Robert J. Hariri

Survey of critical care management of comatose, head-injured patients in the United States

OBJECTIVEnThis survey was designed to study current practices in the monitoring and treatment of patients with severe head injury in the United States.nnnDATA SOURCESnThe collected data represent answers to telephone interviews of nurse managers, clinical specialists, and staff nurses specializing in neurotrauma care at 277 randomly selected hospitals from a total pool of 624 trauma centers. Overall, 261 (94%) centers participated in the survey. Of the participating centers, 219 (84%) were providers of care for severely head-injured patients. In order to assess reliability and account for differences among respondents, personnel from 40 (15%) centers were resurveyed 6 months later and a different nursing professional was interviewed, although the questions remained the same.nnnDATA EXTRACTIONnThe largest group of respondents came from level I centers (49%), followed by level II (32%) and level III (2%). Thirty-four percent of the surveyed hospitals had a designated neurologic/neurosurgical intensive care unit, and 24% of all units surveyed were under the direction of either a neurosurgeon or a neurologist. Twenty-eight percent of the centers routinely performed intracranial pressure monitoring, while 7% of the centers reported never using this technique. The use of ventriculostomy catheters for intracranial pressure monitoring was employed in 72% of the centers, but cerebrospinal fluid drainage was utilized by only 44% of the hospitals. The percentage of patients who had their intracranial pressure monitored was significantly higher in level I trauma centers and at hospitals that treated larger numbers of severely head-injured patients (15 to 30 patients per month, which represented 15% of the hospitals surveyed). Hyperventilation and osmotic diuretics were used in 83% of centers to reduce intracranial hypertension. The administration of barbiturates was reported in 33% of the units as a treatment for intracranial hypertension. Corticosteroids were used more than half of the time in 64% of trauma centers. Twenty-nine percent of the centers reported aiming for PaCO2 values of < 25 torr (< 3.3 kPa).nnnCONCLUSIONSnThe survey data indicate that there is a considerable variation in the management of patients with severe head injury in the United States. The establishment of guidelines for the management of head injury based on available scientific data and moderated by practical and financial considerations may lead to improvement in the standard of care.

Fluid percussion barotrauma chamber: A new in vitro model for traumatic brain injury

Advances in the understanding of the pathophysiology of traumatic brain injury have implicated a number of cellular events as fundamental to the evolution of neurologic dysfunction in this process. Following the primary biomechanical insult, a highly complex series of biochemical changes occur, some of which are reversible. The development of fluid percussion injury as an in vivo model for traumatic brain injury has greatly improved our ability to study this disease. However, a comparable in vitro model of biomechanical injury which would enable investigators to study the response to injury in isolated cell types has not been described. We have developed a model of transient barotrauma in cell culture to examine the effects of this form of injury on cell metabolism. This model employs the same fluid percussion device commonly used in in vivo brain injury studies. The effect of this injury was evaluated in monolayers of human glial cells. Cell viability by trypan blue exclusion and the production of leukotrienes following increasing barotrauma was investigated. This model provided a reproducible method of subjecting cells in culture to forces similar to those currently used in animal experimental head injury.

Effect of low dose gamma-butyrolactone therapy on forebrain neuronal ischemia in the unrestrained, awake rat.

Low dose gamma-butyrolactone (GBL) therapy alters the natural history of experimental forebrain ischemia in the awake rat. After 30 minutes of four-vessel ischemia, repeated hydrogen cerebral blood flow determinations in awake rats over 72 hours revealed that low dose GBL therapy prevented the development of regional cerebral hyperemia and later the prolonged cerebral hypoperfusion that was experienced by the nontreated controls. Moreover, the low dose GBL-treated group had significantly less neuronal tissue loss than that in comparable brain regions of the nontreated controls. Before the stroke studies, GBL dose-response experiments performed on normal rats indicated that high dose GBL therapy produced seizures, systemic hypertension, metabolic acidosis, hyperthermia, and death.

Human glial cell production of lipoxygenase-generated eicosanoids: a potential role in the pathophysiology of vascular changes following traumatic brain injury

Acute cerebrovascular changes which occur following traumatic brain injury represent a highly complex, multifactorial pathophysiologic process which is poorly understood. It is now recognized that, under normal conditions, the brain is a source of a variety of arachidonic acid metabolites which are synthesized by both cyclooxygenase and lipoxygenase. The specific cellular source of these highly vasoactive substances remains controversial. Recent work has demonstrated that lipoxygenase products were detected by immunosensitive assay in whole brain samples from a gerbil concussive injury model, yet the production of leukotrienes could not be accounted for by cerebral vessels and their contents alone. It has been theorized that the probable source for these metabolites is the cortical neuron. We sought to elucidate whether cultured human glial cells, obtained from specimens removed at the time of surgery, are a significant source of lipoxygenase products as measured by high performance liquid chromatography (HPLC). We observed that these cells consistently produced 5, 12, and 15-HETE class eicosanoids despite failure to produce significant cyclooxygenase products. These preliminary findings are of considerable interest because these lipoxygenase products are known to be highly vasoactive as well as potent mediators of increased vascular permeability. Since it is known that mechanical perturbation of cell membranes stimulates the release of arachidonic acid from membrane phospholipids, it is conceivable that the production of these eicosanoids following traumatic brain injury could account for local cerebrovascular changes including both vasospasm and interstitial edema formation.

