European Journal of Cardiovascular Medicine

Open cardiac surgery has used cardioplegia solution since the early 1970s. The use of cardioplegia solutions has significantly improved cardiac surgery safety. The use of cardioplegia solution allows for a flaccid myocardium, a silent, bloodless operating field, and the avoidance of air emboli.^[1,2] A reperfusion injury has the potential to grossly outweigh the primary ischemic insult.^[3] Myocardial preservation for heart surgery has often been accomplished utilizing multiple dose hyperkalemic arresting solutions, delivered approxi­mately every 20 minutes during the aortic cross clamp time.^[4] Until the present day, cardioplegic arrest remains the gold standard of cardio protection and requires a potassium-rich solution sending the heart into a depolarized arrest.^[5]

The conventional procedure for treating adult cardiac surgery patients used Buckberg cardioplegic solution for many years. To stop the heart, an induction dosage is injected (diluted with patient blood in a 1:4 ratio); a maintenance solution is then given every 15 to 20 minutes.^[6] Using cardioplegia solution makes it easier to avoid air emboli, a myocardium that isn't contracting properly, and an operating field that is quiet and bloodless.^[7]

St. Thomas' II cardioplegic solution No. 2 (ST) is a popular crystalloid cardioplegia among cardiac surgeons; however, it requires frequent administration at brief intervals throughout the procedure.^[8] Dr. Pedro Del Nido and his colleagues created a cardioplegic solution in the early 1990s to meet the unique requirements of the developing myocardium in cardiac surgery procedures performed on newborns and children. During heart surgery, the procedure-now widely known as Del Nido (DN) cardioplegia-causes a depolarizing arrest. Compared to conventional 4:1 blood cardioplegia, it is more diluted (1:4, blood: crystalloid), has less Ca2+, and contains lidocaine. One potential benefit of the DN is that it can cause a prolonged period of arrest before another dose is required.

The adult cardiac community has been showing an increasing amount of interest in Del Nido solutions due to their simplicity of administration and potential to lower surgical interruption and cost. Charette et al. found that pediatric patients undergoing cross-clamp periods of at least 90 minutes received an average of 1.35 doses of Del Nido CPS, compared to 3.47 doses of modified adult CPS. According to Ginther et al., 90% of their crossclamping patients only received one dosage of Del Nido CPS. Del Nido CPS use has increased in popularity.^[4]

There are few studies comparing the cardioprotective nature of St. Thomas II solution and Del Nido solution. Hence, we propose to study the cardioprotective nature of both solutions.

AIMS AND OBJECTIVES

This study aims to examine the safety and effectiveness of DN versus ST in adult patients undergoing elective CABG (Coronary Artery Bypass Grafting). The purpose of the study is to examine the effects of St. Thomas II Solution and Del Nido (DN) cardioplegia, which has longer periods of arrest, on post-operative ejection fraction (measured on days 5 and 6). It also seeks to compare the times for CPB, aortic CC, ventilator days, and ICU (Intensive Care Unit) days.

The study was a retrospective record based analysis at the Department of Cardiothoracic and Vascular Surgery, Government Medical College Hospital, Thiruvananthapuram. The sample was taken from the case records of patients who underwent CABG in the department of cardiothoracic and vascular surgery at Government Medical College Hospital, Thiruvananthapuram, for 6 years, from January 1, 2012 to January 1, 2018. 200 cases were included by consecutive sampling and cases who underwent emergency CABG and had single vessel disease or double vessel disease were excluded. Based on the type of cardioplegia used after surgery, the patients were split into two groups: 1) intermittent ST (n = 100) and 2) DN cardioplegia (n = 100). We contrasted the two groups' postoperative changes in LVEF as well as the durations of CPB and aortic CC.

Statistical Analysis

SPSS was used for the analysis of the data. The percentage change in the ejection fraction of both groups was analyzed using the Student's t-test. Student's  t-test was used to analyze the aortic cross clamp and cardiopulmonary bypass times of both groups.

A total of 300 record cases were traced, of which 100 were excluded from the study as they did not meet the inclusion criteria. Of the 200 records, 100 were from the St. Thomas II group, and 100 were from the Del-Nido group.

The average age of patients in Del Nido group was 62.07 (SD 5.52) while that of the ST group was 63.66 (SD 5.12). The minimum age in the ST group was 40, while that in the Del Nido group was 45. The maximum age in the ST group was 72, compared to 72 in the Del Nido group.

In the ST group, 95% of patients were residents of Kerala, and the remaining 5% were from various states of India. In the DN group, 96.5% of patients were from Kerala; the rest were from other Indian states. There were 12 females in the ST group and nine in the Del Nido group.

