Del Nido cardioplegia has evolved from a pediatric innovation into a globally adopted myocardial protection strategy for adult cardiac surgery, valued for its single-dose delivery, simplicity, and reliable protection during prolonged ischemic intervals. In this authoritative review, Kantathut synthesizes experimental, observational, and randomized clinical evidence evaluating whether the original Plasma-Lyte A–based del Nido formulation can be safely and effectively modified using alternative base solutions. The motivation for this inquiry is both practical and global: Plasma-Lyte A, while physiologically ideal, is costly and not universally available, particularly in resource-limited settings.
The review begins by revisiting the original del Nido formulation, highlighting the deliberate design choices that enable rapid depolarized arrest and prolonged myocardial quiescence. Potassium chloride induces arrest, lidocaine stabilizes sodium channels, magnesium mitigates calcium overload, mannitol reduces edema and oxidative stress, and sodium bicarbonate buffers acidosis. Plasma-Lyte A was selected as the crystalloid base because of its near-physiologic electrolyte composition, calcium-free profile, and buffering capacity via acetate and gluconate. However, these advantages also define the benchmark against which alternative solutions must be judged.
Normal saline emerges as one of the most widely studied substitutes due to its universal availability and low cost. Despite theoretical concerns related to hyperchloremic metabolic acidosis, lack of intrinsic buffering, and slightly hypertonic properties, cumulative evidence from animal models, adult randomized trials, and even veterinary cardiac surgery demonstrates equivalent myocardial protection when saline-based del Nido cardioplegia is appropriately buffered. Clinical outcomes—including cardiac biomarkers, ventricular function, arrhythmia rates, and survival—are comparable to standard formulations, supporting normal saline as a viable option, particularly where balanced crystalloids are inaccessible.
Lactated Ringer’s solution (LRS) represents the most extensively evaluated balanced alternative. Although it contains calcium and is slightly hypotonic, features that initially raised concern for calcium overload and cellular edema, multiple randomized controlled trials and multicenter experiences—including several led by the author—have demonstrated its safety and efficacy in both adult and pediatric populations. Biochemical markers of myocardial injury and key clinical outcomes such as ejection fraction, ICU stay, arrhythmia incidence, and mortality are largely indistinguishable from Plasma-Lyte A–based del Nido cardioplegia. Minor biochemical differences observed in some studies have not translated into adverse clinical outcomes, reinforcing LRS as a cost-effective and globally practical alternative.
Plain Ringer’s solution, lacking any buffer system, has also been evaluated. While its absence of lactate or acetate theoretically predisposes patients to metabolic acidosis, clinical trials in pediatric and adult cardiac surgery show noninferiority when bicarbonate supplementation is included in the cardioplegia mixture. These findings are particularly relevant for developing regions, where plain Ringer’s is often readily available and inexpensive.
Isolyte S and Ionosteril, both balanced multi-electrolyte solutions designed to mimic plasma composition, are presented as physiologically elegant substitutes. Isolyte S is calcium-free and closely parallels Plasma-Lyte A, while Ionosteril contains small amounts of calcium and magnesium with acetate-gluconate buffering. Evidence from CABG and minimally invasive mitral valve surgery demonstrates equivalent or improved biochemical markers of myocardial protection and favorable clinical outcomes compared with blood cardioplegia or Custodiol. These solutions may be especially attractive in regions where Plasma-Lyte A is unavailable but balanced crystalloids are accessible.
The review also explores whole-blood del Nido cardioplegia, in which the crystalloid component is entirely replaced with oxygenated autologous blood. This approach enhances buffering capacity, oxygen delivery, and oncotic pressure while minimizing hemodilution. Retrospective and observational studies in adult CABG populations, including patients with reduced ejection fraction, suggest reduced myocardial injury markers, improved renal protection, and shorter bypass times without compromising safety.
In its forward-looking discussion, the article emphasizes the need for standardized formulations, multicenter randomized trials, and detailed analyses of final delivered electrolyte compositions after mixing additives and blood. Long-term outcomes, pharmaceutical stability, and personalized cardioplegia strategies tailored to patient-specific factors are identified as critical areas for future research.
Overall, this review convincingly demonstrates that del Nido cardioplegia is not dependent on a single proprietary crystalloid. When appropriately buffered and supplemented, multiple alternative base solutions can provide equivalent myocardial protection, enabling broader, safer, and more cost-effective implementation of this technique worldwide.
