Ian Piper

Motor and somatosensory evoked potentials recorded from the rat

An accurate neurophysiological technique that is able to monitor both the sensory and motor tracts of the spinal cord is required to assess patients with injury or other lesions of the cord, and for the evaluation of experimental studies of cord injury. We have recorded and characterized the motor and somatosensory evoked potentials (MEPs and SSEPs) from 20 normal rats and from 16 rats with cord lesions. MEPs were elicited by applying constant current anodal stimuli to the sensorimotor cortex (SMC) with the responses recorded from microelectrodes in the spinal cord at T10 (MEP-C) and from a bipolar electrode placed on the contralateral sciatic nerve (MEP-N). SSEPs were elicited by stimulating the sciatic nerve and were recorded from the cord at T10 and the contralateral SMC. The MEP-C consisted of an initial D wave (mean latency 1.21 +/- 0.12 msec and 4 subsequent I waves, 11-14). The D wave was elicited at stimulation frequencies exceeding 100 Hz. The initial positive wave of the MEP-N (mean latency 3.09 +/- 0.19 msec) was followed by several slower components which were attenuated by repetition rates exceeding 8.2 Hz. The grand mean SSEP consisted of 7 peaks. Sectioning of the dorsal columns abolished the SSEP but spared the MEP. Complete cord transection abolished both the MEP and SSEP. These experiments demonstrate that the combined recording of MEPs and SSEPs is an accurate and easily performed method of monitoring the functional integrity of the rat cord, and suggest that this technique would be of value in patients, especially those undergoing operative treatment of spinal lesions.

Motor evoked potentials recorded from normal and spinal cord-injured rats

A need exists for an accurate neurophysiological technique that monitors the motor tracts of the cord in patients with spinal cord injury or other cord lesions and for the evaluation of experimental models of cord injury. We have recorded and characterized the motor evoked potentials (MEPs) from 10 normal rats and from 10 rats with the following cord lesions at C-8: 4 animals with complete cord transection and 6 with clip compression injury: 2 at 56.0 g, 2 at 20.0 g, and 2 at 1.5 g. MEPs were elicited by applying constant current anodal stimuli to the sensorimotor cortex with the responses recorded from microelectrodes in the spinal cord at T-10. The MEP consisted of an initial D wave (mean latency, 1.22 +/- 0.09 ms) and 4 subsequent I waves, I1 to I4. The D wave was elicited at stimulation frequencies exceeding 100 Hz, consistent with the hypothesis that it results from direct pyramidal cell excitation. The 56.0-g clip compression injuries and the cord transections abolished the MEP distal to the lesion, whereas the 20.0- and 1.5-g injuries resulted in a latency shift and amplitude decrement of the MEP peaks. These experiments suggest that the recording of MEPs will be an extremely useful and accurate method of monitoring the functional integrity of the cord, of value in patients with cord injury.

Pressure autoregulation monitoring and cerebral perfusion pressure target recommendation in patients with severe traumatic brain injury based on minute-by-minute monitoring data

