Physicochemical and microbiological stability of a del Nido Chikamori modification for pediatric cardiac surgery

Abstract Background Del Nido cardioplegia is a single-dose myocardial protective solution that is widely used in pediatric cardiac surgery. In Japan, several modified formulations have been developed because the original Plasma-Lyte A-based formulation is not available. The original formulation remains stable during refrigerated storage. However, the stability and sterility of the Chikamori-modified del Nido cardioplegia solution remain unknown. Therefore, this study evaluated the physicochemical stability and sterility of the Chikamori-modified del Nido cardioplegia solution during refrigerated storage. Methods Three batches of the Chikamori-modified del Nido solution were prepared aseptically and stored in the refrigerator. To assess electrolytes (sodium ion, potassium ion, chloride ion, magnesium ion, calcium ion, and bicarbonate ion), pH, osmolality, and lidocaine concentration, samples were collected on days 0, 7, 14, 21, and 28. To simulate clinical practice, 1 mL of 8.4% sodium bicarbonate per 100 mL was added immediately before measurement at each time point. Subsequently, gas analysis was performed. Sterility testing was conducted using the Japanese Pharmacopoeia direct method, and endotoxins were measured using a turbidimetric assay. A retrospective clinical review of patients undergoing cardiac arrest surgery with this solution was also carried out. Results The median storage temperature was 4.7 °C (range: 3.5–6.5 °C). The electrolyte levels, pH, and osmolality remained within 4% of the baseline values over 28 days, with lidocaine levels maintained within the acceptable range of 90%–110%. All sterility tests yielded negative results, and the endotoxin levels stayed below 0.8 pg/mL at all time points. In 67 clinical cases, a single dose of the del Nido cardioplegia solution was sufficient to cover ischemic durations with a median of 70 (interquartile range: 45–98) min without the need for additional dosing. The recovery of cardiac rhythm was favorable, and postoperative infections or adverse events were not observed. Conclusions The Chikamori-modified del Nido cardioplegia solution showed physicochemical and microbiological stability for at least 28 days at 3.5–6.5 °C. Extending the storage duration might reduce the frequency of preparation and waste. However, validation via larger, multicenter studies must be performed.