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Cochrane Database of Systematic Reviews

Osmotic therapies added to antibiotics for acute bacterial meningitis

Información

DOI:
https://doi.org/10.1002/14651858.CD008806.pub3Copiar DOI
Base de datos:
  1. Cochrane Database of Systematic Reviews
Versión publicada:
  1. 06 febrero 2018see what's new
Tipo:
  1. Intervention
Etapa:
  1. Review
Grupo Editorial Cochrane:
  1. Grupo Cochrane de Infecciones respiratorias agudas

Copyright:
  1. Copyright © 2018 The Authors. Cochrane Database of Systematic Reviews published by John Wiley & Sons, Ltd. on behalf of The Cochrane Collaboration.
  2. This is an open access article under the terms of the Creative Commons Attribution Licence, which permits use, distribution and reproduction in any medium, provided the original work is properly cited.

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Autores

  • Emma CB Wall

    Correspondencia a: Division of Infection and Immunity, University College London, London, UK

    [email protected]

    [email protected]

  • Katherine MB Ajdukiewicz

    Department of Infectious Diseases, Pennine Acute Hospitals NHS Trust, Manchester, UK

  • Hanna Bergman

    Cochrane Response, Cochrane, London, UK

  • Robert S Heyderman

    Malawi‐Liverpool‐Wellcome Clinical Research Programme, University of Malawi College of Medicine, Blantyre, Malawi

  • Paul Garner

    Department of Clinical Sciences, Liverpool School of Tropical Medicine, Liverpool, UK

Contributions of authors

Emma Wall (EW) was responsible for writing the main text, extracting data from studies and reviewing the analyses; Paul Garner (PG) was responsible for methodological input, help with interpretation and writing the review; Katherine Ajdukiewicz (KA) was responsible for updating the main text, extracting data from studies and updating the analyses with new data, and commented on the text; Robert Heyderman (RH) provided comments on the text; Hannah Bergman carried out data extraction and updated this review.

Sources of support

Internal sources

  • Clare Dooley, Australia.

    Editorial and secretarial

  • Liz Dooley, Australia.

    Editorial

  • Sarah Thorning, Australia.

    Library and searching support

  • Dr David Sinclair, UK.

    Data support

External sources

  • Wellcome Trust, UK.

    Award: 089671/B/09/Z

  • UKAID Grant 5242, UK.

    UKAID does not participate in the selection of topics, in the conduct of the review or in the interpretation of findings

Declarations of interest

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.

Acknowledgements

We wish to thank Sarah Thorning for assistance with the search strategy and support and Dr David Sinclair for his help synthesising the 'Summary of findings' table. We thank the following people for commenting on the draft protocol: Anne Lyddiatt, Teenah Handiside, Amit Kumar, Max Bulsara and Diederik van de Beek. We also thank the following people for commenting on the original review: Sylvia Beamon, Kameshwar Prasad, Matthijs Brouwer, Teresa Neeman and Diederik van de Beek.

Paul Garner and David Sinclair received support from the Effective Health Care Research Consortium, which is funded by UK aid from the UK Government Department for International Development (grant number 5242).

Version history

Published

Title

Stage

Authors

Version

2018 Feb 06

Osmotic therapies added to antibiotics for acute bacterial meningitis

Review

Emma CB Wall, Katherine MB Ajdukiewicz, Hanna Bergman, Robert S Heyderman, Paul Garner

https://doi.org/10.1002/14651858.CD008806.pub3

2013 Mar 28

Osmotic therapies added to antibiotics for acute bacterial meningitis

Review

Emma CB Wall, Katherine MB Ajdukiewicz, Robert S Heyderman, Paul Garner

https://doi.org/10.1002/14651858.CD008806.pub2

2010 Nov 10

Osmotic therapies as adjuncts to antibiotics for acute bacterial meningitis

Protocol

Emma CB Wall, Katherine MB Ajdukiewicz, Robert S Heyderman, Paul Garner

https://doi.org/10.1002/14651858.CD008806

Differences between protocol and review

In the 2017 update, we presented death and disability separately. In the earlier version of this review, this was a composite outcome. We believe this provides greater clarity for patients and clinicians.

