The effects of cerebral pressure autoregulation status and CPP levels on cerebral metabolism in pediatric traumatic brain injury.

BACKGROUND: Cerebral perfusion pressure (CPP) management in the developing child with traumatic brain injury (TBI) is challenging. The pressure reactivity index (PRx) may serve as marker of cerebral pressure autoregulation (CPA) and optimal CPP (CPPopt) may be assessed by identifying the CPP level with best (lowest) PRx. To evaluate the potential of CPPopt guided management in children with severe TBI, cerebral microdialysis (CMD) monitoring levels of lactate and the lactate/pyruvate ratio (LPR) (indicators of ischemia) were related to actual CPP levels, autoregulatory state (PRx) and deviations from CPPopt (ΔCPPopt). METHODS: Retrospective study of 21 children ≤ 17 years with severe TBI who had both ICP and CMD monitoring were included. CPP, PRx, CPPopt and ΔCPPopt where calculated, dichotomized and compared with CMD lactate and lactate-pyruvate ratio. RESULTS: Median age was 16 years (range 8-17) and median Glasgow coma scale motor score 5 (range 2-5). Both lactate (p = 0.010) and LPR (p = < 0.001) were higher when CPP ≥ 70 mmHg than when CPP < 70. When PRx ≥ 0.1 both lactate and LPR were higher than when PRx < 0.1 (p = < 0.001). LPR was lower (p = 0.012) when CPPopt ≥ 70 mmHg than when CPPopt < 70, but there were no differences in lactate levels. When ΔCPPopt > 10 both lactate (p = 0.026) and LPR (p = 0.002) were higher than when ΔCPPopt < -10. CONCLUSIONS: Increased levels of CMD lactate and LPR in children with severe TBI appears to be related to disturbed CPA (PRx). Increased lactate and LPR also seems to be associated with actual CPP levels ≥ 70 mmHg. However, higher lactate and LPR values were also seen when actual CPP was above CPPopt. Higher CPP appears harmful when CPP is above the upper limit of pressure autoregulation. The findings indicate that CPPopt guided CPP management may have potential in pediatric TBI.

Capturing of intracranial pressure treatment during neurointensive care in patients with acute brain injury using a novel tablet-based method.

Critical care is complex and stressful. It is difficult to register in real time data not recorded by automatic systems. Time-specific knowledge of manual measures is important for understanding pathophysiology and for analyzing treatment and quality of care. Therefore, a novel iPad-based method for registration of manual measures was developed, which many can build themselves. Using a configuration for intracranial pressure (ICP) management, the methodology was validated, ICP treatment captured, and the quality of ICP management evaluated. Twenty-two patients with acute brain injuries were studied. The iPad-system was totally used for 2538 h. Thirteen-hundred-five manual measures were entered. Thirty-nine episodes of predefined ICP insults were identified. During 16/39 episodes, ICP treatments were registered. For 4/39 episodes treatments were registered within 90 s before or after the episode. For 3/39 episodes it was registered that treatment was intentionally refrained. In 15/16 episodes without registered treatment, the insult was mild or reasonable explanations were found when medical records and the Patient data management system were reviewed. In one situation without particular circumstances, morphine and clonidine were given to decrease ICP but not registered. No episodes of downtime or loss of data occurred. The developed methodology appears to be stable and robust as well as feasible and user-friendly. It was possible to capture the treatment of ICP insults with high temporal resolution, and to evaluate the quality of ICP management. An own developed novel tablet-based system like our system may be a promising potential tool useful in various future intensive care applications.

Forewarning of hypotensive events using a Bayesian artificial neural network in neurocritical care.

