pharmacological pre-emptive strategies for cardiac surgery : give me the magic bullet , please
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IRCCS Ospedale San Raffaele Milano Università Vita-Salute San Raffaele. Pharmacological pre-emptive strategies for cardiac surgery : give me the magic bullet , please. INTERCEPT 2009 S Donato Milanese, Milan, April 17h 2009. Speaker:Landoni G. - PowerPoint PPT PresentationTRANSCRIPT
Pharmacological pre-emptive Pharmacological pre-emptive strategies for cardiac strategies for cardiac surgery: give me the magic surgery: give me the magic bullet, pleasebullet, please
Speaker:Speaker: Landoni GLandoni G INTERCEPT 2009INTERCEPT 2009
S Donato Milanese, Milan, April 17h 2009S Donato Milanese, Milan, April 17h 2009
IRCCS Ospedale San Raffaele MilanoIRCCS Ospedale San Raffaele MilanoUniversità Vita-Salute San RaffaeleUniversità Vita-Salute San Raffaele
MAGIC BULLETS TO REDUCE MORTALITY IN CARDIAC SURGERY
THERE ARE NO GUIDELINES
THERE IS NO CONSENSUS CONFERENCE
THERE IS NO LARGE RANDOMIZED CONTROLLED STUDY ADEQUATELY POWERED TO SUGGEST A REDUCTION IN MORTALITY
AN OVERVIEW OF META-ANALYSIS
PEXELIZUMAB
LEVOSIMENDAN
FENOLDOPAM
VOLATILE AGENTS (Intercept 2006)
AN OVERVIEW OF META-ANALYSIS
MAGIC BULLET
PEXELIZUMABLEVOSIMENDANFENOLDOPAMVOLATILE AGENTS
NNT TO PREVENT ONE DEATH
1001219 or 2684
LEVOSIMENDAN 1
LEVOSIMENDAN 2
Description of the ten studies included in the meta-analysis.
First author
Journal Year Cardiac surgery procedures Control
Al-Shawaf J Cardiothorac Vasc Anesth 2006 Elective CABG* Milrinone
Alvarez 2005 Rev Esp Anestesiol Reanim 2005 Cardiac surgery with CPB† Dobutamine
Alvarez 2006 Rev Esp Cardiol 2006 Cardiac surgery with CPB† Dobutamine
Barisin J Cardiovasc Pharmacol 2004 OPCABG‡ Placebo
De Hert 2007 Anesth Analg 2007 Elective cardiac surgery with CPB† Milrinone
De Hert 2008 J Cardiothorac Vasc Anesth 2008 Cardiac surgery with CPB† Milrinone
Husedzinovic Croat Med J 2005 OPCABG‡ Placebo
Jarvela J Cardiothorac Vasc Anesth 2008 Aortic valve surgery Placebo
Levin Rev Esp Cardiol 2008 CABG* with CPB† Dobutamine
Tritapepe Br J Anaesth 2006 CABG* with CPB† Placebo
* CABG: coronary artery bypass graft† CPB: cardiopulmonary bypass‡ OPCABG: off-pump coronary artery bypass graft
Number of patients and interventions of included studies.
