|Year : 2022 | Volume
| Issue : 2 | Page : 97-102
Custodiol-HTK Solution Vs. Conventional Cardioplegia for Myocardial Protection During Coronary Artery Bypass Grafting Following Recent ST-Elevation Myocardial Infarction
Walaa Ahmed Saber1, Mohamed El-Ghannam1, Yasser Shaban Mubarak2, Hesham Hassan Mahdy2, Ramy Mohamed Reda Khorshid1
1 Department of Cardiothoracic Surgery, Faculty of Medicine, Ain Shams University, Cairo, Egypt
2 Department of Cardiothoracic Surgery, Faculty of Medicine, Minia University, El-Minya, Egypt
|Date of Submission||16-Jan-2022|
|Date of Decision||27-Feb-2022|
|Date of Acceptance||07-Mar-2022|
|Date of Web Publication||09-May-2022|
Hesham Hassan Mahdy
Department of Cardiothoracic Surgery, Faculty of Medicine, Minia University, El-Minya
Source of Support: None, Conflict of Interest: None
Background: Histidine-tryptophan-ketoglutarate (HTK), Bretschneider’s, or Custodiol is an intracellular crystalloid cardioplegic solution which is claimed to offer single shot cardioplegia for myocardial protection during complex cardiac procedures for up to 3 h. We aimed to compare the clinical outcome of early coronary artery bypass grafting (CABG) using blood cardioplegia vs. Custodiol solution for myocardial protection in patients with recent ST-elevation myocardial infarction (STEMI). Materials and Methods: This prospective comparative study included 100 patients with recent STEMI who underwent early CABG at our institution between January 2019 and December 2020. The patients were divided into two groups: group A (n = 50) received blood cardioplegia and group B (n = 50) received Custodiol-HTK crystalloid cardioplegia. Results: There were non-significant differences in postoperative mortality and complication rates between both the groups except for significantly higher proportion of post-operative arrythmias after Custodiol cardioplegia (26% vs. 8%, P = 0.01). Custodiol was associated with significantly lower levels of blood troponin and higher levels of blood lactate for 6 h after CABG. Custodiol results in significantly shorter durations of mechanical ventilation (11.98 ± 4.03 vs. 18.28 ± 8.84 h, P < 0.001) and intensive care unit (ICU) stay (70.04 ± 14.80 vs. 80.20 ± 19.91 h, P = 0.01), with non-significantly shorter duration of post-operative hospital stay (7.98 ± 2.76 vs. 9.24 ± 3.41 days, P = 0.06). Conclusion: Custodiol as a single shot without interruption of the operative technique offers shorter durations of mechanical ventilation and ICU stay than blood cardioplegia, with more acceptable levels of post-operative troponin in high-risk patients who underwent early CABG for recent STEMI.
Keywords: Cardiac surgery, cardioplegia, coronary artery bypass grafting, Custodiol-HTK solution, myocardial protection
|How to cite this article:|
Saber WA, El-Ghannam M, Mubarak YS, Mahdy HH, Khorshid RM. Custodiol-HTK Solution Vs. Conventional Cardioplegia for Myocardial Protection During Coronary Artery Bypass Grafting Following Recent ST-Elevation Myocardial Infarction. Bali J Anaesthesiol 2022;6:97-102
|How to cite this URL:|
Saber WA, El-Ghannam M, Mubarak YS, Mahdy HH, Khorshid RM. Custodiol-HTK Solution Vs. Conventional Cardioplegia for Myocardial Protection During Coronary Artery Bypass Grafting Following Recent ST-Elevation Myocardial Infarction. Bali J Anaesthesiol [serial online] 2022 [cited 2022 May 26];6:97-102. Available from: https://www.bjoaonline.com/text.asp?2022/6/2/97/344882
| Introduction|| |
Timely reperfusion of the occluded coronary artery is essential to optimize the treatment of patients with ST-elevation myocardial infarction (STEMI)., Early reperfusion with primary percutaneous coronary intervention (PCI) is the preferred modality of treatment; however, coronary artery bypass grafting (CABG) may be indicated when coronary anatomy is unsuitable for PCI in the acute phase of STEMI or after initial stabilization. CABG can be performed after PCI as definitive or adjunctive procedure for myocardial revascularization. Early CABG within 24 h of STEMI can be performed as a primary reperfusion therapy after failed PCI.
