Neurointensive Care, TBI, SAH

Traumatic brain injury (TBI) and subarachnoid hemorrhage (SAH) are common and serious medical conditions. The development of modern neurointensive care has markedly reduced mortality and improved patient outcomes while clinical trials of neuroprotective drug candidates have to date been unsuccessful. Basic research has identified a number of secondary injury mechanisms following TBI and SAH.

The challenge ahead is to translate this knowledge into the clinical setting to find new treatment strategies to hinder secondary injuries and improve patient outcomes even further. The neurointensive care unit (Neuro-ICU) with highly standardised health care, a multitude of monitoring methods and powerful computerised data collection systems provides an excellent platform for this translational research.

Overall goal

To study secondary brain injury mechanisms in patients with TBI and SAH in the Neuro-ICU utilising the available multimodality monitoring and computerised data collection systems.
To specifically study secondary injury mechanisms caused by intracranial secondary insults/complications (e.g. intracranial hypertension owing to brain swelling) and secondary systemic insults (e.g. hypotension with a reduced cerebral blood perfusion).

Methods

Multimodality monitoring – The technical equipment available in our Neuro-ICU allows for continuous monitoring of intracranial pressure, systemic blood pressure, cerebral perfusion pressure, intracerebral neurochemistry changes (e.g. energy metabolic perturbations and biomarkers), neurophysiology (e.g. post traumatic seizure activity), brain temperature, brain tissue oxygen pressure, jugular venous oxygen saturation, cerebral blood flow velocity, intracranial compliance. Neuroimaging (CT, CT/PET and MRI) are important complimentary methods for monitoring the brain injury process.

Computerised data collection system – A computer system has been developed and implemented in the Neuro-ICU allowing for collection, analysis and illustration of clinical data (e.g. type of brain injury, CT findings), physiological data (e.g. intracranial pressure, brain tissue oxygen pressure), treatment data (e.g. ventricular CSF drainage to lower the intracranial pressure).

The Neuro-ICU as a “clinical laboratory” – A standardised clinical protocol corresponding to the concept of “good laboratory practice” has been developed and implemented in the Neuro-ICU. The clinical protocol, the multimodality monitoring system and the computer data collection system together allows for extensive control and monitoring of the clinical condition, resembling a basic science laboratory environment. The facilities thus create an excellent platform for neurointensive care and clinical research of top international quality.

Brain IT group – We have in collaboration with distinguished colleagues in the field established an international research network comprising over 20 centers in Europe with focus on neurointensive care of TBI patients (www.brainit.org). Information technology (IT) is used collect patient data to a common web-based database for TBI research. This will provide a powerful research tool for international multi-center trials on e.g. novel treatment strategies and neurosurgical methods.

Uppsala Brain Injury Center (UBIC) – This is a recently established translational research network with focus on TBI research. The basic objective of this multidisciplinary endeavour is to combat TBI with a broad spectrum of competencies ranging from molecule to man, i.e. from molecular genetics, cellculture systems, animals models, TBI patients in the Neuro-ICU to rehabilitation and follow-up (www.neuro.uu.se/ubic ). The Uppsala Neuro-ICU is of top international class providing one of the major research platforms within the UBIC. The UBIC concept received top marks regarding research quality, research environment and future potential by the external international review board in the recent evaluation “Quality and Reneval 2007” of the research at Uppsala University.

Another multidisciplinary project was lounged in 2007 in a collaborative effort between UBIC and the Uppsala Berzelii Technology Center for Neurodiagnostics (www.berzelii.uu.se) combining clinical microdialysis technology with modern proteomic methodology and Materials Science. The main goal is to find clinically useful diagnostic and prognostic biomarkers for point-of-care use in the Neuro-ICU. The basic working hypothesis is that harvesting of biomarkers directly in the injured brain by microdialysis will improve the spatial and temporal resolution leading to an improved enhanced value of the biomarkers. Modern proteomics methodology is a powerful tool to screen for entirely novel biomarkers of TBI. Materials Science technology is instrumental in optimising protein biomarker sampling performance and combined biosensor technology.

