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The Total Acute Phase Response Predicts Complications in Children with Musculoskeletal Infection
Emilie Amaro, BS, Michael A. Benvenuti, BS, Thomas J. An, BA, Megan E. Mignemi, MD, Jeffrey E. Martus, MD, Jonathan G. Schoenecker, MD, PhD.
Vanderbilt University, Nashville, TN, USA.

PURPOSE:
Pediatric musculoskeletal infection leads to intense activation of the acute phase response (APR) that persists until the infection is cleared by antibiotic therapy and/or surgical management. While the acute phase response is essential for tissue healing and regeneration, over-activation of the acute phase response is maladaptive and may lead to systemic complications including thrombosis, organ failure, and disseminated intravascular coagulation. In the setting of severe infections, continuous activation of the APR has the potential to become dysregulated. The magnitude of the acute phase reaction can be quantified by both the peak concentration of CRP as well as the total duration of CRP elevation through calculating the area under the curve. We hypothesize that the area under the CRP curve is increased in musculoskeletal infection due to continual tissue injury and we believe that this cumulative response over time correlates with the incidence of complications.
METHODS:
Pediatric patients with musculoskeletal infection that presented to the emergency room at a single, tertiary care pediatric hospital were identified between 2008 and 2013. CRP values and complications during hospitalization were obtained from the electronic medical record. Complications were defined as deviations from the standard hospital course for musculoskeletal infection, such as deep venous thrombosis, septic emboli, pulmonary edema, pleural effusion, pericardial effusion, delirium, shock and multi-organ failure. Statistical analysis was performed using MATLAB (Natlick, MA) and GraphPad Prism6 (La Jolla, CA).
RESULTS:
A total of 119 pediatric patients with musculoskeletal infection were included in the study. Seventeen complications occurred (14%) including 4 cases of septic emboli, 3 cases of pleural effusions, 3 cases of DVT, 2 cases of septic emboli plus DVT, 1 case of delirium, 1 case of toxic shock syndrome, 1 case of pulmonary edema, and 1 case of multi-organ failure. The median area under the CRP curve in cases of musculoskeletal infection with complications was 3303.8 mg day/L, compared to 539.2 mg day/L in cases of musculoskeletal infection without complications (p value < .0001).

CONCLUSION:
A dysregulated acute phase response in the setting of musculoskeletal infection has the potential to cause life-threatening complications. The area under the curve is a novel measure of both the intensity and duration of the acute phase response that correlates with the incidence of complications in pediatric patients with musculoskeletal infection. Clinicians should closely monitor for complications in pediatric patients with severe, prolonged musculoskeletal infections.


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