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To investigate the safety and feasibility of performing definitive fracture fixation in multiply injured patients in the presence of an open abdomen after laparotomy.Retrospective observational cohort study.Level-I academic trauma center.Adult polytrauma patients with the presence of an open abdomen after “damage control” laparotomy and associated major fractures of long bones, acetabulum, pelvis, or spine, requiring surgical repair (n = 81).Timing of definitive fracture fixation in relation to the timing of abdominal wall closure.Incidence of orthopedic surgical site infections.During a 15-year time window from January 1, 2000 until December 31, 2014, we identified a cohort of 294 consecutive polytrauma patients with an open abdomen after laparotomy. Surgical fixation of associated fractures was performed after the index laparotomy in 81 patients. In group 1 (n = 32), fracture fixation occurred significantly sooner despite a concurrent open abdomen, compared with group 2 (n = 49) with abdominal wall closure before fixation (mean 4.4 vs. 11.8 days; P = 0.01). The incidence of orthopaedic surgical site infections requiring a surgical revision was significantly lower in group 1 (3.1%) compared to group 2 (30.6%; P = 0.002).Definitive fracture fixation in the presence of an open abdomen is performed safely and associated with a significant decrease in clinically relevant surgical site infections, compared with delaying fracture fixation until abdominal wall closure. These data suggest that the strategy of imposing a time delay in orthopaedic procedures while awaiting abdominal wall closure is unjustified.Therapeutic Level III. See Instructions for Authors for a complete description of levels of evidence.