Intercenter variance in clinical trials of head trauma—experience of the National Acute Brain Injury Study: Hypothermia

2001 ◽  
Vol 95 (5) ◽  
pp. 751-755 ◽  
Author(s):  
Guy L. Clifton ◽  
Sung C. Choi ◽  
Emmy R. Miller ◽  
Harvey S. Levin ◽  
Kenneth R. Smith ◽  
...  
Keyword(s):  
Clinical Trials ◽  
Brain Injury ◽  
Phase Iii ◽  
Severe Brain Injury ◽  
Quality Of Data ◽  
Content Type ◽  
Physiological Variables ◽  
Arterial Blood ◽  
Present On Admission ◽  
Fine Print

Object. In a recently conducted trial of hypothermia in patients with severe brain injury, differences were found in the effects of hypothermia treatment among various centers. This analysis explores the reasons for such differences. Methods. The authors reviewed data obtained in 392 patients treated for severe brain injury. Prerandomization variables, critical physiological variables, treatment variables, and accrual methodologies were investigated among various centers. Hypothermia was found to be detrimental in patients older than the age of 45 years, beneficial in patients younger than 45 years of age in whom hypothermia was present on admission, and without effect in those in whom normothermia was documented on admission. Marginally significant differences (p < 0.054) in the intercenter outcomes of hypothermia-treated patients were likely the result of wide differences in the percentage of patients older than 45 years of age and in the percentage of patients in whom hypothermia was present on admission among centers. The trial sensitivity was likely diminished by significant differences in the incidence of mean arterial blood pressure (MABP) less than 70 mm Hg (p < 0.001) and cerebral perfusion pressure (CPP) less than 50 mm Hg (p < 0.05) but not intracranial pressure (ICP) greater than 25 mm Hg (not significant) among patients in the various centers. Hours of vasopressor usage (p < 0.03) and morphine dose (p < 0.001) and the percentage of dehydrated patients varied significantly among centers (p < 0.001). The participation of small centers increased intercenter variance and diminished the quality of data. Conclusions. For Phase III clinical trials we recommend: 1) a detailed protocol specifying fluid and MABP, ICP, and CPP management; 2) continuous monitoring of protocol compliance; 3) a run-in period for new centers to test accrual and protocol adherence; and 4) inclusion of only centers in which patients are regularly randomized.

The effect of nimodipine on cerebral oxygenation in patients with poor-grade subarachnoid hemorrhage

2004 ◽  
Vol 101 (4) ◽  
pp. 594-599 ◽  
Author(s):  
Michael F. Stiefel ◽  
Gregory G. Heuer ◽  
John M. Abrahams ◽  
Stephanie Bloom ◽  
Michelle J. Smith ◽  
...  
Keyword(s):  
Blood Pressure ◽  
Subarachnoid Hemorrhage ◽  
Brain Tissue ◽  
Cerebral Oxygenation ◽  
Content Type ◽  
Poor Grade ◽  
Physiological Variables ◽  
Arterial Blood ◽  
End Tidal ◽  
Fine Print

Object. Nimodipine has been shown to improve neurological outcome after subarachnoid hemorrhage (SAH); the mechanism of this improvement, however, is uncertain. In addition, adverse systemic effects such as hypotension have been described. The authors investigated the effect of nimodipine on brain tissue PO2. Methods. Patients in whom Hunt and Hess Grade IV or V SAH had occurred who underwent aneurysm occlusion and had stable blood pressure were prospectively evaluated using continuous brain tissue PO2 monitoring. Nimodipine (60 mg) was delivered through a nasogastric or Dobhoff tube every 4 hours. Data were obtained from 11 patients and measurements of brain tissue PO2, intracranial pressure (ICP), mean arterial blood pressure (MABP), and cerebral perfusion pressure (CPP) were recorded every 15 minutes. Nimodipine resulted in a significant reduction in brain tissue PO2 in seven (64%) of 11 patients. The baseline PO2 before nimodipine administration was 38.4 ± 10.9 mm Hg. The baseline MABP and CPP were 90 ± 20 and 84 ± 19 mm Hg, respectively. The greatest reduction in brain tissue PO2 occurred 15 minutes after administration, when the mean pressure was 26.9 ± 7.7 mm Hg (p < 0.05). The PO2 remained suppressed at 30 minutes (27.5 ± 7.7 mm Hg [p < 0.05]) and at 60 minutes (29.7 ± 11.1 mm Hg [p < 0.05]) after nimodipine administration but returned to baseline levels 2 hours later. In the seven patients in whom brain tissue PO2 decreased, other physiological variables such as arterial saturation, end-tidal CO2, heart rate, MABP, ICP, and CPP did not demonstrate any association with the nimodipine-induced reduction in PO2. In four patients PO2 remained stable and none of these patients had a significant increase in brain tissue PO2. Conclusions. Although nimodipine use is associated with improved outcome following SAH, in some patients it can temporarily reduce brain tissue PO2.

