From Critical Care Medicine (PMK, MJB), University of Pittsburgh School of Medicine, Pittsburgh, PA; Department of Medical Informatics and Clinical Epidemiology (NC, SC, KP), Oregon Health & Science University, Portland, OR; Barrow Neurological Institute at Phoenix Children's Hospital (PDA), and Pediatric Neurosurgery/ Children' Neurosciences (PDA), Phoenix, AZ; Division of Child Neurology, Department of Pediatrics (SA) and Section of Neuroradiology (KAT), Loma Linda University School of Medicine, Loma Linda, CA; Pediatric Critical Care Medicine (SB), University of Utah School of Medicine, Salt Lake City, UT; Department of Neurological Surgery (NRS), Oregon Health & Science University, Portland, OR; Orthopedics and Sports Medicine (RMC), University of Washington School of Medicine, Seattle, WA; Neurological Surgery (JG), Weill Cornell Medical College; President of the Brain Trauma Foundation (JG), New York, NY; Translational Science (BG), Ikaria, Inc., Clinton, NJ; Pediatrics (BG), University of Medicine and Dentistry of New Jersey, Robert Wood Johnson Medical School, New Brunswick, NJ; Surgery and Pediatrics (GAG), Duke University School of Medicine, Durham, NC; Pediatrics and Emergency Medicine (NK), British Columbia's Children's Hospital, University of British Columbia, Vancouver, BC; Neurocritical Care (RCT), Children's Hospital Boston; Neurology and Anesthesia (RCT), Harvard Medical School, Boston, MA; Anesthesiology and Pediatrics (MSV), University of Washington School of Medicine, Seattle, WA; Molecular Pharmacology and Biological Chemistry (MSW), Northwestern University Feinberg School of Medicine, Chicago, IL; Emergency Medicine and Pediatrics (CRW), and Pediatric Emergency Services (CRW), Oregon Health & Science University/Doernbercher Children's Hospital, Portland, OR.
Funding provided by the Brain Trauma Foundation and partial funding from the Charles Maddock Foundation.
The authors have not disclosed any potential conflicts of interest.
For information regarding this article, E-mail: email@example.com
This is the second edition of the Guidelines for the Acute Medical Management of Severe Traumatic Brain Injury in Infants, Children, and Adolescents. The first edition was published in 2003, >8 yrs ago (1). Writing the initial guidelines was an exciting but humbling experience, because it quickly became apparent that, based on the available literature, it would be difficult to make recommendations above level III for most categories. Despite this challenge, the guidelines committee maintained its commitment to produce an evidence-based document and did not comingle consensus when crafting the recommendations. It was clear that one of the major contributions of the document would be to identify key gaps in the literature as targets for future research.
For the second edition we were optimistic that sufficient new studies about pediatric traumatic brain injury (TBI) had been generated since 2003 to support a document with higher level evidence and stronger recommendations than the first edition. Without question, several valuable new reports in pediatric TBI have been published since 2003, including randomized controlled trials of hypothermia, additional reports investigating and/or describing optimal cerebral perfusion pressure in children, brain tissue oxygen monitoring, nutrition, cerebrospinal fluid drainage, and the impact of hypocarbia, among others (2–12).
After rigorous application of the criteria for including studies that were prespecified by the guidelines committee, we found 27 new publications for the second edition. However, 25 publications that were included in the 2003 document failed to meet the more rigorous criteria in this second edition (Appendix A). Key reasons for excluding publications were 1) no clear specification of admission Glasgow Coma Scale score; 2) inclusion of patients with pathologies other than severe TBI; 3) inclusion of adult patients without analysis of data by age; and 4) failure to include a relevant health outcome such as mortality or function or even an important surrogate outcome such as intracranial pressure. For example, a recent study by Bar-Joseph et al (13) on the use of ketamine as a sedative in pediatric brain injury could not be included as evidence because the admission Glasgow Coma Scale was not specified, and the sample included children with pathologies other than severe TBI.
It is important to distinguish between inclusion criteria and quality criteria. Publications were not excluded based on their quality. The purposes of the inclusion criteria were to 1) clearly define the target patient population; 2) identify the independent variables (treatments) and dependent variables (outcomes); 3) identify the scope of the treatment phases; and 4) use sample sizes and study designs capable of providing a baseline level of data (see “Methods” section). All publications meeting these criteria, regardless of their quality, were included in the final library and constitute the body of evidence. If a publication did not meet these criteria, regardless of its quality, it was excluded.
