“Investigation of Optimal Timing of Blood Transfusion During Neonatal Cardiopulmonary Bypass in Order to Minimize Inflammatory Response and Limit Blood Utilization”

Doctor's Name: 
Ross Ungerleider MD
Hospital/Institution: 
Wake Forest, NC /Brenner Children’s Hospital

“Investigation of optimal timing of blood transfusion during neonatal cardiopulmonary bypass in order to minimize inflammatory response and limit blood utilization.”

Conventional cardiopulmonary bypass (CPB) in very small infants requires filling (“priming”) the CPB circuit with blood from a donor.  Priming with blood in this fashion is necessary because priming the circuit with non-blood constituents (bloodless prime) would otherwise result in massive hemodilution of the baby.  Evidence is accumulating to suggest that the blood received in the CPB prime has a significantly detrimental impact on the infant by triggering a profound inflammatory response.  The magnitude of the inflammatory response during CPB is known to be responsible for many of the potentially life-threatening complications of cardiac surgery.

Our research program has been pursuing the concept of performing bloodless-prime CPB in young infants.  This concept is only possible through progressive miniaturization of the circuit and therefore limiting the extent to which hemodilution takes place.  We now have experimental models that routinely place newborn piglets as small as 2 kg on CPB.  In order to fuel the transition of this experimental technology to the clinical arena, it has been necessary to formally characterize the inflammatory benefits of miniaturized bloodless prime (MBP) bypass.  In addition, it will ultimately be critical to refine the technology from an experimental setup into a reliable, reproducible and safe clinical application.

We have been exploring both the feasibility and benefits of miniaturized bloodless prime (MBP) bypass in neonatal piglet models.  Our previous work has confirmed that pulmonary compliance, alveolar gas exchange and pulmonary vascular resistance are improved through the use of bloodless prime neonatal CPB.  Furthermore, the systemic TNFα load is significantly reduced following MBP bypass.  Lastly, cerebral no-reflow is avoided and intra-cerebral production of TNFα is reduced following deep hypothermic circulatory arrest with MBP.  We may be able to adapt what is learned in this study to clinically available Minimal Extracorporeal Circuits (MECC) once we can solve the challenges of patient venous reservoir size required for neonatal CPB.

Although our previous studies provide convincing evidence that avoidance of blood during CPB has a beneficial effect on reducing CPB induced inflammation and its clinical consequences, there are still important questions that need to be addressed in order to establish routine and evidence-based protocols for adoption of this form of minimally invasive open cardiac surgery.  Our own experience, as well as the experience reported by others has established the clinical feasibility of applying our miniaturized circuitry to human infants weighing less than 5 kg.  It is apparent that while it is important to avoid blood in the CPB prime, it is occasionally necessary to administer a blood transfusion during or following surgery in order to elevate the hematocrit and increase oxygen carrying capacity to a group of patients that may have vulnerability to injury from decreased oxygen saturations (related to intracardiac mixing lesions) or to temporarily abnormal cardiac output (including increased cardiac output demands).  The specific aim of the proposed study is to elucidate:

At what time following initial exposure to asanguinous CPB can blood be given to infants without risk of causing deleterious inflammation?

The combination of circuit miniaturization, the protective effect of systemic hypothermia (which can be applied during CPB to partially protect the infant from the effects of reduced hematocrit from hemodilution) and ultrafiltration (to provide hemoconcentration without blood transfusion) all play a role in reducing the need for blood transfusion during CPB.  Nevertheless, some patients exposed to these efforts to reduce blood utilization during CPB may benefit from an increased hematocrit following initiation of asanguinous prime CPB.  While it is unequivocal from our previous work that blood in the CPB prime can cause significant inflammation with deleterious consequences to the heart, lungs, brain and immune system (among others), it is not known whether blood transfusion during or immediately following CPB has a similar effect.  This is important information that can have a significant and immediate impact on minimally invasive CPB management strategies and protocols.

Award Date 1: 
2011
Award Amount 1: 
$93,178