A total of 4896 relevant literature were obtained in the initial examination, and after layer by layer screening, 10 RCT studies [4, 9,10,11,12,13,14,15,16,17] were finally included, with a total of 1796 adult patients, including 889 patients in the DNC group and 907 patients in the CBC group. The literature screening process and results are shown in Fig. 1. The basic characteristics of the included studies are shown in Table 1.
Table 1 Characteristics of included studiesFig. 1PRISMA flowchart of studies included in the meta-analysis
The 10 RCT studies were all published between 2018 and 2023 (Table 1). Mean trial duration was 18 months (range 9 months to 36 months). More than half of patients underwent Coronary artery bypass grafting (CABG) surgery and three included studies focusing on mixed adult cardiac surgery procedures, one trail focused on aortic valve replacement (AVR) surgery, and one trail included adult patients who underwent CABG or valve surgery (VS) surgery. All 10 randomized trials were single-center, one study was stopped early [9], one study was s finished with a delay due to the coronavirus pandemic situation [15]. 3 were registered in Clinicaltrials.gov [4, 9, 16], and 1 was registered in Thai clinical trial registry [10], 5 trials reported detailed descriptions of methods for generating random sequence [9, 12, 14,15,16], 3 trials specified blind method for participants [4, 12, 16]. The results of bias risk assessment of included studies are shown in Supplementary Figures S1.
Intraoperative outcomeSeven studies assessed intraoperative reperfusion volume of cardioplegia. Pooling data of these studies showed that DNC led to lower volume during operation than CBC [MD=-1.06, 95%CI (− 1.49, -0.63), P < 0.0001] (Fig. 2). Six studies assessed ventricular fibrillation after aortic cross-clamp removal. The results of meta-analysis showed that the defibrillation requirement was lower in the DNC group (Fig. 2). and the DNC group had a higher spontaneous cardiac rhythm recovery rate [MD = 0.37, 95%CI (0.30, 0.45), P < 0.00001]. Eight and nine studies respectively assessed CPB time and ACC time. Pooling the data of these studies showed no significant difference in the CPB time [MD=-1.95, 95%CI (-5.08, 1.18), P = 0.22] and ACC time [MD=-6.19, 95%CI (-13.12, 0.74), P = 0.08] with DNC compared with CBC (Fig. 2).
Fig. 2Meta-analyses of del Nido cardioplegia versus cold blood Cardioplegia, comparing the cardioplegia volume, CPB time, ACC time and intraoperative defibrillation. A, Cardioplegia volume; B, CPB time; C, ACC time; D, Defibrillation
Levels of myocardial injury biomarker and postoperative cardiac functionThree, four and five studies assessed the levels of CTnI, CTnT and CK-MB at 24 h after surgery, respectively. The results showed that compared with the CBC group, the CTnI level in the DNC group had no significant difference [MD= -0.26, 95%CI (-0.96, 0.44), P = 0.47]. The CTnT level and CK-MB level in the DNC group were significantly lower than those in the CBC group [MD=-0.47, 95%CI (-0.91, -0.04), P = 0.03; MD=-2.29, 95%CI (-3.97, -0.61), P = 0.008] (Fig. 3).
Fig. 3Meta-analyses of del Nido cardioplegia versus cold blood Cardioplegia, comparing the levels of myocardial injury markers 24 h after surgery and postoperative left ventricular ejection fraction. A, CTn I; B, CTn T; C, CK-MB; D, LVEF
Seven studies assessed postoperative LVEF, there were no differences in preoperative ejection fraction in selected studies. Pooling the data of these studies showed that the postoperative LVEF in DNC group was better than that in CBC group, and the difference between the two groups was not statistically significant [MD = 0.73, 95%CI (-0.44, 1.89), P = 0.22] (Fig. 3).
Postoperative clinical outcomeFive, seven and six studies were included in the evaluation of mechanical ventilation time, ICU stay time and hospital stay, respectively. The results of meta-analysis showed that there were no statistically significant differences in mechanical ventilation time, ICU stay time and hospital stay between DNC group and CBC group [MD=-0.17, 95%CI (-0.46, -0.13), P = 0.27; MD=-0.02, 95%CI (-0.34, -0.30), P = 0.92; MD = 0.12, 95%CI (-0.04, 0.28), P = 0.14] (Fig. 4).
Fig. 4Meta-analyses of del Nido cardioplegia versus cold blood Cardioplegia, comparing clinical outcome. Outcomes assessed are (A) Mechanical ventilation time, (B) Intensive care unit stay time, (C) Hospital stay time, (D) Postoperative new-onset atrial fibrillation, (E) Postoperative stroke, (F) postoperative heart failure requiring intra-aortic balloon pump mechanical circulation support, and (G) In-hospital mortality. For each estimate, the grey shaded area is the weight of the estimate in proportion to the overall effect
The incidence of postoperative adverse events such as new atrial fibrillation, stroke, IABP support, and hospital death were evaluated. The results of meta-analysis showed that there were no statistically significant differences between the DNC group and the CBC group in postoperative adverse events, including postoperative new-onset atrial fibrillation, stroke, IABP requirement and in-hospital mortality[MD = 0.86, 95%CI (0.60, 1.22), P = 0.4; MD = 0.56, 95%CI (0.30, 1.08), P = 0.09; MD = 0.97, 95%CI(0.59, 1.59), P = 0.90; MD = 1.25, 95%CI (0.62, 2.51), P = 0.54] (Fig. 4).
Sensitivity analysis and publication bias assessmentSensitivity analysis showed that there was no significant change in the combined effect size of outcome indicators after one article was excluded separately. The funnel-plot was used to evaluate publication bias, the points in the image converge into a roughly symmetrical (inverted) funnel (Supplementary Figures S2).
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