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Fluid therapy for acute bacterial meningitis

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References

References to studies included in this review

Duke 2002 {published data only}

Duke T, Mokela D, Frank D, Michael A, Paulo T, Mgone J, et al. Management of meningitis in children with oral fluid restriction or intravenous fluid at maintenance volumes: a randomised trial. Annals of Tropical Paediatrics 2002;22(2):145‐57.

Powell 1990 {published data only}

Powell K, Sugarman L, Eskenazi A, Woodin K, Kays M, McCormick K, et al. Normalization of plasma arginine vasopressin concentrations when children with meningitis are given maintenance plus replacement fluid therapy. Journal of Pediatrics 1990;117(4):515‐22.

Singhi 1995 {published data only}

Singhi S, Singhi P, Srinivas B, Narakesri H, Ganguli N, Sialy R, et al. Fluid restriction does not improve the outcome of acute meningitis. Pediatric Infectious Diseases Journal 1995;14(6):495‐503.

References to studies excluded from this review

Berkley 2004 {published data only}

Berkley JA, Versteeg AC, Mwangi I, Lowe BS, Newton CR. Indicators of acute bacterial meningitis in children at a rural Kenyan district hospital. Pediatrics 2004;114(6):e713‐9.

Brown 1994 {published data only}

Brown L, Feigin R. Bacterial meningitis: fluid balance and therapy. Pediatrics Annals 1994;23(2):93‐8.

Duke 1998 {published data only}

Duke T. Fluid management of bacterial meningitis in developing countries. Archives of Diseases in Childhood 1998;79(2):181‐5.

Floret 1999 {published data only}

Floret D. Hydration and meningitis. Archives de Pediatrie 1999;6(2):199‐202.

Maitland 2013 {published and unpublished data}

Maitland K, George EC, Evans JA, Kiguli S, Olupot‐Olupot P, Akech SO, et al. Exploring mechanisms of excess mortality with early fluid resuscitation: insights from the FEAST trial. BMC Medicine 2013;11:68. [DOI: 10.1186/1741‐7015‐11‐68]

Baraff 1993

Baraff L, Lee S, Schriger D. Outcomes of bacterial meningitis in children: a meta‐analysis. Pediatric Infectious Diseases Journal 1993;12(5):389‐94.

Bedford 2001

Bedford H, De Louvois J, Halket S, Peckham C, Hurley R, Harvey D. Meningitis in infancy in England and Wales: follow up at age 5 years. BMJ 2001;323(7312):533‐6.

Bohr 1983

Bohr V, Hansen B, Kjersem H, Rasmussen N, Johnsen N, Kristensen HS, et al. Sequelae from bacterial meningitis and their relation to the clinical condition during acute illness, based on 667 questionnaire returns. Part II of a three part series. Journal of Infection 1983;7(2):102‐10.

Brouwer 2013

Brouwer MC, McIntyre P, Prasad K, van de Beek D. Corticosteroids for acute bacterial meningitis. Cochrane Database of Systematic Reviews 2013, Issue 6. [DOI: 10.1002/14651858.CD004405.pub4]

Conner 1980

Conner W, Minielly J. Cerebral oedema in fatal meningococcaemia. Lancet 1980;2(8201):967‐9.

Dodge 1965

Dodge P, Swartz M. Bacterial meningitis: a review of selected aspects, II. Special neurologic problems, postmeningitic complications and clinicopathological correlations. New England Journal of Medicine 1965;272:1003‐10.

Feigin 1977

Feigin R, Kaplan S. Inappropriate secretion of antidiuretic hormone in children with bacterial meningitis. American Journal of Clinical Nutrition 1977;30(9):1482‐4.

Feigin 1992

Feigin R, McCracken G, Klein J. Diagnosis and management of meningitis. Pediatric Infectious Diseases Journal 1992;11(9):785‐814.

Feldman 1977

Feldman W. Relation of concentrations of bacteria and bacterial antigen in cerebrospinal fluid to prognosis in patients with bacterial meningitis. New England Journal of Medicine 1977;296(8):433‐5.

GRADE 2012 [Computer program]

Brozek J, Oxman A, Schunemann H. GRADEpro. Version 3.6 for Windows. GRADE Working Group, 2012.

Higgins 2003

Higgins JPT, Thompson SG, Deeks JJ, Altman DG. Measuring inconsistency in meta‐analyses. BMJ 2003;327(7414):557‐60.

Higgins 2011

Higgins JPT, Green S (editors). Cochrane Handbookfor Systematic Reviews of Interventions Version 5.1.0 [updated March 2011]. The Cochrane Collaboration, 2011. Available from www.cochrane‐handbook.org.

Kaplan 1983

Kaplan S, Feigin R. Treatment of meningitis in children. Pediatric Clinics of North America 1983;30(2):259‐69.

