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Peri-operative cardiac Peri-operative cardiac protectionprotection
Relatore:Relatore: Dott. Giovanni LandoniDott. Giovanni Landoni Tutorial in General Anesthesia,Tutorial in General Anesthesia,
Milano, 28 Marzo 2009Milano, 28 Marzo 2009
IRCCS Ospedale San Raffaele MilanoIRCCS Ospedale San Raffaele MilanoUniversità Vita-Salute San RaffaeleUniversità Vita-Salute San Raffaele
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”
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
Could VOLATILE anaesthetics have non-anaesthetic properties?
Could VOLATILE anaesthetics influence outcome?
Volatile AnestheticsVolatile Anesthetics
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
INOTROPESin ICU
OFF-PUMP CABG
35.1%versus56.4%
*P=0.04
ON-PUMP CABG
32.0%versus41.3%
*P=0.04
MITRAL SURGERY
42.4%versus54.1%
P=0.3
NEWQ WAVES
OFF-PUMP CABG
11%versus17%
P=0.8
ON-PUMP CABG
6.7%versus18.7%
*P=0.049
MITRAL SURGERY
1.7%Versus1.6%
P=0.7
I Meta-analysis and/or large randomized studies
II Randomized trials III Non-randomized prospective trialsIV Retrospective studies V Case reports and Expert Opinion VI Animal / Laboratories Studies
Evidence?
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!
Mortality
NNT=84
Treat 84 to save one
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!
Myocardial infarction
NNT=37
Treat 37 to save one
PEAK CARDIAC TROPONIN IEvidence!
WMD -2.35 ng/dL [-3.09,-1.60], p<0.00001
INOTROPE USE IN ICU
Evidence!
OR 0.47 [0.29, 0.76], p < 0.002
Mechanical ventilationEvidence!
WMD -0.49 hours [-0.97,-0.02], p = 0.4
ICU STAYEvidence!
WMD -7.10 hours [-11.47,-2.73], p < 0.001
HOSPITAL STAYEvidence!
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 OSPEDALE SAN RAFFAELE MILANO 0,36%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: Conclusions: Volatile Anesthetics in cardiac surgeryVolatile Anesthetics in cardiac surgery
Volatile Anesthetics
Direct and indirect protection
Sevoflurane&Desflurane:Sevoflurane&Desflurane:↓post cardiac surgery mortality
Desflurane in CABG surgery:Desflurane in CABG surgery:• ↓postoperative cTnI release• ↓postoperative inotropic support• ↓hospitalization +/- cardiopulmonary bypass
Have we forgotten about noncardiac surgery?
A meta-analysis in noncardiac surgery
6219 patients
2842 sevoflurane609 desflurane
2768 propofol
Evidence?
4281 citations retrieved from database searches
3936 titles/abstracts excludedbecause 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 reports51 no TIVA group75 cardiac surgery46 retrospective25 non randomised21 paediatric12 not available
A meta-analysis in noncardiac surgery
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?
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
16
SEVOFLURANE 0,5 MAC
+ oxygen/air
14
Oxygen/air
Endpoint primario:
TnI postprocedurale
20’
PTCA+stenting
SEVOFLURANE IN STENTING PROCEDURES: A RANDOMIZED CONTROLLED STUDY.
