Biomedical subjects

David K Menon

Publications and source records attributed to David K Menon.

48 records · Page 3Linked to original sources

PubMed2003

Responses of posttraumatic pericontusional cerebral blood flow and blood volume to an increase in cerebral perfusion pressure.

In and around traumatic contusions, cerebral blood flow (CBF) is often near or below the threshold for ischemia. Increasing cerebral perfusion pressure (CPP) in patients with head injuries may improve CBF in these regions. However, the pericontusional response to this intervention has not been studied. Using positron emission tomography (PET), we have quantified the response to an increase in CPP in and around contusions in 18 contusions in 18 patients. Regional CBF and cerebral blood volume (CBV) were measured with PET at CPPs of 70 and 90 mmHg using norepinephrine to control CPP. Based upon computed tomography, regions of interest (ROIs) were placed as two concentric ellipsoids, each of 1-cm width, around the core of the contusions. Measurements were compared with a control ROI in tissue with normal anatomic appearance. Baseline CBF and CBV increased significantly with increasing distance from the core of the lesion. The increase in CPP led to small increases in CBF in all ROIs except the core. The largest absolute CBF increase was found in the control ROI. Relative CBF increases did not differ between ROIs so that ischemic areas remained ischemic. Pericontusional oedema on computed tomography was associated with lower absolute values of CBF and CBV but did not differ from nonoedematous tissue in the relative response to CPP elevation.

Adolescent↗

PubMed2003

The effects of large-dose propofol on cerebrovascular pressure autoregulation in head-injured patients.

UNLABELLED: In healthy individuals, cerebrovascular pressure autoregulation is preserved or even improved when propofol is infused. We examined the effect of an increase in propofol plasma concentration on pressure autoregulation in 10 head-injured patients. Using target-controlled infusions, the static rate of autoregulation was determined at a moderate (2.3 +/- 0.4 microg/mL) and a large (4.3 +/- 0.04 microg/mL) plasma target concentration of propofol. Using norepinephrine to control cerebral perfusion pressure, transcranial Doppler measurements from the middle cerebral artery were made at a cerebral perfusion pressure of 70 and 85 mm Hg at each propofol concentration. Middle cerebral artery flow velocities at the large propofol concentration were significantly lower than at the moderate concentration, without any concurrent increase in arterio-jugular difference in oxygen content, a finding compatible with maintained flow-metabolism coupling. Despite this, static rate of autoregulation decreased significantly from 54% +/- 36% to 28% +/- 35% (P = 0.029). Our data suggest that after head injury, the cerebrovascular effects of propofol are different from those observed in healthy individuals. We propose that large doses of propofol should be used cautiously in head-injured patients, because there is the potential to increase the injured brain's vulnerability to secondary insults. IMPLICATIONS: Propofol is used for sedation and control of intracranial pressure in head-injured patients. In contrast to previous data from healthy individuals, we show a deterioration of cerebrovascular pressure autoregulation with fast propofol infusion rates after head injury. Large propofol doses may increase the injured brain's vulnerability to secondary insults.

Adult↗

PubMed2003

Positron emission tomographic cerebral perfusion disturbances and transcranial Doppler findings among patients with neurological deterioration after subarachnoid hemorrhage.

OBJECTIVE: After aneurysmal subarachnoid hemorrhage, approximately 30% of patients experience delayed neurological deficits, related in part to arterial vasospasm and dysautoregulation. Transcranial Doppler (TCD) ultrasonography is commonly used to noninvasively detect arterial vasospasm. We studied cerebral perfusion patterns and associated TCD indices for 25 patients who developed clinical signs of delayed neurological deficits. METHODS: Patients were treated in a neurosurgical intensive care unit and were studied if they exhibited delayed focal or global neurological deterioration. Positron emission tomographic cerebral blood flow (CBF) studies and TCD studies measuring the mean flow velocity (FV) of the middle cerebral artery and the middle cerebral artery FV/internal carotid artery FV ratio (with the internal carotid artery FV being measured extracranially at the cranial base) were performed. Glasgow Outcome Scale scores were assessed at 6 months. RESULTS: A markedly heterogeneous pattern of CBF distribution was observed, with hyperemia, normal CBF values, and reduced flow being observed among patients with delayed neurological deficits. TCD indices were not indicative of the cerebral perfusion findings. The mean CBF value was slightly lower for patients who did not survive (32.3 ml/100 g/min), compared with those who did survive (36.0 ml/100 g/min, P = 0.05). CONCLUSION: Among patients who developed delayed neurological deficits after aneurysmal subarachnoid hemorrhage, a wide range of cerebral perfusion disturbances was observed, calling into question the traditional concept of large-vessel vasospasm. Commonly used TCD indices do not reflect cerebral perfusion values.

