Steven C. Dronen

Comparison of the effects of bolus vs. slow infusion of 7.5% NaCl/6% dextran-70 in a model of near-lethal uncontrolled hemorrhage

Bolus infusion of of 7.5% NaCl/6% dextran-70 (HSD-B) improves outcome from controlled hemorrhage. In contrast, HSD-B during uncontrolled hemorrhage increases bleeding and short-term mortality. The purpose of this study was to compare the effects of bolus vs. slow infusion of HSD in a near-fatal vascular injury hemorrhage model. Sixteen (15-20 kg) swine with 4-mm aortic tears were hemorrhaged to a pulse pressure of 5 mmHg. An ultrasonic flow probe was placed proximal to the aortic tear for continuous blood flow (AF) measurements. Group I (slow infusion; n = 8) was resuscitated with 8 mL/kg of HSD at 0.4 mL/kg/min. Group II (bolus infusion; n = 8) was resuscitated with 8 mL/kg of HSD at 1.33 mL/kg/min. In both groups, HSD infusion was followed by administration of 30 mL/kg of shed blood at 3 mL/kg/min. Hemorrhage volume and 90-min mortality were greater in group II (79+/-11 mL/kg; 75%) compared with group I (43+/-9 mL/kg; 12.5%) (P(Hem) < 0.001; P(Mort) = 0.04). Mean arterial pressure (MAP) and AF were greater in group II compared with group I during the first 15 min of resuscitation. In group I, MAP, AF, cardiac indices, and O2 delivery gradually returned to baseline levels and were significantly greater than group II at 30 min and throughout the remainder of the protocol. In this model of near-lethal uncontrolled hemorrhage, slow infusion of HSD restored cardiodynamics while minimizing hemorrhage volume and mortality. Resuscitation regimens that cause early increases in blood flow and pressure may result in greater hemorrhage and mortality than those regimens that yield comparable flow and pressure increases late in resuscitation.

Effect of supplemental perfluorocarbon administration on hypotensive resuscitation of severe uncontrolled hemorrhage

Recent animal studies of acute hemorrhage in the presence of a vascular injury have demonstrated improved survival and decreased hemorrhage volume with hypotensive resuscitation, but this has occurred at the expense of tissue perfusion. It was hypothesized that addition of an oxygen-carrying perfusate would improve tissue oxygen delivery during hypotensive resuscitation. Hypotensive resuscitation of severe uncontrolled hemorrhage was compared with and without supplementation with Oxygent HT, an emulsion of perflubron (perfluorooctylbromide; PFOB; Alliance Pharmaceutical Corporation, San Diego, CA), an oxygen-carrying perfusate. Fifteen swine (15 to 22 kg) with 4-mm aortic tears were bled to a pulse pressure of 5 mm Hg and then resuscitated (estimated blood loss, 40 to 50 mL/kg). All animals were resuscitated with normal saline (6 mL/kg/min) infused as needed to maintain a mean arterial pressure of 40 mm Hg. One group (PFC) of animals also received an infusion of 6 mL/kg perfluorooctylbromide emulsion. Another group served as controls and received an equal volume of placebo (normal saline). Animals were observed for 120 minutes or until death. Data were compared using repeated measures analysis of variance (ANOVA) the Students t test, and Fishers exact. A P value < .05 was considered significant. Two-hour mortality rates were 12.5% and 43% for PFC-treated animals and controls, respectively (P > .05; 95% confidence interval [95% CI] for this difference in mortality is -13% to 74%). Oxygen content and delivery were significantly greater in the treatment group. In conclusion, administration of an oxygen-carrying perfusate significantly improves oxygen delivery in hypotensive crystalloid resuscitation of severe uncontrolled hemorrhage.

Funding Strategies for Emergency Medicine Research

The importance of adequate funding for sustaining research efforts cannot be overemphasized. This article addresses funding strategies for emergency physicians including the necessity of establishing a research track record, developing a well-written grant proposal, and anticipating the grant review process. Funding sources are reviewed with an emphasis on federal institute support and private foundations (including the Emergency Medicine Foundation) in the United States. Sources of current grant support information available from the Internet are provided. Recommendations for enhancing research funding in emergency medicine are made, including enhancement of formal research training, promotion of emergency medicine research and investigators, federal study section membership, and collaboration with established investigators.