An update on traumatic brain injuries.

Severe traumatic brain injury (TBI) represents a major cause of neurological mortality and morbidity throughout the world. Several challenges have been faced in the conduct of clinical research in TBI in past decades, including inclusion of a broad heterogeneity of injuries, difficulties with standardization and consistency of complex medical management, and lack of sophisticated outcomes measures to sufficiently detect differences in outcomes. Consequently, evidence-based guidelines for targeted therapeutic approaches remain for the most part at the level of Class II or III evidence. Harnessing the power of computing is paramount to our understanding of different prognostic groups in order to devise treatments of the future. Multimodality bedside monitoring of various physiological parameters and events can be deployed in the intensive care unit (ICU) but better data repositories and analytics are required. Recent developments in neuroimaging and definition of potential genetic and biological markers in TBI are also aiding in the sub-categorization of patients into finer diagnostic and prognostic groups. Using mathematical prediction models incorporating the plethora of data gathered, future research will provide means of tailoring therapies to individuals based upon best evidence in populations similar to them, and according to their own biological and physiological situation.

alpha2-Adrenergic receptor-mediated modulation of calcium current in neocortical pyramidal neurons.

Noradrenergic projections to the cortex modulate a variety of cortical activities and calcium channels are one likely target for such modulation. We used the whole-cell patch-clamp technique to study noradrenergic modulation of barium currents in acutely dissociated pyramidal neurons from rat sensorimotor cortex. Extracellular application of specific agonists and antagonists revealed that norepinephrine (NE) reduced Ca2+ current. A major component of this modulation was due to activation of alpha2 receptors. Activation of alpha2-adrenergic receptors resulted in a fast, voltage-dependent pathway involving Gi/Go G-proteins. This pathway targeted N- and P-type calcium channels The alpha2 modulation was partially reversed by repeated action potential waveforms (APWs). N- and P-type channels have been implicated in synaptic transmission and activation of afterhyperpolarizations in these cells. Our findings suggest that NE can regulate these cellular processes by mechanisms sensitive to spike activity.

Spectral characteristics of B-waves and other low-frequency activity.

Low frequency oscillations of intracranial pressure (ICP) between 0.5 to 2.0 cycles/min have been termed B-waves. While such low frequency activity may be generated by cerebral vasomotor activity, activity in the B-wave band may also be related to other causes. The objective of this study is to: 1) describe the low frequency characteristics of ICP and arterial blood pressure (ABP) recordings with a mathematical model based on ventilator-induced intrathoracic pressure (ITP) modulation of arterial blood pressure; and 2) use the model to eliminate low frequency activity within the B-wave range unrelated to vasomotor activity. The model describes the frequency locations of spectra associated with ventilation about both the principal and first harmonic cardiac frequency to within 1% error. Spectra within the B-wave range harmonically related to the ventilator frequency were classified as caused by patient-ventilator interaction. Of 11 patients with severe head-injury, 64% (7/11) demonstrated B-wave activity, and 4 patients demonstrated the activity solely in the ICP recording. Variation of heart rate did not correspond to the occurrence of B-waves. The proposed model describes the low frequency spectra found within ABP and ICP recordings and can be used to eliminate spectra with the B-wave range related to ventilation.

An estimated compliance index derived from intracranial pressure recording.

The purpose of this study is to test the validity of a proposed compliance index, percent change of compliance per mmHg of intracranial pressure (%CC/mmHg), by comparison of values of the index with corresponding experimentally derived values of compliance. The derivation of %CC/mmHg is based on two assumptions: 1) the pressure-volume characteristic of the craniospinal sac can be linearized for small perturbations about an equilibrium; and 2) during a brief interval in which these perturbations occur the pathophysiologic state of the sac does not significantly change. By rapid infusion of 0.2 ml of mock cerebrospinal fluid (CSF) experimental values of compliance (n = 44) were obtained from 10 piglets during monitoring of intracranial pressure (ICP). A strong correlation (r = 0.89, p < .001, n = 44) was obtained between values of %CC/mmHg and corresponding values of experimentally derived compliance (ml/mmHg). The value of the proposed index of compliance, %CC/mmHg, needs to be evaluated in the clinical setting. However, from the view of validation of ICP instrumentation, high values of both mean ICP and mean %CC/mmHg are contradictory and indicative of the occurrence of instrumentation error due to electronic direct current drift.

Effects of fiberoptic bronchoscopy on intracranial pressure in patients with brain injury: a prospective clinical study.

BACKGROUND: Fiberoptic bronchoscopy (FB) plays an important role in making the diagnosis of nosocomial pneumonia and resolving lobar atelectasis in critically injured trauma patients. It has been shown to be a safe procedure with only occasional complications. However, in patients with head injuries, FB can lead to intracranial hypertension. Sustained increases in intracranial pressure (ICP) leads to poor outcome in these patients. Because of this, a prospective study was done not only to assess the effect of FB on ICP and cerebral perfusion pressure (CPP) in patients with brain injuries, but also to identify a regimen of sedation and anesthesia that could prevent significant increases in ICP during FB. METHODS: Twenty-six FB were performed in 23 patients with ICP monitors or ICP monitors and ventriculostomy drains in place for Glasgow Coma Scale score < 8 or management of postcraniotomy trauma. FB was performed to aid in the diagnosis of nosocomial pneumonia or to aid in resolving lobar atelectasis. Before FB, all patients received a standard anesthetic regimen consisting of vecuronium (10 mg), morphine sulfate (4 mg), and midazolam (2.5 mg). Patients with diminished cranial compliance, defined as ICP > 10 mm Hg, also received a nebulizer treatment of 3 mL of 4% lidocaine before FB. All patients were preoxygenated with FIO2 = 1.0 for 10 minutes. Intracranial pressure, mean arterial pressure, and CPP were monitored continuously throughout the procedure. These same variables were also recorded at baseline and at 2-minute intervals during the procedure. The time to return to baseline ICP was also recorded. RESULTS: The mean ICP at baseline (immediately before FB) was 12.6 mm Hg. After introduction of the bronchoscope, the ICP rapidly increased in 21 procedures (81%) and the mean highest ICP was 38.0 mm Hg. There was also a concomitant increase in mean arterial pressure such that there was no substantial change in CPP. The mean lowest CPP was 73.1 mm Hg. The average time for return of ICP to baseline was 13.9 minutes. In the subgroup of patients with ICP > 10, attempting to blunt the tracheal stimulation by anesthetizing the trachea with 4% nebulized lidocaine did not seem to be successful. The mean highest ICP in this subgroup was 41.8 mm Hg. The CPP changed in a similar manner, as the mean lowest CPP was 74.0 mm Hg. The mean time to return to baseline was 12.5 minutes. No patient had acute neurologic deterioration secondary to FB. CONCLUSIONS: Although FB is an important procedure in the pulmonary care of head injured patients, it produces substantial, but transient, increases in ICP and should be used with caution in patients with diminished cranial compliance. Sedation, analgesia, paralysis, and topical tracheal anesthesia did not completely prevent the rise in ICP. Although no acute deterioration in condition occurred, secondary brain injury caused by localized cerebral ischemia is certainly possible. Because of the substantial increases in ICP, herniation may be precipitated in an occasional patient. Further study is needed to identify a regimen that will confer protection.