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Scandinavian guidelines for initial management of minimal, mild and moderate head injuries in adults: An evidence and consensus-based update

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Background The management of minimal, mild and moderate head injuries is still controversial. In 2000, the Scandinavian Neurotrauma Committee (SNC) presented evidence-based guidelines for initial management of these injuries. Since then, considerable new evidence has emerged. Methods General methodology according to the Appraisal of Guidelines for Research and Evaluation (AGREE) II framework and the Grading of Recommendations Assessment, Development and Evaluation (GRADE) system. Systematic evidence-based review according to Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) methodology, based upon relevant clinical questions with respect to patient-important outcomes, including Quality Assessment of Diagnostic Accuracy Studies (QUADAS) and Centre of Evidence Based Medicine (CEBM) quality ratings. Based upon the results, GRADE recommendations, guidelines and discharge instructions were drafted. A modified Delphi approach was used for consensus and relevant clinical stakeholders were consulted. Conclusions We present the updated SNC guidelines for initial management of minimal, mild and moderate head injury in adults including criteria for computed tomography (CT) scan selection, admission and discharge with suggestions for monitoring routines and discharge advice for patients. The guidelines are designed to primarily detect neurosurgical intervention with traumatic CT findings as a secondary goal. For elements lacking good evidence, such as in-hospital monitoring, routines were largely based on consensus. We suggest external validation of the guidelines before widespread clinical use is recommended.
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Scandinavian guidelines for initial management
of minimal, mild and moderate head injuries in
adults: an evidence and consensus-based update
Undén et al.
Undén et al. BMC Medicine 2013, 11:50
http://www.biomedcentral.com/1741-7015/11/50 (25 February 2013)
GUID ELI NE Open Access
Scandinavian guidelines for initial management
of minimal, mild and moderate head injuries in
adults: an evidence and consensus-based update
Johan Undén
1*
, Tor Ingebrigtsen
2
and Bertil Romner
3
, for the Scandinavian Neurotrauma Committee (SNC)
See related commentary article here http://www.biomedcentral.com/1 741-7015/11/51
Abstract
Background: The management of minimal, mild and moderate head injuries is still controversial. In 2000, the
Scandinavian Neurotrauma Committee (SNC) presented evidence-based guide lines for initial management of these
injuries. Since then, considerable new evidence has emerged.
Methods: General methodology according to the Appraisal of Guidelines for Research and Evaluation (AGREE) II
framework and the Grading of Recommendations Assessment, Development and Evaluation (GRADE) system.
Systematic evidence-based review according to Preferred Reporting Items for Systematic Reviews and Meta-
Analyses (PRISMA) methodology, based upon relevant clinical questions with respect to patient-important
outcomes, including Quality Assessment of Diagnostic Accuracy Studies (QUADAS) and Centre of Eviden ce Based
Medicine (CEBM) quality ratings. Based upon the results, GRADE recommendations, guidelines and discharge
instructions were drafted. A modified Delphi approach was used for consensus and relevant clinical stakeholders
were consulted.
Conclusions: We present the updated SNC guidelines for initial management of minimal, mild and moderate head
injury in adults including criteria for computed tomography (CT) scan selection, admission and discharge with
suggestions for monitoring routines and discharge advice for patients. The guidelines ar e design ed to primarily
detect neurosurgical interve ntion with traumatic CT findings as a seconda ry goal. For elements lacking good
evidence, such as in-hospital monitoring, routines were largely based on consensu s. We suggest external validation
of the guidelines before widespread clinical use is recomme nded.
Keywords: computed tomography, GRADE, guidelines, head/brain injury/trauma, management, prediction rule,
routines, S100/S100B/S100BB
Background
Traumatic brain injury (TBI) is one of the most common
reasons f or emergency department (ED) care [1]. Cases
of TBI account for over 1 million visits per year in both
the USA and the UK [2,3] and are responsible for two-
thirds of all trauma deaths [4]. Only a small proportion
of these are classed as severe head injury [1], with a Glas-
gow Coma Scale (GCS) score of 3 to 8. The majority of
patients are instead classed as minimal, mild and
moderat e head injuries [5] and ar e generally conscious in
the ED with varying degrees of neurological symptoms. A
minority of these patients will have intracranial pathology
on computed tomography (CT) scanning and an even
smaller proportion will need neurosurgical intervention
[6,7]. In particular, the inte rmediate risk group of mild
head injury (MHI) has been notoriously difficult to man-
age as these patients have a very low, but not negligi ble,
risk of needing neurosurgical intervention [7,8].
Over the past decade, initial management strategies have
become focused on selective CT use based upon presence
or absence of specific aspects of patient history and/or
clinical examination [6,9-11], in order to effectively use
* Correspondence: dr.johan.unden@gmail.com
1
Department of Intensive Care and Perioperative Medicine, Institute for
Clinical Sciences, Södra Förstadsgatan 101, 20502 Malmö, Sweden
Full list of author information is available at the end of the article
Undén et al. BMC Medicine 2013, 11:50
http://www.biomedcentral.com/1741-7015/11/50
© 2013 Undén et al; licensee BioMed Central Ltd. This is an Open Access articl e distribut ed under the terms of the Creat ive Commons
Attribution License (http://creativecommons.org/licenses/by/2.0), which permits unrestricted use, distribution, and reproduction in
any medium, provided the original work is properly cited.
health care resources. This selective management has
received more attention following reports of increased
cancer risks from CT scans, estimated at 1 in 5,000 to
10,000 for a single head CT scan in young adults [12].
Following a normal CT scan after mild head injury,
consensus is generally to discharge patients from the hos-
pital [13,14], although subgroups of patients may still be
at risk of developing delaye d intracranial complication s
of varying significance [15,16].
In 2000, the Scandinavian Neurotrauma Committee
(SNC) presented evidence-based guidelines for the initial
management of minimal, mild a nd moderate head inju-
ries [5]. Alt hough external and independent validation
has shown the guidelines to function favorably [17,18], it
is likely that new evidence exists which needs to be con-
sidered. The SNC has therefore mandated an update of
the guidelines. The aim of the present report is to present
these updated guidelines for adults, including the metho-
dology and considerations behind the workflow.
Methods
The overall policy was to follow the Appraisal of G uide-
lines for Research and Evaluation ( AGREE) II guideline
development framework [19], complemented by the
Grading of Recommendations Assessment, Development
and Evaluation (GRADE) system [20]. Consensus was that
these two aids would result in a transparent and systematic
methodology and the best possible workflow from available
evidence to guideline construction and implementation.
The overall workflow process is shown in Figure 1.
Task force, working group and stakeholders
The SNC consists of neurosurgeons and anesthesiologists
from Scandin avia with expertise in neurotrauma. A task
force was init iated within the SNC, consi sting of three
authors wit h experience within the field (JU, TI, BR), to
propose evidence-based recommendations and a draft for
the updated guidelines. For the consensus stage of devel-
opment, a working group was formed consisting of SNC
members. Important stak eholde rs from gener al surgery,
emergency medicine and orthopedics were also involved
in this process. These specialties initially manage the vast
majority of head injury pati ents in Scandina via. We also
considered including members of the public in the pro-
cess but unanimously decided against this as we did not
believe it would facilitate optimal guideline development
in the present scenario.
Scope, purpose and target population
The objective of the guidelines c reated in the present
work would be to assist ED physicians with initial (the
first 24 h) management of all adult patients with minimal,
mild and moderate head injury, specifically to decide
which patients are to receive CT scanning, admission or
discharge (or combinations of these) from the ED. Head
injury severity was predefined according to the Head
Injury Severity Score (HISS [21]) where minimal repre-
sents patients with a GCS score of 15 and no risk factor s,
mild is a GCS score of 14 or 15 with risk factors (such as
amnesia or loss of consciousness (LOC)) and moderate is
a GCS score of 9 to 13.
The rationale was primarily to identify all patients
needing neurosurgical intervention, i ncluding medica l
intervention for high intracranial pressure (assigned a
critical level with regard to patient-important outcomes).
The secondary goals (assigned important, but n ot c riti-
cal, wit h regar d to patient-import ant out comes) were
identification of non-neurosurgical intracran ial trau-
matic co mplications and also strong consider ation of
resource use with minimizati on of unnecessary (normal)
CT scans and/or admission.
The task force decided a priori to make an attempt to
keep the guidelines applicable to the complete patient
spectrum within EDs, that is, to ensure that a ll adult
patients with minimal, mild and moderate head injury
can be managed according to the guidelines.
Certain assumptions were also made a priori concern-
ing aspects of management that were deemed unneces-
sary for critical review. The task force all agreed that
magnetic resonance imaging (MRI) would not be con-
sidered in these guidelines conc erning initial manage-
ment and that in-hospital observation, instead of CT,
would be r egarded only as a secondary management
option. The use of plain skull films was addressed and
rejected in the previous g uidelines. A dditionally, we
chose not to consider later aspects of management, such
as detection and treatment of post-concussion syndrome
(PCS) and chronic subdural hematomas. We also agreed
that all pathological findings on head CT should lead
to hospital admission. Finally, we would not address
the surgical or medical management of intracranial
complications.
