Head injury remains the leading cause of traumatic death, being responsible for 50-60% of fatalities. Of those dying of head injury, 66% have evidence of secondary insults due to reduced cerebral oxygen delivery. Most of these secondary insults are due to intracranial hypertension due to intracranial hematoma, swelling or vasogenic edema. Swelling and vasogenic edema can be exacerbated by intravenous fluid therapy which is necessary to treat hypovolemia and maintain a normal state of hydration. Recent laboratory investigations of head injury suggest that hypertonic fluid may adequately restore and maintain systemic hemodynamics while at the same time reducing intracranial pressure. If such results could be reproduced in patients with head injuries, hypertonic fluid could decrease the frequency of intracranial hypertension and lessen the incidence of secondary injury. We propose to compare a hypertonic fluid regimen to a hypotonic fluid regimen in patients with moderate and severe brain injury by determining the effects of fluid infusion on intracranial pressure. Specifically, we will compare hypertonic saline (1.6%) to a slightly hypotonic saline (0.7%) in the treatment of hypotension or intraoperative blood loss. For those patients without hypotension and who do not require operation, we will compare a hypertonic maintenance fluid (0.9%) to a hypotonic maintenance fluid (0.45%) fluid. Patients will be stratified by injury type and severity prior to randomization which will be done prospectively at the time entry criteria are fulfilled. Patients will be followed throughout the hospital course and at 6 weeks, 6 months and 1 year post discharge.

Agency
National Institute of Health (NIH)
Institute
National Institute of Neurological Disorders and Stroke (NINDS)
Type
Exploratory Grants (P20)
Project #
5P20NS030324-02
Application #
3847142
Study Section
Project Start
Project End
Budget Start
Budget End
Support Year
2
Fiscal Year
1992
Total Cost
Indirect Cost
Name
University of Vermont & St Agric College
Department
Type
DUNS #
066811191
City
Burlington
State
VT
Country
United States
Zip Code
05405
Shackford, S R; Bourguignon, P R; Wald, S L et al. (1998) Hypertonic saline resuscitation of patients with head injury: a prospective, randomized clinical trial. J Trauma 44:50-8
Shackford, S R (1997) Effect of small-volume resuscitation on intracranial pressure and related cerebral variables. J Trauma 42:S48-53
Chappell, J E; Shackford, S R; McBride, W J (1997) Effect of hemodilution with diaspirin cross-linked hemoglobin on intracranial pressure, cerebral perfusion pressure, and fluid requirements after head injury and shock. J Neurosurg 86:131-8
Gourin, C G; Shackford, S R (1997) Production of tumor necrosis factor-alpha and interleukin-1beta by human cerebral microvascular endothelium after percussive trauma. J Trauma 42:1101-7
Shatos, M A; Doherty, J M; Penar, P L et al. (1996) Suppression of plasminogen activator inhibitor-1 release from human cerebral endothelium by plasminogen activators. A factor potentially predisposing to intracranial bleeding. Circulation 94:636-42
Chappell, J E; McBride, W J; Shackford, S R (1996) Diaspirin cross-linked hemoglobin resuscitation improves cerebral perfusion after head injury and shock. J Trauma 41:781-8
Luh, E H; Shackford, S R; Shatos, M A et al. (1996) The effects of hyperosmolarity on the viability and function of endothelial cells. J Surg Res 60:122-8
Gourin, C G; Shackford, S R (1996) Influence of percussion trauma on expression of intercellular adhesion molecule-1 (ICAM-1) by human cerebral microvascular endothelium. J Trauma 41:129-35
Schmoker, J D; Shackford, S R; Zhuang, J (1996) The effect of lesion volume on cerebral vasomotor tone after focal brain injury and shock. J Neurotrauma 13:67-78
Shatos, M A; Orfeo, T; Doherty, J M et al. (1995) Alpha-thrombin stimulates urokinase production and DNA synthesis in cultured human cerebral microvascular endothelial cells. Arterioscler Thromb Vasc Biol 15:903-11

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