Traumatic Brain Injury Literature Summaries

Reviewed and revised Chris Nickson and Sarah Yong

STEROIDS AND TBI

Roberts I, Yates D, Sandercock P, et al: CRASH trial collaborators: Effect of intravenous corticosteroids on death within 14 days in 10008 adults with clinically significant head injury (MRC CRASH trial): randomised placebo-controlled trial. Lancet. 2004 Oct 9-15;364(9442):1321-8. [PMID 15474134]

Edwards P, Arango M, Balica L, et al: CRASH trial collaborators: Final results of MRC CRASH, a randomised placebo-controlled trial of intravenous corticosteroidin adults with head injury-outcomes at 6 months. Lancet. 2005 Jun 4-10;365(9475):1957-9. [PMID 15936423]

• n = 10,000
  inclusion: all severity of HI
• 48 hours of IV steroids vs placebo
  -> stopped early as…
  -> increased mortality within 14 days
  -> increases mortality @ 6 months
  -> increased risk of severe disability

THERAPEUTIC HYPOTHERMIA AND TBI

Clifton GL et al. Lack of effect of induction of hypothermia after acute brain injury. N Engl J Med. 2001 Feb 22;344(8):556-63. [PMID 11207351]

• MRCT, US, 9 centers
• n = 392
• inclusion: severe TBI
• normothermia VS moderate hypothermia (T 33C for 48 hrs)
  -> improves ICP but no reduction in mortality
  -> patients older than 45 do worse with induced hypothermia
  -> if they arrive hypothermic -> do not warm to 37 C (poorer outcome)
  -> if you have a low temperature on arrival you have a more significant TBI

BTF GUIDELINES

Brain Trauma Foundation Guidelines – Guidelines for the Management of Severe TBI

• consensus guidelines
• covers:
  -> classification
  -> resuscitation
  -> management of ICP
  -> seizure prophylaxis
  -> poor outcome prediction
  -> CPP lowered to 60mmHg from 70mmHg (increased risk of ARDS)

ERYTHROPOIETIN

Robertson CS, Hannay J, Yamal JM et al and the EPO Severe TBI Trial Investigators. Effect of erythropoietin and transfusion threshold on neurological recovery after traumatic brain injury: a randomised clinical trial. JAMA 2014, 312 (1): 36 – 47. PMID: 25058216

• Prospective RCT, 2×2 factorial design, 2 US level 1 trauma centres
  • N = 200
  • Closed head injury, moderate to severe, unable to follow commands after resuscitation, within 6 hrs of injury
• Background
  • Anaemia is common in TBI and many contribute to secondary brain injury
  • Suggestion from smaller studies that EPO associated with neuroprotective effects in TBI: anti-inflammatory, anti-apoptotic, vascular neuroprotective effects
  • Red cell transfusion in TBI is controversial with little evidence to guide practice
• Intervention
  • EPO Vs placebo
  • Hb transfusion threshold 7 vs 10 g/dL
• Outcomes
  • Glasgow Outcome Scale at 6 months post-injury, dichotomised as
    • Favourable: good recovery and moderate disability, or
    • Unfavourable: severe disability, vegetative, dead
  • Results
    • No improvement in neurologic outcomes with EPO
    • No improvement in neurologic outcomes with maintaining Hb > 10g/dL
    • Higher rate thromboembolic events with transfusion threshold > 10g/dL
  • Comments
    • No benefit with higher transfusion threshold (this may cause harm) nor EPO in TBI
    • EPO formulation changed during trial: initial EPO-1 regiment showed promising neurological outcome results compared to EPO-2 or placebo, however the switch resulted in insufficient numbers to assess
    • Switched from EPO-1 to EPO-2 in response to the EPO Stroke Trial, which showed patients with regimen similar to EPO-1 had higher mortality

EPO-TBI – ANZICS Trial currently in progress

• currently recruiting
• MCRCT
• moderate to severe TBI: EPO vs placebo
• there is some data that EPO can prevent the degree of secondary brain injury

DECOMPRESSIVE CRANIECTOMY

Cooper, D, J, et al Decompressive craniectomy in diffuse traumatic brain injury. N Engl J Med. 2011 Apr 21;364(16):1493-502 [PMID 21434843]

• ANZICS Trial
• 15 tertiary centres (Australia, NZ and Saudi Arabia)
• n = 155
• early bifrontotemporoparietal decompression (within 6 hours) vs conventional treatment
• inclusion: age 15-59 years, severe, nonpenetrating severe TBI
• exclusion: not for full active treatment, dilated, unreactive pupils, mass lesions that required surgery, spinal cord injury, cardiac arrest at the scene.
• randomized at:
  • -> > 20mmHg
  • -> > 15min
  • -> post first tier ICP management: sedation, normal PaCO2, mannitol, hypertonic saline, paralysis and EVD
• post surgery or not second tier management introduced: mild hypothermia (35 C), barbiturates
• patients could undergo life threatening decompression after 72 hours.
• primary outcome: functional out come as per Extended Glasgow Outcome Scale
• secondary outcomes: hourly ICP, intracranial hypertension index, proportion of survivors with a EGOS of 2-4 (severe disability and requiring assessment with ADLs), days in ICU, days in hospital, mortality at 6 months.

-> less raised ICP
-> shorter duration of MV
-> shorter stay in ICU
-> no change in duration in hospital
-> more medical and surgical complications
-> worse functional outcome @ 6 months (when adjusting for pupil reactivity this difference disappeared)

Strengths

• no patients lost to follow up
• adequately powered base on adjusted interim analysis (except more of the craniectomy group has unreactive pupils)
• 96% success with interventions
• only 5% of the standard care group had a violation (received decompression within 72 hours of admission)

Weaknesses

• surgical technique not standardised.
• craniectomy group may have been sicker (pupil reactivity difference)
• one centre recruited 1/3 of the patients
• non-blinding for obvious reasons
• change of primary outcome during trial (although when analysed this did not change outcomes)

AN APPROACH

• evacuate haematoma.
• control ICP as much as I can medically.
• use decompressive craniectomy as a rescue therapy.
• less is more.
• await RESCUE-ICP trial

OSMOTHERAPY AND TBI

Whyte, Cook, VENKATESH, The Use of Hypertonic Saline for Treating Intracranial Hypertension After TBI Anesth Analg 2006

– review presenting advantages and use of HTS in TBI

References and Links

• Brain Trauma Foundation Guidelines – Guidelines for the Management of Severe TBI