IRCCS Ospedale San Raffaele Milano
Università Vita-Salute San Raffaele
Peri-operative cardiac
protection
Relatore:
Dott. Giovanni Landoni
Tutorial in General Anesthesia,
Milano, 28 Marzo 2009
Cardioprotection & anaesthesia
Volatile Anesthetics
 b blockers
“recommended”
 Statins
“suggested” in selected pts
 a2 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”
REDUCING PERIOPERATIVE
MYOCARDIAL INFARCTION
 EPIDURAL ANESTHESIA (non-cardiac surgery)
 BETA BLOCKERS (non-cardiac surgery) ??!!
 VOLATILE AGENTS (cardiac surgery)
 LEVOSIMENDAN (cardiac surgery)
REDUCING PERIOPERATIVE
MORTALITY AND MYOCARDIAL INFARCTION
 VOLATILE AGENTS (cardiac surgery)
 LEVOSIMENDAN (cardiac surgery)
REDUCING PERIOPERATIVE
MORTALITY
 FENOLDOPAM
 PEXELIZUMAB (cardiac surgery)
 DOPEXAMINE
 EARLY ENTERAL NUTRITION (intestinal surgery)
 INSULINE !!??
 STATINS
Anaesthesia and Outcome
Volatile Anesthetics
Could VOLATILE anaesthetics
influence outcome?
Could VOLATILE anaesthetics have
non-anaesthetic properties?
DESFLURANE
versus
PROPOFOL
(fentanyl-based cardiac anesthesia)
RCT
(382 PATIENTS)
OFF-PUMP CABG
(112 PATIENTS)
ON-PUMP CABG
(150 PATIENTS)
MITRAL SURGERY
(120 PATIENTS)
Peak
TROPONIN I
ng/ml
OFF-PUMP CABG
ON-PUMP CABG
MITRAL SURGERY
1.2 (0.9-1.9)
versus
2.7 (2.1-4.0)
2.5 (1.1-5.3)
versus
5.5 (2.3-9.5)
11.0 (7.5-17.4)
versus
11.5 (6.9-18.8)
*P<0.001
*P<0.001
P=0.7
Troponin I after OFF-PUMP CABG
Troponin I after CABG (CPB)
10
p<0,001
9
8
cTnI, ng/ml
7
6
p=0,03
5
total
intravenous
anaesthesia
4
3
p=0,7
2
volatile
anaesthetics
1
0
preop
0
4
time, hour
18
Troponin I after MITRAL SURGERY
18
p=0,7
16
p=0,8
14
total
intravenous
anaesthesia
cTnI, ng/ml
12
10
p=0,4
p=0,9
8
6
4
volatile
anaesthetics
2
0
preop
ICU arrival
4 hours
time, hour
day I
day II
INOTROPES
in ICU
OFF-PUMP CABG
ON-PUMP CABG
MITRAL SURGERY
35.1%
versus
56.4%
32.0%
versus
41.3%
42.4%
versus
54.1%
*P=0.04
*P=0.04
P=0.3
NEW
Q WAVES
OFF-PUMP CABG
ON-PUMP CABG
MITRAL SURGERY
11%
versus
17%
6.7%
versus
18.7%
1.7%
Versus
1.6%
P=0.8
*P=0.049
P=0.7
Evidence?
I
II
III
IV
V
VI
Meta-analysis and/or large randomized
studies
Randomized trials
Non-randomized prospective trials
Retrospective studies
Case reports and Expert Opinion
Animal / Laboratories Studies
Volatile 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)
Evidence!
Mortality
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
Mortality
NNT=84
Treat 84 to save one
Evidence!
Myocardial infarction
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
Myocardial infarction
NNT=37
Treat 37 to save one
Evidence!
PEAK CARDIAC TROPONIN I
WMD -2.35 ng/dL [-3.09,-1.60], p<0.00001
Evidence!
INOTROPE USE IN ICU
OR 0.47 [0.29, 0.76], p < 0.002
Evidence!
Mechanical ventilation
WMD -0.49 hours [-0.97,-0.02], p = 0.4
Evidence!
ICU STAY
WMD -7.10 hours [-11.47,-2.73], p < 0.001
Evidence!
