Sevoflurane and organ protection Chatchai Prechawai Department of Anesthesiology Faculty of Medicine Prince of songkla University Perioperative myocardial infarction (PMI) is associated with mortality rates of up to 40% Lee Th. Circulation 1999; 100: 1043-9.
Poldermans D. N Engl J Med 1999;341: 1789-94. Non fatal PMI increases the risk of both cardiovascular death and a further non-fatal myocardial infarction in the first 6 months after major non-cardiac surgery Mangano DT. JAMA 1992; 268: 233-9. Therapeutic strategies
Infraction Acute occlusion and cell death Ischaemic Precondit ioning
ISCHA ISCHA EMIA EMIA Chronic ischaemia Hibernati ng
Myocardi um Spectrum of myocardial ischemia Shot, controlled ischaemic episodes
with intervenin g reperfusio Prolonged, n acute ischaemic event Stunned
followed Myocardiu by reperfusion m Ischemic preconditioning
Brief episodes of ischemia in the heart, occurring before a subsequent longer interruption of blood flow, provides protection against dysfunction and necrosis 4 cycles of 5-min left circumflex coronary artery occlusions, before a 40-min occlusion, reduced myocardial infarction by 75%
ss Adenosin e Bradykini n Norepine phrine Effect Effect
Nitric oxide ors ors KATP channels HSP AOE Signal
Signal Amplifi Amplifi cation cation Gprotein s PKC PKC= protein kinase C
HSP= heat stress proteins AOE= antioxidant enzymes KATP channels= ATP-dependent K channels Hyperpola rization Ca2+ lnflux Myocardial Energy
Consumpti on Nucl eus K + AP
duration P K C AOE P K
C HSP DAG+ ITP A1 PKC= protein kinase C
Ade= adenosine Ad HSP= heat stress Br= Bradykinin e proteins Ne= norepinephrine AOE= antioxidant PLC= phospholipase C enzymes
DAG= diacetylglycerol A1= AdenosineITP= inositol triphosphate G Prote B in 1 2 Br
N e PL C Ischemic preconditioning Ischemic preconditioning in other organs Brain Lung
Liver Kidney Small intestine Dirnagl U, Trends Neurosci 2003; 26: 248-54. Koti RS, Dig Surg 2003; 20: 383-96. Mc Laren AJ, Transpl Int 2003: 16: 701-8. Kosieradzki M, Surgery 2003; 133: 81-90. Head BP, Curr Opin Anaesthesiol 2007; 20: 395-99. Clarkson AN. Life Sci 2007; 80: 1157-75. Kitano H, J Cereb Blood Flow Me tab 2007; 27: 1108-28.
Lee TH, Anesthesiology 2004; 101: 1313-24. Bedirli N, Anesth Analg 2008; 106: 830-7. Sevoflurane and cardioprotection Volatile and IV anesthetics that effect ATP channels Isoflurane Sevoflurane Desflurane
Morphine Fentanyl K Zaugg M, et al. Br J Anaesth 2003; 91: 551-65. Zaugg M, et al. Br J Anaesth 2003; 91: 566-76. Sevoflurane and cardioprotection
Sevoflurane but not propofol preserved LV function after CPB with less evidence of myocardial damage in the first 36 hr postoperatively. Suggest a cardioprotective effect of sevoflurane during coronary artery surgery De Hert SG. Anesthesiology 2002; 97: 42-9 Also in high-risk coronary patients De Hert SG. Anesthesiology 2003; 99: 314-23.
De Hert SG. Anesthesiology 2002; 97: 42-9 De Hert SG. Anesthesiology 2003; 99: 314-23. Sevoflurane and cardioprotection In patients undergoing CABG surgery with CPB, the cardioprotective effects of sevoflurane were clinically most
apparent when it was administered throughout the operation De Hert SG, et al. Anesthesiology 2004; 101: 299-310. De Hert SG, et al. Anesthesiology 2004; 101: 299-310. De Hert SG, et al. Anesthesiology 2004; 101: 299-310. Sevoflurane and
cardioprotection Patients receiving sevoflurane for offpump coronary artery surgery had less myocardial injury during the first 24 postoperative hours then patient receiving propofol. Conzen PF. Anesthesiology 2003;99: 826-33. Sevoflurane group Propofol group
Conzen PF. Anesthesiology 2003;99: 826-33. Sevoflurane and cardioprotection Sevoflurane suppressed the production of IL-6 and IL-8, but not IL-10 and IL-1ra. Changes in the balance between pro- and anti-inflammatory cytokines may be one of the most important mechanisms of
myocardial protection caused by sevoflurane Kawamura T. J Cardiothorac Vasc Anesth 2006; 20: 503-8. Sevoflurane and cardioprotection Sevoflurane decreases the inflammatory response after CPB, as measured by the release of IL-6, CD11b/CD18, and TNF-. Myocardial function after CPB, as assessed by
RWMA and LVSWI, was also improved with sevoflurane. Nader DN. J Cardiothorac Vasc Anesth 2004; 18: 269-7. RWMA = regional wall motion abnormality LVSWI=left ventricular stroke work index Period A IV anesthetics Period B volatile anesthetics (sevoflurane 0.5-2%) Van der Linden PJ, Anesthesiology 2003; 99: 516-7.
