Patient Characterization Protocols for Psychophysiological Studies of Traumatic Brain Injury and Post-TBI Psychiatric Disorders.

Psychophysiological investigations of traumatic brain injury (TBI) are being conducted for several reasons, including the objective of learning more about the underlying physiological mechanisms of the pathological processes that can be initiated by a head injury. Additional goals include the development of objective physiologically based measures that can be used to monitor the response to treatment and to identify minimally symptomatic individuals who are at risk of delayed-onset neuropsychiatric disorders following injury. Research programs studying TBI search for relationships between psychophysiological measures, particularly ERP (event-related potential) component properties (e.g., timing, amplitude, scalp distribution), and a participant's clinical condition. Moreover, the complex relationships between brain injury and psychiatric disorders are receiving increased research attention, and ERP technologies are making contributions to this effort. This review has two objectives supporting such research efforts. The first is to review evidence indicating that TBI is a significant risk factor for post-injury neuropsychiatric disorders. The second objective is to introduce ERP researchers who are not familiar with neuropsychiatric assessment to the instruments that are available for characterizing TBI, post-concussion syndrome, and psychiatric disorders. Specific recommendations within this very large literature are made. We have proceeded on the assumption that, as is typically the case in an ERP laboratory, the investigators are not clinically qualified and that they will not have access to participant medical records.

Profound hypothermia is superior to ultraprofound hypothermia in improving survival in a swine model of lethal injuries.

BACKGROUND: Rapid induction of profound hypothermia can improve survival from uncontrolled lethal hemorrhage. However, the optimal depth of hypothermia in this setting remains unknown. This experiment was designed to compare the impact of deep (15 degrees C), profound (10 degrees C), and ultraprofound (5 degrees C) hypothermia on survival and organ functions. METHODS: Uncontrolled lethal hemorrhage was induced in 32 swine (80-120 lb) by creating an iliac artery and vein injury, followed 30 minutes later by laceration of the descending thoracic aorta. Hypothermia was induced rapidly (2 degrees C/min) by infusing cold organ preservation solution into the aorta through a thoracotomy. The experimental groups were (n = 8 per group): a normothermic control, and 3 hypothermic groups in which the core temperature was reduced to 15 degrees C, 10 degrees C, and 5 degrees C. Vascular injuries were repaired during 60 minutes of hypothermia. Animals were then rewarmed (0.5 degrees C/min) and resuscitated on cardiopulmonary bypass, and monitored for 6 weeks for neurologic deficits, cognitive function, and organ dysfunction. RESULTS: All normothermic animals died, whereas 6-week survival rates for the 15 degrees C, 10 degrees C, and 5 degrees C groups were 62.5%, 87.5%, and 25%, respectively (P < .05: normothermic vs 15 degrees C and 10 degrees C; 10 degrees C vs 5 degrees C). The surviving animals from the 15 degrees C and 10 degrees C groups were neurologically intact, displayed normal learning capacity, and had no long-term organ dysfunction. The survivors from the 5 degrees C group displayed slower recovery and impaired cognitive functions. CONCLUSIONS: In a model of lethal injuries, rapid induction of profound hypothermia can prevent death. The depth of hypothermia influences survival, with a better outcome associated with a core temperature of 10 degrees C compared with 5 degrees C.

Does the rate of rewarming from profound hypothermic arrest influence the outcome in a swine model of lethal hemorrhage?

