PPT on all important trials of traumatic brain injury. - includes design, setting, statistical analysis,outcome, strength, limitations, conclusion#DECRA#RESCUEicp#BEST TRIP#CRASH1#CRASH3#SAFE TBI#EUROTHERM3939#POLAR TRIAL Also includes trial related BTF guidelines

1. TRIALS OF TBI
DR AMRITA SHAH

2.  Treatments
• 1. Decompressive Craniectomy  DECRA, RESCUEicp
• 2. Prophylactic Hypothermia EUROTHERM 3235 TRIAL, POLAR TRIAL
• 3. Hyperosmolar Therapy  META-ANALYSIS
• 4. Steroids  CRASH-1
 Monitoring
• 5. Intracranial Pressure BEST TRIP
 Others
• Fluids -SAFE TRIAL
• Tranexemic acid- CRASH 3

3. DECOMPRESSIVE CRANIECTOMY
DECRA, RESCUEicp

4.  Level II A
 New
• Secondary DC performed for
– Late refractory ICP elevation is recommended to improve mortality and
favorable outcomes.
– Early refractory ICP elevation is not recommended to improve mortality and
favorable outcomes
– It is suggested to reduce ICP and duration of intensive care, though the
relationship between these effects and favorable outcome is uncertain.

5. Decompressive Craniectomy
• A large FTP DC (not <12 × 15 cm or 15 cm in diameter) is recommended over a
small FTP DC for reduced mortality and improved neurological outcomes in
patients with severe TBI.
 Whats out?
• “Bifrontal DC is not recommended to improve outcomes as measured by GOS-E
score at 6 months post-injury in severe TBI patients that are refractory to first-tier
therapies.”This recommendation was based on the 6-mo outcomes from
DECRA.
• 12-mo outcome data from DECRA and RESCUEicp.(Class1 evidence)

6. • Multi-centeric, randomised controlled trial
 Setting:
• December 2002 – April 2010
• 15 tertiary care hospitals in Australia, New Zealand, and Saudi Arabia
• Randomization – automated telephone/ allocation system
• Intention to treat analysis
• Stratified according to center and the technique to measure ICP

7.  Sample size - 210 patients ,to detect a favorable outcomes (defined as a
score of 5 to 8 on the Extended Glasgow Outcome Scale) from 30% -
standard care to 50% among patients undergoing craniectomy, a power of
80% , type 1 error- 0.05To allow the trial to be completed within a
reasonable time frame, the sample size was ↓150 to detect in- between
group difference of 1.5
 Early refractory elevation in ICP
- increase in ICP > 15 minutes (continuously or intermittently) within a 1-
hour period.

8.  Inclusion criteria:
• diffuse TBI: GCS < 9 and CT scan swelling OR GCS >9 pre intubation + severe CT
swelling (Grade DIII or IV), < 72 hrs since accident, ICP in situ (EVD, Codman
acceptable)
 Exclusion criteria:
• arrest at scene; GCS 3 + F&D pupils; age > 60, mass lesion + craniectomy, spinal
cord injury, neurosurgery contraindicated, no chance of survival.
 Primary outcome: functional outcome at 6 months (GOS-E)

9.  Common to both groups
• CT Findings, TISS score
• Hourly intracranial pressure and
• MAP measurements were
recorded for 12 hours before
randomization and 36 hours
after randomization.
• 1st tier treatment
• 2nd tier treatment
 Procedure: Bi-FTP Craniectomy
(Polin’s technique)

10. OUTCOMES
At 12 mo, trend to worse functional outcomes in the craniectomy group

11. • Primary outcome -worse in the craniectomy group (median score, 3 vs 4; odds ratio
in the craniectomy group, 1.84; 95% CI, 1.05 to 3.24; P = 0.03)
• Unfavorable outcomes occurred in 51 patients (70%) in the craniectomy group and
in 42 patients (51%) in the standard care group (odds ratio, .21; 95% CI, 1.14 to
4.26; P = 0.02)
 Authors conclusion:
• Decompressive craniectomy group  Decreased intracranial pressure, the
duration of mechanical ventilation and the time in the ICU.
• Had a lower median score on the GOS-E and a higher risk of an unfavorable
outcome than patients receiving standard care.

