Background/Objectives: The optimal choice of cardioplegia solution in minimally invasive cardiac surgeries (MICS) remains debated, as prolonged myocardial protection is essential to avoid interruptions to the surgical flow, which can prolong aortic cross-clamp time and cardiopulmonary bypass time, especially in the constrained surgical field. We conducted a network meta-analysis to evaluate the safety and efficacy of the del Nido (DN), histidine-tryptophan-ketoglutarate (HTK), blood cardioplegia (BC), and St. Thomas’ (STH) solutions in MICS. 

 

Methods: Medical electronic databases were thoroughly searched without time restrictions, including all types of studies except for study protocols and animal research. The final search was completed in June 2024. Subsequently, a network meta-regression was performed on both primary and secondary endpoints, utilizing R (The R Foundation for Statistical Computing, version 3.6.2) for the analysis. Meta-analyses were carried out using Review Manager software. 

 

Results: A total of 15 studies, enrolling 2282 patients, were included in the analysis. None of the comparisons showed statistically significant differences in in-hospital mortality between the four cardioplegia solutions (BC vs. HTK, OR: 3.21, 95% CI: 0.13–80.84; DN vs. HTK, OR: 1.42, 95% CI: 0.28–7.23; STH vs. HTK, OR: 1.25, 95% CI: 0.19–8.20).

 

 Conclusions: In this network meta-analysis of cardioplegia solutions in MICS, no significant differences were observed in major clinical outcomes across the solutions. Cardioplegia solutions that provide long-lasting myocardial protection with a single dose, such as DN and HTK, were found to be safely applied in MICS. DN was associated with shorter CPB times and HTK was associated with shorter hospital stays, though these differences may not have clinical implications.