The task force was unclear concerning the selection of
patients for CT scanning or discharge, following minimal,
mild and moderate head injuries. We were also unclear
concerning which patients, irrespective of initial CT scan
results, should have hospital admission for clinical obser-
vation, a repeat CT scan, or both. Theref ore, consensus
was achieved to addr ess two important clinical questions
that would require systematic review of eviden ce and
would form the basis of the updated guidelines, shown
below.
Clinical question 1: Which adult patients with mini-
mal, mild and moderate head injury need a head CT
and which patients may be directly discharged?.
Clinical question 2: Which adult patients with mini-
mal, mild and moderate head injury need in-hospital
observation and/or a repeat head CT?.
Undén et al. BMC Medicine 2013, 11:50
http://www.biomedcentral.com/1741-7015/11/50
Page 2 of 13
Search strategy
In order to address the clinical questions we performed
two separate systematic reviews of the literature, in
accordance to the Preferred Reporting Items for Systema-
tic Reviews and Meta-Analyses (PRISMA) statement [22].
Both utilized broad searches of t he MEDLINE and
EMBASE databases, from 1985 until January 2010 and
then complemented to July 2012, using prespecified
Medical Subject Headings (MeS H) terms and key words
depicted by the task force. MeSH terms were pretested
for vali dity through identification of several key articles.
It was deemed unlikely that studies prior to 1985 would
be useful considering the wide-scale introduction of CT
scanning around this period. We did not ap ply any other
limitations to the search.
For the first clinical question, the MeSH terms and key-
words were; ((head trauma) OR (brain injury) OR (head
injury) OR (traumatic head injury) OR (traumatic brain
injury)) AND (minimal OR mild OR minor OR moder-
ate) AND (management OR predictors OR predictor).
For the second clinical question we used; ((head trauma)
OR (brain injury) OR (head injury) OR (traumatic head
injury) OR (traumatic brain injury)) AND (minimal OR
mild OR minor OR moderate) AND (hospitalization OR
hospitalisation OR observation OR admission OR dis-
charge OR delayed OR ((normal OR negative OR repeat
Literature search
Final Guideline
Literature Selection
Evidence Grading
Evaluation of Clinical
Predictors
Evidence Summary and Draft
Recommendation
Recommendation and
Guideline development
Step in work process
Method Description/Result
PRISMA In text
In text Figures 2 and 3
CEBM Additional files 2 and 4: Tables S2 and S4
QUADAS Additional files 3 and 5: Tables S3 and S5
In text Additional file 1: Table S1
GRADE Table 1
Deplhi process Tables 2, ͵ and Ͷ
In text Additional files 6-7: Figures S1-2
Figure 1 Flow diagram showing the overall work process.
Undén et al. BMC Medicine 2013, 11:50
http://www.biomedcentral.com/1741-7015/11/50
Page 3 of 13
OR multiple OR serial OR follow-up) AND (CT OR CCT
OR computed tomography)).
Additional papers were identified by hand-searching
bibliographies of retrieved studies.
Selection criteria and study eligibility
Titles were examined by one author (JU) and borderline
titl es were included. Titles that were obviously not rele-
vant were excluded. A bstracts were e xamined indepe n-
dently by two authors (JU, BR) and the third (TI) was
consulted when discrepancies arose. Selected full papers
were independently reviewed by all authors (JU, TI, BR)
and discrepancies were resolved through discussion.
Review art icles, letters, expert opi nion and editorials
coul d be retrieved for exa mination of bibliographies but
were excluded from the analysis. Papers reporting only
children (<18 years) were excluded in both searches. In
cases where essential data was missing or unclear, we
made an attempt to contact corresponding authors for
clarification. Studies including patients with all severit ies
of head injury were only inc luded if at least 50% of
patients were within the GCS 9 to 15 range.
For the first c linical ques tion, we included studies
reporting patients with admission/initial GCS scores 9
and that included one or more predictive risk factors for
the reference standards of CT findings, intracranial
injury (ICI) and/or neurosurgical intervention. We
decided apriorito only include stu dies where informa-
tion concerning true positives (TP), false posit ives (FP),
true negatives (TN) and false negatives (FN) could be
extracted. This information would be necessary to fully
appreciate the possible clinical effect and role of a risk
factor, allowing consideration of other effects than the
positive predictive power. Studies reporting less than 50
patients were excluded. Definitions for risk factors were
defined a priori.
For the second clinical question, we included studies
reporting patients with admission/initial GCS scores 9
with an initial CT scan (norma l or abnormal) a nd con-
tained info rmation regarding clinical characteristics that
were associated with a positive or worsening repeat CT
scan, ICI and/or neurosurgical intervention within 1
week following trauma.
CT findings were defined as any traumatic finding on
head CT. ICI was defined as any intracranial ( isolated
non-depressed cranial f ract ures not included ) traumatic
finding on CT. Also, s ince not all patients can be sub-
jected to CT, absence of ICI was defined as relevant and
robust clinical follow-up suggestive of normal neurologi-
cal functioning ( with the exception of classical PCS
symptoms). The decision to consider any CT findings
and ICI as separate reference standards was due to the
difference in cl inical importance of these measures. This
approach should also stratify reference standards in a
more homogenous selection compared to a combined
definition. Finally, neurosurgical intervention was
defined as any neurosurgical procedure for a cranial or
intracranial injury with in the f irst week following
trauma. Medical treatment for elevated intracranial pres-
sure, within the first week f ollowing trauma, was also
included in this group since some patients with diffuse
brain injury cannot be managed surgically.
Data extraction and quality assessment
Data was extracted by one author (JU) and checked by
another (BR). Data was entered into a predefined protocol
and then inputted into Excel (Microsoft; Redmond, WA,
USA). Evidentiary tables were constructed to summaries
the studies. We decided to address the quality of papers in
different phases, due to the nature of the studies and the
phase of assessment. Firstly, all retrieved studies w ere
independent ly graded by all authors in the task force (JU,
TI, BR) according to the Centre of Evidence Based Medi-
cine (CEBM) diagnosis criteria [23]. Discrepancies in grad-
ing were resolved through discussion. Quality ratings
ranged from 1 (strongest evidence, for instance reports of
clinical decision rules and high quality validation studies)
to 5 (weakest evidence, oftenexpertopinion).Studies
receiving CEBM scores of 5 were excluded.
Studies were then graded according to the Quality
Assessment of Diagnostic Accuracy Studies (QUADAS)
tool [24], which was modified for the purpose of the
review. This tool considers 14 criteria relevant to diagnos-
tic studies accounting for bias (items 3 to 7, 10 to 12),
variability (items 1 and 2) and reporting (items 8 and 9).
Items 4 (regarding the time period between index and
reference test) and 7 (regarding the inde pend ency of the
reference test) wer e omitted with regard to the selection
criteria and the previously applied CEBM criteria. Addi-
tionally, item 3 (regarding the ability of the reference test
to correctly classify the target condition) was applied to
CT findings, ICI and neurosurgery separately.
Data analysis
Although extracted data regarding the first clinical ques-
tion, predictors of CT f indings, ICI and neurosurgery,
could theoretically be summarized in a meta-analysis, the
task force decided apriorinot to perform such an analysis
for the purpose of development of the guidelines, indepen-
dent of heterogeneity between studies. We felt combining
the d ata in this way could mislead the working group in
the consensus process and opted to instead present
uncombined data for studies including their quality assess-
ment. We therefo re calculated individual positive likeli-
hood ratios (PLR) and negative likelihood ratios (NLR) for
each risk factor with respect to the corresponding refer-
ence test (CT, ICI or neurosurgery) and the prevalence
of both the reference test and the risk factor in the
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population. We felt that these indices would represent the
most relevant clinical applications for the working group
when considering the recommendations. For the second
clinical question, we presented only descriptive analysis.
Evidence summary and recommendations draft
Recommendations were formed by the task force (JU, TI,
BR)basedupontheevidenceinaccordancewiththe
GRADE system [ 20,25]. This system is increasingly been
used in the development of recommend ations and allows
consideration of aspects other than level of evidence in
determining the strength of a recommendation [25].
Clinical predictors were chosen based upon the summar-
ized evidence (see Additional fi le 1, Table S1). Focus was
put on the more severe outcome variables (need for neu-
rosurgery being of critical importance), but ICI and any
CT findings were also c onsidered, especially in cases
where the evidence concerning neurosurgery was poor
and/or inconsistent. We also considered the prevalence
of the risk factors in the studied cohorts. Risk factors
relatively co mmon in a population would lead to many
CT scans and these risk factors would therefore need to
show high predictive abilities to be included.