Traumatically brain injured (TBI) patients are at risk from secondary insults. Arterial hypotension, critically low blood pressure, is one of the most dangerous secondary insults and is related to poor outcome in patients. The overall aim of this study was to get proof of the concept that advanced statistical techniques (machine learning) are methods that are able to provide early warning of impending hypotensive events before they occur during neuro-critical care. A Bayesian artificial neural network (BANN) model predicting episodes of hypotension was developed using data from 104 patients selected from the BrainIT multi-center database. Arterial hypotension events were recorded and defined using the Edinburgh University Secondary Insult Grades (EUSIG) physiological adverse event scoring system. The BANN was trained on a random selection of 50% of the available patients (n = 52) and validated on the remaining cohort. A multi-center prospective pilot study (Phase 1, n = 30) was then conducted with the system running live in the clinical environment, followed by a second validation pilot study (Phase 2, n = 49). From these prospectively collected data, a final evaluation study was done on 69 of these patients with 10 patients excluded from the Phase 2 study because of insufficient or invalid data. Each data collection phase was a prospective non-interventional observational study conducted in a live clinical setting to test the data collection systems and the model performance. No prediction information was available to the clinical teams during a patient's stay in the ICU. The final cohort (n = 69), using a decision threshold of 0.4, and including false positive checks, gave a sensitivity of 39.3% (95% CI 32.9-46.1) and a specificity of 91.5% (95% CI 89.0-93.7). Using a decision threshold of 0.3, and false positive correction, gave a sensitivity of 46.6% (95% CI 40.1-53.2) and specificity of 85.6% (95% CI 82.3-88.8). With a decision threshold of 0.3, > 15 min warning of patient instability can be achieved. We have shown, using advanced machine learning techniques running in a live neuro-critical care environment, that it would be possible to give neurointensive teams early warning of potential hypotensive events before they emerge, allowing closer monitoring and earlier clinical assessment in an attempt to prevent the onset of hypotension. The multi-centre clinical infrastructure developed to support the clinical studies provides a solid base for further collaborative research on data quality, false positive correction and the display of early warning data in a clinical setting.

Optimal Cerebral Perfusion Pressure in Centers With Different Treatment Protocols.

OBJECTIVES: The three centers in this study have different policies regarding cerebral perfusion pressure targets and use of vasopressors in traumatic brain injury patients. The aim was to determine if the different policies affected the estimation of cerebral perfusion pressure which optimizes the strength of cerebral autoregulation, termed "optimal cerebral perfusion pressure." DESIGN: Retrospective analysis of prospectively collected data. SETTING: Three neurocritical care units at university hospitals in Cambridge, United Kingdom, Groningen, the Netherlands, and Uppsala, Sweden. PATIENTS: A total of 104 traumatic brain injury patients were included: 35 each from Cambridge and Groningen, and 34 from Uppsala. INTERVENTIONS: None. MEASUREMENTS AND MAIN RESULTS: In Groningen, the cerebral perfusion pressure target was greater than or equal to 50 and less than 70 mm Hg, in Uppsala greater than or equal to 60, and in Cambridge greater than or equal to 60 or preferably greater than or equal to 70. Despite protocol differences, median cerebral perfusion pressure for each center was above 70 mm Hg. Optimal cerebral perfusion pressure was calculated as previously published and implemented in the Intensive Care Monitoring+ software by the Cambridge group, now replicated in the Odin software in Uppsala. Periods with cerebral perfusion pressure above and below optimal cerebral perfusion pressure were analyzed, as were absolute difference between cerebral perfusion pressure and optimal cerebral perfusion pressure and percentage of monitoring time with a valid optimal cerebral perfusion pressure. Uppsala had the highest cerebral perfusion pressure/optimal cerebral perfusion pressure difference. Uppsala patients were older than the other centers, and age is positively correlated with cerebral perfusion pressure/optimal cerebral perfusion pressure difference. Optimal cerebral perfusion pressure was significantly lower in Groningen than in Cambridge. There were no significant differences in percentage of monitoring time with valid optimal cerebral perfusion pressure. Summary optimal cerebral perfusion pressure curves were generated for the combined patient data for each center. These summary curves could be generated for Groningen and Cambridge, but not Uppsala. The older age of the Uppsala patient cohort may explain the absence of a summary curve. CONCLUSIONS: Differences in optimal cerebral perfusion pressure calculation were found between centers due to demographics (age) and treatment (cerebral perfusion pressure targets). These factors should be considered in the design of trials to determine the efficacy of autoregulation-guided treatment.

Decompressive craniectomy in traumatic brain injury: usage and clinical outcome in a single centre.

