Custodiol versus Plegisol: A phase 3 multicentre myocardial protection study.

Background: While considered simple and effective, crystalloid antegrade cardioplegia solutions have had few prospective multicentre comparison trials.

Methods: A commercial intracellular-type histidine-tryptophan-ketoglutarate (HTK) cardioplegia solution (Custodiol HTK; Köhler Chemie GmbH, Germany) designed for 4 h of protection after a single administration was compared with a standard extracellular multidose product (Plegisol [PL]; Hospira Inc, USA) in an open-label, randomized, prospective seven-institution trial. A total of 136 isolated coronary bypass patients were randomly assigned into two groups and stratified by ejection fraction into categories of 40% or greater (n=118) and 20% to 39% (n=18).

Results: The mean age of the study cohort was 62 years, of which 94% were men. Seventy per cent of patients had Canadian Cardiovascular Society class III angina and 75% had three-vessel disease anatomy. Cross-clamp times were nearly identical for patients in both cardioplegia groups; however, defibrillation was needed less often for patients who were treated with HTK (64% versus 91%, P<0.01). Hospital and intensive care unit stays, creatine kinase isoenzyme MB curves, cardiac outputs, inotrope levels, and deaths or serious adverse events (PL=13, HTK=14) were very similar between groups. Logistic regression showed that myocardial infarction or possible treatment-related adverse events were associated with high cardiac troponin I (cTn-I) levels 6 h after the procedure (P=0.001), and HTK treatment (OR 3.5, P=0.01). The primary study end point (6 h post-ischemia cTn-I) favoured PL (16.7±13.2 μg/L versus 20.3±13.5 μg/L, P=0.01). Patients who underwent circumflex grafting had higher cTn-I levels with HTK (P<0.001) and 48% required reinfusions due to cardiac warming. Longer intervals between doses correlated with high cTn-I levels (P=0.02). HTK provided prolonged protection with low cTn-I release (10 μg/L or less), although this occurred less frequently than with PL (17 versus 27 patients, P=0.06).

Conclusions: HTK caused more structural protein release and adverse events than PL, even when reinfusion was implemented.