The summarized quality of evidence, from studies
forming the basis of a recomm endation, was graded from
high quality to very low quality, see Table 1. Evidence
was initially considered high quality when derived from
cohort studies reporting patients with diagnostic uncer-
tainty and appropriate reference standards, as described
earlier. Evidence could be downgraded due to risk of bias
(selection (population indirectness), verification, observer
and reporting), outcome indirectness (balance between
the presumed influence on patient outcome of the test
result (combination of risk factors) in relation to the
complications and resource use of the test), inconsistency
(large differences in prevalence of reference tests, preva-
lence of risk f actors, PLR or NLR) or differing general
results between studies), impreciseness (studies with
small number of patients and few positive CT, ICI or
neurosurgery events) and suspicion of publication bias
(small number of studies, industry funding).
Recommendations, relating to the clinical questions,
were classed as strong (we recommend...), weak (w e
suggest...) or uncertain (we cannot recommend...) (see
Table 1). For this process, careful consideration was again
made to risk/benefit aspects of patient-important outcomes
(need for neurosurgery was classed as the most important)
in relation to test results, including assumptions for pretest
probabilities (different magnitudes of risk for a positive
reference result of CT, ICI or neurosurgery) for different
patients, quality of evidence, uncertainty of the preferences
and values for outcomes and the use of health care
resources. Therefore, it is theoretically possible to achieve a
strong recommendation despite low quality evidence or vice
versa.
Recommendations and guideline development
Based upon the recommendations, a draft for the updated
guidelines was constructed by the task force. Following
this, a modified Delphi process w as used [26], involving
the working grou p previously described, consisting o f at
least two rounds of consensus. The aprioricriteria to
determine acceptance, rejection or lack of consensus are
shown in Table 2. In the first round, the recommenda-
tions, including data from included studies with CEBM,
QUADAS and GRADE evaluations together with a guide-
line draft were sent via email to the working group.
Ratings, including feedback, were anonym ously collected.
The task force adjusted the recommendations and draft
based upon the se responses. Then, in conjunction with a
2-day SNC meeting in September 2012 outside Copenha-
gen, Denmark, results were discussed and suggestions for
improvements made. Following this, the second round of
Delh i was completed via email. Additional rounds would
be undertaken if necessary. The task force and working
group were urged to consider the GRADE aspects pre-
viously mentioned, espe cially health risk/benefit aspects
including resource use, as well as side effects and risks
(misclassification of patients), at all stages of development.
The final guidel ines w ere evaluated, independently of
the task force an d working group, in the ED of Skane
University Hospital, Malmo, Sweden, to judge clarity o f
presentation and ease of use. Simultaneously, the guide-
lines were evaluated by importa nt stakeholders from
specialties directly involved in the everyday management
of these patients. Feedback was documented and appro-
priate changes were made, if necessary, but only to con-
sensus aspects. Finally, the working group reapproved
the guidelines after presentation of changes and feed-
back from the evaluation.
Implementation, monitoring and future updates
Guidelines will only be successful if they are used correctly
and on a wide scale. Previous experience with the 2000
Scandinavian guidel ines has shown poor compliance and
varying degrees of implementation success [27,28]. Imple-
mentation and monitoring strategies were discussed within
the working group in order to facilitate long-term successful
use of the guidelines in Scandinavia. Focus was put on over-
coming barriers to application and effectively using available
resources. The working group also outlined a procedure
and approximate time period for updating the guidelines.
Results
The search and selection process is shown in Figures 2
and 3 for the two clinical questions.
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For the first clinical question, we found 72 studies that
adhered to our inclusion criteria (see Additional File 2,
Table S2 for evidentiary information). These studies
included 226,606 individual patients. The level of evidence
according to CEBM was variable and overall judged to be
moderate (see Additional file 2, Table S2). Quality assess-
ment with the QUADAS tool (see Additional file 3, Table
S3)showedsubstantialbiasinthe studies, particularly
concerning the rep resentativeness of the studied popula-
tion (selection bias, criteria 1), blinding of the index test
(criteria 8) and withdrawals (criteria 12). Studies scored
better regarding the reporting of selection criteria (criteria
2) and most had acceptable reference standards (criteria
3), although they were often described poorly.
Clinical predictors, with according source study, PLR,
NLR, reference test prevalence and risk factor preva-
lence are shown in Additional file 1, Table S1.
With regard to the second clinical question, w e f ound
21 stud ies a dhering t o o ur inclusion criteria (see Addi-
tional file 4, Table S 4 for evidentiary information and
relevant results). The CEBM rating was generally low,
with several studies reporting non-independent reference
standards (see Addit ional file 4, Table S 4). QUADAS
assessment showed selection bias in most studies (criteria
1). Other consistent weaknesses of the studies were a lack
of reference test description and blinding (see Additional
file 5, Table S5 for details).
Recommendations
Based upon the evidence, drafts for recommendations,
guidelines and written discharge advice were constructed
by the task force. These, with according presentation of
the evidence (Additional files 1, 2, 3, 4, 5, Tables S1-S5),
were reviewed by the working group using the predefined
Delphi process. Foll owing round 1 (see Table 3), discus-
sion in the working group concerned points 4 and 7. Since
point 7 regarded the overall guidelines, minor adjustments
were also made to other points. Only consensus points
were changed (the risk factors shunt-treated hydrocepha-
lus and the combination of age >65 and antiplatelet medi-
cation were added, discharge advice was simplified,
monitoring routines were ad justed and the graphical lay-
out of the guidelines was improved).
Following round 2 (see Table 4), consensus was achieved
in favor o f all recommendations, the guidelines and the
discharge instructions. One recommendation, concerning
Table 1 Grading of Recommendations Assessment, Development and Evaluation (GRADE) system [24] for rating
quality of evidence and strength of recommendation
Factor Description
Evidence:
High quality Considerable confidence of the estimate of effect. Further research is very unlikely to change our confidence in the
estimated effect.
Moderate quality Confidence that the estimate is close to the truth. Further research is likely to have an important impact on our
confidence in the estimate effect and may change the estimate.
Low quality Limited confidence in the effect. Further research is likely to have an important impact on our confidence in the
estimate effect and is likely to change the estimate.
Very low quality Little confidence in the effect estimate. Any change of effect is uncertain.
Recommendation:
Strong: We recommend... A strong recommendation indicates that most well informed people will make the same choice
Weak: We suggest... A weak recommendation indicates that the majority of well informed people will make the same choice but a
substantial minority will not
Uncertain: We cannot
recommend...
No specific recommendation for or against
Factors influencing the strength of the recommendation include evidence quality, risk/benefit aspects of presumed patient-important outcomes, costs and
uncertainty concerning values and preferences.
Table 2 A priori established seven-point response scale and criteria to determine acceptance, rejection or lack of
consensus for recommendations and guidelines for the working group using a modified Delphi process [25]
Level of agreement
Strongly
disagree
Disagree Moderately
disagree
Neither agree or disagree Moderately
agree
Agree Strongly
agree
Score 1 2 3 4 5 6 7
Criteria 75% of respondents score 3 on the 7-point scale All other situations 75% of respondents score 5 on the 7-
point scale
Result Consensus against No consensus Consensus in favor
Action Reject recommendation Indicates no consensus has been
reached
Accept recommendation
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clinical question 1, was removed due to the working group
finding the information irrelevant, despite consensus. This
rec ommendation was an unce rtain recommendation (we
cannot recommend...) for risk factors not included in the
other recommendations (such as headache, intoxication,
nausea and amnesia). The working group felt this recom-
mendation was unnecessary and confusing, shifting focus
from the important recommendations below.
The final recomm endations, based purely on evidence,
are presented below.
Clinical question 1: Which adult patients with minimal,
mild and moderate head injury need a head CT and
which patients may be directly discharged?
(1) We recommend that adult patients after mild and
moderate head injury with GCS 14, loss of consciousness,
repeated (2) vomiting, anticoagulant therapy or coagula-
tion disorders, clinical signs of depressed or basal skull
fracture, post-traumatic seizures or focal neurological defi-
cits should have a CT scan (moderate quality, strong
recommendation).
Excluded by title
n=3295
Abstracts
n=401
Titles initially screened
n=3696
Full-text papers
n=201
Additional papers from
reference lists of retrieved
papers
n=27
Excluded by abstract
n=200
Papers included in review
n=72
Excluded by full-text n=156
Not relevant n=79
No data n=24
Reporting only
children n=43
<50 patients n=6
Duplicate data n=4
Full-text papers
n=228
Figure 2 Adapted Preferred Reporting It ems for Systematic Reviews and Meta-Analyses (PRISMA) diagram showing the review
process with reference to the clinical question: Which adult patients with minimal, mild and moderate head injury need a head CT
and which patients may be directly discharged?.
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The evidence was initially of high quality but was down-
graded due to limitations in study design (mostly selection
bias), indirectness (outcomes were rarely reported) and
impreciseness (different magnitudes of predictive power of
risk factors between studies). However, the strength of the
recommendation was view as strong by the working
group, considering the seriousness of the complication
and h ealth/economic impact of missing a patient with a
neurosurgical lesion. The working group also discussed
older age (60 years and 65 years) as well as antiplatelet
medication as risk factors of importance, partly due to the
presence of these criteria in other guidelines and decision
rules. However, the predictive ability was only moderate
and these individual risk factors would lead to an unaccep-
table CT increase and so consensus was not to include
these in our recommendation.