BACKGROUND: Two randomised controlled trials (RCTs) of decompressive craniectomy (DC) in traumatic brain injury (TBI) have shown poor outcome, but there are considerations of how these protocols relate to real practice. The aims of this study were to evaluate usage and outcome of DC and thiopental in a single centre. METHOD: The study included all TBI patients treated at the neurointensive care unit, Akademiska sjukhuset, Uppsala, Sweden, between 2008 and 2014. Of 609 patients aged 16 years or older, 35 treated with DC and 23 treated with thiopental only were studied in particular. Background variables, intracranial pressure (ICP) measures and global outcome were analysed. RESULTS: Of 35 DC patients, 9 were treated stepwise with thiopental before DC, 9 were treated stepwise with no thiopental before DC and 17 were treated primarily with DC. Six patients received thiopental after DC. For 23 patients, no DC was needed after thiopental. Eighty-eight percent of our DC patients would have qualified for the DECRA study and 38% for the Rescue-ICP trial. Favourable outcome was 44% in patients treated with thiopental before DC, 56% in patients treated with DC without prior thiopental, 29% in patients treated primarily with DC and 52% in patients treated with thiopental with no DC. CONCLUSIONS: The place for DC in TBI management must be evaluated better, and we believe it is important that future RCTs should have clearer and less permissive ICP criteria regarding when thiopental should be followed by DC and DC followed by thiopental.

Increased risk of critical CBF levels in SAH patients with actual CPP below calculated optimal CPP.

BACKGROUND: Cerebral pressure autoregulation can be quantified with the pressure reactivity index (PRx), based on the correlation between blood pressure and intracranial pressure. Using PRx optimal cerebral perfusion pressure (CPPopt) can be calculated, i.e., the level of CPP where autoregulation functions best. The relation between cerebral blood flow (CBF) and CPPopt has not been examined. The objective was to assess to which extent CPPopt can be calculated in SAH patients and to investigate CPPopt in relation to CBF. METHODS: Retrospective study of prospectively collected data. CBF was measured bedside with Xenon-enhanced CT (Xe-CT). The difference between actual CPP and CPPopt was calculated (CPP∆). Correlations between CPP∆ and CBF parameters were calculated with Spearman's rank order correlation coefficient (rho). Separate calculations were done using all patients (day 0-14 after onset) as well as in two subgroups (day 0-3 and day 4-14). RESULTS: Eighty-two patients with 145 Xe-CT scans were studied. Automated calculation of CPPopt was possible in adjunct to 60% of the Xe-CT scans. Actual CPP < CPPopt was associated with higher numbers of low-flow regions (CBF <10 ml/100 g/min) in both the early phase (day 0-3, n = 39, Spearman's rho = -0.38, p = 0.02) and late acute phase of the disease (day 4-14, n = 35, Spearman's rho = -0.39, p = 0.02). CPP level per se was not associated with CBF. CONCLUSIONS: Calculation of CPPopt is possible in a majority of patients with severe SAH. Actual CPP below CPPopt is associated with low CBF.

The effects of ventricular drainage on the intracranial pressure signal and the pressure reactivity index.

In subarachnoid hemorrhage (SAH) patients intracranial pressure (ICP) is usually monitored via an extraventricular drain (EVD), which can produce false readings when the drain is open. It is established that both the ICP cardiac pulse frequency and long term trends over several hours are often seriously corrupted. The aim of this study was to establish whether or not the intermediate frequency bands [respiratory, Mayer wave and very low frequency (VLF)] were also corrupted. The VLF range is of special interest because it is important in cerebral autoregulation studies. Using a pattern recognition algorithm we retrospectively identified 718 cases of EVD opening in 80 SAH patients. An analysis of differences between closed and open-drain periods showed that ICP amplitude decreased significantly in all of the three lower frequency bands when the EVD was open. A similar analysis of systemic arterial pressure signal revealed similar changes in the same frequency bands that were positively correlated with the ICP changes. Therefore we concluded that the changes in the ICP signal represented real, physiological changes and not artifact. Pressure reactivity index (PRx) values were also computed during closed and open-drain periods. We found a small but statistically significant decrease during open-drain periods. Based on analysis of the change in the PRx distribution during open drainage we concluded that this decrease also represented physiological changes rather than artifact. In summary the ICP respiratory, Mayer wave, and VLF frequency bands are not corrupted when the EVD is open, and it safe to use these for autoregulation studies.

Bedside Xenon-CT Shows Lower CBF in SAH Patients with Impaired CBF Pressure Autoregulation as Defined by Pressure Reactivity Index (PRx).

