A randomized trial of 58 adults compared lactated Ringer’s–based modified del Nido with Custodiol cardioplegia. Modified del Nido produced lower 24-hour troponin I, faster arrest, fewer episodes of ventricular fibrillation, and less inotropic support. Ventilation and ICU recovery also favored modified del Nido, but ejection fraction and myocardial infarction did not differ significantly. The small single-center sample and reporting concerns limit confidence in broad clinical adoption. Read more.
Why this cardioplegia comparison matters
Choosing a cardioplegia solution involves balancing myocardial protection, workflow, availability, and the needs of the individual operation. Long-acting solutions can reduce interruptions during aortic cross-clamping, but fewer interruptions alone do not demonstrate better protection. Abdelhady and colleagues compared modified del Nido cardioplegia with Custodiol in adults undergoing elective cardiac surgery. Their study provides a useful direct comparison, with favorable biochemical and early recovery findings for modified del Nido. Its results warrant attention, although they do not establish a universal preferred solution.
The distinction between modified and conventional del Nido is important. This investigation used lactated Ringer’s as the crystalloid base rather than Plasma-Lyte A. The authors describe this modification as relevant where Plasma-Lyte A is difficult to obtain. Findings from this specific preparation and administration protocol should therefore not automatically be applied to every formulation called del Nido, every dosing strategy, or every surgical population.
Study design and patient selection
The prospective randomized trial enrolled 58 adults at Fayoum University Hospitals in Egypt between February 2022 and November 2023. Twenty-nine received modified del Nido and 29 received Custodiol. Eligible operations were elective coronary artery bypass grafting or single-valve replacement. Emergency procedures, redo operations, chronic kidney disease, hepatic impairment, and severe psychiatric illness were excluded. Participants were relatively young for an adult cardiac surgery population, with mean ages of approximately 42 years in both groups.
Investigators report computer-generated randomization, allocation using opaque envelopes, and blinding of participants, researchers, and data collectors. A separate anesthesiology intern prepared and administered the solution. Ethical approval and trial registration, NCT05221294, are reported. These are methodological strengths, but the published description does not fully clarify how differences in solution preparation and delivery were concealed from every clinician involved in perioperative decisions.
The primary endpoint was troponin I measured 24 hours after surgery. Secondary endpoints included arrest time, reperfusion ventricular fibrillation, inotropic support, CK-MB, lactate, ejection fraction, ventilation duration, ICU and hospital stays, myocardial infarction, and mortality. The sample-size calculation targeted a troponin difference using earlier research; it was not designed to reliably establish differences in rare complications or survival.
What the teams actually compared
Both groups received cold antegrade cardioplegia through the aortic root or coronary ostia as appropriate. The modified del Nido solution used a crystalloid-to-blood ratio of 4:1, with a reported initial dose of 20 mL/kg capped at 1,000 mL and possible redosing after 90 minutes. Custodiol was given at 25 mL/kg over six to eight minutes. Reported administration temperatures were 4°C for modified del Nido and 4–8°C for Custodiol.
This was a comparison of complete treatment protocols, rather than an experiment isolating a single ingredient. The solutions differed in composition, blood content, delivery characteristics, and redosing provisions. Total cardioplegia volume had a median of 1,500 mL in each group and did not differ significantly. Cross-clamp and bypass durations also showed no statistically significant between-group differences. Thus, the reported benefit cannot simply be attributed to demonstrated reductions in ischemic time or total bypass exposure.
Biochemical myocardial injury and rhythm recovery
Median 24-hour troponin I was 2.9 µg/L with modified del Nido versus 3.6 µg/L with Custodiol, with interquartile ranges of 2.7–3.2 and 3.1–4.1, respectively; the reported p value was below 0.001. CK-MB was also lower: medians were 41 versus 44 U/L, with p = 0.043. These findings support a signal of lower postoperative myocardial enzyme release under the study conditions. They do not independently establish fewer clinically important infarctions or better long-term function.
Arrest occurred more quickly with modified del Nido: median 20 versus 30 seconds, p < 0.001. Ventricular fibrillation after cross-clamp removal occurred in 4 of 29 patients, or 13.8%, compared with 12 of 29, or 41.4%, in the Custodiol group. The reported relative risk was 0.333, with a 95% confidence interval of 0.122–0.913. Inotropic support was required in 15 of 29 versus 23 of 29 patients, corresponding to 51.7% versus 79.3%.
