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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.

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.

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.

Aim: To describe the outcomes and complication rates in 236 patients with idiopathic normal pressure hydrocephalus (INPH) after treatment., Patients and Methods: Among a cohort of 257 patients with suspected INPH, 244 were shunted and 236 were followed up at 6 months after shunting (145 men [61.4%] and 91 women [38.6%] with a median age of 75 years). The study protocol of these patients included clinical, radiological, neuropsychological and functional assessment. The decision to shunt patients was based on continuous intracranial pressure monitoring and CSF dynamics studies. A differential low-pressure valve system, always combined with a gravity compensating device, was implanted in 99% of the patients., Results: After shunting, 89.9% of the patients showed clinical improvement (gait improved in 79.3% of patients, sphincter control in 82.4%, and dementia in 63.7%). Two patients (0.8%) died. Early postsurgical complications were found in 13 of the 244 shunted patients (5.3%). Six months after shunting, the follow-up CT showed asymptomatic hygromas in 8 of the 236 (3.4%). Additional postsurgical complications were found in 7 patients (3%), consisting of 6 subdural hematomas (3 acute and 3 chronic) and 1 distal catheter infection., Conclusions: Currently, a high percentage of patients with INPH can improve after shunting, with early and late complication rates of less than 12%.

Aim: Low levels of hypocretin-1 (HC-1) have been associated with hypersomnia, obesity, depression, and chronic headaches. These conditions are frequently present in patients with idiopathic intracranial hypertension (IIH) and may be associated with abnormalities of the hypocretin system. The aim of this study was to determine HC-1 concentrations in cerebrospinal fluid (CSF) in a series of patients with IIH and to compare these concentrations with those in a control group with no neurological alterations., Patients and Methods: This prospective study included a cohort of 26 consecutive patients with IIH who were mostly women (25 vs. 1) with a mean age of 42.5 ± 13.2. CSF samples were obtained from a lumbar puncture performed between 08:00 and 10:00 a.m. HC-1 was determined by a competitive radioimmunoassay (RIA) using I(125) as the isotope. Samples of normal CSF were obtained during spinal anesthesia for urological, general or vascular surgery from 40 patients (10 women and 30 men with a mean age of 63.7 ± 14.8) with no previous neurological or psychiatric history, a normal neurological examination, and MMSE scores of ≥ 24., Results: No statistically significant differences were found between HC-1 levels in the CSF of patients with IIH (119.61 ± 21.63 pg/mL) and those of the control group (119.07 ± 20.30 pg/mL; p = 0.918)., Conclusions: HC-1 is not associated with the clinical symptoms present in patients with IIH.

Malignant middle cerebral artery (MMCA) infarction is associated with a mortality rate of 80% under conservative treatment. Decompressive hemicraniectomy (DH) reduces mortality and improves the functional outcome of surviving patients. The purpose of this study was to examine quality of life (QoL) and neurobehavioral deficits in patients with space-occupying infarctions of the right- or left-sided hemisphere at 6 months after stroke. The Sickness Impact Profile (SIP) was used to assess QoL in 19 out of 29 consecutive patients that underwent DH after a malignant MCA infarction (14 on the right and 5 on the left hemisphere). Behavioral changes were evaluated with the Frontal Behavioral Inventory and the Beck Depression Inventory. Patients and relatives were also asked if, knowing the present outcome, they would agree again, in retrospect, to a DH. Barthel Index >60 was seen in 37% of our patients. Functional outcome was related to age. We found a higher reduction in the SIP's physical domain than in the psychosocial domain. Depressive symptoms were present in 50% of the patients. We didn't find significant differences in QoL or functional outcome between patients with right or left-sided infarctions. The most frequent neurobehavioral symptoms were decreased speech output, apathy, reduced spontaneity and irritability. Most patients and their relatives would again give consent to hemicraniectomy. The results show that younger patients had a significantly better outcome. QoL seems to be acceptable in both left- and right-sided infarctions, and retrospective agreement to hemicraniectomy is high in both patients and their relatives.

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.

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.

Background: Brain contusions are inflammatory evolutive lesions that induce intracranial pressure increase and edema, contributing to neurological outcome. Matrix metalloproteinases (MMPs) 2 and 9 can degrade the majority of the extracellular matrix components, and are implicated in blood-brain barrier disruption and edema formation. The aim of this study was to investigate MMP-2 and MMP-9 profiles in human brain contusions using zymography., Methods: A prospective study was conducted in 20 traumatic brain injury patients where contusion brain tissue was resected. Brain tissues from lobectomies were used as controls. Brain homogenates were analysed by gelatin zymography and in situ zimography was performed to confirm results, on one control and one brain contusion tissue sample., Findings: MMP-2 and MMP-9 levels were higher in brain contusions when compared to controls. MMP-9 was high during the first 24 hours and at 48 to 96 hours, whereas MMP-2 was slightly high at 24 to 96 hours. In situ zymography confirmed gelatin zymography results. A relation between outcome and MMP-9 levels was found; MMP-9 levels were higher in patients with worst outcome., Conclusions: Our results indicate strong time-dependent gelatinase expression primarily from MMP-9, suggesting that the inflammatory response induced by focal lesions should be considered as a new therapeutic target.

