[show abstract][hide abstract] ABSTRACT: BACKGROUND: Intracranial hemorrhage occurs in over 60% of severe head injuries in one of three types: extradural (EDH); subdural (SDH); and intraparenchymal (TICH). Prompt surgical removal of significant SDH and EDH is established and widely accepted. However, TICH is more common and is found in more than 40% of severe head injuries. It is associated with a worse outcome but the role for surgical removal remains undefined. Surgical practice in the treatment of TICHs differs widely around the world. The aim of early surgery in TICH removal is to prevent secondary brain injury. There have been trials of surgery for spontaneous ICH (including the STICH II trial), but none so far of surgery for TICH. METHODS: The UK National Institutes of Health Research has funded STITCH(Trauma) to determine whether a policy of early surgery in patients with TICH improves outcome compared to a policy of initial conservative treatment. It will include a health economics component and carry out a subgroup analysis of patients undergoing invasive monitoring. This is an international multicenter pragmatic randomized controlled trial.Patients are eligible if: they are within 48 h of injury; they have evidence of TICH on CT scan with a confluent volume of attenuation significantly raised above that of the background white and grey matter that has a total volume >10 mL; and their treating neurosurgeon is in equipoise.Patients will be ineligible if they have: a significant surface hematoma (EDH or SDH) requiring surgery; a hemorrhage/contusion located in the cerebellum; three or more separate hematomas fulfilling inclusion criteria; or severe pre-existing physical or mental disability or severe co-morbidity which would lead to poor outcome even if the patient made a full recovery from the head injury.Patients will be randomized via an independent service. Patients randomized to surgery receive surgery within 12 h. Both groups will be monitored according to standard neurosurgical practice. All patients have a CT scan at 5 days (+/-2 days) to assess changes in hematoma size. Follow-up is by postal questionnaire at 6 and 12 months. The recruitment target is 840 patients.Trial registrationCurrent Controlled Trials ISRCTN19321911.
[show abstract][hide abstract] ABSTRACT: Hypotension is recognized as a potentially damaging secondary insult after traumatic brain injury. Systems to give clinical teams some early warning of likely hypotensive instability could be added to the range of existing techniques used in the management of this group of patients. By using the Edinburgh University Secondary Insult Grades (EUSIG) definitions for -hypotension (systolic arterial pressure <90 mmHg OR mean arterial -pressure <70 mmHg) we collected a group of ∼2,000 events by analyzing the Brain-IT database. We then constructed a Bayesian Artificial Neural Network (an advanced statistical modeling technique) that is able to provide some early warning when trained on this previously collected demographic and physiological data.
Using EUSIG defined event data from the Brain-IT database, we identified a Bayesian artificial neural network (BANN) topology and constructed a series of datasets using a group of clinically guided input variables. This allowed us to train a BANN, which was then tested on an unseen set of patients from the Brain-IT database. The initial tests used a particularly harsh assessment criterion whereby a true positive prediction was only allowed if the BANN predicted an upcoming event to the exact minute. We have now developed the system to the point where it is about to be used in a two-stage Phase II clinical trial and we are also researching a more realistic assessment technique.
We have constructed a BANN that is able to provide early warning to the clinicians based on a model that uses information from the physiological inputs; systolic and mean arterial pressure and heart rate; and demographic variables age and gender. We use 15-min SubWindows starting at 15 and 30 min before an event and process mean, slope and standard deviations. Based on 10 simulation runs, our current sensitivity is 36.25% (SE 1.31) with a specificity of 90.82% (SE 0.85). Initial results from a Phase I clinical study shows a model sensitivity of 40.95% (SE 6%) and specificity of 86.46% (SE 3%) Although this figure is low it is considered clinically useful for this dangerous condition, provided the false positive rate can be kept sufficiently low as to be practical in an intensive care environment.
We have shown that using advanced statistical modeling techniques can provide clinical teams with useful information that will assist clinical care.
