Nancy Carney

A Trial of Intracranial-Pressure Monitoring in Traumatic Brain Injury

BACKGROUND Intracranial-pressure monitoring is considered the standard of care for severe traumatic brain injury and is used frequently, but the efficacy of treatment based on monitoring in improving the outcome has not been rigorously assessed. METHODS We conducted a multicenter, controlled trial in which 324 patients 13 years of age or older who had severe traumatic brain injury and were being treated in intensive care units (ICUs) in Bolivia or Ecuador were randomly assigned to one of two specific protocols: guidelines-based management in which a protocol for monitoring intraparenchymal intracranial pressure was used (pressure-monitoring group) or a protocol in which treatment was based on imaging and clinical examination (imaging-clinical examination group). The primary outcome was a composite of survival time, impaired consciousness, and functional status at 3 months and 6 months and neuropsychological status at 6 months; neuropsychological status was assessed by an examiner who was unaware of protocol assignment. This composite measure was based on performance across 21 measures of functional and cognitive status and calculated as a percentile (with 0 indicating the worst performance, and 100 the best performance). RESULTS There was no significant between-group difference in the primary outcome, a composite measure based on percentile performance across 21 measures of functional and cognitive status (score, 56 in the pressure-monitoring group vs. 53 in the imaging-clinical examination group; P=0.49). Six-month mortality was 39% in the pressure-monitoring group and 41% in the imaging-clinical examination group (P=0.60). The median length of stay in the ICU was similar in the two groups (12 days in the pressure-monitoring group and 9 days in the imaging-clinical examination group; P=0.25), although the number of days of brain-specific treatments (e.g., administration of hyperosmolar fluids and the use of hyperventilation) in the ICU was higher in the imaging-clinical examination group than in the pressure-monitoring group (4.8 vs. 3.4, P=0.002). The distribution of serious adverse events was similar in the two groups. CONCLUSIONS For patients with severe traumatic brain injury, care focused on maintaining monitored intracranial pressure at 20 mm Hg or less was not shown to be superior to care based on imaging and clinical examination. (Funded by the National Institutes of Health and others; ClinicalTrials.gov number, NCT01068522.).

Guidelines for the acute medical management of severe traumatic brain injury in infants, children, and adolescents--second edition.

Author Affiliations Patrick M. Kochanek, MD, FCCM, Professor and Vice Chair, Department of Critical Care Medicine, University of Pittsburgh School of Medicine Nancy Carney, PhD, Associate Professor, Department of Medical Informatics and Clinical Epidemiology, Oregon Health & Science University P. David Adelson, MD, FACS, FAAP, Director, Barrow Neurological Institute at Phoenix Children’s Hospital, Chief, Pediatric Neurosurgery/ Children’s Neurosciences Stephen Ashwal, MD, Distinguished Professor of Pediatrics and Neurology, Chief of the Division of Child Neurology, Department of Pediatrics, Loma Linda University School of Medicine Michael J. Bell, MD, Associate Professor of Critical Care Medicine, University of Pittsburgh School of Medicine Susan Bratton, MD, MPH, FAAP, Professor of Pediatric Critical Care Medicine, University of Utah School of Medicine Susan Carson, MPH, Senior Research Associate, Department of Medical Informatics and Clinical Epidemiology, Oregon Health & Science University Randall M. Chesnut, MD, FCCM, FACS, Professor of Neurological Surgery, Orthopedics and Sports Medicine, University of Washington School of Medicine Jamshid Ghajar, MD, PhD, FACS, Clinical Professor of Neurological Surgery, Weill Cornell Medical College, President of the Brain Trauma Foundation Brahm Goldstein, MD, FAAP, FCCM, Senior Medical Director, Clinical Research, Ikaria, Inc., Professor of Pediatrics, University of Medicine and Dentistry of New Jersey, Robert Wood Johnson Medical School Gerald A. Grant, MD, Associate Professor of Surgery and Pediatrics, Duke University School of Medicine Niranjan Kissoon, MD, FAAP, FCCM, Professor of Paediatrics and Emergency Medicine, British Columbia’s Children’s Hospital, University of British Columbia Kimberly Peterson, BSc, Research Associate, Department of Medical Informatics and Clinical Epidemiology, Oregon Health & Science University Nathan R. Selden, MD, PhD, FACS, FAAP, Campagna Professor and Vice Chair of Neurological Surgery, Oregon Health & Science University Robert C. Tasker, MBBS, MD, FRCP, Chair and Director, Neurocritical Care, Children’s Hospital Boston, Professor of Neurology and Anesthesia, Harvard Medical School Karen A. Tong, MD, Associate Professor of Radiology, Loma Linda University Monica S. Vavilala, MD, Professor of Anesthesiology and Pediatrics, University of Washington School of Medicine Mark S. Wainwright, MD, PhD, Director, Pediatric Neurocritical Care, Associate Professor of Pediatrics, Northwestern University Feinberg School of Medicine Craig R. Warden, MD, MPH, MS, Professor of Emergency Medicine and Pediatrics, Chief, Pediatric Emergency Services, Oregon Health & Science University/Doernbecher Children’s Hospital