BACKGROUND: Rapid induction of profound hypothermic arrest (suspended animation) can provide valuable time for the repair of complex injuries and improve survival. The optimal rate for re-warming from a state of profound hypothermia is unknown. This experiment was designed to test the impact of different warming rates on outcome in a swine model of lethal hemorrhage from complex vascular injuries. METHODS: Uncontrolled lethal hemorrhage was induced in 40 swine (80-120 lbs) by creating an iliac artery and vein injury, followed 30 minutes later (simulating transport time) by laceration of the descending thoracic aorta. Through a thoracotomy approach, a catheter was placed in the aorta and hyperkalemic organ preservation solution was infused on cardiopulmonary bypass to rapidly (2 degrees C/min) induce profound (10 degrees C) hypothermia. Vascular injuries were repaired during 60 minutes of hypothermic arrest. The 4 groups (n = 10/group) included normothermic controls (NC) where core temperature was maintained between 36 to 37 degrees C, and re-warming from profound hypothermia at rates of: 0.25 degrees C/min (slow), 0.5 degrees C/min (medium), or 1 degrees C/min (fast). Hyperkalemia was reversed during the hypothermic arrest period, and blood was infused for resuscitation during re-warming. After discontinuation of cardiopulmonary bypass, the animals were recovered and monitored for 6 weeks for neurologic deficits, cognitive function (learning new skills), and organ dysfunction. Detailed examination of brains was performed at 6 weeks. RESULTS: All the normothermic animals died, whereas survival rates for slow, medium and fast re-warming from hypothermic arrest were 50, 90, and 30%, respectively (p < 0.05 slow and medium warming versus normothermic control, p < 0.05 medium versus fast re-warming). All the surviving animals were neurologically intact, displayed normal learning capacity, and had no long-term organ dysfunction. CONCLUSIONS: Rapid induction of hypothermic arrest maintains viability of brain during repair of lethal vascular injuries. Long-term survival is influenced by the rate of reversal of hypothermia.

Profound hypothermia protects neurons and astrocytes, and preserves cognitive functions in a Swine model of lethal hemorrhage.

BACKGROUND: Lethal injuries can be repaired under asanguineous hypothermic arrest (suspended animation) with excellent survival. This experiment was designed to test the impact of this strategy on neuronal and astroglial damage in a swine model of lethal hemorrhage. Furthermore, our goal was to correlate the histological changes in the brain with neurological outcome, and the levels of circulating brain specific markers. MATERIALS AND METHODS: Uncontrolled hemorrhage was induced in 32 female swine (80-120 lbs) by creating an iliac artery and vein injury, followed 30 min later by laceration of the thoracic aorta. Through a thoracotomy approach, organ preservation fluid was infused into the aorta using a roller pump. Experimental groups included normothermic controls (no cooling, NC), and groups where hypothermia was induced at three different rates: 0.5 degrees C/min (slow, SC), 1 degrees C/min (medium, MC), or 2 degrees C/min (fast, FC). Profound hypothermia (core temperature of 10 degrees C) was maintained for 60 min for repair of vascular injuries, after which the animals were re-warmed (0.5 degrees C/min) and resuscitated on cardiopulmonary bypass (CPB). Circulating levels of neuron specific enolase (NSE) and S-100beta were serially measured as markers of damage to neurons and astrocytes, respectively. Light microscopy and quantitative immunohistochemical techniques were used to evaluate hippocampal CA1 area and caudate putamen for neuronal injury and astrogliosis (astrocyte hyperplasia/hypertrophy). Surviving animals were observed for 6 weeks and neurological status was documented on an objective scale, and cognitive functions were evaluated using a technique based upon the concept of operant conditioning. RESULTS: Normothermic arrest resulted in clinical brain death in all of the animals. None of the surviving hypothermic animals displayed any neurological deficits or cognitive impairment. On histological examination, normothermic animals were found to have ischemic changes in the neurons and astrocytes (hypertrophy). In contrast, all of the hypothermic animals had histologically normal brains. The circulating levels of brain specific proteins did not correlate with the degree of brain damage. The changes in NSE levels were not statistically significant, whereas S-100beta increased in the circulation after CPB, largely independent of the temperature modulation. CONCLUSIONS: Profound hypothermia can preserve viability of neurons and astrocytes during prolonged periods of cerebral hypoxia. This approach is associated with excellent cognitive and neurological outcome following severe shock. Circulating markers of central nervous system injury did not correlate with the actual degree of brain damage in this model.