(2) We recommend that adult patients after mild head
injury with GCS 14 and no risk factors (anticoagulant
therapy or coagulation disorders, post-traumatic seizures,
clinical signs of depressed or basal skull fracture, focal
Excluded by title
n=2795
Abstracts
n=131
Titles initially screened
n=2926
Full-text papers
n=33
Additional papers from
reference lists of retrieved
papers
n=12
Excluded by abstract
n=98
Papers included in review
n=21
Excluded by full-text n=24
Not relevant n=20
No data n=2
Reporting only
children n=2
Full-text papers
n=45
Figure 3 Adapted Preferred Reporting It ems for Systematic Reviews and Meta-Analyses (PRISMA) diagram showing the review
process with reference to the clinical question: Which adult patients with minimal, mild and moderate head injury need in-hospital
observation and/or a repeat head CT?.
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neurological d eficits), or GCS 15 with loss of conscious-
ness or rep eated (2) vomiting and no other risk factors,
be sampled for analysis of S100B if less than 6 h have
elapsed following trauma. If S100B is less than 0.10 μg/l,
the patient may be discharged without a CT (moderate
quality, strong recommendation).
The evidence was initially of high quality but was
downgraded due to study design (m ostly selection bias)
and indirectness (outcomes were rarely reported). How-
ever, studies consistently show that low S100B levels
can be used to s elect patie nts who do not need a CT
scan and, hence, may save valuable resources. Of the
few miss ed patients in the literature, almost all are non-
neurosurgical lesions. Some studies include risk factors
such as GCS 13, anticoagulation and focal neurological
deficits in the inclusion criteria. The working group,
however, found these risk factors to be too predi ctive of
intracranial injury.
This recommendation may seem conflicting with
recommendation 1, above. However, S100B is recom-
mended as an option for reducing unnecessary CT
scans in a subgroup of Mild head injury patients with
low risk for intracranial complication and/or neurosurgi-
cal intervention.
(3) We recommend that adult patients after minimal
and mild head injury with GCS 15 and without risk fac-
tors (loss of consciousness, repeated (2) vomiting,
anticoagulation therapy or coagulation disorders, post-
traumatic seizures, clinical signs of d epressed or basal
skull f racture, focal neurological deficits) can be dis-
charged from the hospital without a CT scan (moderate
quality, strong recommendation).
The evidence was initially of high quality but was
downgraded due to limitations in study design (mostly
selection bias), indirectness (outcomes were rarely
reported) and impreciseness (different magnitudes of
predictive power of risk factors between studies). The
working group felt, however, that the large proportion
of patients with head injury would fall into th is category
and that a CT policy in all these p atients would not be
health/economically viable considering the very low risk
of intracranial injury, and even lower risk of neurosur-
gery, in this patient group. As previously discussed,
older age and antiplatelet medication was again consid-
ered but rejected by the working group.
Clinical question 2: Which adult patients with minimal,
mild and moderate head injury need in-hospital
observation and/or a repeat head CT?
(1) We suggest that all adult patients after head injury
with GCS 1 3, clinical signs of depresse d or basa l skull
fracture, anticoagulation therapy or coagulation disorder,
post-traumatic seizure or focal neurological deficit
should have a CT scan and be admitted to hospital for
observation, irrespective of CT findings (low quality,
weak recommendation).
The evidence was sparse and also of low quality due to
study limitations (selection bias) and inconsistency in
findings. The working group felt that it would not be
good clinical prac tice to discharge patients with any of
these risk factors, despite the low quality of evidence.
(2) We recommend that repeat CT scans should be per-
formed in patients with neurological and/or GCS (2
points) deterioration (low quality, strong recommendation).
The evidence was of moderate quality and was down-
graded due to serious limitations in study design and
some inconsistency. Most of the evidenc e indicates that
routine repeat CT of these patients with or without CT
findings is unnecessary in the absence of clinical deteriora-
tion, specifically dete rioration of GCS >2 points and/or
Table 3 Results of the modified Delphi process, round 1
Delphi point Working group member Result Cf/nC/Ca
12345678910
1 6666266577 90% Cf
2 666- 366647 78% Cf
3 7676366717 80% Cf
4 5446266662 60% nC
5 6 5 6 6 7 6 6 7 6 6 100% Cf
6 6674766677 90% Cf
7 6656266- 43 67% nC
8 55666667- 3 89% Cf
9 5 - 5 6 6 6 6 6 - 5 100% Cf
Delphi points 1 to 3 refer to recommendations 1 to 3 concerning clinical
question 1, point 4 refers to a recommendation that was dropped due to
irrelevance (see main text), points 5 and 6 refer to recommendations 1 and 2
concerning clinical question 2, point 7 refers to the guideline draft including
the help sheet, point 8 refers to the written discharge advice and point 9 to
the in-hospital monitoring routines.
Ca = consensus against; Cf = consensus in favor; nC = no consensus.
Table 4 Results of the modified Delphi process, round 2
Delphi point Working group member Result Cf/nC/Ca
12345678910
1 76367767 88% Cf
2 - 6466667 86% Cf
3 76366677 88% Cf
4 76666376 88% Cf
5 7 6 7 6 7 - 6 7 100% Cf
6 7 7 7 6 7 - - 7 100% Cf
7 7 6 7 6 6 7 5 7 100% Cf
8 7 6 4 - - - 6 7 80% Cf
9 7 6 6 5 7 - 6 7 100% Cf
Two members did not reply. Delphi points 1 to 3 refer to recommendations 1
to 3 concerning clinical question 1, point 4 refers to a recommendation that
was finally dr opped due to irrelevance (see main text), points 5 and 6 refer to
recommendations 1 and 2 concerning clinical question 2, point 7 refers to the
guideline draft including the help sheet, point 8 refers to the written
discharge advice and point 9 to the in-hospital monitoring routines.
Ca = consensus against; Cf = consensus in favor; nC = no consensus.
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neurological status. A strong recommendation was chosen
in spite of weak evidence due to the seriousn ess of the
condition. Clinical aspects such as anticoagulation and
persistent neurological findings were discussed but the
working group could not reach consensus on a recom-
mendation for follow-up scans in these patients.
Guidelines
Based upon the recommendations, guidelines were con-
structed. The addition of shunt-treated hydrocephalus
was bas ed upon consensus in the working g roup with
little evidence to support this. T he working group dis-
cussed risk factors relating to trauma mechanism and
multitrauma injuries but found these difficult to recom-
mend, mainly due to practical i ssues with clinical appli-
cation. We considered serious extracranial injuries
(defined as Abbreviated Injury Score (AI S) >3 to any
organ system, for instan ce large (for example, femur)
fractures or serious thoracic or abdominal injuries) as a
risk factor due to the probability of a higher magnit ude
of trauma, need for extracranial CT and the poorer
prognosis of brain injury in these patients. However, we
finally decided to omit this as a risk factor primari ly due
to the difficulty of classifying this risk factor in a busy
clinical scenario. Additionally, predictive abilit y was gen-
erally only moderate for these risk factors. Also, loss of
consciousness was expanded to suspected/confirmed
loss of consciousness, as it is often d ifficult to confirm
this finding in the clinical setting. Patients who could
not clearly deny any loss of consciousness should be
classed as suspected. Finally, the working group could
not recommend older age or antiplatelet medication as
individual risk factors due to the unacceptable CT
increase such a recommendation would cause, in combi-
nation wit h only moderate predictive abilities. However,
consensus was reached to combine these into one risk
factor, namely age 65 years and antiplatelet medication.
Written instructions for patients being discharged wer e
adapted from the 2000 guidelines with consideration of
the National Institute of Clinical Excellence (NICE)
instructions [29] and a proposal for evidence-based
instructions from Fung et al. [30], (see Additional file 6,
Figure S1). With the Scandinavian setting in mind, the
discharge sheet was heavily simplified for clarity. Obser-
vation and monitoring routines for admitted patients
were based on consensus in the working group. We dis-
cussed the intensity of monitoring routines in relation to
the severity o f t he complications and burden on hospital
wards and finally decided that these should be relatively
frequent shortly after trauma (the first 4 h) with de-esca-
lation over time. Reasonably, most admitted patients will
arrive to a ward after at least 4 h and h ence already have
passed the 15-minute interval period. Also, these moni-
toring routines will only be used in small minority of
patients as mode rate and high-risk patients are relatively
uncommon and other patients should preferentially have
a CT.
Feedback from ED evaluation and from stakeholders
resulted in mi nor changes to wording and general
appearance of the guidelines. All stakeholders and the
working group approved the final version, see Additional
file 7, Figure S2.
Implementation, monitoring and future updates
The working group decided on implementat ion by S NC
members in their respective countries. This would be
performed through a combination of written and oral
presentations in national medical journals and national
meetings, respectively. We discussed barriers to imple-
mentation and decided that the most important of these
was probably the absence of sufficient education co n-
cerning head injury management in Scandinavia. We
would attempt to further facilitate implementation by
printing flyers and placards with the guidelines and to
send these to Scandinavian hospitals. We would also
initiate national training initiatives within the respective
Scandinavian countries.
