Neurology Literature Summaries

HYPOXIC ENCEPHALOPATHY

Zandbergen, E.G., et al (1998) “Systematic review of early prediction of poor outcome in anoxic-ischaemic coma” Lancet 352:1808-1812

• 33 studies
• 14 prognostic variables looked at
• 3 variable had a specificity of 100% for poor outcome:
  1. absent pupillary reflexes @ day 3
  2. absent motor response to pain (worse than withdrawal) on day 3
  3. bilateral absence of early cortical SSEP within the first week
• other poor prognostic factors = an isoelectric EEG, burst suppression, myoclonus on stimulation.

SEDATION IN ICU

Kress, J.P., et al (2000) “Daily interruption of sedative infusions in critically ill patients undergoing mechanical ventilation” N Engl J Med 342:1471-1477

• single centre RCT
• n = 128
• sedative infusions interrupted daily until patient awake VS at discretion of treating clinicians

-> reduction in the duration of MV
-> reduction in length of stay in ICU
-> decrease investigation for coma (CT, MRI, LP)
-> significant increase in days awake

Kress, J.P., et al (2003) – Am J Respir Crit Care Med 168:1457-1461

• daily interruption of sedative infusions

-> does not result in adverse psychological sequalae
-> reduces PTSD

other studies:

-> reduced vasoactive drug therapy
-> reduced fluid administration
-> reduced duration of MV
-> reduced stay in ICU
-> reduced stay in hospital

Girard, T. D., et al (2008)– “The Awake and Breathing Controlled Trial” Lancet; 371:126-134

• 4 Centers is North American
• RCT – 2003-2006
• inclusion criteria: > 18 years, on MV for > 12 hours
• exclusion criteria: post cardiac arrest, moribund, > 2 weeks ventilatory support, severe dementia, co-enrolled in another trial
• intervention = SBT vs SAT -> SBT
• primary end points = ventilator free days
• secondary end points = delirium, 28 day -> 1 year mortality, length of stay in ICU and hospital
• n = 334 (powered of 80%)
• intention to treat analysis

RESULTS

-> reduction in ventilator free days
-> reduced mortality at 1 year
-> similar delirium rates but less coma
-> increased risk of extubation -> however, risk of re-intubation same in control arm
-> higher rate of successful extubation
-> lower trachestomy rate

STRENGTHS

• protocolised
• multi-centre

WEAKNESSES

• not blinded
• not generalisable to Australasia (North America has Ventilator Technician)
• surgical patients not enrolled
• sedation time and practice not recorded

ISCHAEMIC STROKE

Chen, Z.M., et al (2000) “Indications for early aspirin use in acute ischemic stroke: a combined analysis of 40,000 randomized patients from the Chinese acute stroke trial and the international stroke trial.” On behalf of the CAST and IST Collaborative Group. Stroke 31:1240-1249

• combined results of two large RCT
• n = 40,000
  -> starting aspirin promptly in patients with suspected acute ischaemic stroke -> reduces immediate risk of further stroke in hospital + in hospital death.
  -> no significant increase in haemorrhage in patients given aspirin prior to CT
  -> no increase in mortality or further strokes in those who were given aspirin inadvertently after a haemorrhage stroke.

The National Institute of Neurological Disorders and Stroke rt-PA Stroke Study Group. (1995) “Tissue plasminogen activator for acute ischemic stroke” N Engl J Med 333:1581-1587

• RCT (double-blind)
• n = 624
• rt-PA for ischaemic stoke delivered within 3 hours of onset of signs
  -> lack of early benefit but significant improvement in functional status @ 3 months
  -> significant increase in intracranial haemorrhage in the rtPA group (6.4% vs 0.6%)
  -> other studies in the 90’s carried out: no benefit and increased risk of bleeding

Vahedi, K. et al (2007) “Early decompressive surgery in malignant infarction of the middle cerebral artery: a pooled analysis of three randomised controlled trials” Lancet 6:215-22

• 3 European MRCT’s (DECIMAL, DESTINY, HAMLET) looking at decompressive craniectomy for malignant infarction of MCA vs conservative management.
• mortality = 80% with medical treatment
• aim = to assess wheter decompressive surgery reduces mortality without an increase in the number of severely disabled survivors (mRS score of 5)
• inclusion criteria: age 18-60, treated within 48 hours, decreased LOC, signs on CT of an infarct of atleast 50% of MCA territory +/- anterior or posterior artery involvement on the same side, consent
• exclusion criteria: prestroke score of mRS > 2, fixed dilated pupils, contralateral ischaemia or brain lesion, space occupying haemorrhagic transformation, life expectancy < 3 years, other serious illnesses that could effect outcome, coagulopathy, contraindication to anaesthesia, pregnancy
• primary outcomes = modified Rankin scale @ 1 year (favourable or unfavourable)
• secondary outcomes = case fatality @ 1 year, dichotomisation of modified Rankin scale mRS 0 = no symptoms 3 = moderate disability (requiring some help, walk without assistance) 6 = death – n = 93 – base line characteristics similar
• NNT for survival = 2!
  -> post decompression anti-oedema treatment rarely needed
  -> increases survival and favourable outcome (mRS < 3 after 12 months)

OTHER

Plasma Exchange/Sandoglobulin Guillain-Barre Syndrom Trial Group. (1997) “Randomized trial of plasma exhange, intravenous immunoglobulin, and combined treatments in Guillian-Barre syndrome” Lancet 349:225-230

• MRCT
• n = 383
• plasma exchange VS IV IgG VS plasma exchange + IgG
  -> no significant difference in disability
  -> no significant difference in time to independent mobility
  -> no significant difference in duration of MV
  -> IgG is fine and simpler than plasma exchange

van de Beek D, de Gans J, McIntyre P, et al: Corticosteroids for acute bacterial meningitis. Cochrane Database Syst Rev 2007; 1

de Gans J, van de Beek D: European Dexamethasone in Adulthood Bacterial Meningitis Study Investigators: Dexamethasone in adults with bacterial meningitis. N Engl J Med 2002; 347:1549-1556

• systematic reviews
• dexamethasone with first antibiotics in community acquired bacterial meningitis
  -> reduces mortality
  -> reduces severe hearing loss
  -> reduces neurological sequelae