[show abstract][hide abstract] ABSTRACT: Hypotension is a recognized -secondary insult after traumatic brain injury (TBI). There are many definitions of hypotension, an often cited example being the Brain Trauma Foundation's current (2007) "Guidelines for the Management of Severe Traumatic Brain Injury," which defines hypotension as systolic pressure <90 mmHg. However, this same document declares "The importance of mean arterial pressure, as opposed to systolic pressure should also be stressed, …." Our work shows that when using the Edinburgh University Secondary Insult Grades (EUSIG) definitions, which require monitoring of both systolic and mean arterial pressures, that most hypotensive events are in fact triggered by a breach of the mean arterial level of 70 mmHg. We suggest that close monitoring of mean arterial pressure would enable clinical teams to avoid more potentially damaging hypotensive events.
An analysis of 100 patients from the Brain-IT database was performed. Using the EUSIG definitions, 2,081 events can be obtained by analyzing the systolic and mean blood pressures on a minute by minute basis. A software program was written to identify and classify the trigger pattern for each event. A categorical analysis of these triggering patterns has been carried out.
Our analysis shows that most events are triggered by a drop in mean arterial pressure. In fact a large number of events (91%) occur where the mean arterial pressure is below the threshold limits whereas the systolic pressure does not cross the 90 mmHg limit at all.
We suggest that more emphasis should be placed on closely monitoring mean arterial pressure as well as systolic pressure when trying to guard against hypotensive problems in traumatically brain injured patients. In future work we will study the underlying physiological mechanisms and attempt to further classify concomitant conditions that may be contributing to the onset of a hypotensive event.
[show abstract][hide abstract] ABSTRACT: There are many serious and acute physiological conditions about which we have incomplete medical knowledge that can support optimal healthcare intervention. To develop effective treatments a wealth of clinical data is required for collection, analysis and feedback. Such data often does exist but is typically held in a variety of different formats and locations. This paper describes the EU FP7-funded Avert-IT project (www.avert-it.org), which has developed an integrated, real-time physiological data grid infrastructure (Hypo Net) to address the specific issue of prediction of hypotensive events in the brain trauma domain and is currently being used as part of a large multi-centre clinical trial. The implementation and application of the Hypo Net system is described here.
Sixth International Conference on e-Science, e-Science 2010, 7-10 December 2010, Brisbane, QLD, Australia; 01/2010
[show abstract][hide abstract] ABSTRACT: The ability to predict adverse hypotensive events, where a patient's arterial blood pressure drops to abnormally low (and dangerous) levels, would be of major benefit to the fields of primary and secondary health care, and especially to the traumatic brain injury domain. A wealth of data exist in health care systems providing information on the major health indicators of patients in hospitals (blood pressure, temperature, heart rate, etc.). It is believed that if enough of these data could be drawn together and analysed in a systematic way, then a system could be built that will trigger an alarm predicting the onset of a hypotensive event over a useful time scale, e.g. half an hour in advance. In such circumstances, avoidance measures can be taken to prevent such events arising. This is the basis for the Avert-IT project (http://www.avert-it.org), a collaborative EU-funded project involving the construction of a hypotension alarm system exploiting Bayesian neural networks using techniques of data federation to bring together the relevant information for study and system development.
Philosophical Transactions of The Royal Society A Mathematical Physical and Engineering Sciences 08/2009; 367(1898):2679-90. · 2.89 Impact Factor
[show abstract][hide abstract] ABSTRACT: The aim of this study was to evaluate the robustness and zero-drift of an intracranial pressure sensor, Neurovent-P (Raumedic AG, Münchberg, Germany), when used in the clinical environment.
A prospective multicenter trial, conforming to the International Organization for Standardization 14155 Standard, was conducted in 6 European BrainIT centers between July 2005 and December 2006. Ninety-nine catheters were used. The study was observational, followed by a centralized sensor bench test after catheter removal.
The mean recorded value before probe insertion was 0.17 +/- 1.1 mm Hg. Readings outside the range +/-1 mm Hg were recorded in only 3 centers on a total of 15 catheters. Complications were minimal and mainly related to the insertion bolt. The mean recorded pressure value at removal was 0.8 +/- 2.2 mm Hg. No relationship was identified between postremoval reading and length of monitoring. The postremoval bench test indicated the probability of a system failure, defined as a drift of more than 3 mm Hg, at a range between 12 and 17%.
The Neurovent-P catheter performed well in clinical use in terms of robustness. The majority of technical complications were associated with the bolt fixation technology. Adverse events were rare and clinically nonsignificant. Despite the earlier reported excellent bench test zero-drift rates, under the more demanding clinical conditions, zero-drift rate remains a concern with catheter tip strain gauge technology. This performance is similar, and not superior, to other intracranial pressure devices.
