Header bg
  • Users Online: 94
  • Print this page
  • Email this page
Header bg


 
 
Table of Contents
REVIEW ARTICLE
Year : 2022  |  Volume : 6  |  Issue : 3  |  Page : 145-151

The use of blood and crystalloid cardioplegia in adult open-heart surgery on postsurgical outcomes: A systematic review of atrial fibrillation incidence, myocardial infarction, inotropic use, length of stay in ICU, and postoperative mortality


1 Department of Anesthesiology and Intensive Therapy, Faculty of Medicine, Universitas Sebelas Maret, Dr. Moewardi Hospital, Surakarta, Indonesia
2 Department of Anesthesiology and Intensive Therapy, Faculty of Medicine, Universitas Indonesia, Jakarta, Indonesia

Date of Submission18-May-2022
Date of Decision12-Jul-2022
Date of Acceptance23-Jul-2022
Date of Web Publication27-Jul-2022

Correspondence Address:
Bambang Novianto Putro
Department of Anesthesiology and Intensive Therapy, Faculty of Medicine, Universitas Sebelas Maret, Dr. Moewardi Hospital, Kolonel Sutarto Street No.132, Jebres, Surakarta 57126, Central Java
Indonesia
Login to access the Email id

Source of Support: None, Conflict of Interest: None


DOI: 10.4103/bjoa.bjoa_148_22

Rights and Permissions
  Abstract 

Background: Myocardial ischemia can occur due to hypotension, shock, coronary heart disease, and aortic cross-clamping during open-heart surgery using a cardiopulmonary bypass machine. As the cardioprotective method, cardioplegia is classified into blood or crystalloid base. This systematic review is aimed to describe the effectiveness of blood and crystalloid cardioplegic solutions in adult open-heart surgery procedures by focusing on their effects on cardiac enzymes. Materials and Methods: This study investigated the effect of blood and crystalloid cardioplegia on troponin (cTn) and creatinine kinase myocardial bound. The literature search was carried out on several Cochrane, PubMed, PMC, and Google Scholar databases from January 2014 to August 2020 using the MeSH keywords and Boolean operator. Results: We obtained 346 articles and identified six prospective randomized studies from four countries. The majority discussed the comparison of blood cardioplegia and crystalloids in coronary revascularization cardiac surgery (coronary artery bypass grafting). Overall, the articles used have a low risk of bias despite their high level of homogenicity. Conclusions: The current literatures on cardioplegia in adults do not provide adequate advanced-phase trials. Both types of cardioplegia provide a reasonable protection for myocardium. However, several studies reveal that crystalloid cardioplegia increases cardiac enzymes more significantly than blood cardioplegia. This research has been registered with PROSPERO with the number CRD42022312548.

Keywords: Blood cardioplegia, cardiac enzyme, cardiac surgery, cardioplegia, crystalloid, myocardial ischemia


How to cite this article:
Putro BN, Hidayat JK, Soenarto RF. The use of blood and crystalloid cardioplegia in adult open-heart surgery on postsurgical outcomes: A systematic review of atrial fibrillation incidence, myocardial infarction, inotropic use, length of stay in ICU, and postoperative mortality. Bali J Anaesthesiol 2022;6:145-51

How to cite this URL:
Putro BN, Hidayat JK, Soenarto RF. The use of blood and crystalloid cardioplegia in adult open-heart surgery on postsurgical outcomes: A systematic review of atrial fibrillation incidence, myocardial infarction, inotropic use, length of stay in ICU, and postoperative mortality. Bali J Anaesthesiol [serial online] 2022 [cited 2022 Aug 10];6:145-51. Available from: https://www.bjoaonline.com/text.asp?2022/6/3/145/352402




  Introduction Top


Cardiac surgery, especially those using a cardiopulmonary bypass (CPB) machine, can lead to myocardial ischemia due to ischemia reperfusion, aortic cross-clamping, surgical trauma, and oxidative stress, which can result in myocyte death and myocardial damage. A 45-min period of normothermic global ischemia may cause myocardial contractility dysfunction, whereas regional ischemia without infarction of just 15 min may lead to cardiac stunning. Myocardial protection should prevent myocardial damage.[1]

