Journal of neurotrauma
-
Journal of neurotrauma · Dec 2005
Randomized Controlled Trial Multicenter StudyA single dose, three-arm, placebo-controlled, phase I study of the bradykinin B2 receptor antagonist Anatibant (LF16-0687Ms) in patients with severe traumatic brain injury.
Traumatic brain injury (TBI) mortality and morbidity remains a public health challenge. Because experimental studies support an important role of bradykinin (BK) in the neurological deterioration that follows TBI, a double-blind, randomized, placebo-controlled study of Anatibant (LF16- 0687Ms), a selective and potent antagonist of the BK B(2) receptor, was conducted in severe (Glasgow Coma Scale [GCS] < 8) TBI patients (n = 25) at six sites in the United States. At 8-12 h after injury (9.9 +/- 2.8 h), patients received a single subcutaneous injection of Anatibant (3.75 mg or 22.5 mg, n = 10 each) or placebo (n = 5). ⋯ Anatibant, administered as single subcutaneous injections of 3.75 g and 22.5 mg, was well tolerated in severe TBI patients with no unexpected clinical adverse events or biological abnormalities observed. Interestingly, plasma and CSF levels of BK1-5 were significantly and markedly increased after trauma (e.g., 34,700 +/- 35,300 fmol/mL in plasma vs. 34.9 +/- 5.6 fmol/mL previously reported for normal volunteers), supporting the use of Anatibant as a treatment of secondary brain damage. To address this issue, a dose-response trial that would investigate the effects of Anatibant on the incidence of raised ICP and on functional outcome in severe TBI patients is needed.
-
Journal of neurotrauma · Jun 2005
Randomized Controlled Trial Multicenter Study Comparative Study Clinical TrialEfficacy of standard trauma craniectomy for refractory intracranial hypertension with severe traumatic brain injury: a multicenter, prospective, randomized controlled study.
To compare the effect of standard trauma craniectomy (STC) versus limited craniectomy (LC) on the outcome of severe traumatic brain injury (TBI) with refractory intracranial hypertension, we conducted a study at five medical centers of 486 patients with severe TBI (Glasgow Coma Scale score = 8) and refractory intracranial hypertension. In all 486 cases, refractory intracranial hypertension, caused by unilateral massive frontotemporoparietal contusion, intracerebral/subdural hematoma, and brain edema, was confirmed on a CT scan. The patients were randomly divided into two groups, one of which underwent STC (n = 241) with a unilateral frontotemporoparietal bone flap (12 x 15 cm), and the second of which underwent LC (n = 245) with a routine temporoparietal bone flap (6 x 8 cm). ⋯ In addition to these findings, the incidence of delayed intracranial hematoma, incisional hernia, and CSF fistula was lower in the STC group than in the LC group (p < 0.05), although the incidence of acute encephalomyelocele, traumatic seizure, and intracranial infection was not significantly different in the two groups (p > 0.05). The results of the study indicate that STC significantly improves outcome in severe TBI with refractory intracranial hypertension resulting from unilateral frontotemporoparietal contusion with or without intracerebral or subdural hematoma. This suggests that STC, rather than LC, be recommended for such patients.
-
Journal of neurotrauma · Sep 2004
Multicenter Study Comparative StudyAssessment of the macrophage marker quinolinic acid in cerebrospinal fluid after pediatric traumatic brain injury: insight into the timing and severity of injury in child abuse.
This study measured quinolinic acid (QUIN), a macrophage-microglia derived neurotoxin, in the cerebrospinal fluid (CSF) of children after non-inflicted and inflicted traumatic brain injury (nTBI, iTBI), and correlated QUIN concentrations with age, mechanism of injury (nTBi vs. iTBI), Glasgow Coma Scale (GCS) score and 6-month Glasgow Outcome Score. One hundred fifty-two CSF samples were collected from 51 children with severe TBI (GCS < or = 8). CSF was collected at the time an intraventricular catheter was placed and daily thereafter. ⋯ Despite the lack of a history of trauma in 82% of children with iTBI, 100% had a peak QUIN concentration of >100 nM. There was a significant increase in the CSF concentrations of QUIN following severe nTBI and iTBI in children. Higher initial and peak QUIN concentrations after iTBI may be due to severity of injury, young age, and/or delay in seeking medical care, which allows for increased secondary injury.
-
Journal of neurotrauma · Sep 2004
Multicenter Study Comparative StudyInaccurate early assessment of neurological severity in head injury.
Intubation, which requires sedation and myorelaxants, may lead to inaccurate neurological evaluation of severely head-injured patients. Aims of this study were to describe the early clinical evolution of traumatic brain injured (TBI) patients admitted to intensive care unit (ICU), to identify cases of over-estimated neurological severity, and to quantify the risk factors for this over-estimation. A total of 753 TBI patients consecutively admitted to ICU of three academic neurosurgical hospitals (NSH) were assessed. ⋯ The main features distinguishing MS from truly severe cases were younger age, higher Glasgow Coma Scale (GCS) score at all time points, Marshall classification of Computerized Tomographic (CT) scan mostly Diffuse Injury I and II, fewer pupillary abnormalities, and a lower frequency of hypoxia, hypotension, and extra-cranial injuries. In a certain proportion of non-surgical TBI patients, mostly intubated and sedated, neurological examination is difficult and severity can be over-estimated. Risk factors for this inaccurate evaluation can be identified, and clinical decisions should be based on further examination.
-
Journal of neurotrauma · Sep 2004
Multicenter Study Comparative StudyContinuous versus intermittent cerebrospinal fluid drainage after severe traumatic brain injury in children: effect on biochemical markers.
Drainage of cerebrospinal fluid (CSF) is routinely used in the treatment of severe traumatic brain injury (TBI), either continuously or intermittently in response to increases in intracranial pressure (ICP). There has been little study of the effect of CSF drainage method on the biochemistry, pathophysiology or outcome of TBI in adults or children. Having previously reported that a variety of markers of injury or repair increase in CSF after severe TBI, we chose to evaluate directly the effect of CSF drainage method on the biochemistry and volume of CSF drained as well as ICP. ⋯ We conclude that the method of CSF drainage greatly affects concentrations of CSF markers after TBI and may influence ICP. The influence of method on CSF marker concentration must be kept in mind when interpreting studies of CSF biomarkers. The striking difference in biomarker concentration, CSF volume drained, and ICP suggests the need for a randomized trial directly comparing these two approaches in infants and children with severe TBI.