Cerebral perfusion during neonatal cardiac surgery: Can we improve outcome?

Neonates with a congenital heart defect (CHD) often need to undergo early
cardiac surgery. In complex heart defects, cardiopulmonary bypass (CPB) is
usually employed, with or without deep hypothermic circulatory arrest (DHCA).
During this procedure two main mechanisms are thought to induce a systemic
inflammatory response syndrome (SIRS). These are the ischemic-reperfusion
injury and the contact of blood with foreign material. An imbalance in both the
innate and adaptive immune system is thought to cause the inflammatory response
which subsequently occurs. It can lead to a state of systemic inflammation,
endothelial damage and, ultimately, to multi-organ failure.

The brain is especially vulnerable to ischemic injury, which puts neonates
undergoing complex operations at high risk of neurodevelopmental disorders.
Selective antegrade cerebral perfusion (ACP) instead of DHCA during these
complex operations may contribute to less brain injury, but research performed
has not been conclusive on this issue.

In a randomized controlled trial, the effects of DHCA and ACP during complex
neonatal cardiac surgery on organ function and injury will be compared,
especially focusing on cerebral damage and neurological outcome.

The primary research question is whether ACP reduces cerebral damage compared
to DHCA, as assessed by MRI-lesions. Secondary research questions focus on the
effects of ACP and DHCA on inflammatory response, endothelial damage and organ
failure.

In a randomized controlled trial 30-50 infants (age < 4 months), undergoing
aortic arch reconstruction, will undergo surgery using either DHCA or ACP. The
primary outcome will be the rate of new or worsened MRI-lesions
postoperatively, compared to pre-operative MRI- scans. Secondary outcomes will
be cerebral damage, organ failure and inflammation. Cerebral damage will be
measured by serum cerebral damage markers, aEEG, NIRS, acute neurological
abnormalities and adverse neurodevelopmental outcome (until 9 months after the
operation). Organ failure will be measured serum organ injury markers, clinical
organ failure and mortality. Inflammation will be measured by cytokine and
activated T-cell and monocyte levels.

The results of this study will be the basis for a long term follow-up study on
DHCA and ACP.

One group will receive DHCA and the other group will receive ACP.

The neonates will be randomly assigned to either DHCA or ACP. Currently,
worldwide, both perfusion techniques are used. In our hospital both techniques
are used in a standardized way. Therefore, there is no specific burden or risk
of the application of either perfusion techniques. Blood will be drawn in
accordance to the hemodynamic stability of the infant and is safe as
demonstrated in previous studies on neonates by our research group (METC
03/039, 04/144, 05/041). The cerebral monitoring used is already part of the
standard of care at our department. MRI scans are known to be a safe imaging
technique, and will be performed under direct supervision of a pediatric
cardiac anesthesiologist. MRI*s are often already performed perioperatively and
is a standard in asphyxiated neonates.

The greatest burden, is the time consumption of this study for the child and
his/ her parents during the follow-up after the operation at the out-patient
clinic (two check-ups of 45 minutes each during the first year of life).