12. LIMITATIONS
• 88% of patients from Australia or New Zealand- External validity?
• Imbalance in baseline characteristic:
• Medical and surgical teams aware, but assessors were not
• Low threshold for decompression – 20 mmHg
• Large proportion of cases "mass lesions" excluded(1222)
• Though “intention to treat”, 18% crossover rate to patient group initially
randomised for medical management.
• The recruitment rate (4.5 per cent) limits the study to a selected subpopulation.
Its population size is insufficient to detect 10 per cent differences between
groups; it would have been needed to study 321 patients randomized on a 1:1
basis

13.  Sample Size-
– 400 patients was calculated to detect a 15% difference in favourable outcome rate(from 45% to
60%) between the two groups. A power of 80% allowed for a loss of follow-up of up to 15%
 Surgical procedure-either
– large unilateral FTP craniectomy  unilateral hemispheric swelling, or
– bifrontal craniectomy with diffuse brain swelling that affected both hemispheres on imaging
studies.

14.  Inclusion Criteria
• Age 10 - 65 years
• TBI as assessed by abnormal CT scan brain
• Intracranial pressure monitor in place
• ICP > 25 mmHg** for 1-12 hours despite stage 1 and 2 measures
• Mass lesion (but not a “decompressive” craniectomy)**
 Exclusion Criteria
• Craniectomy performed for evacuation of intracranial hematoma
• Bilateral fixed and dilated pupils
• Bleeding diathesis
• Injury deemed to be unsurvivable
• **Difference with DECRA

15. • The primary endpoint is
the GOS-E at 6 months
• The characteristics of the
two groups were similar at
baseline

16.  At 6 months, the patients in DC group resulted in:
• lower mortality and
• higher rates of vegetative state, lower severe disability and upper severe
disability than ongoing medical care group.
• The rates of moderate disability and good recovery were similar in the two
groups

17. • GCS at discharge from hospital
-18.9% in the craniectomy group vs. 12.2% in the medical group had GCS of
8 or less
• Assessment of intracranial pressure control: favoured the craniectomy group
• Time to death or discharge from ICU: no statistical difference
• The median lengths of stay in ICU are 15 days in the craniectomy group and 20.8
days in the medical group
• % of patients with at least one reported complication or adverse event:
statistically significant increase in the craniectomy group 15.3% vs. 9.2%
Authors’ Conclusions
• At 6 months, decompressive craniectomy in patients with refractory ICP resulted in
• lower mortality and
• higher rates of vegetative state, lower severe disability, and upper severe disability
than medical care

18. Strengths
• All trial sites had immediate access to 24 hour neurosurgical services
• Exploratory analyses examining the effect of covariate adjustment were pre-
specified
• Similar numbers of patients in the two groups received stage 1 and stage 2
treatments
• Timing for initiation of stage 3 treatment was similar in both groups
• Randomisation code was not released until the patient had reached stage 3 of
the protocol

19. Limitations: RESCUE icp
• 71% of patients were recruited in the UK- Ext validity
• 37% of patient in medical management group underwent decompressive
craniectomy. It does not say when, why or what technique was used.
• Recruitment of all 408 patients took 10 years. Half the centres recruited
only 3 patients, or fewer(inclusion rate of 20.36 per cent )
• The medical therapeutics was ‘‘at the discretion of the treating medical
team’’  heterogeneous way and without a uniform protocol.
• There are no data on the level of therapeutic intensity prior to
randomization
• Therapeutic hypothermia one of the optional Stage 2 rescue therapies -
may confer a survival disadvantage.

20. Upper Severe
disability
considered a
favourable outcome
in RESCUEicp**

21. Early Surgery versus Initial Conservative Treatment in Patients with
Traumatic Intracerebral Hemorrhage STITCH[Trauma]):
• International, multicenter, prospective, randomized, parallel group, pragmatic
• 170 patients  from 31 registered centres in 13 countries
• December 2009 to September 2012
• Randomization  centrally 24-h telephonic and Web randomization service
• Stratified by geographical region
• Appropriate concealment of allocation until randomisation
• Open-label – patients, families and treating clinicians aware
• Outcome assessed at 6 months by postal questionnaire or interview (blinded)
• Intention to treat analysis

22.  Sample size:
• 840 patients required
• Power- 80% to detect a 10% absolute increase in the rate of favourable
outcome from an expected incidence of 50% with conservative treatment
and an alpha level of 0.05
– The funding agency halted this study from end of September 2012 for
“failure to recruit in the UK”
– Modified protocol powered at 80% to detect a 21% absolute increase
in the rate of favourable outcome