Cardioplegia is one of the myocardial protectors that prevents iatrogenic injury due to extracorporeal circulation, aortic cross-clamping, ischemic segment revascularization, and cross-clamp release.[2] There are various kinds of cardioplegic compositions to carry out the needs of cardiac surgery techniques. They are usually characterized by a hypothermic and high-level potassium solution or a crystalloid–blood combination.[3] Cardioplegia reduces ischemic injury by decreasing oxygen demand, excess calcium ions, and edema. It also increases material supply and utilization.[4]

There are two types of cardioplegia: crystalloid and blood cardioplegia solution.[5] Both of them have their advantages and disadvantages. Crystalloid cardioplegia leads to mild-to-moderate hypothermia, reduces oxygen consumption, and provides a better view of the distal coronary artery anastomoses. Still, it is associated with myocardial edema resulting in low cardiac output syndrome (LCOS).[5] Blood cardioplegia nourishes the endothelium and myocardium, has efficient transport of oxygen and nutrients, increases buffering ability, has oncotic variations reducing cellular lesions, and reduces the free radicals providing a better effect on ischemic injury. However, it may cause temperature-related perfusion disturbances, increase the risk of excess sodium and calcium ions, lead to complex fabrication, and need to add complementary circuits to the CPB machine, thereby encouraging additional priming.[5],[6]

The cardiac enzyme can be a sensitive marker in myocardial injury. A cohort study by Greenberg et al.[7] reported that postoperative cardiac enzyme elevations were associated with the risk of LCOS, atrial fibrillation, arrhythmias, prolonged intensive care unit (ICU) stays, and 30-day postoperative mortality.[7],[8] Stahel et al. and Mey et al. in their retrospective study stated that there was an increase in troponin T and creatinine kinase myocardial bound (CKMB) after surgery using a CPB machine.[9],[10]

Controversy regarding the protective effect of the myocardium using blood cardioplegia over crystalloids has long existed. A meta-analysis comparing the effects of blood cardioplegia and crystalloid cardioplegia on cardiac enzyme elevation in the pediatric population has been carried out by Mylonas et al.[11] Many randomized controlled trials (RCT) studies on the use of blood cardioplegia and crystalloids are conducted to address this controversy. However, none of them reported conclusive in adult population.

The authors performed a study to investigate the myocardium protective’s effectiveness of blood and crystalloids cardioplegic solutions in adult open-heart surgical procedures.


  Materials and Methods Top


The processes of this review used the Preferred Reporting Items for Systematic reviews and Meta-Analyses (PRISMA) guidelines. Two independent reviewers performed searching and reviewing. Another independent reviewer extracted the eligible articles meeting the inclusion criteria into a table. In case of disagreement, the author resolved as the sole decision-maker.

The search process was carried out in the Cochrane Library, PubMed/Medline, PMC, and Google Scholar electronic databases. The authors included full-text cross-sectional and experimental research articles on adult patients undergoing first open-heart surgery written in English involving the cardiac enzyme as the primary outcome and atrial fibrillation, myocardial infarction, length of stay at ICU, the use of inotropic support, and mortality as the secondary outcome. The database was selected using the MeSH-related English words: “cardioplegic,” “cardioplegic solution,” “cardioplegia,” “cardiac surgery” with a combination of Boolean operators (AND, OR). Relevant articles were obtained from the reference list systematically with the “snowball” procedure.

The articles written in non-English, involving pediatric patients, in vivo, or in vitro experiments were excluded from the study. The irrelevant articles, including the literature review, editorial letter, editorial perspective, were also excluded. The data collected include the author’s name, year of publication, location, sample size, method, and primary and secondary outcomes. The data were reported in a descriptive method using Microsoft Excel 2013 software.

Risk of bias was analyzed with a risk of bias (RoB) tool of the Cochrane Library, to evaluate the studies’ methodological quality and internal validity. It classifies into a high, low, or uncertain risk of bias. The applied criteria were: generation of the randomization sequence; confidentiality of allocation; concealment of allocation; masking (blinding) of participants and the team of researchers; masking (blinding) in the evaluation of outcomes; incomplete data of outcomes; selective report of outcomes; and other sources of bias identified by the reviewer.[12]

This research has been registered in PROSPERO with the number CRD42022312548.


