Effectiveness of Cardiopulmonary Bypass Priming with Albumin, Gelofusine and Crystalloids with Retrograde Autologous Priming in Preventing Microcirculatory Dysfunction in Patients during Coronary Artery Bypass Graft Surgery - (PRIME) a Double-Blind Randomized Trial

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Abstract

Introduction

Cardiopulmonary bypass (CPB) can cause endothelial dysfunction, leading to edema formation, disturbed microcirculatory perfusion, and impaired tissue oxygenation. Together, these factors contribute to organ dysfunction in patients undergoing cardiac surgery. We hypothesis that the composition of CPB prime fluids influences endothelial function and prevents microcirculatory dysfunction. We assessed the impact of three different CPB prime fluid strategies on microcirculatory perfusion in adult patients undergoing coronary artery bypass graft surgery.

Methods

Thirty-four patients were subjected to CPB primed with 1500 mL of either albumin/ringers, gelofusine/ringers, or solely ringers plus retrograde autologous priming (RAP). All three priming solutions included 100 mL of mannitol. The primary outcome was perfused vessel density (PVD) assessed by sublingual microcirculatory imaging at 5 time points (after anesthesia induction, aortic cross-clamping, weaning from CPB, upon intensive care unit arrival (ICU), and 24 hrs after ICU arrival) as main marker of microcirculatory perfusion. Secondary outcomes included total vessel density, proportion of perfused vessels, microvascular flow-, and heterogeneity index (as additional markers of microcirculatory perfusion), colloid oncotic pressure (COP), albumin, glycocalyx shedding-, endothelial-, inflammation- and renal injury markers, hemoglobin, hematocrit, hemolysis index, transfusion volumes, fluid balance and fluid requirements.

Results

CPB immediately impaired PVD across all groups (albumin/ringers estimated mean difference between baseline and arrival ICU -7.56 95% CI [-11.53 to -3.59] mm mm −2 , gelofusine/ringers -4.10 [-7.53 to -0.67] mm mm −2 , and ringers plus RAP -3.77 [-6.64 to -0.90] mm mm −2 ), persisting until ICU arrival without differences between groups. In patients receiving gelofusine/ringers COP was preserved after aortic cross clamping, and was associated with lower intraoperative fluid requirements and fluid balances compared to those receiving albumin/ringers or ringers plus RAP. Levels of inflammatory (interleukin-6) and endothelial damage markers (angiopoietin-2) were higher in patients receiving albumin/ringers compared with those receiving gelofusine/ringers, and ringers plus RAP.

Conclusion

All of the three CPB priming strategies - albumin/ringers, gelofusine/ringers or ringers plus RAP – similarly induced perioperatieve microcirculatory dysfunction in patients undergoing CABG surgery. These findings suggest that none of these prime fluid strategies confers protection for microcirculatory perfusion during cardiac surgery. Albumin priming resulted in increased inflammatory markers at 24 hrs after surgery.

Trial registration

ClinicalTrials.gov, NCT05647057 . Registered on 04/25/2023. ClinicalTrials.gov PRS: Record Summary NCT05647057 , all items can be found in the protocol.

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