Proper myocardial protection with cardioplegic solutions is an essential step during cardiac surgery, especially with inclusion of elderly patients and more severe conditions. Blood cardioplegia is the most common form of hyperkalemic cardioplegia. The blood cardioplegia was mixed at a ratio of 1:4 (1 part of hyperkalemic crystalloid solution and 4 parts of blood), inducing a rapid depolarized arrest.
Histidine-tryptophan-ketoglutarate (HTK) or Custodiol was first described by Bretschneider et al. in the 1970s as an intracellular crystalloid cardioplegic solution. Nowadays, Custodiol is used by some centers for myocardial protection in complex cardiac surgeries and for organ preservation in transplant surgeries. It is preferred to conventional cardioplegia as it can be administrated in a single dose and it is claimed to offer myocardial protection for a period of up to 3 h. Moreover, Custodiol solution has low sodium and calcium content, thus its mechanism of action differs from extracellular cardioplegic solutions which have high potassium content and can result in cardiac arrest in diastole due to hyperpolarization of the myocyte plasma membrane. Therefore, the aim of this study was to compare the clinical outcome after early CABG in patients with recent STEMI, using blood or Custodiol solution for cardioplegia.
| Materials and Methods|| |
This prospective comparative study was conducted at our institution between January 2019 and December 2020. The study included 100 patients who underwent early CABG with recent STEMI. The patients were divided into two groups: group A (n = 50) received blood cardioplegia infusion and group B (n = 50) received Custodiol-HTK crystalloid cardioplegia infusion. Our inclusion criteria were adult patients (age ≥40 years) of both genders, patients undergoing isolated on-pump CABG, recent STEMI (ECG changes—positive enzymes) within 1 month before surgery, and failed or unavailable PCI. We excluded patients with previous CABG, concomitant cardiac procedure, pre-operative intra-aortic balloon (IABP), Child C liver diseases (bilirubin >3, albumin <2.8, and INR >2.3), renal impairment (serum creatinine more than 2), or cardiogenic shock. The study considered the ethical principles of Helsinki declaration, and it was conducted after obtaining an approval from a Research Ethics Committee (registry number 298/2018 dated on September 16, 2018) at our institution and informed consents from patients.
The patients had routine pre-operative preparation for CABG including ECG, cardiac enzymes, chest X-ray, echocardiography, and full laboratory workup. Both groups underwent standard technique for isolated on-pump CABG through median sternotomy with aorto-caval cannulation. Patients in group A received intermittent cold blood-enriched cardioplegia at 28–32°C esophageal temperature [the crystalloid solution is obtained by adding 40 mL of 10% potassium chloride (80 mEq) and 30 mL of 10% NaHCO3 (30 mEq) to 1 L Ringer’s solution given as loading dose and giving maintenance dose of 200 mL every 20 min]. In group B, a single shot of Custodiol (already made) was given at a dose of 15–20 mL/kg as a single dose and last for 2–3 h. After performing distal and proximal coronary anastomosis, the patients were weaned from cardiopulmonary bypass (CPB) followed by hemostasis, placement of chest drains, and anatomical closure of the sternal wound.
The estimated post-operative outcomes included: any post-operative complication [particularly inotropic support >24 h, re-operation for bleeding, ventricular fibrillation (VF), renal dysfunction, pulmonary complications, neurological complications, gastrointestinal complications, and wound infection], 30-day mortality (death during hospital stay or within 30 days after CABG), hospital durations [mechanical ventilation, intensive care unit (ICU) stay, and total hospital stay]. Blood lactate levels were determined using a blood gas analyzer at 1, 6, 12, and 24 h of ICU admission. Troponin T was measured post-operatively at 1, 6, 12, and 24 h by a one-step enzyme immunoassay.