OBJECTnIn severe traumatic brain injury, a universal target for cerebral perfusion pressure (CPP) has been abandoned. Attempts to identify a dynamic CPP target based on the patients cerebrovascular autoregulatory capacity have been promising so far. Bedside monitoring of pressure autoregulatory capacity has become possible by a number of methods, Czosnykas pressure reactivity index (PRx) being the most frequently used. The PRx is calculated as the moving correlation coefficient between 40 consecutive 5-second averages of intracranial pressure (ICP) and mean arterial blood pressure (MABP) values. Plotting PRx against CPP produces a U-shaped curve in roughly two-thirds of monitoring time, with the bottom of this curve representing a CPP range corresponding with optimal autoregulatory capacity (CPPopt). In retrospective series, keeping CPP close to CPPopt corresponded with better outcomes. Monitoring of PRx requires high-frequency signal processing. The aim of the present study is to investigate how the processing of the information on cerebrovascular pressure reactivity that can be obtained from routine minute-by-minute ICP and MABP data can be enhanced to enable CPPopt recommendations that do not differ from those obtained by the PRx method, show the same associations with outcome, and can be generated in more than two-thirds of monitoring time.nnnMETHODSnThe low-frequency autoregulation index (LAx) was defined as the moving minute-by-minute ICP/MABP correlation coefficient calculated over time intervals varying from 3 to 120 minutes. The CPPopt calculation was based on LAx-CPP plots and done for time windows between 1 and 24 hours and for each LAx type. The resulting matrix of CPPopts were then averaged in a weighted manner, with the weight based on the goodness of fit of a U-shape and the lower value of the LAx corresponding to the U-bottom, to result in a final CPPopt recommendation. The association between actual CPP/CPPopt and outcome was assessed in the multicenter Brain Monitoring with Information Technology Research Group (BrainIT) database (n = 180). In the Leuven-Tübingen database (60-Hz waveform data, n = 21), LAx- and PRx-based CPPopts were compared.nnnRESULTSnIn the BrainIT database, CPPopt recommendations were generated in 95% of monitoring time. Actual CPP being close to LAx-based CPPopt was associated with increased survival. In a multivariate model using the Corticosteroid Randomization After Significant Head Injury (CRASH) model as covariates, the average absolute difference between actual CPP and CPPopt was independently associated with increased mortality. In the high-frequency data set no significant difference was observed between PRx-based and LAx-based CPPopts. The new method issued a CPPopt recommendation in 97% of monitoring time, as opposed to 44% for PRx-based CPPopt.nnnCONCLUSIONSnMinute-by-minute ICP/MABP data contain relevant information for autoregulation monitoring. In this study, the authors new method based on minute-by-minute data resolution allowed for CPPopt calculation in nearly the entire monitoring time. This will facilitate the use of pressure reactivity monitoring in all ICUs.

Improvement in Post-traumatic Spinal Cord Blood Flow with a Combination of a Calcium Channel Blocker and a Vasopressor

We have recently shown that nimodipine, a calcium channel blocker, can increase spinal cord blood flow (SCBF) in normal rats and can improve SCBF after spinal cord trauma if the mean systemic arterial pressure (mSAP) is restored to normal levels by the vasopressor, adrenalin. The present study is a further analysis of the improvement in post-traumatic SCBF (measured with the hydrogen clearance technique) with the combination of adrenalin and nimodipine. In addition, image analysis was used to study the potential risk of this combination for exacerbating intramedullary hemorrhage in the injured spinal cord. SCBF, mSAP, and other physiologic parameters were measured preinjury, postinjury, and post-treatment. A 53.0-gram clip compression injury at the T1 spinal segment was delivered for 1 minute to three treatment groups (saline, adrenalin, and adrenalin plus nimodipine) comprised of five rats each. Injury caused a marked decline in SCBF and mSAP. Treatment with adrenalin alone or combined with nimodipine (1.5 micrograms/kg/min IV) improved mSAP to 100-125 mm Hg. However, adrenalin alone failed to improve SCBF, whereas nimodipine plus adrenalin produced a marked improvement of approximately 60% in post-traumatic SCBF. Morphometric analysis showed no significant difference between per cent area or volume of hemorrhage between the three treatment groups, although there was a trend for increased hemorrhage in the adrenalin-alone group perhaps due to the higher post-traumatic mSAP in this group. Further studies are required to find the minimal elevation in mSAP produced by a vasopressor that would still cause an improvement in post-traumatic SCBF by nimodipine, and to determine whether this combination improves function after spinal cord injury.

Novel methods to predict increased intracranial pressure during intensive care and long-term neurologic outcome after traumatic brain injury: development and validation in a multicenter dataset.

