ABSTRACT
OBJECTIVES: Validated optimal cerebral perfusion pressure (CPP) treatment thresholds in children do not exist. To improve the intensive care unit (ICU) management of the paediatric traumatic brain injury (TBI) population, we are forming a new paediatric multi-centre collaboration to recruit standardised ICU data for running and reporting upon models for assessing autoregulation and optimal CCP (CPPopt). MATERIALS AND METHODS: We are adapting the adult BrainIT group's approach to develop a new Paediatric Brain Monitoring and Information Technology Group (KidsBrainIT), which will include a repository to store prospectively collected high-resolution physiological, clinical, and outcome data. In the first phase of this project there are 7 UK Paediatric Intensive Care Units, 1 Spanish, 1 Belgium, and 1 Romanian Centre interested in participating. In subsequent phases, we plan to open recruitment to other centres both within Europe, US and abroad. We are collaborating with the Leuven Group and plan to use their LAx (low-frequency autoregulation index), DATACAR (dynamic adaptive target of active cerebral autoregulation), CPPopt and visualisation methodologies. We also plan to use the continuous diffuse optical monitoring and tomography technology developed in Barcelona as an acute surrogate end-point for optimising brain perfusion. This technology allows non-invasive continuous monitoring of deep tissue perfusion and oxygenation in adults but its clinical application in infants and children with TBI has not been studied previously. RESULTS: We report on the current status of setting up this new collaboration and also on pilot analyses in two centres which are the basis of our rationale for the need for a prospective validation study of CPPopt in children. Specifically, we demonstrated that CPPopt varied with time for each patient during their paediatric intensive care unit (PICU) stay, and the median overall CPPopt levels for children aged 2-6 years, 7-11 years and 12-16 years were 68.83, 68.09, and 72.17 mmHg respectively. Among survivors and patients with favourable outcome (GOS 4 and 5), there were significantly higher proportions with CPP monitoring time within CPPopt (p = 0.04 and p = 0.01 respectively). CONCLUSIONS: There is a need and an interest in forming a multi-centre PICU collaboration for acquiring data and performing analyses for determining validated CPPopt thresholds in the paediatric TBI population. KidsBrainIT is being formed to meet that need.
Subject(s)
Brain Injuries, Traumatic/therapy , Brain/physiopathology , Cerebrovascular Circulation , Intracranial Pressure/physiology , Monitoring, Physiologic , Adolescent , Belgium , Brain/diagnostic imaging , Brain Injuries, Traumatic/diagnostic imaging , Brain Injuries, Traumatic/physiopathology , Child , Child, Preschool , Cooperative Behavior , Disease Management , Europe , Female , Homeostasis , Humans , Intensive Care Units, Pediatric , Male , Pilot Projects , Romania , Spain , Tomography, X-Ray Computed , United Kingdom , United StatesABSTRACT
Studies on piglets have shown that cranial bioimpedance (Z) measurements correlate well with invasively measured intracranial pressure (ICP). We have tested the feasibility of collecting transcranial impedance from a clinical device for measuring whole-body water content (ImpediMed SFB7). In the clinical study, 50 normal healthy volunteers had transcranial impedance measured using nine different head montages (forehead to mastoid (left/right), temporal to mastoid (left/right), forehead to temporal (left/right), forehead to occipital (left/right) and temporal to temporal). Impedance was measured 20 times over a frequency range per montage and ANOVA used to test for effects of electrode position upon recorded value. For the experimental study, five sedated and ventilated Marino sheep were instrumented for intraventricular ICP and transcranial impedance measurement. Measures of ICP were recorded while ICP was increased from baseline to greater than 50 mmHg in five steps using an intraventricular infusion of mock CSF. There is a significant effect of electrode position and gender upon transcranial impedance (p < 0.001). The temporal-mastoid electrode position had significantly lower impedance values in keeping with its shorter path length. ICP correlated with craniospinal compliance measurements and Impedance vs Freq by ICP step shows a clear ICP dependence (p = 0.007) across the sheep.
