1. Peri-operative cardiac protection
IRCCS Ospedale San Raffaele Milano
Università Vita-Salute San Raffaele
Peri-operative cardiac protection
Tutorial in General Anesthesia,
Milano, 28 Marzo 2009
Relatore: Dott. Giovanni Landoni

2. 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”

3. REDUCING PERIOPERATIVE MYOCARDIAL INFARCTION
EPIDURAL ANESTHESIA (non-cardiac surgery)
BETA BLOCKERS (non-cardiac surgery) ??!!
VOLATILE AGENTS (cardiac surgery)
LEVOSIMENDAN (cardiac surgery)

4. REDUCING PERIOPERATIVE MORTALITY AND MYOCARDIAL INFARCTION
VOLATILE AGENTS (cardiac surgery)
LEVOSIMENDAN (cardiac surgery)

5. REDUCING PERIOPERATIVE MORTALITY
FENOLDOPAM
PEXELIZUMAB (cardiac surgery)
DOPEXAMINE
EARLY ENTERAL NUTRITION (intestinal surgery)
INSULINE !!??
STATINS

6. Anaesthesia and Outcome
Volatile Anesthetics
Could VOLATILE anaesthetics influence outcome?
Could VOLATILE anaesthetics have non-anaesthetic properties?

7. DESFLURANE versus PROPOFOL (fentanyl-based cardiac anesthesia)

13. Troponin I after OFF-PUMP CABG

14. Troponin I after CABG (CPB)

15. Troponin I after MITRAL SURGERY

19. I Meta-analysis and/or large randomized studies
Evidence?
I Meta-analysis and/or large randomized studies
II Randomized trials
III Non-randomized prospective trials
IV Retrospective studies
V Case reports and Expert Opinion
VI Animal / Laboratories Studies

21. Volatile Anesthetics

22. 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)

23. Evidence!
Mortality

24. Mortality 4/977=0.4% v 14/872=1.6% NNT=84 RRR=(1,6-0,4)/1,6=75%
Evidence!
Mortality
4/977=0.4% v 14/872=1.6%
NNT=84
RRR=(1,6-0,4)/1,6=75%
OR: 0.31( )
P=0.02

25. Mortality
NNT=84
Treat 84 to save one

26. Myocardial infarction
Evidence!
Myocardial infarction

27. Myocardial infarction
Evidence!
Myocardial infarction
24/979=2.4% v 45/874=5.1%
NNT=37
RRR: ( )/5.1 = 53%
OR: 0.51( )
p=0.008

28. Myocardial infarction
NNT=37
Treat 37 to save one

29. PEAK CARDIAC TROPONIN I
Evidence!
PEAK CARDIAC TROPONIN I
WMD ng/dL [-3.09,-1.60], p<

30. Evidence!
INOTROPE USE IN ICU
OR [0.29, 0.76], p < 0.002

31. Mechanical ventilation
Evidence!
Mechanical ventilation
WMD hours [-0.97,-0.02], p = 0.4

32. Evidence!
ICU STAY
WMD hours [-11.47,-2.73], p < 0.001

33. Evidence!
HOSPITAL STAY
WMD days [-3.83,-0.68], p = 0.005

36. 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%

37. Conclusions: Volatile Anesthetics in cardiac surgery
Sevoflurane&Desflurane:
↓post cardiac surgery mortality
Volatile Anesthetics
Direct and indirect protection
Desflurane in CABG surgery:
↓postoperative cTnI release
↓postoperative inotropic support
↓hospitalization +/- cardiopulmonary bypass

38. Have we forgotten about noncardiac surgery?

39. A meta-analysis in noncardiac surgery
Evidence?
A meta-analysis in noncardiac surgery
6219 patients
2842 sevoflurane
609 desflurane
2768 propofol

40. A meta-analysis in noncardiac surgery
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

41. A meta-analysis in noncardiac surgery
Evidence?
A meta-analysis in noncardiac surgery
Total 79
Anesth analg 20
BJA 14
EJA 11
Acta anaesthesiol scand 8
Anaesthesia 5
J Anesth 4
Anesthesiology 3
Minerva anestesiol 2
Altri 13

