All 324 subjects survived at least 24 hours. The 7-day ΔMODS was on average lower (more favorable) by 1.55 points (SE = 0.53, P = .004) for high platelet:RBC transfusion ratio, compared with low platelet:RBC ratio, after adjusting for plasma:RBC transfusion ratio, baseline MODS, the total number of blood products received in the 24-hour window, and randomized treatment arm (Table 3). The subjects receiving a high plasma:RBC transfusion ratio also had a 1.24 point lower 7-day ΔMODS compared with the low plasma:RBC ratio (SE = 0.45, P = .007), independent of the effect of platelet:RBC transfusion ratio and baseline MODS, the total number of blood products received in the 24-hour window, and randomized treatment arm. The subjects who received a high platelet:RBC transfusion ratio also had a 28-day ΔMODS score that was 1.49 points lower compared with low platelet:RBC ratio (SE = 0.65, P = .022). The subjects who were transfused with a high plasma:RBC ratio had a 1.26 lower 28-day ΔMODS score compared with low platelet:RBC ratio (SE = 0.56, P = .024). The interactions between patients who received both plasma:RBC and PLT:RBC in high or low ratios were explored and not found to be significant.
Cox proportional hazards regression models, controlling for baseline MODS, aortic cross-clamp, CPB, and total number of blood products received, showed that high plasma:RBC ratio transfusion was associated with a lower risk of death; hazard ratio of 0.23 (95% CI, 0.05, 1.01, P = .052) through 7 days and a hazard ratio of 0.36 (95% CI, 0.14, 0.97, P = .042) through 28 days. This association was not seen with the high platelet:RBC ratio at either time point. Kaplan−Meier survival analysis showed consistently better survival in the high plasma:RBC ratio subjects (Figure). Deaths began to accrue on day 1 and continued to accrue throughout the postoperative period, but the majority of all excess deaths had occurred by day 10. By the end of 28 days of follow-up, there was a 3-fold increased survival benefit in the high plasma:RBC ratio (Log rank, P = .0135) (Table 4). Analyses of hospital and ICU discharge by day 31 did not find an association with either platelet:RBC or plasma:RBC ratios (data not shown).
The only laboratory value to be statistically significantly associated with the ratios was hemoglobin. Patients with high plasma:RBC tended to have values of hemoglobin on day 2 that were 0.36 g/L lower than those with low plasma:RBC ratios (P = .016, Table 5). Patients with high platelet: RBC in the longer blood storage arm tended to have values of hemoglobin on day 2 that were 0.62 g/L lower than those with low platelet:RBC ratios (P = .009). This hemoglobin difference is not likely to be of clinical significance and was not associated with any excess mortality either in the original trial or in our reanalysis.
In this retrospective analysis, high transfusion-risk cardiac surgery patients who were part of a randomized prospective trial and received ≥6 units of RBCs or ≥8 total blood components appeared to have a survival benefit when receiving plasma in a high ratio to RBCs. This observation is consistent with retrospective and prospective studies in trauma patients, which suggest that the transfusion of high ratio plasma and PLTs during resuscitation decreases the risk of hemorrhagic death.9,18,19 Because these associations between ratios and outcomes in cardiac surgery patients were derived from a retrospective analysis, they must be considered to be hypothesis generating, and they will require further prospective studies to confirm them and before considering any practice changes.
Recent analyses in trauma and nontrauma settings have focused on survival after massive transfusion. In RECESS, there were 52 deaths; 31(9.5%) in our massively transfused group. This is consistent with survival rates reported by Dzik et al1 among nontrauma patients undergoing massive transfusion in different clinical settings. In this study, 22% of patients who received ≥20 RBC units in 48 hours were cardiac and vascular surgery patients. The authors found an overall survival of 71% (5-day) and 60% (30-day). The ratio of plasma and platelets to RBCs was noted in this study, but the association with patient survival was not reported.
In our study, we found that a high PLT transfusion ratio was associated with a small reduction in MODS. It is not clear whether the MODS is a reliable predictor of mortality in the massively transfused patients, but if it is, then the high frequency of platelet transfusions in this population may contribute to unexpected increased survival in that analysis.
There are several limitations with this analysis: it is retrospective, the examined population is small, and the statistical power of the conclusion is weak; additional subgroup analyses were not undertaken given the relatively small sample size. The subjects in this analysis were a subset of the RECESS study population who were entered into RECESS based on a predicted higher risk of RBC transfusion, that is, by having a TRUST score that predicted a 60% chance of transfusion. The TRUST score was developed using robust statistical modeling of more than 15,000 subjects and found that low hemoglobin, female gender, low body weight, greater age, elevated creatinine, and type of surgery (repeat sternotomy, nonelective, or nonisolated procedure), were risk factors for RBC transfusion (ie, favors a higher score). These selection criteria weight these characteristics in this analysis. In addition, the RECESS data set did not include center-specific transfusion policies, and so this could not be compared in this exploratory analysis. The center-to-center variation was presumably minimized by the fact that randomization was balanced by center. Surgeon skill (or a surrogate such as years of experience) was not included in the original RECESS dataset, so it was not able to be incorporated into this analysis. Despite these limitations, it is the largest population of massively transfused cardiac surgery patients in which the association of blood component ratios with clinical outcomes has been investigated.
These data suggest that transfusion of higher ratios of plasma to RBCs in massively transfused cardiac surgery patients was associated with improved outcomes. Further studies are needed to gain a deeper understanding about the impact of transfusion ratios in other cardiac surgery patient populations that are at high risk for transfusion. In the PROPPR trial, giving plasma at a 1:1 ratio with RBCs was not associated with any excess in a number of complications, more patients achieved hemostasis, and hemorrhage stopped sooner for patients at risk of hemorrhagic death. Further study on the best approach to massive transfusions in cardiac surgery is warranted to deepen our knowledge and improves patient care.
The authors thank Joe Gu for his assistance with the data analysis.
Name: Meghan Delaney, DO, MPH.
Contribution: This author helped conceive of the project idea, design the study, interpret the results, and write and revise the manuscript.
Name: Paul C. Stark, MS, ScD.
Contribution: This author helped perform analyses, interpret the results, and write and revise the manuscript.
Name: Minhyung Suh, MPH.
Contribution: This author helped formulate and perform analyses, and revise the manuscript.
Name: Darrell J.Triulzi, MD.
Contribution: This author helped design the project, interpret the results, and revise the manuscript.
Name: John R. Hess, MD, MPH.
Contribution: This author helped design the project, interpret the results, and revise the manuscript.
Name: Marie Steiner, MD, MS.
Contribution: This author helped lead the primary RECESS study, design the project, interpret the results, and revise the manuscript.
Name: Christopher P. Stowell, MD, PhD.
Contribution: This author helped design the study, interpret the results, and revise the manuscript.
Name: Steven R. Sloan, MD, PhD.
Contribution: This author helped design the study, interpret the and revise the results, and revise the manuscript.
This manuscript was handled by: Roman M. Sniecinski, MD.
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