Magnetic resonance imaging changes in the pituitary gland following acute traumatic brain injury.

OBJECTIVE: The objective was to study the anatomical changes in the pituitary gland following acute moderate or severe traumatic brain injury (TBI). DESIGN: Retrospective, observational, case-control study. SETTING: Neurosciences Critical Care Unit of a university hospital. PATIENTS: Forty-one patients with moderate or severe TBI who underwent magnetic resonance imaging (MRI) during the acute phase (less than seven days) of TBI. MRI scans of 43 normal healthy volunteers were used as controls. INTERVENTIONS: None. MEASUREMENTS AND MAIN RESULTS: Patient demographics, Acute Physiology and Chronic Health Evaluation II (APACHE II) score, Injury Severity Score (ISS), post-resuscitation Glasgow Coma Score (GCS), Glasgow Outcome Score (GOS), mean intracranial pressure (ICP), mean cerebral perfusion pressure (CPP), computed tomography (CT) data, pituitary gland volumes and structural lesions in the pituitary on MRI scans. The pituitary glands were significantly enlarged in the TBI group (the median and interquartile range were as follows: cases 672 mm3 (range 601-783 mm3) and controls 552 mm3 (range 445-620 mm3); p value<0.0001). APACHE II, GCS, GOS and ICP were not significantly correlated with the pituitary volume. Twelve of the 41 cases (30%) demonstrated focal changes in the pituitary gland (haemorrhage/haemorrhagic infarction (n=5), swollen gland with bulging superior margin (n=5), heterogeneous signal intensities in the anterior lobe (n=2) and partial transection of the infundibular stalk (n=1). CONCLUSIONS: Acute TBI is associated with pituitary gland enlargement with specific lesions, which are seen in approximately 30% of patients. MRI of the pituitary may provide useful information about the mechanisms involved in post-traumatic hypopituitarism.

Use of T2-weighted magnetic resonance imaging of the optic nerve sheath to detect raised intracranial pressure.

INTRODUCTION: The dural sheath surrounding the optic nerve communicates with the subarachnoid space, and distends when intracranial pressure is elevated. Magnetic resonance imaging (MRI) is often performed in patients at risk for raised intracranial pressure (ICP) and can be used to measure precisely the diameter of optic nerve and its sheath. The objective of this study was to assess the relationship between optic nerve sheath diameter (ONSD), as measured using MRI, and ICP. METHODS: We conducted a retrospective blinded analysis of brain MRI images in a prospective cohort of 38 patients requiring ICP monitoring after severe traumatic brain injury (TBI), and in 36 healthy volunteers. ONSD was measured on T2-weighted turbo spin-echo fat-suppressed sequence obtained at 3 Tesla MRI. ICP was measured invasively during the MRI scan via a parenchymal sensor in the TBI patients. RESULTS: Measurement of ONSD was possible in 95% of cases. The ONSD was significantly greater in TBI patients with raised ICP (>20 mmHg; 6.31 +/- 0.50 mm, 19 measures) than in those with ICP of 20 mmHg or less (5.29 +/- 0.48 mm, 26 measures; P < 0.0001) or in healthy volunteers (5.08 +/- 0.52 mm; P < 0.0001). There was a significant relationship between ONSD and ICP (r = 0.71, P < 0.0001). Enlarged ONSD was a robust predictor of raised ICP (area under the receiver operating characteristic curve = 0.94), with a best cut-off of 5.82 mm, corresponding to a negative predictive value of 92%, and to a value of 100% when ONSD was less than 5.30 mm. CONCLUSIONS: When brain MRI is indicated, ONSD measurement on images obtained using routine sequences can provide a quantitative estimate of the likelihood of significant intracranial hypertension.

Extracellular Brain pH and Outcome following Severe Traumatic Brain Injury.

The ability to measure brain tissue chemistry has led to valuable information regarding pathophysiological changes in patients with traumatic brain injury (TBI). Over the last few years, the focus has been on monitoring changes in brain tissue oxygen to determine thresholds of ischemia that affect outcome. However, the variability of this measurement suggests that it may not be a robust method. We have therefore investigated the relationship of brain tissue pH (pH(b)) and outcome in patients with TBI. We retrospectively analyzed prospectively collected data of 38 patients admitted to the Neurosciences Critical Care Unit with TBI between 1998 and 2003, and who had a multiparameter tissue gas sensor inserted into the brain. All patients were managed using an evidence-based protocol targeting CPP > 70 mm Hg. Physiological variables were averaged over 4 min and analyzed using a generalized least squares random effects model to determine the temporal profile of pH(b) and its association with outcome. Median (IQR) minimum pH(b) was 7.00 (6.89, 7.08), median (IQR) maximum pH(b) was 7.25 (7.18, 7.33), and median (IQR) patient averaged pH(b) was 7.13 (7.07, 7.17). pH(b) was significantly lower in those who did not survive their hospital stay compared to those that survived. In addition, those with unfavorable neurological outcome had lower pH(b) values than those with favorable neurological outcome. pH(b) differentiated between survivors and non-survivors. Measurement of pH(b) may be a useful indicator of outcome in patients with TBI.

Pharmacokinetics and pharmacodynamics of dopamine and norepinephrine in critically ill head-injured patients.

