Roberts et al.

(2004)

International

RCT

PEDro=10

N=10,008

Population: ABI; Mean Age=37 yr; Gender: Male=6104, Female=1904; Median Time Post Injury=3 hr; Severity: Mild=3002, Moderate=3040, Severe=3966.

Intervention: Patients were randomized to receive either methylprednisolone (n=5007) or placebo (n=5001). Methylprednisolone was administered intravenously at a loading dose of 2 g/hr in a 100 mL infusion, and maintained at 0.4 g/hr for 48 hr in a 20 mL/hr infusion. Outcomes were assessed at 2 wk post treatment.

Outcome Measure: Mortality.

1.        Compared with the placebo group, the risk of death was higher in the methylprednisolone group (RR=1.18; p=0.0001).

2.        Relative risk of death did not differ by injury severity (p=0.22) or time post injury (p=0.05).

Giannotta et al.

(1984)

USA

RCT

PEDro=7

N=88

Population: TBI; Time Post Injury≤6 hr; GCS Range≤8.

Intervention: Patients were randomized to receive high-dose methylprednisolone (n=38; 30 mg/kg/6 hr for 2 doses, 250 mg/6 hr for 8 doses, then tapered), low-dose methylprednisolone (n=34; 1.5mg/kg/6hr for 2 doses, 25 mg/6 hr for 8 doses, then tapered), or placebo (n=16) over 8 days.

Outcome Measures: Glasgow Outcome Scale (GOS), Mortality.

1.        At 6 mo, there was no significant difference in mortality or morbidity between groups.

2.        For patients younger than 40 yr, there was a combined 43% mortality in the low dose and placebo groups compared to a 6% mortality in the high dose group (p<0.05).

Saul et al.

(1981)

USA

RCT

PEDro=4

N=100

Population: TBI; Mean Age=31 yr; Time Post Injury≤6 hr; GCS Range≤7.

Intervention: Patients were randomized receive to either intravenous methylprednisolone (250 mg bolus followed by a continuous 125 mg/6 hr infusion) or no drug.

Outcome Measure: Glasgow Outcome Scale (GOS).

Oliynyk et al.

(2016)

Ukraine & Poland

Case Series

N=267

Population: Severe TBI.

Intervention: Retrospective analysis of patients with sepsis and acute respiratory distress syndrome (ARDS) secondary to severe TBI who were administered Solu-Medrol (methylprednisolone) for 3 days (500 mg/ day), followed by reductions in dosage by one-half every 3 days after.  Patients were further analysed based on the type of respiratory support they received to treat their ARDS: controlled volume forced expiration, or Biphasic Positive Airway Pressure [BiPAP]).

Outcome Measure: Mortality.

1.        Patient mortality decreased by 1.24x when BiPAP mechanical ventilation was used compared to volume-controlled forced ventilation (5-7mL/kg) (p=0.01). For the patients who survived, the duration of BiPAP ventilation was 1.32x shorter than forced ventilation with volume control duration.

2.        Corticosteroids improved mortality rate with both ventilation systems. For dead patients, corticosteroids prolonged ventilation time (all p<0.01) and for surviving patients, the ventilation period was shortened (both p<0.01).

Dearden et al.

(1986)

UK

RCT

PEDro=4

N=130

Population: TBI; Age Range=3-79 yr; Gender: Male=93, Female=37; Time Post Injury: ≤8 hr=93, >8 hr=37; Severity: Mild/Moderate=23, Severe=107.

Intervention: Patients randomized to receive either IV bolus of dexamethasone (n=68) or placebo (n=62). Dexamethasone was administered intravenously at 100 mg/ days on days 1-3, 50 mg/ days on day 4, and 25 mg on day 5.

Outcome Measure:  Glasgow Outcome Scale (GOS).

1.        GOS score at 6 mo was worse in the steroid group than the placebo group (49% versus 35.5% dead or vegetative), but the difference was not significant (p>0.05).

2.        Patients in the steroid group with ICP >20 mmHg and >30 mmHg showed significantly poorer outcomes on GOS compared to similar patients in the placebo group (p<0.05).

