Conventional resuscitation (CR) from hemorrhagic shock often culminates in multisystem organ failure and death, commonly attributed to a progressive splanchnic vasoconstriction and hypoperfusion, a gut-derived systemic inflammatory response (SIR), and fluid sequestration. Direct peritoneal resuscitation (DPR) produces a sustained state of tissue hyperperfusion in splanchnic and distant organs. In this study we evaluated the therapeutic potential of DPR on the SIR and fluid sequestration as parameters of treatment outcome. Anesthetized nonheparinized rats continuously monitored for hemodynamics were bled to 40% of mean arterial pressure for 60 minutes. Animals were randomized for CR or CR plus DPR under aseptic conditions. Sham nonhemorrhaged rats served as control. Qualitatively, animals were blindly observed for body weight, illness score, or death for 72 hours. Tissues were harvested from survivors, and SIR was measured by interleukin (IL)-6, IL-10, tumor necrosis factor-α, and enzyme-linked immunosorbent assay, and fluid sequestration was measured by dry weight/wet weight ratio (DW/WW). Adjunct DPR caused a marked increase (P >. 01 by analysis of variance) in the immunoregulator IL-10 in the liver (10,990 ± 1,470 pg/g) and gut (1815 ± 640 pg/g), compared to CR rats (6450 ± 1000 pg/g and 1555 ± 590, respectively), which is associated with down-regulation of IL-6 and tumor necrosis factor-α in liver and gut, from 57 ± 4 and 20 ± 3 pg/g, respectively, to 42 ± 4 and 9 ± 2 pg/g in DPR-treated animals. CR animals had a lower DW/WW ratio in liver (-36%), spleen (-22%), and lung (-24%) compared to DPR (P <. 05), where the DW/WW ratio did not differ from control animals. This fluid sequestration is consistent with a 12% and 5% gain in prehemorrhage body weight at 24 and 72 hours after treatment in the CR animals. Thirty percent of CR animals died within 24 hours, and survivors were squeaking, cold, and pale in eyes and ears and oliguric despite features of fluid overload. In comparison, DPR animals exhibited normal appearance by 24 hours and demonstrated a 100% survival at 72 hours. This study demonstrates that DPR as adjunct to CR has beneficial effects on the pathophysiology of resuscitated hemorrhagic shock. In addition to restoration of tissue perfusion, DPR has immunomodulation and anti-fluid sequestration effects. These modulations result in improved outcome.
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