Studies on piglets have shown that cranial bioimpedance (Z) measurements correlate well with invasively measured intracranial pressure (ICP). We have tested the feasibility of collecting transcranial impedance from a clinical device for measuring whole-body water content (ImpediMed SFB7). In the clinical study, 50 normal healthy volunteers had transcranial impedance measured using nine different head montages (forehead to mastoid (left/right), temporal to mastoid (left/right), forehead to temporal (left/right), forehead to occipital (left/right) and temporal to temporal). Impedance was measured 20 times over a frequency range per montage and ANOVA used to test for effects of electrode position upon recorded value. For the experimental study, five sedated and ventilated Marino sheep were instrumented for intraventricular ICP and transcranial impedance measurement. Measures of ICP were recorded while ICP was increased from baseline to greater than 50 mmHg in five steps using an intraventricular infusion of mock CSF. There is a significant effect of electrode position and gender upon transcranial impedance (p < 0.001). The temporal-mastoid electrode position had significantly lower impedance values in keeping with its shorter path length. ICP correlated with craniospinal compliance measurements and Impedance vs Freq by ICP step shows a clear ICP dependence (p = 0.007) across the sheep.
A dose escalation, safety, and tolerability study of a competitive antagonist to the N-methyl-D-aspartate (NMDA) glutamate receptor (CGS 19755, Selfotel) in patients with severe head injury is reported. The drug was administered i.v. on two separate occasions, 24 h apart, to 31 patients. The dosage was escalated during the study from 1 mg/kg to 6 mg/kg. Continuous monitoring of mean arterial pressure (MABP), intracranial pressure (ICP), cerebral pressure (CPP), arterial oxygen saturation (SaO2), jugular bulb oxygen saturation (SjO2), and temperature was performed. Intermittent measurements of middle cerebral artery (MCA) velocity via transcranial Doppler ultrasound were also made 2 h before drug administration and continued for 24 h after dosing. The patients were ventilated and sedated with morphine and either midazolam or propofol. There were no behavioral changes during or after administration of the drug, and disorders of perception were reported by only three subjects, several days after relatively low doses; these were transient and were not recalled at later follow-up. We did not detect consistent changes in any of the hemodynamic parameters monitored, up to dosages of 3 mg/kg. After higher doses, some patients showed changes in MABP, ICP, and temperature during the 4 to 8-h period following the first bolus of the drug, with a return toward baseline afterwards. No consistent, serious, adverse events were considered to be due to drug effects, and death, in the one patient who died, was due to the effects of the injury. Our results indicate that CGS 19755 may be given at dosages < or = 3-5 mg/kg with acceptable safety and tolerability in stable, ventilated, and carefully monitored severe head-injured patients.
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