Subject(s)
Electric Impedance , Intracranial Pressure/physiology , Adult , Animals , Diagnosis, Computer-Assisted , Electrodes , Female , Humans , Middle Aged , Monitoring, Physiologic , Regression Analysis , Sheep , Young AdultABSTRACT
Preparation of a specific quantum state is a required step for a variety of proposed quantum applications. We report an experimental demonstration of optical quantum state inversion in a single semiconductor quantum dot using adiabatic rapid passage. This method is insensitive to variation in the optical coupling in contrast with earlier work based on Rabi oscillations. We show that when the pulse power exceeds a threshold for inversion, the final state is independent of power. This provides a new tool for preparing quantum states in semiconductor dots and has a wide range of potential uses.
ABSTRACT
OBJECTIVE: To assess the use of hyperventilation and the adherence to Brain Trauma Foundation-Guidelines (BTF-G) after traumatic brain injury (TBI). SETTING: Twenty-two European centers are participating in the BrainIT initiative. DESIGN: Retrospective analysis of monitoring data. PATIENTS AND PARTICIPANTS: One hundred and fifty-one patients with a known time of trauma and at least one recorded arterial blood-gas (ABG) analysis. MEASUREMENTS AND RESULTS: A total number of 7,703 ABGs, representing 2,269 ventilation episodes (VE) were included in the analysis. Related minute-by-minute ICP data were taken from a 30 min time window around each ABG collection. Data are given as mean with standard deviation. (1) Patients without elevated intracranial pressure (ICP) (< 20 mmHg) manifested a statistically significant higher P(a)CO(2) (36 +/- 5.7 mmHg) in comparison to patients with elevated ICP (> or = 20 mmHg; P(a)CO(2): 34 +/- 5.4 mmHg, P < 0.001). (2) Intensified forced hyperventilation (P(a)CO(2) < or = 25 mmHg) in the absence of elevated ICP was found in only 49 VE (2%). (3) Early prophylactic hyperventilation (< 24 h after TBI; P(a)CO(2) < or = 35 mmHg, ICP < 20 mmHg) was used in 1,224 VE (54%). (4) During forced hyperventilation (P(a)CO(2) < or = 30 mmHg), simultaneous monitoring of brain tissue pO(2) or S(jv)O(2) was used in only 204 VE (9%). CONCLUSION: While overall adherence to current BTF-G seems to be the rule, its recommendations on early prophylactic hyperventilation as well as the use of additional cerebral oxygenation monitoring during forced hyperventilation are not followed in this sample of European TBI centers. DESCRIPTOR: Neurotrauma.
Subject(s)
Blood Gas Analysis , Brain Injuries/blood , Brain Injuries/therapy , Respiration, Artificial , Adult , Brain Injuries/classification , Databases, Factual , Europe , Female , Humans , Male , Multicenter Studies as Topic , Retrospective StudiesABSTRACT
BACKGROUND: The ability to quantify non-invasively the effect of posture on intracranial physiology by using cine phase-contrast MRI may lead to the development of new diagnostic tests to evaluate such functions as regulation of CBF and ICP, and the effect of pathologies on these functions. METHODS: Results similar to MRI technology can be obtained using non-invasive ultrasonic method (Vittamed) for intracranial blood volume pulse wave (IBVPW) measurement and intracraniospinal compliance (ICC) monitoring. FINDINGS: IBVPW have been investigated in supine and upright positions of healthy volunteers using Vittamed technology. A group of 13 healthy volunteers (nine females, four males, mean age 25.1 +/- 3.4) was studied. More than 3,000 IBVPW were analysed in order to show the difference of shape and amplitude in supine and upright positions. Averaged shape of ten IBVPW waves was presented in the normalized window with dimensions 1.0 x 1.0. CONCLUSIONS: The results show significant difference between averaged IBVPW shapes in upright (highest intracraniospinal compliance) and supine (lower intracraniospinal compliance) body positions. Body posture caused IBVPW subwave P2 and P3 changes deltaP2 = 18% and deltaP3 = 11%. Amplitude of IBVPW in upright body position was significantly higher than in the supine one. The value of IBVPW amplitude's ratio in supine and upright positions was 1.55 +/- 0.61.
