Numerous corticosteroids have been used in brain injury care including dexamethasone, methylprednisolone, prednisolone, betamethasone, cortisone, hydrocortisone, prednisone and triamcinolone (Alderson & Roberts 2005). Using such a broad spectrum of agents within diverse patient groups has made understanding corticosteroid efficacy difficult. With respect to its mechanism of action, Grumme et al. (1995) report that laboratory studies have associated reductions in wet brain weight, facilitation of synaptic transmission, reduction of lipid peroxidation, enhanced blood flow, preservation of electrolyte distribution, and membrane stabilization with corticosteroid use (Grumme et al. 1995). It is thought that benefits may arise from reductions in ICP as well as neuroprotective activity. However, several studies also suggest some limitations of corticosteroid use. Focal lesions seem to respond well to corticosteroid therapy while diffuse intracerebral lesions and hematomas are less responsive (Beauchamp et al. 2008; Cooper et al. 1979; Grumme et al. 1995).
Questions regarding the safety of corticosteroid administration have been brought to light in the wake of several large scale trials. Alderson and Roberts (1997) conducted a systematic review of corticosteroids and concluded that there was a 1.8% improvement in mortality associated with corticosteroid use (Alderson & Roberts 1997). However, their 95% confidence interval ranged from a 7.5% reduction to a 0.7% increase in deaths. A later study by Roberts et al. (2004) studied corticosteroid use in 10,008 patients with brain injury, at which point the study was stopped due to corticosteroid use causing significant increases in mortality (Roberts et al. 2004). The American Association of Neurological Surgeons stated that steroid use was not recommended for improving outcomes or reducing ICP and that high-dose methylprednisolone was associated with increased mortality and was contraindicated (Bratton et al. 2007).
Three RCTs assessed methylprednisolone in ABI management (Giannotta et al. 1984; Roberts et al. 2004; Saul et al. 1981). Giannotta et al. (1984) conducted a RCT of patients with Glasgow Coma Scale scores of ≤8 treated with methylprednisolone. The study found no difference in mortality rates between groups at a six month follow-up. When the low dose and placebo groups were compressed, patients less than 40 years old in the high dose group showed significant decreases in mortality when compared to the low dose/placebo group (Giannotta et al. 1984). However, there appears to be no significant difference in beneficial outcomes for those treated with the drug and those who were not (Giannotta et al. 1984; Saul et al. 1981). Thus even if the decreases in death are taken into account, decreasing mortality without decreasing morbidity may not be valuable (Giannotta et al. 1984). A very large multinational RCT assessing early methylprednisolone administration was initiated in 1999 and brought clarity to this issue (Roberts et al. 2004). The study found that the relative risk of death was significantly higher in the corticosteroid group than the placebo group, and that it did not differ by injury severity or time post injury. The conclusion then is that corticosteroids should not be used in head injury care, no matter what the severity of injury (Roberts et al. 2004).
Four randomized trials were found that assessed dexamethasone in ABI. Overall dexamethasone was not found to significantly improve outcomes, based on the Glasgow Outcome Scale (Braakman et al. 1983; Cooper et al. 1979; Dearden et al. 1986). However, Dearden et al. (1986) noted that patients experiencing ICP levels >20mmHg showed significantly poorer outcomes based on Glasgow Outcome Scale scores at 6 months. In one study post-mortem examinations were performed and indicated that often patients initially diagnosed with focal lesions were in fact suffering from diffuse injuries which are not amenable to corticosteroid treatment (Cooper et al. 1979). Braakman et al. (1983) found no differences between patients treated with dexamethasone compared to placebo for one month survival rates. Finally, when comparing the administration of low-dose (16mg/day) and high-dose (14mg/day) dexamethasone, no differences were noted in ICP at any point during the 72 hour follow-up period (Kaktis & Pitts 1980).
Grumme et al. (1995) conducted a RCT that assessed Glasgow Outcome Scale scores at one year after treatment with the synthetic corticosteroid triamcinolone. While no overall effect was seen between groups, a significant increase in beneficial outcomes was seen in patients who had both a GCS <8 and a focal lesion (Grumme et al. 1995). The last study, compared those receiving any form of glucocorticoid therapy (dexamethasone 98%, prednisone 2.4%, methylprednisone 1.6%, or hydrocortisone 1.6%) to patients treated without corticosteroids for risk of development of PTS (Watson et al. 2004).
Glucocorticoid treatment provided on the first day post injury was found to increase the risk of developing first late seizures, but this was not true when administered after the first day.
There is Level 1b evidence that methylprednisolone increases mortality rates in patients with ABI and should not be used.
There is Level 1b evidence that triamcinolone can improve outcomes in patients with both a Glasgow Coma Scale <8 and a focal lesion.
There is Level 2 evidence that dexamethasone does not improve intracranial pressure.
There is Level 1b evidence that dexamethasone does not improve outcomes and Level 2 evidence that it can worsen outcomes in patients with levels >20mmHg.
There is Level 2 evidence that glucocorticoid administration within the first day post injury only, increases the risk of developing first late seizures.
Methylprednisolone increases mortality rates in patients with ABI and should not be used.
Triamcinolone has been shown to improve outcomes in patients with both a Glasgow Coma Scale <8 and a focal lesion.
Dexamethasone does not improve intracranial pressure (ICP) levels and may worsen outcomes in patients with ICP >20mmHg.
Glucocorticoid administration increases the risk of developing first late seizures when administered within one day post injury; however, it does not impact late seizures when administered outside that time frame.