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reply to luca siracusano, viviana girasole (26 October 2007)
- PIRIOU Vincent, MANTZ Jean (20 November 2007)
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sevoflurane and cardioprotection
- luca siracusano, viviana girasole (26 October 2007)
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PIRIOU Vincent , MANTZ Jean
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Dear Dr Siracusano, Thank you very much for your interest to our study. As you highlighted in your letter, Julier et al (1) found similar results as us. The common point between both studies (1,2) was that they were multicenter studies, conversely to other studies showing a protective effect. From the results of our study, we can not rule out that volatile agents exert a protective effect by preconditioning, as shown by animal experimental data (3), in selected patients. However, in experimental studies, all parameters are carefully controlled. It is not the case in clinical studies, in which so many factors might interfere, the major one been the surgeon skill, others are anatomy of the patients, evolution of the coronary disease, duration of aortic cross clamping, concomitant treatment, cardioprotective strategy, cardiopulmonary bypass… By performing such multicenter studies, we increase the number of confounding factors, which is one of the explanation of our results (2) and those of Julier et al (1). Myocardial protection is multimodal, the magic bullet being still not discovered, cardioplegia being the major cardioprotective factor. As in non cardiac surgery, to improve the chance to show a cardioprotective effect, we have to select carefully the population of patients who will benefit the most of the protective effect. By selecting a very high risk population of patients, Poldermans et al showed a protective effect of beta blocker (4), although all the 3 recent studies (5,6,7), by including more, but less selected patients (lower risk patients) showed no effect. We think that in cardiac surgery, the same reflection can apply, cardioplegia is highly efficient in most of the patients, but additional cardioprotection, such as this one afforded by volatile anaesthetics, is needed for high risk patients. As it is very difficult to predict a priori which patients will present a myocardial infarction, and as there is no arm to use systematically volatile anaesthetics for all patients, we believe that, although our study, and the Julier’s one, did not show significant results, that we have to consider the systematic use of volatile anaesthetics for all coronary surgery. For the conflicting results of PKc activation, we do not have a clear explanation, and, as you hypothesise, these results could be linked to the sevoflurane administration protocol (dose, duration, sequences, time of administration…); further clinical studies are needed to clarify this point. Vincent PIRIOU, Jean MAZNTZ 1 Julier K, da Silva R, Garcia C, Bestmann L, Frascarolo P, Zollinger A, Chassot PG, Schmid ER, Turina MI, von Segesser LK, Pasch T, Spahn DR, Zaugg M. Preconditioning by sevoflurane decreases biochemical markers for myocardial and renal dysfunction in coronary artery bypass graft surgery: a double-blinded, placebo-controlled, multicenter study. Anesthesiology. 2003;98:1315-27. 2 Piriou V, Mantz J, Goldfarb G, Kitakaze M, Chiari P, Paquin S, Cornu C, Lecharny JB, Aussage P, Vicaut E, Pons A, Lehot JJ. Sevoflurane preconditioning at 1 MAC only provides limited protection in patients undergoing coronary artery bypass surgery: a randomized bi-centre trial. Br J Anaesth. 2007;99:624-31. 3 Piriou V, Chiari P, Lhuillier F, Bastien O, Loufoua J, Raisky O, David JS, Ovize M, Lehot JJ. Pharmacological preconditioning: comparison of desflurane, sevoflurane, isoflurane and halothane in rabbit myocardium. Br J Anaesth. 2002;89:486-91 4 Poldermans D, Boersma E, Bax JJ, Thomson IR, van de Ven LL, Blankensteijn JD, Baars HF, Yo TI, Trocino G, Vigna C, Roelandt JR, van Urk H. The effect of bisoprolol on perioperative mortality and myocardial infarction in high-risk patients undergoing vascular surgery. Dutch Echocardiographic Cardiac Risk Evaluation Applying Stress Echocardiography Study Group. N Engl J Med 1999; 341: 1789-94 5 Juul AB, Wetterslev J, Kofoed-Enevoldsen A, Callesen T, Jensen G, Gluud C. The Diabetic Postoperative Mortality and Morbidity (DIPOM) trial: rationale and design of a multicenter, randomized, placebo-controlled, clinical trial of metoprolol for patients with diabetes mellitus who are undergoing major noncardiac surgery. Am Heart J 2004; 147: 677-83 6 Yang H, Raymer K, Butler R, Parlow J, Roberts R. The effects of perioperative beta-blockade: results of the Metoprolol after Vascular Surgery (MaVS) study, a randomized controlled trial. Am Heart J 2006; 152: 983-90 7 Brady AR, Gibbs JS, Greenhalgh RM, Powell JT, Sydes MR. Perioperative beta-blockade (POBBLE) for patients undergoing infrarenal vascular surgery : results of a randomized double-blind controlled trial. J Vasc Surg 2005; 41: 602-9 Conflict of Interest:None declared |