With respect to monitoring aspects, the working group
decided to plan a questionnaire to Scandinavian physi-
cians treating head injury to determine the present use of
guidelines, similar to previous efforts [31]. At 1 year fol-
lowing implementation, a follow-up questionnaire will be
sent out to establish changes in management routines.
We will also initiate studies examining compliance wit h
the guidelines, as previously established in Norway
[27,28], and at tempt to improve insufficient use of the
guidelines depending on these results. Finally, we will
initiate a prospective validation study, also comparing the
performance of our guidelines with other guidelines,
decision rules and, importantly, unstructured physician
judgment [32].
The working group decided that an update of the
guidelines would be necessary in 2015. This would
include evidence updates concerning the clinical ques-
tions addressed in the present update and would further
examine the observation and monitoring routines for
admitted patients.
Discussion
Since 2000, considerable evidence has emerged conce rn-
ing the initial management, particularly risk factors for
CT selection, of minimal, mild and moderate head injury.
The work presented here is, in contrast to our previous
guidelines, confined to adults but a similar effort regard-
ing management of children is underway. Although these
guidelines can theoretically be used in any settin g, they
were designed with the Scandinavian emergency care set-
ting in mind. They are also designed to primarily iden tify
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patients needing neurosurgical or medical intervention,
with traumatic CT findings being the secondary identifi-
cation goal.
In summary, the evidence was of reasonable quality
referring to the predictive ability of risk factors for compli-
cations following head injury in these patients. Unsurpris-
ingly, many of the risk factors included here are also
found in other guidelines and decision rules [6,9-11,29,33].
However, several differences can be noted. We found that
the predictive power of amnesia was too low to be
included. This risk fac tor was present in the SNC guide-
lines from 2000, mostly due to the difficultly in ruling out
loss of consciousness in some patients. For this reason, we
include suspected loss of consciousness as a risk factor.
Risk factors such as intoxication, trauma above the cla-
vicles, nausea, vertigo and headache were not included
due to poor predictive ability combined with a high pre-
valence of these factors in the head injury population.
The working group found injury mechanisms compli-
cated to use p ractically in initial management and
decided not to include these as risk factors.
Older age, most often defined as 60 or 65 years, is
often included in other guidelines. The predictive ability of
this risk factor was only moderate and there was consider-
able uncertainty in the group with regard to patient
important outcomes and resource use. The number of
people in older age groups in industrialized coun tries is
increasing [34] and the increased CT rate that would be
associated with this risk factor was deemed unacceptable.
Also, the risk factor is common in the head injury cohorts,
with between 10% and 45% of patients being over 65 years
of age in reported cohorts of mild [10,35-38] and moder-
ate [39] TBI. Fabbri et al. recently presented results con-
sidering the combination of older age and antiplatelet
agents [40]. Despite the lack of good evidence for this
combination, consensus wa s reached to include age 65
years in combination with any antiplatelet agent as a risk
factor. It is reasonable t o expect that the combination
would be more predictive of complications after h ead
injury and result in a smaller CT rate increase when com-
pared to the risk factors used individually. Additionally, it
has been suggested that antiplatelet medication may be at
least partly responsible for the higher risks for intracranial
complications seen after head injury in older patients [40].
Shunt-treated hydrocephalus was added purely based
on consensus, with evidence derived from exp ert opinion
in the group. We acknowledge the poor evidence-based
background to this decision but this patient group is
uncommon and will not lead to a noticeable increase in
CT scanning.
Evidence concerning repeat CT was reasonable but lack-
ing concerning both written discharge advice and observa-
tion routines. These aspects were therefore based heavily
upon consensus with special weight put o n adaptation to
the Scandinavian health care system. Since in-hospital
observation consumes valuable resources, there is a need
for stronger evidence examining the need and magnitude
of these routines.
For the first time, a brain biomarker has been intro-
duced into clinical practice guidelines. Using a low cut-
off of 0.10 μg/l, the biomarker has shown considerable
ability to predict the absence of CT pathology and neuro-
surgical intervention [36,41,42] . Th is negative prediction
is welcomed since all other risk factors are of positive
predictive nature. S100B allows for a safe reduction in
CT scans in a subpopulation of patients with mild head
injury. In order to maintain the theoretical safety and
cost-saving ability, the biomarker should pri marily not
exhibit fal se negative results . Al so, the biomarker should
only be taken in patients that would usually rece ive a CT
scan and the fraction of negative S100B results (below
cut-off) should be as large as possible. S100B is clinically
unspecific [43,44] and has a short half-life [45]. There-
fore, patients with extracranial injuries and those seeking
care more than 6 h after trauma are not good candidates
for S100B sampling due to a risk of false positives and
negatives, respectively. Some patients have risk f actors
with higher predictive abilities and also factors that
would usually warrant admission irrespective of CT find-
ings. This group is therefore also not suit able for S100B
sampling. Despite the rel atively good evidence for S100B
in this setting, biomarkers have historically had different
effects in actual management and the clinical impact and
health economic implications may alter future recom-
mendations. Based upon the current evidence and clinical
setting, however, this biomarker should safely reduce
resource use if used correctly since low levels are very
uncommon in patients needing neurosurgical interven-
tion in this setting.
There are limitations to the process outli ned in this
paper. Although the recommendations are based upon
evidence, there were elemen ts of consensus input to the
final guidelines. This is inevitable when dealing with
these injuries and we attempted to minimize the negative
effects of this through our stringent and extensive metho-
dology using the best available tools. Particularly, the
GRADE system [20] allows consideration of other impor-
tant aspects other than the level of evidence in recom-
mendations. The derivation and validation of predictive
risk factors as performed by other authors [6,10,18]
would hardly be feasible in Scandinavia and would only
account for one aspect of the management guidelines.
Our methodology was judged as the most feasible consid-
ering the target population. However, external clinical
validation of our guidelines is welcomed and would natu-
rally support successful implementation.
Finally, these guidelines are, by definition, guidelines
andshouldbeutilizedaccordingly.Theyareprimarily
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designed as evidence and consensus-based guidance for
physicians who are not experts in the field. Physicians
whohaveconsiderableexperiencewiththesepatients
should naturally be allowed to defer from the guidelines
according to clinical judgment.
Conclusions
We present guidelines for initial management of adults
with minimal, mild and moderate head injury based upon
a thorough evidence and consensus-based methodology.
The guidelines are primarily designed to detect complica-
tions after head injury needing either neurosurgical or
medical intervention. They can be applied to all adult
patients and include aspects such as CT and admission
selection, repeat CT selection, monitoring routines and
discharge aspects. However, we suggest external valida-
tion before they are widely implemented. Furthermore,
areas with poor evidence, such as clinical monitoring
routines for patients following head injury, should be
addressed in future studies.
Additional material
Additional file 1: Table S1. Predictive risk factors with according studies
derived from the clinical question: Which adult patients with minimal,
mild and moderate head injury need a head CT and which patients may
be directly discharged? showing corresponding positive likelihood ratio
(PLR), negative likelihood ratio (NLR), prevalence for the reference test
(CT findings (CT)), intracranial injury (ICI) and neurosurgery (NS)) and the
risk factor prevalence. CT = computed tomography.
Additional file 2: Table S2. Evidentiary table of studies with reference
to the clinical question: Which adult patients with minimal, mild and
moderate head injury need a head CT and which patients may be
directly discharged?. CT = computed tomography.
Additional file 3: Table S3. Modified Quality Assessment of Diagnostic
Accuracy Studies (QUADAS) grading of studies referring to the clinical
question: Which adult patients with minimal, mild and moderate head
injury need a head CT and which patients may be directly discharged?.
CT = computed tomography.
Additional file 4: Table S4. Evidentiary table of studies with reference
to the clinical question: Which adult patients with minimal, mild and
moderate head injury need in-hospital observation and/or a repeat head
CT?. CT = computed tomography.
Additional file 5: Table S5. Modified Quality Assessment of Diagnostic
Accuracy Studies (QUADAS) grading of studies referring to the clinical
question: Which adult patients with minimal, mild and moderate head
injury need in-hospital observation and/or a repeat head CT?.CT=
computed tomography.
Additional file 6: Figure S1. Discharge advice for adults following
minimal, mild and moderate head injury.
Additional file 7: Figure S2. Final management guidelines for adults
following minimal, mild and moderate head injury (including help sheet).
Authors contributions
This work was initiated and designed by JU with input from the SNC
committee. JU, TI and BR all participated in the review process and
recommendation/guideline draft, see text for details. For the Delphi process,
the entire SNC working group (see below), including JU, TI and BR, was
involved. Clinical stakeholders were involved in later processes of guideline
approval, see main text. All main authors approved the final manuscript.
Competing interests
JU and BR are organizers of the international BMBD conference (http://www.
bmbd.org) concerning neurological biomarkers in brain injury. Some SNC
meetings have been sponsored by Roche Diagnostics Scandinavia AB. These
sponsors have had no involvement or influence on any aspects of the SNC
work. JU and BR have been invited to speak at educational meetings
arranged by Roche Diag nostics Scandinavia AB but Roche have always
remained strictly independent from the scientific program and content and
these took place before the present work was initiated. JU, TI and BR have
in previous research received compensation for travel expenses and lab
analysis from Roche AB, Diasorin AB and Sangtec Medical AB. None of these
had any involvement or influence on any scientific aspects.