Cerebral oxygenation following decompressive hemicraniectomy for the treatment of refractory intracranial hypertension

2004 ◽  
Vol 101 (2) ◽  
pp. 241-247 ◽  
Author(s):  
Michael F. Stiefel ◽  
Gregory G. Heuer ◽  
Michelle J. Smith ◽  
Stephanie Bloom ◽  
Eileen Maloney-Wilensky ◽  
...  
Keyword(s):  
Brain Injury ◽  
Intracranial Hypertension ◽  
Brain Tissue ◽  
Medical Management ◽  
Cerebral Oxygenation ◽  
Severe Brain Injury ◽  
Content Type ◽  
Decompressive Hemicraniectomy ◽  
Gcs Score ◽  
Fine Print

Object. Medically intractable intracranial hypertension is a major cause of morbidity and mortality after severe brain injury. One potential treatment for intracranial hypertension is decompressive hemicraniectomy (DCH). Whether and when to use DCH, however, remain unclear. The authors therefore studied the effects of DCH on cerebral O2 to develop a better understanding of the effects of this treatment on the recovery from injury and disease. Methods. The study focused on seven patients (mean age 30.6 ± 9.7 years) admitted to the hospital after traumatic brain injury (five patients) or subarachnoid hemorrhage (two patients) as part of a prospective observational database at a Level I trauma center. At admission the Glasgow Coma Scale (GCS) score was 6 or less in all patients. Patients received continuous monitoring of intracranial pressure (ICP), cerebral perfusion pressure (CPP), blood pressure, and arterial O2 saturation. Cerebral oxygenation was measured using the commercially available Licox Brain Tissue Oxygen Monitoring System manufactured by Integra NeuroSciences. A DCH was performed when the patient's ICP remained elevated despite maximal medical management. Conclusions. All patients tolerated DCH without complications. Before the operation, the mean ICP was elevated in all patients (26 ± 4 mm Hg), despite maximal medical management. After surgery, there was an immediate and sustained decrease in ICP (19 ± 11 mm Hg) and an increase in CPP (81 ± 17 mm Hg). Following DCH, cerebral oxygenation improved from a mean of 21.2 ± 13.8 mm Hg to 45.5 ± 25.4 mm Hg, a 114.8% increase. The change in brain tissue O2 and the change in ICP after DCH demonstrated only a modest relationship (r2 = 0.3). These results indicate that the use of DCH in the treatment of severe brain injury is associated with a significant improvement in brain O2.

No reduction in cerebral metabolism as a result of early moderate hyperventilation following severe traumatic brain injury

2000 ◽  
Vol 92 (1) ◽  
pp. 7-13 ◽  
Author(s):  
Michael N. Diringer ◽  
Kent Yundt ◽  
Tom O. Videen ◽  
Robert E. Adams ◽  
Allyson R. Zazulia ◽  
...  
Keyword(s):  
Traumatic Brain Injury ◽  
Brain Injury ◽  
Oxygen Content ◽  
Cerebral Metabolism ◽  
Oxygen Extraction Fraction ◽  
Content Type ◽  
Arterial Blood ◽  
Venous Oxygen Content ◽  
Severe Tbi ◽  
Fine Print