Objectives: Our aim was to evaluate corpus callosum functioning in a group of patients with normal pressure hydrocephalus (NPH) before and after shunting., Methods: Left ear-extinction under a dichotic listening task was evaluated in twenty-three patients with NPH, 30 patients with Alzheimer's disease and 30 aged controls., Results: Patients with NPH had higher levels of left ear extinction than the control and Alzheimer's groups. Sixty-one percent of NPH patients exhibited left ear suppression, compared with 13% of Alzheimer's patients and 17% of controls. Following surgery, NPH patients showed a significant change in the degree of asymmetry in the dichotic listening task., Conclusions: Hydrocephalus was associated with left-ear extinction,which diminished after surgery. Our results may indicate reversible functional damage in the corpus callosum.

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.

The RESCUEicp (Randomized Evaluation of Surgery with Craniectomy for Uncontrollable Elevation of intracranial pressure) study has been established to determine whether decompressive craniectomy has a role in the management of patients with traumatic brain injury and raised intracranial pressure that does not respond to initial treatment measures. We describe the concept of decompressive craniectomy in traumatic brain injury and the rationale and protocol of the RESCUEicp study.

Previous reports have suggested an association between the insertion/deletion (I/D) polymorphism of the angiotensin-converting enzyme (ACE), cardiovascular disease, and cognitive performance. Normal pressure hydrocephalus (NPH) is considered to be an example of reversible dementia although the clinical improvement after shunting varies from subject to subject. An association has been suggested between vascular risk factors and the development of NPH. The ACE plays a major role in vascular pathology and physiology. In the present study we investigated the distribution of an ACE gene insertion/deletion polymorphism in 112 patients diagnosed with NPH and in 124 controls. We also evaluated the role of this genetic polymorphism in cognitive functioning before and following surgery in a subgroup of 72 patients. No differences in genetic or allele distributions were found between patients and healthy subjects, but among patients, carriers of D/D or D/I genotypes obtained less cognitive benefit following shunt surgery, especially on measures of memory and frontal function. Our data support previous findings in other conditions indicating that possession of at least one D allele is associated with poorer cognitive performance.

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.

The aim of our study was to perform and in-depth analysis of several episodes of regional brain hypoxia detected by monitoring brain partial pressure of oxygen (PtiO2) in which simultaneous measurements of cerebral oxygen extraction fraction (O2EF) suggested a normally perfused or even a hyperemic brain. To gain deeper insight into these episodes, we used the model of tissue hypoxia described by Siggaard-Andersen. In 244 simultaneous measurements, 31 episodes (12.7%) of brain hypoxia (PtiO2 < or = 15 mmHg) were detected simultaneously with an O2EF within the normal range or below the lowest normal percentile. Using Siggaard-Andersen methodology, we classified 6 episodes (19%) as high-affinity hypoxia and 25 (81%) as shunt hypoxia or dysperfusion hypoxia. Siggaard-Andersen's comprehensive classification of tissue hypoxia can be used as an integrative model to build coherent algorithms for diagnosing and managing neurocritical patients that are at risk of brain hypoxia due to either intracranial or extracranial conditions.

Objectives: The aims of the study were 1) to assess the degree of agreement between CSF flow dynamics determined by MR and ICP monitoring in the diagnosis of NPH, and 2) to determine the sensitivity and specificity of CSF flow dynamics studied by MR in predicting improvement after shunting., Patients and Methods: A prospective study was carried out in 35 consecutive patients with suspected NPH. CSF velocity (Phase Contrast) through the aqueduct was determined in sagittal plane. Patients were classified as "normal" or hyperdynamic in comparison with a control group of 27 healthy volunteers. Continuous extradural ICP monitoring was performed for at least 72 hours and patients were classified as having active, compensated, or ex-vacuo hydrocephalus. Patients with active or compensated hydrocephalus were shunted., Results: The degree of agreement between MR dynamics and ICP monitoring was 82%. Sensitivity of CSF velocity was 90% and specificity was 50%., Conclusions: The degree of agreement between ICP monitoring and CSF velocity is high. High CSF velocity through the aqueduct is a good predictor of improvement after surgery. However, patients with normal velocity in MR required additional tests before a diagnosis of NPH is ruled out.

Objective: To determine ICP changes in patients with Chiari type I malformation after posterior fossa reconstruction (PFR)., Patients and Methods: We continuously monitored ICP before and after PFR in 12 patients with Chiari I malformation and with an Evans' Index below or equal to 0.33. Mean ICP (epidural sensor) and percentage of B waves were calculated 24 hours before surgery and during the first 7 days after surgery., Results: Mean ICP and percentage of B waves significantly increased after surgery despite a significant increase in the volume of the posterior fossa. The main finding revealed by control CT scans was compression of the quadrigeminal cistern with a reduction in size of the fourth ventricle. In six patients, a small transitory increase in supratentorial ventricular size was found., Conclusions: A transitory increase in ICP is common after PFR. This increase could be explained by an initial reperfusion phenomena in the cerebellum that provokes a transitory deterioration in CSF dynamics. The effacement of the quadrigeminal cistern and the reduction in size of the fourth ventricle suggests this hypothesis.

The adequate management of cerebral perfusion pressure (CPP) continues to be a controversial issue in head-injured patients. The purpose of our study was to test two hypotheses. The first was that in patients with a CPP below 70 mm Hg, oxygen delivery is compromised and that therefore signs of tissue hypoxia would be reflected in low PtiO2 measurements. The second hypothesis was that manipulating mean arterial blood pressure to increase CPP improves oxygen delivery, particularly in patients with a CPP below 70 mm Hg. Twenty-five moderately or severely head-injured patients were included in the study. In all of them PtiO2 was monitored in the non-injured hemisphere using the Licox system (GMS, Kiel-Mielkendorf, Germany). Arterial hypertension was induced with phenylephrine 29 times. To quantify the effect of increasing mean arterial blood pressure (MABP) on oxygen delivery to the brain, the PtiO2-BP index was calculated (PtiO2-BP index = delta PtiO2/delta MABP). In 16 tests (55%) baseline CPP was above or equal to 70 mm Hg and in the remaining 13 (45%) it was below 70 mm Hg. Mean increase in MABP after phenylephrine was 23.7 +/- 10.2 mm Hg. Mean PtiO2 was 29.5 +/- 14.7 mm Hg in patients with a basal CPP of below 70 mm Hg and 28.9 +/- 10.6 mm Hg in patients in the high CPP group. These differences being not statistically significant. The PtiO2-BP index was 0.29 +/- 0.23 in patients with a basal CPP of below 70 mm Hg and in patients with a CPP of above 70 mm Hg this index was 0.16 +/- 0.11 Hg. These differences were not statistically significant (Student's t-test, P = 0.09). In our study a low PtiO2 was not observed in patients with marginally low CPPs (48-70 mm Hg) and readings below 15 mm Hg were observed in cases with both normal or supranormal CPPs. We conclude that episodes of low PtiO2 could not be predicted on the basis of CPP alone. On the other hand, raising CPP did not increase oxygen availability in the majority of cases, even if the CPP was markedly improved.

False autoregulation has been described as an alteration of autoregulation in which the apparent maintenance of a constant cerebral blood flow (CBF) when increasing cerebral perfusion pressure (CPP) is due to an increase in brain tissue pressure. The objective of our study was to investigate how often false autoregulation occurred in patients with a severe head injury. In forty-six patients with a moderate or severe head injury autoregulation was studied using arteriojugular differences of oxygen (AVDO2) to estimate changes in CBF after inducing arterial hypertension with phenylephrine. Changes in mean arterial blood pressure (MABP), intracranial pressure (ICP), cerebral perfusion pressure (CPP) and AVDO2 were calculated before and after inducing hypertension. Ninety-five episodes of provoked hypertension were studied in 46 patients. In 28 tests (29.5%) a constant or even reduced CBF was detected simultaneously with a median increase in parenchymal ICP of 8.5 mm Hg (false autoregulation). In this group the median of the induced increase in MABP was 20.6 mm Hg with a median increase in CPP of 11.5 mm Hg. From our data we can conclude that false autoregulation is frequently found in patients after a severe head injury. Increasing MABP to obtain a better CPP in these patients is not beneficial because CBF is not modified or may even be reduced.

The present study was undertaken to elucidate the status of autoregulation and CO2-reactivity soon after injury in patients with a post-traumatic diffuse bilateral brain swelling. A prospective study was carried out in 31 consecutively admitted patients with a severe head injury and a Diffuse Brain Injury type III, following the definition stated by the Traumatic Coma Data Bank classification. To evaluate CO2-reactivity, AVDO2 was measured before and after ventilator manipulations. Assuming a constant CMRO2 during the test, changes in 1/AVDO2 reflect changes in CBF. Patients with changes in estimated CBF below or equal to 1% were included in the impaired/abolished CO2-reactivity group. To test autoregulation, hypertension was induced using phenylephrine. Arterial and jugular blood samples were taken to calculate AVDO2 before and after a steady state of MABP was obtained. Cerebrovascular response to CO2 was globally preserved in all but two cases (6.5%). In contrast, autoregulation was globally preserved in 10 (32.3%) and impaired/abolished in 21 cases (67.7%). Our data do not support the premise that increasing cerebral perfusion pressure by inducing arterial hypertension is beneficial in those patients with a diffuse brain swelling in whom autoregulation is impaired or abolished. Clinical implications for treatment are discussed.