[show abstract][hide abstract] ABSTRACT: The BrainIT group works collaboratively on developing standards for collection and analyses of data from brain injured patients towards providing a more efficient infrastructure for assessing new health technology. Materials and methods Over a 2 year period, core dataset data (grouped by nine categories) were collected from 200 head-injured patients by local nursing staff. Data were uploaded by the BrainIT web and random samples of received data were selected automatically by computer for validation by data validation (DV) research nurse staff against gold standard sources held in the local centre. Validated data was compared with original data sent and percentage error rates calculated by data category. Findings Comparisons, 19,461, were made in proportion to the size of the data received with the largest number checked in laboratory data (5,667) and the least in the surgery data (567). Error rates were generally less than or equal to 6%, the exception being the surgery data class where an unacceptably high error rate of 34% was found.
Conclusions The BrainIT core dataset (with the exception of the surgery classification) is feasible and accurate to collect. The surgery classification needs to be revised.
[show abstract][hide abstract] ABSTRACT: The aim of this study was to determine the relationship between apolipoprotein E (APO E) alleles, the amount of cerebral perfusion pressure (CPP) insult and outcome in children after brain trauma.
In a prospective two-centre case-control study, the APO E genotypes of 65 critically ill children admitted after brain trauma were correlated with age-related CPP insult quantification, conscious state at the time of discharge from intensive care and global outcome at 6 months post-injury. One hundred sixty healthy age- and sex-matched children were genotyped as controls.
The CPP insult level among the e4 carriers with poor outcome was significantly less than the non-e4 carriers (p=0.03). Homozygotic e3 patients with good recovery did so despite having suffered nearly 26 times more CPP insult than those who were not e3 homzygous (p=0.02).
Different APO E alleles may potentially affect cerebral ischaemic tolerance differently in children after brain trauma.
Child s Nervous System 11/2008; 25(1):47-54. · 1.24 Impact Factor
[show abstract][hide abstract] ABSTRACT: Secondary pathophysiological CPP insult is related to outcome after head injury, and improved management would be expected to reduce secondary brain insult. Paediatric head injury management guidelines have been published in recent years, by SIGN (2000), RCPCH (2001), NICE (June 2003), and jointly by Critical/Intensive Care Societies (C/ICS July 2003). We investigated whether outcome of children's head injury (and total burden of secondary CPP insult) has changed (1) annually; (2) before and after the introduction of any HI guidelines, and (3) following other service changes.
Seventy-six children (aged 1-14 years with severe HI) were admitted to the Edinburgh Regional Head Injury Service between 1989 and 2006, and dichotomised at various time points and compared in terms of: demographic factors, intracranial pressure (ICP), cerebral perfusion pressure (CPP) insults [e.g. age-banded pressure-time index (PTI)], and Glasgow Outcome Scale (GOS) score (assessed at 6 months post injury).
When dichotomised around the SIGN guidelines, there were no statistically significant differences between the two group's demography or in primary brain injury, but the outcomes were different (p = 0.03), with 6 vs 4 GOS1 (died), 2 vs 4 GOS3 (severely disabled), 5 vs 16 GOS4 (moderately disabled) and 23 vs 14 GOS5 (good recovery), when comparing before and after year 2000. GOS4 was significantly different (chi-square = 7.99, p < 0.007). There was a (non-significant) trend for the later years to have longer insult durations of ICP, hypertension, CPP, hypoxia, pyrexia, tachycardia and bradycardia, greater PTI for both CPP and ICP, and more CPP insults (p = 0.003). There was, however, significantly less CPP insult (p = 0.030) after the introduction of the more management-oriented C/ICS guidelines.
The most recent paediatric HI guidelines appear to have reduced the burden of secondary insult, but more time is required to determine if this will be reflected in improved outcomes.
[show abstract][hide abstract] ABSTRACT: Useful information (both clinical and pathophysiological) which may be extracted from intracranial pressure (ICP) recordings include: (1) the mean level of ICP (and CPP), (2) cerebrovascular autoregulation status, (3) the intracranial pulse pressure (the pulse wave index, ICPpp/ICPm) or the pressure-volume compensatory reserve index (RAP) and (4) the presence of any abnormal ICP waveform. This paper describes a slow frequency ICP waveform in children with TBI and postulates the pathophysiological basis and whether it contains clinically useful detail.
