Although the application of del Nido cardioplegia solution (DNC) in adult cardiac surgery is accumulating, the feasibility and safety of this myocardial protection strategy in adults remains controversial. We aimed to update our previous meta-analysis to determine the myocardial protective effect of DNC versus conventional cardioplegia (CC) in adult cardiac surgery.
Methods:
A comprehensive literature search was performed using PubMed, EMBASE, the Cochrane Library, and International Clinical Trials Registry Platform databases through November 2020.
Results:
Thirty-seven observational studies and four randomized controlled trials (RCTs) including 21,779 patients were identified. The DNC group was associated with decreased postoperative cardiac enzymes [troponin T (cTnT) and creatine kinase-MB (CK-MB)] [standardized mean differences (SMD): −0.59, 95% confidence interval (CI): −0.99 to −0.19, p = 0.004], cardiopulmonary bypass (CPB) time (MD: −9.31, 95% CI: −13.10 to −5.51, p < 0.00001), aortic cross-clamp (ACC) time (MD: −7.20, 95% CI: −10.31 to −4.09, p < 0.00001), and cardioplegia volume (SMD: −1.95, 95% CI: −2.46 to −1.44, p < 0.00001). Intraoperative defibrillation requirement was less in the DNC group [relative risk (RR): 0.50, 95% CI: 0.33 to 0.75, p = 0.0007]. The pooled analysis revealed no significant difference in operative mortality among the patients assigned to DNC and those undergoing CC.
Conclusion:
In adult cardiac surgery, compared to CC, myocardial protection used with DNC yield similar or better short-term clinical outcomes. More high-quality trials and RCTs reflecting long-term follow-up morbidity and mortality are required in the future to confirm these findings.
BuckbergGDAthanasuleasCL. Cardioplegia: solutions or strategies?Eur J Cardiothorac Surg2016; 50: 787–791.
2.
MatteGSdel NidoPJ. History and use of del Nido cardioplegia solution at Boston Children’s Hospital. J Extra Corpor Technol2012; 44: 98–103.
3.
ValooranGJNairSKChandrasekharanK, et al. Del Nido cardioplegia in adult cardiac surgery – scopes and concerns. Perfusion2015; 31: 6–14.
4.
SanetraKPawlakICisowskiM. Del Nido cardioplegia – what is the current evidence?Kardiochir Torakochirurgia Pol2018; 15: 114–118.
5.
KotaniYTweddellJGruberP, et al. Current cardioplegia practice in pediatric cardiac surgery: a North American multiinstitutional survey. Ann Thorac Surg2013; 96: 923–929.
6.
O’BrienJDHowlettSEBurtonHJ, et al. Pediatric cardioplegia strategy results in enhanced calcium metabolism and lower serum troponin T. Ann Thorac Surg2009; 87: 1517–1523.
7.
MarzoukMLafreniere-BessiVDionneS, et al. Transitioning to del Nido cardioplegia for all-comers: the next switching gear?BMC Cardiovasc Disord2020; 20: 215.
8.
O’DonnellCWangHTranP, et al. Utilization of del Nido cardioplegia in adult coronary artery bypass grafting – a retrospective analysis. Circ J2019; 83: 342–346.
9.
Task ForceMKunstGMilojevicM, et al. 2019 EACTS/EACTA/EBCP guidelines on cardiopulmonary bypass in adult cardiac surgery. Br J Anaesth2019; 123: 713–757.
10.
GorgyAShore-LessersonL. Del Nido cardioplegia should be used in all adults undergoing cardiac surgery: con. J Cardiothorac Vasc Anesth2019; 33: 1791–1794.
11.
LiYLinHZhaoY, et al. Del Nido cardioplegia for myocardial protection in adult cardiac surgery: a systematic review and meta-analysis. ASAIO J2018; 64: 360–367.
12.
LiberatiAAltmanDGTetzlaffJ, et al. The PRISMA statement for reporting systematic reviews and meta-analyses of studies that evaluate health care interventions: explanation and elaboration. J Clin Epidemiol2009; 62: e1–e34.
13.
StroupDFBerlinJAMortonSC, et al. Meta-analysis of observational studies in epidemiology: a proposal for reporting. Meta-analysis Of Observational Studies in Epidemiology (MOOSE) group. JAMA2000; 283: 2008–2012.
14.
