Role of the specialized neuro intensive care nurse in neuroscience research.

It is widely acknowledged that the quality of research is greatly improved when nurses are involved at the investigators' site. Many papers highlight the knowledge, skills and expertise required by nurses for the conduct of trials. The known skills include reliability, organization, communication, motivation, self-discipline and critical thought. The responsibilities of nurses in the conduction of research trials are wide ranging from the collection and recording of data, recruitment and screening of patients, ensuring informed consent has been gained, randomization of drugs, the follow-up of patients to development and training for staff to the required international standards. In the past, clinical research nurses have been considered as data collectors by their peers, due to the lack of knowledge of the true extent of the role of the clinical research nurse. The rise in popularity of the role and the publication of an employment brief for clinical research nurses by the Royal College of Nursing (RCN) and the UK Clinical Research Collaboration (UKCRC) publication on 'Developing the best research professionals' has readdressed this prior imbalance; recognizing in detail their role, knowledge, skills, expertise with appropriate grading and remuneration. The role of the clinical research nurse in the neuroscience setting is equally as diverse with the added requirement of a higher level of knowledge and understanding of the pathophysiology of neurological diseases and specific skills required to work in the intensive care environment. This paper will attempt to explore the role of the specialized neurosciences intensive care nurse and the relationship with high-quality neuroscience research.

Predictive value of initial clinical status, intracranial pressure and transcranial Doppler pulsatility after subarachnoid haemorrhage.

BACKGROUND: We examined the predictive value of initial clinical status, mean arterial blood pressure (MABP), intracranial pressure (ICP) and transcranial Doppler (TCD)-derived pulsatility and resistance indices for outcome and quality of life one year following aneurysmal subarachnoid haemorrhage (SAH). METHOD: Neuromonitoring was performed in 29 patients following clipping or coiling of an aneurysm. Mean arterial blood pressure was measured in the radial artery and intracranial pressure was assessed via a closed external ventricular drainage. Based on transcranial Doppler-recordings of the middle cerebral artery, Gosling's pulsatility (PI) and Pourcelot's resistance (RI) index were calculated. Glasgow outcome score (GOS) and short form-36 (SF-36) scores were determined one year after SAH. FINDINGS: An unfavourable outcome (GOS 1-3) was observed in 34% of patients and correlated significantly (p < 0.05) with a poor initial clinical status, as determined by Glasgow Coma Scale (r = 0.55), Hunt and Hess (r = -0.62), World Federation of Neurosurgical Societies (WFNS) (r = -0.48) and Fisher (r = -0.58) score. Poor outcome was significantly associated with high mean arterial blood pressure (r = -0.44) and intracranial pressure (r = -0.48) as well as increased pulsatility (r = -0.46) and resistance (r = -0.43) indices. Hunt and Hess grade > or = 4 (OR 12.4, 5-95% CI: 1.9-82.3), mean arterial blood pressure > 95 mmHg (19.5, 2.9-132.3), Gosling's pulsatility >0.8 (6.5, 1.6-27.1) and Pourcelot's resistance >0.57 (15.4, 2.3-103.4) were predictive for unfavourable outcome in logistic regression, however TCD-diagnosed vasospasm was not. Except for mental health, significantly reduced scores were observed in all short form-36 domains. Initial clinical status correlated significantly with the physical functioning, role physical, bodily pain, social functioning and physical component summary of short form-36. CONCLUSIONS: Mortality and morbidity following SAH remains high, especially in poor-grade patients. Outcome is mainly correlated with initial clinical status, mean arterial blood pressure, intracranial pressure, pulsatility and resistance indices. Those factors seem to be stronger than the influence of vasospasm.

Changes over time in cognitive and structural profiles of head injury survivors.

Survivors of traumatic head injury often suffer chronic cognitive deficits. Considerable evidence implicates the cholinergic system in these deficits. Recently, we reported cognitive and structural abnormalities in a cohort of head injured survivors consistent with this hypothesis [see Salmond, C. H., Chatfield, D. A., Menon, D. K., Pickard, J. D., & Sahakian, B. J. (2005). Cognitive Sequelae of Head Injury: Involvement of Basal Forebrain and associated structures. Brain, 128(1), 189-200]. The stability of the cognitive and structural MRI profiles was investigated in a longitudinal study. Twenty-one survivors of moderate-severe head injury completed two comprehensive neuropsychological assessments and two structural MRI scans at least six months apart. A cohort of controls also completed these investigations. The results revealed that the cognitive and structural profiles are relatively stable from six months post-injury forward up to 3 years post-injury. Deficits in memory, attention and reaction time were found, with relative preservation of working memory, consistent with abnormalities in the cholinergic system. These findings suggest that cholinergic enhancers may be an effective treatment for cognitive deficits post-head injury in survivors up to three years post-injury.