Acknowledgements
SNC working group: Carsten Kock-Jensen (SNC president), Hammel,
Denmark; Johan Undén, Malmo, Sweden; Bertil Romner, Copenhagen,
Denmark; Tor Ingebrigtsen, Tromso, Norway; Terje Sundstrom, Bergen,
Norway; Jacob Springborg, Copenhagen, Denmark; Knut Wester, Bergen,
Norway; Per Olof Grände, Lund, Sweden; Vagn Eskesen, Copenhagen,
Denmark; Snorre Sollid, Tromso, Norway; Niels Juul, Aarhus, Denmark; Bo-
Michael Bellander, Stockholm, Sweden; Bent Dahl, Aarhus, Denmark; Christina
Rosenlund, Aarhus, Denmark; Peter Reinstrup, Lund, Sweden.
Additional clinical stakeholders: Per Wihlborg, Malmo, Sweden; Louis Riddez,
Stockholm, Sweden; Steen Mejdahl, Copenhagen, Denmark; Jesper Erdal,
Copenhagen, Denmark; Ole Molgaard, Aarhus, Denmark; Knut Melhuus, Oslo,
Norway; Martine Enger, Oslo, Norway; Kenneth Thors, Stavanger, Norway.
This work was funded by the non-commercial Swedish state sources of:
Region Skåne, Södra Sjukvårdsregionen and Vetenskapsrådet Hallands
Sjukhus, all in Sweden. None of the funding bodies had any involvement or
influence on any aspects of the work.
Author details
1
Department of Intensive Care and Perioperative Medicine, Institute for
Clinical Sciences, Södra Förstadsgatan 101, 20502 Malmö, Sweden.
2
Department of Neurosurgery, Institute for Clinical Medicine, Sykehusveien
38, 9038 Tromsö, Norway.
3
Department of Neurosurgery, Institute for Clinical
Medicine, Blegdamsvej 9, 2100 Copenhagen, Denmark.
Received: 18 October 2012 Accepted: 25 February 2013
Published: 25 February 2013
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Pre-publication history
The pre-publication history for this paper can be accessed here:
http://www.biomedcentral.com/1741-7015/11/50/prepub
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Cite this article as: Undén et al.: Scandinavian guidelines for initial
management of minimal, mild and moderate head injuries in adults: an
evidence and consensus-based update. BMC Medicine 2013 11:50.
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... Use of biomarkers as an additive to clinical decision rules might increase guideline-adherence, and thereby reduce unnecessary radiation exposure, emergency department time, and health care costs. The Scandinavian Neurotrauma Committee (SNC) guidelines for management of minimal, mild and moderate head trauma in adults recommend the use of S100 astroglial calcium-binding protein B (S100B) as a screening tool for early detection of traumatic intracranial lesions in mTBI [7]. Single test of S100B can help determine the need for head-CT within 6 h of injury. ...
... The sensitivity and negative predictive value of a S100B single test in detecting traumatic intracranial lesions in adults is 97-100% and 92-100%, respectively [8][9][10]. Yet, S100B cannot be used in pediatric head trauma, with concomitant extracranial injuries or beyond 6 h after the injury, which challenge clinical implementation of S100B [7,11]. The introduction of a combination test of glial fibrillary acidic protein (GFAP) and ubiquitin C-terminal hydrolase (UCH-L1) in mTBI have therefore gained much interest [12][13][14][15][16]. ...
... To allow a more direct comparison with prior studies, we evaluated the diagnostic performance of S100B and GFAP/UCH-L1 separately in all cohorts. In sub-cohort 2, S100B had a sensitivity and a negative predictive value as reported in prior studies [7,8,31,33,34]; however, when applied more broadly among the unselected trauma cohort and the sub-cohort 1, the performance declined. By contrast, GFAP/UCH-L1 had a sensitivity and a negative predictive value of 100% across all three cohorts, which is also comparable to prior studies [14,17,31]. ...
Article
Full-text available
Background Few countries recommend glial fibrillary protein (GFAP) and ubiquitin C-terminal hydrolase-L1 (UCH-L1) as a substitute for S100 astroglial calcium-binding protein B (S100B) in early detection of traumatic intracranial lesions in mild TBI (mTBI). This study aims to evaluate the classification agreement between S100B and GFAP/UCH-L1 in a Scandinavian trauma cohort, to evaluate the performance characteristics of S100B and GFAP/UCH-L1 for detection of traumatic intracranial lesions, and lastly to evaluate the laboratory performance of the GFAP/UCH-L1 assay. Methods Prospectively collected data from an unselected cohort of 379 adult trauma patients admitted to a level I trauma center at Aarhus University Hospital, Denmark, were retrospectively analyzed. Analyses were performed in the unselected cohort, in sub-cohort 1 (n = 218) i.e. patients with any evidence of TBI in their chart as well as in sub-cohort 2 (n = 105) i.e. patients with mTBI defined as Glasgow Coma Scale score ≥ 14, an injury severity score ≤ 15, and blood sampling within 6 h or 12 h after trauma. Plasma-samples were used for GFAP/UCH-L1 measurement and serum-samples were used for S100B measurement. Data analysis involved agreement analysis using Cohens kappa and sensitivity, specificity, positive predictive value and negative predictive value for each biomarker in each of the three cohorts. Lastly, levels of GFAP/UCH-L1 measured by the Alinity-I platform and the Simoa platform were compared. Results Classification agreement between GFAP/UCH-L1 and S100B was high in all three cohorts, but Cohens kappa improved with increasing proximity to clinical biomarker use and reached an almost perfect identity in sub-cohort 2 (0.70, 95% CI 0.62–0.92). S100b had a sensitivity and negative predictive value of 100% in sub-cohort 2, while GFAP/UCH-L1 reached 100% across all three cohorts. The specificities for both S100B and GFAP/UCH-L1 were relatively low. Comparing GFAP/UCH-L1 levels between platforms revealed a low concordance with the Alinity-I platform measuring GFAP levels on average 65% lower and UCH-L1 levels 84% higher than the Simoa platform. Conclusions In this study, S100B and GFAP/UCH-L1 had an almost perfect agreement for classification of mTBI patients and comparable diagnostic performances for detecting traumatic intracranial lesions. Our results therefore support GFAP/UCH-L1 as a feasible alternative to S100B for detecting traumatic intracranial lesions in mTBI.
... The Scandinavian Neurotrauma Committee (SNC) is an independent, not-for-profit organization comprised of neurosurgeons, neurointensivists, and neuroanesthesiologists from the Nordic countries dedicated to improving the care of patients with traumatic injuries to the central nervous system (CNS). The committee has previously published guidelines for the management of traumatic brain injuries [17,18]. The aim of this survey was to evaluate current clinical practices for TSCI across centers in the Nordic countries. ...
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Full-text available
Background Management of traumatic spinal cord injury is complex and depends on a multidisciplinary approach involving pre-hospital services, spinal surgery, intensive care unit treatment and specialized rehabilitation. International clinical practice guidelines for the handling of these patients offer specific recommendations regarding transportation, radiological investigations, timing of surgery, intensive care management and rehabilitation. We performed a comprehensive multicenter survey to assess the agreement between the Nordic countries on the different aspects of traumatic spinal cord injury management. Methods Sequential, cross-sectional, structured survey comprising the key clinical domains (pre-hospital services, spinal surgery, intensive care management and rehabilitation) in all tertiary spine trauma centers in Sweden, Denmark, Norway, Iceland and Finland. Data are presented descriptively. Results A total of 109 respondents from 22 Nordic centers were invited to take the survey, with a response rate of 90% (98/109). Overall, clinical practices were comparable within the domains. Prehospital services had similar practices for airway management, clinical spine clearance and patient transport. Preoperative magnetic resonance imaging was available to 33/35 of the spine surgeons (94%) on a 24/7 basis. This examination was considered mandatory prior to surgery by 66% (23/35) of the surgeons. Surgery was defined as early if performed within 24 h of the injury by all surveyed surgeons. Augmented blood pressure regimens were widely applied in the intensive care units, with mean arterial pressure targets varying between > 80 and > 90 mmHg. Postoperative thromboprophylaxis was administered within 48 h by all centers and rehabilitation policies were similar overall. Notable variations in practice were the occasional steroid administration and the use of lumbar drains in 54% (14/26) of intensive care units. Conclusion Although there is some variability in the current management of traumatic spinal cord injury in the Nordic countries at the center- and country-level, practices in most key clinical domains are similar and follow established international guidelines.
... TBI affects people of all ages and genders in both developed and developing countries and is the leading cause of death and disability (16). Mortality rates as high as 30-40% have been reported in patients with severe TBI (17,18). Gursoy et al. (19) from Turkiye reported that 57% of patients with Scores to Predict Mortality in TBI Original Article TBI were male, the mean age was 47±17 years, and the most common diagnoses were subarachnoid hemorrhage and subdural hematoma. ...
