Automated closed-loop resuscitation of multiple hemorrhages: a comparison between fuzzy logic and decision table controllers in a sheep model.

Background: Hemorrhagic shock is the leading cause of trauma-related death in the military setting. Definitive surgical treatment of a combat casualty can be delayed and life-saving fluid resuscitation might be necessary in the field. Therefore, improved resuscitation strategies are critically needed for prolonged field and en route care.

Intramuscular versus Intraosseous Delivery of Nerve Agent Antidote Pralidoxime Chloride in Swine.

Objective: Exposure to nerve agents requires prompt treatment. We hypothesized that intraosseous (IO) injections of drug antidotes into the vascularized bone marrow will provide a more rapid and effective means to treat exposure to nerve agents than standard intramuscular (IM) injections. We compared the pharmacokinetics of IM and IO administration of pralidoxime chloride (2-PAM Cl) during normovolemia and hypovolemia, as well as their combined administration during normovolemia in swine.

γ-tocopherol nebulization decreases oxidative stress, arginase activity, and collagen deposition after burn and smoke inhalation in the ovine model.

More than 20,000 burn injury victims suffer from smoke inhalation injury in the United States annually. In an ovine model of acute lung injury, γ-tocopherol had a beneficial effect when nebulized into the airway. We hypothesize that γ-tocopherol scavenges reactive oxygen species (ROS) and reactive nitrogen species resulting from burn and smoke inhalation injury and that these ROS/reactive nitrogen species activate the arginase pathway, leading to increased collagen deposition and decreased pulmonary function.

Development of a long-term ovine model of cutaneous burn and smoke inhalation injury and the effects of early excision and skin autografting.

Unlabelled: Smoke inhalation injury frequently increases the risk of pneumonia and mortality in burn patients. The pathophysiology of acute lung injury secondary to burn and smoke inhalation is well studied, but long-term pulmonary function, especially the process of lung tissue healing following burn and smoke inhalation, has not been fully investigated. By contrast, early burn excision has become the standard of care in the management of major burn injury.

Substance P antagonist CP-96345 blocks lung vascular leakage and inflammation more effectively than its stereoisomer CP-96344 in a mouse model of smoke inhalation and burn injury.

The recently developed murine model of smoke inhalation and burn (SB) injury was used to study the effect of the substance-P antagonist CP96345. C57BL/6 mice were pre-treated with an i.v.

Mechanisms of toxic smoke inhalation and burn injury: role of neutral endopeptidase and vascular leakage in mice.

The effects of neutral endopeptidase (NEP) in acute inflammation in the lung were studied using a newly developed murine model of smoke and burn (SB) injury. C57BL/6 mice were pretreated with an i.v.

Pulmonary changes in a mouse model of combined burn and smoke inhalation-induced injury.

The morbidity and mortality of burn victims increase when burn injury is combined with smoke inhalation. The goal of the present study was to develop a murine model of burn and smoke inhalation injury to more precisely reveal the mechanistic aspects of these pathological changes. The burn injury mouse group received a 40% total body surface area third-degree burn alone, the smoke inhalation injury mouse group received two 30-s exposures of cotton smoke alone, and the combined burn and smoke inhalation injury mouse group received both the burn and the smoke inhalation injury.

Assessment of lung inflammation in a mouse model of smoke inhalation and burn injury: strain-specific differences.

ABSTRACT To test concepts developed in our ovine model of acute respiratory distress syndrome, specifically the roles of neuropeptides and other peptide mediators, a recently developed murine model of combined smoke inhalation and burn (SB) injury was extended by applying methods for quantitative assessment of acute inflammation in the lung. Mice received SB injury per protocol, n = 5 to 7 per group. Mice were anesthetized with i.

Optional active compliance chamber performance in a pulmonary artery-pulmonary artery configured paracorporeal artificial lung.

Introduction: Our group has developed a paracorporeal artificial lung (PAL) attached in a pulmonary artery (PA) to PA in series configuration to address profound respiratory failure and serve as a bridge to transplant and/or recovery. We recently designed, developed and converted our passive pre-PAL compliance chamber to an active, synchronized, counterpulsating assist device to relieve right heart strain and offset increased work placed on the right ventricle when the PAL is attached. In this study, we evaluated the safety and performance of both a valved and non-valved optional active compliance chamber (OACC) in a PA-PA PAL for right heart assistance in normal adult sheep.