An investigation of auto-reactivity after head injury.

Murine models of CNS injury show auto-reactive T cell responses directed at myelin antigens, associated with improved neuronal survival and functional recovery. This pilot study shows, for the first time, that similar immune responses against myelin occur in human traumatic brain injury (TBI), with an expansion of lymphocytes recognising myelin basic protein observed in 40% of patients studied. "Reactive" patients did not have greater contusion volume on imaging, but were younger than the "unreactive" subgroup and tended towards a more favorable outcome. These findings are consistent with the concept of "beneficial autoimmunity".

Diffusion tensor imaging in chronic head injury survivors: correlations with learning and memory indices.

Diffusion tensor imaging (DTI) provides a unique insight into the cellular integrity of the brain. While conventional magnetic resonance imaging underestimates the extent of pathology following closed head injury, diffusion-weighted imaging has been shown to more accurately delineate the extent of cerebral damage. There have only been a few case studies of DTI in chronic head injury survivors. This study used DTI to investigate changes in anisotropy and diffusivity in survivors of head injury at least 6 months after their injury. The relationship between cognition and diffusion abnormality was also investigated. The voxel-based analysis revealed significant bilateral decreases in anisotropy, in major white matter tracts and association fibers in the temporal, frontal, parietal and occipital lobes. Statistically significant increases in diffusivity were also found in widespread areas of the cortex. A significant positive correlation was found between diffusivity and impairment of learning and memory in the left posterior cingulate, left hippocampal formation and left temporal, frontal and occipital cortex. The common pattern of abnormality despite heterogeneous injury mechanism and lesion location in the group suggests that these cellular changes reflect secondary insults. The importance of diffusion abnormalities in head injury outcome is emphasized by the significant correlation between a learning and memory index and diffusivity in areas known to subserve this cognitive function.

Metallic neurosurgical implants for cranial reconstruction and fixation: assessment of magnetic field interactions, heating and artefacts at 3.0 Tesla.

The objective of this study was to evaluate the magnetic resonance imaging (MRI) compatibility of metallic neurosurgical implants commonly used for cranial reconstruction and fixation, in association with a 3.0 Tesla (T) MR system. Ten metallic neurosurgical implants used for cranioplasty operations were evaluated. The implants were tested ex vivo for magnetic field interactions (translational attraction and torque), heating (using saline and gel phantoms), and artefact production [using dual echo spin echo (DSE) and gradient echo (GRE) sequences] at 3.0 Tesla. None of the implants displayed translational attraction or torque, and heating was physiologically insignificant (maximal temperature elevation was 0.5 degrees C). MR artefacts were minimal with spin echo sequences; gradient echo sequences produced much larger artefacts. The neurosurgical implants evaluated in this study should not present a risk to patients undergoing MRI in the 3.0 T MR system. Although the implants do produce susceptibility artefacts, especially with gradient echo sequences, useful imaging should still be possible.

Deficits in decision-making in head injury survivors.

Many survivors of head injury suffer chronic personality changes, such as increased impulsivity and a lack of insight and poor judgment. These changes are well recognized and likely to affect the ability to make decisions. However, systematic investigations into their nature have been limited. This study aims to explore the nature of decision making in head injury survivors using a computerized task. Forty-three head injury survivors and a group of 29 matched controls completed the computerized task. The task required participants to make a probability-based choice and to further qualify this choice with an associated "bet." This betting component allows an assessment of the participant's level of confidence in the decision, via the affective evaluation of its possible consequences in terms of points won or lost. The survivors were found to be slow at making the probability- based choice. Whilst at highly favorable odds, the survivors chose the most likely option in a similar manner to the controls, they chose the most likely option less often than the controls at less favorable odds. Examination of the survivors' betting behavior revealed that they responded impulsively compared to controls. This pattern of prolonged decision making and poor quality of decisions is similar to that found in patients with orbitofrontal cortex lesions, whilst impulsive betting has been associated with abnormalities of the dopamine system. These complex deficits in decision making may contribute to difficulties with poor judgment and inhibition in head injury survivors.

Physiological thresholds for irreversible tissue damage in contusional regions following traumatic brain injury.