The rate of induction of hypothermic arrest determines the outcome in a Swine model of lethal hemorrhage.

BACKGROUND: Lethal injuries can be surgically repaired under asanguineous hypothermic condition (suspended animation) with excellent outcome. However, the optimal rate for the induction of hypothermic metabolic arrest following uncontrolled lethal hemorrhage (ULH) is unknown. METHODS: ULH was induced in 32 female swine (80-120 lbs) by creating an iliac artery and vein injury, followed 30 minutes later by laceration of the descending thoracic aorta. Through a left thoracotomy approach, total body hypothermic hyperkalemic metabolic arrest was induced by infusing organ preservation fluids into the aorta. Experimental groups were: normothermic controls (no cooling, NC), or hypothermia induced at a rate of 0.5 degrees C/min (slow, SC), 1 degrees C/min (medium, MC), or 2 degrees C/min (fast, FC). Vascular injuries were repaired during the 60 minutes of profound (10 degrees C) hypothermic arrest. Hyperkalemia was reversed by hypokalemic fluid exchange, and blood was infused for resuscitation during the re-warming (0.5 degrees C/ minute) period. The survivors were monitored for 6 weeks. RESULTS: The 6 week survival rates were 0% (NC), 37.5% (SC), 62.5% (MC), and 87.5% (FC) respectively (p < 0.05 MC&FC versus NC). All of the surviving hypothermic arrest animals were neurologically intact and displayed no long term organ dysfunction. CONCLUSION: Hypothermic metabolic arrest can be used to maintain viability of key organs during repair of lethal injuries. Survival is influenced by the rate of cooling with the best outcome following rapid induction of hypothermia.

Application of a zeolite hemostatic agent achieves 100% survival in a lethal model of complex groin injury in Swine.

BACKGROUND: Techniques for better hemorrhage control after injury could change outcome. We have previously shown that a zeolite mineral hemostatic agent (ZH) can control aggressive bleeding through adsorption of water, which is an exothermic process. Increasing the residual moisture content (RM) of ZH can theoretically decrease heat generation, but its effect on the hemostatic properties is unknown. We tested ZH with increasing RM against controls and other hemostatic agents in a swine model of battlefield injury. METHODS: A complex groin injury was created in 72 swine (37 +/- 0.8 kg). This included semitransection of the proximal thigh and complete division of the femoral artery and vein. After 3 minutes, the animals were randomized to 1 of 10 groups: group 1, no dressing (ND); group 2, standard dressing (SD); group 3, SD + 3.5 oz ZH with 1% RM (1% ZH); group 4, SD + 3.5 oz ZH with 4% RM (4% ZH); group 5, SD + 2 oz ZH with 1% RM (1% ZH 2oz); group 6, SD + 3.5 oz ZH with 8% RM (8% ZH); group 7, SD + chitosan-based hemostat, HemCon (HC); group 8, SD + 3.5 oz nonzeolite mineral hemostat, Quick Relief (NZH); group 9, SD + bovine clotting factors-based hemostat, Fast Act (FA); and group 10, SD + 30 g of starch-based hemostat, TraumaDex (TDex). Resuscitation (500 mL of Hespan over 30 minutes) was started 15 minutes after injury and hemodynamic monitoring was performed for 180 minutes. Primary endpoints were survival for 180 minutes and blood loss. In addition, maximum wound temperatures were recorded, and histologic damage to artery, vein, nerve, and muscle was documented. RESULTS: Use of 1% ZH decreased blood loss and reduced mortality to 0% (p < 0.05). Increasing the RM adversely affected efficacy without any significant decrease in wound temperatures. Minimal histologic tissue damage was seen with ZH independent of the percentage of RM. CONCLUSION: The use of zeolite hemostatic agent (1% residual moisture, 3.5 oz) can control hemorrhage and dramatically reduce mortality from a lethal groin wound.