  Results Top


Of the 346 articles obtained, the authors identified six prospective randomized studies from 2014 to 2020 [Figure 1], with a total of 796 subjects undergoing open-heart surgery (coronary artery bypass grafting [CABG], valve surgery, and heart transplantation). Of these subjects, 431 of them received blood cardioplegia treatment, whereas the other 365 subjects had crystalloid cardioplegic treatment. [Table 1] depicts the characteristics of the study subjects.
Figure 1: PRISMA diagram

Click here to view
Table 1: Characteristics of the six studies included in the analysis

Click here to view


The number of study subjects per article varies from a minimum of 60 to a maximum of 297 subjects. Most articles compared the use of blood cardioplegia to crystalloids in CABG [Table 2]. Overall, the articles had a low risk of bias [Figure 2].
Table 2: Inclusion criteria and results related to serum levels of CKMB, CTn-T, CTn-I, AF, MI, inotropic, LoS in ICU, and mortality in the six studies included in the systematic review

Click here to view
Figure 2: Risk of bias analysis

Click here to view



  Discussion Top


The authors performed this systematic review to investigate the comparative effectiveness of blood versus crystalloids cardioplegic solutions in adult open-heart surgical procedures. A heart–lung bypass machine causes more damage to red blood cells than the regular human cardiovascular system. The trauma from using this machine is not only structural but can be functional. Stress–strain, the impact of exposure of blood cells to the extracorporeal machine hose system, and the turbulent flow in them can cause hemolysis or shorten the lifespan of blood cells. However, the use of blood as cardioplegia is considered safe and effective for cardioplegia with more cardioprotective effects when compared with crystalloids.

This review included six randomized controlled studies comparing the effectiveness of blood cardioplegia to crystalloids in open-heart surgery.

Cardiac enzyme is a sensitive marker for myocardial injury. The elevation of myocardial enzymes was the primary outcome of our study. Myocardial injury is significantly associated with cardiac troponin levels.[7] Two out of five studies,[2],[6] which examined the effect of blood versus crystalloid cardioplegia on enzyme troponin I, significantly higher levels of troponin-I, were reported in patients who received crystalloid as compared to blood cardioplegia.[2],[6] A similar pattern of higher levels of CKMB was observed in two studies[2],[6] for patients who received crystalloids. The troponin T has only been reported in one study, in which there was no significant difference among the patients who received crystalloid or blood.[1]

Both of the studies that employed warm blood cardioplegia[2],[6] reported a significantly lower release of CKMB and troponin I, compared with crystalloid cardioplegia. Besides this, authors observed a higher use of inotropic and increased length of ICU stay in patients who received crystalloid cardioplegia compared with warm blood cardioplegia. Guru et al. reported in their meta-analysis of 34 studies that blood cardioplegia significantly reduced the incidence of LCOS and CKMB release.[18] Owing to a better oxygen-carrying capacity, buffer capacity, and physiological oncotic properties, the use of blood as cardioplegia is considered safe and effective for cardioplegia, compared with crystalloids.[8]

The authors also sought to explore whether theoretical benefits of blood over crystalloid cardioplegia translate into better clinical outcomes. Atrial fibrillation, myocardial infarction, length of stay at ICU, the use of inotropic support, and mortality were the secondary outcomes of our review. Surprisingly, an insignificant difference between both groups of cardioplegia was reported for atrial fibrillation,[1],[4] myocardial infarction,[1],[2],[3],[4] and mortality.[1],[2],[4],[6] Similar findings were also reported by Mylonas et al. in their meta-analysis, where both cardioplegia modalities showed comparative clinical effectiveness in pediatric patients.[11]

However, a significant increase in the length of ICU stay was reported in only one study out of three studies, which examined this parameter.[2],[4],[6] Similarly, among the three studies that examined the use of inotropic support, Mourad et al. observed a significantly higher use of inotropic support in crystalloid group.[4] In line with our review findings, a significantly lower concentration of cTn and CKMB in patients who underwent cardiac surgery by employing warm blood cardioplegia was reported by Fan et al. (2010) in their meta-analysis of 41 RCTs.[19]

There are several limitations in this systematic review. One of the limitations of this review is the variation of cardioplegic temperature, composition, and the route among the included studies, which can affect the clinical outcomes. Second, most of the studies included in this review were performed in patients of CABG surgery, and authors cannot extrapolate these findings to the adult patients undergoing other cardiac surgeries. Second, the studies included were RCTs with a small sample size.


