Transfusion of standard-issue packed red blood cells induces pulmonary vasoconstriction in critically ill patients after cardiac surgery-A randomized, double-blinded, clinical trial

Abstract

Background: Experimental and volunteer studies have reported pulmonary vasoconstriction during transfusion of packed red blood cells (PRBCs) stored for prolonged periods. The primary aim of this study was to evaluate whether transfusion of PRBCs stored over 21 days (standard-issue, siPRBCs) increases pulmonary artery pressure (PAP) to a greater extent than transfusion of PRBCs stored for less then 14 days (fresh, fPRBCs) in critically ill patients following cardiac surgery. The key secondary aim was to assess whether the pulmonary vascular resistance index (PVRI) increases after transfusion of siPRBCs to a greater extent than after transfusion of fPRBCs.

Methods: The study was performed as a single-center, double-blinded, parallel-group, randomized clinical trial. Leukoreduced PRBCs were transfused while continuously measuring hemodynamic parameters. Systemic concentrations of syndecan-1 were measured to assess glycocalyx injury. After randomizing 19 patients between January 2014 and June 2016, the study was stopped due to protracted patient recruitment.

Results: Of 19 randomized patients, 11 patients were transfused and included in statistical analyses. Eight patients were excluded prior to transfusion, 6 patients received fPRBCs (10±3 storage days), whereas 5 patients received siPRBCs (33±4 storage days). The increase in PAP (7±3 vs. 2±2 mmHg, P = 0.012) was greater during transfusion of siPRBCs than during transfusion of fPRBCs. In addition, the change in PVRI (150±89 vs. -4±37 dyn·s·cm-5·m2, P = 0.018) was greater after transfusion of siPRBCs than after transfusion of fPRBCs. The increase in PAP correlated with the change of systemic syndecan-1 concentrations at the end of transfusion (R = 0.64,P = 0.034).

Conclusion: Although this study is underpowered and results require verification in larger clinical trials, our findings suggest that transfusion of siPRBCs increases PAP and PVRI to a greater extent than transfusion of fPRBCs in critically ill patients following cardiac surgery. Glycocalyx injury might contribute to pulmonary vasoconstriction associated with transfusion of stored blood.

Fig 1. Study participation flow diagram.

Abbreviations: PAC, pulmonary artery catheter; Hb, hemoglobin; ICU, intensive care unit; SAE, serious adverse event; PRBCs, packed red blood cells.

Fig 2. Changes in pulmonary arterial pressure and pulmonary vascular resistance index at 15 minutes after initiation of transfusion.

Change in (A) pulmonary arterial pressure (Δ PAP) and (B) pulmonary vascular resistance index (Δ PRVI) at 15 minutes after initiation of transfusion in patients receiving fresh packed red blood cells (fresh PRBCs, white bars) or standard-issue packed red blood cells (standard-issue PRBCs, grey bars). Black dots represent respective changes in individual patients. P-values indicate differences among patients receiving fresh PRBCs and standard-issue PRBCs.