BACKGROUND: Subarachnoid hemorrhage (SAH) is a disease with a high rate of unfavorable outcome, often related to delayed cerebral ischemia (DCI), i.e., ischemic injury that develops days-weeks after onset, with a multifactorial etiology. Disturbances in cerebral pressure autoregulation, the ability to maintain a steady cerebral blood flow (CBF), despite fluctuations in systemic blood pressure, have been suggested to play a role in the development of DCI. Pressure reactivity index (PRx) is a well-established measure of cerebral pressure autoregulation that has been used to study traumatic brain injury, but not extensively in SAH. OBJECTIVE: To study the relation between PRx and CBF in SAH patients, and to examine if PRx can be used to predict DCI. METHODS: Retrospective analysis of prospectively collected data. PRx was calculated as the correlation coefficient between mean arterial blood pressure (MABP) and intracranial pressure (ICP) in a 5 min moving window. CBF was measured using bedside Xenon-CT (Xe-CT). DCI was diagnosed clinically. RESULTS: 47 poor-grade mechanically ventilated patients were studied. Patients with disturbed pressure autoregulation (high PRx values) had lower CBF, as measured by bedside Xe-CT; both in the early (day 0-3) and late (day 4-14) acute phase of the disease. PRx did not differ significantly between patients who developed DCI or not. CONCLUSION: In mechanically ventilated and sedated SAH patients, high PRx (more disturbed CBF pressure autoregulation) is associated with low CBF, both day 0-3 and day 4-14 after onset. The role of PRx as a monitoring tool in SAH patients needs further studying.

An optimal frequency range for assessing the pressure reactivity index in patients with traumatic brain injury.

The objective of this study was to identify the optimal frequency range for computing the pressure reactivity index (PRx). PRx is a clinical method for assessing cerebral pressure autoregulation based on the correlation of spontaneous variations of arterial blood pressure (ABP) and intracranial pressure (ICP). Our hypothesis was that optimizing the methodology for computing PRx in this way could produce a more stable, reliable and clinically useful index of autoregulation status. The patients studied were a series of 131 traumatic brain injury patients. Pressure reactivity indices were computed in various frequency bands during the first 4 days following injury using bandpass filtering of the input ABP and ICP signals. Patient outcome was assessed using the extended Glasgow Outcome Scale (GOSe). The optimization criterion was the strength of the correlation with GOSe of the mean index value over the first 4 days following injury. Stability of the indices was measured as the mean absolute deviation of the minute by minute index value from 30-min moving averages. The optimal index frequency range for prediction of outcome was identified as 0.018-0.067 Hz (oscillations with periods from 55 to 15 s). The index based on this frequency range correlated with GOSe with ρ=-0.46 compared to -0.41 for standard PRx, and reduced the 30-min variation by 23%.

Should the neurointensive care management of traumatic brain injury patients be individualized according to autoregulation status and injury subtype?

INTRODUCTION: The status of autoregulation is an important prognostic factor in traumatic brain injury (TBI), and is important to consider in the management of TBI patients. Pressure reactivity index (PRx) is a measure of autoregulation that has been thoroughly studied, but little is known about its variation in different subtypes of TBI. In this study, we examined the impact of PRx and cerebral perfusion pressure (CPP) on outcome in different TBI subtypes. METHODS: 107 patients were retrospectively studied. Data on PRx, CPP, and outcome were collected from our database. The first CT scan was classified according to the Marshall classification system. Patients were assigned to "diffuse" (Marshall class: diffuse-1, diffuse-2, and diffuse-3) or "focal" (Marshall class: diffuse-4, evacuated mass lesion, and non-evacuated mass lesion) groups. 2 × 2 tables were constructed calculating the proportions of favorable/unfavorable outcome at different combinations of PRx and CPP. RESULTS: Low PRx was significantly associated with favorable outcome in the combined group (p = 0.002) and the diffuse group (p = 0.04), but not in the focal group (p = 0.06). In the focal group higher CPP values were associated with worse outcome (p = 0.02). In diffuse injury patients with disturbed autoregulation (PRx >0.1), CPP >70 mmHg was associated with better outcome (p = 0.03). CONCLUSION: TBI patients with diffuse injury may differ from those with mass lesions. In the latter higher levels of CPP may be harmful, possibly due to BBB disruption. In TBI patients with diffuse injury and disturbed autoregulation higher levels of CPP may be beneficial.