Lefebvre 2011

Lefebvre C, Manheimer E, Glanville J. Chapter 6: Searching for studies. In: Higgins JPT, Green S (editors). Cochrane Handbook for Systematic Reviews of Interventions Version 5.1.0 [updated March 2011]. The Cochrane Collaboration, 2011. Avaiable from www.cochrane‐handbook.org.

Maher 2011

Maher D, Ford N. Action on noncommunicable diseases: balancing priorities for prevention and care. Bulletin of the World Health Organization 2011;89(8):547‐547A. [DOI: 10.2471/BLT.11.091967.]

Mustafa 1990

Mustafa M, Ramilo O, Saez‐Llorens X, Olsen K, Magness R, McCracken G. Cerebrospinal fluid prostaglandins, interleukin 1 beta, and tumor necrosis factor in bacterial meningitis. Clinical and laboratory correlations in placebo‐treated and dexamethasone‐treated patients. American Journal of Diseases of Children 1990;144(8):883‐7.

Pfister 1993

Pfister H, Feiden W, Einhaupl K. Spectrum of complications during bacterial meningitis in adults. Results of a prospective clinical study. Archives of Neurology 1993;50(6):575‐81.

Prasad 2007

Prasad K, Kumar A, Singhal T, Gupta PK. Third generation cephalosporins versus conventional antibiotics for treating acute bacterial meningitis. Cochrane Database of Systematic Reviews 2007, Issue 4. [DOI: 10.1002/14651858.CD001832.pub3]

RevMan 2012 [Computer program]

The Nordic Cochrane Centre, The Cochrane Collaboration. Review Manager (RevMan). Version 5.2. Copenhagen: The Nordic Cochrane Centre, The Cochrane Collaboration, 2012.

Saez‐Llorens 1990

Saez‐Llorens X, McCracken G. Bacterial meningitis in neonates and children. Infectious Disease Clinics in North America 1990;4(4):623‐44.

Saez‐Llorens 2003

Saez‐Llorens X, McCracken G. Bacterial meningitis in children. Lancet 2003;361(9375):2139‐48.

Schunemann 2011

Schünemann HJ, Oxman AD, Vist GE, Higgins JPT, Deeks JJ, Glasziou P, et al. Chapter 12: Interpreting results and drawing conclusions. In: Cochrane Handbook for Systematic Review of Interventions. Version 5.1.0 [updated March 2011]. The Cochrane Collaboration, 2011. Available from www.cochrane‐handbook.org.

Waage 1987

Waage A, Halstensen A, Espevik T. Association between tumour necrosis factor in serum and fatal outcome in patients with meningococcal disease. Lancet 1987;1(8529):335‐7.

Williams 1964

Williams C, Swanson A, Chapman J. Brain swelling with acute purulent meningitis. Report of treatment with hypertonic intravenous urea. Pediatrics 1964;34:220‐7.

References to other published versions of this review

Maconochie 2008

Maconochie I, Baumer H, Stewart MER. Fluid therapy for acute bacterial meningitis. Cochrane Database of Systematic Reviews 2008, Issue 1. [DOI: 10.1002/14651858.CD004786.pub3]

Maconochie 2011

Maconochie I, Baumer H. Fluid therapy for acute bacterial meningitis. Cochrane Database of Systematic Reviews 2011, Issue 2. [DOI: 10.1002/14651858.CD004786.pub3]

Oates‐Whitehead 2005

Oates‐Whitehead RM, Maconochie I, Baumer H, Stewart MER. Fluid therapy for acute bacterial meningitis. Cochrane Database of Systematic Reviews 2005, Issue 3. [DOI: 10.1002/14651858.CD004786.pub2]

Characteristics of studies

Characteristics of included studies [ordered by study ID]

Jump to:

Duke 2002

Methods

Setting: Hospital Inpatient department

Study design: Randomised, parallel group, multi‐centre, controlled trial

Location: Papua New Guinea
Timing and duration: September 1997 to October 2000

Number of centres: 3

Source of funding: Roche, World Health Organization, and Royal Australasian College of Physicians

Participants

Children with clinical signs of meningitis, cloudy or turbid CSF with moderate or large amounts of leucocytes and protein on dipstick testing (Multistix 10SG, Bayer Australia Ltd, Sydney, Australia) were eligible for inclusion. Children with renal failure, congenital heart disease, who had received parenteral antibiotics for 48 hours or more in the week prior to presentation or who were septic or in hypovolaemic shock were excluded from enrolment

Age: > 1 month to < 12 years

Interventions

Nasogastric tube fluids at 60% of maintenance fluids, (maintenance fluids defined by "100 ml/kg/day for the first 10 kg of body weight, 50 ml/kg for the second 10 kg, and 20 ml/kg for over 20 kg") as expressed breast milk or other milk feed, divided into feeds given every 3 hours

versus

100% of normal maintenance fluids (defined as above) administered intravenously (given nasogastrically in 7 children because an intravenous cannula could not be inserted) given as a solution containing 0.45% sodium chloride and 5% dextrose plus 10 mmol/L of potassium chloride per litre