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Objective: Since traumatic brain injury (TBI) has high mortality rates, it is essential to identify patients with poor prognosis. In this study, the mortality prediction performances of the Glasgow Coma Scale (GCS), Acute Physiology and Chronic Health Assessment-II (APACHE-II), Marshall, and Rotterdam scores were compared in patients with TBI in the intensive care unit (ICU) of a tertiary center. Methods: Patients followed up in the ICU due to moderate to severe TBI between January 2020 and January 2022 were retrospectively reviewed. Patients were classified as survivor and nonsurvivor groups. The patient's clinical characteristics and the scoring systems' performance in predicting 28-day mortality were investigated. Results: A total of 150 patients were included in the study, and 82.4% (n=98) were male. GCS scores were significantly lower in the nonsurvivor group, while APACHE-II, Marshall, and Rotterdam scores were significantly higher (p < .001 for all). GCS, APACHE-II, and Rotterdam scores were independent predictors of mortality (p = .002, p = .012, and p = .003, respectively). Receiver operating characteristics curve analysis revealed that GCS cutoff value was ≥6.5, area under the curve (AUC)=0.851, APACHE-II cutoff value was ≥ 21.5, AUC=0.866, Marshall cutoff value was ≥ 3.5, AUC=0.827 and Rotterdam cutoff value was ≥ 3.5, AUC=0.864. Conclusion: GCS, APACHE-II, Marshall, and Rotterdam scores are valid in predicting mortality in patients with TBI. Their performance in predicting mortality is ranked from highest to lowest as APACHE-II, Rotterdam, GCS, and Marshall.
... Acute elevations of S100B are associated with the presence of acute intracranial injury, and the assessment of S100B levels was incorporated into the Scandinavian CT guidelines in 2013. 51 Additionally, serum levels of S100B have been shown to increase 3-36 hours after sports-related concussions [52][53][54] and following exposure to subconcussive head impacts. [55][56][57][58] Repetitive exposure to transient hypoxia and/or ischemia, which could occur during partnered sexual strangulation, 59 triggers inflammatory responses similar to those that occur in the secondary injury after TBI. 60 In contrast, the potential mechanism of injury in partnered sexual strangulation differs from TBI in that it is not characterized by blunt trauma or rapid acceleration/deceleration. Thus, axonal integrity may be unaffected by partnered strangulation. ...
Article
Background “Choking” or partnered strangulation is an emerging and popular sexual behavior that is more often experienced by young women, yet the neurobiological consequences of partnered sexual strangulation remain unclear. Aim The aim of the present study was to assess differences in 5 brain-injury blood biomarkers in young adult women who frequently engaged in sexual strangulation. Methods Young adult women were recruited from a large Midwestern university and assigned to groups based on sexual strangulation experience: (1) at least 4 instances of being strangled by a partner during sexual activities in the past 30 days or (2) no prior experience being strangled by a sexual partner. Choking/strangulation history during partnered sexual activities was assessed using a self-report questionnaire. Blood samples were collected via venipuncture. Data from 32 female participants (median 21.5 years old [IQR 20-24]) were available for analysis: 15 with a history of recent, frequent partnered strangulation exposure and 17 without any history of partnered sexual strangulation. Outcomes Serum levels of 5 blood biomarkers for brain injury were measured using sandwich enzyme-linked immunosorbent assay (S100B) and single-molecule array digital immunoassay (neurofilament light, tau, ubiquitin C-terminal hydrolase L1, and glial fibrillary acidic protein). Results Group differences for the 5 biomarkers were examined using 1-way multivariate analysis of covariance, adjusting for age and alcohol use. We observed a significant multivariate effect of group, Pillai’s trace = 0.485, F(5, 24) = 4.235, P = .007, η2 = 0.47. Univariate results indicated that female college students who were recently, frequently strangled during partnered sexual activities exhibited elevated S100B levels compared to their peers who had never engaged in this partnered sexual behavior, F(1,28) = 11.165, P = .002, η2 = 0.29. Clinical Implications Engaging in this partnered sexual behavior may elicit neuroinflammation, with unknown long-term consequences for brain health. Strengths and Limitations Strengths include the recruitment of a novel population, as this investigation was the first of its kind to examine neurobiological correlates of repetitive exposure to partnered sexual strangulation. Another strength is the panel of 5 blood biomarkers that were assessed, providing information from multiple cell types and pathophysiological processes. Limitations were the relatively small sample size and the cross-sectional design, which prevents causal inference. Conclusion Young adult women with a history of recent, frequent experience being strangled by a sexual partner exhibited higher serum S100B, an astrocyte-enriched protein, compared to their biomarkers, meriting future work to determine a causal mechanism between partnered sexual strangulation and neuroinflammatory processes.
Article
OBJECTIVE The aim of this study was to investigate whether the biomarkers neuron-specific enolase (NSE), glial fibrillary acidic protein (GFAP), neurofilament light chain (NfL), and tau (total [t] and brain-derived [BD]) are elevated in plasma preoperatively; if there is a dynamic biomarker response to surgery; and if the biomarker levels are related to long-term outcome in chronic subdural hematomas (CSDHs). METHODS Eighty-five CSDH patients surgically treated between 2022 and 2023 at Uppsala University Hospital, Uppsala, Sweden, were included in this prospective, observational study. NSE, GFAP, NfL, t-tau, and BD-tau were evaluated in plasma pre- and postoperatively (6–24 hours after surgery) and in the CSDH fluid. Health-related quality of life was evaluated using the 5-level EQ-5D (EQ-5D-5L) at 6 months postoperatively. RESULTS GFAP, NfL, and tau levels decreased after CSDH surgery (p < 0.02). NSE and BD-tau levels also decreased, but not significantly. Older age and larger CSDH volume were associated with higher preoperative GFAP, NfL, and BD-tau levels (p < 0.05). Higher preoperative values and greater dynamics (Δ [postoperative value − preoperative value]) of GFAP, NfL, and BD-tau correlated significantly with worse levels of several EQ-5D-5L domains (p < 0.05). A higher preoperative NfL level in plasma was independently associated with a lower EQ-5D-5L visual analog scale score (p < 0.001). CONCLUSIONS Surgical CSDH patients exhibit ongoing central nervous system cellular injury, demonstrated via increased fluid biomarkers for brain injury preoperatively, which immediately improved after surgery and was strongly related to long-term outcome. The extent of preoperative biomarker elevation could aid in the decision-making for surgical indication and urgency.
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Background Glial fibrillary acidic protein (GFAP) and ubiquitin C-terminal hydrolase-L1 (UCH-L1) are blood biomarkers that able to aid in the assessment of mild traumatic brain injury (mTBI) patients and reduce computed tomography (CT) overuse. Objectives The aim of this study was to evaluate the predictive performance of individual biomarkers and their combination (i.e. mTBI assay) in detecting clinically significant intracranial injuries in mTBI. Furthermore, the influence of older age on the predictive performance of individual biomarkers and their combination was investigated. Methods This prospective multicenter study was conducted in 12 European healthcare centers. Adults with suspected mTBI presenting to the emergency department (ED) of each participating healthcare center within 12 h of head trauma were enrolled. GFAP and UCH-L1 were determined in blood samples collected from each participant. Head CT was considered as reference standard for the presence of intracranial injury. Results The mTBI assay yielded the highest sensitivity [95.5%, 95% confidence interval (CI): 89.9–98.5] and the highest negative predictive value (NPV) value (97.3%, 95% CI: 93.9–98.9) for the exclusion of intracranial lesions in mTBI. The sensitivities and NPVs of individual biomarkers were lower compared with the mTBI assay. In adults over 65 years, the individual biomarkers and the mTBI assay displayed the weakest diagnostic performances. After optimizing cutoff values for the mTBI assay for older adults, the following diagnostic accuracy measures were obtained: sensitivity 87.7%, 95% CI: 77.2–94.5 and NPV: 94.4%, 95% CI: 89.6–97.0 ( P < 0.001). Conclusion The mTBI assay yielded high sensitivity and NPV for the exclusion of significant intracranial injuries in mTBI patients presenting to the ED within 12 h from injury, performing better than individual biomarkers. A significant age-dependent influence on the predictive performances of the individual biomarkers and the mTBI assay was demonstrated.
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INTRODUCTION: Due to the characteristics of brain-injured patients, early complications of aneurysmal subarachnoid hemorrhage (aSAH) can easily go undetected for a period of time, resulting in the delay of accurate treatment. Serum biomarkers of neuronal damage, such as glial fibrillary acidic protein (GFAP), neuron-specific enolase (NSE), and S100B protein, may serve as diagnostic tools to improve care in neurocritical illness. This preliminary observation aimed to evaluate the absolute values of those markers of neuronal damage in aSAH or a planned embolization. MATERIAL AND METHODS: The study group consisted of 12 patients in need of emergency (i.e. due to aneurysmal aSAH) (n = 4) or planned (n = 8) embolization. GFAP, NSE, and S100B were assessed before and 24 hours after the procedure completion. Descriptive statistics were applied to elucidate the dynamics of markers in the peri-procedural period. RESULTS: Brain aneurysm embolization was associated with an increase in NSE and S100B, but not GFAP. A greater increase in the concentrations of these proteins is observed in emergency procedures. CONCLUSIONS: Brain aneurysm embolization is likely to be associated with an increase in NSE and S100B, but not GFAP. There are differences in the concentrations of these proteins between patients with aSAH and controls. More research is needed to assess the impact of their dynamics on the clinical consequences of neuronal injury.