23.  Inclusion criteria:
• Adults within 48 h of TBI and had evidence of a TICH on CT with a confluent
volume of attenuation >10 mL
 Exclusion criteria:
• A significant surface hematoma (EDH or SDH) requiring surgery; three or more
separate hematomas fulfilling the inclusion criteria; a cerebellar
hemorrhage/contusion;
• Surgery could not be performed within 12 h;
• Severe pre-existing physical or mental disability or comorbidity
• Permanent residence outside study country; and
• Strong preference for one treatment modality by family

24. Intervention
• Early evacuation of the
haematoma by a method of the
surgeon’s choice (within 12h of
randomisation), combined with
appropriate best medical
treatment
Control
• Best medical treatment combined
with delayed (>12 h after
randomisation) evacuation
Management Common to Both Groups
• Coagulopathies corrected prior to randomisation
• Best medical treatment -monitoring of ICP or other modalities and management of
metabolism, sodium osmotic pressure, temperature, and blood gasses
• All patients had a CT scan at 5 days (+/–2 days) after randomisation

26. Outcome
• Primary outcome- Benefit of early surgery on the GOS dichotomized into:
– Favourable outcome= good recovery or moderately dependent
– Unfavourable outcome = severely dependent, vegetative, or dead

27.  Strengths
• Relevant clinical question, Randomised, Multi-centre
• Outcome assessor blinded
• Intention-to-treat analysis
 Limitations
 Poor Internal validity
• Change of protocol-but subsequently modified due to premature termination
of trial and decreased sample size
• Inclusion criteria changed-24 h to 48 h during the trial to increase recruitment
• 111 patients recruited from centres where screening logs were not collated

28. Limitations
• Lot of cross-overs:
– Of the 82 patients in the early surgery group, only 61 (74%) had surgery, 57
(93%) of these within 12 h of randomisation
– Of the 86 patients randomized to initial conservative treatment, 31 (36%) had
surgery within 14 days of randomization, 10 (32%) of these within 12 h.
 External validity:
• ICP monitoring only undertaken in 24 (14%) patients
• Underpowered study, most patients recruited from India and China
 Authors’ Conclusions
• A larger trial is needed to confirm this potentially very beneficial effect of
earlier surgery
• There is a strong case for operating on patients with TICH who have a GCS of
9–12

30.  Advantages of decompression in TBI include
• Maybe some sort of mortality benefit - RESCUEicp
• Shorter ICU stay, less ICP-targeting interventions, lower ICP
 Disadvantages include:
• Conflicting evidence for mortality benefit (19% vs 18% in the DECRA Trial, versus
26.9% vs 48.9% in RESCUIicp)
• Worse neurological outcome in survivors
• Multiple complications associated with decompressive craniectomy

31. PROPHYLACTIC HYPOTHERMIA
Eurotherm3235, POLAR

32.  Level I and II A
• Insufficient evidence to support a Level I or II A
 Level II B
• Early (within 2.5 hours), short-term (48 hours post-injury) prophylactic
hypothermia is not recommended to improve outcomes in patients with
diffuse injury.

33. • Multi-centric, multi-country RCT -55 centres in 18 countries-53% patients
recruited in UK
• Nov 2009 – Oct 2014(pilot phase- September 15, 2011)
• Centralised randomisation
• Open-label ; Appropriate allocation concealment until inclusion
• Pilot trial period  subsequent adjustment of inclusion criteria and target
sample size
• 600 patients ; Powered at 80% to detect a 9% absolute reduction in
unfavourable outcomes(GOS-E 1 TO 4)-51% vs 60%
• The sample size for the full trial was reduced from 1800 to 600 patients

34. • Inclusion:
• Adults, primary closed TBI and ICP> than 20mmHg for at least 5 minutes after
stage 1 treatments with no obvious reversible cause
– an initial head injury within <10 days
– availability of a cooling device or technique for > 48 hours
– core temperature -36°C at time of randomisation
– abnormal CT brain
• Exclusion: patients already receiving therapeutic hypothermia or were unlikely to
survive for the next 24 hours; barbiturates infused prior to randomisation;
temperature <34°C at hospital admission, and pregnancy

