The Never-Ending Quest To Reduce Donor Exposure
Susan Nicolson MD, James DiNardo MD, Viviane Nasr MD, and Lindsey Loveland Baptist, MD
As John Fiadjoe and I promised, we are expanding the PAAD and its reviewers/writers. Indeed, we had our first editorial meeting at last week’s SPA/ASA meetings. Starting today and about once or twice a month going forward, Susan, Jim, Viviane and Lindsey will be reviewing cardiac articles for us. Susan and Lindsey are from Children’s Hospital of Philadelphia and Jim and Viviane are from THE Boston Children’s Hospital. Both institutions and their congenital heart programs are amongst the best in the world. Myron Yaster MD
Audrey Dieu, Maria Rosal Martins, Stephane Eeckhoudt, Amine Matta, David Kahn, Céline Khalifa, Jean Rubay, Alain Poncelet, Astrid Haenecour, Emilien Derycke, Dominique Thiry, André Gregoire, Mona Momeni; Fresh Frozen Plasma versus Crystalloid Priming of Cardiopulmonary Bypass Circuit in Pediatric Surgery: A Randomized Clinical Trial. Anesthesiology 2020; 132:95–106 PMID: 31658115
There is a continuous quest to minimize perioperative bleeding and the need for transfusion in the pediatric cardiac surgical population. In 2019, the Network for the Advancement of Patient Blood Management, Haemostasis and Thrombosis (NATA, www.nataonline.com) published patient blood management guidelines to consolidate what is known and to specify where gaps in the knowledge base exist. (1)
A strategy that has been commonly employed in pediatric cardiac surgery is addition of fresh frozen plasma (FFP) to the cardiopulmonary bypass (CPB) prime that contains packed red blood cells (PRBCs) with the intent of mitigating post CPB coagulopathy by decreasing the dilutional effects of the priming volume on platelet count and coagulation factors. However, the actual benefit of the practice of prophylactic addition of FFP to a circuit primed with PRBCs has been questioned and prior trials comparing crystalloid to FFP in the pump prime have produced conflicting results.
This study published by our colleagues in Belgium, Audrey Dieu et al. was a rigorous double blind, randomized, controlled study. Inclusion and exclusion criteria accounted for institutional practices with the intent to minimize sources of variability in the study groups by using one CPB circuit. All infants and children weighing between 7 and 15 kg were randomized 1:1 to CPB priming with either 15 ml/kg PlasmaLyte or 15 ml/kg FFP in addition to a predefined amount of PRBCs to reach a target on CPB hematocrit. The presence of red cells in the prime blinded the care team to the prime allocation. Post CPB transfusion decisions were driven by a rigorous ROTEM and multiplate platelet aggregation testing algorithm.
The primary endpoints included 6-hour postoperative chest tube output, number of patients transfused with any additional blood products, and the total number of additional blood products administered (donor exposures) intra- and postoperatively. The results demonstrated that in this study cohort, priming CPB with crystalloid did not result in a difference in the risk of postoperative bleeding nor in a need for transfusion of allogeneic blood products.
While encouraging these results must be interpreted in the context of the study design and their generalizability carefully considered. The following should be considered:
· This study did not include patients at high risk of bleeding such as neonates, those with cyanosis, those undergoing repeat sternotomy, and those with complex procedures involving extensive great vessel suture lines
The extent of dilutional coagulopathy, given the volume of the CPB circuit relative to patient blood volume was minimal. The circuit utilized included an oxygenator with a 87 mL prime volume. Although not reported by the authors, the total CPB prime volume was likely no more than 300-400 mL. The total blood volume of the patients, at 75 mL/kg, on average was 750 mL. Thus, there would be anticipated to be about 30-35% dilution of coagulation factors in the crystalloid group. This degree of dilution in a patient population at low risk of bleeding is likely to be inconsequential. Both groups would be exposed to dilutional thrombocytopenia however as shown in Table 4 of the paper.
If there was a benefit effect of FFP in the prime it was negated by the strategy of using cell salvage to process the residual blood in the CPB circuit. Coagulation factors are removed from patient blood at the time they are needed to facilitate coagulation after reversal of heparin. Transfusion of cell salvage blood from an FFP prime is no different than transfusion of cell salvage blood from a crystalloid prime as regards coagulation factors.
Use of modified utrafiltration (MUF) serves to concentrate red cell mass and coagulation factors at the end of CPB. It was not permitted in this study with good reason. Use of MUF would have made assessment of the isolated effect of an FFP versus crystalloid prime more complicated. Use of MUF in conjunction with a crystalloid prime is a useful strategy when considering a CPB prime without FFP.
The limitations of this study cited above coupled with the difficulty transferring the findings of any study to other institutions where many of the variables influencing blood loss and transfusion are vastly different, many non-modifiable, requires each institution to systematically identify interventions that reduce donor exposure in their patient populations.
1. Faroni, David, Meier, Jens, New, Helen, Van der Lindsen, Philippe, Hunt, Beverley: Special Article. Patient Blood Management for Neonates and Children Undergoing Cardiac Surgery: 2019 NATA Guidelines. JCVA; 33:12, Dec 2019, 3249-3263