Subject(s)
Brain/blood supply , Intracranial Pressure/physiology , Monitoring, Physiologic/methods , Adult , Blood Volume Determination/methods , Cerebrovascular Circulation/physiology , Compliance/physiology , Female , Humans , Magnetic Resonance Imaging , Male , Pulsatile Flow , Supine Position/physiology , Ultrasonics , Young AdultABSTRACT
BACKGROUND: 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. METHODS: 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. RESULTS: 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. CONCLUSION: 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.
Subject(s)
Biomedical Research/organization & administration , Craniocerebral Trauma/epidemiology , Critical Care/statistics & numerical data , Database Management Systems , Databases, Factual , Information Storage and Retrieval/methods , Medical Records Systems, Computerized/organization & administration , Community Networks/organization & administration , Europe , Humans , Information Dissemination/methods , InternetABSTRACT
The Spiegelberg Compliance Device (Spiegelberg KG, Hamburg, Germany) has been available for the automated measurement and calculation of minute by minute intracranial compliance. Widespread practical use has been somewhat limited by the instability of values: especially at low intracranial pressures. We looked at two aspects of a methodology in an attempt to increase the value of the Spiegelberg device in the clinical setting. Firstly, we discussed the difference in representing measured values as elastance (dp/dv) instead of compliance (dv/dp); and secondly we proposed the use of an averaging algorithm called the Exponentially Weighted Moving Average (ewma), which could be applied as a flexible method to follow trends and rapid changes in the elastance (or compliance). Clinical data from sixteen patients were gathered and statistical analysis was focused on three particular aspects, the coefficient of variation which indicates the variability of data values, the correlation between the elastance (or compliance) time series and the underlying ICP signal and the percentage of outliers greater than 2.5 standard deviations from the mean. Our results showed that expressing elastance (dp/dv) instead of compliance (dv/dp) yielded fewer outliers and had a better correlation to ICP, and the ewma method had a better correlation to ICP than the Spiegelberg method.
Subject(s)
Algorithms , Brain Diseases/diagnosis , Brain Diseases/physiopathology , Brain/physiopathology , Diagnosis, Computer-Assisted/methods , Intracranial Pressure , Monitoring, Physiologic/methods , Adult , Aged , Compliance , Data Interpretation, Statistical , Diagnosis, Computer-Assisted/instrumentation , Equipment Design , Equipment Failure Analysis , Female , Humans , Male , Middle Aged , Monitoring, Physiologic/instrumentation , Organ Size , Reproducibility of Results , Sensitivity and SpecificityABSTRACT
INTRODUCTION: An open collaborative international network has been established which aims to improve inter-centre standards for collection of high-resolution, neurointensive care data on patients with traumatic brain injury. The group is also working towards the creation of an open access, detailed and validated database that will be useful for hypothesis generation. In Part A, we describe the underlying concept of the group and it's aims and in Part B we describe the current status of the groups development. METHODS: Four group meetings funded by the EEC have enabled definition of a "Core Dataset" to be collected from all centres regardless of specific project aim. A form based feasibility study was conducted and a prospective data collection exercise of core data using PC and hand held computer based methods is in progress. FINDINGS: A core-dataset was defined and can be downloaded from the BrainIT web-site (go to "Core dataset" link at: www.brainit.org). A form based feasibility study was conducted showing the overall feasibility for collection of the core data elements was high. Software tools for collection of the core dataset have been developed. Currently, 130 patient's data from 16 European centres have been recruited to the joint database as part of an EEC funded proof of concept study. INTERPRETATION: The BrainIT network provides a more standardised and higher resolution data collection mechanism for research groups, organisations and the device industry to conduct multicentre trials of new health care technology in patients with traumatic brain injury.
Subject(s)
Brain Injuries/diagnosis , Brain Injuries/therapy , Critical Care/organization & administration , Databases, Factual/trends , Information Dissemination/methods , International Cooperation , Medical Records Systems, Computerized/organization & administration , Brain Injuries/epidemiology , Cooperative Behavior , Database Management Systems , Humans , Internet , Monitoring, PhysiologicABSTRACT
BACKGROUND: BrainIT 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. METHODS: Minute-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. CONCLUSION: Advances 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.
