BETA-BLOCKERS IN CARDIAC SURGERY

PRO CONTRO

Giovanni Landoni Luigi Tritapepe

Stefano TuriOspedale 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 beta-blockers, 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 second-third 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 beta-blockers 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 beta-blockers 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 500-300 ug/kg/min or 1.5-3 mg/kg ev or 100-200 mg ev

• 6 Metoprolol 2 or 4 mg ev or 50-100-200 mg os• 4 Atenolol 5 mg ev or 50 mg os (MANGANO)• 3 Labetalol 5 or 10 mg ev or 0.25-1 mg/kg ev

or 100 mg os• 1 Oxprenolol 20 mg os• 1 Timolol 10 mg os• 1 Propranolol 10 mg os• 1 Bisoprolol 5 mg os (POLDERMANS)

Stabilizzazione dellaplacca

Migliora domanda/apporto

di O2Effetto antiaritmico

Possibile effetto diretto su PTL (infiammazione)

Diminuisce lo stress emodinamico

Diminuisce lo stress di parete sistolico, la contrattilità e la frequenza cardiaca

Aumenta la durata della diastole, migliora la distribuzione del flusso ematico miocardico

Diminuiscono le aritmie ventricolari, aumenta la soglia della fibrillazione ventricolare

EFFETTI BENEFICI

DEIBETABLOCCANTI

TERAPIA FARMACOLOGICABETA-BLOCCANTI

TERAPEUTICOControllo

emodinamico

PROFILATTICODiminuzione di morbidità/

mortalità cardiaca

perioperatoria

ControlloIpertensione/tachicardia

Trattamento aritmie

Trattamento Ischemia

miocardica

Induzione di ipotensione

UTILIZZO PERIOPERATORIO

DEI BETABLOCCANTI

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

ESMOLOLPharmacological 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 post-CPB (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 moderate-severe 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 AnestheticsVolatile Anesthetics

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!

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

Myocardial infarctionEvidence!

LEVOSIMENDAN VS CONTROLMortality in cardiac surgery

11/235=4.7% v 26/205=12.7% P=0.007

Evidence!

LEVOSIMENDAN VS CONTROLMyocardial Infarction in cardiac surgery

2/183=1.1% v 9/153=5.9% P=0.04

Evidence!

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.

CONCLUSIONSBETA-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 POPOLOPERCHE’ SIAM DIVISI”

MAMELI

ITACTA ONGOING RCTsTOPICS HOSPITALS PATIENTS GRANTS

• VOLATILE ANESTHETICS

• FENOLDOPAM

• DESMOPRESSIN

• ESMOLOL• LEVOSIMENDAN• VALVOLE PERCUTANEE

landoni.giovanni@hsr.itwww.itacta.org

• 4 200 AIFA 2006

• 34 1.000 MINISTRY 2008

• 3 200

• 3 200• 28 1.000• 3 150

“.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 beta-blockers, angiotensin converting enzyme (ACE) inhibitors, antiplatelet agents, and statins in eligible individuals”.

• Class I Preoperative or early postoperative administration of beta-blockers 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 RCTsTOPICS HOSPITALS PATIENTS GRANTS

• VOLATILE ANESTHETICS

• FENOLDOPAM

• DESMOPRESSIN

• ESMOLOL• LEVOSIMENDAN• VALVOLE PERCUTANEE

landoni.giovanni@hsr.itwww.itacta.org

• 4 200 AIFA 2006

• 34 1.000 MINISTRY 2008

• 3 200

• 3 200• 28 1.000• 3 150

For these and further slides on these topics please feel free to visit the

metcardio.org website:

http://www.metcardio.org/slides.html