Duration: 48 hours

Outcomes

Death
Neurological sequelae
Oedema (including cerebral)
Serum and urinary sodium
Seizures

Notes

260 of the 357 children had confirmed bacterial meningitis. The paper states that although no bacteria were isolated in the other children the diagnosis was "definitely meningitis". Numbers of children without isolated bacteria was similar between groups

Severe sequelae were considered to be present if 14 days after commencing treatment there was a severe motor deficit (marked spasticity, hemiplegia, severe hypotonia) and at least one of the following: a major sensory deficit (inability to fix and follow in an age‐appropriate way or no response to sound), persistent convulsions or coma

All children received phenobarbitone, and received oxygen for the first 48 hours. The 1st 150 children received chloramphenicol, the rest ceftriaxone. Mechanical ventilation was not available

Risk of bias

Bias

Authors' judgement

Support for judgement

Random sequence generation (selection bias)

Low risk

Adequate, with comparable treatment and control groups at entry

Allocation concealment (selection bias)

Low risk

Adequate, using sealed envelopes

Blinding (performance bias and detection bias)
All outcomes

High risk

Clearly not

Incomplete outcome data (attrition bias)
All outcomes

Low risk

Adequate overall with 11 of 357 excluded post‐randomisation as found not to have meningitis. However, over 10% of participants lost to follow‐up at 3 months

Selective reporting (reporting bias)

Low risk

Adequate, with a good range of appropriate outcomes reported. 14 days is somewhat early to judge whether severe sequelae were present

Other bias

Low risk

A large and well‐described study

Powell 1990

Methods

Setting: Hospital Inpatient department

Study design: Randomised, parallel group, single‐centre, controlled trial

Location: USA
Timing and duration: July 1985 to June 1988

Source of funding: Hoffmann‐La Roche, Praxis Biologies, National Institute of Health

Participants

Previously healthy children with a clinical diagnosis of meningitis, and confirmed by CSF cytology and by chemical studies were eligible for inclusion. Children with central nervous system disease, renal disease, who were prematurely delivered (at less than 36 weeks gestation), who have congestive heart failure, chronic pulmonary disease, malignancy, immunodeficiency, hepatic disease, on were on morphine/phenobarbitone/phenytoin/dexamethazone or lithium were excluded from enrolment.

Age: 3 months to 16 years

Interventions

2/3 maintenance fluids (maintenance defined as 100 ml/kg for the first 10 kg of body weight, plus 50 ml/kg for the next 10 kg (10 to 20 kg), plus 20 ml/kg for each kilogram in excess of 20 kg)

versus

Full maintenance fluids (as defined above), plus replacement fluids for any estimated deficit over 24 hours. Rehydration was begun by administering 10 or 15 ml/kg by rapid intravenous infusion

Duration: 24 hours

Outcomes

Serum osmolality
Serum sodium

Notes

13 children with bacterial meningitis and 6 with aseptic meningitis were enrolled. Results were reported separately. However, the initially pathology of the 6 exclusions was not documented

Risk of bias

Bias

Authors' judgement

Support for judgement

Random sequence generation (selection bias)

Unclear risk

Not described

Allocation concealment (selection bias)

Low risk

Adequate, using sealed envelopes

Blinding (performance bias and detection bias)
All outcomes

High risk

Clearly not

Incomplete outcome data (attrition bias)
All outcomes

High risk

Did not account for all participants. 5 out of 24 participants were not included in final analysis

Selective reporting (reporting bias)

High risk

Reporting of outcome data not adequate. No reporting of important outcomes of death, intact survival

Other bias

High risk

Most eligible participants not randomised. Poor reporting of details of study

Singhi 1995

Methods

Setting: Hospital Inpatient department

Study design: Randomised, parallel group, single‐centre, controlled trial

Location: India
Timing and duration: not stated

Source of funding: not stated

Participants

Children with a diagnosis of bacterial meningitis were eligible for inclusion. Children with heart disease, respiratory illness, gastrointestinal disease, renal disease, central nervous system disease, malnutrition (less than 60% of weight expected for age), endocrinopathy, malignancy, immunodeficiency, or who had received previous anticonvulsant therapy were excluded

Age: 2 months to 7 years

Interventions

65% calculated maintenance fluid requirement, given as intravenous 1/5th normal saline in 5% dextrose for 24 hours, followed by "a gradual liberalisation at a rate of 10 ml/kg/8 hours after 24 hours of hospital stay if serum sodium and plasma osmolality had returned to normal and if there were no clinical signs of dehydration versus maintenance fluid requirements (110 ml/kg for first 10 kg, 50 ml/kg for next 10 kg and 25 ml/kg for subsequent weight) given as intravenously and comprising 1/5th normal saline in 5% dextrose" as long as they required intravenous fluids

Outcomes

Intact survival with sequelae
Death
Total body water
Extracellular water
Serum sodium plasma osmolality
Urine sodium
Urine osmolality