Subject(s)
Brain Injuries/diagnosis , Critical Care/statistics & numerical data , Databases, Factual , Information Dissemination/methods , Information Storage and Retrieval/methods , Medical Records Systems, Computerized/organization & administration , Monitoring, Physiologic/statistics & numerical data , Brain Injuries/epidemiology , Brain Injuries/therapy , Cooperative Behavior , Data Collection/methods , Database Management Systems , Humans , International Cooperation , Internet , Monitoring, Physiologic/methodsABSTRACT
BACKGROUND: The aim of this study was to obtain basic knowledge about the current local conditions and neurointensive care of traumatic brain injury (TBI) in the new multi-centre collaborative BrainIT group. MATERIALS AND METHODS: The survey comprised a background part on local policies (Part A), and a case study section (Part B). The information was gathered by questionnaire followed by telephone interviews. Twenty-three BrainIT centres participated in the survey and answers from two respondents were available from 18 of the sites. RESULTS: The average proportion of agreement between duplicate respondents was 0.778 (range 0.415-1.00). All BrainIT centres monitored ICP. The treatment protocols seem to have a pattern concerning escalation of treatment of intracranial hypertension: 1/ evacuation of mass lesions and head elevation; 2/ increased sedation and mannitol; 3/ hyperventilation; 4/ ventricular drainage; 5/ craniectomy and barbituates. CONCLUSIONS: There seemed to be an agreement on neurointensive care policies within the BrainIT group. The suggested order of treatment was generally in accordance with published guidelines although the suggested order and combinations of different treatments varied. Variation of treatment within the range of prescribed standards provides optimal conditions for an interesting future analysis of treatment and monitoring data in reality using the BrainIT database.
Subject(s)
Brain Injuries/diagnosis , Brain Injuries/therapy , Critical Care/statistics & numerical data , Monitoring, Physiologic/statistics & numerical data , Neurology/statistics & numerical data , Practice Patterns, Physicians'/statistics & numerical data , Quality Assurance, Health Care/methods , Brain Injuries/epidemiology , Europe/epidemiology , Humans , International Cooperation , Surveys and QuestionnairesABSTRACT
BACKGROUND: Cerebral compliance expresses the capability to buffer an intracranial volume increase while avoiding a rise in intracranial pressure (ICP). The autoregulatory response to Cerebral Perfusion Pressure (CPP) variation influences cerebral blood volume which is an important determinant of compliance. The direction of compliance change in relation to CPP variation is still under debate. The aim of the study was to investigate the relationship between CPP and compliance in traumatic brain injured (TBI) patients by a new method for continuous monitoring of intracranial compliance as used in neuro-intensive care (NICU). METHOD: Three European NICU's standardised collection of CPP, compliance and ICP data to a joint database. Data were analyzed using an unpaired student t-test and a multi-level statistical model. RESULTS: For each variable 108,263 minutes of data were recorded from 21 TBI patients (19 patients GCS=8; 90% male; age 10-77 y). The average value for the following parameters were: ICP 15.1+/-8.9 mmHg, CPP 74.3+/-14 mmHg and compliance 0.68+/-0.3 ml/mmHg. ICP was >/=20 mmHg in 20% and CPP<60 mmHg for 10.7% of the time. Compliance was lower (0.51+/-0.34 ml/mmHg) at ICP>/=20 than at ICP<20 mmHg (0.73+/-0.37 ml/mmHg) (p<0.0001). Compliance was significantly lower at CPP<60 than at CPP>/=60 mmHg: 0.56+/-0.36 and 0.70+/-0.37 ml/mmHg respectively (p<0.0001). The CPP - compliance relationship was different when ICP was above 20 mmHg compared with below 20 mmHg. At ICP<20 mmHg compliance rose as CPP rose. At ICP>/=20 mmHg, the relation curve was convexly shaped. At low CPP, the compliance was between 0.20 and 0.30 ml/mmHg. As the CPP reach 80 mmHg average compliance was 0.55 ml/mmHg., but compliance fell to 0.40 ml/mmHg when CPP was 100 mmHg. CONCLUSIONS: Low CPP levels are confirmed to be detrimental for intracranial compliance. Moreover, when ICP was pathological, indicating unstable intracranial equilibrium, a high CPP level was also associated with a low volume-buffering capacity.
