Adenosine in cold blood cardioplegia - a placebo-controlled study

Abstract

OBJECTIVE Adenosine as an additive in blood cardioplegia is cardioprotective in animal studies, but its clinical role in myocardial protection remains controversial. The aim of this study was to investigate whether the addition of adenosine in continuous cold blood cardioplegia would enhance myocardial protection. METHODS In a prospective double-blind study comparing adenosine 400 μmol l(-1) to placebo in continuous cold blood cardioplegia, 80 patients undergoing isolated aortic valve replacement were randomized into four groups: antegrade cardioplegia with adenosine (n = 19), antegrade cardioplegia with placebo (n = 21), retrograde cardioplegia with adenosine (n = 21) and retrograde cardioplegia with placebo (n = 19). Myocardial arteriovenous differences in oxygen and lactate were measured before, during and after aortic occlusion. Myocardial concentrations of adenine nucleotides and lactate were determined from left ventricular biopsies obtained before aortic occlusion, after bolus cardioplegia, at 60 min of aortic occlusion and at 20 min after aortic occlusion. Plasma creatine kinase (CK-MB) and troponin T were measured at 1, 3, 6, 9, 12 and 24 h after aortic occlusion. Haemodynamic profiles were obtained before surgery and 1, 8 and 24 h after cardiopulmonary bypass. Repeated-measures analysis of variance was used for significance testing. RESULTS Adenosine had no effects on myocardial metabolism of oxygen, lactate and adenine nucleotides, postoperative enzyme release or haemodynamic performance. When compared with the antegrade groups, the retrograde groups showed higher myocardial oxygen uptake (17.3 ± 11.4 versus 2.5 ± 3.6 ml l(-1) at 60 min of aortic occlusion, P < 0.001) and lactate accumulation (43.1 ± 20.7 versus 36.3 ± 23.0 µmol g(-1) at 60 min of aortic occlusion, P = 0.052) in the myocardium during aortic occlusion, and lower postoperative left ventricular stroke work index (27.2 ± 8.4 versus 30.1 ± 7.9 g m m(-2), P = 0.034). CONCLUSIONS Adenosine 400 μmol l(-1) in cold blood cardioplegia showed no cardioprotective effects on the parameters studied. Myocardial ischaemia was more pronounced in patients receiving retrograde cardioplegia.

The Effects of Cold Blood Cardioplegia with and without Adenosine on Hemodynamic Status of Patients Undergoing Mitral Valve Surgery

“…Thus, despite demonstrating clinical benefits of adenosine to prevent cardiac ischemic injuries, due to the probability of drug-related adverse events, adenosine may not be used in patients candidate for valvular procedures, however our low study power because of small sample size and considering minimum dose of drug as a supportive, emphasizes further studies to prove or reject of our initial hypotheses. Similar to our study, Ahlsson et al in 2012 demonstrated that a combination of cold blood cardioplegia and adenosine 400 µmol/L showed no cardioprotective effects with regard to oxygen myocardial metabolism, lactate and adenine nucleotides, hemodynamic performance or postoperative enzyme release (13). No differences were found in two other large studies of pre-ischemic delivery of adenosine in either clinical performance or cardiac enzymatic release (14,15).…”

Hyperkalemic cardioplegia for adult and pediatric surgery: end of an era?

“…More recently, the same group showed in humans that the adenosine cardioplegia resulted in shorter times to arrest (11 vs. 44 s, P < 0.001) and lower postoperative atrial fibrillation (19 vs. 54% p = 0.01) compared with high potassium cardioplegia (20 mM) (Jakobsen et al, 2013). The discrepancy between Jacobsen's and previous adenosine cardioplegia studies (Schubert et al, 1989; Mentzer et al, 1999; Vinten-Johansen et al, 2003; Ahlsson et al, 2012) may be explained by their addition of local anesthetic (procaine) (Vinten-Johansen and Dobson, 2013). Dobson and colleagues have shown that adenosine plus a local anesthetic confers superior protection than adenosine alone (Dobson and Jones, 2004) (see Section Adenosine and Lidocaine (AL): A More Natural Way to Arrest, Protect, and Preserve the Heart).…”

Guidelines for enhanced recovery after cardiac surgery. Consensus document of Spanish Societies of Anesthesia (SEDAR), Cardiovascular Surgery (SECCE) and Perfusionists (AEP)

“…La miniplejia o solución de Calafiore, al carecer de otros componentes salvo sangre, potasio y magnesio, es especialmente eficaz a la vez que limita los efectos deletéreos de la hemodilución 324 Aunque se han propuesto modificaciones y aditivos a la composición de las soluciones de cardioplejia, no puede emitirse recomendación alguna ante la debilidad de la evidencia hallada, recomendándose respetar la formulación original de todas ellas; bien sean comercializadas, bien sean elaboradas en cada institución [325][326][327][328] . Si bien las soluciones de Del Nido, Custodiol, St. Thomas II o Celsior, permiten tiempos superiores al de las anteriormente citadas para la redosificación en pacientes adultos, no existe consenso sobre el protocolo de redosificación óptima, debiendo establecerse protocolos internos en cada institución basados en la literatura y respetados durante el procedimiento quirúrgico.…”