35. 2498 patients were screened, 387 were randomised, 386 received intended
treatment, 376 were evaluated in an intention to treat analysis
 Stage 2 treatments
if hypothermia
failed
• mannitol;
hypertonic saline;
inotropes
 Therapeutic
hypothermia (32-35°C)
for 48 hours + standard
care
• Cooling by bolus of 20-
30mls/kg of
refrigerated, 0.9% NaCl
IV
• Core temperature
reduced <ICP of
20mmHg
 Stage 3 treatments
• Barbiturate
therapy;
Decompressive
craniectomy
Rewarming strategy was controlled at 0.25°C per hour once ICP was controlled
Control-Standard care

36. Favourable outcomes less with hypothermia group
6 month mortality was statistically significantly increased in the hypothermia group
Failure of all stage 2 therapies to control ICP occurred less often in the hypothermia group

37.  Strengths:
• Participating centres had expertise with ICP monitoring and therapeutic cooling
• Rewarming strategy was controlled at 0.25°C per hour
• Patient centred outcomes rather than physiological measure (e.g. ICP)
• Pragmatic and based on existing guidelines (Stage 1, 2 and 3 therapy for raised
ICP)
 Limitations:
• The inclusion criteria was changed –
– to remove an upper age limit (previously 65 years) and
– to increase the time from injury from 72 hours to 10 days
• Loss of outcome data for 10 cases (given fragility index was 3)- could have
changed results
• Lack of data on additional Stage 2 therapies
 Authors’ Conclusions:
Did not result in better outcomes compared with standard care alone

38. Effect of Early Sustained Prophylactic Hypothermia on Neurologic
Outcomes Among Patients With Severe Traumatic Brain Injury-The
POLAR Randomized Clinical Trial

39. HYPEROSMOLAR THERAPY

40. • Recommendations from prior edition not supported by evidence meeting
current standards:
• Mannitol is effective for control of raised ICP at doses of 0.25 to 1g/kg BW.
Arterial hypotension (SBP <90mmHg) should be avoided.
Reference Study Data Class Conclusion
Mangat, 2014
HTS vs. mannitol in
treating ICP after severe
TBI
Class 2 HTS was more effective in
lowering ICP burden but
did not have a significant
effect on mortality.
Cottenceau 2011
HTS vs. MAN
Class 3 GOS at 6 months: no
significant difference
Ichai, 2009
LAC vs. MAN
Class 3 Better 1-year GOS scores
for LAC, but study not
powered to test this
question.
GOS=Glasgow Outcome Scale, HTS=hypertonic saline, ICP=intracranial pressure, LAC=sodium lactate,
MAN=mannitol, NS= Normal Saline, RCT=randomized controlled trial, TBI=traumatic brain injury.

41. STUDY(meta-analyses) CASES INCLUDED OUTCOME
Kamel et al 2011
HTS VS MAN
5 trials/112 patients
undergoing some method
of quantitative ICP
measurement for any
pathology
HTS>>MAN
Mortazavi et al 2012
HTS VS MAN
HTS VS NS
(TRAUMATIC + NON
TRAUMATIC)
HTS given as either a bolus
or continuous infusion
>>mannitol in reducing ICP.
Rickard et al 2014
HTS VS MAN
6 STUDIES/171 patients
in haemodynamically
stable adults with TBI
better ICP control with HTS,
but both mannitol and HTS
are equally effective, with
no statistically significant
difference.
Li M et al 2015
MAN VS HTS
7 TRIALS/169 PATIENTS
TBI HTS>>MAN
Berger-Pelleiter M et al
2016
HTS VS OTHERS
11 studies /1,820 patients
Severe TBI no mortality benefit or
effect on the control of ICP
with HTS when compared
to other solutions

42. • No clear superiority of one option over the other.
• The optimal agent, their optimal means of administration(i.e., dose and
bolus vs. continuous infusion), and their precise mechanisms of action
continues to be investigated in patients with severe traumatic injury.

43. STEROIDS
CRASH -1

44. Level I
• The use of steroids is not recommended for improving outcome or
reducing ICP.
• In patients with severe TBI, high-dose methylprednisolone was
associated with increased mortality and is contraindicated.
• Randomised, controlled trial
• 2 types of randomisation: Centralised (21%) and non-centralised (79%)
randomised concealed allocation -allocation sequence based on a block
size of 8.
• Blinding of clinicians, patients, and data analysts
• Intention-to-treat analysis