Subject(s)
Blood Pressure/physiology , Blood Volume/physiology , Brain Injuries/physiopathology , Brain/blood supply , Intracranial Pressure/physiology , Adolescent , Adult , Aged , Aged, 80 and over , Brain/physiopathology , Child , Compliance , Critical Care , Female , Glasgow Coma Scale , Homeostasis/physiology , Humans , Male , Microcomputers , Middle Aged , Models, Theoretical , Monitoring, Physiologic , Pilot Projects , Signal Processing, Computer-Assisted , Vascular Resistance/physiologyABSTRACT
Following investigation of a large number of new ligands based upon propylene amine oxime (PnAO) the d,l-diastereoisomer of hexamethyl propyleneamine oxime (HM-PAO) was selected as the preferred ligand for 99mTc as a tracer for cerebral perfusion imaging. The neutral, lipophilic 99mTc complex of d,l-HM-PAO was formed in high yield by stannous reduction of 99Mo/99mTc generator eluate using a kit formulation of the ligand. Two minutes following i.v. administration of this complex in rats, 2.25% of the injected dose appears in the brain. Little washout of the tracer is observed up to 24 hr postinjection. By qualitative autoradiographic comparison with iodoantipyrine this new radiopharmaceutical displays blood flow dependent brain uptake with little redistribution of the tracer over time. The lipophilic 99mTc complex converts slowly in vitro to a secondary complex. This conversion process may account for the ability of [99mTc]d,l-HM-PAO to be retained within the brain without redistribution.
Subject(s)
Brain/diagnostic imaging , Cerebrovascular Circulation , Oximes , Technetium , Tomography, Emission-Computed , Animals , Autoradiography , Female , Isotope Labeling/methods , Male , Models, Molecular , Oximes/chemical synthesis , Oximes/metabolism , Rabbits , Rats , Rats, Inbred Strains , Stereoisomerism , Technetium/chemical synthesis , Technetium/metabolism , Technetium Tc 99m Exametazime , Tissue DistributionABSTRACT
1. The ability of several potassium (K+) channel openers to inhibit spasm of the uterus of the nonpregnant rat and their susceptibility to antagonism by glibenclamide was assessed in vitro and in vivo. 2. In the isolated uterus exposed to oxytocin (0.2 nM), cromakalim, RP 49356 and pinacidil were of similar potency (mean pD2 = 6.4, 6.0 and 6.2 respectively) while minoxidil sulphate was of lower potency (pD2 = 4.7). Glibenclamide antagonized cromakalim and RP 49356 with the interactions consistent with competitive antagonism (mean pA2 of 6.57 and 7.00 respectively). Glibenclamide also antagonized pinacidil (pA2 = 6.22) but the slope of the Schild plot was significantly greater than -1. Neither salbutamol nor minoxidil sulphate was antagonized by glibenclamide (10 microM). 3. Cromakalim (1 and 10 microM), RP 49356 (1 and 10 microM), pinacidil (1 microM) and minoxidil sulphate (100 microM) suppressed spasm evoked by low (less than 40 mM) but not high (greater than or equal to 40 mM) KCl concentrations. Glibenclamide (10 microM) prevented cromakalim (10 microM)-, RP 49356 (10 microM)- and pinacidil (10 microM)-induced suppression of KCl (20 mM)-evoked spasm. Pinacidil (10 and 100 microM), cromakalim (100 microM) and salbutamol (0.01-1 microM) inhibited spasm evoked by all concentrations of KCl (10-80 mM). Suppression of spasm evoked by KCl (10-80 mM) by cromakalim (100 microM) and pinacidil (100 microM) was insensitive to glibenclamide (10 microM). 4. Cromakalim (0.1 mg kg-1) and RP 49356 (0.1 mg kg-1), given by i.v. bolus injection, inhibited uterine contractions, produced a fall in blood pressure and a slight tachycardia in the conscious ovariectomized rat. Glibenclamide (20mgkg-'), given by i.v. infusion, antagonized the vascular and uterine smooth muscle relaxant properties of cromakalim and RP 49356. 5. Several K+ channel openers are uterine relaxants. The antagonism of cromakalim, RP 49356 and pinacidil, at low concentrations, by glibenclamide suggests their actions may involve an ATP-sensitive K+channel. High concentrations of pinacidil (10 and 100 microM) and cromakalim (100 microM) may exert an additional action in the uterus. The low potency of minoxidil sulphate and its insensitivity to glibenclamide in the isolated uterus suggests that its mechanism of action may differ from that of the other K+ channel openers.