High-frequency percussive ventilation with systemic heparin improves short-term survival in a LD100 sheep model of acute respiratory distress syndrome.

We undertook an assessment of high-frequency percussive ventilation (HFPV) and systemic heparin on survival in our LD100 sheep model of smoke/burn-induced acute respiratory distress syndrome (ARDS). This was a prospective controlled outcomes study in a large animal critical care laboratory. ARDS was induced in 13 sheep by a combination of 48 cotton smoke breaths and 40% full-thickness cutaneous burn (LD100) followed by mechanical ventilation (15 ml/kg tidal volume).

Normotensive and hypotensive closed-loop resuscitation using 3.0% NaCl to treat multiple hemorrhages in sheep.

Objective: NaCl solutions (7.5%) have been reported to be effective for resuscitation in animals and trauma patients, but these solutions are not approved for use in the United States. We hypothesized that infusion of Food and Drug Administration-approved 3% NaCl provides superior cardiovascular and metabolic function while reducing the overall fluid requirement for resuscitation of hemorrhage.

Optoacoustic monitoring of blood hemoglobin concentration: a pilot clinical study.

The optoacoustic technique is noninvasive, has high spatial resolution, and potentially can be used to measure the total hemoglobin concentration ([THb]) continuously and accurately. We performed in vitro measurements in blood and in vivo tests in healthy volunteers. Our clinical protocol included rapid infusion of intravenous saline to simulate rapid change in the [THb] during fluid therapy or surgery.

Optoacoustic, noninvasive, real-time, continuous monitoring of cerebral blood oxygenation: an in vivo study in sheep.

Background: Current, invasive cerebral oxygenation monitors require either retrograde jugular venous bulb cannulation or intraparenchymal probe insertion. There is no accurate, noninvasive, continuous monitor of cerebral blood oxygenation.

Methods: The authors designed, built, and tested novel optoacoustic instrumentation that continuously measures blood oxygenation in the superior sagittal sinus (SSS) in vivo in 12 anesthetized sheep.

Hypotensive resuscitation of multiple hemorrhages using crystalloid and colloids.

Hypotensive resuscitation has been advocated as a better means to perform field resuscitation of penetrating trauma. Our hypothesis is that hypotensive resuscitation using either crystalloid or colloid provides equivalent or improved metabolic function while reducing the overall fluid requirement for resuscitation of hemorrhage. We compared hypotensive and normotensive resuscitation of hemorrhage using lactated Ringer's (LR) with hypotensive resuscitation using Hextend (Hex), 6% hetastarch in isotonic buffered saline.

Continuous, noninvasive monitoring of total hemoglobin concentration by an optoacoustic technique.

Measurement of total hemoglobin concentration [Hgb] is a blood test that is widely used to evaluate outpatients, hospital inpatients, and surgical patients, especially those undergoing surgery associated with extensive blood loss, rapid fluid administration, and transfusion of packed red blood cells. Current techniques for measurement of [Hgb] are invasive (requiring blood sampling) and cannot provide real-time, continuous monitoring. We propose to use an optoacoustic technique for noninvasive and continuous monitoring of [Hgb].

Hemodynamic and cardiac contractile function during sepsis caused by cecal ligation and puncture in mice.

Sepsis is among the leading causes of death in the critically ill, yet the pathophysiology of sepsis is incompletely understood. Genetically engineered mice offer a unique opportunity to explore the cellular and molecular pathogenesis of sepsis. However, the hemodynamic responses of mice during sepsis are not completely understood because of the difficulty in performing cardiovascular measurements in mice.

Short term performance evaluation of a perfluorocopolymer coated gas exchanger for arteriovenous CO2 removal.

