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Database analyses documented that unduly long surgical procedures undertaken early after trauma increase the risk of acute respiratory distress syndrom (ARDS), especially when femoral shaft fractures are stabilized. Animal research and prospective clinical studies also support the fact that the type of stabilization of a femoral shaft fracture may influence the systemic response to trauma. Reamed intramedullary reaming and nailing for a femoral shaft fracture is associated with an increased risk of pulmonary fat embolization from the medullary canal. This can result in pulmonary compromise if certain cofactors are also present. Modified reamers have been developed to reduce this side effect. The mediating effects are immunologic changes, varying according to the magnitude of the surgical procedure. Pro\u2010inflammatory markers (e.g., Interleukins) may be used to assess the inflammatory response to injury as well as the magnitude of surgery and the systemic impact induced by surgery. Serum levels of such markers can be used clinically to tailor the amount of surgery that is performed to the clinical condition of the patient. The potentially negative impact of excessive surgery in high\u2010risk patients can be avoided by using a new grading system for the assessment of the clinical status of the injured patient. Most recently, a large prospective randomized multicenter study has documented that this grading system is effective for identifying these borderline patients, and that in the borderline patient a staged surgical approach, such as temporary femoral stabilization with an external fixator, reduces the incidence of systemic complications. This work has changed the surgical management of multiply injured patients toward an approach that is tailored to the clinical condition of the patient, as indicated by well\u2010defined clinical parameters as well as objective measurements of serum cytokine levels. \u00a9 2008 Orthopaedic Research Society. 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