Subject(s)
Glyburide/pharmacology , Potassium Channels/drug effects , Uterus/drug effects , Animals , Benzopyrans/pharmacology , Blood Pressure/drug effects , Cromakalim , Female , Guanidines/pharmacology , Heart Rate/drug effects , Hemodynamics/drug effects , In Vitro Techniques , Oxytocin/pharmacology , Parasympatholytics/pharmacology , Picolines/pharmacology , Pinacidil , Potassium Chloride/pharmacology , Pregnancy , Pyrans/pharmacology , Pyrroles/pharmacology , Rats , Rats, Inbred Strains , Vasodilator Agents/pharmacologyABSTRACT
Treatment of rats with bromocriptine between days 5 and 8 after the post-partum mating resulted in suppression of serum prolactin levels and caused luteal regression. Although this treatment led to embryonic resorption when suckling was prevented by removing litters soon after birth, the diapausing embryos of animals nursing a litter of eight pups were unaffected by the treatment. These results suggest that the high levels of prolactin and progesterone in the circulation during lactation are not responsible for maintenance of the diapausing state.
Subject(s)
Bromocriptine/pharmacology , Embryo, Mammalian/physiology , Lactation , Pregnancy, Animal/drug effects , Prolactin/metabolism , Animals , Corpus Luteum/drug effects , Depression, Chemical , Embryo Implantation/drug effects , Female , Pregnancy , Progesterone/pharmacology , RatsABSTRACT
The present study was undertaken to establish an experimental trauma model where it was possible to alter intracranial pressure (ICP) dynamics without raising intracranial pressure to abnormal levels and monitor metabolic disturbances with microdialysis. Thirty rats were intubated and mechanically ventilated before and after trauma. ICP was measured in the left ventricle. A weight-drop technique (21 g from 35 cm) with a brain compression of 1.5 mm was used to produce the injury. Intracranial compensatory volume was decreased 20 or 60 microL by placement of rubber film between the dura mater and bone. A bolus injection technique was used for the pressure volume response. ICP remained within normal limits for 2 h after trauma irrespective of the reduction in compensatory intracranial volume. Pressure-volume index decreased from 0.0825 +/- 0.009 to 0.0779 +/- 0.011 mL in the sham trauma and from 0.0871 +/- 0.018 to 0.0748 +/- 0.017 mL in the trauma groups (p < 0.015) when the intracranial volume was reduced by 60 microL. Intracranial compliance was not affected significantly. The present study shows that it is possible to vary ICP dynamics in a traumatic brain injury model without causing pathological increases in baseline ICP. This model may be used to study the effects of secondary insults (i.e., hypotension, hypoxia, hypercarbia, and hyperthermia) on the injured brain when ICP is normal but intracranial compensatory volume is impaired.