First author Time of administrationSetting
Bolus dose Continuous infusion dose Length of infusion
Al-Shawaf LCOS# 12 g/kg 0.1-0.2g/kg/min 24 hours
Alvarez 2005 LCOS# 12g/kg 0.2g/kg/min 24 hours
Alvarez 2006 LCOS# 12g/kg 0.2g/kg/min 24 hours
Barisin Before surgery 12/24g/kg
no no
De Hert 2007 After CPB† No bolus 0.1g/kg/min 19+4 hours
De Hert 2008 First group : after induction of anesthesiaSecond group : after CPB†
No bolus 0.1g/kg/min 22+4 hours in the first group, 23+3 hours in the second one
Husedzinovic Before surgery 12g/kg no no
Jarvela After induction No bolus 0.2g/kg/min 24 hours
Levin LCOS# 10g/kg 0.1g/kg/min 24 hours
Tritapepe Before CPB† 24g/kg no no
† CPB: cardiopulmonary bypass# LCOS: low cardiac output syndrome
Levosimendan and Mortality in Cardiac Surgery
Review: LEVOSIMENDAN CCH (12/1/2009)Comparison: 01 perioperative levosimendan Outcome: 02 Mortality
Study Levosimendan Control Peto OR Peto ORor sub-category n/N n/N 95% CI 95% CI
Al-Shawaf 1/14 1/16 1.15 [0.07, 19.41] Alvarez 2005 1/15 0/15 7.39 [0.15, 372.38] Alvarez 2006 1/25 1/25 1.00 [0.06, 16.45] Barisin 0/21 0/10 Not estimable De Hert 2007 0/15 3/15 0.12 [0.01, 1.22] De Hert 2008 1/40 4/20 0.11 [0.02, 0.72] Husedzinovic 0/12 0/12 Not estimable Jarvela 1/12 0/12 7.39 [0.15, 372.38] Levin 6/69 17/68 0.31 [0.13, 0.77] Tritapepe 0/12 0/12 Not estimable
Total (95% CI) 235 205 0.35 [0.18, 0.71]Total events: 11 (Levosimendan), 26 (Control)Test for heterogeneity: Chi² = 8.27, df = 6 (P = 0.22), I² = 27.4%Test for overall effect: Z = 2.95 (P = 0.003)
0.001 0.01 0.1 1 10 100 1000
Favours levosimendan Favours control
11/235=4.7% v 26/205=12.7% P=0.007 NNT = 12
Levosimendan and Mortality in Cardiac Surgery
Levosimendan and Myocardial Infarction
Review: LEVOSIMENDAN CCH (12/1/2009)Comparison: 01 perioperative levosimendan Outcome: 04 Myocardial infarction
Study Levosimendan Control OR (fixed) OR (fixed)or sub-category n/N n/N 95% CI 95% CI
Al-Shawaf 1/14 0/16 3.67 [0.14, 97.49] Barisin 0/21 1/10 0.15 [0.01, 3.96] De Hert 2007 0/15 0/15 Not estimable De Hert 2008 0/40 0/20 Not estimable Husedzinovic 0/12 0/12 Not estimable Levin 1/69 8/68 0.11 [0.01, 0.91] Tritapepe 0/12 0/12 Not estimable
Total (95% CI) 183 153 0.26 [0.07, 0.97]Total events: 2 (Levosimendan), 9 (Control)Test for heterogeneity: Chi² = 3.25, df = 2 (P = 0.20), I² = 38.5%Test for overall effect: Z = 2.01 (P = 0.04)
0.001 0.01 0.1 1 10 100 1000
Favours levosimendan Favours control
LEVOSIMENDAN VS CONTROLMyocardial Infarction in cardiac surgery
2/183=1.1% v 9/153=5.9% P=0.04
Evidence!
