title: Meta-analysis of pre-clinical studies of early decompression in acute spinal cord injury: a battle of time and pressure.
abstract: BACKGROUND
  The use of early decompression in the management of acute spinal cord injury (SCI) remains contentious despite many pre-clinical studies demonstrating benefits and a small number of supportive clinical studies. Although the pre-clinical literature favours the concept of early decompression, translation is hindered by uncertainties regarding overall treatment efficacy and timing of decompression.
  
  
  METHODS
  We performed meta-analysis to examine the pre-clinical literature on acute decompression of the injured spinal cord. Three databases were utilised; PubMed, ISI Web of Science and Embase. Our inclusion criteria consisted of (i) the reporting of efficacy of decompression at various time intervals (ii) number of animals and (iii) the mean outcome and variance in each group. Random effects meta-analysis was used and the impact of study design characteristics assessed with meta-regression.
  
  
  RESULTS
  Overall, decompression improved behavioural outcome by 35.1% (95%CI 27.4-42.8; I(2)=94%, p<0.001). Measures to minimise bias were not routinely reported with blinding associated with a smaller but still significant benefit. Publication bias likely also contributed to an overestimation of efficacy. Meta-regression demonstrated a number of factors affecting outcome, notably compressive pressure and duration (adjusted r(2)=0.204, p<0.002), with increased pressure and longer durations of compression associated with smaller treatment effects. Plotting the compressive pressure against the duration of compression resulting in paraplegia in individual studies revealed a power law relationship; high compressive forces quickly resulted in paraplegia, while low compressive forces accompanying canal narrowing resulted in paresis over many hours.
  
  
  CONCLUSIONS
  These data suggest early decompression improves neurobehavioural deficits in animal models of SCI. Although much of the literature had limited internal validity, benefit was maintained across high quality studies. The close relationship of compressive pressure to the rate of development of severe neurological injury suggests that pressure local to the site of injury might be a useful parameter determining the urgency of decompression.
authors.affiliation: Florey Institute of Neuroscience and Mental Health, Heidelberg, Victoria, Australia.
authors.forename: Peter E
authors.initials: PE
authors.lastname: Batchelor
authors.forename: Taryn E
authors.initials: TE
authors.lastname: Wills
authors.forename: Peta
authors.initials: P
authors.lastname: Skeers
authors.forename: Camila R
authors.initials: CR
authors.lastname: Battistuzzo
authors.forename: Malcolm R
authors.initials: MR
authors.lastname: Macleod
authors.forename: David W
authors.initials: DW
authors.lastname: Howells
authors.forename: Emily S
authors.initials: ES
authors.lastname: Sena
mesh_terms: D000818:Animals; D019299:Decompression, Surgical; D004195:Disease Models, Animal; D017594:Publication Bias; D013119:Spinal Cord Injuries / Q000473:pathology / Q000503:physiopathology / Q000601:surgery*; D013997:Time Factors; D016896:Treatment Outcome