Adult↗

PubMed2002

Specialist neurocritical care and outcome from head injury.

OBJECTIVES: To document the effect of neurocritical care, delivered by specialist staff and based on protocol-driven therapy aimed at intracranial pressure (ICP) and cerebral perfusion pressure (CPP) targets, on outcome in acute head injury. DESIGN: Retrospective record review to compare presentation, therapy and outcome in patients with head injury referred to a regional neurosurgical centre, before and after establishment of protocol-driven therapy. SETTING: Neurosciences Critical Care Unit (NCCU). PARTICIPANTS: Two hundred and eighty-five patients aged 18-65 years with at least one reactive pupil, referred with a diagnosis of head injury, requiring tracheal intubation and mechanical ventilation. INTERVENTIONS: Measurement of Glasgow Outcome Scale 6 months after injury. RESULTS: Patients from the two epochs were well matched for admission Glasgow Coma Scale and extracranial injuries. When all referred patients were considered, institution of protocol-driven therapy was not associated with a statistically significant increase in favourable outcomes (56.0% vs. 66.4%). However, we observed a significant increase in favourable outcomes in the severely head injured patients studied (40.4% vs. 59.6%). The proportion of favourable outcomes was also high (66.6%) in those presenting with evidence of raised ICP in the absence of a mass lesion and (60.0%) in those that required complex interventions to optimise ICP/CPP. CONCLUSIONS: Specialist neurocritical care with protocol-driven therapy is associated with a significant improvement in outcome for all patients with severe head injury. Such management may also benefit patients requiring no surgical therapy, some of whom may need complex therapeutic interventions. We found it impossible to predict need for such interventions from clinical features at presentation. These data suggest that specialist critical care with ICP/CPP guided therapy may benefit patients with severe head injury.

Adult↗

PubMed2002

Integrated image analysis solutions for PET datasets in damaged brain.

OBJECTIVE: To identify and discuss the problems inherent in the processing of multiparametric functional imaging datasets from patients with acute brain injury, using "triple oxygen" positron emission tomography (PET) as an example. To present an integrated imaging solution for analysis of such datasets and report on its use in practice. METHODS: Structured analysis of the steps in image analysis for triple oxygen studies in patients with acute brain injury, subarachnoid haemorrhage and carotid artery disease was undertaken. Systematic identification of the drawbacks of conventional manual processing techniques, which make use of modules from different commercially available software packages was carried out. This analysis informed the construction of an image analysis gateway that addressed these issues. RESULTS: We describe an integrated image analysis gateway (PETAn) that provides for the automated integration of all processing steps, along with outputs that detail analysis stages, error logs and results. Implementation of PETAn allowed batch processing of clinical PET data sets, reduced the level of technical expertise required for analysis, improved the quality of results and achieved significant reductions in operator analysis time. CONCLUSIONS: While modules from several imaging software suites can be usefully combined to allow analysis of multiparametric PET data sets from patients with acute brain injury, sequential use of these modules for various steps in image analysis is fraught with difficulty. Careful automation and integration of these steps greatly facilitates the interrogation of information-rich data sets and increases research productivity.

Algorithms↗

PubMed2002

Arteriojugular endothelin-1 gradients in aneurysmal subarachnoid haemorrhage.

Plasma endothelin (ET) is elevated in patients with vasospasm following subarachnoid haemorrhage (SAH). However, systemic levels provide no indication regarding local production in the brain, and late elevation may be a consequence rather than a cause of vasospasm. We measured arteriojugular (AJ) gradients of ET-1 in 17 patients over the first week after SAH, and related these to the subsequent development of vasospasm. Daily, paired arterial and jugular bulb blood samples were obtained up to seven days post SAH, and assayed for ET-1 using radioimmunoassay. Systemic levels and AJ gradients were compared in patients with and without vasospasm. Significant AJ gradients were observed for ET-1 (P<0.01). These differences remained significant in the subgroup of patients who developed vasospasm (0.12+/-0.05 pmol/l; P<0.05), in whom AJ gradients represented 25+/-7% of systemic levels (0.84+/-0.05 pmol/l). AJ gradients did not reach significance in patients who did not develop vasospasm (0.09+/-0.07 pmol/l; P=0.2). Systemic ET-1 levels and AJ gradients were unrelated to SAH grade, surgical or endovascular interventions, or extracranial complications. AJ gradients in the first week following SAH suggest early production of ET-1 in the cerebrovascular bed. However, early systemic ET-1 levels did not discriminate between patients with and without vasospasm. Larger AJ differences may predict vasospasm, but further work is needed to confirm this observation. AJ gradient measurement may provide a useful technique for investigating the role of other peptides in acute brain injury.