HigginsJPAltmanDGGotzschePC, et al. The Cochrane collaboration’s tool for assessing risk of bias in randomised trials. BMJ2011; 343: d5928.
van der LaarseADavidsHAHollaarL, et al. Recognition and quantification of myocardial injury by means of plasma enzyme and isoenzyme activities after cardiac surgery. Br Heart J1979; 41: 660–667.
17.
HozoSPDjulbegovicBHozoI. Estimating the mean and variance from the median, range, and the size of a sample. BMC Med Res Methodol2005; 5: 13.
18.
HigginsJPThompsonSGDeeksJJAltmanDG. Measuring inconsistency in meta-analyses. BMJ2003; 327: 557–560.
19.
BorensteinMHedgesLVHigginsJP, et al. A basic introduction to fixed-effect and random-effects models for meta-analysis. Res Synth Methods2010; 1: 97–111.
20.
RaiKKarmacharyaRAdhikariAB, et al. Comparative study between the use of St. Thomas’ II cardioplegia and del Nido cardioplegia in patients who underwent open-heart surgery. Nepal Heart J2020; 17: 23–27.
21.
KuserliYTurkyilmazSTurkyilmazG, et al. Comparison of del Nido cardioplegia and blood cardioplegia in aortic root surgery. Heart Surg Forum2020; 23: E376–E384.
22.
SchutzAZhangQBertapelleK, et al. Del Nido cardioplegia in coronary surgery: a propensity-matched analysis. Interact Cardiovasc Thorac Surg2020; 30: 699–705.
23.
LenoirMBouhoutIJelassiA, et al. Del Nido cardioplegia versus blood cardioplegia in adult aortic root surgery. J Thorac Cardiovasc Surg. Epub ahead of print 30 January 2020. DOI: 10.1016/j.jtcvs.2020.01.022.
24.
KirisciMKocarslanAAltintas AykanD, et al. Evaluation of the cardioprotective effects of crystalloid del Nido cardioplegia solution via a rapid and accurate cardiac marker: heart-type fatty acid-binding protein. Turk J Med Sci2020; 50: 999–1006.
25.
ChenHWangLWanL, et al. Use of del Nido cardioplegia in acute aortic dissection surgery. Perfusion2021; 36: 233–238.
26.
KodaYKitaharaHNishidaH, et al. A proposed redosing interval of del Nido cardioplegia solution in adult cardiac surgery: a propensity-matched study. Perfusion2021; 36(5): 463–469.
27.
ShiHLuoHQiX, et al. Del Nido cardioplegia in surgery for aortic root disease: a historically controlled study. J Thorac Dis2020; 12: 4105–4114.
28.
AlgarniKD. Routine use of del Nido cardioplegia compared with blood cardioplegia in all types of adult cardiac surgery procedures. J Card Surg2020; 35(12): 3340–3346.
29.
OrakYKocarslanABoranOF, et al. Comparison of the operative and postoperative effects of del Nido and blood cardioplegia solutions in cardiopulmonary bypass surgery. Braz J Cardiovasc Surg2020; 35: 689–696.
30.
ElassalAAAl-EbrahimKAl-RadiO, et al. Myocardial protection by blood-based del Nido versus St. Thomas cardioplegia in cardiac surgery for adults and children. Heart Surg Forum2020; 23: E689–E695.
31.
KucinskiJGorskaADejaMA. Del Nido cardioplegia as a safe and effective method of myocardial protection in adult patients undergoing cardiac surgery: a single center experience. Kardiol Pol2019; 77: 1040–1046.
32.
PragliolaCHassanEIsmailH, et al. Del Nido cardioplegia in adult patients: a propensity-matched study of 102 consecutive patients. Heart Lung Circ2020; 29: 1405–1411.
33.
TimekTABeuteTRobinsonJA, et al. Del Nido cardioplegia in isolated adult coronary artery bypass surgery. J Thorac Cardiovasc Surg2020; 160: 1479–1485.
34.
BarbosaFMMoyanoCColichelliDA, et al. First Argentine experience with del Nido cardioplegia in adults. Comparison with Buckberg cardioplegia. Rev Argent Cardiol2019; 87: 363–366.
35.
LuoHQiXShiH, et al. Single-dose del Nido cardioplegia used in adult minimally invasive valve surgery. J Thorac Dis2019; 11: 2373–2382.
36.