All statistical analyses are carried out using IBM-SPSS software version 20.0 (IBM Corp., Released 2011, IBM SPSS Statistics for Windows, Version 20.0, Armonk, NY, USA). Continuous data were expressed as mean and standard deviation, whereas categorical data were expressed as number and percent. Comparisons were carried out using Student’s t-test for continuous data and χ2 test for categorical data. A P-value was considered significant if less than 0.05.
| Results|| |
There was no significant difference between both the groups regarding the comparison of pre-operative demographic characteristics and comorbid conditions in the studied groups [Table 1]. Regarding comparison of intra-operative data [Table 2], there was a significant difference between both the groups regarding cross clamp time with non-significant difference regarding comparisons of CPB time, cross-clamp time, number of anastomoses, the need for defibrillation and intra-aortic balloon pump (IABP).
Post-operative outcome is presented in [Table 3]. There was no significant difference between both the groups with regard to comparison of inotropic support >24 h, re-opening for bleeding, renal dysfunction, pulmonary complications, neurological complications, gastrointestinal complications, wound infection, and 30-day mortality. There was a significant higher incidence of VF in group B (26% vs. 8%). There was a significant difference between time of mechanical ventilation (11.98 ± 4.03 vs. 18.28 ± 8.84 h, P < 0.001) and ICU stay (70.04 ± 14.80 vs. 80.20 ± 19.91 h, P = 0.01), whereas the total post-operative hospital stay was non-significantly lower than that in group B (7.98 ± 2.76 vs. 9.24 ± 3.41 days, P = 0.06).
Intergroup comparisons of troponin levels are presented in [Figure 1], which revealed that group B had significantly lower troponin levels at 1 and 6 h after surgery. Inter-group comparisons of lactate concentrations are shown in [Figure 2]. Group B had significantly higher lactate concentrations at 1 and 6 h after surgery, but these significant differences disappear at 12 and 24 h.
|Figure 1: Error bars for mean and range of post-operative troponin levels within 24 h after surgery in the studied groups|
Click here to view
|Figure 2: Error bars for mean and range of post-operative lactate concentration within 24 h after surgery in the studied groups|
Click here to view
| Discussion|| |
This study focussed on the outcomes of early CABG, within 1 month, after STEMI. Although it seems clear that patients who undergo CABG after acute MI possess a higher risk of short-term mortality compared with elective CABG, the optimal timing of surgical revascularization is controversial. The previously reported association between early CABG and mortality was seen to be particularly important for transmural infarcts.
Many studies reported elevation of the levels of cardiac enzymes after cardiac surgery, which indicates additional myocardial damage during surgery. Thus, there is an increasing interest for myocardial protection during the period of global ischemia. The optimal cardioplegia during cardiac surgery should result in complete myocardial preservation for a long duration by decreasing cardiac metabolism during cardiac arrest and less post-operative organ injury. Nowadays, there is a need for myocardial protection without interruption of the surgical techniques, due to performance of more complex procedures and inclusion of high-risk and elder patients for cardiac procedures. CABG in patients with recent STEMI is challenging as it needs optimal myocardial protection. Polarized cardiac arrest by Custodiol-HTK solution has some potential benefits and advantages as it is given as a single shot with minor effect on cardiac metabolism.
In our series, we did not find a significant difference in post-operative complications and mortality between blood and Custodiol cardioplegia, except for significantly higher incidence of VF in the Custodiol group (26% vs. 8%). The reason for an increased rate of VF after reperfusion with Custodiol-HTK cardioplegia remains unclear. Similar to our findings, Edelman et al. have reported that using Custodiol-HTK cardioplegia in isolated CABG leads to a significantly increased risk of spontaneous VF after releasing of the aortic clamp. On the contrary, Braathen et al. reported that cardioplegia with Custodiol for arresting hearts shows more spontaneous recovery without use of defibrillator and reduced necessity for inotropic drugs when compared with the use of cold blood cardioplegia.