Children admitted to the Regional Head Injury Service in Edinburgh with TBI have continuously monitored ICP, MAP, CPP, and other physiological data (stored at a 1-min resolution). Slow frequency waveforms were noted, prompting a review of the stored monitoring from all cases over a 10 year period.
Episodic slow pressure waves were detected in 11 of 122 severely head-injured (HI) children. The waveforms were detected in children of all ages (1.6-15 years) in the ICP signal, which were in phase with similar fluctuations in the MAP, CPP, and HR signals. Their mean periodicity was 1 per 7 min (range 1 per 5-10 min), with a mean ICP pulse wave amplitude of 5.45 mmHg (range 4-7.5), and mean MAP pulse wave amplitude (pulse pressure) of 10.4 mmHg (range 4-15 mmHg). The duration was variable (range approx 2 h to 4.5 days). They were detected in the preterminal phase after serious HI, as well as in those children who made an independent recovery (GOS 4/5). The waves were not related to the mean levels of ICP, CPP, MAP, temperature or the state of cerebrovascular autoregulation.
We postulate that these previously unreported slow waveforms may reflect the very low frequency (VLF) and ultra low frequency (ULF; < or = 1 per 5 min) components of heart rate and arterial blood pressure variability.
[show abstract][hide abstract] ABSTRACT: The BrainIT project was conceived in 1997 and has grown into an international collaboration with the purpose of gathering high time resolution data from head injured patients utilising standardised methodologies.
From 1998, 22 participating neuroscience centres collected three main types of information: demographic, physiological data and clinical treatment information. A data collection solution was provided for each centre dependent on their existing facilities and data were collected for the duration of monitoring as defined by the routine care in each centre. On completion of ICP monitoring all personal information was removed and then transferred to Glasgow via the internet where it was converted into a standard format and entered into a central database. Outcome was measured using the extended Glasgow Outcome Score using an interview questionnaire.
Data has been obtained from a total of 349 patients (277 male and 72 female) The age of these patients ranged from 1 to 87 years (median 31); 145 had been involved in a traffic accident and 32 were pedestrians; 78 had suffered a fall; 24 were assaulted and the remaining 70 of other causes. A large amount of physiological data was collected (e.g. BP 2,531 days, ICP 2,212 days in total). This dataset has provided the opportunity to perform unique analysis and these include the statistical features of blood pressure, diurnal variations in ICP, optimal sampling rate determination and a comparison of summary measures of secondary insults.
This challenging collaboration has brought together a large number of centres and developed a successful clinical research network focussed on improving the treatment of head injured patients. It has successfully collected a vast quantity of high quality data that provides a rich source for analysis and hypothesis testing.
[show abstract][hide abstract] ABSTRACT: The BrainIT group works collaboratively on developing standards for collection and analyses of data from brain injured patients towards providing a more efficient infrastructure for assessing new health technology.
Over a 2 year period, core dataset data (grouped by nine categories) were collected from 200 head-injured patients by local nursing staff. Data were uploaded by the BrainIT web and random samples of received data were selected automatically by computer for validation by data validation (DV) research nurse staff against gold standard sources held in the local centre. Validated data was compared with original data sent and percentage error rates calculated by data category.
Comparisons, 19,461, were made in proportion to the size of the data received with the largest number checked in laboratory data (5,667) and the least in the surgery data (567). Error rates were generally less than or equal to 6%, the exception being the surgery data class where an unacceptably high error rate of 34% was found.
The BrainIT core dataset (with the exception of the surgery classification) is feasible and accurate to collect. The surgery classification needs to be revised.
[show abstract][hide abstract] ABSTRACT: There is considerable interest in surgical decompression as a management strategy (RescueICP) for intractable intracranial hypertension. After such an operation measurements of intracranial pressure (ICP) and thus cerebral perfusion pressure (CPP) become less meaningful. Measurements of the biomechanical properties of the brain may be one measure capable of detecting changing status of such patients. However these properties of the brain are neither documented or well understood. We have developed an indentation probe capable of making measurements of human brain stiffness.
The device consists of an indenting tip of depth 2 mm and diameter 12 mm surrounded by an annular body of 20 mm diameter. Measurements are made by two load cells, connected through interface electronics to a laptop computer.
