What is the data in favor of or against the use of dexamethasone for the management of acute traumatic brain injury or acutely elevated intracranial pressure?

Comment by InpharmD Researcher

Data is scarce for dexamethasone use in acute traumatic brain injury (TBI) management. A Cochrane meta-analysis analyzing the subacute phase of general TBI management observed no significant benefits in outcomes of death with corticosteroid use. Only one study from 1974 that included dexamethasone reported a lower risk ratio of death compared to placebo, however, the study was limited in quality and design. A more recent study found a significant decrease in volume of vasogenic edema in TBI patients, but this result has not been translated to improved functional outcomes nor was it specific to acute care.

  

Pubmed: dexamethasone acute traumatic brain injury = 25 results; dexamethasone acute intracranial pressure = 61 results

Background

According to the 2017 guidelines for the management of severe traumatic brain injury (TBI) published by the Brain Trauma Foundation, the general use of corticosteroids is not recommended for improving outcomes in TBI or reducing intracranial pressure (ICP). The recommendation is based on the CRASH trial which found that high-dose methylprednisolone was associated with increased mortality in severe TBI patients, for which it is now considered contraindicated. No dexamethasone-specific recommendation was made. [1], [2]

A 2005 Cochrane meta-analysis investigated the efficacy and safety of corticosteroid use for the treatment of acute TBI. While a total of 20 randomized controlled studies were included, an analysis for risk of death could not be performed due to significant heterogeneity. The largest study (CRASH) reported a significant increase in death with steroid use (risk ratio 1.15; 95% confidence interval [CI] 1.07 to 1.24). An individual analysis on dexamethasone was not performed. Identified studies for dexamethasone were older with the most recent being from 1994. Their meta-analysis table suggested that only one study comparing dexamethasone to placebo was significantly in favor of steroids for outcome of death with a risk ratio of 0.42 (95% CI 0.24 to 0.71). The specific study by Faupel et al. was conducted in 1976 and consisted of adults with severe closed head injury who received dexamethasone at various injected doses versus placebo. Because of the age of the study and lack of formal study design at the time of publication, data is limited. Effect on ICP was not observed in the study nor the Cochrane meta-analysis. [3], [4]

A 2016 review article investigated the evidence for corticosteroid use in TBI. The potential benefits from corticosteroids is believed to be exerted by reduction in vasogenic edema and swelling secondary to cerebral neoplasms. However, when reviewing 5 RCTs with a sample size ≥ 100 patients, there was no evidence of benefit. Two of the 5 RCTs observed use of dexamethasone. The first study dosed dexamethasone at 100 mg bolus on day 1, followed by a taper regimen up to day 10. No significant difference in functional or mortality outcomes were reported at 1 and 6 months. The second study included 300 patients with moderate or severe brain injury treated with 500 mg of dexamethasone within the first 3 hours, followed by 200 mg after 3 hours, and 200 mg every 6 hours for 48 hours. There was no difference versus placebo for improvement in glasgow coma scale scores on day 5 or up to 10 months after brain injury. Rates of death and neurologic recovery were also similar. Because of these findings, the authors do not recommend routine use of corticosteroids in TBI patients and even dissuade further investigations towards their use. [5]

Another 2017 article discussing acute management of TBI does not support the use of corticosteroids based on the CRASH trial. Acute management should be focused on preventing hypotension and hypoxia while maintaining cerebral pressure and blood flow. Elevated ICP should be managed using a multimodal strategy consisting of bedside maneuvers, hyperosmolar therapy, cerebrospinal fluid drainage, pentobarbital coma, and decompressive craniectomy. [6]

References:

[1] Carney N, Totten AM, O'Reilly C, et al. Guidelines for the Management of Severe Traumatic Brain Injury, Fourth Edition. Neurosurgery. 2017;80(1):6-15. doi:10.1227/NEU.0000000000001432
[2] Roberts I, Yates D, Sandercock P, et al. Effect of intravenous corticosteroids on death within 14 days in 10008 adults with clinically significant head injury (MRC CRASH trial): randomised placebo-controlled trial. Lancet. 2004;364(9442):1321-1328. doi:10.1016/S0140-6736(04)17188-2
[3] Alderson P, Roberts I. Corticosteroids for acute traumatic brain injury. Cochrane Database Syst Rev. 2005;2005(1):CD000196. Published 2005 Jan 25. doi:10.1002/14651858.CD000196.pub2
[4] Faupel G, Reulen HJ, Müller D, Schürmann K. Double-blind study on the effects of steroids on severe closed head injury. In: Pappius HM, Feindel W, eds. Dynamics of Brain Edema. Springer Berlin Heidelberg; 1976:337-343. doi: 10.1007/978-3-642-66524-0_52
[5] Hoshide R, Cheung V, Marshall L, Kasper E, Chen CC. Do corticosteroids play a role in the management of traumatic brain injury?. Surg Neurol Int. 2016;7:84. Published 2016 Sep 13. doi:10.4103/2152-7806.190439
[6] Vella MA, Crandall ML, Patel MB. Acute Management of Traumatic Brain Injury. Surg Clin North Am. 2017;97(5):1015-1030. doi:10.1016/j.suc.2017.06.003

Literature Review

A search of the published medical literature revealed 1 study investigating the researchable question:

What is the data in favor of or against the use of dexamethasone for the management of acute traumatic brain injury or acutely elevated intracranial pressure

Level of evidence

D - Case reports or unreliable data  Read more→



Please see Table 1 for your response.