Keywords

MeSH

PICO

Population
Intervention
Comparison
Outcome

El uso y la enseñanza del modelo PICO están muy extendidos en el ámbito de la atención sanitaria basada en la evidencia para formular preguntas y estrategias de búsqueda y para caracterizar estudios o metanálisis clínicos. PICO son las siglas en inglés de cuatro posibles componentes de una pregunta de investigación: paciente, población o problema; intervención; comparación; desenlace (outcome).

Para saber más sobre el uso del modelo PICO, puede consultar el Manual Cochrane.

Study screening flow diagram
Figuras y tablas -
Figure 1

Study screening flow diagram

'Risk of bias' graph: review authors' judgements about each risk of bias item presented as percentages across all included studies
Figuras y tablas -
Figure 2

'Risk of bias' graph: review authors' judgements about each risk of bias item presented as percentages across all included studies

'Risk of bias' summary: review authors' judgements about each risk of bias item for each included study
Figuras y tablas -
Figure 3

'Risk of bias' summary: review authors' judgements about each risk of bias item for each included study

Comparison 1 Glycerol versus no osmotic diuretic, Outcome 1 Death.
Figuras y tablas -
Analysis 1.1

Comparison 1 Glycerol versus no osmotic diuretic, Outcome 1 Death.

Comparison 1 Glycerol versus no osmotic diuretic, Outcome 2 Neurological disability.
Figuras y tablas -
Analysis 1.2

Comparison 1 Glycerol versus no osmotic diuretic, Outcome 2 Neurological disability.

Comparison 1 Glycerol versus no osmotic diuretic, Outcome 3 Seizures.
Figuras y tablas -
Analysis 1.3

Comparison 1 Glycerol versus no osmotic diuretic, Outcome 3 Seizures.

Comparison 1 Glycerol versus no osmotic diuretic, Outcome 4 Hearing loss.
Figuras y tablas -
Analysis 1.4

Comparison 1 Glycerol versus no osmotic diuretic, Outcome 4 Hearing loss.

Comparison 1 Glycerol versus no osmotic diuretic, Outcome 5 Adverse effects: nausea, vomiting, diarrhoea.
Figuras y tablas -
Analysis 1.5

Comparison 1 Glycerol versus no osmotic diuretic, Outcome 5 Adverse effects: nausea, vomiting, diarrhoea.

Comparison 1 Glycerol versus no osmotic diuretic, Outcome 6 Adverse effects: gastrointestinal bleeding.
Figuras y tablas -
Analysis 1.6

Comparison 1 Glycerol versus no osmotic diuretic, Outcome 6 Adverse effects: gastrointestinal bleeding.

Summary of findings for the main comparison. Glycerol for acute bacterial meningitis

Glycerol for acute bacterial meningitis

Patient or population: children and adults with acute bacterial meningitis
Settings: Finland, India, South America, Malawi
Intervention: glycerol with or without steroids compared with placebo. All participants received broad‐spectrum antibiotics

Outcomes

Illustrative comparative risks* (95% CI)

Relative effect
(95% CI)

Number of participants
(studies)

Quality of the evidence
(GRADE)

Comments

Assumed risk

Corresponding risk

Control

Glycerol

Death

19 per 100

21 per 100
(17 to 25)

RR 1.08
(0.90 to 1.30)

1272
(5 studies)

⊕⊕⊕⊝
Moderate1,2,3,4

Downgraded for imprecision.

Glycerol probably has little or no effect on death

Neurological disability

9 per 100

6 per 100

(5 to 9)

RR 0.73

(0.53 to 1.00)

1270

(5 studies)

⊕⊕⊝⊝

Low1,3,4,5

Downgraded for imprecision and inconsistency.

Glycerol may reduce disability

Seizures

32 per 100

35 per 100
(29 to 42)

RR 1.08
(0.90 to 1.30)

1090
(4 studies)

⊕⊕⊝⊝
Low1,3,4,6

Downgraded for inconsistency and imprecision.

Glycerol may have little or no effect on seizures

Hearing loss

16 per 100

10 per 100
(7 to 15)

RR 0.64
(0.44 to 0.93)

922
(5 studies)

⊕⊕⊕⊝
Moderate1,2,3,7

Downgraded for imprecision.

