Rational Study Design is Important for Assessing Myocardial Protection of Anesthetics.

Abstract

To the Editor: In a single-center, prospective randomized clinical study including 122 elderly patients undergoing the carotid endarterectomy (CEA), Wang et al.[1] showed that compared with propofol-based total intravenous anesthesia, low-dose sevoflurane inhalation along with propofol reduced the incidence of postoperative myocardial injury. Given the postoperative myocardial injury is a common cardiovascular adverse event and has been shown as an independent predictor of increased short-term mortality after noncardiac surgery, their findings have potential implications. We congratulate the authors for conducting this clinically useful research, but would like to ask some questions about their methodology. First, the authors stated that patients were excluded if the fasting blood glucose was >7.0 mmol/L. However, the two study groups included 32 patients with diabetes mellitus. We would like to know what diagnostic standards of diabetes mellitus were used in this study. Second, this study did not include perioperative hemoglobin levels of the patients. It has been shown that in patients undergoing vascular surgery, preoperative hemoglobin levels, postoperative hemoglobin levels, and intraoperative hemoglobin decreases are all related to an increased risk of 30-day postoperative cardiovascular adverse events and mortality, especially for postoperative hemoglobin levels.[2] Third, the bispectral index (BIS) was used for monitoring of anesthetic levels and was maintained at a large range between 40 and 60 throughout the surgery. The authors did not specify whether the BIS values at all observed points were comparable between groups. This is an important prerequisite to rightly compare intraoperative consumptions of anesthetic and opioid drugs between groups. We noted that in this study, total dosages of fentanyl and remifentanil used in the two groups are comparable. Because sevoflurane has intrinsic analgesic property, whereas, propofol does not; it is difficult to homogenize anesthetic levels between groups, especially for the analgesic component. This may constitute a bias on the homogeneity between groups. Furthermore, only 0.8% end-tidal sevoflurane (about 0.5 minimum alveolar concentration [MAC]) was added to propofol-based total intravenous anesthesia in the treatment group. It has been reported that only when concentrations of sevoflurane are 1 MAC or more, pharmacological preconditioning by sevoflurane can produce a significant protection against myocardial ischemia-reperfusion injury in the rat heart in vivo.[3] Thus, we would argue that decrease incidence of postoperative myocardial injury in the treatment group may only be attributable to the improved anesthetic level, rather than the myocardial protection provided by sevoflurane. Fourth, comparing means of intraoperative heart rate and mean arterial pressure between groups are barely meaningful. The authors should provide and compare the occurrence of intraoperative hemodynamic disorders in the two groups. In the patients undergoing noncardiac surgery, intraoperative hypotension, tachycardia, and hypertension have been associated independently with postoperative myocardial injury and adverse outcomes.[4,5] In fact, even short duration of an intraoperative mean arterial pressure <55 mmHg (1 mmHg = 0.133 KPa) can result in postoperative myocardial injury, with an independent graded relationship between duration of intraoperative hypotension and postoperative myocardial injury.[6] Finally, it is somewhat surprising about the results of this study that incidence of postoperative myocardial injury is significantly higher in the treatment group than in the control group, but postoperative cardiovascular adverse events are not significantly different between groups. Besides a small sample size may not exclude a high-risk of α statistical error, a 3-day postoperative follow-up period also was too short to assess the clinically important variables, such as the duration of hospital stay, intensive care unit admission, medical costs, and in-hospital mortality, etc. Thus, an important question that remains unanswered in this study is whether the favorable effect of low-dose sevoflurane inhalation along with propofol on myocardial injury following CEA can be translated to clinical benefit. To address this issue, we believe that the large-scale clinical trials are still required, and these new studies should have enough power for clinically important endpoints, especially for postoperative cardiovascular adverse events and mortality.