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 10 SG) 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 of participants and personnel (performance bias)
All outcomes

High risk

Clearly not

Blinding of outcome assessment (detection bias)
All outcomes

Low risk

Low risk for outcomes of death and acute severe neurological sequelae

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

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, or 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 kg 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 ml/kg 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 of participants and personnel (performance bias)
All outcomes

High risk

Clearly not

Blinding of outcome assessment (detection bias)
All outcomes

Low risk

Low risk for outcomes of death and acute severe neurological sequelae

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

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 1/5^th 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 1/5^th 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 of participants and personnel (performance bias)
All outcomes

High risk

Clearly neither participant's nor treatment providers blinded

Blinding of outcome assessment (detection bias)
All outcomes

Low 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