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This investigation sought to identify risk factors for immediate postoperative morbidity and mortality among a large series of patients undergoing spine surgery who were prospectively entered into a national registry.The database of the National Surgical Quality Improvement Program was queried to identify all patients undergoing spine surgery in the years 2005 to 2008. Demographic data, comorbidities, medical history, body-mass index, and the type of procedure performed were obtained for all patients. Postoperative complications and mortality within thirty days after the spinal procedure were also documented. The chi-square test and univariate and multivariate logistic regression analyses were used to evaluate the effect of individual risk factors on mortality, as well as the probability of the development of complications.From 2005 to 2008, 3475 patients undergoing spine surgery were registered in the database. The average age of patients was 55.5 years (range, sixteen to ninety years), and 54% of the cohort were men. Ten patients (0.3%) died after surgery, and there were 407 complications in 263 patients (7.6%). Increased patient age and contaminated or infected wounds were identified as independent predictors of mortality. Increased patient age, cardiac disease, preoperative neurologic abnormalities, prior wound infection, corticosteroid use, history of sepsis, American Society of Anesthesiologists classification of >2, and prolonged operative times were independent predictors for the development of one or more complications.Patient age, female sex, longer procedural times, and several types of medical comorbidities influenced the risk of postoperative complications or mortality. This information enhances estimates of morbidity and mortality following spine surgery and may improve patient selection for spine surgery as well as preoperative discussions related to the risks of spine surgery.Prognostic Level II. See Instructions to Authors for a complete description of levels of evidence.