Adult↗

PubMed2002

Detecting residual cognitive function in persistent vegetative state.

Despite converging agreement about the definition of persistent vegetative state, recent reports have raised concerns about the accuracy of diagnosis in some patients, and the extent to which, in a selection of cases, residual cognitive functions may remain undetected. Objective assessment of residual cognitive function can be extremely difficult as motor responses may be minimal, inconsistent, and difficult to document in many patients, or may be undetectable in others because no cognitive output is possible. Here we describe strategies for using H(2)(15)O positron emission tomography activation studies to study covert cognitive processing in patients with a clinical diagnosis of persistent vegetative state. Three cases are described in detail. Of these, two exhibited clear and predicted regional cerebral blood flow responses during well-documented activation paradigms (face recognition and speech perception) which have been shown to produce specific, robust and reproducible activation patterns in normal volunteers. Some months after scanning, both patients made a significant recovery. In a third case, blood flow data were acquired during a speech perception task, although methodological difficulties precluded any systematic interpretation of the results. In spite of the multiple logistic and procedural problems involved, these results have major clinical and scientific implications and provide a strong basis for the systematic study of possible residual cognitive function in patients diagnosed as being in a persistent vegetative state.

Adult↗

PubMed2002

Continuous monitoring of cerebrovascular pressure reactivity allows determination of optimal cerebral perfusion pressure in patients with traumatic brain injury.

OBJECTIVES: To define optimal cerebral perfusion pressure (CPPOPT) in individual head-injured patients using continuous monitoring of cerebrovascular pressure reactivity. To test the hypothesis that patients with poor outcome were managed at a cerebral perfusion pressure (CPP) differing more from their CPPOPT than were patients with good outcome. DESIGN: Retrospective analysis of prospectively collected data. SETTING: Neurosciences critical care unit of a university hospital. PATIENTS: A total of 114 head-injured patients admitted between January 1997 and August 2000 with continuous monitoring of mean arterial blood pressure (MAP) and intracranial pressure (ICP). MEASUREMENTS AND MAIN RESULTS: MAP, ICP, and CPP were continuously recorded and a pressure reactivity index (PRx) was calculated online. PRx is the moving correlation coefficient recorded over 4-min periods between averaged values (6-sec periods) of MAP and ICP representing cerebrovascular pressure reactivity. When cerebrovascular reactivity is intact, PRx has negative or zero values, otherwise PRx is positive. Outcome was assessed at 6 months using the Glasgow Outcome Scale. A total of 13,633 hrs of data were recorded. CPPOPT was defined as the CPP where PRx reaches its minimum value when plotted against CPP. Identification of CPPOPT was possible in 68 patients (60%). In 22 patients (27%), CPPOPT was not found because it presumably lay outside the studied range of CPP. Patients' outcome correlated with the difference between CPP and CPPOPT for patients who were managed on average below CPPOPT (r =.53, p <.001) and for patients whose mean CPP was above CPPOPT (r = -.40, p <.05). CONCLUSIONS: CPPOPT could be identified in a majority of patients. Patients with a mean CPP close to CPPOPT were more likely to have a favorable outcome than those whose mean CPP was more different from CPPOPT. We propose use of the criterion of minimal achievable PRx to guide future trials of CPP oriented treatment in head injured patients.

Adolescent↗

PubMed2002

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.

Adolescent↗

PubMed2002

Correlation between cerebral blood flow, substrate delivery, and metabolism in head injury: a combined microdialysis and triple oxygen positron emission tomography study.