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OBJECTIVE Mild traumatic brain injuries (mTBIs) account for approximately 90% of traumatic brain injuries and are a common cause for hospitalization. Cranial CT (CCT) is the preferred diagnostic tool, but 85%–99% of mTBI patients show no visible lesions on CCT, making its use controversial due to radiation risks and costs. To identify mTBI patients requiring CCT, serum S100B concentrations have been integrated in international guidelines. However, its short half-life and low specificity to detect intracranial hemorrhages (IHs) in mTBI are frequently discussed limitations. The aim of this study was to determine the clinical benefit of S100B in reducing unnecessary CCT studies at a high-volume trauma center. METHODS The authors retrospectively analyzed the data of mTBI patients who were admitted to an urban level I trauma center between January 2017 and December 2022. They included all adult mTBI patients who underwent S100B measurement and had a subsequent CCT study. Patients who underwent immediate CCT on admission per the Canadian CT Head Rule or in the case of antithrombotic therapy were excluded. RESULTS A total of 391 patients with a mean age of 46 years were included. IH was detected in 23 mTBI patients (5.9%), with 2 patients (0.51%) requiring neurosurgical intervention. The mean S100B level was 0.21 μg/L (range 0.03–2.27 μg/L), with a cutoff at 0.105 μg/L. Patients with positive CCT findings had a mean S100B level of 0.31 μg/L, compared with 0.21 μg/L for negative CCT cases (p = 0.011). IHs occurred in 6.1% of patients with elevated S100B levels and in 4.2% of patients with normal S100B values. The specificity of S100B for positive CCT findings was 12.5%, with a positive predictive value of 6.1% and a negative predictive value of 95.8%. False-positive results led to 57 unnecessary CCT studies annually. CONCLUSIONS This study emphasizes the need for careful consideration when integrating S100B into mTBI management protocols for patients with a low risk for IHs. The low specificity in a younger population suggests that the risks of radiation from unnecessary CCT studies may outweigh the benefits. Although international guidelines were followed, integrating S100B into the mTBI protocol did not reduce CCT use as expected. In the absence of ongoing or new onset of neurological symptoms, elevated S100B values should not trigger CCT studies in a low-risk mTBI population.
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In the era of evidence based medicine, with systematic reviews as its cornerstone, adequate quality assessment tools should be available. There is currently a lack of a systematically developed and evaluated tool for the assessment of diagnostic accuracy studies. The aim of this project was to combine empirical evidence and expert opinion in a formal consensus method to develop a tool to be used in systematic reviews to assess the quality of primary studies of diagnostic accuracy. METHODS: We conducted a Delphi procedure to develop the quality assessment tool by refining an initial list of items. Members of the Delphi panel were experts in the area of diagnostic research. The results of three previously conducted reviews of the diagnostic literature were used to generate a list of potential items for inclusion in the tool and to provide an evidence base upon which to develop the tool. RESULTS: A total of nine experts in the field of diagnostics took part in the Delphi procedure. The Delphi procedure consisted of four rounds, after which agreement was reached on the items to be included in the tool which we have called QUADAS. The initial list of 28 items was reduced to fourteen items in the final tool. Items included covered patient spectrum, reference standard, disease progression bias, verification bias, review bias, clinical review bias, incorporation bias, test execution, study withdrawals, and indeterminate results. The QUADAS tool is presented together with guidelines for scoring each of the items included in the tool. CONCLUSIONS: This project has produced an evidence based quality assessment tool to be used in systematic reviews of diagnostic accuracy studies. Further work to determine the usability and validity of the tool continues
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Health providers face the problem of trying to make decisions in situations where there is insufficient information and also where there is an overload of (often contradictory) information. Statistical methods such as meta-analysis have been developed to summarise and to resolve inconsistencies in study findings-where information is available in an appropriate form. Consensus methods provide another means of synthesising information, but are liable to use a wider range of information than is common in statistical methods, and where published information is inadequate or non-existent these methods provide a means of harnessing the insights of appropriate experts to enable decisions to be made. Two consensus methods commonly adopted in medical, nursing, and health services research-the Delphi process and the nominal group technique (also known as the expert panel)-are described, together with the most appropriate situations for using them; an outline of the process involved in undertaking a study using each method is supplemented by illustrations of the authors' work. Key methodological issues in using the methods are discussed, along with the distinct contribution of consensus methods as aids to decision making, both in clinical practice and in health service development.
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Systematic reviews and meta-analyses are essential to summarize evidence relating to efficacy and safety of health care interventions accurately and reliably. The clarity and transparency of these reports, however, is not optimal. Poor reporting of systematic reviews diminishes their value to clinicians, policy makers, and other users. Since the development of the QUOROM (QUality Of Reporting Of Meta-analysis) Statement-a reporting guideline published in 1999-there have been several conceptual, methodological, and practical advances regarding the conduct and reporting of systematic reviews and meta-analyses. Also, reviews of published systematic reviews have found that key information about these studies is often poorly reported. Realizing these issues, an international group that included experienced authors and methodologists developed PRISMA (Preferred Reporting Items for Systematic reviews and Meta-Analyses) as an evolution of the original QUOROM guideline for systematic reviews and meta-analyses of evaluations of health care interventions. The PRISMA Statement consists of a 27-item checklist and a four-phase flow diagram. The checklist includes items deemed essential for transparent reporting of a systematic review. In this Explanation and Elaboration document, we explain the meaning and rationale for each checklist item. For each item, we include an example of good reporting and, where possible, references to relevant empirical studies and methodological literature. The PRISMA Statement, this document, and the associated Web site (www.prisma-statement.org) should be helpful resources to improve reporting of systematic reviews and meta-analyses.
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Whether the strategy for care of mild head injury should be in-hospital observation or computed tomography (CT) investigation and home care has been discussed lately. A necessary requirement for guidelines and the design of clinical trials would be knowledge about the risks of the condition. These have not been reliably summarised. The study aims to estimate as accurately as possible the mortality, the complication rates, and the frequency of pathological findings on CT in patients with mild head injury. Mild head injury was defined as head trauma involving loss of consciousness or amnesia, but where neurological findings on arrival at hospital are normal (GCS 15). Large databases were searched to find relevant scientific literature, and the retrieved studies were critically appraised. Findings were used from all representative patient data sets that met predefined standards for minimum quality. Meta-analysis using the random-effects model was performed on the data collected. The search yielded 24 studies on 24249 patients fulfilling the requirements. The mean mortality of patients was low, 0.1% (CI 0.05-0.15). Complications, mostly requiring surgery, occurred in 0.9% (CI 0.6-1.2) of the cases. In approximately 8% (CI 6.1-9.5), pathological CT findings, dominated by haemorrhages, were identified in the acute phase. Of 1000 patients arriving at hospital with mild head injury, 1 will die, 9 will require surgery or other intervention, and about 80 will show pathological findings on CT. At least these 8% of patients will probably need in-hospital care.
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Of the 500,000 brain injuries in the United States annually, 80% are considered mild (mild traumatic brain injury). Unfortunately, 2% to 3% of them will subsequently deteriorate and result in severe neurologic dysfunction. Intracerebral changes in the elderly, chronic oral anticoagulation, and platelet inhibition may contribute to the development of intracranial bleeding after minor head injury. We sought to investigate the association of age and the use of anticoagulation and antiplatelet therapy with neurologic deterioration and the need for neurosurgical intervention in patients presenting with mild traumatic brain injury. A retrospective review of all adult (>14 years) patients admitted to our Level I trauma service with a Glasgow Coma Scale (GCS) score of 14 to 15 who underwent neurosurgical intervention during their hospital stay was performed. Patients were stratified into two groups, age <65 years and age ≥ 65 years. Each group was then further stratified by the use of anticoagulants: warfarin, aspirin, clopidogrel, or a combination. Mechanism of injury, prehospital complaints, admission GCS, type of neurosurgical intervention, intensive care unit length of stay, hospital length of stay, and discharge disposition were evaluated. Z test and logistic regression were used to compare proportions or percentages from different groups. Of the 7,678 patients evaluated during the study period, 101 (1.3%) required neurosurgical intervention. The ≥ 65 years population underwent significantly more interventions as did those patients on anticoagulants. All patients aged 65 years or older who present with a GCS score of >13 after head trauma should undergo a screening computed tomography of the head regardless of prehospital use of anticoagulation. Patients younger than 65 years can be selectively screened based on presenting complaints and mechanism of injury provided they are not on anticoagulation.