DECRA trial Decompressive craniectomy trial

1. The DECRA trial
Dr. Joe M Das

3. Introduction
• Among patients who are hospitalized with severe
traumatic brain injury, 60% either die or survive with
severe disability.
• After severe traumatic brain injury, medical and
surgical therapies are performed to minimize
secondary brain injury.
• Many patients with severe traumatic brain injury have
raised intracranial pressure that is refractory to firsttier therapies.
• In such cases, surgical decompressive craniectomy is
performed with increasing frequency to control ICP.

4. • The multicenter, randomized, controlled trial to
test the efficacy of bifrontotemporoparietal
decompressive craniectomy in adults under the
age of 60 years with traumatic brain injury in
whom first-tier intensive care and neurosurgical
therapies had not maintained intracranial
pressure below accepted targets
• Principal Investigator: D. J. Cooper (The Alfred
Hospital & National Trauma Research Institute)

5. Trial design
• From December 2002 through April
2010, adults with severe traumatic brain
injury in the intensive care units (ICUs) of 15
tertiary care hospitals in Australia, New
Zealand, and Saudi Arabia were recruited
• The trial protocol was designed by the study’s
executive committee and approved by the
ethics committee at each study center.

6. Patients
• Inclusion criteria:
– Severe diffuse Traumatic Brain Injury defined as:
• GCS < 9 and CT scan with evidence of brain swelling (DII +
swelling, DIII or DIV)
• OR
• GCS >8 before intubation and DIII or DIV (basal cistern
compression ± midline shift)
– Age 15 – 60 years
– First 72 hours from time of injury
– ICP monitor in situ. EVD strongly recommended.
Parenchymal ICP catheter (Codman) acceptable when
technical difficulties or other factors mean that an EVD is
not in place. Some patients will have an EVD occluded by
brain swelling. These should then have a Codman type
catheter inserted additionally to enable ICP
measurements, and appropriate therapies. If an EVD is
used it must be inserted and drained before
randomisation.

7. Patients
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Exclusion criteria:
Intracranial haemorrhage > 3 cm diameter
Intracranial mixed haemorrhagic contusion >5cm in long
axis
Previous craniectomy
EDH/SDH/ or large contusion requiring evacuation
EDH/SDH >0.5 cm thickness
Spinal cord injury
Penetrating brain injury
Arrest at scene
Unreactive pupils >4mm, and GCS=3
Neurosurgery contraindicated (eg: severe coagulopathy)
No chance of survival after consideration of CT and clinical
findings following Neurosurgical consultant assessment (eg
hemispheric infarct after carotid dissection).

8. Study Procedures
• Treated in ICUs with ICP monitors
• Patients received treatment for intracranial
hypertension whenever the intracranial pressure was
>20 mm Hg.
• An early refractory elevation in ICP was defined as a
spontaneous increase in intracranial pressure for >15
minutes (continuously or intermittently) within a 1hour period, despite optimized first-tier interventions.
• 1st tier interventions included optimized sedation, the
normalization of arterial carbon dioxide pressure, and
the use of mannitol, hypertonic saline, neuromuscular
blockade and EVD.

9. • Within the first 72 hours after injury, patients
were randomly assigned either to undergo
decompressive craniectomy plus standard
care or to receive standard care alone, using
an automated telephone randomisation /
allocation system.

10. Surgical technique – Polin
• The operation will comprise bi-frontal decompressive
craniectomies with a single fronto-temporal bone flap
extending across the midline.
• The temporalis muscles will be reflected inferiorly.
• Burr holes are located either side of the sagittal sinus at the
posterior extent and bilaterally at the keyhole and at the
root of the zygoma. This will create a large bifrontal
craniectomy defect extending posteriorly to the coronal
sutures. Bilateral large sub-temporal decompressions will
be performed down to the skull base.
• The final bone cut is made along the supraorbital ridges
with an attempt to preserve the frontal sinus. Burr holes
will be placed either side of the sagittal sinus inferiorly and
the bone will be lifted out.

11. • The dura will be opened in one of two
alternative ways:
– 1. The dura is opened with a cruciate incision
bilaterally.
– OR
– 2. A large L shaped incision with the lower corner
of the L facing laterally. The advantage to this
method is that the cerebral veins are not
disturbed medially by this incision.

12. • The dural opening should be covered with a dural or facial
patch, so that the brain does not adhere to the scalp. Water
tight dural closure is not necessarily aimed for.
• For patients receiving EVD monitoring, an ICP monitor with
ventricular catheter (± optional PO2 and temperature
monitor) may be placed prior to closure.
• The bone flap is replaced once bone swelling has resolved
and the patient has improved and left the intensive care
unit (6-12 weeks). The bone flap is stored at - 20 to -70°C
until reinsertion or it may be implanted in the
subcutaneous tissue of the abdominal wall as an
alternative.