After identification as “included,” each study was then assessed for its quality based on the quality criteria provided in detail in the “Methods” section. The purpose of the quality criteria is to determine the potential for bias and uncontrolled confounding based on 1) study design; and 2) flaws in the conduct of the studies. Regardless of quality (class I, II, or III), all included studies were used as evidence. However, the level and strength of the recommendations were derived from the quality of the overall body of evidence used to address each topic.
We rated the quality of randomized controlled trials using predefined criteria designed to assess study design factors that are widely accepted as important indicators of internal validity: use of adequate randomization, allocation concealment, and blinding methods; similarity of compared groups at baseline; maintenance of comparable groups; use of an intention-to-treat analysis; overall follow-up rate of ≥85%; and no differential loss to follow-up. We used separate predefined criteria to rate the quality of cohort and case–control studies designed to reflect the most important aspects of those study designs: nonbiased patient selection methods, identification and ascertainment of events, adequate sample size, follow-up rate of at least 85%, and use of adequate statistical methods to control for potentially confounding variables.
One of the major problems in crafting guidelines in many fields, and in particular in pediatric TBI, is the lack of Utstein-stylea data collection for key parameters in the published studies. This resulted in the inability to include otherwise valuable studies as evidence in this document. Lack of Utstein-style data collection also created other difficulties. For example, data on intracranial pressure were collected and/or reported by investigators in a number of manners such as peak value, mean value, or number of values greater than a given threshold. This lack of a systematic approach to data collection and reporting created important problems in a number of chapters for our committee to generate cogent recommendations. Until we have an Utstein-style template for pediatric TBI that is widely accepted and used to conduct research, we strongly encourage the TBI community to consider use of the inclusion and quality criteria specified in these guidelines when designing studies.
There are several new additions and/or modifications to the second edition: 1) The levels of recommendation were changed from “standard, guideline, and option” to “level I, level II, and level III,” respectively; 2) new chapters include Advanced Neuromonitoring and Neuroimaging with the focus of these additions on management rather than diagnosis or prognosis; 3) chapters from the first edition which were eliminated from the second edition include Trauma Systems, Prehospital Airway Management,b Resuscitation of Blood Pressure and Oxygenation,c Intracranial Pressure Monitoring Technology,d and the Critical Pathway for Treatment of Intracranial Hypertensione'; 4) broader representation on the committee of the relevant specialties in the field, including pediatric anesthesiology, child neurology, and neuroradiology; and 5) international representation on the guidelines committee includes Drs. Kissoon and Tasker.
As indicated, some publications included in the first edition were eliminated, because the methods team found they did not meet criteria (Appendix A, publications from the first edition not included in the second edition).
Table 1 summarizes changes in the recommendations from the first edition to the second edition of these guidelines.
The field is moving forward and it is clear that with advances in neuromonitoring and imaging and the publication, subsequent to the first edition of the guidelines, of the results of the first major multicentered randomized controlled trials in pediatric TBI, we are on the right track. Given the importance of severe TBI to the overall burden of childhood morbidity and mortality, we hope that these new guidelines aid caregivers and stimulate the pediatric TBI community to generate additional answers.
The authors thank the 14 external peer reviewers who further improved the quality of this document through independent review, including Drs. Mark Dias, Richard Ellenbogen, Stuart Friess, Jeffrey Greenfield, Ann-Marie Guerguerian, Mary Hartman, Mark Helfaer, John Kuluz, Yi-Chen Lai, Leon Moores, Jose Pineda, Paul Shore, Kimberley Statler-Bennett, and Michael Whalen. The authors also thank Dr. Hector Wong, who served as the guest editor of this document for Pediatric Critical Care Medicine. Finally, we are extremely grateful to the Brain Trauma Foundation for taking on this project and providing the resources necessary to ensure its success and for their commitment to improving the care of infants, children, and adolescents with severe TBI.
a The Utstein style is a set of guidelines for uniform reporting that has been used by the American Heart Association and other organizations for reporting of cases of cardiac arrest. The name derives from the location of a consensus conference held at the Utstein Abbey in Norway. This standardized approach has greatly facilitated research and registry development in the field of resuscitation medicine. Cited Here...
b Prehospital treatment of pediatric patients with TBI is addressed in the Guidelines for Prehospital Management of Severe Traumatic Brain Injury (14). Cited Here...
c There were no publications that met the inclusion criteria for this topic. Cited Here...
d This topic is addressed in the Guidelines for the Management of Severe Traumatic Brain Injury, Third Edition (15). Cited Here...
e The critical pathway will be developed and published as a separate document. Cited Here...
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