A new perfluorocopolymer coating for micropore hollow fiber gas exchangers was developed to improve gas exchange, reduce plasma leakage, and reduce blood-surface interactions. The present authors evaluated gas exchanger performance using this new coating in a prospective, randomized, controlled, unblinded, large animal model of CO2 retention. Adult sheep (30-40 kg), under general anesthesia, underwent cannulation of the carotid artery (12 F) and jugular vein (14 F).

Toward ambulatory arteriovenous CO2 removal: initial studies and prototype development.

Extracorporeal arteriovenous carbon dioxide removal (AVCO2R) using percutaneous cannulae and a low resistance gas exchanger achieves near total CO2 removal, allowing lung rest and potentially improving survival. AVCO2R, redesigned to allow ambulation, has potential as treatment for severe chronic obstructive pulmonary disease or rehabilitation before lung transplant. The purposes of this study were to 1) determine the optimal ambulatory access for AVCO2 removal and 2) develop a prototype Ambulatory-AVCO2R gas exchanger.

Lubeluzole and conditioned learning after cerebral ischemia.

Lubeluzole [S-4-(2-benzothiazolylmethylamino)-alpha-((3,4-difluorophenoxy)methyl)-1-piperidineethanol] reduces the severity of cerebral injury in animal models of brain ischemia. Its beneficial effects may include decreased concentration of extracellular glutamate, blockade of sodium and calcium channels, and attenuation of nitric oxide-mediated neuronal death. Previous studies have shown that global cerebral ischemia in rabbits impaired the subsequent acquisition of a trace-conditioned eyeblink reflex.

Paracorporeal artificial lung: perioperative management for survival study in sheep.

An artificial lung may offer a bridge to recovery or transplant. Utilizing our recently developed paracorporeal artificial lung (PAL) in survival studies in sheep, we critically review our perioperative/anesthetic protocol. Adult Suffolk ewes (n = 15) underwent general anesthesia induced by ketamine (7-15 mg/kg, im) and isoflurane by mask, then intubated and maintained by 4.

Near-infrared spectroscopy-guided closed-loop resuscitation of hemorrhage.

Background: Endpoint resuscitation has been suggested as a better means to resuscitate penetrating injury. We performed computer-controlled closed-loop resuscitation using invasive cardiac output (CO) or noninvasive skeletal muscle oxygen saturation (SkMusSO(2)) via near infrared spectroscopy (NIRS).

Methods: Conscious sheep received a 4.

The effect of augmented hemodynamics on blood flow during arteriovenous carbon dioxide removal.

Arteriovenous carbon dioxide removal (AVCO2R) as an alternative treatment for acute respiratory distress syndrome uses a low resistance gas exchanger in a simple arteriovenous shunt to achieve total CO2 removal and allow lung rest. We have previously shown in our clinically relevant LD40 ovine model of smoke/burn induced acute respiratory distress syndrome that AVCO2R allows significant decreases in respiratory rate, tidal volume, peak airway pressure, and FiO2, as compared with standard mechanical ventilation. In addition, we have shown in a prospective randomized outcomes study that AVCO2R increases ventilator free days, decreases ventilator dependent days, and significantly improves survival.

The paracorporeal artificial lung improves 5-day outcomes from lethal smoke/burn-induced acute respiratory distress syndrome in sheep.

Background: Our low-impedence, paracorporeal artificial lung (PAL) prototype is well-tolerated in-series with the normal sheep pulmonary circulation. Using our lethal dose 80% to 100% smoke/burn acute respiratory distress syndrome (ARDS) sheep model, we compared PAL to volume-controlled mechanical ventilation (VCMV) in a prospective, randomized, controlled, unblinded, 5-day outcome study.

Methods: Fourteen sheep were randomized to PAL (n = 8) versus VCMV (n = 6) to assess outcome.

Hemodynamic benefit of positive end-expiratory pressure during acute descending aortic occlusion.

Background: Acute aortic occlusion in vascular surgery patients abruptly increases arterial resistance and blood pressure, which, in turn, makes subsequent volume expansion during cross-clamp application difficult. The use of vasodilatory drugs or volatile anesthetic agents to attenuate this response may have persistent detrimental effects after clamp removal. Another potential therapy that produces rapid effects on myocardial loading conditions is positive end-expiratory pressure (PEEP).