Notes

Trial was stopped prematurely "when a trend toward poor outcome in the restricted‐fluid group became obvious"

Risk of bias

Bias

Authors' judgement

Support for judgement

Random sequence generation (selection bias)

Unclear risk

Use of a list or table. Treatment and control groups were comparable at study entry

Allocation concealment (selection bias)

Unclear risk

Unclear, with the use of a list or table

Blinding (performance bias and detection bias)
All outcomes

High risk

Clearly neither outcome assessors, participants nor treatment providers blinded

Incomplete outcome data (attrition bias)
All outcomes

Low risk

Appeared to account for all participants

Selective reporting (reporting bias)

High risk

Mixed neurological outcomes and complications, so some important outcomes unavailable

Other bias

High risk

Study was stopped prematurely, with no a priori stopping rules, with a "trend towards poor outcome" in one group

CSF: cerebrospinal fluid

Characteristics of excluded studies [ordered by study ID]

Jump to:

Study

Reason for exclusion

Berkley 2004

Interventions and comparators not relevant

Brown 1994

Not a RCT

Duke 1998

Not a RCT

Floret 1999

Not a RCT

Maitland 2013

Sufficient data on culture‐positive bacterial meningitis not available

RCT: randomised controlled trial

Data and analyses

Open in table viewer
Comparison 1. Maintenance fluids versus restricted fluids

Outcome or subgroup title

No. of studies

No. of participants

Statistical method

Effect size

1 Death Show forest plot

2

Risk Ratio (M‐H, Fixed, 95% CI)

Subtotals only

Analysis 1.1

Comparison 1 Maintenance fluids versus restricted fluids, Outcome 1 Death.

Comparison 1 Maintenance fluids versus restricted fluids, Outcome 1 Death.

1.1 All participants

2

407

Risk Ratio (M‐H, Fixed, 95% CI)

0.82 [0.53, 1.27]

1.2 Participants with hyponatraemia

1

26

Risk Ratio (M‐H, Fixed, 95% CI)

0.15 [0.01, 2.50]

1.3 Participants without hyponatraemia

1

24

Risk Ratio (M‐H, Fixed, 95% CI)

0.79 [0.16, 3.90]

2 Severe neurological sequelae Show forest plot

2

Risk Ratio (M‐H, Fixed, 95% CI)

Subtotals only

Analysis 1.2

Comparison 1 Maintenance fluids versus restricted fluids, Outcome 2 Severe neurological sequelae.

Comparison 1 Maintenance fluids versus restricted fluids, Outcome 2 Severe neurological sequelae.

2.1 Acute (within the first 4 weeks)

2

407

Risk Ratio (M‐H, Fixed, 95% CI)

0.67 [0.41, 1.08]

2.2 Chronic (after the first 4 weeks)

1

351

Risk Ratio (M‐H, Fixed, 95% CI)

0.42 [0.20, 0.89]

2.3 Participants without hyponatraemia

1

24

Risk Ratio (M‐H, Fixed, 95% CI)

0.59 [0.13, 2.64]

2.4 Participants with hyponatraemia

1

26

Risk Ratio (M‐H, Fixed, 95% CI)

0.91 [0.34, 2.47]

3 Mild to moderate neurological sequelae Show forest plot

1

Risk Ratio (M‐H, Fixed, 95% CI)

Totals not selected

Analysis 1.3

Comparison 1 Maintenance fluids versus restricted fluids, Outcome 3 Mild to moderate neurological sequelae.

Comparison 1 Maintenance fluids versus restricted fluids, Outcome 3 Mild to moderate neurological sequelae.

3.1 At 14 days

1

Risk Ratio (M‐H, Fixed, 95% CI)

0.0 [0.0, 0.0]

4 Hemiparesis/hemiplegia Show forest plot

1

Risk Ratio (M‐H, Fixed, 95% CI)

Totals not selected

Analysis 1.4

Comparison 1 Maintenance fluids versus restricted fluids, Outcome 4 Hemiparesis/hemiplegia.

Comparison 1 Maintenance fluids versus restricted fluids, Outcome 4 Hemiparesis/hemiplegia.

4.1 At 14 days

1

Risk Ratio (M‐H, Fixed, 95% CI)

0.0 [0.0, 0.0]

5 Spasticity Show forest plot

1

Risk Ratio (M‐H, Fixed, 95% CI)

Totals not selected

Analysis 1.5

Comparison 1 Maintenance fluids versus restricted fluids, Outcome 5 Spasticity.

Comparison 1 Maintenance fluids versus restricted fluids, Outcome 5 Spasticity.

5.1 At 14 days

1

Risk Ratio (M‐H, Fixed, 95% CI)

0.0 [0.0, 0.0]

6 Seizures Show forest plot

1

Risk Ratio (M‐H, Fixed, 95% CI)

Totals not selected

Analysis 1.6

Comparison 1 Maintenance fluids versus restricted fluids, Outcome 6 Seizures.