Braakman et al.

(1983)

Netherlands

RCT

PEDro=4

N=161

Population: TBI; Time Post Injury<6 hr; Severity: Severe.

Intervention: Patients were randomized to receive either high-dose dexamethasone (n=81) or placebo (n=80). After a 100 mg intravenous (IV) dose, Dexamethasone was administered IV at 100 mg/ day from days 1-4, at 16 mg/ day IV or intramuscularly (IM) from days 5 to 7, and at 12 mg, 8 mg, 4 mg IV or IM on day 8 9, and 10, respectively.

Outcome Measures: Glasgow Outcome Scale (GOS), Mortality.

Kaktis & Pitts et al.

(1980)

USA

RCT

PEDro=4

N=115

Population: ABI.

Intervention: Patients were randomized to receive one of “mega dose” dexamethasone (50 mg, then 25 mg/ 6hr), conventional dose dexamethasone (10 mg, then 4 mg/6 hr) or saline placebo for a maximum of 7 days or until awakening.

Outcome Measures: Infections of Cerebrospinal Fluid (CSF), Syndrome of Inappropriate Antidiuretic Hormone Secretion (SIADH), Hyperglycemia.

1.        Infections of the cerebrospinal fluid was significantly higher in the mega dose group than conventional dose and placebo groups (8% versus 0% versus 0%, p<0.025).

2.        SIADH was significantly more prevalent in the conventional dose group than the mega dose and placebo groups (19% versus 10% versus 0%, p<0.05).

3.        Hyperglycemia was more prevalent in the mega and conventional dose groups than the placebo (35% versus 34% versus 11%, p=0.05).

Cooper et al.

(1979)

USA

RCT

PEDro=8

N=76

Population: TBI; Mean Age=25.6 yr; Gender: Male=59, Female=17; Mean GCS=5.23.

Intervention: Patients were randomized to receive one of low-dose dexamethasone (n=25; 10 mg initially, then 4 mg every 6 hr), high-dose dexamethasone (n=24; 60 mg initially, then 24 mg every 6 hr), or placebo (n=27).

Outcome Measures: Intracranial Pressure (ICP), Glasgow Outcome Scale (GOS).

1.        No significant difference was seen between groups in terms of ICP or 6 mos GOS score.

Watson et al.

(2004)

USA

Cohort

N=404

Population: TBI; Glucocorticoid (n=125): Mean Age=33 yr; Gender: Male=100, Female=25. Control (n=279): Mean Age=35 yr; Gender: Male=209, Female=70.

Intervention: Patients treated with glucocorticoids were compared to those not receiving them (control).

Outcome Measures: Incidence of Post-Traumatic Seizures (PTS).

1.        One hundred and five patients received glucocorticoids within 1 day of their injury, and 20 received them ≥2 days.

2.        Patients receiving glucocorticoids within 1 day were more likely to develop first late PTS than were those without (HR=1.74, p=0.04).

3.        Those receiving glucocorticoids ≥2 days post injury had no similar associations with PTS (HR=0.77, p=0.66).

4.        Glucocorticoid administration was not associated with second late PTS development in any group.

Grumme et al.

(1995)

Germany

RCT

PEDro=9

N=396

Population: TBI; Triamcinolone (n=187): Mean Age=31 yr; Gender: Male=154, Female=33. Placebo (n=209): Mean Age=31 yr; Gender: Male=168, Female=41.

Intervention: Patients were randomized to receive either triamcinolone or placebo. Triamcinolone was administered intravenously at 200 mg within 4 hr of injury, followed by 3×40 mg/day for 4 days and 3×20 mg/ day for 4 days.

Outcome Measure: Glasgow Outcome Scale (GOS).

1.        No significant difference was observed between groups in GOS at discharge or at 1 yr follow-up.

2.        A significantly greater proportion of patients with GCS<8 and focal lesions treated with triamcinolone achieved good outcomes on GOS compared to those treated with placebo (16/46 versus 10/47, p=0.0145).