Aortic collagenase activity as affected by laparotomy, cecal resection, aortic mobilization, and aortotomy in rats

Recent biochemical evidence that aneurysm formation may be related to higher activated collagenase levels within aneurysmal aortic walls in association with reports of asymptomatic aneurysm rupture after laparotomy has led to speculation that operative trauma unrelated to direct aortic injury may increase the chance of aneurysm rupture by inducing collagenase activation within the aortic wall. The purpose of this study was to determine whether aortic collagenase can be activated by distant operative trauma and the kinetics of activation after injury. Ninety-six rats were divided into four groups: group 1--laparotomy alone; group 2--cecal resection; group 3--aortic mobilization; and group 4--aortotomy and repair. Animals within each group were sacrificed 1,3, and 6 hours and 1,2,3,4, and 5 days after surgery. The abdominal aortas were removed and assayed for collagenase activity by incubation with and digestion of tritium-labeled collagen. Collagenase activity was significantly elevated up to 6 hours after direct aortic injury (p less than 0.05) and decreased to normal levels within 2 days. Laparotomy, colon resection, and aortic mobilization had no significant effect on aortic collagenase activity compared to the controls. These data suggest that collagenase activity is a local phenomenon related to wound healing at the site of initial injury. Operative trauma without direct aortic injury had no effect on aortic collagenase activity.

Changes of MPO activity and brain water accumulation in traumatic brain injury experiments.

Comparison of brain tissue water content (BWC) data with myeloperoxidase activity assay (MPO) allows for analysis of the complex pathophysiological mechanisms of cerebral edema following catastrophic brain injuries. The neuroprotective effect of an experimental anti inflammatory drug (FL1003, butyrolactone) was tested in a traumatic brain injury (TBI) model using BWC and MPO analysis. We conducted these studies on a mini-pig model of severe TBI that is well characterized in our laboratory. The animals were divided into three animal groups: no injury, no treatment (control), injured and treated with FL1003, and injured, untreated with FL1003. They were maintained with fluids for 24 hours under general anesthesia. We employed the MPO assay to identify the degree of inflammatory cellular response (polymorphonuclear leukocytes, PMNLs) 24 hours following TBI and calculated brain density from the data of the gravimetric (Percoll) column method for BWC on brain samples. Our results demonstrated increased infiltration of PMNLs and a shift of water into the extravascular space in the injured animals. These changes were significantly (P < 0.05) attenuated in the animal group treated with FL1003.

A method for monitoring intracranial temperature via tunneled ventricular catheter: technical note.

A simple technique for monitoring intracerebral temperature in humans via a ventricular catheter is described. This differs from a previously described method by enabling such measurements to be accomplished with a commercially available thermistor, a standard ventricular catheter, and common hospital supplies. In contrast to the earlier device, this system allows for the subcutaneous tunneling of the distal ventricular catheter. This is an easily assembled and cost-effective technique with which to conduct investigations on human intracerebral temperature.

Leukotriene Production by Human Glia

Elevated intracranial pressure and acute cerebrovascular changes following head injury remain the principle challenge in the management of traumatic brain injury. Recent work has demonstrated that leukotrienes can induce increases in blood brain barrier permeability and alter cerebrovascular dynamics. We investigated whether human astroglia in culture: 1. generate specific leukotrienes; 2. how they metabolize leukotrienes, and; 3. if astroglia generate leukotrienes in response to barotraumatic injury. Human astroglial cultures established from normal human brain obtained at surgery were exposed to either ionophore, exogenous 3H-LTC4, or barotraumatic injury. Supernatants were assayed for specific leukotrienes by one of three methods: HPLC, radioimmunoassay, or enzyme-immunoassay. Glial cells exposed to exogenous LTC4 metabolized nearly all of the LTC4 to LTD4 and LTE4 within 20 minutes. Glial cells stimulated with ionophore produced mostly LTC4 at five minutes after stimulation and LTD4 and LTE4 at fifteen minutes after stimulation. Glial cells subject to barotraumatic injury produced LTC4 in concentrations of 40-200 pg/ml 15 minutes after injury. These results demonstrate that human astroglial cells are capable of rapidly generating and degrading LTC4 and this capability of glial cells may play an important role in the pathophysiology of cerebrovascular changes following head injury.

Extravascular Lung Water and High-Frequency Ventilationa

High-frequency ventilation (HFV) is a relatively new technique that provides alveolar ventilation at rates well above the usual despite tidal volumes a t or near the volume of the anatomical dead space. These characteristics have created a need for new techniques of measurement and challenged basic concepts of mechanical ventilation. This study was performed to assess the effect of high-frequency ventilation on extravascular lung water as measured by the thermal-dye