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Review
, 2 (2), CD008806

Osmotic Therapies Added to Antibiotics for Acute Bacterial Meningitis

Affiliations
Review

Osmotic Therapies Added to Antibiotics for Acute Bacterial Meningitis

Emma Cb Wall et al. Cochrane Database Syst Rev.

Abstract

Background: Every day children and adults die from acute community-acquired bacterial meningitis, particularly in low-income countries, and survivors risk deafness, epilepsy and neurological disabilities. Osmotic therapies may attract extra-vascular fluid and reduce cerebral oedema, and thus reduce death and improve neurological outcomes.This is an update of a Cochrane Review first published in 2013.

Objectives: To evaluate the effects of osmotic therapies added to antibiotics for acute bacterial meningitis in children and adults on mortality, deafness and neurological disability.

Search methods: We searched CENTRAL (2017, Issue 1), MEDLINE (1950 to 17 February 2017), Embase (1974 to 17 February 2017), CINAHL (1981 to 17 February 2017), LILACS (1982 to 17 February 2017) and registers of ongoing clinical trials (ClinicalTrials.com, WHO ICTRP) (21 February 2017). We also searched conference abstracts and contacted researchers in the field (up to 12 December 2015).

Selection criteria: Randomised controlled trials testing any osmotic therapy in adults or children with acute bacterial meningitis.

Data collection and analysis: Two review authors independently screened the search results and selected trials for inclusion. Results are presented using risk ratios (RR) and 95% confidence intervals (CI) and grouped according to whether the participants received steroids or not. We used the GRADE approach to assess the certainty of the evidence.

Main results: We included five trials with 1451 participants. Four trials evaluated glycerol against placebo, and one evaluated glycerol against 50% dextrose; in addition three trials evaluated dexamethasone and one trial evaluated acetaminophen (paracetamol) in a factorial design. Stratified analysis shows no effect modification with steroids; we present aggregate effect estimates.Compared to placebo, glycerol probably has little or no effect on death in people with bacterial meningitis (RR 1.08, 95% CI 0.90 to 1.30; 5 studies, 1272 participants; moderate-certainty evidence), but may reduce neurological disability (RR 0.73, 95% CI 0.53 to 1.00; 5 studies, 1270 participants; low-certainty evidence).Glycerol may have little or no effect on seizures during treatment for meningitis (RR 1.08, 95% CI 0.90 to 1.30; 4 studies, 1090 participants; low-certainty evidence).Glycerol may reduce the risk of subsequent deafness (RR 0.64, 95% CI 0.44 to 0.93; 5 studies, 922 participants; low to moderate-certainty evidence).Glycerol probably has little or no effect on gastrointestinal bleeding (RR 0.93, 95% CI 0.39 to 2.19; 3 studies, 607 participants; moderate-certainty evidence). The evidence on nausea, vomiting and diarrhoea is uncertain (RR 1.09, 95% CI 0.81 to 1.47; 2 studies, 851 participants; very low-certainty evidence).

Authors' conclusions: Glycerol was the only osmotic therapy evaluated, and data from trials to date have not demonstrated an effect on death. Glycerol may reduce neurological deficiency and deafness.

Conflict of interest statement

Emma Wall: none known. Katherine Ajdukiewicz: none known. Hanna Bergman: works for Cochrane Response, a healthcare evidence consultancy that take commissions from healthcare guideline developers and policy makers. Hanna received payment for updating this review from UKAID through the grant held by PG. Robert Heyderman: none known Paul Garner: This review and the salary of PG is supported by UKAID aimed at ensuring systematic reviews, particularly Cochrane Reviews, are completed on topics relevant to the poor in low‐ and middle‐income countries (grant number 5242). UKAID does not participate in the selection of topics, in the conduct of the review or in the interpretation of findings.

Figures

Figure 1
Figure 1
Study screening flow diagram
Figure 2
Figure 2
'Risk of bias' graph: review authors' judgements about each risk of bias item presented as percentages across all included studies
Figure 3
Figure 3
'Risk of bias' summary: review authors' judgements about each risk of bias item for each included study
Analysis 1.1
Analysis 1.1
Comparison 1 Glycerol versus no osmotic diuretic, Outcome 1 Death.
Analysis 1.2
Analysis 1.2
Comparison 1 Glycerol versus no osmotic diuretic, Outcome 2 Neurological disability.
Analysis 1.3
Analysis 1.3
Comparison 1 Glycerol versus no osmotic diuretic, Outcome 3 Seizures.
Analysis 1.4
Analysis 1.4
Comparison 1 Glycerol versus no osmotic diuretic, Outcome 4 Hearing loss.
Analysis 1.5
Analysis 1.5
Comparison 1 Glycerol versus no osmotic diuretic, Outcome 5 Adverse effects: nausea, vomiting, diarrhoea.
Analysis 1.6
Analysis 1.6
Comparison 1 Glycerol versus no osmotic diuretic, Outcome 6 Adverse effects: gastrointestinal bleeding.

Update of

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References

References to studies included in this review

    1. Ajdukiewicz KM. Glycerol adjuvant therapy in adult bacterial meningitis in Malawi [MD thesis]. Liverpool (UK): University of Liverpool, 2012.
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    1. CTRI/2012/05/002650. The effects of cerebral perfusion pressure and intracranial pressure targeted therapy in children with raised intracranial pressure and acute central nervous system infections [A pilot study to compare the outcome of CPP targeted therapy versus ICP targeted therapy in children with acute meningitis]. ctri.nic.in/Clinicaltrials/pmaindet2.php?trialid=4595 (first received 14 May 2012).
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Additional references

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    1. Blaser C, Klein M, Grandgirard D, Wittwer M, Peltola H, Weigand M, et al. Adjuvant glycerol is not beneficial in experimental pneumococcal meningitis. BMC Infectious Diseases 2010;10:84. - PMC - PubMed
    1. Brouwer M, Beek D. Glycerol in bacterial meningitis: one strike and out?. Lancet Infectious Diseases 2011;11(4):257‐8. - PubMed
    1. Brouwer MC, McIntyre P, Gans J, Prasad K, Beek D. Corticosteroids for acute bacterial meningitis. Cochrane Database of Systematic Reviews 2015, Issue 9. [DOI: 10.1002/14651858.CD004405.pub5] - DOI - PMC - PubMed

References to other published versions of this review

    1. Wall ECB, Ajdukiewicz KMB, Heyderman RS, Garner P. Osmotic therapies as adjuncts to antibiotics for acute bacterial meningitis. Cochrane Database of Systematic Reviews 2010, Issue 11. [DOI: 10.1002/14651858.CD008806] - DOI
    1. Wall ECB, Ajdukiewicz KMB, Heyderman RS, Garner P. Osmotic therapies added to antibiotics for acute bacterial meningitis. Cochrane Database of Systematic Reviews 2013, Issue 3. [DOI: 10.1002/14651858.CD008806.pub2] - DOI - PMC - PubMed

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