Amicar Pharmacokinetics of Children Having Craniofacial Surgery
Condition: Craniosynostosis
MeSH terms: Craniosynostoses
Study type: Interventional
Phase: Phase 1

Summary: 
      Craniofacial reconstruction surgery involves a surgical approach to the craniofacial region
      to repair cranial vault and facial deformities. The surgery is extensive, often requiring
      wide scalp dissections and multiple osteotomies and has been associated with significant
      morbidity. Some of the most severe and commonly seen problems are associated with the rate
      and extent of blood loss.

      Efforts to minimize surgical bleeding may translate to reduced transfusion requirements and a
      lessening of associated risks Epsilon-aminocaproic acid (EACA), an inhibitor of fibrinolysis,
      reduces transfusion requirements in children undergoing procedures on cardiopulmonary bypass
      (CPB), as well as in older children undergoing spinal surgery for scoliosis (1-6).

      Before controlled studies to assess efficacy of EACA in a craniofacial surgical population
      can be done, appropriate pharmacokinetic (PK) data are needed to determine the optimal dosing
      strategy. PK data exist for EACA in children undergoing operations on CPB and hypothermia.

      The aim of this study is to determine the pharmacokinetics of EACA in infants and children
      undergoing craniofacial reconstruction procedures.
    

Detailed description: 
      Craniosynostosis is the condition in which there is premature fusion of one or more of these
      sutures between the bones of the skull. Craniosynostosis limits the ability of the cranial
      vault to expand to accommodate the rapidly growing brain in infancy and early childhood.
      Deformation of skull shape results as cranial vault expansion occurs in areas of the skull
      that have not abnormally fused. Left uncorrected, craniosynostosis may adversely impact
      neurologic and psychosocial development. In some cases, increased intracranial pressure may
      also result.

      Craniofacial (CF) reconstruction procedures to treat craniosynostosis are undertaken in young
      children to improve appearance, prevent functional disturbances, and enhance psychosocial
      development. Optimal surgical results are achieved when these procedures are performed in
      infancy. These procedures are extensive, often requiring wide scalp dissections and multiple
      osteotomies and have been associated with significant morbidity. Reported complications
      include massive blood loss, intraoperative cardiac arrest, transfusion reactions, venous air
      embolism, hypotension, coagulopathy, bradycardia, postoperative seizures, surgical site
      infections, facial swelling, and unplanned postoperative mechanical ventilation (7-13). Many
      of the most severe and commonly seen problems are associated with the rate and extent of
      blood loss.

      Intraoperatively, the presence of hyperfibrinolysis has been demonstrated in children
      undergoing CF reconstruction procedures (8,14), although the extent of its contribution to
      bleeding is unclear.

      Epsilon-aminocaproic acid (EACA), another inhibitor of fibrinolysis, is an attractive
      alternative. EACA 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 EACA in this population.
    

Intervention name(s): Epsilon-Aminocaproic Acid; Epsilon-Aminocaproic Acid; Epsilon-Aminocaproic Acid; Epsilon-Aminocaproic Acid
Intervention type(s): Drug; Drug; Drug; Drug
Intervention description(s): Group C (high dose) will receive a loading dose of EACA of 100 mg/kg over ten minutes followed by a continuous EACA infusion at 40 mg/kg/hr, which will be continued until the end of surgery.; Group A (low dose) will receive a loading dose of EACA of 25 mg/kg over ten minutes followed by a continuous EACA infusion at 10 mg/kg/hr, which will be continued until the end of surgery; Group B (intermediate dose) will receive a loading dose of EACA of 50 mg/kg over ten minutes followed by a continuous EACA infusion at 20 mg/kg/hr, which will be continued until the end of surgery; Group D (extra low dose) will receive a loading dose of EACA of 12.5 mg/kg over ten minutes followed by a continuous EACA infusion at 5 mg/kg/hr, which will be continued until the end of surgery
Other intervention name(s): Amicar; 6-aminohexanoic acid; Amicar; 6-aminohexanoic acid; Amicar; 6-aminohexanoic acid; Amicar; 6-aminohexanoic acid
Intervention MeSH terms: Aminocaproic Acid
Allocation: Non-Randomized
Intervention model: Single Group Assignment
Masking: None (Open Label)
Primary purpose: Treatment
Keywords: craniofacial surgery; pharmacokinetics; cranial vault abnormalities; homologous blood products; wide scalp dissections; transfusion requirements