Guidelines for the Management of Severe Traumatic Brain Injury, Fourth Edition.

The scope and purpose of this work is 2-fold: to synthesize the available evidence and to translate it into recommendations. This document provides recommendations only when there is evidence to support them. As such, they do not constitute a complete protocol for clinical use. Our intention is that these recommendations be used by others to develop treatment protocols, which necessarily need to incorporate consensus and clinical judgment in areas where current evidence is lacking or insufficient. We think it is important to have evidence-based recommendations to clarify what aspects of practice currently can and cannot be supported by evidence, to encourage use of evidence-based treatments that exist, and to encourage creativity in treatment and research in areas where evidence does not exist. The communities of neurosurgery and neuro-intensive care have been early pioneers and supporters of evidence-based medicine and plan to continue in this endeavor. The complete guideline document, which summarizes and evaluates the literature for each topic, and supplemental appendices (A-I) are available online at https://www.braintrauma.org/coma/guidelines.

Effect of cognitive rehabilitation on outcomes for persons with traumatic brain injury: A systematic review

We evaluated evidence for the effectiveness of cognitive rehabilitation methods to improve outcomes for persons with traumatic brain injury (TBI). A search of MEDLINE, HealthSTAR, CINAHL, PsycINFO, and the Cochrane Library produced 600 potential references. Thirty-two studies met predetermined inclusion criteria and were abstracted; data from 24 were placed into evidence tables. Two randomized controlled trials and one observational study provided evidence that specific forms of cognitive rehabilitation reduce memory failures and anxiety, and improve self-concept and interpersonal relationships for persons with TBI. The durability and clinical relevance of these findings is not established. Future research utilizing control groups and multivariate analysis must incorporate subject variability and must include standard definitions of the intervention and relevant outcome measures that reflect health and function.

Hypothermia Treatment for Traumatic Brain Injury: A Systematic Review and Meta-Analysis

