Efficacy of Amicar for Children Having Craniofacial Surgery

Craniosynostosis is a condition in which there is premature fusion of one or more of the
sutures between the bones of the skull. Premature fusion of sutures in the skull limits the
ability of the cranial vault to expand to accommodate the rapidly growing brain in infancy
and early childhood and leads to bony deformation. Left uncorrected, craniosynostosis may
adversely impact both neurologic and psychosocial development and in some cases, can result
in high intracranial pressure and blindness.

Craniofacial (CF) reconstructive surgery is performed in young children with craniosynostosis
to improve physical appearance, prevent functional neurologic disturbances, and enhance
psychosocial development. Due to the complexities of the surgery as well as the young age and
size of the patients, CF reconstruction carries potential life threatening risks and can
result in significant morbidity. Reported complications include massive intraoperative
hemorrhage, intraoperative cardiac arrest, transfusion-related reactions, venous air
embolism, hypotension, coagulopathy, bradycardia, postoperative seizures, surgical site
infections, facial swelling with airway compromise, and unplanned postoperative mechanical
ventilation. The most severe and most common perioperative issues relate to the rate and
extent of blood loss.

Fibrinolysis, which impairs adequate hemostasis, has been shown to occur in children during
CF reconstruction. This most certainly contributes to the magnitude of blood loss in these
types of operations. Thus, targeting this defect in clot hemostasis with the use of
antifibrinolytics is a reasonable therapeutic approach.

Amicar (ε-aminocaproic acid) is a synthetic lysine analog that blocks the lysine binding
sites on plasminogen, resulting in antifibrinolytic activity through inhibition of plasmin
formation. We have chosen to study Amicar in this clinical context for a number of reasons.
First, major hemorrhage continues to be a significant perioperative issue in this cohort.
Secondly, Amicar is commonly and safely administered to children undergoing other types of
high-risk surgery (i.e., spinal fusion surgery and open heart surgery). In addition, Amicar
is inexpensive and easily administered, making it a viable and novel therapeutic option if
shown to be effective for this type of surgery.

Inclusion Criteria:

- Any child diagnosed with craniosynostosis in need of surgical repair

- Males and females between the ages of 2 - 36 months (minorities will be included)

- Surgical procedure involving complex craniofacial reconstruction and craniotomy

- Written informed consent from parent/guardian

Exclusion Criteria:

- Subjects with known or suspected hypersensitivity reaction to Amicar or history of
prior Amicar exposure

- Presence or prior history of a known coagulation disorder or hypercoagulable state

- Preoperative laboratory values that indicate clinically significant hematologic
disease (hemoglobin, platelet count, prothrombin time, or partial thromboplastin time
outside of normal range)

- Subjects who are on anticoagulant therapy (Coumadin, heparin, aspirin, etc.)

- Subjects with a prior history of a thrombotic event

- History of renal malformation

- Presence of hematuria

- History of abnormal renal function - serum creatinine or blood urea nitrogen (BUN)
value greater than 1.5 times the upper limit of the normal range

- Craniofacial reconstruction surgery performed in conjunction with an additional
surgical procedure associated with blood loss

- Subjects who have been previously enrolled in this protocol may not be enrolled again