Sevoflurane and cardioprotection
Messina, Italy
* E-mail: lsiracusano{at}unime.it
Editor—We read with interest the study by Piriou and colleagues1 who observed limited cardioprotection after 1 MAC sevoflurane in humans undergoing cardiopulmonary bypass (CPB). Julier2 obtained similar results by a higher concentration of sevoflurane (2 MAC) given 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 However, a protective effect of sevoflurane inhalation has been 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 were observed in the group treated with sevoflurane throughout operation and the highest in the propofol group. Sevoflurane throughout the operative procedure showed a 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 shorter (31±15 min compared with 53 and 54 min in the two groups studied by Piriou and 60±24 min and 66±22 min in Julier's study). There was, however, 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 ischaemia–reperfusion injury and troponin I release,5 it could be possible that the lack of cardioprotection in the studies by Piriou and Julier was determined by a more prolonged mean cross-clamp time. The absence of PKC induction in the study by Piriou could be linked to the lower dose of sevoflurane used compared with that used in the study by Julier. Cardioprotection by continuous administration of sevoflurane, as stated by Piriou, may be responsible for the superior protection observed by De Hert, supported by the haemodynamic effects of volatile anaesthetics and, perhaps (De Hert did not study PKC translocation) also by preconditioning, whose induction could be dose and time dependent.
Lyon, France
* E-mail: piriou{at}univ-lyon1.fr
Editor—We wish to thank Drs Siracusano and Girasole for their interest in our study. As you highlighted in your letter, Julier and colleagues2 found similar results. The common point of the studies1 2 was that they were multi-centre studies, in contrast to studies showing a protective effect. From our results, we cannot rule out that volatile agents exert a protective effect by preconditioning, as shown by animal experimental data,6 in selected patients. However, in experimental studies, all variables can be carefully controlled. It is not the case in clinical studies, where many factors might interfere, for example, surgical skills, patient anatomy, evolution of the coronary disease, duration of aortic cross-clamping, concomitant treatment, cardioprotective strategy, and CPB. By performing multi-centre studies, we increase the number of confounding factors, which is one explanation of our results1 and those of Julier and colleagues.2 Myocardial protection is multimodal and the ‘magic bullet’ has still not been discovered, with cardioplegia being the major cardioprotective factor. As in non-cardiac surgery, to improve the chance of showing a cardioprotective effect, we have to select carefully the population of patients who will benefit the most from the protective effect. By selecting a very high-risk population of patients, Poldermans and colleagues7 found a protective effect for beta-blockers, although three recent studies8–10 which included more, but less selected patients (i.e. lower risk patients), showed no effect. We think that in cardiac surgery, this may apply; cardioplegia is efficacious in most 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 have a myocardial infarction, and as there is no harm in using volatile anaesthetics for all patients, we believe that although our study, and the Julier's one, did not show significant results, we have to consider the systematic use of volatile anaesthetics for all coronary surgery. We do not have a clear explanation for the conflicting results of PKC activation, and, as you hypothesize, these results could be linked to the sevoflurane administration protocol (dose, duration, sequences, and time of administration). Further clinical studies are needed to clarify this point.
References
1 Piriou V, Mantz J, Goldfarb G, et al. Sevoflurane preconditioning at 1 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.[CrossRef][Web of Science][Medline]
3 Siracusano L, Girasole V, Alvaro S, et al. Myocardial preconditioning and cardioprotection by volatile anaesthetics. J Cardiovascular Med (2006) 2:86–95.
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.[CrossRef][Web of Science][Medline]
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. Clin Chem (2004) 50:1560–7.
6 Piriou V, Chiari P, Lhuillier F, et al. Pharmacological preconditioning: comparison of desflurane, sevoflurane, isoflurane and halothane in rabbit myocardium. Br J Anaesth (2002) 89:486–91.
7 Poldermans D, Boersma E, Bax JJ, et al. 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.
8 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.[CrossRef][Web of Science][Medline]
9 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.[CrossRef][Web of Science][Medline]
10 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.[CrossRef][Web of Science][Medline]
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