Date Published: March 11, 2019
Publisher: Public Library of Science
Author(s): Joanna Baron-Stefaniak, Gerda C. Leitner, Nina K. I. Küntzel, Elias L. Meyer, Michael J. Hiesmayr, Roman Ullrich, David M. Baron, Iratxe Puebla.
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.
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.
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).
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.
Current transfusion practice allows for storage of packed red blood cells (PRBCs) up to 42 days, with the oldest compatible PRBC unit being assigned for transfusion (standard-issue PRBCs, siPRBCs). Observational studies indicate that transfusion of PRBCs stored for prolonged periods increases the risk of kidney injury and infection, and prolongs the length of hospital stay and time to extubation in patients undergoing cardiac surgery [1–3]. Furthermore, a meta-analysis in this patient population revealed that transfusion of stored PRBCs increases mortality risk . In contrast, recent randomized controlled trials suggest that transfusion of siPRBCs does not negatively affect survival in a general population of hospitalized patients , in critically ill patients , or in patients following cardiac surgery .
This study was performed as a double-blinded, parallel-group, randomized clinical trial at the General Hospital of Vienna in accordance with the ethical standards stated in the Declaration of Helsinki. The CONSORT (Consolidated Standards of Reporting Trials) guidelines were used to guide the preparation of this article. Ethical approval for this study (reference number 1239/2013) was provided by the Ethical Committee of the Medical University of Vienna, Vienna, Austria. The study was registered at clinicaltrials.gov (NCT02050230) on January 17, 2014. Written informed consent was obtained from each patient before enrollment. Patients were screened for enrollment from January 2014 until June 2016.
Nineteen patients were randomized between January 2014 and June 2016, of which 7 patients were not transfused and excluded prior to study procedures and measurements (Fig 1). One patient developed a severe adverse event due to a hemolytic reaction (from which she fully recovered) and was excluded from analysis. Eleven patients completed the study and were included in the final analysis.
In this double-blinded, randomized clinical study we investigated whether transfusion of PRBCs induces pulmonary vasoconstriction in critically ill patients following cardiac surgery. The study was terminated due to protracted patient recruitment and remained underpowered. In the 11 critically ill patients included in the study, transfusion of siPRBCs increased PAP and PVRI to a greater extent than transfusion of fPRBCs. Additionally, SVRI increased after transfusion of siPRBCs, but not after transfusion of fPRBCs. Mean arterial pressure and cardiac output did not differ among groups. Furthermore, the increase in PAP was associated with an increase in concentrations of SDC, a marker of glycocalyx injury.