  Conclusion Top


The findings of our systematic review revealed that both types of cardioplegia provide reasonable protection for myocardium. It is still unclear which of cardioplegic solution is providing the best myocardial protection. However, several studies suggested that crystalloid cardioplegia increases cardiac enzymes (CKMB and troponin I) than blood cardioplegia does.

The limited sample size and different outcome measures elicit a limited evidence base to inform in everyday clinical practice. It must be noted that, in general, clinical outcomes are also affected by many factors such as a severity of heart problems, comorbidities, duration of CPB use, difficulty in surgical procedure, and infection process.

Physician and researcher should do further research to assess myocardial protection in adults to improve the open-heart surgery outcome. A clearer understanding of these perioperative conditions is the key to improve myocardial protection during the open-heart surgery.

Acknowledgements

This study was supported by the Department of Anesthesiology and Intensive Therapy of Dr. Moewardi General Hospital Surakarta, Faculty of Medicine, Universitas Sebelas Maret, Surakarta.

Financial support and sponsorship

Nil.

Conflicts of interest

There are no conflicts of interest.

Authors’ contributions

The first and second authors designed the study and collected the data. The second and third authors conducted the analysis and wrote the article. All authors read and approved the final version of the article.

Ethical approval and consent to participate

This research has been registered with PROSPERO with the number CRD42022312548 and was carried out under the permission and approval obtained from Health Research Ethics Committee, Dr. Moewardi General Hospital with Ethical Clearance Reference Number 159/II/HREC/2021.



 
  References Top

1.
Sef D, Szavits-Nossan J, Predrijevac M, Golubic R, Sipic T, Stambuk K, et al. Management of perioperative myocardial ischaemia after isolated coronary artery bypass graft surgery. Open Heart 2019;6:e001027.  Back to cited text no. 1
    
2.
Whittaker A, Aboughdir M, Mahbub S, Ahmed A, Harky A Myocardial protection in cardiac surgery: How limited are the options? A comprehensive literature review. Perfusion 2021;36:338-51.  Back to cited text no. 2
    
3.
Drury NE, Yim I, Patel AJ, Oswald NK, Chong CR, Stickley J, et al. Cardioplegia in paediatric cardiac surgery: A systematic review of randomized controlled trials. Interact Cardiovasc Thorac Surg 2019;28:144-50.  Back to cited text no. 3
    
4.
Mourad FA, Fadala MA, Ibrahim AA, Ammar AM, Elnahas YM, Elghanam MA, et al. Myocardial protection during CABG: Warm blood versus cold crystalloid cardioplegia, is there any difference? J Egypt Soc Cardio-Thoracic Surg 2016;24:215-22.  Back to cited text no. 4
    
5.
Nardi P, Pisano C, Bertoldo F, Vacirca SR, Saitto G, Costantino A, et al. Warm blood cardioplegia versus cold crystalloid cardioplegia for myocardial protection during coronary artery bypass grafting surgery. Cell Death Discov 2018;4:23.  Back to cited text no. 5
    
6.
James TM, Nores M, Rousou JA, Lin N, Stamou SC Warm blood cardioplegia for myocardial protection: Concepts and controversies. Tex Heart Inst J 2020;47:108-16.  Back to cited text no. 6
    
7.
Greenberg JW, Lancaster TS, Schuessler RB, Melby SJ Postoperative atrial fibrillation following cardiac surgery: A persistent complication. Eur J Cardiothorac Surg 2017;52:665-72.  Back to cited text no. 7
    