Significance

The organisation of neurointensive care into a ”laboratory-like” environment with powerful multimodality monitoring and computerised data collection provides a unique opportunity to monitor the acute brain injury process and the effect of treatment strategies, enabling the study of pathophysiological and neurochemical mechanisms of acute brain injury directly in the human brain. We hypothesise that this opportunity will be instrumental in the translation of promising basic science results to the Neuro-ICU setting improving outcome of patients with acute brain injury.

Multimodality Monitoring (Anders Lewén)

Background

The advances in neurocritical care science have to a great extent been dependent on technical development of monitoring equipment which has enabled more detailed information on pathological events occurring in patients in the NIC unit. The techniques used include conventional NIC monitoring of intracranial pressure (ICP), cerebral perfusion pressure, arterial blood pressure, ECG, central venous pressure, pulse oxymetry and temperature. New monitoring techniques have also been introduced, e.g. intracerebral microdialysis for neurochemical monitoring, EEG for electrophysiological monitoring, Licox probes for regional monitoring of brain tissue oxygenation, jugular bulb catheters for monitoring of global brain oxygenation, transcranial Doppler probes for blood flow velocity measurements and Spiegelbergs compliance monitor for monitoring of intracranial compliance. How data generated from multimodality monitoring shall lead to better guidelines for treatment of TBI patients is the main focus of this research project.

Aims autoregulation studies

We have found in our retrospective study that autoregulation guided therapy may improve outcome. Most measures of cerebral vascular autoregulation used are based on the response of ICP to changes in systemic blood pressure. The best available measure for continuous assessment of autoregulation status is the Pressure-Reactivity Index (PRx) calculated as a moving correlation coefficient between 40 consecutive samples of values for ICP and mean arterial blood pressure averaged for a period of 5 seconds.
PRx will be used as a measure of pressure autoregulation and the results will be related to other monitoring methods.

Aims compliance studies

Decreased intracranial compliance (decreased ability to compensate for added intracranial volume) may increase the vulnerability of the brain for secondary insults. Unfortunately, the Spiegelberg compliance monitor proved to be difficult to use on a routine basis in NIC. It has long been suspected that pulse wave amplitude and morphology carries information about cerebral compliance and hence the vulnerability of the patient to increases in ICP. Subsequent studies have had varying degrees of success in attempting to establish standard methodologies for assessing compliance and evaluating its clinical implications. One continuous measure of compliance based on waveform analysis is the RAP index, which measures the correlation of ICP amplitude and mean ICP.
We intend to perform comparative studies between the different compliance measures in order to find the most suitable tool for routine clinical compliance monitoring in neurointensive care. The significance of decreased intracranial compliance for the development of secondary brain injury will also be studied by relating intracranial compliance levels to neurochemical microdialysis and brain tissue oxygenation reactions on different secondary insults, e.g. high ICP.

Aims Brain tissue oxygenation studies

We have used the Neurovent-PTO® sensor in combination with intracerebral microdialysis in the recently established standardized experimental brain death model in pigs in which ICP is gradually increased by step-wise filling of an epidural balloon catheter.
We will analyze the microdialysis results to assess the critical brain tissue oxygenation threshold for brain ischemia reflected by increase of the microdialysis lactate-pyruvate ratio. The critical CPP ischemia threshold will also be assessed.
The Neurovent-PTO® sensor will also be included in the multimodality monitoring in the NIC unit. Our plan is to analyze the brain tissue oxygenation data in relation to CPP, microdialysis and Jugular bulb oxygenation to identify threshold levels in humans.

Aims TBI in elderly

The aims of this study are to characterize specific age related features of traumatic brain injury (TBI) and to develop a more tailored neurointensive care specifically suited for the elderly, by identifying age specific injury thresholds of intracranial pressure (ICP), cerebral perfusion pressure (CPP), mean arterial blood pressure (MAP), compliance, autoregulation, cerebral tissue oxygenation and metabolism, in order to meet the tremendous challenge that the management of the elderly TBI patients will constitute in the near future. Currently the lack of knowledge within this field is substantial and it is of outmost importance to increase our understanding of these specific questions in order to optimally treat elderly with TBI.

Contact

Section chief:

Prof Per Enblad

E-mail: per.enblad@neuro.uu.se

Centre of Excellence Neurotrauma

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