Abstract
Introduction: Histamine is an integral mediator following traumatic injury. Histamine-2 receptors have previously been identified on lymphocytes and monocytes.
Materials and methods: Two rodent models (1) Bilateral femoral fracture and intramedullary nailing, with resulting indirect lung injury (n=30). (2) In vivo model of orthopaedic implant contaminated by Staphylococcus epidermidis (n=36). Animals were randomised to receive ranitidine or placebo (saline).
Results: Markers of lung injury (MPO activity, BAL proteins and wet:dry ratios) increased 24 hours following bilateral femoral fracture, but were reduced if ranitidine was administered systemically after the injury. Production of Th-1 cytokines was blocked by ranitidine, whilst Th-2 cytokine production remained unaffected by ranitidine. These suggest an anti-inflammatory effect of ranitidine, blocking the early (Th-1) pro-inflammatory response following major injury.
Ranitidine’s effect on implant infection rates showed higher rates (44% versus 17%, relative risk 1.8 (95% CI 1.0 to 3.3)) when systemic ranitidine was delivered peri-operatively, suggesting an immunosuppressive effect.
Conclusions: The findings highlight the complex balance in vivo, a double-edged sword: the risk of increasing implant infection versus reducing indirect lung injury following major injury. The administration of ranitidine in major trauma patients with severe pro-inflammatory responses may block and reduce early multi-organ dysfunction and improve survival. However, owing to infection, the peri-operative administration of ranitidine should be avoided in elective cases.
The abstracts were prepared by Emer Agnew. Correspondence should be addressed to Irish Orthopaedic Association, Secretariat, c/o Cappagh National Orthopaedic Hospital, Finglas, Dublin 11, Ireland.