45. Powered at 90% to detect 2% difference in mortality from baseline of 15%,
with accepted type I error of 0.01 , 20,000 patients were recruited
239 hospitals from 49 countries
April 1999 to May 2004
 Inclusion:
• Adults > 16 years with TBI,
• within 8 hours of injury
• with GCS ≤ 14
 Exclusion:
• contraindication for steroids
 Methylprednisolone for 48 hours
• Loading dose of 2 g over 1 hour in
100 ml 0.9% NaCl
• Maintenance of 0.4 g per hour for
48 hours in 20 ml per hour 0.9%
NaCl

46.  Authors’ Conclusions
• “Corticosteroids should not be used routinely to treat head injury,
whatever the severity.”

47.  Strengths
• Excellent external validity
• Robust statistical thresholds in planning phase (⍺<0.01, β=90%)
• Primary outcome data available for over 99% of patients
• Rapid publication of important outcome with secondary outcomes published
later
 Limitations
• Halting at interim stage results may be an extreme play of chance
• Hyperglycaemia from corticosteroid administration may have unblinded
clinicians and / or led to unbalanced management of the two groups
• Cause of death not investigated

48. • Randomized, Placebo controlled
• Setting: 175 hospitals, 29 countries
• July 20, 2012, and Jan 31, 2019
• Random allocation through removal of the lowest numbered treatment pack
available
-Packs prepared with randomisation codes from an independent statistician
• Participants and study staff blinded
• Intention to treat analysis

49. • Initial power calculations 10000 patients to have 90% power (two sided α of
1%) to detect a 15% relative reduction (3 % ARR, from 20% to 17%) in mortality
• Sample size increased to 13000 as primary outcome changed to in-hospital
death within 28 days and
• Recruitment limited to < 3 hours of injury from 8 hrs (July 2016)
 Inclusion:
– Adults ,TBI within 3 hrs of injury ,GCS <=12 or intracranial bleeding on CT
– No major external bleeding
 Primary outcome – In hospital death within 28 days of injury , within 3 h of
injury
 Intervention -Tranexamic acid
– 1g over 10 minutes followed by IV infusion of 1g over 8 hours

50. • 12737 patients randomised
– 6406 to TXA of which 4649 were randomised < 3 hrs
• 4613 / 4649 analysed
– 6331 to placebo of which 4553 were randomised < 3 hrs
• 4514 / 4553 analysed
• Baseline characteristics well matched
• 28 day in-hospital mortality -no significant difference

51.  Pre-specified Subgroup Analysis of Primary Outcome
• Excluding those with GCS 3 or bilateral unreactive pupils-no significant
difference
– 28 day mortality in TXA group 485/3880 (12.5%) vs. 525/3757 (14.0%) in
placebo
• RR 0.89 (95% CI 0.80 – 1.00)
• ARR 1.47% (95% CI -0.05 – 2.99%)
• Patients with Mild to Moderate TBI (GCS 9-15) -significantly reduced in TXA
group
– 28 day mortality in TXA group 166/2846 (5.8%) vs. 207/2769 (7.5%) in
placebo
• RR 0.78 (95% CI 0.64 – 0.95)
• ARR 1.64% (95% CI 0.34 – 2.95%)

52.  Other secondary outcomes:
• Timing of TXA:
– < 1 hr RR 0.96 (95% CI 0.79 – 1.17)
– 1-3 hr RR 0.93 (0.85 – 1.02)
– Early treatment was more effective than later treatment in mild –
moderate injury (p=0.005), but timing had no effect in severe injury
• Disability Measures:
– No difference between groups
• Complications:
– No increased risk of vaso-occlusive events or seizures

53.  Authors’ Conclusions
• TXA safe in TBI and that treatment within three hours reduces head injury
associated deaths

54.  Strengths
• Good external and internal validity
• Sensible pre-specified subgroups – GCS and pupillary reaction
• Patient focused outcomes (eg. Patient Derived Disability Measures) in addition to
mortality
 Limitations
• The primary outcome of 28 day mortality could miss certain cohorts of patients
• The inclusion criteria were changed
• Differences between clinicians may exist -TBI associated death (this could lead to
recall and observer bias)
• No mention was made of pre-hospital interventions or management common in
both groups
• The overall rate of head injury-related death was 12% in the CRASH-2 sub-study,
versus 19% in CRASH-3- Dilution

55. ICP THRESHOLD
BEST TRIP

56. ICP threshold
 LEVEL IIB
• Treating ICP>22mmHg is recommended.
 LEVEL III
• A combination of ICP values, clinical and CT findings may be used to make
management decisions.
 BEST –TRIP TRIAL
• Clinical Question
• In patients with severe TBI does monitoring ICP improve mortality and
improve neurological function?

