Conclusions
In the present study, both types of cardioplegia were similar in mortality and major postoperative complications. However, DNC was associated with significantly shorter CPB and aortic cross clamp times. Importantly, DNC was also independently associated with lower levels of postoperative Troponin release which may indicate less myocardial injury. Moreover, the duration of inotropic support and ICU stay were significantly lower in the DNC group (Graphical summary is depicted inFigure 2 ).
DNC seems to reduce postoperative troponin release which may indicates less myocardial damage. This is perhaps related to one or more components of the solution. The DNC has an electrolyte composition that mimics extracellular fluids with addition of potassium chloride, sodium bicarbonate, mannitol, magnesium sulphate and lidocaine.1 Lidocaine act as a sodium channel blocker and magnesium act as a calcium competing agent which results in reduction of intracellular calcium level. As such, myocardial excitability, cellular metabolism, and energy consumption are reduced.2,16 This is one potential explanation for the extended period of myocardial protection with the DNC and perhaps the reduced myocardial injury as indicated by significantly lower Troponin leak in the present study which was independent of aortic cross clamp time.
Additionally, DNC may have a better distribution throughout the coronary bed due to the vasodilatory effect of Lidocaine.17This may provide more myocardial preservation and lessen myocyte injury. Furthermore, the shorter cross clamp time with DNC (p < .0001) is potentially another factor that may have contributed to lower postoperative troponin levels in the DNC group. Indeed, Erkut et al. found a direct and linear relationship between aortic cross clamp duration and postoperative Troponin levels in patients undergoing isolated CABG.18
Nonetheless, the lower level of postoperative troponin in our study was independent of the aortic cross clamp time. In addition, since all procedures were performed by a single surgeon, the potential confounding effect of differences in surgical and myocardial protection techniques is likely minimized. This include factors such as the degree of systemic hypothermia, use of topical ice, cardioplegia route, coronary surgery techniques among others which were similar between the groups in the present study. Therefore, the observed advantage of lower Troponin release with DNC in the present study is perhaps related to one or more components of the DNC solution itself.
The findings from our study, which included a wide range of simple and complex, low and high risk adult cardiac surgery procedures, are consistent with a recent randomized controlled trial (RCT) that included primarily low risk patients with first-time coronary artery bypass grafting and/or first-time single valve procedures. In this RCT, Ad and associates found several advantages with use of DNC which has led them to prematurely end the study after the data safety interim analyses. They found a higher return to spontaneous rhythm (97.7% vs 81.6%; P = .023) and fewer patients required inotropic support (65.1% vs 84.2%; P = .050), with the use of DNC. They also found a trend of lower Troponin levels with DNC which did not reach a statistical significance (P= .04). In their study, an alpha level of P < .001 was determined to be required for statistical significance because of the effect of early ending of study on alpha level.12
In another RCT which also included relatively low risk patients, Sanerta and coauthors randomized 150 patients who underwent isolated aortic valve replacement to DNC or cold blood cardioplegia. They also found a trend of lower Troponin values in the DNC that did not reach a statistical significance. Their study however was not powered to detect such a difference.13
Similarly, safety and potential advantages of DNC in adult cardiac surgery has been reported in several observational studies.5-11 In a large systematic review and meta-analysis included more than 2000 patients (mostly isolated CABG and single valve procedures), An et al found no difference between DNC and BC in mortality or major morbidity. However, DNC reduced cardioplegia volume requirements (P < 0.001), aortic cross-clamp (P < 0.001), and CPB times (P = 0.03). Likewise, and similar to our findings, DNC was associated with reduced Troponin release (P = 0.001).19
In contrast to aforementioned studies that included mostly low risk and relatively simple adult cardiac surgery procedures. Reports on use of DNC for more complex procedures have been limited.14,15 deLenoir and associates20 compared DNC to blood cardioplegia in 283 patients undergoing complex aortic root procedures. Similar to our findings and findings of others, aortic cross-clamp and CPB times were shorter with DNC (P=0.006). Interestingly, in contrast to findings by us and others, they found a non-significant trend toward higher troponin T levels with DNC (P=0.07) and in patients with myocardial ischemia longer than 180 minutes, median CK-MB was higher in DNC group (75.1 (59.3-300) μg/L than in BCS 60.5 (16.5-116) μg/L (P=0.01). In view of findings by deLenoir and colleagues, we performed a post-hoc sub-group analyses to examine the trend in postoperative Troponin T levels in patients with ischemia time longer than 180 minutes (n= 32) and we found a trend of lower peak Troponin T level in the DNC group that did not reach a statistical significance with the limited sample size (1.5 ± .8 ng/ml vs. 1.8 ± .7 ng/ml, P = 0.2).
Similar to our findings, Hamad and associates 15compared DNC to blood cardioplegia in patients undergoing combined CABG and aortic valve replacement and found that postoperative creatine kinase, MB isotype (P = 0.011) and troponin T levels \sout(P = 0.028) were significantly lower in the DNC group compared to BC. Additionally, our findings regarding lower Troponin T level is in line with findings from a recent important meta-analysis by Gambardella and associates.21
In conclusion, DNC was associated with significantly shorter CPB and cross clamp time, significantly lower post-operative troponin release and shorter duration of inotropic support and ICU length of stay. These benefits were observed for all categories of adult cardiac surgery including high risk procedures.