In this study, we conducted an updated meta-analysis of the effects of hypothermia therapy on mortality, favorable neurologic outcome, and associated adverse effects in adults with traumatic brain injury (TBI) for use by Brain Trauma Foundation (BTF)/American Association of Neurological Surgeons (AANS) task force to develop evidence-based treatment guidelines. Our data sources relied on handsearches of four previous good-quality systematic reviews, which all conducted electronic searches of primarily MEDLINE (OVID), EMBASE, and Cochrane Library. An independent, supplemental electronic search of MEDLINE was undertaken as well (last searched June 2007). Only English-language publications of randomized controlled trials of therapeutic hypothermia in adults with TBI were selected for analysis. Two reviewers independently abstracted data on trial design, patient population, hypothermia and cointervention protocols, patient outcomes, and aspects of methodological quality. Pooled relative risks (RR) and associated 95% confidence intervals (CIs) were calculated for each outcome using random-effects models. In the current study, only 13 trials met eligibility criteria, with a total of 1339 randomized patients. Sensitivity analyses revealed that outcomes were influenced by variations in methodological quality. Consequently, main analyses were conducted based on eight trials that demonstrated the lowest potential for bias (n = 781). Reductions in risk of mortality were greatest (RR 0.51; 95% CI 0.33, 0.79) and favorable neurologic outcomes much more common (RR 1.91; 95% CI 1.28, 2.85) when hypothermia was maintained for more than 48 h. However, this evidence comes with the suggestion that the potential benefits of hypothermia may likely be offset by a significant increase in risk of pneumonia (RR 2.37; 95% CI 1.37, 4.10). In sum, the present studys updated meta-analysis supports previous findings that hypothermic therapy constitutes a beneficial treatment of TBI in specific circumstances. Accordingly, the BTF/AANS guidelines task force has issued a Level III recommendation for optional and cautious use of hypothermia for adults with TBI.

Guidelines for prehospital management of traumatic brain injury 2nd edition

The information contained in these Guidelines, which reflects the current state of knowledge at the time of completion of the literature search (July 2006), is intended to provide accurate and authoritative information about the subject matter covered. Because there will be future developments in scientific information and technology, it is anticipated that there will be periodic review and updating of these Guidelines. These Guidelines are distributed with the understanding that the Brain Trauma Foundation, the National Highway Traffic Safety Administration, and the other organizations that have collaborated in the development of these Guidelines are not engaged in rendering professional medical services. If medical advice or assistance is required, the services of a competent physician should be sought. The recommendations contained in these Guidelines may not be appropriate for use in all circumstances. The decision to adopt a particular recommendation contained in these Guidelines must be based on the judgment of medical personnel, who take into consideration the facts and circumstances in each case, and on the available resources.

Increased mortality in patients with severe traumatic brain injury treated without intracranial pressure monitoring

OBJECT Evidence-based guidelines recommend intracranial pressure (ICP) monitoring for patients with severe traumatic brain injury (TBI), but there is limited evidence that monitoring and treating intracranial hypertension reduces mortality. This study uses a large, prospectively collected database to examine the effect on 2-week mortality of ICP reduction therapies administered to patients with severe TBI treated either with or without an ICP monitor. METHODS From a population of 2134 patients with severe TBI (Glasgow Coma Scale [GCS] Score <9), 1446 patients were treated with ICP-lowering therapies. Of those, 1202 had an ICP monitor inserted and 244 were treated without monitoring. Patients were admitted to one of 20 Level I and two Level II trauma centers, part of a New York State quality improvement program administered by the Brain Trauma Foundation between 2000 and 2009. This database also contains information on known independent early prognostic indicators of mortality, including age, admission GCS score, pupillary status, CT scanning findings, and hypotension. RESULTS Age, initial GCS score, hypotension, and CT scan findings were associated with 2-week mortality. In addition, patients of all ages treated with an ICP monitor in place had lower mortality at 2 weeks (p = 0.02) than those treated without an ICP monitor, after adjusting for parameters that independently affect mortality. CONCLUSIONS In patients with severe TBI treated for intracranial hypertension, the use of an ICP monitor is associated with significantly lower mortality when compared with patients treated without an ICP monitor. Based on these findings, the authors conclude that ICP-directed therapy in patients with severe TBI should be guided by ICP monitoring.

Summary report: evidence for the effectiveness of rehabilitation for persons with traumatic brain injury.

We evaluated the evidence for effectiveness of rehabilitation methods throughout the phases of recovery from traumatic brain injury (TBI) in adults. MEDLINE, HealthSTAR, CINAHL, PsycINFO, and the Cochrane Library were searched, and a total of 3,098 abstracts were reviewed. The strongest studies were critically appraised and their data placed in evidence tables. Results showed that to determine the effectiveness of rehabilitation interventions for persons with TBI, a commitment must be made to population-based studies, strong controlled research design, standardization of measures, adequate statistical analysis, and specification of health outcomes of importance to persons with TBI and their families.