Levosimendan and Acute Renal FailureNNT = 6
Review: LEVOSIMENDAN CCH (12/1/2009)Comparison: 01 perioperative levosimendan Outcome: 05 Acute renal failure
Study Levosimendan Control OR (fixed) OR (fixed)or sub-category n/N n/N 95% CI 95% CI
Al-Shawaf 2/14 5/16 0.37 [0.06, 2.29] Alvarez 2005 1/15 0/15 3.21 [0.12, 85.20] Barisin 0/21 0/10 Not estimable Levin 5/69 21/68 0.17 [0.06, 0.50]
Total (95% CI) 119 109 0.26 [0.12, 0.60]Total events: 8 (Levosimendan), 26 (Control)Test for heterogeneity: Chi² = 2.95, df = 2 (P = 0.23), I² = 32.1%Test for overall effect: Z = 3.16 (P = 0.002)
0.001 0.01 0.1 1 10 100 1000
Favours levosimendan Favours control
LEVOSIMENDAN 2
ITACTA ONGOING RCTsTOPICS HOSPITALS PATIENTS GRANTS
VOLATILE ANESTHETICS
FENOLDOPAM
DESMOPRESSIN
ESMOLOL LEVOSIMENDAN VALVOLE PERCUTANEE
4 200 AIFA 2006
34 1.000 MINISTRY 2008
3 200
3 200 10 1.000 3 150
AIM OF THE STUDY
To evaluate the renoprotective action of fenoldopam
in a selected high-risk group of patients
undergoing cardiac surgery
RESULTSVariables Fenoldopa
mN=40
DopamineN=40
p
ARF(25%Creatinine increase), n(%)
17(42.5%)
16(40.0%)
0.9
ARF(50% Creatinine increase), n(%)
10(25%) 10(25%) 0.8
Renal Replacement Therapy.,n(%)
4(10%) 4(10%) 0.9
Exitus,n(%) 4(10%) 3(7.5%) 0.5
Transfusion,n(%) 21(56.8) 18(51.4) 0.8
Post-operative inotropes,n(%)
27(67.5) 26(65.0) 0.9
Post-operative hemolysis,n(%)
6(15) 1(2.5) 0.054
Mechanical ventilation hours
20.5(11.5-77) 21(10.5-96) 0.7
ICU stay,days 3(1-6) 3(1-8.5) 0.9
Hospital stay,days 13(7-19) 10.5(6-20.5) 0.8
Post-operative data
Am J Kidney Dis. 2007;4956-68. IF 4.4
Fenoldopam and Death in Critically ill patients
81/487(17%) versus 109/531 (21%) p=0.01 NNT=26
Pooled estimates of risk for need for renal replacement therapy
34/526 (6%) versus 59/570 (10%) p=0.007 NNT=26
Fenoldopam and Death in Cardiovascular Surgery
28/503 (6%) versus 55/503 (11%) p=0.002 NNT=19
Fenoldopam and renal replacement therapy in cardiovascular surgery
30/528 (6%) versus 71/531 (13%) p<0.001 NNT=13
ITACTA ONGOING RCTsTOPICS HOSPITALS PATIENTS GRANTS
VOLATILE ANESTHETICS
FENOLDOPAM
DESMOPRESSIN
ESMOLOL LEVOSIMENDAN VALVOLE PERCUTANEE
4 200 AIFA 2006
34 1.000 MINISTRY 2008
3 200
3 200 10 1.000 3 150
FENO-HSR
FENOLDOPAM E INSUFFICIENZA RENALE
• Fenoldopam vs placebo
• randomized
• double blind
• multicenter (32 centers, 1000 patients)
DESIGN
“R” (RIFLE) after cardiac surgeryWhich patients?
Serum creatinine increase by 50%
or
Urinary output <0,5 ml/kg/h for 6 h Planned ICU stay > 24 hours
AIM OF THE STUDY
Reduction of the need for renal replacement therapy
From 10% to 5%
DESFLURANEDESFLURANEversusversus
PROPOFOLPROPOFOL((fentanyl-based cardiac anesthesia)fentanyl-based cardiac anesthesia)
RCT(382 PATIENTS)
OFF-PUMP CABG(112 PATIENTS)
ON-PUMP CABG(150 PATIENTS)
MITRAL SURGERY(120 PATIENTS)
PeakTROPONIN I
ng/ml
OFF-PUMP CABG
1.2 (0.9-1.9) versus
2.7 (2.1-4.0)
*P<0.001
ON-PUMP CABG
2.5 (1.1-5.3)versus
5.5 (2.3-9.5)
*P<0.001
MITRAL SURGERY
11.0 (7.5-17.4)versus
11.5 (6.9-18.8)
P=0.7
Troponin I after OFF-PUMP CABG
Troponin I after CABG (CPB)
volatile anaesthetics
total intravenous anaesthesia
p=0,7
p<0,001
p=0,03
0
1
2
3
4
5
6
7
8
9
10
preop 0 4 18time, hour
cTn
I,
ng/m
l
Troponin I after MITRAL SURGERY
total intravenous anaesthesia
volatile anaesthetics
p=0,4
p=0,7
p=0,8
p=0,9
0
2
4
6
8
10
12
14
16
18
preop ICU arrival 4 hours day I day I I
time, hour
cTnI,
ng/m
l
Volatile AnestheticsVolatile Anesthetics
META-ANALYSIS(cardiac anaesthesia)
22 randomized studies (15 CPB-CABG; 6 OP-CABG; 1 mitral valve surgery)
1922 patients (904 TIVA and 1018 DES or SEVO)
16 studies administered volatile anesthetics throughout all the procedure (6 studies for 5-30 minutes)
MortalityEvidence!
