Fluid Flow In Tumesced Subcutaneous Pig Tissue
John P. Koulakis, Joshua Rouch, Nhan Huynh, Holden H. Wu, James C. Y. Dunn, Seth Putterman.
UCLA, Los Angeles, CA, USA.
BACKGROUND: Administration of pharmaceuticals such as monoclonal antibodies is commonly done via subcutaneous injection, and stability limits on drug concentration require large volume doses that tumesce the extracellular matrix near the injection site. The properties of tissue in the tumesced state are not well known.
METHODS: We investigate the flow properties of externally tumesced subcutaneous pig tissue with magnetic resonance imaging, computed tomography, and 3D scanning. The evolution of 24 bolus injections of saline of various volumes between 2.5-40 mL was monitored on timescales from minutes to several hours.
RESULTS: Bolus injection of fluid into subcutaneous tissue results in accumulation of fluid at the injection site. The fluid does not form a pool. Rather, the injection pressure forces the interstitial matrix to expand to accommodate the excess fluid in its volume, and the fluid gets bound similar to that in a hydrogel. Our measures indicate that subcutaneous tissue can expand to a few times its initial volume to accommodate the injected fluid, which is dispersed thoroughly throughout the tumescent volume. Stress around the tumesced region acts to spread the fluid to peripheral unexpanded regions over the course of a few minutes following the injection, after which it remains in place for several hours. Eventually systemic circulation absorbs the excess fluid and the tissue returns to its original state.
CONCLUSIONS: The expansion of subcutaneous tissue and the corresponding decrease in hydraulic resistance while tumesced is an opportunity for the dispersal of large pharmaceuticals. Beyond that, the data raise an interesting hypothesis: given the evidence for dense fluid dispersal and several hour residence time, a procedure is proposed whereby tumescent antibiotic injections are used to treat drug-resistant skin infections and chronic wounds that extend into the subcutaneous tissue. The procedure has the potential to effectively treat otherwise untreatable wounds by keeping drug concentrations above minimum inhibitory levels for extended lengths of time.
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