Characteristics of included studies [ordered by study ID]
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| Methods | Randomized controlled trial |
|
| | Participants | Children aged 6-60 months with WHO definition of cerebral malaria |
|
| | Interventions | Mannitol 20% (5 mg/kg) intravenously over 20 minutes compared with placebo (matched volume of saline 0.9%) |
|
| | Outcomes | Primary outcome measures: death, hypersensitivity and vomiting
Secondary outcome measures: median time to regain consciousness.
Length of stay, requirements for ventilation and cardio-pulmonary resuscitation were not reported. |
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| | Notes | |
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| | Risk of bias |
| | Item | Authors' judgement | Description |
| | Adequate sequence generation? | Yes | Quote:"Study numbers were computer generated
and sent to the manufacturer for labelling of the drug bottles".
Comment: probably done |
| | Allocation concealment? | Yes | Quote:"Randomization was done in blocks of variable sizes
(4–10) to ensure equal distribution in each group"
Comment: probably done |
| Blinding?
All outcomes | Yes | Quote:"The caretakers and investigators were blinded to group
assignments"
Comment: no detail of blinding or matching of placebo given. Probably adequate |
| Incomplete outcome data addressed?
All outcomes | Unclear | Quote:"Twenty two children died and one was lost to follow up.
Since the analysis was by intention to treat, this patient
was assigned the worst possible outcome (death)."
Comment: incomplete outcome data addressed in the analysis |
| | Free of selective reporting? | Yes | All outcome measures reported |
| | Free of other bias? | Yes | No other bias identified |
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Comparison 1. Mannitol versus placebo
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| Outcome or subgroup title | No. of studies | No. of participants | Statistical method | Effect size |
|---|
| | 1 Death | 1 | 156 | Risk Ratio (M-H, Fixed, 95% CI) | 0.81 [0.38, 1.74] |
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|
Summary of findings for the main comparison.
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| Mannitol compared with placebo for cerebral malaria |
| Patient or population: Children aged 6-60 months with cerebral malaria
Settings: Malaria endemic countries
Intervention: Intravenous mannitol administered at the same time as commencing intravenous quinine
Comparison: Placebo (5 mL/kg of saline 0.9% administered in the same way as mannitol) |
| | Outcomes | Illustrative comparative risks* (95% CI) | Relative effect
(95% CI) | No of participants
(studies) | Quality of the evidence
(GRADE) | Comments |
| | Assumed risk | Corresponding risk |
| | Placebo | Mannitol |
| | Death | 162 per 1000 | 132 per 1000
(62 to 284) | RR 0.81
(0.38-1.74) | 156
(1 study1) | low2,3,4,5 | |
| | Major neurological sequelae | - | - | - | - | | Not reported |
| | Coma recovery time | | - | | 156
(1 study1) | low2,3,6,7 | |
| | Time to hospital discharge | - | - | - | - | | Not reported |
| | Need for ventilation | - | - | - | - | | Not reported |
| | Need for cardiopulmonary resuscitation | - | - | - | - | | Not reported |
| | Adverse events | 0 | 0 | | 156
(1 study1) | low3,4,5,6 | |
| 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. |
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1 Only one randomized controlled trial of mannitol compared to placebo in children with cerebral malaria has been conducted (Namutangula 2007)
2 No serious study limitations. This study adequately randomized participants, and blinded participants to be considered at low risk of bias. The method of allocation concealment was not clearly stated but was probably done
3 No serious inconsistency. Not applicable as only one study
4 No serious indirectness. Children aged 6-60 months who met the WHO case definition of cerebral malaria were included. Children with renal disease, cardiac failure or pulmonary congestion were excluded. 5 mL/kg of 20% mannitol (1 g/kg) or 5 mL/kg of saline as matched placebo were administered in a single dose over 20 minutes at the same time as parenteral quinine.
5 Very serious imprecision. This study is not adequately powered to detect a clinically important effect on mortality. The 95% CI is wide and includes both appreciable benefit and harm with mannitol.
6 Serious indirectness. This outcome is an indirect or surrogate indicator for poor outcomes, and on its own is not informative.
7 Serious imprecision. The article presents median times to regain conciousness, to oral intake, to sit unsupported and total coma time. The differences between the groups are not statistically significant (P > 0.05).
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