To the Editor:—
We read with interest the article by De Hert et al. 1in which the cardioprotective properties of sevoflurane were investigated. A well-designed study by Conzen et al. ,2published in 2003, investigating off-pump procedures, came to similar conclusions. Troponin I was the marker of myocardial damage in this study. It is well established that troponin is a specific marker of myocardial injury and a risk predictor, especially in patients with acute coronary disease without ST-segment elevation.3However, there are other causes of troponin increases, such as acute pericarditis, myocarditis, renal failure, acute pulmonary emboli, sepsis, congestive heart failure, tachycardia, heavy exercise, and heterophilic antibodies.4,5Measurable troponin concentrations may also occur after procedures such as coronary angioplasty, electrophysiologic ablation, and cardioversion. Furthermore, the relevance of troponin and its correlation to the magnitude of myocardial injury after cardiac surgery has not been validated. Only in an animal model has such a correlation been established.6Although some studies, such as that of Fellahi et al. ,7have demonstrated that patients with a high concentration of troponin I have an increased risk of death postoperatively, it is not clear that the troponin concentration differences in this study correlate with clinical outcome. It is also not clear that these differences in the context of a multidrug regimen are due to sevoflurane alone. Propofol was used in all groups for induction of anesthesia and continued postoperatively, weakening the cause-and-effect relation.
Substantial efforts were made by the investigators to demonstrate the effect of sevoflurane as a function of the duration of its use. Unfortunately, sevoflurane concentrations varied between 0.5 and 2.5% (not mentioned if related to minimum alveolar concentration, vapor setting, or expiratory concentration) according to the Bispectral Index. Because other medications, temperature, ventilation, and age have effects on the Bispectral Index, a large variation in the partial pressure of sevoflurane among the subjects might have resulted, making an estimate of dose dependency impossible. In addition, as acknowledged by the investigators, troponin differences among the sevoflurane groups were not significant; therefore, a conclusion that effects of sevoflurane were most clinically apparent in the “SEVO all” group is not statistically supported because the sevoflurane groups are not different from one another.
With a half-life of 7–9 days, troponin remains in the circulation for a long time. Consequently, one would assume that when the concentrations have reached a peak, they would remain high, making the repeated sampling unnecessary and even confusing.
Troponin measurements are a sensitive and expensive marker whose utility is to establish whether myocardial injury is present. The value of multiple sampling used in this study is unclear and needs validation.
In this study, troponin concentrations may have been influenced by the extent of the surgical manipulation. Distribution of the individual surgeons among the patient groups would be valuable for the interpretation of the results. Furthermore, localization of the bypassed vessels would give useful insight into whether the procedures were comparable.2The significance of troponin increases in patients with abnormal renal function is an important and still-debated issue.8,9Although the study excluded patients with a baseline creatinine concentration of greater than 1.5 mg/dl, it is well known that renal injury can occur during cardiopulmonary bypass; no information is presented on the patients’ postoperative renal function, which, if impaired, could further cloud the meaning of troponin increases.
Another interesting question could have been answered if the study design had included a group in which sevoflurane was used only during the cardiopulmonary bypass to assess its effect on myocardium when administered only during the most traumatic phase of the operation.
In other studies, isoflurane has been shown to exert protective properties on the heart.10Isoflurane is considerably less expensive than sevoflurane. We look forward to studies including an isoflurane arm in the experimental design.
* Harvard Medical School, Brigham and Women’s Hospital, Boston, Massachusetts. email@example.com