Subject(s)
Brain Injuries/physiopathology , Brain/physiopathology , Disease Models, Animal , Intracranial Pressure/physiology , Animals , Brain/metabolism , Brain/pathology , Brain Injuries/metabolism , Male , Microdialysis , Rats , Rats, Sprague-Dawley , Time FactorsABSTRACT
We have characterized the early brain pathology in Sprague-Dawley rats subjected to a modified Richmond impact acceleration model of closed head injury (CHI). This model was modified to produce maximal traumatic brain injury (TBI) in the absence of skull fracture, extracerebral or intracerebral hemorrhage, or brain contusion. We then used this model to assess the neuropathologic effects of superimposed secondary insults, which were designed to reflect a clinically relevant combination of hypotension and pyrexia. Acute neuronal injury, blood-brain barrier (BBB) integrity, axonal injury (AI), and glial activation were studied 4 1/2 hours following either CHI (group A), CHI plus secondary insults (group B), secondary insults alone (group C), or sham control injury (group D). There was evidence of limited AI following CHI in the lower medulla and upper cervical cord region, which was not modified by addition of secondary insult. Loss of dendritic microtubule-associated protein MAP2 immunoreactivity proved a reliable marker of acute neuronal damage, which was confined to subimpact and inferolateral cortical locations following CHI and was widespread after secondary insult. The pattern of plasma protein extravasation paralleled that of acute neuronal injury. We found no evidence of microglial activation, either local or generalized, by 4 1/2 hours. However, by this time CHI and secondary insults had combined to produce evidence of subimpact astrocyte activation, which was not apparent with either insult or injury alone. We conclude that in this modified Richmond model of CHI, when combined with secondary insults, there is no convincing potentiation of brain damage with the minor exception of astrocyte activation.
Subject(s)
Brain/pathology , Head Injuries, Closed/pathology , Animals , Antibodies, Monoclonal , Axons/pathology , Blood Proteins/metabolism , Blood-Brain Barrier/physiology , Capillary Permeability/physiology , Disease Models, Animal , Fever/etiology , Fever/physiopathology , Head Injuries, Closed/complications , Head Injuries, Closed/physiopathology , Hypotension/etiology , Hypotension/physiopathology , Immunohistochemistry , Macrophage Activation/physiology , Male , Microtubule-Associated Proteins/metabolism , Neuroglia/pathology , Rats , Rats, Sprague-DawleyABSTRACT
Raised intracranial pressure (ICP) occurs at some time in 50-75% of severely head injured patients. Measurement of ICP alone is not sufficient. Arterial pressure must also be monitored: the important physiological variable is cerebral perfusion pressure. Detailed analysis of the ICP recording yields valuable information on the nature and cause of ICP, with implications for appropriate therapy. Additional measurements of importance include brain electrical activity, arterial and jugular venous oxygen saturation, and blood flow velocity in major intracranial arteries measured by transcranial Doppler sonography. These assessments not only add information about the cause of intracranial hypertension (vascular vs. nonvascular) but also help to regulate therapy, providing early warning that a treatment for reducing the ICP is actually producing global brain ischemia. In the management of raised ICP, all correctable factors must first of all be dealt with, then a choice made between hypnotic drugs and osmotic therapy according to whether the cause of raised ICP is, respectively, vascular or nonvascular.
Subject(s)
Brain Injuries/physiopathology , Craniocerebral Trauma/physiopathology , Intracranial Pressure , Papilledema/prevention & control , Blood Volume , Brain Injuries/therapy , Cerebrovascular Circulation , Craniocerebral Trauma/therapy , Humans , Monitoring, PhysiologicABSTRACT
OBJECTIVE: To investigate the role of the endothelin system in pressure autoregulation of cerebral blood flow (CBF) in rats. DESIGN: We tested pressure autoregulation by increasing cerebral perfusion pressure (CPP; mean arterial pressure-intracranial pressure) with norepinephrine (0.08 microgram.kg-1.min-1 for 30 min) twice in ten anesthetized normocapnic rats. The first test was performed without (control test) and the second test after administration of the combined endothelin ETA/B receptor antagonist, bosentan, i.v. (30 mg/kg; drug test). CBF was measured by the hydrogen clearance technique. RESULTS: During the control test, norepinephrine infusion increased CPP by 21 +/- 2 (23 +/- 2%) mmHg (mean +/- SEM; p < 0.001) and CBF by 3.6 +/- 3.1 (6 +/- 8%) ml/100 g/min (p = 0.5, Fig. 1); during the drug test, norepinephrine infusion increased CPP by 18 +/- 1 (20 +/- 2%) mmHg (p < 0.001) and CBF by 15.8 +/- 4.1 (46 +/- 13%) ml/100 g/min (p = 0.004). Mean arterial pressure was not affected by bosentan infusion (p = 0.2). PaCO2 levels were stable during the tests (40.2 +/- 1.4 mmHg). CONCLUSIONS: The endothelin system is involved in cerebral pressure autoregulation in a rodent model in vivo. The role of this system under pathophysiologic conditions such as subarachnoid hemorrhage, where basal vascular tone and its regulation may be altered, remains to be defined.