Decompressive craniectomy as a second/third-tier intervention in traumatic brain injury: A multicenter observational study.

OBJECTIVES: RESCUEicp studied decompressive craniectomy (DC) applied as third-tier option in severe traumatic brain injury (TBI) patients in a randomized controlled setting and demonstrated a decrease in mortality with similar rates of favorable outcome in the DC group compared to the medical management group. In many centers, DC is being used in combination with other second/third-tier therapies. The aim of the present study is to investigate outcomes from DC in a prospective non-RCT context. METHODS: This is a prospective observational study of 2 patient cohorts: one from the University Hospitals Leuven (2008-2016) and one from the Brain-IT study, a European multicenter database (2003-2005). In thirty-seven patients with refractory elevated intracranial pressure who underwent DC as a second/third-tier intervention, patient, injury and management variables including physiological monitoring data and administration of thiopental were analysed, as well as Extended Glasgow Outcome score (GOSE) at 6 months. RESULTS: In the current cohorts, patients were older than in the surgical RESCUEicp cohort (mean 39.6 vs. 32.3; p < 0.001), had higher Glasgow Motor Score on admission (GMS < 3 in 24.3% vs. 53.0%; p = 0.003) and 37.8% received thiopental (vs. 9.4%; p < 0.001). Other variables were not significantly different. GOSE distribution was: death 24.3%; vegetative 2.7%; lower severe disability 10.8%; upper severe disability 13.5%; lower moderate disability 5.4%; upper moderate disability 2.7%, lower good recovery 35.1%; and upper good recovery 5.4%. The outcome was unfavorable in 51.4% and favorable in 48.6%, as opposed to 72.6% and 27.4% respectively in RESCUEicp (p = 0.02). CONCLUSION: Outcomes in DC patients from two prospective cohorts reflecting everyday practice were better than in RESCUEicp surgical patients. Mortality was similar, but fewer patients remained vegetative or severely disabled and more patients had a good recovery. Although patients were older and injury severity was lower, a potential partial explanation may be in the pragmatic use of DC in combination with other second/third-tier therapies in real-life cohorts. The findings underscore that DC maintains an important role in managing severe TBI.

Early warning of EUSIG-defined hypotensive events using a Bayesian Artificial Neural Network.

BACKGROUND: 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. MATERIALS AND METHODS: 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. KEY RESULTS: 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. CONCLUSION: We have shown that using advanced statistical modeling techniques can provide clinical teams with useful information that will assist clinical care.

Trigger characteristics of EUSIG-defined hypotensive events.

BACKGROUND: 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. MATERIALS AND METHODS: 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. KEY RESULTS: 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. CONCLUSION: 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.

Neurointensive care is justified in elderly patients with severe subarachnoid hemorrhage--an outcome and secondary insults study.

PURPOSE: The aim was to study the outcome and the occurrence of secondary brain insults in elderly patients with severe subarachnoid hemorrhage (SAH) in comparison to younger patients. METHODS: Ninety-nine patients with severe SAH requiring a ventriculostomy and management at the neurointensive care unit with at least 120 h of multimodality monitoring data during the first 240 h following SAH were included. Data were continuously recorded for intracranial pressure (ICP), cerebral perfusion pressure, blood pressure, oxygen saturation, and temperature. Secondary insult levels were defined and quantified as percent of good monitoring time at insult level. Outcome according to the Glasgow Outcome Scale was evaluated at 6 months after the SAH. Age-dependent differences in occurrence of secondary insults and clinical characteristics were analyzed with multiple regression analysis. RESULTS: Good recovery or moderate disability was achieved in 24.1% of the elderly and in 42.9% of the younger patients. The frequency of severe disability was 41.4% in the elderly and 37.1% in the younger patients. The occurrence of ICP insults was lower and the occurrence of hypertensive, hypotensive, and hypoxemic insults were higher in the elderly patients. CONCLUSIONS: An independent outcome was achieved in a substantial proportion of the elderly with severe SAH, and the proportion of severe disability was not greater than among the younger patients, which justifies neurointensive care also in elderly patients. The occurrence of secondary insults was age dependent. Future studies of multimodality monitoring may provide age-specific secondary insult levels necessary for a tailored neurointensive care specific for elderly patients with severe SAH.