57.  Design
• Randomised controlled trial, Parallel-group
• Computer generated randomisation
• Stratified according to study site, severity of injury and age
• Blinding of examiners assessing neuro-functional outcome
• Sample size calculation
– 324 patients would give 80% power to detect an increase of 10% of
patients with a good outcome or moderate disability according to the
Extended Glasgow Outcome Scale (GOS-E)
• 6 sites in Bolivia and Ecuador
• September 2008 – October 2011

58.  Inclusion:
• Age ≥13; on admission or within 48 hours of injury: GCS 3-8
 Exclusion:
• GCS 3 and bilateral fixed and dilated pupils, Injury thought to be
unsurvivable
 Intervention
• Intracranial pressure monitoring
– Intra-parenchymal monitor placed as soon as possible
– Treated to maintain ICP <20mmHg , for median 3.6 days
 Control
• Treatment based on clinical finding and CT scan results
– Hyperosmolar therapy, optional mild hyperventilation + optional
ventricular drainage
– If continuing oedema high dose barbiturates, decompressive
craniectomy

59.  Intracranial pressure definitions
• Treatable intracranial hypertension: ICP > 20 mmHg for > 5 minutes
• Treatment failure: ICP not reduced to ≤ 20 mmHg within 20 minutes after
a treatment intervention is initiated
 Comparing intervention vs. control groups
• Significantly more patients in control group vs. intervention group treated
with: Hypertonic saline 72% vs. 58%, P=0.008, Hyperventilation 73% vs
60%, P=0.003
• Significantly more patients in intervention vs. control group treated with:
Barbiturates 24% vs. 13%, P=0.02

60.  Outcome
• Primary outcome: Composite of 21 components including survival time,
duration of impaired consciousness and neuropsychological status, at 6
months – no significant difference
• Secondary outcomes:
– No significant difference in mortality or GOS-E Scale
– Significant increase in Decubitus ulcers in ICP monitoring group
 Authors’ Conclusions
• Management guided by ICP monitoring is not superior to management
guided by neurological examination and serial CT imaging in patients
 Limitations: Not powered for mortality, Study performed in Bolivia and
Ecuador.

61.  There is no high level evidence supportive beneficial outcomes from ICP
monitoring
 BTF Guidelines lists the following indications:
• moderate -> severe head injury who can’t be serially neurologically
assessed
• severe head injury (GCS < 8) + abnormal CT scan
• severe head injury (GCS < 8) + normal CT if 2 of the following are present:
– Age > 40 yrs
– BP < 90mmHg
– Abnormal motor posturing

62. FLUIDS
SAFE TBI

63. • Multicenter, randomized, double-blind trial
• To compare the effect of fluid resuscitation with albumin or saline on
mortality in a heterogeneous ICU population.
• 16 ICUs in Australasia
• November 2001 – June 2003
• Stratified by centre and according to diagnosis of trauma
• Randomization: centrally with the use of a minimization algorithm
• 7000 patients, a power of 90 percent to detect a 3 percent difference in
absolute mortality rates between the two groups from an estimated
baseline mortality rate of 15 percent.

65. • Traumatic brain injury –
– diagnosis of trauma + GCS
≤13 at first hospital
presentation + an abnormal
CT head consistent with TBI
• The primary outcome  the
mortality rate and functional
neurologic outcome 24 months
• Baseline covariates was adjusted
accordingly.

66. • In critically ill patients with TBI, fluid resuscitation with albumin was associated
with higher mortality rates than was resuscitation with saline

68. References
• Guidelines for the Management of Severe TBI, 4th Ed. (Brain Trauma Foundation 2016)
• Guidelines for the Management of Severe Traumatic Brain Injury: 2020 Update of the
Decompressive Craniectomy Recommendations
• Decompressive craniectomy: RESCUEicp (NEJM 2016), DECRA trial (NEJM 2011)
• Early surgery versus initial conservative treatment in patients with traumatic intracerebral
hemorrhage (STITCH [Trauma]): the first randomized trial. J Neurotrauma 32:1312-1323,
2015
• Osmotherapy – Meta-analysis
• Hypothermia: EUROTHERM 3235 trial (NEJM 2015),POLAR(JAMA 2018)
• ICP- BEST TRIP Trial NEJM 2012
• Saline vs Albumin: SAFE-TBI trial (NEJM 2007)

69. THANK YOU