Cerebral ischaemia appears to be an important mechanism of secondary neuronal injury in traumatic brain injury (TBI) and is an important predictor of outcome. To date, the thresholds of cerebral blood flow (CBF) and cerebral oxygen utilization (CMRO(2)) for irreversible tissue damage used in TBI studies have been adopted from experimental and clinical ischaemic stroke studies. Identification of irreversibly damaged tissue in the acute phase following TBI could have considerable therapeutic and prognostic implications. However, it is questionable whether stroke thresholds are applicable to TBI. Therefore, the aim of this study was to determine physiological thresholds for the development of irreversible tissue damage in contusional and pericontusional regions in TBI, and to determine the ability of such thresholds to accurately differentiate irreversibly damaged tissue. This study involved 14 patients with structural abnormalities on late-stage MRI, all of whom had been studied with (15)O PET within 72 h of TBI. Lesion regions of interest (ROI) and non-lesion ROIs were constructed on late-stage MRIs and applied to co-registered PET maps of CBF, CMRO(2) and oxygen extraction fraction (OEF). From the entire population of voxels in non-lesion ROIs, we determined thresholds for the development of irreversible tissue damage as the lower limit of the 95% confidence interval for CBF, CMRO(2) and OEF. To test the ability of a physiological variable to differentiate lesion and non-lesion tissue, we constructed probability curves, demonstrating the ability of a physiological variable to predict lesion and non-lesion outcomes. The lower limits of the 95% confidence interval for CBF, CMRO(2) and OEF in non-lesion tissue were 15.0 ml/100 ml/min, 36.7 mumol/100 ml/min and 25.9% respectively. Voxels below these values were significantly more frequent in lesion tissue (all P < 0.005, Mann-Whitney U-test). However, a significant proportion of lesion voxels had values above these thresholds, so that definition of the full extent of irreversible tissue damage would not be possible based upon single physiological thresholds. We conclude that, in TBI, the threshold of CBF below which irreversible tissue damage consistently occurs differs from the classical CBF threshold for stroke (where similar methodology is used to define such thresholds). The CMRO(2) threshold is comparable to that reported in the stroke literature. At a voxel-based level, however (and in common with ischaemic stroke), the extent of irreversible tissue damage cannot be accurately predicted by early abnormalities of any single physiological variable.

Effects of moderate hyperventilation on cerebrovascular pressure-reactivity after head injury.

In volunteers, hyperventilation improves autoregulation. However, in head-injured patients, hyperventilation-induced deterioration and improvement of autoregulation have been reported. We have re-examined this question using an index of pressure reactivity. Thirty patients with severe or moderate head-injury were studied. Arterial blood pressure, cerebral perfusion pressure (CPP), and intracranial pressure (ICP) were recorded over 20 minute epochs separated by ten minutes of equilibration at baseline and during moderate (>3.5 kPa) hyperventilation. End-tidal CO2 was constant during each phase of data acquisition. Pressure reactivity was assessed using an index 'PRx' based on the response of ICP to spontaneous blood pressure changes. Hyperventilation decreased PaCO2 from 5.1 +/- 0.4 to 4.4 +/- 0.4 kPa (p < 0.0001). ICP decreased by 3.7 +/- 2.2 mmHg (p < 0.001). CPP increased by 5.9 +/- 8.2 mmHg (p < 0.001). Overall, PRx did not change significantly with hyperventilation. However, there was a significant negative correlation between baseline PRx and the change in PRx (r = -0.71, p < 0.0001). This suggests that patients with disturbed pressure-reactivity may improve, whereas patients with intact pressure reactivity remain largely unchanged. Our data suggest that the response of pressure reactivity to hyperventilation is heterogeneous. This could be due to hyperventilation-induced changes in cerebral metabolism, or the change in CPP.

Imaging of cerebral blood flow and metabolism in brain injury in the ICU.

The heterogeneity of the initial insult and subsequent pathophysiology has made both the study of human head injury and design of randomised controlled trials exceptionally difficult. The combination of multimodality bedside monitoring and functional brain imaging positron emission tomography (PET) and magnetic resonance (MR), incorporated within a Neurosciences Critical Care Unit, provides the resource required to study critically ill patients after brain injury from initial ictus through recovery from coma and rehabilitation to final outcome. Methods to define cerebral ischemia in the context of altered cerebral oxidative metabolism have been developed, traditional therapies for intracranial hypertension re-evaluated and bedside monitors cross-validated. New modelling and analytical approaches have been developed.

Cognitive sequelae of head injury: involvement of basal forebrain and associated structures.