13. The DECRA operation procedure
• The procedure does not involve a fish-mouth opening of the
dura and dividing the sagittal sinus.
• The craniectomy extends from just above the supra-orbital
ridge inferiorly to the coronal suture superiorly and
posteriorly.
• An extension of the craniectomy is performed from the lower
edge of the bone cut in the temporal region so that the
squamous temporal bone is removed by rongeurs extending
inferiorly close to the floor of the middle fossa on each side.
• In order to avoid opening the frontal sinus the bone can be
left in place in the inferior cut so that the sinus is not entered.
• There is no mid-line strip of bone left in place.
• There is no problem with potential kinking of the sagittal sinus
at the superior bone incision margin.

14. • The dura is opened on each side and this can be done with
a generous cruciate incision centred on the frontal pole on
each side or with an 'L' shaped incision with the vertical
limb of the 'L' laterally and the horizontal limb pointing
inwards toward the sagittal sinus. There is a theoretical
advantage in the protection of the bridging veins if this
technique is used although the coordinating site has not
encountered any problem with cruciate incision.
• A dural patch is placed over the durotomy and this can be
temporalis fascia and pericranium or synthetic dura and
does not necessarily need to be water-tight. It is there to
protect the surface of the brain from adhering to the scalp
and to act as a further barrier to infection.
• The excision of bone does not proceed posterior to the
coronal suture on either side.
• The bone can be stored in a subcutaneous pouch in the
abdominal region or preserved in the refrigerator.
• The ventricular catheter should be passed through a
separate burr hole posterior to the superior margin of the
bone cut and brought out through a separate incision

15. • After all swelling and infection had resolved, 2 to 3
months after craniectomy, the bone was replaced.
• Standard care from the time of enrollment followed
clinical practice guidelines that were based on those
recommended by the Brain Trauma Foundation.
• In the two study groups, second-tier options for
refractory elevation of ICP included mild hypothermia
(to 35°C), the optimized use of barbiturates, or both.
• For patients receiving standard care, the trial protocol
permitted the use of lifesaving decompressive
craniectomy after a period of 72 hours had elapsed
since admission.

16. Assessments & Data Collection
• All source data were verified in every patient by monitors.
At baseline, demographic and clinical characteristics were
recorded from medical files. These data included the initial
CT findings, which were scored with the use of the Marshall
criteria, and the Injury Severity Score
• The Trauma Score–Injury Severity Score was also
calculated.
• Hourly ICP and MAP measurements were recorded for 12
hours before randomization and 36 hours after
randomization.
• Also recorded were first- and second-tier therapeutic
interventions and surgical complications of craniectomy
and of subsequent cranioplasty.

17. Outcome Measures
• Outcome measures were evaluated by telephone by three
trained assessors who were unaware of study-group
assignments.
• The original primary outcome was the proportion of
patients with an unfavorable outcome, a composite of
death, a vegetative state, or severe disability, as assessed
with the use of a structured, validated telephone
questionnaire at 6 months after injury.
• After the interim analysis in January 2007, the primary
outcome was revised to be the functional outcome at 6
months after injury on the basis of proportion proportional
odds analysis of the Extended GOS.
• Secondary outcomes were ICP measured hourly, the
intracranial hypertension index, the proportion of survivors
with a score of 2 to 4 on the Extended GOS, the numbers of
days in the ICU and in the hospital, and mortality in the
hospital and at 6 months.

18. Study Oversight
• Funding was provided by the National Health
and Medical Research Council of Australia; the
Transport Accident Commission of
Victoria, Australia; the Intensive Care
Foundation of the Australian and New Zealand
Intensive Care Society; and the Western
Australian Institute for Medical Research.

19. Statistical analysis
• The trial was originally designed to identify an increase in
the proportion of favorable outcomes (defined as a score of
5 to 8 on the Extended GOS) from 30% among patients
receiving standard care to 50% among patients undergoing
craniectomy, with a sample size of 210 patients.
• To allow the trial to be completed within a reasonable time
frame, the sample size was decreased to 150, with an
additional enrollment of 15 patients permitted if necessary
to replace patients lost to follow-up.
• Ordinal logistic regression for univariate between-group
comparisons of scores on the Extended Glasgow Outcome
Scale and logistic regression for comparisons of unfavorable
outcomes
• Stata statistical software

23. • Of 3478 patients who were assessed for trial
eligibility, 155 were enrolled
• The first 5 patients who were enrolled in the trial
participated in a pilot study
• The most common reasons for exclusion from the trial
were the presence of a cerebral mass lesion and
successful control of ICP with the use of first-tier
therapies.
• The patients were randomly assigned to one of the two
treatment groups: 73 to undergo early decompressive
craniectomy and 82 to receive standard care.