Subject(s)
Antihypertensive Agents/pharmacology , Brain/blood supply , Endothelin-1/physiology , Homeostasis/drug effects , Norepinephrine/pharmacology , Sulfonamides/pharmacology , Vasoconstrictor Agents/pharmacology , Analysis of Variance , Animals , Blood Pressure/drug effects , Bosentan , Brain/drug effects , Intracranial Pressure/drug effects , Male , Rats , Rats, Sprague-Dawley , Regional Blood Flow/drug effectsABSTRACT
OBJECTIVE: To obtain knowledge about the conditions and management of traumatic brain injury (TBI) in a collaborative network of Brain Information Technology centres. DESIGN: The Brain IT (Brain monitoring with Information Technology) survey comprised two parts: local conditions and policies (part A), and a case study part (part B). The information was gathered by written questionnaires followed by telephone interviews. PARTICIPANTS: Twenty-four Brain IT centres participated (two respondents from 18 sites). RESULTS: The average proportion of agreement between duplicate respondents was 0.79 (range 0.44-1.00). All Brain IT centres monitored ICP. The reported order of treatment for intracranial hypertension was: evacuation of mass-lesions and head elevation (1), increase of sedation and Mannitol scheme (2), hyperventilation (3), ventricular drainage (4), craniectomy and pentothal coma (5), and decompressive lobectomy (6). The respondents were less prone to evacuate expansive contusions in relation to extra cerebral hematomas. The most common suggested interventions (alone or in combination) for treatment of intracranial hypertension without mass lesions was the Mannitol scheme (included in 71% of the suggestions), CSF drainage (included in 56%), hyperventilation (included in 32%), and pentothal coma (included in 22%). CONCLUSIONS: The suggested management of TBI was mainly in accordance with published guidelines, although a minor proportion of the answers deviated to some extent. The suggested order and combinations of different treatment interventions varied. Variation of treatment within the range of prescribed standards provides optimal conditions for an interesting future analysis of treatment and monitoring data as collected prospectively in a Brain IT database.
Subject(s)
Brain Injuries/therapy , Intensive Care Units , Quality of Health Care , Adult , Brain Injuries/diagnosis , Case Management/organization & administration , Europe , Guideline Adherence , Health Care Surveys , Humans , Intensive Care Units/organization & administration , Male , Organizational Policy , Practice Guidelines as TopicABSTRACT
OBJECTIVE: To ascertain if norepinephrine can be used as part of the cerebral perfusion pressure (CPP) management to increase arterial blood pressure (MAP) without causing cerebral hyperemia after severe head injury (HI). DESIGN: Prospective, interventional study. SETTING: Intensive care unit in a university hospital. PATIENTS: Twelve severely HI patients; median Glasgow Coma Scale was 6 (range 3-8). INTERVENTIONS: CPP management ( = 70 mmHg). Pressure autoregulation (assessed by norepinephrine infusion) was defined intact if % CPP/%CVR < or = 2. RESULTS: Cerebral blood flow (CBF: Xe133 inhalation technique), jugular bulb oxygen saturation (SjO2) and transcranial Doppler (TCD) were recorded during the test. Norepinephrine increased CPP by 33 % (+/- 4). Autoregulation was found to be intact in ten patients and defective in two. In the ten patients with preserved autoregulation, CBF decreased from 31 +/- 3 to 28 +/- 3 ml/ 100 g/min; in the two patients with impaired autoregulation CBF increased respectively from 16 to 35 and from 21 to 70 ml/100 g/min. SjO2 did not change significantly from baseline. TCD remained within the normal range. CONCLUSIONS: During CPP management norepinephrine can be used to increase MAP without potentiating hyperemia if pressure autoregulation is preserved. The assessment of pressure autoregulation should be considered as a guide for arterial pressure-oriented therapy after HI.