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Low Volume Resuscitation with Cell Impermeants

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Annual rept. 30 Sep 2012-29 Sep 2013

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Severe hemorrhagic shock and trauma on the battlefield have poor outcomes if evacuation and advanced treatment are delayed. The objective of this study was to increase the low volume hypotensive time on the field by using cell impermeants in the low volume resuscitation LVR solution. The hypothesis is that local tissue ischemia due to shock causes significant cell swelling in vital tissues and that alleviation of cell swelling with early administration of cell impermeants prevents this, which increases the golden hour on the field and survival after full resuscitation at the forward hospital. To test this hypothesis, first, the impermeant effects of a family of agents were tested in a liver slice ischemia model in-vitro. All impermeants prevented tissue slice cell swelling after 1 hour of hypoxic tissue culture, which was proportional to the concentration and molecular weight of the impermeant. The best timing was to administer impermeants after the start of ischemia and not after reperfusion resuscitation. Next, anesthetized rats were shocked to a pressure of 30-35 mm Hg until their lactate rose to 10 mM, then they were given a saline low volume resuscitation solution, then fully resuscitated when their lactate rose to 10mM again, and finally recovered for 24 hrs. Impermeants given into the LVR solution significantly increased the LVR time, which is the time between administration of the LVR solution and full resuscitation. This is a marker of tolerance to the low volume period golden time. Gluconate 10-15 in the LVR solution produced the best individual protection. Mixtures of trehalose, raffinose, gluconate, and sorbitol at a specific ratio was optimal. This mixture doubled the LVR time and significantly improved cardiovascular, hepatic, renal, and metabolic function during the LVR period and 24 hrs after full resuscitation. Gluconate seems to produce salutary effects beyond what is attributable to its impermeant effects.

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  • Medicine and Medical Research

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