24. • The median age was 23.7 years in the craniectomy
group and 24.6 in the standard-care group.
• The median ICP during the 12 hours before
randomization was 20 mm Hg.
• The median time from randomization to surgery in the
craniectomy group was 2.3 hours
• Fifteen patients (18%) in the standard-care group
underwent delayed decompressive craniectomy as a
lifesaving intervention, according to the protocol.
• In four patients (5%) in the standard-care
group, craniectomy was performed less than 72 hours
after admission, contrary to the protocol.

25. Outcomes

27. • Of patients, 70% in the craniectomy group had
an unfavourable outcome versus 51% in the
standard care group.

28. • Among adults with severe diffuse TBI and refractory
intracranial hypertension in the ICU, decompressive
craniectomy decreased ICP, the duration of mechanical
ventilation, and the time in the ICU, as compared with
standard care.
• In the craniectomy group, the duration of the hospital stay
was unchanged, and the rate of surgical complications was
low.
• However, patients in the craniectomy group had a lower
median score on the Extended Glasgow Outcome Scale and
a higher risk of an unfavorable outcome (as assessed on
that scale) than patients receiving standard care.

29. • Craniectomy or cranioplasty may also have
had other harmful complications, including
hydrocephalus.
• The rates of most complications were similar
in the two study groups.

30. Limitations
• The medical and surgical teams were obviously aware of
study-group assignments, although the assessors were not.
• One center recruited more than one third of trial participants.
• There were imbalances in some baseline characteristics of the
patients, particularly the proportion of patients without pupil
reactivity at hospital admission.
• The primary outcome measure was revised during the course
of the trial, though with preservation of blinded study-group
assignments. Such a change in protocol is not optimal from
the standpoint of trial design, although ultimately, the same
results were observed for both the original primary outcome
measure and the final primary outcome measure.

31. • It is unlikely that the findings were due to an increased rate
of survival of severely injured patients in a vegetative state
, because even though the number of such patients
increased after craniectomy, the rates of death were similar
in the two study groups.
• Decompressive craniectomy instead shifted survivors from
a favorable outcome to an unfavorable outcome
• One possible explanation is that craniectomy allowed
expansion of the swollen brain outside the skull and caused
axonal stretch. Alterations in cerebral blood flow and
metabolism may also be relevant.
• Some surgeons prefer a unilateral procedure, with studies
suggesting that the bilateral approach may have more
complications. Some surgeons divide the sagittal sinus and
falx cerebri, which is a component of the original Polin
procedure, but others do not. Complications are possible
with both alternatives.
• The results of this trial can be said to apply only to the
specific craniectomy procedure that was performed; they
may not necessarily apply to other approaches or in other
types of brain injury.

34. Criticisms
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The median ICP in the hours prior to randomization was 20 mm Hg, which raises
the important question of whether the patients in the study truly had intracranial
hypertension and whether the patients should have ever been considered for
surgery.
27% of the patients randomized to surgery had bilateral nonreactive
pupils, compared to only 12% of the patients in the medical group. This key
discrepancy was statistically significant, and when accounting for this betweengroup difference, there was no difference in outcomes between patients in the
decompressive craniectomy and medical management groups.
Performing their analysis via an “intention-to-treat” design, despite an 18%
crossover rate to surgery in the patient group initially randomized to medical
management.
Managing ICPs for 15 minutes prior to randomization, changing the study design at
the midpoint analysis instead of stopping the trial for futility, and enrolling in the
study only 4% of screened patients over 7 years.
The DECRA trial contains no data or valuable information to inform modern
management of TBI and thus should be ignored by practitioners evaluating
treatment options for severe TBI.

35. Conclusion
In patients with severe diffuse traumatic brain
injury and increased intracranial pressure that
was refractory to first-tier therapies, the use
of craniectomy, as compared with standard
care, decreased the mean intracranial
pressure and the duration of both ventilatory
support and the ICU stay but was associated
with a significantly worse outcome at 6
months, as measured by the score on the
Extended GlasgowOutcome Scale.

36. • Intracranial hypertension index – the number
of end-hourly measures of ICP of > 20 mm Hg
divided by the total number of
measurements, multiplied by 100

37. MARSHALL CT BRAIN GRADING
SCORE

38. Extended Glasgow Outcome Score