Session III - Polytrauma Fracture Healing

*The Effect of Femoral Nailing on the Inflammatory System: Is There a Second Hit?

Peter V. Giannoudis, MD (a-AO Foundation); R. Malcolm Smith, MD (a-AO Foundation); Mark C. Bellamy, MA (a-AO Foundation); Robert A. Dickson, MA (a-AO Foundation); Pierre J. Guillou, MD (a-AO Foundation), St. James' University Hospital, Leeds, United Kingdom

Purpose: It has been suggested that femoral nailing may produce an additional injury (the second hit) and may be associated with the development of the Adult respiratory distress syndrome (ARDS) and multiple organ failure (MOF). Significant changes in the inflammatory system have been noted after trauma and implicated in the pathogenesis of these complications. In order to assess the effect of femoral reaming on the inflammatory system we have prospectively studied the changes in serum Interlukin-6 (IL6) (proinflammatory cytokine), neutrophil CD11-b (C3) receptor expression (activated neutrophil adhesion molecule), sICAM-1 (soluble product of endothelial adhesion molecule) and plasma elastase (neutrophil protease) in a series of patients with femoral fractures treated by RFN (reamed femoral nailing group) or URFN (unreamed femoral nailing group). In addition; the immuno-suppressive effect of femoral nailing was assessed by measurement of the IL10 levels (anti-inflammatory cytokine) and degree of suppression of monocyte MHC class II molecules (HLA-DR expression); an index of cellular immunity.

Methods: Thirty-two patients with a mean injury severity score of 11.9 (range 9-34) presenting with an acute femoral fracture following blunt trauma were studied. Research Ethical Committee approval was obtained and all patients or their representatives gave informed consent. All patients arrived in hospital within 2 hours of injury and were managed initially according to ATLS protocol. None of the patients had suffered abdominal trauma. All patients were nailed acutely, 15 after reaming (using a traction table, the femur was reamed to at least 1mm greater than the nail diameter using AO reamers), and 17 with an unreamed technique (the femoral canal was opened with a drill prior to nail insertion). Venous blood samples were taken at presentation, anaesthetic induction, immediately after nail insertion and subsequently at 1, 4 and 24 hours and at 3, 5 and 7 days. Serum IL-6, IL-10, s-ICAM-1 and plasma elastase were measured by ELISA immunoassays. Neutrophil CD11b expression and Monocyte HLA-DR expression were quantified by flow cytometry after the staining of fresh polymorphonuclear leukocytes and monocytes in whole blood with fluorescent labelled antibodies. Twenty uninjured individuals were also studied to establish normal values.

Results: In all patients (32) serum IL-6, serum IL-10, plasma elastase levels and CD11b expression were significantly raised above control levels (P<0.0001) on admission, slowly returning towards control values over the study period. sICAM-1 levels were slightly elevated initially and increased with time reaching significance above control values after day 3. Monocyte HLA-DR expression was significantly reduced below control levels on admission (p<0.001) reaching control values at day seven post injury.

Serum IL-6, IL10, elastase and HLA-DR expression showed a clear response to the nailing procedure illustrating a measurable "second hit". There was no clear response in CD11-b expression or sICAM-1 levels. There was a trend to an increased inflammatory effect in every parameter with the reamed as opposed to the unreamed technique, but this only reached statistical significance with the IL-10 assay. All patients had an uncomplicated postoperative course except one patient in the reamed group with bilateral femoral fractures who died of ARDS 3 days following surgery. At initial presentation his immunoinflammatory system was massively stimulated as illustrated by his IL-6 level of 272 pg/ml (mean of survivors 97.7 CI (89-106 pg/ml) and elastase level of 325mg/l (mean of survivors 168 CI (151-185 mg/l). After injury he also demonstrated a significantly increased response (second hit) illustrated by his peak IL-6 level of 293 pg/ml (mean of survivors 172 CI (161-197pg/ml) ) and elastase level of 600 mg/l (mean of survivors 198 CI (173 - 238 mg/l) ) suggesting the importance of an excessive inflammatory reaction in the pathogenesis of ARDS.

Conclusion: This study shows that there is a second hit associated with femoral nailing and suggests that the degree of the inflammatory reaction may be important in the pathogenesis of ARDS and MOF. We are unable to make a firm conclusion with regard to the use of a reamed technique. The patient who died was hyperstimulated before nailing, suggesting that a number of factors may combine to produce ARDS.