SanetraKGerberWShresthaR, et al. The del Nido versus cold blood cardioplegia in aortic valve replacement: a randomized trial. J Thorac Cardiovasc Surg2020; 159: 2275–2283.
37.
MukdadLToppenWSanaihaY, et al. Incidence of cerebral microemboli in single-dose vs. multidose cardioplegia in adult cardiac surgery. J Extra Corpor Technol2018; 50: 143–148.
38.
SabikJFRazaSChavinKD. Safety and benefits of new techniques and technologies in less invasive mitral valve repair. J Card Surg2018; 33: 609–619.
39.
UcakHAUncuH. Comparison of del Nido and intermittent warm blood cardioplegia in coronary artery bypass grafting surgery. Ann Thorac Cardiovasc Surg2019; 25: 39–45.
40.
KavalaAATurkyilmazS. Comparison of del Nido cardioplegia with blood cardioplegia in coronary artery bypass grafting combined with mitral valve replacement. Braz J Cardiovasc Surg2018; 33: 496–504.
41.
KoeckertMSSmithDEViningPF, et al. Del Nido cardioplegia for minimally invasive aortic valve replacement. J Card Surg2018; 33: 64–68.
42.
CayirMCYukselA. The use of del Nido cardioplegia for myocardial protection in isolated coronary artery bypass surgery. Heart Lung Circ2020; 29: 301–307.
43.
AdNHolmesSDMassimianoPS, et al. The use of del Nido cardioplegia in adult cardiac surgery: a prospective randomized trial. J Thorac Cardiovasc Surg2018; 155: 1011–1018.
44.
HamadRNguyenALalibertéÉ, et al. Comparison of del Nido cardioplegia with blood cardioplegia in adult combined surgery. Innovations (Phila)2017; 12: 356–362.
45.
KimWKKimHRKimJB, et al. Del Nido cardioplegia in adult cardiac surgery: beyond single-valve surgery. Interact Cardiovasc Thorac Surg2018; 27: 81–87.
46.
MongeroLBTesdahlEAStammersAH, et al. Does the type of cardioplegia solution affect intraoperative glucose levels? A propensity-matched analysis. J Extra Corpor Technol2018; 50: 44–52.
47.
StammersAHTesdahlEAMongeroLB, et al. Does the type of cardioplegic technique influence hemodilution and transfusion requirements in adult patients undergoing cardiac surgery?J Extra Corpor Technol2017; 49: 231–240.
48.
ZiazadehDMaterRHimelhochB, et al. Single-dose del Nido cardioplegia in minimally invasive aortic valve surgery. Semin Thorac Cardiovasc Surg. Epub ahead of print 2 November 2017. DOI: 10.1053/j.semtcvs.2017.10.001.
49.
MishraPJadhavRBMohapatraCK, et al. Comparison of del Nido cardioplegia and St. Thomas hospital solution – two types of cardioplegia in adult cardiac surgery. Kardiochir Torakochirurgia Pol2016; 13: 295–299.
50.
Guajardo SalinasGENuttRRodriguez-AraujoG. Del Nido cardioplegia in low risk adults undergoing first time coronary artery bypass surgery. Perfusion2017; 32: 68–73.
51.
VistariniNLaliberteEBeauchampP, et al. Del Nido cardioplegia in the setting of minimally invasive aortic valve surgery. Perfusion2017; 32: 112–117.
52.
KimJSJeongJHMoonSJ, et al. Sufficient myocardial protection of del Nido cardioplegia regardless of ventricular mass and myocardial ischemic time in adult cardiac surgical patients. J Thorac Dis2016; 8: 2004–2010.
53.
TimekTWillekesCHulmeO, et al. Propensity matched analysis of del Nido cardioplegia in adult coronary artery bypass grafting: initial experience with 100 consecutive patients. Ann Thorac Surg2016; 101: 2237–2241.
54.
YammineMNeelyRCLobermanD, et al. The use of lidocaine containing cardioplegia in surgery for adult acquired heart disease. J Card Surg2015; 30: 677–684.
55.
OtaTYerebakanHNeelyRC, et al. Short-term outcomes in adult cardiac surgery in the use of del Nido cardioplegia solution. Perfusion2016; 31: 27–33.
56.
SorabellaRAAkashiHYerebakanH, et al. Myocardial protection using del Nido cardioplegia solution in adult reoperative aortic valve surgery. J Card Surg2014; 29: 445–449.
57.
