Combined hemorrhagic shock (Shock) and unilateral common carotid artery occlusion (Stroke) results in a decrease of oxygen availability to peripheral tissues and organs and the central nervous system (CNS). A variety of biochemical processes ensue, including organ failure, cellular apoptosis, and necrosis. The present study used male, Sprague-Dawley rats to assess the impact of cerebral insult. Using heat-shock protein 25 and 70 (HSP25, HSP70) as biomarkers, measured 24 h after injury, we tested the hypothesis that pharmacological induction of preconditioning can offer cytoprotection from combined Stroke and Shock. The compound, diazoxide (DZ), is known to induce preconditioning through its effect as a mitochondrial potassium ATP (mK(ATP)) channel opener and succinate dehydrogenase inhibitor. When administered 24 h prior to Stroke and Shock (delayed preconditioning), DZ increased cerebral cortical and hippocampal levels of HSP25 and HSP70. A more clinically relevant treatment paradigm was tested, where DZ was administered after the induction of Stroke and Shock (postconditioning). When administered 60 min (but not 10 min) after the induction of Stroke and Shock, DZ significantly increased HSP25 and HSP70 expression in the ipsilateral cerebral cortex and hippocampus. Taken together, these results suggest that DZ treatment may be efficacious for CNS injury resulting from blood loss and anoxia from combined cerebral ischemia and hemorrhagic shock. "Postconditioning" triggered by DZ, immediately before resuscitation, is a potentially effective treatment for ischemia-reperfusion injury from combined Stroke and Shock.

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Objective: Early administration of epinephrine increases the incidence of return of spontaneous circulation (ROSC) and improves outcomes among pediatric cardiac arrest victims. Rapid endotracheal (ET) intubation can facilitate early administration of epinephrine to pediatric victims. To date, no studies have evaluated the use of ETepinephrine in a pediatric hypovolemic cardiac arrest model to determine the incidence of ROSC.Methods: This prospective, experimental study evaluated the pharmacokinetics and/or incidence of ROSC following ET administered epinephrine and compared it to these experimental groups: intravenous (IV) administered epinephrine, cardiopulmonary resuscitation only (CPR), and CPR + defibrillation (CPR + Defib).Results: Endotracheal administered epinephrine, at the Pediatric Advanced Life Support (PALS) recommended dose, was not significantly different than IV administered epinephrine in maximum plasma concentrations, time to maximum plasma concentration, area under the curve, or ROSC, or mean plasma concentrations at various time points (P > 0.05). The odds of ROSC in the ET group were 2.4 times greater than the IV group. The onset to ROSC in the ET group was significantly shorter than the IV group (P < 0.0001).Conclusions: These data support that ET epinephrine administration remains an alternative to IV administered epinephrine and faster at restoring ROSC among pediatric hypovolemic cardiac arrest victims in the acute setting when an endotracheal tube is present. Although further research is required to determine long-term outcomes of high-dose ET epinephrine administration, these data reinforce the therapeutic potential of ET administration of epinephrine to restore ROSC before IV access.

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BackgroundAims of the study were to determine the effects of humerus intraosseous (HIO) versus intravenous (IV) administration of epinephrine in a hypovolemic, pediatric pig model. We compared concentration maximum (Cmax), time to maximum concentration (Tmax), mean concentration (MC) over time and return of spontaneous circulation (ROSC).MethodsPediatric pig were randomly assigned to each group (HIO (n=7); IV (n=7); cardiopulmonary resuscitation (CPR)+defibrillation (defib) (n=7) and CPR-only group (n=5)). The pig were anesthetized; 35% of the blood volume was exsanguinated. pigs were in arrest for 2 min, and then CPR was performed for 2 min. Epinephrine 0.01 mg/kg was administered 4 min postarrest by either route. Samples were collected over 5 min. After sample collection, epinephrine was administered every 4 min or until ROSC. The Cmax and MC were analyzed using high-performance liquid chromatography. Defibrillation began at 3 min postarrest and administered every 2 min or until ROSC or endpoint at 20 min after initiation of CPR.ResultsAnalysis indicated that the Cmax was significantly higher in the IV versus HIO group (p=0.001). Tmax was shorter in the IV group but was not significantly different (p=0.789). The MC was significantly greater in the IV versus HIO groups at 90 and 120 s (p<0.05). The IV versus HIO had a significantly higher MC (p=0.001). χ2 indicated the IV group (5 out of 7) had significantly higher rate of ROSC than the HIO group (1 out of 7) (p=0.031). One subject in the CPR+defib and no subjects in the CPR-only groups achieved ROSC.DiscussionBased on the results of our study, the IV route is more effective than the HIO route.

ObjectiveWe compared the efficacy of tibial intraosseous (TIO) administration of epinephrine in a pediatric normovolemic versus hypovolemic cardiac arrest model to determine the incidence of return of spontaneous circulation (ROSC) and plasma epinephrine concentrations over time.MethodsThis experimental study evaluated the pharmacokinetics of epinephrine and/or incidence of ROSC after TIO administration in either a normovolemic or hypovolemic pediatric swine model.ResultsAll subjects in the TIO normovolemia cardiac arrest group experienced ROSC after TIO administration of epinephrine. In contrast, subjects experiencing hypovolemia and cardiac arrest were significantly less likely to experience ROSC when epinephrine was administered TIO versus intravenous (TIO hypovolemia: 14% [1/7] vs IV hypovolemia: 71% [5/7]; P = 0.031). The TIO hypovolemia group exhibited significantly lower plasma epinephrine concentrations versus IV hypovolemia at 60, 90, 120, and 150 seconds (P < 0.05). Although the maximum concentration of plasma epinephrine was similar, the TIO hypovolemia group exhibited significantly slower time to maximum concentration times versus TIO normovolemia subjects (P = 0.004).ConclusionsTibial intraosseous administration of epinephrine reliably facilitated ROSC among normovolemic cardiac arrest pediatric patients, which is consistent with published reports. However, TIO administration of epinephrine was ineffective in restoring ROSC among subjects experiencing hypovolemia and cardiac arrest. Tibial intraosseous–administered epinephrine during hypovolemia and cardiac arrest may have resulted in a potential sequestration of epinephrine in the tibia. Central or peripheral intravascular access attempts should not be abandoned after successful TIO placement in the resuscitation of patients experiencing concurrent hypovolemia and cardiac arrest.

The 67th Combat Support Hospital at Camp Bondsteel, Kosovo, treated victims of trauma on an almost daily basis at the beginning of U.S. peacekeeping efforts in the region. Military health care personnel must respond quickly and efficiently when confronted with patient wounds resulting in massive blood losses. The limited medical resources of a field hospital often complicate efforts to treat the most severe injuries. One such case involved a young farmer riddled with gunshot wounds. Early volume/blood resuscitation before, during, and after surgery led to a massive blood coagulopathy. This case study describes the actions the physicians and nurses initiated to save this victim of violence. The subsequent discussion delineates methods to reduce intraoperative blood losses, blood transfusion alternatives, and technological advances in trauma resuscitation.

The results suggest that in swine models, the optimal treatment for venlafaxine overdose would include vasopressin with lipids.