Microdialysis continuously monitors the chemistry of a small focal volume of the cerebral extracellular space. Conversely, positron emission tomography (PET) establishes metabolism of the whole brain, but only for the duration of the scan. The objective of this study was to apply both techniques to head-injured patients simultaneously to assess the relation between microdialysis (glucose, lactate, lactate/pyruvate [L/P] ratio, and glutamate) and PET (cerebral blood flow [CBF], cerebral blood volume, oxygen extraction fraction (OEF), and cerebral metabolic rate of oxygen) parameters. Microdialysis catheters were inserted into the frontal cerebral cortex and adipose tissue of the anterior abdominal wall of 17 severely head-injured patients. Microdialysis was performed during PET scans, with regions of interest defined by the location of the microdialysis catheter membrane. An intervention (hyperventilation) was performed in 13 patients. The results showed that combining PET and microdialysis to monitor metabolism in ventilated patients is feasible and safe, although logistically complex. There was a significant relation between the L/P ratio and the OEF (Spearman r = 0.69, P = 0.002). There was no significant relation between CBF and the microdialysis parameters. Moderate short-term hyperventilation appeared to be tolerated in terms of brain chemistry, although no areas were sampled by microdialysis where the OEF exceeded 70%. Hyperventilation causing a reduction of the arterial carbon dioxide tension by 0.9 kPa resulted in a significant elevation of the OEF, in association with a reduction in glucose, but no significant elevation in the L/P ratio or glutamate.

Adolescent↗

PubMed2002

Measurement of brain tissue oxygenation performed using positron emission tomography scanning to validate a novel monitoring method.

OBJECT: The benefits of measuring cerebral oxygenation in patients with brain injury are well accepted; however, jugular bulb oximetry, which is currently the most popular monitoring technique used has several shortcomings. The goal of this study was to validate the use of a new multiparameter sensor that measures brain tissue oxygenation and metabolism (Neurotrend) by comparing it with positron emission tomography (PET) scanning. METHODS: A Neurotrend sensor was inserted into the frontal region of the brain in 19 patients admitted to the neurointensive care unit. After a period of stabilization, the patients were transferred to the PET scanner suite where C15O, 15O2, and H2(15)O PET scans were obtained to facilitate calculation of regional cerebral blood volume, O2 metabolism, blood flow, and O2 extraction fraction (OEF). Patients were given hyperventilation therapy to decrease arterial CO2 by approximately 1 kPa (7.5 mm Hg) and the same sequence of PET scans was repeated. For each scanning sequence, end-capillary O2 tension (PvO2) was calculated from the OEF and compared with the reading of brain tissue O2 pressure (PbO2) provided by the sensor. In three patients the sensor was inserted into areas of contusion and these patients were eliminated from the analysis. In the subset of 16 patients in whom the sensor was placed in healthy brain, no correlation was found between the absolute values of PbO2 and PvO2 (r = 0.2, p = 0.29); however a significant correlation was obtained between the change in PbO2 (deltaPbO2) and the change in PvO2 (deltaPvO2) produced by hyperventilation in a 20-mm region of interest around the sensor (p = 0.78, p = 0.0035). CONCLUSIONS: The lack of correlation between the absolute values of PbO2 and PvO2 indicates that PbO2 cannot be used as a substitute for PvO2. Nevertheless, the positive correlation between deltaPbO2 and deltaPvO2 when the sensor had been inserted into healthy brain suggests that tissue PO2 monitoring may provide a useful tool to assess the effect of therapeutic interventions in brain injury.

Adult↗

PubMedDate not supplied

Residual auditory function in persistent vegetative state: a combined PET and fMRI study.

In recent years, a number of studies have demonstrated an important role for functional neuroimaging in the identification of residual cognitive function in persistent vegetative state. Such studies, when successful, may be particularly useful where there is concern about the accuracy of the diagnosis and the possibility that residual cognitive function has remained undetected. Unfortunately, functional neuroimaging in persistent vegetative state is extremely complex and subject to numerous methodological, clinical and theoretical difficulties. Here, we describe the strategy used to study residual auditory and speech processing in a single patient with a clinical diagnosis of persistent vegetative state. Identical positron emission tomography studies, conducted nine months apart, revealed preserved and consistent responses in predicted regions of auditory cortex in response to intelligible speech stimuli. Moreover, a preliminary functional magnetic resonance imaging examination at the time of the second session revealed partially intact responses to semantically ambiguous stimuli, which are known to tap higher aspects of speech comprehension. In spite of the multiple logistic and procedural problems involved, these results have major clinical and theoretical implications and provide a strong basis for the systematic study of possible residual cognitive function in patients diagnosed as being in a persistent vegetative state.

Adult↗