The average ejection fraction in the ST group was 44.77 with a SD of 3.78, whereas the DN group was 44.43 with a SD of 3.85.

The average total pump time in the ST group and DN groups was 130.11 with a SD of 12.67, 120.05 (10.64) and the average aortic cross clamp time was 97.55 with a SD of 10.56. , 89.42 (9.75), respectively. The values in each group were statistically analysed using the student’s t-test and found to be statistically significant with a p-value less than 0.005.

In both the ST group and the DN group, the average number of ventilator days was 1.09. The average number of ICU days was 4.12 in the ST group, while it was 4.09 in the DN group. The values in each group were statistically analyzed using the student t-test and were found to be statistically insignificant with a p-value greater than 0.005.

In both groups, the average percentage change in ejection fraction was 5.42 with a SD of 2.19 and 8.17 with a SD of 2.91, respectively .The values in each group were statistically analyzed using the student t-test and were found to be statistically significant with a p-value less than 0.005.

The average ejection fraction in the ST group was 44.77 with a SD of 3.78, whereas the DN group was 44.43 with a SD of 3.85.

The average total pump time in the ST group and DN groups was 130.11 with a SD of 12.67, 120.05 (10.64), and the average aortic cross clamp time was 97.55 with a SD of 10.56., 89.42 (9.75), respectively. We statistically analyzed the values in each group using the Student T test and found them to be statistically significant with a p-value less than 0.005.

During open-heart surgery, cardioplegic solutions play a crucial role in shielding the heart from myocardial damage. Documentation of the DN solution's application in adult cardiac surgery is relatively recent, despite its effective use in juvenile cardiac surgery. Shorter cross clamp periods are anticipated as a result of this solution's avoidance of the necessity for repeated procedure interruptions to deliver several doses of traditional cardioplegia. This retrospective analysis compares individuals receiving elective CABG to those who received ST cardioplegia, focusing on DN cardioplegia outcomes.^[9]

The main conclusions of this analysis were shorter CC and CPB periods in the DN surgeries, which is in line with previous research on adult patients who underwent DN. This is explained by the fact that fewer doses of cardioplegia need to be given repeatedly. However, the CC and CPB periods in this study were longer than those found in other published investigations including with adult patients. Given that the facility serves as a training facility and performs longer surgeries, such as CABG with repeated grafts, we anticipated this outcome. Seventy percent of our patients in the DN group had a single dose of cardioplegia; rates in adult studies from other centers range from forty to eighty-four percent. Smigla et al.'s reported rate of 40% is lower than ours, and our study's 90-minute re-dosing approach is likely the reason for this. Reducing the frequency of doses minimizes the chance of contamination and permits the surgeon to work without interruption. DN's benefits could help to protect the heart after adult heart surgery.^[10]

Our results showed lower rates of death and acute postoperative problems when DN was used, however, the changes were not statistically significant. Nevertheless, the higher postoperative LVEF in the DN group seen in our investigation suggests that DN will provide better protection than ST and have a similar safety profile. The faster build-up of intracellular Ca2+ during myocardial ischemia mediates the early reperfusion injury during heart surgery. To deal with this high intracellular Ca2+, the heart cell uses active transport pathways that use a lot of energy. This leads to myocardial dysfunction after reperfusion. Lidocaine, a substance in the DN that stabilizes membranes, makes it more likely that Na+ channels will be blocked and lessens the chance of a Na+ window current. These are the proposed methods by which DN cardioplegia shields the heart against elevated intracellular Ca2+, in conjunction with its Mg2+ content, which functions as a Ca2+ antagonist.

A study by O'Blenes et al. said that DN cardioplegia during cardiac arrest stopped Ca2+-induced hypercontraction during early reperfusion and decreased spontaneous activity during ischemia in isolated aged rat cardiomyocytes compared to standard cardioplegia.^[11] They subsequently demonstrated a link between single-dose DN cardioplegia and improved functional recovery, reduced myocardial damage, and superior calcium management of cardiomyocytes in an environment similar to that of old hearts. These results must, however, be verified using more therapeutically applicable techniques, and their impact on long-term postoperative ventricular function needs to be investigated.

In a systematic review by Putro et al.,^[12] they studied 346 research articles on the use of CK-MB (creatine kinase) and troponin I as markers of myocardial injury. They observed that 2 studies that involved blood cardioplegia had lower levels of elevation of CK-MB and troponin I, indicating lower levels of myocardial injury. Two of the five studies found that colloids had higher levels of Ck-MB and Troponin I than blood cardioplegia. Mourad et al.^[13] suggested a higher need for inotropic support with blood cardioplegia. We noted an insignificant difference in atrial fibrillation, myocardial infarction, and mortality between both groups of cardioplegia.