In our study, intergroup comparisons of troponin levels are presented. Custodiol results in significantly lower troponin levels at 1 and 6 h after surgery. Troponin levels are usually elevated after cardiac surgery, but it varies in accordance to the type of operation. Elevation of troponin levels determined for 6 h after cardiac surgery is common, but these elevations are normalized to the 24-h value. Early troponin release may be attributed to common factors including surgical impact of surgery, whereas continued troponin release may also reflect peri-operative/post-operative events, such as ongoing myocardial ischemia/necrosis, that affect subsequent outcomes.
A controversy exists regarding the changes in troponin levels after cardiac surgery in relation to used cardioplegic solutions. Fannelop et al. in an experimental study found that cold blood cardioplegia provides better myocardial protection and preservation of left ventricular function than HTK in the early hours after de-clamping. Braathen et al. in a randomized study measured markers of myocardial injury and reported that HTK in elective mitral surgery protects the myocardium as much as the repetitive ante-grade cold blood cardioplegia. Takeuchi et al. also demonstrated that administration of histidine containing cardioplegia solution promotes anaerobic glycolysis and improves recovery of high-energy phosphates and contractile function in the hypertrophied myocardium. Sirvinskas et al. reported an incidence of 2.5% of new ECG changes and elevated cardiac enzymes after 12 and 24 h with slightly higher statistically insignificant numbers in the cold crystalloid group.
In our study, Custodiol had significantly higher lactate concentrations at 1 and 6 h after surgery. Then lactate clearance had occurred and no significant difference was seen between both the groups after 12 and 24 h. CPB is associated with impaired tissue oxygenation and suggests that tissue hypoxia may be involved in the genesis of early onset hyperlactatemia. Microcirculatory dysfunction, secondary to the proinflammatory effects of prolonged CPB, contributes to early onset hyperlactatemia. Ascione et al. reported that a time-dependent increase in blood lactate was seen immediately following the release of aortic cross-clamp and remained elevated at 48 h post-operatively when compared with pre-operative levels.
Limitations of our study were no randomization, small sample size, and absence of long-term follow-up with inability to compare our results of using two different solutions on long term. In conclusion, there were no significant differences in post-operative mortality and morbidity using Custodiol cardioplegia when compared with blood cardioplegia for CABG in high-risk patients with recent STEMI. Custodiol is preferred as it is given as a single shot without interruption of the surgical technique, in addition to shorter durations of mechanical ventilation and ICU stay and little influence on post-operative troponin levels.
| Conclusion|| |
Custodiol as a single shot without interruption of the operative technique offers shorter durations of mechanical ventilation and ICU stay than blood cardioplegia, with more acceptable levels of post-operative troponin in high-risk patients who underwent early CABG for recent STEMI.
Financial support and sponsorship
Conflicts of interest
There are no conflicts of interest.
All authors had
1. substantial contributions to the conception or design of the work; or the acquisition, analysis, or interpretation of data for the work;
2. Drafting the work or revising it critically for important intellectual contents;
3. Final approval of the version to be published;
4. Agreement to be accountable for all aspects of the work in ensuring that questions related to the accuracy or integrity of any part of the work are appropriately investigated and resolved.
| References|| |
De Luca G, Suryapranata H, Ottervanger JP, Hoorntje JC, Gosselink AT, Dambrink JH, et al
. Postprocedural single-lead ST-segment deviation and long-term mortality in patients with ST-segment elevation myocardial infarction treated by primary angioplasty. Heart 2008;94:44-7.
Kalla K, Christ G, Karnik R, Malzer R, Norman G, Prachar H, et al
; Vienna STEMI Registry Group. Implementation of guidelines improves the standard of care: The Viennese registry on reperfusion strategies in ST-elevation myocardial infarction (Vienna STEMI registry). Circulation 2006;113:2398-405.
Keeley EC, Boura JA, Grines CL. Primary angioplasty versus intravenous thrombolytic therapy for acute myocardial infarction: A quantitative review of 23 randomised trials. Lancet 2003;361:13-20.
