
left ventricular outflow tract obstruction and moderatesevere mitral regurgitation.
• The management of systolic anterior motion in the
operative room remains controversial
Administration of Esmolol during
cardioplegia
• Reduction of oxydative damage
• Not increase of lactate concentrations
• Less ICAM-I expression
• Less expression of inducible NOS (associated
to myocardial injury)
NEW RCT
•
•
•
•
New large multicenter randomized trial
Esmolol during extracorporeal circulation
DTD>60 and FE< 50% patients
Administration just before aortic clamping
and with cardioplegia (1-2 mg/kg)
Reducing perioperative myocardial infarction
with anesthetic drugs and techniques.
Current Drug Targets 2009, in press
Volatile Anesthetics
Evidence!
Mortality
4/977=0.4% v 14/872=1.6%
NNT=84
RRR=(1,6-0,4)/1,6=75%
OR: 0.31(0.12-0.80)
P=0.02
Evidence!
Myocardial infarction
24/979=2.4% v 45/874=5.1%
NNT=37
RRR: (5.1-2.4)/5.1 = 53%
OR: 0.51(0.32-0.84)
p=0.008
Evidence!
LEVOSIMENDAN VS CONTROL
Mortality in cardiac surgery
11/235=4.7% v 26/205=12.7%
P=0.007
Evidence!
LEVOSIMENDAN VS CONTROL
Myocardial Infarction in cardiac surgery
2/183=1.1% v 9/153=5.9%
P=0.04
CONCLUSION:
Volatile agents and levosimendan
consistently reduce perioperative
myocardial infarction and mortality in
cardiac surgery but they have not been
properly studied in non-cardiac surgery.
CONCLUSIONS
BETA-BLOCKERS
• Reduction of arrhythmias after
cardiopulmonary bypass (FV)
• Reduction of ischemia
• Reduction ICU stay and time for
mechanical ventilation
• Reduction of mortality at thirty days
“PERCHE’ NON SIAM POPOLO
PERCHE’ SIAM DIVISI”
MAMELI
ITACTA ONGOING RCTs
TOPICS
HOSPITALS PATIENTS
GRANTS
•
VOLATILE
ANESTHETICS
•
4
200
AIFA 2006
•
FENOLDOPAM
•
34
1.000
MINISTRY 2008
•
DESMOPRESSIN
•
3
200
•
•
•
ESMOLOL
LEVOSIMENDAN
VALVOLE PERCUTANEE
•
•
•
3
28
3
200
1.000
150
landoni.giovanni@hsr.it
www.itacta.org
“.For
patients with elevated biomarkers after CABG, it
is it is particularly important that attention be given to
optimal medical therapy, including the use of betablockers, angiotensin converting enzyme (ACE)
inhibitors, antiplatelet agents, and statins in eligible
individuals”.
• Class I Preoperative or early
postoperative administration of betablockers in patients without
contraindications should be used as
the standard therapy to reduce the
incidence and/or clinical sequelae of
atrial fibrillation after CABG. (Level of
Evidence: B)
• Withdrawal of beta-blockers in the
perioperative period doubles the incidence
of postoperative atrial fibrillation after
CABG.
In this large North American observational analysis,
preoperative beta-blocker therapy was associated with a
small but consistent survival benefit for patients undergoing
CABG, except among patients with a left ventricular
ejection fraction of less than 30%. This analysis further
suggests that preoperative beta-blocker therapy may be a
useful process measure for CABG quality improvement
assessment.
Administration of Esmolol during
cardioplegia
• Reduction of oxydative damage
• Not increase of lactate concentrations
• Less ICAM-I expression
• Less expression of inducible NOS (associated
to myocardial injury)
Reducing perioperative myocardial infarction
with anesthetic drugs and techniques.
Current Drug Targets 2009, in press
ITACTA ONGOING RCTs
TOPICS
HOSPITALS PATIENTS
GRANTS
•
VOLATILE
ANESTHETICS
•
4
200
AIFA 2006
•
FENOLDOPAM
•
34
1.000
MINISTRY 2008
•
DESMOPRESSIN
•
3
200
•
•
•
ESMOLOL
LEVOSIMENDAN
VALVOLE PERCUTANEE
•
•
•
3
28
3
200
1.000
150
landoni.giovanni@hsr.it
www.itacta.org
For these and further slides on these
topics please feel free to visit the
metcardio.org website:
http://www.metcardio.org/slides.html