Comparison 1 Maintenance fluids versus restricted fluids, Outcome 6 Seizures.

6.1 Within the first 72 hours

1

Risk Ratio (M‐H, Fixed, 95% CI)

0.0 [0.0, 0.0]

6.2 At 14 days

1

Risk Ratio (M‐H, Fixed, 95% CI)

0.0 [0.0, 0.0]

7 Visual impairment Show forest plot

1

Risk Ratio (M‐H, Fixed, 95% CI)

Totals not selected

Analysis 1.7

Comparison 1 Maintenance fluids versus restricted fluids, Outcome 7 Visual impairment.

Comparison 1 Maintenance fluids versus restricted fluids, Outcome 7 Visual impairment.

7.1 At 14 days

1

Risk Ratio (M‐H, Fixed, 95% CI)

0.0 [0.0, 0.0]

8 No response to sound Show forest plot

1

Risk Ratio (M‐H, Fixed, 95% CI)

Totals not selected

Analysis 1.8

Comparison 1 Maintenance fluids versus restricted fluids, Outcome 8 No response to sound.

Comparison 1 Maintenance fluids versus restricted fluids, Outcome 8 No response to sound.

8.1 At 14 days

1

Risk Ratio (M‐H, Fixed, 95% CI)

0.0 [0.0, 0.0]

9 Oedema Show forest plot

1

Risk Ratio (M‐H, Fixed, 95% CI)

Totals not selected

Analysis 1.9

Comparison 1 Maintenance fluids versus restricted fluids, Outcome 9 Oedema.

Comparison 1 Maintenance fluids versus restricted fluids, Outcome 9 Oedema.

9.1 Acute facial oedema

1

Risk Ratio (M‐H, Fixed, 95% CI)

0.0 [0.0, 0.0]

9.2 Acute pulmonary oedema

1

Risk Ratio (M‐H, Fixed, 95% CI)

0.0 [0.0, 0.0]

9.3 Acute hydrocephalus

1

Risk Ratio (M‐H, Fixed, 95% CI)

0.0 [0.0, 0.0]

10 Total body water ‐ fall after 48 hours Show forest plot

1

Mean Difference (IV, Fixed, 95% CI)

Totals not selected

Analysis 1.10

Comparison 1 Maintenance fluids versus restricted fluids, Outcome 10 Total body water ‐ fall after 48 hours.

Comparison 1 Maintenance fluids versus restricted fluids, Outcome 10 Total body water ‐ fall after 48 hours.

10.1 Participants without hyponatraemia

1

Mean Difference (IV, Fixed, 95% CI)

0.0 [0.0, 0.0]

10.2 Participants with hyponatraemia

1

Mean Difference (IV, Fixed, 95% CI)

0.0 [0.0, 0.0]

11 Extracellular water ‐ fall after 48 hours Show forest plot

1

Mean Difference (IV, Fixed, 95% CI)

Totals not selected

Analysis 1.11

Comparison 1 Maintenance fluids versus restricted fluids, Outcome 11 Extracellular water ‐ fall after 48 hours.

Comparison 1 Maintenance fluids versus restricted fluids, Outcome 11 Extracellular water ‐ fall after 48 hours.

11.1 Participants without hyponatraemia

1

Mean Difference (IV, Fixed, 95% CI)

0.0 [0.0, 0.0]

11.2 Participants with hyponatraemia

1

Mean Difference (IV, Fixed, 95% CI)

0.0 [0.0, 0.0]

12 Serum sodium Show forest plot

2

Mean Difference (IV, Fixed, 95% CI)

Totals not selected

Analysis 1.12

Comparison 1 Maintenance fluids versus restricted fluids, Outcome 12 Serum sodium.

Comparison 1 Maintenance fluids versus restricted fluids, Outcome 12 Serum sodium.

12.1 All participants (24 hours)

1

Mean Difference (IV, Fixed, 95% CI)

0.0 [0.0, 0.0]

12.2 Participants with hyponatraemia (48 hours)

1

Mean Difference (IV, Fixed, 95% CI)

0.0 [0.0, 0.0]

12.3 Participants without hyponatraemia (48 hours)

1

Mean Difference (IV, Fixed, 95% CI)

0.0 [0.0, 0.0]

12.4 Change from baseline at 48 hours ‐ without hyponatraemia

1

Mean Difference (IV, Fixed, 95% CI)

0.0 [0.0, 0.0]

12.5 Change from baseline at 48 hours ‐ with hyponatraemia

1

Mean Difference (IV, Fixed, 95% CI)

0.0 [0.0, 0.0]

13 Urinary sodium Show forest plot

1

Mean Difference (IV, Fixed, 95% CI)

Totals not selected

Analysis 1.13

Comparison 1 Maintenance fluids versus restricted fluids, Outcome 13 Urinary sodium.

Comparison 1 Maintenance fluids versus restricted fluids, Outcome 13 Urinary sodium.