Henriques JP, de Boer MJ, van’t Hof AW, Hoorntje JC, Miedema K, Ottervanger JP, et al
. Prognostic importance of left ventricular function after angioplasty or thrombolysis for acute myocardial infarction. Neth Heart J 2001;9:160-5.
Eagle KA, Guyton RA, Davidoff R, Edwards FH, Ewy GA, Gardner TJ, et al
. American College of Cardiology; American Heart Association. ACC/AHA 2004 Guideline Update for Coronary Artery Bypass Graft Surgery: A report of the American College of Cardiology/American Heart Association Task Force on Practice Guidelines (Committee to Update the 1999 Guidelines for Coronary Artery Bypass Graft Surgery). Circulation2004;110:e340-437 .
Antman EM, Anbe DT, Armstrong PW, Bates ER, Green LA, Hand M, et al
; American College of Cardiology; American Heart Association Task Force on Practice Guidelines; Canadian Cardiovascular Society. ACC/AHA guidelines for the management of patients with ST-elevation myocardial infarction: A report of the American College of Cardiology/American Heart Association Task Force on practice guidelines (Committee to Revise the 1999 Guidelines for the Management of Patients with Acute Myocardial Infarction). Circulation 2004;110:e82-292.
Braathen B, Jeppsson A, Schersten H, Hagen OM, Vengen O, Rexius H, et al
. One single dose of histidine-tryptophan-ketoglutarate solution gives equally good myocardial protection in elective mitral valve surgery as repetitive cold blood cardioplegia: A prospective randomized study. J Thorac Cardiovasc Surg 2011;141:995-1001.
Chambers DJ, Fallouh HB. Cardioplegia and cardiac surgery: Pharmacological arrest and cardioprotection during global ischemia and reperfusion. Pharmacol Ther 2010;127:41-52.
Bretschneider HJ, Hübner G, Knoll D, Lohr B, Nordbeck H, Spieckermann PG. Myocardial resistance and tolerance to ischemia: Physiological and biochemical basis. J Cardiovasc Surg (Torino) 1975;16:241-60.
Chambers DJ. Mechanisms and alternative methods of achieving cardiac arrest. Ann Thorac Surg 2003;75:S661-6.
Assmann A, Boeken U, Akhyari P, Lichtenberg A. Appropriate timing of coronary artery bypass grafting after acute myocardial infarction. Thorac Cardiovasc Surg 2012;60:446-51.
Gaudino M, Angelini GD, Antoniades C, Bakaeen F, Benedetto U, Calafiore AM, et al
; Arterial Grafting International Consortium (ATLANTIC) Alliance. Off-pump coronary artery bypass grafting: 30 years of debate. J Am Heart Assoc 2018;7:e009934.
Edelman JJ, Seco M, Dunne B, Matzelle SJ, Murphy M, Joshi P, et al
. Custodiol for myocardial protection and preservation: A systematic review. Ann Cardiothorac Surg 2013;2:717-28.
Fannelop T, Dahle GO, Salminen PR, Moen CA, Matre K, Mongstad A, et al
. Multidose cold oxygenated blood is superior to a single dose of Bretschneider HTK-cardioplegia in the pig. Ann Thorac Surg 2009;87:1205-13.
Takeuchi K, Akimoto H, Maida K, Munakata M. Myocardial protection of the pressure overload hypertrophied heart in human cardiac surgery by acceleration of anaerobic glycolysis. J Cardiothorac Surg 2002;43:37.
Sirvinskas E, Nasvytis L, Raliene L, Vaskelyte J, Toleikis A, Trumbeckaite S. Myocardial protective effect of warm blood, tepid blood, and cold crystalloid cardioplegia in coronary artery bypass grafting surgery. Croat Med J 2005;46:879-88.
Ascione R, Venturini A, Polesel E, Mangino D, Zanchettin C, Zoffoli G, et al
. Source, triggers and clinical implications of hyperlactemia in patients undergoing mitral valve surgery using Custodiol cardioplegia. World J Cardiothorac Surg 2013;3:131-8.
[Figure 1], [Figure 2]
[Table 1], [Table 2], [Table 3]