Poloxamer 188 (P188) as an Adjunct in Prolonged Hypotensive Resuscitation
Technical Report,01 Jul 2007,31 May 2008
University of Texas-Houston Houston United States
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The goal of this project was to evaluate adjunctive use of purified poloxamer 188 P188 in hypotensive shock resuscitation.The efficacy threshold specified by the RFA was to sustain hemorrhaging casualty through 4 hours of hypotensive resuscitation using specified protocols. Our studies using the proscribed model demonstrated a mean survival time was 9.6hours with a range of 5-20 hours. The mean animals in this study was more than 3 hours longer that the controls treated with Hextend in a protocol designed to simulate current protocols in use by the military. P188 also improved auto resuscitation and reduced fluid requirements. Additional studies assessed tissue damage after shock and hypotensive resuscitation with Hextend followed by full resuscitation with crystalloid. In these studies, P188 blunted the no reflow phenomenon and largely prevented myocardial injury, pulmonary inflammation, small bowel damage, renal tubular necrosis, hepatic central lobular necrosis and apoptosis of splenic germinal centers that occurred during full resuscitation compared with the formulation currently used by Special Forces Medics in a rat model designed to simulate current battlefield practices. Finally, P188increased survival from 0 to 75 in 50 volume controlled hemorrhage and did not increase bleeding in uncontrolled hemorrhage.
- Medicine and Medical Research