13.1 Participants without hyponatraemia (48 hours)

1

Mean Difference (IV, Fixed, 95% CI)

0.0 [0.0, 0.0]

13.2 Participants with hyponatraemia (48 hours)

1

Mean Difference (IV, Fixed, 95% CI)

0.0 [0.0, 0.0]

13.3 Change from baseline at 48 hours ‐ without hyponatraemia

1

Mean Difference (IV, Fixed, 95% CI)

0.0 [0.0, 0.0]

13.4 Change from baseline at 48 hours ‐ with hyponatraemia

1

Mean Difference (IV, Fixed, 95% CI)

0.0 [0.0, 0.0]

14 Plasma osmolality ‐ change after 48 hours Show forest plot

1

Mean Difference (IV, Fixed, 95% CI)

Totals not selected

Analysis 1.14

Comparison 1 Maintenance fluids versus restricted fluids, Outcome 14 Plasma osmolality ‐ change after 48 hours.

Comparison 1 Maintenance fluids versus restricted fluids, Outcome 14 Plasma osmolality ‐ change after 48 hours.

14.1 Participants without hyponatraemia

1

Mean Difference (IV, Fixed, 95% CI)

0.0 [0.0, 0.0]

14.2 Participants with hyponatraemia

1

Mean Difference (IV, Fixed, 95% CI)

0.0 [0.0, 0.0]

Risk of bias graph: review authors' judgements about each risk of bias item presented as percentages across all included studies.
Figures and Tables -
Figure 1

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.
Figures and Tables -
Figure 2

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

Comparison 1 Maintenance fluids versus restricted fluids, Outcome 1 Death.
Figures and Tables -
Analysis 1.1

Comparison 1 Maintenance fluids versus restricted fluids, Outcome 1 Death.

Comparison 1 Maintenance fluids versus restricted fluids, Outcome 2 Severe neurological sequelae.
Figures and Tables -
Analysis 1.2

Comparison 1 Maintenance fluids versus restricted fluids, Outcome 2 Severe neurological sequelae.

Comparison 1 Maintenance fluids versus restricted fluids, Outcome 3 Mild to moderate neurological sequelae.
Figures and Tables -
Analysis 1.3

Comparison 1 Maintenance fluids versus restricted fluids, Outcome 3 Mild to moderate neurological sequelae.

Comparison 1 Maintenance fluids versus restricted fluids, Outcome 4 Hemiparesis/hemiplegia.
Figures and Tables -
Analysis 1.4

Comparison 1 Maintenance fluids versus restricted fluids, Outcome 4 Hemiparesis/hemiplegia.

Comparison 1 Maintenance fluids versus restricted fluids, Outcome 5 Spasticity.
Figures and Tables -
Analysis 1.5

Comparison 1 Maintenance fluids versus restricted fluids, Outcome 5 Spasticity.

Comparison 1 Maintenance fluids versus restricted fluids, Outcome 6 Seizures.
Figures and Tables -
Analysis 1.6

Comparison 1 Maintenance fluids versus restricted fluids, Outcome 6 Seizures.

Comparison 1 Maintenance fluids versus restricted fluids, Outcome 7 Visual impairment.
Figures and Tables -
Analysis 1.7

Comparison 1 Maintenance fluids versus restricted fluids, Outcome 7 Visual impairment.

Comparison 1 Maintenance fluids versus restricted fluids, Outcome 8 No response to sound.
Figures and Tables -
Analysis 1.8

Comparison 1 Maintenance fluids versus restricted fluids, Outcome 8 No response to sound.

Comparison 1 Maintenance fluids versus restricted fluids, Outcome 9 Oedema.
Figures and Tables -
Analysis 1.9

Comparison 1 Maintenance fluids versus restricted fluids, Outcome 9 Oedema.

Comparison 1 Maintenance fluids versus restricted fluids, Outcome 10 Total body water ‐ fall after 48 hours.
Figures and Tables -
Analysis 1.10

Comparison 1 Maintenance fluids versus restricted fluids, Outcome 10 Total body water ‐ fall after 48 hours.

Comparison 1 Maintenance fluids versus restricted fluids, Outcome 11 Extracellular water ‐ fall after 48 hours.
Figures and Tables -
Analysis 1.11

Comparison 1 Maintenance fluids versus restricted fluids, Outcome 11 Extracellular water ‐ fall after 48 hours.

Comparison 1 Maintenance fluids versus restricted fluids, Outcome 12 Serum sodium.
Figures and Tables -
Analysis 1.12

Comparison 1 Maintenance fluids versus restricted fluids, Outcome 12 Serum sodium.

Comparison 1 Maintenance fluids versus restricted fluids, Outcome 13 Urinary sodium.
Figures and Tables -
Analysis 1.13

Comparison 1 Maintenance fluids versus restricted fluids, Outcome 13 Urinary sodium.