The brain monitoring with Information Technology (BrainIT) collaborative network: EC feasibility study results and future direction.

BACKGROUND: The BrainIT group works collaboratively on developing standards for collection and analyses of data from brain-injured patients and to facilitate a more efficient infrastructure for assessing new health care technology with the primary objective of improving patient care. European Community (EC) funding supported meetings over a year to discuss and define a core dataset to be collected from patients with traumatic brain injury using IT-based methods. We now present the results of a subsequent EC-funded study with the aim of testing the feasibility of collecting this core dataset across a number of European sites and discuss the future direction of this research network. METHODS: Over a 3-year period, data collection client- and web-server-based tools were developed and core data (grouped into nine categories) were collected from 200 head-injured patients by local nursing staff in 22 European neuro-intensive care centres. Data were uploaded through the BrainIT website and random samples of received data were selected automatically by computer for validation by data validation staff against primary sources held in each local centre. Validated data were compared with originally transmitted data and percentage error rates calculated by data category. Feasibility was assessed in terms of the proportion of missing data, accuracy of data collected and limitations reported by users of the IT methods. FINDINGS: Thirteen percent of data files required cleaning. Thirty "one-off" demographic and clinical data elements had significant amounts of missing data (>15%). Validation staff conducted 19,461 comparisons between uploaded database data with local data sources and error rates were commonly less than or equal to 6%, the exception being the surgery data class where an unacceptably high error rate of 34% was found. Nearly 10,000 therapies were successfully recorded with start-times but approximately a third had inaccurate or missing "end-times" which limits the analysis of duration of therapy. Over 40,000 events and procedures were recorded but events with long durations (such as transfers) were more likely to have end-times missed. CONCLUSIONS: The BrainIT core dataset is a rich dataset for hypothesis generation and post hoc analyses, provided that studies avoid known limitations in the dataset. Limitations in the current IT-based data collection tools have been identified and have been addressed. In order for multi-centre data collection projects to be viable, the resource intensive validation procedures will require a more automated process and this may include direct electronic access to hospital-based clinical data sources for both validation purposes and for minimising the duplication of data entry. This type of infrastructure may foster and facilitate the remote monitoring of patient management and protocol adherence in future trials of patient management and monitoring.

Temperature disturbances in traumatic brain injury: relationship to secondary insults, barbiturate treatment and outcome.

OBJECTIVES: To describe the occurrence of spontaneous hyper- and hypothermia in patients with traumatic brain injury using a computerized data collecting system, to show how temperature correlates with other secondary insults, to describe how temperature affects outcome and to show how barbiturate treatment influences those analyses. METHODS: Patients with > or = 54 hours of valid monitoring within the first 120 hours after trauma (one value/min) for temperature, intracranial pressure, cerebral perfusion pressure, systolic blood pressure, mean blood pressure and heart rate were included. Correlation analyses were performed between temperature and other secondary insult variables. The non-linear relationship between temperature and outcome (measured by Glasgow outcome scale 6 months post-trauma) was illustrated using a neural network. RESULTS: Of the 53 patients, 44 experienced hyperthermia (>38 degrees C) and 29 experienced hypothermia (<36 degrees C). Hyperthermia correlated with occurrence of high blood pressure and high CPP. In individuals, hyperthermia also correlated with ICP and tachycardia. There was a trend towards better outcome for patients with normal temperature than those with hyper- or hypothermia (favorable outcome 64% versus 29 and 33% respectively). When patients treated with barbiturates were excluded, 60% showed favorable outcome in the hypothermia group as well. Barbiturate treatment also confounded analyses regarding temperature and other secondary insults. DISCUSSION: Patients with hyperthermia, hypertension, high CPP and tachycardia may suffer from a hyperdynamic state. This may worsen outcome and hence clinical awareness is important. Barbiturate treatment confounds several analyses which have not been shown before. We recommend those patients to be analysed separately in future studies.

The brain monitoring with Information Technology (BrainIT) collaborative network: data validation results.

BACKGROUND: 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.

BrainIT collaborative network: analyses from a high time-resolution dataset of head injured patients.

