Cardiac surgery requiring cardiopulmonary bypass exposes the heart to a period of global ischemia followed by reperfusion. Although cardioplegia is specifically designed to protect the myocardium during this process, ischemia-reperfusion injury remains an important cause of postoperative myocardial damage. Oxidative stress, calcium overload, mitochondrial dysfunction, inflammation, and cellular injury all contribute to this phenomenon. Postoperative cardiac troponin elevation provides an important measure of myocardial injury and has also been associated with adverse outcomes after cardiac surgery. Against this background, researchers have investigated whether propofol might provide additional myocardial protection when incorporated directly into cardioplegic solutions.
Propofol is best known as an intravenous anesthetic, but experimental research has suggested several potentially cardioprotective properties. These include antioxidant, anti-inflammatory, and antiapoptotic effects. Laboratory studies indicate that propofol can decrease lipid peroxidation and reactive oxygen species while influencing mitochondrial mechanisms involved in ischemia-reperfusion injury. These biological effects created a compelling rationale for supplementing cardioplegia with propofol. However, individual randomized clinical trials have produced conflicting results, raising the question of whether laboratory cardioprotection actually translates into meaningful benefits for cardiac surgery patients.
To address that question, Rios Esparza and colleagues conducted a systematic review and meta-analysis of randomized controlled trials comparing propofol-supplemented cardioplegia with control cardioplegia. Their analysis was notable for combining traditional frequentist statistics with Bayesian modeling. The investigators searched PubMed, Cochrane, and Web of Science through April 2026 and ultimately identified five eligible randomized controlled trials involving 523 adult patients. Of these, 261 received propofol-supplemented cardioplegia and 262 received control treatment. The trials included patients undergoing coronary artery bypass grafting, aortic valve replacement, or mixed cardiac surgical procedures requiring cardiopulmonary bypass.
The primary endpoint was postoperative cardiac troponin. Across all five trials, conventional meta-analysis found no statistically significant difference between propofol and control groups. The Bayesian model similarly produced a pooled standardized mean difference of −0.05, with a 95% credible interval extending from −0.33 to 0.24. Importantly, the Bayesian analysis estimated a 70.8% posterior probability that propofol produced some reduction in postoperative troponin.
That result requires careful interpretation. A 70.8% probability of any benefit does not mean there is strong evidence that propofol provides clinically important myocardial protection. Instead, the available evidence leans modestly toward benefit while retaining considerable uncertainty regarding both the size and even the direction of the true treatment effect. The credible interval crosses the point of no effect, and the authors therefore concluded that the evidence is insufficient to establish definitive cardioprotection.
Secondary clinical outcomes told a similar story. Postoperative creatinine demonstrated a 59.8% Bayesian probability of benefit, while serious complications had a 70.3% probability of benefit. Postoperative arrhythmias had only a 56.4% probability of improvement. None of these findings established a convincing treatment advantage. Propofol supplementation also failed to produce a meaningful improvement in intensive care unit or hospital length of stay. The posterior probability of benefit for ICU length of stay was just 46.2%.
The study also highlights the substantial variation among existing propofol cardioplegia protocols. Propofol concentrations in the included trials ranged from 4 to 10 mg/mL, while cardioplegic strategies included warm blood, cold blood, cold crystalloid, and St. Thomas cardioplegia. These differences matter because temperature and the cardioplegic vehicle could affect propofol pharmacokinetics and myocardial exposure. Propofol is highly lipophilic and protein bound, potentially making its biological availability different in blood-based versus crystalloid cardioplegia.
Another possible explanation for the absence of a clear incremental benefit is therapeutic overlap. Many patients in the included trials were already exposed to systemic propofol or volatile anesthetics during anesthesia. Because these anesthetic strategies may themselves influence myocardial protection, adding propofol directly to cardioplegia could provide little additional benefit beyond the protection already present.
Methodologically, the analysis has several strengths. Four of the five included randomized trials were judged to have a low risk of bias, while one raised some concerns. The investigators performed leave-one-out sensitivity analyses, prespecified subgroup analyses, GRADE assessments, and both frequentist and Bayesian random-effects modeling. The Bayesian methodology is particularly useful because it moves beyond the simple question of whether a result crosses a conventional statistical significance threshold and estimates the probability that an intervention actually provides benefit.
Nevertheless, the evidence base remains limited. Only five randomized trials and 523 patients were available, reducing statistical power for detecting modest treatment effects and uncommon complications. Several secondary outcomes demonstrated substantial heterogeneity. The trials also varied in surgical population, cardioplegia composition, temperature, propofol concentration, and anesthetic management. Long-term mortality could not be meaningfully pooled because it was not consistently reported.
The authors therefore conclude that adding propofol to cardioplegic solution does not currently have sufficient evidence to justify routine clinical use. Importantly, the analysis does not demonstrate that the strategy is harmful or prove that propofol has absolutely no cardioprotective effect. Rather, existing randomized evidence fails to demonstrate a sufficiently certain or clinically meaningful advantage over standard cardioplegia.
For cardiac surgery teams, the practical message is straightforward: propofol-supplemented cardioplegia remains biologically interesting but clinically unproven. The Bayesian findings suggest a possible signal toward myocardial protection, yet the magnitude of that potential benefit remains uncertain. Larger randomized trials employing standardized cardioplegia protocols, consistent propofol dosing, and clinically important outcomes will be necessary to determine whether particular patient or procedural groups can benefit. Until stronger evidence emerges, routine addition of propofol to cardioplegia cannot be recommended and should remain at the discretion of the institutional heart surgery team.