42. A meta-analysis in noncardiac surgery
Evidence?
A meta-analysis in noncardiac surgery
400 authors
240 reviewers
90 editors
0 deaths
0 myocardial infarctions

43. Have we forgotten about CARDIAC MORBIDITY and MORTALITY in noncardiac surgery?

46. WHAT’S NEXT

47. 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

48. RESULTS SEVOFLURANE PLACEBO
SEVOFLURANE IN STENTING PROCEDURES: A RANDOMIZED CONTROLLED STUDY.
RESULTS
SEVOFLURANE
TnI, median (25°-75° percentile)
0.15 (0-4.73) ng/dl
PLACEBO
TnI, median (25°-75° percentile)
0.14 (0-0.87) ng/dl vs
P = 0,4
Landoni et al. JCVA 2008

49. 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

50. Cardioprotection & anaesthesia Epidural analgesia

51. CLINICAL IMPLICATIONS AND RISKS
The risk of epidural haematoma or other serious complications ( before systemic heparitation) is 1: 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:
Rosen DA et al, Anesth Analg 2004;98:

52. Our response to the issues:
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)

53. 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 ( )
P for effect = 0.04
P for heterogeneity = 0.56
Number to treat (NNT) = 84

54. 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

55. Epidural analgesia Results 3
EPIDURAL ANESTHESIA REDUCES THE TIME OF MECHANICAL VENTILATION
P for effect < 0.001
P for heterogeneity <0.001

56. 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

57. 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

59. 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

60. β-blockers and Non-cardiac surgery
Pro
β blockers “recommended”
Cons
Pro

61. β-blockers and Non-cardiac surgery
Cons: POISE trial
Pro
Cons

62. β-blockers and Non-cardiac surgery
CONS..
Perioperative βblock was associated to increased mortality following stroke

63. 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.

64. RIDUZIONE ISCHEMIA β-blockers: Our reviews on esmolol Ischemia 5/55
(9%)
12/ 51 (23%)
0.01

65. ESMOLOLO IN NON -CARDIOCHIRURGIA
β-blockers:
Our 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

66. β-blockers:
Our reviews on esmolol
ESMOLOL IN CARDIAC SURGERY. A META-ANALYSIS OF RANDOMISED CONTROLLED STUDIES JCVA 2009, IN PRESS

67. 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

68. β-blockers: Our reviews on esmolol
 Non differenze per mortalità ed infarto

69. RIDUZIONE ISCHEMIA β-blockers: Our reviews on esmolol Ischemia
15/122 (12%)
36/140 (27%)
0.009

70. RIDUZIONE INOTROPI β-blockers: Our reviews on esmolol Inotropi
29/153 (18%)
48/146 (32%)
0.002

71. 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

72. LEVOSIMENDAN VS CONTROL Mortality in cardiac surgery
Evidence!
LEVOSIMENDAN VS CONTROL Mortality in cardiac surgery
11/235=4.7% v 26/205=12.7%
P=0.007

73. LEVOSIMENDAN VS CONTROL Myocardial Infarction in cardiac surgery
Evidence!
LEVOSIMENDAN VS CONTROL Myocardial Infarction in cardiac surgery
2/183=1.1% v 9/153=5.9%
P=0.04

74. “PERCHE’ NON SIAM POPOLO PERCHE’ SIAM DIVISI”
MAMELI

75. ITACTA ONGOING RCTs TOPICS HOSPITALS PATIENTS GRANTS
VOLATILE ANESTHETICS
FENOLDOPAM
DESMOPRESSIN
ESMOLOL
LEVOSIMENDAN
VALVOLE PERCUTANEE
AIFA 2006
MINISTRY 2008
3 200
3 150

76. GRUPPI DI INTERESSE ITACTA (COORDINATI DA ANESTESISTI UNDER 40)
Gruppi esistenti ad oggi (per piu’ informazioni aperti ad iscrizioni
1. Sostituzioni valvolari percutanee
2. Monitoraggio emodinamico mini-invasivo
3. Statistica in anestesia e terapia intensiva
4. Analgesia selettiva in chirurgia toracica

77. For these and further slides on these topics please feel free to visit the metcardio.org website: