Search

Purpose: To assess the impact of the duration and intensity of episodes of increased intracranial pressure on 6-month neurological outcome in adult and paediatric traumatic brain injury., Methods: Analysis of prospectively collected minute-by-minute intracranial pressure and mean arterial blood pressure data of 261 adult and 99 paediatric traumatic brain injury patients from multiple European centres. The relationship of episodes of elevated intracranial pressure (defined as a pressure above a certain threshold during a certain time) with 6-month Glasgow Outcome Scale was visualized in a colour-coded plot., Results: The colour-coded plot illustrates the intuitive concept that episodes of higher intracranial pressure can only be tolerated for shorter durations: the curve that delineates the duration and intensity of those intracranial pressure episodes associated with worse outcome is an approximately exponential decay curve. In children, the curve resembles that of adults, but the delineation between episodes associated with worse outcome occurs at lower intracranial pressure thresholds. Intracranial pressures above 20 mmHg lasting longer than 37 min in adults, and longer than 8 min in children, are associated with worse outcomes. In a multivariate model, together with known baseline risk factors for outcome in severe traumatic brain injury, the cumulative intracranial pressure-time burden is independently associated with mortality. When cerebrovascular autoregulation, assessed with the low-frequency autoregulation index, is impaired, the ability to tolerate elevated intracranial pressures is reduced. When the cerebral perfusion pressure is below 50 mmHg, all intracranial pressure insults, regardless of duration, are associated with worse outcome., Conclusions: The intracranial pressure-time burden associated with worse outcome is visualised in a colour-coded plot. In children, secondary injury occurs at lower intracranial pressure thresholds as compared to adults. Impaired cerebrovascular autoregulation reduces the ability to tolerate intracranial pressure insults. Thus, 50 mmHg might be the lower acceptable threshold for cerebral perfusion pressure.

Background: Retinal hemorrhages (RHs) occur in inflicted traumatic brain injury (ITBI), accidental traumatic brain injury (ATBI), and some medical conditions, although the reported number, distribution, type, and frequency vary greatly between these different etiologies. We hypothesize that these RH characteristics reliably help to distinguish ITBI from ATBI and nontraumatic etiologies., Methods: A 6-year prospective observational study using wide-field retinal imaging (RetCam) was conducted within 24 hours of admission to PICU, on serially recruited children with traumatic and nontraumatic encephalopathies. "Definite" and "probable" ITBI cases were confirmed by multiagency child protection case conferences. Image analysis used digital color and grayscale images for retinal "zoning" and "layering" of hemorrhages., Results: Significant differences were found between the mean numbers of hemorrhages in ATBI/ITBI, and ITBI/nontraumatic etiologies for the 3 retinal zones (range, P = .003-.009) and for the dot-blot hemorrhages (range P = .001-.002). The mean numbers of RHs per ITBI patient in the peripapillary, macula, and peripheral zones were 14, 28, and 31 respectively. RHs in ATBI were near the optic disc and more superficial than in ITBI, where hemorrhages involved deeper layers (range, P = .003-.039) and were more peripheral (P = .03). The positive predictive value for ITBI in children <3 years with >25 dot-blot (intraretinal) hemorrhages was 93%., Conclusions: This prospective study, which included all potential causes of RHs, with objective retinal methodology, has confirmed that a young age and a high dot-blot count are strong predictors of ITBI. This high predictive value may support medicolegal deliberations.

This study aims to determine if pairing the Glasgow Coma Scale (GCS) with serum biomarker levels may achieve higher outcome predictive values than using either the GCS or biomarker levels alone in childhood brain trauma. Twenty-eight critically ill children with isolated accidental brain trauma were studied in a prospective observational study. The GCS was recorded at various time points post injury. Enzyme-linked immunosorbent assay (ELISA) was used to quantify eight different serum biomarker levels (S100b, NSE, IL-6, IL-8, IL-10, L-selectin, SICAM, and endothelin) on day 1 post injury. The Glasgow Outcome Score (GOS) was used to assess global outcome at 6 months post injury. Outcome predictive values of the GCS, individual biomarker levels, and paired combinations of the GCS and biomarkers were compared using receiver operator characteristic (ROC) curve analysis and its multivariate extension, multivariate ROC curve (MultiROC). When using either the GCS or individual biomarker levels alone to predict unfavorable outcome, only the PICU discharge summated GCS achieved an area under the ROC curve (AUC) of more than 0.95. This high degree of outcome predictability was also achieved by pairing the GCS with a single biomarker level. The most pronounced improvement in outcome prediction was observed by pairing the post-resuscitation summated GCS with the day-1 serum IL-8 level, which increased the AUC from 0.78 to 0.98 and the sensitivity and specificity from 75% to 100% and 96% respectively. Paired combinations of the GCS and serum biomarker levels greatly enhanced the accuracy of post-traumatic unfavorable outcome prediction than may be achieved using either the GCS or individual biomarker levels alone.

Objectives: Post-traumatic hypopituitarism is well described amongst adult traumatic brain injury (TBI) survivors. We aimed to determine the prevalence and clinical significance of pituitary dysfunction after head injury in childhood., Design: Retrospective exploratory study., Patients: 33 survivors of accidental head injury (27 boys). Mean (range) age at study was 13·4 years (5·4-21·7 years) and median (range) interval since injury 4·3 years (1·4-7·8 years). Functional outcome at study: 15 good recovery, 16 moderate disability, two severe disability., Measurements: Early morning urine osmolality and basal hormone evaluation were followed by the gonadotrophin releasing hormone (GnRH) and insulin tolerance (n = 25) or glucagon tests (if previous seizures, n = 8). Subjects were not primed. Head injury details were extracted from patient records., Results: No subject had short stature (mean height SD score +0·50, range -1·57 to +3·00). Suboptimal GH responses (<5 μg/l) occurred in six peri-pubertal boys (one with slow growth on follow-up) and one postpubertal adolescent (peak GH 3·2 μg/l). Median peak cortisol responses to insulin tolerance or glucagon tests were 538 and 562 nm. Nine of twenty-five and two of eight subjects had suboptimal responses, respectively, two with high basal cortisol levels. None required routine glucocorticoid replacement. In three, steroid cover was recommended for moderate/severe illness or injury. One boy was prolactin deficient. Other basal endocrine results and GnRH-stimulated LH and FSH were appropriate for age, sex and pubertal stage. Abnormal endocrine findings were unrelated to the severity or other characteristics of TBI or functional outcome., Conclusions: No clinically significant endocrinopathy was identified amongst survivors of accidental childhood TBI, although minor pituitary hormone abnormalities were observed., (© 2010 Blackwell Publishing Ltd.)

Many potential brain trauma biomarkers have been reported, but no previous study has described outcome prediction using combinations of biomarker levels. We aimed to investigate the outcome predictive values of multiple biomarkers from different mediator families and to determine whether combinations of two serum biomarkers may achieve higher outcome predictive values than individual biomarker levels. A prospective observational study was conducted involving 28 children requiring intensive care management following brain trauma. Day 1 post-injury serum concentrations of eight different biomarkers--S100b protein (S100b), neuron-specific enolase (NSE), interleukin-6 (IL-6), interleukin-8 (IL-8), interleukin-10 (IL-10), soluble intracellular adhesion molecule (SICAM), L-selectin, and endothelin--were quantified using enzyme-linked immunosorbent assay (ELISA). Global outcome was assessed at 6 months post-injury using the Glasgow Outcome Score (GOS). Receiver operator characteristic curve (ROC) analysis and its multivariate extension, Multivariate ROC (MultiROC), were used to assess the outcome predictive values of the individual and the paired biomarkers. None of the eight biomarkers assessed individually achieved an area under the ROC curve (AUC) of more than 0.95 for predicting unfavorable outcome, but five of the 20 biomarker pairs assessed had this high degree of outcome predictability. Two combinations using S100b as the "screening marker" and either L-selectin or IL-6 as the "varying marker" achieved an AUC of 0.98, and their specificity and sensitivity for unfavorable outcome prediction were 96% and 100%, respectively. Prognostic pairs combining serum levels of two biomarkers (inflammatory mediators and brain-specific proteins) offer better outcome predictive values for unfavorable outcome after childhood brain trauma than may be achieved using individual marker levels.

Objective: To report the use of high frequency oscillatory ventilation (HFOV) in two children with severe traumatic brain injury and concurrent lung pathology where conventional mechanical ventilation was ineffective., Design: : Case report., Setting: Regional intensive care unit in a pediatric teaching hospital., Patients: Two severely head-injured children (both with postresuscitation Glasgow Coma Scores of 3), one of whom was age 11 yrs and developed an invasive fungal (rhizomucor) pneumonia, while the other age 5 yrs had bilateral lung contusions. Both were treated according to local head injury guidelines, which included conventional ventilation. Despite increasing conventional ventilatory support, CO2 removal became problematic in both cases, making the intracranial pressure control and consequent maintenance of adequate cerebral perfusion pressure difficult. In both patients, a dramatic reduction in intracranial pressure and improvement in cerebral perfusion pressure was observed soon after the use of HFOV. Additionally, inotropic support was weaned by 50% in both children after commencing HFOV. A significant increase in the mean arterial blood pressure occurred in one child with HFOV., Intervention: Use of HFOV as an alternative to conventional mechanical ventilation., Conclusion: HFOV may have utility in the management of selected cases of severe brain trauma with concurrent lung pathology where conventional ventilation is ineffective.

Object: The aim of this study was to compare the effects of two different treatment protocols on physiological characteristics and outcome in patients with brain trauma. One protocol was primarily oriented toward reducing intracranial pressure (ICP), and the other primarily on maintaining cerebral perfusion pressure (CPP)., Methods: A series of 67 patients in Uppsala were treated according to a protocol aimed at keeping ICP less than 20 mm Hg and, as a secondary target, CPP at approximately 60 mm Hg. Another series of 64 patients in Edinburgh were treated according to a protocol aimed primarily at maintaining CPP greater than 70 mm Hg and, secondarily, ICP less than 25 mm Hg for the first 24 hours and 30 mm Hg subsequently. The ICP and CPP insults were assessed as the percentage of monitoring time that ICP was greater than or equal to 20 mm Hg and CPP less than 60 mm Hg, respectively. Pressure reactivity in each patient was assessed based on the slope of the regression line relating mean arterial blood pressure (MABP) to ICP. Outcome was analyzed at 6 months according to the Glasgow Outcome Scale (GOS). The prognostic value of secondary insults and pressure reactivity was determined using linear methods and a neural network. In patients treated according to the CPP-oriented protocol, even short durations of CPP insults were strong predictors of death. In patients treated according to the ICP-oriented protocol, even long durations of CPP insult-mostly in the range of 50 to 60 mm Hg--were significant predictors of favorable outcome (GOS Score 4 or 5). Among those who had undergone ICP-oriented treatment, pressure-passive patients (MABP/ICP slope > or = 0.13) had a better outcome. Among those who had undergone CPP-oriented treatment, the more pressure-active (MABP/ICP slope < 0.13) patients had a better outcome., Conclusion: Based on data from this study, the authors concluded that ICP-oriented therapy should be used in patients whose slope of the MABP/ICP regression line is at least 0.13, that is, in pressure-passive patients. If the slope is less than 0.13, then hypertensive CPP therapy is likely to produce a better outcome.

Object: Decision tree analysis highlights patient subgroups and critical values in variables assessed. Importantly, the results are visually informative and often present clear clinical interpretation about risk factors faced by patients in these subgroups. The aim of this prospective study was to compare results of logistic regression with those of decision tree analysis of an observational, head-injury data set, including a wide range of secondary insults and 12-month outcomes., Methods: One hundred twenty-four adult head-injured patients were studied during their stay in an intensive care unit by using a computerized data collection system. Verified values falling outside threshold limits were analyzed according to insult grade and duration with the aid of logistic regression. A decision tree was automatically produced from root node to target classes (Glasgow Outcome Scale [GOS] score). Among 69 patients, in whom eight insult categories could be assessed, outcome at 12 months was analyzed using logistic regression to determine the relative influence of patient age, admission Glasgow Coma Scale score, Injury Severity Score (ISS), pupillary response on admission, and insult duration. The most significant predictors of mortality in this patient set were duration of hypotensive, pyrexic, and hypoxemic insults. When good and poor outcomes were compared, hypotensive insults and pupillary response on admission were significant. Using decision tree analysis, the authors found that hypotension and low cerebral perfusion pressure (CPP) are the best predictors of death, with a 9.2% improvement in predictive accuracy (PA) over that obtained by simply predicting the largest outcome category as the outcome for each patient. Hypotension was a significant predictor of poor outcome (GOS Score 1-3). Low CPP, patient age, hypocarbia, and pupillary response were also good predictors of outcome (good/poor), with a 5.1% improvement in PA. In certain subgroups of patients pyrexia was a predictor of good outcome., Conclusions: Decision tree analysis confirmed some of the results of logistic regression and challenged others. This investigation shows that there is knowledge to be gained from analyzing observational data with the aid of decision tree analysis.

Aim: To explore the relationship between raised intracranial pressure (RICP) and retinal haemorrhages in traumatic and non-traumatic childhood encephalopathies.Method: A prospective study of 112 children (35 females and 77 males, age range 0.01mo-17y 8.3mo; mean 5y 8.6mo, median 4y 5.6mo) included 57 accidental traumatic brain injuries (ATBIs), 21 inflicted traumatic brain injuries (ITBIs), and 34 non-traumatic encephalopathy cases. Measurements included intracranial pressure (ICP), cerebral perfusion pressure, pressure-time index of ICP, and number, zone, and layer of retinal haemorrhages on retinal imaging.Results: Group I had measured elevated ICP (n=42), Group II had clinical and/or radiological signs of RICP (n=21), and Group III had normal ICP (n=49). In the combined Groups I and II, 38% had retinal haemorrhages. Multiple logistic regression confirmed that the presence of retinal haemorrhages was significantly related to the presence of RICP independent of age and aetiology; however, the occurrence and overall numbers were not significantly related to the specific ICP level. The numbers of intraretinal (nerve-fibre layer and dot blot) retinal haemorrhages were significantly greater in those with RICP. The ITBI population was significantly different from the other combined aetiological categories.Interpretation: The study results indicate a complex RICP/retinal haemorrhage relationship. There was no evidence of existing retinal haemorrhages being exacerbated or new retinal haemorrhages developing during periods of confirmed RICP. [ABSTRACT FROM AUTHOR]

To validate the intracranial pressure (ICP) dose-response visualization plot for the first time in a novel prospectively collected pediatric traumatic brain injury (pTBI) data set from the multi-center, multi-national KidsBrainIT consortium. Prospectively collected minute-by-minute ICP and mean arterial blood pressure time series of 104 pTBI patients were categorized in ICP intensity-duration episodes. These episodes were correlated with the 6-month Glasgow Outcome Score (GOS) and displayed in a color-coded ICP dose-response plot. The influence of cerebrovascular reactivity and cerebral perfusion pressure (CPP) were investigated. The generated ICP dose-response plot on the novel data set was similar to the previously published pediatric plot. This study confirmed that higher ICP episodes were tolerated for a shorter duration of time, with an approximately exponential decay curve delineating the positive and negative association zones. ICP above 20 mm Hg for any duration in time was associated with poor outcome in our patients. Cerebrovascular reactivity state did not influence their respective transition curves above 10 mm Hg ICP. CPP below 50 mm Hg was not tolerated, regardless of ICP and duration, and was associated with worse outcome. The ICP dose-response plot was reproduced in a novel and independent pTBI data set. ICP above 20 mm Hg and CPP below 50 mm Hg for any duration in time were associated with worse outcome. This highlighted a pressing need to reduce pediatric ICP therapeutic thresholds used at the bedside. [ABSTRACT FROM AUTHOR]

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. [ABSTRACT FROM AUTHOR]