Marked reduction in mortality in patients with severe traumatic brain injury.

OBJECT In spite of evidence that use of the Brain Trauma Foundation Guidelines for the Management of Severe Traumatic Brain Injury (Guidelines) would dramatically reduce morbidity and mortality, adherence to these Guidelines remains variable across trauma centers. The authors analyzed 2-week mortality due to severe traumatic brain injury (TBI) from 2001 through 2009 in New York State and examined the trends in adherence to the Guidelines. METHODS The authors calculated trends in adherence to the Guidelines and age-adjusted 2-week mortality rates between January 1, 2001, and December 31, 2009. Univariate and multivariate logistic regression analyses were performed to evaluate the effect of time period on case-fatality. Intracranial pressure (ICP) monitor insertion was modeled in a 2-level hierarchical model using generalized linear mixed effects to allow for clustering by different centers. RESULTS From 2001 to 2009, the case-fatality rate decreased from 22% to 13% (p < 0.0001), a change that remained significant after adjusting for factors that independently predict mortality (adjusted OR 0.52, 95% CI 0.39-0.70; p < 0.0001). Guidelines adherence increased, with the percentage of patients with ICP monitoring increasing from 56% to 75% (p < 0.0001). Adherence to cerebral perfusion pressure treatment thresholds increased from 15% to 48% (p < 0.0001). The proportion of patients having an ICP elevation greater than 25 mm Hg dropped from 42% to 29% (p = 0.0001). CONCLUSIONS There was a significant reduction in TBI mortality between 2001 and 2009 in New York State. Increase in Guidelines adherence occurred at the same time as the pronounced decrease in 2-week mortality and decreased rate of intracranial hypertension, suggesting a causal relationship between Guidelines adherence and improved outcomes. Our findings warrant future investigation to identify methods for increasing and sustaining adherence to evidence-based Guidelines recommendations.

Response to intracranial hypertension treatment as a predictor of death in patients with severe traumatic brain injury.

OBJECT The normalization of increased intracranial pressure (ICP) in patients with severe traumatic brain injury (TBI) is assumed to limit secondary brain injury and improve outcome. Despite evidence-based recommendations for monitoring and treatment of elevated ICP, there are few studies that show an association between response to ICP-directed therapeutic regimens and adjusted mortality rate. This study utilizes a large prospective database to examine the effect of response to ICP-lowering therapy on risk of death within the first 2 weeks of injury in patients who sustained TBI and are older than 16 years. METHODS The current study is based on 1426 patients with severe TBI (Glasgow Coma Scale [GCS] score < 9) of whom 388 were treated for elevated ICP (> 25 mm Hg) between 2000 and 2008 at 22 trauma centers enrolled in a New York State quality improvement program. This prospectively collected database also contains information including age, admission GCS score, pupillary status, CT scanning parameters, and hypotension, which are all known early prognostic indicators of death. Treatment of elevated ICP consisted of administration of mannitol, hypertonic saline, barbiturates, and/or drainage of CSF or decompressive craniectomy. The factors predicting ICP response to treatment and predicting death at 2 weeks were evaluated using logistic regression analyses. RESULTS Increasing age and fewer hours of elevated ICP on Day 1 were found to be significant predictors (p = 0.001 and 0.0003, respectively) of a positive response to treatment. Response to ICP-lowering therapy (p = 0.03), younger age (p < 0.0001), fewer hours of elevated ICP (p < 0.0001), and absence of arterial hypotension on Day 1 (p = 0.001) significantly predicted reduced risk of death. CONCLUSIONS Patients who responded to ICP-lowering treatment had a 64% lower risk of death at 2 weeks than those who did not respond after adjusting for factors that independently predict risk of death.