Laboratory measurements show the probe to provide accurate and repeatable measurements over a range of zero to 10N. Inter-operator variability from six healthcare professionals had a coefficient of variance of 8.75%. Measurements obtained during surgery from a patient undergoing tumour resection were towards the lower end of the device's measurable range.
We have determined that this indentation device has a linear response and that the inter- and intra-operator variability is low. Although the device is still in an early stage of development, preliminary results during intracranial surgery demonstrate that this device is capable of measuring in-vivo tissue stiffness. Further work is required to derive a quantitative "stiffness index" from the two load curves. In addition a standard operation method is required so that consistent and repeatable measurements are made. The device may be of value in assessing patients after decompressive craniectomy.
[show abstract][hide abstract] ABSTRACT: To determine the statistical characteristics of blood pressure (BP) readings from a large number of head-injured patients.
The BrainIT group has collected high time-resolution physiological and clinical data from head-injured patients who require intracranial pressure (ICP) monitoring. The statistical features of this dataset of BP measurements with time resolution of 1 min from 200 patients is examined. The distributions of BP measurements and their relationship with simultaneous ICP measurements are described.
The distributions of mean, systolic and diastolic readings are close to normal with modest skewing towards higher values. There is a trend towards an increase in blood pressure with advancing age, but this is not significant. Simultaneous blood pressure and ICP values suggest a triphasic relationship with a BP rising at 0.28 mm Hg/mm Hg of ICP, for ICP up to 32 mm Hg, and 0.9 mm Hg/mm Hg of ICP for ICP from 33 to 55 mm Hg, and falling sharply with rising ICP for ICP >55 mm Hg.
Patients with head injury appear to have a near normal distribution of blood pressure readings that are skewed towards higher values. The relationship between BP and ICP may be triphasic.
Journal of neurology, neurosurgery, and psychiatry 04/2007; 78(4):399-402. · 4.87 Impact Factor
[show abstract][hide abstract] ABSTRACT: The clinical estimation of pupil size and reactivity is central to the neurological assessment of patients, particularly those with or at risk of neurological damage. Health care professionals who examine pupils have differing levels of skill and training, yet their recordings are passed along the patient care pathway and can influence care decisions. The aim of this study was to determine if any statistical differences existed in the estimation of pupil size by different groups of health care professionals.
A total of 102 health care professionals working in the critical care environment were asked to estimate and record the pupil size of a series of 12 artificial eyes with varying pupil diameter and iris colour. All estimations were performed indoors under ambient lighting conditions.
Our results established a statistically significant difference between staff groups in the estimation of pupil size.
The demonstrated variability in pupil size estimation may not be clinically significant. However, it remains desirable to have consistency of measurement throughout the patient care pathway.
Emergency Medicine Journal 07/2006; 23(6):440-1. · 1.65 Impact Factor
[show abstract][hide abstract] ABSTRACT: The principal strategy for managing head injury is to reduce the frequency and severity of secondary brain insults from intracranial pressure (ICP) and cerebral perfusion pressure (CPP), and hence improve outcome. Precise critical threshold levels have not been determined in head injured children.
To create a novel pressure-time index (PTI) measuring both duration and amplitude of insult, and then employ it to determine critical insult thresholds of ICP and CPP in children.
Prospective, observational, physiologically based study from Edinburgh and Newcastle, using patient monitored blood pressure, ICP, and CPP time series data. The PTI for ICP and CPP for 81 children, using theoretical values derived from physiological norms, was varied systematically to derive critical insult thresholds which delineate Glasgow outcome scale categories.
The PTI for CPP had a very high predictive value for outcome (receiver operating characteristic analyses: area under curve = 0.957 and 0.890 for mortality and favourable outcome, respectively) and was more predictive than for ICP. Initial physiological values most accurately predicted favourable outcome. The CPP critical threshold values determined for children aged 2-6, 7-10, and 11-15 years were 48, 54, and 58 mm Hg. respectively.
The PTI is the first substantive paediatric index of total ICP and CPP following head injury. The insult thresholds generated are identical to age related physiological values. Management guidelines for paediatric head injuries should take account of these CPP thresholds to titrate appropriate pressor therapy.