Unlabelled: Intracranial hypertension (ICH) is a frequent finding in patients with a severe head injury. High intracranial pressure (ICP) has been associated with certain computerized tomography (CT) abnormalities. The classification proposed by Marshall et al. based on CT scan findings, uses the status of the mesencephalic cisterns, the degree of midline shift, and the presence or absence of focal lesions to categorize the patients into different prognostic groups. Our aim in this study was to analyze the ICP evolution pattern in the different groups of lesions of this classification., Patients and Methods: We present the results of a prospective study in 94 patients with severe head injury, in whom ICP was monitored for at least 6 hours. ICP evolution was classified into three different categories: 1) ICP always < 20 mm Hg, 2) Intracranial hypertension at some time during monitoring, but controlled by medical or surgical treatment, 3) Uncontrollable ICP. The ICP pattern was correlated with the final CT diagnostic category., Conclusions: 3 patients had a normal CT scan, and none of them presented intracranial hypertension. In diffuse injury type II, the ICP evolution may be quite different. Patients with bilateral brain swelling (Diffuse Injury III) have a high risk of increased ICP (63.2%). Although in our study the frequency of Diffuse Injury IV was low, all patients in this category had a refractory ICP. In the category of evacuated mass lesions, two thirds of the patients presented an intracranial hypertension. In one third, ICP was refractory to treatment. 85% of patients with a non-evacuated mass lesion showed an increased ICP.

Despite opioids are routinely used for analgesia in head injured patients, the effects of such drugs on ICP and cerebral hemodynamics remain controversial. Cerebrovascular autoregulation (CAR) could be an important factor in the ICP increases reported after opioid administration. In order to describe the effects on intracranial pressure of fentanyl and correlated such effects with autoregulation status, we studied 30 consecutive severe head injury patients who received fentanyl (2 micrograms/kg) intravenously over one minute. Prior to study, CAR was assessed. Monitoring included MAP, HR, SaO2, ETCO2, SjO2 and ICP. Changes in cerebral blood flow (CBF) were estimated from relative changes in AVDO2. Patients mean GCS was 5.7 +/- 1.7 (mean +/- STD) and mean ICP on admission was 23.8 +/- 16.3 mmHg. Fentanyl caused significant increases in ICP and decreases in MAP and CPP, but CBF remained unchanged when estimated by AVDO2. In patients with preserved CAR (34.5%), opioid-induced ICP increase was greater (but not statistically significant) than in those with impaired CAR (65.5%). We conclude than fentanyl moderately increased ICP and decreased MAP and CPP. Our data suggests that in patients with preserved CAR, potent opioids could cause greater increases of ICP, probably due to activation of the vasodilatadory cascade.

Hyperventilation (HV) is routinely used in the management of increased intracranial pressure (ICP) in severe head injury. However, this treatment continues to be controversial because it has been reported that long-lasting reduced cerebral blood flow (CBF) due to profound sustained hypocapnia may contribute to the development or deterioration of ischemic lesions. Our goal in this study was to analyze the effects of sustained hyperventilation on cerebral hemodynamics (CBF, ICP) and metabolism (arterio jugular differences of lactates = AVDL). CO2-reactivity and CBF was estimated using AVDO2 (arteriojugular differences of oxygen content). Global cerebral ischemia and increased anaerobic metabolism were considered according to AVDO2 and AVDL respectively. Thirty-three patients with severe and moderate head injury and increased ICP were included. Within 72 hours after accident, patients were hyperventilated for a period of 4 hours. During this time jugular oxygen saturation (SjO2), arterial oxygen saturation (SaO2), ICP, mean arterial blood pressure (MABP), AVDO2 and AVDL were recorded. In our study, most patients preserved CO2-reactivity (88.2%). In these cases HV was very effective in lowering ICP. Our findings showed that this reduction was due to a CBF decrease. According to basal AVDO2 twenty-five patients (75.7%) were considered as hyperemic and eight (24.2%) as not hyperemic. Global ischemia and increased anaerobic metabolism were detected in one case in the non-hyperemic group. According to AVDO2 and AVDL, no adverse effects were found during four hours of HV in hyperemic patients. Nevertheless, AVDO2 and AVDL are global measurements and might not detect regional ischemia surrounding focal lesions such as contusions and haematomas. We suggest that monitoring of AVDO2 or other haemometabolic variables should be mandatory when sustained HV is used in the management of head injury patients.