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luca siracusano messina university, viviana girasole
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Sir I read with interest the study by Piriou el al (1) who observed a limited cardioprotection determined by inhalation of 1 MAC sevoflurane in humans undergoing CPB. Similar results have been obtained by Julier et al (2) by a higher concentration of sevoflurane ( 2 MAC) administrated for 10 min through a vaporizer integrated into the CPB machine. Julier but not Piriou, observed PKC translocation in the myocardium, an event related to the protection conferred by preconditioning (3). A protective effect of sevoflurane inhalation, has been, on the contrary, observed by De Hert’s group in a series of studies, in the last of which (4), different protocols were used, characterized by administration of propofol only throughout the operative period, sevoflurane only before CPB, sevoflurane only after completion of the coronary anastomoses, and sevoflurane throughout. The lowest Troponin I values have been observed in the group treated by administration of sevoflurane throughout operation, the highest in the propofol throughout group: the sevoflurane administration throughout operative procedure showed therefore a sensible cardioprotective effect. Another substantial difference could be observed between the group of patients treated by De Hert and the ones treated by Piriou and Julier: in the study group of the former the mean aortic cross-clamp time was sensibly shorter (31±15 min), whilst it was 53 and 54 min in the two groups studied by Piriou and the cross-clamp time was 60±24 min in the placebo group and 66±22 min in the sevoflurane group in the Julier’s study ; there was, on the contrary, no significant difference in the mean CPB time. Since it is well known that the cross-clamp time is related to the extent of the ischemia-reperfusion injury and to the troponin I release (5), it could be possible that the lack of cardioprotection in the study by Piriou and Juriel was determined by a more prolonged mean cross-clamp time. The absence of PKC induction in the study by Piriou instead could be linked to the lower dose of sevoflurane used compared to that used in the study by Julier. The cardioprotection by continous administration of sevoflurane, as states Piriou, may be responsible for the superior protection observed by De Hert, justified, by the hemodynamic effects of volatile anesthetics and, perhaps ( De Hert did not study PKC translocation ) , also by preconditioning, whose induction could be dose and time dependent. Luca Siracusano, Viviana Girasole Department of Neuroscience, Psychiatric and Anesthesiological Sciences, University of Messina, School of Medicine. Messina, Italy. e-mail: lsiracusano@unime.it References 1)Piriou V, Mantz J, Goldfarb G, et al. Sevoflurane preconditioning at1 MAC only provides limited protection in patients undergoing coronary artery bypass surgery: a randomized bicentre trial. Br J Anaesth 2007; 99: 624–31. 2)Julier K, da Silva R, Garcia C, et al. Preconditioning by sevoflurane decreases biochemical markers for myocardial and renal dysfunction in coronary artery bypass graft surgery: a double-blinded, placebo- controlled, multicenter study. Anesthesiology 2003; 98: 1315–27 3)Siracusano L, Girasole V, Alvaro S et al: Myocardial preconditioning and cardioprotection by volatile anaesthetics. Journal of Cardiovascular Medicine 1;2:86-95,2006. 4) De Hert SG, Van der Linden PJ, Cromheecke S, et al.Cardioprotective properties of sevoflurane in patients undergoing coronary surgery with cardiopulmonary bypass are related to the modalities of its administration. Anesthesiology 2004; 101: 299–310 5)Lehrke S, Steen H, Sievers HH et al: Cardiac Troponin T for Prediction of Short- and Long-Term Morbidity and Mortality after Elective Open Heart Surgery. Clinical Chemistry 2004 50;9:1560–1567. Conflict of Interest:None declared |
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