Period A IV anesthetics Period B volatile anesthetics (sevoflurane 0.5-2%) Van der Linden PJ, Anesthesiology 2003; 99: 516-7. Anesthetic preconditioning 22 studies, involving 1,922 patients Volatiles anesthetics were associated with significant reductions of MI (2.4% vs 5.1%) and mortality (0.4% vs 1.6%)
Landoni G. J Cardiothorac Vasc Anesth 2007; 21: 502-11. Nucleus of PKC Lipofuscin pigment Percentages of PKC
Translocation of PKC to cardiomyocytes in CABG patients right atrial tissues samples Julier K, et al. Anesthesiology 2003; 98: 1315-27. Troponin T brain natriuretic peptide: a sensitive biochemical marker of myocardial contractile dysfunction Creatinine kinase
Julier K, et al. Anesthesiology 2003; 98: 1315-27. Pooled estimates risk for MI Landoni G. J Cardiothorac Vasc Anesth 2007; 21: 502-11. Pooled estimates of 30-day postoperative mortality Landoni G. J Cardiothorac Vasc Anesth 2007; 21: 502-11. Anesthetic
preconditioning Sevoflurane has cardioprotective effects that result in decreased morbidity and mortality. Choice of anesthetic regimen based on administration of haloganated anesthetics is associated with a better outcome after cardiac surgery Kaplan-Meier curves for adverse cardiac events
during 1 yr of follow up after sevoflurane and placebo preconditioning in 72 pts undergo CABG surgery Garcia C. Br J Anaesth 2005; 94: 159-65. Sevoflurane and neuroprotection Transient ischemic attack can induce ischemic preconditioning within the brain Wegener S, et al. Stroke 2004; 35: 616-21.
CNS has been highlighted as being the most vulnerable organ system in the body to an ischemic insult. A brief disruption (5 min) to CBF has been shown to cause neuronal injury, while cardiomyocytes and kidney cells require 20-40 min of ischemia to induce cellular damage. Lee JM, et al. J Clin Invest 2000; 106: 723-31.
Sevoflurane and neuroprotection Clear evidence exists that demonstrates exposing adult rats to volatile anesthetics can trigger both acute and late phases of ischemic tolerance within the brain Kapinya K, et al. brain Res 2002; 872: 282-93. Zheng S, Zuo Z. Neuroscience 2003;118: 99-106. Zheng S , Zuo Z. Mol Pharm 2004; 65: 1172-80.
Control No cardiac arrest Early sevoflurane (15 min) before cardiac arrest Cardiac arrest Late sevoflurane (24 hr)
before cardiac arrest Sevoflurane- induced preconditioning protects against cerebral ischemic neuronal damage in rats Payne RS. Brain Res 2005; 1034: 147-52. Neuronal cell damage Pape, M. et al. Anesth Analg 2006;103:173-179
Double immunostaining of activated caspase-3 and NeuN (key proteins of apoptosis) Pape, M. et al. Anesth Analg 2006;103:173-179 A high, but clinically usable, concentration of sevoflurane increases the time during hypoxia until the postsynaptic evoked response is blocked and improves recovery of the response after 5 min of hypoxia
Matei G. J Neurosurg Anesth 2002; 14: 293-8. Sevoflurane and kidney protection Sevoflurane has direct antiinflammatory and antinecrotic effects in vitro in a renal cell type particularly sensitive to injury following IR injury
Lee TH, Am J Physiol Renal Physiol 2006; 291: F67-F78. Biomarkers for perioperative renal function at various time points in CABG surgery Postoperative plasma cystatin C conc. Increased significantly less in sevoflurane-preconditioned patients Julier K, et al. Anesthesiology 2003; 98: 1315-27.
Sevoflurane and liver protection Significant decrease in serum alanine and aspartate aminotransferase (ALT, AST) levels Hepatic tissue blood flow (HTBF) was remarkably better in sevoflurane group Tumor necrosis factor- (TNF-) and IL-1 values were lowest in sevoflurane group Bedirli N, et al. Anesth Analg 2008; 106:830-7.
Bedirli N, et al. Anesth Analg 2008; 106:830-7. Liver sections of rat after 4 hr reperfusion Control group Isoflurane group Sevoflurane group
Bedirli N, et al. Anesth Analg 2008; 106:830-7. Easy titration anesthetic depth Low incidence adverse airway events Exellent bronchodilation Safe use above 1 MAC Hemodynamic stability Proven beneficial cardiac profile Rapid and predictable recovery
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