HOSPITAL STAY
WMD -2.26 days [-3.83,-0.68], p = 0.005
Name of the Hospital
% mortality
at 30 days
CLINICA SAN ROCCO - BRESCIA
0,26%
OSPEDALE SAN RAFFAELE MILANO
0,36%
PRESIDIO OSPEDALIERO "C. POMA" MANTOVA
0,48%
OSPEDALE CIVILE LEGNANO - MI
0,67%
OSPEDALE SANTA CROCE E CARLE CUNEO
1,15%
OSPEDALE S. CHIARA TRENTO
1,16%
NUOVO POLO CARDIOLOGICO - TRIESTE
1,22%
HESPARIA HOSPITAL S.R.L. MODENA
1,32%
Conclusions:
Volatile Anesthetics in cardiac surgery
Volatile Anesthetics
Sevoflurane&Desflurane:
↓post cardiac surgery
mortality
Direct and indirect
protection
Desflurane in CABG surgery:
• ↓postoperative cTnI
release
• ↓postoperative inotropic
support
• ↓hospitalization +/cardiopulmonary bypass
Have we forgotten about noncardiac surgery?
Evidence?
A meta-analysis in noncardiac surgery
6219 patients
2842 sevoflurane
609 desflurane
2768 propofol
Evidence?
A meta-analysis in noncardiac surgery
4281 citations retrieved
from database searches
3936 titles/abstracts excluded
because non-relevant
344 studies assessed according
to the selection criteria
79 Randomised Controlled Trials
finally included
in the systematic review
265 studies excluded according to
explicit exclusion criteria
35 duplicate reports
51 no TIVA group
75 cardiac surgery
46 retrospective
25 non randomised
21 paediatric
12 not available
Evidence?
A meta-analysis in noncardiac surgery
Total
79
Anesth analg
20
BJA
14
EJA
11
Anesth analg
Acta anaesthesiol scand
8
Anaesthesia
5
EJA
J Anesth
4
Acta anestesiol scand
Anesthesiology
3
Anaesthesia
Minerva anestesiol
2
Altri
13
BJA
J anesth
Anesthesiology
Minerva anestesiol
Altri
Evidence?
A meta-analysis in noncardiac surgery
400 authors
240 reviewers
90 editors
0
deaths
0
myocardial infarctions
Have we forgotten about CARDIAC
MORBIDITY and MORTALITY in noncardiac
surgery?
WHAT’S NEXT
SEVOFLURANE IN STENTING PROCEDURES: A
RANDOMIZED CONTROLLED STUDY.
METHODS
30 patients
20’
16
SEVOFLURANE 0,5 MAC
+ oxygen/air
14
Oxygen/air
PTCA+stenting
Endpoint primario:
TnI postprocedurale
SEVOFLURANE IN STENTING PROCEDURES: A
RANDOMIZED CONTROLLED STUDY.
RESULTS
SEVOFLURANE
PLACEBO
TnI, median (25°-75° percentile)
TnI, median (25°-75° percentile)
vs
0.15 (0-4.73) ng/dl
0.14 (0-0.87) ng/dl
P = 0,4
Landoni et al. JCVA 2008
Take home message
RCTs should confirm the promising results of
volatile anesthetics in noncardiac surgery
Cardiac Troponin I could be an excellent
intermediate (surrogate?) outcome in cardiac
and non-cardiac high risk surgical patients
Cardioprotection & anaesthesia
Epidural analgesia
CLINICAL IMPLICATIONS AND
RISKS
The risk of epidural haematoma or other serious
complications ( before systemic heparitation) is 1:4500
Ruppen W et al, BMC Anesthesiol. 2006;6:10
No epidural haematoma has ever been described in a
randomized setting
Two case reports have been recently published
Sharma S et al, J Cardiothorac Vasc Anesth. 2004;18:759762
Rosen DA et al, Anesth Analg 2004;98:966-969
Epidural analgesia
Our response to the issues:
A meta-analysis of
33 trials randomized
2366 patients ( 1231 receiving general
anaesthesia and 1135 receiving
epidural anaesthesia)
Epidural analgesia
Results 1
EPIDURAL ANESTHESIA REDUCES
THE RISK OF PERIOPERATIVE
MYOCARDIAL INFARCTION
15/987 ( 1.5%) vs 30/1109 (2.7%)
OR= 0.53 (0.29-0.97)
P for effect = 0.04