RESULTS
SEVOFLURANETnI, median (25°-75° percentile)
0.15 (0-4.73) ng/dl
PLACEBOTnI, median (25°-75° percentile)
0.14 (0-0.87) ng/dl
P = 0,4
vs
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 analgesiaEpidural 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;18:759-762
Rosen DA et al, Anesth Analg 2004;98:966-969
Epidural analgesiaEpidural analgesia
Our response to the issues: Our response to the issues:
A meta-analysis of 33 trials randomized2366 patients ( 1231 receiving
general anaesthesia and 1135 receiving epidural anaesthesia)
Epidural analgesiaEpidural analgesiaResults 1Results 1
EPIDURAL ANESTHESIA REDUCES THE RISK OF PERIOPERATIVE
MYOCARDIAL INFARCTION15/987 ( 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 analgesiaEpidural analgesiaResults 2Results 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 analgesiaEpidural analgesiaResults 3Results 3
EPIDURAL ANESTHESIA REDUCES THE TIME OF MECHANICAL VENTILATION
P for effect < 0.001
P for heterogeneity <0.001
Epidural analgesiaEpidural analgesiaResults 4Results 4
MORTALITY
8/975 ( 0.8%) vs 12/1071 (1.1%)
OR = 0.69
P for effect = 0.4
P for heterogeneity = 0.4
THIS IS THE FIRST TIME THAT LOCOREGIONAL ANAESTHESIA IS SHOWN
TO HAVE AN IMPACT ON CLINICALLY RELEVANT ENDPOINTS FOLLOWING
CARDIAC SURGERYThis 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
Epidural analgesiaEpidural analgesiaConclusionsConclusions
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
430
12713
1135
2220
718
1846
5005
87584
3687
11377
10
100
1000
10000
100000
Epidural Group General Anesthesia Group
po
sto
per
ativ
e N
T-p
roB
NP
val
ues
, p
g/m
l
ββ-blockers-blockers and and Non-cardiac surgeryNon-cardiac surgery
ββ blockers blockers “recommended” “recommended”
ProPro
ProPro ConsCons
ββ-blockers-blockers and and Non-cardiac surgeryNon-cardiac surgery
ProPro ConsCons
Cons: POISE trial
ββ-blockers-blockers and and Non-cardiac surgeryNon-cardiac surgery
Perioperative Perioperative ββblock was associated toblock was associated to increased mortality increased mortality following following strokestroke
CONS..CONS..
““Interventions for preventing post-operative Interventions for preventing post-operative atrial fibrillation in patients undergoing heart atrial fibrillation in patients undergoing heart
surgerysurgery””
E Crystal, MS Garfinkle, SS Connolly, TT Ginger, K Sleik, SS Yusuf
Cochrane Database of Systematic Reviews 2004 in Issue 4, 2004
ββ-blockers-blockers and and Cardiac surgeryCardiac surgery
..the lack of evidence for a possible negative inotropic effect has limited the use of β block in cardiac surgery.
RIDUZIONE ISCHEMIARIDUZIONE ISCHEMIA
IschemiIschemiaa
5/555/55
(9%)(9%)12/ 51 12/ 51 (23%)(23%)
0.010.01
ββ-blockers: -blockers: Our reviews on esmololOur reviews on esmolol
ESMOLOLO IN NON -CARDIOCHIRURGIA
•• Non riportata mortalità ed infarto nei due gruppi (34 studi, 1739 pazienti)
Esmololo Controllo P value
Morte
Infarto
ββ-blockers: -blockers: Our reviews on esmololOur reviews on esmolol
ββ-blockers: -blockers: Our reviews on esmololOur reviews on esmolol
ESMOLOL IN ESMOLOL IN CARDIACCARDIAC SURGERY. SURGERY. A META-ANALYSIS OF A META-ANALYSIS OF RANDOMISED CONTROLLED RANDOMISED CONTROLLED STUDIESSTUDIES
JCVA 2009, IN PRESSJCVA 2009, IN PRESS
ββ-blockers: -blockers: Our reviews on esmololOur 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
ββ-blockers: -blockers: Our reviews on esmololOur reviews on esmolol
Non differenze per mortalità ed infarto
ββ-blockers: -blockers: Our reviews on esmololOur reviews on esmolol
RIDUZIONE ISCHEMIA
Ischemia 15/122 (12%) 36/140 (27%) 0.009
ββ-blockers: -blockers: Our reviews on esmololOur reviews on esmolol
RIDUZIONE INOTROPI
Inotropi 29/153 (18%)
48/146 (32%)
0.002
ESMOLOLO IN CEC
Studio randomizzato200 pazienti (100 esmololo-100
placebo)DTD>60%, FE< 50%Bolo esmololo in CEC (circa 3mg/kg
durante cardioplegia)Incidenza di FV in uscita CECValutazione danno miocardico,
degenza
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!
“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 these and further slides on these topics please feel free to visit the
metcardio.org website:
http://www.metcardio.org/slides.html
