The morbidity and mortality associated with cardiac surgery using CPB remains high despite advances in surgical technique, anesthesia management and CPB technology. However, myocardial I/R injury is still an important factor affecting patients' cardiac function and clinical prognosis. Ischemic preconditioning and/or postconditioning[23,24] has been reported to be effective in reducing myocardial I/R injury. This method did not translate into clinical practice partially due to difficulty in application of ischemic conditioning[24]. Remote ischemic preconditioning (RIPC) prior to cardiac surgery is non-invasive, but recent clinical studies and meta-analysis did not show its benefits on clinical outcomes[25]. Therefore, pharmacological preconditioning or postconditioning has better research and clinical prospects. Even multiple drugs were assessed[1,20], but none proved to be beneficial in large scale studies for myocardial protection. Now, intralipid may play a novel and potential role in cardioprotection with bright prospect[ 3-7].
Intralipid, a safe fat emulsion for human use, is used commonly as a component of parenteral nutrition in clinical practice. It also is used as therapy for severe cardiotoxicity secondary to accidental overdose of local anesthetics, an effect that has been confirmed in animals and humans[8-11]. Because patients with local anesthetic-induced cardiac arrest are considered to be less responsive for standard resuscitation methods, currently infusion of lipid emulsion is considered the primary treatment for local anesthetic toxicity[10,11]. In recent years, another striking experimental finding is that intralipid postconditioning(ILPC) could reduce myocardial I/R injuries and thus improve cardiac function, where intralipid was administered as a bolus at the onset of reperfusion[12-17]. So, intralipid may represents a novel and clinically feasible cardioprotective strategy that is highly effective in remodeled hearts. Does the protective effect of lipid emulsion play some role in the effects of propofol (where 10% lipid emulsion is the vehicle) that have been noted in myocardial I/R injury[26]? Therefore, it is necessary that the cardioprotective effects of intralipid need to be clinically verified separately.
Our research group has conducted a pilot study and showed promising results that ILPC induced a significant reduction of postoperative cTnT and CK-MB release in patients undergoing cardiac valve replacement surgery[18,19]. Moreover, a single intravenous bolus of intralipid(2 mL/kg, 20% intralipid) did not bring abnormal lipid metabolism and was found to be safe, with no perioperative hepatic or renal dysfunction or any other significant related complications[18,19]. However, the sample size of the pilot study is small, and it is uncertain to know its influence on patient outcome. Here, we continue to conduct a large sample RCT to further study whether it could improve the cardiac function, the short-term and long-term clinical prognosis of adult cardiac surgery patients, not limited to valve replacement surgery. To our knowledge, this is the first clinical trial investigating the effects of intralipid postconditioning on patient outcome, including mortality, morbidity and long-term life quality. Our data will provide a rationale for the evaluation of the potentially clinically relevant benefit of intralipid therapy.
Our research has certain limitations. First of all, due to intralipid being white emulsion, it was difficult to achieve the blinding of anesthetists and perfusionists. So even they will provide the trial intervention, but they will not be involved in either the postoperative treatment or the analysis. Secondly, since the inhaled anesthetic sevoflurane is considered to be significantly cardioprotective and the high-dose propofol has also been reported to have a certain myocardial protective effect[26-28], both of which are currently widely used in clinical anesthetics, how to reduce their interference on the results of intralipid postconditioning is of great importance. In our previous pilot study[18,19], all included patients were given total intravenous anesthesia to eliminate the interference of sevoflurane. However, this does not rule out the role of propofol and is also not consistent with clinical practice. Therefore, in this large-sample RCT, we do not limit the anesthesia methods, but will make strict statistics on the dosage of various anesthetics in the intervention group and the control group, so as to ensure the baseline data be comparable. Thus, the confounding factors and interference of the anesthetics will be effectively avoided, and at the same time, it was more consistent with the clinical routine.
In summary, this large sample RCT will be the first to explore the intralipid postconditioning on the clinical outcome of adult cardiac surgery patients. The results are expected to provide potential evidences about whether intralipid postconditioning could reduce the morbidity and mortality, improve the cardiac function and quality of life. Therefore, provide a rationale for the evaluation of the potentially clinically relevant benefit of intralipid therapy.