Objective:Intracranial pressure monitoring is standard of care after severe traumatic brain injury. Episodes of increased intracranial pressure are secondary injuries associated with poor outcome. We developed a model to predict increased intracranial pressure episodes 30 mins in advance, by using the dynamic characteristics of continuous intracranial pressure and mean arterial pressure monitoring. In addition, we hypothesized that performance of current models to predict long-term neurologic outcome could be substantially improved by adding dynamic characteristics of continuous intracranial pressure and mean arterial pressure monitoring during the first 24 hrs in the ICU. Design:Prognostic modeling. Noninterventional, observational, retrospective study. Setting and Patients:The Brain Monitoring with Information Technology dataset consisted of 264 traumatic brain injury patients admitted to 22 neuro-ICUs from 11 European countries. Interventions:None. Measurements:Predictive models were built with multivariate logistic regression and Gaussian processes, a machine learning technique. Predictive attributes were Corticosteroid Randomisation After Significant Head Injury-basic and International Mission for Prognosis and Clinical Trial design in TBI-core predictors, together with time-series summary statistics of minute-by-minute mean arterial pressure and intracranial pressure. Main Results:Increased intracranial pressure episodes could be predicted 30 mins ahead with good calibration (Hosmer-Lemeshow p value 0.12, calibration slope 1.02, calibration-in-the-large −0.02) and discrimination (area under the receiver operating curve = 0.87) on an external validation dataset. Models for prediction of poor neurologic outcome at six months (Glasgow Outcome Score 1–2) based only on static admission data had 0.72 area under the receiver operating curve; adding dynamic information of intracranial pressure and mean arterial pressure during the first 24 hrs increased performance to 0.90. Similarly, prediction of Glasgow Outcome Score 1–3 was improved from 0.68 to 0.87 when including dynamic information. Conclusion:The dynamic information in continuous mean arterial pressure and intracranial pressure monitoring allows to accurately predict increased intracranial pressure in the neuro-ICU. Adding information of the first 24 hrs of intracranial pressure and mean arterial pressure monitoring to known baseline risk factors allows very accurate prediction of long-term neurologic outcome at 6 months.

Automated Time-averaged Analysis of Craniospinal Compliance (Short Pulse Response)

We have developed an automated method [Short Pulse Response (SPR)] of measuring craniospinal compliance using an electronic square wave pressure generator to produce a small (0.05 ml) and reproducible transient volume increase in the CSF space (pulse duration 100 msec). In experimental models of intracranial hypertension, arterial hypertension, arterial hypotension and arterial hypercarbia in cats, the new method accurately followed physiological changes in compliance when compared to the manual volume-pressure injection method. The VPR overestimated compliance compared to the new SPR method (by 20% to 162%, mean = 77%). The SPR method was less variable between sequential measurements with a coefficient of variation (CV) ranging from 0.6% to 9.6% (mean CV = 2.6%), compared with a CV ranging from 5.6% to 48% (mean CV = 17%) for the VPR method. Repeated compliance measurements by the new method over a 12 hour period, produced no neuropathological evidence of either blood brain barrier breakdown or tissue damage resulting from the repeated volume injections.

Importance of textual data in multimodality monitoring

OBJECTIVESnThe use of multimodality monitoring of patients in the intensive care unit (ICU) and the subsequent collection and analysis of such data are increasing. The aim of this work was to assess the importance of recording complementary textual data referring to patient care maneuvers, calibrations, and other incidents, in addition to the raw numerical values.nnnDESIGNnA retrospective analysis of multimodality monitoring data, which included comments entered concurrently at the bedside, collected from head-injured patients admitted to an ICU.nnnPATIENTSnOne hundred forty-seven patients with a postresuscitation Glasgow Coma Scale score of < or = 12 were monitored for a total of nearly 1 million minutes on up to eight commonly used channels.nnnMEASUREMENTS AND MAIN RESULTSnApproximately 13,000 comments were added to the raw data at the time of collection. The data were subsequently validated using these comments as indicators of artifactual values. The comments were classified into a surprisingly small number of important categories, with the most frequent referring to monitor calibrations and regular ICU care maneuvers. The difference between validated and unvalidated data on the quantity of secondary insult observed was in some cases nearly 50%.nnnCONCLUSIONSnThis work demonstrates that such textual information should be recorded concurrently with the raw monitoring values to ensure proper interpretation of the data in any retrospective analysis. Furthermore, it also suggests that a small number of prespecified categories could be used in the on-line validation of such data.