Comparison 1 Maintenance fluids versus restricted fluids, Outcome 14 Plasma osmolality ‐ change after 48 hours.
Figures and Tables -
Analysis 1.14

Comparison 1 Maintenance fluids versus restricted fluids, Outcome 14 Plasma osmolality ‐ change after 48 hours.

Summary of findings for the main comparison. Maintenance fluids versus restricted fluids for acute bacterial meningitis in paediatric populations

Maintenance fluids versus restricted fluids for acute bacterial meningitis in paediatric populations

Patient or population: patients with acute bacterial meningitis in paediatric populations 1
Settings: Hospital Inpatient Department
Intervention: Maintenance fluids versus restricted fluids

Outcomes

Illustrative comparative risks* (95% CI)

Relative effect
(95% CI)

No. of participants
(studies)

Quality of the evidence
(GRADE)

Comments

Assumed risk

Corresponding risk

Control

Maintenance fluids versus restricted fluids

Death ‐ all patients

Study population

RR 0.82
(0.53 to 1.27)

407
(2 studies)

⊕⊕⊕⊝
moderate2,3

186 per 1000

153 per 1000
(99 to 237)

Moderate

213 per 1000

175 per 1000
(113 to 271)

Severe neurological sequelae ‐ acute (within the first 4 weeks)

Study population

RR 0.67
(0.41 to 1.08)

407
(2 studies)

⊕⊝⊝⊝
very low3,4

176 per 1000

118 per 1000
(72 to 191)

Moderate

252 per 1000

169 per 1000
(103 to 272)

Severe neurological sequelae ‐ chronic (after the first 4 weeks)

Study population

RR 0.42
(0.2 to 0.89)

351
(1 study)

⊕⊕⊕⊝
moderate5,6

121 per 1000

51 per 1000
(24 to 107)

Moderate

121 per 1000

51 per 1000
(24 to 108)

Mild to moderate neurological sequelae

Study population

RR 1.24
(0.58 to 2.65)

357
(1 study)

⊕⊕⊕⊝
moderate7

62 per 1000

78 per 1000
(36 to 166)

Moderate

63 per 1000

78 per 1000
(37 to 167)

*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) 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.

1 No studies were found comparing different intravenous fluid regimens in adult populations in the systematic review.
2Duke 2002 and Singhi 1995 both have high risk of performance and detection bias, but this would not affect the mortality outcome. We did not downgrade in spite of the unclear risk of selection bias since it contributed to only 16.4% of weight and sensitivity analysis did not alter the effect estimates much. There was no risk of reporting bias for Singhi 1995 for the outcome of death.
3 The upper and lower limits of the 95% CI of the pooled estimate are very wide and thus indicate serious imprecision.
4 In Singhi 1995 selection bias was unclear and in both Duke 2002 and Singhi 1995 the performance and detection bias were at high risk. All this indicates very serious risk of bias for this outcome.
5 In Duke 2002 performance and detection bias were at high risk.
6 There was just one study so no downgrading was done for imprecision.
7Duke 2002 had a high risk of performance and detection bias which will cause serious risk of bias for evalulation of mild to moderate neurological sequelae.

Figures and Tables -
Summary of findings for the main comparison. Maintenance fluids versus restricted fluids for acute bacterial meningitis in paediatric populations
Comparison 1. Maintenance fluids versus restricted fluids

Outcome or subgroup title

No. of studies

No. of participants

Statistical method

Effect size

1 Death Show forest plot

2

Risk Ratio (M‐H, Fixed, 95% CI)

Subtotals only

1.1 All participants

2

407

Risk Ratio (M‐H, Fixed, 95% CI)

0.82 [0.53, 1.27]

1.2 Participants with hyponatraemia

1

26

Risk Ratio (M‐H, Fixed, 95% CI)

0.15 [0.01, 2.50]

1.3 Participants without hyponatraemia

1

24

Risk Ratio (M‐H, Fixed, 95% CI)

0.79 [0.16, 3.90]

2 Severe neurological sequelae Show forest plot

2

Risk Ratio (M‐H, Fixed, 95% CI)

Subtotals only

2.1 Acute (within the first 4 weeks)

2

407

Risk Ratio (M‐H, Fixed, 95% CI)

0.67 [0.41, 1.08]

2.2 Chronic (after the first 4 weeks)

1

351

Risk Ratio (M‐H, Fixed, 95% CI)

0.42 [0.20, 0.89]

2.3 Participants without hyponatraemia

1

24

Risk Ratio (M‐H, Fixed, 95% CI)

0.59 [0.13, 2.64]

2.4 Participants with hyponatraemia

1

26

Risk Ratio (M‐H, Fixed, 95% CI)

0.91 [0.34, 2.47]

3 Mild to moderate neurological sequelae Show forest plot

1

Risk Ratio (M‐H, Fixed, 95% CI)

Totals not selected

3.1 At 14 days

1

Risk Ratio (M‐H, Fixed, 95% CI)

0.0 [0.0, 0.0]

