E. Sander Connolly Jr.
Mary E. Kerr, Barbara B. Weber, Susan M. Sereika, Jack Wilberger and Donald W. Marion
Intracranial hypertension remains a common complication of traumatic brain injury (TBI). Ventriculostomy drainage is a recommended therapy to decrease intracranial pressure (ICP), but little empirical evidence exists to guide treatment. The authors conducted a study to examine systematically the effect of cerebral spinal fluid (CSF) drainage on ICP and indices of cerebral perfusion.
Intracranial pressure, cerebral perfusion pressure (CPP), cerebral blood flow velocity (CBFV), and near-infrared spectroscopy–determined regional cerebral oxygenation (rSO2) were measured in 58 patients (with Glasgow Coma Scale scores ≤ 8) before, during, and after ventriculostomy drainage. Three randomly ordered CSF drainage protocols varied in the volume of CSF removed (1 ml, 2 ml, and 3 ml). Physiological variables were time averaged in 1-minute blocks from baseline to 10 minutes after cessation of ventricular drainage.
There was a significant dose–time interaction for ICP with the three-extraction volume protocol, with incremental decreases in ICP (F [20, 1055] = 6.10; p = 0.0001). There was a significant difference in the CPP depending on the amount of CSF removed (F [2, 1787] = 3.22; p = 0.040) and across time (F [10, 9.58] = 11.9; p = 0.0003) without a significant dose–time interaction. A 3-ml withdrawal of CSF resulted in a 10.1% decrease in ICP and a 2.2% increase in CPP, which were sustained for 10 minutes. There was no significant dose, time or dose–time interaction with CBFV or rSO2.
Cerebrospinal fluid drainage (3 ml) significantly reduced ICP and increased CPP for at least 10 minutes. Analysis of these findings supports the use of ventriculostomy drainage as a means of at least temporarily reducing elevated ICP in patients with TBI.
Martina Stippler, Elizabeth Crago, Elad I. Levy, Mary E. Kerr, Howard Yonas, Michael B. Horowitz and Amin Kassam
Despite the application of current standard therapies, vasospasm continues to result in death or major disability in patients treated for ruptured aneurysms. The authors investigated the effectiveness of continous MgSO4 infusion for vasospasm prophylaxis.
Seventy-six adults (mean age 54.6 years; 71% women; 92% Caucasian) were included in this comparative matched-cohort study of patients with aneurysmal subarachnoid hemorrhage on the basis of computed tomography (CT) findings. Thirty-eight patients who received continuous MgSO4 infusion were matched for age, race, sex, treatment option, Fisher grade, and Hunt and Hess grade to 38 historical control individuals who did not receive MgSO4 infusion. Twelve grams of MgSO4 in 500 ml normal saline was given intravenously daily for 12 days if the patient presented within 48 hours of aneurysm rupture. Vasospasm was diagnosed on the basis of digital substraction angiography, CT angiography, and transcranial Doppler ultrasonography, and evidence of neurological deterioration.
Symptomatic vasospasm was present at a significantly lower frequency in patients who received MgSO4 infusion (18%) compared with patients who did not receive MgSO4 (42%) (p = 0.025). There was no significant difference in mortality rate at discharge (p = 0.328). A trend toward improved outcome as measured by the modifed Rankin Scale (p = 0.084), but not the Glasgow Outcome Scale (p = 1.0), was seen in the MgSO4-treated group.
Analysis of the results suggests that MgSO4 infusion may have a role in cerebral vasospasm prophylaxis if therapy is initiated within 48 hours of aneurysm rupture.
Amy K. Wagner, Dianxu Ren, Yvette P. Conley, Xiecheng Ma, Mary E. Kerr, Ross D. Zafonte, Ava M. Puccio, Donald W. Marion and C. Edward Dixon
Dopamine (DA) pathways have been implicated in cognitive deficits after traumatic brain injury (TBI). Both sex and the dopamine transporter (DAT) 3′ variable number of tandem repeat polymorphism have been associated with differences in DAT protein density, and DAT protein affects both presynaptic DA release, through reverse transport, and DA reuptake. Catecholamines and associated metabolites are subject to autooxidation, resulting in the formation of reactive oxygen species that may contribute to subsequent oxidative injury. The purpose of this study was to determine associations between factors that affect DAT expression and cerebrospinal fluid (CSF) DA and metabolite levels after severe TBI.
Sixty-three patients with severe TBI (Glasgow Coma Scale score ≤ 8) were evaluated. The patients' genotypes were obtained using previously banked samples of CSF, and serial CSF samples (416 samples) were used to evaluate DA and metabolite levels. High-performance liquid chromatography was used to determine CSF levels of DA, 3,4-dihydroxyphenylacetic acid (DOPAC), and homovanillic acid (HVA) during the first 5 days after injury.
Mixed-effects multivariate regression modeling revealed that patients with the DAT 10/10 genotype had higher CSF DA levels than patients with either the DAT 9/9 or DAT 9/10 genotypes (p = 0.009). Females with the DAT 10/10 genotype had higher CSF DA levels than females with the DAT 9/9 or DAT 9/10 genotypes, and sex was associated with higher DOPAC levels (p = 0.004). Inotrope administration also contributed to higher DA levels (p = 0.002).
In addition to systemic administration of DA, inherent factors such as sex and DAT genotype affect post-TBI CSF DA and DA metabolite levels, a phenomenon that may modulate susceptibility to DA-mediated oxidative injury.