Traumatic brain injury is the most common cause of death and disability in young people and survivors often suffer from chronic cognitive deficits. From animal, post-mortem and cognitive studies, there is now increased evidence that abnormalities in the cholinergic system may be underlying some of these deficits. This study investigated this hypothesis in a group of survivors of moderate-severe head injury (n = 31). Patients completed a comprehensive neuropsychological assessment and an MRI scan. Compared with a group of controls (matched on age, sex and premorbid intelligence quotient), the patients showed deficits in sustained attention, paired associate learning and reaction time, but comparative preservation of spatial working memory. Voxel-based morphometry revealed reduced grey matter density in the head injured group in the basal forebrain, the hippocampal formation and regions of the neocortex. These cognitive and structural results are consistent with cholinergic dysfunction. These preliminary findings suggest that cholinergic enhancers may be an effective treatment of cognitive deficits post head injury.

Predictive value of Glasgow Coma Scale after brain trauma: change in trend over the past ten years.

BACKGROUND: Age and the Glasgow Coma Scale (GCS) score on admission are considered important predictors of outcome after traumatic brain injury. We investigated the predictive value of the GCS in a large group of patients whose computerised multimodal bedside monitoring data had been collected over the previous 10 years. METHODS: Data from 358 subjects with head injury, collected between 1992 and 2001, were analysed retrospectively. Patients were grouped according to year of admission. Glasgow Outcome Scores (GOS) were determined at six months. Spearman's correlation coefficients between GCS and GOS scores were calculated for each year. RESULTS: On average 34 (SD: 7) patients were monitored every year. We found a significant correlation between the GCS and GOS for the first five years (overall 1992-1996: r = 0.41; p<0.00001; n = 183) and consistent lack of correlations from 1997 onwards (overall 1997-2001: r = 0.091; p = 0.226; n = 175). In contrast, correlations between age and GOS were in both time periods significant and similar (r = -0.24 v r = -0.24; p<0.002). CONCLUSIONS: The admission GCS lost its predictive value for outcome in this group of patients from 1997 onwards. The predictive value of the GCS should be carefully reconsidered when building prognostic models incorporating multimodality monitoring after head injury.

Effects of propofol on cerebral oxygenation and metabolism after head injury.

BACKGROUND: Flow-metabolism coupling is thought to be deranged after traumatic brain injury, while the effects of propofol on flow-metabolism coupling are controversial. We have used a step increase in target plasma propofol concentration in head injured patients to explore flow-metabolism coupling in these patients. METHODS: Ten patients with a moderate to severe head injury received a step increase in propofol target controlled infusion of 2 microg x ml(-1). Cerebral tissue gas measurements were recorded using a multimodal sensor, and regional chemistry was assessed using microdialysis. Arterial-jugular venous oxygen differences (AVDO(2)) were measured and all patients had cortical function monitoring (EEG). RESULTS: The step increase in propofol led to a large increase in EEG burst-suppression ratio (0% (range 0-1.1) to 46.1% (range 0-61.7), P<0.05); however, this did not significantly change tissue gas levels, tissue chemistry, or AVDO(2). CONCLUSIONS: Flow-metabolism coupling remains intact during a step increase in propofol after traumatic brain injury. The EEG burst-suppression induced by propofol after traumatic brain injury does not appear to be a useful therapeutic tool in reducing the level of regional ischaemic burden.

Cerebrovascular pressure reactivity is related to global cerebral oxygen metabolism after head injury.

BACKGROUND: After head injury, impaired cerebrovascular autoregulation has been associated with abnormally high or low cerebral blood flow. The physiological relevance of cerebral blood flow levels is difficult to assess in these patients, whose cerebral metabolic rate for oxygen (CMRO(2)) is known to be abnormal. Investigation of these relations requires quantitative measures of cerebral blood flow and CMRO(2), to allow assessment of oxygen supply and demand relations. OBJECTIVES: To investigate the relation between dysautoregulation and global cerebral oxygen metabolism following head injury. METHODS: Using positron emission tomography, global cerebral blood flow, CMRO(2), and oxygen extraction fraction were determined in 22 patients who were investigated in 26 examinations on days 1 to 11 (mean (SD), 3.5 (2.3)) after head injury. Cerebrovascular pressure reactivity was assessed using a pressure reactivity index, calculated as the moving linear correlation coefficient between mean arterial blood pressure and intracranial pressure. Outcome was assessed six months after injury using the Glasgow outcome scale. RESULTS: Low CMRO(2) was associated with disturbed pressure reactivity (inverse function, R(2) = 0.21, p = 0.018) and there was a correlation between disturbed pressure reactivity and oxygen extraction fraction (quadratic function, R(2) = 0.55, p = 0.0001). There was no significant relation between pressure reactivity and cerebral blood flow. An unfavourable outcome was associated with disturbed pressure reactivity. There was no significant relation between outcome and CMRO(2) or oxygen extraction fraction. CONCLUSIONS: There is a close relation between dysautoregulation and abnormal cerebral metabolism but not blood flow. Further studies are needed to determine whether metabolic dysfunction is a result of or a cause of disturbed pressure reactivity, and to establish if there is a relation between cerebral oxygen metabolism and outcome.