Object. Hyperventilation has been used for many years in the management of patients with traumatic brain injury (TBI). Concern has been raised that hyperventilation could lead to cerebral ischemia; these concerns have been magnified by reports of reduced cerebral blood flow (CBF) early after severe TBI. The authors tested the hypothesis that moderate hyperventilation induced early after TBI would not produce a reduction in CBF severe enough to cause cerebral energy failure (CBF that is insufficient to meet metabolic needs).Methods. Nine patients were studied a mean of 11.2 ± 1.6 hours (range 8–14 hours) after TBI occurred. The patients' mean Glasgow Coma Scale score was 5.6 ± 1.8 and their mean age 27 ± 9 years; eight of the patients were male. Intracranial pressure (ICP), mean arterial blood pressure, and jugular venous oxygen content were monitored and cerebral perfusion pressure was maintained at a level higher than 70 mm Hg by using vasopressors when needed. Measurements of CBF, cerebral blood volume (CBV), cerebral metabolic rate for oxygen (CMRO2), oxygen extraction fraction (OEF), and cerebral venous oxygen content (CvO2) were made before and after 30 minutes of hyperventilation to a PaCO2 of 30 ± 2 mm Hg. Ten age-matched healthy volunteers were used as normocapnic controls.Global CBF, CBV, and CvO2 did not differ between the two groups, but in the TBI patients CMRO2 and OEF were reduced (1.59 ± 0.44 ml/100 g/minute [p < 0.01] and 0.31 ± 0.06 [p < 0.0001], respectively). During hyperventilation, global CBF decreased to 25.5 ± 8.7 ml/100 g/minute (p < 0.0009), CBV fell to 2.8 ± 0.56 ml/100 g (p < 0.001), OEF rose to 0.45 ± 0.13 (p < 0.02), and CvO2 fell to 8.3 ± 3 vol% (p < 0.02); CMRO2 remained unchanged.Conclusions. The authors conclude that early, brief, moderate hyperventilation does not impair global cerebral metabolism in patients with severe TBI and, thus, is unlikely to cause further neurological injury. Additional studies are needed to assess focal changes, the effects of more severe hyperventilation, and the effects of hyperventilation in the setting of increased ICP.

Vascular compression of the duodenum following severe brain injury

1973 ◽  
Vol 39 (3) ◽  
pp. 405-407 ◽  
Author(s):  
William F. Bouzarth ◽  
J. N. Crowley ◽  
Harris R. Clearfield
Keyword(s):  
Weight Loss ◽  
Differential Diagnosis ◽  
Brain Injury ◽  
Vascular Compression ◽  
Severe Brain Injury ◽  
Content Type ◽  
Brain Injured ◽  
Progressive Weight Loss ◽  
Injured Patients ◽  
Fine Print

✓ A patient with severe brain injury began vomiting 12 weeks after admission. This magnified a progressive weight loss of 34 kg. Vascular compression of the duodenum was confirmed as the cause of the vomiting. With hyperalimentation, vomiting stopped and weight gain occurred. This easily reversible syndrome should be considered in the differential diagnosis of vomiting in brain-injured patients with weight loss.

Terson's syndrome in subarachnoid hemorrhage and severe brain injury accompanied by acutely raised intracranial pressure

1998 ◽  
Vol 88 (5) ◽  
pp. 851-854 ◽  
Author(s):  
Ralph J. Medele ◽  
Walter Stummer ◽  
Arthur J. Mueller ◽  
Hans-Jakob Steiger ◽  
Hans-Jürgen Reulen
Keyword(s):  
Brain Injury ◽  
Vitreous Hemorrhage ◽  
Raised Intracranial Pressure ◽  
Severe Brain Injury ◽  
Content Type ◽  
Terson’S Syndrome ◽  
Terson's Syndrome ◽  
Acute Event ◽  
Fine Print ◽  
Similar Incidence

Object. The syndrome of retinal or vitreous hemorrhage in association with subarachnoid hemorrhage (SAH) is known as Terson's syndrome. The authors' purpose was to determine whether intraocular hemorrhage occurs with similar incidence when caused by severe brain injury accompanied by acutely raised intracranial pressure (ICP). Methods. Prospective ophthalmological examination was performed in 22 consecutive patients with SAH or severe brain injury and elevated ICP. Thirteen patients were admitted for SAH (World Federation of Neurological Surgeons Grades II–IV) and nine for severe brain injury (Glasgow Coma Scale scores 3–10). Monitoring of ICP was performed at the time of admission via a ventricular catheter. Initial ICP exceeded 20 mm Hg in all patients. Indirect ophthalmoscopy without induced mydriasis was performed within the 1st week after the acute event. Retinal or vitreous hemorrhage was seen in six (46%) of 13 patients with SAH and in four (44%) of nine patients with severe brain injury. Ocular bleeding was found bilaterally in three patients with SAH and in one patient with severe brain injury (18%). Six of the 10 patients with Terson's syndrome died as a result of their acute event. Conclusions. The present results indicate that Terson's syndrome may be related to acute elevation of ICP, independent of its causes, and may occur with similar incidence in patients with severe brain injury and those with SAH. Because recognition and treatment of Terson's syndrome may prevent visual impairment and associated secondary damage to the eye, increased awareness of this entity in all patients with acute raised intracranial hypertension is recommended.