[show abstract][hide abstract] ABSTRACT: Studies of therapeutic interventions and management strategies on head injured patients are difficult to undertake. BrainIT provides validated data for analysis available to centers that contribute data to allow post-hoc analysis and hypothesis testing.
Both physiological and intensive care management data are collected. Patient identification is eliminated prior to transfer of data to a central database in Glasgow. Requests for missing/ ambiguous data are sent back to the local center. Country coordinating centers provide advice, training, and assistance to centers and manage the data validation process.
Currently 30 centers participate in the group. Data collection started in January 2004 and 242 patients have been recruited. Data validation tools were developed to ensure data accuracy and all analysis must be undertaken on validated data.
BrainIT is an open, collaborative network that has been established with primary objectives of i) creating a core data set of information, ii) standardizing the collection methodology, iii) providing data collection tools, iv) creating and populating a data base for future analysis, and v) establishing data validation methodologies. Improved standards for multi-center data collection should permit the more accurate analysis of monitoring and management studies in head injured patients.
[show abstract][hide abstract] ABSTRACT: A non-invasive method of assessing intracranial pressure (ICP) would be of benefit to patients with abnormal cerebral pathology that could give rise to changes in ICP. In particular, it would assist the regular monitoring of hydrocephalus patients. This study evaluated a technique using tympanic membrane displacement (TMD) measurements, which has been reported to provide a reliable, non-invasive measure of ICP. A group of 135 hydrocephalus patients was studied, as well as 13 patients with benign intracranial hypertension and a control group of 77 volunteers. TMD measurements were carried out using the Marchbanks measurement system analyser and compared between the groups. In 36 patients, invasive measurements of ICP carried out at the same time were compared with the TMD values. A highly significant relationship was found between TMD and ICP but intersubject variability was high and the predictive value of the technique low. Taking the normal range of ICP to be 10-15 mmHg, the predictive limits of the regression are an order of magnitude wider than this and therefore Vm cannot be used as a surrogate for ICP. In conclusion, TMD measurements do not provide a reliable non-invasive measure of ICP in patients with shunted hydrocephalus.
[show abstract][hide abstract] ABSTRACT: An ultrasonic method was used to non-invasively measure intracranial blood volume (IBV) pulse waveforms. This technology has previously shown a strong association between invasively recorded ICP pulse waves and non-invasively recorded IBV pulse waves. The objective of the present study was to investigate the diagnostic value of non-invasively measured IBV pulse waves in the cases of different pathologies. A total of 75 patients were examined and these included cases of acute, chronic and stabilized hydrocephalus, spinal cord injury and terminal blood flow. These were compared to a control group of 53 healthy volunteers. The object of comparison was normalized and averaged IBV pulse waves. Pathological IBV pulse waveforms were compared with IBV pulse waveforms of the normal group using sub-wave values, the area under waveform curve and the Euclidean distance calculation. The non-invasively measured IBV pulse waveform is not significantly dependent on acoustic path, gender or age. A detectable change in IBV pulse waveform shape was observed in situations when disturbance in intracranial hydrodynamics was present, e.g. during hypoventilation tests, in cases of terminal blood flow and hydrocephaly, depicting the level of hydrocephalus activity and the patient's compensatory capabilities as well as the effect of treatment.
[show abstract][hide abstract] ABSTRACT: BackgroundStudies of therapeutic interventions and management strategies on head injured patients are difficult to undertake. BrainIT
provides validated data for analysis available to centers that contribute data to allow post-hoc analysis and hypothesis testing.
MethodsBoth physiological and intensive care management data are collected. Patient identification is eliminated prior to transfer
of data to a central database in Glasgow. Requests for missing/ambiguous data are sent back to the local center. Country coordinating
centers provide advice, training, and assistance to centers and manage the data validation process.
ResultsCurrently 30 centers participate in the group. Data collection started in January 2004 and 242 patients have been recruited.
Data validation tools were developed to ensure data accuracy and all analysis must be undertaken on validated data.
ConclusionBrainIT is an open, collaborative network that has been established with primary objectives of i) creating a core data set
of information, ii) standardizing the collection methodology, iii) providing data collection tools, iv) creating and populating
a data base for future analysis, and v) establishing data validation methodologies. Improved standards for multi-center data
collection should permit the more accurate analysis of monitoring and management studies in head injured patients.