BACKGROUND: 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. MATERIALS AND METHODS: 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. FINDINGS: 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. CONCLUSIONS: 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.

Hemodynamic Disturbances in the Early Phase After Subarachnoid Hemorrhage: Regional Cerebral Blood Flow Studied by Bedside Xenon-enhanced CT.

BACKGROUND: The mechanisms leading to neurological deterioration and the devastating course of delayed cerebral ischemia (DCI) after subarachnoid hemorrhage (SAH) are still not well understood. Bedside xenon-enhanced computerized tomography (XeCT) enables measurements of regional cerebral blood flow (rCBF) during neurosurgical intensive care. In the present study, CBF characteristics in the early phase after severe SAH were explored and related to clinical characteristics and early clinical course outcome. MATERIALS AND METHODS: Patients diagnosed with SAH and requiring mechanical ventilation were prospectively enrolled in the study. Bedside XeCT was performed within day 0 to 3. RESULTS: Data from 64 patients were obtained. Median global CBF was 34.9 mL/100 g/min (interquartile range [IQR], 26.7 to 41.6). There was a difference in CBF related to age with higher global CBF in the younger patients (30 to 49 y). CBF was also related to the severity of SAH with lower CBF in Fisher grade 4 compared with grade 3. rCBF disturbances and hypoperfusion were common; in 43 of the 64 patients rCBF<20 mL/100 g/min was detected in more than 10% of the region-of-interest (ROI) area and in 17 patients such low-flow area exceeded 30%. rCBF was not related to the localization of the aneurysm; there was no difference in rCBF of ipsilateral compared with contralateral vascular territories. In patients who initially were in Hunt & Hess grade I to III, median global CBF day 0 to 3 was significantly lower for patients who were in poor neurological state at discharge compared with patients in good neurological state, 25.5 mL/100 g/min (IQR, 21.3 to 28.3) versus 37.8 mL/100 g/min (IQR, 30.5 to 47.6). CONCLUSIONS: CBF disturbances are common in the early phase after SAH. In many patients, CBF was heterogenic and substantial areas with low rCBF were detected. Age and CT Fisher grade were factors influencing global cortical CBF. Bedside XeCT may be a tool to identify patients at risk of deteriorating so they can receive intensified management, but this needs further exploration.

Intracranial pressure elevations in diffuse axonal injury: association with nonhemorrhagic MR lesions in central mesencephalic structures.

OBJECTIVE: Increased intracranial pressure (ICP) in patients with severe traumatic brain injury (TBI) with diffuse axonal injury (DAI) is not well defined. This study investigated the occurrence of increased ICP and whether clinical factors and lesion localization on MRI were associated with increased ICP in patients with DAI. METHODS: Fifty-two patients with severe TBI (median age 24 years, range 9-61 years), who had undergone ICP monitoring and had DAI on MRI, as determined using T2*-weighted gradient echo, susceptibility-weighted imaging, and diffusion-weighted imaging (DWI) sequences, were enrolled. The proportion of good monitoring time (GMT) with ICP > 20 mm Hg during the first 120 hours postinjury was calculated and associations with clinical and MRI-related factors were evaluated using linear regression. RESULTS: All patients had episodes of ICP > 20 mm Hg. The mean proportion of GMT with ICP > 20 mm Hg was 5%, and 27% of the patients (14/52) spent more than 5% of GMT with ICP > 20 mm Hg. The Glasgow Coma Scale motor score at admission (p = 0.04) and lesions on DWI sequences in the substantia nigra and mesencephalic tegmentum (SN-T, p = 0.001) were associated with the proportion of GMT with ICP > 20 mm Hg. In multivariable linear regression, lesions on DWI sequences in SN-T (8% of GMT with ICP > 20 mm Hg, 95% CI 3%-13%, p = 0.004) and young age (-0.2% of GMT with ICP > 20 mm Hg, 95% CI -0.07% to -0.3%, p = 0.002) were associated with increased ICP. CONCLUSIONS: Increased ICP occurs in approximately one-third of patients with severe TBI who have DAI. Age and lesions on DWI sequences in the central mesencephalon (i.e., SN-T) are associated with elevated ICP. These findings suggest that MR lesion localization may aid prediction of increased ICP in patients with DAI.