OBJECTIVE: To explore the pharmacokinetics and pharmacodynamics of dopamine and norepinephrine. DESIGN: Prospective, controlled, trial. SETTING: Neurosciences critical care unit. PATIENTS: Eight patients with a head injury, requiring dopamine or norepinephrine infusions to support cerebral perfusion pressure (CPP). INTERVENTION: Patients received in randomised order, either dopamine or norepinephrine to achieve and maintain a CPP of 70 mmHg, and then, following a 30-min period of stable haemodynamics, a CPP of 90 mmHg. Data were then acquired using the second agent. Haemodynamic measurements were made during each period and a blood sample was obtained at the end of each study period for analysis of plasma catecholamine concentrations MEASUREMENTS AND RESULTS: Plasma levels of norepinephrine and dopamine were significantly related to infusion rates but did not have a simple linear relationship to haemodynamic parameters. However, there was a significant quadratic relationship between the infusion rate of dopamine and cardiac index (r2=0.431), and systemic vascular resistance index (r2=0.605), with a breakpoint (at which cardiac index reduced and SVRI increased) at a dopamine plasma level of approximately 50 nM/l (corresponding to an infusion rate of approximately 15 microg.kg(-1).min(-1)). CONCLUSIONS: Norepinephrine and dopamine have predictable pharmacokinetics; however, those of dopamine do not fit a simple first-order kinetic model. The pharmacodynamic effects of dopamine and norepinephrine show much inter-individual variability and unpredictability. Plasma levels of dopamine appear to relate to variations in adrenergic receptor effects with break points that reflect expectations from infusion-rate related pharmacodynamics.

Research collaboration.

Collaborative interdisciplinary research can contribute to bridging the gap between research and practice. This paper by Leslie Gelling and Dot Chatfield considers the nature of collaborative research, describes three models of collaboration and suggests some potential benefits of successful research collaboration to individuals, groups, organisations and consumers.

Hyperglycemia and brain tissue pH after traumatic brain injury.

OBJECTIVE: Hyperglycemia occurring after head injury is associated with poor neurological outcome. We tested the hypothesis that blood glucose levels are associated with brain tissue pH (pH(b)) and that the correction of hyperglycemia would result in an improvement in pH(b). METHODS: This is a retrospective analysis of a prospectively collected database. Thirty-four patients in a tertiary care neuroscience critical care unit with major traumatic brain injury underwent pH(b) monitoring. RESULTS: A total of 428 glucose measurements were recorded during pH(b) monitoring. Mean glucose level was 7.1 mmol/L (range, 2.8-21.7 mmol/L) and median (interquartile range) pH(b) was 7.11 mmol/L (7.00-7.19 mmol/L). To account for the correlated, unbalanced nature of the data, a linear generalized estimating equation model was created. This model predicted that for each 1 mmol/L increase in blood glucose, pH(b) changed by -0.011 mmol/L (95% confidence interval, -0.016 to -0.005 mmol/L; P < 0.001). This relationship remained significant in a multivariable model that included cerebral perfusion pressure, brain tissue oxygen and carbon dioxide tension, and brain temperature. Twenty-one episodes of significant hyperglycemia (>or=11.1 mmol/L) treated with intravenous insulin were identified. Insulin therapy significantly reduced blood glucose concentration from a median (interquartile range) of 11.9 mmol/L (range, 11.4-13.6 mmol/L) to 8.8 mmol/L (range, 7.3-9.6 mmol/L; P < 0.001). Baseline pH(b) was not significantly different from pH(b) associated with the subsequent glucose reading of less than 11.1 mmol/L (P = 0.29), but there was a suggestion of improvement if the change in blood glucose was large. CONCLUSION: Blood glucose is associated with brain tissue acidosis in patients with major head injury. Prospective studies are required to confirm these results and to determine whether treatment of hyperglycemia improves outcome.

Effect of hyperventilation on cerebral blood flow in traumatic head injury: clinical relevance and monitoring correlates.

OBJECTIVE: To investigate the effect of hyperventilation on cerebral blood flow in traumatic brain injury. DESIGN: A prospective interventional study. SETTING: A specialist neurocritical care unit. PATIENTS: Fourteen healthy volunteers and 33 patients within 7 days of closed head injury. INTERVENTIONS: All subjects underwent positron emission tomography imaging of cerebral blood flow. In patients, PaCO2 was reduced from 36 +/- 1 to 29 +/- 1 torr (4.8 +/- 0.1 to 3.9 +/- 0.1 kPa) and measurements repeated. Jugular venous saturation (SjvO2 ) and arteriovenous oxygen content differences (AVDO2 ) were monitored in 25 patients and values related to positron emission tomography variables. MEASUREMENTS AND MAIN RESULTS: The volumes of critically hypoperfused and hyperperfused brain (HypoBV and HyperBV, in milliliters) were calculated based on thresholds of 10 and 55 mL.100g(-1).min(-1), respectively. Whereas baseline HypoBV was significantly higher in patients ( p<.05), baseline HyperBV was similar to values in healthy volunteers. Hyperventilation resulted in increases in cerebral perfusion pressure (p <.0001) and reductions in intracranial pressure (p <.001), whereas SjvO2 (>50%) and AVDO2 (<9 mL/mL) did not exceed global ischemic thresholds. However, despite these beneficial effects, hyperventilation shifted the cerebral blood flow distribution curve toward the hypoperfused range, with a decrease in global cerebral blood flow (31 +/- 1 to 23 +/- 1 mL.100g(-1).min(-1); p<.0001) and an increase in HypoBV (22 [1-141] to 51 [2-428] mL; p<.0001). Hyperventilation-induced increases in HypoBV were apparently nonlinear, with a threshold value between 34 and 38 torr (4.5-5 kPa). CONCLUSIONS: Hyperventilation increases the volume of severely hypoperfused tissue within the injured brain, despite improvements in cerebral perfusion pressure and intracranial pressure. Significant hyperperfusion is uncommon, even at a time when conventional clinical management includes a role for modest hyperventilation. These reductions in regional cerebral perfusion are not associated with ischemia, as defined by global monitors of oxygenation, but may represent regions of potentially ischemic brain tissue.