Cytokine Hemoadsorption versus Standard Care in Cardiac Surgery Using the Oxiris Membrane: The OXICARD Single-center Randomized Trial

Abstract

Background: Cardiac surgery can lead to dysregulation with a proinflammatory state, resulting in adverse outcomes. Hemadsorption using the AN-69 membrane (Oxiris membrane, Baxter, USA) has the properties to chelate inflammatory cytokines. The authors hypothesized that in patients at high risk of inflammation, the use of the Oxiris membrane could decrease inflammation, preserve endothelial function, and improve postoperative outcomes.

Methods: The authors conducted a randomized single-center study at Amiens University Hospital (Amiens, France). The study population consisted of adult patients admitted for scheduled cardiac surgery with an expected cardiopulmonary bypass (CPB) time greater than 90 min. The patients were allocated to either the standard group or the Oxiris group. The intervention consisted of using the Oxiris membrane on a Prismaflex device (Baxter, USA) at a blood flow rate of 450 ml/min during CPB. The primary outcome was the assessment of microcirculation on day 1 after surgery by measuring sublingual microcirculation using the microvascular flow index. Microvascular flow index reflects the microcirculation flow type and is graded from 0 to 3 as follows: 0, no flow; 1, intermittent flow; 2, sluggish flow; 3, continuous flow. The secondary outcome was a composite adverse outcome within 30 days after surgery. Cytokines and endothelial biomarkers were measured in all patients at different time points. An intention-to-treat analysis was performed.

Results: From October 2019 to November 2022, the study included 70 patients. Two patients were excluded from the Oxiris group: one patient did not undergo surgery, and one procedure was performed under deep hypothermia. The microvascular flow index did not differ between groups on day 1 from baseline: difference (95% CI) Oxiris minus standard at -0.17 (-0.44 to 0.10); P = 0.2. The occurrence of a composite adverse outcome did not significantly differ between groups (14 [42%] for the Oxiris group vs. 12 [35%] for the standard group; P = 0.7). The overall variation in cytokines and angiopoietins did not significantly differ between groups.

Conclusions: In patients scheduled for a cardiac surgery with prolonged CPB, the authors could not demonstrate the benefit on microcirculation and major cardiovascular events.

Fig. 1.

Study flow chart. Cytocam device (Braedius Medical, The Netherlands); Oxiris (Baxter, USA).

Fig. 2.

Sublingual microcirculation evolution from baseline to day 2 after surgery. Oxiris (Baxter, USA). CPB, cardiopulmonary bypass; MFI, microcirculatory flow index.

Fig. 3.

Cytokines and angiopoietin levels from baseline to day 2 after surgery. Oxiris (Baxter, USA). ANG, angiopoietin; CPB, cardiopulmonary bypass; IL, interleukin; TIE, tyrosine kinase with immunoglobulin; TNF, tumor necrosis factor.

Fig. 4.

Human umbilical vein endothelial cells viability at baseline and at 6 h after cardiopulmonary bypass (CPB). Coincubation with plasma from the standard group and the Oxiris (Baxter, USA) group. ns, nonsignificant.