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Systematic review.To determine the definition and incidence of significant hemorrhage in adult spine fusion surgery, and to assess whether measures to decrease hemorrhage are effective.Significant hemorrhage and associated comorbidities in spine fusion surgery have not yet been clearly identified. Several preoperative and intraoperative techniques are currently available to reduce blood loss and transfusion requirements such as cell saver (CS), recombinant factor VIIa, and perioperative antifibrinolytic agents, such as aprotinin, tranexamic acid, and ε-aminocaproic acid. Their effectiveness and safety in spine surgery is uncertain.A systematic review of the English-language literature was undertaken for articles published between January 1990 and April 2009. Electronic databases and reference lists of key articles were searched to identify published studies examining blood loss in major spine surgery. Two independent reviewers assessed the quality of the literature using the Grading of Recommendations Assessment, Development, and Evaluation criteria. Disagreements were resolved by consensus.A total of 90 articles were initially screened, and 17 ultimately met the predetermined inclusion criteria. No studies were found that attempted to define significant hemorrhage in adult spine surgery. We found that there is a high level of evidence that antifibrinolytic agents reduce blood loss and the need of transfusion in adult spine surgery; however, the safety profile of these agents is unclear. There is very low evidence to support the use of CS, recombinant factor VIIa, activated growth factor platelet gel, or normovolemic hemodilution as a method to prevent massive hemorrhage in spine fusion surgery.There is no consensus definition of significant hemorrhage in adult spine fusion surgery. However, definition in the anesthesiology literature of massive blood loss is somewhat arbitrary but is commonly accepted to entail loss of 1 volume of the patient's total blood (60 mL/kg in adults) in <24 hours. On the basis of the current literature, there is little support for routine use of CS during elective spinal surgery. Concerns related to the use of aprotinin were such that our panel of experts unanimously recommended against its use in spine surgery on the basis of the reports of increased complications. With respect to the antifibrinolytics of the lysine analog class (tranexamic acid and aminocaproic acid), on the basis of the available efficacy and safety data, we recommend that they be considered as possible agents to help reduce major hemorrhage in adult spine surgery.