From: British Medical Journals (BMJ)

Predicting outcome after traumatic brain injury:

practical prognostic models based on large
cohort of international patients
Medical Research Council (MRC) CRASH Trial Collabolators
Editorial by Menon and Harrison
BMJ/ February 23
rd
2008/ Vol. 336/ page: 425-429

Presented by:
Zulhijrian Noor
Irana Priska

Advisor: Ahmad Zuhro Maruf, dr., SpBS
JOURNAL READING
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INTRODUCTION
Traumatic brain injury is a leading cause of death
and disability worldwide 1.5 million / year
Most of the burden (90%) low and middle
income countries
Clinicians treating by assesment of prognosis,
80% believed the accurate assesment of
prognosis was important decisions to specific
treatment such as hyperventilation,barbiturates
and mannitol ( by survey, 2005 )
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Prognostic models
statistic models that combine data from
patients to predict outcame more accurate
then simple clinical predictions
Computers based prediction of outcome
Increase certain therapeutic interventions in
predicted good outcome, reduces it in poor
outcome
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Many prognostic model have been reported
but non are widely used
No were developed in populations from low
and middle income countries
MRC CRASH trial, the cohort study
prospectively included patient within 8
hours of the injury and achieved almost
complete follow up at 6 month
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Develoved and validated prognostic models
for death at 14 dayy and death and disabilityat
6 month in patient with traumatic brain injury
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METHODS
Patients 10.008 adult patients with
traumatic brain injury ( GCS 14 ), within 8
hours of injury
Outcomes death of a patient was recorded
on a early outcome form that was completed
at hospital discharge,death, or 14 days after
randomisation. Unfavourable outcome ( death
or severe disability ) at 6 months was defined
with Glasgow outcome scale
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Glasgow outcome scale
5 categories
1. Good recovery: able to return to work or school
2. Moderate disability: able to live indipendently;
unable to return to work or school
3. Severe disability : able to follow
commands/unable to live independently
4. Persistent vegetative state : unable to interact
with environment; unresponsive
5. dead
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prognostic variables age,sex,cause of injury,time
from injury to randomisation,Glasgow coma score at
randomisation,pupil reactivity,result of CT,level
income in country.
analysis included all of variables in a first
multivariable logistic regression analysis. Explored
liniearity between age and mortality at 14 days
prognostic models developed different models for
each of the two outcomes: a basic models (only
clinical and demographic variables ),CT model ( result
CT ).
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Performance of models assessed
performance of the models in term of
calibration with the Hosmer-Lemeshow and
discrimination was assessed with the C
statistic.
Internal validation the internal validity of
the final models was assessed by the
bootstrap re-sampling technique
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External validation externally validated the
model in an external cohort of 8509 patients
with moderate and severe traumatic brain
injury from 11 studies conduted in high
income countries.
Score development a clinical score base on
regression coefficient
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General characteristics
more patients were men (81%), more come from
low-middle income countries (75%)
58% of participants were included within three
hours of injury.
Road traffic crashes were the most common
cause of injury (65%)
79% underwent computed tomography
1948 patient (19%) died in 2 weeks,2323 (24%)
dead at 6 month,3556 (37%) were dead or
severly dependent at 6 month
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Low middle vs high income countries
in comparison from low-middle income
countries were younger,more men,were recruited
later, had less severeTBI ( as defined by GCS and
pupil reactivity ), abnormal result on CT.
Older age was a stronger predictor of 14 day
mortality in high income countries, also
obliteration 3th ventricle and non-evacuated
haematoma.
Lower GCS was a stronger predictor in low-
middle countries

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Multivariable predictive models
o Basic models 4 predictors : age,GCS, pupil
reactivity and the presence of major
extracranial injury.
o CT models characteristics on CT were
strongly assosiated with the outcomes.
Petechial haemorrhages,obliteration of the
third ventricle or basal cystern,SAH,Midline
shift,and non-evacuated haematoma.

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o obliteration of the third ventricle and midline
shift strongest predictor of mortality at 14
days
o non-evacuated haematoma strongest
predictor of mortality at 14 unfavourable
outcome at 6 months
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o Performance of models good calibration when
evaluated with the Hosmer-Lemesshow test.
o Clinical score for example : a 26 year old
patient froom low-middle income countries with
GCS 11,one pupil reactive,and absen of a major
extracranial injury, according to basic models :
probably dead at 14 days of 10% and 23.9% risk
of death or severe disability at 6 month.
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DISCUSSION
There are differences in outcomes and on the
strenght of predictors of outcomes on patient
from high and middle-low income countries.
Older age, Low GCS, absent pupil reactivity,
absent major extracranial injury poor
prognosis



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GCS showed a clear linier relation with
mortality
GCS 3 was lower than in patient with a score
of 4 may be because scores of sedated
patients are reported as 3
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Increasing age was associated with worse
outcome but this association was apparent
only after age 40
Plausible explanation extracranial
comorbidities, changes in brain plastisity,
differences in clinical management associated
with increasing age
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Present of obliteration of 3
rd
ventricle or basal
cistern as on Ct Scan associated with the
worse prognosis at 14
th
days
Recent findings absnce of basal cistern is a
strongets predictors of sixth month mortality
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Patient from low-middle income countries had
worse early prognosis than those from high
income countries
The strength of association between some
predictors and outcomes differed by region:
Low GCS (poorer in low-middle income countries)
quality of care and greater use of sedation
Incresing age (poorer in high income countries)
CT-Scan technology and accurate diagnosis


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STRENGTHS AND WEAKNESS
Strength
The use of a well described cohort of patients
Prospective and standadised collection of data on
prognostic factor
Low loss to follow up
The use of a validated outcome measure at a fixed
time after the injury
The large sample size

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STRENGTHS AND WEAKNESS
Weakness
Data from wich models were developed come
from a clinicl trial and this could therefore limit
external validity
For the validation they were forced to exclude the
variabels major extracranial injury and petechial
haemorrages because they were not available in
the IMPACT sample


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IMPLICATIONS
They have developed a methodology valid,
simple, accurate model that may help
decisions about health care for individual
patients
Help in the design and analysis of clinical
trials, through prognostic stratification.
Can be used in clinical audit by allowing
adjustment for case mix
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FUTURE RESEARCHE
Future research could also evaluate
different ways, or formats, for presenting the
models to physicians; their use in clinical
practice; and whether ultimately they have
any impact on the management and
outcomes of patients with traumatic brain
injury.
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SUMMARY
Traumatic brain injury is a leading cause of death
and disability worldwide with most cases
occurring in lowmiddle income countries
Prognostic models may improve predictions of
outcome and help in clinical research
Many prognostic models have been published but
methodological quality is generally poor, sample
sizes small, and only a few models have included
patients from low-middle income countries
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(www.crash2.lshtm.ac.uk/)
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