Brzeska and colleagues, in their review of three different cardioplegic agents, Del Nido, CBC, and HTk, come to the equivocal conclusion that none of the cardioplegic agents have an advantage over the others in cardioprotection with regard to myocardial injury, post-operative complications, echocardiographic changes, or inotropic support.^[14]

Stoitsev, in his study, identifies that modified Del Nido cardioplegia, with a longer duration of cross-clamping time, has comparable cardioprotective effects to Kirklin cardioplegia.^[15]

In a dog mitral valve surgery animal model, the modified Del Nido group demonstrated lower cardioplegia doses and a shorter procedure time compared to the St. Thomas II cardioplegia group.^[16]

In comparison to the St. Thomas II solution, Del Nido cardioplegia helps reduce the length of cardiopulmonary bypass, the rate of defibrillation, and the length of hospital stay in both adult and pediatric cardiac surgery. A systematic evaluation of 12 trials revealed this. Adults with Del Nido cardioplegia have shorter aortic cross clamp periods without a discernible change in mortality from all causes, length of stay in an intensive care unit, or need for mechanical ventilation.^[17]

Malvindi et al., in their meta-analysis of 42 articles, found Del Nido cardioplegia to have comparable safety with blood cardioplegia in terms of early postoperative mortality and troponin levels.^[18] Tan J. et al., found in their network meta-analysis of 55 studies, that DN cardioplegia is superior to HTk and BC in lowering postoperative mortality.^[19] Zhai et al., in their network meta-analysis of 41 studies, found DN cardioplegia to have better outcomes in comparison to conventional cardioplegia.^[20] In a retrospective comparative study similar to ours, CPB time and aortic cross clamp time were lower with Del Nido cardioplegia.^[21]

During open heart surgery, cardioplegic solution plays a critical role in protecting the heart. While juvenile heart surgery successfully utilizes the DN solution, its application in adult heart surgery is still in its infancy. Shorter cross clamp periods are anticipated as a result of this solution's avoidance of the necessity for repeated procedure interruptions to deliver several doses of traditional cardioplegia. There was a statistically significant decrease in both CPB time and aortic cross clamp time in patients who had CABG surgery while using the Del Nido solution for cardioplegic arrest. There was also a significant increase in LVEF after surgery.

However, a larger cohort of subjects should be studied prospectively before introducing the Del Nido cardioplegic solution to all adult cardiac surgery patients undergoing CABG.

• Charette K, Gerrah R, Quaegebeur J, Chen J, Riley D, Mongero L, et al. Single dose myocardial protection technique utilizing del Nido cardioplegia solution during congenital heart surgery procedures. Perfusion 2012;27(2):98-103.
• Melrose DG, Dreyer B, Bentall HH, Baker JBE. Elective cardiac arrest. The Lancet 1955;266(6879):21-3.
• Habertheuer A, Kocher A, Laufer G, Andreas M, Szeto WY, Petzelbauer P, et al. Cardio protection: a review of current practice in global ischemia and future translational perspective [Internet]. BioMed Research International. 2014 [cited 2019 Jan 9]. Available from: https://www.hindawi.com/journals/bmri/2014/325725/
• Valooran GJ, Nair SK, Chandrasekharan K, Simon R, Dominic C. del Nido cardioplegia in adult cardiac surgery - scopes and concerns. Perfusion 2016;31(1):6–14.
• Habertheuer A, Kocher A, Laufer G, Andreas M, Szeto WY, Petzelbauer P, et al. Cardioprotection: a review of current practice in global ischemia and future translational perspective [Internet]. BioMed Research International. 2014 [cited 2019 Jan 9]. Available from: https://www.hindawi.com/journals/bmri/2014/325725/
• Buckberg GD. Antegrade/retrograde blood cardioplegia to ensure cardioplegic distribution: operative techniques and objectives. J Card Surg 1989;4(3):216-38.
• Stammers AH, Tesdahl EA, Mongero LB, Stasko AJ, Weinstein S. Does the type of cardioplegic technique influence hemodilution and transfusion requirements in adult patients undergoing cardiac surgery? J Extra Corpor Technol 2017;49(4):231-40.
• Donnelly AJ, Djuric M. Cardioplegia solutions. Am J Hosp Pharm 1991;48(11):2444-60.
• Ginther RM, Gorney R, Forbess JM. Use of del Nido cardioplegia solution and a low-prime recirculating cardioplegia circuit in pediatrics. J Extra Corpor Technol 2013;45(1):46-50.
• Mdaki KS, Larsen TD, Weaver LJ, Baack ML. Age related bioenergetics profiles in isolated rat cardiomyocytes using extracellular flux analyses. PLoS One 2016;11(2):e0149002.