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 infarctionEvidence!
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!
DURATION OF USE OF INHALATORY ANESTHETICS
DURING SURGERY
RIS
K-A
DJU
STED
MO
RTA
LIT
Y (
%) 8
6
4
2
0
NO USEALL OF THE OPERATION
ONLY INCISION/
STERNOTOMY
PART OF THE
OPERATION
P=0.022
RIS
K-A
DJU
STED
MO
RTA
LIT
Y (
%)
P=0.007
8
6
4
2
0
USE OF INHALATORY ANESTHETICS
0% TO <50%
OF CASES
≥50% OF CASES
P=0.007
NON-CARDIAC SURGERY
Cardioprotection & anaesthesia
Volatile AnestheticsVolatile Anesthetics
blockers “recommended”
Statins “suggested” in selected pts
2 agonists “may be considered” in selected pts
Ca++ antagonists “may be considered” in selected pts
Insulin “reasonable” in hyperglycaemic pts
Volatile Anesthetics “can be beneficial”
Every 1.000 patients receiving extended release METOPROLOL
PREVENTION OF 15 MYOCARDIAL INFARCTON PREVENTION OF 3 CABG PREVENTION OF 7 ATRIAL FIBRILLATION
Every 1.000 patients receiving extended release METOPROLOL
EXCESS OF 8 DEATHS EXCESS OF 5 STROKE EXCESS 53 HYPOTENSION EXCESS 42 BRADICARDIA
A meta-analysis in noncardiac surgery
6219 patients
2842 sevoflurane609 desflurane
2768 propofol
Evidence?
Total 79
Anesth analg 20
BJA 14
EJA 11
Acta anaesthesiol scand 8
Anaesthesia 5
J Anesth 4
Anesthesiology3
Minerva anestesiol 2
Altri 13
Anesth analg
BJA
EJA
Acta anestesiol scand
Anaesthesia
J anesth
Anesthesiology
Minerva anestesiol
Altri
A meta-analysis in noncardiac surgery
Evidence?
400 authors 240 reviewers 90 editors
0 deaths
0 myocardial infarctions
A meta-analysis in noncardiac surgery
Evidence?
TAKE HOME MESSAGE
MAGIC BULLET
PEXELIZUMABLEVOSIMENDANFENOLDOPAMVOLATILE AGENTS
NNT TO PREVENT ONE DEATH
1001219 or 2684
“PERCHE’ NON SIAM POPOLOPERCHE’ SIAM DIVISI”
MAMELI
ITACTA ONGOING RCTsTOPICS HOSPITALS PATIENTS GRANTS
VOLATILE ANESTHETICS
FENOLDOPAM
DESMOPRESSIN
ESMOLOL LEVOSIMENDAN VALVOLE PERCUTANEE
4 200 AIFA 2006
34 1.000 MINISTRY 2008
3 200
3 200 10 1.000 3 150
GRUPPI DI INTERESSE ITACTA(COORDINATI DA ANESTESISTI UNDER 40)
Gruppi esistenti ad oggi 27-3-2009 (per piu’ informazioni www.itacta.org), aperti ad iscrizioni
1. Sostituzioni valvolari percutanee ([email protected])
2. Monitoraggio emodinamico mini-invasivo ([email protected])
3. Statistica in anestesia e terapia intensiva ([email protected])
4. Analgesia selettiva in chirurgia toracica (
For further slides on these topics please feel free to visit the
metcardio.org website:
http://www.metcardio.org/slides.html