For perfusionists, arrest time and rhythm recovery are meaningful operational observations. Nevertheless, the inotrope endpoint was recorded as a yes-or-no requirement. Without a standardized vasoactive-inotropic score, duration of support, cardiac output, or cardiac index, it cannot quantify the severity of postoperative circulatory dysfunction. A reduced requirement for any inotrope is encouraging, but is not equivalent to proof that low cardiac output syndrome was prevented.
Recovery outcomes and findings that did not change
Median time to liberation from mechanical ventilation was four hours with modified del Nido and five hours with Custodiol, p = 0.004. Median ICU stay was two versus three days, p = 0.015. Hospital stay also differed statistically, p = 0.018, but both groups had a median hospital stay of four days; their interquartile ranges differed. Reporting this as a one-day reduction in median hospital stay would therefore be inaccurate.
Neither postoperative ejection fraction nor its percentage change differed significantly. Myocardial infarction occurred in one modified del Nido patient and two Custodiol patients, a nonsignificant difference. No deaths and no new postoperative atrial fibrillation were reported. Lactate at 24 hours did not differ significantly. These negative findings are central to interpretation: a small study with few events cannot prove equivalent safety, and favorable biomarker results should not be presented as demonstrated survival or infarction benefits.
Limitations and reporting concerns
Several issues temper confidence. This was a small study from one center with a selected elective population and short follow-up. Emergency surgery, reoperations, and important organ dysfunction were excluded. The authors acknowledge that preoperative risk scoring, such as EuroSCORE, was not incorporated. A single postoperative enzyme measurement also provides less information than serial measurements or a clearly defined peak or cumulative release.
The published troponin confidence interval is internally problematic: Table 2 gives a median difference of −0.7 µg/L with a 95% interval written as −1.0 to −3.0. That interval is reversed and does not contain the stated estimate. The methods also appear to give an inconsistent unit for the potassium chloride stock solution. These are reporting concerns requiring author clarification; this review does not silently correct them or reproduce the preparation as a validated compounding recipe.
Numerous secondary endpoints were tested, and the report does not describe adjustment for multiple comparisons. Length of stay and ventilation depend partly on local care and discharge practices. A statistically significant secondary result, especially with a small sample and a borderline p value, should be interpreted alongside these factors. The absence of a difference in a rare event is especially uninformative when each group contains only 29 people.
Clinical interpretation for perfusion practice
This trial supports further investigation of lactated Ringer’s–based modified del Nido as an alternative to Custodiol for selected adult CABG and single-valve procedures. Its strongest contribution is the primary troponin finding, accompanied by faster arrest and favorable early rhythm recovery. It does not justify claiming superior survival, confirmed protection against infarction, or universal suitability for complex or prolonged operations.
Institutional evaluation should consider the exact formulation, validated preparation processes, delivery system, redosing strategy, patient selection, and team experience. The paper discusses potential resource and cost advantages, but it did not conduct a formal economic evaluation. Larger multicenter trials with standardized hemodynamic endpoints, serial biomarkers, longer follow-up, and reliable reporting are needed to determine whether the observed biochemical differences translate into durable patient benefit.
Keywords: Modified Del Nido, Custodiol, Cardioplegia, Myocardial Protection, Adult Cardiac Surgery, Cardiopulmonary Bypass, Troponin I, Randomized Clinical Trial, Reperfusion Arrhythmias, Lactated Ringer’s.
Source: Abdelhady MA, Goda AS, Sayed Gomaa MS, Hamed MA, Hassan AA. Modified Del Nido Versus Custodiol® Cardioplegia for Myocardial Protection in Adult Patients Undergoing Cardiac Surgery: A Prospective Randomized Double-Blinded Clinical Trial. Annals of Cardiac Anaesthesia. 2025;28(4):451–458. doi:10.4103/aca.aca_35_25. Original paper © 2025 the authors, published by Wolters Kluwer–Medknow under CC BY-NC-SA 4.0. This educational summary is an iPerfusion editorial appraisal of the uploaded paper.