YerebakanHSorabellaRANajjarM, et al. Del Nido cardioplegia can be safely administered in high-risk coronary artery bypass grafting surgery after acute myocardial infarction: a propensity matched comparison. J Cardiothorac Surg2014; 9: 141.
58.
MickSLRobichMPHoughtalingPL, et al. Del Nido versus Buckberg cardioplegia in adult isolated valve surgery. J Thorac Cardiovasc Surg2015; 149: 626–634.
59.
SpellmanJ. Pro: in favor of more generalized use of del Nido cardioplegia in adult patients undergoing cardiac surgery. J Cardiothorac Vasc Anesth2019; 33: 1785–1790.
60.
KimKBallCGradyP, et al. Use of del Nido cardioplegia for adult cardiac surgery at the cleveland clinic: perfusion implications. J Extra Corpor Technol2014; 46: 317–323.
61.
MetraMBettariLPaganiF, et al. Troponin T levels in patients with acute heart failure: clinical and prognostic significance of their detection and release during hospitalisation. Clin Res Cardiol2012; 101: 663–672.
62.
BodyRCarleySMcDowellG, et al. Rapid exclusion of acute myocardial infarction in patients with undetectable troponin using a high-sensitivity assay. J Am Coll Cardiol2011; 58: 1332–1339.
63.
ChristensonRHAzzazyHM. Cardiac point of care testing: a focused review of current National Academy of Clinical Biochemistry guidelines and measurement platforms. Clin Biochem2009; 42: 150–157.
64.
MagnoniMMassonSAndreiniD, et al. Usefulness of high-sensitivity cardiac troponin T for the identification of outlier patients with diffuse coronary atherosclerosis and low-risk factors. Am J Cardiol2016; 117: 1397–1404.
65.
LerASazzadFOngGS, et al. Comparison of outcomes of the use of del Nido and St. Thomas cardioplegia in adult and paediatric cardiac surgery: a systematic review and meta-analysis. Perfusion2020; 35: 724–735.
66.
ChoiYHCowanDBWahlersTC, et al. Calcium sensitisation impairs diastolic relaxation in post-ischaemic myocardium: implications for the use of Ca(2+) sensitising inotropes after cardiac surgery. Eur J Cardiothorac Surg2010; 37: 376–383.
67.
ParkJLLucchesiBR. Mechanisms of myocardial reperfusion injury. Ann Thorac Surg1999; 68: 1905–1912.
68.
DobsonGPJonesMW. Adenosine and lidocaine: a new concept in nondepolarizing surgical myocardial arrest, protection, and preservation. J Thorac Cardiovasc Surg2004; 127: 794–805.
69.
DobsonGPLetsonHL. Adenosine, lidocaine, and Mg2+ (ALM): from cardiac surgery to combat casualty care—teaching old drugs new tricks. J Trauma Acute Care Surg2016; 80: 135–145.
70.
NajjarMGeorgeIAkashiH, et al. Feasibility and safety of continuous retrograde administration of del Nido cardioplegia: a case series. J Cardiothorac Surg2015; 10: 176.
71.
FurnissGShiBJimenezA, et al. Cardiac troponin levels following implantable cardioverter defibrillation implantation and testing. Europace2015; 17: 262–266.
72.
ParkSKHurMKimE, et al. Risk factors for acute kidney injury after congenital cardiac surgery in infants and children: a retrospective observational study. PLoS One2016; 11: e0166328.
73.
SalisSMazzantiVVMerliG, et al. Cardiopulmonary bypass duration is an independent predictor of morbidity and mortality after cardiac surgery. J Cardiothorac Vasc Anesth2008; 22: 814–822.
74.
DoenstTBorgerMAWeiselRD, et al. Relation between aortic cross-clamp time and mortality—not as straightforward as expected. Eur J Cardiothorac Surg2008; 33: 660–665.
75.
SiddiqiSBlackstoneEHBakaeenFG. Bretschneider and del Nido solutions: are they safe for coronary artery bypass grafting? If so, how should we use them?J Card Surg2018; 33: 229–234.
Supplementary Material
Please find the following supplemental material available below.
For Open Access articles published under a Creative Commons License, all supplemental material carries the same license as the article it is associated with.
For non-Open Access articles published, all supplemental material carries a non-exclusive license, and permission requests for re-use of supplemental material or any part of supplemental material shall be sent directly to the copyright owner as specified in the copyright notice associated with the article.