Characterization of edema by diffusion-weighted imaging in experimental traumatic brain injury

1996 ◽  
Vol 84 (1) ◽  
pp. 97-103 ◽  
Author(s):  
Junki Ito ◽  
Anthony Marmarou ◽  
Pál Barzó ◽  
Panos Fatouros ◽  
Frank Corwin
Keyword(s):  
Traumatic Brain Injury ◽  
Brain Injury ◽  
Control Level ◽  
Cytotoxic Edema ◽  
Content Type ◽  
Apparent Diffusion Coefficients ◽  
Secondary Insult ◽  
Arterial Blood ◽  
Diffusion Weighted ◽  
Fine Print

✓ The objective of this study was to use diffusion-weighted magnetic resonance imaging (DWI) to help detect the type of edema that develops after experimental trauma and trauma coupled with hypotension and hypoxia (THH). Reduction in the apparent diffusion coefficients (ADCs) is thought to represent cytotoxic edema. In a preliminary series of experiments, the infusion edema model and middle cerebral artery occlusion models were used to confirm the direction of ADC change in response to purely extracellular and cytotoxic edema, respectively. The ADCs increased (p < 0.05) in the case of extracellular edema and decreased (p < 0.001) in cytotoxic edema. Following these initial experiments, a new impact acceleration model was used to induce traumatic brain injury. Thirty-six adult Sprague-Dawley rats were separated into four groups: sham, trauma alone, hypoxia and hypotension (HH), and THH. Following trauma, a 30-minute insult of hypoxia (PaO2 of 40 mm Hg) and hypotension (mean arterial blood pressure (MABP) of 30 mm Hg) were imposed and the animals were resuscitated. The DWI was carried out at four 1-hour intervals postinjury, and MABP, intracranial pressure (ICP), cerebral perfusion pressure (CPP), and cerebral blood flow (CBF) were monitored. The ADCs in the control and HH groups remained unchanged. The ADCs in the THH group rapidly decreased from a control level of 0.68 ± 0.05 × 10−3 mm2/second to 0.37 ± 0.09 3 10−3 mm2/second by 3 hours posttrauma (p < 0.001). In this group, the decreased CBF and CPP during secondary insult remained low despite resuscitation, with the ICP increasing to 56 6 7 mm Hg by 3 hours. In the trauma alone group, the rise in ICP reached a maximum value (28 ± 3 mm Hg) at 30 minutes with a significant and sustained increase in CBF despite a gradual decrease in CPP. The ADCs in this group were not significantly reduced. The data lead the authors to suggest that the rise in ICP following severe trauma coupled with secondary insult in this model is predominately caused by cytotoxic edema and that ischemia plays a major role in the development of brain edema after head injury.

Early immunological defects in comatose patients after acute brain injury

2001 ◽  
Vol 94 (5) ◽  
pp. 706-711 ◽  
Author(s):  
Baruch Wolach ◽  
Leon Sazbon ◽  
Ronit Gavrieli ◽  
Arieh Broda ◽  
Menachem Schlesinger
Keyword(s):  
Immune System ◽  
Brain Injury ◽  
Vegetative State ◽  
Persistent Vegetative State ◽  
Acute Brain Injury ◽  
High Rate ◽  
Mechanical Trauma ◽  
Severe Brain Injury ◽  
Content Type ◽  
Fine Print

Object. The aim of this prospective study was to evaluate the phagocytic, humoral, and cellular arms of the immune system in comatose patients shortly after severe brain injury and to compare the findings with those reported earlier in patients in a persistent vegetative state. The study was conducted in intensive care units and immunology laboratories of university-affiliated hospitals in central Israel. Methods. The study group consisted of 14 men aged 16 to 65 years who were comatose as a result of acute brain injury due to mechanical trauma. All were studied within 72 hours of injury. Brain damage was severe in all cases (Glasgow Coma Scale score < 8). Healthy age- and sex-matched volunteers served as simultaneous controls. Infections arose in nine (75%) of the 12 patients in whom data were available; the cumulative mortality rate was 38% (five of 13 patients in whom outcome data were available). Every patient exhibited one or more defects in at least one arm of the immune system. Significant deficiencies were noted in neutrophil superoxide release, immunoglobulin (Ig)G, IgG1, IgM, C1q, C2, properdin, alternate C pathway, T cells, T helper cells, T suppressor cells, and natural killer cells. In an earlier series of patients examined by the authors months after the primary insult, these impairments were absent in most of the patients in the vegetative state. Conclusions. Significant deficiencies of the immune system, particularly the cellular arm, are precipitated by severe brain injury within 72 hours of the event. These impairments probably play a role in the high rate of complicating infections and multiple organ failure. Together with earlier findings, the results of this study indicate that if brain-injured patients survive these hazards, their immune system will eventually recover.

