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Why is Direct Peritoneal Resuscitation (DPR) from Hemorrhagic Shock?

High morbidity and mortality from conventionally resuscitated hemorrhagic shock and the subsequent multiple organ failure remains a very significant and a costly clinical problem. The current treatment of trauma patients with hemorrhagic shock consists of rapid correction of the vascular deficit. However, despite the provision of overtly adequate volume resuscitation, in a number of patients, it is clear that simple correction of the volume deficit does not fully restore tissue perfusion. There are still major alterations in organ microcirculation and tissue metabolism associated with the genesis of a gut-derived exaggerated systemic inflammatory response and a massive fluid shift. Numerous interventions have been used to protect organ systems and cellular viability from the lethal injury accompanying hypoperfusion and ischemia. Some measures have been directed to improve perfusion, while others have attempted to enhance the metabolic processes or have used specific antagonists or synthesis inhibitors to modify the state of shock. While blockade of one mediator might provide some protection or give insight into its role in the pathophysiology of shock, none of these efforts have been sufficient to halt or reverse the main course of the pathophysiology noted with conventional resuscitated shock. Thus, the issue of an overall therapy that modifies the pathophysiologic process in hemorrhagic shock/resuscitation remains to be resolved.

Recently we have shown that hemorrhagic shock/resuscitation-mediated intestinal microvascular vasoconstriction and hypoperfusion can be reversed by direct peritoneal resuscitation (DPR) regardless of the timing of DPR. This technique utilizes a clinical peritoneal dialysis solution. Initiation of DPR as adjunct to conventional resuscitation from hemorrhagic shock produces an instant and sustained vasodilation and hyperperfusion of the gut. Subsequent studies have demonstrated that DPR-mediated enhancement of blood flow is not restricted to the gut, but that whole organ blood flow measured with colored microspheres increased by >50% in spleen and pancreas and >100% in lung, psoas muscle and diaphragm compared to conventional resuscitation alone. Furthermore, this splanchnic and distal hyperperfusion occurs without adverse effect on hemodynamics. This study was designed to evaluate the therapeutic potentials of DPR on the systemic inflammatory response and the fluid sequestration associated with CR from hemorrhagic shock. In other studies, adjunct DPR caused a marked increase (p > 0.01 by ANOVA) in the immunoregulator IL-10 in the liver (10988 ±1465 pg/g) and gut (1813±640 pg/g), compared to CR rats (6450±997 pg/g and 1555±587 respectively). This is associated with downregulation of IL-6 and TNFa in liver and gut, from 57.3±3.8, 20.1±3.2 pg/g, respectively, to 41.9±4.1 and 9.1±1.7 pg/g in DPR-treated animals, respectively. CR animals had a significantly (p < 0.05) lower DW/WW ratio in liver (-36%), spleen (-22%), and lung (-24%). In the DPR rats, the DW/WW ratio was not different from naïve animals. This fluid sequestration is consistent with a 12% and 5% gain in pre-hemorrhage body weight at 24 and 72h post-treatment in the CR animals. 30% of CR animals died within 24 h, and survivors were squeaking, cold and pale in eyes and ears, and oligureic despite features of fluid overload. In comparison, DPR animals exhibited normal appearance by 24h and demonstrated a 100% survival at 72h. This study demonstrates that DPR as adjunct to CR has beneficial effects on the multifaceted pathophysiology of traditionally resuscitated hemorrhagic shock. In addition to restoration of tissue perfusion, DPR has immunomodulation and anti-fluid sequestration effects. These modulations result in improved outcome.