8.
Rashid S, Malik A, Khurshid R, Faryal U, Qazi S The diagnostic value of biochemical cardiac markers in acute myocardial infarction; 2019. Available from: https://www.intechopen.com/chapters/62951. [Last accessed on 13 Mar 2022].  Back to cited text no. 8
    
9.
Tevaearai Stahel HT, Do PD, Klaus JB, Gahl B, Locca D, Göber V, et al. Clinical relevance of troponin T profile following cardiac surgery. Front Cardiovasc Med 2018;5:182.  Back to cited text no. 9
    
10.
Mey N De, Cammu G, Brandt I, Belmans A, Mieghem C Van, Foubert L, et al. High-sensitivity cardiac troponin release after conventional and minimally invasive cardiac surgery. SAGE J Anesth Intensive Care 2019;47:255-66.  Back to cited text no. 10
    
11.
Mylonas KS, Tzani A, Metaxas P, Schizas D, Boikou V, Economopoulos KP Blood versus crystalloid cardioplegia in pediatric cardiac surgery: A systematic review and meta-analysis. Pediatr Cardiol 2017;38:1527-39.  Back to cited text no. 11
    
12.
Higgins J, Thomas J, Chandler J, Cumpston M Cochrane handbook for systematic reviews of interventions. 6.0. Cochrane Library; 2019. Available from: https://training.cochrane.org/handbook/archive/v6. [Last accessed on 13 Mar 2022].  Back to cited text no. 12
    
13.
Sanetra K, Gerber W, Shrestha R, Domaradzki W, Krzych Ł, Zembala M, et al. The del nido versus cold blood cardioplegia in aortic valve replacement: A randomized trial. J Thorac Cardiovasc Surg 2020;159:2275-83.e1.  Back to cited text no. 13
    
14.
Ad N, Holmes SD, Massimiano PS, Rongione AJ, Fornaresio LM, Fitzgerald D The use of del nido cardioplegia in adult cardiac surgery: A prospective randomized trial. J Thorac Cardiovasc Surg 2018;155:1011-8.  Back to cited text no. 14
    
15.
Ucak HA, Uncu H Comparison of del nido and intermittent warm blood cardioplegia in coronary artery bypass grafting surgery. Ann Thorac Cardiovasc Surg 2019;25:39-45.  Back to cited text no. 15
    
16.
Ulugol H, Aksu U, Kocyigit M, Kilercik M, Karduz G, Okten M, et al. Comparative effects of blood and crystalloid cardioplegia on cellular injury and oxidative stress in cardiovascular surgery. Ann Thorac Cardiovasc Surg 2019;25:10-7.  Back to cited text no. 16
    
17.
Mahrose R, Shorbagy MS, Shahin KM, Elwany SE Warm blood cardioplegia versus cold crystalloid cardioplegia for coronary artery bypass grafting (CABG) in patients with low ejection fraction. Ain-Shams J Anesthesiol 2020;12:1-7.  Back to cited text no. 17
    
18.
Guru V, Omura J, Alghamdi AA, Weisel R, Fremes SE Is blood superior to crystalloid cardioplegia? A meta-analysis of randomized clinical trials. Circulation 2006;114:I331-8.  Back to cited text no. 18
    
19.
Fan Y, Zhang A-M, Xiao Y-B, Weng Y-G, Hetzer R Warm versus cold cardioplegia for heart surgery: A meta-analysis. Eur J Cardio-Thorac Surg 2010;37:912-9.  Back to cited text no. 19
    


    Figures

  [Figure 1], [Figure 2]
 
 
    Tables

  [Table 1], [Table 2]



 

Top
 
  Search
 
    Similar in PUBMED
   Search Pubmed for
   Search in Google Scholar for
 Related articles
    Access Statistics
    Email Alert *
    Add to My List *
* Registration required (free)  

 
  In this article
Abstract
Introduction
Materials and Me...
Results
Discussion
Conclusion
References
Article Figures
Article Tables

 Article Access Statistics
    Viewed228    
    Printed2    
    Emailed0    
    PDF Downloaded45    
    Comments [Add]    

Recommend this journal