Flushing in relation to a possible rise in intracranial pressure: documentation of an unusual clinical sign

2000 ◽  
Vol 92 (6) ◽  
pp. 1040-1044 ◽  
Author(s):  
Gregory W. Hornig
Keyword(s):  
Traumatic Brain Injury ◽  
Brain Injury ◽  
Intracranial Pressure ◽  
Intraventricular Hemorrhage ◽  
Pneumococcal Meningitis ◽  
Clinical Importance ◽  
Neurological Deterioration ◽  
Content Type ◽  
Transient Nature ◽  
Fine Print

✓ This report documents clinical features in five children who developed transient reddening of the skin (epidermal flushing) in association with acute elevations in intracranial pressure (ICP). Four boys and one girl (ages 9–15 years) deteriorated acutely secondary to intracranial hypertension ranging from 30 to 80 mm Hg in the four documented cases. Two patients suffered from ventriculoperitoneal shunt malfunctions, one had diffuse cerebral edema secondary to traumatic brain injury, one was found to have pneumococcal meningitis and hydrocephalus, and one suffered an intraventricular hemorrhage and hydrocephalus intraoperatively. All patients were noted to have developed epidermal flushing involving either the upper chest, face, or arms during their period of neurological deterioration. The response was transient, typically lasting 5 to 15 minutes, and dissipated quickly. The flushing reaction is postulated to be a centrally mediated response to sudden elevations in ICP. Several potential mechanisms are discussed. Flushing has clinical importance because it may indicate significant elevations in ICP when it is associated with neurological deterioration. Because of its transient nature, the importance of epidermal flushing is often unrecognized; its presence confirms the need for urgent treatment.

Cerebral acid-base and gas metabolism in brain injury

1970 ◽  
Vol 33 (5) ◽  
pp. 498-505 ◽  
Author(s):  
R. Zupping
Keyword(s):  
Metabolic Acidosis ◽  
Brain Injury ◽  
Brain Damage ◽  
Close Correlation ◽  
Respiratory Alkalosis ◽  
Acid Base ◽  
Content Type ◽  
Arterial Blood ◽  
Gas Metabolism ◽  
Permanent Brain Damage

✓ Acid-base and gas parameters of CSF, jugular venous and arterial blood were measured in 45 patients with brain injury in the first 12 days after trauma or operation. CSF metabolic acidosis together with respiratory alkalosis and hypoxemia in the cerebral venous and arterial blood were the most characteristic findings. A close correlation between the severity of brain damage and the intensity of the CSF metabolic acidosis and arterial hypocapnia was revealed. It was concluded that brain hypoxia and acidosis play an important role in the development of cerebral edema and permanent brain damage.

Resolution of brain edema in severe brain injury at controlled high and low intracranial pressures

1984 ◽  
Vol 61 (4) ◽  
pp. 707-712 ◽  
Author(s):  
Meihong Cao ◽  
He Lisheng ◽  
Sun Shouzheng
Keyword(s):  
Cerebrospinal Fluid ◽  
Brain Injury ◽  
Brain Edema ◽  
External Ventricular Drainage ◽  
Blue Dye ◽  
Severe Brain Injury ◽  
Content Type ◽  
Intracranial Pressures ◽  
Low Levels ◽  
Cerebrospinal Fluid Protein

✓ A series of 87 patients with severe brain injury were studied. Intracranial pressure (ICP) monitoring and external ventricular drainage were used to control ICP at high and low levels. Clearance of ytterbium-169-labeled diethylenetriaminepentaacetic acid (169Yb-DTPA), Evans blue dye, and ventricular cerebrospinal fluid protein was measured at the two ICP levels over consecutive periods of 4 hours to confirm clearance of brain edema. The results support the hypothesis that brain edema is in part absorbed in the cerebrospinal fluid via transventricular flow.

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