Clinical experience in the use of the Spiegelberg automated compliance device in the assessment of patients with hydrocephalus.

Deciding upon shunting in patients with hydrocephalus with possibly related symptomatology, is difficult. The Spiegelberg automated device allows continuous measurements of intracranial compliance. We aimed to evaluate the added information that this new technology can provide, in addition to standard continuous ICP monitoring. Thirty-three patients with hydrocephalus were continuously monitored for ICP and compliance. Patients with abnormal ICP or compliance profiles were selected for shunting. Thirteen patients underwent ventriculo-peritoneal shunting on this basis, with 12 obtaining benefit and one dying as a complication of shunt-related sepsis. The 13 patients undergoing shunting had abnormalities in either intracranial pressure or compliance or both. Only 1 patient had normal ICP, but abnormal compliance and so the true complementary role of continuous compliance measurements cannot be determined. It is proposed that further recruitment be on a larger multi-centre basis. Determination of benefit is required, particularly as a possible time lag of abnormal ICP abnormal compliance over appearing during monitoring can be demonstrated.

Early detection of increased intracranial pressure episodes in traumatic brain injury: external validation in an adult and in a pediatric cohort

Objective: A model for early detection of episodes of increased intracranial pressure in traumatic brain injury patients has been previously developed and validated based on retrospective adult patient data from the multicenter Brain-IT database. The purpose of the present study is to validate this early detection model in different cohorts of recently treated adult and pediatric traumatic brain injury patients. Design: Prognostic modeling. Noninterventional, observational, retrospective study. Setting and Patients: The adult validation cohort comprised recent traumatic brain injury patients from San Gerardo Hospital in Monza (n = 50), Leuven University Hospital (n = 26), Antwerp University Hospital (n = 19), Tübingen University Hospital (n = 18), and Southern General Hospital in Glasgow (n = 8). The pediatric validation cohort comprised patients from neurosurgical and intensive care centers in Edinburgh and Newcastle (n = 79). Interventions: None. Measurements and Main Results: The model’s performance was evaluated with respect to discrimination, calibration, overall performance, and clinical usefulness. In the recent adult validation cohort, the model retained excellent performance as in the original study. In the pediatric validation cohort, the model retained good discrimination and a positive net benefit, albeit with a performance drop in the remaining criteria. Conclusions: The obtained external validation results confirm the robustness of the model to predict future increased intracranial pressure events 30 minutes in advance, in adult and pediatric traumatic brain injury patients. These results are a large step toward an early warning system for increased intracranial pressure that can be generally applied. Furthermore, the sparseness of this model that uses only two routinely monitored signals as inputs (intracranial pressure and mean arterial blood pressure) is an additional asset.

Accurate data collection for head injury monitoring studies: a data validation methodology.

BACKGROUNDnBrainIT is a multi centre, European project, to collect high quality continuous data from severely head injured patients using a previously defined [6] core data set. This includes minute-by-minute physiological data and simultaneous treatment and management information. It is crucial that the data is correctly collected and validated.nnnMETHODSnMinute-by-minute physiological monitoring data is collected from the bedside monitors. Demographic and clinical information, intensive care management and secondary insult management data, are collected using a handheld computer. Data is transferred from the handheld device to a local computer where it is reviewed and anonymised before being sent electronically, with the physiological data, to the central database in Glasgow. Automated computer tools highlight missing or ambiguous data. A request is then sent to the contributing centre where the data is amended and returned to Glasgow. Of the required data elements 20% are randomly selected for validation against original documentation along with the actual number of specific episodic events during a known period. This will determine accuracy and the percentage of missing data for each record.nnnCONCLUSIONnAdvances in patient care require an improved evidence base. For accurate, consistent and repeatable data collection, robust mechanisms are required which should enhance the reliability of clinical trials, assessment of management protocols and equipment evaluations.