Histidine–tryptophan–ketoglutarate solution versus multidose cardioplegia for myocardial protection in cardiac surgeries: a systematic review and meta-analysis

Abstract

Background Surgical procedures in the heart requires protection of the heart from ischemia–reperfusion injury. Cardioplegia is the primary myocardial protective method in use. Histidine–tryptophan–ketoglutarate (HTK) solution is an intracellular cardioplegic solution that was initially used to preserve organs for transplantation. Methods A systematic electronic search was conducted in July 2021, in four databases; PubMed, Scopus, Web of Science, and Cochrane Library for eligible randomized controlled trials. The results were screened and the eligible trials were identified. Thereafter, the relevant data were extracted and pooled as mean difference or risk ratio, and 95% confidence interval in an inverse variance method using RevMan software. Results This review included 12 trials (n = 1327). HTK solution has resulted significantly in shorter intensive care unit stay (MD = − 0.09; 95% CI [− 0.15, − 0.03], p = 0.006), and shorter hospital stay (MD = − 0.51; 95% CI [− 0.71, − 0.31], p < 0.00001). Moreover, the patients who received the HTK solution had significantly lower levels of creatine kinase (after 4–7 h (MD = − 157.52; 95% CI [− 272.31, − 42.19], p = 0.007), and 24 h (MD = − 136.62; 95% CI [− 267.20, − 6.05], p = 0.04)), as well as creatine kinase muscle brain band (after 44–48 h (MD = − 3.35; 95% CI [− 5.69, − 1.02], p = 0.005)). Conclusion HTK solution had the same efficacy and safety as other cardioplegic solutions in most of the clinical parameters. Furthermore, the solution showed superiority in fastening the recovery and protecting the myocardium at the biochemical level. HTK solution provides longer myocardial protection; therefore, it limits surgical interruption. HTK solution can be used as an alternative to the currently used cardioplegic solutions.

Comparison of Bretschneider’s Histidine–tryptophan–ketoglutarate Cardioplegia Solution and Conventional Blood Cardioplegia Solution in Terms of Postoperative Acute Kidney Injury and Outcome Parameters

“…The mannitol in the solution contributes to the maintenance of cellular osmolarity. [10] The cardiac effects of the BHTK solution have been extensively studied in the literature; however, the number of studies systematically investigating the metabolic changes induced by these solutions in other vital organs remains limited.…”

“…Based on the results of a recent large meta-analysis comparing BHTK and blood cardioplegia for myocardial protection, BHTK solution was found to have the same efficacy and safety as other cardioplegic solutions in most clinical parameters. [10] IS or the need for inotropes, IABP use, arrhythmia incidence, and cardiac biomarkers are the parameters evaluated while detecting myocardial damage in an openheart surgery. [9,[14][15][16] In a prospective randomized study comparing blood and BHTK cardioplegia with a total of 345 patients undergoing AVR, no significant difference was found between the two groups in terms of spontaneous sinus rhythm, inotropic agent use, AF development, mechanical ventilation duration, perioperative myocardial ischemia, and mortality after opening the aortic cross-clamp.…”

Comparison of “Huaxi-1” or “histidine-tryptophan-ketoglutarate” cardioplegia in an animal model

“…Chinese hospitals typically prepare cardioplegia solutions in-house according to internal practices, or they purchase the entirely crystalloid cardioplegia solution “histidine-tryptophan-ketoglutarate” (HTK) ( 4 ), which is the only cardioplegia formulation commercially available in the country and is widely used in other countries ( 5 , 6 ). HTK cardioplegia can effectively protect the myocardium by reducing energy metabolism ( 1 , 7 ). Nevertheless, our medical center, where more than 2,000 cardiac surgeries are performed each year, routinely uses an in-house formulation called “Huaxi-1” cardioplegia solution, which was developed in 2007 by mixing blood and custom-designed crystalloid.…”

Datasheet1.xls

“…Chinese hospitals typically prepare cardioplegia solutions in-house according to internal practices, or they purchase the entirely crystalloid cardioplegia solution "histidinetryptophan-ketoglutarate" (HTK) (4), which is the only cardioplegia formulation commercially available in the country and is widely used in other countries (5,6). HTK cardioplegia can effectively protect the myocardium by reducing energy metabolism (1,7). Nevertheless, our medical center, where more than 2,000 cardiac surgeries are performed each year, routinely uses an in-house formulation called "Huaxi-1" cardioplegia solution, which was developed in 2007 by mixing blood and custom-designed crystalloid.…”