Fibrinogen therapy for massive blood loss during elective surgery for craniosynostosis repair, a double blinded randomized controlled study

The management of massive blood loss in children during multiple trauma or
major surgery is still an unsolved problem. No clear strategies and no
evidence-based treatment protocols exist.
Primary non-syndromic craniosynostosis occurs in 1:2000 births. Primary
operative repair of craniosynostosis in infants and young children is
recommended. Unfortunately, this procedure can lead to excessive blood loss and
is associated with an average loss of 60 to 100 % (!) of the estimated blood
volume. Our institution (Prof Dr L. van Adrichem) performs more than 100 of
these craniofacial surgeries per year. These well-planned operations in a
homogenous group of young children are a model for excessive acute blood loss
especially in children

In a recent prospective pilot study (METC 2008-321) we could prove that
monitoring of massive blood loss in children during surgical repair of
craniosynostosis with thromboelastography provided evidence for a remarkable
dilution coagulopathy. The application of different intraoperative strategies
and early interventions have reduced the amount of transfused blood products in
adults. Intra-operative monitoring with thromboelastography was helpful in
decision making. No studies have evaluated this in children.

Primary outcome parameter is the amount of intra- and postoperative
transfusions required.

Secondary outcome parameters include intra- and postoperative blood loss,
operation time, and postoperative complications and the outcome of
thromboelastographic monitoring

Single-center, randomized, controlled double-blinded trial comparing the
efficacy of fibrinogen intervention versus placebo during massive blood loss in
children. In order to study the effects of massive blood loss on the
coagulation system in otherwise healthy children we selected the primary
operative repair of craniosynostosis.

The intervention being studied is the application of fibrinogen concentrate
(=50 ml) given IV in an individually targeted dose dependent on the
preoperative individual plasma fibrinogen level immediately at the start of
surgery (in order to reach a level of 3 g/l plasma fibrinogen), followed by 60
mg/kg BW in a continuous infusion during the next hour in the experimental
group versus 50 ml of a placebo solution of NaCl 0.9% in the control group at
the start of surgery followed by a continuous infusion during the next hour.
Repeated TEG measurements will be obtained during surgery, and additional
coagulation tests will be performed to monitor the effect of the intervention.

The intervention takes place during the operative procedure by the surgical
team of Prof L van Adrichem (plastic surgeon) and Mrs Dr van Veelen
(neurosurgeon). Treatment with fibrinogen or with the placebo NaCL 0.9% at the
start of surgery will be performed within the protocol for craniosynostosis
surgery. According to this protocol standardized blood sampling is done during
and after surgery.