Transfusion of higher ratios of fresh frozen plasma (FFP) platelets to red blood cells (RBC) may be associated with decreased mortality in cardiac surgery patients with massive intraoperative hemorrhage, a study has found. According to the researchers, the results point to optimal management that includes aggressive, early hemostatic resuscitation followed by aggressive volume removal.
“When patients with high and low transfusion ratios were compared, patients with higher FFP-to-RBC transfusion ratios had fewer reoperations and decreased deep sternal wound infections as well as less renal failure and the associated need for hemodialysis,” said Michael A. Mazzeffi, MD, assistant professor of anesthesiology at the University of Maryland School of Medicine (UMSM), in Baltimore.
“However, patients with higher FFP-to-RBC ratios also had more prolonged postoperative mechanical ventilation and pneumonia, presumably because of the increased transfusion volume,” added Dr. Mazzeffi, the senior author of the study, which was presented at the Society of Cardiovascular Anesthesiologists’ 2016 annual meeting (abstract 59).
Evan Chriss, MD, an anesthesiology resident at UMSM, reported the findings at the meeting. He cited a study (Transfusion 2004;44:1453-1462) that found up to 8% of cardiac surgery patients require massive transfusions, with severe hemorrhage increasing the odds of death eightfold.
While observational studies (e.g., JAMA Surg 2013;148:127-136) have suggested that transfusion of equal ratios of FFP and RBC improves survival in trauma patients, the optimal ratio remains unknown, Dr. Chriss noted.
A recent randomized controlled trial, comparing 1:1 and 1:2 ratios of FFP to RBC, showed no difference in mortality (JAMA 2015;313:471-482). Furthermore, data are limited on patients undergoing cardiac surgery.
“This issue has never been looked at in cardiac surgery patients who were massively transfused,” Dr. Mazzeffi explained. “We thought that these patients might benefit from high ratios of plasma, but there was also the possibility that they would do worse because cardiac surgery patients often have poor ventricular functions, especially after weaning from bypass.”
Using their institution’s Society of Thoracic Surgeons database, the researchers screened patients having cardiac surgery requiring cardiopulmonary bypass (CPB) for massive transfusion (≥8 units of RBC transfused intraoperatively). The high-ratio group was defined as patients who received a ratio of FFP to RBC of 1:1 or greater. The low-ratio group was defined as patients receiving a FFP-to-RBC ratio of 1:2 or lower.
Statistical analysis included Wilcoxon rank-sum tests for non-normally distributed data and a Cox proportional hazard ratio model to identify the effect of patient variables on 30-day mortality. Finally, to account for baseline characteristics between groups, adjusted odds ratios for variables were calculated using propensity scoring and inverse probability of treatment weighting (IPTW).
As Dr. Chriss reported, 7,492 patients underwent cardiac surgery on CPB between 2006 and 2014, with 452 patients (6.0%) requiring massive intraoperative transfusions. Of these patients, 141 received a high FFP-to-RBC transfusion ratio, while 115 received a low ratio.
Unadjusted in-hospital mortality for patients receiving a high FFP-to-RBC ratio was 25.5%. For patients receiving a low ratio, the mortality rate was 33.0%.
Patients who received a high FFP-to-RBC ratio were younger and more likely to be male, to have undergone long CPB times and to be on warfarin before surgery. These patients were also less likely to be on hemodialysis, to have peripheral vascular disease and to have had a previous myocardial infarction, the researchers noted.
Cox proportional hazards ratios showed that significant variables affecting 30-day mortality included age, preoperative platelet count, international normalized ratio, CPB time and intraoperative FFP-to-RBC ratio.
When comparing both unadjusted and IPTW-adjusted odds ratios for the outcome variables, there was no significant difference in mortality between the groups. Patients receiving a high ratio of FFP to RBC had fewer reoperations for bleeding, less postoperative renal failure and fewer deep sternal wound infections.
However, the researchers also observed an increased incidence of postoperative mechanical ventilation and pneumonia in this group.
Interpretation and Future Directions
“Based on our data, transfusions below a ratio of 1 plasma unit to every 2 red cell units carry a risk of poor resuscitation and ongoing bleeding,” said Dr. Mazzeffi. “If you’re between 1:1 and 1:2 or higher, you’re probably going to have better hemostasis.
“Our data suggest that anesthesiologists who are really aggressive and give a lot of plasma run the risk of prolonged ventilation time or pneumonia,” he explained. “For ratios of FFP to RBC greater than 1:1, I think the practical point is to get the volume off aggressively in the ICU afterward.”
The researchers acknowledged several limitations to the study, including observational bias, a heterogeneous patient population and the ad hoc calculation of transfusion ratios, which lacked information related to timing.
“I think it would be interesting to do a clinical trial in patients who are at risk based on either complex surgery or abnormal coagulation tests before surgery in order to better understand the way we transfuse,” said Dr. Mazzeffi. “Is it possible to give more plasma during cardiopulmonary bypass and then hemoconcentrate to limit the total transfusion volume?
“You could also do a trial with patients who are very heavily transfused during surgery, randomized to either aggressive volume removal afterward or regular standard of care,” he said. “I think those would be important questions to think about in the future.”