Criteria abstracted from The Users' Guide to Medical Literature, from the Health Information Research Unit and Clinical Epidemiology and Biostatistics, McMaster University

Highlighted lines and questions below provide links to the pertinent description of criteria in The EBM User's Guide, now available at the Canadian Centres for Health Evidence

Article Reviewed:

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Corticosteroids in acute traumatic brain injury: Systematic review of randomised controlled trials.

Alderson P and Roberts I.

Br Med J 1997; 314:1855-9. [abstract]

Reviewed by Scot Bateman

Review posted September 2, 1997

I. Are the results of the study valid?

A. Primary questions:

1. Did the overview address a focused clinical question?

Yes. The authors attempted to answer the defined question of outcomes of death or disability after corticosteroid treament in traumatic brain injury.

2. Were the criteria used to select articles for inclusion appropriate?

Yes. Inclusion criteria were: randomized controlled trials of corticosteroid treatment of any type within seven days of injury and a clinical diagnosis of acute traumatic brain injury of any severity. The goal was assessing an overall effect of steroids so they included studies with all types of steroid types and doses. (i.e. dexamethasone 1mg/kg, 6mg/kg, or methylprednisolone 30 mg/kg lasting 3 days or up to 14 days). The definition of acute brain injury for them was very broad but all patients had "severe head injury" not further defined. The subsequent death rate after the injury ranged widely from 14.3 to 57%. There was no mention of co-treatment strategies for head injury. They did not specify length of follow up as a criteria.

B. Secondary questions:

3. Is it unlikely that important, relevant studies were missed?

Yes. They used a very thorough search technique; MEDLINE 1966-1995, Embase 1974-1996, and a Cochrane Library (8/96) search. They had independent neurological societies search their databases. They also looked at all references of the trials found. Personal communications were attempted in all cases. Two unpublished trials were located and suitable for inclusion in the study. No language restrictions were used.

4. Was the validity of the included studies appraised?

Yes. The studies' data were all extracted independently. They determined their own outcomes of death or disability (which included persistent vegatative state, severe disability and moderate disability). Multiple dose trials were put together as treatment (any dose) vs. placebo. They ranked each study 1 (poorest) to 3 (strongest) based on the study's strategy for concealment of allocation. They report that the quality of concealment of allocation particularly affects the results of studies. They use these rankings as subgroups for analysis of only the studies with a ranking of 3.

5. Were assessments of studies reproducible?

Maybe. The two authors each ranked and reviewed the data independently. It is unclear how much variation they had in their rankings because they state only that differences were resolved by discussion. The authors did not report a kappa value for level of agreement. Personal communication was attempted if reported results needed clarification.

6. Were the results similar from study to study?

Yes. The population studied was somewhat variable as would be expected with their broad inclusion criteria. The death rate ranged from 14% to 57% suggesting a highly variable pretreatment morbidity. Calculated disability ranged from 19% to 62%. Nevertheless, the effect size from treatment were very similar from study to study. The odds ratios of the studies were on both sides of 1 (representing both beneficial and harmful effects of therapy), but the confidence intervals, save one study, all included 1 (results not statistically significant). The authors state that none of the tests for heterogeneity yielded significant results (indicating reasonable consistency of results between studies).

II. What are the results?

1. What are the overall results of the review?

Thirteen trials were included comprising 2073 patients. The odds ratio for death was 0.91 (95% CI 0.74 to 1.12), and the death or disability odds ratio was 0.90 (95% CI 0.72 to 1.11). The absolute risk reduction was 1.8% (-2.5% to 5.7%). Similar results were found when only strict allocation studies were included. The majority of the weight of the overall effect size can be attributed to two large studies, one by Gaab and the other by Grumme (which together contribute 50.9% of the weight).

2. How precise were the results?

The two main outcomes of death and death or disability included 1 in their confidence intervals, indicating no significant difference for either. The subgroup analysis of the more strict studies improved the precision by narrowing the 95% CI but it still included 1.

III. Will the results help me in caring for my patients?

1. Can the results be applied to my patient care?

Depends. Only one of the included trials focused specifically on children and that study had a poor design (poor concealment, no mention of placebo). The other studies primarily deal with adults or patients above 15 years of age. The results most likely can only apply to the teenage population in the PICU.

2. Were all clinically important outcomes considered?

Mostly. The authors attempted looking at other variables. They were able to extract data on rates of gastrointestinal bleeding and infections for analysis. The odds ratios for them also were non-significant suggesting no increased risk, but co-treatment was not addressed. They did not differentiate level of disability in their analysis. Careful follow-up analysis is probably needed in order to find if subtler outcome benefits/harms may be effected. Combining all steroid regimens may have missed an effect size related to absolute steroid dose.

3. Are the benefits worth the harms and costs? No. This study provides no evidence to support the use of steroids in acute traumatic brain injury in the teenage/adult population. However, uncertainty remains. The Brain Trauma Foundation guidelines state that in managing severe head injury, "the uses of glucocorticoids is not recommended." (1) The question remains unanswered in the pediatric population.

References:

1. Bullock R, Chesnut RM, Clifton G, Ghajar J, Marion DW, Narayan RK, Newell DW, Pitts LH, Rosner MJ, Wilberger JW. Guidelines for the management of severe head injury. Brain Trauma Foundation. European Journal of Emergency Medicine. 1996; 3:109-27. [citation (no abstract available)]

 

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