P for heterogeneity = 0.56
Number to treat (NNT) = 84
Epidural analgesia
Results 2
EPIDURAL ANESTHESIA REDUCES
THE RISK OF ACUTE RENAL FAILURE
8/426 ( 1.9%) vs 21/440 (4.8%)
OR= 0.43
P for effect = 0.03
P for heterogeneity = 0.8
Number to treat (NNT) = 35
Epidural analgesia
Results 3
EPIDURAL ANESTHESIA REDUCES THE
TIME OF MECHANICAL VENTILATION
P for effect < 0.001
P for heterogeneity <0.001
Epidural analgesia
Results 4
MORTALITY
8/975 ( 0.8%) vs 12/1071 (1.1%)
OR = 0.69
P for effect = 0.4
P for heterogeneity = 0.4
Epidural analgesia
Conclusions
THIS IS THE FIRST TIME THAT
LOCOREGIONAL ANAESTHESIA IS
SHOWN TO HAVE AN IMPACT ON
CLINICALLY RELEVANT ENDPOINTS
FOLLOWING CARDIAC SURGERY
This analysis suggests that epidural analgesia
reduces perioperative myocardial infarction in
low risk patients undergoing cardiac surgery
While awaiting the results of large randomized
controlled studies in high risk patients
NT-proBNP in the 46 patients with epidural anaesthesia
(median, interquartile and range values in a logarithmic
scale) compared to the 46 patients who received standard
general anaesthesia
postoperative NT-proBNP values, pg/ml
100000
10000
87584
12713
3687
1846
1000
1135
430
11377
5005
2220
718
100
10
Epidural Group
General Anesthesia Group
β-blockers and
Non-cardiac surgery
Pro
 β blockers “recommended”
Pro
Cons
β-blockers and
Non-cardiac surgery
Cons: POISE trial
Pro
Cons
β-blockers and
Non-cardiac surgery
CONS..
Perioperative βblock was associated to increased mortality following
stroke
β-blockers and
Cardiac surgery
“Interventions for preventing post-operative
atrial fibrillation in patients undergoing heart
surgery”
E Crystal, MS Garfinkle, SS Connolly, TT Ginger, K Sleik, SS Yusuf
Cochrane Database of Systematic Reviews 2004 in Issue 4, 2004
..the lack of evidence for a
possible negative inotropic
effect has limited the use of
β block in cardiac surgery.
β-blockers:
Our reviews on esmolol
RIDUZIONE ISCHEMIA
Ischemia 5/55
(9%)
12/ 51
(23%)
0.01
β-blockers:
Our reviews on esmolol
ESMOLOLO IN NON CARDIOCHIRURGIA
•
Non riportata mortalità ed infarto nei
due gruppi (34 studi, 1739 pazienti)
Esmololo
Morte
Infarto
Controllo
P value
β-blockers:
Our reviews on esmolol
ESMOLOL IN CARDIAC SURGERY.
A META-ANALYSIS OF
RANDOMISED CONTROLLED
STUDIES
JCVA 2009, IN PRESS
β-blockers:
Our reviews on esmolol
▪
▪
▪
▪
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
β-blockers:
Our reviews on esmolol
 Non differenze per mortalità ed infarto
β-blockers:
Our reviews on esmolol
RIDUZIONE ISCHEMIA
Ischemia
15/122 (12%)
36/140 (27%)
0.009
β-blockers:
Our reviews on esmolol
RIDUZIONE INOTROPI
Inotropi
29/153
(18%)
48/146
(32%)
0.002
ESMOLOLO IN CEC
Studio randomizzato
200 pazienti (100 esmololo-100 placebo)
DTD>60%, FE< 50%
Bolo esmololo in CEC (circa 3mg/kg
durante cardioplegia)
Incidenza di FV in uscita CEC
Valutazione danno miocardico, degenza
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
“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
3
10
3
200
1.000
150



ESMOLOL
LEVOSIMENDAN
VALVOLE PERCUTANEE
[email protected]
www.itacta.org



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 ([email protected])
For these and further slides on these
topics please feel free to visit the
metcardio.org website:
http://www.metcardio.org/slides.html