Abstract

BackgroundEvery 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.ObjectivesTo evaluate the effects of osmotic therapies added to antibiotics for acute bacterial meningitis in children and adults on mortality, deafness and neurological disability.Search methodsWe 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 criteriaRandomised controlled trials testing any osmotic therapy in adults or children with acute bacterial meningitis.Data collection and analysisTwo 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 resultsWe 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' conclusionsGlycerol 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.

Highlights

  • Every day children and adults die from acute community-acquired bacterial meningitis, in low-income countries, and survivors risk deafness, epilepsy and neurological disabilities

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

  • All included patients with suspected m eningitis and cerebrospinal f luid (CSF) changes suggestive of bacterial infection. 4Downgraded by one level for imprecision: the 95% confidence intervals (CI) includes what might be a clinically important harm and no effect with glycerol. 5Downgraded by one level for inconsistency: in the Finnish trial the risk of neurological sequelae was reduced with glycerol (RR 0.50, 95% CI 0.32 to 0.78, N = 329), but this was not f ound in the other studies and the m eta-analysis did not detect a dif f erence (I2 = 59%)

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Summary

Introduction

Every day children and adults die from acute community-acquired bacterial meningitis, in low-income countries, and survivors risk deafness, epilepsy and neurological disabilities. Osmotic therapies may attract extra-vascular fluid and reduce cerebral oedema, and reduce death and improve neurological outcomes. This is an update of a Cochrane Review first published in 2013. Another systematic review of individual patient data from five randomised studies suggests that the effect of dexamethasone on outcomes for bacterial meningitis in these countries is limited to reducing the incidence of hearing loss in survivors (van de Beek 2010). A long-held concern exists over excessive fluids contributing to brain oedema; a further Cochrane Review suggests that judicious fluid resuscitation guided by the clinical condition is appropriate to maximise brain perfusion without contributing to brain oedema (Maconochie 2016)

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