Discordant temporal patterns of S100beta and cleaved tau protein elevation after head injury: a pilot study.

There is considerable interest in S100beta protein as a potential marker that can be used to quantify central nervous system injury. However, increasing appreciation that S100beta may be produced by non-neural tissue (specifically adipocytes), has led to a search for more specific markers of brain injury. Recent interests have focused on a cleaved form of tau protein (c tauP) which is elevated in CSF from patients suffering traumatic brain injury. We have investigated whether levels in peripheral blood are a satisfactory alternative to provide an accessible marker of CNS injury severity. We measured levels of S100beta and c tauP in arterial blood from 20 patients with severe head injury. When compared with normal values S100beta was elevated 10-fold in the first 24 hours and c tauP was elevated at all time points, but showed a reversal of the temporal trend observed with S100beta. Patients with a poor outcome (GOS 1-3) had significantly higher S100beta levels on day one. Plasma c tauP levels did not correlate with outcome following head injury.

Assessment of the Caradyne WhisperFlow for administration of continuous positive airway pressure in a 3 Tesla magnetic resonance scanner.

Demand for magnetic resonance investigations in critically ill patients is increasing. While these patients frequently need ventilatory support, not all of them require controlled ventilation and many may be treated with continuous positive airway pressure. Controlled ventilation, with the concurrent need for sedation, may be inappropriate when airway physiology is being studied and may retard weaning. No commercially available ventilator designed for the magnetic resonance environment can deliver high flow continuous positive airway pressure. We tested the Caradyne Whisperflow flow generator and five Whisperflow valves (2.5-15 cmH2O airway pressure) within a 3 Tesla environment for safety and possible dysfunction. All components had minimal ferromagnetic properties and tests showed no clinically relevant change in flow delivery or oxygen concentration in the magnetic field. In addition, the airway pressure generated by the valves was not affected by the magnetic field. We conclude that the tested system can be safely used in a 3 Tesla magnetic resonance environment.

Investigation of the effect of chlormethiazole on cerebral chemistry in neurosurgical patients: a combined study of microdialysis and a neuroprotective agent.

AIMS: Promising pre-clinical results from laboratory studies of neuro-protective drugs for the treatment of patients with stroke and head injury have not been translated into benefit during clinical trials. The objective of the study was to assess the feasibility of administrating a potential neuro-protective drug (chlormethiazole) in conjunction with multimodality monitoring (including microdialysis) to patients with severe head injury in order to determine the effect of the agent on surrogate endpoints and penetration into the brain. METHODS: Multimodality monitoring including cerebral and peripheral microdialysis was applied to five head-injured patients on the neuro-intensive care unit. Chlormethiazole (0.8%) was administered as a rapid (10 ml min(-1)) intravenous loading infusion for 5 min followed by a slow (1 ml min(-1)) continuous infusion for 60 min. The following parameters were monitored: heart rate, mean arterial blood pressure, intracranial pressure, cerebral perfusion pressure, peripheral oxygen saturation, continuous arterial oxygen partial pressure, arterial carbon dioxide partial pressure, arterial pH, arterial temperature, cerebral tissue oxygen pressure, cerebral tissue carbon dioxide pressure, cerebral pH, cerebral temperature, electroencephalograph (EEG), bi-spectral index, plasma glucose, plasma chlormethiazole, and cerebral and peripheral microdialysis assay for chlormethiazole, glucose, lactate, pyruvate and amino acids. RESULTS: Despite achieving adequate plasma concentrations, chlormethiazole was not detected in the peripheral or cerebral microdialysis samples. The drug was well tolerated and did not induce hypotension, hyperglycaemia or withdrawal seizures. The drug did not change the values of the physiological or chemical parameters including levels of GABA, lactate/pyruvate ratio and glutamate. The drug did, however, induce EEG changes, including burst suppression in two patients. CONCLUSIONS: Chlormethiazole can be safely given to ventilated patients with severe head injury. There was no evidence of hypotension or withdrawal seizures. Combining a pilot clinical study of a neuro-protective agent with multimodality monitoring is feasible and, despite the lack of effect on physiological and chemical parameters in this study, may be a useful adjunct to the development of neuro-protective drugs in the future. Further investigation of the capability of microdialysis in this setting is required. By investigating the effect of a drug on surrogate end-points, it may be possible to identify promising agents from small pilot clinical studies before embarking on large phase III clinical trials.