Glycerol probably reduces hearing loss

Adverse effects: nausea, vomiting, diarrhoea

47 per 100

51 per 100

(38 to 69)

RR 1.09

(0.81 to 1.47)

851
(2 studies)

⊕⊝⊝⊝
Very low1,3,4,8,9

Downgraded for serious inconsistency and imprecision.

The effect of glycerol on adverse events: nausea, vomiting and diarrhoea is uncertain

Adverse effects: gastrointestinal bleeding

3 per 100

3 per 100

(13 to 8)

RR 0.93

(0.39 to 2.19)

607
(3 studies)

⊕⊕⊕⊝
Moderate1,2,3,4

Downgraded for imprecision.

Glycerol probably has little or no effect on adverse events: gastrointestinal bleeding

*The basis for the assumed risk (e.g. the median control group risk across studies) is provided in footnotes. The corresponding risk (and its 95% confidence interval (CI)) is based on the assumed risk in the comparison group and the relative effect of the intervention (and its 95% CI).
CI: confidence interval
RR: risk ratio

GRADE Working Group grades of evidence
High quality: Further research is very unlikely to change our confidence in the estimate of effect
Moderate quality: Further research is likely to have an important impact on our confidence in the estimate of effect and may change the estimate
Low quality: Further research is very likely to have an important impact on our confidence in the estimate of effect and is likely to change the estimate
Very low quality: We are very uncertain about the estimate

1No serious risk of bias: allocation concealment was adequate in four trials and unclear (not reported) in one trial.
2Not downgraded for inconsistency.

3Not downgraded for indirectness. The five trials were conducted in Finland, Malawi, India and South America. Four were in children and one in adults. All included patients with suspected meningitis and cerebrospinal fluid (CSF) changes suggestive of bacterial infection.
4Downgraded by one level for imprecision: the 95% 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 found in the other studies and the meta‐analysis did not detect a difference (I² = 59%).

6Downgraded by one level for inconsistency: in the trial with adults the risk of seizures was higher with glycerol (RR 1.62, 95% CI 1.18 to 2.23, N = 250), but this was not found in the other studies and the meta‐analysis did not detect a difference (I² = 62%).
7Downgraded by one level for imprecision: the number of patients with reported hearing loss was low in these studies and the 95% CI includes both no effect and what might be a clinically important benefit with glycerol. Larger studies would be necessary to have full confidence in this effect.

8Another two trials reported on this outcome but the results could not be added to the meta‐analysis; one reported more cases of vomiting with glycerol and the other that the incidence of vomiting was "similar" in the treatment groups.

9Downgraded by two levels for inconsistency: in the South American and Finnish trials the risk of adverse effects was increased with glycerol, but this was not found in the Malawi and India trials, and the meta‐analysis did not detect a difference (I² = 79%).

Figuras y tablas -
Summary of findings for the main comparison. Glycerol for acute bacterial meningitis
Table 1. Available osmotic therapies

Drug

Class

Mechanism of action

Dose range and route

Studied/used in

Glycerol

Sugar alcohol

Probably osmosis plus possible vascular and metabolic benefit

IV 5% to 10% solution or 50 g

Oral 1.5 g/kg

Meningitis (Peltola 2007), stroke (Righetti 2004)

Mannitol

Sugar alcohol

Osmotic diuretic

IV 20% solution

1 mL/kg to 10 mL/kg or 1 g/kg

Brain trauma (Wakai 2013), cerebral malaria (Namutangula 2007), stroke (Bereczki 2007)

 

Sorbitol

Sugar alcohol

Osmotic diuretic (weak)

Oral, IV

Experimental brain perfusion, stroke

Hypertonic

saline

Hypertonic solutions

Osmosis

IV

Brain trauma (Choi 2005), stroke (Schwarz 2002)

Sodium

lactate

Hydroxy acids

Osmosis (weak)

IV

Brain trauma (Ichai 2009)

IV: intravenous

Figuras y tablas -
Table 1. Available osmotic therapies
Table 2. Comparison of included study interventions

Name of study

Population

Intervention and dose

Control used

Treatment duration

Study arms

Kilpi 1995

Children in Finland

Oral glycerol 4.5 g/kg max 180 g/24 h in 3 divided doses

Dexamethasone (dex) 1.5 mg/kg max 60 mg/day

No oral placebo

IV saline

3 days

4 arms: IV dexamethasone + glycerol, oral glycerol, IV dexamethasone, neither treatment