 

Effects of dexamethasone in traumatic brain injury patients with pericontusional vasogenic edema

Design

Prospective, observational study

N= 30

Objective

To study the effect of dexamethasone in patients with brain contusions, and to assess its effect on the vasogenic component of the pericontusional edema

Study Groups

Dexamethasone (n= 15)

No dexamethasone (n= 15)

Inclusion Criteria

Patients with brain contusions and pericontusional edema visualized in conventional computed tomography (CT)

Exclusion Criteria

Patients with a previous traumatic brain injury (TBI), other neurological diseases, or any contraindication to magnetic resonance imaging (MRI)

Methods

Dexamethasone was administered to TBI patients presenting with brain contusions and pericontusional edema observed on their CT in order to treat the vasogenic component of the edema. Dexamethasone administration was based on each patient's symptoms and CT findings and was at the discretion of the attending physician. A gradual dexamethasone weaning regimen was provided to patients as follows: 4 mg every 6  hours (Q6H) for 2 days; 4 mg Q8 H for 2 days; 2 mg Q6 H for 2 days; 2 mg Q8 H for 2 days and 1 mg Q8 H for 2 days. MRI scans were used to quantify the volume of vasogenic edema before and after 10 days of dexamethasone use.

Duration

Treatment: 10 days

Outcome Measures

The volume of vasogenic edema, Apparent Diffusion Coefficient (ADC), and Fractional Anisotropy (FA)

Baseline Characteristics

 

Dexamethasone (n= 15)

No dexamethasone (n= 15)

Median age, years

62 (32 to 75) 58 (36-74) 

Female

20% 13%

Mechanism of injury

RTC*

Fall

Assault

 

13%

74%

13% 

 

20%

74%

6% 

Median Injury Severity Score

16 (16 to 29)  22 (9 to 29)

Median Glasgow Coma Score

Median Glasgow outcome scale-extended score at 6 months

14 (9 to 15) 

7 (1 to 8) 

14 (6 to 15)

7 (1 to 8)

Motor score 

M6 (obeys commands)

M5 (localizes pain)

M4 (withdrawal pain)

 

86%

7%

7% 

 

73%

20%

7%

Median volume of contusion, mL

9 (3 to 25)  7 (3 to 30) 

Intracranial pressure monitoring

33% 33%

Craniotomy

0 13%

Median time from injury to first scan, days

Median time from injury to second scan, days

4.4 (2 to 8) 

14.4 (11 to 17) 

4.9 (1 to 15) 

13.1 (10 to 16)

Median length of stay, days

Intensive care unit

Hospital

 

8 (0 to 18) 

16 (6 to 31) 

 

3 (0 to 46) 

11 (4 to 67)

*Not definied

Results

Endpoint

Dexamethasone (n= 15)

No dexamethasone (n= 15)

Median volume of vasogenic edema

Before treatment, mL

After treatment, mL

p-value comparing before and after

 

22 (2 to 45)

19 (1 to 40)

<0.05 

 

11 (3 to 79)

15 (1 to 80)

-- 

Median apparent diffusion coefficient 

Before treatment, 10-9m2/sec

After treatment, 10-9m2/sec

p-value comparing before and after

 

1.78 (1.2 to 2.2)

1.59 (1.2 to 2)

<0.05 

 

1.67 (0.08 to 1.9)

1.7 (1.27 to 1.84)

--

Median fractional anisotropy

Before treatment

After treatment

p-value comparing before and after

 

0.09 (0.07 to 0.14)

0.11 (0.08 to 0.16)

<0.05 

 

0.14 (0.08 to 0.28)

0.12 (0.07 to 0.14)

-- 

Adverse Events

Not disclosed

Study Author Conclusions

In summary, in this prospective observational study using diffusion tensor imaging-MRI, we have shown in a selected group of TBI patients with vasogenic pericontusional edema, a reduction of edema volume, a decrease in the ADC value, and an increase in the FA value after treatment with dexamethasone. However, we have no data on whether such results are beneficial in terms of improving functional outcome. For this reason, a firm recommendation for the clinical use of this treatment requires a clinical trial.

InpharmD Researcher Critique

The study is limited by its observational design and small sample size. The sample population was mostly male and patients had a specific type of TBI (TBI with pericontusional vasogenic edema) which may limit the applicability of results to other populations. 



References:

Moll A, Lara M, Pomar J, et al. Effects of dexamethasone in traumatic brain injury patients with pericontusional vasogenic edema: A prospective-observational DTI-MRI study. Medicine (Baltimore). 2020;99(43):e22879. doi:10.1097/MD.0000000000022879