Pretreatment with glucose–insulin–potassium improves ventricular performances after coronary artery bypass surgery: a randomized controlled trial

Abstract

Heart failure is the main cause of poor outcome following open heart surgery and experimental studies have demonstrated that glucose-insulin-potassium (GIK) infusion exerts cardioprotective effects by reducing myocardial ischemia-reperfusion injuries. This randomized controlled trial was designed to assess the effects of GIK on left ventricular function in moderateto-high risk patients undergoing on-pump isolated coronary artery bypass surgery (CABGS), or combined with aortic valve replacement. The primary outcomes were the effects of GIK on two-and three-dimensional left ventricular ejection fraction (2D and 3D-LVEF), and on transmitral flow propagation velocity (Vp), that occurred between the pre-and post-CPB periods. GIK administration was associated with favorable interaction effects (p < 0.001) on 2D-LVEF, 3D-LVEF and Vp changes over the study periods. In GIK pretreated patients (N = 54), 2-D and 3D-LVEF and Vp increased slightly during surgery (mean difference [MD] + 3.5%, 95% confidence interval [95% CI] − 0.2 to 7.1%, MD + 4.0%, 95% CI 0.6-7.4%, and MD + 22.2%, 95% CI 16.0-28.4%, respectively). In contrast, in the Placebo group (N = 46), 2D-and 3D-LVEF, as well as Vp all decreased after CPB (MD − 7.5% [− 11.6 to − 3.4%], MD − 12.0% [− 15.2 to − 8.8%] and MD − 21.3% [− 25.7 to − 16.9%], respectively). In conclusion, the administration of GIK resulted in better preservation of systolic and diastolic ventricular function in the early period following weaning from CPB.

Cardiometabolism as an Interlocking Puzzle between the Healthy and Diseased Heart: New Frontiers in Therapeutic Applications

“…Resulting findings confirmed an improvement of clinical outcomes [282,283]. Moreover, a randomized controlled trial on patients undergoing cardiopulmonary bypass found that GIK administration contributes to preserve cardiac muscle function [284] (Table 3).…”

Problems of subgroup analysis in randomized controlled trial

“…The principal findings of both publications and of another very recent publication by the same group of authors [ 3 ] are basically identical, that is, glucose-insulin-potassium (GIK) infusion before start of cardiopulmonary bypass (CPB) improves LV function after open heart surgery. This creates the impression that three independent investigations [ 1 – 3 ] have documented a benefit of GIK-infusion during on-pump cardiac surgery. However, the publication by Licker et al [ 1 ] reports findings in a post hoc defined subgroup of patients already included and analyzed in the first publication assessing the identical outcome, although the title states that this is a secondary analysis of the previously reported randomized controlled trial [ 2 ].…”

“…Foremost, all of the reported patients were included in a previous publication by the same group of authors [2]. The principal findings of both publications and of another very recent publication by the same group of authors [3] are basically identical, that is, glucose-insulin-potassium (GIK) infusion before start of cardiopulmonary bypass (CPB) improves LV function after open heart surgery. This creates the impression that three independent investigations [1][2][3] have documented a benefit of GIK-infusion during on-pump cardiac surgery.…”

Accountability, research transparency and data reporting

“…Given the bulk of data collected over the perioperative period (> 300 items), the main clinical results of this randomized controlled trial were first reported [ 2 ] and the functional results were separately reported and focusing on subsets of patients with coronary artery disease and severe aortic stenosis (given the different baseline-characteristics of the TEE parameters) [ 1 , 3 ]. As stated in the protocol approved by the ethics committee, TEE measurements were pre-specified and the analysis of the functional changes occurring after GIK infusion and following weaning from cardiopulmonary bypass provided the unique opportunity to investigate the inotropic and lusitropic effects induced by GIK administration before aortic cross-clamping as well as the cardioprotective effects related to GIK infusion following the myocardial ischemic period.…”