Systematic Review of Interventions for Minimizing Perioperative Blood Transfusion for Surgery for Craniosynostosis

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Surgery for craniosynostosis is associated with the potential for significant blood loss. Multiple technologies have been introduced to reduce the volume of blood transfused. These are preoperative autologous donation; preoperative erythropoietin; intraoperative cell salvage (CS); acute normovolemic hemodilution; antifibrinolytic drugs such as tranexamic acid, ε-aminocaproic acid, and aprotinin; fibrin sealants or fibrin glue; and postoperative drain reinfusion.


All comparative studies with a treatment group and a control group were considered. There was a range of different study types from randomized controlled trials to case series with historic controls. These were intervention versus no intervention or a comparison of 2 interventions. Studies were identified by searching Cochrane CENTRAL, MEDLINE, and EMBASE; manufacturer’s Web sites; and bibliographies of relevant published articles. The primary outcome measures were the number of allogeneic blood donor exposures, the volume of allogeneic blood transfused, and the postoperative hemoglobin or hematocrit levels.


A total of 696 studies were identified. After removal of duplicates and after exclusion criteria were applied, there were 18 studies to be included. Fourteen were case series with controls and 4 were randomized controlled trials.


The production of high-quality evidence on the interventions to minimize blood loss and transfusion in children undergoing surgery for craniosynostosis is difficult. Most of the literature is nonrandomized and noncomparative. Several areas remain unaddressed. Erythropoietin and tranexamic acid are comparatively well studied; CS, acute normovolemic hemodilution, and aprotinin are less so. There is only 1 comparative study on the use of fibrin glue and drain reinfusion, with no studies on preoperative autologous donation and [Latin Small Letter Open E]-aminocaproic acid. Tranexamic acid is clinically effective in reducing allogeneic blood transfusion. There is some evidence that CS and erythropoietin may be clinically effective. None of the interventions studied are shown to be cost-effective because of lack of evidence.

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