Sankar 2007

Children in India

Oral glycerol 1.5 g/kg 3 x daily

Dexamethasone 0.15 mg/kg 3 x daily

Oral carboxymethylcellulose 2%

IV saline

Not detailed

4 arms: placebo oral and IV, IV dexamethasone + oral glycerol, IV placebo + oral glycerol, IV dexamethasone + oral placebo

Peltola 2007

Children in South America

Oral glycerol 1.5 g/kg 3 x daily

Dexamethasone 0.15 mg/kg 3 x daily

Oral carboxymethylcellulose 2%

IV saline

2 days

4 arms: oral and IV placebo, IV dexamethasone + oral glycerol, IV placebo + oral glycerol, IV dexamethasone + oral placebo

Ajdukiewicz 2011

Adults in Malawi, Southern Africa

Oral glycerol 75 mg 4 x daily diluted in water or 50% dextrose solution

Oral 50% dextrose solution

4 days

Oral glycerol versus oral 50% dextrose

Molyneux 2014

Children in Malawi, Southern Africa

Oral glycerol 25 mL/dose (maximum dose) = 100 mL/24 hours.

Acetaminophen 35 mg/kg 6‐hourly

Oral carboxymethylcellulose 2%

2 days

3 arms: oral glycerol and oral acetaminophen, oral placebo and glycerol, oral acetaminophen and oral placebo

IV: intravenous

Figuras y tablas -
Table 2. Comparison of included study interventions
Comparison 1. Glycerol versus no osmotic diuretic

Outcome or subgroup title

No. of studies

No. of participants

Statistical method

Effect size

1 Death Show forest plot

5

1272

Risk Ratio (M‐H, Fixed, 95% CI)

1.08 [0.90, 1.30]

1.1 No steroids

5

853

Risk Ratio (M‐H, Fixed, 95% CI)

1.10 [0.90, 1.33]

1.2 With steroids

3

419

Risk Ratio (M‐H, Fixed, 95% CI)

1.02 [0.60, 1.74]

2 Neurological disability Show forest plot

5

1270

Risk Ratio (M‐H, Fixed, 95% CI)

0.73 [0.53, 1.00]

2.1 No steroids

5

851

Risk Ratio (M‐H, Fixed, 95% CI)

0.71 [0.49, 1.01]

2.2 With steroids

3

419

Risk Ratio (M‐H, Fixed, 95% CI)

0.82 [0.38, 1.77]

3 Seizures Show forest plot

4

1090

Risk Ratio (M‐H, Fixed, 95% CI)

1.08 [0.90, 1.30]

3.1 No steroids

4

755

Risk Ratio (M‐H, Fixed, 95% CI)

1.15 [0.92, 1.44]

3.2 With steroids

2

335

Risk Ratio (M‐H, Fixed, 95% CI)

0.96 [0.70, 1.33]

4 Hearing loss Show forest plot

5

922

Risk Ratio (M‐H, Fixed, 95% CI)

0.64 [0.44, 0.93]

4.1 No steroids

4

572

Risk Ratio (M‐H, Fixed, 95% CI)

0.63 [0.41, 0.99]

4.2 With steroids

3

350

Risk Ratio (M‐H, Fixed, 95% CI)

0.66 [0.32, 1.35]

5 Adverse effects: nausea, vomiting, diarrhoea Show forest plot

2

851

Risk Ratio (M‐H, Random, 95% CI)

1.09 [0.81, 1.47]

5.1 No steroids

2

546

Risk Ratio (M‐H, Random, 95% CI)

1.22 [0.81, 1.83]

5.2 With steroids

1

305

Risk Ratio (M‐H, Random, 95% CI)

0.86 [0.66, 1.13]

6 Adverse effects: gastrointestinal bleeding Show forest plot

3

607

Risk Ratio (M‐H, Random, 95% CI)

0.93 [0.39, 2.19]

6.1 No steroids

3

296

Risk Ratio (M‐H, Random, 95% CI)

0.39 [0.06, 2.60]

6.2 With steroids

3

311

Risk Ratio (M‐H, Random, 95% CI)

1.16 [0.44, 3.04]

Figuras y tablas -
Comparison 1. Glycerol versus no osmotic diuretic