4 Hemiparesis/hemiplegia Show forest plot

1

Risk Ratio (M‐H, Fixed, 95% CI)

Totals not selected

4.1 At 14 days

1

Risk Ratio (M‐H, Fixed, 95% CI)

0.0 [0.0, 0.0]

5 Spasticity Show forest plot

1

Risk Ratio (M‐H, Fixed, 95% CI)

Totals not selected

5.1 At 14 days

1

Risk Ratio (M‐H, Fixed, 95% CI)

0.0 [0.0, 0.0]

6 Seizures Show forest plot

1

Risk Ratio (M‐H, Fixed, 95% CI)

Totals not selected

6.1 Within the first 72 hours

1

Risk Ratio (M‐H, Fixed, 95% CI)

0.0 [0.0, 0.0]

6.2 At 14 days

1

Risk Ratio (M‐H, Fixed, 95% CI)

0.0 [0.0, 0.0]

7 Visual impairment Show forest plot

1

Risk Ratio (M‐H, Fixed, 95% CI)

Totals not selected

7.1 At 14 days

1

Risk Ratio (M‐H, Fixed, 95% CI)

0.0 [0.0, 0.0]

8 No response to sound Show forest plot

1

Risk Ratio (M‐H, Fixed, 95% CI)

Totals not selected

8.1 At 14 days

1

Risk Ratio (M‐H, Fixed, 95% CI)

0.0 [0.0, 0.0]

9 Oedema Show forest plot

1

Risk Ratio (M‐H, Fixed, 95% CI)

Totals not selected

9.1 Acute facial oedema

1

Risk Ratio (M‐H, Fixed, 95% CI)

0.0 [0.0, 0.0]

9.2 Acute pulmonary oedema

1

Risk Ratio (M‐H, Fixed, 95% CI)

0.0 [0.0, 0.0]

9.3 Acute hydrocephalus

1

Risk Ratio (M‐H, Fixed, 95% CI)

0.0 [0.0, 0.0]

10 Total body water ‐ fall after 48 hours Show forest plot

1

Mean Difference (IV, Fixed, 95% CI)

Totals not selected

10.1 Participants without hyponatraemia

1

Mean Difference (IV, Fixed, 95% CI)

0.0 [0.0, 0.0]

10.2 Participants with hyponatraemia

1

Mean Difference (IV, Fixed, 95% CI)

0.0 [0.0, 0.0]

11 Extracellular water ‐ fall after 48 hours Show forest plot

1

Mean Difference (IV, Fixed, 95% CI)

Totals not selected

11.1 Participants without hyponatraemia

1

Mean Difference (IV, Fixed, 95% CI)

0.0 [0.0, 0.0]

11.2 Participants with hyponatraemia

1

Mean Difference (IV, Fixed, 95% CI)

0.0 [0.0, 0.0]

12 Serum sodium Show forest plot

2

Mean Difference (IV, Fixed, 95% CI)

Totals not selected

12.1 All participants (24 hours)

1

Mean Difference (IV, Fixed, 95% CI)

0.0 [0.0, 0.0]

12.2 Participants with hyponatraemia (48 hours)

1

Mean Difference (IV, Fixed, 95% CI)

0.0 [0.0, 0.0]

12.3 Participants without hyponatraemia (48 hours)

1

Mean Difference (IV, Fixed, 95% CI)

0.0 [0.0, 0.0]

12.4 Change from baseline at 48 hours ‐ without hyponatraemia

1

Mean Difference (IV, Fixed, 95% CI)

0.0 [0.0, 0.0]

12.5 Change from baseline at 48 hours ‐ with hyponatraemia

1

Mean Difference (IV, Fixed, 95% CI)

0.0 [0.0, 0.0]

13 Urinary sodium Show forest plot

1

Mean Difference (IV, Fixed, 95% CI)

Totals not selected

13.1 Participants without hyponatraemia (48 hours)

1

Mean Difference (IV, Fixed, 95% CI)

0.0 [0.0, 0.0]

13.2 Participants with hyponatraemia (48 hours)

1

Mean Difference (IV, Fixed, 95% CI)

0.0 [0.0, 0.0]

13.3 Change from baseline at 48 hours ‐ without hyponatraemia

1

Mean Difference (IV, Fixed, 95% CI)

0.0 [0.0, 0.0]

13.4 Change from baseline at 48 hours ‐ with hyponatraemia

1

Mean Difference (IV, Fixed, 95% CI)

0.0 [0.0, 0.0]

14 Plasma osmolality ‐ change after 48 hours Show forest plot

1

Mean Difference (IV, Fixed, 95% CI)

Totals not selected

14.1 Participants without hyponatraemia

1

Mean Difference (IV, Fixed, 95% CI)

0.0 [0.0, 0.0]

14.2 Participants with hyponatraemia

1

Mean Difference (IV, Fixed, 95% CI)

0.0 [0.0, 0.0]

Figures and Tables -
Comparison 1. Maintenance fluids versus restricted fluids