Corticosteroids for managing tuberculous meningitis

Kameshwar Prasad, Mamta B Singh, Hannah Ryan, Kameshwar Prasad, Mamta B Singh, Hannah Ryan

Abstract

Background: Tuberculous meningitis is a serious form of tuberculosis (TB) that affects the meninges that cover a person's brain and spinal cord. It is associated with high death rates and with disability in people who survive. Corticosteroids have been used as an adjunct to antituberculous drugs to treat people with tuberculous meningitis, but their role has been controversial.

Objectives: To evaluate the effects of corticosteroids as an adjunct to antituberculous treatment on death and severe disability in people with tuberculous meningitis.

Search methods: We searched the Cochrane Infectious Diseases Group Specialized Register up to the 18 March 2016; CENTRAL; MEDLINE; EMBASE; LILACS; and Current Controlled Trials. We also contacted researchers and organizations working in the field, and checked reference lists.

Selection criteria: Randomized controlled trials that compared corticosteroid plus antituberculous treatment with antituberculous treatment alone in people with clinically diagnosed tuberculous meningitis and included death or disability as outcome measures.

Data collection and analysis: We independently assessed search results and methodological quality, and extracted data from the included trials. We analysed the data using risk ratios (RR) with 95% confidence intervals (CIs) and used a fixed-effect model. We performed an intention-to-treat analysis, where we included all participants randomized to treatment in the denominator. This analysis assumes that all participants who were lost to follow-up have good outcomes. We carried out a sensitivity analysis to explore the impact of the missing data.

Main results: Nine trials that included 1337 participants (with 469 deaths) met the inclusion criteria.At follow-up from three to 18 months, steroids reduce deaths by almost one quarter (RR 0.75, 95% CI 0.65 to 0.87; nine trials, 1337 participants, high quality evidence). Disabling neurological deficit is not common in survivors, and steroids may have little or no effect on this outcome (RR 0.92, 95% CI 0.71 to 1.20; eight trials, 1314 participants, low quality evidence). There was no difference between groups in the incidence of adverse events, which included gastrointestinal bleeding, invasive bacterial infections, hyperglycaemia, and liver dysfunction.One trial followed up participants for five years. The effect on death was no longer apparent at this time-point (RR 0.93, 95% CI 0.78 to 1.12; one trial, 545 participants, moderate quality evidence); and there was no difference in disabling neurological deficit detected (RR 0.91, 95% CI 0.49 to 1.69; one trial, 545 participants, low quality evidence).One trial included human immunodeficiency virus (HIV)-positive people. The stratified analysis by HIV status in this trial showed no heterogeneity, with point estimates for death (RR 0.90, 95% CI 0.67 to 1.20; one trial, 98 participants) and disability (RR 1.23, 95% CI 0.08 to 19.07; one trial, 98 participants) similar to HIV-negative participants in the same trial.

Authors' conclusions: Corticosteroids reduce mortality from tuberculous meningitis, at least in the short term.Corticosteroids may have no effect on the number of people who survive tuberculous meningitis with disabling neurological deficit, but this outcome is less common than death, and the CI for the relative effect includes possible harm. However, this small possible harm is unlikely to be quantitatively important when compared to the reduction in mortality.The number of HIV-positive people included in the review is small, so we are not sure if the benefits in terms of reduced mortality are preserved in this group of patients.

Conflict of interest statement

KP is a co‐author of two of the included trials (Kumarvelu 1994; Prasad 2006). HR independently conducted 'Risk of bias' assessments and data entry and interpretation with the CIDG Co‐ordinating Editor, Paul Garner.

Figures

1
1
Study flow diagram.
2
2
'Risk of bias' graph: review authors' judgements about each 'Risk of bias' item presented as percentages across all included trials.
3
3
'Risk of bias' summary: review authors' judgements about each 'Risk of bias' item for each included trial.
4
4
Forest plot of comparison: 1 Any corticosteroid versus control, outcome: 1.1 Death.
5
5
Forest plot of comparison: 1 Any corticosteroid versus control, outcome: 1.2 Disabling neurological deficit.
6
6
Forest plot of comparison: 1 Any corticosteroid versus control, outcome: 1.4 Adverse events.
7
7
Forest plot of comparison: 2 Any corticosteroid versus control: stratified by severity of illness, outcome: 2.1 Death.
8
8
Forest plot of comparison: 3 Any corticosteroid versus control: stratified by HIV status, outcome: 3.1 Death.
9
9
Funnel plot of risk ratio (RR) from the included trials with the log of their standard error (SE) values.
1.1. Analysis
1.1. Analysis
Comparison 1 Any corticosteroid versus control, Outcome 1 Death.
1.2. Analysis
1.2. Analysis
Comparison 1 Any corticosteroid versus control, Outcome 2 Disabling neurological deficit.
1.3. Analysis
1.3. Analysis
Comparison 1 Any corticosteroid versus control, Outcome 3 Death or disabling neurological deficit.
1.4. Analysis
1.4. Analysis
Comparison 1 Any corticosteroid versus control, Outcome 4 Adverse events.
2.1. Analysis
2.1. Analysis
Comparison 2 Any corticosteroid versus control: stratified by severity of illness, Outcome 1 Death.
3.1. Analysis
3.1. Analysis
Comparison 3 Any corticosteroid versus control: stratified by HIV status, Outcome 1 Death.
3.2. Analysis
3.2. Analysis
Comparison 3 Any corticosteroid versus control: stratified by HIV status, Outcome 2 Disabling neurological deficit.
3.3. Analysis
3.3. Analysis
Comparison 3 Any corticosteroid versus control: stratified by HIV status, Outcome 3 Death or disabling residual neurological deficit.
4.1. Analysis
4.1. Analysis
Comparison 4 Sensitivity analysis, Outcome 1 Worst case scenario analysis.

References

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Source: PubMed

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